Sheri Spunt, MD, MBA

  • Sheri L Spunt



Trabajo y Educación

Formación Profesional

University of Michigan GME Training Verifications, Ann Arbor, MI, 1992


UCLA, Los Angeles, CA, 1995


Johns Hopkins School of Medicine, Baltimore, MD, 1998

Certificaciones Médicas

Hematology/Oncology, American Board of Pediatrics

Pediatrics, American Board of Pediatrics

Condiciones Tratadas

Bone and soft tissue sarcoma

Germ cell tumors

Wilms tumor

Todo Publicaciones

Association of Tumor [18F]FDG Activity and Diffusion Restriction with Clinical Outcomes of Rhabdomyosarcomas. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Pourmehdi Lahiji, A., Jackson, T., Nejadnik, H., von Eyben, R., Rubin, D., Spunt, S. L., Quon, A., Daldrup-Link, H. 2018


PURPOSE: To evaluate whether the extent of restricted diffusion and 2-deoxy-2-[18F] fluoro-D-glucose ([18F]FDG) uptake of pediatric rhabdomyosarcomas (RMS) on positron emission tomography (PET)/magnetic resonance (MR) images provides prognostic information.PROCEDURE: In a retrospective, IRB-approved study, we evaluated [18F]FDG PET/CT and diffusion-weighted (DW) MR imaging studies of 21 children and adolescents (age 1-20years) with RMS of the head and neck. [18F]FDG PET and DW MR scans at the time of the initial tumor diagnosis were fused using MIM software. Quantitative measures of the tumor mass with restricted diffusion, [18F]FDG hypermetabolism, or both were dichotomized at the median and tested for significance using Gray's test. Data were analyzed using a survival analysis and competing risk model with death as the competing risk.RESULTS: [18F]FDG PET/MR images demonstrated a mismatch between tumor areas with increased [18F]FDG uptake and restricted diffusion. The DWI, PET, and DWI+PET tumor volumes were dichotomized at their median values, 23.7, 16.4, and 9.5cm3, respectively, and were used to estimate survival. DWI, PET, and DWI+PET overlap tumor volumes above the cutoff values were associated with tumor recurrence, regardless of post therapy COG stage (p=0.007, p=0.04, and p=0.07, respectively).CONCLUSION: The extent of restricted diffusion within RMS and overlap of hypermetabolism plus restricted diffusion predict unfavorable clinical outcomes.

View details for DOI 10.1007/s11307-018-1272-1

View details for PubMedID 30187233

Undifferentiated Sarcomas in Children Harbor Clinically Relevant Oncogenic Fusions and Gene Copy-Number Alterations: A Report from the Children's Oncology Group CLINICAL CANCER RESEARCH Laetsch, T. W., Roy, A., Xu, L., Black, J. O., Coffin, C. M., Chi, Y., Tian, J., Spunt, S. L., Hawkins, D. S., Bridge, J. A., Parsons, D., Skapek, S. X. 2018; 24 (16): 388897


Purpose: A comprehensive analysis of the genomics of undifferentiated sarcomas (UDS) is lacking. We analyzed copy-number alterations and fusion status in patients with UDS prospectively treated on Children's Oncology Group protocol ARST0332.Experimental Design: Copy-number alterations were assessed by OncoScan FFPE Express on 32 UDS. Whole-exome and transcriptome libraries from eight tumors with sufficient archived material were sequenced on HiSeq (2 100 bp). Targeted RNA-sequencing using Archer chemistry was performed on two additional cases.Results: Five-year overall survival for patients with UDS was 83% (95% CI, 69%-97%) with risk-adapted therapy (surgery, chemotherapy, and radiotherapy). Both focal and arm-level copy-number alterations were common including gain of 1q (8/32, 25%) and loss of 1p (7/32, 22%), both of which occurred more often in clinically defined high-risk tumors. Tumors with both loss of 1p and gain of 1q carried an especially poor prognosis with a 5-year event-free survival of 20%. GISTIC analysis identified recurrent amplification of FGF1 on 5q31.3 (q = 0.03) and loss of CDKN2A and CDKN2B on 9p21.3 (q = 0.07). Known oncogenic fusions were identified in eight of 10 cases analyzed by next-generation sequencing.Conclusions: Pediatric UDS generally has a good outcome with risk-adapted therapy. A high-risk subset of patients whose tumors have copy-number loss of 1p and gain of 1q was identified with only 20% survival. Oncogenic fusions are common in UDS, and next-generation sequencing should be considered for children with UDS to refine the diagnosis and identify potentially targetable drivers. Clin Cancer Res; 24(16); 3888-97. 2018 AACR.

View details for DOI 10.1158/1078-0432.CCR-18-0672

View details for Web of Science ID 000441804700013

View details for PubMedID 29691299

Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Hawkins, D. S., Chi, Y., Anderson, J. R., Tian, J., Arndt, C. A., Bomgaars, L., Donaldson, S. S., Hayes-Jordan, A., Mascarenhas, L., McCarville, M. B., McCune, J. S., McCowage, G., Million, L., Morris, C. D., Parham, D. M., Rodeberg, D. A., Rudzinski, E. R., Shnorhavorian, M., Spunt, S. L., Skapek, S. X., Teot, L. A., Wolden, S., Yock, T. I., Meyer, W. H. 2018: JCO2018779694


Purpose Intermediate-risk rhabdomyosarcoma (RMS) includes patients with either nonmetastatic, unresected embryonal RMS (ERMS) with an unfavorable primary site or nonmetastatic alveolar RMS (ARMS). The primary aim of this study was to improve the outcome of patients with intermediate-risk RMS by substituting vincristine and irinotecan (VI) for half of vincristine, dactinomycin, and cyclophosphamide (VAC) courses. All patients received a lower dose of cyclophosphamide and earlier radiation therapy than in previous trials. Patients and Methods Patients were randomly assigned at study entry to either VAC (cumulative cyclophosphamide dose, 16.8 g/m2) or VAC/VI (cumulative cyclophosphamide dose, 8.4 g/m2) for 42 weeks of therapy. Radiation therapy started at week 4, with individualized local control plans permitted for patients younger than 24 months. The primary study end point was event-free survival (EFS). The study design had an 80% power (5% one-sided alpha-level) to detect an improved long-term EFS from 65% (with VAC) to 76% (with VAC/VI). Results A total of 448 eligible patients were enrolled in the study. At a median follow-up of 4.8 years, the 4-year EFS was 63% with VAC and 59% with VAC/VI ( P = .51), and 4-year overall survival was 73% for VAC and 72% for VAC/VI ( P = .80). Within the ARMS and ERMS subgroups, no difference in outcome by treatment arm was found. Severe hematologic toxicity was less common with VAC/VI therapy. Conclusion The addition of VI to VAC did not improve EFS or OS for patients with intermediate-risk RMS. VAC/VI had less hematologic toxicity and a lower cumulative cyclophosphamide dose, making VAC/VI an alternative standard therapy for intermediate-risk RMS.

View details for DOI 10.1200/JCO.2018.77.9694

View details for PubMedID 30091945

Magnetic Resonance Imaging of Tumor Associated Macrophages: Clinical Translation. Clinical cancer research : an official journal of the American Association for Cancer Research Aghighi, M., Theruvath, A. J., Pareek, A., Pisani, L., Alford, R., Muehe, A. M., Sethi, T. K., Holdsworth, S. J., Hazard, F. K., Gratzinger, D., Luna-Fineman, S., Advani, R. H., Spunt, S. L., Daldrup-Link, H. E. 2018


Tumor associated macrophages (TAM) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with non-invasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults.In a first-in-patient, IRB-approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI. To confirm ferumoxytol enhancement, five pilot patients (2 lymphoma, 3 bone sarcoma) underwent pre- and post-contrast MRI. Subsequently, 20 patients (10 lymphoma, 10 bone sarcoma) underwent ferumoxytol-enhanced MRI 24-48 hours after intravenous injection, followed by tumor biopsy/resection and macrophage staining. To determine if ferumoxytol-MRI can differentiate tumors with different TAM content, we compared T2* relaxation times of lymphomas and bone sarcomas. Tumor T2* values of 20 patients were correlated with CD68+ and CD163+ TAM quantities on histopathology.Significant ferumoxytol tumor enhancement was noted on post-contrast scans compared to pre-contrast scans (P = 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density (P < 0.05). Within each tumor group, T2* signal enhancement on MR images correlated significantly with the density of CD68+ and CD163+ TAM (P < 0.05).Ferumoxytol-enhanced MRI is immediately clinically applicable and could be used to stratify patients with TAM-rich tumors to immune-targeted therapies and to monitor tumor response to these therapies.

View details for DOI 10.1158/1078-0432.CCR-18-0673

View details for PubMedID 29764855

Nonrhabdomyosarcoma Soft Tissue Sarcoma (NRSTS) in Pediatric and Young Adult Patients: Results From a Prospective Study Using Limited-Margin Radiotherapy CANCER Tinkle, C. L., Fernandez-Pineda, I., Sykes, A., Lu, Z., Hua, C., Neel, M. D., Bahrami, A., Shulkin, B. L., Kaste, S. C., Pappo, A., Spunt, S. L., Krasin, M. J. 2017; 123 (22): 441929


Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long-term treatment outcomes and toxicities for pediatric and young adult patients with high-grade NRSTS who were treated on a prospective trial using limited-margin radiotherapy.Sixty-two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external-beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan-Meier method estimated survival, competing-risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0.At a median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced local failure. The 5-year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9% (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P=.004). The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%-25.3%).The delivery of limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment-related morbidity. Cancer 2017;123:4419-29. 2017 American Cancer Society.

View details for DOI 10.1002/cncr.30793

View details for Web of Science ID 000414403100016

View details for PubMedID 28759114

View details for PubMedCentralID PMC5673566

Pre-Operative Intensity-Modulated Radiotherapy Compared to Three-Dimensional Conformal Radiotherapy for High Grade Extremity Sarcomas in Children: Analysis of Childrens Oncology Group (COG) Study ARST0332 Rao, A., Chen, Q., Million, L., Spunt, S., FitzGerald, T., Laurie, F., Kessel, S., Morano, K., Terezakis, S. WILEY. 2017: S338S339
Preoperative Intensity-Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High Grade Extremity Sarcomas in Children: An Analysis of Children's Oncology Group (COG) Study ARST 0332 Rao, A. D., Chen, Q., Million, L., Spunt, S., FitzGerald, T. J., Laurie, F., Kessel, S., Morano, K., Terezakis, S. A. ELSEVIER SCIENCE INC. 2017: S28S29
Phase 1/2 study of the selective TRK inhibitor larotrectinib, in pediatric patients with cancer Melcon, S., Casanova, M., Bielack, S., Chisholm, J., van Tilburg, C. S., Federman, N., Albert, C. M., Mascarenhas, L., Turpin, B., Nagasubramanian, R., Shukla, N., Spunt, S., Cox, M. C., Hawkins, D. S., Pappo, A. S., Doz, F., Bisogno, G., Dubois, S. G., Laetsch, T. W., Geoerger, B. OXFORD UNIV PRESS. 2017
Surgery alone is sufficient therapy for children and adolescents with low-risk synovial sarcoma: A joint analysis from the European paediatric soft tissue sarcoma Study Group and the Children's Oncology Group. European journal of cancer Ferrari, A., Chi, Y., De Salvo, G. L., Orbach, D., Brennan, B., Randall, R. L., McCarville, M. B., Black, J. O., Alaggio, R., Hawkins, D. S., Bisogno, G., Spunt, S. L. 2017; 78: 1-6


Multimodal risk-adapted treatment is used in paediatric protocols for synovial sarcoma (SS). Retrospective analyses suggest that low-risk SS patients can be safely treated with surgery alone, but no prospective studies have confirmed the safety of this approach. This analysis pooled data from the two prospective clinical trials to assess outcomes in SS patients treated with a surgery-only approach and to identify predictors of treatment failure.Patients with localised SS enrolled on the European paediatric Soft tissue sarcoma Study Group (EpSSG) NRSTS2005 and on the Children Oncology Group (COG) ARST0332 trials, treated with surgery alone were eligible for this analysis. Patients must have undergone initial complete resection with histologically free margins, with a grade 2 tumour of any size or a grade 3 tumour 5cm.Sixty patients under 21 years of age were eligible for the analysis; 36 enrolled in the COG (from 2007 to 2012) and 24 in the EpSSG study (from 2005 to 2012). The 3-year event-free survivalwas 90% (median follow-up 5.2 years, range 1.9-9.1). All eight events were local tumour recurrence, whereas no metastatic recurrences were seen. All patients with recurrence were effectively salvaged, resulting in 100% overall survival.This joint prospective analysis showed that patients with adequately resected 5cm SS, regardless of grade, can be safely treated with a surgery-only approach. Avoiding the use of adjuvant chemotherapy and radiotherapy in this low-risk patient population may decrease both short- and long-term morbidity and mortality.

View details for DOI 10.1016/j.ejca.2017.03.003

View details for PubMedID 28391003

Pleomorphic myxoid liposarcoma in an adolescent with Li-Fraumeni syndrome. Pediatric surgery international Sinclair, T. J., Thorson, C. M., Alvarez, E., Tan, S., Spunt, S. L., Chao, S. D. 2017


We present the case of a 15-year-old female with a right perineal mass that was found to be pleomorphic myxoid liposarcoma, a recently recognized, rare subtype of liposarcoma. The patient had a strong family history of malignancy and genetic screening revealed a pathogenic TP53 mutation consistent with Li-Fraumeni syndrome.

View details for DOI 10.1007/s00383-017-4063-x

View details for PubMedID 28160093

Whole-body PET/MRI of Pediatric Patients: The Details That Matter. Journal of visualized experiments : JoVE Pareek, A., Muehe, A. M., Theruvath, A. J., Gulaka, P. K., Spunt, S. L., Daldrup-Link, H. E. 2017


Integrated PET/MRI is a hybrid imaging technique enabling clinicians to acquire diagnostic images for tumor assessment and treatment monitoring with both high soft tissue contrast and added metabolic information. Integrated PET/MRI has shown to be valuable in the clinical setting and has many promising future applications. The protocol presented here will provide step-by-step instructions for the acquisition of whole-body 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/MRI data in children with cancer. It also provides instructions on how to combine a whole-body staging scan with a local tumor scan for evaluation of the primary tumor. The focus of this protocol is to be both comprehensive and time-efficient, which are two ubiquitous needs for clinical applications. This protocol was originally developed for children above 6 years, or old enough to comply with breath-hold instructions, but can also be applied to patients under general anesthesia. Similarly, this protocol can be modified to fit institutional preferences in terms of choice of MRI pulse sequences for both the whole-body scan and local tumor assessment.

View details for DOI 10.3791/57128

View details for PubMedID 29286486

Influence of Time to Detection (TTD) on Clinical Outcomes in Paediatric Testicular Tumors Brennan, R., Walsh, M., Wu, H., Wu, J., Billups, C., Spunt, S. WILEY-BLACKWELL. 2016: S30
Non-Rhabdomyosarcoma Soft Tissue Sarcoma in Pediatric and Young Adult Patients: Results From a Prospective Study Using Limited Margin Radiation Therapy Tinkle, C. L., Fernandez-Pineda, I., Li, Y., Hua, C. H., Neel, M. D., Kaste, S. C., Merchant, T. E., Kun, L. E., Spunt, S. L., Krasin, M. ELSEVIER SCIENCE INC. 2016: S119
Pulmonary Function after Treatment for Childhood Cancer. A Report from the St. Jude Lifetime Cohort Study (SJLIFE). Annals of the American Thoracic Society Green, D. M., Zhu, L., Wang, M., Ness, K. K., Krasin, M. J., Bhakta, N. H., McCarville, M. B., Srinivasan, S., Stokes, D. C., Srivastava, D., Ojha, R., Shelton, K., Pui, C., Armstrong, G. T., Mulrooney, D. A., Metzger, M., Spunt, S. L., Navid, F., Davidoff, A. M., Rao, B. N., Robison, L. L., Hudson, M. M. 2016; 13 (9): 1575-1585


The relationship between treatment-related impairment of pulmonary function in adult survivors of childhood cancer and subsequent physical function has not been studied.In this prospective evaluation of 606 adult survivors of childhood cancer, we sought to determine the risk factors for, as well as the functional impact of, clinically ascertained pulmonary function impairment.We measured FEV1, FVC, total lung capacity (TLC), and single-breath diffusing capacity of the lung for carbon monoxide corrected for hemoglobin (DlCOcorr), expressing the results as percent predicted and lower limit of normal (LLN) values, and we also assessed functional exercise capacity (6-minute-walk distance). Lung radiation exposure was expressed as the estimated percentage of lung tissue that received at least 10 Gy (V10). Associations of clinical and treatment factors with pulmonary function measures were assessed using log-binomial regression to calculate relative risks and 95% confidence intervals.The participants' median age at evaluation was 34.2 years, and the median elapsed time from diagnosis was 21.9 years. Among the sample population, 50.7% had an FEV1 percent predicted less than 80%, 47.2% had an FVC percent predicted less than 80%, 31.2% had a TLC percent predicted less than 75%, and 44.6% had DlCOcorr percent predicted less than 75%. Also, 49.0% had FEV1 less than the LLN on the basis of the Global Lung Function Initiative (GLI) criteria, and 45.4% had FVC less than LLN. Obstructive lung defects (FEV1/FVC, <0.7) were found in 0.8%, but none had obstructive lung defects on the basis of the GLI criterion of FEV1/FVC less than the LLN. Restrictive lung defects (TLC, <75%) were found in 31.2% of participants. V10 and elapsed time since diagnosis were associated with abnormal FEV1 and FVC based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 criteria, and with abnormal FEV1 using the GLI criterion. Age at diagnosis was an additional risk factor for abnormal FVC based on the GLI criteria. Age at diagnosis and V10 were associated with abnormal TLC. Increased body mass index, V10, and elapsed time since diagnosis were risk factors for abnormal DlCOcorr. Abnormal pulmonary function tests were associated with decreased 6-minute walk distance.Impaired pulmonary function in adult survivors of childhood cancer is associated with decreased physical function. These patients may benefit from interventions designed to preserve and/or improve pulmonary function.

View details for DOI 10.1513/AnnalsATS.201601-022OC

View details for PubMedID 27391297

Opportunities for Improvement in Pathology Reporting of Childhood Nonrhabdomyosarcoma Soft Tissue Sarcomas: ?A Report From Children's Oncology Group (COG) Study ARST0332. American journal of clinical pathology Black, J. O., Coffin, C. M., Parham, D. M., Hawkins, D. S., Speights, R. A., Spunt, S. L. 2016; 146 (3): 328-338


Treatment of soft tissue tumors in young patients relies on the diagnostic information conveyed in the pathology report. We examined pathology reports from Children's Oncology Group ARST0332 for inclusion of data elements required in published guidelines.Pathology reports for 551 eligible patients were examined for required data elements defined by the College of American Pathologists, including tissue type, procedure, tumor site, tumor maximum diameter, macroscopic extent of tumor, histologic type, mitotic rate, extent of necrosis, tumor grade, margin status, use of ancillary studies, and pathologic stage.Only 65 (12%) of 551 reports included all required data elements. Of reports containing synoptic templates, 57% were complete.This study reveals significant opportunity to improve the quality of pathology reports in young patients with soft tissue tumors. Use of templates or checklists improves completeness of reports.

View details for DOI 10.1093/ajcp/aqw114

View details for PubMedID 27510717

Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control. International journal of radiation oncology, biology, physics Talleur, A. C., Navid, F., Spunt, S. L., McCarville, M. B., Wu, J., Mao, S., Davidoff, A. M., Neel, M. D., Krasin, M. J. 2016; 96 (1): 119-126


To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors 8cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS).Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8cm at diagnosis, received a standard dose of 55.8Gy and tumors 8cm, an escalated dose to 64.8Gy. Patients with microscopic residual disease after resection received adjuvant RT to 50.4Gy. Adjuvant brachytherapy was permitted in selected patients.Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0years (2.9-24.7years), 9.0cm (2.4-17.0cm), and 54.5months (1.9-122.2months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failuresincluded 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4%3.1%, with no statistical difference seen between RTtreatment groups and no local failures in the escalated-dose RT treatment group.Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.

View details for DOI 10.1016/j.ijrobp.2016.04.001

View details for PubMedID 27319287

Measurement of glomerular filtration rate by dynamic contrast-enhanced magnetic resonance imaging using a subject-specific two-compartment model. Physiological reports Tipirneni-Sajja, A., Loeffler, R. B., Oesingmann, N., Bissler, J., Song, R., McCarville, B., Jones, D. P., Hudson, M., Spunt, S. L., Hillenbrand, C. M. 2016; 4 (7)


Measuring glomerular filtration rate (GFR) by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as part of standard of care clinicalMRIexams (e.g., in pediatric solid tumor patients) has the potential to reduce diagnostic burden. However, enthusiasm for this relatively newGFRtest may be curbed by the limited amount of cross-calibration studies with referenceGFRtechniques and the vast variety ofMRtracer model algorithms causing confusion on the choice of model. To advanceMRI-basedGFRquantification via improvedGFRmodeling and comparison with associated(99m)Tc-DTPA-GFR, 29 long-term Wilms' tumor survivors (19.0-43.3years, [median 32.06.0years]) treated with nephrectomy, nonnephrotoxic chemotherapy radiotherapy underwentMRIwith Gd-DTPAadministration and a(99m)Tc-DTPA GFRtest. ForDCE-MRI-basedGFRestimation, a subject-specific two-compartment (SS-2C) model was developed that uses individual hematocrit values, automatically defines subject-specific uptake intervals, and fits tracer-uptake curves by incorporating these measures. The association between reference(99m)Tc-DTPA GFRandMR-GFRs obtained bySS-2C, three published 2C uptake, and inflow-outflow models was investigated via linear regression analysis. Uptake intervals varied from 64sec to 141sec [96sec21sec] and hematocrit values ranged from 30% to 49% [41%4%]; these parameters can therefore not be assumed as constants in 2C modeling. OurMR-GFRestimates using theSS-2C model showed accordingly the highest correlation with(99m)Tc-DTPA-GFRs (R(2)=0.76,P<0.001) compared with other models (R(2)-range: 0.36-0.66). In conclusion,SS-2C modeling ofDCE-MRIdata improved the association betweenGFRobtained by(99m)Tc-DTPAand Gd-DTPA DCE-MRIto such a degree that this approach could turn into a viable, diagnosticGFRassay without radiation exposure to the patient.

View details for DOI 10.14814/phy2.12755

View details for PubMedID 27081161

Potential pitfalls of mass spectrometry to uncover mutations in childhood soft tissue sarcoma: A report from the Children's Oncology Group. Scientific reports Xu, L., Wilson, R. A., Laetsch, T. W., Oliver, D., Spunt, S. L., Hawkins, D. S., Skapek, S. X. 2016; 6: 33429-?


Mass spectrometry-based methods have been widely applied - often as the sole method - to detect mutations in human cancer specimens. We applied this approach to 52 childhood soft tissue sarcoma specimens in an attempt to identify potentially actionable mutations. This analysis revealed that 25% of the specimens harbored high-confidence calls for mutated alleles, including a mutation encoding FLT3(I836M) that was called in four cases. Given the surprisingly high frequency and unusual nature of some of the mutant alleles, we carried out ultra-deep next generation sequencing to confirm them. We confirmed only three mutations, which encoded NRAS(A18T), JAK3(V722I) and MET(R970C) in three specimens. Beyond highlighting those mutations, our findings demonstrate potential pitfalls of primarily utilizing a mass spectrometry-based approach to broadly screen for DNA sequence variants in archived, clinical-grade tumor specimens. Duplicate mass spectrometric analyses and confirmatory next generation sequencing can help diminish false positive calls, but this does not ameliorate potential false negatives due in part to evaluating a limited panel of sequence variants.

View details for DOI 10.1038/srep33429

View details for PubMedID 27642091

View details for PubMedCentralID PMC5027578

MRI and CT of Low-Grade Fibromyxoid Sarcoma in Children: A Report From Children's Oncology Group Study ARST0332 AMERICAN JOURNAL OF ROENTGENOLOGY Sargar, K., Kao, S. C., Spunt, S. L., Hawkins, D. S., Parham, D. M., Coffin, C., McCarville, M. B. 2015; 205 (2): 414-420


The purpose of this article is to determine the MRI and CT features of low-grade fibromyxoid sarcoma in children.We retrospectively analyzed images of 11 pediatric patients with low-grade fibromyxoid sarcoma from a phase 3 clinical trial of nonrhabdomyosarcoma soft-tissue sarcoma (Children's Oncology Group Protocol ARST0332). MRI and CT were performed in 10 and four patients, respectively. Location, size, margin, and composition on imaging were correlated with pathologic findings.Tumors were located in the extremities in nine patients, and one tumor each was located in the tongue and lung. Tumors were deep in seven patients and superficial in four patients. All tumors were well defined, solitary, and nonmetastatic at presentation. Tumors were complex solid-cystic in eight patients and completely solid in three patients. On T1-weighted images, all tumors had at least some areas hypointense to muscles, and six had a split-fat sign. On STIR or T2-weighted images, eight tumors had areas hypointense to adjacent muscle, and eight tumors had fluid signal intensity. On contrast-enhanced MRI studies, eight tumors had thick enhancing internal septations, and three had peripheral nodular gyriform enhancement. When we correlated imaging to pathologic findings, areas with hypointense signal intensity on both T1- and T2-weighted images were likely related to fibrous component; areas with fluid signal intensity on T2-weighted images were likely related to myxoid component. On CT, all four tumors were hypodense to muscle, and one tumor showed punctate calcific foci.Low-grade fibromyxoid sarcoma is hypodense to muscle on CT. MRI may identify both fibrous and myxoid components of this rare pediatric soft-tissue sarcoma.

View details for DOI 10.2214/AJR.14.13972

View details for Web of Science ID 000358436000045

Delayed primary excision with subsequent modification of radiotherapy dose for intermediate-risk rhabdomyosarcoma: A report from the Children's Oncology Group Soft Tissue Sarcoma Committee INTERNATIONAL JOURNAL OF CANCER Rodeberg, D. A., Wharam, M. D., Lyden, E. R., Stoner, J. A., Brown, K., Wolden, S. L., Paidas, C. N., Donaldson, S. S., Hawkins, D. S., Spunt, S. L., Arndt, C. A. 2015; 137 (1): 204-211


The majority of intermediate-risk rhabdomyosarcoma (RMS) patients have gross residual disease (Group III) after their first operative procedure. It is currently not known if local control rates can be maintained when, following induction chemotherapy, the radiation therapy (RT) dose is decreased after a delayed primary excision (DPE). To answer this question we evaluated patients enrolled on COG D9803 (1999-2005) who had Group III tumors of the bladder dome, extremity or trunk (thorax, abdomen and pelvis) were candidates for DPE at Week 12 if the primary tumor appeared resectable. RT dose was then adjusted by the completeness of DPE: no evidence of disease 36 Gy, microscopic residual 41.4 Gy and gross residual disease (GRD) 50.4 Gy. A total of 161 Group III patients were evaluated (24 bladder dome, 63 extremity and 74 trunk). Seventy-three patients (45%) underwent DPE which achieved removal of all gross disease in 61 (84%) who were then eligible for reduced RT dose (43/73 received 36 Gy, 19/73 received 41.4 Gy). The local 5-year failure rate (0% for bladder dome, 7% for extremity and 20% for trunk) was similar to IRS-IV, which did not encourage DPE and did not allow for DPE adapted RT dose reduction. In conclusion, DPE was performed in 45% of Group III RMS patients with tumors at select anatomic sites (bladder dome, extremity and trunk) and 84% of those who had DPE were eligible for RT dose reduction. Local control outcomes were similar to historic results with RT alone.

View details for DOI 10.1002/ijc.29351

View details for Web of Science ID 000353297600020

View details for PubMedID 25418440

View details for PubMedCentralID PMC4474372

Risk-based treatment for synovial sarcoma in patients under 30 years of age: Children's Oncology Group study ARST0332. Venkatramani, R., Anderson, J., Million, L., Coffin, C. M., McCarville, B., Randall, R., Parham, D., Kao, S. C., Hayes-Jordan, A., Wolden, S. L., Terezakis, S., Black, J. O., Laurie, F., Speights, R., Skapek, S., Hawkins, D. S., Spunt, S. L. AMER SOC CLINICAL ONCOLOGY. 2015
Pulmonary function in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort Study (SJLIFE). Green, D. M., Zhu, L., Krasin, M. J., Srinivasan, S., Stokes, D. C., Srivastava, D., Ness, K. K., McCarville, B., Mulrooney, D. A., Armstrong, G. T., Pui, C., Spunt, S. L., Metzger, M., Navid, F., Davidoff, A. M., Rao, B. N., Robison, L. L., Hudson, M. M. AMER SOC CLINICAL ONCOLOGY. 2015
Bilateral internal hemipelvectomy for osteosarcoma in a pediatric patient previously treated for rhabdomyosarcoma ORTHOPAEDICS & TRAUMATOLOGY-SURGERY & RESEARCH Fernandez-Pineda, I., McCarville, M. B., Brennan, R. C., Spunt, S. L., Neel, M. D., Rao, B. N. 2015; 101 (3): 395-397


The surgical treatment of malignant bone tumors involving the pelvis represents a great challenge in terms of local control. Internal hemipelvectomy is a major surgical procedure that involves the resection of the entire hemipelvis or of a portion of the hemipelvis with preservation of the ipsilateral extremity. The need for a bilateral internal hemipelvectomy is an extraordinary situation. We describe the case of an 11-year-old girl with a primary diagnosis of rhabdomyosarcoma of the bladder at the age of two years who subsequently developed a right pelvis osteosarcoma at the age of six years and a left pelvis osteosarcoma at the age of nine years. She ultimately underwent sequential bilateral internal hemipelvectomies and she postoperatively ambulates without an assist device.

View details for DOI 10.1016/j.otsr.2015.01.012

View details for Web of Science ID 000353977600022

View details for PubMedID 25817906

Growth Plate Abnormalities in Pediatric Cancer Patients Undergoing Phase 1 Anti-Angiogenic Therapy: A Report From the Children's Oncology Group Phase I Consortium PEDIATRIC BLOOD & CANCER Voss, S. D., Glade-Bender, J., Spunt, S. L., DuBois, S. G., Widemann, B. C., Park, J. R., Leary, S. E., Nelson, M. D., Adamson, P. C., Blaney, S. M., Weigel, B. 2015; 62 (1): 45-51


Pre-clinical studies suggest that anti-angiogenic agents may be toxic to the developing growth plate. The purpose of this study was to evaluate the incidence of growth plate abnormalities in children with refractory cancer undergoing anti-angiogenic therapy.Targeted radiographic studies from 53 subjects enrolled on six separate Children's Oncology Group Phase 1 and Pilot Consortium clinical trials evaluating new anti-cancer agents interfering with angiogenesis were reviewed. Subjects received tyrosine kinase inhibitors with anti-angiogenic effects (n = 35), monoclonal antibodies targeting vascular endothelial growth factor (VEGF) (n = 13), or angiopoietin (n = 5). Radiographs of their distal femur/proximal tibia were obtained at baseline. Follow-up radiographs were obtained after odd-numbered treatment cycles in patients with open growth plates who did not experience disease progression prior to cycle 3.Baseline and follow-up growth plate radiographs were acquired in 48/53 (90%) of patients. Five patients (9.4%), all of whom received a specific VEGF/VEGFR blocking agent (sunitinib [n = 1] or pazopanib [n = 4]), had growth plate abnormalities. Four patients had growth plate widening that was apparent on at least two successive radiographs, but was not confirmed by MRI. The fifth patient had progressive growth plate widening and evidence of physeal cartilage hypertrophy on MRI. Subsequent off treatment radiographs showed that the growth plate changes were reversible.Growth plate abnormalities occur in a small, but relevant number of patients undergoing anti-angiogenic therapy. These results support the need for growth plate monitoring in children with open growth plates who are receiving anti-angiogenic therapy, and for improved methods to assess toxicity of anti-angiogenic agents to the developing skeleton.

View details for DOI 10.1002/pbc.25229

View details for Web of Science ID 000345319300010

View details for PubMedCentralID PMC4237627

Phase I Clinical Trial of Ifosfamide, Oxaliplatin, and Etoposide (IOE) in Pediatric Patients With Refractory Solid Tumors JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Lam, C. G., Furman, W. L., Wang, C., Spunt, S. L., Wu, J., Ivy, P., Santana, V. M., McGregor, L. M. 2015; 37 (1): E13-E18


Oxaliplatin, although related to cisplatin and carboplatin, has a more favorable toxicity profile and may offer advantages in combination regimens. We combined oxaliplatin, ifosfamide, and etoposide (IOE) and estimated the regimen's maximum tolerated dose (MTD) in children with refractory solid tumors. Dose-limiting toxicity (DLT) and MTD were assessed at 3 dose levels in a 21-day regimen: day 1, oxaliplatin 130 mg/m (consistent dose); days 1 to 3, ifosfamide 1200 mg/m/d (level 0) or 1500 mg/m/d (levels 1 and 2) and etoposide 75 mg/m/d (levels 0 and 1) or 100 mg/m/d (level 2). Course 1 filgrastim/pegfilgrastim was permitted after initial DLT determination, if neutropenia was dose limiting. Seventeen patients received 59 courses. Without filgrastim (n=9), DLT was neutropenia in 2 patients at dose level 1. No DLT was observed after adding filgrastim (n=8). There was no ototoxicity, nephrotoxicity >grade 1, or neurotoxicity >grade 2. One patient experienced a partial response and 9 had stable disease after 2 courses. In conclusion, the IOE regimen was well tolerated. Without filgrastim, neutropenia was dose limiting with MTD at ifosfamide 1200 mg/m/d and etoposide 75 mg/m/d. The MTD with filgrastim was not defined due to early study closure. Filgrastim allowed ifosfamide and etoposide dose escalation and should be included in future studies.

View details for Web of Science ID 000346633800003

View details for PubMedID 24942022

View details for PubMedCentralID PMC4269576

Subsequent Malignant Neoplasms in Pediatric Patients Initially Diagnosed With Neuroblastoma JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Federico, S. M., Allewelt, H. B., Spunt, S. L., Hudson, M. M., Wu, J., Billups, C. A., Jenkins, J., Santana, V. M., Furman, W. L., McGregor, L. M. 2015; 37 (1): E6-E12


Most prior studies evaluating subsequent malignant neoplasms (SMNs) in patients with neuroblastoma are restricted to long-term survivors and/or their treatment exposures. This study investigates SMNs in patients diagnosed with neuroblastoma at our institution.Records of 646 patients treated for neuroblastoma at St Jude Children's Research Hospital between 1961 and 2005 were reviewed. Data from patients with SMNs were analyzed and the 20- and 30-year cumulative incidence of SMNs and standardized incidence ratio were calculated.Twenty-one patients had a SMN. The 20- and 30-year cumulative incidences of a SMN were 2.6%0.7% and 4.6%1.1%, respectively. The standardized incidence ratio was 8.3 (95% confidence interval, 5.0-13.0). Five patients developed a SMN within 5 years from diagnosis. The median latency for the development of acute myeloid leukemia/myelodysplastic syndrome (n=4), sarcomas (n=7), and carcinomas (n=5) were 3.6, 9, and 24.2 years, respectively. Nine patients died from their SMN, including all with acute myeloid leukemia/myelodysplastic syndrome.Patients with neuroblastoma have an increased risk of secondary neoplasia. Modification of risk-adapted therapies will likely alter the affected patient population and the incidence of SMNs. Future studies are necessary to link SMNs to treatment exposures and to evaluate the risk of SMNs beyond 30 years from diagnosis.

View details for Web of Science ID 000346633800002

View details for PubMedID 24633303

View details for PubMedCentralID PMC4266626

Clinical features and outcomes of young patients with head and neck non-rhabdomyosarcoma soft tissue sarcomas HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Federico, S. M., Gilpin, D., Samant, S., Billups, C. A., Spunt, S. L. 2015; 37 (1): 76-83


The history, prognostic factors, and outcome of young patients with head and neck non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) have not been adequately characterized.Medical records of 58 patients with head and neck NRSTS treated at St. Jude Children's Research Hospital were reviewed.The majority of tumors were 5 cm and high grade. Lymph node and/or distant metastases were present in 17% at presentation. Patients received a combination of surgery, chemotherapy, and radiotherapy. The 10-year event-free and survival rates were 53.1%7.3% and 63.2%7.1%, respectively. Features associated with inferior survival included high histologic grade (p=.006), tumor diameter >5 cm (p < .001), invasiveness (p < .001), and incomplete resection at diagnosis (p=.005).Most head and neck NRSTS in young patients are small, high grade, and nonmetastatic. The outcome is poor compared to NRSTS at other anatomic sites. Innovative approaches to local control and improved systemic therapy are needed.

View details for DOI 10.1002/hed.23564

View details for Web of Science ID 000346252200015

View details for PubMedID 24327514

Imaging Features of Alveolar SoftPart Sarcoma: A Report From Children's Oncology Group Study ARST0332 AMERICAN JOURNAL OF ROENTGENOLOGY McCarville, M. B., Muzzafar, S., Kao, S. C., Coffin, C. M., Parham, D. M., Anderson, J. R., Spunt, S. L. 2014; 203 (6): 1345-1352


There are few studies in the literature regarding the imaging features of alveolar soft-part sarcoma (ASPS). We performed a comprehensive assessment of the imaging characteristics of this rare tumor to determine whether there are features that suggest the diagnosis.Twenty-two subjects with ASPS underwent pretherapy imaging as part of enrollment in Children's Oncology Group protocol ARST0332 for the treatment of nonrhabdomyosarcoma soft-tissue sarcomas: 16 patients underwent MRI; three, CT; and three, both MRI and CT. Two radiologists retrospectively reviewed the imaging studies by consensus and recorded tumor location, size, contour, internal architecture, signal characteristics, presence of flow voids, and enhancement patterns.The 12 females and 10 males in the study group ranged in age from 8 to 23 years 7 months (mean, 15 years 8 months). The most common anatomic site was the lower extremity (12/22, 55%) followed by the upper extremity (4/22, 18%). The maximal tumor diameter ranged from 2.3 to 20.0 cm (median, 5.9 cm). All tumors imaged with MRI had flow voids (19/19, 100%), and 19 (19/22, 86%) had large peripheral vessels, lobulated margins, and nodular internal architecture. Unenhanced T1-weighted MRI was available for 18 tumors: 14 (14/18, 78%) appeared slightly hyperintense to muscle. Of the 16 tumors imaged with contrast material, 11 (11/16, 69%) showed intense enhancement and five (5/16, 31%), moderate enhancement. Six tumors (6/16, 38%) had a thick enhancing peripheral rim with a nonenhancing center consistent with necrosis.The imaging features of ASPS include flow voids, large peripheral vessels, internal nodularity, and lobulated margins. Contrast administration produces intense to moderate enhancement, sometimes with a thick enhancing peripheral rim around central necrosis. Extremity tumors with these imaging features in a child or young adult should suggest the diagnosis of ASPS.

View details for DOI 10.2214/AJR.14.12462

View details for Web of Science ID 000347527500050

View details for PubMedID 25415714

Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study LANCET ONCOLOGY Green, D. M., Liu, W., Kutteh, W. H., Ke, R. W., Shelton, K. C., Sklar, C. A., Chemaitilly, W., Pui, C., Klosky, J. L., Spunt, S. L., Metzger, M. L., Srivastava, D., Ness, K. K., Robison, L. L., Hudson, M. M. 2014; 15 (11): 1215-1223


Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer.We did semen analysis on 214 adult male survivors of childhood cancer (median age 77 years [range 001-203] at diagnosis, 290 years [184-561] at assessment, and a median of 210 years [105-416] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for oligospermia (sperm concentration >0 and <15 million per mL) and azoospermia were calculated with logistic regression modelling.Azoospermia was noted in 53 (25%) of 214 participants, oligospermia in 59 (28%), and normospermia (sperm concentration 15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m(2) were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=-037, p<00001). Mean CED was 10830 mg/m(2) (SD 7274) in patients with azoospermia, 8480 mg/m(2) (4264) in patients with oligospermia, and 6626 mg/m(2) (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m(2) CED for azoospermia (OR 122, 95% CI 111-134), and for oligospermia (114, 104-125), but age at diagnosis and age at assessment were not.Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m(2). Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services.US National Cancer Institute, American Lebanese Syrian Associated Charities.

View details for DOI 10.1016/S1470-2045(14)70408-5

View details for Web of Science ID 000343096800047

View details for PubMedCentralID PMC4192599

Alkylating agent exposure and sperm concentration in adult survivors of childhood cancer: A report from the St. Jude Lifetime (SJLIFE) Cohort Study. Green, D. M., Liu, W., Kutteh, W. H., Ke, R. W., Shelton, K. C., Sklar, C. A., Chemaitilly, W., Pui, C., Klosky, J., Spunt, S. L., Metzger, M., Navid, F., Srivastava, D., Ness, K. K., Robison, L. L., Hudson, M. M. AMER SOC CLINICAL ONCOLOGY. 2014
Vincristine, dactinomycin, cyclophosphamide (VAC) versus VAC/V plus irinotecan (VI) for intermediate-risk rhabdomyosarcoma (IRRMS): A report from the Children's Oncology Group Soft Tissue Sarcoma Committee. Hawkins, D. S., Anderson, J., Mascarenhas, L., McCowage, G., Rodeberg, D. A., Wolden, S. L., Parham, D., Million, L., Donaldson, S. S., Hayes-Jordan, A., Brown, K. B., Teot, L. A., Spunt, S. L., Meyer, W. H. AMER SOC CLINICAL ONCOLOGY. 2014
Risk-based treatment for nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) in patients under 30 years of age: Children's Oncology Group study ARST0332. Spunt, S. L., Million, L., Anderson, J., Coffin, C. M., McCarville, B., Randall, R., Parham, D., Kao, S. C., Hayes-Jordan, A., Wolden, S. L., Terezakis, S., Black, J., Laurie, F., Kawashima, E., Speights, R., Skapek, S., Meyer, W. H., Hawkins, D. S., Pappo, A. S. AMER SOC CLINICAL ONCOLOGY. 2014
Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma CANCER CELL Chen, X., Stewart, E., Shelat, A. A., Qu, C., Bahrami, A., Hatley, M., Wu, G., Bradley, C., McEvoy, J., Pappo, A., Spunt, S., Valentine, M. B., Valentine, V., Krafcik, F., Lang, W. H., Wierdl, M., Tsurkan, L., Tolleman, V., Federico, S. M., Morton, C., Lu, C., Ding, L., Easton, J., Rusch, M., Nagahawatte, P., Wang, J., Parker, M., Wei, L., Hedlund, E., Finkelstein, D., Edmonson, M., Shurtleff, S., Boggs, K., Mulder, H., Yergeau, D., Skapek, S., Hawkins, D. S., Ramirez, N., Potter, P. M., Sandoval, J. A., Davidoff, A. M., Mardis, E. R., Wilson, R. K., Zhang, J., Downing, J. R., Dyer, M. A. 2013; 24 (6): 710-724


Rhabdomyosarcoma is a soft-tissue sarcoma with molecular and cellular features of developing skeletal muscle. Rhabdomyosarcoma has two major histologic subtypes, embryonal and alveolar, each with distinct clinical, molecular, and genetic features. Genomic analysis shows that embryonal tumors have more structural and copy number variations than alveolar tumors. Mutations in the RAS/NF1 pathway are significantly associated with intermediate- and high-risk embryonal rhabdomyosarcomas (ERMS). In contrast, alveolar rhabdomyosarcomas (ARMS) have fewer genetic lesions overall and no known recurrently mutated cancer consensus genes. To identify therapeutics for ERMS, we developed and characterized orthotopic xenografts of tumors that were sequenced in our study. High-throughput screening of primary cultures derived from those xenografts identified oxidative stress as a pathway of therapeutic relevance for ERMS.

View details for DOI 10.1016/j.ccr.2013.11.002

View details for Web of Science ID 000328443200006

View details for PubMedID 24332040

View details for PubMedCentralID PMC3904731

Surgical Treatment of Pediatric Desmoid Tumors. A 12-Year, Single-Center Experience ANNALS OF SURGICAL ONCOLOGY Soto-Miranda, M. A., Sandoval, J. A., Rao, B., Neel, M., Krasin, M., Spunt, S., Jenkins, J. J., Davidoff, A. M., Halen, J. P. 2013; 20 (11): 3384-3390


Pediatric desmoid tumors (PDTs) represent a group of rare, distinct lesions. While sparse, available literature suggests that PDT are particularly aggressive and difficult to control when compared with their adult counterpart.A retrospective review identified 39 patients who underwent treatment of PDT at St. Jude Children's Research Hospital over a 12-year period. Clinicopathologic and treatment characteristics were analyzed to identify predictors of outcome.A total of 39 patients were treated during the study period, with a total number of 67 resections. Median age was 12.2years; 49% of patients were male, and 51% were female. Median tumor size was 9.8cm. PDT most commonly arose in the extremities (40%), thorax (23%), head and neck (21%), and trunk (16%). Also, 18% of resections had negative margins (R0), 48% were microscopic positive (R1), and 30% were macroscopic positive (R2). The 1- and 5-year recurrence-free survival (RFS) was 97.1 and 73.1%, respectively. Factors associated with worse RFS were patient age>12years (HR=5.08, p=0.038) and tumor size>5cm (HR=1.22, p=0.0597). Margin status did not affect RFS. Selective use of radiation therapy appeared to improve RFS.Our study suggests that margin status alone at the time of extirpation is not a predictor of ultimate cure or likelihood of recurrence. Many patients received adjuvant therapy, with benefits suggested after analysis. For patients with PDT, surgical extirpation should not come at the expense of functional preservation, as overall survival is excellent.

View details for DOI 10.1245/s10434-013-3090-7

View details for Web of Science ID 000324060100007

View details for PubMedID 23838914

Histologic and Clinical Characteristics Can Guide Staging Evaluations for Children and Adolescents With Rhabdomyosarcoma: A Report From the Children's Oncology Group Soft Tissue Sarcoma Committee JOURNAL OF CLINICAL ONCOLOGY Weiss, A. R., Lyden, E. R., Anderson, J. R., Hawkins, D. S., Spunt, S. L., Walterhouse, D. O., Wolden, S. L., Parham, D. M., Rodeberg, D. A., Kao, S. C., Womer, R. B. 2013; 31 (26): 3226-3232


To simplify the recommended staging evaluation by correlating tumor and clinical features with patterns of distant metastasis in newly diagnosed patients with embryonal rhabdomyosarcoma (ERMS) or alveolar rhabdomyosarcoma (ARMS).Patient data from the Intergroup Rhabdomyosarcoma Study Group and the Children's Oncology Group over two periods were analyzed: 1991 to 1997 and 1999 to 2004. We used recursive partitioning analyses to identify factors (including histology, age, regional nodal and distant metastatic status, tumor size, local invasiveness, and primary site) that divided patients into subsets with the most different rates of metastatic disease.Of the 1,687 patients analyzed, 5.7% had lung metastases, 4.8% had bone involvement, and 6% had bone marrow (BM) involvement. Rhabdomyosarcoma (RMS) without local invasion (T1) had a low rate of metastasis for all distant sites, especially ERMS (0% bone, 0% BM). ARMS with local invasion (T2) had a higher rate of metastasis for all distant sites (13% lung, 18% bone, 23% BM). ERMS, T2 also had a higher rate of metastatic lung involvement (9%). The likelihood of bone or BM involvement increased in the presence of lung metastases (41% with, 6% without). Regional nodal metastases (N1) predicted a high rate of metastasis in all distant sites (14% lung, 14% bone, 18% BM). A staging algorithm was developed.Staging studies in childhood RMS can be tailored to patients' presenting characteristics. Bone marrow aspirate and biopsy and bone scan are unnecessary in at least one third of patients with RMS.

View details for DOI 10.1200/JCO.2012.44.6476

View details for Web of Science ID 000330541000012

View details for PubMedID 23940218

View details for PubMedCentralID PMC3757291

Chemotherapy-Related Neuropathic Symptoms and Functional Impairment in Adult Survivors of Extracranial Solid Tumors of Childhood: Results From the St. Jude Lifetime Cohort Study ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION Ness, K. K., Jones, K. E., Smith, W. A., Spunt, S. L., Wilson, C. L., Armstrong, G. T., Srivastava, D. K., Robison, L. L., Hudson, M. M., Gurney, J. G. 2013; 94 (8): 1451-1457


To ascertain prevalence of peripheral sensory and motor neuropathy, and to evaluate impairments in relation to function.St. Jude Lifetime Cohort Study, a clinical follow-up study designed to evaluate adverse late effects in adult survivors of childhood cancer.A children's research hospital.Eligibility required treatment for an extracranial solid malignancy between 1962 and 2002, age 18 years, 10 years postdiagnosis, and no history of cranial radiation. Survivors (N=531) were included in the evaluation with a median age of 32 years and a median time from diagnosis of 25 years.Not applicable.Primary exposure measures were cumulative doses of vinca-alkaloid and platinum-based chemotherapies. Survivors with scores 1 on the sensory subscale of the Modified Total Neuropathy Score were classified with prevalent sensory impairment. Those with sex-specific z scores of -1.3 for dorsiflexion strength were classified with prevalent motor impairment. Participants completed the 6-minute walk test (endurance), the Timed Up & Go test (mobility), and the Sensory Organization Test (balance).The prevalence of sensory and motor impairment was 20% and 17.5%, respectively. Vinca-alkaloid exposure was associated with an increased risk of motor impairment (adjusted odds ratio [OR]=1.66; 95% confidence interval [CI], 1.04-2.64) without evidence for a dose response. Platinum exposure was associated with increased risk of sensory impairment (adjusted OR=1.62; 95% CI, .97-2.72) without evidence of a dose response. Sensory impairment was associated with poor endurance (OR=1.99; 95% CI, .99-4.0) and mobility (OR=1.65; 95% CI, .96-2.83).Vincristine and cisplatin exposure may increase risk for long-term motor and sensory impairment, respectively. Survivors with sensory impairment are at increased risk for functional performance limitations.

View details for DOI 10.1016/j.apmr.2013.03.009

View details for Web of Science ID 000322801600004

View details for PubMedID 23537607

View details for PubMedCentralID PMC3929944

Comparison of PET-CT and conventional imaging in staging pediatric rhabdomyosarcoma PEDIATRIC BLOOD & CANCER Federico, S. M., Spunt, S. L., Krasin, M. J., Billup, C. A., Wu, J., Shulkin, B., Mandell, G., McCarville, M. B. 2013; 60 (7): 1128-1134


Over the past decade, PET-CT has been used to assess rhabdomyosarcoma (RMS) in children. However, the role of PET-CT in staging RMS is unknown.Thirty subjects with RMS, median age 7.3 years, underwent PET-CT before therapy. PET-CTs and conventional imaging (CI) were independently reviewed by two radiologists and two nuclear medicine physicians to determine the presence of metastases. Accuracy, sensitivity, and specificity of PET-CT for detecting metastases were compared to CI using biopsy and clinical follow-up as reference standards. Maximum standardized uptake values (SUV(max)) of primary tumors, lymph nodes, and pulmonary nodules were measured.Primary tumors had an average SUV(max) of 7.2 (range, 2.5-19.2). Accuracy rates for 17 subjects with nodal disease were 95% for PET-CT and 49% for CI. PET-CT had 94% sensitivity and 100% specificity for nodal disease. Of seven pulmonary nodules detected by CI, three were not identified by PET-CT, two were indeterminate, and one was malignant with a SUV(max) (3.4) > twice that of benign nodules. Two subjects had bone disease; both were identified by PET-CT but only one by CI. Four subjects had bone marrow disease, two had positive PET-CTs but none had positive CI. Two subjects had soft tissue metastases detected by PET-CT but not CI.PET-CT performed better than CI in identifying nodal, bone, bone marrow, and soft tissue disease in children with RMS. CI remains essential for detection of pulmonary nodules. We recommend PET-CT for staging of children with RMS. CI with Tc(99m) bone scan can be eliminated.

View details for DOI 10.1002/pbc.24430

View details for Web of Science ID 000319361300020

View details for PubMedID 23255260

View details for PubMedCentralID PMC4266929

Relevance of historical therapeutic approaches to the contemporary treatment of pediatric solid tumors PEDIATRIC BLOOD & CANCER Green, D. M., Kun, L. E., Matthay, K. K., Meadows, A. T., Meyer, W. H., Meyers, P. A., Spunt, S. L., Robison, L. L., Hudson, M. M. 2013; 60 (7): 1083-1094


Children with solid tumors, most of which are malignant, have an excellent prognosis when treated on contemporary regimens. These regimens, which incorporate chemotherapeutic agents and treatment modalities used for many decades, have evolved to improve relapse-free survival and reduce long-term toxicity. This review discusses the evolution of the treatment regimens employed for management of the most common solid tumors, emphasizing the similarities between contemporary and historical regimens. These similarities allow the use of historical patient cohorts to identify the late effects of successful therapy and to evaluate remedial interventions for these adverse effects.

View details for DOI 10.1002/pbc.24487

View details for Web of Science ID 000319361300013

View details for PubMedID 23418018

View details for PubMedCentralID PMC3810072

Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: Results of a Children's Oncology Group (COG) Phase II Study PEDIATRIC BLOOD & CANCER Skapek, S. X., Anderson, J. R., Hill, D. A., Henry, D., Spunt, S. L., Meyer, W., Kao, S., Hoffer, F. A., Grier, H. E., Hawkins, D. S., Raney, R. B. 2013; 60 (7): 1108-1112


Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children's Oncology Group.Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging.Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10-18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23-0.48) and 96%, respectively. All three deaths were due to progressive DT.Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates.

View details for DOI 10.1002/pbc.24457

View details for Web of Science ID 000319361300016

View details for PubMedID 23281268

View details for PubMedCentralID PMC4646066

Children's Oncology Group's 2013 blueprint for research: Soft tissue sarcomas PEDIATRIC BLOOD & CANCER Hawkins, D. S., Spunt, S. L., Skapek, S. X. 2013; 60 (6): 1001-1008


In the US, approximately 850-900 children are diagnosed each year with soft tissue sarcomas (STS). Key findings from recent Children's Oncology Group (COG) clinical trials include safe reduction in therapy for low risk rhabdomyosarcoma (RMS), validation of FOXO1 fusion as a prognostic factor, a modest improvement in outcome for high-risk RMS, and a biologically designed non-cytotoxic therapy for pediatric desmoid tumor. Planned Phase 2 trials include targeted agents for VEGF/PDGF, mTOR, and IGF-1R for children with RMS and VEGF for children with non-RMS STS (NRSTS). For RMS, COG Phase 3 trials potentially will explore VEGF/mTOR inhibition or chemotherapy interval compression. For NRSTS, a COG Phase 3 trial will explore VEGF inhibition.

View details for DOI 10.1002/pbc.24435

View details for Web of Science ID 000317934800029

View details for PubMedID 23255356

View details for PubMedCentralID PMC3777409

A randomized, double-blinded, placebo-controlled, multi-institutional, cross-over, phase II. 5 study of saracatinib (AZD0530), a selective Src kinase inhibitor, in patients with recurrent osteosarcoma localized to the lung. Baird, K., Reinke, D. K., Pressey, J., Mascarenhas, L., Federman, N., Marina, N., Chawla, S. P., Lagmay, J., Goldberg, J. M., Milhem, M. M., Loeb, D., Butrynski, J. E., Janeway, K. A., Turpin, B., Staddon, A. P., Spunt, S. L., Rodler, E. T., Schuetze, S., Okuno, S. H., Heiman, L. J. AMER SOC CLINICAL ONCOLOGY. 2013
Lack of Specificity of Plasma Concentrations of Inhibin B and Follicle-Stimulating Hormone for Identification of Azoospermic Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study JOURNAL OF CLINICAL ONCOLOGY Green, D. M., Zhu, L., Zhang, N., Sklar, C. A., Ke, R. W., Kutteh, W. H., Klosky, J. L., Spunt, S. L., Metzger, M. L., Navid, F., Srivastava, D., Robison, L. L., Hudson, M. M. 2013; 31 (10): 1324-1328


Many male survivors of childhood cancer are at risk for azoospermia. Although both the levels of follicle-stimulating hormone (FSH) and inhibin B are correlated with sperm concentration, their ability to predict azoospermia in survivors of childhood cancer remains uncertain.Semen analysis was performed and serum levels of FSH and inhibin B were measured in 275 adult male survivors of childhood cancer who had received gonadotoxic therapy. Receiver operating characteristic (ROC) analysis was performed to determine the optimal inhibin B and FSH values for identifying patients with azoospermia. The patient sample was divided into a learning set and a validation set. Sensitivity, specificity, and positive and negative predictive value were calculated.Inhibin B was dichotomized as 31 ng/L or more than 31 ng/L and FSH was dichotomized as 11.5 mIU/mL or more than 11.5 mIU/mL based on results of the ROC analysis. Using these values, the specificity of the serum level of inhibin B for identifying azoospermic survivors was 45.0%, and the positive predictive value was 52.1%. The specificity for FSH was 74.1%, and the positive predictive value was 65.1%.Neither serum inhibin B nor FSH is a suitable surrogate for determination of sperm concentration in a semen sample. Young men and their physicians should be aware of the limitations of these measures for assessment of fertility potential.

View details for DOI 10.1200/JCO.2012.43.7038

View details for Web of Science ID 000317003300020

View details for PubMedID 23423746

View details for PubMedCentralID PMC3607671

Overcoming autopsy barriers in pediatric cancer research PEDIATRIC BLOOD & CANCER Alabran, J. L., Hooper, J. E., Hill, M., Smith, S. E., Spady, K. K., Davis, L. E., Peterson, L. S., Malempati, S., Ryan, C. W., Acosta, R., Spunt, S. L., Keller, C. 2013; 60 (2): 204-209


More than 13,000 children annually in the United States and Canada under the age of 20 will be diagnosed with cancer at a mortality approaching 20% 1,2. Tumor samples obtained by autopsy provide an innovative way to study tumor progression, potentially aiding in the discovery of new treatments and increased survival rates. The purpose of this study was to identify barriers to autopsies and develop guidelines for requesting autopsies for research purposes.Families of children treated for childhood cancer were referred by patient advocacy groups and surveyed about attitudes and experiences with research autopsies. From 60 interviews, barriers to autopsy and tumor banking were identified. An additional 14 interviews were conducted with medical and scientific experts.Ninety-three percent of parents of deceased children did or would have consented to a research autopsy if presented with the option; however, only half of these families were given the opportunity to donate autopsy tissue for research. The most significant barriers were the physicians' reluctance to ask a grieving family and lack of awareness about research opportunities.The value of donating tumor samples to research via an autopsy should be promoted to all groups managing pediatric cancer patients. Not only does autopsy tumor banking offer a potentially important medical and scientific impact, but the opportunity to contribute this Legacy Gift of autopsy tumor tissue also creates a positive outlet for the grieving family. Taking these findings into account, our multidisciplinary team has developed a curriculum addressing key barriers.

View details for DOI 10.1002/pbc.24320

View details for Web of Science ID 000312557600006

View details for PubMedID 23015377

View details for PubMedCentralID PMC3522778

Phase I and Clinical Pharmacology Study of Bevacizumab, Sorafenib, and Low-Dose Cyclophosphamide in Children and Young Adults with Refractory/Recurrent Solid Tumors CLINICAL CANCER RESEARCH Navid, F., Baker, S. D., McCarville, M. B., Stewart, C. F., Billups, C. A., Wu, J., Davidoff, A. M., Spunt, S. L., Furman, W. L., McGregor, L. M., Hu, S., Panetta, J. C., Turner, D., Fofana, D., Reddick, W. E., Leung, W., Santana, V. M. 2013; 19 (1): 236-246


To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, and pharmacodynamics of sorafenib, bevacizumab, and low-dose oral cyclophosphamide in children and young adults with recurrent/refractory solid tumors.Sorafenib dose was escalated from 90 to 110 mg/m(2) twice daily with fixed doses of bevacizumab at 5 mg/kg every 3 weeks and cyclophosphamide at 50 mg/m(2) daily. Once sorafenib's MTD was established, bevacizumab dose was escalated. Each course was of 21 days. Pharmacokinetics and pharmacodynamics studies were conducted during the first course.Nineteen patients (11 males; median age, 9.2 years) received a median of four courses (range, 1-23). DLTs during course 1 included grade 3 rash (two), increased lipase (one), anorexia (one), and thrombus (one). With an additional 71 courses of therapy, the most common toxicities grade 3 included neutropenia (nine), lymphopenia (nine), and rashes (four). Five of 17 evaluable patients had partial tumor responses, and five had disease stabilization (>2 courses). Median day 1 cyclophosphamide apparent oral clearance was 3.13 L/h/m(2). Median day 1 sorafenib apparent oral clearance was 44 and 39 mL/min/m(2) at the 2 dose levels evaluated, and steady-state concentrations ranged from 1.64 to 4.8 mg/L. Inhibition of serum VEGF receptor 2 (VEGFR2) was inversely correlated with sorafenib steady-state concentrations (P = 0.019).The recommended phase II doses are sorafenib, 90 mg/m(2) twice daily; bevacizumab, 15 mg/kg q3 weeks; and cyclophosphamide, 50 mg/m(2) once daily. This regimen is feasible with promising evidence of antitumor activity that warrants further investigation.

View details for DOI 10.1158/1078-0432.CCR-12-1897

View details for Web of Science ID 000313051100025

View details for PubMedID 23143218

View details for PubMedCentralID PMC3537913

Primary Intrathoracic Dermatofibrosarcoma Protuberans AMERICAN JOURNAL OF SURGICAL PATHOLOGY King, L., Lopez-Terrada, D., Jakacky, J., McCarville, M. B., Spunt, S. L., Bridge, J. A., Bahrami, A. 2012; 36 (12): 1897-1902


Dermatofibrosarcoma protuberans (DFSP) is defined as a low-grade sarcoma derived from an uncertain cell of origin in the reticular dermis. We report a fibrosarcomatous variant of DFSP (FS-DFSP) that arose primarily in the deep thoracic soft tissue. The patient was a 9-year-old girl who presented with dyspnea and low-grade fevers without a clinically detectable mass or a history of skin lesion. Imaging studies revealed a 10-cm mass entirely confined within the thoracic cavity. Three years after a marginal excision with adjuvant chemotherapy and radiotherapy, the tumor recurred in the paraspinal region. Histologically, the primary and recurrent tumors comprised a high-grade spindle cell sarcoma, with a small component of storiform, low-grade, CD34-positive spindle cells, classic for an ordinary DFSP. The diagnosis of FS-DFSP was confirmed molecularly by the demonstration of a COL1A1-PDGFB fusion by fluorescence in situ hybridization and reverse transcription-polymerase chain reaction analyses. To our knowledge, this is the first documented case of a genetically confirmed deep-seated DFSP without an associated superficial soft tissue or dermal component. The implication of this case on expanding the clinical spectrum of DFSP will have to be elucidated in future studies by applying molecular pathologic tools in deep-seated sarcomas in the proper morphologic context.

View details for DOI 10.1097/PAS.0b013e31826b7919

View details for Web of Science ID 000311233500019

View details for PubMedID 23108023

Association of bone mineral density with incidental renal stone in long-term survivors of childhood acute lymphoblastic leukemia JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE Gawade, P. L., Ness, K. K., Sharma, S., Li, Z., Srivastava, D. K., Spunt, S. L., Nottage, K., Krasin, M. J., Hudson, M. M., Kaste, S. C. 2012; 6 (4): 388-397


Our objective was to evaluate the association between low bone mineral density (BMD) and incidental renal stones among long-term survivors of childhood acute lymphoblastic leukemia (ALL).Adult participants who were 10+years from their childhood ALL diagnosis and members of the St. Jude Lifetime Cohort study were recruited between December 2007 and March 2011. During their risk-based medical evaluations, they underwent quantitative computed tomography (QCT) to evaluate BMD. Incidental renal stones were identified by radiologists' review of axial QCT source images. Demographic and dietary information were abstracted from health surveys and the Block Food Frequency questionnaire, respectively. The multivariable logistic regression model was used for analysis.At a median of 26.1years from diagnosis, BMD Z scores were -2 in 34 of 662 (5.2%) and renal stones detected in 73 of 662 (11%) participants. Adjusted for age, renal radiation, dietary vitamin D, gender, and body mass index, when compared to those with BMD Z scores 0, the risk of renal stones was increased among those with BMD Z scores -2 (odds ratio [OR], 2.92; 95% confidence interval [CI] 1.14-7.48). Risk of renal stones significantly increased for older age (45-54 vs.18-24years; OR, 3.70; 95% CI 1.11-12.35) whereas the risk was higher but nonsignificant for >141.5IU (sample median) daily intake of vitamin D (OR, 1.64; 95% CI 0.98-2.75).Older ALL survivors with BMD Z scores -2 are at risk for renal stones and should be counseled so that appropriate follow-up care can be provided for those among whom renal stones are detected.

View details for DOI 10.1007/s11764-012-0241-y

View details for Web of Science ID 000311534600005

View details for PubMedID 22956305

View details for PubMedCentralID PMC3529472

Parent-Clinician Communication Intervention during End-of-Life Decision Making for Children with Incurable Cancer JOURNAL OF PALLIATIVE MEDICINE Hinds, P. S., Oakes, L. L., Hicks, J., Powell, B., Srivastava, D. K., Baker, J. N., Spunt, S. L., West, N. K., Furman, W. L. 2012; 15 (8): 916-922


In this single-site study, we evaluated the feasibility of a parent-clinician communication intervention designed to: identify parents' rationale for the phase I, do-not-resuscitate (DNR), or terminal care decision made on behalf of their child with incurable cancer; identify their definition of being a good parent to their ill child; and provide this information to the child's clinicians in time to be of use in the family's care.Sixty-two parents of 58 children and 126 clinicians participated. Within 72 hours after the treatment decision, parents responded to 6 open-ended interview questions and completed a 10-item questionnaire about the end-of-life communication with their child's clinicians. They completed the questionnaire again two to three weeks later and responded to three open-ended questions to assess the benefit:risk ratio of their study participation three months after the intervention. Clinicians received the interview data within hours of the parent interview and evaluated the usefulness of the information three weeks later.All preestablished intervention feasibility criteria were met; 77.3% of families consented; and in 100% of interventions, information was successfully provided individually to 3 to 11 clinicians per child before the child died. No harm was reported by parents as a result of participating; satisfaction and other benefits were reported. Clinicians reported moderate to strong satisfaction with the intervention.The communication intervention was feasible within hours of decision making, was acceptable and beneficial without harm to participating parents, and was acceptable and useful to clinicians in their care of families.

View details for DOI 10.1089/jpm.2012.0006

View details for Web of Science ID 000307095200014

View details for PubMedID 22734685

View details for PubMedCentralID PMC3396144

The clinical, research, and social value of autopsy after any cancer death CANCER Spunt, S. L., Vargas, S. O., Coffin, C. M., Skapek, S. X., Parham, D. M., Darling, J., Hawkins, D. S., Keller, C. 2012; 118 (12): 30029

View details for DOI 10.1002/cncr.26620

View details for Web of Science ID 000304761000001

View details for PubMedID 22006470

View details for PubMedCentralID PMC3274663

Treatment Outcomes in Black and White Children With Cancer: Results From the SEER Database and St Jude Children's Research Hospital, 1992 Through 2007 JOURNAL OF CLINICAL ONCOLOGY Pui, C., Pei, D., Pappo, A. S., Howard, S. C., Cheng, C., Sandlund, J. T., Furman, W. L., Ribeiro, R. C., Spunt, S. L., Rubnitz, J. E., Jeha, S., Hudson, M. M., Kun, L. E., Merchant, T. E., Kocak, M., Broniscer, A., Metzger, M. L., Downing, J. R., Leung, W., Evans, W. E., Gajjar, A. 2012; 30 (16): 2005-2012


Treatment outcome for black patients with cancer has been significantly worse than for their white counterparts. We determined whether recent improved treatment had narrowed the gap in outcome between black and white pediatric patients.In a parallel comparison, we analyzed survival by disease category between black and white patients with childhood cancer registered in one of the 17 cancer registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program or treated at St Jude Children's Research Hospital, which provides comprehensive treatment to all patients regardless of their ability to pay, from 1992 to 2000 and from 2001 to 2007.Analysis of the SEER data indicated that in both study periods, black patients had significantly poorer rates of survival than did white patients, with the exception of a few types of cancer. Despite significantly improved treatment outcomes for patients who were treated from 2001 to 2007, the racial difference in survival has actually widened for acute myeloid leukemia and neuroblastoma. By contrast, in the cohorts treated at St Jude Children's Research Hospital, there were no significant differences in survival between black and white patients in either study period, regardless of the cancer type. Importantly, the outcome of treatment for acute lymphoblastic leukemia, acute myeloid leukemia, and retinoblastoma has improved in parallel for both races during the most recent study period.With equal access to comprehensive treatment, black and white children with cancer can achieve the same high cure rates.

View details for DOI 10.1200/JCO.2011.40.8617

View details for Web of Science ID 000304596800023

View details for PubMedID 22547602

View details for PubMedCentralID PMC3383176

The clinical phenotype of children with Fanconi anemia caused by biallelic FANCD1/BRCA2 mutations PEDIATRIC BLOOD & CANCER Myers, K., Davies, S. M., Harris, R. E., Spunt, S. L., Smolarek, T., Zimmerman, S., McMasters, R., Wagner, L., Mueller, R., Auerbach, A. D., Mehta, P. A. 2012; 58 (3): 462-465


Fanconi anemia (FA) is characterized by progressive marrow failure, congenital anomalies, and predisposition to malignancy. Biallelic FANCD1/BRCA2 mutations are the genetic basis of disease in a small proportion of children with FA with earlier onset and increased incidence of leukemia and solid tumors. Patients with FA have increased sensitivity to chemotherapy and radiation, and upon development of a solid tumor, require modification of these therapies. We report clinical and molecular features of three patients with FA associated with FANCD1/BRCA2 mutations, including two novel mutations, and discuss treatment of malignancy and associated side effects in this particularly vulnerable group.

View details for DOI 10.1002/pbc.23168

View details for Web of Science ID 000298953700027

View details for PubMedID 21548014

Pulmonary function after whole lung irradiation in pediatric patients with solid malignancies CANCER Motosue, M. S., Zhu, L., Srivastava, K., Stokes, D. C., Hudson, M. M., McPherson, V., Srinivasan, S., Krasin, M. J., Green, D. M., Spunt, S. L., Inaba, H. 2012; 118 (5): 1450-1456


Although whole lung irradiation is used to treat pulmonary metastases of pediatric solid malignancies, few studies have addressed its long-term pulmonary consequences.The authors conducted a retrospective study of longitudinal changes in 171 pulmonary function tests (PFTs) and their relation with clinical features in 48 survivors of pediatric malignant solid tumors treated with whole lung irradiation.Although active respiratory symptoms were seen in only 9 patients (18.8%), abnormalities in forced vital capacity (FVC; 58.3%), forced expiratory volume in 1 second (FEV(1) ; 64.6%), total lung capacity (TLC; 72.9%), and diffusion capacity of the lung for carbon monoxide corrected for hemoglobin (DLCO(corr) ; 70.8%) were common. At a median follow-up of 9.7 years after whole lung irradiation, FVC, FEV(1) , and TLC significantly declined longitudinally (P = .04, .03, and .02, respectively). Focal pulmonary boost irradiation was significantly associated with abnormal FEV(1) /FVC (P = .03), forced expiratory flow between 25% and 75% forced vital capacity (P = .005), residual volume (RV; P = .005), and RV/TLC (P = .002). Ten patients had baseline PFTs, and FVC, FEV(1) , TLC, and DLCO(corr) worsened immediately after radiation, followed by transient improvement but subsequent decline. Thirteen of 32 (40.6%) patients aged >18 years were smokers.Pulmonary dysfunction was prevalent after whole lung irradiation and worsened over time, although most patients were asymptomatic. Boost irradiation impaired pulmonary function, and a significant proportion of patients were smokers. Further studies are planned to assess the predictors and clinical consequences of progressive PFT abnormalities and to evaluate educational interventions.

View details for DOI 10.1002/cncr.26371

View details for Web of Science ID 000300667800033

View details for PubMedID 21800284

View details for PubMedCentralID PMC3233655

Patterns of chemotherapy-induced toxicities in younger children and adolescents with rhabdomyosarcoma 16th Annual Meeting of the Connective-Tissue-Oncology-Society Gupta, A. A., Anderson, J. R., Pappo, A. S., Spunt, S. L., Dasgupta, R., Indelicato, D. J., Hawkins, D. S. WILEY-BLACKWELL. 2012: 113037


Patients aged >10 years with rhabdomyosarcoma have an inferior outcome compared with patients ages 1 to 9 years, which may be explained by toxicities (adverse events [AEs]) that result in chemotherapy dose reductions.AEs observed during 1 of 3 randomized chemotherapy regimens (vincristine, dactinomycin, and cyclophosphamide [VAC]; vincristine, dactinomycin, and ifosfamide [VAI]; or vincristine, ifosfamide, and etoposide [VIE]) in the Fourth Intergroup Rhabdomyosarcoma Study were recorded. The incidence of toxicities by age and treatment regimen was determined. The odds of developing AEs in a particular age group (ages 5-9 years, 10-14 years, and 15-20 years) were compared with the odds in the control group of patients ages 1 to 4 years.In total, 657 patients were eligible for analysis. The estimated 5-year event-free survival rates were 78%, 83%, 67%, and 58% for the groups ages 1 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 20 years, respectively. Patients ages 15 to 20 years experienced less neutropenia (odds ratio [OR], 0.43; P < .0001), thrombocytopenia (OR, 0.41; P < .0001), anemia (OR, 0.34; P < .0001), and infection (OR, 0.41; P < .0001) compared with younger patients, although they received similar amounts of chemotherapy. In contrast, peripheral nervous system toxicity was higher in adolescents aged >10 years (OR, 4.18; P < .0001). Females experienced more neutropenia (OR, 1.28; P = .05) and thrombocytopenia (OR, 1.26; P = .06) compared with males.Adolescents who received treatment for rhabdomyosarcoma experienced significantly less hematologic toxicity and more peripheral nervous system toxicity compared with younger children despite receiving similar amounts of chemotherapy. Although outcomes were inferior in adolescents, it was unclear whether the differences in toxicity observed in the current study had an impact on outcome. The authors concluded that future studies examining the age-related and sex-related differences in pharmacokinetics of chemotherapy are necessary.

View details for DOI 10.1002/cncr.26358

View details for Web of Science ID 000299834300032

View details for PubMedID 21761400



To investigate the relationship between jaw function, patient and treatment variables, and radiation dosimetry of the mandibular muscles and joints in children and young adults receiving radiation for soft-tissue and bone sarcomas.Twenty-four pediatric and young adult patients with head-and-neck sarcomas were treated on an institutional review board-approved prospective study of focal radiation therapy for local tumor control. Serial jaw depression measurements were related to radiation dosimetry delivered to the medial and lateral pterygoid muscles, masseter muscles, and temporomandibular joints to generate mathematical models of jaw function.Baseline jaw depression was only influenced by the degree of surgical resection. In the first 12 weeks from initiation of radiation, surgical procedures greater than a biopsy, administration of cyclophosphamide containing chemotherapy regimes, and large gross tumor volumes adversely affected jaw depression. Increasing dose to the pterygoid and masseter muscles above 40 Gy predicted loss of jaw function over the full course of follow-up.Clinical and treatment factors are related to initial and subsequent jaw dysfunction. Understanding these complex interactions and the affect of specific radiation doses may help reduce the risk for jaw dysfunction in future children and young adults undergoing radiation therapy for the management of soft-tissue and bone sarcomas.

View details for DOI 10.1016/j.ijrobp.2010.09.031

View details for Web of Science ID 000298526100052

View details for PubMedID 21093167

View details for PubMedCentralID PMC3117097

Endometrial cancer in a 15-year-old girl: A complication of Cowden Syndrome. Gynecologic oncology case reports Elnaggar, A. C., Spunt, S. L., Smith, W., Depas, M., Santoso, J. T. 2012; 3: 1819


The youngest case of endometrial carcinoma in the English literature Endometrial cancer is diagnosed in approximately 13-19% of women with Cowden Syndrome. Screening guidelines should follow that of Lynch Syndrome.

View details for DOI 10.1016/j.gynor.2012.10.006

View details for PubMedID 24371656

Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma EUROPEAN JOURNAL OF CANCER Geoerger, B., Kieran, M. W., Grupp, S., Perek, D., Clancy, J., Krygowski, M., Ananthakrishnan, R., Boni, J. P., Berkenblit, A., Spunt, S. L. 2012; 48 (2): 253-262


A phase II study of temsirolimus was conducted in children and adolescents with high-grade glioma, neuroblastoma or rhabdomyosarcoma.Temsirolimus 75 mg/m(2) was administered once weekly until disease progression or intolerance. Using the Simon 2-stage design, further enrolment in each disease cohort required 2 objective responses within the first 12 weeks for the first 12 evaluable patients (those who received 3 temsirolimus doses).Fifty-two heavily pretreated patients with relapsed (12%) or refractory (88%) disease, median age 8 years (range 1-21 years), were enroled and treated. One patient with neuroblastoma achieved confirmed partial response within the first 12 weeks; thus, none of the 3 cohorts met the criterion for continued enrolment. Disease stabilisation at week 12 was observed in 7 of 17 patients (41%) with high-grade glioma (5 diffuse pontine gliomas, 1 glioblastoma multiforme and 1 anaplastic astrocytoma), 6 of 19 (32%) with neuroblastoma and 1 of 16 (6%) with rhabdomyosarcoma (partial response confirmed at week 18). In the three cohorts, median duration of stable disease or better was 128, 663 and 75 d, respectively. The most common treatment-related adverse events were thrombocytopaenia, hyperlipidaemia and aesthenia. Pharmacokinetic findings were similar to those observed in adults.Temsirolimus administered weekly at the dose of 75 mg/m(2) did not meet the primary objective efficacy threshold in children with high-grade glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable disease merits further evaluation in combination therapy.

View details for DOI 10.1016/j.ejca.2011.09.021

View details for Web of Science ID 000300199800013

View details for PubMedID 22033322

View details for PubMedCentralID PMC3539305

Soft Tissue Sarcoma Across the Age Spectrum: A Population-Based Study From the Surveillance Epidemiology and End Results Database PEDIATRIC BLOOD & CANCER Ferrari, A., Sultan, I., Huang, T. T., Rodriguez-Galindo, C., Shehadeh, A., Meazza, C., Ness, K. K., Casanova, M., Spunt, S. L. 2011; 57 (6): 943-949


Soft tissue sarcomas (STS) are a heterogeneous group of mesenchymal malignancies that occur throughout the lifespan. The impact of age on disease features and outcome is unclear.We analyzed the clinical features and outcome of all STS cases registered between 1973 and 2006 in the SEER database.There were 48,012 cases that met the selection criteria. Individuals less than 20 years of age represented 5.6%, with rhabdomyosarcoma being the most common subtype. In adults, the most common types were Kaposi sarcoma, fibrohistiocytic tumors, and leiomyosarcoma. Rhabdomyosarcoma was the only entity with a median age <20 years. Male predominance (male/female of 1.5:1) was noticed for almost all types of STS, except for alveolar soft part sarcoma and leiomyosarcoma. Tumor stage was similar across different age groups. Younger patients (<50 years) had significantly better survival than older patients (88.8 0.2% vs. 40 0.3%, P < 0.001), but for most histologies the survival decline with advancing age was gradual and did not occur abruptly at the onset of adulthood. The decline in survival with advancing age was particularly significant for rhabdomyosarcoma.With few exceptions, the clinical features of STS are similar in children and adults. However, individuals over 50 years of age have an inferior survival.

View details for DOI 10.1002/pbc.23252

View details for Web of Science ID 000295257700010

View details for PubMedID 21793180

View details for PubMedCentralID PMC4261144

Liposarcoma in Children and Young Adults: A Multi-Institutional Experience PEDIATRIC BLOOD & CANCER Huh, W. W., Yuen, C., Munsell, M., Hayes-Jordan, A., Lazar, A. J., Patel, S., Wang, W., Barahmani, N., Okcu, M. F., Hicks, J., Debelenko, L., Spunt, S. L. 2011; 57 (7): 1142-1146


There are limited data regarding the differences in clinical presentation and outcome of liposarcomas between adult and pediatric patients. The role of adjuvant radiotherapy in the treatment of childhood liposarcoma is unclear.A multi-institutional retrospective analysis of medical records was performed for patients 21 years of age presenting with a verified histologic diagnosis of liposarcoma.Thirty-three patients were evaluable for this study, 23 of whom were male. Median age was 17.2 years. Twenty-four cases were myxoid subtype and 7 were pleomorphic subtype. In myxoid cases, 17 (71%) presented with extremity tumors; none had metastases. Eleven of these patients with myxoid subtype were treated with surgery only, seven with surgery + radiation, three with surgery + radiation + chemotherapy. Median radiation therapy dose for patients with myxoid tumors was 60 Gy. At median follow-up of 4.2 years (range 0.1-32.2 years), two patients relapsed with one death from progressive disease. In seven pleomorphic cases, four patients had primary tumors at central axial sites. Six patients (86%) received multimodal therapy, but six patients experienced relapse of disease. Four patients died from progressive disease.Pediatric liposarcoma has a different spectrum of presentation compared to adult cases. Myxoid liposarcoma is the more common subtype, usually occurs in extremities, and has an excellent prognosis. Pleomorphic liposarcoma occurs in axial sites, and despite multimodal therapy, outcome is poor. Further study is needed to identify the optimal therapy for pediatric liposarcoma.

View details for DOI 10.1002/pbc.23095

View details for Web of Science ID 000296200800013

View details for PubMedID 21394894

View details for PubMedCentralID PMC3134599

Implementation and Evaluation of an Automated Patient Death Notification Policy at a Tertiary Pediatric Oncology Referral Center JOURNAL OF PAIN AND SYMPTOM MANAGEMENT Baker, J. N., Harper, J., Kane, J. R., Kane, J. R., Hicks, J., Ward, D., Hinds, P. S., Spunt, S. L. 2011; 42 (5): 652-656


Not knowing about a child's death can result in poor quality of care coordination among staff and poor quality bereavement care for families. The purpose of this project was to create, implement, and evaluate an automated Patient Death Notification policy and procedure (PDNPP).Baseline and follow-up surveys of clinical staff.Implementation of a PDNPP that created an automated, systematic process for staff notification of patient deaths.Ninety-six percent of the staff rated the PDNPP as a significant improvement; 91% reported being "very" or "somewhat" satisfied with the PDNPP, whereas only 44% of the staff were satisfied with the process at baseline.Implementation of an automated PDNPP was feasible and improved staff satisfaction about how they were informed of patient deaths. Staff also reported being notified about patient deaths more quickly, performing their jobs more efficiently, being able to avoid doing something that might upset the deceased patient's family, and being able to better provide support to bereaved families.

View details for DOI 10.1016/j.jpainsymman.2011.07.002

View details for Web of Science ID 000297011800002

View details for PubMedID 22045367

View details for PubMedCentralID PMC3463934

Vaginal tumors in childhood: the experience of St. Jude Children's Research Hospital JOURNAL OF PEDIATRIC SURGERY Fernandez-Pineda, I., Spunt, S. L., Parida, L., Krasin, M. J., Davidoff, A. M., Rao, B. N. 2011; 46 (11): 2071-2075


The aim of this study was to retrospectively analyze the clinical presentation, histology, treatment, and outcomes of children with vaginal tumors who were treated at a single institution.A retrospective review of medical records and pathologic materials of all children with vaginal tumors treated at St Jude Children's Research Hospital between 1970 and 2009 was conducted.Eighteen patients (median age, 3.7 years; range, 0.1-15 years) were identified. Three different histologies were found: rhabdomyosarcoma (RMS; n = 13), germ cell tumor (n = 3), and clear cell adenocarcinoma (n = 2). Bleeding or blood-tinged discharge was the most common clinical presentation (66%), followed by a protruding mass (39%). Vaginal and uterine salvage was 44.4% (8 of 18 patients). Thirteen patients (72.2%) remain disease-free, with a median follow-up of 23.2 years (range, 2-39 years). Four patients (22.2%) died of disease progression (1 RMS, 2 germ cell tumor, and 1 clear cell adenocarcinoma), and 1 patient with RMS died of colon cancer 12 years after the primary diagnosis had been made.Vaginal tumors are extremely rare in the pediatric population. Early recognition of symptoms like bleeding and a protruding vaginal mass may prevent morbidity and mortality. Our findings confirm the good prognosis of vaginal RMS.

View details for DOI 10.1016/j.jpedsurg.2011.05.003

View details for Web of Science ID 000296869100012

View details for PubMedID 22075335

View details for PubMedCentralID PMC3476720

Pulmonary Outcomes in Survivors of Childhood Cancer A Systematic Review CHEST Huang, T., Hudson, M. M., Stokes, D. C., Krasin, M. J., Spunt, S. L., Ness, K. K. 2011; 140 (4): 881-901


The purpose of this article is to summarize the literature that documents the long-term impact of cancer treatment modalities on pulmonary function among survivors of cancer and to identify potential areas for further research.Systematic reviews of clinical trials, observational studies, case series, and review articles were conducted. Articles were limited to the studies that discussed pulmonary toxicity or late effects among pediatric cancer survivors and to follow-up investigations that were conducted a minimum of 2 years after completion of cancer-related treatment or 1 year after hematopoietic stem cell transplant.Sixty publications (51 clinical studies/reports and nine reviews) published from January 1970 to June 2010 in PubMed met the inclusion criteria. Data showed an association between radiotherapy, alkylating agents, bleomycin, hematopoietic stem cell transplant, and thoracic surgery and pulmonary toxicity, as well as possible interactions among these modalities.Pulmonary toxicity is a common long-term complication of exposure to certain anticancer therapies in childhood and can vary from subclinical to life threatening. Pulmonary function and associated loss of optimal exercise capacity may have adverse effects on long-term quality of life in survivors. Lung function diminishes as a function of normal aging, and the effects of early lung injury from cancer therapy may compound these changes. The information presented in this review is designed to provide a stimulus to promote both observational and interventional research that expands our knowledge and aids in the design of interventions to prevent or ameliorate pulmonary late effects among survivors of childhood cancer.

View details for DOI 10.1378/chest.10-2133

View details for Web of Science ID 000295900300013

View details for PubMedID 21415131

View details for PubMedCentralID PMC3904488

Phase I Study of Temsirolimus in Pediatric Patients With Recurrent/Refractory Solid Tumors JOURNAL OF CLINICAL ONCOLOGY Spunt, S. L., Grupp, S. A., Vik, T. A., Santana, V. M., Greenblatt, D. J., Clancy, J., Berkenblit, A., Krygowski, M., Ananthakrishnan, R., Boni, J. P., Gilbertson, R. J. 2011; 29 (21): 2933-2940


To determine dose-limiting toxicities, maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of weekly intravenous temsirolimus, a mammalian target of rapamycin (mTOR) signaling pathway inhibitor, in pediatric patients with recurrent or refractory solid tumors.Cohorts of three to six patients 1 to 21 years of age with recurrent or refractory solid tumors were treated with a 1-hour intravenous infusion of temsirolimus weekly for 3 weeks per course at one of four dose levels: 10, 25, 75, or 150 mg/m(2). During the first two courses, pharmacokinetic and pharmacodynamic evaluations (phosphorylation of S6, AKT, and 4EBP1 in peripheral-blood mononuclear cells) were performed.Dose-limiting toxicity (grade 3 anorexia) occurred in one of 18 evaluable patients at the 150 mg/m(2) level, which was determined to be tolerable, and an MTD was not identified. In 13 patients evaluable for response after two courses of therapy, one had complete response (CR; neuroblastoma) and five had stable disease (SD). Four patients (three SDs + one CR) remained on treatment for more than 4 months. The sum of temsirolimus and sirolimus areas under the concentration-time curve was comparable to values in adults. AKT and 4EBP1 phosphorylation were inhibited at all dose levels, particularly after two courses.Weekly intravenous temsirolimus is well tolerated in children with recurrent solid tumors, demonstrates antitumor activity, has pharmacokinetics similar to those in adults, and inhibits the mTOR signaling pathway in peripheral-blood mononuclear cells. Further studies are needed to define the optimal dose for use in combination with other antineoplastic agents in pediatric patients.

View details for DOI 10.1200/JCO.2010.33.4649

View details for Web of Science ID 000292819700024

View details for PubMedID 21690471

View details for PubMedCentralID PMC3138720

Tumor Volume and Patient Weight as Predictors of Outcome in Children With Intermediate Risk Rhabdomyosarcoma A Report From the Children's Oncology Group CANCER Rodeberg, D. A., Stoner, J. A., Garcia-Henriquez, N., Randall, R. L., Spunt, S. L., Arndt, C. A., Kao, S., Paidas, C. N., Million, L., Hawkins, D. S. 2011; 117 (11): 2541-2550


The objectives of this study were to compare tumor volume and patient weight versus traditional factors of tumor size (greatest dimension) and patient age and to determine which parameters best discriminated outcome among pediatric patients with intermediate-risk rhabdomyosarcoma (RMS).Complete information was available for 370 patients with nonmetastatic RMS who were enrolled in the Children's Oncology Group (COG) intermediate-risk study D9803 (1999-2005). The Kaplan-Meier method was used to estimate survival distributions. A recursive partitioning model was used to identify prognostic factors that were associated with event-free survival (EFS). Cox proportional hazards regression models were used to estimate the association between patient characteristics and the risk of failure or death.For all patients with intermediate-risk RMS, a recursive partitioning algorithm for EFS suggested that prognostic groups should be defined optimally by tumor volume (with a transition point at 20 cm(3) ), patient weight (with a transition point at 50 kg), and embryonal histology. Tumor volume and patient weight added significant outcome information to the standard prognostic factors, including greatest tumor dimension and patient age (P = .02). The ability to resect the tumor completely was not associated significantly with the size of the patient, and patient weight did not significantly modify the association between tumor volume and EFS after adjustment for standard risk factors (P = .2).The factors that had the strongest association with EFS were tumor volume, patient weight, and histology. On the basis of regression modeling, tumor volume and patient weight were superior predictors of outcome compared with greatest tumor dimension and patient age in children with intermediate-risk RMS. The current results indicated that the prognostic performance of tumor volume and patient weight should be assessed in an independent prospective study.

View details for DOI 10.1002/cncr.25719

View details for Web of Science ID 000290859900027

View details for PubMedID 24048802

A phase I study of ifosfamide, oxaliplatin, and etoposide (IOE) in pediatric patients with refractory solid tumors. McGregor, L. M., Spunt, S. L., Ward, D., Wu, J., Billups, C., Ivy, S. P., Santana, V. M., Fouladi, M., Furman, W. L. AMER SOC CLINICAL ONCOLOGY. 2011
Prospective Medical Assessment of Adults Surviving Childhood Cancer: Study Design, Cohort Characteristics, and Feasibility of the St. Jude Lifetime Cohort Study PEDIATRIC BLOOD & CANCER Hudson, M. M., Ness, K. K., Nolan, V. G., Armstrong, G. T., Green, D. M., Morris, E. B., Spunt, S. L., Metzger, M. L., Krull, K. R., Klosky, J. L., Srivastava, D. K., Robison, L. L. 2011; 56 (5): 825-836


To facilitate prospective medical assessment of adults surviving pediatric malignancies and advance knowledge about long-term childhood cancer survivor health, St. Jude Children's Research Hospital (SJCRH) is establishing a lifetime cohort of survivors.Eligibility criteria for inclusion in the St. Jude Lifetime Cohort (SJLIFE) study include: (1) diagnosis of childhood malignancy treated at SJCRH; (2) survival 10 years from diagnosis; and (3) current age 18 years. Three levels of participation are offered: (1) comprehensive evaluation on SJCRH campus; (2) limited home evaluation; or (3) completion of health surveys only. A systematic recruitment structure based upon blocks of 50 patients initially focused on leukemia and lymphoma survivors and patients eligible for pilot studies.As of January 1, 2010, 1,625 (42%) of 3,900 eligible 10-year survivors have been contacted. Among the first 1,000 potentially eligible survivors selected for recruitment, 971 were subsequently confirmed to fulfill eligibility criteria. To date, 898/971 (92.5%) have been successfully contacted of whom 825 (91.8%) have agreed to participate. Among participants, 88.6% agreed to comprehensive medical evaluation, 0.4% limited local evaluation, and 11.0% survey only. Anticipated minimum overall participation rate for medical evaluation is 75.3% (731/971). Comparison of those contacted who agreed versus declined to participate revealed a greater proportion of males who declined participation (P = 0.001).Early results of the SJLIFE study support its feasibility to recruit aging childhood cancer survivors to research investigations evaluating late health outcomes by medical assessments.

View details for DOI 10.1002/pbc.22875

View details for Web of Science ID 000288132100021

View details for PubMedID 21370418

View details for PubMedCentralID PMC3088729

Non-metastatic unresected paediatric non-rhabdomyosarcoma soft tissue sarcomas: Results of a pooled analysis from United States and European groups EUROPEAN JOURNAL OF CANCER Ferrari, A., Miceli, R., Rey, A., Oberlin, O., Orbach, D., Brennan, B., Mariani, L., Carli, M., Bisogno, G., Cecchetto, G., De Salvo, G. L., Casanova, M., Vannoesel, M. M., Kelsey, A., Stevens, M. C., Devidas, M., Pappo, A. S., Spunt, S. L. 2011; 47 (5): 724-731


Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with initially unresected tumours represent a particular subset of patients with a poor outcome. Various international research groups pooled their data in a joint study in order to investigate prognostic variables and treatment modalities.The study population consisted of 304 patients <21 years old treated between 1980 and 2005 using a multimodality therapeutic strategy.Synovial sarcoma and malignant peripheral nerve sheath tumour (MPNST) were the most frequent histotypes. Most patients received initial chemotherapy: major responses were recorded in 41% and minor in 16% of cases. Overall survival (OS) was 60.0% and 51.5% at 5 and 10 years, respectively, and it was significantly associated with patient's age, histological subtype, tumour site and size, quality of delayed surgical resection, radiotherapy administration and response to induction chemotherapy. MPNST associated to neurofibromatosis type 1 was the tumour type with the worst rate of response to chemotherapy and the worst outcome.In unresected NRSTS patients, radiotherapy and delayed surgery are of crucial importance. Patients who respond to chemotherapy have better chance of survival. However, given the relatively poor prognosis, research on intensive multimodal treatment approaches and novel strategies is warranted.

View details for DOI 10.1016/j.ejca.2010.11.013

View details for Web of Science ID 000288881700011

View details for PubMedID 21145727

View details for PubMedCentralID PMC3539303



Rhabdomyosarcoma, a neoplasm composed of skeletal myoblast-like cells, represents the most common soft tissue sarcoma in children. The application of intensive chemotherapeutics and refined surgical and radiation therapy approaches have improved survival for children with localized disease over the past 3 decades; however, these approaches have not improved the dismal outcome for children with metastatic and recurrent rhabdomyosarcoma. Elegant studies have defined the molecular mechanisms driving skeletal muscle lineage commitment and differentiation, and the machinery that couples differentiation with irreversible cell proliferation arrest. Further, detailed molecular analyses indicate that rhabdomyosarcoma cells have lost the capacity to fully differentiate when challenged to do so in experimental models. We review the intersection of normal skeletal muscle developmental biology and the molecular genetic defects in rhabdomyosarcoma with the underlying premise that understanding how the differentiation process has gone awry will lead to new treatment strategies aimed at promoting myogenic differentiation and concomitant cell cycle arrest.

View details for DOI 10.1016/13978-0-12-380916-2.00007-3

View details for Web of Science ID 000287717300007

View details for PubMedID 21295688

Pediatric Cutaneous Angiosarcomas: A Clinicopathologic Study of 10 Cases AMERICAN JOURNAL OF SURGICAL PATHOLOGY Deyrup, A. T., Miettinen, M., North, P. E., Khoury, J. D., Tighiouart, M., Spunt, S. L., Parham, D. M., Shehata, B. M., Weiss, S. W. 2011; 35 (1): 70-75


Cutaneous angiosarcomas are rare tumors, which predominantly arise in the sun-exposed skin of the head and neck of adult and elderly patients. Rarely, these tumors can be seen in children. We identified cutaneous angiosarcomas in 10 children and assessed clinical (patient age, tumor site, tumor size, and tumor focality) and histologic features including growth pattern (vasoformative vs. solid), mitotic rate (mitotic figures per 10 high power field), necrosis (present vs. absent), and cell shape (epithelioid vs. nonepithelioid). Tumors predominated in the lower extremities (6 of 10) of female patients (2 male and 8 female); age at diagnosis ranged from 1.5 months to 15 years. Four patients had preexisting conditions: congenital hemihypertrophy of the contralateral limb, the Aicardi syndrome, congenital lymphedema, and congenital hemangioma treated with radiation therapy. Tumors were located in the lower extremity (6), flank (1), elbow (1), and buccal mucosa (1), and ranged in size from 0.6 to 6.5 cm. Eight cases showed predominantly epithelioid morphology, 1 case showed mixed epithelioid and spindled morphology and 1 case was entirely spindled. Mitotic activity ranged from 1 to 55 mitotic figures per 10 high power field. Necrosis was seen in 5 cases. Clinical follow-up was obtained for 9 patients: 4 died of disease (range, 12 to 49 mo; mean, 25 mo) and 5 patients were alive without disease (18 mo to 28 y). Five patients had metastatic disease; sites of involvement included the lung, soft tissue, lymph node, pleura, liver, and bone. Cutaneous angiosarcomas in children are rare tumors, which are commonly associated with a preexisting condition, suggesting a greater role for genetics as opposed to environmental factors in the pathogenesis of these tumors.

View details for DOI 10.1097/PAS.0b013e3181ffd9d5

View details for Web of Science ID 000285409900008

View details for PubMedID 21164289



To provide a radiation pneumonitis risk estimate and investigate the correlation of clinical and dosimetric factors in pediatric patients receiving chest irradiation.A total of 122 patients diagnosed with sarcoma or Hodgkin lymphoma who received radiotherapy to the chest were evaluated for symptomatic radiation pneumonitis (Common Toxicity Criteria Grade 1 with respiratory symptom or higher grade). Pneumonitis data were collected from either prospective toxicity screenings as part of a clinical trial or through chart review. Dosimetric parameters including V(10)-V(25), mean lung dose, binned lung dose, and tissue complication probability models were used, as well as clinical features to correlate with the development of pneumonitis.The 1- and 2-year cumulative incidence of symptomatic radiation pneumonitis for all patients was 8.2% and 9.1%, respectively. Nine patients experienced symptomatic Grade 1 toxicity, and 2 experienced Grade 2. From univariate analysis, chemotherapy containing bleomycin (chi(2) test, p = 0.027) and V(24) (logistic regression, p = 0.019) were the clinical and dosimetric factors that resulted in statistically significant differences in the occurrence of pneumonitis. The probability of pneumonitis increased more dramatically with increasing V(24) in patients receiving bleomycin than in those who did not. Adult tissue complication models did not differentiate pediatric patients with radiation pneumonitis from those without.The incidence of symptomatic radiation pneumonitis in pediatric patients is low and its severity mild. Parameters frequently used in adult radiation oncology provide some guidance as to risk, but pediatric patients warrant their own specific models for risk assessment, incorporating dosimetry and clinical factors.

View details for DOI 10.1016/j.ijrobp.2009.07.1709

View details for Web of Science ID 000281304600021

View details for PubMedID 20056346

View details for PubMedCentralID PMC3539302

Decision Making by Parents of Children With Incurable Cancer Who Opt for Enrollment on a Phase I Trial Compared With Choosing a Do Not Resuscitate/Terminal Care Option JOURNAL OF CLINICAL ONCOLOGY Maurer, S. H., Hinds, P. S., Spunt, S. L., Furman, W. L., Kane, J. R., Baker, J. N. 2010; 28 (20): 3292-3298


Parents of children with incurable cancer make complex and difficult decisions about remaining treatment options. We compared the self-reported rationale, good parent definition, and desired clinical staff behaviors of parents who recently decided for phase I (P1) chemotherapy with parents who chose a do not resuscitate (DNR) or terminal care (TC) option.Sixty-two parents of 58 children were asked for the basis of their decision, their definition of a good parent, and what staff behaviors supported their good parent role. After semantic content analysis, results were compared in the P1 versus DNR/TC groups. These categories were mutually exclusive but did not necessarily represent an either/or decision.Thirty-one decisions were for P1 chemotherapy and 27 for DNR/TC. Median survival time after study enrollment was greater in the P1 group (0.4 v 0.1 years). Most P1 group parents reported having felt compelled to continue cancer-directed therapy (71% v 7%), whereas those who opted for DNR/TC cited quality of life (QOL; 74% v 3%) and patient wishes (67% v 13%). Decision factors common to both groups were medical facts, doing right, and others' opinions. Both groups believed that a good parent did right, provided support and presence, and sacrificed for the child. The groups desired similar support from clinicians and expressed gratitude.Despite similar definitions of a good parent and desired staff behaviors, parents in the P1 group reported having felt compelled to continue cancer-directed therapy, whereas QOL and patient wishes were emphasized in decisions for DNR/TC.

View details for DOI 10.1200/JCO.2009.26.6502

View details for Web of Science ID 000279637600015

View details for PubMedID 20498399

View details for PubMedCentralID PMC2903327

Grading of Nonrhabdomyosarcoma Soft Tissue Sarcoma in Children and Adolescents A Comparison of Parameters Used for the Federation Nationale des Centers de Lutte Contre le Cancer and Pediatric Oncology Group Systems CANCER Khoury, J. D., Coffin, C. M., Spunt, S. L., Anderson, J. R., Meyer, W. H., Parham, D. M. 2010; 116 (9): 2266-2274


Two systems for grading soft tissue sarcoma are widely used currently: the National Cancer Institute (NCI) and the Fdration Nationale des Centers de Lutte Contre le Cancer (FNCLCC) systems. Both were developed using cohorts of predominantly adult patients. The Pediatric Oncology Group (POG) system, based on the NCI system, was adapted for grading pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). The applicability and prognostic utility of the FNCLCC system in pediatric NRSTS has not been assessed or compared with the POG system.Tumors from 130 patients with malignant NRSTS enrolled on 3 completed multi-institutional clinical trials were assessed. Of 130 tumors, 102 (78%) were localized and 28 (22%) metastatic. Of the localized tumors, 55 of 102 (54%) were >5 cm. The estimated 5-year event-free survival (EFS) for the entire group was 47%.As expected, stage and tumor sizes were predictive of EFS (P < .001). Both systems were predictive of 5-year EFS (POG, P = .0095 and FNCLCC, P = .0075). Patients whose tumors received discrepant grades (POG-G3 vs FNCLCC-G2/G1) (n = 44) had an intermediate outcome between those with concordant (G3 [n = 44] or G1/G2 [n = 42]) grades on both systems (P = .0018). By multivariate analysis, the mitotic index was predictive of EFS, using a cutoff of 10 mitotic figures per 10 high-power fields (P < .001).In conclusion, both FNCLCC and POG systems provide an adequate prognostic measure of outcome for pediatric NRSTS; albeit, a sizeable subset of cases with apparently intermediate prognosis was graded differently by the 2 systems. The mitotic index appears to be a key parameter in grading pediatric NRSTS.

View details for DOI 10.1002/cncr.24929

View details for Web of Science ID 000277111900027

View details for PubMedID 20166208

View details for PubMedCentralID PMC2987713

Factors That Distinguish Symptoms of Most Concern to Parents from Other Symptoms of Dying Children JOURNAL OF PAIN AND SYMPTOM MANAGEMENT Pritchard, M., Burghen, E. A., Gattuso, J. S., West, N. K., Gajjar, P., Srivastava, D., Splint, S. L., Baker, J. N., Kane, J. R., Furman, W. L., Hinds, P. S. 2010; 39 (4): 62736


In a previous study, we conducted telephone interviews with parents 6 to 10 months after their child's death from cancer, using open-ended questions to identify the type and frequency of cancer-related symptoms that most concerned them during the last week of their child's life. Because the parents identified many clinically striking symptoms (n=109) that were not of most concern to them, we conducted a secondary analysis of these interviews (48 mothers and four fathers of 52 patients) to identify descriptive factors associated with the parents' level of concern. Six descriptive factors were associated with symptoms of most concern and 10 factors with symptoms not of most concern. Ten of these 16 factors occurred in both categories, indicating that clinicians should directly query parents to identify the symptoms that concern parents the most. Six factors differed between the two categories, and only one (the continuous distress caused by a symptom that is unrelieved) was unique to the category of symptoms of most concern. Five factors (symptom present for at least one week, symptom not seen as remarkable by the parent or causing no distress to the child, symptom well managed, symptom improved, and symptoms for which the parent felt adequately prepared) were unique to the category of symptoms not of most concern. By inquiring about symptoms of most concern and factors that influence parental concern, clinicians may be better able to direct care efforts to reduce patients' and parents' distress and support parents during the difficult end-of-life period.

View details for DOI 10.1016/j.jpainsymman.2009.08.012

View details for Web of Science ID 000277372800001

View details for PubMedID 20413052

View details for PubMedCentralID PMC2941146

Phase II, Randomized, Open- Label Study of Pegfilgrastim-Supported VDC/IE Chemotherapy in Pediatric Sarcoma Patients 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Spunt, S. L., Irving, H., Frost, J., Sender, L., Guo, M., Yang, B., Dreiling, L., Santana, V. M. AMER SOC CLINICAL ONCOLOGY. 2010: 132936


This multicenter, randomized, open-label study evaluated the efficacy, safety, and pharmacokinetics of a single subcutaneous pegfilgrastim injection with daily subcutaneous filgrastim administration in pediatric patients receiving myelosuppressive chemotherapy for sarcoma. PATIENTS AND METHODS Forty-four patients with previously untreated, biopsy-proven sarcoma stratified into three age groups (0-5, 6-11, and 12-21 years) were randomly assigned in a 6:1 randomization ratio to receive a single pegfilgrastim dose of 100 microg/kg (n = 38) or daily filgrastim doses of 5 microg/kg (n = 6) after chemotherapy (cycles 1 and 3: vincristine-doxorubicin-cyclophosphamide; cycles 2 and 4: ifosfamide-etoposide). The duration of grade 4 neutropenia, time to neutrophil recovery, incidence of febrile neutropenia, and adverse events were recorded. Results Pegfilgrastim and filgrastim were similar for all efficacy and safety end points, and their pharmacokinetic profiles were consistent with those in adults. Younger children experienced more protracted neutropenia and had higher median pegfilgrastim exposure than older children. CONCLUSION A single dose of pegfilgrastim at 100 microg/kg administered once per chemotherapy cycle is comparable to daily injections of filgrastim at 5 microg/kg for pediatric sarcoma patients receiving myelosuppressive chemotherapy.

View details for DOI 10.1200/JCO.2009.24.8872

View details for Web of Science ID 000275312300011

View details for PubMedID 20142595

View details for PubMedCentralID PMC2834494



To demonstrate the safety and efficacy of limited margin radiotherapy in the local control of pediatric and young adult patients with high-grade nonrhabdomyosarcoma soft tissue sarcoma (NRSTS).Pediatric patients with high-grade NRSTS requiring radiation were treated on an institutional review board approved prospective institutional study of conformal/intensity-modulated/interstitial brachytherapy using a 2-cm anatomically constrained margin.A total of 32 patients (median age, 15.3 years; range, 2-22 years) received adjuvant (27 patients) or definitive (5 patients) irradiation. With a median follow-up of 32 months, the 3-year cumulative incidence of local failure was 3.7% for patients undergoing irradiation after surgical resection. Four patients experienced local failure; the mean dose to the volume of recurrence was >or=97% of the prescribed dose.Delivery of limited margin radiotherapy using external beam or brachytherapy provides a high rate of local tumor control without marginal failure. Further follow-up is required to determine whether normal tissue effects are minimized using this approach.

View details for DOI 10.1016/j.ijrobp.2009.02.074

View details for Web of Science ID 000275072200031

View details for PubMedID 19625137

View details for PubMedCentralID PMC2823850

Human Papillomavirus Vaccination in Survivors of Childhood Cancer CANCER Klosky, J. L., Gamble, H. L., Spunt, S. L., Randolph, M. E., Green, D. M., Hudson, M. M. 2009; 115 (24): 5627-5636


Effective vaccination is now available to prevent human papillomavirus (HPV), the most common sexually transmitted infection and the cause of cervical cancer, which is the second most common cancer among women worldwide. HPV vaccine uptake is particularly important for females surviving cancer, some of whom are at high risk for HPV complications because of the direct and indirect effects of cancer treatment. Thus, version 3.0 of the Children's Oncology Group's Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer recommends HPV vaccination for all eligible females surviving childhood cancer. Because this vaccine was only approved by the US Food and Drug Administration in 2006, little is known regarding the complexity of vaccination uptake among those surviving cancer. The purpose of this article was to describe the HPV vaccine and its usefulness in the survivorship population, provide a rationale for describing cancer survivors as being at increased risk for HPV complications, identify factors associated with HPV vaccination, and discuss the utilization of these predictors in designing strategies to promote adherence to HPV vaccination recommendations within the survivorship context.

View details for DOI 10.1002/cncr.24669

View details for Web of Science ID 000272545400007

View details for PubMedID 19813272

View details for PubMedCentralID PMC2801897

"Trying to Be a Good Parent" As Defined By Interviews With Parents Who Made Phase I, Terminal Care, and Resuscitation Decisions for Their Children JOURNAL OF CLINICAL ONCOLOGY Hinds, P. S., Oakes, L. L., Hicks, J., Powell, B., Srivastava, D. K., Spunt, S. L., Harper, J., Baker, J. N., West, N. K., Furman, W. L. 2009; 27 (35): 5979-5985


When a child's cancer progresses beyond current treatment capability, the parents are likely to participate in noncurative treatment decision making. One factor that helps parents to make these decisions and remain satisfied with them afterward is deciding as they believe a good parent would decide. Because being a good parent to a child with incurable cancer has not been formally defined, we conducted a descriptive study to develop such a definition.In face-to-face interviews, 62 parents who had made one of three decisions (enrollment on a phase I study, do not resuscitate status, or terminal care) for 58 patients responded to two open-ended questions about the definition of a good parent and about how clinicians could help them fulfill this role. For semantic content analysis of the interviews, a rater panel trained in this method independently coded all responses. Inter-rater reliability was excellent.Among the aspects of the definition qualitatively identified were making informed, unselfish decisions in the child's best interest, remaining at the child's side, showing the child that he is cherished, teaching the child to make good decisions, advocating for the child with the staff, and promoting the child's health. We also identified 15 clinician strategies that help parents be a part of making these decisions on behalf of a child with advanced cancer.The definition and the strategies may be used to guide clinicians in helping parents fulfill the good parent role and take comfort afterward in having acted as a good parent.

View details for DOI 10.1200/JCO.2008.20.0204

View details for Web of Science ID 000272652700022

View details for PubMedID 19805693

View details for PubMedCentralID PMC2793041

Body wall and visceral nonrhabdomyosarcoma soft tissue sarcomas in children and adolescents JOURNAL OF PEDIATRIC SURGERY Navid, F., Billups, C. A., Krasin, M. J., Davidoff, A. M., Harper, J., Rao, B. N., Spunt, S. L. 2009; 44 (10): 1965-1971


Predictors of outcome have not been established for pediatric visceral and body wall nonrhabdomyosarcoma soft tissue sarcomas (NRSTS).The study used a retrospective review of clinical features and outcome of 61 patients with visceral and body wall NRSTS evaluated at our institution between March 1962 and December 1999.Median age at diagnosis was 9.9 years (range, birth to 17.4 years). Tumors were greater than 5 cm in 43 (70%), high grade in 33 (54%), invasive in 25 (41%), and metastatic at presentation in 14 (23%) patients. Visceral tumors (n = 27) were more likely than body wall tumors (n = 34) to be greater than 5 cm (93% vs 53%; P < .001) and invasive (70% vs 18%; P < .001) and were less likely to be resected at diagnosis (44% vs 85%; P = .001). Estimated 10-year event-free survival (EFS) and overall survival (OS) for the entire cohort were 45.5% +/- 6.9% and 56.8% +/- 6.7%, respectively. The 10-year EFS and OS were better for patients with body wall sites than for those with visceral sites (61.8% +/- 8.5% and 67.5% +/- 8.2% vs 24.2% +/- 9.4% and 43.0% +/- 10.3%; P = .004 and P = .004). The 10-year estimated cumulative incidence (CI) of local recurrence was higher for patients with visceral sites than for those with body wall sites (64.3% +/- 9.8% vs 26.5% +/- 7.7%; P = .004), whereas CI of distant recurrence was similar for the 2 sites (15.2% +/- 7.2% vs 23.5% +/- 7.4%; P = .39).Pediatric patients with visceral NRSTS are more likely to have invasive, large, and unresectable tumors compared to those with body wall tumors. More than two thirds of visceral NRSTS recur locally, and fewer than half of patients with visceral tumors survive.

View details for DOI 10.1016/j.jpedsurg.2009.02.066

View details for Web of Science ID 000271331700017

View details for PubMedID 19853756

View details for PubMedCentralID PMC2768617

Retrospective study of the surgical management and outcome of nonrhabdomyosarcoma soft tissue sarcomas of the groin and axilla in children JOURNAL OF PEDIATRIC SURGERY Karplus, G., Krasin, M. J., Rodriguez-Galindo, C., McCarville, B., Jenkins, J., Rao, B., Spyridis, G., Spunt, S. L. 2009; 44 (10): 1972-1976


The incidence of pediatric nonrhabdomyosarcoma soft tissue sarcomas (NRSTSs) of the groin and axilla is unknown, and the optimal surgical approach to these patients is unclear.We conducted a retrospective study of patients treated at St Jude Children's Research Hospital from January 1962 to March 2007 for NRSTSs of the groin and axilla. Demographic variables, tumor pathology, clinical management, and outcome were reviewed.Of the 300 patients treated for NRSTSs, only 10 had tumors of the axilla or groin (6 of whom had synovial sarcoma). Surgical interventions included wide resection of the tumor (n = 7), marginal resection (n = 1), subtotal resection (n = 1), and biopsy only (n = 1). Six patients underwent lymph node sampling; all were negative for tumor. Short- and long-term surgical complications were rare. Four patients received adjuvant chemotherapy (n = 3) and/or radiotherapy (n = 2). At a median follow-up of 8.5 years, 7 of the 10 were surviving free of disease. Two of these patients died of tumor progression (1 with metastases at diagnosis and 1 with an unresectable tumor at diagnosis), and one patient who was free of NRSTS died of secondary breast carcinoma.Pediatric NRSTSs of the axilla and groin are rare, but outcomes are similar to those of other patients with NRSTS. Wide local excision of the tumor with preservation of good limb function should be the surgical goal and may be sufficient therapy in some cases.

View details for DOI 10.1016/j.jpedsurg.2009.02.052

View details for Web of Science ID 000271331700018

View details for PubMedID 19853757

View details for PubMedCentralID PMC3748624

Bereaved Parents' Perceptions About When Their Child's Cancer-Related Death Would Occur JOURNAL OF PAIN AND SYMPTOM MANAGEMENT Pritchard, M., Srivastava, D. K., Okuma, J. O., Powell, B., Burghen, E., West, N. K., Gattuso, J. S., Spunt, S. L., Baker, J. N., Kane, J., Furman, W. L., Hinds, P. S. 2009; 38 (4): 561-567


Parents of terminally ill children with cancer frequently ask clinicians when their child will die. Such information helps parents prepare for the child's death. To identify how parents perceived when their child's cancer-related death would occur, we conducted a secondary analysis of telephone interviews with 49 bereaved parents 6-10 months after their child's death to extract their descriptions of this occurrence. The parents knew in advance that their child was going to die, but they described when their child's death would occur in three different ways: anticipated (parents observed changes that alerted them that death was imminent; n=22, 52.4%), surprising (parents were surprised that their child died on that particular day; n=13, 31.0%), and overdue (parents had been waiting for the end of their child's apparent suffering; n=7, 16.7%). These categories did not differ by patients' diagnosis, sex, or location of death but differed slightly by symptom patterns. Parents who reported the occurrence of their child's death as surprising reported fewer symptom changes on the last day of their child's life, compared with the last week of life, than did the parents in the other two categories. These findings indicate that parents of children with terminal cancer can perceive when their child's death would occur very differently: Some are surprised, whereas others feel they have waited too long for their child's release from suffering. Clinicians can use these descriptions and the associated symptom patterns to help families prepare for their child's last week and last day.

View details for DOI 10.1016/j.jpainsymman.2009.01.005

View details for Web of Science ID 000271297000009

View details for PubMedID 19822277

View details for PubMedCentralID PMC2941143

Tyrosine Kinase Inhibitor Enhances the Bioavailability of Oral Irinotecan in Pediatric Patients With Refractory Solid Tumors 40th Annual Meeting of the American-Society-of-Clinical-Oncology Furman, W. L., Navid, F., Daw, N. C., McCarville, M. B., McGregor, L. M., Spunt, S. L., Rodriguez-Galindo, C., Panetta, J. C., Crews, K. R., Wu, J., Gajjar, A. J., Houghton, P. J., Santana, V. M., Stewart, C. F. AMER SOC CLINICAL ONCOLOGY. 2009: 45994604


To assess the maximum-tolerated dosages (MTDs), and dose-limiting toxicities (DLTs) of the epidermal growth factor receptor inhibitor gefitinib and of intravenous (IV) irinotecan when administered together in children with refractory solid tumors. To assess the effect of gefitinib on the pharmacokinetics of IV irinotecan and on the bioavailability of a single oral dose of irinotecan.IV irinotecan (15 or 20 mg/m(2)) was given daily for 5 days of 2 consecutive weeks. Oral gefitinib (150 or 112.5 mg/m(2)) was concomitantly given daily for 12 or 21 days. A single oral dose of irinotecan was given on day 9 of course 2 to allow pharmacokinetic analysis.The study enrolled 29 patients with recurrent solid tumors. The 21-day regimen of oral gefitinib with irinotecan was not tolerated. Diarrhea was the most common DLT. The MTD of the combination regimen was 15 mg/m(2)/d of IV irinotecan for 5 days of 2 consecutive weeks and 112.5 mg/m(2)/d of gefitinib given for 12 days. Gefitinib increased the bioavailability of oral irinotecan by four-fold over that observed in historical controls (median, 0.09 v 0.42; P < .000001), reducing the apparent clearance (an inverse measure of exposure) of irinotecan and SN-38 by 37% and 38%, respectively (P < .0001). A partial response was observed in a patient with refractory Ewing sarcoma.IV irinotecan given with 12 days of oral gefitinib is well tolerated in children. We observed one partial response. Gefitinib significantly enhances the bioavailability of oral irinotecan. This combination warrants further investigation, particularly with orally administered irinotecan.

View details for DOI 10.1200/JCO.2008.19.6642

View details for Web of Science ID 000270019900026

View details for PubMedID 19687340

View details for PubMedCentralID PMC2754908

Pegfilgrastim in pediatric sarcoma patients undergoing dose-intensive chemotherapy: Phase II study results Spunt, S. L., Irving, H., Frost, J., Sender, L., Yang, B., Santana, V. M. AMER SOC CLINICAL ONCOLOGY. 2009
Pulmonary function after whole lung radiation in pediatric patients with malignant solid tumors Inaba, H., Zhu, L., Srivastava, K., Hudson, M. M., Motosue, M. S., Stokes, D. C., McPherson, V., Srinivasan, S., Krasin, M. J., Green, D. M., Spunt, S. L. AMER SOC CLINICAL ONCOLOGY. 2009
Phase 1 Study of Oxaliplatin and Irinotecan in Pediatric Patients With Refractory Solid Tumors CANCER McGregor, L. M., Spunt, S. L., Furman, W. L., Stewart, C. F., Schaiquevich, P., Krailo, M. D., Speights, R., Ivy, P., Adamson, P. C., Blaney, S. M. 2009; 115 (8): 1765-1775


For this report, the authors estimated the maximum tolerated dose (MTD) and investigated the toxicities of oxaliplatin combined with irinotecan in children with refractory solid tumors.Oxaliplatin was administered on Days 1 and 8 in combination with irinotecan on Days 1 through 5 and Days 8 through 12 of a 21-day cycle. An oral cephalosporin was administered daily to ameliorate irinotecan-associated diarrhea. Pharmacokinetic studies of oxaliplatin and uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotyping were performed.Thirteen patients were enrolled. Dose-limiting diarrhea (n = 3), serum lipase elevation (n = 3), serum amylase elevation (n = 2), colitis, abdominal pain, and headache (n = 1 each) occurred at the first dose level (oxaliplatin at a dose of 60 mg/m(2); irinotecan at a dose of 20 mg/m(2)). Only 1 of 7 patients who received reduced doses of both agents (40 mg/m(2)/dose oxaliplatin; 15 mg/m(2)/dose irinotecan) experienced a dose-limiting toxicity (DLT): diarrhea. When the oxaliplatin dose was re-escalated (60 mg/m(2)) with irinotecan at a dose of 15 mg/m(2), 2 of 3 patients had a DLT (1 episode of diarrhea, 1 episode of hypokalemia). Myelosuppression was minimal. One patient had a complete response, and another patient had stable disease for 6 cycles of therapy. The median oxaliplatin area under the concentration versus time curve (AUC(0-->infinity)) was 5.9 microg . hour/mL (range, 1.8-7.6 microg . hour/mL). The frequency of the 6/6, 6/7, and 7/7 UGT1A1 promoter genotypes was 5 of 10, 4 of 10, and 1 of 10, respectively.The oxaliplatin MTD was 40 mg/m(2) per dose on Days 1 and 8 in combination with irinotecan 15 mg/m(2) per dose on Days 1-5 and Days 8-12. There was some evidence of antitumor activity; however, severe toxicity, both expected (diarrhea) and unexpected (elevation in pancreatic enzymes), was observed.

View details for DOI 10.1002/cncr.24175

View details for Web of Science ID 000264918700021

View details for PubMedID 19170226

View details for PubMedCentralID PMC2897817

Late Effects on the Urinary Bladder in Patients Treated for Cancer in Childhood: A Report From the Children's Oncology Group PEDIATRIC BLOOD & CANCER Ritchey, M., Ferrer, F., Shearer, P., Spunt, S. L. 2009; 52 (4): 439-446


Childhood cancer survivors who have had pelvic or central nervous system surgery or have received alkylator-containing chemotherapy or pelvic radiotherapy as part of their cancer therapy may experience urinary bladder late effects. This article reviews the medical literature on long-term bladder complications in survivors of childhood cancer and outlines the Children's Oncology Group Long-Term Follow-up (COG LTFU) Guidelines related to bladder function. An overview of the treatment of bladder late effects and recommended counseling for survivors with these complications are presented.

View details for DOI 10.1002/pbc.21826

View details for Web of Science ID 000263532500004

View details for PubMedID 18985721

View details for PubMedCentralID PMC2917580

A Phase 1/Pilot Study of Radiofrequency Ablation for the Treatment of Recurrent Pediatric Solid Tumors CANCER Hoffer, F. A., Daw, N. C., Xiong, X., Anghelescu, D., Krasin, M., Yan, X., Davidoff, A. M., Furman, W. L., Rodriguez-Galindo, C., Spunt, S. L. 2009; 115 (6): 1328-1337


This prospective study was designed to be the first to evaluate the toxicity of radiofrequency ablation (RFA) in patients with recurrent pediatric solid tumors.From 2003 through 2008, a phase 1/pilot study of RFA for recurrent pediatric solid tumors was conducted. A multidisciplinary cancer management team selected appropriate candidates for the study. Imaging-guided RFA was performed percutaneously. Repeat RFA was performed for recurrences when appropriate. Toxicity and imaging response was assessed at 1 month and 3 months prospectively. Accrual stopped in 2006, and data collection stopped in 2008.Sixteen patients (ages 4 years-33 years; median age, 15 years) and 56 tumor sites were treated in 37 RFA sessions including 38 pulmonary, 11 musculoskeletal, and 7 hepatic lesions (82 lesion-treatments). Postprocedural pain was moderate (median 5 on a scale from 1 to 10) and lasted a median of 9 days. Prolonged hospitalization (beyond 1 day) occurred 17 times (range, 2 days-25 days; median, 3 days). Hypoxia supported by supplemental oxygen occurred in 8 of 16 patients and resolved within 1 month after each RFA. No patient had tumor lysis syndrome but myoglobinuria/hemoglobinuria occurred in 6 of 16 patients, all without renal damage. Serious complications from pulmonary RFA included 2 diaphragmatic hernias. Of 82 lesions imaged, 24 (29%) remained ablated at the end of the study.The toxicity from RFA of recurrent pediatric solid tumors was real but limited, and RFA may offer a local tumor control alternative in carefully selected cases.

View details for DOI 10.1002/cncr.24158

View details for Web of Science ID 000264148300023

View details for PubMedID 19180637

View details for PubMedCentralID PMC2814781

Angiosarcomas Arising in the Viscera and Soft Tissue of Children and Young Adults A Clinicopathologic Study of 15 Cases AMERICAN JOURNAL OF SURGICAL PATHOLOGY Deyrup, A. T., Miettinen, M., North, P. E., Khoury, J. D., Tighiouart, M., Spunt, S. L., Parham, D., Weiss, S. W., Shehata, B. M. 2009; 33 (2): 264-269


Angiosarcomas are rare tumors that predominantly affect adult and elderly patients and pursue an aggressive clinical course with high mortality. Although angiosarcomas are well described in a variety of clinical settings, they have been incompletely characterized. We identified 15 high-grade angiosarcomas arising from the viscera and soft tissue of patients 21 years old and younger from institutional and consultation files. Both clinical (patient age, tumor site, tumor size, tumor focality) and histologic features including growth pattern (vasoformative vs. solid), nuclear grade (high vs. low), mitotic rate (mitotic figures/10 high-power fields), necrosis (present vs. absent), and cell shape (epithelioid vs. nonepithelioid) were assessed. Tumors arose in both sexes (8 males; 7 females); age at diagnosis ranged from 3 months to 19 years (mean, 10 y, 5 mo; median, 11 y). Tumors were located in the mediastinum (7), visceral organs (2 in liver, 1 in spleen), breast (2), mesentery (1), pelvis (1), and deep soft tissue of upper extremity (1). Tumor size was documented for 8 patients (range 3.5 to 13 cm; mean 8.1 cm). Eight cases showed epithelioid morphology and 7 cases were primarily spindled. Of 8 cases assessed for podoplanin expression by immunohistochemistry, 7 were negative and 1 was positive. Clinical follow-up was obtained for all patients: 10 (67%) died of disease (range, 27 mo to 11 y; mean, 6 y 8 mo) and 4 patients were alive without disease (range, 27 to 132 mo; mean, 79 mo). Although extremely rare, angiosarcomas do affect children and young adults and this diagnosis should be considered in atypical vascular tumors occurring in the mediastinum and those with brisk mitotic activity and/or necrosis.

View details for Web of Science ID 000262920400013

View details for PubMedID 18987547

Phase 1 Study of an Oxaliplatin and Etoposide Regimen in Pediatric Patients With Recurrent Solid Tumors CANCER McGregor, L. M., Spunt, S. L., Santana, V. M., Stewart, C. F., Ward, D. A., Watkins, A., Laningham, F. H., Ivy, P., Furman, W. L., Fouladi, M. 2009; 115 (3): 655-664


The combination of a platinating agent and etoposide has induced responses in various pediatric tumors. The study estimated the maximum tolerated dose (MTD) of an oxaliplatin and etoposide regimen in children with recurrent solid tumors.Oxaliplatin was administered on Day 1 and etoposide on Days 1 to 3 of each 21-day course. Cohorts of 3 to 6 patients were enrolled at 3 dose levels: 1) oxaliplatin at a dose of 130 mg/m(2) and etoposide at a dose of 75 mg/m(2), 2) oxaliplatin at a dose of 130 mg/m(2) and etoposide at a dose of 100 mg/m(2), and 3) oxaliplatin at a dose of 145 mg/m(2) and etoposide at a dose of 100 mg/m(2). Calcium and magnesium infusions were used at dose level 3 in an attempt to escalate the oxaliplatin dose past the single-agent MTD.The 16 patients received a total of 63 courses. At dose level 1, dose-limiting epistaxis, neuropathy, and neutropenia occurred in 1 of 6 patients. No dose-limiting toxicity (DLT) occurred at dose level 2 (n = 6). At dose level 3, 2 of 4 patients experienced dose-limiting neutropenia; none experienced grade 3 or 4 acute neuropathy. Six patients required prolongation of the oxaliplatin infusion because of acute sensory neuropathy. Responses were observed in patients with medulloblastoma (1 complete response) and pineoblastoma (1 partial response); 3 others with atypical teratoid rhabdoid tumor, ependymoma, and soft tissue sarcoma had prolonged disease stabilization.The MTD of this regimen was found to be oxaliplatin at a dose of 130 mg/m(2) given on Day 1 and etoposide at a dose of 100 mg/m(2)/d given on Days 1 to 3. Neutropenia was found to be the DLT. Calcium and magnesium infusions did not allow escalation of the oxaliplatin dose. The combination was well-tolerated and demonstrated antitumor activity.

View details for DOI 10.1002/cncr.24054

View details for Web of Science ID 000263003400024

View details for PubMedID 19117350

View details for PubMedCentralID PMC2852396

SPERM CRYOPRESERVATION PRACTICES AMONG ADOLESCENT CANCER PATIENTS AT RISK FOR INFERTILITY PEDIATRIC HEMATOLOGY AND ONCOLOGY Klosky, J. L., Randolph, M. E., Navid, F., Gamble, H. L., Spunt, S. L., Metzger, M. L., Daw, N., Morris, E. B., Hudson, M. M. 2009; 26 (4): 252-260


To assess sperm cryopreservation among males newly diagnosed with cancer aged 13 years and older, attending oncologists assigned infertility risk (yes/no) to patients and reported whether their patients engaged in sperm cryopreservation. Only 28.1% of informed at-risk patients banked sperm. Utilization of sperm banking was significantly associated with a diagnosis of central nervous system (CNS) malignancy or non-CNS solid tumor diagnosis, higher socioeconomic status, and not being a member of an Evangelical religious group. These results suggest that sperm banking is underutilized among adolescent males newly diagnosed with cancer, and that strategies to increase the engagement in this fertility preservation method are needed.

View details for DOI 10.1080/08880010902901294

View details for Web of Science ID 000266026400010

View details for PubMedID 19437327

View details for PubMedCentralID PMC2801903

Renal Late Effects in Patients Treated for Cancer in Childhood: A Report From the Children's Oncology Group PEDIATRIC BLOOD & CANCER Jones, D. P., Spunt, S. L., Green, D., Springate, J. E. 2008; 51 (6): 724-731


Improvements in childhood cancer therapy have led to increasing numbers of long-term survivors. These survivors are at risk for a variety of late effects due to the disease itself, treatment exposures (surgery, chemotherapy, and radiotherapy), underlying medical problems, and health behaviors. The COG LTFU Guidelines are risk-based, exposure-related recommendations for the identification and management of late effects due to therapies utilized in the treatment of childhood cancer, and are designed for asymptomatic survivors presenting for routine medical follow-up 2 or more years after completion of cancer therapy. The COG Guidelines Task Force on Urinary Tract Complications conducted an extensive review of the medical literature via MEDLINE. Specific treatment exposures which were reviewed include nephrectomy, chemotherapy regimens known to be nephrotoxic (cisplatin, carboplatin, ifosfamide, and methotrexate), and renal irradiation. Literature sources were ranked according to the strength of evidence and are cited in the review. This review summarizes the literature that supported the recommendations for cancer survivors at risk for nephrotoxicity previously outlined in the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers (COG LTFU Guidelines).

View details for DOI 10.1002/pbc.21695

View details for Web of Science ID 000260289300003

View details for PubMedID 18677764

View details for PubMedCentralID PMC2734519

Bone mineral density deficits in pediatric patients treated for sarcoma PEDIATRIC BLOOD & CANCER Kaste, S. C., Ahn, H., Liu, T., Liu, W., Krasin, M. J., Hudson, M. M., Spunt, S. L. 2008; 50 (5): 1032-1038


Children treated for sarcoma are at risk of treatment-associated deficits in bone mineral density (BMD). We investigated the severity of risk factors for BMD deficits in this patient population.Using signed-rank test and logistic regression analysis, we retrospectively analyzed the relation of treatment variables and other potential risk factors to BMD (using quantitative computed tomography (QCT)) of 99 patients treated for pediatric sarcoma who had completed therapy at least 1 year previously.The study group (38% rhabdomyosarcoma (RMS), 25% osteosarcoma (OS), 24% Ewing-family tumors, and 12% non-rhabdomyosarcoma soft-tissue sarcoma (NRSTS)) represented 22% of the sarcoma survivors treated between 1982 and 2003 who remained in follow-up at St. Jude. These patients underwent QCT between July 1, 1997 and February 5, 2003. Their median age was 8.7 years (range, 0.2-21.3 years) at diagnosis and 17.4 years (range, 3.3-30.2 years) at the time of BMD measurement; 58% were male and 82% Caucasian. Median BMD Z-score was -0.75 (range, -3.33-3.02), and median BMD was 168.0 mg/cc (range, 89.2-264.8 mg/cc). Risk of BMD deficit increased significantly with younger age at diagnosis (P = 0.044) and higher cumulative cyclophosphamide dose (P = 0.007). Patients with lower extremity primary disease had a significantly lower risk of BMD deficits than others. We found no association between BMD and body habitus, primary disease, lifestyle factors, or endocrinopathy.A significant subset of sarcoma survivors are at risk of BMD deficits warranting prospective study of BMD to verify our results and refine risk factors contributing to BMD deficits.

View details for DOI 10.1002/pbc.21281

View details for Web of Science ID 000254642900017

View details for PubMedID 17570705

Primary care management of the childhood cancer survivor JOURNAL OF PEDIATRICS Kurt, B. A., Armstrong, G. T., Cash, D. K., Krasin, M. J., Morris, E. B., Spunt, S. L., Robison, L. L., Hudson, M. M. 2008; 152 (4): 458-466

View details for DOI 10.1016/j.jpeds.2007.10.002

View details for Web of Science ID 000254543200014

View details for PubMedID 18346496

Integration of palliative care practices into the ongoing care of children with cancer: Individualized care planning and coordination PEDIATRIC CLINICS OF NORTH AMERICA Baker, J. N., Hinds, P. S., Spunt, S. L., Barfield, R. C., Allen, C., Powell, B. C., Anderson, L. H., Kane, J. R. 2008; 55 (1): 223-?


Most parents of children with cancer have dual primary goals: a primary cancer-directed goal of cure and a primary comfort-related goal of lessening suffering. Early introduction of palliative care principles and practices into their child's treatment is respectful and supportive of these goals. The Individualized Care Planning and Coordination Model is designed to integrate palliative care principles and practices into the ongoing care of children with cancer. Application of the model helps clinicians to generate a comprehensive individualized care plan that is implemented through Individualized Care Coordination processes as detailed here. Clinicians' strong desire to provide compassionate, competent, and sensitive care to the seriously ill child and the child's family can be effectively translated into clinical practice through these processes.

View details for DOI 10.1016/j.pcl.2007.10.011

View details for Web of Science ID 000253794400012

View details for PubMedID 18242323

View details for PubMedCentralID PMC2577813

Prolactinoma as the first manifestation of Gardner's syndrome PEDIATRIC BLOOD & CANCER Goodin, G. S., McCarville, M. B., Thibodeau, S. N., Skapek, S. X., Khoury, J. D., Spunt, S. L. 2008; 50 (2): 409-412


Familial adenomatous polyposis (FAP) is an inherited condition causing numerous adenomatous colorectal polyps and a markedly elevated risk of colon cancer. FAP may be associated with various extracolonic manifestations such as desmoid fibromatosis and osteomas (termed Gardner's syndrome) and brain tumors, usually medulloblastoma or glioma [termed Brain Tumor Polyposis (BTP) syndrome type 2]. We describe a pediatric patient who initially presented with prolactinoma and later was found to have Gardner's syndrome. A germline mutation of the APC (adenomatous polyposis coli) gene was identified. Our case illustrates the association between prolactinoma and FAP, which may represent a rare subtype of Gardner's and BTP syndromes.

View details for DOI 10.1002/pbc.20985

View details for Web of Science ID 000252006000055

View details for PubMedID 16862550

Hematometrocolpos in an adolescent female treated for pelvic Ewing sarcoma PEDIATRIC BLOOD & CANCER Gaillard, P., Krasin, M. J., Laningham, F. H., Hoffer, F. A., Davidoff, A. M., Spunt, S. L., Smiley, L., Skapek, S. X. 2008; 50 (1): 157-160


Radiation therapy is often used to achieve local control of pelvic Ewing sarcoma in children. The effects of radiation on the female reproductive tract have been well documented in adults with gynecological malignancies, but the long-term consequences of pelvic radiation in pre-pubertal or adolescent girls are not as well described. We report a case of hematometrocolpos developing in an adolescent previously treated with chemotherapy and radiation therapy for pelvic Ewing sarcoma. We describe the clinical presentation, radiographic features, gross pathology, treatment strategies, outcome, as well as putative predisposing factors and preventative interventions.

View details for DOI 10.1002/pbc.20833

View details for Web of Science ID 000251410400035

View details for PubMedID 16550535

Pediatric nonrhabdomyosarcoma soft tissue sarcomas ONCOLOGIST Spunt, S. L., Skapek, S. X., Coffin, C. M. 2008; 13 (6): 668-678


The nonrhabdomyosarcoma soft tissue sarcomas (NRSTSs) are a heterogeneous group of mesenchymal cell neoplasms that account for about 4% of childhood cancers. Because each histologic subtype of NRSTS is rare, they have been poorly studied and little is known about their biology, natural history, or optimal treatment. Data from adults with soft tissue sarcomas provide some helpful insight, but adult and childhood NRSTSs differ considerably in the distribution of their histologic subtypes, and certain entities are known to behave differently in young children. The greater risks posed to children by treatment, particularly by radiotherapy, also must be considered in treatment planning for children. This article summarizes what is known to date about childhood NRSTS, including the epidemiology, pathogenesis, and clinical approach to diagnosis and treatment of these tumors.

View details for DOI 10.1634/theoncologist.2007-0182

View details for Web of Science ID 000257428500006

View details for PubMedID 18586922

Colorectal carcinoma in childhood and adolescence: A clinicopathologic review JOURNAL OF CLINICAL ONCOLOGY Hill, D. A., Furman, W. L., Billups, C. A., Riedley, S. E., Cain, A. M., Rao, B. N., Pratt, C. B., Spunt, S. L. 2007; 25 (36): 5808-5814


Pediatric colorectal carcinoma (CRC) is rare, but the available data suggest that it is more likely than adult CRC to be advanced at presentation and to have a poor outcome. We sought to better characterize pediatric CRC.We reviewed the clinical and pathologic features, prognostic factors, and outcome of CRC in 77 children and adolescents (ages 7 to 19 years) referred to St Jude Children's Research Hospital between 1964 and 2003.At presentation, 76 patients had one or more signs or symptoms of CRC (abdominal pain, altered bowel habits, weight loss, anemia). Tumors were evenly distributed between the right and left colon; 62% were mucinous adenocarcinoma. At presentation, 86% of patients had advanced-stage disease; more than half had distant metastases. Overall outcome was poor. Advanced stage and mucinous histology were significant predictors of adverse outcome. Stage-specific survival at 10 years was 67% +/- 27% (stage 1), 38% +/- 15% (stage 2), 28% +/- 11% (stage III), and 7% +/- 4% (stage 4). Although no patient had a diagnosis of polyposis syndrome before diagnosis of CRC, 17 (22%) had colon polyps and eight (including two who previously underwent pelvic radiotherapy) had multiple polyps.Initial signs and symptoms of CRC are similar in pediatric and adult patients. The strikingly higher frequency of mucinous histology suggests that the biology of CRC differs in pediatric and adult patients and may contribute to poor outcomes. Children should be included in prospective clinical trials for CRC.

View details for DOI 10.1200/JCO.2007.12.6102

View details for Web of Science ID 000253886600021

View details for PubMedID 18089879

Phase I study of everolimus in pediatric patients with refractory solid tumors JOURNAL OF CLINICAL ONCOLOGY Fouladi, M., Laningham, F., Wu, J., O'Shaughnessy, M. A., Molina, K., Broniscer, A., Spunt, S. L., Luckett, I., Stewart, C. F., Houghton, P. J., Gilbertson, R. J., Furman, W. L. 2007; 25 (30): 4806-4812


To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetic and pharmacodynamic properties of the mammalian target of rapamycin (mTOR) inhibitor, everolimus, in children with refractory or recurrent solid tumors.Everolimus was administered orally at a daily dose of 2.1, 3, 5, or 6.5 mg/m2 in cohorts of three to six patients per dosage level. Pharmacokinetic and pharmacodynamic studies were performed during the first course. The phosphorylation status of various components of the mTOR signal pathway was assessed in peripheral-blood mononuclear cells (PBMCs) isolated from treated patients.There were 26 patients enrolled; 18 were assessable. DLTs included diarrhea (n = 1), mucositis (n = 1), and elevation of ALT (n = 1) at 6.5 mg/m2. At the MTD of 5 mg/m2, the median everolimus clearance was 15.2 L/h/m2, with a plasma everolimus concentration-time area under the curve (AUC) from 0 to infinity of 239.6 ng/mL x h. Significant inhibition of mTOR pathway signaling was observed in PBMCs from patients achieving AUCs 200 ng/mL x h, equivalent to dosages of 3 to 5 mg/m2 of everolimus. No objective tumor responses were observed.Continuous, orally administered everolimus is well tolerated in children with recurrent or refractory solid tumors and demonstrates similar pharmacokinetic properties to those observed in adults. Everolimus significantly inhibits the mTOR signaling pathway in children at the MTD. The recommended phase II dose in children with solid tumors is 5 mg/m2.

View details for DOI 10.1200/JCO.2007.11.4017

View details for Web of Science ID 000251073900017

View details for PubMedID 17947729

Creating a palliative and end-of-life program in a cure-oriented pediatric setting: The zig-zag method JOURNAL OF PEDIATRIC ONCOLOGY NURSING Harper, J., Hinds, P. S., Baker, J. N., Hicks, J., Spunt, S. L., Razzouk, B. I. 2007; 24 (5): 246-254


Children living with and dying of advanced-stage cancer suffer physically, emotionally, and spiritually. Relief of their suffering requires comprehensive, compassionate palliative and end-of-life (EoL) care.However, an EoL care program might appear inconsistent with the mission of a pediatric oncology research center committed to seeking cures. Here the authors describe the methods used to achieve full institutional commitment to their EoL care program and those used to build the program's philosophical, research, and educational foundations after they received approval. The authors convened 10 focus groups to solicit staff perceptions of the hospital's current palliative and EoL care. They also completed baseline medical record reviews of 145 patient records to identify key EoL characteristics. The authors then crafted a vision statement and a strategic plan, implemented new research protocols,and established publication and funding trajectories. They conclude that establishing a state-of-the-art palliative and EoL program in a cure-oriented pediatric setting is achievable via consensus building and recruitment of diverse institutional resources.

View details for DOI 10.1177/1043454207303882

View details for Web of Science ID 000249143400002

View details for PubMedID 17827490

Analysis of prognostic factors in ewing sarcoma family of tumors - Review of St. Jude Children's Rresearch Hospital studies CANCER Rodriguez-Galindo, C., Liu, T., Krasin, M. J., Wu, J., Billups, C. A., Daw, N. C., Spunt, S. L., Rao, B. N., Santana, V. M., Navid, F. 2007; 110 (2): 375-384


Advances in systemic and local therapies have improved outcomes for patients with the Ewing sarcoma family of tumors (ESFT). As new treatments are developed, a critical review of data from past treatment eras is needed to identify clinically relevant risk groups.The authors reviewed the records of 220 patients with ESFT who were treated on protocols at St. Jude Children's Research Hospital from 1979 to 2004. Two treatment eras were defined. Factors predictive of outcome were analyzed to identify distinct risk groups.The median age at diagnosis was 13.7 years (range, 1.1-25.2 years). Metastatic disease was associated with tumors measuring >8 cm (P = .002) and axial location (P = .014). The 5-year overall survival (OS) estimate (63.5% +/- 3.5%) did not appear to differ by protocol. Tumor stage and size were found to be the only independent predictors of outcome. Treatment era and type of local control therapy were found to influence the outcome of patients with localized disease. Four risk groups were defined: favorable risk (age <14 years with localized, nonpelvic tumors), intermediate risk (localized, age >/=14 years, or pelvic tumors), unfavorable-pulmonary (isolated lung metastases), and unfavorable-extrapulmonary (extrapulmonary metastases). The 5-year OS estimates for these groups were 88.1% +/- 4.4%, 64.9% +/- 5.2%, 53.8% +/- 9.4%, and 27.2% +/- 7.3%, respectively (P < .001). The incidence of therapy-related leukemia was significantly higher during the second treatment era, when more intensified regimens were used (6.1% +/- 2.7% vs 0% +/- 0%; P = .005).Risk stratification schemes such as this should be used to prospectively evaluate novel risk-based therapies. Studies of biologic pathways may help to refine this model.

View details for DOI 10.1002/cncr.22821

View details for Web of Science ID 000247985600019

View details for PubMedID 17569105

Phase I clinical trial of oxaliplatin in children and adolescents with refractory solid tumors JOURNAL OF CLINICAL ONCOLOGY Spunt, S. L., Freeman, B. B., Billups, C. A., McPherson, V., Khan, R. B., Pratt, C. B., Stewart, C. E. 2007; 25 (16): 2274-2280


To evaluate the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK), and adverse effect profile of oxaliplatin in pediatric patients with refractory solid tumors and to determine whether carbamazepine reduces oxaliplatin-induced neurotoxicity.Three regimens of oxaliplatin (given intravenously over 2 hours) were tested: regimen A (100 mg/m2, 130 mg/m2, or 160 mg/m2 every 3 weeks to determine the MTD of oxaliplatin); regimen B (to determine whether carbamazepine starting 24 hours before and ending 48 hours after oxaliplatin reduced the dose-limiting neurotoxicity and increased the MTD of regimen A); and regimen C (to evaluate the safety of a fixed dose two-thirds the MTD of regimen A given every 2 weeks [more frequent administration but comparable dose intensity]).Twenty-six patients were enrolled on regimens A (n = 11), B (n = 6), and C (n = 9). The DLT was grade 3 pharyngolaryngeal dysesthesia, sensory neuropathy, and ataxia at 160 mg/m2. The MTD was 130 mg/m2 every 3 weeks. At the MTD, the median clearance rate of ultrafiltrable platinum was 9.7 L/h/m2 (range, 6.5 to 15.5 L/h/m2). Addition of carbamazepine permitted dose escalation to 160 mg/m2 without DLT. DLT was not observed with a fixed dose of 85 mg/m2 given every 2 weeks. On all regimens, hematologic toxicity was mild. No significant nephrotoxicity, ototoxicity, or cumulative neurologic toxicity was observed.The DLT, MTD, PK, and adverse effect profile of oxaliplatin in pediatric patients with refractory solid tumors are similar to those observed in adults. Carbamazepine may reduce the dose-limiting neurotoxicity of oxaliplatin.

View details for DOI 10.1200/JCO.2006.08.2388

View details for Web of Science ID 000247010400022

View details for PubMedID 17538173

Distinguishing undifferentiated embryonal sarcoma of the liver from biliary tract rhabdomyosarcoma: A children's oncology group study PEDIATRIC AND DEVELOPMENTAL PATHOLOGY Nicol, K., Savell, V., Moore, J., Teot, L., Spunt, S. L., Qualman, S. 2007; 10 (2): 89-97


Morphologically, the distinction between undifferentiated embryonal sarcoma of the liver (UESL) and biliary tract rhabdomyosarcoma (RMS) can be uncertain because of some shared pathologic similarities. Patients with UESL have been consistently but erroneously enrolled in Children's Oncology Group (COG) treatment protocols because UESL was equated with RMS, despite the differing primary treatment modalities of these entities. Review of COG pathology files yielded 20 cases of UESL that were compared to 25 cases of biliary tract RMS. Clinicopathologic features including immunohistochemical staining were examined. In the UESL cases, the male:female ratio was 1:1 and the median age was 10.5 years. Histologically, hyaline globules and diffuse anaplasia were consistently present. The cases of RMS had a male:female ratio of 1.8:1 with a median age of 3.4 years and routinely lacked diffuse anaplasia and hyaline globules. Polyclonal desmin and muscle-specific actin were variably immunoreactive in UESL and RMS; however, myogenin and myogenic regulatory protein D1 (MyoD1) were uniformly negative in UESL and routinely positive in the majority of biliary tract RMS. Myogenin, in particular, was highly significant (P = 0.0003) in distinguishing RMS from UESL. With a median follow-up of 8 months, 11 of 18 patients with UESL were still alive. The estimated 5-year survival for biliary tract RMS was 66%. Establishing the correct diagnosis of these distinct clinical and pathologic entities is important, as surgery alone may be curative in UESL, whereas initial chemotherapy is often recommended for the treatment of biliary tract RMS.

View details for Web of Science ID 000247949700001

View details for PubMedID 17378682

A model for quantitative changes in the magnetic resonance parameters of muscle in children after therapeutic irradiation MAGNETIC RESONANCE IMAGING Krasin, M. J., Xiong, X., Reddick, W. E., Ogg, R. J., Hoffer, F. A., McCarville, B., Kaste, S. C., Spunt, S. L., Navid, F., Davidoff, A. M., Zhang, L., Kun, L. E., Merchant, T. E. 2006; 24 (10): 1319-1324


This study aimed to develop objective models of radiation effects on musculature in children with soft tissue sarcoma using treatment dosimetry and clinical and quantitative magnetic resonance imaging (MRI) parameters that may be used to guide treatment planning or predict side effects.In the initial 13 patients undergoing external beam radiation therapy (RT) on a Phase II study of conformal or intensity-modulated RT for the treatment of soft tissue sarcoma approved by an Institutional Review Board, we evaluated quantitative MRI changes in the musculature to assess radiation-related treatment effects. Patients with soft tissue sarcoma, including Ewing's sarcoma, had quantitative T1, T2 and dynamic enhanced MRI (DEMRI) performed before, during (Week 4) and after RT (Week 12). Regions of interest were selected in consistent locations within and outside the high-dose regions (on ipsilateral and contralateral sides when available). Mean RT dose, T1, T2 and DEMRI parameters were calculated and modeled using a mixed random coefficient dose model.The mean doses to the high- and low-dose regions were 56.4 Gy (41.8-75.3 Gy) and 13.0 Gy (0.1-37.5 Gy), respectively. Compared with tissues distant from the tumor bed, maximal enhancement was significantly increased in tissues adjacent to the tumor/tumor bed prior to RT (60.6 vs. 44.2, P=.045) and remained elevated after 12 weeks. T1 was significantly elevated in tissues adjacent to the tumor bed prior to RT (942.4 vs. 759.0, P=.0078). The slope of longitudinal change in T1 was greater for tissues that received low-dose irradiation than those that received high-dose irradiation (P=.0488). The effect of dose on the slope of T2 was different (P=.0333) when younger and older patients are compared.Acute affects of irradiation in muscle are quantifiable via MRI. These models provide evidence that quantifiable MRI parameters may be correlated with patient parameters of radiation dose and clinical factors including patient age. Long-term follow-up will be required to determine if acute changes correlate with clinically significant late effects.

View details for DOI 10.1016/j.mri.2006.08.004

View details for Web of Science ID 000242946800006

View details for PubMedID 17145403

St. Jude Children's Research Hospital, Memphis, Tennessee: gestational choriocarcinoma. Pediatric blood & cancer Weiss, A., Khoury, J. D., Kaste, S. C., Spunt, S. L. 2006; 47 (5): 640-646


This paper describes a recent tumor board presentation conducted at our institution involving an adolescent with gestational choriocarcinoma. Despite its rarity in pediatrics, gestational choriocarcinoma offers unique diagnostic, treatment and off-therapy considerations in adolescent patients who have become pregnant. Key features and findings of the case as well as important management issues will be discussed.

View details for PubMedID 16220549

Ewing sarcoma-family tumors that arise after treatment of primary childhood cancer CANCER Spunt, S. L., Rodriguez-Galindo, C., Fuller, C. E., Harper, J., Krasin, M. J., Billups, C. A., Khoury, J. D. 2006; 107 (1): 201-206


Unlike osteosarcoma, the Ewing sarcoma family of tumors (ESFT) has rarely been reported as secondary malignant neoplasms after treatment of childhood cancer. ESFT arising as a second cancer was reviewed and characterized at our childhood cancer center.A retrospective review was undertaken of 11,183 patients age <21 years who were treated for a primary cancer between March 1962 and December 2003 at St. Jude Children's Research Hospital. All cases of ESFT were confirmed to have a rearranged EWS gene.Six cases of ESFT (1.3% of 479 second cancers) were identified in patients previously treated for lymphoma (n = 3), leukemia (n = 1), retinoblastoma (n = 1), or Wilms tumor (n = 1). None of these patients had a family history suggestive of a familial cancer syndrome. The median time between diagnosis of primary cancer and diagnosis of ESFT was 5.9 years (range, 3.1-18.3 years). ESFT occurred in typical anatomic locations: rib (n = 2), chest wall soft tissues (n = 2), pelvis (n = 1), and extremity (n = 1). One tumor arose at the margin of a previous radiotherapy field and 1 arose distant from previous radiotherapy fields; all other patients had not received radiotherapy. Three patients are alive at the time of this report, including 2 whose ESFT was diagnosed more than 8 years ago.ESFT occurs rarely after treatment of a primary cancer during childhood, and most cases do not appear to be related to radiation therapy. Long-term survival can be achieved in some patients, and therefore secondary ESFT should be treated with curative intent.

View details for DOI 10.1002/cncr.21962

View details for Web of Science ID 000238469500026

View details for PubMedID 16721801

Neonatal epithelioid sarcoma: a distinct clinical entity? JOURNAL OF PEDIATRIC SURGERY Gupta, H., Davidoff, A. M., Rao, B. N., Jenkins, J. J., Spunt, S. L. 2006; 41 (7)


Epithelioid sarcoma is a rare soft tissue sarcoma with a propensity for local aggressiveness, regional nodal spread, and pulmonary metastases. We report a case of epithelioid sarcoma in a neonate with bilateral optic nerve hypoplasia who developed liver, kidney, and bone metastases. The unusual presenting features and pattern of disease progression in this patient suggest that a different disease evaluation strategy should be considered for infants with epithelioid sarcoma.

View details for DOI 10.1016/j.jpedsurg.2006.03.014

View details for Web of Science ID 000239279200035

View details for PubMedID 16818048

Concomitant administration of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for high-risk sarcomas - The St. Jude Children's Research Hospital experience CANCER Navid, F., Santana, V. M., Billups, C. A., Merchant, T. E., Furman, W. L., Spunt, S. L., Cain, A. M., Rao, B. N., Hale, G. A., Pappo, A. S. 2006; 106 (8): 1846-1856


Intensified chemotherapy may improve the outcome of patients with high-risk pediatric sarcomas. Vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide are highly effective against pediatric sarcomas. The authors investigated the feasibility of administering these agents concomitantly within a defined period.In the prospective high-risk sarcoma (HIRISA) Phase II trial HIRISA1, pediatric patients with high-risk sarcomas received 3 cycles of intensive vincristine, ifosfamide, etoposide, cyclophosphamide, and doxorubicin (VACIE) before radiotherapy and/or surgery began at Week 9 with concurrent vincristine, cyclophosphamide, and doxorubicin (Week 9) and vincristine and ifosfamide (Week 12). Three additional cycles of VACIE were then given. After delayed hematologic recovery in the first 11 patients, the protocol was modified (HIRISA2) to delay local control therapy until after 5 cycles of VACIE (to be completed within 18 weeks). Patients who responded to the protocols were eligible for myeloablative consolidation with autologous stem cell support.Eleven of 24 patients (median age, 14.9 years) had Ewing sarcoma family of tumors, 9 patients had rhabdomyosarcoma, and 4 patients had unresectable desmoplastic small round cell tumors. Seven of 13 patients on HIRISA2, but none of 11 patients on HIRISA1, completed therapy within the specified time. Reversible Grade 4 myelosuppression was the most common toxicity. Major nonhematologic toxic effects were mucositis, nutritional impairment, hypotension, and peripheral neuropathy. Three patients died of toxicity. The 5-year survival and 5-year event-free survival estimates both were 45.8% +/- 11.2%.The feasibility of administering intensive chemotherapy regimens like VACIE was dependent in part on the timing of local control therapy. This regimen was associated with significant toxicity.

View details for DOI 10.1002/cncr.21810

View details for Web of Science ID 000236787500028

View details for PubMedID 16541446

End-of-life care preferences of pediatric patients with cancer JOURNAL OF CLINICAL ONCOLOGY Hinds, P. S., Drew, D., Oakes, L. L., Fouladi, M., Spunt, S. L., Church, C., Furman, W. L. 2005; 23 (36): 9146-9154


The viewpoint of the terminally ill child at the time of an end-of-life decision has not been formally investigated. We identified the preferences of children and adolescents with advanced cancer about their end-of-life care and the factors that influenced their decisions.Pediatric patients 10 or more years of age were interviewed within 7 days of participating in one of the following three end-of-life decisions: enrollment onto a phase I trial (n = 7), adoption of a do not resuscitate order (n = 5), or initiation of terminal care (n = 8). The patient, a parent, and the primary pediatric oncologist were interviewed separately by using open-ended interview questions.Twenty patients, aged 10 to 20 years (mean, 17 years and 4 months), with a refractory solid tumor (n = 12), brain tumor (n = 4), or leukemia (n = 4) participated. Eighteen patients (90%) accurately recalled all of their treatment options and identified their own death as a consequence of their decision. The factors that were most frequently identified included the following: for patients, caring about others (n = 19 patients); for parents, the child's preferences (n = 18 parents); and for physicians, the patient's prognosis and comorbid conditions (n = 14 physicians).These children and adolescents with advanced cancer realized that they were involved in an end-of-life decision, understood the consequences of their decision, and were capable of participating in a complex decision process involving risks to themselves and others. The decision factors most frequently reported by patients were relationship based; this finding is contrary to existing developmental theories.

View details for DOI 10.1200/JCO.2005.10.538

View details for Web of Science ID 000234230400019

View details for PubMedID 16172453

Predictors of outcome in children and adolescents with rhabdomyosarcoma of the trunk - the St Jude Children's Research Hospital experience JOURNAL OF PEDIATRIC SURGERY Chui, C. H., Billups, C. A., Pappo, A. S., Rao, B. N., Spunt, S. L. 2005; 40 (11): 1691-1695


The aim of this study was to determine predictors of outcome in childhood truncal rhabdomyosarcoma.Retrospective chart review evaluating the impact of demographic features, disease characteristics, and the extent and timing of surgical intervention on outcome was performed.Thirty-three patients with a median age of 8 years were identified. Most had advanced Intergroup Rhabdomyosarcoma Study group III (n = 13) or group IV (n = 9) disease. Primary site included 20 (61%) chest wall, 6 (21%) paraspinal, 5 (15%) periscapular, and 1 (3%) abdominal wall. Most tumors were embryonal (n = 21), larger than 5 cm (n = 27), and locally invasive (n = 13); 7 had positive nodes. Tumor size, nodal status, and gross total tumor resection (upfront or delayed) were significant predictors of event-free and overall survival. Tumors 5 cm or smaller were amenable to upfront surgical resection (P = .007). In patients with tumors larger than 5 cm, resection at any time was associated with a 10-year overall survival 57% +/- 13% compared with 8% +/- 5% in those who had no surgery (P = .003). Tumor recurrence was local in 44% of cases, and survival after local recurrence was rare (1 of 8).Tumor size, nodal status, and gross total resection at any time are significant predictors of outcome in truncal rhabdomyosarcoma. Gross tumor excision should be the goal of surgical intervention in this disease.

View details for DOI 10.1016/j.jpedsurg.2005.07.042

View details for Web of Science ID 000233926000003

View details for PubMedID 16291153

Late effects of pelvic rhabdomyosarcoma and its treatment in female survivors JOURNAL OF CLINICAL ONCOLOGY Spunt, S. L., Sweeney, T. A., Hudson, M. M., Billups, C. A., Krasin, M. J., Hester, A. L. 2005; 23 (28): 7143-7151


To document the spectrum and severity of late effects in female survivors of pelvic rhabdomyosarcoma.We reviewed the demographic, diagnostic, treatment, and outcome data of the 26 females treated for pelvic rhabdomyosarcoma at our institution between March 1962 and December 1996 who survived free of disease for 5 or more years. Adverse effects that occurred 5 or more years after diagnosis were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.The most common tumor sites were vagina (n = 7), pelvis/retroperitoneum (n = 6), and bladder (n = 4). All patients received chemotherapy (alkylating agent, n = 23; doxorubicin, n = 16); 22 received radiotherapy (median dose, 46 Gy). Median follow-up of the 23 survivors was 20.3 years. Late effects occurred in 24 patients, 23 of whom had grade 3/4 late effects (median grade 3/4 late effects per patient, three; range, zero to 14). Fourteen patients (54%) required surgery for late complications. The 22 patients who had received radiotherapy had a greater median number of late effects per patient than did the remaining four (9.5 v one; P = .002). The median number of late effects per patient was higher in the 12 patients treated during or after 1984 than in the 14 treated earlier (12.5 v 6.5; P = .041).The burden of late effects in girls treated for pelvic rhabdomyosarcoma is significant and does not seem to be diminishing with advances in treatment. Prospective studies are needed to better assess the impact of these late effects on quality of life and functional outcome, and to refine the treatment approach to pelvic rhabdomyosarcoma.

View details for DOI 10.1200/JCO.2005.12.096

View details for Web of Science ID 000232232000042

View details for PubMedID 16192598

PET/CT in the evaluation of childhood sarcomas AMERICAN JOURNAL OF ROENTGENOLOGY McCarville, M. B., Christie, R., Daw, N. C., Spunt, S. L., Kaste, S. C. 2005; 184 (4): 1293-1304


Our objective was to review our preliminary experience with PET/CT in evaluating childhood sarcomas including rhabdomyosarcoma (n = 28), the Ewing's sarcoma family of tumors (n = 14), nonrhabdomyosarcoma soft-tissue sarcoma (n = 9), osteosarcoma (n = 8), chondrosarcoma (n = 1), and embryonal sarcoma (n = 1).We found PET/CT useful in depicting an unknown primary rhabdomyosarcoma and detecting unsuspected and unusual metastatic sites of childhood sarcomas. It was useful in monitoring response to chemotherapy, radiation therapy, and radiofrequency ablation and aided the postoperative evaluation of tumor resection sites.

View details for Web of Science ID 000228035600044

View details for PubMedID 15788613

Cyclophosphamide dose intensification during induction therapy for intermediate-risk pediatric rhabdomyosarcoma is feasible but does not improve outcome: A report from the soft tissue sarcoma committee of the children's oncology group 38th Annual Meeting of the American-Society-of-Clinical-Oncology Spunt, S. L., Smith, L. M., Ruymann, F. B., Qualman, S. J., Donaldson, S. S., Rodeberg, D. A., Anderson, J. R., Crist, W. M., Link, M. P. AMER ASSOC CANCER RESEARCH. 2004: 607279


More than half of pediatric rhabdomyosarcoma cases have intermediate-risk features and suboptimal outcome (3-year failure-free survival estimates, 55 to 76%). Dose intensification of known active agents may improve outcome.This pilot study evaluated the feasibility of dose intensification of cyclophosphamide in previously untreated patients ages < 21 years with intermediate-risk rhabdomyosarcoma. Induction therapy comprised four 3-week cycles of VAC: vincristine (V) 1.5 mg/m2 on days 0, 7, and 14; actinomycin D (A) 1.35 mg/m2 on day 0; and dose-intensified cyclophosphamide (C) on days 0, 1, and 2. The three cyclophosphamide dose levels tested were as follows: (a) 1.2 g/m2/dose; (b) 1.5 g/m2/dose; and (c) 1.8 g/m2/dose. Continuation therapy comprised nine additional cycles of VAC with 2.2 g/m2/cycle of C. Radiotherapy was administered at week 0 (parameningeal tumors with intracranial extension) or week 12 or 15 (all others).Between October 1996 and August 1999, 115 eligible patients were enrolled. Three of 15 patients treated at dose level 2 experienced life-threatening dose-limiting toxicity (typhlitis +/- other severe toxicity). Dose level 1 was the maximum-tolerated dose, and 91 evaluable patients were treated at this level. The 3-year failure-free and overall survival estimates for patients treated at the maximum-tolerated dose were 52% (95% confidence interval, 41-64%) and 67% (95% confidence interval, 56-77%), respectively, at a median follow-up of 3 years.A 64% increase in the standard cyclophosphamide dosage during induction (to 3.6 g/m2/cycle) was tolerated. However, outcomes were similar to those observed at lower dosages, suggesting that alkylator dose intensification does not benefit patients with intermediate-risk rhabdomyosarcoma.

View details for Web of Science ID 000224080200014

View details for PubMedID 15447992

Late events occurring five years or more after successful therapy for childhood rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group EUROPEAN JOURNAL OF CANCER Sung, L., Anderson, J. R., Donaldson, S. S., Spunt, S. L., Crist, W. M., Pappo, A. S. 2004; 40 (12): 1878-1885


The aim of our study was to describe late failures in children who initially survived event-free five years from a diagnosis of rhabdomyosarcoma. Charts of children enrolled in the Intergroup Rhabdomyosarcoma Study Group (IRSG) trials III, IV pilot and IV (1984-1997) who survived five years event-free and subsequently experienced an adverse event (disease recurrence, second malignant neoplasm or death from other causes) were reviewed. Of the 2534 enrolled patients, 1160 were event-free at five years and 48 subsequently experienced a late event. The estimated 10-year event rate for the 1160 patients who were alive and event-free at five years was 9% (95% Confidence Interval (CI) 5%, 13%). Patients with both advanced disease (Group III/IV) and large primary tumours at diagnosis (> 5 cm) were at the highest risk for late events (19%; 95% CI 8%, 30%). Late events after successful treatment for rhabdomyosarcoma occur in 9%. Those with advanced disease and large primary tumours have the highest risk of late events.

View details for DOI 10.1016/j.ejca.2004.04.005

View details for Web of Science ID 000223456600018

View details for PubMedID 15288290

Brain metastases of malignant germ cell tumors in children and adolescents CANCER Spunt, S. L., Walsh, M. F., Krasin, M. J., Helton, K. J., Billups, C. A., Cain, A. M., Pappo, A. S. 2004; 101 (3): 620-626


Brain metastases of pediatric germ cell tumors are uncommon, and there is limited information regarding their incidence, clinical presentation, response to treatment, and influence on survival.The authors reviewed the experience with brain metastases from pediatric germ cell tumors at St. Jude Children's Research Hospital (Memphis, TN) over a 40-year period.Between March 1962 and February 2002, 16 of 206 patients with germ cell tumors (7.8%) had brain metastases at the time of initial presentation (n = 2), later in the course of the illness (n = 12), or at autopsy (n = 2). Twelve of 16 patients (75%) had symptoms referable to the brain (nausea/emesis, headaches, or seizures), and 14 (88%) had pulmonary metastases at the time brain metastases were identified. Patients with brain metastases were more likely to have an extragonadal primary tumor (P = 0.013), advanced-stage disease at initial presentation (P = 0.016), and choriocarcinoma within the primary tumor (P < 0.001). The incidence of brain metastases was significantly lower in the second 2 decades of the study period (5 of 135 patients [3.7%]) than in the first 2 decades (11 of 71 patients [15.5%]; P = 0.005). Two of the 16 patients in the current study are long-term survivors.Brain metastases are uncommon in childhood germ cell tumors, and their incidence appears to be decreasing. In the current study, most patients with such metastases were symptomatic and had pulmonary metastases at the time brain metastases were identified. Patients with the highest risk of developing brain metastases include those with extragonadal tumors, those with high disease stage at initial presentation, and those with choriocarcinoma as a component of the primary tumor. The probability of survival is poor, although a small proportion of patients may become long-term survivors.

View details for DOI 10.1002/cncr.20411

View details for Web of Science ID 000222770100021

View details for PubMedID 15274076

Soft tissue sarcomas of childhood CANCER TREATMENT REVIEWS Meyer, W. H., Spunt, S. L. 2004; 30 (3): 269-280

View details for DOI 10.1016/j.ctrv.2003.11.001

View details for Web of Science ID 000220831700004

View details for PubMedID 15059650

Thyroid carcinoma presenting in childhood or after treatment of childhood malignancies: An institutional experience and review of the literature JOURNAL OF PEDIATRIC SURGERY Gow, K. W., Lensing, S., Hill, D. A., Krasin, M. J., McCarville, M. B., Rai, S. N., Zacher, M., Spunt, S. L., Strickland, D. K., Hudson, M. M. 2003; 38 (11): 1574-1580


Thyroid carcinomas can occur as a primary malignancy (PTM) or secondary after another malignancy (STM). Information about the presentations and outcomes of patients with STM are limited. The authors sought to compare the clinical characteristics, course, and outcomes of patients with primary or secondary thyroid malignancies.The authors reviewed the medical records of 8 children with PTM and 17 children with STM referred to St Jude Children's Research Hospital between February 1962 and February 2002 for evaluation and treatment of malignant thyroid carcinoma.The 8 children who had primary thyroid carcinoma had it diagnosed at a median age of 12.5 years (range, 7.3 to 16.3 years). Seven patients had papillary carcinoma, and 1 patient had follicular carcinoma. Three of the 8 (37.5%) had metastatic disease involving regional lymph nodes; 2 patients (25.0%) had lung metastases. Six patients required radioactive iodine (I 131) ablation for residual or metastatic disease after surgical resection. All 8 patients remain alive a median of 22.6 years after diagnosis (range, 0.7 to 30.5 years); 1 continues to receive radioactive iodine (I 131) ablation for persistent disease. Seventeen patients had thyroid carcinoma as a second malignant neoplasm after treatment for acute lymphoblastic leukemia (n = 6), Hodgkin's disease (n = 5), central nervous system tumor (n = 2), Wilms' tumor (n = 1), retinoblastoma (n = 1), non-Hodgkin's lymphoma (n = 1), or neuroblastoma (n = 1). Patients with secondary thyroid carcinoma presented at a median age of 21.5 years (range, 15.3 to 42.6 years), a median of 16.2 years (range, 0.9 to 29.2 years) after diagnosis of the primary cancer. Twelve of the 17 patients (70.6%) had received radiation to the thyroid gland during therapy for the primary cancer. Four patients (23.5%) had metastatic disease involving regional lymph nodes. Six patients (35.3%) required I(131) ablation for residual or metastatic disease after thyroidectomy. At the time of this report, all 17 patients are alive and in continue to be free of disease.Pediatric thyroid carcinoma is uncommon and responds well to current therapy. Given the limited period of follow-up of our cohort of secondary malignant thyroid tumors that arise after childhood cancer, these lesions appear to have similar presentations and outcomes when compared with primary carcinomas and can therefore be managed in the same manner.

View details for DOI 10.1016/S0022-3468(03)00563-3

View details for Web of Science ID 000186565200003

View details for PubMedID 14614703

Pediatric extraadrenal paraganglioma JOURNAL OF PEDIATRIC SURGERY Tekautz, T. M., Pratt, C. B., Jenkins, J. J., Spunt, S. L. 2003; 38 (9): 1317-1321


Pediatric paraganglioma is rare and extraadrenal paraganglioma has not been characterized in children.The authors reviewed the medical records and pathology samples of children with extraadrenal paraganglioma treated at our institution between December 1978 and September 2000. Clinical presentation, treatment, and outcome were evaluated.Eight patients (median age, 11.4 years) were identified, 4 were boys and none had a family history of paraganglioma or associated syndromes. Primary tumors arose in the retroperitoneum (n = 3), carotid body (n = 2), jugulotympanic ganglion (n = 1), cervical-paraspinal region (n = 1), and lung (n = 1). Extraadrenal paraganglioma had not been suspected at presentation in any patient. Of 5 patients who underwent gross total resection at the time of diagnosis, 4 remain disease free, 1 had microscopic residual tumor and died of disease. Three patients had initially unresectable disease, 2 are disease free after neoadjuvant therapy and delayed surgery, and 1 has persistent disease after tumor embolization and radiotherapy.Pediatric extraadrenal paraganglioma occurs most commonly in the retroperitoneum and head and neck, and the diagnosis usually is not suspected at the time of presentation. Surgery is the mainstay of treatment, and outcome is good after gross total resection. Neoadjuvant therapy can facilitate complete resection of initially unresectable tumors.

View details for DOI 10.1016/S0022-3468(03)00388-9

View details for Web of Science ID 000185741600008

View details for PubMedID 14523812

Treatment of Ewing sarcoma family of tumors: Current status and outlook for the future MEDICAL AND PEDIATRIC ONCOLOGY Rodriguez-Galindo, C., Spunt, S. L., Pappo, A. S. 2003; 40 (5): 276-287


The Ewing sarcoma family of tumors (ESFT) comprises a group of well-characterized neoplasms with aggressive behavior. Despite significant progress with the use of intensive multiagent chemotherapy and local control measures, a significant proportion of patients die of disease progression. Chemotherapy dose intensification and autologous hematopoietic stem cell transplant (HSCT) have been explored by many institutions without obvious benefit in high-risk patients. Our current understanding in the biology and treatment of ESFT suggests that a more rational approach to the development of risk-adapted therapy should be undertaken.We performed a review of the most relevant data regarding the current status in the treatment of ESFT. The results of the major American and European cooperative groups were analyzed, including the treatment strategies used and the prognostic factors identified for both localized and metastatic ESFT.The intensification of alkylating agents and topoisomerase-II inhibitors is feasible and has resulted in some survival improvement for selected patients. This benefit seems to be restricted to patients with localized disease, and a proportion of survivors are at risk of developing treatment-related hematologic malignancies. Nevertheless, these advances have resulted in a re-definition of prognostic factors, which may help to define risk groups based on tumor load parameters as well as biologic factors (type of fusion transcript and histologic response to chemotherapy). Patients with advanced metastatic disease may benefit from HSCT. New strategies such as immunotherapy and the use of biologic modifiers may have a role in the treatment of ESFT.Future treatment for ESFT should consider risk-adapted strategies and the inclusion of newer therapies such as biologic modifiers for the minimal residual disease. A modified risk-adapted therapy is proposed.

View details for DOI 10.1002/mpo.10240

View details for Web of Science ID 000181946200002

View details for PubMedID 12652615

A chemosensitive pediatric extraosseous osteosarcoma: Case report and review of the literature JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Wodowski, K., Hill, D. A., Pappo, A. S., Shochat, S. J., Kun, L. E., Spunt, S. L. 2003; 25 (1): 73-77


Osteosarcoma arising in soft tissues is exceedingly rare in children. The tumor most often affects older adults, involves the lower extremity, responds poorly to chemotherapy, and carries a grave prognosis. The authors describe a 12-year-old girl with an extraosseous osteosarcoma of the left sternocleidomastoid muscle with pulmonary metastases. The patient responded well to neoadjuvant chemotherapy and remains disease-free nearly 3 years after her initial diagnosis. The authors review available information about this disease in children and adults. Children with extraosseous osteosarcoma may have a more favorable response to treatment than adults; thus, a curative approach using combined modality therapy appears warranted.

View details for Web of Science ID 000180289900014

View details for PubMedID 12544778

Is reexcision in pediatric nonrhabdomyosarcoma soft tissue sarcoma necessary after an initial unplanned resection? JOURNAL OF PEDIATRIC SURGERY Chui, C. H., Spunt, S. L., Liu, T., Pappo, A. S., Davidoff, A. M., Rao, B. N., Shochat, S. J. 2002; 37 (10): 1424-1429


The aim of this study was to determine the importance of pretreatment reexcision (PRE) of pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) after initial unplanned resection.The authors retrospectively reviewed the records of 116 consecutive patients with surgically resected NRSTS treated at their institution between February 1978 and September 1999. Ninety-four (81.0%) patients had undergone unplanned resections before referral to their institution for further therapy. Demographic data, tumor characteristics, treatment administered, and outcomes were recorded.Sixty-nine patients (73.4%) underwent PRE at a median interval after the initial unplanned resection of 29 days. Twenty-five patients were thought unsuitable for PRE because of the proximity to vital neurovascular bundles. Tumors deemed not feasible for PRE were more likely to be greater than 5 cm (P =.0094) and high grade (P =.0200). Tumor was found in 33 (47.8%) of the PRE specimens, and 24 of these patients (72.7%) were deemed disease free after achieving negative surgical margins. Residual tumor was more likely to be found after PRE in head and neck primary tumors than in trunk wall or extremity primary tumors (P =.0128). There were no local failures in the 60 PRE patients who achieved clear margins. The estimated 5-year event-free and 5-year overall survival rates in these 60 patients were 98.3% +/- 2.0% and 98.2% +/- 2.1%, respectively.Pretreatment reexcision should be performed whenever feasible in pediatric patients with NRSTS who had an initial unplanned resection. The proportion of patients with residual tumor in the PRE specimen is high, and negative microscopic margins can be achieved after PRE in most patients with residual tumor. Despite delay in obtaining a complete surgical resection, no local recurrences were seen. The possibility of NRSTS should be considered when resecting a soft tissue mass in children, and diagnostic incisional biopsy followed by wide local excision with negative microscopic margins should be the surgical goal.

View details for DOI 10.1053/jpsu.2002.35405

View details for Web of Science ID 000178353600008

View details for PubMedID 12378447

Synovial sarcoma in pediatric patients AMERICAN JOURNAL OF ROENTGENOLOGY McCarville, M. B., Spunt, S. L., Skapek, S. X., Pappo, A. S. 2002; 179 (3)

View details for Web of Science ID 000177574600045

View details for PubMedID 12185067

Proceedings of the tumor board of St. Jude Children's Research Hospital, Memphis, Tennessee MEDICAL AND PEDIATRIC ONCOLOGY Spunt, S. L., Collins, M. H., D'Angio, G. J. 2002; 39 (2): 120-124

View details for DOI 10.1002/mpo.10099

View details for Web of Science ID 000176535100007

Retroperitoneal paraganglioma. Medical and pediatric oncology Barfield, R., Hill, D. A., Hoffer, F. A., Tekautz, T., Spunt, S. L. 2002; 39 (2): 120-124

View details for PubMedID 12116060

Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma JOURNAL OF CLINICAL ONCOLOGY Spunt, S. L., Hill, D. A., Motosue, A. M., Billups, C. A., Cain, A. M., Rao, B. N., Pratt, C. B., Merchant, T. E., Pappo, A. S. 2002; 20 (15): 3225-3235


To describe the clinical features, response to therapy, and outcome of pediatric patients with initially unresected nonmetastatic nonrhabdomyosarcoma soft tissue sarcoma (NRSTS).We retrospectively reviewed the presenting clinical features and tumor characteristics of all 40 pediatric patients with initially unresected nonmetastatic NRSTS who were seen at our institution between March 1962 and December 1996. A subset of 27 patients for whom complete treatment information was available was analyzed to determine whether response to therapy was associated with local disease control and event-free and overall survival.More than 70% of the 40 patients had tumors with high-risk features (tumor size > 5 cm, high grade, invasiveness). For the 27 patients included in the outcome analysis, 5-year event-free survival and survival estimates were 33% +/- 9% and 56% +/- 10%, respectively. Ten (37%) of these patients had a complete or partial response to neoadjuvant chemotherapy and/or radiotherapy, and only two of the 10 had residual tumor after surgery. Combined chemotherapy and radiotherapy seemed more effective than either modality alone in inducing a response, but the response to neoadjuvant therapy did not predict outcome. Most treatment failures were local, and postrelapse survival was poor (19% +/- 10%).Initially unresected NRSTS constitutes a unique subgroup of pediatric sarcomas that commonly present with high-risk features and respond poorly to neoadjuvant therapy. Only about one third of patients treated with multimodal therapy remain disease-free, and local control is the major limiting factor in achieving cure. More effective risk-directed treatments are needed for this unique subgroup of patients.

View details for DOI 10.1200/JCO.2002.06.066

View details for Web of Science ID 000177286100010

View details for PubMedID 12149295

Complex t(X;18)(p11.2;q11.2) with a pericentric inversion of the X chromosome in an adolescent boy with synovial sarcoma CANCER GENETICS AND CYTOGENETICS Mathew, S., Dalton, J., Riedley, S., Spunt, S. L., Hill, D. A. 2002; 132 (2): 136-140


Synovial sarcoma is the most common nonrhabdomyosarcomatous soft-tissue sarcoma in children and young adults. It is characterized by the common t(X;18)(p11.2;q11.2) that results in the fusion of SYT on chromosome 18 to one of two closely related and adjacent genes on the X chromosome, SSX1 or SSX2. Here we describe a poorly differentiated, monophasic synovial sarcoma in a 17-year-old adolescent boy. Hyperdiploidy, a t(X;18)(q13;q11), and other structural abnormalities were detected by conventional cytogenetic analysis. Fluorescence in situ hybridization with the PAC probe RP3-519N18, which is specific for the Xp11 region, resulted in a signal on the der(Xq), a finding consistent with a pericentric inversion of the X chromosome that resulted in a t(X;18)(p11.2;q11.2)inv(X)(p11.2q13). Real-time polymerase chain reaction using primer sets specific for SYT-SSX1 and SYT-SSX2 confirmed the presence of an SYT-SSX1 fusion transcript. Our finding of this unique and complex translocation in synovial sarcoma demonstrates the utility of molecular methods in confirming the diagnosis of synovial sarcoma.

View details for Web of Science ID 000174032900009

View details for PubMedID 11850075

Selective use of whole-lung irradiation for patients with Ewing sarcoma family tumors and pulmonary metastases at the time of diagnosis (vol 23, pg 93, 2001) JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Spunt, S. L., McCarville, B., Kun, L. E. 2001; 23 (9): 637-637
Routine brain imaging is unwarranted in asymptomatic patients with rhabdomyosarcoma arising outside of the head and neck region that is metastatic at diagnosis - A report from the Intergroup Rhabdomyosarcoma Study Group 36th Annual Meeting of the American-Society-of-Clinical-Oncology Spunt, S. L., Anderson, J. R., Teot, L. A., Breneman, J. C., Meyer, W. H., Pappo, A. S. JOHN WILEY & SONS INC. 2001: 12125


To the authors' knowledge, the incidence of brain metastases at the time of diagnosis in children with metastatic rhabdomyosarcoma (RMS) arising outside the head and neck region is unknown, and routine imaging to identify metastatic brain involvement is costly.The authors retrospectively reviewed the results of computed tomography (CT) or magnetic resonance imaging (MRI) scans of the head, which was mandated by protocol, in patients with metastatic RMS arising outside the head and neck region who were enrolled on the fourth Intergroup Rhabdomyosarcoma Study (IRS-IV; 1991--1997).Of 100 eligible patients with metastatic RMS arising outside the head and neck region, 56 (56%) underwent head CT (n = 51) and/or MRI (n = 11) scans. Seven of these 56 patients (12.5%) had abnormal scans. Three patients with physical findings suggesting head or neck pathology underwent imaging that confirmed the presence of metastases in bone (one patient), orbit (one patient), or lymph nodes (one patient). One patient who presented with seizures had imaging findings consistent with cerebral embolic infarctions. Of three asymptomatic patients, one had bone metastases that also were identified on skeletal survey and one had bone metastases in the base of the skull that were not identified on bone scan. The remaining asymptomatic patient had a retroperitoneal paraspinal tumor with spinal canal extension and subsequently developed leptomeningeal disease dissemination.Brain metastases are uncommon at the time of initial diagnosis of metastatic RMS arising outside the head and neck region, and the majority of abnormalities detected on head CT or MRI scans are evident clinically or on other imaging studies. Patients with clinical findings suggesting intracranial pathology and those with paraspinal tumors may benefit from brain imaging, but cost savings may be realized by foregoing imaging in patients without these features.

View details for Web of Science ID 000169666200016

View details for PubMedID 11443617

Rhabdomyosarcoma in pediatric patients: The good, the bad, and the unusual AMERICAN JOURNAL OF ROENTGENOLOGY McCarville, M. B., Spunt, S. L., Pappo, A. S. 2001; 176 (6): 1563-1569

View details for Web of Science ID 000168929900039

View details for PubMedID 11373233

Selective use of whole-lung irradiation for patients with Ewing sarcoma family tumors and pulmonary metastases at the time of diagnosis JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Spunt, S. L., McCarville, M. B., Kun, L. E., Poquette, C. A., Cain, A. M., Brandao, L., Pappo, A. S. 2001; 23 (2): 93-98


The benefit of whole-lung irradiation (WLI) for patients who have pulmonary metastases (PM) of Ewing sarcoma family tumors (ESFT) is unclear. At our institution, WLI is reserved for patients with PM that do not respond completely to induction chemotherapy. We reviewed our experience to assess the impact of WLI on clinical outcome.Twenty-eight patients with ESFT and PM were treated in three consecutive institutional trials (1979-1996). Extent of pulmonary involvement at diagnosis, response of PM after induction chemotherapy, local treatment of PM thereafter, and clinical outcome were recorded. Treatment included primary tumor surgery and/or radiotherapy and 42 to 58 weeks of multiagent chemotherapy.Only eight patients (29%) received WLI. For the entire study group, the estimated 5-year event-free survival was 22.9% +/- 9.0%; the 5-year survival was 37.3% +/- 9.8%. Complete resolution of PM after induction chemotherapy was not correlated with survival (P = 0.53), nor was treatment with WLI (P = 0.87).The comparable survival of patients with poor and good response of PM to induction chemotherapy suggests that WLI may benefit poor responders. The use of WLI in good responders may provide similar benefit and merits further study.

View details for Web of Science ID 000166903000004

View details for PubMedID 11216713

Brain metastases in paediatric solid tumours. Forum (Genoa, Italy) Spunt, S. L., Thompson, S. J., Pappo, A. S. 2001; 11 (1): 75-86


Brain metastases in children with cancer are rare and their incidence is significantly lower (5-10%) than that reported in adults. The development of metastatic brain tumours in children is usually a manifestation of advanced disease and commonly occur after, or at the time of progression at other sites. This review summarises the salient clinical features of the most common paediatric solid tumours that metastasize to the brain including neuroblastoma, musculoskeletal sarcomas, germ cell tumours and melanoma.

View details for PubMedID 11734866

Childhood carcinoid tumors: The St Jude Children's Research Hospital experience JOURNAL OF PEDIATRIC SURGERY Spunt, S. L., Pratt, C. B., Rao, B. N., Pritchard, M., Jenkins, J. J., Hill, D. A., Cain, A. M., Pappo, A. S. 2000; 35 (9): 1282-1286


To better characterize childhood carcinoid tumors, the authors reviewed the clinical presentation, treatment, and outcomes of pediatric patients with these rare tumors.A retrospective review was conducted of medical records and pathologic materials of all children with carcinoid tumors treated at St Jude Children's Research Hospital between December 1977 and March 1999.Eight patients (median age, 12.7 years) were identified; 2 were boys, and 7 were white. Primary tumor sites were the appendix (n = 5), small intestine (n = 1), bronchus (n = 1), and 1 unknown site. In 7 cases, carcinoid tumor was not suspected at the time the tumor was identified. Seven patients had localized disease; 5 remain disease-free after complete resection, and 2, whose carcinoid tumors were identified incidentally, died of metastatic mucinous adenocarcinoma of the colon. One patient who presented with symptoms of carcinoid syndrome had metastatic disease that responded poorly to cytotoxic chemotherapy and remains alive with active disease.Although most pediatric carcinoid tumors arise in the appendix, these tumors also occur in other primary sites. Clinical awareness and early diagnosis are important factors in preventing morbidity and mortality. Outcomes are excellent for patients with localized disease that is completely resected, but those with metastatic disease fare poorly. New therapeutic strategies are needed for these patients.

View details for Web of Science ID 000089146600002

View details for PubMedID 10999679

Nonrhabdomyosarcoma soft tissue sarcomas in children: Is age at diagnosis an important variable? Annual Meeting of the Section on Surgery of the American-Academy-of-Pediatrics Hayes-Jordan, A. A., Spunt, S. L., Poquette, C. A., Cain, A. M., Rao, B. N., Pappo, A. S., Shochat, S. J. W B SAUNDERS CO-ELSEVIER INC. 2000: 94853


The associations between age at diagnosis, tumor characteristics, and outcome in children diagnosed with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) were studied.Retrospective review was conducted of 192 children from 1962 through 1996. Patients were divided into groups: birth to 1 year (n = 13), 1 to 5 years (n = 26), 5 to 10 years (n = 49), 10 to 15 years (n = 55), and older than 15 years (n = 49) of age at diagnosis. Characteristics including IRS group, histological grade and pattern, tumor size, and invasiveness were investigated. Survival rate was estimated by age group. The median follow-up was 8.8 years (range, 2 to 28 years).There were 81 group I patients, 40 group II, 41 group III, and 30 group IV. A significant difference of IRS groups among the age groups was seen (P = .034). There were no IRS group IV patients less than 1 year of age; 50% of IRS group IV patients were older than 15 years. A significant difference in the distribution of histological grade among the age groups (P = .032) was seen. Ten of 13 (77%) children less than 1 year of age had low-grade tumors, whereas 42%, 45%, 60%, and 37% of patients aged 1 to 5, 5 to 10, 10 to 15, and older than 15 years, respectively, had low-grade tumors. Patients older than 15 years had the highest incidence of invasive tumors (59%). Histological pattern also varied with age. The most prevalent histology in the less-than-1-year age group was infantile fibrosarcoma. No predominant histology was seen in the 1- to 5-year age group. Malignant fibrous histiocytoma was the most frequent histological subtype in children between 5 and 10 years of age. In the 10- to 15-year age group and children older than 15 years the malignant peripheral nerve sheath tumor and synovial sarcoma were the most prevalent subtypes. Without adjusting for any other factors, age group was prognostic of survival (P = .007). Patients less than 1 year at diagnosis had the best outcome, with a 5-year survival rate of 92% +/- 9%. Five-year estimates were lowest for patients older than 15 years (49% +/- 7%).Significant differences in IRS group, histological grade, and histological subtype were observed in different age groups. Infants with NRSTS were more likely to have low grade, less invasive, and lower stage tumors. These characteristics may account for their improved prognosis.

View details for Web of Science ID 000087429900043

View details for PubMedID 10873042

Aggressive surgery is unwarranted for biliary tract rhabdomyosarcoma 30th Annual Meeting of the American-Pediatric-Surgical-Association Spunt, S. L., Lobe, T. E., Pappo, A. S., Parham, D. M., Wharam, M. D., Arndt, C., Anderson, J. R., Crist, W. M., Paidas, C., Wiener, E., Andrassy, R. J., Schwartz, C. L. W B SAUNDERS CO-ELSEVIER INC. 2000: 30916


Rhabdomyosarcoma (RMS) of the biliary tract is rare, and, in addition to multiagent chemotherapy with or without radiotherapy (RT), some investigators recommend aggressive surgery. To assess the role of surgery, records of all 25 eligible patients with biliary RMS enrolled in IRSG studies I through IV from 1972 to 1998 were reviewed.Treatment included surgery with or without vincristine, dactinomycin, cyclophosphamide, doxorubicin, cisplatin, etoposide, ifosfamide, and with or without RT. Data evaluated included clinical presentation, treatment, complications, and outcome.Diagnostic imaging identified the primary tumor but failed to identify regional metastases. Despite aggressive surgery, gross total resection at diagnosis was possible in only 6 cases, 2 of which had negative surgical margins. Although only 6 (29%) patients without distant metastases underwent gross total resection, estimated 5-year survival rate was 78% (95% CI 58%, 97%). Infectious complications were common and frequently associated with external biliary drains. Five (20%) died within the first 2 months, 3 of sepsis.Surgery is critical for establishing an accurate diagnosis and determining the extent of regional disease. Gross total resection is rarely possible despite aggressive surgery, and outcome is good despite residual disease after surgery. External biliary drains increase the risk of postoperative infectious complications.

View details for Web of Science ID 000085128700056

View details for PubMedID 10693686

Prognostic factors for children and adolescents with surgically resected nonrhabdomyosarcoma soft tissue sarcoma: An analysis of 121 patients treated at St Jude Children's Research Hospital JOURNAL OF CLINICAL ONCOLOGY Spunt, S. L., Poquette, C. A., Hurt, Y. S., Cain, A. M., Rao, B. N., Merchant, T. E., Jenkins, J. J., Santana, V. M., Pratt, C. B., Pappo, A. S. 1999; 17 (12): 3697-3705


The rarity and heterogeneity of pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) has precluded meaningful analysis of prognostic factors associated with surgically resected disease. To define a population of patients at high risk of treatment failure who might benefit from adjuvant therapies, we evaluated the relationship between various clinicopathologic factors and clinical outcome of children and adolescents with resected NRSTS over a 27-year period at our institution.We analyzed the records of 121 consecutive patients with NRSTS who underwent surgical resection between August 1969 and December 1996. Demographic data, tumor characteristics, treatment, and outcomes were recorded. Univariate and multivariate analyses of prognostic factors for survival, event-free survival (EFS), and local and distant recurrence were performed.At a median follow-up of 9.2 years, 5-year survival and EFS rates for the entire cohort were 89% +/- 3% and 77% +/- 4%, respectively. In univariate models, positive surgical margins (P =.004), tumor size > or = 5 cm (P <.001), invasivene (P =.002), high grade (P =.028), and intra-abdominal primary tumor site (P =.055) adversely affected EFS. All of these factors except invasiveness remained prognostic of EFS and survival in multivariate models. Positive surgical margins (P =.003), intra-abdominal primary tumor site (P =.028), and the omission of radiation therapy (P =.043) predicted local recurrence, whereas tumor size > or = 5 cm (P <.001), invasiveness (P <.001), and high grade (P =.004) predicted distant recurrence.In this largest single-institution analysis of pediatric patients with surgically resected NRSTS, we identified clinicopathologic features predictive of poor outcome. These variables should be prospectively evaluated as risk-adapted therapies are developed.

View details for Web of Science ID 000084043300002

View details for PubMedID 10577841

Absence of TSG101 transcript abnormalities in human cancers ONCOGENE Trink, B., Pai, S. I., Spunt, S. L., Raman, V., Cairns, P., Jen, J., Gabrielson, E., Sukumar, S., Sidransky, D. 1998; 16 (21): 2815-2818


The human TSG101 gene was cloned and mapped to chromosome 11p15, a site suspected to contain a tumor suppressor gene involved in a variety of human cancers. Subsequent investigation described the presence of abnormally spliced transcripts and point mutations of TSG101 in breast cancer. Thus, we performed RT-PCR amplification of the entire open reading frame of TSG101 to test for aberrant transcripts in various human tumor cell lines derived from breast, bladder, head and neck, and lung cancer. In addition, we performed RT-PCR on cDNA from primary human breast and Wilms' tumor tissue. We found a single band of the expected size in 10 of 11 breast cancers and 6 of 6 Wilms' tumor samples after the first round of PCR. The remaining breast cancer sample displayed a barely visible smaller band. However, aberrant bands appeared in most cases after performing nested PCR casting doubt on the physiologic relevance of these spliced variants. We then searched for small intragenic mutations by complete sequence analysis of TSG101 in breast cancer cell lines and tumors, as well as in Wilms' tumors and normal fetal and adult kidney. No point mutations were found in any of the samples, including four breast tumors with chromosomal loss at 11p15. We found no consistent evidence of aberrant splicing or point mutations in breast cancer or Wilms' tumor suggesting that TSG101 is not a primary target of inactivation in human cancer.

View details for Web of Science ID 000073812200014

View details for PubMedID 9652749