Citations

PURPOSE The primary aim of this phase III randomized trial was to test whether the addition of vincristine, topotecan, and cyclophosphamide (VTC) to interval compressed chemotherapy improved survival outcomes for patients with previously untreated nonmetastatic Ewing sarcoma. METHODS Patients were randomly assigned to receive standard five-drug interval compressed chemotherapy (regimen A) for 17 cycles or experimental therapy with five cycles of VTC within the 17 cycles (regimen B). Patients were stratified by age at diagnosis (< 18 years and ≥18 years) and tumor site (pelvic bone, nonpelvic bone, and extraosseous). Tumor volume at diagnosis was categorized as < 200 mL or ≥ 200 mL. Local control occurred following six cycles. Histologic response was categorized as no viable or any viable tumor. Event-free survival (EFS) and overall survival (OS) were compared between randomized groups with stratified log-rank tests. RESULTS Of 642 enrolled patients, 309 eligible patients received standard and 320 received experimental therapy. The 5-year EFS and OS were 78% and 87%, respectively. There was no difference in survival outcomes between randomized groups (5-year EFS regimen A v regimen B, 78% v 79%; P = .192; 5-year OS 86% v 88%; P = .159). Age and primary site did not affect the risk of an EFS event. However, age ≥ 18 years was associated with an increased risk of death at 5 years (hazard ratio 1.84; 95% CI, 1.15 to 2.96; P = .009). The 5-year EFS rates for patients with pelvic, nonpelvic bone, and extraosseous primary tumors were 75%, 78%, and 85%, respectively. Tumor volume ≥ 200 mL was significantly associated with lower EFS. CONCLUSION While VTC added to five-drug interval compressed chemotherapy did not improve survival, these outcomes represent the best survival estimates to date for patients with previously untreated nonmetastatic Ewing sarcoma.

Abstract Ewing sarcoma is a rare tumor that requires complex multidisciplinary management. This report describes the general management and standard radiotherapy guidelines in both North America (Children's Oncology Group) and Europe (International Society of Pediatric Oncology). Standard treatment involves multiagent induction chemotherapy followed by local treatment with surgery, definitive radiation, or a combination of surgery and radiation followed by additional chemotherapy and consolidation local treatment to metastatic sites. The data supporting the role of chemotherapy, surgery, and radiation and specific radiation therapy guidelines are presented.

Abstract Osteosarcoma is a rare tumor that requires complex multidisciplinary management. This paper reviews the general management and standard radiotherapy guidelines for osteosarcoma in both North America and Europe in a joined effort between the Children's Oncology Group and International Society of Pediatric Oncology. Standard treatment involves multiagent induction chemotherapy followed by surgical resection for local tumor control and consolidation local control to metastatic sites. Radiotherapy is reserved for cases with a marginal or incomplete resection or for definitive treatment in the case of unresectable disease. We present supporting data for the role of chemotherapy, surgery, and radiation therapy.

AbstractThis report by the Radiation Oncology Discipline of Children's Oncology Group (COG) describes the practice patterns of pediatric image‐guided radiotherapy (IGRT) based on a member survey and provides practice recommendations accordingly. The survey comprised of 11 vignettes asking clinicians about their recommended treatment modalities, IGRT preferences, and frequency of in‐room verification. Technical questions asked physicists about imaging protocols, dose reduction, setup correction, and adaptive therapy. In this report, the COG Radiation Oncology Discipline provides an IGRT modality/frequency decision tree and the expert guidelines for the practice of ionizing image guidance in pediatric radiotherapy patients.

BackgroundCurative therapy for ES requires both chemotherapy and local control of primary tumor. There is no universally accepted standard approach to local control modalities. This survey was conducted to determine practice patterns and factors influencing the choice to offer various local control modalities to patients with ES of the spine and pelvis.MethodsThe survey consisted of four scenarios involving a 15‐year‐old girl who presented with Ewing sarcoma of thoracic vertebra, sacrum, iliac wing, and acetabulum with or without neurologic compromise. The questionnaire was sent to oncologists, orthopedic surgeons, and radiation oncologists, asking their recommendations for local control modality.ResultsAmong 94 respondents, radiotherapy was most frequently chosen for sacral tumors (68.1%) and T10 vertebral tumors (46.2%) whereas surgery was preferred for iliac wing pelvic tumors (45.7%) and acetabular tumors (43.6%). Orthopedic surgeons were significantly more likely to offer surgery than radiation oncologists (OR 3.07, 95%CI 1.37‐6.88, P = 0.007). Providers outside North America were more likely to offer combined surgery plus radiotherapy (OR 10.58, 95%CI 5.41‐20.70, P < 0.001).ConclusionConsiderable heterogeneity exists in local control modalities for Ewing sarcoma of the spine and pelvis. Specialty and location of practice may influence treatment recommendations.

AbstractPurposeTo evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs).Materials and methodsWe retrospectively reviewed records of 34 patients diagnosed with primary intracranial NGGCT between 1988 and 2014.ResultsThirty‐four patients received induction chemotherapy followed by radiation with or without surgery. Median follow‐up was 11.1 years (0.8–23.3). Outcomes were significantly improved in these 34 patients (5‐year overall survival [OS]: 88% versus 50%, P = 0.0092), so analysis is restricted to that subset. Disease‐free survival (DFS) was 67, 60, and 54% at 5, 10, and 15 years, respectively. Elevated cerebrospinal fluid–α‐fetoprotein (CSF–AFP) at diagnosis was associated with poorer DFS (37 vs. 89% at 10 years; P = 0.01). There was no statistically significant difference in OS, or DFS, or patterns of failure for limited radiotherapy volumes versus larger volumes; however, patients receiving initial local radiotherapy had 32% distant central nervous system (CNS) recurrence at 10 years compared to 0% for those receiving initial larger field irradiation (P = 0.09). Fifteen patients recurred. All four patients who relapsed in the spine had received local radiotherapy and had elevated serum and CSF‐AFP at baseline. All three patients with ventricular relapse received local radiation therapy.ConclusionsNGGCT patients continue to relapse beyond 5 years. Late ventricular relapse occurred even in patients without clear evidence of germinoma component. Elevated CSF‐AFP at diagnosis is associated with poor DFS and risk for distant CNS relapse. Patients with residual radiographic disease after chemotherapy or residual malignant histologies after second‐look surgery have inferior outcomes. Our data support consideration of treatment intensification for these patients.

AbstractPurposeLocal control for Ewing sarcoma (ES) has improved in modern studies. However, it is unclear if these gains have also been achieved for pelvis tumors. The purpose of this study is to evaluate local control and survival in pelvis ES patients treated in the modern era.MethodsAll pelvis ES patients diagnosed from 1990 to 2012 and seen at Mayo Clinic were identified. Factors relevant to survival and local control were analyzed.ResultsThe cohort consisted of 48 patients. Fifty‐two percent had metastatic disease at diagnosis. The 5‐year overall survival and event‐free survival was 73% and 65%, respectively, for localized disease. The 5‐year cumulative incidence of local recurrence was 19%, with a 26% incidence for radiation, 13% for surgery, and 0% for surgery + radiation (P = 0.54). All local failures occurred in‐field. Sacral involvement by tumor trended toward a higher incidence of local recurrence (hazard ratio 3.06, P = 0.09). Patients treated with definitive radiation doses ≥5,600 cGy had a lower incidence of local recurrence (17% vs. 28%, P = 0.61).ConclusionsOur study demonstrates excellent survival for localized tumors in the modern era. Anatomical localization within the pelvis likely correlates with outcomes. Local control remains problematic, especially for patients treated with definitive radiation. Though statistically not significant, surgery + radiation and definitive radiation dose ≥5,600 cGy were associated with the lowest incidence of local failure, suggesting treatment intensification may improve local control for pelvis ES.