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Purpose The primary objective of Children's Oncology Group study P9641 was to demonstrate that surgery alone would achieve 3-year overall survival (OS) ≥ 95% for patients with asymptomatic International Neuroblastoma Staging System stages 2a and 2b neuroblastoma (NBL). Secondary objectives focused on other low-risk patients with NBL and on those who required chemotherapy according to protocol-defined criteria. Patients and Methods Patients underwent maximally safe resection of tumor. Chemotherapy was reserved for patients with, or at risk for, symptomatic disease, with less than 50% tumor resection at diagnosis, or with unresectable progressive disease after surgery alone. Results For all 915 eligible patients, 5-year event-free survival (EFS) and OS were 89% ± 1% and 97% ± 1%, respectively. For patients with asymptomatic stage 2a or 2b disease, 5-year EFS and OS were 87% ± 2% and 96% ± 1%, respectively. Among patients with stage 2b disease, EFS and OS were significantly lower for those with unfavorable histology or diploid tumors, and OS was significantly lower for those ≥ 18 months old. For patients with stage 1 and 4s NBL, 5-year OS rates were 99% ± 1% and 91% ± 1%, respectively. Patients who required chemotherapy at diagnosis achieved 5-year OS of 98% ± 1%. Of all patients observed after surgery, 11.1% experienced recurrence or progression of disease. Conclusion Excellent survival rates can be achieved in asymptomatic low-risk patients with stages 2a and 2b NBL after surgery alone. Immediate use of chemotherapy may be restricted to a minority of patients with low-risk NBL. Patients with stage 2b disease who are older or have diploid or unfavorable histology tumors fare less well. Future studies will seek to refine risk classification.

Purpose: This phase II, open-label, multicenter study assessed the efficacy and safety of the potential radiation enhancer RSR13 plus cranial radiation therapy (RT) in patients with brain metastases. The primary end point was patient survival in comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database (RTOG RPA BMD). Patients and Methods: Eligibility criteria were age ≥ 18 years, Karnofsky performance score ≥ 70, and brain metastases with solid tumor histology. Patients received cranial RT, 30 Gy in 10 fractions of 3 Gy each, preceded by RSR13, 50 to 100 mg/kg intravenously over 30 minutes. Univariate and multivariate comparisons of survival and cause of death were made between class II study patients and RTOG BMD patients. Results: Fifty-seven RPA class II patients were enrolled. With a minimum follow-up of 24 months, the median survival time and 1- and 2-year survival rates were 6.4 months, 23%, and 11% for the RSR13-treated patients compared with 4.1 months, 15%, and 3% for the RTOG BMD patients (P = .0174). In an exact-matched case analysis (n = 38), median survival time for RSR13 patients was 7.3 months versus 3.4 months for the RTOG BMD patients (P = .006). There was a 54% reduction in the risk of death for RSR13 patients (P = .0267). RSR13-related adverse events of greater than or equal to grade 3 toxicity that occurred in more than one patient included hypoxia, headache, anemia, fatigue, hypertension, and intracranial hypertension. Conclusion: RSR13 plus cranial RT resulted in a significant improvement in survival, as well as a reduction in death due to brain metastases, compared with class II patients in the RTOG BMD.

e15076 Background: With the advent of colon cancer screening, patients with early stage colon cancer will be more common in our clinics. The evidence supporting the absolute benefit of chemotherapy in resected Stage II and (to a lesser extent) Stage IIIA disease is poor. Not all patients benefit from chemotherapy and toxicity is a problem. There is a need for validated biomarkers to assess individual patient recurrence risk and discriminate absolute treatment benefit. Several studies have validated the role of the OncotypeDX testing in Stage II/IIIA disease. Our objective is to characterize whether this test impacted oncologists’ decisions in treating patients with Stage II/IIIA in the adjuvant setting. Methods: :The Onco typeDX assay is a multi-gene reverse-transcriptase-polymerase-chain-reaction test that analyses the expression of 12 genes involved in key biologic pathways in colon cancer. Stage II and Stage IIIA colon cancers were studied in affiliated hospitals of our region in southwest Ireland. All data collected is prospective and each colon cancer was assigned a recurrence risk score. Oncologists were blinded to this score and the decision to prescribe adjuvant chemotherapy was recorded. After un-blinding the score, a second decision was recorded and comparisons made. Results: :From August 2015 to September 2016, 70 patients have been recruited with M: F of 2:1. Median age at diagnosis was 65 years. Most patients (80%) had stage II disease, 11 of whom had mismatch repair loss on IHC. OncotypeDX testing has been carried out and reported for 59 patients (85%), MMR intact. Recurrence scores: < 30 in 46 patients (77.9%), 30-40 in 10 patients, and > 40 in 3 patients. The treatment plan was altered in 16 patients (27%), of whom 12 patients (20%) received none or less intense chemotherapy. Conclusions: We have shown that the decision to prescribe adjuvant chemotherapy was changed in 27% of patients. This test has helped to define patients with low scores, where chemotherapy-related toxicity is a concern especially in older patients. Absolute benefit of adjuvant chemotherapy versus the risk of toxicity should be discussed. . Hospital managers may be interested in cost savings due to a reduction in chemotherapy use.

PURPOSE Definitive chemoradiation (CR) has replaced radical surgery as the preferred treatment of epidermoid carcinoma of the anal canal. To determine the importance of mitomycin (MMC) in the standard CR regimen and to assess the role of salvage CR in patients who have residual tumor following CR, a phase III randomized trial was undertaken by the Radiation Therapy Oncology Group (RTOG)/Eastern Cooperative Oncology Group (ECOG). PATIENTS AND METHODS Between August 1988 and December 1991, 310 patients were randomized to receive either radiotherapy (RT) and fluorouracil (5-FU) or radiotherapy, 5-FU, and MMC. Of 291 assessable patients, 145 received 45 to 50.4 Gy of pelvic RT plus 5-FU at 1,000 mg/m2/d for 4 days, and 146 received RT, 5-FU, and MMC (10 mg/m2 per dose for two doses). Patients with residual tumor on posttreatment biopsy were treated with a salvage regimen that consisted of additional pelvic RT (9 Gy), 5-FU, and cisplatin (100 mg/m2). RESULTS Posttreatment biopsies were positive in 15% of patients in the 5-FU arm versus 7.7% in the MMC arm (P = .135). At 4 years, colostomy rates were lower (9% v 22%; P = .002), colostomy-free survival higher (71% v 59%; P = .014), and disease-free survival higher (73% v 51%; P = .0003) in the MMC arm. A significant difference in overall survival has not been observed at 4 years. Toxicity was greater in the MMC arm (23% v 7% grade 4 and 5 toxicity; P < or = .001). Of 24 assessable patients who underwent salvage CR, 12 (50%) were rendered disease-free. CONCLUSION Despite greater toxicity, the use of MMC in a definitive CR regimen for anal cancer is justified, particularly in patients with large primary tumors. Salvage CR should be attempted in patients with residual disease following definitive CR before resorting to radical surgery.

PURPOSE This study was a prospective phase I/II trial performed by the Radiation Therapy Oncology Group (RTOG) to test the tolerance and efficacy of preirradiation cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) chemotherapy followed by large-volume, high-dose brain radiation therapy (RT) for patients with primary CNS lymphoma (PCNSL). PATIENTS AND METHODS Fifty-four (52 assessable) human immunodeficiency virus (HIV)-negative patients with PCNSL were entered on study and received two (n = 20) or three (n = 32) cycles of CHOD (six patients with positive CSF cytology received intrathecal methotrexate in addition to CHOD). Whole-brain RT to 41.4 Gy and tumor boost to 18 Gy (total dose, 59.4 Gy) followed chemotherapy. RESULTS As of July 1994, with a minimum potential follow-up time of 20 months, 12 of 52 assessable patients remain alive without evidence of progression. The median survival time for the entire group is 16.1 months, with a 2-year survival rate of 42%. By univariate analysis, patient age was found to be a significant prognostic factor with respect to survival (P = .005) in favor of age less than 60 years. Karnofsky performance status (KPS) was of borderline significance (P = .057). Survival for patients treated on RTOG 88-06 was compared with that of patients treated on RTOG 83-15, which tested RT alone. No difference in overall survival was found (P = .53). Grade 4 neutropenia developed in 29 of 51 patients during chemotherapy. There were two deaths during chemotherapy: one as a result of sepsis and one of a pulmonary embolus. The worst toxicity during RT was < or = grade 2 in 50 of 52 patients. CONCLUSION Preirradiation CHOD chemotherapy does not significantly improve survival over RT alone for patients with PCNSL. Age remains a powerful prognostic factor independent of therapy and must be considered in testing alternative combined approaches.

PURPOSE To report the long-term results of central lymphatic irradiation for stage III nodular malignant lymphoma. PATIENTS AND METHODS Between 1969 and 1985, 34 patients (26 with nodular poorly differentiated lymphoma, four with nodular mixed lymphocytic/histiocytic lymphoma, and four with nodular histiocytic lymphoma) were treated with central lymphatic irradiation. Median age of the group was 51 years (range, 30 to 73). There were 15 men and 19 women. Staging work-up included a physical examination and bone marrow biopsy in all patients. Seventy-four percent had a lymphangiogram (LAG) and 44% a laparotomy (LAP). Eighty-two percent had either a LAP or a LAG. Thirty-two patients were Ann Arbor stage IIIA and two were stage IIIB. All patients received lymphatic irradiation that encompassed cervical, supraclavicular, axillary, mediastinal, paraaortic, mesenteric, pelvic, and femoral lymphatics to total doses ranging from 20 to 30 Gy in 1.0- to 1.8-Gy fractions. Waldeyer's ring was initially treated in 17 patients. Follow-up information is available on all 34 patients. Median follow-up is 9 years, 8 months (range, 15 to 244 months). RESULTS Life-table actuarial overall, disease-free, and cause-specific survival rates at 15 years are 28%, 40%, and 46%, respectively. Only one relapse was observed after 9 years. Disease-free survival was significantly improved in patients with five or fewer sites of involvement (P = .02). Age, sex, B symptoms, histology, and technique of irradiation were not prognostically significant. Salvage therapy, including further irradiation and/or chemotherapy, was delivered to 20 patients. Ten percent of these patients remain alive without evidence of disease. Toxicity data were available for the patients treated at the Medical College of Wisconsin (MCW). Radiation Therapy Oncology Group (RTOG) acute hematologic, gastrointestinal, and salivary toxicity scores were < or = 2 in 83% of patients. Late toxicity scores were < or = 2 in 96%. Persistent xerostomia was noted in 23% of patients who received initial treatment to Waldeyer's ring. CONCLUSION These results suggest that initial comprehensive central lymphatic irradiation may be the preferred approach to achieve a durable relapse-free interval for this group of patients.