Guy Kantor

BACKGROUND: There is no community standard for the treatment of glioblastoma in patients 70 years of age or older. We conducted a randomized trial that compared radiotherapy and supportive care with supportive care alone in such patients. METHODS: Patients 70 years of age or older with a newly diagnosed anaplastic astrocytoma or glioblastoma and a Karnofsky performance score of 70 or higher were randomly assigned to receive supportive care only or supportive care plus radiotherapy (focal radiation in daily fractions of 1.8 Gy given 5 days per week, for a total dose of 50 Gy). The primary end point was overall survival; secondary end points were progression-free survival, tolerance of radiotherapy, health-related quality of life, and cognition. RESULTS: We randomly assigned 85 patients from 10 centers to receive either radiotherapy and supportive care or supportive care alone. The trial was discontinued at the first interim analysis, which showed that with a preset boundary of efficacy, radiotherapy and supportive care were superior to supportive care alone. A final analysis was carried out for the 81 patients with glioblastoma (median age, 73 years; range, 70 to 85). At a median follow-up of 21 weeks, the median survival for the 39 patients who received radiotherapy plus supportive care was 29.1 weeks, as compared with 16.9 weeks for the 42 patients who received supportive care alone. The hazard ratio for death in the radiotherapy group was 0.47 (95% confidence interval, 0.29 to 0.76; P=0.002). There were no severe adverse events related to radiotherapy. The results of quality-of-life and cognitive evaluations over time did not differ significantly between the treatment groups. CONCLUSIONS: Radiotherapy results in a modest improvement in survival, without reducing the quality of life or cognition, in elderly patients with glioblastoma. (ClinicalTrials.gov number, NCT00430911 [ClinicalTrials.gov].).

BACKGROUND: Surgery is the main prognostic factor in retroperitoneal sarcoma. However, despite progress, surgery alone is rarely curative, and analysis of the causes of failures and of other prognostic factors are warranted to ascertain treatment orientations. METHODS: Data of patients treated from 1.80 to 12.94 for primary retroperitoneal sarcoma were extracted from the French Federation of Cancer Centers Sarcoma Group registry. Univariate and multivariate analysis were performed for initial local control and for local and general outcome. One hundred sixty-five patients (median age, 54 years; range, 16--82 years) were identified. Median tumor size was 15 cm (range, 2--70 cm); 31% of tumors presented with neurovascular or bone involvement. Liposarcoma, leiomyosarcoma, and malignant fibrous histiocytoma represented 66% of the tumors. Eighty-four percent of the tumors were of high or intermediate grade. Twenty patients had initial metastases. Multimodality treatment included surgery (150 patients), radiotherapy (92 patients), and chemotherapy (77 patients). Complete excision was achieved in 94 of 145 nonmetastatic patients. Median follow-up was 47 months (range, 3--160 months). RESULTS: Actuarial overall 5-year survival rate (median) was 46% (51 months). The main prognostic factors for survival were initial metastases and surgery, which represented the major treatment-linked factor. High-grade of tumors affected local recurrence, metastatic recurrence, and survival. Adjuvant radiotherapy was significantly associated with reduced local recurrence. Various evolutive patterns were observed with histologic subtypes. CONCLUSIONS: Aggressive surgery remains mandatory in retroperitoneal sarcoma, but a randomized trial is needed to evaluate the place of radiotherapy for local control.

Abstract Purpose: This phase I study aimed to determine the recommended dose (RD), safety profile, and feasibility of a procedure combining intratumoral injection of hafnium oxide nanoparticles (NBTXR3; a radioenhancer) and external beam radiotherapy (EBRT) for preoperative treatment of adults with locally advanced soft tissue sarcoma (STS). Experimental Design: Patients had a preoperative indication of EBRT for STS of the extremity or trunk. Baseline tumor volume (TV) was calculated by MRI. NBTXR3 was injected percutaneously into tumors at 53.3 g/L. Dose escalation was based on four levels equivalent to 2.5%, 5%, 10%, and 20% of baseline TV. NBTXR3 was visualized in the tumor 24 hours postinjection, and EBRT was initiated (50 Gy over 5 weeks). Surgery was performed 6 to 8 weeks after EBRT completion. Results: Twenty-two patients completed NBTXR3 injection, EBRT, and surgery and were followed for a median 22 months (range, 6–40). At NBTXR3 20% of TV, two dose-limiting toxicities occurred: injection-site pain and postoperative scar necrosis. The RD was defined as 10%. No leakage of NBTXR3 into surrounding tissues occurred; intratumor NBTXR3 levels were maintained during radiotherapy. At the RD, median tumor shrinkage was 40% (range 71% shrinkage, 22% increase); median percentage of residual viable tumor cells was 26% (range, 10%–90%). Patients receiving 20% of TV demonstrated pathologic complete responses. Seven grade 3 adverse events occurred, which were reversible. Conclusions: A single intratumoral injection of NBTXR3 at 10% of TV with preoperative EBRT was technically feasible with manageable toxicity; clinical activity was observed. Clin Cancer Res; 23(4); 908–17. ©2016 AACR.