Sunitinib with concomitant radiation therapy in inoperable sarcomas: Final results from the dose escalation and expansion parts of a multicenter phase I study.

INTRODUCTION: Local control in sarcoma is rarely achieved with exclusive radiotherapy (RT). We aim to assess the feasibility and safety of sunitinib continuously administrated with concomitant RT in inoperable non-GIST sarcomas patients. METHODS: This multicentric French 3 + 3 dose escalation study included patients with inoperable locally advanced or recurrent sarcoma, ECOG-PS <2, ≤2 metastatic sites and no brain metastases, adequate organ functions and absence of uncontrolled hypertension, who had never received sunitinib or radiotherapy. The escalation phase planned to use sunitinib dose levels (DL1: 25; DL2: 37.5; DL3: 50 mg/day) with standard RT (60 Gy, 30 fractions, 5 fractions/week/6 weeks). The primary endpoint was to determine the incidence of dose-limiting toxicities (DLT) in the first 14 weeks and the maximal tolerated dose (MTD). Secondary endpoints included safety (acute and late toxicities), local control at 6 months including local progression free rate (L-PFR) progression free survival (PFS), overall survival (OS), proportion of patients eligible for surgery after treatment. RESULTS: From May 2011 to April 2016, the dose-escalation phase enrolled 10 patients (DL1 N = 4; DL2 N = 6). No DLT was observed in at DL1. One DLT (grade 4 thrombopenia) occurred at DL2. The 19 patients treated at DL2 (including the 13 patients from the expansion phase) received sunitinib for a median duration of 42.7 (2.8-79.1) days, and radiotherapy for 6.4 (1-8) weeks; all but 3 patients received 60 Gy (40 Gy, early progression (N = 1); 8 Gy, early death (N = 1), prescribed dose, 50 Gy (N = 1)). With a median follow-up of 19.5 (14-36.5) months, the median PFS was 6.5 (1.9-31.1) months. Median OS was not reached. At 6 months, L-PFR was 73.3% (95%CI 44.9%-92.2%). One patient was amendable to surgery after treatment. Sunitinib-related grade ≥ 3 adverse events occurred in 58% of the patients treated at DL2 (Escalation N = 4; Expansion N = 7). Seven (36.8%) deaths related to disease progression were reported. CONCLUSION: This is the first trial assessing the combination of continuous administration of sunitinib 37.5 mg with exclusive RT in non-GIST sarcoma. Whereas this combination was found feasible, efficient, further investigations of combinations of more recent multikinase inhibitors with RT need to be explored.

American Brachytherapy Society (ABS) consensus statement for soft-tissue sarcoma brachytherapy.

PURPOSE: Growing data supports the role of radiation therapy in the treatment of soft tissue sarcoma (STS). Brachytherapy has been used for decades in the management of STS and can be utilized as monotherapy or as a boost to external beam radiation. We present updated guidelines from the American Brachytherapy Society regarding the utilization of brachytherapy in the management of STS. METHODS AND MATERIALS: Members of the American Brachytherapy Society with expertise in STS and STS brachytherapy created an updated clinical practice guideline including step-by-step details for performing STS brachytherapy based on a literature review and clinical experience. RESULTS: Brachytherapy monotherapy should be considered for lower-recurrence risk patients or after a local recurrence following previous external beam radiation; a brachytherapy boost can be considered in higher-risk patents meeting implant criteria. Multiple dose/fractionation regimens are available, with determination based on tumor location and treatment intent. Techniques to limit wound complications are based on the type of wound closure; wound complication can be mitigated with a delay in the start of brachytherapy with immediate wound closure or by utilizing a staged reconstruction technique, which allows an earlier treatment start with a delayed wound closure. CONCLUSIONS: These updated guidelines provide clinicians with data on indications for STS brachytherapy as well as guidelines on how to perform and deliver high quality STS brachytherapy safely with minimal toxicity.