Interim Results of a Phase II Trial on Hypofractionated Radiation Therapy for Inoperable Soft Tissue Sarcoma.

Abstract

PURPOSE/OBJECTIVE(S)\nFor patients with localized soft tissue sarcoma (STS) who cannot or choose not to undergo surgery, radiation alone can be used for local tumor control. Conventionally fractionated radiation has been reported to achieve local control in < 50% of STS patients. Recent retrospective studies suggest that hypofractionated radiation therapy (HXRT) may achieve greater local control of STS. However, clinical experience of definitive HXRT in STS remains limited, with no trials to date that examine the role of HXRT for inoperable STS. We hypothesized that HXRT could be used to safely deliver conformal high dose radiation to patients with inoperable STS and that this would afford local tumor control at higher rates than have been reported in historical studies using conventionally fractionated radiation therapy.\n\n\nMATERIALS/METHODS\nWe are conducting an IRB-approved, single institution, prospective phase II clinical trial enrolling patients with STS that was unresectable or who opted against surgery. Patients underwent HXRT in 8 or fewer fractions using either CT- (11, 61%) or MRI-guided radiation treatments (7, 39%). Data on patient characteristics, radiation, local tumor control, acute and late toxicity, and overall survival was collected. Local control was defined as stable disease, partial response, or complete response on standard-of-care follow up imaging. Toxicity was graded on the Common Terminology Criteria for Adverse Events (CTCAEv5.0) during treatment, at 1 month, and at standard-of-care follow-up visits.\n\n\nRESULTS\nEighteen patients were enrolled, 7 with an unresectable primary STS tumor only, 5 with oligometastatic STS, and 6 with widespread metastatic STS. Thirty-eight total lesions were treated - 2 in the neck, 25 in the chest, 1 in the abdomen, 3 in the retroperitoneum, 4 in the pelvis, and 3 in the extremities. Radiation dose ranged from 5-12 Gy per fraction in 3-8 fractions for a total of 18-60 Gy (median dose/fractionation was 50 Gy/5 fractions). Patients were followed for a median of 283 days (range 46 - 532 days). Local tumor control was achieved in all cases for which follow up imaging was obtained (15 patients): 8 patients (53%) had a stable response, 6 (40%) had a partial response, and 1 (7%) had a complete response. Three patients died prior to follow up imaging being obtained. Ten patients (56%) experienced any acute toxicity, with 1 having CTCAE grade 3 toxicity (pain) and 9 having grades 1-2 toxicity, most commonly grade 1-2 arthralgia or myositis (5 patients, 28%).\n\n\nCONCLUSION\nInterim analysis of this prospective clinical trial suggests that HXRT can be safely delivered to STS locations throughout the body and provides local tumor control. All evaluable patients exhibit local tumor control thus far, with only 1 acute toxicity of grade 3 or greater. Additional patient enrollment and follow up is needed to further evaluate these outcomes and to evaluate for potential late toxicities.