Initial Results of a Phase II Trial of Hypofractionated Radiation Therapy for Inoperable Soft Tissue Sarcoma

For patients with soft tissue sarcoma (STS) who cannot or choose not to have surgery, radiation can provide local tumor control in both palliative and definitive settings. Conventionally fractionated radiation provides modest (< 50%) rates of local control (LC) for STS at 2 years. To our knowledge, no prospective studies to date have evaluated the safety and efficacy of dose-escalated hypofractionated radiation therapy as treatment of inoperable STS. We hypothesized that dose-escalated, hypofractionated radiation therapy (RT) for inoperable STS could achieve higher rates of LC than reported in trials of conventionally fractionated RT.An IRB-approved single institution prospective phase II clinical trial of dose-escalated, hypofractionated RT as local control for STS was designed and completed planned accrual. Exclusion criteria included anti-cancer systemic therapy within the preceding two weeks. Patients underwent hypofractionated RT utilizing either CT-guided radiation (24, 50%) or MRI-guided radiation treatments (24, 50%). Data on patient characteristics, RT dose and fractionation, LC, toxicity, and overall survival (OS) was collected. The primary endpoint was local tumor control (stable, partial, or complete response according to RECIST) at 2-years after completion of radiation. Secondary endpoints were acute and late toxicity, rates of complete response, 5-year local tumor control, and progression-free and overall survival. Acute toxicity was graded on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale during treatment and at 3 months following RT.Forty-eight patients were enrolled, 17 with non-metastatic localized disease and 31 with metastatic disease. Median patient age was 64. Twenty-five men and 23 women were treated. Ninety-six total lesions were treated (36 lung, 7 extremity, 37 abdominopelvic, 16 other). Radiation dose per fraction ranged from 6-12 Gy for a total of 1-12 fractions (median dose was 52.5 Gy in 6 fractions. Median patient follow-up is 8.6 months (range 1 - 36 months). Six patients (13%) did not complete initial 3-month follow-up imaging. Of the 40 patients who have undergone 3-month follow up imaging, 32 (80%) had stable disease, 5 (12.5%) had partial response, 0 had complete response, and 3 (7.5%) had disease progression. Median PFS was 17.2 months at time of last follow up. Median OS was 12.9 months at time of last follow up. Twenty-five patients (52%) experienced an acute toxicity likely or possibly related to radiation. Three (6%) patients experienced CTACE grade 3 or greater treatment-related toxicity (pain, weakness, decreased range of motion, dermatitis).In this initial report of a prospective, single-institution clinical trial of hypofractionated RT for STS not undergoing resection, we report low rates of acute grade 3 or greater toxicity and high rates of tumor response. We will continue to follow these patients to assess late toxicity and durability of tumor control.