Hypofractionated Radiation Therapy for Unresectable or Metastatic Sarcoma Lesions Provides Durable Tumor Control and Effective Palliation

Abstract

Given the relative radioresistance of sarcomas and their often large size, conventional palliative radiation therapy (RT) provides limited tumor control and poor symptom relief. In select patients that warranted dose-escalated treatment, we have used hypofractionated (HF) RT as a strategy to affect durable control of targeted lesions. We evaluated this treatment approach in a sarcoma cohort.We retrospectively reviewed 73 consecutive patients with sarcoma who received > 10 fractions of HFRT from 2017-2020. Clinical scenarios included: 1) palliative intent (34%), 2) an unresectable primary (27%), 3) or oligometastatic (16%) or 4) oligoprogressive (23%) disease.The median follow-up was 9 months (m) (interquartile range [IQR] 5-13). The HFRT target was a primary tumor in 64% of patients. Most tumors were of soft tissue origin (73%) and the median target size was 7cm (IQR 4-12). Prior to HFRT, most tumors were radiographically progressing (77%). The median HFRT dose to the GTV was 45 Gy (IQR 42-45) over a median of 15 once daily fractions with 59% of patients receiving ≥45 Gy. For 27% of cases, heterogeneity of dose was planned to increase the central tumor to a median of 52.5 Gy (IQR 48-52.5). The 1-year DSS was 59%, which was more favorable for patients receiving HFRT for oligometastatic (1-y 100%) or oligoprogressive (1-y 73%) disease (P = 0.001). The 1-y targeted lesional control (TLC) was 73% with 26% developing progression at a median time of 7.5 m (IQR, 5.5-13). A metastatic target (1-y 95% vs 60% primary, P = 0.02; HR 0.27, P = 0.04) and soft tissue origin (1-y 78% vs 61% bone, P = 0.01; HR 0.33, P = 0.02) were associated with better TLC on univariate and multivariable analyses. The rate of distant failure was high with a 6-month DMFS of only 43%. HFRT use for unresectable (P < 0.001, HR 0.14) and oligometastatic (P = 0.003, HR 0.25) disease were the only factors associated with improved DMFS on multivariable analysis. For patients not planned for adjuvant systemic therapy (n = 53), the median systemic therapy break was 9 m (IQR, 4-23), and notably longer in oligometastatic (13 m), oligoprogressive (12 m) or unresectable (13 m) disease. HFRT provided palliative relief in 95% of cases with symptoms. It was well tolerated; 49% of patients developed acute G1/2 RT toxicities (no acute grade 3-5), most commonly a pain flare (36%). No late grade 2-5 toxicities were observed.HFRT is an effective treatment strategy for patients with unresectable or metastatic sarcoma to provide durable TLC, symptom relief, and meaningful systemic therapy breaks with limited toxicity. Patients with unresectable or oligo-metastatic/progressive disease benefited from longer systemic therapy breaks and lower rates of distant relapse. If overall disease control is the primary goal for HFRT, patient selection remains crucial as distant relapse is high.