Clinical Characteristics, Patterns of Care, and Treatment Outcomes of Radiation-Associated Sarcomas

Abstract

In this study, we describe the clinical presentation, patterns of care, and treatment outcomes for radiation-associated sarcomas (RAS) patients seen at our institution. Patients with RAS treated at The Ohio State University Comprehensive Cancer Center between January 1, 2015 and January 20, 2021 were included. Demographic and clinical variables, as well as outcomes, were abstracted from chart review. Differences in outcomes were assessed based on log-rank test. A total of 38 patients with a diagnosis of RAS were identified (17 males, 21 females). The median age at radiotherapy for index malignancy was 55.3 years (range 0.2-77.5). The median latency following index radiotherapy until the RAS diagnosis was 9.1 years (range 3.7-46.3). The median age at RAS diagnosis was 68.4 years (range 27.9-85.4). The most common index malignancy associated with a subsequent RAS was breast carcinoma (n = 9 [23.7%]). The most common RAS histology was angiosarcoma (n = 10 [26.3%]). Median RAS tumor size was 5.25 cm (range 0.4-30.5). RAS grade was most commonly grade 3 (n = 25 [65.8%]). RAS locations included abdominopelvic (n = 15 [39.5%]); head & neck (n = 10 [26.3%]); and thorax (n = 10 [26.3%]). Genomic profiling identified mutations in TP53 (n = 12 [31.6%]); MYC (n = 6 [15.8%]); and CDK2A/4 (n = 5 [13.2%]). Median tumor mutation burden (TMB) was 2.6 mutations/megabase (range 0.5-6.3). Among the 33 patients with non-metastatic RAS at presentation, 78.8% (n = 26) underwent oncologic resection. Margins were R0 in 69.2% (n = 18), R1 in 19.2% (n = 5), and R2 in 11.5% (n = 3). 54.5% (n = 18) received systemic therapy and 24.2% (n = 8) received radiotherapy as part of curative-intent treatment (median dose 50.4 Gy [range 45-57.5]). For the entire cohort, median PFS was 9.0 months and median OS was 11.1 months. Among patients who presented with non-metastatic RAS, the median LRFS was 9.5 months (range 2.0-34.7); median PFS was 9.0 months (range 2.0-34.7); and median OS was 10.6 months (range 0.6-31.6). Amongst patients with metastatic RAS at presentation, median PFS was 7.4 months (range 1.4-15.8) and median OS was 13.1 months (range 6.0-14.9). Patients who presented with non-metastatic vs metastatic RAS had a significantly longer PFS (p = 0.025) and OS (p = 0.033). Amongst non-metastatic RAS, an R0 resection was associated with significantly improved mean OS (75.3 months [95% CI 54.9-95.8]) in comparison to R1 (15.2 months [95% CI 5.3-25.1]) and R2 margins (19.7 months [95% CI 10.7-28.7]), p = 0.016. Among patients managed with curative intent, there was no significant association between receipt of either systemic therapy or radiotherapy and duration of LC, PFS, or OS. Outcomes for RAS are strikingly poor. Patients with non-metastatic RAS had a significantly longer PFS and OS compared to patients who presented with metastatic RAS. As part of a curative-intent treatment, R0 surgical margins, but not receipt of systemic therapy or radiotherapy, were associated with improved OS in our cohort.