Outcomes of a Large Single Institutional Series of Radiation Associated Sarcomas

Abstract

Radiation associated sarcoma (RAS) is a rare complication from radiation therapy. We investigated the clinicopathological characteristics, treatment strategies, and oncologic outcomes of these patients. An institutional review board approved institutional database of 12,961 primary bone or soft tissue sarcomas (1960-2016) was queried to find sarcomas arising within prior RT field of distinct prior malignancies at least 1 year after completion. Cases meeting criteria were further analyzed. Two hundred twenty-nine RAS were identified, representing 1.77% of sarcomas seen at our institution. Features of prior malignancies included: breast cancer (23.2%), Hodgkin lymphoma (11.8%), prostate (5.9%), cervical SCC (4.9%), non-Hodgkin lymphoma (4.4%), retinoblastoma (3.9%), colorectal (3.5%), ALL (3.0%), neuroblastoma (4, 2.0%), embryonal rhabdomyosarcoma (2.0%), Ewing sarcoma (1.5%), and medulloblastoma (1%); 2 had Li Fraumeni’s syndrome. Prior malignancies were treated with RT (median 55 Gy, 10-79.2 Gy); 46% had chemotherapy. Median age at prior malignancy was 49.5 years (2 mo-87 years) and for RAS was 60 years (10-93 years). Median interval from prior malignancy to RAS was 11 years (1-50 years). Features of RAS included: female (57.1%), male (42.9%), soft tissue (70.4%), bone (29.65), trunk (63.1%), head/neck (19.2%), extremity (17.7%), abdomen (14.4%), spine/bony pelvis (13.5%), and others; histologies osteosarcoma (27.6%), angiosarcoma (18.2%), fibrosarcoma (9.9%), UPS/MFH (9.9%), leiomyosarcoma (5.9%), MPNST (4.9%), and others (23.6%); median size 7.5 cm (1-25 cm), grades 1 (635), 2 (635), and 3 (48.8%). 77.8% were M0. Treatment of RAS consisted of surgery only (48%), surgery + RT (43.3%), RT only (7.4%), or neither (1.3%); 42.4% had chemotherapy. On Cox multivariate analysis, age (P < 0.001) and size >5 cm (P = 0.001) predicted worse OS whereas surgery predicted better OS (HR = 0.486, P = 0.002). Radiation associated (RA)-MPNST has worse CSS survival (HR = 2.51, P = 0.03), whereas RA-UPS/MFH predicted better CSS (HR = 0.36, P = 0.039) versus RA-osteosarcoma, angiosarcoma, fibrosarcoma, or leiomyosarcoma. Head/neck RAS (HR = 0.37, P = 0.017) and size 5-8 cm (HR = 2.2, P = 0.013) predicted worse LC. Size 5 to 8 cm (HR = 2.6, P = 0.012) also predicted lower DMFS. Of 158 M0 patients (median follow-up 33.4 mo., 1-548.7 mo.), 5 year OS was 41.8%, CSS, 53.8%, LC 53.7%, and DMFS 60.3%. Increasing age (P = 0.018) and RA-MPNST (HR = 3.60, P = 0.015) had worse OS5 versus spontaneous bone and soft tissue sarcomas (HR = 2.67, P < 0.01) and CSS (HR = 3.32, P < 0.01) independent of other factors. RAS have worse outcomes than spontaneous bone and soft tissue sarcomas with variability across histologies, size, age, and sites. Further understanding of clinical and biological differences/similarities across and between RAS vs. spontaneous sarcomas may improve treatment strategies.