Clinico-demographic characteristics and outcomes of radiation-induced sarcomas (RIS): a CanSaRCC study

Mauricio Fernando Ribeiro; Hagit Peretz Soroka; Zainab Bhura; Ian Hirsch; Jay Wunder; Peter Ferguson; Kim Tsoi; Savtaj Brar; Rebecca Gladdy; Carol Swallow; Peter Chung; Charles Catton; Philip Wong; Geoffrey Watson; Albiruni Ryan Abdul Razak; Abha A Gupta; David Shultz

doi:10.1177/17588359231198943

Clinico-demographic characteristics and outcomes of radiation-induced sarcomas (RIS): a CanSaRCC study

Ther Adv Med Oncol. 2023 Sep 28:15:17588359231198943. doi: 10.1177/17588359231198943. eCollection 2023.

Authors

Mauricio Fernando Ribeiro¹, Hagit Peretz Soroka¹, Zainab Bhura¹, Ian Hirsch¹, Jay Wunder^{2

3}, Peter Ferguson^{2

3}, Kim Tsoi^{2

3}, Savtaj Brar², Rebecca Gladdy^{2

3}, Carol Swallow^{2

3}, Peter Chung⁴, Charles Catton⁴, Philip Wong⁴, Geoffrey Watson⁵, Albiruni Ryan Abdul Razak^{1

5}, Abha A Gupta¹, David Shultz⁶

Affiliations

¹ Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, ON, Canada.
² Department of Surgery, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
³ Department of Surgical Oncology, Princess Margaret Cancer Centre, University of Toronto, ON, Canada.
⁴ Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, ON, Canada.
⁵ Division of Medical Oncology, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
⁶ Department of Radiation Oncology, Princess Margaret Cancer Centre - University of Toronto, 610 University Avenue, Toronto, ON M5G 2M9, Canada.

Abstract

Background: Radiation-induced sarcomas (RIS) tend to have aggressive behaviour and because of their rarity, the most appropriate management for these malignancies is uncertain.

Objectives: Using the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) database, a national sarcoma registry, we aimed to investigate prognostic factors and outcomes for RIS.

Design: Retrospective study of RIS patients treated from 1996 to 2021 at three Canadian centres.

Methods: RIS was defined as a sarcoma arising in a previously irradiated field following a 3+ year latency period, whose histology was distinct from the initially irradiated tumour. Clinicopathologic and treatment-related information was extracted from the CanSaRCC database. Overall survival (OS) was defined as the time from RIS diagnosis to death from any cause. Response rate (RR) to neoadjuvant chemotherapy (NACT) was based on physician assessment. Time-to-event analyses were estimated using the Kaplan-Meier method, with Cox regression for multivariate analysis. We considered a two-tailed p-value of <0.05 as statistically significant.

Results: One hundred seven tumours met the criteria for RIS and were divided into three subgroups: breast angiosarcoma (BAS, n = 54), osteosarcoma (OST, n = 16), and other soft-tissue sarcomas (STS, n = 37). Patients were mostly female (n = 85, 79%), treated initially for breast carcinomas (n = 54, 50.5%), and diagnosed with high-grade tumours (n = 61/71, 86%). None had evidence of synchronous metastasis. Patients with OST were younger (median age: 48 years, p < 0.001), and BAS had the shortest latency interval (8 versus 18 years for OST/STS, p < 0.001). Most patients underwent surgery, 76% (n = 76/100) R0; 24% (n = 26) received radiation therapy, mostly (n = 15, 57.7%) neoadjuvant. Among those receiving chemotherapy, 30 (75%) underwent NACT; among patients with documented response assessment, the RR was 68% (n = 17/25), being even higher in the BAS population (89.5%, n = 13/17). Median OS was 53 months (95% CI 34-101), with a 5-year OS of 47.6%; larger tumour size, high histologic grade and older age were independent prognostic factors for worse OS.

Conclusion: Surgery is standard, and NACT might be useful to downsize large lesions, especially in BAS patients. Raising RIS awareness is fundamental to promoting appropriate management and fostering research through multi-institutional collaborations.

Keywords: angiosarcoma; breast sarcoma; radiation-induced cancers; radiation-induced sarcoma; radiotherapy; soft-tissue sarcoma.