RILA blood biomarker as a predictor of radiation-induced sarcoma in a matched cohort study

Purpose: Radiation-induced sarcoma (RIS) is a rare but serious event. Its occurrence has been discussed during the implementation of new radiation techniques and justified appropriate radioprotection requirements. New approaches targeting intrinsic radio-sensitivity have been described, such as radiation-induced CD8 T-lymphocyte apoptosis (RILA) able to predict late radio-induced toxicities. We studied the role of RILA as a predisposing factor for RIS as a late adverse event following radiation therapy (RT). Patients and methods: In this prospective biological study, a total of 120 patients diagnosed with RIS were matched with 240 control patients with cancer other than sarcoma, for age, sex, primary tumor location and delay after radiation. RILA was prospectively assessed from blood samples using flow cytometry. Results: Three hundred and forty-seven patients were analyzed (118 RIS patients and 229 matched control patients). A majority (74%) were initially treated by RT for breast cancer. The mean RT dose was comparable with a similar mean (+/- standard deviation) for RIS (53.7 +/- 16.0 Gy) and control patients (57.1 +/- 15.1 Gy) (p=.053). Median RILA values were significantly lower in RIS than in control patients with respectively 18.5% [5.5-55.7] and 22.3% [3.8-52.2] (p =.0008). Thus, patients with a RILA N21.3% are less likely to develop RIS (p < .0001, OR: 0.358, 95% CI [0.221-0.599]. Conclusion: RILA is a promising indicator to predict an individual risk of developing RIS. Our results should be followed up and comparedwithmolecular and genomic testing in order to better identify patients at risk. A dedicated strategy could be developed to define and inform high-risk patients who require a specific approach for primary tumor treatment and long term follow-up. (c) 2019 The Authors. Published by Elsevier B. V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).