Purpose: To study the response of irradiated and out-of-field normal tissues during localized curative intent radiotherapy (RT). Experimental Design: Sixteen patients with non-small cell lung carcinoma (NSCLC) received 60 Gy in 30 fractions of definitive thoracic RT with or without concurrent chemotherapy (chemoRT). Peripheral blood lymphocytes (PBL) and eyebrow hairs were sampled prior, during, and after RT. Clinical variables of RT plan dose/volume, patient age and use of chemoRT were tested for association with γ-H2AX foci, a biomarker of DNA damage, that underlies cellular response to irradiation. Results: RT induced an elevation of γ-H2AX foci in PBL, representing normal tissues in the irradiated volume, 1 hour after fraction one. The changes correlated directly with mean lung dose and inversely with age. γ-H2AX foci numbers returned to near baseline values in 24 hours, and were not significantly different from controls at 4 weeks during RT or 12 weeks after treatment completion. In contrast, unirradiated hair follicles, a surrogate model for out-of-field normal tissues, exhibited delayed "abscopal" DNA damage response. γ-H2AX foci significantly increased at 24 hours post-fraction one, and remained elevated during treatment, in a dose-independent manner. This observed abscopal effect was associated with changes in plasma levels of MDC/CCL22 and MIP-1α/CCL3 cytokines. No concordant changes in size and concentration of circulating plasma exosomes were observed. Conclusions: Both localized thoracic RT and chemoRT induce pronounced systemic DNA damage in normal tissues. Individual assessment of biological response to dose delivered during RT may allow for therapeutic personalization for patients with NSCLC.
- Received January 23, 2016.
- Revision received April 15, 2016.
- Accepted May 11, 2016.
- Copyright ©2016, American Association for Cancer Research.