Lymphocyte Apoptosis As A Predictive Biomarker For Radiotherapy De-Intensification In Ebv-Associated Nasopharynx Cancer.

e17545 Background: Emerging evidence in viral-associated head and neck cancers supports the concept of dose de-intensification in these radiosensitive tumors, but different strategies exist in selecting patients for treatment de-intensification. We hypothesize that patients who develop severe late toxicities (LT) to radiation (RT) have better tumor control, due to a common radiosensitivity index. Here, we investigate the utility of a normal tissue radiosensitivity assay (RT-induced lymphocyte apoptosis, RILA) in predicting clinical outcomes (tumor control and normal tissue toxicity) of patients with EBV-associated nasopharynx cancer (NPC). Methods: RILA assay was assessed in a cohort of locally advanced NPC patients from a randomized controlled phase III trial (N = 172, NCC0901) of cisplatin-RT with or without induction gemcitabine, carboplatin and paclitaxel. LT was assessed by CTCAE v.2 at the following intervals (2 mo yr 1, 4 mo yr 2, 6 mo yr 3-5, annually thereafter). We performed the RILA assay (48 h post 8 Gy) in a subset of cases (N = 87). Results: At a median follow-up of 5.7y, DFS (3y 74.9% GCP vs 67.4% Control, p = 0.362) and incidence of severe Grade ≥3 LT did not differ between the treatment arms. In keeping with our hypothesis, onset of severe LT was associated with reduced risk of disease relapse; OR 0.19 (95% CI = 0.02 – 1.59, p = 0.168). High %RILA, stratified by top quartile, was associated with severe LT (OR 1.92 [95% CI = 0.67-5.5], p = 0.26); and lower rate of recurrence (4.5% (1/22), high %RILA vs19.7% (12/61), low %RILA, p = 0.086). Interestingly, subset analyses revealed that CD8+, but not CD4+ subpopulation of immune cells, was strongly associated with recurrence; OR 8.58 for low %CD8-RILA (p = 0.001). Conclusions: Herein, we showed that %RILA may be a useful biomarker for tumor and normal tissue radiosensitivity of EBV-associated NPC. If validated, this predictive assay will enable precision matching of RT-sensitive patients for de-intensification in EBV- and other viral-associated head and neck cancers. The association between tumor control and CD8-subset of immune cells suggests an immune dependency for RT.