Cell-free DNA for treatment monitoring and outcome predictor in head and neck cancer.

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6055 Background: Copy number instability (CNI) signatures of cancers can be readily detected by Next Generation Sequencing of plasma cell-free DNA (cfDNA). HPV detected in oropharyngeal carcinomas is currently the only prognostic biomarker available. We report here CNI scores for disease monitoring of Head and Neck Cancers (HNC) with potential predictive value for personalized therapeutic options. Methods: A total of 132 plasma samples were collected from 54 HNC patients under informed consent and IRB approval. cfDNA was extracted from plasma, ~20M paired-end NGS mappable reads (reference: HG19) per sample were generated and CNI scores were calculated by read counting statistics. After unblinding CNI scores were evaluated as diagnostic parameter for association with disease characteristics and progression. Survival analysis was conducted after dichotomization of baseline CNI scores at a value of 31 corresponding to the 97.5thpercentile of a normal reference group (RG, n = 141). Results: CNI scores above the 97.5th RG percentile were detected in 40 out of 54 (74%) treatment naïve baseline samples. 29 patients with tumors ≤ T3 (62%, n = 42) and 11 out of 12 (92%) with T4 tumors had CNI scores > 31, with significantly higher CNI scores (p = 0.04) seen for T4 tumors. Higher CNI scores were also found in patients with tumor lymph node invasion (n = 37; median: 381, Q25-Q75: 57-1573) compared to negative lymph nodes (pN0, n = 17; 27, 19-64, p= 0.0004). A steep decline of CNI scores was detected after surgical resection, with increasing CNI scores in later disease progression. The pre-operative CNI scores were a stronger predictor of time to recurrence (p = 7*10-5) than the pN status (p = 0.05) (Cox regression). High baseline CNIs ( > 31) strongly correlated with time to recurrence (Kaplan-Meier log-rank p = 0.018) with a median of 20 months and median overall survival of 30 months in the high CNI group, neither reached in the low CNI-score group (60 m follow-up). Conclusions: Chromosomal instability within HNC was quantified from plasma cfDNA as CNI score. The CNI score may serve as better predictor for the time to recurrence interval than pN status. The data suggests that cfDNA analysis as CNI score may serve as real-time marker of treatment efficacy and outcome.