Postoperative Human Papilloma Virus Circulating Tumor DNA Guided Adjuvant Therapy for Human Papilloma Virus-Related Oropharyngeal Carcinoma (PATH Study).
Academic Article
Overview
abstract
PURPOSE: Human papillomavirus (HPV) circulating tumor DNA (ctDNA) is a biomarker which detects minimal residual disease for HPV-associated oropharyngeal carcinoma (OPC) (HPV+ OPC). We conducted the first prospective study using HPV ctDNA as an integral biomarker to select patients for postoperative radiation therapy omission. We tested the hypothesis that undetectable postoperative HPV ctDNA can be used to omit or delay adjuvant radiation until patients develop detectable HPV ctDNA using the NavDx (Naveris, Inc) tumor tissue-modified viral (TTMV) HPV DNA score. Eligible HPV+ OPC patients had a preoperative TTMV-HPV DNA score of ³50 and at least 1 pathologic risk factor to warrant standard adjuvant radiation therapy. METHODS AND MATERIALS: Postoperatively, eligible patients had no evidence of disease on postoperative magnetic resonance imaging and 2 negative TTMV-HPV DNA test results. Patients with non-HPV-16 genotype, positive margins, and extranodal extension were excluded. Patients were monitored with TTMV-HPV DNA testing, imaging, and physical exams. Delayed adjuvant radiation was initiated if patients developed detectable TTMV-HPV DNA without radiographic recurrence. The primary endpoint was the proportion of patients without gross recurrent disease. RESULTS: Fifty-five HPV+ OPC patients were screened; 12 patients were enrolled. The median follow-up was 26.6 months (range, 18.3-40.3). One patient (8%) developed detectable HPV ctDNA 6 months after surgery without evidence of recurrence and was treated with delayed adjuvant radiation therapy. Three additional patients (25%) developed radiographic recurrence 6 months after surgery. Radiographic recurrence was not preceded by detectable TTMV-HPV DNA. TTMV-HPV DNA detection was synchronous with radiographically evident disease in 2 of 3 patients. Recurrence was associated with N2b disease pretreatment (P = .01). The high gross recurrence rate (3 of 12 patients) led to closure of this cohort due to a prespecified stopping rule. CONCLUSIONS: Deferring adjuvant radiation therapy based on HPV ctDNA using NavDx TTMV-HPV DNA testing resulted in a high rate of disease recurrence.
