SS 22 - Late-Breaking Abstracts Special Session
LBA6 - Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-associated Oropharyngeal Cancer
Tuesday, October 23
8:15 AM - 8:25 AM
Location: Room 007 C/D
Bhisham Chera, MD
University of North Carolina School of Medicine
University of North Carolina Hospitals: Assistant Professor: Employee
Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-associated Oropharyngeal Cancer
B. S. Chera1, S. Kumar2, C. Shen3, R. J. Amdur4, R. Dagan5, J. Weiss6, J. Grilley-Olson7, A. Zanation6, T. Hackman6, J. Blumberg8, S. Patel6, B. Thorp6, M. Weissler6, N. C. Sheets6, W. M. Mendenhall4, and G. P. Gupta2; 1Lineberger Comprehensive Cancer Center, University of North Carolina Hospitals, Chapel Hill, NC, 2The University of North Carolina, Chapel Hill, NC, 3Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, 4Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, 5Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, FL, 6University of North Carolina Hospitals, Chapel Hill, NC, 7Department of Medicine, Division of Hematology Oncology, University of North Carolina School of Medicine, Chapel HIll, NC, 8Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, NC
To assess the performance of plasma circulating tumor HPV DNA (ctHPVDNA) as a surveillance blood test in patients with p16 positive oropharyngeal squamous cell carcinoma (OPSCC).
A prospective biomarker trial was conducted in 89 patients with p16 positive OPSCC who had no evidence of distant metastatic disease at baseline. All patients received definitive chemoradiotherapy (CRT) with 78 receiving de-intensified CRT on clinical trial (60Gy). Remaining patients received standard CRT (70Gy). All patients had a 3 month post-CRT PET/CT and were thereafter surveilled with clinical examinations every 2 - 4 months for years 1 - 2, then every 6 months for years 3 - 5. Chest x-rays or chest CT’s were performed every 6 months. Blood specimens were collected at baseline (58/89), weekly during treatment (30/89), and with each follow-up visit (89) for plasma circulating nucleic acid extraction (Qiagen). Multianalyte droplet digital PCR assays were developed for ultra-sensitive detection of ctHPVDNA -16, -18, -31, -33, and -35 DNA on the Bio-Rad QX200 platform. Additional imaging was obtained if ctHPVDNA became detectable in the blood. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of ctHPVDNA testing at detecting recurrence were calculated. Events were defined as recurrence after the 3 month post-CRT PET/CT.
Clinical characteristics were the following: 89% T0-2, 80% N2, 80% never/≤ 10 pack years. Mean f/u was 19.8 months (range 3.7 – 44.7). Baseline ctHPVDNA was detectable in 51/58 (88%), with a median value of 582 copies/mL (range 8 - 22,579). 53/58 evaluable patients had undetectable ctHPVDNA within 3 months of completing CRT. 73/89 patients in the surveillance cohort had undetectable ctHPVDNA at all timepoints beyond 3 months post-CRT. 16/89 patients developed a positive ctHPVDNA test result with a median interval from CRT of 16.7 months (range 7.8 – 30.4) and a median value of 75 copies/mL (range 9 – 28,369). 8/16 patients who developed a positive ctHPVDNA test result during surveillance were diagnosed with recurrence (0 local, 1 regional, 7 distant). 8 patients currently have detectable ctHPVDNA (range 23 – 28,369 copies/ml) but have no evidence of recurrence and are being monitored with repeat ctHPVDNA and imaging. 0/73 patients with undetectable ctHPVDNA at all follow-up visits have developed recurrence. Sensitivity, specificity, NPV, and PPV of ctHPVDNA testing was: 100%, 90%, 100%, 50%.
Performance of an optimized multianalyte ctHPVDNA blood test for the detection of cancer recurrence was exceptional (NPV = 100%). Future studies should be done to evaluate whether ctHPVDNA testing may improve early detection of cancer recurrence while also reducing costs by targeting radiographic surveillance to the subset of patients who are at greatest risk of relapse.
Author Disclosure: B.S. Chera: Consultant; RO-HAC. S. Kumar: None. C. Shen: None. R.J. Amdur: Partnership; RadOnc eLearning Center, Inc. Head and Neck Oral Exam Director; ABR. RRC Member; ACGME. Editorial Board; AJCO, JCO, PRO. R. Dagan: Research Grant; Eleckta. Travel Expenses; Eleckta. J. Grilley-Olson: None. A. Zanation: None. T. Hackman: None. W.M. Mendenhall: Employee; University of Florida. Advisory Board; Sensus Healthcare.