Head and Neck Cancer

SS 31 - H&N 3 - Strategies to Improve Outcomes and Minimize Toxicity in Oropharyngeal Cancer

229 - HPV-16 ctDNA kinetics predict for pathologic persistent disease in oropharyngeal cancer patients treated with deintensified chemoradiation

Tuesday, October 23
5:45 PM - 5:55 PM
Location: Room 214 A/B

HPV-16 ctDNA kinetics predict for pathologic persistent disease in oropharyngeal cancer patients treated with deintensified chemoradiation
B. Beaty1, S. Kumar2, R. J. Amdur3, J. Weiss4, J. Grilley-Olson4, A. Zanation4, T. Hackman4, B. Thorp4, J. Blumberg4, S. Patel4, N. C. Sheets4, M. Weissler4, W. M. Mendenhall3, R. Dagan5, G. P. Gupta2, and B. Chera6; 1University of North Carolina, Chapel Hill, NC, 2The University of North Carolina, Chapel Hill, NC, 3Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, 4University of North Carolina Hospitals, Chapel Hill, NC, 5Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, FL, 6U North Carolina, Chapel Hill, NC

Purpose/Objective(s): Post-treatment PET/CT scans are standardly used to assess treatment response and guide planned neck dissection after chemoradiation (CRT) for oropharyngeal squamous cell carcinoma (OPSCC). Many patients have radiographic partial responses (rPR; i.e. equivocal scans). We collected HPV-16 circulating tumor DNA (ctDNA) to determine if it could aid in deciding to proceed with surveillance or neck dissection in patients with rPR on PET/CT.

Materials/Methods: Plasma HPV-16 ctDNA was analyzed for 45 patients, over 90% of whom were enrolled on two phase II clinical trials of deintensified CRT for OPSCC (NCT02281955 / NCT03077243). The following inclusion criteria were used on the trials: T0-3, N0-2c, M0 p16/HPV-positive OPSCC. Patients with T3 or N2 disease received 60 Gy intensity-modulated radiation with concurrent cisplatin (30mg/m2). Treatment response was assessed by PET/CT and clinical exam 12 weeks after CRT. Neck dissections were performed if there was concern for persistent disease. We used digital droplet PCR to quantify plasma HPV-16 ctDNA copy number at baseline, weekly during treatment and at follow-up visits. Descriptive statistics were used.

Results: Twenty-six of 45 patients had HPV-16 ctDNA assessed at the time of post-treatment PET/CT. HPV-16 ctDNA was undetectable in all but one patient. Eighteen of 26 patients had a radiographic complete response (rCR) and 8/26 had rPR. Four patients with rPR and undetectable HPV-16 ctDNA underwent repeat PET/CT that demonstrated rCR and did not undergo a planned neck dissection. Four patients with rPR had a planned neck dissection: 1) two had pathologically positive neck specimens and undetectable HPV-16 ctDNA at time of PET/CT; 2) two had negative neck specimens - one had undetectable HPV-16 ctDNA and the other had low ctDNA (47 copies/ml) at time of PET/CT. We then analyzed whether HPV-16 ctDNA kinetics during treatment correlated with a positive neck specimen (Table 1; n=45). Patients with undetectable HPV-16 ctDNA at all timepoints or low HPV-16 were more likely to have positive neck specimens than those with rapid (by day 28) or delayed (after day 28) ctDNA clearance.

Conclusion: HPV-16 ctDNA levels at the time of 12-week PET/CT may not correlate with radiographic or pathologic response in the neck. Patients with undetectable ctDNA at all timepoints or low HPV-16 had higher occurrences of positive neck dissection specimens. A lower threshold for planned neck dissection may be advisable in patients with undetectable or low HPV-16 ctDNA and rPR on 12-week PET/CT.
Type of HPV-16 ctDNA kinetics Patients with planned neck dissection/total (%) Patients with positive neck dissection/total (%)
Undetectable ctDNA at all timepoints 2/7 (29%) 2/2 (100%)
Low ctDNA (< 200 copies/mL at peak) 1/10 (10%) 1/1 (100%)
Delayed kinetics 5/20 (25%) 2/5 (40%)
Rapid kinetics 1/8 (13%) 0/1 (0%)
Total 9/45 (20%) 5/9 (56%)

Author Disclosure: B. Beaty: None. R.J. Amdur: Partnership; RadOnc eLearning Center, Inc. Head and Neck Oral Exam Director; ABR. RRC Member; ACGME. Editorial Board; PRO, JCO, AJCO. J. Grilley-Olson: None. A. Zanation: None. T. Hackman: None. N.C. Sheets: Employee; UNC Healthcare. W.M. Mendenhall: Employee; University of Florida. R. Dagan: Research Grant; Eleckta. Travel Expenses; Eleckta.

Brian Beaty, MD, PhD

Disclosure:
Employment
University of North Carolina: Employee: Employee

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