Z. S. Rentiya1, J. Garneau1, V. Kaur1, P. W. Read1, N. S. Kalman2, K. L. Fedder1, E. Dowling1, D. C. Shonka1, and C. McLaughlin1; 1University of Virginia, Charlottesville, VA, 2Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL
Purpose/Objective(s): Circulating tumor HPV DNA (ctHPVDNA) is a biomarker with a growing body of evidence for HPV-associated oropharyngeal squamous cell carcinoma (HPV+OPC). Prior studies have demonstrated its usefulness in surveillance and as a prognostic marker at week 4 of radiotherapy (RT), but there is limited data on its use to adapt therapy. At our institution, we discontinue RT for HPV+OPC due to severe acute toxicity after 60 Gy. We also have started to measure ctHPVDNA at week 4 of RT (with or without concurrent chemotherapy) for all definitive cases of HPV+OPC. We hypothesize that in patients who convert to a negative ctHPVDNA by week 4 and stop after 6 weeks due to toxicity, progression free survival (PFS) will be superior to those who do not convert to negative and receive a full 7 weeks of RT. Materials/
Methods: In this single center, retrospective cohort study, we included patients with HPV+OPC who underwent definitive RT or chemoradiotherapy from 2020 to 2023; we started routine ctHPVDNA testing during this period. We compared groups based on known risk factors for disease recurrence. We calculated 1-year PFS and compared patients with a negative mid-treatment ctHPVDNA who stopped treatment early to those with a positive mid-treatment ctHPVDNA who received a full 7 weeks. 1-year PFS was estimated via Kaplan Meier, and log-rank testing was performed to compare survival between the groups. Results: We identified 63 patients with HPV+OPC who underwent definitive RT or chemoradiotherapy in the last 3 years. Of these, 25 patients experienced at least CTCAE grade 3 toxicity and were considered for early cessation of therapy; 19 of these patients underwent ctHPVDNA testing at week 4 of RT. 11 patients had negative mid-treatment tests and stopped at 6 weeks of RT (group A), and 8 patients were persistently positive for ctHPVDNA at week 4, and so they received the full 7 weeks of treatment (group B). There were no patients with greater than 10 pack years of smoking history in either group, and both groups had similar median age and stage. There have been no deaths or recurrences in group A, with median follow up of 19 months. There were 2 recurrences and 1 death in group B; one recurrence was regional and the other was regional and distant. The 1-year PFS rate for patients in group A was 100% versus 74% in group B (p=0.072). Conclusion: ctHPVDNA represents an exciting new assay that provides high sensitivity and specificity for the presence of active disease. As such, it may be useful for guiding treatment decisions at this time point, as we explored in this study. A negative ctHPVDNA result at week 4 of RT, in spite of discontinuing therapy 1 week earlier than planned, was still associated with excellent outcomes. Although this study is limited by its retrospective nature and small sample size, it demonstrates the feasibility of this approach. Future studies may use this test as a biomarker to guide radiotherapy de-escalation for HPV+OPC.
