316 - The Preliminary Analysis of Circulating Human Papillomavirus DNA in a Phase III Trial of Concurrent Chemoradiation (CRT) with Intensity Modulated Proton Therapy (IMPT) vs. IMRT in Oropharyngeal Squamo

L. Wang¹, Y. Zhang¹, N. Ausat¹, M. Hernandez¹, D. I. Rosenthal¹, A. S. Garden¹, R. Ferrarotto¹, G. B. Gunn¹, C. D. Fuller², J. Phan¹, W. H. Morrison¹, A. Lee¹, A. C. Moreno², N. D. Gross¹, M. T. Spiotto¹, and S. J. Frank¹; ¹The University of Texas MD Anderson Cancer Center, Houston, TX, ²Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Purpose/Objective(s): Treatment de-escalation is an effective strategy to mitigate treatment toxicities in human papillomavirus (HPV) related OPSCC. To avoid compromise of tumor control, reliable biomarkers to identify patients with high risk of treatment failure (TF) are critical. We evaluated the clearance of circulating tumor tissue modified viral (TTMV)-HPV DNA and its reverting positive (RP) score in predicting TF in patients with HPV+ OPSCC who received CRT. Materials/

Methods: Patients were enrolled from a single institution in a multicenter Phase III randomized trial comparing IMRT vs IMPT (CRT) in OPSCC. RT dose was 70 Gy, followed by restaging, with or without lymph node dissection (ND). Blood samples were collected in EDTA tubes from 10/23/2013 – 6/5/2023 prior to RT (baseline), during RT (at 2, 4, and 6 weeks), and post RT (at 3, 6, 9, 12, 16, 20, 24, 30 months). Isolated plasma (0.5 ml) was used for analysis of TTMV-HPV DNA (droplet digital PCR assay). Kaplan-Meier was used for the comparisons of TTMV-HPV DNA clearance post IMPT vs IMRT, and TF prediction by RP-TTMV-HPV DNA vs imaging. The association of RP-TTMV-HPV DNA score and TF was analyzed.

Results: A total of 1,352 plasma samples were analyzed (155 patients, median age: 59 [range: 33-84], 92.3% males). Clinical stages (AJCC 7) were: III 6.5%, IVA 92.9%, and IVB 0.7%. TTMV-HPV DNA resolved to undetectable in 11/17 patients (64.7%) post induction chemotherapy (IC). The data of 130 evaluable patients with detectable TTMV-HPV DNA at baseline (IMRT N = 71; IMPT N = 59) were further analyzed. In 20 patients with ND, TTMV-HPV DNA cleared in 3/7 patients (42.9%) post ND. Post CRT and ND, the TTMV-HPV DNA score in 128 patients (98.5%) resolved to undetectable (the mean and median time [months]: IMRT were 2.1 ± 0.4 and 1.0 [range: 0.5 – 24]; IMPT were 1.4 ± 0.2 and 1.0 [range: 0.5 – 6]). In patients with RP-TTMV-HPV DNA score at certain time points, 14/19 of them (73.7%) experienced TF; while 14 /18 patients (77.8%) with TF had a RP-TTMV-HPV DNA score. The presence of a RP-TTMV-HPV DNA score was significantly correlated with TF (p < 0.01) (Table 1). In patients with TF, the mean and median time (months) of appearing RP-TTMV-HPV DNA score (9.6 ± 1.6 and 6.0 [range: 0 – 20]) was shorter than that of the appearing of positive imaging (21.3 ± 5.6 and 12.0 [range: 3 – 96]).

Conclusion: RP-TTMV-HPV DNA score is a potential robust biomarker for TF in OPSCC. The clearance of TTMV-HPV DNA is similar in IMPT vs IMRT. RP-TTMV-HPV DNA score may predict the potential of TF earlier than imaging in OPSCC.

Abstract 316 – Table 1: RP-TTMV-HPV DNA score in predicting Treatment Failure

	Value (%)	95% CI (%)
Sensitivity	77.8	52.4 - 93.6
Specificity	95.5	89.9 - 98.5
+ Predictive Value	73.7	53.4 - 87.2
- Predictive Value	96.4	91.8 - 98.5