TTMV and association with relapse in patients with HPV related SCCHN undergoing CRT.
Authors: Misiukiewicz Krzysztof , Ramos Emily J , Worona Leslie Anne , Sindhu Kunal K. , Bakst Richard Lorne , Roof Scott , Genden Eric Michael , Westra William , Posner Marshall R. 
Published: June 2024

6067 Background: Circulating Tumor tissue-modified viral HPV DNA (TTMV) is a highly specific and predictive plasma test for active HPV SCCHN. The clearance kinetics of TTMV during chemoradiotherapy (CRT) has been associated with disease control and monitoring. TTMV can guide therapy, enable earlier identification of recurrence compared to PET, and guide modification of curative therapy, including CRT. Methods: Patients with local or locally advanced HPV+ SCCHN were treated with adjuvant post-surgical CRT at 66Gy or 56Gy or definitive CRT at 70Gy between 7/1/21-10/17/23. All patients received cisplatin with CRT. All patients had a PET at baseline and 12 weeks after the CRT to assess their response to treatment. All patients had pre and post TTMV done and then as a part of surveillance. PET confirmed residual, recurrent, or metastatic diseases were defined as treatment failures in TTMV + patients only if PET was confirmed. Results: 21 patients were treated with either adjuvant post-surgical CRT at 66Gy (2/21) and 1 at 56Gy, or definitive CRT at 70Gy (18/21). 8/21 were treated with protons, and 13/21 were treated with standard IMRT photons. All patients who had pre- and post-treatment TTMV data were included in our analysis. The median pre-treatment TTMV was 9682 (5 – 166667), and the median follow-up time from treatment start was 15 months (3-40). 19/21 patients had negative TTMV after completion of CRT. 1/21 had elevated TTMV at the CRT completion and developed lung metastases PET+; biopsy confirmed. 2nd patient underwent resection of the right (R) tonsil and bilateral LND followed by adjuvant CRT at 56Gy with protons to R tonsil and R neck. PreCRT/post-op negative TTMV changed to positive and rose at weeks 1 and 3 of CRT. After completing CRT, underwent contralateral additional L LND with post-op continuously negative TTMV and no recurrence on PET. 14/21 patients undergoing CRT had TTMV testing done during CRT, and 7/21 had only pre and post-CRT and not during CRT. 7/14 had elevated TTMV and 7/14 had negative TTMV during CRT. Among 19/21 patients with post-CRT negative TTMV, only 2 recurrences were reported. Both patients developed distant metastases in their lungs and both were TTMV positive confirmed with PET and biopsy. The first patient had negative TTMV (1/7), and 2nd patient with TTMV was not done in the middle of CRT treatment. No recurrences were reported in any 7/21 patients with persistently elevated TTMV in the middle of CRT. 1/21 patients treated was altered based on the TTMV change from negative to positive. Conclusions: Unlike PET, TTMV lacks the capability to localize recurrences and cannot replace PET. Nevertheless, TTMV can identify recurrence or persistence and can synergize with PET to guide therapy, as evidenced in our study, where all 3 post-CRT recurrences were detected using TTMV and confirmed with PET and biopsy. Validation in a larger cohort is necessary to confirm the efficacy of combining TTMV with PET for response assessment.