Sep 28

SS 09 - Head and Neck 1: Highest-Rated Abstracts for Virally-Mediated Head and Neck Cancer

153 - HPV ctDNA Kinetics during Radiation and in Surveillance in a Phase II De-Escalation Trial for Early-Stage p16+ Oropharynx Cancer

04:55pm - 05:05pm PT

Room 305/306/309

Presenter(s)

Luke Higgins, MD - University of Michigan, Ann Arbor, MI

L. Higgins¹, A. Dinesh², K. Suresh¹, B. S. Rosen¹, R. Akhdar³, C. Bhambhani⁴, M. Tewari⁵, Y. Cao⁶, M. P. Aryal¹, P. L. Swiecicki⁷, C. Brummel², H. Walline³, J. L. Shah¹, F. Worden⁷, M. L. Mierzwa⁸, and C. Brenner²; ¹Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, ²University of Michigan, Ann Arbor, MI, ³Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, ⁴Department of Hematology and Oncology, University of Michigan Cancer Center, Ann Arbor, MI, ⁵Department of Internal Medicine, Hematology/Oncology Division, Univeristy of Michigan, Ann Arbor, MI, ⁶Departments of Radiology and Biomedical Engineering, University of Michigan, Ann Arbor, MI, ⁷Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, ⁸Rogel Cancer Center, University of Michigan, Ann Arbor, MI

Purpose/Objective(s): A prospective Phase II multicenter trial was conducted to evaluate chemoradiation (CRT) de-escalation by mid-treatment FDG-PET response in early-stage p16+ oropharyngeal squamous cell carcinoma (OPSCC). Circulating tumor DNA (ctDNA) kinetics during CRT and in surveillance were evaluated as an exploratory endpoint and were hypothesized to predict disease recurrence.

Materials/Methods: Patients with Stage I/II p16+ OPSCC treated with radiation and concurrent weekly carboplatin/paclitaxel underwent FDG-PET directed RT dose de-escalation to 70Gy in 35 fractions or 54 Gy in 27 fractions. Blood samples were collected pre-treatment, weekly during CRT, and every 3 months during post-treatment surveillance. CLIA-certified MyHPVscore assay was completed to quantify plasma ctDNA. Cox proportional hazards models were used to examine the association between weekly HPV ctDNA metrics and progression-free survival (PFS), locoregional PFS (LRPFS), locoregional control (LRC) and distant metastasis-free survival (DMFS).

Results: Fifty-five patients with evaluable mid-treatment samples and positive pre-treatment ctDNA were included in analysis of ctDNA kinetics during CRT. Median follow up was 18.8 months. During CRT, week 1 percentage increase in ctDNA relative to baseline was associated with worse PFS (HR=1.037 per 10 percent increase in ctDNA, 95% CI: 1.0017-1.073; p=0.040), LRC (HR=1.048, 95% CI: 1.0008-1.010; p=0.046), and LRPFS (HR=1.043, 95% CI: 1.0065-1.078; p=0.021). Neither percentage change at weeks 2, 4, or last week of treatment nor week 4 clearance of ctDNA were associated with outcomes.

During surveillance, 254 evaluable samples were tested, of which 240 had a negative MyHPVscore. MyHPVscore had a negative predictive value (NPV) of 99.2% for any clinical recurrence. Further, 5 of 5 patients with recurrence and available serum sample within 6 months prior to recurrence had a positive HPV ctDNA test prior to failure. Mean biochemical lead time was 102.2 days (range: 28-161 days). The initial positive biochemical recurrence was detected with an average test value of 23% of the baseline/pretreatment test value (range: 1-46%), while the subsequent positive MyHPVscore test was on average 199% of the baseline/pretreatment value (range: 5-395%), showing the rapid increase in ctDNA values prior to detection of recurrence by imaging. Two low-value positive single tests at 6 months post-treatment occurred in patients without clinical recurrence to date and without subsequent detectable measurements (12 and 18 months after CRT).

Conclusion: In our cohort, early ctDNA increase relative to baseline in the first week of treatment was predictive of oncologic outcome(s), albeit with small effect. Early ctDNA kinetics during CRT, which is optimal timing for clinical decision making, may be of utility to guide future (de)escalation strategies in early-stage HPV-associated OPSCC. In surveillance, MyHPVScore had high NPV for clinical exclusion of recurrence.