331 - Imaging Metrics and HPV ctDNA Kinetics in a Phase II Immuno-Chemoradiation Trial for Locoregionally Advanced p16+ Oropharynx Cancer

S. N. Regan¹, M. P. Aryal¹, K. Suresh¹, B. S. Rosen¹, H. Walline², M. E. Prince², K. Malloy², K. Casper², A. Shuman², S. B. Chinn², M. E. Heft-Neal², P. L. Swiecicki³, F. Worden³, J. L. Shah¹, Y. Cao¹, C. Brenner², and M. L. Mierzwa¹; ¹Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, ²Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, ³Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI

Purpose/Objective(s): We conducted a single arm prospective phase II trial evaluating the addition of priming, concurrent, and adjuvant nivolumab to definitive chemoradiation (CRT) in locoregionally advanced p16+ oropharynx squamous cell carcinoma (OPSCC). Exploratory endpoints included pre- and mid-treatment quantitative imaging metrics and circulating tumor DNA (ctDNA) kinetics, which we hypothesized would predict disease recurrence. Materials/

Methods: Eligible patients had p16+ OPSCC with =1 high-risk feature: cT4, cN3, matted lymph nodes/radiographic extracapsular extension, and/or retropharyngeal adenopathy. Patients were treated with RT to 70Gy with concurrent weekly carboplatin, paclitaxel, and nivolumab followed by adjuvant nivolumab. Physiologic MRI and FDG-PET were performed pre-treatment and between fractions 8-12. For both primary and nodal gross tumor volumes (GTV), the mean blood volume (BV), sub-volume with low BV (LBV), mean apparent diffusion coefficient (ADC), sub-volume of low ADC (LADC), and metabolic tumor volume (MTV50%) were calculated. Blood was collected pre-treatment and weekly during CRT and was analyzed with the MyHPVScore CLIA-certified ctDNA assay. Cox models were used to test imaging and HPV ctDNA metrics for prediction of LRPFS, DMFS and PFS, with p-values and c-indices to describe their predictive performance.

Results: Twenty-six patients were enrolled; most had cT4 disease (n = 17/26, 65%), with median GTVp = 36cc (0-110) and median GTVtotal = 60cc (35-165). Estimated 2-year progression-free survival (PFS) was 65% (90% CI 53% - 84%) with 4, 3 and 1 patients having local only, distant only, and local+distant failures, respectively. Both pre- and mid-treatment mean BV and mean ADC were lower in the primary versus nodal tumors. Increasing values of primary tumor GTV, LBV, LADC, and MTV50% from pre- and mid-treatment imaging were significantly associated with inferior PFS and DMFS but not LRPFS (Table). Nodal imaging metrics were not predictive of outcome. Neither relative change in HPV ctDNA at weeks 1 or 2 nor week 4 or 7 clearance were significantly associated with PFS.

Conclusion: In a single institution prospective trial of concurrent and adjuvant immuno-chemoradiation in high-risk HPV+ OPSCC, we were able to validate prior findings that pre and mid-treatment primary tumor sub-volumes on MRI and PET correlated with disease control. Albeit with small numbers, pre- or mid-treatment ctDNA kinetics were not predictive of outcome. Imaging metrics may guide future therapy escalation strategies in locally advanced OPSCC.

Abstract 331 – Table 1

Primary Tumor Imaging Metric	PFS HR	PFS Adjusted p-value	PFS c-index
Pre-RT, GTV	1.54	0.03	0.72
Pre-RT, LBV	2.02	0.06	0.74
Pre-RT, LADC	2.20	0.03	0.71
Pre-RT, MTV50%	2.41	0.04	0.69
Mid-RT, Primary GTV	1.60	0.02	0.78
Mid-RT, LBV	24.36	0.02	0.65
Mid-RT, LADC	5.61	0.05	0.66
Mid-RT, MTV50%	2.26	0.05	0.57