312 - Phase II Study of Radiation Volume and Dose De-Intensification Following Tors and Neck Dissection for p16+ Oropharyngeal Squamous Cell Carcinoma - Long-Term Results of Expanded Cohort

J. N. Lukens¹, E. MacDuffie², T. Siegal¹, K. Poirier³, G. Weinstein¹, J. G. Newman⁴, A. Chalian⁵, R. Brody⁶, K. Rajasekaran⁵, S. B. Cannady⁵, D. Basu⁶, C. Rassekh⁵, K. Montone¹, L. Sun⁷, A. Singh⁸, R. Cohen⁷, R. J. L. Maxwell², M. S. Gentile⁹, and A. Lin⁶; ¹University of Pennsylvania, Philadelphia, PA, ²Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, ³Hospital of University of Pennsylvania, Philadelphia, PA, ⁴Department of Otolaryngology - Head & Neck Surgery, Medical University of South Carolina, Charleston, SC, ⁵Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, ⁶U. Pennsylvania, Philadelphia, PA, ⁷Department of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, ⁸Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, ⁹Massachusetts General Hospital; University of Pennsylvania, Department of Radiation Oncology, Boston, MA

Purpose/Objective(s): We conducted a prospective Phase II single institution study that combined radiation volume and dose de-intensification in patients with pT0-T3 pN0-N2c p16+ oropharyngeal squamous cell carcinoma (OPSCC) with the goal of maintaining high rates of locoregional control (LRC) while reducing treatment-related toxicity. We provide long-term follow up on the full expansion cohort (n=150). Materials/Methods: Eligible patients had pT0-T3 N0-N2c p16+ OPSCC (per AJCC 7^th Ed), s/p TORS and neck dissection, with < 5 positive lymph nodes, who met indications for adjuvant radiation (RT) +/- chemotherapy. Adjuvant RT was delivered in 25 fractions over 5 weeks. The primary site was spared in patients with pT1-T2 tumors resected with negative margins and no LVI or PNI. The neck level(s) with confirmed pathologic disease received 50 Gy, while other at-risk ipsilateral nodal regions received 45 Gy. When contralateral neck RT was indicated, the treated volume of the contralateral neck was reduced to mirror the pathologically involved nodal levels in the ipsilateral neck and received 45 Gy. Concurrent chemotherapy was prescribed per NCCN guidelines, but was optionally omitted in patients with ENE = 1 mm. The initial cohort (n=118) was expanded to 150 patients to gather additional ctHPV DNA data.

Results: 150 patients were enrolled between October 2018 and June 2022. Due to one patient withdrawal prior to RT initiation, data from 149 patients treated per protocol were analyzed. Patient characteristics are detailed in Table 1. Median follow-up is 44 months (range 19-63 months). No patients developed local recurrence, but two experienced regional recurrences. One of them developed distant metastatic (DM) disease and then developed bilateral neck recurrence (contralateral untreated surpraclavicular and ipsilateral treated neck) one year later. The second recurred 47 months after completion of RT in the treated contralateral neck, both within and below the 45 Gy volume. The estimated 4-year LRC rate is 97.7% (95% CI, 90-99.5%). Ten patients (6.7%) developed DM and two patients died of DM disease. The TORS bed was spared in 52% of patients; the median dose to the spared primary site was 30.9 Gy (range 16.5 – 46 Gy). The 24 patients with ENE > 1 mm (“high risk” per ECOG 3311) did not experience LRF. At 24 months post-RT, median MDASI-HN scores scaled from 0 to 10 (most severe) were dysphagia-3, xerostomia-3.5, and interference with work-1.

Conclusion: Long-term results of our clinical trial of selected p16+ OPSCC patients treated with a combination of radiation dose de-intensification and volume reduction demonstrate high rates of locoregional control, supporting the efficacy of this approach. Abstract 312 – Table 1

Margins	All treated patients (n=149)
Negative	88 (59%)
Close (<2 mm); Positive	48 (32%); 13 (9%)
Extranodal extension (ENE)	41 (28%)
Primary Site Treated?
Yes	72 (48%)
No	77 (52%)
Concurrent chemotherapy
Yes	35 (23.5%)
No	114 (76.5%)