A Phase II Study of Volume and Dose De-Intensification Following Transoral Robotic Surgery (TORS) and Neck Dissection for p16+ Oropharyngeal Squamous Cell Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> Current efforts to de-intensify adjuvant therapy for patients with p16+ Oropharyngeal Squamous Cell Carcinoma (OPSCC) have focused on dose de-escalation (ECOG 3311) or volume reduction (AVOID trial). We conducted this prospective Phase II single institution study combining volume and dose de-intensification, in patients with pT0-T3 pN0-N2c p16+ OPSCC, with the goal of maintaining high rates of locoregional control (LRC) and reducing treatment-related toxicity. <h3>Materials/Methods</h3> Eligible patients had pT0-T3 N0-N2c p16+ OPSCC (per AJCC 7th Ed), s/p TORS and neck dissection, with < 5 positive lymph nodes, who met standard indications for adjuvant radiotherapy +/- 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, as per the AVOID trial. If RT to the primary operative bed was indicated, patients received 50, 52.5, or 55 Gy for negative, close, or positive margins, respectively. The neck level(s) with confirmed pathologic disease received 50 Gy, and areas of minor or macroscopic ENE were boosted to 52.5 or 55 Gy, respectively. Other at-risk ipsilateral nodal regions received 45 Gy. 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 according to guidelines, but could be omitted in patients with ENE ≤ 1 mm. The trial was powered to demonstrate 2-year LRC rate > 90%. <h3>Results</h3> 118 patients were enrolled between October 2018 and July 2021. Patient characteristics are detailed in the Table. Median follow up is 23 months (range 6 - 40 months). One patient developed regional recurrence after developing distant metastases (DM). No other patients had locoregional failure (LRF), yielding an estimated 2-year LRC rate of 98.8% (95% CI, 92-99.8%). Eight patients (7%) developed DM, and one patient has died of metastatic disease. The TORS resection bed was spared in 55% of patients; due to proximity to level 2, the median dose to the operative bed in these cases was 32.5 Gy (range 16.5 – 46 Gy). Twenty patients had ENE > 1 mm (considered "high risk" per ECOG 3311) and none had LRF. At one-year post-RT, the median MDASI-HN "difficulty swallowing/chewing at its worst" score was 2 (IQR, 1-3), and "choking/coughing with swallowing at its worst" score was 1 (IQR, 0-3), on a scale from 0 (not present) to 10 (as bad as you can imagine). <h3>Conclusion</h3> The combination of adjuvant RT dose de-intensification over 5 weeks and volume reduction, with omission of the primary site in appropriate patients, and reducing the volume of the treated contralateral neck, appears safe. Additional follow up is warranted and ongoing.