Tailoring Radiation to the Contralateral Neck for Midline HPV-Mediated Oropharyngeal Squamous Cell Carcinoma (p16+ OPSCC)

Abstract

De-intensification strategies for locally advanced p16+ OPSCC are under active investigation, including omission of contralateral neck radiation (RT) for well-lateralized T1-2N0-2a. This study evaluates the outcomes of omitting contralateral neck nodal levels for p16+ OPSCC that are not well-lateralized. A retrospective review was done of 134 consecutive patients with non-metastatic p16+ OPSCC that were not well-lateralized (< 1 cm from midline or ≥ 1 cm extension to soft palate or base of tongue) who were treated with definitive chemoradiation from 2013 to 2019. IMRT to an EQD2 6364-6735 cGy (200-220 cGy per fraction) was used to treat the primary tumor and ipsilateral or bilateral neck, with tailored nodal level coverage and dose, and with concurrent paclitaxel and carboplatin. Contralateral neck RT was tailored in 121 patients: omitted in 11, limited to level II in 9, and limited to level II and III in 101 (contralateral lower neck omitted); the remaining 13 had bilateral level II-IV neck RT. Local and regional recurrences were evaluated. Median follow up was 45.34 months. Local and/or regional recurrence was noted in 9/134 (6.7%). 3 (2%) recurred in the contralateral neck in unirradiated tissue (out-of-field). All three were salvaged. The remaining 6 recurrences (4%) were in-field; one was at the primary site and 5 were nodal (all ipsilateral). 4 of the 5 regional recurrences were in a location that was treated to EQD2 7000 cGy (all had PET avid nodal disease upfront that was included in the high dose level); the other region of recurrence was treated to an EQD2 6353 cGy (the only recurrence in a never smoker). 4 of the 5 neck recurrences underwent neck dissection; one further underwent adjuvant RT to 5940 cGy in 33 fractions and remains disease-free. 2 of those who underwent salvage neck dissection alone subsequently developed distant metastases. The majority of first recurrences were distant, 19.4% (26/134). 3-year progression free survival (PFS) was 74.41% (95% CI, 65.63-81.26). Taken together, regional recurrence rate in the contralateral, unirradiated neck was 2.5% (3/121) and ultimate locoregional control was 99% (132/134). Our tailored approach demonstrates a contralateral neck local control of 97.5% (118/121) regardless of tumor lateralization; those who recurred in unirradiated cervical lymph nodes were successfully salvaged. Limiting this analysis is moderate sample size and retrospective nature, but it raises important alternative de-escalation strategies (RT volume reduction) for p16+ OPSCC aside from dose reduction, which is under active investigation in phase II/III trials. Improved systemic therapies are needed to combat distant metastases. Prospective randomized clinical trials are needed for further evaluation of nodal omission for definitive chemoradiation of non-well-lateralized p16+ OPSCC.