Recurrence and Quality-of-Life Following Elective Nodal Volume and Dose De-Escalation for Oropharyngeal and Laryngeal Cancer: Initial Results from the Infield Trial

Abstract

The required elective nodal dose and volumes for head and neck intensity-modulated radiotherapy (IMRT) have largely been extrapolated from conventional radiotherapy fields. The combination of CT and PET-CT imaging with surgically established patterns-of-nodal-spread provides an opportunity to meaningfully reduce the elective dose and volume, with a significant gain in acute and long-term morbidity. In this prospective phase II study, we investigated the efficacy and tolerability of reduced elective nodal volume and dose in oropharyngeal and laryngeal squamous cell carcinoma. Patients with newly-diagnosed squamous cell carcinoma of the oropharynx and larynx were eligible for enrollment; only stage I-II glottic larynx were excluded. In collaboration with a nuclear radiologist, each lymph node was characterized as involved or suspicious based on anatomic and PET criteria. Lymph nodes whose cross-sectional diameter was at least 17 mm and/or nodes with FDG uptake greater than the adjacent blood pool were considered suspicious. For oropharynx cancer, only involved nodal stations plus one adjacent station (and retropharynx) were treated to 40 Gy in 20 fractions. In larynx patients, at least bilateral levels II and III were treated to 40 Gy, with level IV treated only if level III was involved. Involved and suspicious nodes were then boosted with 30 Gy and 24 Gy in 15 fractions, respectively. The primary gross tumor and clinical target volumes were irradiated to 70 and 64 Gy, respectively, in the same fractionation. Concurrent chemotherapy was required for stage T3N0-1 and IVA/B patients. The primary endpoint of the study was solitary elective volume recurrence, with secondary endpoints including patterns-of-failure and patient reported outcomes. A total of 72 patients completed treatment on this trial from January 2017 through November 2018. The study was composed of 19 larynx and 53 oropharyngeal patients, 77% of whom were p16-positive. The stages at presentations were 5, 17, and 50 stage I-II, III, and IV, respectively, with 8% and 92% treated with accelerated radiotherapy and chemoradiotherapy, respectively. Average contralateral mean parotid and SMG doses for non-N2c patients were 16.5 Gy and 36.7 Gy, respectively. With a median follow-up of 11.9 months for surviving patients, there have been no recurrences in the 40 Gy or untreated elective nodal stations. Gastrostomy was placed in 32 (44%), with median removal after 2.9 months for disease-free patients; only one disease-free patient is still dependent. At 3 months, the mean composite MDADI score was 79, and the mean EORTC HN35 dry mouth and sticky saliva scores were 59 and 40, respectively. Preliminary results suggest that elective dose and volume reduction is oncologically sound for oropharyngeal and laryngeal cancer treated with IMRT, with promising quality-of-life outcomes. Longer follow-up is needed to confirm these results.