Recurrence and Quality-of-Life Following Involved Node Radiotherapy for Head and Neck Squamous Cell Carcinoma: Initial Results From the Phase II INRT-Air Trial

Abstract

Elective neck irradiation (ENI) has long been considered mandatory when treating head and neck squamous cell carcinoma (HNSCC) with definitive radiotherapy (RT). However, ENI is often responsible for the majority of the dose to the salivary glands and swallowing organs-at-risk (OAR), and recent prospective studies have supported reduced elective neck volume and dose. Moreover, with sensitive staging studies and artificial intelligence (AI), our ability to identify occult lymphadenopathy is greatly improving. In this prospective phase II study, we investigated the efficacy and tolerability of eliminating ENI and strictly treating involved and suspicious lymph nodes (LN) with intensity modulated radiation therapy.Patients with newly-diagnosed squamous cell carcinoma of the oropharynx, larynx and hypopharynx were eligible for enrollment, excluding stage I-II glottic larynx. Each LN was characterized as involved or suspicious based on CT (e.g., cross-sectional size, enhancement pattern) and PET criteria and an in-house AI-based classification model. Gross disease and the primary clinical target volume were irradiated to 70 and 63 Gy in 35 fractions, respectively, and suspicious LN were treated to 66.5 Gy. Concurrent chemotherapy was required for stage T3N0-1 and IVA/B patients. The primary endpoint of the study was risk of solitary elective volume LN recurrence (i.e., LN recurrence in a classic ENI field without synchronous in-field or distant failure), with secondary endpoints including patterns-of-failure and patient reported outcomes.Sixty-seven patients were enrolled, with 18 larynx/hypopharynx and 49 oropharynx cancer (88% p16+). In total, 10% and 90% of patients were treated with accelerated RT and chemoRT, respectively. Average contralateral/ipsilateral mean parotid and contralateral submandibular doses were 11.9/18.4 Gy and 34.1 Gy, respectively, and average mean larynx/inferior constrictor/esophagus doses for oropharynx patients were 18.9/12.2/6.7 Gy. With a median follow-up of 12.8 months for surviving patients, there have been no solitary elective volume LN recurrences. Four patients have died from unrelated causes, and one died from in-field local progression. Gastrostomy was placed in 14 (21%), with median removal after 2.8 months for disease-free patients; only one patient is still dependent. Grade 1/2 dermatitis was seen in 90%/10% patients. There was no significant difference in MDADI score between baseline and months 3 and 6 post-RT; for patients with baseline MDADI score > 75, the scores at 3/6 months were 84/83.Preliminary results suggest that eliminating ENI is oncologically sound for HNSCC, with highly favorable OAR dosimetry and promising quality-of-life outcomes. Longer follow-up is needed to confirm these results.