Individualized Super Selective Nodal Radiation Therapy for Clinically Negative Lymph Nodes (cN0) in Head and Neck Squamous Cell Carcinoma Patients Based on Sentinel Node(s) Identification: A Prospective Phase 2 Study of SPECT/CT-guided Volume De-escalation

Abstract

Due to a risk of 18% to 45% of occult metastases among the clinically free of nodes head and neck squamous cell carcinoma (HNSCC) patients, prophylactic neck irradiation is often mandatory. Based on international guidelines for the selection of the neck node levels, this prophylactic treatment still leads to unnecessary large irradiation of normal tissues because bilateral drainage is the rule in only 30% to 50% of individuals, and 15% to 30% of the tumors drain in unpredicted nodal basins. Sentinel lymph node (SLN) single-photon emission computerized tomography (SPECT/CT) lymphoscintigraphy makes it possible to individually predict cervical subregions requiring prophylactic irradiation in cN0 patients. This ongoing prospective phase 2 study analyzes its oncological safety. Twenty-one patients with newly diagnosed cN0 SCC of the oral cavity, oropharynx, larynx, or hypopharynx were included. All patients were imaged with SPECT/CT after 99mTc nanocolloid injection around the tumor. The neck levels containing up to 4 hottest nodes were identified and selected for prophylactic irradiation (CTVn-LS) by volumetric modulated arc therapy. A comparative virtual planning was performed with volumes selected according to international guidelines (CTVn-IG). Migration was observed in all of the 21 patients (1 with gamma probe only) with an average of 2.7 sentinel nodes detected per patient. CTVn-LS was totally encompassed by CTVn-IG in all patients but 2 with an unpredicted drainage in retropharyngeal levels. On average, CTVn-LS and related planning target volume (PTV) were 2 times smaller than IG ones. This led to significant dose decrease in identified organs at risk as well as remaining volume at risk. With a median follow-up of 14 months, no regional relapse was observed, while 2 patients had a local one (9%). Currently, 3 patients have died (1 patient from geriatric degradation and 2 experienced fatal local relapse). SPECT/CT lymphoscintigraphy of SLN allows individualization of prophylactic node CTV in cN0 HNSCC patients eligible for definitive radiation therapy. Both CTV and PTV are significantly reduced, which results in a significant dose decrease in all identified organs at risk. At a median follow-up of 14 months, no regional relapse was observed, but further follow-up and recruitment are necessary to ensure the oncological safety.