The prognostic value of image-identified extranodal extension in laryngeal and hypopharyngeal carcinoma following definitive (chemo-)radiotherapy

Objectives

Clinical extranodal extension (cENE) is a cN modifier in TNM-8 for laryngo-hypopharygeal carcinoma (LHC). We hypothesize that image-detected ENE (iENE) can provide additional prognostic value over cENE in LHC.

Methods

Baseline CTs/MRIs of cN+ LHC patients treated with definitive (chemo-)radiotherapy between 2010–2019 were re-reviewed by a neuroradiologist using internationally accepted criteria for iENE-positive/negative (iENE+/iENE–). Overall survival (OS) was compared by iENE status. Multivariable analysis (MVA) was performed to confirm the prognostic value of iENE, adjusted for known potential confounders.

Results

A total of 232 LHC patients were identified, including 154 iENE–/cENE–, 60 iENE+/cENE–, and 18 iENE+/cENE+. A higher proportion of iENE+ (vs iENE–) patients had lymph node (LN) size > 3 cm [53 (67 %) vs 4 (3 %)], >=5 LNs [51 (65 %) vs 33 (21 %)], and retropharyngeal LN [12 (15 %) vs 6 (4 %)] (all p < 0.01). Median follow-up was 4.8 years. iENE+/cENE– and iENE+/cENE+patients had similarly low 5-year OS [28 % (18–44) and 29 % (13–63)] vs iENE–/cENE– [53 % (45–62)] (p < 0.001). On MVA, mortality risk was higher with iENE+vs iENE– [hazard ratio (HR) 2.22 (95 % CI 1.47–3.36)]. The prognostic value of iENE remained with MVA in larynx (n = 124) (HR 2.51 [1.35–4.68], p = 0.004] or hypopharynx (n = 108) (HR 1.87 [1.02–3.43], p = 0.04) patients, separately.

Conclusions

Our study confirms the independent prognostic importance of iENE for LHC following definitive (chemo-)radiotherapy beyond TNM-8 cN status that already contains the cENE parameter. Further research is needed to explore whether iENE could replace cENE for future cN classification.