Abstract

Background Head and neck cancer (HNC) patients face an increased risk of malnutrition due to lifestyle, tumor localization, and treatment effects. While skeletal muscle area (SMA) and radiation attenuation (SM-RA) at the third lumbar vertebra (L3) are established prognostic markers, L3 is not routinely available in head and neck imaging. The prognostic value of SM-RA at the third cervical vertebra (C3) remains unclear. This study assesses whether SMA and SM-RA at C3 predict locoregional control (LRC) and overall survival (OS) in HNC.

Methods We analyzed 904 HNC cases with head and neck CT scans. A deep learning pipeline identified C3, and SMA/SM-RA were quantified via automated segmentation with manual verification. Cox proportional hazards models assessed associations with LRC and OS, adjusting for clinical factors.

Results Median SMA and SM-RA were 36.64 cm² (IQR: 30.12–42.44) and 50.77 HU (IQR: 43.04–57.39). In multivariate analysis, lower SMA (HR 1.62, 95% CI: 1.02–2.58, p = 0.04), lower SM-RA (HR 1.89, 95% CI: 1.30–2.79, p < 0.001), and advanced T stage (HR 1.50, 95% CI: 1.06–2.12, p = 0.02) were prognostic for LRC. OS predictors included advanced T stage (HR 2.17, 95% CI: 1.64–2.87, p < 0.001), age ≥70 years (HR 1.40, 95% CI: 1.00–1.96, p = 0.05), male sex (HR 1.64, 95% CI: 1.02–2.63, p = 0.04), and lower SM-RA (HR 2.15, 95% CI: 1.56–2.96, p < 0.001).

Conclusion Deep learning-assisted SM-RA assessment at C3 outperforms SMA for LRC and OS in HNC, supporting its use as a routine biomarker and L3 alternative.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study did not receive any funding

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee of of University Hospital RWTH Aachen waived ethical approval for this work

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

AbbreviationsC3Third Cervical VertebraCIConfidence IntervalCSACross-sectional areaDFSDisease-Free SurvivalHNCHead and Neck CancerHNSCCHead and Neck Squamous Cell CarcinomaHRHazard RatioIMATintermuscular adipose tissueL3Third Lumbar VertebraLRCLocoregional controlOROdds RatioOSOverall SurvivalPFSProgression-Free SurvivalRCTRadiochemotherapyRTRadiotherapySMASkeletal Muscle AreaSMISkeletal Muscle IndexSMMSkeletal Muscle MassSM-RASkeletal Muscle Radiation Attenuation