Involved neck only versus mucosal radiotherapy for head and neck squamous cell cancer of unknown primary (HNSCCUP): a national retrospective multicentre cohort study

TY - JOUR

T1 - Involved neck only versus mucosal radiotherapy for head and neck squamous cell cancer of unknown primary (HNSCCUP)

T2 - a national retrospective multicentre cohort study

AU - Peters, Adam L.

AU - Poon, Wai-Yan

AU - Walters, Sarah

AU - Iyizoba-Ebozue, Zsuzsanna

AU - Hannon, Clare

AU - Kingdon, Sarah

AU - Yogalingam, Kohgulakuhan

AU - Kennedy, Laura

AU - Peck, Josie

AU - Cavanagh, Kirsty

AU - Fernandes, Rania

AU - Wang, Yifei

AU - Thomas, Solly

AU - Rowe, Michael

AU - Grellier, Katarzyna

AU - MacTier, Karen

AU - Baxter, Mark

AU - Growcott, Siona A.

AU - Muse, Adam

AU - Kitson, Rob

AU - Gbenebichie, Osanmofe

AU - Laws, Kirsten

AU - Hardman, John

AU - Denholm, Mary

AU - Purshouse, Karin

AU - Prestwich, Robin

AU - Wilson, Christina

AU - Noble, David J.

AU - Paterson, Claire

N1 - Copyright: © 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

PY - 2026/6/1

Y1 - 2026/6/1

N2 - Introduction: Target volumes for irradiation remain ill-defined for head and neck squamous cell cancer of unknown primary (HNSCCUP). The aim of this study was to compare two commonly used radiotherapy strategies for patients diagnosed with HNSCCUP: ipsilateral or involved neck only (INO) versus bilateral neck and/or mucosal (MUC) radiotherapy, evaluating disease related outcomes and enteral feeding rates.Methods and materials: This was a retrospective, observational, multi-centre cohort study. Patients diagnosed with unilateral HNSCCUP between 2015 and 2023 who underwent radical (chemo) radiotherapy were eligible for analysis. All patients underwent FDG PET-CT. HNSCCUP was a diagnosis of exclusion made on the basis of negative investigations to detect a primary site. Patient and tumour characteristics, treatment details, toxicities and disease control were recorded and compared between the two radiotherapy strategies.Results: 195 patients were eligible for analysis, 66% had human papillomavirus (HPV) associated disease. 73 patients received INO (37%) and 122 patients received MUC radiotherapy (63%). The median duration of follow up was 58 months (IQR 42-72 months). The rate of primary site emergence was 2.7% in the INO and 0.8% in the MUC cohorts, p=0.56. 5-year overall survival was 80% (95% CI 70-90%) for INO and 82% (95% CI 75-90%) for MUC radiotherapy, p=0.74. Those undergoing INO radiotherapy were more likely to die from HNSCCUP (17.8% vs 5.7%) and those receiving MUC to die from a non-HNSCCUP cause (15.6% vs 4.1%). The need for enteral feeding ≥ 12 months from radiotherapy was 5.7% for MUC vs 0% for INO, p=0.046.Conclusions: This is the largest series to date of patients with unilateral HNSCCUP treated radically with radiotherapy in the HPV and FDG PET-CT era. Acceptably low rates of primary site emergence, lower toxicity and no difference in overall survival when compared with prophylactic mucosal radiotherapy suggests that involved neck only radiotherapy in HNSCCUP may be a feasible alternative in contemporary practice.

AB - Introduction: Target volumes for irradiation remain ill-defined for head and neck squamous cell cancer of unknown primary (HNSCCUP). The aim of this study was to compare two commonly used radiotherapy strategies for patients diagnosed with HNSCCUP: ipsilateral or involved neck only (INO) versus bilateral neck and/or mucosal (MUC) radiotherapy, evaluating disease related outcomes and enteral feeding rates.Methods and materials: This was a retrospective, observational, multi-centre cohort study. Patients diagnosed with unilateral HNSCCUP between 2015 and 2023 who underwent radical (chemo) radiotherapy were eligible for analysis. All patients underwent FDG PET-CT. HNSCCUP was a diagnosis of exclusion made on the basis of negative investigations to detect a primary site. Patient and tumour characteristics, treatment details, toxicities and disease control were recorded and compared between the two radiotherapy strategies.Results: 195 patients were eligible for analysis, 66% had human papillomavirus (HPV) associated disease. 73 patients received INO (37%) and 122 patients received MUC radiotherapy (63%). The median duration of follow up was 58 months (IQR 42-72 months). The rate of primary site emergence was 2.7% in the INO and 0.8% in the MUC cohorts, p=0.56. 5-year overall survival was 80% (95% CI 70-90%) for INO and 82% (95% CI 75-90%) for MUC radiotherapy, p=0.74. Those undergoing INO radiotherapy were more likely to die from HNSCCUP (17.8% vs 5.7%) and those receiving MUC to die from a non-HNSCCUP cause (15.6% vs 4.1%). The need for enteral feeding ≥ 12 months from radiotherapy was 5.7% for MUC vs 0% for INO, p=0.046.Conclusions: This is the largest series to date of patients with unilateral HNSCCUP treated radically with radiotherapy in the HPV and FDG PET-CT era. Acceptably low rates of primary site emergence, lower toxicity and no difference in overall survival when compared with prophylactic mucosal radiotherapy suggests that involved neck only radiotherapy in HNSCCUP may be a feasible alternative in contemporary practice.

UR - https://www.scopus.com/pages/publications/105024925440

U2 - 10.1016/j.ijrobp.2025.11.013

DO - 10.1016/j.ijrobp.2025.11.013

M3 - Article

C2 - 41253268

SN - 0360-3016

VL - 125

SP - 404

EP - 417

JO - International Journal of Radiation Oncology• Biology• Physics

JF - International Journal of Radiation Oncology• Biology• Physics

IS - 2

ER -