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. 2025 Jun:165:107299.
doi: 10.1016/j.oraloncology.2025.107299. Epub 2025 Apr 21.

Outcomes following IMRT alone in head and neck squamous cell carcinoma ordinarily managed with concurrent chemo-radiotherapy

Marc Vincent N Barcelona  1 , John Waldron  2 , Brian O' Sullivan  3 , Jie Su  4 , Scott V Bratman  5 , John Byoung Cho  6 , Ezra Hahn  7 , Andrew J Hope  8 , Ali Hosni  9 , John Kim  10 , Andrew McPartlin  11 , Jolie Ringash  12 , Nauman Malik  13 , Lillian L Siu  14 , Anna Spreafico  15 , Lawson Eng  16 , Enrique Sanz-Garcia  17 , Christopher Michael Kai-Lup Yao  18 , John de Almeida  19 , Li Tong  20 , Wei Xu  21 , Chaojung Jillian Tsai  22 , Shao Hui Huang  23
Affiliations

Outcomes following IMRT alone in head and neck squamous cell carcinoma ordinarily managed with concurrent chemo-radiotherapy

Marc Vincent N Barcelona et al. Oral Oncol. 2025 Jun.

Abstract

Purpose/objective(s): We report outcomes following IMRT-alone in patients with head-and-neck squamous cell carcinoma (HNSCC) ordinarily managed with concurrent chemo-radiotherapy.

Materials/methods: HNSCC (excluding T1-2 N0) patients treated with IMRT-alone from 2005 to 2019 were included and restaged according to TNM-8. Overall survival (OS) was stratified by TNM-8 stage subgroups within HPV-positive (HPV + ) and separately within HPV-negative (HPV-) HNSCC. Multivariable analysis (MVA) identified prognostic factors for OS.

Results: A total of 460 patients with HPV + and 623 HPV- HNSCC were identified. Reasons for chemotherapy omission were: age > 70 years and/or frailty (n = 551, 51 %), cisplatin contraindication (n = 241, 22 %), patient' preference (n = 106, 10 %), and clinician's decision (n = 185, 17 %). IMRT was delivered mostly using altered-fractionation: moderately-accelerated (70 Gy/35 fractions [f]/6 weeks [w], 55 %), hypofractionated (60 Gy/25f/5w, 14 %), and hyperfractionated-accelerated (64 Gy/40f/4w, 25 %). Median follow-up was 5.0 years. Five-year OS for HPV + stage-I-single node, stage-I-multiple nodes, stage-II-T1-2 N2, stage-II-T3 N0-N2, and stage-III were 90 %, 79 %%, 80 %, 64 %, and 33 %, and for HPV- stage III, IVA, and IVB were 47 %, 27 %, and 13 %, respectively. MVA confirmed lower OS in HPV + stage-I-multiple nodes (p = 0.03), II-T3 N0-N2 and III (vs stage-I-single node) and HPV- stage IVA/IVB (vs III) (p < 0.01), and marginally lower OS in HPV + stage-II-T3 N0-2 (vs I-single node) (p = 0.07).

Conclusion: Altered fractionated IMRT-alone is a valid option for patients with HPV + stage I-single node HNSCC, and an acceptable alternative for elderly/frail or cisplatin ineligible patients with HPV + stage I-multiple nodes and T1-2 N2 HNSCC. Patients with HPV + T3-T4 or N3 and HPV- stage III/IV HNSCC had unsatisfactory OS, requiring further research into alternative options.

Keywords: Cisplatin ineligible; Head and neck cancer; Human papillomavirus; Outcomes; Radiotherapy alone.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Scott Bratman reports ownership and a leadership position of a biotechnology company, Adela. Ali Hosni Abdalaty reports leadership in the technical group for the Elekta MRL-consortium. John Kim reports ownership equity with ImmVue Therapeutics. Lilian Siu reports membership in the advisory board of Merck, AstraZeneca/MedImmune, Roche, Voronoi Inc., Oncorus, GSK, Seattle Genetics, Arvinas, Navire, Janpix, Relay Therapeutics, Daiichi Sankyo/UCB Japan, Janssen, Hookipa Pharma, InterRNA, Tessa Therapeutics, Sanofi, Amgen and research funding from Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Pfizer, AstraZeneca, Boehringer Ingelheim, Bayer, Amgen, Astellas Pharma, Shattuck Labs, Symphogen, Avid, Mirati Therapeutics, Intensity Therapeutics, Karyopharm Therapeutics, Amgen. She also reports stock ownership of an immediate family member with Agios and a leadership position at Treadwell Therapeutics. Anna Spreafico reports membership in the advisory board Merck, Bristol-Myers Squibb Oncorus Jannsen Medison & Immunocore and research funding from Novartis Bristol-Myers Squibb, Symphogen, AstraZeneca/Medimmune, Merck, Bayer, Surface Oncology, Northern Biologics, Janssen Oncology/Johnson & Johnson, Roche, Regeneron, Alkermes, Array Biopharma/Pfizer, GSK, NuBiyota, Oncorus, Treadwell, and Amgen. Chiaojung Jillian Tsai reports advisory board membership at Varian Medical Inc. All other authors report no conflict of interest.

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