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Six versus five fractions per week (chemo)-radiotherapy for locally advanced head and neck squamous cell carcinoma – A nationwide cohort study from the Swedish head and neck cancer register

Adrian, Gabriel LU orcid ; Falklind, Niclas Rudolfson LU ; McDowell, Lachlan and Gebre-Medhin, Maria LU (2026) In Radiotherapy and Oncology 219.
Abstract

Purpose: Radiotherapy (RT) for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) can be intensified by delivering 6 (6fx/w) instead of 5 (5fx/w) fractions per week. Randomized trials have demonstrated superiority for 6fx/w in patients treated without concurrent chemotherapy (CRT). This real-world analysis compares 6 vs 5 fx/w in LA-HNSCC all-comers, treated predominantly with CRT, where fractionation schedules were determined by region-specific guidelines, resembling a natural experiment. Methods: All RT-treated patients from 2017 onwards across the six Swedish health care regions with T3-4 (all sites), T1-2 N3 (p16/HPV-positive oropharynx (HPV+ OPSCC)), T1-2N2c-N3 (all other sites) ≤ 70 years were... (More)

Purpose: Radiotherapy (RT) for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) can be intensified by delivering 6 (6fx/w) instead of 5 (5fx/w) fractions per week. Randomized trials have demonstrated superiority for 6fx/w in patients treated without concurrent chemotherapy (CRT). This real-world analysis compares 6 vs 5 fx/w in LA-HNSCC all-comers, treated predominantly with CRT, where fractionation schedules were determined by region-specific guidelines, resembling a natural experiment. Methods: All RT-treated patients from 2017 onwards across the six Swedish health care regions with T3-4 (all sites), T1-2 N3 (p16/HPV-positive oropharynx (HPV+ OPSCC)), T1-2N2c-N3 (all other sites) ≤ 70 years were included. Treatment schedules followed regional guidelines: three regions used 5fx/w, three used 6fx/w. Overall survival (OS) was the primary endpoint; loco-regional control (LRC) secondary. Multivariable Cox-Regressions and adjusted Kaplan-Meier estimates compared outcomes for patients treated at centers utilizing 5fx/w or 6fx/w. Data was acquired from the prospective Swedish Head and Neck Cancer Register. Results: 405 (320 with CRT) treated at 6fx/w centers and 535 (352 with CRT) patients at 5fx/w centers were included. Median overall treatment time was 40 days (IQR 38–43) for 6fx/w and 46 days (IQR 46–49) for 5fx/w centers. Baseline characteristics were similar. Five-year OS was 67% for 6fx/w and 66% for 5fx/w (HR 0.93, 95%CI 0.73–1.19). Five-year LRC was significantly improved with 6fx/w (84%) vs 5fx/w (78%), HR 0.69 (95%CI 0.49–0.97). Findings remained in subgroup analyses, although the absolute benefit was larger for p16-negative HNSCC. Conclusion: Moderately accelerated RT with 6fx/w improved loco-regional control in LA-HNSCC patients treated mainly with CRT, without OS benefit.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Radiotherapy and Oncology
volume
219
article number
111481
publisher
Elsevier
external identifiers
  • scopus:105033254974
  • pmid:41802706
ISSN
0167-8140
DOI
10.1016/j.radonc.2026.111481
language
English
LU publication?
yes
id
e91c46e8-f02f-4dc9-9a51-d214080ab329
date added to LUP
2026-04-20 11:44:46
date last changed
2026-07-29 02:39:01
@article{e91c46e8-f02f-4dc9-9a51-d214080ab329,
  abstract     = {{<p>Purpose: Radiotherapy (RT) for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) can be intensified by delivering 6 (6fx/w) instead of 5 (5fx/w) fractions per week. Randomized trials have demonstrated superiority for 6fx/w in patients treated without concurrent chemotherapy (CRT). This real-world analysis compares 6 vs 5 fx/w in LA-HNSCC all-comers, treated predominantly with CRT, where fractionation schedules were determined by region-specific guidelines, resembling a natural experiment. Methods: All RT-treated patients from 2017 onwards across the six Swedish health care regions with T3-4 (all sites), T1-2 N3 (p16/HPV-positive oropharynx (HPV+ OPSCC)), T1-2N2c-N3 (all other sites) ≤ 70 years were included. Treatment schedules followed regional guidelines: three regions used 5fx/w, three used 6fx/w. Overall survival (OS) was the primary endpoint; loco-regional control (LRC) secondary. Multivariable Cox-Regressions and adjusted Kaplan-Meier estimates compared outcomes for patients treated at centers utilizing 5fx/w or 6fx/w. Data was acquired from the prospective Swedish Head and Neck Cancer Register. Results: 405 (320 with CRT) treated at 6fx/w centers and 535 (352 with CRT) patients at 5fx/w centers were included. Median overall treatment time was 40 days (IQR 38–43) for 6fx/w and 46 days (IQR 46–49) for 5fx/w centers. Baseline characteristics were similar. Five-year OS was 67% for 6fx/w and 66% for 5fx/w (HR 0.93, 95%CI 0.73–1.19). Five-year LRC was significantly improved with 6fx/w (84%) vs 5fx/w (78%), HR 0.69 (95%CI 0.49–0.97). Findings remained in subgroup analyses, although the absolute benefit was larger for p16-negative HNSCC. Conclusion: Moderately accelerated RT with 6fx/w improved loco-regional control in LA-HNSCC patients treated mainly with CRT, without OS benefit.</p>}},
  author       = {{Adrian, Gabriel and Falklind, Niclas Rudolfson and McDowell, Lachlan and Gebre-Medhin, Maria}},
  issn         = {{0167-8140}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Radiotherapy and Oncology}},
  title        = {{Six versus five fractions per week (chemo)-radiotherapy for locally advanced head and neck squamous cell carcinoma – A nationwide cohort study from the Swedish head and neck cancer register}},
  url          = {{http://dx.doi.org/10.1016/j.radonc.2026.111481}},
  doi          = {{10.1016/j.radonc.2026.111481}},
  volume       = {{219}},
  year         = {{2026}},
}