Photobiomodulation Therapy in Head and Neck Cancer Patients Undergoing Chemoradiotherapy: Role in Toxicities Prevention

Background: Chemoradiotherapy (CRT) for head and neck cancer (HNC) is frequently associated with severe acute toxicities that compromise treatment adherence and quality of life. This study evaluated the effectiveness of photobiomodulation (PBM) in reducing CRT-induced toxicities in a real-world cohort. Methods: Between May 2021 and July 2024, we retrospectively analyzed 117 HNC patients treated with definitive or adjuvant CRT and concomitant PBM: a non-invasive application of red or near-infrared light to cutaneous and mucosal surfaces to modulate inflammatory responses, using 620/820 nm or 650 nm devices, with irradiation times of 2–12 min and energy densities of 3–12 J/cm2 according to the treatment protocol. Toxicities were graded according to CTCAE v 5.0 at baseline, during treatment, at treatment completion, and throughout follow-up. Associations with toxicity were assessed with logistic regression for repeated measurements (generalized estimating equations). Patients were stratified according to PBM exposure (<10 vs. ≥10 sessions). Results: Median follow-up was 16 months. At treatment completion, grade 2–3 oral mucositis and radiodermatitis occurred in 38.5% and 25.6% of patients, respectively, both lower than rates reported in historical cohorts without PBM. Patients receiving ≥10 PBM sessions (72 pts) experienced significantly lower rates of grade 2–3 odynophagia at treatment completion (16.7% vs. 42.2%, p = 0.005) and persistent dysphagia at the last follow-up (12.5% vs. 33.3%, p = 0.009). PBM exposure was not associated with significant differences in weight loss, progression-free survival, or overall survival. Conclusions: This study provides real-world data on toxicity outcomes among HNC patients receiving PBM, with lower rates of selected toxicities observed among patients receiving ≥10 PBM sessions. Although the retrospective design and lack of a control group limit causal inference, these findings provide a strong rationale for prospective randomized trials to define the optimal PBM schedule and validate its clinical impact.