Pain Associated With Head and Neck Cancer Photoimmunotherapy

Head and neck photoimmunotherapy (HN-PIT) achieves local control in unresectable locally advanced or recurrent head and neck cancer; however, acute post-treatment pain remains clinically important. This retrospective study evaluated pain timing and intensity, the association between a revised analgesic protocol and pain, the relationship between tumor diameter and pain, and adverse events after HN-PIT.

Patients who underwent HN-PIT at Tokyo Medical University Hospital between February 2021 and November 2025 were reviewed. Pain outcomes were analyzed in 47 patients during the first HN-PIT cycle; adverse events were evaluated in 48 patients, including one excluded from pain assessment because of intubation. Numerical Rating Scale (NRS) scores were recorded from illumination day to day 7, with the highest score defined as maximum NRS. Maximum NRS scores were compared between 2021-2023 and 2024-2025, before and after implementation of a multimodal analgesic protocol. Pearson's correlation coefficient and simple linear regression assessed the relationship between maximum tumor diameter and maximum NRS. Adverse events were graded according to CTCAE v5.0.

Among 45 patients who experienced pain during the first week, 28 (62%) had peak NRS scores on illumination day. Maximum NRS was lower in 2024-2025 than in 2021-2023 (5.17±3.16 vs. 7.08±2.36). Maximum tumor diameter was not significantly associated with maximum NRS. Among 48 patients evaluated for adverse events, pain (97.9%), mucositis (70.8%), and laryngeal edema (58.3%) were most common.

Pain after HN-PIT peaked on illumination day. A standardized multimodal analgesic protocol was associated with reduced pain intensity. Tumor diameter was not a major pain severity determinant.