Nutritional and Inflammatory Markers Associated with Complete Response to Near-Infrared Photoimmunotherapy in Recurrent Head and Neck Squamous Cell Carcinoma

<b>Background/Objectives</b>: Near-infrared photoimmunotherapy (NIR-PIT) provides tumor-selective cytotoxicity with minimal collateral tissue damage and has emerged as a novel treatment option for recurrent head and neck squamous cell carcinoma (HNSCC). However, biomarkers that predict treatment response to NIR-PIT remain poorly defined. Therefore, this study aimed to exploratorily determine whether baseline nutritional and inflammatory composite biomarkers are associated with complete response to NIR-PIT in patients with recurrent HNSCC. <b>Methods</b>: Fifteen non-surgical candidates with recurrent HNSCC underwent NIR-PIT between January 2022 and December 2025. Baseline composite nutritional indices and inflammatory markers, including the systemic inflammation response index (SIRI), were assessed before and 4-8 weeks post-treatment. Tumor response was evaluated according to RECIST version 1.1. Exploratory comparisons between complete response (CR) and non-CR groups were performed using Wilcoxon rank-sum tests with effect size estimation. <b>Results</b>: Five of 15 patients achieved CR (33.3%). Baseline SIRI was significantly lower in the CR group than in the non-CR group (median 70.7 vs. 120.2; <i>p</i> = 0.03), with a large effect size (r = 0.55). In contrast, baseline composite nutritional indices and other inflammatory markers showed no significant association with treatment response. Nutritional status remained stable after NIR-PIT, as reflected by preserved nutritional index values. SIRI tended to increase post-treatment in patients who achieved CR. <b>Conclusions</b>: NIR-PIT achieved encouraging local tumor responses in recurrent HNSCC while preserving early nutritional status. Baseline SIRI may represent a potential inflammation-based correlate of CR, reflecting the balance between systemic inflammation and host immune status, and warrants validation in larger prospective cohorts.