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

## TL;DR

The study finds that lower inflammation before treatment predicts better outcomes in a new cancer therapy for head and neck cancer, while nutritional status remains stable.

## Contribution

Identifies baseline systemic inflammation as a potential predictor of treatment response in near-infrared photoimmunotherapy for head and neck cancer.

## Key findings

- Patients with lower baseline systemic inflammation were more likely to achieve complete response to NIR-PIT.
- Nutritional status remained stable after treatment, indicating no short-term negative impact on nutrition.
- Baseline SIRI showed a large effect size in distinguishing complete responders from non-responders.

## Abstract

Recurrent head and neck cancer remains challenging to manage, particularly in patients for whom salvage surgery or re-irradiation is not suitable. Near-infrared photoimmunotherapy (NIR-PIT) has recently been introduced as a tumor-selective treatment option; it may stimulate the immune system and spare normal tissues. However, which patients benefit the most remains unclear, and little is known about how this treatment affects nutritional status, which is important for quality of life and treatment continuation. This study analyzed 15 patients treated with near-infrared photoimmunotherapy. Patients with lower systemic inflammation before treatment were more likely to achieve a complete response. Conversely, nutritional measurements remained stable after treatment, suggesting that near-infrared photoimmunotherapy did not worsen nutritional condition in the short term. These findings highlight inflammation as a potential predictive factor for treatment benefit and support the nutritional safety of near-infrared photoimmunotherapy.

Background/Objectives: 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. Methods: 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. Results: 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; p = 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. Conclusions: 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.