Feasibility of Near-infrared Photoimmunotherapy Combined With Immune Checkpoint Inhibitor Therapy in Unresectable Head and Neck Cancer.

BACKGROUND/AIM: Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer treatment modality that selectively kills cancer cells and may induce a therapeutic host immune response. The aim of this study was to determine the feasibility of combining NIR-PIT with immune checkpoint inhibitor (ICI) therapy for unresectable recurrent head and neck cancer. PATIENTS AND METHODS: Five patients underwent NIR-PIT at Ryukyu University Hospital between January 2022 and April 2024. These patients had unresectable recurrent head and neck squamous cell carcinoma. Among these five patients, four received a combination NIR-PIT and pembrolizumab administration. RESULTS: A total of seven lesions in the oropharynx and oral cavity were targeted. One patient was treated for three different target lesions. The best observed response (BOR) rate was 100%, with three complete responses and four partial responses. The most common treatment-related adverse event was Grade 1 or 2 local pain lasting one to two days postoperatively, which occurred in all patients. Grade 3 adverse events occurred in three cases (42.9%), including pneumonia, pharynx-cutaneous fistula, and trismus. Three patients received ICI therapy following NIR-PIT, achieving a 60% BOR rate. No immune-related adverse events were noted, and the aforementioned Grade 3 adverse events did not worsen during ICI therapy. At a median follow-up of 376 days (range=157-845 days), four target lesions showed no recurrence, while three had recurred. All five patients were alive, including three with no evidence of disease. CONCLUSION: The combination of NIR-PIT and ICI therapy for unresectable recurrent head and neck cancer was feasible.

Prospective Analysis of Squamous Cell Carcinoma Antigen-1 and -2 for Diagnosing Sinonasal Inverted Papilloma.

Background: The goal of this research was to confirm whether preoperative serum squamous cell carcinoma antigen (SCCA)-1 and -2 levels are useful diagnostic markers for sinonasal inverted papilloma (IP) in a prospective study. Methods: Participants were 102 patients who underwent consecutive endoscopic sinus surgery: 18 with IP, two with other types of papilloma, 77 with chronic rhinosinusitis, four with sinonasal cancer, and one with hemangioma. SCCA-1 and SCCA-2 were measured preoperatively by an automatic chemiluminescence immunoassay and an enzyme-linked immunosorbent assay, respectively. Results: SCCA-1 and SCCA-2 values were significantly correlated (r = 0.603, p < 0.001). Receiver operating characteristic analysis for differentiating papilloma (IP and other types of papilloma) from other diseases yielded an area under the curve of 0.860, with a Youden index of 1.75. Combined with SCCA-2 analysis, the detection system had a sensitivity and specificity of 0.65 and 0.98, respectively. While our study did not find a strong link between SCCA levels and skin or lung diseases, smoking status may influence SCCA levels in IP patients (p = 0.035). We recommend a cutoff value of 1.8 ng/mL for SCCA-1 in IP diagnosis. Conclusions: SCCA-1 and SCCA-2 when combined with imaging and pathology hold promise for enhancing the preoperative detection of IP, which would be a valuable contribution to clinical practice.

Butyrate inhibits type 2 inflammation in eosinophilic chronic rhinosinusitis.

Butyrate and other Short-chain fatty acids (SCFAs) are microbial metabolites from Bacteroides and Clostridium species that may suppress type 2 inflammation. However, the mechanisms of SCFAs in the nasal sinuses are not fully understood. We aimed to clarify the in vitro and in vivo roles of SCFAs in eosinophilic chronic rhinosinusitis (ECRS) pathophysiology. We investigated whether SCFAs induced changes in type 2 cytokines, IgE, and apoptosis and the roles of GPR41, GPR43, and histone deacetylase. Analysis of the control subjects demonstrated that butyrate of SCFAs effectively inhibited type 2 cytokine production in PBMCs, ILC2s, and CD4+ T cells and IgE production in CD19+ B cells. In annexin V analysis, butyrate also induced late apoptosis of PBMCs. The butyrate-induced inhibition of type 2 cytokines appeared involved in histone deacetylase inhibition but not in GPR41 or GPR43. In an analysis of ECRS in humans, butyrate inhibited type 2 cytokine production in PBMCs and nasal polyp-derived cells. The butyrate concentration in nasal lavage fluid was significantly decreased in ECRS patients compared to controls and non-ECRS patients. Our findings confirm that butyrate can inhibit type 2 inflammation and may be a potential therapeutic target for ECRS.

Biomarkers for Predicting Anti-Programmed Cell Death-1 Antibody Treatment Effects in Head and Neck Cancer.

In recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC), survival outcomes are significantly better in patients who receive anti-programmed cell death-1 (PD-1) monoclonal antibody therapy than in those who receive standard therapy. However, there is no established biomarker that can predict the anti-PD-1 antibody treatment effect and immune-related adverse events (irAEs) in these patients. This study investigated the inflammatory and nutritional status in 42 patients with R/M-HNSCC and programmed cell death ligand-1 (PD-L1) polymorphisms (rs4143815 and rs2282055) in 35 of the 42 patients. The 1- and 2-year overall survival was 59.5% and 28.6%, respectively; the 1- and 2-year first progression-free survival was 19.0% and 9.5%, respectively, and the respective second progression-free survival was 50% and 27.8%. Performance status and inflammatory and nutritional status (assessed by the geriatric nutritional risk index, modified Glasgow prognostic score, and prognostic nutritional index) were identified as significant indicators of survival outcomes in multivariate analysis. Patients with ancestral alleles in PD-L1 polymorphisms had less frequent irAEs. Performance status and inflammatory and nutritional status before treatment were closely related to survival outcomes after PD-1 therapy. These indicators can be calculated using routine laboratory data. PD-L1 polymorphisms may be biomarkers for predicting irAEs in patients receiving anti-PD-1 therapy.

[Maxillary Cancer with Metastasis to the Rouviere Nodes -- Complete Response to Chemoradiotherapy Using a Selective Intra-Arterial Infusion Technique].

We report a case of advanced maxillary cancer with multiple lymph node metastases, including metastasis to the Rouviere nodes, which were successfully treated with chemoradiotherapy using a selective intra-arterial infusion technique.A 71-yearold man presented to our hospital with complaints of a staggering gait and epistaxis.He was diagnosed with maxillary cancer (squamous cell carcinoma)classified as T4a disease.Because multiple lymph node metastases were detected, including metastasis to the Rouviere nodes, radical surgical treatment was considered inadequate.Thus, the patient was treated with concurrent chemoradiotherapy with selective intra-arterial infusion of nedaplatin and docetaxel.After chemoradiotherapy, the maxillary cancer and lymph metastasis nearly resolved and the patient achieved a complete response.No additional surgery was needed, and the patient was discharged.We suggest that chemoradiotherapy using a selective intra-arterial infusion technique is a highly effective treatment option for patients with maxillary cancer and metastasis to the Rouviere nodes.