Background: There is increasing evidence that immunotherapy with nivolumab, an anti‐programmed death 1 monoclonal antibody, is effective in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the predictive role of hematological inflammatory markers such as neutrophil‐to‐lymphocyte ratio (NLR) and the modified Glasgow prognostic score (mGPS) in patients with R/M SCCHN treated with nivolumab remains unclear.Methods: We conducted a multi‐institutional cohort study to evaluate the impact of pretreatment NLR and mGPS on overall survival (OS) and progression‐free survival (PFS) in patients with R/M SCCHN treated with nivolumab in Japan. From 2012 to 2013, 102 patients were eligible, of whom 88 were finally included in the analysis. mGPS was calculated as follows: mGPS of 0, C‐reactive protein (CRP) ≤1.0 mg/dL; 1, CRP > 1.0 mg/dL; and 2, CRP > 1.0 mg/dL and albumin < 3.5 mg/dL. Optimal cutoff point of dichotomized NLR was calculated using the area under the receiver operating characteristic curve (AUROC). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox proportional hazard models adjusted by potential confounders.Results: Higher NLR was significantly associated with worse survival (1‐year OS: 45.3% vs 16.3%, log‐rank P‐value < .001, adjusted HR: 4.40 (95% CIs: 1.78‐10.88); one‐year PFS: 39.1% vs 9.0%, P‐value = .001, adjusted HR: 3.37 (95% CI: 1.64‐6.92)). In addition, high mGPS (=2) was significantly associated with worse survival compared to low mGPS (=0) (1‐year OS: 37.4% vs 26.1%, P‐value = .004, adjusted HR: 4.20 (95% CI:1.54‐11.49); 1‐year PFS: 41.5% vs 24.8%, P‐value = .007, adjusted HR: 2.01 (95% CI: 0.87‐4.68)). These associations were consistent with subgroup analyses stratified by potential confounders.Conclusions: Pretreatment NLR and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with nivolumab.

No real-world, long-term outcomes of immunotherapy with nivolumab for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have yet been reported. Furthermore, the prognostic impact of the best overall response (BOR) of this therapy remains unclear. We conducted a multi-institutional cohort study of the long-term efficacy and safety of this therapy and investigated prognostic factors associated with survival. Further, we evaluated the relationship between BOR and survival. Median follow-up time was 25.9 months. Median overall survival (OS) was 9.6 months, and two-year survival rate was 25.0%. Median progression-free survival (PFS) was 3.7 months, and two-year PFS rate was 19.6%. BOR was assessed as complete response (CR) in 6%, partial response (PR) in 13%, stable disease (SD) in 30%, and progressive disease (PD) in 52% of the patients. Overall response rate was 18%, and disease control rate was 48%. For immune-related adverse events (irAEs), 38 irAEs were detected in 29 patients. On multivariate analysis, the development of irAEs was significantly associated with better OS and PFS. Better BOR was significantly associated with longer OS and PFS. These findings demonstrate the long-term efficacy and safety of nivolumab therapy for R/M SCCHN in a real-world setting. The magnitude of BOR and the development of irAEs might be useful surrogate markers of survival.

Background/Aim: The predictive role of hematological markers in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) treated with pembrolizumab remains unclear. Patients and Methods: We conducted a multicenter retrospective cohort study to investigate the predictive impact of the pre-treatment hematological markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP-albumin-lymphocyte (CALLY) index, and the modified Glasgow prognostic score (mGPS) on overall survival (OS) and progression-free survival (PFS) in patients with R/M SCCHN treated with pembrolizumab. From December 2019 to February 2022, 119 and 28 patients were treated with pembrolizumab alone and pembrolizumab plus chemotherapy, respectively. The optimal cut-off point of dichotomized hematological markers was calculated using the area under the receiver operating characteristic curve. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders. Results: In the pembrolizumab monotherapy group, patients with higher NLR, PLR, and mGPS and a lower CALLY index showed significantly shorter OS after adjustment for potential confounders. In addition, all hematological markers examined in this study tended to be associated with clinical response, such as overall response rate or disease control rate (DCR); in particular, a lower CALLY index and higher mGPS were significantly associated with poor DCR. In the pembrolizumab with chemotherapy group, these hematological markers had a similar association with OS but not with clinical response. Conclusion: Pre-treatment NLR, PLR, CALLY index, and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with pembrolizumab.

Background: Disseminated cryptococcosis is a well-characterized complication in immunocompromised patients with cryptococcal pneumonia or meningitis; however, isolated cryptococcal osteomyelitis is a rare entity that occurs in approximately 5% of patients with cryptococcosis. Cryptococcal osteomyelitis in the head and neck region is extremely rare. To the best of our knowledge, no cases of cryptococcal osteomyelitis affecting only the zygomatic bone have been reported to date. Case presentation: A 78-year-old man without other comorbidities presented with progressive swelling of the right cheek along with pain and trismus. Clinical examination revealed a tender swelling in the right zygomatic region; the maximal mandibular opening was about 2 cm. Laboratory data showed mildly elevated inflammatory indices (C-reactive protein: 0.45 mg/dL; erythrocyte sedimentation rate: 35 mm/h). Computed tomography showed a 30-mm-diameter lesion at the right zygomatic arch. A part of the lesion has extended to the subcutaneous area of the cheeks with signs of bone destruction and surrounding contrast effects. Histopathological examination of fine-needle aspirate and needle biopsy showed cryptococcus. Furthermore, culture of the aspirate showed growth of Cryptococcus neoformans. No evidence of any other site involvement was observed. Therefore, the patient was diagnosed with isolated cryptococcal osteomyelitis and was initiated on fluconazole therapy. The treatment was effective, and all symptoms were resolved in 4 weeks. Fluconazole therapy was stopped after 6 months. There are no signs of recurrence as of 15-month follow-up. The patient has no cosmetic abnormalities or sequelae. Conclusions: Fine-needle aspiration cytology, needle biopsy, and fungal culture were useful for definitive diagnosis. Immunocompetent patients with isolated osteomyelitis may be cured with oral fluconazole alone.