Abstract
Simple SummaryTumors of head and neck cancer are a heterogenous collection of malignancies affecting the upper aerodigestive tract, the majority of which are head and neck squamous cell carcinomas (HNSCCs). Development of immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HNSCCs, albeit only in a minority of patients. Due to the low clinical response rates for HNSCCs and the potential for immune-related adverse side effects, predictive biomarkers are necessary to characterize patients who are most likely to respond to treatment. Previous studies have indicated that patient nutritional status may impact immune response. However, the effects of pretreatment nutritional status, specifically on immunotherapy-treated HNSCC patients, remains unclear. The aim of our study is to explore the associations between baseline prognostic nutritional index and pretreatment body mass index trends on the outcomes of HNSCC patients treated with anti-PD-1 or anti-CTLA-4 immunotherapy, or both.The association between pretreatment nutritional status and immunotherapy response in patients with advanced head and neck cancer is unclear. We retrospectively analyzed a cohort of 99 patients who underwent treatment with anti-PD-1 or anti-CTLA-4 antibodies (or both) for stage IV HNSCC between 2014 and 2020 at the Johns Hopkins Hospital. Patient demographics and clinical characteristics were retrieved from electronic medical records. Baseline prognostic nutritional index (PNI) scores and pretreatment body mass index (BMI) trends were calculated. Associations between PNI and BMI were correlated with overall survival (OS), progression-free survival (PFS), and immunotherapy response. In univariate analysis, there was a significant correlation between OS and PFS with baseline PNI (OS: HR: 0.464; 95% CI: 0.265–0.814; PFS: p = 0.007 and HR: 0.525; 95% CI: 0.341–0.808; p = 0.003). Poor OS was also associated with a greater decrease in pretreatment BMI trend (HR: 0.42; 95% CI: 0.229–0.77; p = 0.005). In multivariate analysis, baseline PNI but not BMI trend was significantly associated with OS and PFS (OS: log (HR) = −0.79, CI: −1.6, −0.03, p = 0.041; PFS: log (HR) = −0.78, CI: −1.4, −0.18, p = 0.011). In conclusion, poor pretreatment nutritional status is associated with negative post-immunotherapy outcomes.
Highlights
Head and neck cancers are a heterogeneous collection of malignancies, typically diagnosed in association with heavy tobacco and alcohol use or infection with the human papillomavirus (HPV) [1]
Among the study cohort of 112 patients with advanced head and neck cancer who underwent immunotherapy, we identified 99 patients who had albumin and absolute lymphocyte count
We have demonstrated that a low baseline prognostic nutritional index (PNI) but not body mass index (BMI) significantly impacts immune checkpoint blockade treatment sensitivity in patients with advanced head and neck cancer, who may be prone to malnutrition
Summary
Head and neck cancers are a heterogeneous collection of malignancies, typically diagnosed in association with heavy tobacco and alcohol use or infection with the human papillomavirus (HPV) [1]. Despite improvements in diagnosis and treatment, prognosis for patients with locally advanced or recurrent or metastatic head and neck squamous cell carcinomas (HNSCCs) remains poor [1,3]. The development of immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 (anti-PD-1) therapies, have demonstrated promising outcomes and improved overall survival in the treatment of advanced head and neck cancer [4,5]. Due to the low clinical response rates for HNSCC and the potential for immune-related adverse side effects, predictive biomarkers are necessary to characterize patients who are most likely to respond to treatment. Other biomarkers have been evaluated, including HPV status, interferon gamma (IFN-γ) signature, neutrophil to lymphocyte ratio (NLR), and the host microbiome status [9], few studies have investigated nutritional status as a potential biomarker or its effects on immunotherapy outcomes in HNSCC. Assessment of nutritional status prior to immunotherapy administration may serve as an additional prognostic tool within the contexts of a patient’s global performance status in predicting treatment outcomes
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