Body Mass Index and Nutritional Status With Immunotherapy Response in Head and Neck Cancer

Importance: Malnutrition, common in patients with head and neck squamous cell carcinoma (HNSCC), may impair the effectiveness of immunotherapy. Understanding whether nutritional status affects outcomes can emphasize the importance of pretreatment nutritional optimization. Objective: To evaluate the associations of body mass index (BMI), pretreatment BMI change, and prognostic nutritional index (PNI) with progression-free survival (PFS) in patients with advanced HNSCC treated with immunotherapy. Design, Setting, and Participants: Cohort study using deidentified electronic health records from the Flatiron Health database between January 2014 to January 2024, with follow-up of 3000 days in multiple cancer institutions across the US. Patients were from community and academic practices in the US, diagnosed with all types of advanced head and neck cancer who received immunotherapy (nivolumab, pembrolizumab, cemiplimab, durvalumab, atezolizumab, avelumab, or ipilimumab) between January 2014 and January 2024. Exclusion criteria included age younger than 18 years, patients without a diagnosis of squamous cell carcinoma, missing stage information, missing treatment information (eg, a gap in documented care of ≥90 days or more), and incomplete data needed to calculate BMI or PNI prior to initiation of therapy. Exposures: Baseline BMI, pretreatment BMI change (≥2% decrease vs stable), and PNI (low <45 vs normal ≥45). Main Outcomes and Measures: PFS following treatment with immunotherapy. Results: Among 1108 patients (mean [SD] age, 66.2 [10.2] years; 236 [21.3%] female; 872 [78.7%] male), 214 (79%) experienced 2% or more pretreatment BMI loss. BMI loss was associated with worse PFS (hazard ratio, 1.17; 95% CI, 1.02-1.35); median PFS was 271 (IQR, 121-603) days with loss vs 415 days with stable BMI. In the 471 patients with laboratory data, 320 (67.9%) had a low PNI. Low PNI was associated with shorter PFS (adjusted hazard ratio, 1.58; 95% CI, 1.39-1.79); median PFS was 213 (IQR, 98-445) days for low vs 566 (IQR, 307-1094) days for patients with a normal PNI. Baseline BMI category was not independently associated with PFS. Conclusions and Relevance: In this large, nationally representative cohort of patients with advanced head and neck squamous cell carcinoma treated with immunotherapy, pretreatment BMI loss and low PNI were independently associated with PFS, while baseline BMI was not. These findings suggest that dynamic measures of nutrition and immune status provide more meaningful prognostic information than static measures. Nutritional optimization may represent a modifiable factor to improve outcomes in patients receiving immunotherapy for advanced head and neck squamous cell carcinoma.