Obesity and Pathologic Response to Neoadjuvant Immunotherapy in Head and Neck Cancer: Preliminary Results From a Pilot Study

Objective To evaluate associations between obesity and pathologic response to neoadjuvant immune checkpoint inhibitors (ICI) in patients with head and neck squamous cell carcinoma (HNSCC). Methods This was a retrospective cohort study conducted at a single tertiary academic center. We identified 42 patients with HNSCC treated with neoadjuvant ICI with or without chemotherapy. Obesity was defined as body mass index (BMI) ≥ 30 kg/m 2 . The primary outcome was any pathologic response (partial, major, or complete response). Multivariable logistic regression was performed to assess associations between obesity and response, adjusting for smoking status and Eastern Cooperative Oncology Group (ECOG) performance status. BMI was also analyzed as a continuous variable. Adjusted predicted probabilities of response were estimated across BMI. Results Seven patients (17%) were obese. Obese patients had lower rates of pathologic response compared to non‐obese patients (29% vs. 69%). On multivariable analysis, obesity was associated with decreased odds of response (OR 0.10, 95% CI 0.02–0.72; p = 0.021). Increasing BMI was independently associated with lower odds of response, with a 15% decrease per 1 kg/m 2 increase [OR 0.85 (0.72–0.99), p = 0.039]. Adjusted predicted probability of response declined from ~85% at BMI 18 to 25% at BMI 40. In a subset of patients receiving immunotherapy alone, increasing BMI remained associated with decreased response [OR 0.66 (0.44–0.99), p = 0.045]. Conclusion In a small pilot cohort, obesity was associated with decreased pathologic response to neoadjuvant ICI in HNSCC. These findings contrast with the “obesity paradox” observed in recurrent/metastatic settings and suggest the relationship between metabolic state and immunotherapy response may be context‐dependent. Further validation in larger cohorts is needed. Level of Evidence III.