Radiologic predictors of immune checkpoint inhibitor response in advanced head and neck squamous cell carcinoma

Radiologic predictors of response to immune checkpoint blockade (ICPi) in advanced head and neck squamous cell carcinoma (HNSCC) patients could help guide patient selection and management. We analyzed a large institutional cohort of 100 consecutive HNSCC patients treated with ICPi to investigate associations between molecular and radiologic phenotype and assess radiologic predictors of response and survival. Of particular interest was the impact of increased total tumor burden (TB), calculated as the sum of the largest diameter of all measurable lesions according to RECIST 1.1, and early radiologic indicators of response versus progression. Within our cohort, 42% of patients had HPV+ associated disease, 64% had persistent/recurrent head and neck lesions, and 77% had distant metastases. Median TB was 5.4 cm. HPV+ disease and increased total mutational burden were associated with distant disease in the absence of locoregional disease (p < 0.01 and p = 0.03, respectively). Forty patients (40%) demonstrated clinical benefit to ICPi, and the median overall survival (OS) on PD-1 therapy was 4.5 months. A lower tumor burden at baseline was associated with clinical benefit (p = 0.03) and improved OS (p < 0.01, HR 2.33). There was only one instance of pseudoprogression; indeed any increase in TB on first interval scan was associated with poor OS (p = 0.02, HR 2.39). These data suggest that HNSCC patients who benefit from ICPi are more likely to have lower tumor burden at the onset of treatment and minimal increase in tumor burden while on treatment.