Simple Summary Immunotherapy may induce early treatment response in head and neck squamous cell carcinoma (HNSCC) for some patients. Routine imaging parameters fail to diagnose these responses;... Show moreSimple Summary Immunotherapy may induce early treatment response in head and neck squamous cell carcinoma (HNSCC) for some patients. Routine imaging parameters fail to diagnose these responses; however, magnetic resonance (MR) diffusion-weighted imaging (DWI) may be able to do so. This study sought to correlate DWI parameters with treatment response early after immunotherapy treatment in HNSCC. We analyzed 24 patients with advanced HNSCC with imaging before and after the immunotherapy. We found that rounder tumors that were smaller in diameter before treatment were more likely to respond. A decrease in skewness of the tumor after treatment compared to before treatment, as well as an overall low skewness post-treatment, were linked to better treatment response. Though this study was explorative in nature, these results are promising for the predictive use of MR-DWI in HNSCC treated with immunotherapy. Background: Neoadjuvant immune checkpoint blockade (ICB) prior to surgery may induce early pathological responses in head and neck squamous cell carcinoma (HNSCC) patients. Routine imaging parameters fail to diagnose these responses early on. Magnetic resonance (MR) diffusion-weighted imaging (DWI) has proven to be useful for detecting HNSCC tumor mass after (chemo)radiation therapy. METHODS: 32 patients with stage II-IV, resectable HNSCC, treated at a phase Ib/IIa IMCISION trial (NCT03003637), were retrospectively analyzed using MR-imaging before and after two doses of single agent nivolumab (anti-PD-1) (n = 6) or nivolumab with ipilimumab (anti-CTLA-4) ICB (n = 26). The primary tumors were delineated pre- and post-treatment. A total of 32 features were derived from the delineation and correlated with the tumor regression percentage in the surgical specimen. Results: MR-DWI data was available for 24 of 32 patients. Smaller baseline tumor diameter (p = 0.01-0.04) and higher sphericity (p = 0.03) were predictive of having a good pathological response to ICB. Post-treatment skewness and the change in skewness between MRIs were negatively correlated with the tumor's regression (p = 0.04, p = 0.02). Conclusion: Pre-treatment DWI tumor diameter and sphericity may be quantitative biomarkers for the prediction of an early pathological response to ICB. Furthermore, our data indicate that ADC skewness could be a marker for individual response evaluation. Show less
