Objectives: To evaluate whether the use of oral stents during intensity modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC) is associated with long-term patient reported symptoms. Materials and methods: Data was obtained from a prospective observational study of disease-free head and neck cancer survivors. Radiation-associated patient reported symptoms were assessed using the MD Anderson Symptom Inventory Head and Neck module (MDASI-HN). Scores of 5 (11-point Likert scale, 0-10) were considered moderate/severe. Stratification was performed regarding IMRT volume (uni-versus bilateral neck) and stent utilization, with non-parametric analyses between groups. Results: 462 OPC survivors formed the cohort (54% tonsil, 46% base of tongue primaries). A tonguedeviating stent was used in 17%, tongue-depressing stent in 46%, and no stent in 37%. Median prescribed dose to the high dose clinical target volume was 66.0 Gy. Median follow-up from RT to MDASI-HN assessment was 68 months. Twenty percent had received unilateral neck RT (all had tonsil primaries), in whom a significant improvement in the proportion of patients with moderate/severe taste impairment (2% vs. 15%, p = 0.047) and lack of appetite (0% vs. 9%, p = 0.019) was associated with the use of tonguedeviating stents compared to no oral stent. In those who had received bilateral neck RT, a significant improvement in the proportion of patients with moderate/severe difficulty swallowing/chewing was associated with use of a tongue-depressing stent (21% vs. 31% without oral stent, p = 0.013). Conclusion: Disease-site specific select use of oral stents during IMRT was associated with reduced longterm patient reported symptoms in OPC survivors.

Immunotherapy has emerged as a novel treatment modality for recurrent/metastatic head and neck cancer (R/M HNC) patients, although overall survival remains poor. Given the reliance of immunotherapy on circulating immune cells, we hypothesized that metabolic signatures of nontumoral hematopoietic tissues derived from quantitative analysis of pre-treatment 18-fluorodeoxyglucose-positron emission tomography-computed tomography (PET/CT) could aid in predicting response to immunotherapy. Materials/Methods: We performed a retrospective analysis of 51 R/M HNC patients treated at a single-institution who received salvage immunotherapy following clinical, pathologic, or radiographic failure after upfront management with adjuvant or definitive radiotherapy. The pretreatment PET/CT closest to immunotherapy initiation (limit of 180 days) was analyzed. Metabolic standardized uptake value (SUV) of predefined nontumoral hematopoietic tissues (liver, spleen and bone marrow) were calculated. Patient demographics including clinical stage, primary disease site, p16 status, and hematologic counts were assessed. Univariable and stepwise multivariable (UVA and MVA, respectively) Cox proportional hazard regression analyses were performed for overall survival (OS) and progression-free survival (PFS). Results: Median follow up is 11.1 months (95% CI 9.7-24). Median OS was 10.8 months (95% CI 7.5-18.9), and median PFS was 3.8 months (95% CI 2.3-10.1). Median time to progression is 6 months (95% CI 3.0-NA). UVA showed worse OS is associated with higher neutrophillymphocyte ratio (NLR) (HR 1.1; 95% CI 1.0-1.1, p<0.01), higher bone marrow SUV mean (BMMean) (HR 7.5; 95% CI 2.3-24.7, p<0.01), and higher bone marrow-liver SUV ratio (BLR) (HR 9.2; 95% CI 1.2-68.3, p Z 0.03). Disease progression was more likely with higher NLR (HR 1.07; 95% CI 1.02-1.12, p<0.01), and higher BMMean (HR 5.72; 95% CI 1.91-17.1, p<0.01). UVA revealed no significant association between PFS or OS and T-stage at diagnosis, performance status, p16 status, tobacco use, and quantitative imaging features of the liver and spleen. On MVA, NLR and BMMean were predictive for OS (HR 1.1; 95% CI 1.0-1.1, p<0.01 and HR 4.8; 95% CI 1.5-15.4, p<0.01, respectively) which was also true for PFS (HR 1.06; 95% CI 1.02-1.10, p<0.01 and HR 4.47; 95% CI 1.53-13.1 p<0.01, respectively). Conclusion: This exploratory analysis identified bone marrow SUV and NLR as important predictors for response to immunotherapy in R/M HNC. Given the limited data maturity, longer follow up in a larger cohort of patients is needed to verify these results. These results suggest that the combination of novel pre-treatment biomarkers may help guide future efforts for treatment intensification in poor-prognosis R/M HNC patients.

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