Ryan J. Li

Background: Head and neck cancer (HNC) carries high morbidity, and its treatment can be functionally devastating, impacting a patient's ability to work. While most patients have medical insurance benefits, studies on the impact of HNC on overall household finances have been limited. Objectives: This study explored the effect of HNC treatment on household finances and the feasibility of catastrophic income loss insurance. Methods: This cross-sectional study was based on a population-level survey of American adults. Participants, aged 35 to 64 years, were respondents to the US Federal Reserve 2023 Survey on Household Economics and Decisionmaking (SHED). Results: With total income loss, 16% of simulated HNC patients were insolvent after 3 months, rising to 49% at 6 months. With a 50% loss in income, 3% of patients were insolvent at 3 months, increasing to 5% at 6 months. If savings were liquid, 0.5% of patients were insolvent at 3 months, rising to 1.3% at 6 months. Discussion: Our findings underscore the substantial financial vulnerability faced by patients undergoing treatment for HNC. Even in a simulated model based on national economic data, nearly half of patients experiencing total income loss were insolvent by 6 months. Given the intensive and prolonged nature of HNC treatment, these financial challenges may compound physical and psychosocial stressors, affecting overall recovery and quality of life. Conclusion: The model suggested a need for more substantial income loss protection programs. Financial hardship applies to other cancer types and merits further study into the household financial impact of HNC and other cancers.

Background: Head and neck cancer (HNC) carries high morbidity, and its treatment can be functionally devastating, impacting a patient’s ability to work. While most patients have medical insurance benefits, studies on the impact of HNC on overall household finances have been limited. Objectives: This study explored the effect of HNC treatment on household finances and the feasibility of catastrophic income loss insurance. Methods: This cross-sectional study was based on a population-level survey of American adults. Participants, aged 35 to 64 years, were respondents to the US Federal Reserve 2023 Survey on Household Economics and Decisionmaking (SHED). Results: With total income loss, 16% of simulated HNC patients were insolvent after 3 months, rising to 49% at 6 months. With a 50% loss in income, 3% of patients were insolvent at 3 months, increasing to 5% at 6 months. If savings were liquid, 0.5% of patients were insolvent at 3 months, rising to 1.3% at 6 months. Discussion: Our findings underscore the substantial financial vulnerability faced by patients undergoing treatment for HNC. Even in a simulated model based on national economic data, nearly half of patients experiencing total income loss were insolvent by 6 months. Given the intensive and prolonged nature of HNC treatment, these financial challenges may compound physical and psychosocial stressors, affecting overall recovery and quality of life. Conclusion: The model suggested a need for more substantial income loss protection programs. Financial hardship applies to other cancer types and merits further study into the household financial impact of HNC and other cancers.

Key points: Virtual reality (VR) and Fitbit devices are well tolerated by patients after skull base surgery. Postoperative recovery protocols may benefit from incorporation of these devices. However, challenges including patient compliance may impact optimal device utilization.

Background: Massive oropharyngeal bleeding post‐chemoradiotherapy is a life‐threatening condition that requires emergent management.Methods: This retrospective case series included 11 patients with oropharyngeal squamous cell carcinoma who suffered from massive bleeding during or following treatment with definitive chemoradiotherapy. Details of acute and definitive management of oropharyngeal bleeding are reported.Results: Nine of 11 hemorrhagic events occurred a mean (SD) of 88.6 days (53.6) after radiotherapy. Airway intubation and embolization were performed in 10 of 11 patients, followed by surgery in 7 of 11 patients. The most commonly embolized vessels were the external carotid and lingual arteries. At the time of discharge, 3 of 11 patients had a tracheostomy, and 7 of 11 continued to use a gastrostomy tube. Four patients died.Conclusions: Hemorrhagic complications in oropharyngeal cancer treatment require emergent responses. Developing a workflow for coordination between multidisciplinary teams can maximize probability of survival and decrease morbidity.

Importance: Optimal postoperative pain management is challenging. Virtual reality (VR) provides immersive, 3-dimensional experiences that may improve pain control and reduce reliance on pharmacologic pain management.Objective: To evaluate use of VR on postoperative pain management after head and neck surgery.Design, Setting, and Participants: This prospective, pilot randomized clinical trial was conducted at Oregon Health & Science University from July 2020 to October 2021 and included patients hospitalized after major head and neck surgery.Interventions: Similar 15-minute interactive gaming experiences (Angry Birds) using an Oculus Quest VR headset (VR intervention) or a handheld smartphone device (control).Main Outcomes and Measures: The primary outcome was postintervention pain reduction. Pain scores were obtained preintervention, immediately after intervention, and then hourly for 4 hours. Secondary outcomes included changes in opioid use, measured as milligram morphine equivalents (MMEs), and patient experiences with their intervention using 5-point Likert scales.Results: Of the 30 patients randomized for inclusion, the final population included 14 patients in the VR cohort and 15 patients in the control cohort; the majority of patients were male (26 of 29 [90%]), and the mean (SD) age was 58.3 (13.8) years. After outlier removal, there were clinically meaningful reductions in postintervention pain among patients in the VR group immediately after intervention (mean difference, −1.42; 95% CI, −2.15 to −0.70; d = 1.50), at 1 hour (mean difference, −0.86; 95% CI, −1.90 to 0.14; d = 0.67), 2 hours (mean difference, −1.07; 95% CI, −2.30 to 0.14; d = 0.69), and 3 hours (mean difference, −1.36; 95% CI, −2.80 to 0.13; d = 0.71) compared with patients in the control group. Patients in the VR group also demonstrated reductions in 4-hour postintervention opioid use compared with 4-hour preintervention opioid use (mean difference, −9.10 MME; 95% CI, −15.00 to −1.27 MME; d = 0.90) and 8-hour postintervention opioid use compared with 8-hour preintervention opioid use (mean difference, −14.00 MME; 95% CI, −25.60 to −2.40 MME; d = 0.94). There were no meaningful differences in subjective patient experiences with their respective interventions.Conclusions and Relevance: In this randomized clinical trial, VR reduced pain scores and opioid use compared with a control intervention. Virtual reality may be a useful adjunct for postoperative pain management after head and neck surgery.Trial Registration: ClinicalTrials.gov Identifier: NCT04464304

In this study, we report a differential response of mitogen-activated protein kinase–kinase (MEK) inhibitor trametinib in 20 head and neck squamous cell carcinoma (HNSCC) patients’ tumor-derived cell cultures. Relatively sensitive and resistant cases to trametinib were identified using high throughput metabolic assays and validated in extended dose response studies in vitro. High throughput metabolic assays exploring combination therapies with trametinib were subjected to synergy models and maximal synergistic dose analyses. These yielded several candidates, including axtinib, GDC-0032, GSK-690693, and SGX-523. The combination regimen of trametinib and AXL/MET/VEGFR inhibitor glesatinib showed initial efficacy both in vitro and in vivo (92% reduction in tumor volume). Sensitivity was validated in vivo in a patient-derived xenograft (PDX) model in which trametinib as a single agent effected reduction in tumor volume up to 72%. Reverse Phase Protein Arrays (RPPA) demonstrated differentially expressed proteins and phosphoproteins upon trametinib treatment. Furthermore, resistant cell lines showed a compensatory mechanism via increases in MAPK and non-MAPK pathway proteins that may represent targets for future combination regimens. Intrinsic-targeted options have potential to address paucity of medical treatment options for HNSCC cancer patients, enhance response to extrinsic targeted agents, and/or reduce morbidity as neoadjuvant to surgical treatments.

The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of Fusobacterium and Peptostreptococcus in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, Fusobacterium nucleatum abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of F. nucleatum was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes LXN and SMARCA2, for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host–microbe interactions between F. nucleatum enrichment and clinical outcomes or host gene methylation imply a potential role of F. nucleatum as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.