Purpose/Objective Stereotactic Radiation Therapy (SBRT) has been implemented for re-iradiation of recurrent or second primary cancers of the head and neck to improve the therapeutic ratio in this difficult scenario. We reviewed our experience at a single institution. Material/Methods After IRB approval, a database of patients receiving re-irradiation was queried. Patients were excluded if receiving conventionally fractionated radiotherapy (RT), non-squamous histology, were enrolled on non-published clinical trials, or metastatic disease. All patients were seen in a multi-disciplinary clinic and/or reviewed in multi-disciplinary tumor board. All patients were ineligible for or refused surgical intervention. Patients were simulated with thermoplastic masks and 2 mm cuts on CT scan with and without contrast. Additional imaging including PET and/or MRI were fused. Gross tumor volume (GTV) was delineated and expanded 2-3 mm for the planning target volume. Elective nodes were not targeted. Minimum dose to PTV was 90% of prescription, with 110 - 130% prescription allowed within GTV/PTV. SBRT was delivered every other day for 5 fractions, with daily cone beam CT imaging, and 6 degree of freedom couch correction. Locoregional control (LRC), progression free survival (PFS), and overall survival (OS) were calculated from the end of RT and estimated via Kaplan-Meier method and comparisons made via log-rank test. Multi-variate cox regression model of OS was performed. Acute (during within three months from completion of treatment) and late (three or more months from completion of treatment) grade 3-5 CTCAE toxicities were collected. Results A total of 76 patients were available for analysis, with a median follow up of 31.5 months for patients alive at last contact, and 12 months for the entire cohort. Median age was 66 (range 36 – 92) with a median RT interval of 29.5 months (range 5 -315). Median dose of initial RT was 70 Gy (range 44 – 79.2 Gy). The majority of patients were former smokers (n=45, 59.2%), followed by never smokers (n=20, 26.3%), and current smokers (n=11, 14.5%). There were 56 men (73.7%) and 20 women (26.3%). Performance status was zero (n=22, 28.9%) and 1-2 (n=54, 71.1%), with 50 patients being recurrent (65.8%) and 26 having a second primary (34.2%). All patients were treated with 5 fractions to a median dose of 40 Gy (range 25 – 40 Gy). Systemic therapy was utilized in 29 patients (38.2%), primarily concurrently (n=27). Concurrent systemic therapy was cisplatin (n=20, 26.3%), cetuximab (n=4, 5.3%), or immunotherapy (n=3, 3.9%). Median gross tumor volume (GTV) was 11.42 cc (range 0.93 – 58.31 cc). Acute grade 3-4 toxicity was seen in 5 patients (6.6%), consisting of feeding tube in 2, aspiration pneumonia in 1, tracheostomy in 1, and stroke in 1. Actuarial rates for the entire cohort at 1 and 2-years for LRC were 43.5% and 33.3%, for PFS, 40.6% and 31.1%, and OS 49.6% and 33.1%. On univariate analysis median GTV, treatment site (nasopharynx/base of skull/neck/skin vs other), and recurrence were prognostic for OS. On multivariate analysis, GTV (HR 1.037, 95% CI 1.018 – 1.056, p < 0.001) and recurrent disease (HR 0.344, 95% CI 0.194 – 0.609, p < 0.001). For the subset of patients (n=26) with a GTV ≤ 11.4 cc and recurrent disease, 2-year OS was 80.1% with a median OS of 37 months. Of 73 patients followed for more than 3 months post treatment, 15 (20.5%) developed a late grade 3-4 toxicity, including feeding tubes in 7, aspiration pneumonia in 3, soft tissue necrosis in 3, or a cranial neve deficit in 3. Conclusion SBRT for re-irradiation for patients with smaller, recurrent squamous cell carcinomas of the head and neck had the best performance. While severe acute toxicities are low, additional studies are needed to improve survival and decrease the risk of late toxicity.

BackgroundThere has been limited study of oncology professionals' perspectives on optimizing delivery of presurgical education for individuals with head and neck cancer (HNC). Therefore, we assessed oncology professionals' perspectives about presurgical education for laryngectomy and free flap surgeries, which have a significant impact on patients' quality of life.MethodsInterviews were conducted with 27 oncology professionals from an NCI-designated Comprehensive Cancer Center and a community oncology setting.ResultsParticipants identified six recommendations to improve presurgical education: (1) establishing preoperative consultations with allied health professionals; (2) educating patients and providers on the concept of team-based care; (3) optimizing education through multimodal strategies; (4) connecting patients with other HNC surgical patients; (5) preparing caregivers for their role; and (6) educating patients on insurance navigation.ConclusionsStudy findings demonstrate gaps in the timing, content, and mode of delivery for presurgical education and suggest strategies for further evaluation in future studies.

Introduction: Myxopapillary ependymomas are WHO grade 2 slow-growing glial tumors that typically are found in young adults and are slightly more common in males than in females. The vast majority of these tumors are located in the lumbosacral or thoracolumbar spine. Nevertheless, these tumors have the propensity for seeding of the neuraxis.

Despite the critical need, progress in developing cell-free DNA (cfDNA) liquid biopsy biomarkers for the diagnosis and risk stratification of head and neck squamous cell carcinoma (HNSC) has been limited. In this study, we present a comprehensive paired-sample differential methylation region (psDMR) analysis in HNSC, aimed at identifying reliable and HNSC-specific regions for cfDNA biomarker discovery. Traditional DMR analyses often overlook paired-sample information and fail to account for the heterogeneity within HNSC tissues. Our findings reveal a substantial overlap of hypermethylated DMRs across two independent HNSC methylation datasets, demonstrating the robustness and clinical relevance of these regions for cfDNA biomarker development. Furthermore, we identified consistent DMRs in both HNSC and lung squamous cell carcinoma (LSCC), suggesting the potential for pan-squamous cell carcinoma biomarkers. Notably, gene clusters such as HOXD, ZNF, and NKX2 were frequently hypermethylated, providing new insights into the shared epigenetic landscape of HNSC and LSCC. This study underscores the importance of incorporating matched normal tissues in cancer methylome analyses and establishes a foundation for advancing cfDNA-based biomarker discovery across squamous cell carcinomas.

e18028 Background: Metastatic HNSCC continues to have very poor prognosis. Only a fraction of patients respond to immune checkpoint blocker therapy (ICB), with no effective treatment options for non-responders. Gut microbial composition and diversity have been associated with response to ICB in many cancers including HNSCC. We have previously demonstrated that TRE significantly improved progression free survival via modulation of gut microbiota. We herein report our mechanistic data demonstrating critical role of microbially mediated butyric and tryptophan metabolic pathways in augmenting antitumor immune response to ICB. Methods: Paired blood and stool samples, at baseline and at first response assessment, from 43 HNSCC patients enrolled in the TRE study (NCT05083416) was collected and analyzed using untargeted and targeted metabolomics, focusing on tryptophan and short chain fatty acid pathway. Further shot gun metagenomic sequencing was conducted on stool samples. Finally, we performed an in vitro luciferase cytotoxicity assay using SCC-4 human cancer cells to demonstrate TRE mediated antitumor immune response. We co-cultured MHC-I and NY-ESO-1, and NY-ESO-1-specific TCR-transduced T cells. tumor cells and the T cells under different conditions of butyrate concentration and T cell-to-tumor cell ratio (1:5, 1:10) and evaluated T cell mediated tumors killing. Results: We noted significantly higher abundance of clostridium butyricum (OR-1004, p-0.0002) with corresponding higher expression of butyrate kinase enzyme in stool of patients who observed TRE (OR-1.9, p-0.0003) vs those who did not, leading to higher concentration of fecal butyric acid and hydroxy indole acetic acid (HIAA) (OR-4.2, p-0.003), both of which were independently associated with longer progression free survival (HR-0.9, p<0.01). Higher abundance of butyric acid in gut is known to enhance the gut barrier function with consequent decrease in plasma butyrate and HIAA, lower systemic levels of which, was found to be associated with longer progression free survival in our cohort (OR-0.9, p-0.05). Both butyrate and 5HIAA are known activators of immunosuppressive aryl hydrocarbon receptor (AhR) expressed on cytotoxic CD8T cells, inhibiting CD8 mediated antitumor response. In line with our hypothesis, we observed that butyrate and 5HIAA impaired CD8 T mediated T cell killing of tumor cells in a dose-dependent manner. Conclusions: These results suggest that TRE favorably modulates ICB response via enrichment of gut microbiota with butyrate producing microbial organism, leading to increased abundance of gut butyrate and microbial tryptophan metabolites and their consequent reduction in systemic circulation, ultimately enhancing antitumor immune response.

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.

Purpose Patients with head and neck cancer (HNC) experience significant symptom burden from combination chemotherapy and radiation (chemoradiation) that affects acute and long-term health-related quality of life (HRQOL). However, psychosocial impacts of HNC symptom burden are not well understood. This study examined psychosocial consequences of treatment-related symptom burden from the perspectives of survivors of HNC and HNC healthcare providers. Methods This was a cross-sectional, mixed-method study conducted at an NCI-designated comprehensive cancer center. Participants ( N = 33) were survivors of HNC who completed a full course of chemoradiation ( n = 20) and HNC healthcare providers ( n = 13). Participants completed electronic surveys and semi-structured interviews. Results Survivors were M = 61 years old (SD = 9) and predominantly male (75%), White (90%), non-Hispanic (100%), and diagnosed with oropharynx cancer (70%). Providers were mostly female (62%), White (46%) or Asian (31%), and non-Hispanic (85%) and included physicians, registered nurses, an advanced practice nurse practitioner, a registered dietician, and a speech-language pathologist. Three qualitative themes emerged: (1) shock, shame, and self-consciousness, (2) diminished relationship satisfaction, and (3) lack of confidence at work. A subset of survivors (20%) reported clinically low social wellbeing, and more than one-third of survivors (35%) reported clinically significant fatigue, depression, anxiety, and cognitive dysfunction. Conclusion Survivors of HNC and HNC providers described how treatment-related symptom burden impacts psychosocial identity processes related to body image, patient-caregiver relationships, and professional work. Results can inform the development of supportive interventions to assist survivors and caregivers with navigating the psychosocial challenges of HNC treatment and survivorship.

PURPOSE: There has been limited study of the implementation of suicide risk screening for patients with head and neck cancer (HNC) as a part of routine care. To address this gap, this study assessed oncology providers' and professionals' perspectives about barriers and facilitators of implementing a suicide risk screening among patients with HNC. MATERIALS AND METHODS: All patients with HNC with an in-person visit completed a suicide risk screening on an electronic tablet. Patients reporting passive death wish were then screened for active suicidal ideation and referred for appropriate intervention. Interviews were conducted with 25 oncology providers and professionals who played a key role in implementation including nurses, medical assistants, patient access representatives, advanced practice providers, physicians, social workers, and informatics staff. The interview guide was based on the Consolidated Framework for Implementation Research. Interviews were transcribed and analyzed for themes. RESULTS: Participants identified multilevel implementation barriers, such as intervention level (eg, patient difficulty with using a tablet), process level (eg, limited nursing engagement), organizational level (eg, limited clinic Wi-Fi connectivity), and individual level (eg, low clinician self-efficacy for interpreting and acting upon patient-reported outcome scores). Participants noted facilitators, such as effective care coordination across nursing and social work staff and the opportunity for patients to be screened multiple times. Participants recommended strengthening patient and clinician education and providing patients with other modalities for data entry (eg, desktop computer in the waiting room). CONCLUSION: Participants identified important intervention modifications that may be needed to optimize suicide risk screening in cancer care settings.

e13681 Background: The onset of the coronavirus disease 2019 (COVID-19) pandemic changed the landscape of oncology practice and placed tele-oncology at the center of cancer care delivery. As tele-oncology will likely remain a key part of cancer care delivery, healthcare organizations need to determine how to implement tele-oncology programs. We conducted an instrumental case study at a National Cancer Institutes -designated comprehensive cancer center that successfully implemented tele-oncology. Methods: Data were collected from three sources between June 2020–February 2022. We conducted semi-structured interviews among stakeholders directly involved in implementing and/or managing tele-oncology and surveys of administrators of the center’s tele-oncology and clinicians who used the program. Document analysis of implementation deliverables were also analyzed. Data collection and analyses were guided by the Consolidated Framework for Implementation Research, and Clinical Transformation in Technology. We used the Implementation Research Logic Model (IRLM) to develop a framework depicting determinants and key steps for implementing tele-oncology. Results: We interviewed 40 clinicians. We also invited 364 employees to complete online surveys, of which 151 (41.5%) responded. Most respondents were physicians (41.7%), nurse practitioners (26.5%), or physician assistants (26.5%). To implement tele-oncology program, three elements should be considered: (1) platform, (2) people, and (3) process. We found hospitals should: 1) adopt a safe and adaptable platform to deliver tele-oncology; 2) build a multidisciplinary tele-oncology team to provide the administrative, legal, workflow, and clinical support; 3) provide training and resources to make sure all the team members can deliver their responsibilities; 4) identify and appreciate early adopters, departments, and clinicians with successful experiences; 5) frequently evaluate the clinical and implementation outcomes; 6) secure reimbursement comparable with in-person rate and ; 7) advocate for policies that are supportive of tele-oncology in the future. Conclusions: Using IRLM we presented the tele-oncology implementation framework that can be used by hospitals around the world to implement their own tele-oncology.

IMPORTANCE Patients with cancer typically have greater financial hardships and time costs than individuals without cancer. The COVID-19 pandemic has exacerbated this, while posing substantial challenges to delivering cancer care and resulting in important changes in care-delivery models, including the rapid adoption of telehealth. OBJECTIVE To estimate patient travel, time, and cost savings associated with telehealth for cancer care delivery. DESIGN, SETTING, AND PARTICIPANTS An economic evaluation of cost savings from completed telehealth visits from April 1, 2020, to June 30, 2021, in a single-institution National Cancer Institute-Designated Comprehensive Cancer Center. All patients aged 18 to 65 years who completed telehealth visits within the designated time frame and had a Florida mailing address documented in their electronic medical record were included in the study cohort. Data were analyzed from April 2020 to June 2021. MAIN OUTCOMES AND MEASURES The main outcome was estimated patient cost savings from telehealth, which included 2 components: costs of travel (defined as roundtrip distance saved from car travel) and potential loss of productivity due to the medical visit (defined as loss of income from roundtrip travel plus loss of income from in-person clinic visits). Two different models with a combination of 2 different mileage rates ($0.56 and $0.82 per mile) and census tract-level median hourly wages were used. RESULTS The study included 25496 telehealth visits with 11688 patients. There were 4525 (3795 patients) new or established visits and 20971 (10049 patients) follow-up visits. Median (IQR) age was 55.0 (46.0-61.0) years among the telehealth visits, with 15663 visits (61.4%) by women and 18360 visits (72.0%) by Hispanic non-White patients. According to cost models, the estimated mean (SD) total cost savings ranged from $147.4 ($120.1) at $0.56/mile to $186.1 ($156.9) at $0.82/mile. For new or established visits, the mean (SD) total cost savings per visit ranged from $176.6 ($136.3) at $0.56/mile to $222.8 ($177.4) at $0.82/mile, and for follow-up visits, the mean (SD) total cost savings per visit was $141.1 ($115.3) at $0.56/mile to $178.1 ($150.9) at $0.82/mile. CONCLUSIONS AND RELEVANCE In this economic evaluation, telehealth was associated with savings in patients time and travel costs, which may reduce the financial toxicity of cancer care. Expansion of telehealth oncology services may be an effective strategy to reduce the financial burden among patients with cancer.

BACKGROUND:Adverse pathological features following surgery in head and neck squamous cell carcinoma (HNSCC) are strongly associated with survival and guide adjuvant therapy. We investigated molecular changes associated with these features. METHODS:We downloaded data from the Cancer Genome Atlas and Cancer Proteome Atlas HNSCC cohorts. We compared tumors positive versus negative for perineural invasion (PNI), lymphovascular invasion (LVI), extracapsular spread (ECS), and positive margins (PSM), with multivariable analysis. RESULTS:All pathological features were associated with poor survival, as were the following molecular changes: low cyclin E1 (HR = 1.7) and high PKC-alpha (HR = 1.8) in tumors with PNI; six of 13 protein abundance changes with LVI; greater tumor hypoxia and high Raptor (HR = 2.0) and Rictor (HR = 1.6) with ECS; and low p38 (HR = 2.3), high fibronectin (HR = 1.6), low annexin A1 (HR = 3.1), and high caspase-9 (HR = 1.6) abundances with PSM. CONCLUSIONS:Pathological features in HNSCC carry specific molecular changes that may explain their poor prognostic associations.

Head and neck squamous cell carcinoma (HNSCC), a highly heterogeneous disease that involves multiple anatomic sites, is a leading cause of cancer-related mortality worldwide. Although the utility of noninvasive biomarkers based on circulating cell-free DNA (cfDNA) methylation profiling has been widely recognized, limited studies have been reported so far regarding the dynamics of cfDNA methylome in oral cavity squamous cell carcinoma (OCSCC). It is hypothesized in this study that comparison of methylation profiles in pre- and postsurgery plasma samples will reveal OCSCC-specific prognostic and diagnostic biomarkers. As a strategy to further prioritize tumor-specific targets, top differential methylated regions (DMRs) were called by reanalyzing methylation data from paired tumor and normal tissue collected in the the cancer genome atlas head-neck squamous cell carcinoma (TCGA) head and neck cancer cohort. Matched plasma samples from eight patients with OCSCC were collected at Moffitt Cancer Center before and after surgical resection. Plasma-derived cfDNA was analyzed by cfMBD-seq, which is a high-sensitive methylation profiling assay. Differential methylation analysis was then performed based on the matched samples profiled. In the top 200 HNSCC-specific DMRs detected based on the TCGA data set, a total of 23 regions reached significance in the plasma-based DMR test. The top five validated DMR regions (ranked by the significance in the plasma study) are located in the promoter regions of genes PENK, NXPH1, ZIK1, TBXT, and CDO1, respectively. The genome-wide cfDNA DMR analysis further highlighted candidate biomarkers located in genes SFRP4, SOX1, IRF4, and PCDH17. The prognostic relevance of candidate genes was confirmed by survival analysis using the TCGA data. This study supports the utility of cfDNA-based methylome profiling as a promising noninvasive biomarker source for OCSCC and HNSCC.

Background: Patients with cancer require timely access to care so that healthcare providers can prepare an optimal treatment plan with significant implications for quality of life and mortality. The COVID-19 pandemic spurred rapid adoption of telemedicine in oncology, but study of patient experience of care with telemedicine in this population has been limited. We assessed overall patient experience of care with telemedicine at an NCI-designated Comprehensive Cancer Center during the COVID-19 pandemic and examined changes in patient experience over time. Patients and Methods: This was a retrospective study of outpatient oncology patients who received treatment at Moffitt Cancer Center. Press Ganey surveys were used to assess patient experience. Data from patients with appointments between April 1, 2020, and June 30, 2021, were analyzed. Patient experience was compared between telemedicine and in-person visits, and patient experience with telemedicine over time was described. Results: A total of 33,318 patients reported Press Ganey data for in-person visits, and 5,950 reported Press Ganey data for telemedicine visits. Relative to patients with in-person visits, more patients with telemedicine visits gave higher satisfaction ratings for access (62.5% vs 75.8%, respectively) and care provider concern (84.2% vs 90.7%, respectively) ( P <.001). When adjusted for age, race/ethnicity, sex, insurance, and clinic type, telemedicine visits consistently outperformed in-person visits over time regarding access and care provider concern ( P <.001). There were no significant changes over time in satisfaction with telemedicine visits regarding access, care provider concern, telemedicine technology, or overall assessment ( P >.05). Conclusions: In this study, a large oncology dataset showed that telemedicine resulted in better patient experience of care in terms of access and care provider concern compared with in-person visits. Patient experience of care with telemedicine visits did not change over time, suggesting that implementing telemedicine was effective.

BACKGROUND The onset of the coronavirus disease 2019 (COVID-19) pandemic changed the landscape of oncology practice and placed tele-oncology at the center of cancer care delivery. As tele-oncology will likely remain a key part of cancer care delivery, healthcare organizations need to determine how to implement tele-oncology programs. OBJECTIVE We conducted an instrumental case study at a National Cancer Institute-designated Comprehensive Cancer Center that successfully implemented tele-oncology. METHODS Data were collected from three sources between June 2020–February 2022. We conducted semi-structured interviews among clinicians directly involved in implementing and/or managing tele-oncology and surveys of administrators of the center’s tele-oncology and clinicians who used the program. Document analysis of implementation deliverables was also analyzed. Data collection and analyses were guided by the Consolidated Framework for Implementation Research. We used the Implementation Research Logic Model to develop a framework depicting determinants and key steps for implementing tele-oncology. RESULTS We interviewed 40 clinicians. Of 364 employees invited to complete online surveys, 151 (41.5%) responded. We found that hospitals should: 1) adopt an easy-to-use and adaptable platform to deliver tele-oncology; 2) build a multidisciplinary tele-oncology team to provide the administrative, legal, workflow, and clinical support; 3) provide training and resources to ensure all team members can complete their responsibilities; 4) identify early adopters, departments, and clinicians with successful experiences; 5) evaluate clinical and implementation outcomes frequently; 6) advocate for policies that are supportive of tele-oncology in the future. CONCLUSIONS We presented the tele-oncology implementation framework that can be used by hospitals to implement tele-oncology. CLINICALTRIAL N/A

INTRODUCTION:The COVID-19 pandemic led to telemedicine adoption for many medical specialties, including surgical cancer care. To date, the evidence for patient experience of telemedicine among patients with cancer undergoing surgery is limited to quantitative surveys. Thus, this study qualitatively assessed the patient and caregiver experience of telehealth visits for surgical cancer care. METHODS:We conducted semistructured interviews with 25 patients with cancer and three caregivers who had completed a telehealth visit for preanesthesia or postoperative visits. Interviews covered visit descriptions, overall satisfaction, system experience, visit quality, what roles caregivers had, and thoughts on what types of surgery-related visits would be appropriate through telehealth versus in-person. RESULTS:Telehealth delivery for surgical cancer care was generally viewed positively. Multiple factors influenced the patient experience, including prior experience with telemedicine, ease of scheduling visits, smooth connection experiences, having access to technical support, high communication quality, and visit thoroughness. Participants identified use cases on telehealth for surgical cancer care, including postoperative visits for uncomplicated surgical procedures and educational visits. CONCLUSIONS:Patient experiences with telehealth for surgical care are influenced by smooth system experiences, high-quality patient-clinician communications, and a patient-centered focus. Interventions are needed to optimize telehealth delivery (e.g., improve telemedicine platform usability).

6051 Background: Advanced head and neck cancer continues to have very poor prognosis. Only a fraction of patients respond to immune checkpoint blocker therapy (ICB), with no effective treatment options for non-responders. Gut microbiome composition and diversity have been associated with response to ICB in many cancers including HNSCC. We, therefore hypothesized that modulation of gut microbiota may improve response to ICB. Time restricted eating represents an attractive strategy to favorably alter the microbiome and improve ICB responses. We conducted a phase I/II nonrandomized study to evaluate safety, feasibility and efficacy of TRE in improving response rates in treatment naïve metastatic HNSCC patients receiving single agent ICB. Methods: TRE is a form of circadian aligned nightly fast of 14 hours without reduction in calories. Patients were assigned to TRE vs control in 1:2 ratio, with first response evaluation at 12+/- 3 weeks as end point. Compliance to TRE was monitored via an app (“my circadian app”) and daily food logs. Blood and stool samples were collected at therapy initiation, at 1 st response assessment and at 6 months. We evaluated stool metagenomics, untargeted stool/plasma metabolomics and serum cytokines as correlatives. We focused on microbial metabolites including indoles and short chain fatty acids (SCFA), which are potent aryl hydrocarbon receptor agonist and immunosuppressive. We also evaluated serum cytokines associated with insulin signaling pathways. Results: A total of 43 HNSCC patients receiving single agent pembrolizumab were accrued, 15 in the TRE arm and 28 in control arm. TRE was well tolerated without any study dropouts, weight loss or any adverse events attributable to the intervention. TRE was associated with significant improvement in disease control rate (DCR) at 3 months and at 6 months (3 month DCR 85% in TRE vs 50% in the control arm, p<0.0001, 6 month DCR 64% in TRE vs 39% in control arm, p=0.0004). Responders in both TRE and control arm had lower relative abundance of microbial immunosuppressive indole metabolites, butyric acid (NR vs R: 0.67 vs 0.58, p=0.05) and IGF1 (NR vs R: 0.42 vs 0.39, p=0.02). TRE led to a similar change in microbial metabolites including decrease in abundance of 5 Hydroxyindole acetic acid, Indole 3 acetic acid (IAA), Indole Carboxaldehyde, Indole acrylic acid, butyric acid (control vs TRE: 0.68 vs 0.58, p=0.03) and IGF1 (control vs TRE: 0.4 vs 0.3, p=0.03.) Conclusions: We report a novel phase I/II study of TRE in HNSCC patients and demonstrate excellent safety, feasibility and marked improvement in efficacy of ICB. The effect of TRE may be mediated via changes in microbial metabolome and insulin signaling pathways. TRE represents an attractive and safe strategy to improve treatment responses to ICB and needs to be explored in phase III expansion studies. Humaira Sarfraz, MD, and Shahla Bari, MD, both 1st authors/equal contributors. Clinical trial information: NCT05083416 .

Abstract Objectives Head and neck cancer (HNC) patients experience greater financial toxicity than other cancer patients. Research on financial toxicity has concentrated on patients despite many informal caregivers sharing finances and reducing work hours to provide patient care. Thus, our pilot study: (1) assessed the feasibility of financial toxicity screening of HNC patients and their caregivers, and (2) described financial toxicity levels of HNC patients and their caregivers. Methods We surveyed English‐speaking adult HNC patients initiating treatment at a National Cancer Institute‐designated Comprehensive Cancer Center and their informal caregivers. This survey assessed demographics and financial toxicity through the Comprehensive Score for Financial Toxicity (COST) measure (0–44 range; lower score indicates higher financial toxicity). Screening feasibility was defined as ≥50% consent rate and ≥60% data completion rate. Results Our sample included 27 HNC patients and 9 caregivers. They both had slightly lower consent and completion rates than our goals. Patients reported a median COST score of 27 while caregivers reported a median COST score of 16. Approximately 25.9% of patients and 44.4% of caregivers reported high financial toxicity (COST < 17.5). Caregivers reported high concerns about their future financial health and their ability to control the amount of their financial contributions to the patient's care. Conclusions Patients and caregivers may require additional outreach approaches beyond emailed questionnaires to screen for their financial toxicity systematically. Future research is needed to replicate our results to determine whether differences in financial toxicity occur between patients and caregivers and identify areas of focus for interventions. Level of evidence IV.

Liquid biopsy analysis of cell-free DNA (cfDNA) has revolutionized cancer research by enabling non-invasive assessment of tumor-derived genetic and epigenetic changes. In this study, we conducted a comprehensive paired-sample differential methylation analysis (psDMR) on reprocessed methylation data from two large datasets, CPTAC and TCGA, to identify and validate differentially methylated regions (DMRs) as potential cfDNA biomarkers for head and neck squamous cell carcinoma (HNSC). Our hypothesis is that the paired sample test provides a more suitable and powerful approach for the analysis of heterogeneous cancers like HNSC. The psDMR analysis revealed a significant number of overlapped hypermethylated DMRs between two datasets, indicating the reliability and relevance of these regions for cfDNA methylation biomarker discovery. We identified several candidate genes, including CALCA, ALX4, and HOXD9, which have been previously established as liquid biopsy methylation biomarkers in various cancer types. Furthermore, we demonstrated the efficacy of targeted region analysis using cfDNA methylation data from oral cavity squamous cell carcinoma and nasopharyngeal carcinoma patients, further validating the utility of psDMR analysis in prioritizing cfDNA methylation biomarkers. Overall, our study contributes to the development of cfDNA-based approaches for early cancer detection and monitoring, expanding our understanding of the epigenetic landscape of HNSC, and providing valuable insights for liquid biopsy biomarker discovery not only in HNSC and other cancer types.

ImportanceWhile the health care community advocates broadly for climate change policy, medical professionals can look within care practices to assess their contribution to carbon dioxide (CO2) emissions, and provide solutions wherever possible. Telemedicine can help in mitigating climate change by providing care from a distance.ObjectiveTo assess the carbon savings achieved from telemedicine visits.Design, Setting, and ParticipantsThis cross-sectional study of telemedicine visits was conducted at a single-institution National Cancer Institute (NCI)-designated comprehensive cancer center. Eligible patients were aged 18 years and above, completed telemedicine visits from April 1, 2020, to June 20, 2021, and had a Florida mailing address documented in their electronic medical record. Groups were divided between those within driving time of 60 minutes (1-way) to the cancer center vs those living beyond 60 minutes of drive time. Data were analyzed between April 2020 and June 2021.Main Outcomes and MeasuresCarbon emission savings from telemedicine, measured in total and average per-visit savings.ResultsA total 49 329 telemedicine visits with 23 228 patients were conducted from April 1, 2020, to June 30, 2021. A total 21 489 visits were for patients with driving time of 60 minutes or less (median [IQR] age, 62.0 [52.0-71.0] years; 12 334 [57.4%] female; 1685 [7.8%] Black, 1500 [7.0%] Hispanic, 16 010 [74.5%] non-Hispanic White), while 27 840 visits were for patients with driving time greater than 60 minutes (median [IQR] age, 67.0 [57.0-74.0] years; 14 372 [51.6%] female; 1056 [3.8%] Black, 1364 [5.0%] Hispanic, 22 457 [80.7%] non-Hispanic White). For patients living within a driving time of 60 minutes from the cancer center, 424 471 kg CO2 emissions were saved (mean [SD] emissions savings, 19.8 [9.4] kg CO2 per visit) due to telemedicine—equivalent to 91.5 passenger vehicles driven for 1 year. For patients whose driving distance was greater than 60 minutes, 2 744 248 kg CO2 emissions were saved (mean emissions savings, 98.6 [54.8] kg CO2 per visit)—equivalent to 591 passenger vehicles driven for 1 year.Conclusions and RelevanceUsing a large data set, this cross-sectional analysis highlighted the carbon emissions savings due to telemedicine in oncology. This has important implications in reducing health care–related carbon footprint.