Patterns of virtual reality and Fitbit wearable activity device use after skull base surgery.

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.

Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit). Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4-96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure. Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment. Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.

Acute and definitive management of oropharyngeal hemorrhage in patients with squamous cell carcinoma of the oropharynx.

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.

Use of Perioperative Virtual Reality Experiences on Anxiety and Pain: A Randomized Comparative Trial.

OBJECTIVE: To evaluate the effect of different virtual reality (VR) experiences on perioperative anxiety and pain among patients undergoing head and neck surgery. METHODS: Prospective, randomized, comparative trial among patients undergoing outpatient head and neck surgery from December 2021 to April 2022 at a single academic institution. Group 1 utilized a preoperative VR gaming experience and a postoperative VR mindfulness experience, while Group 2 utilized the same interventions in the reverse order. Anxiety and pain were measured using visual analog scales (VAS). Primary outcomes were changes in post-intervention anxiety and pain. Secondary outcomes included vital sign changes and subjective patient experiences using a 5-point Likert scale. RESULTS: There were 32 patients randomized for inclusion, with 16 patients per group. The majority of patients were female (65.6%) and mean (standard deviation) age was 47.3 (16.7) years. After outlier exclusion, there were no differences in post-intervention preoperative anxiety reduction (Group 1 vs. Group 2, median [IQR]: -12.0 [15] vs. -10.5 [13], p = 0.62). There were minor differences in vital sign changes (p < 0.05). Among the 10 patients in Group 1 and 12 patients in Group 2 who completed postoperative VR use, there were no differences in post-intervention pain reduction (-8.5 [22.3] vs. -7.5 [19.3], p = 0.95) or vital sign changes (p > 0.05). There were no differences in questionnaire responses, with high satisfaction in both groups (p > 0.05). No adverse events encountered. CONCLUSIONS: Use of different VR experiences among patients undergoing outpatient head and neck surgery appears associated with similar reductions in perioperative anxiety and pain. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:1197-1202, 2024.

Comparison of da Vinci Single Port vs Si Systems for Transoral Robotic-Assisted Surgery: A Review With Technical Insights.

Importance: Transoral robot-assisted surgery (TORS) continues to have a major role in the treatment of oropharyngeal cancer. As new iterations of robotic technology are increasingly utilized, it is important to share learning experiences and clinical outcomes data, to optimize technical efficiency and clinical care. Observations: This was a retrospective review of a large academic institution's initial clinical use of the da Vinci Single Port (SP) compared with the da Vinci Si (Si) system. A total of 205 TORS cases were reviewed: 109 in the SP group (November 22, 2018, through September 30, 2020), and 96 in the Si group (January 1, 2016, through November 12, 2018). Both groups had comparable operative times, rates of postoperative pharyngeal hemorrhage, length of hospital stay, and duration of nasogastric feeding tube use. There was no difference in pathological characteristics, rates of positive margins, or indications for or time to initiation of adjuvant therapy between the groups. The collective experience of 6 faculty members-who have trained 139 TORS surgeons for the SP system rollout-was compiled to provide a summary of learning experiences and technical notes on safe and efficient operation of the SP system. Conclusions and Relevance: This Review found that the functional and oncologic outcomes were comparable between TORS cases performed with the Si and SP systems, and they had similar complication rates. Recognized advantages of the SP over the Si system include the availability of bipolar-energized instruments, a usable third surgical arm, and improved camera image quality.

Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment.

PURPOSE: Cancer drug development is currently limited by a paradigm of preclinical evaluation that does not adequately recapitulate the complexity of the intact human tumor microenvironment (TME). To overcome this, we combined trackable intratumor microdosing (CIVO) with spatial biology readouts to directly assess drug effects in patient tumors in situ. EXPERIMENTAL DESIGN: In a first-of-its-kind phase 0 clinical trial, we explored the effects of an investigational stage SUMOylation-activating enzyme (SAE) inhibitor, subasumstat (TAK-981) in 12 patients with head and neck carcinoma (HNC). Patients scheduled for tumor resection received percutaneous intratumor injections of subasumstat and vehicle control 1 to 4 days before surgery, resulting in spatially localized and graded regions of drug exposure (∼1,000-2,000 µm in diameter). Drug-exposed (n = 214) and unexposed regions (n = 140) were compared by GeoMx Digital Spatial Profiler, with evaluation at single-cell resolution in a subset of these by CosMx Spatial Molecular Imager. RESULTS: Localized regions of subasumstat exposure revealed SUMO pathway inhibition, elevation of type I IFN response, and inhibition of cell cycle across all tumor samples. Single-cell analysis by CosMx demonstrated cell-cycle inhibition specific to the tumor epithelium, and IFN pathway induction commensurate with a TME shift from immune-suppressive to immune-permissive. CONCLUSIONS: Pairing CIVO with spatial profiling enabled detailed investigation of response to subasumstat across a diverse sampling of native and intact TME. We demonstrate that drug mechanism of action can be directly evaluated in a spatially precise manner in the most translationally relevant setting: an in situ human tumor.

Prevalence and correlates of high-dose opioid use among survivors of head and neck cancer.

BACKGROUND: We characterized prescription opioid medication use up to 2 years following the head and neck cancer (HNC) diagnosis and examined associations with moderate or high daily opioid prescription dose. METHODS: Using administrative data from Veterans Health Administration, we conducted a retrospective cohort analysis of 5522 Veterans treated for cancers of the upper aerodigestive tract between 2012 and 2019. Data included cancer diagnosis and treatments, pain severity, prescription opioid characteristics, demographics, and other clinical factors. RESULTS: Two years post-HNC, 7.8% (n = 428) were receiving moderate or high-dose opioid therapy. Patients with at least moderate pain (18%, n = 996) had 2.48 times higher odds (95% CI = 1.94-3.09, p < 0.001) to be prescribed a moderate opioid dose or higher at 2 years post diagnosis. CONCLUSIONS: Survivors of HNC with at least moderate pain were at elevated risk of continued use of moderate and high dose opioids.

Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit.

PURPOSE: Neoadjuvant targeted therapy provides a brief, preoperative window of opportunity that can be exploited to individualize cancer care based on treatment response. We investigated whether response to neoadjuvant therapy during the preoperative window confers survival benefit in patients with operable head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: A pooled analysis of treatment-naïve patients with operable HNSCC enrolled in one of three clinical trials from 2009 to 2020 (NCT00779389, NCT01218048, NCT02473731). Neoadjuvant regimens consisted of EGFR inhibitors (n = 83) or anti-ErbB3 antibody therapy (n = 9) within 28 days of surgery. Clinical to pathologic stage migration was compared with disease-free survival (DFS) and overall survival (OS) while adjusting for confounding factors using multivariable Cox regression. Circulating tumor markers validated in other solid tumor models were analyzed. RESULTS: 92 of 118 patients were analyzed; all patients underwent surgery following neoadjuvant therapy. Clinical to pathologic downstaging was more frequent in patients undergoing neoadjuvant targeted therapy compared with control cohort (P = 0.048). Patients with pathologic downstage migration had the highest OS [89.5%; 95% confidence interval (CI), 75.7-100] compared with those with no stage change (58%; 95% CI, 46.2-69.8) or upstage (40%; 95% CI, 9.6-70.4; P = 0.003). Downstage migration remained a positive prognostic factor for OS (HR, 0.22; 95% CI, 0.05-0.90) while adjusting for measured confounders. Downstage migration correlated with decreased circulating tumor markers, SOX17 and TAC1 (P = 0.0078). CONCLUSIONS: Brief neoadjuvant therapy achieved pathologic downstaging in a subset of patients and was associated with significantly better DFS and OS as well as decreased circulating methylated SOX17 and TAC1.

Novel stapler-assisted technique for closure of persistent tracheoesophageal puncture fistula.

Tracheoesophageal puncture (TEP) is a reliable method to restore voice and is an important part of voice rehabilitation following laryngectomy. However, complications following this procedure, including peri-prosthetic leakage and resulting aspiration pneumonia, may necessitate surgical closure. In this study, we present an effective and reliable method for TEP closure using a stapler-assisted technique. Case series study for patients who underwent stapler-assisted TEP closure reviewed from 2017 to 2021. All five patients had successful closure of their TEP tract without further leakage. No postoperative bleeding, wound infection, or esophageal stenosis occurred. One patient had postoperative stomal stenosis. The stapler-assisted technique for TEP closure is easy, quick, and effective. The reliability and quick return to oral intake post-operatively make it a preferable option over previous techniques.

Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck.

PD-L1 testing guides therapeutic decision-making for head and neck squamous cell carcinoma (HNSCC). We sought to understand whether chemoradiation therapy (CRT) influences the PD-L1 combined positive score (CPS) and other biomarkers of response to immunotherapy. PD-L1 expression was assessed using immunohistochemistry, and bulk RNA sequencing was performed on 146 HNSCC patients (65 primary sites, 50 paired local recurrences, and 31 paired regional recurrences). PD-L1 was scored using the CPS of ≥1, ≥20, and ≥50. Overall, 98 %, 54 %, and 17 % of HNSCCs had a CPS ≥1, ≥20, and ≥50, respectively. When using a cut-off of ≥1, CRT did not significantly change CPS at the locoregional recurrent site. However, there were significant changes when using CPS ≥20 or ≥50. The CPS changed for 32 % of patients when using a CPS ≥20 (p < 0.001). When using a CPS ≥50, there was a 20-23 % (p = 0.0058-0.00067) discordance rate at the site of locoregional recurrence. Oral cavity cancers had a significantly higher discordant rate than other primary sites for CPS ≥50, 44 % (8/18, p = 0.0058) and 58 % (7/12, p = 0.00067) discordance at the site of local and regional recurrence, respectively. When evaluating the 18 gene IFN-É£ signature predictive of response to anti-PD-1 blockade, there was a statistically significant increase in the IFN-É£ signature in recurrent larynx cancer (p = 0.02). Our study demonstrates that when using a higher cut-off of CPS ≥20 and ≥50, a repeat biopsy may be warranted after CRT for local and regional recurrent HNSCCs.

Monitoring postoperative ambulation and sleep after head and neck surgery: Feasibility and utility study using wearable devices.

BACKGROUND: To evaluate use of wearable activity devices to monitor trends in ambulation and sleep after head and neck surgery. METHODS: Patients utilized Fitbit devices after surgery. Daily activity and sleep scores, step counts, and total sleep time (TST) were obtained. RESULTS: There were 30 patients within the final cohort. Trends in step counts after specific procedures were identified, and higher subjective activity level correlated with step counts (r = 0.25, 95% CI = 0.07-0.41). Among patients with complete step data (n = 24), POD1 steps ≥200 were associated with reduced length of stay (4.5 ± 1.7 days vs. 7.2 ± 4.0 days, 95% CI = 0.33-5.0). Mean TST was 5.4 ± 2.5 h, TST correlated with subjective sleep scores (r = 0.25, 95% CI = 0.03-0.044), and clinical events associated with sleep-wake transitions on Fitbit devices were identified. CONCLUSIONS: Wearable activity devices appear feasible for monitoring trends in postoperative ambulation and sleep. Use of these devices may facilitate postoperative recovery.

Effect of Virtual Reality on Pain Management and Opioid Use Among Hospitalized Patients After Head and Neck Surgery: A Randomized Clinical Trial.

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.

Functional proteomics of patient derived head and neck squamous cell carcinoma cells reveal novel applications of trametinib.

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.

Establishment and Validation of Pre-Therapy Cervical Vertebrae Muscle Quantification as a Prognostic Marker of Sarcopenia in Patients With Head and Neck Cancer.

BACKGROUND: Sarcopenia is prognostic for survival in patients with head and neck cancer (HNC). However, identification of this high-risk feature remains challenging without computed tomography (CT) imaging of the abdomen or thorax. Herein, we establish sarcopenia thresholds at the C3 level and determine if C3 sarcopenia is associated with survival in patients with HNC. METHODS: This retrospective cohort study was conducted in consecutive patients with a squamous cell carcinoma of the head and neck with cross-sectional abdominal or neck imaging within 60 days prior to treatment. Measurement of cross-sectional muscle area at L3 and C3 levels was performed from CT imaging. Primary study outcome was overall survival. RESULTS: Skeletal muscle area at C3 was strongly correlated with the L3 level in both men (n = 188; r = 0.77; p < 0.001) and women (n = 65; r = 0.80; p < 0.001), and C3 sarcopenia thresholds of 14.0 cm2/m2 (men) and 11.1 cm2/m2 (women) were best predictive of L3 sarcopenia thresholds. Applying these C3 thresholds to a cohort of patients with neck imaging alone revealed that C3 sarcopenia was independently associated with reduced overall survival in men (HR = 2.63; 95% CI, 1.79, 3.85) but not women (HR = 1.18, 95% CI, 0.76, 1.85). CONCLUSIONS: This study identifies sarcopenia thresholds at the C3 level that best predict L3 sarcopenia in men and women. In HNC, C3-defined sarcopenia is associated with poor survival outcomes in men, but not women, suggesting sarcopenia may differentially affect men and women with HNC.

Follow-Up Phone Interviews and Attendance Motivation From A Free Head and Neck Cancer Screening.

INTRODUCTION: Head and Neck Cancer Awareness and Screening Programs (HNCASP) are popular community outreach events hosted by academic and community otolaryngology departments. However, long-term follow-up of participants is lacking. PATIENTS AND METHODS: Participants of a HNCASP held at an academic cancer center prospectively filled out demographic and risk factor surveys followed by HNC screening examination. A phone interview was conducted for participants between 2012 and 2016 with suspicious findings to assess outcomes. RESULTS: Participants were largely Caucasian, female, and had health insurance, reflecting the setting at an academic medical center. Despite this, there were 156 (16.8%) positive screenings; 47 of these completed follow up interviews. Twelve (1.1% of all participants) cancer cases were confirmed. DISCUSSION: A significant proportion of HNCASP participants benefited from this screening opportunity. Education regarding HNC is the primary benefit and motivational factor for attendance of HNCASPs, although a significant subset of patients was identified that needed follow-up, and several cancers were detected.

Assessing the learning curve associated with a novel flexible robot in the pre-clinical and clinical setting.

BACKGROUND: Transoral robotic surgery has been successfully used by head and neck surgeons for a variety of procedures but is limited by rigid instrumentation and line-of-sight visualization. Non-linear systems specifically designed for the aerodigestive tract are needed. Ease of use of these new systems in both training and clinical environments is critical in its widespread adoption. METHODS: Residents, fellows, and junior faculty performed four tasks on an anatomical airway mannequin using the Medrobotics FLEX™ Robotic System: expose and incise the tonsil, grasp the epiglottis, palpate the vocal processes, and grasp the interarytenoid space. These tasks were performed once a day for four days; after a 4-month time gap, subjects were asked to perform these same tasks for three more days. Time to task completion and total distance driven were tracked. In addition, a retrospective analysis was performed analyzing one attending physician's experience with clinical usage of the robot. RESULTS: 13 subjects completed the initial round of the mannequin simulation and 8 subjects completed the additional testing 4 months later. Subjects rapidly improved their speed and efficiency at task completion. Junior residents were slower in most tasks initially compared to senior trainees but quickly reached similar levels of efficiency. Following the break there was minimal degradation in skills and continued improvement in efficiency was observed with additional trials. There was significant heterogeneity in the analyzed clinical cases, but when analyzing cases of similar complexity and pathology, clear decreases in overall operative times were demonstrable. CONCLUSION: Novice users quickly gained proficiency with the FLEX™ Robotic System in a training environment, and these skills are retained after several months. This learning could translate to the clinical setting if a proper training regimen is developed. The Medrobotics FLEX™ Robotic System shows promise as a surgical tool in head and neck surgery in this study.

Spatial Profiles of Intratumoral PD-1+ Helper T Cells Predict Prognosis in Head and Neck Squamous Cell Carcinoma.

Background: Functional interactions between immune cells and neoplastic cells in the tumor immune microenvironment have been actively pursued for both biomarker discovery for patient stratification, as well as therapeutic anti-cancer targets to improve clinical outcomes. Although accumulating evidence indicates that intratumoral infiltration of immune cells has prognostic significance, limited information is available on the spatial infiltration patterns of immune cells within intratumoral regions. This study aimed to understand the intratumoral heterogeneity and spatial distribution of immune cell infiltrates associated with cell phenotypes and prognosis in head and neck squamous cell carcinoma (HNSCC). Methods: A total of 88 specimens of oropharyngeal squamous cell carcinoma, categorized into discovery (n = 38) and validation cohorts (n = 51), were analyzed for immune contexture by multiplexed immunohistochemistry (IHC) and image cytometry-based quantification. Tissue segmentation was performed according to a mathematical morphological approach using neoplastic cell IHC images to dissect intratumoral regions into tumor cell nests versus intratumoral stroma. Results: Tissue segmentation revealed heterogeneity in intratumoral T cells, varying from tumor cell nest-polarized to intratumoral stroma-polarized distributions. Leukocyte composition analysis revealed higher ratios of TH1/TH2 in tumor cell nests with higher percentages of helper T cells, B cells, and CD66b+ granulocytes within intratumoral stroma. A discovery and validation approach revealed a high density of programmed death receptor-1 (PD-1)+ helper T cells in tumor cell nests as a negative prognostic factor for short overall survival. CD163+ tumor-associated macrophages (TAM) provided the strongest correlation with PD-1+ helper T cells, and cases with a high density of PD-1+ helper T cells and CD163+ TAM had a significantly shorter overall survival than other cases. Conclusion: This study reveals the significance of analyzing intratumoral cell nests and reports that an immune microenvironment with a high density of PD-1+ helper T cells in tumoral cell nests is a poor prognostic factor for HNSCC.

Risk of Suicidal Self-directed Violence Among US Veteran Survivors of Head and Neck Cancer.

Importance: Head and neck cancer (HNC) survivors are about twice as likely to die by suicide compared with other cancer survivors. Objective: To examine the associations between precancer mental health and pain and postcancer receipt of mental health, substance use disorder (SUD), or palliative care services with risk of suicidal self-directed violence (SSDV). Design, Setting, and Participants: This retrospective cohort study used the Veterans Health Administration data of 7803 veterans with a diagnosis of HNC (stage I-IVB) who received cancer treatment between January 1, 2012, and January 1, 2018. Data were analyzed between May 2020 and July 2021. Exposures: Presence of precancer chronic pain and SUD diagnoses, and postcancer SUD, mental health, or palliative care treatment. Exposures were defined using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes in Veterans Health Administration administrative data. Main Outcomes and Measures: Documented SSDV event, including suicide attempt or death by suicide, after HNC diagnosis. Results: Among the cohort of 7803 veterans (7685 [98.4%] male; mean [SD] age, 65 [10.7] years), 72 (0.9%) had at least 1 documented SSDV event following their cancer diagnosis, and 51 (0.7%) died by suicide. Four adjusted modified Poisson regression analyses identified that precancer chronic pain (incidence rate ratio [IRR], 2.58; 95% CI 1.54-4.32) or mood disorder diagnoses (IRR, 1.95; 95% CI, 1.17-3.24) were associated with higher risk of postcancer SSDV. Those who had at least 1 documented mental health (IRR, 2.73; 95% CI, 1.24-6.03) or SUD (IRR, 3.92; 95% CI, 2.46-6.24) treatment encounter in the 90 days following HNC diagnosis were at higher risk for SSDV. A palliative care encounter within 90 days of postcancer diagnosis was associated with decreased risk of SSVD (IRR, 0.49; 95% CI, 0.31-0.78). Conclusions and Relevance: In this cohort study, a high proportion of HNC survivors with an SSVD event died from their injuries. Identification of risk factors for SSDV among HNC survivors may help direct additional resources to those who are at high risk. Referral to palliative care appears to be an important component of supportive oncologic care to reduce the risk of SSDV.