Abstract Background: This study aims to integrate viral and host genomic analyses with social determinants of health (SDOH) to improve biologic risk stratification in patients with human papillomavirus-associated head and neck cancer (HPV+ HNC). Methods: Patients with biopsy-proven, p16-positive HPV+ HNC were enrolled. Archived or fresh tumor tissue underwent DNA extraction followed by HPV consensus-primer genotyping targeted to the L1 locus (MY09/MY11 primer sequences) to determine viral type. Samples with confirmed HPV infection proceed to short-read sequencing for viral genotype characterization and host mutational profiling, and long-read sequencing to define HPV integration architecture, HPV-host fusion events, and larger structural variants. Demographic, clinical, and SDOH variables were collected to explore associations between patient context and genomic heterogeneity. Results: To date, 10 patients have provided informed consent and have been enrolled in this study. Additionally, eights archived tumor specimens have been analyzed. The cohort consists of seven White male, two Hispanic or Latino male, and one White female patients. Archived specimens were derived from three White, two Asian, two Black, and one Hispanic patient. Preliminary HPV genotyping demonstrates a distribution of high-risk HPV types, including HPV16, HPV18, HPV33, HPV35, and HPV59. These early results suggest a potential variation across ancestry and SDOH-defined clusters, with White patients predominantly demonstrating the HPV16 genotype, while there is a higher prevalence of non-16 types amongst other racial and ethnic groups. Conclusions: These early findings highlight the value of broadening HPV genotype characterization and capturing patient diversity to uncover the full spectrum of viral and host genomic variation in HPV+ HNC. Ongoing expansion of the cohort and completion of sequencing analyses will be critical next steps toward defining clinically meaningful genomic subgroups and developing future frameworks for precision risk stratification, surveillance, and treatment personalization in HPV-associated head and neck cancer. Citation Format: Ella P. Jackert, Shu-Yun Cheng, Swar Vimawala, Liyang Tang, Daniel Kwon, Niels C. Kokot, Uttam Sinha, Albert Y. Han. A multimodal sequencing framework to define viral and host genomic heterogeneity in HPV associated head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3237.

We developed a new C-X-C chemokine receptor 4 (CXCR4)-targeting radiolabeled peptide, [68Ga]Ga/[177Lu]Lu-BL34, using a novel and potent cyclic peptide based on structure-activity relationship studies of LY2510924. Methods: Candidate inhibitors were designed on the basis of structure-activity studies and synthesized using solid-phase techniques, and their CXCR4 binding was assessed using a cell-based assay. An optimized cyclic peptide sequence was modified with a Lys-cysteic acid linker and DOTA chelator to make BL34. Other analogs possessing ornithine or diaminopimelic acid linkers were also synthesized and assessed. All radiotracers were assessed in mice engrafted with a mantle cell lymphoma model (Z138) via PET/SPECT imaging and biodistribution studies. Therapeutic efficacy of [177Lu]Lu-BL34 was assessed in Z138-engrafted mice with groups of 30 and 60 MBq and a control. Results: The optimized cyclic peptide showed a 3-fold improvement in CXCR4 binding compared with that of LY2510924. [68Ga]Ga-BL34 showed high imaging contrast for the tumor at 1 and 2 h after injection. Biodistribution studies confirmed these results, with an uptake of 15.1 ± 3.1 %ID/g in the tumor at 1 h after injection and primarily renal excretion with a kidney uptake of 2.4 ± 0.4 %ID/g. SPECT imaging of [177Lu]Lu-BL34 showed similar results, with rapid renal excretion of [177Lu]Lu-BL34 from nontarget organs and relatively high uptake in tumors up to 72 h after injection. Biodistribution studies confirmed high tumor uptake at all time points, with low uptake across all nontarget organs. Blocking studies with LY2510924 further confirmed specificity. Therapy studies showed dose-dependent survival benefit with [177Lu]Lu-BL34 treatment, with metastatic recurrence in the treatment groups. Changing the side chain length at the linker attachment site did not affect the biodistribution or tumor uptake. Conclusion: We report a new CXCR4-targeting pharmacophore that can be used as a radiotheranostic. [68Ga]Ga-BL34 and [177Lu]Lu-BL34 showed excellent imaging and therapeutic properties in preclinical studies and are promising candidates for clinical translation.

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with Human Papillomavirus (HPV) - 16 infections being a cause. Previous studies have shown that glutamine is a crucial amino acid that provides carbon and nitrogen for proliferating cells. In particular, some cancer cells increase the uptake of glutamine through metabolic reprogramming. However, our understanding of glutamine metabolism and transport remains limited in HNSCC. In this study, we will be investigating glutamine transport, specifically ASCT2, in patient-derived normal tonsil organoid and HPV16-positive tonsil organoids. Methods: Tonsil tissue is obtained from tonsillectomy and process for organoid generation. Through mechanical and enzymatic dissociation, tonsil tissue is dissociated into single cell suspension and plated in extracellular matrices. HPV16 lentivirus is used to infect tonsil organoids and used as premalignant HPV16-positive HNSCC model. RNA of the normal tonsil and HPV+ organoids were extracted for qPCR analysis. V-9302, an ASCT2 competitive antagonist, was treated to the organoids for IC50. Results: In this study, the glutamine transporter, ASCT2, was investigated in patient-derived normal tonsil organoid and HPV16-positive tonsil organoids. Both organoid models exhibit ASCT2 through qPCR analysis, with HPV16-positive tonsil organoids exhibiting less ASCT2 (FC 0.64 p<0.00) than normal tonsil organoids. To see if ASCT2 can be a therapeutic target, V-9302 was treated to normal tonsil organoids and HPV16-positive tonsil organoids. V-9302 IC50 of the organoids were obtained, with HPV16-positive organoids being more sensitive (IC50: 15.37 μM) than normal tonsil organoids (IC50: 20.50 μM). Conclusion: Glutamine is an essential amino acid for cell growth and proliferation, especially in fast growing tumors. With V-9302 being more sensitive to HPV16-positive organoids, V-9302 shows the potential to be used as a therapeutic drug for HNSCC treatment. Future studies will focus on V-9302 sensitivity in patient-derived HNSCC tumor organoids. Citation Format: Shu-Yun Cheng, Ella Jackert, Liyang Tang, Daniel Kwon, Niels Kokot, Uttam Sinha, Yang Chai, Albert Y. Han. Glutamine transporter ASCT2 as a therapeutic target in HPV positive organoid models of HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4720.

Objective Prior studies have highlighted the risk of perioperative mortality due to catastrophic bleeding in patients receiving transoral surgery (TOS) for oropharyngeal squamous cell carcinoma (OPSCC). Although the 30‐day mortality and morbidity remain low, understanding the risk factors associated with complications is still required. The goal of this study is to identify risk factors associated with complications after TOS for OPSCC using the American College of Surgeons National Surgical Quality Improvement Program (ACS‐NSQIP) database. Methods A multi‐institutional retrospective cohort analysis of the ACS‐NSQIP database identified 3,489 patients undergoing TOS for OPSCC between 2010 and 2021. Preoperative risk factors were collected. The primary outcomes were 30‐day readmission, reoperation, hemorrhage, and death. Univariate and multivariate analysis was used to identify preoperative risk factors associated with the primary outcomes. Results The mean age was 60.6 years, and 81.5% were male. There were 24 deaths (0.7% 30‐day mortality rate). The rates of readmission and reoperation were 8.9% and 5.8%, respectively. Smoking (OR = 1.440, 95% CI = 1.097–1.890) and CHF (OR = 3.525, 95% CI = 1.320–9.414) were associated with readmission. Diabetes and ASA 3+ increased the risk of both reoperation (diabetes: OR = 2.679, 95% CI = 1.110–6.468, ASA: OR = 1.701, 95% CI = 1.233–2.346) and hemorrhage (diabetes: OR = 3.488, 95% CI = 1.020–11.926, ASA: OR = 2.290, 95% CI = 1.394–3.764). Conclusion This study redemonstrated the safety of TOS for OPSCC, with low 30‐day readmission and reoperation rates. Smoking, diabetes, CHF, and ASA 3+ were important preoperative risk factors for complications. Level of Evidence: 3. Laryngoscope , 2025

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally, with increasing prevalence driven largely by human papillomavirus (HPV) infection. Current standard therapies frequently leave patients with severe, long-term functional impairments, significantly reducing quality of life. Although HPV-positive HNSCC has improved prognosis and better treatment responses compared to HPV-negative disease, the underlying metabolic distinctions remain poorly defined. Using comprehensive metabolomic profiling via ultra-performance liquid chromatography-mass spectrometry in well-established HPV-positive (SCC47, SCC104) and HPV-negative (Detroit562, SCC9) HNSCC cell lines, we demonstrate for the first time through comprehensive metabolomic analysis that HPV-positive HNSCC uniquely enhances metabolic pathways advantageous for rapid cell proliferation, including glycolysis and nicotinamide metabolism. Conversely, HPV-negative HNSCC primarily relies on downstream components of the tricarboxylic acid cycle for energy production. Identifying these differential metabolic has important implications for precision-oncology in the development of targeted therapeutics for HPV-positive HNSCC patients.

INTRODUCTION:The volume of cervical spine procedures continues to grow. Plastic and reconstructive surgeons (PRSs) commonly address complex wound-related issues in such cases. The present study investigates whether routine PRS closure of cervical spinal wounds improves outcomes compared with those performed without. METHODS:Data of patients operated on for cervical spine procedures by the senior author (P.J.T.) between January 2016 and June 2023 were analyzed. Only posterior surgical approaches were included. Demographics, medical status, procedure indication, and surgical characteristics were reviewed. Wound-related and medical complications were examined within a 30-day postoperative period, along with incidences of unplanned reoperation or readmission. Outcomes were compared with 12,943 CPT-matched cases reported by the American College of Surgeons National Surgical Quality Improvement Program. RESULTS:Five hundred eighty-eight cases were included: 511 (87%) were performed for degenerative spine conditions, 60 (10%) for traumatic injuries, 7 (1%) for neoplasms, 7 (1%) for congenital conditions, and 3 (0.5%) for infected cyst management. The PRS group demonstrated a greater prevalence of diabetes (27% vs 22%, P = 0.016) and chronic obstructive pulmonary disease (10% vs 6%, P < 0.001). Those who received PRS closure were less likely to return to the operating room (1% vs 3%, P = 0.005) or experience a wound-related readmission (2% vs 5%, P < 0.001). CONCLUSION:PRS closure of cervical spine cases minimizes the risk of reoperation and readmission, even among a population with comorbidities known to be associated with wound-related complications. Improved outcomes were especially observed for more complex wounds requiring local flap closure. Thus, there is strong evidence to support PRS involvement in cervical spine surgery.

PURPOSE:Circulating tumor DNA (ctDNA) assays have evolved into transformative tools capable of disrupting current management paradigms, including that of human papillomavirus (HPV)-positive oropharyngeal carcinoma (OPC). Despite readily available assays, guidance on its implementation remains undefined. METHODS:A systematic literature review, an expert physician panel, and patient interviews were used to develop consensus items on circulating tumor HPV DNA (ctHPVDNA) use. A hybrid Delphi approach was applied with California Head and Neck Consortium (CHNC) experts to appraise consensus over iterative rounds of feedback. Voting continued until thematic saturation was achieved. RESULTS:In total, 33 CHNC experts participated, representing various entities (academic medical center, integrated managed care system, county hospital, Veterans Affairs hospital, community cancer center, private practice). Item development led to 32 statements across five domains, which later expanded to 33 items. Thematic saturation was reached after three rounds, with complete participation (33 of 33 votes) achieved in each round. Of these statements, 63.6% (21 of 33) reached strong consensus, 9.1% (3 of 33) reached consensus, 12.1% (4 of 33) was found to have no consensus, and 15.1% (5 of 33) was rejected. Key statements highlighted the strong consensus that ctHPVDNA was a valuable tool appropriate for diagnosis and surveillance settings, but not for screening or treatment modifications in current clinical practice. Despite the promise of this technology, there was strong consensus that randomized clinical trials should be performed to optimize its use in HPV+ OPC in the setting of potential increased costs. CONCLUSION:Using currently available evidence and expertise, we establish a pragmatic framework of consensus recommendations for ctHPVDNA use. Such statements of varying strength will help bridge gaps in knowledge and lead to judicious implementation of assays into clinical practice.

Objective:We sought to determine the incidence and outcomes of head and neck cancer (HNC) among patients with schizophrenia. Study Design:Cohort study utilizing TriNetX, a database containing millions of deidentified clinical records. Setting:Multicenter study utilizing records from 68 healthcare organizations. Methods:A cohort of patients with schizophrenia was analyzed for the annual incidence of HNC diagnosis between 2011 and 2021. TriNetX was queried for adult patients with HNC with and without schizophrenia (or long-term antipsychotic use, as a surrogate). Cohorts were 1:1 propensity-matched based on sociodemographic variables to produce matched cohorts of 25,077 patients each. Outcomes included mortality, recurrence in lymph nodes and lung, systemic treatment, failure to thrive, and hospice enrollment. Outcomes are reported as hazard ratio (HR; Cox proportional hazards model) and odds ratio (OR) with 95% CI. Results:Incidence of HNC in patients with schizophrenia peaked at 0.061% in 2012. HNC patients with schizophrenia have a significantly increased risk of mortality (HR 1.37, 95% CI 1.10-1.72), locoregional recurrence (OR 1.36, 95% CI 1.30-1.43), distant metastases to the lung (OR 1.72, 95% CI 1.59-1.87), chemotherapy (OR 4.26, 95% CI 3.88-4.69), radiation (OR 2.47, 95% CI 2.19-2.78), failure to thrive (OR 2.41, 95% CI 2.32-2.73), and hospice enrollment (OR 3.17, 95% CI 2.66-3.76) compared to HNC patients without schizophrenia. Conclusion:HNC patients with schizophrenia have a significant increase in risk of mortality, recurrence, and poor outcomes compared to those without schizophrenia. These findings support a renewed focus on ensuring safety nets for this vulnerable population to ensure appropriate cancer screening and care.

103 Background: Pts with mCRPC have multiple treatment options and face challenges to IDM. This leads some to make poorly informed or goal-discordant decisions. Consultation audio recordings are known to improve IDM by improving recall, but uptake has been limited. It is unclear whether pt-administered apps are an effective, feasible strategy to increase access to recordings and improve IDM. Methods: We conducted a single-site implementation trial. Pts were English-speaking with progressive mCRPC and an upcoming oncology visit in which treatment options including docetaxel would be discussed. Pre-visit, a coordinator sent instructions, provided coaching, and sent text reminders to help pts create recordings using their mobile device. To evaluate change in IDM pre- vs post- the audio-recorded visit, we used an investigator-developed questionnaire testing pt knowledge about docetaxel (19 items, 0-100% correct) and the decisional conflict scale-informed subscale (3 items, 0=feels extremely uninformed to 100=feels extremely informed). Change was evaluated using the Wilcoxon signed-rank test. We also measured implementation: rates of consent, instruction receipt, recording, and listening, as well as pt-reported helpfulness of the app in decision-making. Lastly, we interviewed pts to understand benefits, barriers, and facilitators. Results: Of 78 pts approached, 44 (56%) consented, and 41 (53%) were evaluable. Top reasons for not consenting were too busy (7, 21%), illness (5, 15%), and inadequate devices (4, 12%). Mean age was 75y [56-90], and 34 (83%) were White. Median knowledge about docetaxel increased from 47 to 53 (P=0.048), corresponding to one additional correct response. Median informed subscore increased from 50 to 75 (P=0.011), corresponding to an improvement from feeling neither informed nor uninformed to feeling informed. All pts received instructions, 38 (93%) recorded their visits, and 28 (68%) listened to the recording. Twenty-six pts (63%) found the app helpful in decision-making. In pt interviews, benefits of recording were better recall of treatment options and toxicities, greater decision confidence, and peace of mind. Most frequently reported barriers to use were technology unfamiliarity and disconnected pt portal, telehealth, and recording applications; facilitators were app simplicity and caregiver/coordinator assistance. Conclusions: Implementation of self-administered mobilerecordings was feasible and associated with increased pt knowledge and feeling more informed about treatment with docetaxel in pts with mCRPC. Future efforts should focus on non-White, no/limited-English-speaking populations, and increasing recording/listening rates by addressing barriers and augmenting facilitators (e.g., integrating recordings in electronic pt portals). Clinical trial information: NCT05127850 .

5105 Background: To tailor care to cancer biology, oncologists offer germline testing to patients with APC. Little is known about whether pre-test counseling conducted by oncologists leads to well-informed, preference-concordant decisions in Veterans with APC. Methods: We conducted a prospective mixed-methods study of consecutive patients with APC who were offered germline testing at an oncology visit at the San Francisco VA. Seven days after the visit, patients were administered the Decisional Conflict Scale (DCS; 16 items scored 0-100, higher = more decisional conflict) and a True/False knowledge test (20 items, scored 0-100% correct). We conducted semi-structured interviews using a theory-informed guide to explore patients’ knowledge, decision-making process, and decisional needs for germline testing. Two coders analyzed the interviews using thematic analysis. Results: Of 68 patients approached, 31 (46%) consented. Mean age was 76y, 21 (68%) were White, and 14 (45%) completed at least college. Mean DCS score was 24 (SD 22); six (19%) patients scored >37.5, which is associated with decision delay. Mean knowledge score was 69% (SD 16); four patients scored < 50%. Patients were least knowledgeable about the results disclosure process (37% correct), presence of privacy laws protecting genetics data (50%), types of test results (50%), and implications of a variant of uncertain significance (50%). Twenty-seven patients (87%) desired germline testing. The most common reasons were to help family and advance research; personal treatment benefits were rarely mentioned. Patients felt the decision was easy, but four experienced uncertainty and decided against testing due to fear of losing service-connected disability benefits. Themes included knowledge deficits about testing benefits/risks, results disclosure process, and impact on disability insurance; presence or absence of autonomy; misconceptions (commercialization or weaponization of genetics data, conflating germline testing and research); disparities due to racial discrimination or homelessness; barriers (poor memory, distress from APC, insufficient details about testing from oncologist, and no access to informational resources); and facilitators (trust in oncologist and the VA, family support, and extra time to make a decision). Patients requested a variable degree of decision support prior to germline testing, ranging from none to a combination of informational materials and coaching. Conclusions: Decisional conflict was low in most but not all patients. Patients’ knowledge deficits, misconceptions, and unawareness of choice due to personal, oncologist, and systemic barriers suggest some did not make informed decisions. To deliver patient-centered oncologist-directed germline testing, future research should focus on developing and implementing decision support personalized to patients’ needs.

71 Background: In a quest to tailor care to tumor biology, oncologists now offer germline testing to all patients with APC. We explored the degree to which germline testing decisions reflect patient preferences about potential benefits and harms discussed by oncologists. Methods: We conducted a prospective qualitative study of consecutive patients with APC who were offered germline testing at an oncology visit at the San Francisco VA. We audio-recorded visits and conducted semi-structured interviews using a theory-informed guide with patients after their visit to understand their decision-making process for germline testing. We analyzed the interviews using the Critical Incident Technique to identify positive or negative deviations from well-informed, preference-based decisions. We also reviewed consent documentation in the electronic health record. Results: Of 61 patients approached, 30 completed interviews after their germline testing discussion. Mean age was 75y; 19 (63%) were White, 9 (30%) Black, and 2 (6%) Other race; and 13 (43%) were service-connected for APC. Twenty-six (87%) patients consented to germline testing; the primary reasons were altruistic (to help family and contribute to knowledge). Four patients (13%) declined testing, all primarily due to the fear of potential loss or reduction of service-connected benefits. All four patients reported they would reconsider testing if assured that these benefits would be protected regardless of test results. Of the four patients, two had initially consented to testing with their oncologist but later changed their minds and did not notify anyone. The two patients received germline testing when they underwent PSA testing, but they were not aware that they had germline testing performed. Both had negative test results, and they therefore did not experience threats to their service-connected benefits. Conclusions: Some Veterans with service-connected benefits for APC decline germline testing due to the fear of potential loss or reduction of these benefits, thereby foregoing potential treatment benefits. An advisory board is working with the Veterans Benefits Administration to protect service-connected benefits for these Veterans. In addition, a few Veterans may agree to germline testing with their oncologist, but then change their minds due to concerns surrounding service-connected benefits. From a quality improvement perspective, the experiences of the patients in this study who changed their minds counts as a near-miss. Although uptake of germline testing was high in this cohort, current workflows may need to be addressed to account for a change of heart, and further research is needed to understand root causes and identify possible remedies of the near-misses. Overall, our findings illustrate the importance of informed consent for germline testing to ensure that results are desired and valued by both oncologist and patient.

599 Background: HER2 immunohistochemistry (IHC) is not routinely assessed in patients (pts) with aUC, but it is an emerging predictive biomarker with the advent of HER2-targeting agents. aUC outcomes with respect to HER2 status following treatment with immune checkpoint inhibitors (ICIs) and enfortumab vedotin (EV) are unknown. Methods: We retrospectively identified pts with aUC and available biopsies tested for HER2 IHC and fluorescence in situ hybridization (FISH). HER2 status was assessed using modified GI criteria as HER2 high (IHC 3+ or IHC 2+/FISH+), HER2 low (IHC 2+/FISH- or IHC 1+) or HER2 negative (IHC 0). Pt characteristics and outcomes were abstracted from chart review. We compared outcomes following ICI monotherapy and EV-based regimens in pts with HER2-high or HER2-low tumors relative to HER2-negative, and HER2-positive (≥IHC 1+) tumors relative to HER2-negative. Observed response rate (ORR) evaluated by local investigator was compared in pts with scans after ≥1 treatment cycles using logistic regression, while progression-free survival (PFS) and overall survival (OS) from treatment start were assessed using the Kaplan-Meier method and Cox proportional hazards model. Results: Biopsies from 181 pts with aUC obtained from 3/2016 – 3/2023 were tested for HER2 (34 high, 88 low, 58 negative, 1 indeterminate). In this group, 43 pts received ICI [38 (88%) pembrolizumab; 5 (12%) atezolizumab] and 37 EV [31 (82%) monotherapy; 6 (18%) combination regimen]. Pt characteristics and outcomes are shown in the Table. Among pts treated with EV, HER2-negative pts had decreased PFS (HR: 0.18, 95% CI 0.03 – 0.94, p=0.04) relative to HER2-high. No other differences were noted for any cross-group comparison. For pts treated with ICI, no differences in outcomes were observed for any comparisons based on HER2 status. Conclusions: In this single institution retrospective analysis, pts with aUC and HER2-high IHC expression had longer PFS relative to pts with HER2-negative expression when treated with EV-based regimens. No differences were observed in ICI outcomes based on HER2 expression. These hypothesis-generating results should be validated in larger cohorts. [Table: see text]

To assess the accuracy, reliability, and readability of publicly available large language models in answering fundamental questions on hepatocellular carcinoma diagnosis and management. Twenty questions on liver cancer diagnosis and management were asked in triplicate to ChatGPT-3.5 (OpenAI), Gemini (Google), and Bing (Microsoft). Responses were assessed by six fellowship-trained physicians from three academic liver transplant centers who actively diagnose and/or treat liver cancer. Responses were categorized as accurate (score 1; all information is true and relevant), inadequate (score 0; all information is true, but does not fully answer the question or provides irrelevant information), or inaccurate (score − 1; any information is false). Means with standard deviations were recorded. Responses were considered as a whole accurate if mean score was > 0 and reliable if mean score was > 0 across all responses for the single question. Responses were also quantified for readability using the Flesch Reading Ease Score and Flesch-Kincaid Grade Level. Readability and accuracy across 60 responses were compared using one-way ANOVAs with Tukey’s multiple comparison tests. Of the twenty questions, ChatGPT answered nine (45

ABSTRACT Introduction Consultation audio recordings improve patient decision‐making but are underutilized. Patient‐administered recording apps on mobile devices may increase access, but implementation has not been evaluated. Methods We conducted a single‐arm study delivering education, coaching, and reminders for patients to record their appointment using a mobile recording app. Patients had progressive, advanced prostate cancer and an upcoming appointment where the option of docetaxel would be discussed. We used the RE‐AIM framework for evaluation. Reach was the proportion of patients who participated. Effectiveness was change in informed decision‐making pre‐ vs. post‐appointment. We used a questionnaire evaluating patient knowledge about docetaxel (0%–100% correct) and the decisional conflict scale‐informed subscale (0 = feels extremely uninformed to 100 = extremely informed) to compare means using the paired t‐test. Adoption was the proportion of providers agreeing to be recorded. Implementation was coordinator adherence to intervention delivery. We conducted semistructured interviews with patients, caregivers, and providers to assess barriers, facilitators, and suggestions for recording implementation. Results Of 102 patients approached, 50 (49%) patients participated. Mean age was 75 years, 38 (76%) were Non‐Hispanic White, and 43 (86%) had telehealth appointments. Knowledge increased from 44.7% to 49.5% (p = 0.019), particularly about palliative care (42% answering correctly to 60%, p = 0.035). Decisional conflict‐informed subscale increased from 48.9 to 70.9 (p < 0.001). Forty‐three patients (85%) made a recording, of whom 33 (77%) reported the recording helped treatment decision‐making. All 17 providers agreed to be recorded. Coordinator adherence was high. Multi‐level barriers, suggestions, and facilitators mostly related to intervention complexity and stakeholder compatibility. Conclusion Patient‐administered audio recordings had a positive effect on decision‐making, particularly for palliative care awareness. For broader implementation, efforts should focus on revising institutional policies; teaching patients or caregivers to use existing recording functions on their devices; leveraging artificial intelligence for transcription and summarization; and integrating recording into telehealth technology and electronic patient portals. Trial Registration: https://clinicaltrials.gov/study/NCT05127850

e13538 Background: No standard care model for hospitalized patients with cancer currently exists. The majority of oncology care is provided in the outpatient setting. Consequently, for many oncologists, inpatient care is a secondary responsibility. To address this issue, several U.S. institutions have changed their inpatient oncology models to include dedicated inpatient oncology-trained attendings (hospital-based oncologists). In this study, we investigate outcomes following such a change on an inpatient solid oncology consult service. Methods: This is a single-institution retrospective study of the University of California, San Francisco (UCSF)’s inpatient solid oncology consult service, which switched from a rotating outpatient oncologist attending model to a dedicated inpatient oncologist model in 2018. Since data prior to the switch were not available, we compared all inpatients who received an oncology consult (n=3974) with a comparison group (CG) of all inpatients with a solid tumor diagnosis who did not receive an oncology consult (n=3200) between fiscal years 2018 and 2023. We analyzed trends in case mix index (case complexity), in-hospital mortality index (observed/expected), 30-day unplanned readmission rate, length of stay index, and direct cost index using the Pearson correlation coefficient. In 2022, we conducted an anonymous retrospective pre/post-switch survey of hospitalists who had worked on the hospital medicine service both before and after the switch and compared mean satisfaction with oncology consultation (5-point scale) using Student’s t test. Results: Following the switch, the number of weeks per year covered by dedicated inpatient oncologists increased from seven (2018) to 39 (2023) out of 52. From 2018 to 2023, we found a significant increase in annual consults (495 to 919, r=0.95, p<0.01) and case mix index (2.30 to 3.30, r=0.90, p=0.01; CG 1.60 to 1.70, r=0.60, p=0.20), and a significant decrease in mortality index (1.59 to 0.70, r=-0.98, p<0.01; CG 0.90 to 0.48, r=-0.66, p=0.15). There were non-significant decreases in 30-day unplanned readmission rate (35.8% to 30.5%, r=-0.77, p=0.07), length of stay index (1.45 to 1.32, r=-0.75, p=0.08), and direct cost index (2.2 to 1.8, r=-0.61, p=0.20), similar to the CG. Mean (standard deviation) satisfaction increased from 3.27 (1.22) pre-switch to 4.53 (0.92) post-switch ( p=0.02, response rate 15/51, 29%). Conclusions: Switching to a dedicated inpatient oncologist model on a consult service was associated with decreased in-hospital mortality and increased satisfaction with oncology consultation despite growing case volume and complexity, while readmission rate, length of stay, and cost remained unchanged. This study adds to growing literature supporting dedicated inpatient oncologist attending models of care and is in line with recent literature from other specialties supporting similar inpatient care models.

5066 Background: FOR46 is an MMAE-containing antibody-drug conjugate (ADC) targeting a tumor-specific conformational epitope on the extracellular domain of CD46 on prostate cancer and other cancer tissues in a lineage independent fashion. A prior phase 1, first-in-human trial of FOR46 demonstrated encouraging preliminary activity in mCRPC. In pre-clinical models, androgen receptor blockade with enzalutamide enhances CD46 epitope expression and achieves additive activity in combination with the CD46 ADC. We sought to evaluate the combination of FOR46 plus enza in mCRPC patients (pts). Methods: Pts with mCRPC with progression on ≥ 1 androgen receptor pathway inhibitor (ARPI) were enrolled. No prior chemotherapy for mCRPC was allowed. A 3+3 dose escalation design was utilized with a starting dose of FOR46 of 1.8 mg/kg adjusted body weight (ABW) in combination with enza 160 mg/day. Dose escalation was explored with and without prophylactic granulocyte colony-stimulating factor (G-CSF) support. The primary endpoint was determination of the maximally tolerated dose (MTD) of FOR46 in combination with enza. A baseline CD46-directed PET imaging probe utilizing the same antibody backbone as FOR46 (89Zr-DFO-YS5) was obtained in a subset of pts. Results: Seventeen pts were enrolled. Median age was 71 years (range 58 – 91) and median PSA was 43.8 ng/mL (range 2.1 – 379.6) at study entry. Twelve pts (70.6%) had ≥ 2 lines of prior ARPI. The median duration of treatment was 5.0 months (range 1– 18). Dose-limiting toxicities (DLTs) included grade 4 neutropenia at a dose of 2.1 mg/kg without G-CSF (n = 2), grade 4 hyponatremia at 2.4 mg/kg (n = 1), and grade 3 elevated transaminases at 2.4 mg/kg (n = 1). The MTD of FOR46 was established at 2.1 mg/kg ABW, with primary G-CSF prophylaxis, in combination with enza 160 mg/day. Grade ≥ 3 treatment-related adverse events (trAEs) were observed in 29.4% of pts. The most common trAEs of any grade were fatigue (n = 11, 64.7%), peripheral sensory neuropathy (n = 8, 47.1%), elevated transaminases (n = 3, 17.6%), alopecia (n = 4, 23.5%), decreased appetite (n = 7, 41.2%), neutropenia (n = 3, 17.6%), and weight loss (n = 3, 17.6%). Grade 2 neuropathy was observed in 2 patients (11.8%). Preliminary anti-tumor activity was observed with PSA declines in 13/16 (81.3%) of evaluable pts, and a disease control rate (stable disease ≥ 6 months) of 41.2%. 89Zr-DFO-YS5 demonstrated tumor uptake on whole body PET with pharmacokinetics typical for an IgG radiopharmaceutical. Conclusions: In combination with enza, the established MTD of FOR46 with primary G-CSF prophylaxis was safe and demonstrated preliminary evidence of efficacy. 89Zr-DFO-YS5 PET demonstrates tumor-specific uptake and will be employed in the ongoing Phase 2 portion of the study as a potential predictive biomarker of response. Clinical trial information: NCT05011188 .

Objectives: Patients with metastatic renal cell carcinoma (mRCC) face complex treatment decisions and frequently turn to the Internet for treatment information. The content of patient educational websites about mRCC treatment has not been evaluated. This study evaluated the accuracy, readability, and quality of websites about the treatment of mRCC. Methods: A total of 2,700 Internet queries were performed. Across 3 Internet search engines, 25 links of 36 permutations of mRCC keywords and their synonyms were screened for eligibility. Eligible websites were English-language websites containing information about mRCC treatments. Sponsored, social media, provider-facing, and news websites were excluded. Accuracy of eligible websites was evaluated in 2 domains: (1) Completeness by calculating the percentage of mRCC facts included in websites using an investigator-created checklist based on the NCI's RCC Treatment (PDQ (R))-patient version, and (2) Correctness by identifying incorrect statements that were inconsistent with guidelines. Websites containing >= 60% of checklist items had a "passing" completeness score. Incorrect statements were tallied and qualitatively categorized. Readability was evaluated using the Fry and SMOG formulae, which calculate reading grade levels. Quality was evaluated using validated instruments that appraise health information quality: QUEST (scored 0-28), which focuses on online information, and DISCERN (scored 16-80), which focuses on treatment choices. Results: Thirty-nine websites were analyzed. Mean completeness score was 30% (range 0%-69%); only 2 (5%) websites had a passing score. Twelve (31%) websites had >= 1 incorrect statement, such as listing homeopathy or hormone therapy as mRCC treatment options, or including outdated statements. Mean readability levels were 11th and 12th grades for the Fry and SMOG methods, respectively. No website had a reading level lower than 9th grade. Mean QUEST score was 19 (range 9-28); authorship, complementarity, and currency items had the lowest scores. Mean DISCERN score was 56 (range 42-76), with 7 (18%) websites rated "excellent", 22 (56%) rated "good", and 10 (26%) rated fair. Conclusions: Many websites about mRCC treatment have incomplete, inaccurate, and unreadable information. Quality is highly variable. Efforts to improve accuracy, readability, and quality are needed to ensure that patients with mRCC can make well-informed treatment decisions and avoid harm from misinformation. Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/)

To better understand Veterans' decisions about germline testing, we conducted a single-site, qualitative study of 32 Veterans with advanced prostate cancer. Seven days after oncologist-patient discussions about germline testing, we conducted semi-structured interviews with patients exploring their decision-making process using an interview guide. Four of 14 Veterans with service-connected disability benefits for prostate cancer declined germline testing for fear of losing benefits, as their livelihood depended on these benefits. All 18 Veterans without service-connected benefits agreed to testing. Veterans declining germline testing for this concern can lead to suboptimal cancer care because targeted treatments that could improve their outcomes may go unrecognized. Our findings contributed to new language in the Veterans Benefits Administration Compensation and Pension Manual clarifying that genetic testing showing hereditary predisposition is insufficient to deny service-connected benefits for conditions presumed to be caused by military exposures. Clinicians should communicate this protection when counseling Veterans about genetic testing.

Little is known about the shared decision-making (SDM) needs, barriers, and facilitators of patients with newly diagnosed advanced cancer in the hospital. Understanding this may improve SDM and cancer care quality in this vulnerable population. A single-site, mixed-methods study of hospitalized patients with newly diagnosed advanced cancer, caregivers, and oncologists was conducted. After discharge, patient ± caregiver semi-structured interviews exploring SDM needs, barriers, and facilitators regarding their most important upcoming cancer-related decision were conducted. Oncologists were surveyed about patient knowledge and SDM needs using closed- and open-ended questions, respectively. Thematic analysis was performed for qualitative data with a focus on themes unique to or amplified by hospitalization. Descriptive statistics and the Chi-squared test were performed for quantitative data. Patients and caregivers reported high SDM needs surrounding treatment and prognostic information, leading to decisional conflict. Eight themes emerged: anticipated cancer treatment decisions, variable control preferences in decision-making, high cancer-related information needs and uncertainty, barriers and facilitators to information gathering during and post hospitalization, and decision-making facilitators. Among 32 oncologists, most (56