Citations

Abstract Background: Epidemiologic studies commonly obtain important exposure and outcome information from patient self-report although these may be influenced by imperfect understanding and/or faulty recall. The Voyage Study is a large-scale, prospective cohort study of long-term health outcomes among participants with a valid multi-target stool DNA (mt-sDNA) test order (N=150, 047). The purpose of this analysis was to evaluate the validity of participant reported mt-sDNA tests, colorectal cancer (CRC), and/or aerodigestive cancers (ADC, including cancers of the head, neck, oral, esophageal, lung, liver, stomach, pancreas, anus) among respondents. Methods: Participants from across the Unites States enrolled in the study completing questionnaires at enrollment and 1 year. The year 1 questionnaire collected data on completion and outcome of their mt-sDNA test, follow up colonoscopies and other procedures as well as a diagnosis of CRC or ADC. The study team contacts those who reported either CRC or ADC for permission to obtain copies of medical records. Records are then reviewed by a trained nurse abstractor and evaluated for validity. Mt-sDNA test results were available from Exact Sciences. Results: At the time of this analysis, year 1 questionnaire data were available on 135, 035 participants. Abnormal mt-sDNA results (n=12, 928) were self-reported by 13, 420 participants with 96.3% accuracy. Of the 111, 556 self-reported normal results, 93.4% (n=104, 150) were reported correctly. The validation process for the Voyage Study is ongoing with 860 self-reported CRC and 318 self-reported aerodigestive cancer diagnoses to date. Complete data are available on 155 individuals with a self-report of a new CRC diagnosis and 63 individuals with a self-report of aerodigestive cancer. Abstraction confirmed 47% (n=73) of those reported as true CRC diagnoses. Participants were better at correctly reporting at least one aerodigestive cancer (73%, n=46). Discussion and Conclusions: Patient reported medical record validation poses a unique challenge in today’s world. The process of requesting participant authorization followed by institutional requests to release the medical records to the research team is slow and painstaking. We found that patients are able to correctly report their mt-sDNA tests but found a relatively low proportion of reported cancer diagnoses reported correctly. This underscores the need to continue to validate key outcomes rather than relying solely on participant responses. As the number of outcomes validated increases, the study team will look at a variety of social and economic factors to better understand what contributes to or hinders an accurate self-report. Citation Format: Emily J. Kirsch, Jessica A. Grimm, Shawn M. Stoddard, Winnie Z. Fan, Kandace A. Bohn, Kathleen J. Yost, Lila J. Finney Rutten, Janet E. Olson. Patient reported outcome validation within the Voyage Study cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7354.

Abstract Introduction: We previously developed a urine liquid biopsy assay to measure urine tumor DNA (utDNA) levels in bladder cancer (BC) patients. Here, we extended this approach significantly by layering in cell-free DNA fragmentomic and cell-free RNA analysis, and extending the method to the full spectrum of genitourinary (GU) cancers, to enable both GU cancer detection and tumor tissue of origin prediction. Methods: A total of 155 GU cancer patients and 34 healthy adults were enrolled in this prospective study. Preoperative urine was collected from 94 bladder cancer (BC) patients, including 65 with muscle-invasive disease, all undergoing cystectomy. Additionally, urine samples were collected from 18 renal cell carcinoma (RCC) patients undergoing nephrectomy and 42 metastatic prostate cancer (mPC) patients. Urine cfDNA and cfRNA were isolated and sequenced, with cfRNA sequenced to 100 million reads per sample on an Illumina NovaSeq X and cfDNA sequenced at 5x genome-wide coverage on a Novoseq S4 flow cell. To identify malignant tissue of origin, we analyzed somatic copy number alterations (CNAs), genome-wide fragment length ratios, and 4-mer end motifs. Tumor fraction (TFx) was estimated using ichorCNA, while DELFI was employed for fragment length ratios in 5 megabase bins across the genome and chromosome arm-level z-scores. Individual logistic regression models were developed based on each fragmentomic feature, and validated using a training and held-out testing approach. Outputs from these models were combined into a single comprehensive model, also trained and held-out tested using the same approach. Urine cfRNA transcript isoform abundance was quantified using Salmon and normalized to Transcripts Per Million (TPM) to account for sequencing depth variations. Results: Bladder cancer (BC) showed the highest mean tumor fraction (TFx, 10.5%), followed by RCC (3.8%) and mPC (3.4%). Among 94 BC patients, 42% achieved a pCR, while 58% had residual disease and did not. Patients without pCR had significantly higher urine TFx compared to those with pCR (14.7% vs. 4.7%, p=0.0008). A machine learning model based on genome-wide fragment length ratios achieved an ROC AUC of 0.74, while models using genome-wide CNAs and end motifs achieved AUCs of 0.81 and 0.88, respectively. Combining all features into a single model yielded an AUC of 0.92, with classification accuracies of 89% for bladder cancer, 80% for RCC, and 60% for prostate cancer. Additionally, urine cfRNA analysis using the top 1, 000 coding transcripts achieved an AUC of 0.95, with classification accuracies of 100% for mPC, 87% for BC, and 78% for RCC. Conclusion: Fragmentomic features from urine cfDNA and transcriptomic features from urine cfRNA demonstrate strong potential for predicting tumor tissue-of-origin in GU cancers, underscoring the promise of non-invasive diagnosis across the spectrum of GU malignancies through urine liquid biopsy. Citation Format: Pradeep Singh Chauhan, Irfan Alahi, Jessica Linford, Arpit Panda, Nathan Colon, Ryan Mueller, Faridi Qaium, Peter K. Harris, John Sheng, Eric H. Kim, Melissa A. Reimers, Zachary L. Smith, Woodson W. Smelser, Aadel A. Chaudhuri. Predicting genitourinary cancer tissue-of-origin using urine cell-free DNA fragmentomics and cell-free RNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3258.

Background Falls in people with multiple sclerosis (pwMS) lead to morbidity and expense. Objective Identify clinical metrics associated with falls. Methods Eighty-six pwMS completed fall surveys, timed 25-foot walk (T25FW), and motion analysis with Clario Opal devices. Logistic regression models were created. Results Median age was 54.5 years (range 21–73), 62% (53) were female. The cohort included 58% with relapsing (50) and 42% with progressive MS (36). Those who reported falling in the last year were older (median age 58 vs 52.5, p = .03) and had a higher Patient Determined Disease Step (PDDS) score (median 3 vs 1, p < .0001). Falls were associated with worse balance metrics including sway area (median 2.3 degrees 2 vs 1.2, p = .01), jerk (median 3.3 m 2 /s 5 vs 1.6, p = .005), and slower T25FW (median 11.5 s vs 8; p < .0001). A multivariable regression model based on gait aid use and T25FW time >10.8 s (c = 0.80) was derived. Having both features portended a probability of falling of 0.97, while having neither, a probability of 0.26. Conclusions Falls in pwMS are more frequent in patients who are older, have higher PDDS, slower walking, and worse balance. Gait aid use and T25FW >10.8 s were strongly associated with falls in the past year.

ABSTRACT Background Guidelines recommend primary care practitioners (“PCPs”) engage women ≥ 75 years in shared decision‐making (SDM) around mammography screening. Therefore, we aimed to develop a web‐based conversation aid about mammography screening for women ≥ 75 using output from established simulation models to provide screening outcomes based on > 23,000 combinations of individual women's health and breast cancer risk factors. Methods We used an end‐user centered design approach to develop a prototype web‐based conversation aid incorporating feedback. From July 2023 to April 2024, 10 PCPs from a Boston‐area health system and a safety‐net hospital used the prototype aid during encounters with women ≥ 75 without breast cancer or dementia ( n = 30; 1–5 patients per PCP). We observed aid use and assessed clinician effort to involve patients in SDM using OPTION5 (assesses five components of SDM, scores range 0–100). We surveyed PCPs and patients about the aid's acceptability. Patients completed the SDM‐process scale (scores range 0–4) to rate the SDM quality experienced. Participants' comments were subject to thematic analysis. Results Of 10 PCP ‐participants, seven were female and four were community‐based. Of 30 patient‐participants, 22 (73%) were non‐Hispanic White, 9 (30%) had ≥ 2 Charlson comorbidities and mean age was 78.5 years ( SD 2.8). Nine PCPs agreed that the aid helped them with SDM and was easy‐to‐use; six felt it had too much information; and seven planned to continue using the aid. Patients rated the SDM ‐process highly (scores = 3.0 [ SD 0.9]) and we observed high SDM (mean OPTION5 = 77.9 [ SD 20.6]). Participants felt the aid was “empowering” and “helpful for decision‐making.” After SDM discussions, seven patients intended to stop screening, nine to screen less frequently, and 14 to continue screening regularly. Conclusions We developed a novel conversation aid that supports SDM about mammography screening with women ≥ 75 years. Lessons learned will guide revisions of a final tool for testing in a clinical trial.

PURPOSE Monitoring with electronic patient-reported outcome (ePRO) systems can improve cancer outcomes and is increasingly recommended. Optimal implementations of ePROs in routine clinical care are not yet known. Perspectives from clinicians, clinic staff, and patients who used ePROs can provide real-world insights for optimizing the design, efficiency, and effectiveness of future implementations. METHODS Providers, clinic staff, and patients receiving treatment for metastatic cancer from community oncology practices that implemented ePROs as part of the national PRO-TECT trial (Alliance AFT-39) participated in semi-structured interviews related to ePROs. Perceptions from clinicians on perceived benefits, usefulness, acceptability, impact on quality of care, and required effort; from staff on clinical integration and effort; and from patients on ease of use, usefulness, and effort were collected. Themes, subthemes, and recommendations were identified via a standardized coding-based directed thematic analytic approach. RESULTS Ninety-eight clinic members and 67 patients participated from 25 intervention sites. Four themes were identified: (1) positive impact of ePROs on cancer care quality, communication, and relationship-building; (2) ePRO system usability; (3) challenges to ePRO integration with clinical workflow; and (4) recommendations for improving ePRO systems and implementation. Subthemes related to the impact of ePROs on cancer care included enhanced communication with care team, increased awareness of symptoms, and increased ability to self-manage symptoms. Actionable recommendations for future initiatives were to engage and train clinicians, staff, and organizational support for ePRO-related activities; tailor content of ePRO surveys to be clinically actionable; integrate ePRO alert notifications and reports with existing information systems; and optimize integration of ePROs with existing clinic workflow processes. CONCLUSION Experiences of care team members and patients were positive, with actionable recommendations identified to guide future ePRO implementations.