Genomic Testing Research Articles

Germline and somatic testing for homologous repair deficiency in patients with prostate cancer (part 1 of 2).

Unfortunately, not all metastatic castration resistant prostate cancer (mCRPC) patients receive available life-prolonging systemic therapies, emphasizing the need to optimize mCRPC treatment selections. Better guidelines are necessary to determine genetic testing in prostate cancer. In this two-part expert opinion-based guide, we provide an expert consensus opinion on the utilization of germline and somatic testing to detect HRR alterations in patients with mCRPC. This guide was developed by a multidisciplinary expert panel that convened in 2023-2024, including representatives from medical oncology, urology, radiation oncology, pathology, medical genomics, and basic science. We argue for the widespread adoption of germline testing in all patients with prostate cancer and for somatic mutations testing in patients at the time of recurrent/metastatic disease. In this first part, we review how genomic testing is performed. We also review how to overcome certain barriers to integrate genetic and biomarker testing into clinical practice.

The Evolving Role of Genomics in Colorectal Cancer

Approximately 75% of colorectal cancers (CRCs) harbour an identifiable driver mutation, 5% of these being heritable. These drivers have recognised implications for prognosis and therapy selection. In addition, potential germline mutations require investigations to inform testing of relatives, as well as surveillance for other malignancies. With increasing numbers of targeted drugs being approved, judicious testing is required to ensure sufficient tumour is available for testing and at the right point in the cancer pathway. Liquid biopsy with circulating tumour DNA (ctDNA) in the blood presents an exciting adjunct to tumour tissue testing for molecular drivers, as well as escalation and de-escalation of therapy. We review the most frequent molecular alterations in CRC, how genomic testing should be integrated into the treatment pathway for CRC, and sources of further education.

Utilization of genomic tumor testing (GTT) among community oncologists participating in SWOG S2108CD.

320 Background: As targeted therapy options increase in oncology, GTT use is also increasing; however, the strategies and barriers to ordering GTT can vary across clinics. S2108CD is a cluster randomized trial comparing an educationally enhanced genomic tumor board intervention to usual practice to increase evidence-based genome-informed therapy based on GTT results. This analysis seeks to understand the utilization of GTT by physicians in rural and community oncology clinics. Methods: Physicians at sites enrolled on S2108CD completed baseline questionnaires collecting demographics, practice characteristics, and physicians’ experience with and use of GTT in practice. We also conducted semi-structured interviews at baseline and mid-study with select physicians in both arms to understand how and when physicians are ordering GTT and how it guides treatment decision making. Descriptive statistics were generated for survey data. Interviews were analyzed using conventional content analysis to identify recurring themes. Results: Surveys were completed by 117 physicians across 18 Recruitment Centers, with 57 from the usual practice and 60 from the intervention arm. Interviews were conducted with 10 physicians at baseline and 10 within 12-18 months of start of the study. Physicians reported feeling confident in determining whether GTT is clinically appropriate for a patient (42% moderately confident, 50% very confident). Some physicians utilize GTT from multiple vendors, with the following vendors used most frequently: Tempus (50% of physicians), Caris Life Sciences (61%), Foundation Medicine (62%) and Guardant Health (69%). Over two-thirds of physicians reported that professional guidelines were “very important” in the decision to utilize GTT. Reasons for not ordering GTT included “not relevant for the patient” (36%) and “difficulty in obtaining sufficient tissue” (20%) as “often” reasons. Notably, lack of access and cost/insurance coverage were “never” or “rarely” a reason for not ordering GTT in 80% physicians. Long waits to receive GTT results reportedly caused a delay in making patient care decisions (47% sometimes and 26% often). Physicians rely on the following sources to learn about new GTT panels: scientific meetings (91%), peer-reviewed literature (92%), and professional societies (90%). Interview data confirmed that physicians are generally confident ordering GTT but there is variability in the processes for ordering GTT and receipt of GTT results amongst clinics. Conclusions: Physicians enrolled on S2108CD self-reported high genomic confidence in ordering GTT. Access to GTT and coverage of GTT do not appear to be barriers to utilization. However, physicians did report delays in decision-making due to result turn-around times, which were sometimes attributed to length of time to tissue sendout and receipt of results into health record. Funding : NIH/NCI/NCORP grant UG1CA189974. Clinical trial information: NCT05455606 .

SY18-2 The current status of comprehensive genomic profile testing in head and neck cancer

SY18-2 The current status of comprehensive genomic profile testing in head and neck cancer

Evaluation of completeness of commonly used data elements for clinical trial eligibility criteria using a registry-enhanced data collection process: Results from patients with non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) at three community oncology practices.

346 Background: Data elements required for clinical trial eligibility assessments are often unstandardized and incomplete in EHR making clinical research participant identification a challenging and biased process. Moreover, the absence of new patient records and disease codes results in monitoring large patient populations until records are completed. These issues can lead to missed opportunities for timely patient identification. N-Power Medicine (NPM) developed a registry-enhanced oncology network platform for unbiased, and real-time quality data collection. We report from this platform on completeness rates of key variables for eligibility assessment in NSCLC and CRC clinical trials. Methods: NPM’s platform consists of 3 parts: patient registry (Kaleido), onsite and remote staff to consent patients and ensure data completeness, quality and standardization, and technology to structure and process the data. Patients with NSCLC and CRC from 3 community oncology practices across different US regions were enrolled in Kaleido and visited the clinic between February and May 2024. Data for 11 key variables were abstracted. To minimize the need for extensive monitoring until a diagnosis was confirmed, we developed a machine learning (ML) model for lung cancer using non-C34 ICD10 codes to construct multiple classes of tunable predictive models. Results: A total of 728 (NSCLC=281, CRC=447) patients were evaluated. The male-to-female ratio was 1 for NSCLC and 1.3 for CRC and 90% of NSCLC and 68% of CRC patients were over 60 years of age. The platform achieved 99% completeness for critical data points such as diagnosis date, histology, metastatic status, recent systemic anti-cancer treatments, ECOG performance status and other cancer diagnoses with diagnosis date. 47% of NSCLC and 43% of CRC patients had metastatic disease at the time of evaluation. Over 90% of patients with metastasis had their current therapy line and relevant genomic test results successfully documented. Imaging-based cancer status completeness was 95% for NSCLC and 89% for CRC. The ML model would identify over 50% of all patients that would eventually receive a lung cancer diagnosis, with over 80% specificity up to 3 weeks before a diagnosis. Conclusions: NPM’s platform demonstrated high completeness rates for the majority of essential data elements, improving the inclusion of all eligible patients in clinical trials. The predictive ML model shows promise in identifying suitable patients before an ICD10 code is assigned, reducing the need for extensive monitoring and ensuring timely completeness of necessary assessments for eligibility. Importantly, these advancements were achieved without adding financial or resource burdens to clinical workflows.

TNBC-DX genomic test in early-stage triple-negative breast cancer treated with neoadjuvant taxane-based therapy

BackgroundIdentification of biomarkers to optimize treatment strategies for early-stage triple-negative breast cancer (TNBC) is crucial. This study presents the development and validation of TNBC-DX, a novel test aimed at predicting both short- and long-term outcomes in early-stage TNBC. MethodsInformation from 1,259 patients with early-stage TNBC (SCAN-B, CALGB-40603, and BrighTNess) were used to establish the TNBC-DX scores. Independent validation of TNBC-DX was carried out in 3 studies: i) WSG-ADAPT-TN, ii) MMJ-CAR-2014-01, and iii) NeoPACT, including 527 patients with stage I-III TNBC undergoing neoadjuvant chemotherapy. In WSG-ADAPT-TN, patients were randomized to receive nab-paclitaxel plus gemcitabine or carboplatin. In MMJ-CAR-2014-01, patients received carboplatin plus docetaxel. In NeoPACT, patients received carboplatin plus docetaxel and pembrolizumab. The objective of this study was to evaluate the association between TNBC-DX and efficacy outcomes (pCR, distant disease-free survival [DDFS] or event-free survival [EFS], and overall survival [OS]) in the validation cohorts. ResultsTNBC-DX test was created incorporating 10-gene core immune gene module, 4-gene tumor cell proliferation signature, tumor size, and nodal staging. In the 2 independent validation cohorts without pembrolizumab, the TNBC-DX pCR score was significantly associated with pCR after adjustment for clinicopathological variables and treatment regimen (odds ratio per 10-units increment=1.34, 95% CI 1.20-1.52, p<0.001). pCR rates for the TNBC-DX pCR-high, -medium, and -low categories were 56.3%, 53.6%, and 22.5% respectively (odds ratio for pCR-high vs pCR-low=3.48 [95% CI 1.72-7.15], p<0.001). Additionally, the TNBC-DX risk score was significantly associated with DDFS (hazard ratio [HR] high-risk vs low-risk=0.24, 95% CI 0.15-0.41, p<0.001) and OS (HR=0.19, 95% CI 0.11-0.35, p<0.001). In the validation cohort with pembrolizumab, the TNBC-DX scores were significantly associated with pCR, EFS, and OS. ConclusionsTNBC-DX predicts pCR to neoadjuvant taxane-carboplatin in stage I-III TNBC and helps to forecast the patient´s long-term survival in the absence of neoadjuvant anthracycline/cyclophosphamide, and independent of pembrolizumab use.

Critically unwell infants and children with mitochondrial disorders diagnosed by ultrarapid genomic sequencing

PurposeTo characterize the diagnostic and clinical outcomes of a cohort of critically ill infants and children with suspected mitochondrial disorders (MD) undergoing ultrarapid genomic testing as part of a national program. MethodsUltrarapid genomic sequencing was performed in 454 families (genome sequencing: n = 290, exome sequencing +/− mitochondrial DNA sequencing: n = 164). In 91 individuals, MD was considered, prompting analysis using an MD virtual gene panel. These individuals were reviewed retrospectively and scored according to modified Nijmegen Mitochondrial Disease Criteria. ResultsA diagnosis was achieved in 47% (43/91) of individuals, 40% (17/43) of whom had an MD. Seven additional individuals in whom an MD was not suspected were diagnosed with an MD after broader analysis. Gene-agnostic analysis led to the discovery of 2 novel disease genes, with pathogenicity validated through targeted functional studies (CRLS1 and MRPL39). Functional studies enabled diagnosis in another 4 individuals. Of the 24 individuals ultimately diagnosed with an MD, 79% had a change in management, which included 53% whose care was redirected to palliation. ConclusionUltrarapid genetic diagnosis of MD in acutely unwell infants and children is critical for guiding decisions about the need for additional investigations and clinical management.

Diagnostic Yield and Clinical Utility of Genomic Testing in Patients with Suspected Genetic Kidney Disease: Singapore's First-Year Experience

Diagnostic Yield and Clinical Utility of Genomic Testing in Patients with Suspected Genetic Kidney Disease: Singapore's First-Year Experience

Kepentingan Bioinformatik Dalam Analisa Genomik Ke Arah Perubatan Jitu Untuk Covid-19

Genomic medicine is the use of an individual's genomic information to benefit the decision making in clinical treatment procedures such as disease diagnosis, prognosis, and therapy. As a result, genomic medicine has implications in cancer, pharmacology, rare and unknown diseases, and infectious diseases. With the advent of high - resolution and rapid genetic testing, thousands of genes have been able to be identified in complex biological samples. Bioinformatics is a crucial step in dealing with big data that may represent a large number of genes or genetic information that are significant in medical and health sciences research. Consequently, bioinformatics has become an essential component of clinical laboratories for the creation, processing, preservation, and interpretation of data from molecular genetic testing. This article provides an overview of the bioinformatics ideas and aspects used in genomic testing. Furthermore, we explore the application of bioinformatics in cancer research, as well as the implications of bioinformatics for the COVID-19 pandemic. Integrating multidisciplinary knowledge is important for overcoming the challenges of acquiring bioinformatics data suited for genomic medicine.

A case of colon cancer implanted on endoscopic resection ulcer certified by cancer genomic testing

A 90 year-old man underwent endoscopic mucosal resection for lesions in the descending and sigmoid colons as well as endoscopic submucosal dissection (ESD) for a lesion in the rectal peritoneal reflection (Ra) 1 month before undergoing laparoscopic resection and D3 dissection for advanced cancer in the descending colon. One year later, he underwent a surveillance colonoscopy, and advanced colorectal cancer was detected on the ESD scar. The history suggested that this newly detected recurrent colorectal neoplasm on the ESD scar may have originated from cancer cells derived from the descending colon cancer that were implanted in the ESD ulcer, thereby initiating a new colorectal neoplasm. Cancer genomic testing further indicated that three of the four pathogenic variants detected in the recurrent colorectal neoplasm were consistent with pathogenic variants of descending colon cancer. This finding strongly supports our contention that cancer cells derived from the descending colon cancer were implanted in the post-ESD ulcer of the rectal Ra and proliferated, forming the recurrent colorectal neoplasm. This case report highlights the potential for tumor cell implantation on endoscopic resection ulcers and the utility of cancer genomic testing in validating this phenomenon.

ASPYRE-Lung: validation of a simple, fast, robust and novel method for multi-variant genomic analysis of actionable NSCLC variants in FFPE tissue.

Genomic variant testing of tumors is a critical gateway for patients to access the full potential of personalized oncology therapeutics. Current methods such as next-generation sequencing are costly and challenging to interpret, while PCR assays are limited in the number of variants they can cover. We developed ASPYRE® (Allele-Specific PYrophosphorolysis REaction) technology to address the urgent need for rapid, accessible and affordable diagnostics informing actionable genomic target variants of a given cancer. The targeted ASPYRE-Lung panel for non-small cell carcinoma covers 114 variants in 11 genes (ALK, BRAF, EGFR, ERBB2, KRAS, RET, ROS1, MET & NTRK1/2/3) to robustly inform clinical management. The assay detects single nucleotide variants, insertions, deletions, and gene fusions from tissue-derived DNA and RNA simultaneously. We tested the limit of detection, specificity, analytical accuracy and analytical precision of ASPYRE-Lung using FFPE lung tissue samples from patients with non-small cell lung carcinoma, variant-negative FFPE tissue from healthy donors, and FFPE-based contrived samples with controllable variant allele fractions. The sensitivity of ASPYRE-Lung was determined to be ≤ 3% variant allele fraction for single nucleotide variants and insertions or deletions, 100 copies for fusions, and 200 copies for MET exon 14 skipping. The specificity was 100% with no false positive results. The analytical accuracy test yielded no discordant calls between ASPYRE-Lung and expected results for clinical samples (via orthogonal testing) or contrived samples, and results were replicable across operators, reagent lots, runs, and real-time PCR instruments with a high degree of precision. The technology is simple and fast, requiring only four reagent transfer steps using standard laboratory equipment (PCR and qPCR instruments) with analysis via a cloud-based algorithm. The ASPYRE-Lung assay has the potential to be transformative in facilitating access to rapid, actionable molecular profiling of tissue for patients with non-small cell carcinoma.

Utility of genomic testing in children, adolescents, and young adults with cancer.

Genomic testing can inform the diagnosis and personalise management of cancers in children, adolescents, and young adults (CAYA). This scoping review explored the clinical utility and impact of genomic testing in general CAYA cancer cohorts. Relevant records published in English between 2017-2024 were identified by searching PubMed. 36 studies (32 original articles; 4 reviews) were identified on genomic testing in CAYA cancers, most of which were advanced cancers. Studies internationally reported that approximately 16-18% of CAYAs with cancer carry an associated pathogenic germline variant where 40% are de-novo, and can guide treatment (eg, DNA repair gene variants). Somatic variants, predominantly copy number or structural rearrangements, inform diagnosis in up to 95% of primary cancers. Between 18-69% of patients have a somatic variant with a matched therapy, but only one third receive the genomic-guided recommendation, predominantly due to declining patient condition. Few studies evaluated the impact of matched therapies on response and survival. Combining comprehensive DNA and RNA sequencing maximises sensitivity. Circulating tumour DNA was detected in most primary cancers and shows high concordance with tumour tissue. In conclusion, genomic testing of CAYA cancers is feasible, informs diagnoses and guides personalised care. Further research is needed on response to genomic-guided treatments.

Socioeconomic and Urban-Rural Disparities in Genome-Matched Treatment Receipt and Survival after Genomic Tumor Testing.

Emerging cancer treatments are often most available to socially advantaged individuals. This study examines the relationship of patient educational attainment, income level, and rurality to the receipt of genome-matched treatment (GMT) and overall survival. Survey and clinical data were collected from patients with cancer (n = 1258) enrolled in the Maine Cancer Genomics Initiative. Logistic regression models examined whether receipt of GMT differed by patient education, income, and rurality. Kaplan-Meier curves and Cox regression were conducted to evaluate 12-month mortality. We completed additional exploratory analyses using Kaplan-Meier curves and Cox models stratified by receipt of GMT. Both logistic and Cox regression models were adjusted for age and gender. Educational attainment, income level, and rurality were not associated with GMT receipt. Of 1258 patients, 462 (36.7%) died within 365 days of consent. Mortality risk was associated with lower educational attainment (hazard ratio (HR): 1.30; 95% CI: 1.06 to 1.59; p = .013). No statistically significant differences in mortality risk were observed for income level or rurality. Exploratory models suggest that patients who did not receive GMT with lower educational attainment had higher mortality risk (HR = 1.36, 95% CI: 1.09 to 1.69, p = .006). For patients who did receive GMT, there was no difference in mortality risk between the education groups (HR: 1.01, 95% CI: 0.56 to 1.81, p > .9). While there were no disparities in who received GMT, we found a disparity in mortality associated with education level, which was more pronounced for patients who did not receive GMT. Future research is warranted to investigate the intersectionality of social disadvantage with clinical outcomes to address survival disparities.

Abstract C070: Barriers to genomic testing reduce clinical trial eligibility for diverse populations

Abstract Tumor genomic testing and cancer clinical trials expand access to precision therapeutics, enhancing patient experience. However, physician and patient barriers impact participation of historically underrepresented patients (HUP), limiting generalizability for those most negatively affected by cancer. We interviewed patients to identify factors impacting genomic testing uptake and clinical trial enrollment. From 09/2021 - 12/2021 we interviewed 16 HUP diagnosed with cancer seen at an ambulatory oncology center: 3 spoke a language other than English, 9 identified as Black, 6 Hispanic/Latinx, 3 other race, and 3 older adult (age 70+). Individual interviews utilized a structured interview guide and lasted 45 minutes. Participants were recruited until thematic saturation was reached and transcripts were coded for major themes. Patients were unsure if they received genomic testing or if testing was recommended (citing possible confusion with medical information). Barriers included education (unclear benefit to participation, investigational drug/device identity, procedures involved), mistrust of research (data privacy concerns), and logistical accessibility (cost, time away from work, transportation). Those tested found it to be an easy process. Several cited that a patient advocate would be a beneficial resource to navigate the process. Barriers around clinical trial enrollment included education (risks of participating, size of the study, investigational drug/device identity), mistrust of research (data privacy, inclusion of HUP in trial, loss of autonomy in decision-making), and logistical accessibility (time commitment). HUP who participated in a trial appreciated additional psychosocial support and clinical monitoring. Patients were emphatically interested in genomic testing and cancer clinical trials when presented as the best course of care, though concerns about side effects from trials persisted. Patient barriers to genomic testing and clinical trials center around education, mistrust in research, and logistical accessibility. Patients who participated in genomic testing and clinical trials had a positive experience. Barriers may be addressed with tailored education, including supportive resources referral. Citation Format: Nadine J. McCleary. Barriers to genomic testing reduce clinical trial eligibility for diverse populations [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C070.

Abstract A084: Journey to understanding indigenous peoples engagement in cancer genomic research

Abstract Introduction: Tribal Nations across the Southwest have striking disparities in cancer incidence and mortality. Compounded by disproportionately low rates of cancer screening and limited access to healthcare, Native Americans are more often diagnosed at later stages of disease and have the poorest outcomes in all types of cancer when compared to any other racial and ethnic group in the United States. At the University of New Mexico Comprehensive Cancer Center, the Participant Engagement Cancer Genomic Sequencing (PE-CGS) Center is developing culturally appropriate materials and strategies to enhance the engagement and recruitment of Native Americans into genomic research. This effort aims to determine participant knowledges, attitudes, cultural beliefs, and communication preferences regarding clinical genomics testing. Ultimately, targeting improvement of cancer outcomes in Southwestern Tribal communities. Cultural adaptations are crucial with regards to biospecimen collection, storage, and usage, due to historical mistrust of research among Native communities. (i.e., Havasupai Tribe v. the Arizona Board of Regents). A Tribal Advisory Committee, consisting of Tribal leaders, Native physicians, and patient advocates oversee all aspects of the research study. The goal is to identify appropriate optimized health literacy strategies for engaging Native peoples in cancer genomic research. Methods: The team conducted semi-structured discussions with participants to understand their perspectives on motivations to join, cultural safety components, and effectiveness of engagement strategies. With participant consent, the discussions were recorded and transcribed. Analysis included the transcripts and notes taken by the interviewer and followed Grounded Theory principles. All transcripts and notes followed line-by-line analysis by three of the authors (JS, JR and TG) who met regularly to identify and discuss emergent themes. Results: As of May 31, 2024, the PE-CGS study has enrolled 112 participants and completed 39 discussions. Participants emphasized altruistic motives tied to family and community, echoing traditional values, in their decision to participate in the study. This notion emerged during interactions with Native team members, where comfort stemmed from shared experiences (healthcare system, barriers), use of Native language, and adherence to Native social norms. Additional considerations included present autonomy throughout various stages of the study (sample use, data sharing, discussions). Return of genetic testing results improved understanding of treatment options, hereditary risk, and health literacy. Conclusion: Feedback highlights the importance of aligning cultural beliefs with Western medicine through a strengths-based approach. The findings will inform improvements in respectful engagement, communication, information exchange, and recruitment processes with Native American cancer patients and cancer survivors to genomic testing studies. Citation Format: Jessica Sanchez, Koby Blackwater, Joseph Rodman, Tamar Ginossar, Andrew Sussman, Shiraz Mishra, Cindy Blair, Mallery Quetawki, Debra MacKenzie, V. Shane Pankratz, Ursa Brown-Glaberman, Jeffery Trent, Cheryl Willman. Journey to understanding indigenous peoples engagement in cancer genomic research [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A084.

Abstract C071: Comprehensive genomics-informed prospective older adult (OA) cancer registry: Initial findings from gastrointestinal (GI) malignancy

Abstract The REACH study (Resilience and Equity in Aging, Cancer, and Health) assesses the impact of geriatric consultation on reducing emergency department and/or unplanned hospitalization visits (EDH) for OA age 70+ diagnosed with GI cancer. We sought to develop an OA GI cancer registry (REACH Registry) within the REACH intervention integrating 1) disease and treatment factors from the PRISSMM cancer taxonomy model with 2) patient reported outcomes and 3) geriatric assessment (GA) measures predictive of function, toxicity, and survival. We reviewed GA measures using the modified Rockwood frailty scale, PROMIS-10 global mental and physical scores, Karnofsky performance status, health-related social needs, and disease/treatment factors using PRISSMM cancer taxonomy for OA consented to REACH in the GI Cancer Center at Dana-Farber Cancer Institute (DFCI) from January 2022–April 2024. OA were eligible if age 70+ at initial DFCI consult visit and diagnosed with any GI cancer. The GA stratifies OA by frailty level on a 0-1 scale: Fit/Robust (score range 0–0.19), Pre-Frail (0.2–0.34), and Frail (0.35–1.0). PRISSMM is a cancer data modeling system developed for the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative; it includes pathology, radiology/imaging, symptoms, and molecular markers curated by trained research staff from unstructured EHR data. From Jan. 2022–Apr. 2024, 50 OA consented to REACH registry (94 eligible). Of those, 44% (n=22) have PRISSMM data available for analysis. Most OA reported white race (90%, n=45) and female gender (52%, n=26). Pancreatic cancer was the most common diagnosis (n=21), followed by colon (9), biliary (5), and esophageal (4). Most OA completed GA (90%, n=45) with 51% screened Fit/Robust (n=23), 47% Pre-Frail (n=21), and 2% Frail (n=1). Type 2 diabetes mellitus was the most commonly reported comorbid condition (26%, n=13), followed by chronic kidney disease (n=6) and congestive heart failure (n=3). Of the 22 OA with available PRISSMM data, 59% (n=13) were diagnosed with stage IV disease and 100% received cancer-directed therapy; 72% (n=16) received standard care, 27% clinical trial (n=6). Most OA consented for tumor somatic genomic testing (77%, n=17). At the time of data curation 24 months from assessment, 20 patients had died, 30 were alive. Evaluation of the REACH intervention geriatric consultation on EDH outcome is forthcoming. REACH registry is the first GI cancer database inclusive of geriatric specific measures alongside curated disease, treatment and genomic data. We observed a higher rate of genomic testing and treatment initiation than reported in the literature. We anticipate that by September 2024, a larger cohort of REACH Registry participants will have completed PRISSMM data available for analysis. Future study will compare EDH for REACH vs. non-REACH OA as well as treatment patterns of this OA cohort evaluated at a large comprehensive cancer center and associated community sites. Citation Format: Tammy T. Hshieh, Rachel L. Weitzner, Siri Rosenberg, Leila Rostamnjad, Lauren K. Brais, Nora Horick, Tamryn Gray, Jiping Wang, Jeffrey Meyerhardt, Nadine J. McCleary. Comprehensive genomics-informed prospective older adult (OA) cancer registry: Initial findings from gastrointestinal (GI) malignancy [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C071.

Abstract C135: The heterogenous impact of healthcare access factors throughout the breast cancer care continuum

Abstract Background: Delays in breast cancer diagnosis and treatment lead to worse survival and quality of life decrements. Racial disparities in care timeliness have been reported, but few studies have examined access at multiple points along the care continuum (diagnosis, treatment initiation, treatment duration, and genomic testing). Methods: The Carolina Breast Cancer Study Phase 3 (CBCS3) is a population-based cohort (n=2998, 50% Black) with invasive breast cancer diagnoses (2008-2013). We used latent class analysis (LCA) to group participants based on patterns of factors within 3 separate domains: “socio-economic status (SES)”, “care barriers”, and “care use.” These classes were evaluated in association with delayed diagnosis (approximated with stage 3 or 4 at diagnosis), delayed treatment initiation (more than 30 days between diagnosis and first treatment), prolonged treatment duration (time between first and last treatment – by treatment modality), and receipt of OncotypeDx genomic testing (evaluated among patients with early stage, ER+, HER2- disease). Associations were evaluated using adjusted linear-risk regression to estimate relative frequency differences (RFDs) with 95% confidence intervals (CIs). Results: Overall, 18% of CBCS participants had late stage/delayed diagnosis, 35% had delayed treatment initiation, 48% had prolonged treatment duration, and 62% did not receive OncotypeDx. Black women had greater frequency of each unfavorable care outcome compared to non-Black women, including diagnostic delay (22% vs 15%, RFD= 6.9, 4.1-9.6), treatment initiation delay (39% vs 31%, RFD=7.9, 4.5-11.3), prolonged treatment (50% vs 46%, RFD= 4.3, 0.5-8.2), and OncotypeDx non-receipt (69% vs 57%, RFD= 12.2, 7.3-16.7). We identified 3 latent classes for SES (“high SES”, “moderate SES,” and “low SES”) 2 classes for care barriers (“few barriers”, “more barriers”), and 5 classes for care use (“short travel/high preventive care”, “short travel/low preventive care,” “medium travel,” “variable travel,” and “high travel”). Low-SES and more barriers to care were associated with greater frequency of delayed diagnosis (RFDadj = 5.5, 2.4-8.5; RFDadj =6.7, 2.8-10.7, respectively) and prolonged treatment (RFDadj = 9.7, 4.8-14.6; RFDadj = 7.3, 2.4-12.2, respectively). Variable travel (short time to diagnosis but long time to surgery) was associated with delayed treatment in the entire study population (RFDadj = 10.7, 2.7-18.8) compared to the short travel, high use referent group. The high travel group (representing long travel to both diagnosis and surgery) was associated with delayed treatment only among Black women relative to the same referent group (RFDadj = 10.0, -3.3-23.2). Conclusions: Black patients face more frequent delays throughout the care continuum, likely stemming from different types of access barriers at key junctures. Improving breast cancer care access will require intervention on multiple aspects of SES and healthcare access. Citation Format: Matthew R. Dunn, Didong Li, Marc A Emerson, Caroline A. Thompson, Hazel B Nichols, Sarah C Van Alsten, Mya L. Roberson, Lisa A. Carey, Terry Hyslop, Jennifer Elston Lafata, Melissa A. Troester. The heterogenous impact of healthcare access factors throughout the breast cancer care continuum [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C135.

Abstract C135: The heterogenous impact of healthcare access factors throughout the breast cancer care continuum

Abstract Background: Delays in breast cancer diagnosis and treatment lead to worse survival and quality of life decrements. Racial disparities in care timeliness have been reported, but few studies have examined access at multiple points along the care continuum (diagnosis, treatment initiation, treatment duration, and genomic testing). Methods: The Carolina Breast Cancer Study Phase 3 (CBCS3) is a population-based cohort (n=2998, 50% Black) with invasive breast cancer diagnoses (2008-2013). We used latent class analysis (LCA) to group participants based on patterns of factors within 3 separate domains: “socio-economic status (SES)”, “care barriers”, and “care use.” These classes were evaluated in association with delayed diagnosis (approximated with stage 3 or 4 at diagnosis), delayed treatment initiation (more than 30 days between diagnosis and first treatment), prolonged treatment duration (time between first and last treatment – by treatment modality), and receipt of OncotypeDx genomic testing (evaluated among patients with early stage, ER+, HER2- disease). Associations were evaluated using adjusted linear-risk regression to estimate relative frequency differences (RFDs) with 95% confidence intervals (CIs). Results: Overall, 18% of CBCS participants had late stage/delayed diagnosis, 35% had delayed treatment initiation, 48% had prolonged treatment duration, and 62% did not receive OncotypeDx. Black women had greater frequency of each unfavorable care outcome compared to non-Black women, including diagnostic delay (22% vs 15%, RFD= 6.9, 4.1-9.6), treatment initiation delay (39% vs 31%, RFD=7.9, 4.5-11.3), prolonged treatment (50% vs 46%, RFD= 4.3, 0.5-8.2), and OncotypeDx non-receipt (69% vs 57%, RFD= 12.2, 7.3-16.7). We identified 3 latent classes for SES (“high SES”, “moderate SES,” and “low SES”) 2 classes for care barriers (“few barriers”, “more barriers”), and 5 classes for care use (“short travel/high preventive care”, “short travel/low preventive care,” “medium travel,” “variable travel,” and “high travel”). Low-SES and more barriers to care were associated with greater frequency of delayed diagnosis (RFDadj = 5.5, 2.4-8.5; RFDadj =6.7, 2.8-10.7, respectively) and prolonged treatment (RFDadj = 9.7, 4.8-14.6; RFDadj = 7.3, 2.4-12.2, respectively). Variable travel (short time to diagnosis but long time to surgery) was associated with delayed treatment in the entire study population (RFDadj = 10.7, 2.7-18.8) compared to the short travel, high use referent group. The high travel group (representing long travel to both diagnosis and surgery) was associated with delayed treatment only among Black women relative to the same referent group (RFDadj = 10.0, -3.3-23.2). Conclusions: Black patients face more frequent delays throughout the care continuum, likely stemming from different types of access barriers at key junctures. Improving breast cancer care access will require intervention on multiple aspects of SES and healthcare access. Citation Format: Matthew R. Dunn, Didong Li, Marc A Emerson, Caroline A. Thompson, Hazel B Nichols, Sarah C Van Alsten, Mya L. Roberson, Lisa A. Carey, Terry Hyslop, Jennifer Elston Lafata, Melissa A. Troester. The heterogenous impact of healthcare access factors throughout the breast cancer care continuum [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C135.

Abstract B167: Genomics and cancer clinical trials navigator training: Results from a systematic review of the literature

Abstract Introduction: Trained cancer navigators have demonstrated success in improving outcomes for cancer patients. Trainings provided by the American Cancer Society and other organizations equip navigators with the knowledge, skills and experience to support patients and address barriers to cancer-related care and survivorship. Racial/ethnic minorities continue to be underrepresented in cancer clinical trials and are less likely to receive genomic counseling and testing. There is a notable gap in the availability of cancer navigator training in genomic and clinical trials. This study used a systematic review of the literature and consultations with Genomics and Cancer Clinical Trial (CCT) experts to inform the development of cancer navigation training curriculum. Methods: Two reviewers searched the PubMed database for peer-reviewed studies published through October 2022. Key MeSH terms included cancer, genetics, and training. An ancestor search of relevant articles was also conducted. Following title screening, eleven articles were selected for abstract and full-text review. Eight articles met all the inclusion criteria from which we extracted the 1) trainee population, 2) theoretical frameworks used, 3) program design and format, 4) curricular components, and 5) outcomes. New Data: Only seven articles on the topic of navigator training in genomics within the context of CCT were identified in the search. Training participants were diverse and were located within the United States and abroad. One training program was developed for bilingual (English/Spanish) navigators, one was tailored for cancer survivors who became navigators and two programs trained navigators for specific cancer types (e.g., colorectal cancer). Social cognitive theory (SCT) was used in two of the training programs. Other adult learning theories and intervention mapping for program development were also used in training development. The process for designing navigator trainings included: conducting discussion groups; interviews and surveys; engaging advisory boards; and adapting the National Human Genomics Research Institute modules and other resources. The curricula components included in-person and web-based; single semester or year-long sessions; formal coursework; lectures; role-playing; video viewing; tours of facilities; demonstrations; short writing assignments; action plans; case studies; story- telling; discussion and networking; assessment/evaluation; and refresher sessions. Modules addressed attitudes, barrier assessment and resolution, knowledge, self-efficacy, and communication. Conclusion: The peer-reviewed literature on navigator training describes some curricular elements that measure and address knowledge about genomics and CCT as well as the skills needed to increase self-efficacy to navigate for genetic studies and cancer clinical trials. However, the field of CCT lacks a consistent and widely used program aimed at training navigators in the integral role of genetics in precision medicine. These findings informed the design of our ACS-funded curriculum. Citation Format: Desiree Rivers, Robina Josiah Willock, Victoria Churchill. Genomics and cancer clinical trials navigator training: Results from a systematic review of the literature [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B167.

Abstract B063: A community-based organization, health equity uplift and growth alliance for triple negative breast cancer and metastatic breast cancer in young women

Abstract Background: Triple Negative Breast Cancer (TNBC) and Metastatic Breast Cancer (MBC) disproportionately affect the Black, indigenous, and people of color (BIPOC) community as well as younger women. Breast cancer (BC) is the leading cause of cancer-related deaths in women less than 40 years old, and survival rates for young women with BC remain lower than for their older counterparts. While more effective treatments and progress in genomic and genetic testing have improved survival of those affected by BC, not everyone has benefited from these advances. Methods: In early 2023, Tigerlily Foundation issued a request for proposal for community-driven initiatives to educate and support young BIPOC women at risk or living with TNBC or MBC in under resourced communities. Fifteen applications were received by Tigerlily over a 6-week period, and 5 community-based organizations (CBOs) in under-resourced metropolitan areas were recommended for $20,000 each in funding by an independent review panel. Tigerlily met with CBO leaders 3 times between May 2023-April 2024 to share experiences, lessons learned and successes. Results: The community- based organization health equity uplift and growth (CBO HUG) alliance resulted in patients and caregivers with increased awareness regarding BC stage, type, and equitable care standards. Approximately, 620 CBO led programs were held over 12 months, where 15,419 BIPOC community members were reached, and 340 community members were referred for screening or health services in partnership with CBOs, Tigerlily’s ANGEL Advocates (Peer Navigators) and NCI Cancer Center Leadership. Programs generally fell into 19 program types, e.g., game nights, radio podcasts, and programs in connection with mobile mammogram units. Twelve Tigerlily ANGEL advocates participated by sharing Tigerlily resources and their stories, providing educational material, facilitating discussion groups, and co-designing content and evaluation instruments. Evaluation reports identified over 40 actionable and notable practices. These practices are categorized by those that worked well and those that need improvement, as noted by CBO leadership and/or ANGEL advocates. Conclusions: The CBO HUG Alliance education and capacity building initiative fostered solutions and bolstered community-based organizations in under-resourced communities. This program leveraged peer navigation and culturally sensitive programming to help young BIPOC persons optimize their health. CBO leaders provided local expertise and community-driven solutions which are at the core of Tigerlily’s commitment to uplift others by listening, learning, leveraging what we learned, and letting the community lead. Next steps include sustained co-curation of tailored content to support empowerment of priority populations. Citation Format: Jeanne M. Regnante, Mandi L. Pratt-Chapman, Belinda Paulicin, Amy Leader, Virginia Leach, LaToya A. Cooper, Sue Steele, Maimah Karmo. A community-based organization, health equity uplift and growth alliance for triple negative breast cancer and metastatic breast cancer in young women [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B063.