tbuckley/cabot-search huggingface dataset:
Understanding barriers to guideline-concordant treatment in foregut cancer: From data to solutions.
Authors: Annabelle L. Fonseca, Krisha Amin, Manish Tripathi, Larry Hearld, Martin J. Heslin, Smita Bhatia
Journal: Journal of Clinical Oncology (2024)

e13521 Background: Receipt of guideline concordant treatment (GCT) is associated with improved prognosis in foregut (gastric, pancreatic, and hepatobiliary) cancers. However, a large proportion of patients with foregut cancers do not receive GCT. This single institution study from the Deep South sought to understand barriers to receipt of GCT using a root cause analysis (RCA) approach. Methods: A retrospective review of 498 patients with foregut adenocarcinoma diagnosed between 2018-2022 was performed. GCT was defined using National Comprehensive Cancer Network guidelines. The Ishikawa cause and effect model was used to establish main contributing factors to non-receipt of GCT. Results: Overall, 170 patients (34.1%) did not receive GCT. Median (Interquartile range [IQR] time from symptoms to start of workup was 8.8 weeks (4.3-16.4); time from diagnosis to first oncology appointment was 4.6 weeks (1.6- 6.6), and time from oncology appointment to start of treatment was 11 weeks (3.7- 18.2). Root causes of non-GCT included Patient, Physician, Institutional Environment and Broader System-related factors. Non-GCT was often a function of multiple intersecting patient, physician, and institutional factors. Barriers to receipt of GCT along the cancer care continuum included: receipt of incomplete therapy due lack of follow-up with surgical oncologist after initial appointment (16.5%), deconditioning on chemotherapy resulting in non-receipt of surgical therapy (15.3%), multiple delays in care due to patient resource constraints resulting in loss to follow-up after receipt of some therapy (11.2%), physician factors including provider knowledge (leading to delayed or non-diagnosis) or specialist non- adherence to GCT (11.2%), lack of documented treatment plan after referral to oncologist (11.2%), loss to follow up before oncology referral without record of health system attempt to re-establish care (10%), non-referral to oncologist (9.4%), non-referral to surgical oncologist in patients with resectable disease (8.8%), and complications during treatment preventing completion of treatment (6.5%). Findings from this study will allow us to propose targeted solutions to improve receipt of GCT, such as development of automated systems to improve patient follow-up and compliance with GCT; institutional prioritization of resources to enhance staffing for navigation, physical therapy, social services, and care coordination; financial counselling and assistance programs; and development and integration of structured prehabilitation programs into cancer treatment pathways. Conclusions: A substantial percentage of patients with foregut cancer do not receive GCT due to multiple barriers along the cancer care continuum. This RCA approach allows us to propose and develop solutions that may improve receipt of GCT.
A cancer center department of supportive oncology: Patient demographic characteristics.
Authors: Beth York, Declan Walsh
Journal: Journal of Clinical Oncology (2024)

e13518 Background: Supportive Oncology is critical to whole-person, modern cancer care. Our Department of Supportive Oncology (DSO) provides the following services: palliative medicine, senior oncology, integrative oncology, cancer survivorship, genetics, cancer rehabilitation, oncology nutrition, patient navigation, and psycho-oncology. Little is known on the patient population who access these services which makes program development difficult. We describe the key demographic variables in a Supportive Oncology Department (DSO) for age, payor, gender, language preference, and race across our health system, geographical locations, and DSO services. Methods: Patient encounters, as noted in the EMR, were analyzed in a Microsoft PowerBI (www.microsoft.com) database using visits from July 1, 2022 through December 31, 2023. Variables were pre-defined by the healthcare system. Descriptive statistics in grouped frequency distribution tables were used. Results: Female, White, English-speakers (respectively) were the top utilizers across our healthcare system (57%,62%,94%), the oncology service line (64%,69%,97%), and DSO (68%,68%,96%). By gender, females were predominant users (84%) of Integrative Oncology &amp; Survivorship services. Males used Senior Oncology &amp; Palliative Medicine most often of all DSO services (45%). Differences in race were noted in geography (Black urban 26% vs rural 18%). In DSO services, Black patients access for senior oncology/palliative medicine (combined) was highest at 26%. Lowest utilization for Blacks was psycho-oncology &amp; genetics at 18 and 13% respectively. While the overall system had more managed care (55%), both the oncology service line and DSO had more Medicare and less Medicaid. DSO had more managed care (46%) than the service line (42%). In rural settings, DSO patients (39%) were more likely to be in managed care than those in the service line (34%). DSO had more patients in younger age groups (ages 45-64, 42%) than both the oncology service line (35%) and the health system (24%), regardless of urban/rural location. In both the health system and the oncology service line, younger patients were more likely to be in urban locations and older were more likely rural. For DSO services, younger patients (ages 18-44) were more involved in psychology (27%), genetics (26%), and integrative &amp; survivorship care (19%). Older patients were more likely to utilize palliative medicine and senior oncology (ages &gt; 65, 47%). Conclusions: This Supportive Oncology population reveals variation in service access related to demographic characteristics that can inform future program development. Important similarities and differences were noted compared to the wider oncology service line and health system. Age, gender, geographic, payor, and racial disparities may influence service utilization in Supportive Oncology.
Predicting therapeutic clinical trial enrollment for underrepresented patients in neuro-oncology using supervised machine learning.
Authors: Mulki Mehari, Gayathri Warrier, Abraham Dada, Aymen Kabir, Ugonma Nnenna Chukwueke, Alyx B. Porter, Shawn L. Hervey-Jumper
Journal: Journal of Clinical Oncology (2024)

1614 Background: Despite the unique ability of machine learning (ML) techniques to uncover complex interactive effects in datasets, studies exploring predictors of clinical trial enrollment have largely used standard statistical methods to discern associations. Furthermore, there have been limited applications of ML to close existing disparities in clinical trial enrollment of underrepresented patients in neuro-oncology. This study aims to use supervised machine learning to define and validate primary contributors of therapeutic clinical trial enrollment for a) all patients, b) women and c) NIH-designated minority patients with low- and high-grade glioma. Methods: Adult glioma patients who received care from the UCSF Brain Tumor Center between 1997- 2017 were identified in a prospective registry. Bootstrap forest (BF) and Recursive Partitioning (RP) models were created by randomly dividing patients in a 70/30 split into development (DEV) and validation (VAL) cohorts among all patients, women, and NIH-designated minority patients, separately. Model performance was assessed using the area under the curve (AUC) in the DEV and VAL cohorts. Results: Among 1042 patients, 350 patients (33.6%) enrolled in a therapeutic clinical trial. There were 445 women (42.7%), of which 144 (32.4%) enrolled, and 141 minority patients (13.5%), of which 39 (27.7%) enrolled. For all patients, in order of decreasing influence, the BF model selected median neighborhood household income, age, neighborhood poverty level, distance from hospital, tumor location, tumor volume, treatment with chemotherapy, occupation, KPS, insurance status, employment status, seizure at presentation, and volumetric extent of resection (EOR) to predict trial enrollment (DEV AUC: 0.984; VAL AUC: 0.746). For women, the BF model selected distance from hospital, age, household income, neighborhood poverty level, tumor location, treatment with chemotherapy, and KPS for trial prediction (DEV AUC: 0.972; VAL AUC: 0.746), whereas for minority patients, the BF model selected neighborhood poverty level, age, occupation, distance from hospital, tumor volume, insurance status, employment status, and EOR to predict trial enrollment (DEV AUC: 0.9830; VAL AUC: 0.769). The RP model for women designated those with non-White race as less likely to enroll (DEV AUC: 0.735; VAL AUC: 0.665) while the RP model for minority patients characterized those who preferred a non-English language or who were divorced or widowed as less likely to enroll (DEV AUC: 0.775; VAL AUC: 0.601). Conclusions: Supervised machine learning models achieved similar predictive performance among patient subgroups, while uncovering interactions between gender identity, minority status, and sociodemographic variables. These findings can guide targeted recruiting efforts to advance equitable trial enrollment for women and minorities.
<i>CCNE1</i> amplification as marker of poor prognosis and novel therapeutic target in advanced breast cancer.
Authors: Antonio Marra, Pier Selenica, Yingjie Zhu, Anton Safonov, Pedram Razavi, Anne Roulston, Maria Koehler, Giuseppe Curigliano, Dara S. Ross, Britta Weigelt, Jorge Reis-Filho, Alison M. Schram, Sarat Chandarlapaty, Ezra Rosen
Journal: Journal of Clinical Oncology (2024)

1040 Background: Cyclin E1 (CCNE1) overexpression or gene amplification is linked to dismal outcomes in various tumors, including breast cancer (BC). Recent studies suggest that CCNE1 amplification is a potential target for new synthetic lethality-based treatments, including CDK2-selective and PKMYT1 inhibition. This study explores the clinical and genomic characteristics of CCNE1-amplified BCs. Methods: We analyzed genomic and clinical data from consecutive BCs that underwent clinical tumor-normal targeted panel sequencing (MSK-IMPACT) between April 2014 and December 2021. Allele-specific copy number, including CCNE1 amplification, and fraction genome altered (FGA) were calculated by FACETS. Mutual exclusivity and co-occurrence analyses were performed using CoMEt. Benjamini–Hochberg method for multiple testing correction (q) was applied. Real-world progression-free survival (rwPFS) was assessed by the Kaplan Meier method and Cox models, focusing on patients with available pre-treatment samples. Results: Out of 3,753 BCs, 125 (3.3%) had CCNE1 amplification. A higher occurrence of CCNE1 amplification was noted in post-treatment (n=2,368) compared to treatment-naïve tumors (n=1,385; 4% vs 2.4%, p=0.007). CCNE1 amplification was less common in hormone receptor (HR)+/HER2- BCs (2%) compared to HER2+ (7.6%) and triple-negative (7.2%) tumors (p&lt;0.001). BCs with CCNE1 amplification showed higher median FGA, indicating increased genomic instability. In primary BC, TP53 alterations were more frequent in CCNE1-amplified tumors (q&lt;0.001), while CDH1 alterations were mutually exclusive (q&lt;0.001) suggesting that lobular BCs rarely harbor CCNE1 amplification. Similar trends were seen in post-treatment samples. CCNE1 amplification detected at baseline was linked to shorter median rwPFS in HR+/HER2- metastatic BCs treated with CDK4/6 inhibitors plus endocrine therapy (8.8 vs 15.2 months in CCNE1-amplified [n=9] vs CCNE1-non amplified [n=402]; hazard ratio [HR] 2.82, 95% CI 1.38-5.75), and in HER2+ metastatic BCs treated with first-line THP regimen (7.3 vs 20.8 months in CCNE1-amplified [n=5] vs CCNE1-non amplified [n=106]; HR 3.1, 95% CI 1.24-7.87). In a CCNE1-amplified triple-negative cell model (HCC1569), treatment with the PKMYT1 inhibitor RP-6306 significantly reduced tumor growth. Conclusions: CCNE1 amplification in BCs is associated with greater genomic instability and characterizes a group of metastatic BCs with poor response to standard of care therapies. Novel therapies targeting CCNE1-amplified tumors are under evaluation in preclinical and clinical studies.
Association of single nucleotide polymorphisms (SNPs) in inflammatory pathways with breast cancer (BC) risk: A multi-ethnic scoping review.
Authors: Erina Quinn, Ruth C. Carlos
Journal: Journal of Clinical Oncology (2024)

1617 Background: Breast cancer is the most prevalent cancer affecting women of every ethnic group in the United States. This is a scoping review assessing SNPs in inflammatory pathways posited to modify BC risk by ethnicity. Methods: We followed PRISMA guidelines for scoping reviews. PubMed, Medline, and OVID databases were interrogated for publications between 1/2000-12/2023 using search terms “breast cancer” AND [BMI OR “body mass index” OR elevated BMI OR obesity] AND [SNP OR “single nucleotide polymorphism” OR polymorphism OR mutation] AND [inflammation OR cytokines OR IL-1 OR IL-2 OR IL-4 OR IL-6 OR IL-8 OR IL-10 OR IL-12 OR TNF-A or TGFB OR CRP] AND [Asian, Black or Hispanic]. A single reviewer assessed 72 unique publications and determined that 42 met inclusion criteria. Two reviewers extracted the following data: demographics, SNP, number of cases and controls by ethnicity. Disagreements were resolved by consensus with a third reviewer. Results: Data were extractable from 42 studies, all case controls. In analyses stratified by ethnicity, we detected effects of SNPs on BC risk (Table). IL-1β rs1143634 and IL-10 (1082 A/G) had a significantly increased BC risk in Asian populations but insignificant in white populations. There were minimal publications for Black and Hispanic populations. Conclusions: The association of inflammatory SNPs and BC risk is complex and can be both protective and predisposing to BC, with ethnicity modifying SNP risk. Future research can be directed at assessment of SNPs and BC risk in diverse populations. [Table: see text]
Incidence of germline genetic testing in Veterans with breast cancer in the Veterans Health Administration.
Authors: Ahmad Sami Halwani, Vikas Patil, Richard Mcshinsky, Deborah Morreall, Kelli M Rasmussen, Chunyang Li, Zachary R. Burningham, Carolyn S. Menendez, Akiko Chiba, Haley Moss, Sarah Violet Colonna, Kerry G. Rowe, Michael J. Kelley
Journal: Journal of Clinical Oncology (2024)

e13531 Background: The Department of Veterans Affairs (VA) has seen a 3-fold increase in breast cancer (BC) diagnoses in recent decades, 90% of which occur in women Veterans. While technological and biomedical advances have increased the availability and actionability of germline genetic testing (GGT), adoption in practice has been slow. The VA National Oncology Program (NOP) recommends that all Veterans with BC be offered GGT. The Making Advances in Mammography and Medical Options for Veterans Act of 2022 mandated that the VA perform a study of GGT in Veterans with BC, the initial results of which are reported here. Methods: Veterans diagnosed with BC between Jan 1, 2021 and Dec 31, 2022 were identified in the VA Cancer Registry System (VACRS) using site code C50 and excluding histology codes 95903, 96803, and 96993. Of those, Veterans receiving care for BC in the VA were defined as those having at least 2 visits within a year with VA hematology, oncology, radiation oncology, or surgery with codes C50.x, D05.x, Z17.x, Z19.x, or Z85.x. We retrieved clinical notes from these visits and used natural language processing (named entity recognition, entity linking) to identify and highlight relevant concepts to expedite chart review. We randomly selected 200 Veterans, loading their notes into a custom-designed chart review application. A team of 5 clinical subject-matter experts reviewed these notes for evidence of GGT. Each Veteran’s notes were reviewed independently by 2 reviewers. Disagreements were adjudicated by the whole team. Results: 1505 Veterans met diagnostic criteria in VACRS; of these, 1201 met utilization criteria and constituted the study population. Table summarizes demographic characteristics. Inter-annotator agreement was 85.5%. Of the 200 Veterans whose charts were reviewed, 118 (59%) were offered testing, referred to a genetic counseling service, or otherwise had evidence of testing found upon chart review, while 61 (31%) had no such evidence. Ten patients (5%) were deemed ineligible for GGT based on practice guidelines at the time, and chart review found that 11 (6%) had no evidence of clinical care within the VA. Among 189 seen by a VA oncology clinician, 118 (62.4%) had or were offered genetic services. Conclusions: Most Veterans with breast cancer are offered germline genetic testing. Future work will evaluate ongoing efforts to improve adherence to VA NOP guidelines to ensure that every Veteran with breast cancer can access germline genetic testing. [Table: see text]
Lessons learned from a genetic counseling randomized clinical trial: Implications for recruiting individuals identifying as Asians in research.
Authors: Constance Wu, Janice Y. Tsoh, Rena Pasick, Claudia Guerra, Karla Kerlikowske, Niharika Dixit
Journal: Journal of Clinical Oncology (2024)

1576 Background: Despite the clinical importance of genetic testing and counseling for cancer risk reduction and treatment, minority populations are less likely to receive genetic testing and counseling or participate in genetics research, contributing to health disparities. In a randomized study of three modes of genetic counseling (GC3) conducted in three safety net hospitals, we noted a lower accrual of participants identifying as Chinese despite the availability of language-concordant study documents and bilingual staff. To understand barriers to recruitment, we conducted a mixed methods study using responses to the San Francisco Mammography Registry (SFMR) Breast Health History questionnaire (used for recruitment for GC3) and qualitative interviews with seven participants of the genetic counseling study. Methods: We extracted data from the SFMR from 2014-2018 for patients self-identifying as Asian and a control group of patients self-identifying as White. The primary outcome was the proportion of patients who agreed to be contacted for future breast health research. Survey data included information for personal history of breast cancer, history of biopsy, first-degree relative with cancer, age, and level of education. Z-tests were conducted for comparisons between groups. For qualitative analysis, seven Chinese-identifying participants were interviewed to understand why they chose to participate in the genetic counseling study and identify potential barriers and facilitators. Results: We included 121,415 patients (n=38,483 Asian). Asian patients had significantly lower rates of accepting future contact for breast health research studies (25.4% for Asians vs. 48.3% for White, p&lt;0.0001). Lower rates were observed across Chinese (23.3%), Filipina (30.2%), Japanese (27.8%), and Vietnamese (23.3%) subgroups (p&lt;0.0001 for all). A history of breast cancer (personal or family) or biopsy was associated with higher rates of acceptance within both Asian and White groups (p&lt;0.001 for all comparisons). Education did not change participation rates as much in Asian patients as in White patients. The qualitative study found barriers across three domains: awareness, opportunity, and acceptance, with a referral from the participant’s medical team identified as a facilitator. Conclusions: Individuals identifying as Asian in the SFMR were less likely to agree to be contacted for future breast health research. We identified multilevel barriers through qualitative interviews. This has important implications for designing recruitment strategies for Asian populations.
Quality of telehealth-provided cancer care in VA.
Authors: Leah L. Zullig, Amy Jeffreys, Whitney Raska, Gina McWhirter, Michael J. Kelley
Journal: Journal of Clinical Oncology (2024)

1633 Background: As the largest integrated health care system in the United States, the Veterans Health Administration (VA) has extensive experience in utilizing telehealth-(TH) to deliver care to the 10 million enrolled Veterans, including the~50,000 patients newly diagnosed with cancer annually and ~500,000 cancer survivors. The VA National TeleOncology (NTO) service was established in 2020 to provide specialized treatment regardless of geographical location. We sought to compare quality in TH-delivered care compared to traditional (TR) in-person VA care. Methods: Using the VA EHR, we identified patients who had an ICD-10 diagnostic code for an incident malignancy from Dec 2016 to March 2021 at three medical centers providing both TR and TH care. We used EHR review to classify patients as TH users, if they received TH services at least once for their cancer care, or TR care if no telehealth was used. Using both structured EHR data and manual review by two trained abstractors, we gathered demographic, clinical, and treatment characteristics to calculate 25 Quality Oncology Practice Initiative (QOPI) measures in the domains of symptoms and toxicity management (2), end of life and palliative care (10), and core measures (13). We report QOPI measures descriptively; and used chi-squared tests with alpha = 0.05 to compare TH and TR. Results: We identified 972 patients with lymphoma, prostate, lung or colorectal cancer. 427 (44%) were TH users and 545 (56%) were TR, and they were predominately white (n=819, 84.3%) men (n=930, 95.7%). TH users had better (n=13), worse (n=9), same (n=2) and unevaluable (n=1) descriptive performance on measures. For example, TH and TR were similar in administration of appropriate antiemetic therapy for high and moderate-risk antineoplastic agents (44.8% vs 42.4%). TH performed better than TR for chemotherapy summary being completed within three months of chemotherapy ending (83.4% vs 75.6%) and for emotional well-being being assessed by the second office visit (92.3% vs 89.9%). Appropriate tobacco use cessation administration within the previous year was statistically higher in TH (85.3% vs 76.2% p=0.0021). No differences were statistically significant for any other QOPI measures. Conclusions: VA is a leader in TH cancer care because of both its volume and quality. VA-provided TH cancer care quality is similar to or better than that of TR in-person care. NTO specifically, and VA teleoncology broadly, provides another option to Veterans for cancer care.