tbuckley/cabot-search huggingface dataset:
Dynamic machine learning model to forecast patient availability for clinical trials.
Authors: Rajeev Kulkarni, Vivek Prabhakar Vaidya, Dhaval Parmar, Abhishek Tibrewal, Ravi Bharat Parikh
Journal: Journal of Clinical Oncology (2024)

e13641 Background: Patient eligibility is a routine concept in clinical research, comprised of simple or complex set of inclusion or exclusion criteria applied in a specific sequence. Our methodology introduces the concept of ‘availability’ as a narrower term that is closer to the actual number that will be considered for a specific study and who may decide to participate. This specific research develops Machine Learning (ML) model that dynamically predicts likelihood of Multiple Myeloma progression and departure from targeted outcomes to sustain therapy and to indicate potential availability for clinical trials – to reduce screening efforts and improve screening precision of clinical research organizations. Methods: The cohort for training these models was drawn from the ConcertAI Oncology Research database, further enriched by key variables derived from unstructured data sources. Eligible patients for the analysis had a diagnosis of Multiple Myeloma made after Jan 1, 2020. Progressions were labelled using International Myeloma Working Group Criteria. Patients that did not satisfy the criteria were censored. Labels were assigned to patients after initial diagnosis of MM, and the duration between diagnosis to label was computed to build time to event (TTE) models. Over 2000 features were created to build this model, e.g., laboratory values, vitals, biomarkers, medications, ECOG, stage, etc. Variable creation preserved temporality of lab variables and vitals and noted presence of other variables. Several ML methods were employed to build the TTE models, with gradient boosting resulting in the highest c-index (0.8) based on 12 clinically relevant features. A temporal validation of the model was performed on a simulated index date. Results: Cohort used for training the model comprised of N = 4315 patients with average age at diagnosis of 72.3 years, and ~11% of the patients labelled as progressing. Temporal validation was performed on N = 1874 patients, with ~9% progression rate. The area under the curve (AUC) and weighted F1 score for this cohort was 87% and 89% respectively. Conclusions: Patient availability assessments are complex, not supported effectively by existing solutions and often require 100’s of hours from highly trained clinical personnel. An AI model predicting Multiple Myeloma progression built using a large-scale real-world dataset demonstrated 2-4x improvement in forecasting patient availability over other approaches. Integrating these solutions into clinical workflows can improve the effectiveness of research teams; enable more patients to have clinical trials as viable options at the right time; and allow care teams to have forward visibility to choices of standard-of-care and clinical trial alternatives in the best interest of patient outcomes. [Table: see text]
NGS panels' capture of biomarkers associated with targeted therapies in clinical trials.
Authors: John Leonard Fox, Sugganth Daniel, Manavi Abrol
Journal: Journal of Clinical Oncology (2024)

e13508 Background: ASCO and NCCN guidelines strongly encourage participation in clinical trials though participation rates remain low. Although up to 60% of trials require biomarker information as a prerequisite to participation, guidelines are silent on biomarker testing to assess eligibility. To help inform policy development, we analyzed commercially available NGS panels to assess the capture rate of the specific gene variants required for targeted therapies in clinical trials. Methods: Publicly available gene variant information on 12 high volume NGS tissue and plasma commercial assays representative of panel size was accessed. The JAX-CKB database was queried to identify genomic prerequisites in active phase I-III clinical trials; mRNA and protein expression biomarkers were excluded. We used unpaired t-testing to compare the ability of large versus small panels to detect variants required for targeted treatments. (Somatic gene variant annotations and related content have been powered by The Jackson Laboratory Clinical Knowledgebase (JAX-CKBTM)). Results: Overall, 185 genes were linked to eligibility for targeted therapies in clinical trials (Table). Large panel assays (&gt;80 genes) had a higher average capture rate compared to smaller panels, (84% vs. 46%, p value &lt; 0.000002). Similarly, capture rates in select cancers were higher in larger panels: lung (85% vs 59%), breast (92% vs 54%), prostate (86% vs 34%), pancreatic (84% vs 54%), colorectal (88% vs 52%). All results were statistically significant (p &lt; 0.05). Smaller panels were more likely to exclude large genes (e.g. BRCA), genome-wide signatures (e.g. TMB), fusions, and copy number variants. Conclusions: NGS-based panels with more than 80 genes had higher capture rates for biomarkers required for clinical trials of targeted therapies. Clinicians searching for all relevant treatment options for patients should include large genomic sequencing panels to maximize identification of potential clinical trial eligibility. Professional societies and policy makers interested in enhancing clinical trial enrollment rates should consider the panel size-related variability in capture rates of genetic variants when developing recommendations. [Table: see text]
Clinical practice guidelines for adolescent and young adult cancer: A literature review.
Authors: Rayann Atway, Dawn Ritzwoller, Elizabeth Moreton, Emily Ruth Haines, Bridgette Thom, Lauren Lux, Andrew Brian Smitherman, Jacob Newton Stein
Journal: Journal of Clinical Oncology (2024)

e13727 Background: Cancers among adolescents and young adults (AYA, aged 15-39) are rising in incidence, yet formal guidelines for diagnosis, treatment, and management of AYA-specific cancers are not widely known or disseminated. Practice patterns vary widely, contributing to a lack of improvement in outcomes for this underserved population. Clinicians and health systems have reported a need for additional guidance in care delivery for AYAs. Methods: We conducted a comprehensive literature review to identify clinical practice guidelines for cancer care delivery specific to AYAs published in PubMed or MEDLINE since 2010. MeSH and other key words were applied, using a search strategy guided by a health science librarian (EM). 795 papers were identified, with 690 excluded based on title and abstract review. 105 papers underwent full text review, and 64 papers underwent complete data extraction. Using Covidence software, two team members independently reviewed articles at the data extraction phase, with disagreements resolved through discussion. Results: We identified 22 papers that met our inclusion criteria as clinical practice guidelines specific to AYA cancer care. Clinical focus included breast cancer (4), sarcoma (4), brain tumors (2), gynecologic malignancies (2), acute lymphoblastic leukemia (1), colorectal cancer (1), NUT carcinoma (1), and proton therapy (1). Six papers covered general principles of caring for AYAs, regardless of cancer diagnosis. Key themes across guidelines included the importance of fertility preservation and psychosocial support, multidisciplinary care provided at specialized centers, and consideration of long-term toxicities of treatment. Conclusions: Clinical practice guidelines exist to inform clinicians and health systems on best practices for caring for AYAs with cancer, a growing and underserved population. Further dissemination of these guidelines may assist with improving outcomes. Comprehensive summary of these and other AYA specific guidelines is forthcoming and may serve as a useful clinical reference. [Table: see text]
A simple and data-driven framework to foster multidisciplinary and timely care in resource-limited settings: A pilot program in Argentina.
Authors: Santiago Ezequiel Melendi, Maria Laura Tribiño, Carolina Feldman, Maria Ines Bianconi, Virginia Perez, Gustavo Jankilevich
Journal: Journal of Clinical Oncology (2024)

e13517 Background: While numerous reports discuss various navigation methods and their effectiveness, implementing these programs in low- and middle-income countries (LMICs) is challenging. This study addresses this gap by assessing the feasibility of implementing a simple strategy using a small set of essential data gathered during routine patient care. The aim was to foster multidisciplinary case discussion and monitor key performance indicators (KPIs) to achieve timely access to treatment. Methods: As part of the BOLD initiative (Barriers or Limits Demolished Against Breast Cancer), we started a pilot program with the Breast Unit and the Medical Oncology Consult in the outpatient setting of a public hospital serving a vulnerable population in Buenos Aires City. Using a web-based spreadsheet accessible to both units, a simple framework collecting relevant consultation dates was implemented to assess the timeliness of specialist referrals and treatment initiation. We configured simple time-based alerts to highlight patients who exceeded prespecified timeframes, enabling healthcare providers to promptly reach out to patients, inquire about the reasons for access issues, and provide counseling to address them when possible. Results: The Breast Cancer Unit admitted 38 newly diagnosed patients from Sep/2023 to Nov/2023, of whom 22 (57.9%) had no health insurance. The main program KPIs are described in the Table. Surgery was the most frequent source of treatment delays (58.3%), mainly because of the scarce availability of operating rooms. Alerts from delayed initiation of systemic oncological treatments were present in 11 patients (28.9%). Navigation of those patients attributed the primary source of delays to administrative issues in the prior authorization process (45.5%, n=5), followed by patient-related factors such as social vulnerability and difficulty in coping with required procedures (n=4). Conclusions: A simple framework based on the prospective register of key consultation dates was feasible to implement in the routine care setting of a public hospital serving a vulnerable population. This model promotes quality and equity for breast cancer patients by providing an accessible way for LMICs to ensure a timely referral process, foster multidisciplinary case discussion, and offer patient support to overcome challenges arising primarily from delays within the health system. [Table: see text]
Barriers to accessing cancer care from patients’ perspective: A single cancer center experience.
Authors: Dhaval Patel, Marshall Isaac Rosenberg, John Charles Leighton, Claudia M. Dourado
Journal: Journal of Clinical Oncology (2024)

e13520 Background: Jefferson Einstein Hospital is a safety-net hospital that serves a diverse and primarily disadvantaged community in North Philadelphia. The population in this city has 21.5% of individuals living in poverty, which is almost double the rate in Pennsylvania. According to the National Cancer Institute’s Center to Reduce Cancer Health Disparities (NCI-CRCHD), people from low socioeconomic backgrounds and specific demographics often bear a more significant disease burden than the general U.S. population. Certain population groups experience cancer disparities due to their likelihood of encountering obstacles or barriers in accessing healthcare. This study aims to identify critical barriers hindering the receipt of quality cancer care for the population served by this hospital. Methods: We identified 51 adult patients who received a new cancer diagnosis between 2022 and 2023. Barriers to accessing cancer care were defined through a literature review and expert consensus. These barriers were assessed via a survey containing fixed-choice items aimed at eliciting obstacles to accessing cancer care among newly diagnosed cancer patients undergoing treatment at the hospital. Information on these barriers was collected prospectively during survey administration and analyzed using descriptive statistics. The frequency of specific barriers within the five categories was calculated, and subjects were classified based on the presence or number of barriers. Results: A total of 51 patient surveys were evaluated. Among these surveys, 24 (47%) reported transportation issues, and 3 (6%) reported caregiving responsibilities. Ten (20%) patients encountered economic barriers, while 11 (22%) faced challenges related to their support system. Nineteen (37%) patients experienced barriers related to health literacy, and 15 (29%) specifically struggled with cancer-related health literacy. Additionally, cultural barriers were identified in 12 (24%) patients. Conclusions: Our study highlights the prevalent barriers faced by newly diagnosed cancer patients in accessing cancer care, including transportation, health literacy, financial constraints, and cultural factors. These findings underscore the importance of integrating patient perspectives into future initiatives aimed at addressing these challenges. By prioritizing patient input and enhancing patient navigation programs, we can effectively mitigate these barriers and improve access to cancer care for individuals in need. [Table: see text]
Utilization of PARP inhibitors in the management of ovarian cancer in Nigeria.
Authors: Precious Akinsanya, Darlington Akahara, Uchenna Samuel Okoro, Susan Okonkwo, Uchenna Anthony Umeh, Nwamaka Lasebikan, Enoch Uche, Adetoro Okafor, Oyindamola Olusunmade, Uchechi Okehi, Marsophia Julemis, Sylvester Orimaye
Journal: Journal of Clinical Oncology (2024)

e13500 Background: Ovarian cancer remains a significant health concern globally, especially in countries with low Human Development Index (HDI), where there is a projected 96% increase in new cases and a 100% increase in associated deaths by 2040 compared to a 19% increase in new cases and a 28% increase in deaths in very High HDI countries. Over the years, significant strides have been made in the treatment of ovarian cancer, leading to a decrease in ovarian cancer-related mortality in High HDI countries. Poly (ADP-ribose) polymerase inhibitors (PARPi) are among the new and emerging treatment options, which have transformed the management of ovarian cancer, especially in patients with BRCA mutations. Methods: A cross-sectional survey was distributed to clinical and gynecologic oncologists practicing in Nigeria via email, text, WhatsApp, and telegram messaging. Clinical and gynecologic oncologists who are not involved in the treatment of patients with ovarian cancer and those who are not currently in practice were excluded. Results: Out of 36 respondents, 34 were analyzed. While PARP inhibitors are increasingly acknowledged (85.29% awareness), actual utilization remains modest (14.71%). The sole PARP inhibitor used is Olaparib. The majority of respondents (48.28%) who did not use PARP inhibitors cited both the lack of availability and the high cost of medications as the reasons. Key barriers to the use of PARP inhibitors include a combination of non-availability and cost (48.28%) and a combination of institutional protocols and socioeconomic status (20.59%). Conclusions: Despite increasing awareness, PARP inhibitor utilization in Nigerian ovarian cancer management is hindered by challenges, predominantly cost and availability. The study highlights a missed opportunity for optimizing advanced ovarian cancer treatment in Nigeria. [Table: see text]
Exploring health disparities in prostate cancer through circulating tumor DNA analysis.
Authors: Samaneh Maleknia, Sanam Rezaei Benam, Rebecca Hassoun, Nabil Adra, Reza Shahbazi
Journal: Journal of Clinical Oncology (2024)

1603 Background: African American men (AAM) suffer from the highest rates of prostate cancer in the world. In addition, AAM experience the highest rates of aggressive prostate cancer and prostate cancer-specific mortality of any ethnic group in the United States [1, 2]. The reasons behind the increased burden of prostate cancer poor outcomes in AAM remain unresolved. A large proportion of variation in prostate cancer mortality remains unexplained solely by epidemiologic risk factors. We investigated genomic differences between AAM and Caucasian men with metastatic castration resistant prostate cancer (mCRPC) utilizing circulating tumor DNA (ctDNA) analysis. Methods: AAM and Caucasian men with mCRPC were enrolled in this study. We collected and analyzed 88 plasma samples, including 66 from Caucasian and 22 from African American patients, with no significant age difference between the groups. The targeted sequencing libraries were prepared following the Agilent SureSelect XT HS2 target enrichment workflow coupled with the SureSelect custom prostate cancer panel (Agilent, Inc.). The final libraries were sequenced on an Illumina NextSeq 2000 to generate 150 bp paired-end reads. Results: A total of 88 men with mCRPC were enrolled. About 60% of African American patients exhibited organ metastasis at the time of diagnosis, while this proportion was 36% for Caucasian patients and they primarily reported metastasis during relapse. Analyzing 1824 variants in 138 genes meeting inclusion criteria, 281 significant mutations across 88 genes revealed racial differences. Notably, 29% of these variants were somatic. Approximately 60 cancer-related pathways, tissues, and diseases were identified from these datasets, encompassing 59 of our significant genes. Among these associated genes, the prevalence of significant variants, higher in AAM, exceeds that in Caucasians in 76% of cases. The top genes that have more contribution in considering pathways are shown (Table). Conclusions: Genomic variations were observed in ctDNA analysis between African American and Caucasian patients diagnosed with metastatic castration-resistant prostate cancer. Our findings highlight the potential inclusion of ctDNA analysis in the clinical assessment of these patients, offering valuable insights for informed therapeutic decision-making. The top genes with the most contribution to prostate-related pathways. [Table: see text]
Persistent poverty impacts survival and National Comprehensive Cancer Network guideline-concordant care for patients with melanoma.
Authors: Hayley Marie Dunlop, Robert Connor Chick, Carson Karakis, Sabrina Catalano, Samilia Obeng-Gyasi, Carlo M. Contreras, Susan Tsai, Timothy M. Pawlik, Joal D. Beane
Journal: Journal of Clinical Oncology (2024)

1598 Background: Based on guidelines from the National Comprehensive Cancer Network (NCCN), sentinel lymph node biopsy (SLNB) should be offered to patients with high-risk stage IB or stage II melanoma and adjuvant systemic therapy is recommended for patients with stage III disease. Persistent poverty census tracts are defined as areas where at least20% of residents were poor as measured by each of the 1980, 1990, 2000 censuses and 2007 American Community Survey 5-year average. The aim of this study was to describe the association between persistent poverty and adherence to NCCN guidelines and cancer-specific survival in patients with cutaneous melanoma. Methods: Patients diagnosed with melanoma from 2006-2018 were identified in Survival, Epidemiology, and End Results (SEER) Program registries. The analytic cohort was restricted to patients with superficial spreading melanoma, nodular melanoma, malignant melanoma with regression, lentigo malignant melanoma, and acral lentiginous melanoma. Patient demographics such as age, race, and ethnicity and tumor characteristics associated with stage at diagnosis were analyzed using adjusted regression analyses for patients of all melanoma stages. Demographics and tumor characteristics associated with receipt of SLNB were analyzed amongst pathologic stage IB and II cases, and demographics and tumor characteristics associated with receipt of adjuvant systemic therapy were analyzed amongst stage III cases. Kaplan-Meier curves and adjusted accelerated failure time models were used to examine disparities in cancer-specific survival. Results: Of 127,308 total patients, 3.13% (n=3994) lived in census tracts with persistent poverty. In adjusted analyses, persistent poverty was an independent predictor of later pathologic stage at diagnosis (OR 1.32 [95% CI 1.21-1.44] p&lt;0.001). Persistent poverty was also associated with lower likelihood of receiving SLNB according to NCCN guidelines (OR 0.717 [SE 0.072] p&lt;0.01) and with worse cancer-specific survival (HR 1.25 [1.06-1.47], p=0.008) when controlling for age, race, ethnicity, pathologic stage at diagnosis, and histology. In univariable models persistent poverty was associated with increased odds of receiving systemic therapy, but this relationship was not significant on multivariable analysis. Conclusions: Patients from areas with persistent poverty had a later pathologic stage at diagnosis, were less likely to receive a SLNB according to NCCN guidelines, and had worse cancer-specific survival. Efforts to better define and resolve disparities in the treatment and survival of patients with melanoma are warranted.
Systematic review of rural interventions addressing barriers and facilitators in recruitment and adherence of oncology clinical trials.
Authors: Rebecca Mulley, Ruhi Thapar
Journal: Journal of Clinical Oncology (2024)

e13675 Background: Rural patients are significantly underrepresented in cancer clinical trials leading to an inequitable distribution of research funding and excluding rural patients from innovative care. Properly understanding the barriers and facilitators to rural patient participation in cancer clinical trials is essential to lessen this disparity in representation. Methods: EBSCO Medline, Embase, Cinahl, Cochrane and PsycInfo were systematically searched for articles related to the primary research objective. The search strategies focused on a combination of keywords pertaining to “rural populations”, “cancer”, and “clinical trials”. Additional search terms included the presence of “barriers” or “facilitators” within the articles. Articles were removed from the study if they were not written in English, were conducted outside the U.S., focused on pediatric populations, or lacked original data. Results: A systematic review of the literature reveals that barriers and facilitators to cancer clinical trial participation by rural populations are present at the patient, physician, and healthcare system levels. Notable barriers found in this review include the burden of travel, lack of patient knowledge about clinical trial participation, insufficient provider communication and awareness of current trials, and strict eligibility criteria. Promising facilitators include caregiver support, close physician support and contact, and programs to increase patient understanding of clinical trials. Potential future interventions include telemedicine, expanding monetary support for clinical trial transportation, utilizing RUCA codes to document disparities and elucidate further interventions, and cultivating stronger partnerships between industry and rural medical facilities, as well as between the NCI, academic institutions, and rural medical facilities. Conclusions: There is a significant and urgent need to strengthen this body of literature as is underscored by the apparent lack of cancer clinical trials in rural counties, specifically in the state of Texas (CPRIT). It is evident that barriers need to be further elucidated to ascertain why rural patients have less participation in clinical trials, and facilitators need to be further explored in order to sufficiently illustrate and thus effectively harness the power of facilitators in the pursuit of lessening disparities and improving cancer outcomes for rural patients.