tbuckley/cabot-search huggingface dataset:
Spectrum and characteristics of germline <i>PALB2</i> pathogenic variants among patients with early-onset breast cancer in China.
Authors: Jing Li, Peng He, Qindong Cai, Lili Chen, Yali Wang, Weifeng Cai, Yibin Qiu, Wenhui Guo, Minyan Chen, Yuxiang Lin, Chuan Wang, Fangmeng Fu
Journal: Journal of Clinical Oncology (2024)

e22536 Background: Partner and localizer of BRCA2 ( PALB2) plays a critical role in homologous recombination repair and recognized as a breast cancer predisposition gene. Early age at onset of breast cancer is considered a hereditary high-risk factor. However, limited information is available about early-onset breast cancer in China. The objective of this study was to investigate the spectrum and characteristics of germline PALB2 pathogenic variants among this population. Methods: A total of 1556 patients with BRCA1/2-negative early-onset breast cancer were included. Peripheral blood samples were collected and all coding regions and exon‒intron boundaries of the PALB2 genes were screened through next-generation sequencing. Results: The prevalence of germline PALB2 pathogenic variants was approximatel 0.77% in entire cohort. Eleven PALB2 pathogenic variants were identified in twelve participants, including five frameshift mutations, four nonsense mutations and one missense mutation. Except for PALB2 c.1056_1057del, which was detected twice, all other variants were detected once. In comparison to non-carriers, PALB2 carriers were more likely to be 30 years old or younger (25% vs. 14.4%), have a positive family history of breast or ovarian cancer (16.7% vs. 6.3%), exhibit metastatic lymph nodes (75% vs. 50.9%), belong to human epidermal growth factor receptor-2 (HER2) -negative and hormone receptor (HR) - positive subtype (75% vs 54.2%), and diagnosed with invasive micropapillary carcinoma (16.7% vs 3.1%). Conclusions: The prevalence of the germline PALB2 pathogenic variants is approximately 0.77% in BRCA1/2 mutation-negative early-onset breast cancer patients in China. Our findings contribute additional insights into the spectrum and characteristics of PALB2 pathogenic variants in Chinese early-onset breast cancer patients, providing valuable information for this population. Key words: PALB2, Germline mutation, Genetic sequencing, early-onset breast cancer, China. [Table: see text]
Knowledge, attitudes, and practices of university students towards risk factors, screening, and perceived barriers of screening regarding colorectal cancer: A multi-country study from the eastern Mediterranean region.
Authors: Zeinab Tarhini, Niki Christou, Jeremy Jost
Journal: Journal of Clinical Oncology (2024)

e22543 Background: Colorectal cancer (CRC) tends to be diagnosed at a younger age and at a more advanced stage. Knowledge and awareness of CRC and its screening in Middle East are suboptimal, and most countries lack national screening programs. Our objective was to assess the knowledge, attitudes and practices of university students regarding risk factors, screening and perceived barriers to CRC screening in Middle Eastern countries. Methods: A cross-sectional study using a convenience sampling method was done in different universities across ten Middle Eastern countries: Lebanon, Iraq, Syria, Palestine, Egypt, Jordan, Saudi Arabia (KSA), and others (Qatar, United Arab Emirates, Kuwait). Data were collected using a questionnaire shared with students in various universities. It comprised five main sections: socio-demographic characteristics, CRC knowledge, risk factors, symptoms and screening, attitudes, practices and barriers related to CRC screening. The questionnaire developed on the basis of a literature review, was properly translated and validated using factorial and reliability analysis. Results: A total of 4597 students participated in the study with a mean age of 24.28 ± 7.62 years. Participants’ countries of residence were Lebanon 1107 (24.1%), Jordan 811 (17.6%), Iraq 769 (16.7%), Palestine 478 (10.4%), Syria 450 (9.8%), Saudi-Arabia 438 (9.5%), Egypt 499 (10.9%) and others 45 (1.0%). Most participants had heard about CRC (87%). 2491 (54.2%) had first or second -degree relatives diagnosed with cancer. 84.2% of participants intend to undergo CRC screening in the future, however, 25.1% wouldn't pay for the screening if it is not covered by health insurance. The majority of students demonstrated good knowledge of CRC (96.5%), with Egypt demonstrating the highest level (98.2%), followed by Lebanon (97.1%) and Iraq (97.1%), and Jordan the lowest (94%). Factors associated with good knowledge were age (aOR = 1.03; 95%CI: 1.00-1.05), health-related studies (aOR = 2.80; 95%CI = 2.00-3.93), and the participant’s country of residence. The most important barrier to CRC screening in Lebanon was the lack of financial resources with high cost of test (52.6%), lack of health insurance in Syria and Jordan (50.4% and 49.3% respectively), poor counseling from doctors in KSA (52%), and the inadequacy of awareness campaigns in Iraq (57.1%), Egypt (56.1%) and Palestine (55%). Conclusions: Students in the Middle East demonstrate good knowledge of CRC. Nevertheless, they perceive barriers to CRC screening, including limited financial resources, high cost of tests not covered by health insurance, and inadequate awareness campaigns.
Pathogenic germline variants among Thai patients with colorectal cancer: A study in Genomics Thailand Project.
Authors: Nutdanai Roila, Manop Pithukpakorn, Chanitra Thuwajit, Atthaphorn Trakarnsanga, Jomjit Chantharasamee
Journal: Journal of Clinical Oncology (2024)

e22534 Background: Germline variant testing in colorectal cancer (CRC) patients (pts) has been applied in many countries. Limited data is known regarding germline CRC prevalence in Thailand and other low to middle-income countries in Southeast Asia. Identifying the variants in different ethnicities may show the variety in frequency of the pathogenic germline variants (PGVs) and their relationship with clinical characteristics. Our study reports on the distribution of PGVs and their clinical findings in Thai CRC pts. Methods: We use the germline testing results from the Genomics Thailand Project during 2020-2023, which performed next-generation sequencing on 50,000 pts in 5 disease groups. CRC pts in our institution with a potential risk of carrying PGVs were sent to a geneticist to obtain a family history prior to undergoing germline testing with 25-96 cancer-predisposing genes. Pts with complete pedigree data and germline testing results were enrolled in our retrospective cohort to analyze the variants and clinical findings from chart reviews. Descriptive statistics, the Cox proportion hazards model, and the Kaplan-Meier method were used to evaluate the results. Results: We included 137 CRC pts with a mean age of 47 years at diagnosis, and 58.4% were male. Of these, 38/137 (27.8%) pts were identified as pathogenic/likely pathogenic(P/LP). 26/38 (68.4%) were pathogenic Lynch syndrome (LS), 16 (42.1%) MLH1, 6 (15.8%) MSH2, 2 (5.3%) MSH6, and 2 (5.3%) PMS2. Among pathogenic non-LS, the most frequent variant was 4 (10.5%) APC, followed by 3 (7.9%) ATM, 2 (5.3%) BRCA2, 1 (2.6%) PTEN, 1 (2.6%) BARD1, and 1 (2.6%) monoallelic MUTYH. The LS group was significantly associated with a family history of CRC (p &lt; 0.001), endometrial cancer (p = 0.001), and a synchronous/metachronous CRC (p = 0.003) compared to the non-PGVs group. Likewise, the presence of CRC in a first-degree relative (p = 0.025), more than one CRC pts in the family (p = 0.027), or early onset CRC (p = 0.012) in a first-degree relative was also significantly higher in the pathogenic non-LS group compared to the non-PGVs group. CRC pts who had more than one primary cancer in a lifetime were not significant in the LS or non-LS group compared to the non-PGVs group. At a median follow-up time of 60 (range 7-453) months, Pts in the PGVs group tended to have a shorter median time from the first CRC diagnosis to a second event defined as any of metachronous/synchronous CRC, recurrent CRC, or second cancer in a different organ compared to the non-PGVs group (135 vs. 228 months, p = 0.11). Conclusions: 27.8% pts in our cohort carried P/LP germline variants. The PGVs group was associated with a shorter time to the second event and a higher rate of familial cancer. Our study supports the benefits of genetic cancer screening. [Table: see text]
Improving clinical trial performance using adult-learning methods.
Authors: Matthew M. Burke, Carolyn Kubitschek Trees, Mukta Maan, Mark Levonyak, Lindsay Johnson, Nicholas Koeppen, Victoria Barrera, Agnes Nemeth, Sree Reddy, Robert L. Coleman, Paula J. Franson
Journal: Journal of Clinical Oncology (2024)

11025 Background: Timely and efficient accrual to oncology treatment trials is among the most vital components of clinical research. However, more than 80% of trials fail to reach enrollment targets, compromising outcome interpretation and cost. We hypothesized that a novel and customized application of adult-learning methods would enhance clinical trial screening and randomization. Methods: In collaboration with a multinational sponsor, Vaniam Group (VG) introduced a structured set of interventions to sites in 3 global randomized trials. Sites choosing to “opt in” formed the experimental group (EG). EG received tailored interventions: interactive Trial Educational Discussions (iTEDs: 30-min virtual meetings), and/or interactive Trial Acceleration Meetings (iTAMs: 4-hr live workshops of 10-30 investigators), and standard study support. Adult-learning techniques including the Socratic Method, case studies, and teach-back were used. Control group (CG) comprised sites receiving only standard study support. Primary endpoints were screening rate (SR) and randomization rate (RdR) compared atbaseline (6 mos prior to intervention) and 6 mos post-intervention (M6). Nonparametric statistical analyses compared between-group (Mann–Whitney U test) and within-group (Wilcoxon Signed-Rank test) differences. Results: Trial 1, a phase 3 placebo-controlled adjuvant trial had been open for 45 mos (54% enrolled) prior to intervention. At baseline, SR and RdR were similar between groups ( P&gt;0.05). At M6, SR increased 100% and RdR increased 37% in the EG; in the CG, SR did not change and RdR decreased 7%. For both endpoints, EG performed better than CG ( P=0.018, P=0.014). Trial 2, a phase 3 neoadjuvant trial had been open for 49 mos (86% enrolled) with a projected 18 mos to completion. At M6, SR increased 3% in the EG, but decreased 39% in the CG. RdR increased 15% in the EG but decreased 33% in the CG. While changes in performance were not significant between groups ( P &gt;0.05), study met its target enrollment goal with no further delays. Trial 3, a phase 2 recurrence trial was 30% behind enrollment with a projected 51 mos to completion. At M6, increases in SR were recorded in both EG and CG at 116% and 18%, respectively. RdR increased in both EG and CG (90% and 50%, respectively), augmented by protocol amendment. Despite increases in both groups, SR and RdR were significantly enhanced by VG intervention ( P=0.009 and P=0.015). Conclusions: Our novel, site-focused intervention strategy structured upon adult-learning methods significantly enhanced clinical trial performance, as measured by SR and RdR. Future work will expand these findings to different trial designs and outcome measures such as endpoint fidelity and cost. [Table: see text]
Impact of obesity on breast cancer clinicopathological characteristics in underserved community dweller women of Chicagoland: An experience from a US safety-net hospital.
Authors: Ekaterina Proskuriakova, Barun Babu Aryal, Dhan Shrestha, Stephanie Valencia, Iuliia Kovalenko, Megan Adams, Mubaraka Boxwala, Larissa Verda, Paramjeet Grewal Khosla
Journal: Journal of Clinical Oncology (2024)

e22519 Background: Breast cancer (BC) continues to pose a significant public health challenge, with its incidence and disproportionate impact on underserved populations in the United States. The relationship between obesity and clinicopathological characteristics at presentation remains a critical area of investigation. Safety-net hospitals catering to diverse, underserved, and often marginalized communities provide a unique setting to explore these associations, shedding light on potential disparities and informing targeted interventions. This study seeks to address a critical gap in knowledge on obesity and BC characteristics in underserved populations in the United States. Methods: In this retrospective study, 927 BC patients were included. Analysis was conducted to assess the association between body mass index (BMI), age of diagnosis, tumor clinicopathologic characteristics, and molecular types. The analysis was stratified by menopausal status at diagnosis. Results: The average age at diagnosis was 57.52 ± 12.40 years; 60.2% were postmenopausal women. Patients were categorized based on BMI into underweight/normal, overweight, and obese categories. One-way ANOVA analysis revealed no significant difference in mean age at presentation between BMI groups (p = 0.08). A significant association was found between BMI and menopausal status (p &lt; 0.05). Disease stage at presentation was significantly associated with BMI (p &lt; 0.05). Further investigation into BMI categories and tumor characteristics revealed a significant correlation in postmenopausal women, with obesity linked to tumor size and lymph node status (p &lt; 0.05). No significant associations were observed between HER-2 status, ER/PR status, and obesity in either premenopausal or postmenopausal groups. In the subgroup analysis focusing on ethnic groups, African American patients (with an average BMI of 32.8 ± 8.2 kg/m 2 ) demonstrated a higher prevalence of obesity at BC diagnosis in both pre and post-menopausal females compared to other ethnic groups (p &lt; 0.05). Conclusions: Obesity was associated with the disease stage and menopause status at diagnosis. In postmenopausal patients, obesity was associated with tumor size and lymph node disease status. Additionally, ethnic variations were evident, with African American patients displaying a higher prevalence of obesity. We need further investigations to tailor interventions addressing diverse demographic factors in BC management.
Blood-based colorectal cancer (CRC) screening implementation into clinical practice in the outpatient clinical setting in the Appalachian highlands.
Authors: Mridula Preetham Talari, William Haynes, Karen Elmore, Rasmiyah Jastan, Charles E Mays, Camelia Chirculescu, Haytham Adada
Journal: Journal of Clinical Oncology (2024)

TPS10622 Background: Maximizing colorectal cancer (CRC) screening participation relies on tests that are acceptable, accessible, and patient-centered. While colonoscopy or stool-based tests have traditionally been the standard of care (SOC), they often present challenges related to timely completion and patient adherence. Blood-based tests (BBTs) detecting circulating tumor DNA (ctDNA) offer a quicker, less invasive alternative to previous methods of screening. While the BBTs exhibit comparable sensitivity and specificity to the existing noninvasive SOC, their user-friendly nature holds the potential to enhance adherence. This study aims to explore the implementation of a BBT and its impact on patient acceptability and adherence to CRC screening. The study focuses on the Appalachian population, known for higher CRC incidence 1 and mortality rates 2 compared to the general US population. Methods: The trial is being conducted at two primary care clinics. It consists of two phases over a 6-month period, aiming to enroll over 300 patients. Participants aged 45-84 years, identified as average risk for CRC according to USPSTF guidelines, and who have opted to be screened for CRC and are willing to participate in the study will be eligible. Exclusion criteria consist of higher-than-average risk for CRC according to the USPSTF standards. During Phase 1 (control period), patients meeting inclusion criteria will be offered SOC (colonoscopy and/or stool-based test) for 3 months followed by Phase 2 (intervention period) where a BBT in addition to SOC will be offered for another 3 months. Informed consent will be obtained prior to any study procedures. The BBT used for the study has a sensitivity of 83% and specificity of 90%. Patients who agree to BBT will undergo a single blood draw of 40 mL. Phase 1 has concluded with enrollment of 75 patients, while Phase 2 is currently ongoing and actively recruiting participants. Upon completion of study, an EMR review will be conducted on participants to evaluate screening rates before and after implementing the BBT and to assess adherence. The primary endpoint of the study involves calculating the total number of consented patients who opted for and completed either BBT or SOC during the interventional period compared to the total number of patients who opted for SOC during the control period. Final data analysis is expected by July 2024. References: 1. Wilson RJ, Ryerson AB, Singh SD, King JB. Cancer Epidemiol Biomarkers Prev. 2016;25(2):250-258. doi:10.1158/1055-9965.EPI-15-0946; 2. Siegel RL, Miller KD, Jemal A. CA Cancer J Clin. 2017;67(1):7-30. doi:10.3322/caac.21387. Clinical trial information: NCT06119425 .
Geographic variations in corporate sponsorship for cancer center charity events.
Authors: Mark W. Shilling, Neda Hashemi-Sadraei, Satyan K. Shah
Journal: Journal of Clinical Oncology (2024)

e23116 Background: Most cancer centers rely on fundraising to support their clinical mission. However, the type and mission of companies sponsoring such events is not well known. Our goal was to determine if the source of philanthropy varies in different regions of the USA. Methods: Institutional websites and search engines were used to identify one signature fundraising event per NCI-designated Comprehensive Cancer Center. An event website and occurrence between January 2021 and January 2025 was required for inclusion. Principal corporate donors were inferred based on level of sponsorship (i.e., presenting, gold, etc.) or order of prominence. These were collapsed into 5 categories based on the Global Industry Classification Standard: 1) Consumer 2) Financial-Real Estate 3) Healthcare 4) IT-Communications, and 5) Materials-Industrial-Energy-Utilities. Chi-square analysis was used to compare sponsorship across 4 regions of the USA and Fischer’s exact test was used to make post-hoc exploratory analyses. All non-major corporate sponsors were excluded. Results: A total 493 corporate sponsorships were identified for 38 events that met inclusion criteria. Specifically, these were run/cycle/walks in 16 (42%), dinner galas in 15 (40%), concerts in 2 (5%) and other in 3 (8%). Most commonly, sponsors came from the Consumer (27%) and Healthcare (23%) industries. The relative number of companies in each category varied significantly among different regions (p &lt; 0.001). Post-hoc testing revealed the health industry favored the northeast region compared to other regions for sponsorship (p = 0.0025). Conclusions: Charity events are philanthropically supported by different corporate sectors in different regions of the United States. This information can help cancer centers become more efficient at fundraising. [Table: see text]
Heterogeneity in methods for estimating renal function in anticancer drug development.
Authors: Alexander B. Karol, Yu Fujiwara, Rodrigo Paredes, Anna Argulian, Himanshu Joshi, Matt D. Galsky
Journal: Journal of Clinical Oncology (2024)

e23002 Background: Accurate assessment of renal function is critical in oncology clinical trials. Many anti-cancer agents are renally excreted or cleared, and impaired kidney function can significantly impact drug safety and efficacy. In an effort to modernize renal eligibility criteria the American Society of Clinical Oncology–Friends of Cancer Research Organ Dysfunction Working Group recommended that if renal toxicity and clearance are not of direct treatment-related concern, then patients with impaired renal function should be included in trials (Lichtman, JCO, 2017). However, a diversity of approaches are available to determine renal function. Methods: We systematically searched the clinicaltrials.gov database to review renal eligibility criteria for phase III clinical trials. These trials evaluated systemic anti-cancer therapies in adult patients between October 28 th 2013, and October 28 th 2023. Studies were excluded if they did not include eligibility criteria related to renal function. The demographics of the trials and methods used for estimating renal function were recorded. Results: 436 trials met criteria for review and 231 trials, enrolling 111,424 patients, met our inclusion criteria. Systemic therapies explored included: immunotherapy (98 trials, 42%), targeted therapy (110 trials, 48%), chemotherapy (17 trials, 7%) or other regimens (6 trials, 3%). Renal function exclusion criteria are shown in the Table. Among studies that estimated renal function with a formula, 140 (61%) studies used Cockcroft-Gault, 3 (1%) used Modification of Diet in Renal Disease, 9 (4%) used an institutional standard, 10 (4%) used a heterogenous combination of estimation equations, and 69 (30%) trials did not specify the estimation approach. Conclusions: In phase III clinical trials involving adult cancer patients, there is substantial heterogeneity in methodologies utilized for determining renal function as related to trial eligibility. Harmonization of approaches to estimate renal function in oncology trials may improve trial accessibility, generalizability, and comparability. [Table: see text]