bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of simulated outcomes between stool- and blood-based colorectal cancer screening tests.
Authors: Fendrick A. , Vahdat Vahab , Chen Jing Voon , Lieberman David A. , Karlitz Jordan J. , Limburg Paul J. , Ozbay A. Burak , Kisiel John B. 
Published: June 2022

10529 Background: The Centers for Medicare & Medicaid Services (CMS) recommends covering blood-based biomarker tests with proposed minimum performance thresholds for colorectal cancer (CRC) screening test every 3 years for average-risk, asymptomatic Medicare beneficiaries ages 50–85 years. A blood-based test is a non-invasive screening method to detect CRC but is limited by low sensitivity to detect adenomas. Using the CRC-AIM microsimulation model, predicted life-years gained (LYG) and CRC incidence and mortality reduction were compared between a blood-based test meeting the CMS minimum thresholds and stool-based screening tests (fecal immunochemical test [FIT], fecal occult blood test [FOBT], and multitarget stool DNA [mt-sDNA]). Methods: Outcomes of blood- and stool-based tests were simulated for average-risk individuals free of diagnosed CRC at age 40 and screened between ages 45–75 years per USPSTF recommendations. Per CMS proposed criteria, CRC sensitivity and specificity for a blood-based test were set at 74% and 90%, respectively, and adenoma sensitivity was set at 10%. Published adenoma and CRC sensitivity and specificity were used for each stool test. For the primary analysis, adherence was assumed to be 100%. For secondary analysis, adherence was set at 30–70%, in 10% increments. Outcomes were per 1000 individuals. Results: At 100% adherence, LYG was 229 for a blood test and ≥305 for stool tests, corresponding to at least 25% lower LYG for a blood test relative to all stool tests (Table). Absolute CRC incidence and mortality reductions were at least 19% and 18% lower, respectively, for a blood test vs all stool tests. Secondary analysis indicates that at identical adherence rates that are less than 100%, a blood test had lower LYG vs all stool tests (Table). When the adherence of any test was 50%–70%, a blood test resulted in at least 20% lower LYG vs any stool test, and absolute reductions in CRC incidence and mortality were at least 9% and 10% lower, respectively, vs any stool test. Conclusions: This model suggests that if blood-based CRC screening tests do not sufficiently detect advanced adenomas, clinical outcomes will be inferior to stool-based testing due to lack of cancer prevention. Further discovery efforts to identify blood-based markers associated with both invasive and preinvasive neoplasia are needed to address this deficiency. [Table: see text]
Phase I study combining pembrolizumab and aromatase inhibitor in patients with metastatic hormone receptor–positive breast cancer.
Authors: Ge Xuan , Yost Susan Elaine , Lee Jin Sun , Frankel Paul Henry , Ruel Christopher , Cui Yujie , Murga Mireya , Tang Aileen , Martinez Norma , Chung Samuel , Yeon Christina Haeyoung , Stewart Daphne B. , Li Daneng , Rajurkar Swapnil Padmakar , Somlo George , Mortimer Joanne E. , Waisman James Ross , Yuan Yuan 
Published: June 2022

1053 Background: Aromatase inhibitor (AI) is standard of care for patients with hormone receptor positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). The current phase I trial was designed to test the safety and efficacy of AI and the immune checkpoint inhibitor pembrolizumab (NCT 02648477). Methods: Key eligibility criteria were HR+ HER2- MBC per ASCO/CAP; RECIST 1.1 measurable disease; adequate organ function; and ECOG 0-1. Eligible patients received 200 mg pembrolizumab IV every 3 weeks plus AI until progression or unacceptable toxicity. Primary objectives were to evaluate the safety and efficacy of this combination. This study employed a 3-at-risk design with a lead-in at the standard dosing of both AI and pembrolizumab with a targeted accrual of 20 patients. Results: A total of 20 patients were accrued between March 2016 and April 2017. Median age was 62 (range 34-79), with 75% white, 15% Asian and 10% unknown. Median lines of therapy were 3 (0, 9). All but one patient received aromatase inhibitor and/or fulvestrant prior to enrollment. The combination was well tolerated, and the most common adverse events were grade 2 fatigue (35%), rash (15%), and hot flashes (10%). Grade 3 adverse events were elevated AST/ALT (5%), rash (5%), and lymphopenia (5%). Responses were 10% partial response and 15% stable disease, resulting in a clinical benefit rate (CBR) of 20% at 6 months. Median follow-up time was 40.1 months (range 31.3 – 46.8 months). Median progression free survival was 1.8 months (95% CI 1.6, 2.6) and median overall survival was 17.2 months (95% CI 9.4, NA). 14 tumor specimens had programmed death ligand 1–positive (PD-L1) by 22C3 testing, including 3 PD-L1-positive and 11 PD-L1 negative. No association between PD-L1 and response was found. Conclusions: The combination of pembrolizumab and AI is well tolerated in patients with HR+ HER2- MBC who were not pre-selected for PD-L1. There was minimal overall clinical activity observed beyond what was to be expected with AI alone in this group of patients. Clinical trial information: NCT 02648477.
Project BRA: Breast cancer risk assessment.
Authors: Nye Lauren Elizabeth , Smith Sharla , Knight Catherine J , Klemp Jennifer R. 
Published: June 2022

10549 Background: In Kansas, breast cancer (BC) incidence is similar in Black and white women, yet Black women are 42% more likely to die from the disease. In models where screening is equal, there is no difference in survival from early-stage BC. Barriers to BC early detection in Black women include provider lack of knowledge in cancer risk, performing risk assessments and providing culturally sensitive education to patients. Our team developed a didactic and case-based learning intervention using Project ECHO (Extension for Community Health Outcomes) to improve provider knowledge on performing BC risk assessment and enhance risk stratified screening in Community Health Clinics (CHCs). A Community Advisory Board (CAB) was established to address barriers to early detection. Methods: CHCs participated in five 1-hour ECHO sessions June thru August 2021. Session topics focused on calculating BC risk, community resources, and cultural sensitivity and were led by experts in breast oncology, risk, genetics, screening, and health care equity. Pre/post surveys administered to participants assessed knowledge and satisfaction and continuing education credits were offered. A CAB member survey gained insight into organizational characteristics and community reach. Asset mapping identified barriers, resources, and opportunities to promote BC screening. Descriptive statistical analyses and the RE-AIM framework were used to assess reach and scalability of the ECHO. Results: Seventy-seven individuals from 16 CHCs registered to participate with a mean of 26 attendees at each session and 34% attending two or more. Participants were physicians (19%), advanced practice providers (18%), nurses (29%), and allied health professionals (34%). Sixty-three (82%) completed the baseline survey and 10 (13%) completed the post-ECHO survey. At baseline, 32% of participants reported lack of training and time as barriers to performing risk assessment. While post-ECHO survey responses were low, 60% reported their knowledge greatly or moderately improved across all topics. Participants reported clinical practice change in assessing personal history of cancer and collecting family history beyond first degree relatives. CAB members reported a broad range of expertise in community engagement and development (44%), direct patient care (15%), healthcare access (15%) and patient advocacy (26%). CAB education and collaboration led to support for tomosynthesis for women screened in our state funded BC screening program, Early Detection Works (EDW). Ongoing asset mapping identified gaps in access for Black women to the EDW program. Conclusions: Project BRA demonstrated successful participation in a limited series Project ECHO and achieved perceived changes in knowledge on performing BC risk assessment. Next steps include incorporating CAB informed opportunities to expand risk-based screening across Kansas and advocate for improved access to risk stratified screening.
Racial and ethnic disparities in lifestyle changes during the COVID-19 pandemic: Exploring the socioeconomic and psychosocial mechanisms.
Authors: Wen Ming , Curtis David , Zhang Donglan , Chen Zhuo , Shi Lu , Chen Liwen , Su Dejun , Wei Yehua , Li Yan , Li Jian , Chen Baojiang , Li Hongmei , Han Xuesong 
Published: June 2022

10558 Background: Obesity, physical inactivity, excessive alcohol consumption, and poor diet are all modifiable risk factors for cancer. These unhealthy behaviors are disproportionally concentrated in racial and ethnic minorities and these disparities may have been exacerbated during the COVID-19 pandemic. This study examined racial and ethnic disparities in weight gain and other undesirable lifestyle changes during the COVID-19 pandemic and explored mechanisms underlying these lifestyle disparities. Methods: We used data from the 2020 Health, Ethnicity and Pandemic Study, a national survey representative of US households conducted in October 2020. Racial and ethnic minorities were oversampled. Participants were asked to report lifestyle behaviors before and during the COVID-19 pandemic. We examined two outcomes in this study: weight gain and experiencing any undesirable lifestyle changes (i.e., reduced exercise time, increased alcohol drinking, or increased fast-food meal consumption). The primary exposure was race-ethnicity (non-Hispanic (NH) white, NH black, Hispanic, NH Asian, NH other race). Four sets of mediators were examined: socioeconomic status (education, household income, and undesirable job changes), family and friend social relationship change, perceived and experienced racism, and psychological distress. Weighted multivariable logistic regression models were performed. Mediation effects were examined with variance decomposition method. Results: A total of 2,709 participants were included in our sample. Compared with white respondents, black (OR = 1.71; p < 0.001) and Hispanic respondents (OR = 2.17; p < 0.001) were more likely to experience weight gain, controlling for age and sex. Among the hypothesized mediators, undesirable job changes during the pandemic, experiencing worse family relationship, and higher levels of psychological distress were all linked to higher odds of weight gain, but none of these variables played a salient role in mediating the black-white and Hispanic-white disparities in weight gain during the pandemic. As to the odds of experiencing undesirable lifestyle changes, black (OR = 1.76; p < 0.001), Hispanic (OR = 2.12; p < 0.001), and Asian respondents (OR = 1.42; p < 0.01) all exhibited disadvantages relative to white respondent. These disadvantages were largely attributable to perceived racism toward one’s own group and psychological distress for all three minority groups. Conclusions: Racial and ethnic minorities were more likely to experience unhealthy lifestyle changes relative to white individuals during the pandemic in the United States, which can be partly attributable to higher levels of perceived racism and psychological distress. The long-term effects of racial/ethnic disparities of lifestyle change during the pandemic on cancer prevention warrant further research.
Variants of unknown significance (VUS) in patients with hereditary CRC without a known pathogenic variant.
Authors: Stojovska Marija , Matevska-Geshkovska Nadica , Bozhinovikj Elizabeta Krstevska , Grozdanovska Biljana , Mitrevski Nenad , Dimovski Aleksandar 
Published: June 2022

10599 Background: Nearly 5-10% of all newly diagnosed colorectal cancer (CRC) cases develop due to the presence of a highly penetrant pathogenic variant in one of the hereditary colorectal cancer (hCRC) associated genes. NGS technology raised the opportunity for fast and efficient detection of these variants, but still in ̃20-30% of patients with hCRC the genetic defect remains unknown. Recent data shows that 6-8% of these cases harbor pathogenic/VUS variant in low/moderate penetrance genes not directly associated with hCRC. Methods: A total of 109 patients with hCRC (43 with polyposis and 66 with non-polyposis syndromes) were analyzed by NGS covering coding and exon/intron sequences of 109 genes, of which 25 associated with known hCRC syndromes and 83 other cancer predisposition genes. Results: Pathogenic variants were detected in 63/109 (57.7%) of analyzed patients; 54/63 (85.7%) of these had a pathogenic variant in one of the genes associated with hCRC (APC, MMR genes, MUTYH, NTHL1, BMPR1A) and 9/63 (14.3%) had a pathogenic variant detected in genes not directly related to hCRC (CHEK2, FANCL, FANCM, ERCC2, BRIP1, FLCN, BLM). In 26/109 (23.8%) patients a rare VUS variant was detected, of which 14/26 (53.8%) in double strand repair (DRG) genes (BLM, CHEK2, PALB2, ATM, MRE11A, BRIP1, FANCM, FANCL and ERCC2), 8/26 (30.8%) in one of the known hCRC genes (APC, MSH6, PMS2 and POLE) and 4/26 (15.4%) in other cancer predisposition genes (KIT, NSD1, CDH1, EZH1 and FH). VUS variants in DRG genes were more common in patients with MSI- HNPCC (9/15, 60%), compared to patients with polyposis syndromes (6/15, 40%). The VUS variants in other cancer predisposition genes were dominantly present in patients with oligopolyposis. Most (21/26, 80.8%) VUS variants were detected as single variants, while only five patients (5/26, 19.2%) had two different variants in two different genes. In 20/109 (18.3%) patients who presented primarily with MSI- HNPCC or oligopolyposis phenotypes, no pathogenic and/or VUS variants were detected in the 109 analyzed genes. Conclusions: Genetic basis of hereditary CRC was not clearly defined in a large proportion (42.3%) of patients in our cohort. Although a VUS variant was detected in a significant portion (23.8%), a major fraction (18.3%) of patients had no known genetic variant detected. The presence of a high frequency of VUS variants in DRG genes indicates that this pathway plays an important role in CRC carcinogenesis. Although we cannot exclude the presence of deep intronic and/or regulatory region pathogenic variants in the analyzed genes, it appears that the current list of identified cancer predisposition genes responsible for the hereditary CRC is far from being complete. The influence of environmental factors in conjunction with polygenic inheritance might also play a key role in a fraction of hCRC in our population.
Genetic risk assessment in primary care settings: An evaluation of NCCN guidelines.
Authors: Milliron Kara J. , Hulswit Bailey , Cook Amanda , Fry Stacy , Schraeder Alec , Tippie Jerry , Hall Kelly , McCain Lynn A. , Keren David , Schroeder Lee , Merajver Sofia , Stoffel Elena Martinez 
Published: June 2022

10605 Background: Lynch syndrome (LS) and hereditary breast and ovarian cancer (HBOC) have a population prevalence of 1/2791 and 1/4002, respectively. Despite this, >80% of patients referred for cancer genetic counseling report personal or family history of breast cancer3. This disparity may be due to increased media attention for HBOC, lower levels of provider awareness of LS, and less discussion of colorectal cancer within families compared to breast cancer4. However, potential biases in National Comprehensive Cancer Network (NCCN) criteria for genetics evaluation (GE) have not been studied. This project examined the performance of NCCN guidelines for identifying individuals meeting criteria for GE ascertained through primary care (PC) settings. Methods: Individuals scheduled for routine PC appointments at three Michigan Medicine affiliated practices from 10/24/18 through 1/24/22 were emailed a link to complete an online personal and family history (P/FHx) risk assessment module (INHERET) collecting information about cancer diagnoses (age/cancer type) in 1st, 2nd, and 3rd degree relatives. The module was written at a 4th grade reading level and could be accessed on any internet-connected device. NCCN guidelines were applied to determine if patients met criteria for GE of HBOC and/or LS. Results: A total of 465 individuals completed the module; nearly one in three (30.6%, 142/465) met NCCN criteria for GE of HBOC or LS. Of those meeting criteria, 132 (92.9%) had no personal history of cancer. The most common indication for GE was HBOC (29.5%, 137/465) and 30 patients (6.5%) met HBOC referral criteria solely based on Ashkenazi Jewish ancestry. Only 17/465 (3.7%) individuals met NCCN criteria for GE of LS. Interestingly, 12/17 (70.6%) who met criteria for GE of LS also met criteria for GE of HBOC. The completion rate was not 100% and cannot be determined; it is not known how many patients were offered the option of completing the module. This limits the study, as ascertainment bias cannot be assessed. Conclusions: Nearly one-third of PC patients who completed the P/FHx module met NCCN criteria for genetic evaluation of HBOC and/or LS. Referrals for HBOC outnumber those for LS, even though LS is just as common1, 2, 3. Further evaluation of NCCN criteria is needed to evaluate whether patients may be over-referred for HBOC and/or under-referred for LS. Unfortunately, we were not able to confirm receipt of email invitations or accurately calculate completion rate of the P/FHX risk assessment module, which limited our ability to assess for ascertainment/response bias. [Table: see text]
Building a multidisciplinary consortium in Iowa to advance genetic counseling and testing in patients with cancer.
Authors: Megally Sandra , nwaneri matthew Obinna , Kim Joseph , Atembina Limaya , Lucas Lorna , Bankert Lu Anne 
Published: June 2022

10609 Background: As cancer clinicians develop increasingly complex treatment plans, the results from somatic and/or germline tests are guiding personalized treatment decisions. Many patients with cancer do not get optimal genetic counseling/testing when indicated. To ensure that cancer clinicians are following the latest clinical recommendations around genetic counseling/testing, the Iowa Oncology Society (IOS), working in collaboration with the Association of Community Cancer Centers (ACCC), developed a multiphase initiative to inform quality improvement (QI) opportunities. Methods: In 2021, IOS launched a multidisciplinary consortium to advance genetic counseling and testing in oncology. Engaging a diverse group of stakeholders, IOS held a focus group to explore the current landscape, conducted three educational lunch and learn sessions, produced a podcast, and hosted a working group meeting. These meetings and activities were designed to explore ways to overcome common barriers in care delivery and identify effective practices to coordinate cancer genetic counseling and testing in clinical practice. Results: Through this initiative, IOS identified several key improvement opportunities for cancer clinicians treating patients in Iowa. Since 43 percent of Iowa’s population is rural, this initiative also identified practical strategies for oncology practices in low-resource areas. The following insights and suggestions were generated from this initiative: 1) Cancer programs may implement creative ways to collect patient history and screen patients for hereditary cancer syndromes. 2) Clinicians may use more effective education materials when referring patients for genetic counseling. 3) Clinicians may clarify language/communication to reduce confusion about somatic vs. germline test results. 4) Cancer programs may form partnerships with local genetic counselors and/or organizations that offer telehealth services. IOS summarized these ideas and disseminated education and resources to guide cancer clinicians in assessing and improving their own practices. Conclusions: This multiphase initiative represents a framework for a state oncology society to engage other stakeholders and lead interdisciplinary efforts to improve care for patients with cancer. As the landscape of genetic counseling evolves, IOS supports legislative efforts aimed at having Medicare recognize certified genetic counselors (CGCs) as healthcare providers. IOS plans to build on this initial work to advance cancer genetic counseling and testing throughout the state by developing additional programming in 2022.
A novel analysis of data from the PALOMA-3 trial confirms the efficacy of palbociclib and provides an option for efficacy assessments that could accelerate drug approvals.
Authors: Yeh Celine , Zhou Mengxi , Bapodra Neil , Rivero Maria , Espinal Dominguez Edward Jose , Moran Marina , Hershman Dawn L. , Fojo Antonio Tito , Bates Susan Elaine 
Published: June 2022

1069 Background: Advances in breast cancer (BC) therapy the past few decades have led to higher survival rates. Beginning with palbociclib, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have emerged as a treatment option for BC. We analyzed data from PALOMA 3 that could release a biomarker of OS in patients that receive palbociclib. Methods: We estimated concurrent rates of growth ( g) and regression ( d) from the 393 women with advanced BC enrolled in PALOMA-3 who had radiographic tumor measurement data including 261 treated with fulvestrant + palbociclib, and 132 with fulvestrant + placebo. We analyzed data using a model defined as SLD (t) = exp (– d x t) + exp ( g x t) – 1, where SLD = sum of longest diameters and t = time. We examined the relationship between g and overall survival (OS) and compared the median growth rates ( g) of various cohorts. Results: g values associate highly with OS (p<0.0001). Emulating results in the clinical trial, palbociclib slowed the median g values of the entire population and those with sensitivity to previous endocrine therapy but not those deemed resistant. Further cohort analyses found greater benefit with palbociclib in those with visceral metastases, and longer disease-free interval, and benefit independent of ECOG PS, menopausal status, prior lines of therapy, and age. With only the baseline and two additional scans obtained, the median g values of the palbociclib and placebo arms were statistically different: p=0.038 after 28 (19/9) patients and p=0.0043 after 40 (26/14) patients. Conclusions: Estimates of palbociclib’s impact on tumor growth rates ( g) confirm its efficacy in PALOMA 3. Our ability to discern differences in g, a value associated with OS, after only two follow up scans in as few as 28 patients merits considering g an early biomarker of OS benefit that could bring effective drugs to patients as rapidly as possible. [Table: see text]