bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting hyperglycemia among patients receiving alpelisib plus fulvestrant for metastatic breast cancer.
Authors: Ge Xuan , Behrendt Carolyn E. , Yost Susan Elaine , Patel Niki , Samoa Raynald , Stewart Daphne B. , Sedrak Mina S. , Lavasani Sayeh Moazami , Waisman James Ross , Yuan Yuan , Mortimer Joanne E. 
Published: June 2022

1060 Background: Although hyperglycemia is recognized as a common adverse event (AE) on alpelisib (ALP), this AE has been little studied outside clinical trials. We report the frequency of ALP-associated hyperglycemia in a real-world setting and evaluate proposed risk factors. Methods: We retrospectively identified patients with PIK3CA-mutated, hormone receptor-positive, metastatic breast cancer who initiated treatment with ALP+fulvestrant (FUL) between August 2019 and December 2021. Five primary characteristics (diabetes, prediabetes, body mass index (BMI), age, Asian ancestry) were evaluated as independent risk factors for ALP-associated hyperglycemia using ordinal logistic regression that considered 3 glycemic levels: normoglycemia, grade 2, and grade 3-4 hyperglycemia. Overall risk of error from multiple hypothesis testing was kept below 5% using the False Discovery Rate method. Results: The study included n = 92 subjects, all but 1 female, mean age 59.9 (+11.9) years, 13.0% with Asian ancestry. One third (33.7%) of patients had pre-existing diabetes, another 9.8% had pre-diabetes only. One third (32.6%) were obese, another third (31.5%) were overweight. Hypertension and hyperlipidemia were present in 53.3% and 41.3%, respectively. On ALP+FUL, 59 (64.1%) current subjects developed hyperglycemia of grade 1-4, a rate no different than the 181/284 (63.7%) reported in the ALP+FUL arm of the SOLAR-1 trial. Among our subjects, risk of grade 2-4 hyperglycemia was independently increased by 4 of 5 hypothesized risk factors, specifically pre-existing diabetes (Odds Ratio 3.75, 95% Confidence Interval: 1.40-10.01), pre-diabetes (6.22, 1.12-34.47), Asian ancestry (7.10, 1.75-28.84), each unit of BMI above 20 (1.17, 1.07-1.28), but not by additional year of age (1.01, 0.97-1.05). Exploratory analysis detected no association with pre-existing hypertension or hyperlipidemia. Conclusions: These findings suggest that Asian ancestry merits further study as a predisposing factor for ALP-associated hyperglycemia. Our study of this AE also demonstrates that pre-existing hyperglycemia and greater BMI are independent risk factors; diabetes and pre-diabetes confer similar degrees of risk; risk from BMI begins after BMI 20 and rises incrementally; and age is not a contributing factor.
Effects of healthcare provider recommendation for genetic testing.
Authors: Delacroix Emerson , Hanson Erika , Austin Sarah , Carr Grant , Kidwell Kelley M. , Stoffel Elena Martinez , Resnicow Ken 
Published: June 2022

10601 Background: This pilot study was conducted to elucidate the barriers and drivers for genetic testing by combining validated measures to inform the content of a clinical trial aimed at increasing uptake of clinically appropriate genetic testing amongst individuals with a personal history of cancer. Previous research shows that the rate of recommendation of genetic testing varies among Healthcare Providers (HCPs) despite national guidelines. Here we evaluate the rate and effect of HCP recommendation on the uptake of clinical cancer genetic testing. Methods: Data for these analyses were obtained from a cross-sectional survey completed by 794 adults (> 18 years) who were diagnosed with cancer in the past 10 years and were seen at an academic medical center within the past two years. Statistical analysis includes logistic regression and crosstabulation with SPSS and R statistical software. Results: Provider recommendation of genetic testing was found to be a very strong indicator of receiving genetic testing across all cancer types (OR = 146.4, p = <.001). HCPs more frequently recommended genetic testing to females (OR = 12.5, p = <.001), younger patients (OR = 1.05, p = <.001). While females are more likely to receive a recommendation, there were no significant differences on genetic testing uptake when a HCP recommended it for any gender. Conclusions: Without the recommendation of their provider, patients were significantly less likely to receive genetic testing that could affect their cancer treatment, surveillance, or family members. More aggressive patient health education is needed in cancer affected patients to decrease knowledge deficits and increase motivation for cancer genetic testing uptake. Education to providers regarding genetic testing recommendation guidelines could increase motivation to refer patients for genetic testing and counseling.
Outcomes of the BRCA quality improvement dissemination program in three health systems.
Authors: Bednar Erica M. , Chen Minxing , Walsh Michael T. , Eppolito Amanda L. , Teed Kelly B. , Klein Molly H. , Chao Han , Berg Jordan , Bowman Erin , Yobbi Cara S. , Krukenberg Rebekah C. , Jenkinson Sandra , Moore Jennifer , Garcia Cassie , Goedde Timothy , Morman Nichole A. , Bowdish Elizabeth C. , Wise Emaline , Rath Kellie S. , Lu Karen H. 
Published: June 2022

10603 Background: The BRCA Quality Improvement Dissemination Program (BQIDP) was disseminated to 3 community-based health systems’ oncology clinics in 2017. The BQIDP occurred over 3 years and aimed to increase rates of guideline-recommended referral (ref), genetic counseling (GC), and germline genetic testing (GT) for patients diagnosed with invasive epithelial ovarian, fallopian tube, and primary peritoneal cancer (OC) and triple-negative breast cancer diagnosed at age 60 or younger (TNBC). The BQIDP applied virtual implementation facilitation to support sites’ development, implementation, and tracking of quality improvement (QI) interventions. Interventions were adapted from prior QI initiatives and published interventions. Methods: Baseline metrics (patients diagnosed 1/1/2015 to site’s BQIDP launch date Autumn 2017) were compared to metrics of patients diagnosed during BQIDP implementation (site launch dates Autumn 2017 to Autumn 2020). Two-sample test of proportions was used to assess for statistically significant change in rates pre and post BQIDP implementation at each site. QI interventions targeted provider and patient education, retrospective and prospective case finding with alerts to providers and patients, case finding by review of somatic test results and genetic counselor tumor board attendance, streamlined ref and scheduling processes, and infusion-suite based GC. Results: All clinics increased rates compared to baseline (Table). Statistically significant improvement was noted for patients with OC in receipt of GC at Site A, ref and receipt of GC at site B, and receipt of GC at site C. Statistically significant improvement was noted for patients with TNBC in ref and GT at sites A and B. Conclusions: Improved rates of ref, GC and GT for patients with OC and TNBC were observed at all 3 sites compared to baseline. Baseline ref, GC, and GT metrics for patients with TNBC were higher than for patients with OC at all sites. Tailored and facilitated QI efforts can promote patients’ receipt of guideline-recommended cancer genetics services in health system oncology clinics. [Table: see text]
Clinical characteristics of patients with PMS2 mutations.
Authors: Pandey Samiksha , Rangarajan Tara , Zakalik Dana 
Published: June 2022

10610 Background: Lynch syndrome is a hereditary cancer predisposition syndrome caused by mutations in mismatch repair genes, MLH1, MSH2, MSH6, and PMS2. The cancer risks and clinical presentation of PMS2 associated Lynch syndrome is not well defined. This study outlines the characteristics of patients with PMS2 mutations identified in a large academic center. Methods: Patients with a pathogenic or likely pathogenic PMS2 variant identified between June 1, 2009 and Dec 31, 2021 were selected from a database at the Nancy and James Grosfeld Cancer Genetics Center at Beaumont Health. Data on demographics, cancer type and molecular testing were retrospectively analyzed. Results: A total of 92 patients from 61 families were found to carry a pathogenic or likely pathogenic variant in PMS2. The mean age at testing was 54 (19 to 95). A majority (50) of the family were Caucasian, while the rest were African American (2), Middle Eastern (2), Multiracial (8). The most common variant was c.137G > T (p.Ser46Ile), seen in twelve of 61 families. Forty-two patients (45.6%) had a personal history of cancer, with a mean age at diagnosis of 63. Of these forty-two patients, four had multiple malignancies, including one patient with six separate cancers. The most common malignancies were breast (16), colon (12), followed by uterine cancer (8), pancreatic (4), prostate (3) and other cancers. The mean age of diagnosis of breast cancer was 56 (41 to 78), colon cancers was 57 (32 to 75), uterine cancer 59 (50 to 72). Tumor IHC was performed in thirteen cases and 11 demonstrated loss of PMS2 protein expression. MSI was performed in 8 cases and 5 were unstable and 3 were stable. Conclusions: This study reveals the the clinical spectrum of cancers in PMS2 related Lynch syndrome. The most common cancers were breast, colon and uterine cancer, with older age of diagnosis. There was evidence of a more severe phenotype, exemplified by a patient with six cancers, suggesting higher penetrance. Further research is needed to better characterize the clinical presentation of PMS2 related Lynch syndrome.
Identifying genetic factors of response and resistance to CDK4/6 inhibitors in metastatic HR+/HER2-breast cancer using real-world data.
Authors: Agrawal Smita , Singh Neeraj , Narayanan Babu 
Published: June 2022

1064 Background: CDK4/6 inhibitors plus endocrine therapy are approved for treatment of HR+/HER2- metastatic breast cancer (MBC) and have shown to provide a significant progression free survival benefit over endocrine therapy alone. But not all patients benefit from this treatment and some develop resistance over time. The molecular mechanisms governing this resistance are poorly understood. We have developed a real world dataset that includes data elements from structured EMR tables as well as deeply curated unstructured data from BC patients (ConcertAI Genome360 BC Dataset) who have been treated with CDK4/6 inhibitors and have undergone DNA sequencing to identify somatic mutations. We have leveraged this linked clinical-genomics dataset to identify genetic drivers of resistance and response to CDK4/6 inhibitors. Methods: This retrospective study uses the Genome360 BC Dataset (N = 1249). The patient’s eligibility to be included in this study (N = 456) was HR+/HER2- MBC patients with age > 18 years treated with at least one of the CDK4/6 inhibitors and have response data based on RECIST criteria (responders = 231, non-responders = 225). For each patient in both cohorts, all pathogenic gene mutations and copy number changes were identified and enrichment analysis was performed. Biomarkers with Z value > 1.96 (p value < 0.05) were considered for further analysis. Pathway analysis was performed using these biomarkers and the CDK4/6 pathway to identify pathways and genes that can potentially be targeted to overcome resistance based on the mutational landscape of the patients receiving therapy. Results: We identified 7 potential segments (similar groups of genes) which predicted response or resistance to CDK4/6 inhibitors. Here we present data on 3 such segments which are closely related. Loss of function mutations in RB1 were enriched in the non-responder population (Z value = 2.33; p value = 0.026; N = 31). This is consistent with previously reported findings. In addition, amplifications and gain of function mutations in MYC and associated genes were also significantly enriched in the non-responder population (Z value = 2.71; P value = 0.01; N = 44). Interestingly, loss of function mutations in TSC1/2 genes which are downstream of MYC were predictors of good response to CDK4/6 inhibitors (Z value = 2.19; P value = 0.036; N = 30), strengthening the role of the parallel MYC signaling pathway in resistance to CDK4/6 inhibitors. Conclusions: Using our Genome360 BC Dataset, we have identified genetic markers affecting response to CDK4/6 inhibitors. In addition to the known role of RB1 in resistance to CDK4/6 inhibitors, the MYC signaling pathway emerged as a strong candidate. Based on these results, patients with mutations in these pathways may benefit from addition of mTOR or PKL1 inhibitors to CDK4/6 inhibitors to overcome resistance and prolong their effect.
Association of 27-gene IO score with outcome in a phase Ib trial of pembrolizumab (pembro) plus chemotherapy (CT) in metastatic triple-negative breast cancer (mTNBC).
Authors: Page David B. , Collins Krystle Louise , Rajamanickam Venkatesh , Moxon Nicole , Mellinger Staci L. , Conlin Alison Katherine , Seitz Robert , McGregor Kim , Nielsen Tyler J. , McArthur Heather L. 
Published: June 2022

1082 Background: The IO score is a is a 27-gene signature developed to classify the tumor immune microenvironment derived from the 101-gene TNBCtype genomic classifications. The IO score predicts clinical outcome following immune checkpoint inhibitor therapy in NSCLC and bladder cancer, and recently was shown to predict benefit by pCR of atezolizumab plus CT over neoadjuvant CT alone in early stage TNBC (NeoTRIPaPDL1 trial). The IO score has not yet been evaluated in mTNBC or with pembro in breast cancer. Methods: We report preliminary associations of IO score with response from a phase Ib trial (NCT02734290). mTNBC subjects received 1st/2nd line pembro (200mg IV q3wk) plus investigator’s choice paclitaxel (80mg/m2 IV q1wk, n = 15) or capecitabine (2000mg PO BID x 7d, q2wk, n = 14). Baseline (n = 23) and on-treatment (at wk 6, n = 10) biopsies were analyzed for IO score and genomic subtype by RNA exome sequencing. Objective response rate (ORR, partial or complete response, 12 weeks) and survival was determined among response-evaluable subjects (n= 21). Tumor PD-L1 was assessed by IHC (combined positive score, CPS > 10%). The IO signature was analyzed as a binary classifier (IO+/IO-) and as a continuous variable (IO score). Results: 39% of evaluable subjects were IO+ (n =9/23). IO+ was associated with improved clinical outcome, including ORR (IO+ 43%, IO- 29%), median progression free survival (mPFS, IO+ 138d, IO- 79d), and median overall survival (mOS, IO+ 687d, IO- 305d). IO+/IO- classification and IO scores were stable across serial biopsies (Cohen’s kappa = 0.74, r = 0.84). IO score was not strongly correlated with PD-L1 CPS (r = 0.27) or sTILs (r =.09). PD-L1-/IO+ tumors constituted 31% (n = 5/16) of PD-L1- cases and exhibited favorable outcome (ORR 40%, mPFS 162d, mOS 556d). IO score and ORR varied across TNBCtype classifications (BL1 subtype: 50% ORR, 66% IO+; BL2 subtype: 0% ORR, 66% IO+; LAR subtype: 50% ORR, 0% IO+, MSL subtype: 33% ORR, 60% IO+). Conclusions: IO score is associated with favorable outcome following pembro + CT, and may identify PD-L1-negative cases that respond to pembro + CT. Further investigation in larger datasets is warranted to ascertain the clinical utility of IO score in this setting. Funding: Drug support and funding provided by Merck Sharpe & Dohme as part of the Merck Investigator Studies Program. Clinical trial information: NCT02734290.
Historical redlining and breast cancer survival in the United States: Evidence from the 2010-2017 SEER Medicare linked dataset.
Authors: Bikomeye Jean C. , Zhou Yuhong M. , McGinley Emily L. , Canales Bethany , Yen Tina W.F. , Beyer Kirsten M. M. 
Published: June 2022

1095 Background: Cancer is the second leading cause of morbidity and mortality in the US. Systemic racism is a critical cause of health disparities and historically disadvantaged people experience poor outcomes including poor breast cancer (BC) survival. This study aims to investigate the impact of historical redlining on all-cause and BC-specific survival among older women in the US. Methods: Historic 1930’s Homeowner’s Loan Corporation (HOLC) boundaries and grades were linked to 2010 Census tracts and the 2010-2017 SEER Medicare BC cohort. Women were included if they were 66+ years old at diagnosis, diagnosed with invasive BC, enrolled in Medicare Part A and Part B for 12 months prior to diagnosis to calculate comorbidity, and a Census tract match for HOLC grade. The independent variable was HOLC grade in two categories: A and B(not redlined), and C and D(redlined). The outcomes were all-cause and BC-specific survival, determined by Kaplan Meier Survival curves and both unadjusted and adjusted Cox regression models. End point for censoring was 12/31/2019 (all-cause) and 12/31/2018 (BC-specific). The final models were stratified by age and tumor stage at diagnosis; and adjusted for comorbidity, race and ethnicity, hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, and interaction term between comorbidity and race. Results: Among 10,113 women, 62.8% resided in historically redlined Census tracts. At a mean (+SD) follow-up time of 48.5 (+28.8) months, 28.9% were deceased; 41.6% of which died of BC. Women residing in historically redlined census tracts experienced poorer BC survival (49.8 +28.2 months) than those residing in non-redlined Census tracts (57.8 +30.7 months). After controlling for covariates, residing in a historically redlined Census tract remained an independent predictor of higher mortality: HR (95%CI) = 1.11 (1.02, 1.20) and 1.24 (1.011, 1.39) for all-cause mortality and BC-specific mortality, respectively. Conclusions: Residing in a formerly redlined Census tract at the time of BC diagnosis is associated with worse all-cause and BC-specific mortality, even after stratifying/adjusting for important patient and tumor characteristics. Public health and government agencies stakeholders should consider historical contexts when designing and implementing equity-focused community and clinical interventions targeted at mitigating and reducing BC disparities and improving health equity.
Medical student clinical cultural awareness in cancer care of sexual and gender minorities.
Authors: Au Cherry , Samuelson Annika , Schabath Matthew B. , Mitchell Edith P. 
Published: June 2022

11003 Background: Health disparities in lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+), or sexual and gender minorities (SGMs), patients are a known in health care. SGMs have higher cancer risk but lower rates of screenings, resulting in a higher likelihood of late-stage disease. Relevant gaps in medical school curricula regarding SGMs must be addressed to prevent these disparities. The purpose of this study is to evaluate medical students’ (MS) clinical cultural awareness in cancer care of SGM patients. Methods: This study was a cross-sectional survey distributed to medical degree students actively enrolled at a large urban academic center. This survey was adapted from a study by Schabath et. Al. The survey had 38 questions on demographics, attitudes, and knowledge of SGM topics. Questions were scored on a Likert scale from ‘strongly disagree’ to ‘strongly agree’ with ‘don’t know’ and ‘prefer not to answer’ as options. Results are reported using descriptive statistics. Results: There were 238 responses. Most respondents were white (63.9%), cis-gender female (57.6%), and heterosexual (78.6%). Distribution according to year are as follows: MS1 36.6%, MS2 14.7%, MS3 27.3%, and MS4 19.3%. Attitudes are listed in the table below. Four of the seven questions on knowledge had “Don’t Know” as the most common response. Notably, 47.1% of respondents did not know if screening gay/bisexual men with anal pap is associated with increased life expectancy. Students were interested in learning guidelines regarding SGM cancer screening and considerations for patients who are on hormone therapy. Conclusions: While most medical students are comfortable treating LGBTQ+ patients, most are not confident in their knowledge. This difference is most profound in knowledge of transgender patients. Schools must consider longitudinal education in SGM topics to improve student knowledge to produce confident and competent providers. Participants Responses to Attitude Items. [Table: see text]
Assessing the landscape in medical oncology medical education scholarship: A scoping study.
Authors: Jin Ruijia , Addison Sean McKay Fenlon , Kitchin Vanessa , Golden Daniel W. , Tam Vincent C. , Ingledew Paris-Ann 
Published: June 2022

11009 Background: Medical oncology and medical education have both expanded exponentially over the past 50 years; as such, it is important to understand the current status of postgraduate medical oncology education and develop ways to advance this field. This study undertakes a scoping review of medical education literature in medical oncology to inform future scholarship in this area. Methods: MEDLINE (Ovid), Embase (Ovid), ERIC (EBSCO), and Web of Science (UBC Core Collection) were searched to find peer-reviewed English language articles on Postgraduate Medical Education in Medical Oncology published between 2009 and 2020. The review was designed in accordance with updated methodological guidance for the conduct of scoping review. Articles were classified by learning specialty, learner training level, region of authorship, single or multi-institution, year of publication, whether the journal was an education journal, quantitative vs qualitative design, study methodology, and category or topic. A modified Kerns framework for curriculum development was used to assess the type of curriculum intervention, Boyer’s definition of scholarship was used to classify the type of scholarship, and the CanMEDS Framework was used to map the domains of physician competency each study aims to address. Results were interpreted using descriptive statistics and collated and summarized utilizing predetermined conceptual frameworks. Results: 2959 references were initially found across the 4 databases. After title and abstract screening, 305 articles remained; after full text review, a total of 144 articles were included in our final analysis. These data showed that postgraduate medical oncology graduate medical education scholarship is increasing and most commonly observed in the United States. Quantitative studies were most common with surveys used as the most popular study approach. In terms of CanMEDS framework, Professional and Medical Expert comprised the large majority of education focuses, while very few articles addressed Leader or Health Advocate. Curriculum development, professional development, and attitudinal skills (communication skills, ethics) were the dominant research themes, while no articles discussed teacher training. Conclusions: By investigating the body of current literature, this research identifies areas of highest priority in postgraduate medical oncology graduate medical education and opportunities for growth. Whereas areas like professionalism and attitudinal skills are well-studied, research is lacking in leadership, health advocacy and teaching training. This study provides guidance for future medical education scholarship in medical oncology and establishes a benchmark to examine changes in medical oncology educational scholarship over time.