bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uptake of genetic counseling and testing in a clinic based population of women with breast cancer.
Authors: Wehbe Alexandra , Manning Mark A. , Assad Hadeel , Purrington Kristen , Simon Michael S. 
Published: June 2021

10524 Background: Carriers of pathogenic variants in cancer susceptibility genes have an elevated risk of developing breast, ovarian, and other cancers.We conducted a medical record review to determine the uptake of genetic counseling and testing in a clinic-based population of women with breast cancer. Methods: Medical records of 150 women with breast cancer seen at the Karmanos Cancer Institute between January-December 2018 were reviewed to determine the proportion eligible for genetic testing according to National Comprehensive Cancer Network guidelines. We also assessed genetics referral rates, appointment completion and results of genetic testing. Using chi-square and ANOVA tests, we analyzed the association of demographic and clinical factors with eligibility and referral to genetic counseling. Results: The average age of diagnosis was 57.1 years old, with 68.7% of women diagnosed with stage I-III disease, and 31.3% diagnosed with stage IV disease. There were 91 (60.7%) women who met NCCN criteria for genetic testing, of which 46.2% ultimately underwent genetic testing. Eligible women were more likely to be younger (52.6 vs. 64.0 years old), White (75.0% vs. 54.5%), and have Medicaid (75.0%) or private insurance (72.9%) vs. Medicare (44.8%). Women who met NCCN criteria were 3.5 times more likely to be referred for genetic counseling than those that did not meet eligibility criteria. Women were also more likely to be referred if they had early-stage disease compared to stage IV (67.8% vs. 48.3%), and Medicaid or private insurance compared to Medicare (71.4%, 72.0% and 40.0%, respectively). Of eligible women, 59.3% had a genetic counseling appointment scheduled, and of those, 78.0% attended their appointment. There were no apparent differences in appointment completion based on race with similar percentages of Black and White women completing their appointments (74.0% and 77.0% respectively). Women with stage IV disease were more likely to complete their appointments (83.0%) compared to women with stages I-III (74.0%) and fewer women with Medicare completed their genetic counseling appointment (56.0%) compared to women with Medicaid (83.0%) and women with private insurance (83.0%). Among women who attended their appointment, 95.9% underwent genetic testing. Of women who had genetic testing, 8.5% had a pathogenic variant and 30.4% had a variant of unknown significance. Conclusions: The results of this study indicate that lack of genetic counseling referrals contribute to a gap between the need for and completion of genetic testing. By understanding barriers to genetic counseling and testing, future clinical initiatives could effectively improve accessibility to genetic counseling services.
Closing the gap: Trends in inconclusive rates on hereditary cancer testing across racial/ethnic groups.
Authors: Ademuyiwa Foluso Olabisi , Horton Carrie , LaDuca Holly , Komala Timothy , Profato Jessica , Pesaran Tina , Couch Fergus 
Published: June 2021

10525 Background: Several groups have described disparities in genetic test results for inherited breast cancer predisposition, with a disproportionate number of variants of unknown significance (VUS) reported in non-Caucasian individuals. These disparities are due in part to the underrepresentation of non-Caucasians in reference databases and clinical genetic testing cohorts. Over the past few years, diversification efforts have been made however, little data exists on how ethnicity- and gene-specific VUS rates have changed over time and whether such disparities have improved or worsened. Methods: We retrospectively reviewed demographic information and test results for individuals who underwent hereditary cancer multigene panel testing between March 2012 and September 2020 at a single laboratory. Individuals who self-reported as African American, Asian, Caucasian, or Hispanic on the test requisition form and whose testing included ATM, BRCA1, BRCA2, CHEK2 and PALB2 (five commonly tested breast cancer predisposition genes with management guidelines) were included in the study (n = 284,130). The frequency of germline variants of unknown significance (VUS) in the five genes was assessed in September 2015 and September 2020. Results: Amongst patients tested between March 2012 and September 2015, 82.8% of the study cohort self-reported as Caucasian and 17.2% were not Caucasian (6.5% African American, 6.0% Hispanic, and 4.6% Asian). The proportion of non-Caucasian individuals in the study cohort increased slightly by September 2020 to 22.8% (77.2% Caucasian, 9.2% African American, 8.4% Hispanic, and 5.3% Asian). Consistent with previous reports, Caucasians had the lowest VUS rate overall in both 2015 and 2020. This was also true at the individual gene level, with the exception of CHEK2. Over time, we observed a relative decrease in VUS rates across all ethnicities. Between 2015 and 2020, the overall VUS rate for the five included genes in non-Caucasian individuals was reduced by 32.0% in non-Caucasians compared to 23.6% in Caucasians. The absolute difference in VUS rate between non-Caucasians and Caucasians decreased from 7.9% in 2015 to 4.5% in 2020. Conclusions: While VUS rates for commonly tested breast cancer predisposition genes remain higher in non-Caucasians relative to Caucasians, our results demonstrate that this gap has been reduced over a five-year time period. These findings may be indicative of efforts by clinicians and laboratories to reduce these disparities. Further studies are necessary to improve the clinical utility of genetic testing in under-represented populations.[Table: see text]
Rare BAP1 variant of unknown significance (VUS) and analysis of BAP1 codon 146 genomics: Potential germline and therapeutic implications.
Authors: Murphy Jo-Ellen , Sadan Sara , Lee Jessica Kim , Pruski-Clark Jana , Sutphen Rebecca , McGregor Kimberly 
Published: June 2021

10533 Background: The BAP1 gene ( B RCA1-Associated Protein) encodes a protein ubiquitin carboxyl-terminal hydrolase (BAP1), which removes ubiquitin moieties and regulates various cellular functions including DNA repair. This association has driven interest in defining if BAP1 variants confer susceptibility to PARP inhibitors (PARPi). Germline and somatic BAP1 alterations are both rare, mostly unique, often classified as VUS’s, and associated with a broad range of overlapping tumor types. Based on the identification of a BAP1 R146K VUS variant in tumor, also previously identified as germline, an analysis of BAP1 codon 146 alterations was initiated to explore potential genetic and therapeutic implications. Methods: 394,756 tumor specimens were tested using hybrid capture-based genomic profiling (Foundation Medicine) for all variant types and Tumor Mutational Burden (TMB). BAP1 codon 146 cases were analyzed for clinicogenomic features and germline results when available. Results: BAP1 codon 146 variants were identified in 23 unique patients across the following tumor types: cholangiocarcinoma (CCA) (4), mesothelioma (4), NSCLC (3), RCC (2), ocular melanoma (2), and carcinoma of unknown primary (CUP) (3); many of which overlap with known and suspected germline associated BAP1 syndromic tumor types. BAP1 R146 mutations were classified as VUS in 16 patients and 7 were likely or known pathogenic. In 20 of the 23 cases where zygosity could be determined 16 (80%) were homozygous and 4 (20%) were heterozygous. In 2 of the 3 NSCLC cases, the BAP1 variant appeared likely somatic and/or associated with a high TMB. A previously reported germline BAP1 variant in a RCC patient, R146K, occurred 5 times in our tumor database. One case which was homozygous in tumor and confirmed in germline occurred in a patient who had both breast and CCA. She also had a sibling with RCC who shared the germline BAP1 R146K variant along with multiple 1st and 2nd degree relatives with RCC, mesothelioma, melanoma, liver cancer, colon cancer, and a cancer of unknown primary. Conclusions: Codon 146 of BAP1 localizes to the UCH (ubiquitin carboxyl hydrolase) domain, which includes the BARD1 interaction region. Loss of BAP1 activity as a consequence of germline or somatic mutation likely impacts ubiquitination status and activity of downstream proteins, such as those involved in DNA repair. For patients with suspected BAP1 inactivating alterations, often seen in non-homologous recombination deficiency related tumor types, PARPi therapy may be relevant. As demonstrated here, variants identified through tumor testing may also aid in re-classification of germline VUS’s. These results support the further investigation and validation of BAP1 alterations for germline risk stratification and therapeutic strategies with either PARPi and/or other therapies specific to tumors with impaired chromatin remodeling.
Genetic ancestry and clinical outcomes to immune checkpoint inhibitors among seven common cancers.
Authors: Nassar Amin , Adib Elio , Abou Alaiwi Sarah , Akl Elie , El Zarif Talal , Nuzzo Pier Vitale , Mouhieddine Tarek H. , El-Khoury Habib , Groha Stefan , Sonpavde Guru P. , Haddad Robert I. , Mouw Kent William , Giannakis Marios , Ananda Guruprasad , Freedman Matthew L. , Kwiatkowski David J. , MacConaill Laura E , Choueiri Toni K. , Gusev Alexander 
Published: June 2021

10536 Background: Prior studies and clinical trials report associations between self-reported race and clinical outcomes to Immune Checkpoint Inhibitors (ICIs). However, comprehensive studies of ancestry-associated differences in clinical outcomes have not been performed. We derived genetic ancestry scores and assessed clinical outcomes in 1341 patients with cancer treated with ICIs. Methods: Patients at the Dana-Farber Cancer Institute treated with ICIs only and with relevant cancer types and targeted exome sequencing data (Oncopanel) were included. Relevant cancer types included colorectal adenocarcinoma (CRC), esophagogastric adenocarcinoma (EGC), head and neck squamous cell carcinoma (HNSCC), melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and urothelial carcinoma (UC). We developed a bioinformatics pipeline to infer fine-scale genetic ancestry for each patient (n=1341) directly from tumor sequencing data by leveraging off and on-target sequenced reads and external ancestry reference panels. Three ancestry scores were determined (African, East Asian, European). Overall survival (OS) and time-to-treatment failure (TTF) were compared by Cox logistic regression between ancestral populations. Hazard ratio (HR) was derived using multivariable analysis, adjusted for single versus combination therapy, prior lines of therapy, and tumor mutational burden (TMB, as percentiles). Results: Median follow-up was 37.8 months (m; interquartile range: 35.7-39.5m). Common cancer types included CRC (n=52), EGC (n=114), HNSCC (n=88), melanoma (n=274), NSCLC (n=571), RCC (n=99), and UC (n=143). A higher East Asian ancestry (EAS) was significantly associated with worse OS ( p=0.03) and TTF ( p=0.002) in patients with RCC, independent of the histologic subtype (Table). There was no significant association between any of the three ancestral populations and clinical outcomes in the other 6 cancer types. Conclusions: We described clinical outcomes to ICIs across three global populations in 7 cancers. As the medical field re-evaluates the use of self-reported race in clinical decision-making, we utilize a novel ancestry pipeline that can be readily applied to tumor-only sequencing panels and better characterize non-white populations. We find no ancestry differences in clinical outcomes except in patients with RCC treated with ICIs which will require future validation. We plan to analyze genomic correlates of response by ancestry in each of the cancer types to better understand these diverge clinical behaviors.[Table: see text]
Analysis of breast cancer screening results in urban areas of Henan Province.
Authors: Lan-Wei Guo 
Published: June 2021

10543 Background: Breast cancer is the most common female cancer in China. Reasonable and effective screening is an important means to reduce the mortality of breast cancer. This study was to evaluate the compliance and efficacy of breast cancer screening in urban areas of Henan province from 2013 to 2019. Methods: A cluster sampling method was used to select the residents of 40-74 years old in Henan province to investigate the risk factors and breast cancer risk assessment. For subjects with high risk of breast cancer, those aged 40-44 conduct breast ultrasound examination; those aged over 45 conduct breast ultrasound combined with mammography examination. BI-RADs classification was used as the evaluation standard in both examinations. BI-RADS 3 class was defined as suspicious and BI-RADS≥4 class was defined as positive. Chi-square test was used to analyze the compliance rate and breast cancer detection rate among different groups. Results: A total of 29 111 residents at high risk for breast cancer were recruited in this study. They were 55.03 ± 7.91 years old, of which 13 760 took the following breast ultrasound or mammography examination, yielding a participation rate of 47.27% (13 760/29 111). The detection rates of suspected positive patients, positive patients and breast cancer patients were 23.40% (3 220/13 760), 2.55% (351/13 760) and 0.30% (41/13 760), respectively. Among the screening population, the highest detection rate of suspected positive patients was found in the 45-49 age group [27.79% (935/3 365)], the highest detection rate of positive patients was found in the 50-54 age group [2.98% (97/3 257)], and the highest detection rate of breast cancer was found in the 65-69 age group [0.49% (5/1 012)]. The detection rate of breast cancer positive patients by breast ultrasound combined with mammography examination was 2.95% (316/10 728), which was significantly higher than that of breast ultrasound alone [1.99% (213/10 728)] or mammography examination alone [1.25% (134/10 728)]. Conclusions: Breast ultrasound combined with mammography examination as a means of screening for breast cancer can significantly increase the detection rate of breast cancer positive patients. The next step should be to improve the compliance of the population, as well as the organization's implementation and service capabilities of the screening provider, to improve screening effectiveness.
Interactive online skin cancer training game “Whack-a-Mole” assesses training strategies and real-time feedback on melanoma identification among U.S. adults.
Authors: Sanchez Margaret , Carcioppolo Nicholas , Kim Soyoon , Lun Di , Malova Kate , Mao Bingjing , Reynolds Ashley Renee , Ewing Clay , Hu Shasa 
Published: June 2021

10564 Background: Cutaneous melanoma is a deadly form of skin cancer. Several studies have shown that early melanoma detection is associated with decreased mortality through self-examination and dermatology full-body skin exams. ABCD rule and the ugly duckling sign (UDS) are used to identify melanomas, but little research has explored the comparative efficacy of these approaches. This investigation compares the effectiveness of different mole identification training strategies and explores the effect of real-time feedback on decision-making. Methods: We developed an online melanoma identification game that tests differences between training types and expert feedback on mole identification. This online RCT tests a 4 (training: ABCD, UDS, both, control) X 3 (feedback: standard, motivational, control) factorial design on melanoma identification, skin cancer beliefs (perceived susceptibility and self-efficacy), and skin cancer prevention intentions. Standard feedback included expert evaluations of moles, whereas motivational feedback added statements grounded in fear appeals theory to encourage skin self-examination. An online research panel service was used to recruit 1025 US adults. Participants were randomly assigned to condition, completed a pretest, participated in the game intervention, and completed a posttest. Gameplay incorporates the same mechanics as Tinder (swipe left on benign moles and swipe right on malignant moles). Results: In total, participants reviewed 48 moles, 12 of which were melanomas. We used two-way ANCOVA for the analysis. ABCD training resulted in significantly higher melanoma identification than the control ( p =.011). Every training type resulted in significantly higher self-efficacy than the control ( p =.007). Additionally, there was a significant main effect of feedback on self-efficacy ( p =.001), where both standard and motivational feedback elicited significantly higher levels of self-efficacy than the control condition. Around 88% of participants intend to conduct skin self-exams and wear sunscreen. Conclusions: Our data suggests that “Whack a Mole” is an efficacious tool for melanoma training. ABCD and UDS training with interactive feedback are important to improve accuracy and ability for melanoma identification.
Outcomes for cancer patients on systemic anti-cancer therapies during the COVID-19 pandemic from the CAPITOL (COVID-19 Cancer PatIenT Outcomes in North London) cohort study.
Authors: Crolley Valerie , Hanna Daire , Joharatnam-Hogan Nalinie , Chopra Neha , Bamac Ekin , Desai Meera , Lam Yuk-Chun , Dipro Sabiq , Kanani Ruhi , Benson Jack , Wilson William , Fox Thomas Andrew , Shiu Kai-Keen , Forster Martin , Bridgewater John A. , Hochhauser Daniel , Khan Khurum Hayat 
Published: June 2021

10567 Background: One of the major challenges with COVID-19 has been the changes to cancer services, including changes to the type of systemic anti-cancer treatment being delivered to patients. There needs to be a better understanding of which cancer patients are at the greatest amount of risk to make informed decisions on how cancer treatment can be altered to protect patients from COVID-19 infection. The CAPITOL (COVID-19 CAncer PatIenT Outcomes in North London) study investigated the outcomes of patients receiving systemic anti-cancer therapies (SACT) with regards to COVID-19 infection, as patients with cancer are hypothesised to be at higher risk. Methods: CAPITOL collected data from all patients receiving SACT at two cancer centres. The effect of clinical characteristics on the incidence and severity of COVID-19 infection in patients on SACT was the primary outcome, and we used univariable and multivariable models in our analysis, adjusting for age, gender and comorbidities. Results: 2871 patients were analysed from 2nd March to 31st May 2020, all of whom received SACT; during this time period 68 (2.4%) were diagnosed with COVID-19. Receiving SACT increased the risk of death when contracting COVID-19 (adjusted (adj.) OR 9.84; 95% CI 5.73 – 16.9). The risk of contracting COVID-19 was increased by receiving chemotherapy (adj. OR 2.99; 95% CI = 1.72 - 5.21), with the risk significantly increased by high dose chemotherapy (adj. OR 2.36, 95% CI 1.35 – 6.48). Patients with comorbidities (adjusted OR 2.29; 95% CI 1.19 - 4.38), or with a respiratory or intrathoracic neoplasm (adj. OR 2.12; 95% CI 1.04 - 4.36) were also at increased risk of contracting COVID-19. Cancer patients who received targeted treatment had a reduced risk of contracting COVID-19 (adj. OR 0.53; 95% CI 0.30 – 0.95), while there was no significant change in risk caused by treatment intent (curative versus palliative), hormonal- or immunotherapy and solid versus haematological cancers. Conclusions: To the best of our knowledge, this is one of the first investigations into the risk of contracting COVID-19 in a cohort of all cancer patients on SACT. We found that patients on SACT are more likely to die if they contract COVID-19. The type of SACT received by cancer patients can affect their likelihood of contacting COVID-19, with chemotherapy increasing risk, targeted therapy decreasing risk and a potential protective effect for hormonal and immunotherapy.
Trends in incidence and mortality of squamous cell carcinoma of the skin: An observational analysis of the Global Burden of Disease database from 1990 to 2017.
Authors: Yang Dorothy , Jani Chinmay , Crowley Conor , Goodall Richard , Shalhoub Joseph , Salciccioli Justin D , Marshall Dominic C 
Published: June 2021

10569 Background: Epidemiological data relating to non-melanoma skin cancer (NMSC), including squamous cell carcinoma (SCC), is highly under-reported and under-studied due to its lower metastatic potential. In recent years, incidence and prevalence of SCC has increased in many countries due to earlier detection, increased ultraviolet light exposure, as well as increasing life expectancy. This investigation compared trends in SCC incidence, mortality and disability-adjusted life years (DALYs) in 33 countries. Methods: We utilized the Global Burden of Disease (GBD) database for 33 countries, including the European Union nations as well as other selected high-income countries including the UK and USA. We extracted data including age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs) and DALYs for SCC of the skin from 1990 to 2017. Joinpoint regression analysis was used to describe the trends. Results: For both sexes, the highest ASIRs were seen in the USA and Australia: ASIRs were 362.8/100,000 and 283.7/100,000 respectively for males, and 171.2/100,000 and 152.4/100,000 respectively for females. Males had higher ASIRs than females at the end of the observation period in all countries. In contrast, the highest ASMRs for males were observed in Australia (2.77/100,000) and Latvia (2.44/100,000), while the highest ASMRs for females were observed in Romania (0.95/100,000) and Croatia (0.90/100,000). The highest DALYs for both sexes were seen in Australia and Romania: DALYs were 58.4/100,000 and 43.8/100,000 respectively for males, and 16.9/100,000 and 14.9/100,000 respectively for females. Over the observation period, there were more countries demonstrating decreasing trends in mortality than in incidence. There was also a disparity between which countries had comparatively high mortality rates and which had high incidence rates – for instance, the USA, which had by far the highest SCC incidence rates, had among the lower mortality rates. Overall reductions in DALYs were observed in 24 of 33 countries for males, and 25 countries for females. Conclusions: Over the past 27 years, although trends in SCC incidence have risen in most countries, there is evidence that mortality rates have been decreasing, especially towards the end of the observation period. Overall, burden of disease as assessed using DALYs has decreased in the majority of countries. Future work will explore potential explanatory factors for the observed disparity in trends in SCC incidence and mortality.