bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital cancer genetic risk assessment in a gynecologic oncology clinic.
Authors: Webster Emily M. , Ahsan Muhammad Danyal , Perez Luiza , Bull Leslie , Keenahan Laura , Levi Sarah R. , Kieran Shannon M. , Cantillo Evelyn , Chapman-Davis Eloise , Holcomb Kevin , Sharaf Ravi N. , Frey Melissa Kristen 
Published: June 2023

10612 Background: Population-based screening for hereditary cancer syndromes and referral of those who screen positive for genetic testing is a cost effective, evidence-based national health priority. However, under-recognition of hereditary cancer syndromes remains a critical concern, with fewer than 20% of individuals with Hereditary Breast and Ovarian Cancer Syndrome and Lynch Syndrome identified. Here, we evaluate the Ambry Genetics Comprehensive, Assessment, Risk, and Education (CARE) Program, a risk-stratification tool to assess eligibility for National Comprehensive Cancer Network (NCCN) genetic testing criteria and lifetime risk for breast cancer based on the Tyrer-Cuzick (version 8.0) risk algorithm. Methods: Between November 2022 and February 2023, new patients in a gynecologic oncology clinic were prompted by text message to complete CARE prior to their appointment. Those using CARE then completed a System Usability Scale (SUS), a validated 10-item questionnaire for the assessment of perceived usability. Results: Sixty patients presented for a new patient gynecologic oncology appointment and were prompted to complete CARE. The median patient age was 55 years (interquartile range, 40-68). The patients self-identified as Non-Hispanic White (44, 73%), Non-Hispanic Black (5, 8%), Asian (5, 8%), Hispanic (3, 5%), other (2, 3%), and unknown (1, 2%). All identified as female. Forty-three patients (72%) completed CARE. Among CARE users, 11 (26%) were identified as meeting criteria for genetic testing; of these, 9 (82%) proceeded with point-of-care same day genetic testing. Nine (21%) patients were eligible for enhanced breast cancer screening based on an estimated lifetime breast cancer risk of 20% or greater; of these, 100% were referred for high-risk breast screening. There were no patient demographics associated with completion of CARE. Forty-one patients (72%) completed the SUS survey; the median SUS score was 80 (interquartile range, 60-92.5), which corresponded to 85-89th percentile and a letter grade of A-. Conclusions: Implementation of a digital tool for cancer genetic risk assessment identified a quarter of patients to be eligible for genetic testing, among whom 82% completed same-day genetic testing. Additionally, the tool was reviewed favorably by patient users. Large randomized controlled trials of health information technology tools are needed to move closer to the goal of population-based hereditary cancer risk assessment.
Impact of risk-reducing mastectomy on quality of life of women with Li-Fraumeni syndrome.
Authors: Polidorio Natalia , Sandoval Renata Lazari , Bioni Pâmela , Achatz Maria Isabel Waddington 
Published: June 2023

10623 Background: Risk-reducing mastectomy (RRM) is a common strategy for managing breast cancer (BC) risk in women with Li-Fraumeni syndrome (LFS). Data on uptake and health-related quality of life (HRQoL) in LFS are limited and often extrapolated from BRCA scenario, despite the lack of evidence on survival benefits in LFS. This study evaluated RRM uptake and its impact on HRQoL in women with LFS. Methods: TP53 PV female carriers from a Brazilian LFS cohort from January 2012 to December 2022 were eligible. After informed consent, 90 women reported oncological status, uptake of RRM, and completed BREAST-Q questionnaire. Scores were compared among different BC risk management strategies and minimal important difference (MID) of ≥ 4 was described. Multivariable analyses were performed to identify surgical factors related to HRQoL outcomes. Results: 71.7% (n=33) of women diagnosed with unilateral BC (n=46) underwent contralateral risk-reducing mastectomy (CRRM) at a median age of 39 years. Among unaffected BC women (n=44), 36.3% underwent bilateral risk-reducing mastectomy (BRRM) at a median age of 36 years. CRRM was associated with lower scores for psychosocial (64[±19] vs 93[±21], p=.05) and physical well-being (72[±16] vs 92[±18], p=.001). BRRM women had lower physical well-being scores (72[±19] vs 92[±13], p=.003). MID associated with worst HRQoL outcomes were seen in all four domains on CRRM women and on satisfaction with breasts and physical well-being of BRRM patients (table). Nipple-sparing mastectomy (NSM) presented better psychosocial (74[±20] vs 52[±19], p=.04) and sexual well-being (60[±20] vs 46[±20], p=.05) when compared to skin-sparing mastectomy (SSM) on CRRM patients and with higher sexual well-being (60[±20] vs 46[±20], p=.05) on BRRM patients. Women with BRRM > 2 years had better physical well-being (83[±14] vs 56 [±12], p<.001). There were no significant differences in scores of women with age £35 years at the time of BRRM, although MID ≥ 4 was observed on psychosocial and sexual well-being and satisfaction with breasts: -23.0, -14.4, and -20.0, respectively. Conclusions: We observed high rates of RRM in LFS women and those were associated with worse outcomes on breast HRQoL in comparison to surveillance. The potential benefits and harms of RRM should be carefully discussed with patients before performing it, especially in LFS women where the survival benefits of these interventions remain uncertain. [Table: see text]
Validation of a breast cancer polygenic risk score in 15,490 Brazilians using exome sequencing.
Authors: Eichemberger Rius Flavia , Guindalini Rodrigo Santa Cruz , Viana Danilo , Salomão Júlia , Gallo Laila , Bertolacini Claudia , Mendes de Freitas Renata , Taniguti Lucas , Imparato Danilo , Zheng Yonglan , Huo Dezheng , Olopade Olufunmilayo I. , Schlesinger David 
Published: June 2023

10631 Background: Brazil has a highly admixed population with significant Southern European, African and Native American genetic ancestries. Approximately 75% of the population has two or more continental ancestries. Therefore, breast cancer polygenic risk scores (PRS) developed in predominantly European populations requires validation in the Brazilian population. Compared with genotyping arrays and whole genome sequencing, affordable and scalable whole exome sequencing (WES) allows genotyping of both rare and common variants in the targeted regions and imputation of common variants not directly captured. In this study we validate a previously developed 3820-variant PRS using WES in 15,490 Brazilians. Methods: The cohort consisted of 6,362 women with a history of breast cancer (mean age 49.6, stddev 11.6) and 9,128 unphenotyped adults as controls (mean age 41.6, stddev 13.3). WES were performed on germline DNA and variants were called and curated. Imputation was done using the 1000 Genomes Phase 3 reference panel for variants falling outside the WES captured regions. After excluding subjects with known pathogenic or likely pathogenic variants in BRCA1, BRCA2, PALB2, PTEN, or TP53, and first or second-degree relatives of the probands, 14,577 individuals remained in the final analysis (5,730 cases and 8,847 controls). We restricted PRS calculation to 2,893 of the original 3,820 variants with an estimated global imputation accuracy of 96%. Odds ratios (OR) were adjusted using the top 10 principal components. Results: The breast cancer PRS showed a highly significant correlation with cancer risk (p-value = 7.1e-81, OR = 1.43, 95% confidence interval (CI) = 1.38-1.48 per PRS standard deviation). Compared with women in the middle deciles, those in the highest 10% had an OR of 1.93, while those in the lowest 10% had an OR of 0.52 (Table). Conclusions: In this study we show that WES can capture 76% of the variants included in a previously developed and validated breast cancer PRS, and the calculated PRS is correlated with breast cancer risk in the admixed Brazilian population. This opens the door for clinical studies into the application of PRS in Brazil, particularly in women without mutations in breast cancer high-penetrance genes. In addition, our WES-based PRS strategy can be quickly, affordably, and seamlessly adopted by labs that already offer Hereditary Breast Cancer panels that use WES as a backbone. [Table: see text]
Pre-diagnosis dietary patterns and risk of multiple myeloma in the NIH-AARP cohort.
Authors: Parikh Richa , Castro Francesca , Eustaquio Jelyn C. , Derkach Andriy , Joseph Janine , Lesokhin Alexander M. , Usmani Saad Zafar , Shah Urvi A 
Published: June 2023

10635 Background: Despite patient interest in knowing whether diet is linked to multiple myeloma (MM), there is limited research on dietary patterns and MM risk (Malik et al. BCJ 2022). Two studies have assessed this risk, albeit with a small number of MM cases. The EPIC-Oxford cohort and Oxford Vegetarian study (65 MM cases) showed that fish eaters, vegetarians and vegans had significantly reduced MM risk compared to meat eaters (Key et al. AJCN 2014). The Nurses’ Health Study and Health Professionals Follow-up Study (478 MM cases) showed a significantly increased MM risk in men with Empirical Dietary Inflammatory Pattern (Lee et al. JNCI Can Spectr 2019). To our knowledge, this is the largest epidemiologic study to date assessing pre-diagnosis dietary patterns and MM risk. Methods: The NIH-AARP Diet and Health study is a prospective cohort of 567,169 persons who completed a food frequency questionnaire in 1995-1996 and were followed until December 2011. Healthy Eating Index-2015 (HEI-2015), Healthy Diet Score (HDS), alternate Mediterranean Diet (aMED) and healthful Plant-based Diet Index (hPDI) scores were calculated using a priori defined methods and grouped into quartiles, with higher scores reflecting healthier eating patterns. We prospectively evaluated the association between pre-diagnosis dietary patterns and MM incidence in this cohort. Hazard ratios (HR) and 95% confidence intervals (95%CI) were estimated using multivariate Cox proportional hazards models adjusted for age at study entry, sex, race, body mass index, education, and total energy intake (by residual method). Sensitivity analysis was conducted to assess reverse causality by excluding MM cases diagnosed within one year of follow-up. Results: Among 392,589 participants (after exclusions), a total of 1,366 MM cases (59% males; 92% non-Hispanic whites) were identified during the follow-up period. Analysis revealed a significant association between hPDI scores and reduced MM risk (highest vs lowest quartile, HR 0.85; 95%CI 0.73-1.0; p=0.043) (Table). In sensitivity analysis (1,302 MM cases), the association was no longer significant (HR 0.87; 95%CI 0.74-1.03; p 0.09) but trended in the same direction. This may be due to small sample size, given MM is a rare disease. HEI-2015, HDS and aMED scores were not associated with MM risk. Conclusions: A healthful plant-based diet was associated with reduced MM risk in the NIH-AARP cohort. These results will help oncologists and patients make informed choices about their diet. [Table: see text]
Indirect treatment comparison of first-line CDK4/6-inhibitors in post-menopausal patients with HR+/HER2- metastatic breast cancer.
Authors: Zhao Joseph J , Fong Khi Yung , Chan Yiong Huak , Tey Jeremy Chee Seong , Dawood Shaheenah S. , Lee Soo-Chin , Finn Richard S. , Sundar Raghav , Lim Joline SJ 
Published: June 2023

1071 Background: In phase III studies, the CDK4/6-inhibitors palbociclib, ribociclib, and abemaciclib all have demonstrated similar clinical efficacy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC) with regards to the primary endpoint of progression-free survival (PFS). However, the lack of overall survival (OS) benefit in the PALOMA-2 study is inconsistent with the OS benefit seen with the other two CDK4/6-inhibitors. This study sought to elucidate indirect treatment survival outcomes between CDK4/6-inhibitors in this setting. Methods: Phase III randomized controlled trials comparing first-line aromatase inhibitor with or without a CDK4/6-inhibitor in post-menopausal patients with HR+/HER2- MBC. A graphical reconstructive algorithm was utilized to retrieve patient level time-to-event data from reported Kaplan-Meier OS and PFS curves. Survival analyses were conducted with Cox proportional hazards model with a shared-frailty term incorporated to account for inter-study differences. Two-stage indirect treatment comparison model was conducted as a sensitivity analysis. Results: Three randomized phase III trials – PALOMA-2, MONALEESA-2 and MONARCH-3 – comprising 1,827 patients were included. Indirect pairwise comparison of all CDK4/6-inhibitor showed no significant PFS differences across one-stage and two-stage models (all p>0.05). Likewise, indirect treatment comparison between ribociclib vs palbociclib (one-stage: HR=0.903, 95%-CI: 0.746-1.094, p=0.297), abemaciclib vs palbociclib (one-stage: HR=0.843, 95%-CI: 0.690-1.030, p=0.094) and abemaciclib vs ribociclib (one-stage: HR=0.933, 95%-CI: 0.753-1.157, p=0.528) failed to demonstrate a significant OS difference. Conclusions: Findings from this indirect treatment comparison suggest no significant PFS or OS differences between CDK4/6-inhibitor agents when combined with an aromatase inhibitor in post-menopausal patients with HR+/HER- MBC. [Table: see text]
Clinical outcomes and correlation with longitudinal circulating tumor (ct)DNA dynamics of a phase I/II study of GSK525762 combined with fulvestrant in patients with hormone receptor-positive/HER2-negative (HR+/HER2−) advanced or metastatic breast cancer.
Authors: Cescon David W. , Hilton John Frederick , Hicks Kirsty , Zhang Qu , Barbash Olena , Dhar Arindam , Oliveira Mafalda , Sparano Joseph A. 
Published: June 2023

1073 Background: Endocrine therapy is the main treatment option for hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (mBC). However, many patients experience disease progression due to resistance to endocrine therapy. Molibresib (GSK525762) is a small-molecule inhibitor of bromodomain and extra-terminal (BET) family proteins (BRD2, BRD3, BRD4, and BRDT). Pre-clinical data suggested that the combination of molibresib with endocrine therapy might overcome endocrine resistance. This study aimed to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy (objective response rate [ORR]) of molibresib combined with fulvestrant in women with HR+/HER2− mBC. The association between early ctDNA dynamics and clinical outcomes was also assessed. Methods: In this phase I/II dose-escalation and expansion study, patients received oral molibresib 60 mg or 80 mg once daily in combination with intramuscular fulvestrant. Patients enrolled had relapsed/refractory, advanced/metastatic HR+/HER2− BC with disease progression on prior treatment with an aromatase inhibitor, with or without a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. Baseline and week 4 plasma samples were collected and tested using a 74-gene ctDNA panel. Molecular response (MR) was defined as at least 50% reduction of baseline ctDNA level calculated as the average allele frequency of detected single nucleotide variants or indels. Results: The study included 123 patients. The 3 most common molibresib-related adverse events (AEs) were nausea (52%), dysgeusia (49%), and fatigue (44%). At molibresib 60 mg, >90% patients experienced treatment-related AEs, with varying incidence of Grade ≥3 AEs (17%–71%) amongst subgroups. The ORR was 13% (95% confidence interval [CI], 8–20), not meeting the 25% threshold for proceeding to phase II. Among 82 patients with detected baseline circulating tumor DNA, a strong association was observed between baseline copy number amplification (CNA) presence and poor progression-free survival (PFS) with hazard ratio (HR) of 2.89 (95% CI, 1.73–4.83; P < 0.0001). MR was significantly correlated with better PFS (HR=0.38; 95% CI, 0.19–0.75; P = 0.0037), which was further improved when MR was refined as no baseline CNA (HR=0.22; 95% CI, 0.09–0.54; P = 0.0003). Conclusions: Molibresib in combination with fulvestrant did not demonstrate clinically meaningful activity in this study. Copy number adjusted ctDNA MR is a promising early marker for clinical benefit. Clinical trial information: NCT02964507 .
Remote delivery of a mindfulness-based intervention to decrease stress levels and promote coping among health-care workers during the COVID-19 pandemic.
Authors: Helou Joelle Antoine , Barry Aisling S , Ye Philip , Liu Fei-Fei , Julius Anet , Letourneau Daniel , Wong Philip , Dawson Laura A. , Elliott Mary 
Published: June 2023

11007 Background: The COVID-19 pandemic has caused significant stress amongst everyone around the world. Healthcare workers (HCW) in particular, experience substantial stress in these challenging environments. In an effort to find supportive interventions for radiation oncology providers, while respecting the requirements of physical distancing, we proposed the remote delivery of a mindfulness-based intervention (MBI). The primary aim of this study is to determine the association of this intervention with a reduction of perceived stress. Secondary aims are to evaluate the impact on coping and burnout amongst HCW in the Radiation Program (RP). Methods: This is a single-centre, single-arm, pilot study. All HCW associated with the RP were eligible. This was a voluntary effort. The intervention - manualized, mindfulness-based group for HCW, entitled Mindfulness-Based Resilience and Well-Being Training, consisted of four 1-hour sessions per week for 4 weeks. From Nov 2020 to Dec 2021, 6 consecutive closed groups MBI were delivered remotely using Zoom. Each group consisted of 5-12 participants and one professional with a background in mindfulness facilitation. The Perceived Stress Scale (PSS), The Maslach Burnout Inventory and the BriefCOPE questionnaire were collected pre-intervention, and at 1, 4 and 12 weeks post-intervention. Linear mixed effect models with a random intercept to account for the repeated measures were used to assess the change of outcomes over time. Results: Amongst 43 HCWs who expressed initial interest, 33 completed the study. At 1-, 4- and 12-weeks post-intervention 25, 24 and 21 participants provided completed questionnaires respectively. Time constraint was the main reason for withdrawal and missing data. There was a significant decrease in perceived stress at week 1, 4 and 12 when compared to baseline [mean baseline PSS score: 22.5 (SD = 4.6), week 1: 18.4 (4.9), p= 0.002, week 4: 16.8 (6.5), p< 0.001, week 12: 16.3 (6.8), p< 0.001]. Overall, 7 (21%) participants reported high PSS (27-40) at baseline while none reported high levels at 1 and 12 weeks. Problem focused coping( p= 0.02), and active coping ( p= 0.009) were significantly higher at 1 week but not at 4 and 12 weeks. Conclusions: The remote delivery of a MBI is feasible and effective to reduce perceived stress levels and to promote coping across HCWs. These findings need to be validated in a larger cohort. Time was a major constraint preventing the participation of interested HCWs. It would be extremely valuable for departments to support such interventions and programs to help HCWs cultivate skills to meet the demands related to working in healthcare environments throughout and beyond this crisis.
Assessment of YouTube as an information source for immune checkpoint inhibitors (ICIs).
Authors: Garg Tulika , Chahal Rutvi , Khosla Atulya Aman , Singh Rohit , Karass Susan Hosny , Sharma Rakesh Kumar , Roy Arya Mariam , Thakkar Astha , Jatwani Karan 
Published: June 2023

11009 Background: YouTube is an open-access source of information. With more than 2.5 billion users, it can play a pivotal role in educating or misinforming cancer patients. ICI has changed the treatment paradigm for cancer over the past decade. There is scarce data to evaluate the quality of information on ICI uploaded on YouTube. We aim to assess the quality and engagement parameters of the 100 most viewed videos on YouTube focusing on ICI. Methods: A systematic search was conducted on YouTube using the search terms (“Immunotherapy AND Cancer”; “Immune Checkpoint Inhibitors AND Cancer”). The 100 most viewed English videos were selected. We utilized the already validated PEMAT1 and DISCERN2 tools to assess the quality of these videos on ICI. Additionally, we looked at the number of views, comments, and likes. Descriptive statistics and Pearson correlation tests were performed using R studio v2022.12.0-353. Results: The videos in our study had up to 42 million views (median views: 17,617). These videos were categorized by sources; academic (54%), media (31%), and industry (15%). The mean DISCERN score for the videos was 43.4. Only 22% videos were in the good or excellent category. Most videos (53%) discussed the benefits of ICI, whereas only 29% discussed the adverse effects of ICI. Shared decision-making was promoted by 34% of videos, and only 6.7% of videos summarized the information at the end, based on the DISCERN criteria. The medical terminologies were defined by 48.5% of videos, and 31% were broken into short sections with informative headers per PEMAT understandability criteria. There was no significant association between the video source and video engagement parameters, including likes, views, and comments. However, a trend towards an increased number of likes (r=-0.195, p=0.04) and comments (r=-0.213, p=0.03) was noticed with lower DISCERN scores (poor quality videos). Conclusions: The majority of YouTube videos are focused on the benefits of ICI. They are less likely to discuss the adverse effects or shared decision-making . In summary, YouTube videos contain biased information on ICI. Further efforts from academic institutions are needed to improve the quality and engagement of these videos. 1. Shoemaker SJ et al. The Patient Education Materials Assessment Tool (PEMAT) and User’s Guide; 2. Charnock D et al. DISCERN: an instrument for judging the quality of written consumer health information on treatment choices. J Epidemiol Community Health. 1999. Pearson correlation coefficient (r) between quality assessment scores and video variables. [Table: see text]