bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of colposcopy for the screening and management of cervical cancer in Africa: A cross-sectional analysis of providers’ training and practices.
Authors: Fokom Domgue Joel , Dille Issimouha , Gnangnon Freddy Houéhanou Rodrigue , Kapambwe Sharon , Bouchard Céline , Mbatani Nomonde , Gauroy Elodie , Ambounda Ledaga Nathalie , Yu Robert K , Sidibe Fatoumata Matokoma , Kamgno Joseph , Tebeu Pierre-Marie , Halle-Ekane Gregory , Diomande Mohenou Isidore , Dangou Jean-Marie , Lecuru Fabrice , Adewole Isaac Folorunso , Plante Marie-Elaine , Basu Partha , Shete Sanjay 
Published: June 2024

10555 Background: Cervical cancer is a public health issue in Africa with devastating socioeconomic consequences due to the lack of organized screening programs. The success of screening programs depends on the appropriate investigation and management of women who test positive for screening. Colposcopic assessment following positive screening results is a critical issue in Africa. This study aimed to assess the utilization of colposcopy by providers in the region. Methods: A cross-sectional study was conducted in 2021-2022 among healthcare providers involved in cervical cancer prevention activities in Africa. They were invited to report prior colposcopy training, whether they performed colposcopy and the indications of colposcopy in their practice. Results: Of the 130 providers from 23 African countries who responded to the survey (mean age [SD]: 39.0 years [9.4]), half were female (65 [50.0%]), and 90.7% were working in urban areas. Overall, only 12.6% of respondents indicated having received prior training on colposcopy, and 11.7% reported that they were performing colposcopy in their current practice. Among the providers who reported performing colposcopy in their practice, colposcopy was indicated for routine visual screening in 21.2% of clinicians, to visualize the transformation zone in 15.2% of respondents, to assess vascularization of cervical mucosa in 33.3% of respondents, and to determine treatment modality in 12.1% of respondents. Conclusions: Providers’ training and utilization of colposcopy for cervical cancer screening remain suboptimal in Africa. To address this situation in the region, further training is needed to improve providers' knowledge and engagement. With the development of lower-cost and portable colposcopes, efforts to equip cervical cancer prevention programs and facilities with colposcopy should be enhanced to ensure that women can be screened and managed appropriately.
Patterns of cancer screening practice and mutational status of cancer-predisposing genes among individuals at high risk for cancer.
Authors: Freeman Jincong Q. , Manirakiza Achille Van Christ , Zhao Fangyuan , Keel Emma , Drogan Christine , Bradley Robin , Huo Dezheng , Olopade Olufunmilayo I. 
Published: June 2024

10557 Background: Research on cancer screening practice and prevention strategies among individuals at high risk for cancer is limited. We explored the patterns of screening practice of seven cancer types in high-risk patients (pts) at a single institution. Methods: Between June-September 2023, we conducted a follow-up survey on pts enrolled in the University of Chicago Cancer Prone Study, a longitudinal cohort of high-risk families initiated in 1992. We assessed breast, cervical, colorectal, prostate (PSA), ovarian, skin (full-body skin exam [FBSE]), and lung cancer screening by mutational status. Results: Of 912 respondents, 80.4% were female. 81.6% were White, followed by 10.6% Black, 4.0% other/multi-racial, and 3.8% Hispanic. Overall, 35.2% reported having cancer-predisposing gene mutations. Mutation carriers were younger than those non-carriers (54.8 [SD 13.7] vs 60.3 [SD 12.8] years). After adjusting for age, carriers were more likely than non-carriers to have had breast MRI ( p<.001), colorectal cancer screening ( p=.039), ovarian cancer screening ( p=.043), and an FBSE ( p=.007) (Table). No statistically significant differences in mammogram (OR=1.50, 95% CI=0.55-2.30; p=.13), cervical cancer (OR=0.92, 95% CI=0.54-1.59; p=.77), PSA (OR=0.70, 95% CI: 0.26-1.88; p=.48), or lung cancer (OR=1.18, 95% CI=0.72-1.92; p=.51) screening between carriers and non-carriers. By race/ethnicity, cervical cancer screening (Hispanic 92%, White 90.6%, other/multiracial 80.7% and Black 76%; p=.002) and colorectal cancer screening (White 83.3%, other/multiracial 71.8%, Black 71.4% and Hispanic 66.6%; p=.004) differed significantly. Conclusions: In this diverse cohort of individuals at high risk for cancer, findings highlight an increased awareness and uptake of cancer screening, though varying by race/ethnicity. Cancer risk assessment clinics can be great avenues to provide comprehensive cancer screening and prevention strategies while addressing racial/ethnic screening disparities. [Table: see text]
Germline variation and risk of immune-related adverse events (irAEs): A real-world BioVU study.
Authors: Balko Justin M. , Yao Lydia , Zhang Siwei , Fahey Catherine , Haugh Alexandra , Davis Andrea , Mukherjee Eric , Hammer Christian , Phillips Elizabeth J , Bejan Cosmin A , Xu Yaomin , Johnson Douglas Buckner 
Published: June 2024

10582 Background: IrAEs are prevalent in patients treated with immune checkpoint inhibitors (ICI) and mimic classical autoimmune diseases. IrAE risk prediction could improve clinical decision making and patient safety for ICI-treated patients. Classical autoimmune diseases show strong associations with germline polymorphisms and with Human Leukocyte Antigen (HLA) variants, though it is unclear if these same genetic risk factors predispose to irAEs. To identify both tolerant and irAE patients, we mined Vanderbilt University Medical Center (VUMC) BioVU, a biorepository of >300K DNA samples linked to de-identified medical records and evaluated genome-wide and imputed HLA class I and II associations with irAE risk. Methods: We identified 1,472 ICI-treated BioVU subjects: 428 with ≥ 1 irAE, and 1044 with no irAEs ≤ 6 months from last ICI treatment. Genotyping was performed by Illumina MEGAEX array. Records were screened for use of irAE therapies ( e.g. systemic corticosteroids, infliximab, levothyroxine) after ICI treatment, with chart adjudication. Association tests were performed using Firth’s logistic regression adjusting for age, sex, ICI regimen, and 3 principal components to assess 1) HLA Class I and II alleles; 2) HLA evolutionary divergence; and 3) GWAS to evaluate total irAEs, organ-specific irAEs, or other specific irAEs (sample size permitting). Endocrine irAEs were excluded to be presented in a separate focused study. Results: In GWAS analyses, 53 SNPs and 23 SNPs were identified significantly (nominal p ≤ 5e-8) associated with GI and neuro-toxicity, respectively. We did not identify any significant HLA class I or II associations with irAE or organ-grouped irAEs, including most evolutionary divergence association tests. We noted marginal association (FDR=0.12, OR=6.85) of rheumatic irAEs with HLA-DRB1*10:01, an HLA class II allele with RA-specific epitope motif. Patients experiencing lung irAEs were more likely to have a high HLA class I and II evolutionary divergence sum (p = 0.013 and p=0.046, respectively). Assessment of associations with specific irAEs, validation of known associations with irAEs or autoimmune disorders, including polygenic risk scores, are underway. Conclusions: We had several SNP-irAE associations, though appropriate classification schemas to maximize power and detect genetic variation remain challenging. We will soon expand with 1,800 additional ICI-treated patients (n=~3,300 in toto), creating a robust resource for irAE genetic associations. [Table: see text]
Risk of secondary leukemias in patients with germline PALB2 pathogenic variants after chemotherapy exposure.
Authors: Ellaithy Hatem , Bear Lauren , Steinberg Kathleen , Micalizzi Douglas Scott , Brunner Andrew Mark , Saini Arushi 
Published: June 2024

10598 Background: Pathogenic variants in germline cancer-predisposing genes (e.g. BRCA1/2, PALB2) confer an increased risk for solid tumors but not de novomyeloid malignancies. Many of these genes are related to DNA repair pathways. It is not known whether exposure to genotoxic therapy increases the risk of secondary hematologic malignancies. Here, we report the incidence of hematologic malignancy after a solid tumor diagnosis among patients with a germline PALB2 pathogenic variant. Methods: Patients were identified at the Massachusetts General Hospital Center for Cancer Risk Assessment among individuals seeking counseling and/or testing for hereditary cancer risk genes. Analyses were conducted using R version 4.2.2 “tidyverse” and “gtsummary” packages. Results: Of the 176 charts reviewed, 102 (57%) had a history of malignancy, of which 68 (66%) received genotoxic chemotherapy. The median follow-up after chemotherapy was 59mo (IQR =17,109). The most common malignancy and chemotherapy were breast cancer (n=76, 75%) and doxorubicin, cyclophosphamide, and paclitaxel (n = 21, 31%). We compared patient outcomes by receipt of chemotherapy or not. There was no difference in race, age at cancer diagnosis, surgery rate, treatment with hormone therapy, or secondary malignancy between the two groups (p > 0.05). There was higher incidence of radiation treatment in those receiving genotoxic therapy compared to those who did not (65% vs 41%, p = 0.024), but no difference Gray or in follow up after radiation. Mortality in the genotoxic therapy group was 15% (n=10) vs. 9% (n=2) in the no genotoxic therapy group (p =0.33). Two subjects developed a hematologic malignancy (one case each of CLL and CML); both had prior chemotherapy and radiation exposure (Table). Conclusions: Cancer survivors with a germline PALB2 pathogenic variant and subsequent exposure to genotoxic therapy appear to have low risk of secondary hematologic malignancy. Although two subjects in the chemotherapy group developed leukemias, given the cases seen it is unlikely that these relate to the treatment exposure. Given the small sample size and retrospective nature of this study, more investigation is necessary to fully quantify the risk of therapy-related myeloid neoplasm in patients with germline PALB2 pathogenic variants. [Table: see text]
Pathogenic germline variant discovery in plasma cell disorders: Insights from genetic counseling referrals and testing.
Authors: Bodnar Saoirse , Brander Tehilla , Balwani Manisha M , Jagannath Sundar , Parekh Samir , Thibaud Santiago 
Published: June 2024

10619 Background: Our research has shown that 10% of multiple myeloma (MM) patients harbor pathogenic or likely-pathogenic germline variants (PGVs) in cancer predisposition genes, with a significant enrichment observed in BRCA1/2 genes. PGVs are notably more common in younger MM patients and those with a personal or familial cancer history. This study presents our experience in referring plasma cell disorder (PCD) patients at increased risk for carrying PGVs, due to either clinical history or suspicious tumor NGS findings, for genetic counseling and subsequent germline testing. Methods: This retrospective study reviewed patient records from our institution's PCD clinic, focusing on those referred for a genetic evaluation between 2020 and 2024 due to suspected cancer predisposition. We compiled demographic and clinical data for these patients, reasons for referral, and cancer history of patients and their families. The uptake of germline testing, identified mutations, and subsequent recommendations for advanced cancer surveillance and prevention, including cascade testing, were also analyzed. Germline testing utilized targeted hereditary cancer panels from five companies and was conducted on DNA samples extracted from peripheral blood, saliva/buccal swabs, or skin biopsies. Results: 52 PCD patients underwent a genetic evaluation and were included in this review, comprising 31 MM, 9 smoldering MM, and 12 MGUS cases. Median age at the time of referral was 63, and 54% of patients were female. Racial composition was 62% White, 15% Black/African-American, 12% Hispanic, 2% Asian, with 10% undisclosed. 8 patients were referred due to suspicious findings in tumor NGS, while the rest were referred due to clinical suspicion. A personal history of cancer was reported by 19 patients (37%), and 49 had a first- or second-degree relative with cancer (94%). 38 patients (73%) underwent germline testing, of which 15 (39%) harbored PGVs (11 had MM, 4 had smoldering MM). 8 PGV carriers had well-established founder variants. The remaining 7 had PGVs in genes including BRCA2 (n=3), PALB2 (n=1), BLM (n=1), SMAD4 (n=1) and NTHL1 (n=1). Of note, all 8 referred for suspicious findings in tumor NGS were confirmed to harbor PGVs. All PGV-positive patients were recommended for cascade testing and enhanced cancer screening. Conclusions: Our findings indicate a 39% PGV detection rate in PCD patients referred for genetic evaluation, underscoring the potential benefit of implementing screening guidelines in this population. PGV detection led to recommendations for intensified surveillance and cascade testing in all cases, impacting both patients and their families. The discovery of BRCA2PGVs in 20% (3/15) of cases reinforces its potential role as a predisposition gene in MM, corroborating our prior findings.
The science of getting published: Key factors influencing publication in pediatric oncology.
Authors: Hovsepyan Shushan , Bedirian Karen , Papyan Ruzanna , Hoveyan Julieta , Sargsyan Amalya , Baloyan Elen , Bardakhchyan Samvel , Tamamyan Gevorg 
Published: June 2024

11024 Background: Childhood cancer is rare, with an annual global incidence of 400,000 cases. Research articles play a crucial role in disseminating significant advancements in this rare field; however, it often experiences delays. We investigated the key factors influencing the transition from abstracts presented at the American Society of Clinical Oncology (ASCO) Annual Meetings to publication of articles in the pediatric oncology field. Methods: We analyzed oral (OA), poster (PA), and publication-only abstracts (PO) presented during pediatric oncology sessions at ASCO Annual Meetings from 2017 to 2023. We cross-referenced abstract titles and authors with PubMed-indexed journals. Each predictor was assessed for its correlation with the publication status using the chi-square test. Additionally, logistic regression was performed to understand the influence of each predictor while controlling for other variables. Results: A total of 521 abstracts were identified. Among these, 93 were OA, 270 were PA, and 158 were PO. Of these, 67%, 60%, and 32% were eventually published, respectively. The mean time to publication was 21.3 months for OA, 17.15 months for PA, and 23.4 months for PO. Female authors comprised 56% of the first authors. Funding was provided for 96% of OA, 87.7% of PA, and 63% of PO. Only 7% of all abstracts were from low-middle-income countries (LMICs). A significant correlation was found between the likelihood of publication and the income level of the authors' country of affiliation (p<0.0001), the number of authors (p=0.001), presentation type (p<0.0001), availability of funding (p<0.0001), and the number of institutions involved (p=0.0001). The gender of the first author was not a significant predictor of publication (p=0.46). However, according to the logistic regression model, only the availability of funding and presentation type had a significant impact on the likelihood of publication (p<0.05), while the other variables were found to be insignificant. Conclusions: Our study underscores the critical role of funding as a driver in the publication process. Researchers from LMICs are less likely to publish, likely due to a lack of funding. Furthermore, we observed a delay in publication, with an average time exceeding a year and a half. These findings emphasize the importance of equitable funding access and enhanced publication processes to improve research dissemination.
Current diagnostic guidelines and perpetuation of inequities in ovarian cancer: A National Cancer Database study.
Authors: Smith Anna Jo Bodurtha , Gleason Emily , Kadiyala Sneha , Wang Xingmei , Howell Elizabeth A , McCarthy Anne Marie 
Published: June 2024

11027 Background: International guidelines use cancer antigen 125 (CA-125) thresholds to recommend which patients with pelvic masses should undergo evaluation by gynecologic oncologists for ovarian cancer and which patients can be observed without intervention. However, CA-125 thresholds were developed from white populations, and CA-125 levels have been shown to be 10-29% lower in healthy Black women than white women. If CA-125 levels also differ among patients with cancer, current guidelines may contribute to missed or delayed ovarian cancer diagnoses among Black women. Our objective was to examine CA-125 levels at cancer diagnosis by patient race and associations of CA-125 elevation with timely treatment. Methods: We conducted a retrospective cohort study of patients with ovarian cancer ages 0 to 90+ years diagnosed from 2018-2020 using the National Cancer Database. CA-125 was defined as positive/borderline or negative/normal by each site. We report descriptive CA-125 elevated by patient characteristics. We use multivariate logistic regression models to examine the association of patient characteristics with CA-125 level overall and for epithelial and high-grade serous cancers. We used generalized linearized models to examine the association of CA-125 with days from diagnosis to chemotherapy start for patients with Stage II-IV disease. Results: Of 38,707 patients diagnosed with ovarian cancer and with reported CA-125, 13.4% of patients did not have an elevated CA-125 at diagnosis. Patients who identified as Black, Asian, or Hispanic were less likely to have an elevated CA-125 at ovarian cancer diagnosis as were patients with early-stage disease. Among patients with high-grade serous cancer (n=18,151), 8% of Black patients had normal CA-125 at diagnosis compared to 6% of white patients. In multivariate analyses, being Black remained associated with lower odds of elevated CA-125 (OR 0.71, 95%CI 0.63-0.81), after adjustment for menopausal status, comorbidities, and stage. Even among patients with high-grade serous ovarian cancer, being black was associated with lower odds of having an elevated CA-125 (OR 0.78, 95%CI 0.64-0.96). Patients with Stage II-IV ovarian cancer who had a normal CA-125 at diagnosis had 12 days longer on average to chemotherapy initiation compared to patients with elevated CA-125. Conclusions: Current thresholds for CA-125 and gynecologic oncology referral likely miss Black patients with ovarian cancer and may delay timely treatment. Work is needed to develop inclusive CA-125 thresholds and guidelines for ovarian cancer diagnosis and not compound disparities.
Examining 1-year mortality risk among patients with malignant melanoma undergoing immune checkpoint inhibitor therapy with a history of cannabis use.
Authors: Waris Imtisaal , Raiker Rahul , Siva Nanda , Goswami Sanya , Pakhchanian Haig , Kamran Amir Shahzad 
Published: June 2024

11046 Background: Cannabis use has become an increased topic of discussion in the United States due to rise in legalization, thereby increasing its accessibility for recreational and medicinal use in diseases like cancer. Immune Checkpoint Inhibitor (ICI) therapy has also recently been increasing in patient with metastatic cancers such as melanoma by targeting PD1 or PD-L1 receptors to manipulate the body’s immune response to induce cancer cell death. Cannabis is mediated in part by the CB1 and CB2 receptors in the endocannabinoid system that is present in the natural immune system. Due to the body’s immune response to cannabis, it is hypothesized this could interfere with the activity of ICI therapy. However, research examining this is sparse. Therefore, the goal was to assess mortality in malignant melanoma patients with a history of cannabis use who undergo ICI therapy. Methods: A retrospective cohort study was performed with TriNetX, a federated database of ~100 million patients across 84 healthcare organizations. Patients >17 years from 2012-2023 were identified based on ICI-therapy initiation within 1 month of malignant melanoma diagnosis. Cohorts were then created by history of those with and without cannabis use disorder. 1:1 propensity score matching was conducted to control for confounding comorbidities and demographics. Unadjusted and adjusted hazard ratios (aHR) with 95% CI were calculated for 1-year mortality after therapy initiation. HR’s were estimated using the Cox proportional hazard model. Survival curves were compared using the log-rank test. Results: A total 14589 melanoma patients who underwent ICI therapy were identified, of which 2.3% had documented cannabis use disorder. Prior to matching, melanoma patients with cannabis history had a statistically significant higher 1-year mortality compared to those with no cannabis history (HR [95%CI] = 1.29 [1.04,1.6], log rank test: p=0.0197). After matching, two balanced cohorts of 344 patients remained and adjusting for confounders revealed that melanoma patients with cannabis history had no significant difference in 1-year mortality risk compared to patients without cannabis history (1.18 [0.87,1.6], log rank test: p=0.293). Conclusions: Cannabis use among melanoma patients was shown to not have any meaningful difference in 1-year mortality risk compared to patients without cannabis use history while undergoing ICI-therapy. Additional studies, such as examining cannabis frequency and dosage, is warranted to further examine its effect.