bluuebunny/crossref_metadata_2025 huggingface dataset:
Constitutional BRCA1 methylation and risk of incident triple-negative breast cancer and high-grade serous ovarian cancer.
Authors: Lonning Per Eystein , Nikolaienko Oleksii , Pan Kathy , Kurian Allison W. , Eikesdal Hans Petter Petter , Pettinger Mary , Anderson Garnet L , Prentice Ross L , Chlebowski Rowan T. , Knappskog Stian
Published: June 2022

10509

Background: About 25% of all triple-negative breast cancer (TNBC) and 10–20% of high-grade serous ovarian cancers (HGSOC) harbor BRCA1 promoter methylation. While constitutional BRCA1 promoter methylation has been observed in normal tissues of some individuals, the potential role of normal tissue methylation as a risk factor for incident TNBC or HGSOC risk is unknown. Methods: The objective of this study was to assess potential correlation between white blood cell (WBC) BRCA1 promoter methylation and subsequent risk of incident TNBC and HGSOC. To do so, we analyzed samples from women participating in the Women’s Health Initiative (WHI) study who had not been diagnosed with either breast or ovarian cancer prior to study entrance. A total of n = 636 women developing incident TNBC and 509 women developing incident HGSOC were matched with cancer-free controls (n = 1838 and 2979) in a nested case-control design. Cancers were confirmed after central medical record review. Blood samples, collected at entry, were analyzed for BRCA1 promoter methylation by massive parallel sequencing. Associations between BRCA1 methylation and incident TNBC and incident HGSOC were analyzed by unconditional logistic regression. Results: Age at entry was 62 (median; range 50 to 79) years, with median interval to diagnosis of 9 (TNBC) and 10 (HGSOC) years. The presence of methylated BRCA1 alleles was significantly associated with higher risk of incident TNBC (OR 2.44, 95% CI 1.79–3.33; P <.001) and incident HGSOC (OR 1.87, 95% CI 1.32–2.61; P <.001). Restricting analyses to individuals with > 5 years between sampling and cancer diagnosis yielded similar results (> 5 years; TNBC: OR 2.53, 95% CI 1.81–3.54; P <.001; HGSOC: OR 1.81, 95% CI 1.21–2.63; P =.003). Across individuals, methylation was not haplotype-specific, arguing against an underlying cis-acting factor. Within individuals, BRCA1 methylation was observed on the same allele, indicating clonal expansion from a single methylation event. Conclusions: Constitutional normal tissue BRCA1 promoter methylation is significantly associated with risk of incident TNBC and HGSOC with implications for prediction of these cancers not associated with germline mutations. These findings warrant further research to determine if constitutional methylation of tumor suppressor genes are pan-cancer risk factors.
Characterization of time to diagnosis indicates shorter interval for screenable versus symptom-driven cancers.
Authors: Gainullin Vladimir , Tong Jing , Li Yali , Gupta Mudit , Lagerman Braxton , Blank Jackie , Limburg Paul J. , Hathaway Christine
Published: June 2022

10526

Background: Cancer screening provides a straightforward diagnostic path compared to non-screening, which often requires complex evaluation for patients with non-specific symptoms. The time to diagnosis (from clinical presentation or screening event to definitive diagnosis) captures the clinical efficiency of the journey. The study characterizes time to diagnosis for cancers with and without USPSTF Grade A/B screening recommendations. This could inform the value of screening in diagnostic management and care efficiency improvements. Methods: The Geisinger Health System Phenomics Initiative Database provides deidentified EHR and tumor registry data. Patients aged 50-74 with encounters at least biennially for six years prior to a cancer diagnosis were frequency-matched to a non-cancer control group by diagnosis year. From 18 months prior to diagnosis, equally-sized random samples were drawn (with replacement) from a time-bounded sliding window at monthly intervals. Aggregated procedure and diagnostic code counts for cancer and non-cancer samples were used to calculate the Bray-Curtis dissimilarity (BCd) statistic. The start of the diagnostic path was defined as the earliest date with a monotonically-increasing statistically-significant difference in BCd (95% CI), and was stratified into cancers with and without screening and by stage. Results: 8188 new cancer cases were identified between 2010-2019; 40% had an established screening modality (breast, lung, colorectal, cervical), 55% of which were screened prior to diagnosis. The time to diagnosis for non-screenable cancers was 6 months versus 3 months for screenable cancers. The BCd for procedures differed by 0.029 (95% CI: 0.021-0.037) between the two groups at 6 months prior to diagnosis. Stages I and IV had a time to diagnosis of 3 months across all cancers versus 7 and 6 months for stages II and III, respectively. Conclusions: We report the first known quantification of time to diagnosis across multiple cancers. Screenable cancers were associated with shorter time to diagnosis than non-screenable cancers. Stage II and III cancers took longer to diagnose than stage I and IV, likely related to early detection by screening in the former and severe symptom presentation in the latter. These novel data highlight improved time to diagnosis as another achievable benefit from expanded, multi-cancer screening.
Robust artificial intelligence-powered imaging biomarker based on mammography for risk prediction of breast cancer.
Authors: Park Eun Kyung , Lee Hyeonsoo , Kim Minjeong , Kim Ki Hwan , Nam Hyeonseob , Chang Yoosoo , Ryu Seungho
Published: June 2022

10533

Background: Accurate risk assessment allows the precise personalized screening of breast cancer. Conventional statistical risk models have been used that estimate the probability of breast cancer incidence with patient demographics, detailed personal and family history. The purpose of this study was to investigate the feasibility of the AI-powered Imaging Biomarker in mammography (IBM) which was developed to predict the risk of future breast cancer beyond the mammographic breast density. Methods: We trained and developed the deep learning risk model, the AI-powered IBM, using a total of 36,955 examinations from 21,438 patients, who underwent at least one mammogram using Hologic or Siemens machines and pathology-confirmed breast cancer outcomes. To discover the feasibility of the AI-powered IBM, mammograms and various clinical information including pathology-confirmed breast cancer outcomes were collected, which were only used for external validation. C-indices and receiver operating characteristic (ROC) curves for 1- to 5-year outcomes were obtained. We compared 5-year ROC area under the curves (AUCs) of our AI-powered IBM and statistical risk models including the Tyrer-Cuzick model and the Gail model, which were most commonly used and widely known, using DeLong’s test. Results: A total of 16,894 mammograms were collected for external validation, of which 4,002 were followed by a cancer diagnosis within 5 years. Our AI-powered IBM obtained C-index of 0.758, and the model demonstrated the risk of breast cancer with AUC of 0.895 (95% CI: 0.880, 0.909) at 1-year, 0.839 (0.824, 0.852) at 2-year, 0.807 (0.794, 0.819) at 3-year, 0.783 (0.7947, 0.819) at 4-year. The 5-year AUC of our AI-powered IBM was 0.808 (0.792, 0.822). Our AI-powered IBM showed significantly higher 5-year AUC than the Gail model (AUC: 0.572, P< 0.001) and the Tyrer-Cuzick model (0.569, P< 0.001). Conclusions: A deep learning AI-powered IBM using mammograms has a substantial potential to advance toward the robust risk prediction of breast cancer over conventional risk models. This approach for risk stratification of breast cancer might be feasible to improve personalized screening programs.
The role of health information technology in improving awareness of HPV and HPV vaccine among U.S. adults: Insights from the health information national trends survey.
Authors: Dosunmu Gideon T , Onyeaka Henry , Kyeremeh Emmanuel , Jalwa Mohammed , Onaku Emmanuella , Ofori Jillian , Amonoo Hermioni L. , Ashfaq Muhammmad Areeb , Khushman Moh'd M.
Published: June 2022

10535

Background: Despite advances in cancer prevention and wide-spread availability of Human papilloma virus (HPV) vaccines, US adults continue to have suboptimal HPV vaccination uptake with less than 50% vaccinated. Strategies aimed at enhancing HPV-related awareness are considered one of the most effective ways to improve HPV vaccine adoption and potentially eliminate HPV-related cancers. Health information technology (HIT) may influence HPV-related awareness and subsequently drive vaccine adoption. This study assessed the impact of HIT utilization on HPV and HPV vaccine awareness. Methods: Data was obtained from Health Information National Trends Survey (HINTS 5 cycles 1 and 2). Cross-sectional sample of 6,522 individuals aged 18 years or more was analyzed. The independent variables were use of smartphone, computer, or electronic means to (i) look up health information, (ii) fill a prescription online, (iii) communicate with a doctor or doctor’s office, (iv) look up test results of and (v) track health care charges. The dependent variables were HPV and HPV vaccine awareness. Chi-square analysis was used to evaluate group differences, and a multiple logistic regression was used to analyze the association between HIT utilization and HPV-related awareness controlling for sociodemographic and health-related factors. Results: Of the total sample, awareness of HPV and HPV vaccine was 62.7% and 61.8% respectively. In adjusted multivariable logistic regression analysis, those who utilized a smartphone, computer, or electronic means to look up health information (aOR 2.23; 95% CI 1.68 – 2.97, p < 0.001), communicate with healthcare provider (aOR 1.53; 95% CI 1.23 – 1.91, p < 0.001), look up test results (aOR 1.67; 95% CI 1.35 – 2.08, p < 0.001), and track health care charges (aOR 1.61; 95% CI 1.26 – 2.05, p < 0.001), were more likely to endorse HPV awareness than those who did not. Similar positive associations were observed for HIT utilization and HPV vaccine awareness. Conclusions: Our findings showed a positive association between HIT utilization and HPV-related awareness. Amid a background of sub-optimal HPV vaccination and explosion in technology, these results emphasize the potential for the role of HIT in preventive medicine. Strategies that integrate HIT into vaccine interventions and communications should be encouraged as a medium to expand HPV awareness and vaccine coverage.
Cross-ancestry polygenic risk score for breast cancer risk assessment.
Authors: Tshiaba Placede , Sun Jiayi , Ratman Dariusz , Tunstall Tate , Levy Brynn , Shah Premal , Rabinowitz Matthew , Kumar Akash , Im Kate
Published: June 2022

10540

Background: Breast cancer (BC) risk is influenced by many common variants with small effects. Polygenic risk scores (PRS) weight these variants based on genome-wide association studies (GWAS) and aggregate them into a single measure. PRS has primarily shown benefit in Caucasian women. We established a cross-ancestry polygenic model (caPRS) which assesses risk of breast cancer across multiple ancestries. Methods: Performance of multiple BC polygenic models, both published and developed in-house, were evaluated for each of five ancestry groups: European, African, South Asian, East Asian, and Admixed American. To account for ancestry-specific mean and variance, we computed principal components (PCs) for all women by projecting their genotypes onto PCs calculated on individuals in the 1000 Genomes Project (1KGP). We next centered each ancestry-specific PRS by subtracting the PRS predicted from a linear regression of PRS against the first four PCs in unaffected individuals. Each centered PRS was then divided by the SD of the corresponding 1KGP population. We defined a cross-ancestry polygenic model as a linear combination of the best performing PRS model for each ancestry group weighted by fractional ancestry. Association of the caPRS with breast cancer risk was tested in a validation cohort of >130,000 women consisting of multiple independent cohorts (the Women’s Health Initiative, the Multiethnic Cohort, the ROOT cohort and the UK Biobank) using a multivariate logistic regression model that included caPRS, age, self-reported ancestry, personal history of ovarian cancer (when available) and first-degree family history of BC. Discrimination was assessed by the odds ratio (OR) per SD and the area under the receiver-operator curve (AUC). Results: This study included women with African/Black, East Asian, Caucasian/White, Hispanic/Latino, South Asian and ‘Other’ self-reported ancestry. The ancestry-specific models included in the caPRS ranged in size from 173 to >800,000 variants. The caPRS was associated with BC risk for women in each self-reported ancestry (Table). The caPRS offered a modest increase in performance over a commonly implemented 313-SNP PRS in non-European ancestries, most significantly in African/Black women where the OR per SD increased from 1.24 (1.08 - 1.43), p-value 2.3x10-3. Conclusions: The caPRS performed well for women of any ancestry and allows flexibility to update ancestry-specific models. These results suggest the caPRS has the potential to improve the clinical utility of existing clinical risk predictors. [Table: see text]
Predictors of use of prevention strategies among women at high-risk for breast cancer.
Authors: Landry Kara , Tuo Ya , Levine Emma , Srikureja Anya , Wood Marie
Published: June 2022

10554

Background: Uptake of chemoprevention and prophylactic surgery among women at high risk for breast cancer is low, despite proven efficacy. We evaluated breast cancer risk factors as predictors of uptake of prevention treatment (PT) to better understand potential associations with these decisions. Methods: An IRB approved registry established in 2003 at the University of Vermont of high-risk women was used to evaluate the association between both modifiable (obesity, sedentary lifestyle and alcohol use) and non-modifiable (age, history of benign breast disease [BDD], genetic predisposition) risk factors and uptake of PT. Women were eligible for inclusion in this analysis if they had one of the following risk factors (BDD, strong family history, > 20% lifetime modeled risk or genetic predisposition) and completed questionnaires regarding diet and physical activity. Alcohol use was assessed using a health questionnaire and physical activity was assessed using a 7-Day Physical Activity Recall questionnaire. We used logistic regression to estimate odds ratios (OR). Results: 504 women were included and had been followed for median of 13 years. Mean age was 44.5 years (range 19 – 75), 98% were Caucasian, and mean BMI was 26.9 (range 17-57). 78% had a family history of breast cancer, 60% had >20% lifetime modeled risk, 14% had a history of benign breast disease (BBD), and 9% of women had confirmed genetic risk in high or moderate risk genes. Women may have had more than one risk factor. 55% were physically active and 55%. 4.2% were sedentary and 12.3% consumed > 1 alcoholic beverage daily. 20.8% of the cohort participated in PT (8.1% took chemoprevention, 2.0% underwent prophylactic bilateral total mastectomy and 10.7% underwent risk reducing salpingo-oophorectomy). Among non-modifiable risk factors, age, genetic predisposition (ORadj 8.66, 95% CI 2.30–32.33, p < 0.0001), and history of benign breast disease (ORadj 4.09, 95% CI 1.89–8.86, p < 0.001) were associated with uptake of PT. Increasing age was associated with increasing uptake (ptrend was > 0.0001) and highest among women aged 60-69 years (ORadj8.19, 95% CI 2.87-23.37 relative to women aged < 40). Women with a strong family history were significantly less likely to take up PT (p = 0.04). BMI, physical activity status and alcohol use were not associated with uptake of PT. Conclusions: Like other studies, we found a low uptake of PT among women at high risk for developing breast cancer. We found that modifiable risk factors were not associated with uptake of PT, which might suggest that high-risk women with modifiable risk factors could be targeted for interventions designed to modify risk (i.e. chemoprevention, weight reduction, etc). Interestingly, women with a strong family history may be less likely to take up PT, and studies to further examine this relationship may identify opportunities for interventions to improve uptake.
An update on the overall epidemiology, clinical characteristics, and outcomes from the COVID-19 and Cancer Consortium (CCC19).
Authors: Shah Dimpy P , Shah Pankil , Warner Jeremy Lyle , Batist Gerald , Friese Christopher Ryan , Griffiths Elizabeth A. , Hwang Clara , Vieira Kendra , McKay Rana R. , Mesa Ruben A. , Puc Matthew , Robilotti Elizabeth M , Ruiz-Garcia Erika , Portuguese Andrew Jay , Schmidt Andrew Lachlan , Weissmann Lisa B. , Wise-Draper Trisha Michel , Barnholtz-Sloan Jill , Peters Solange , Grivas Petros ,   COVID-19 and Cancer Consortium
Published: June 2022

10565

Background: Despite mitigation and treatment strategies, COVID-19 continues to negatively impact patients (pts) with cancer. Identifying factors that remain consistently associated with morbidity and mortality is critical for risk identification and care delivery. Methods: Using CCC19 registry data through 12/31/2021 we report clinical outcomes (30-day case fatality rate [CFR], mechanical ventilation use (MV), intensive care unit admission (ICU), and hospitalization) in adult pts with cancer and laboratory confirmed SARS-CoV-2, stratified by patient, cancer, and treatment-related factors. Results: In this cohort of 11,417 pts (with 4% reported vaccination prior to COVID-19), 55% required hospitalization, 15% ICU, 9% MV, and 12% died. Overall outcome rates remained similar for 2020 and 2021 (Table). Hydroxychloroquine was utilized in 11% and other anti-COVID-19 drugs (remdesivir, tocilizumab, convalescent plasma, and/or steroids) in 30%. Higher CFRs were observed in older age, males, Black race, smoking (14%), comorbidities (pulmonary [17%], diabetes mellitus [16%], cardiovascular [19%], renal [21%]), ECOG performance status 2+ (31%), co-infection (25%), especially fungal (35%), and initial presentation with severe COVID-19 (48%). Pts with hematologic malignancy, active/progressing cancer status, or receiving systemic anti-cancer therapy within 1-3 months prior to COVID-19 also had worse CFRs. CFRs were similar across anti-cancer modalities. Other outcomes (ICU, MV, hospitalization) followed similar distributions by pt characteristics. Conclusions: Unfavorable outcome rates continue to remain high over 2 years, despite fewer case reports in 2021 owing to multiple factors (e.g., pandemic dynamics, respondent fatigue, overwhelmed healthcare systems). Pts with specific socio-demographics, performance status, comorbidities, type and status of cancer, immunosuppressive therapies, and COVID-19 severity at presentation experienced worse COVID-19 severity; and these factors should be further examined through multivariable modeling. Understanding epidemiological features, patient and cancer-related factors, and impact of anti-COVID-19 interventions can help inform risk stratification and interpretation of results from clinical trials. [Table: see text]
Genetic ancestry correlates of the cancer somatic mutational landscape from tumor profiling data of 50,000 patients with cancer.
Authors: De La Vega Francisco , Rhead Brooke , Pouliot Yannick , Guinney Justin
Published: June 2022

10573

Background: The incidence and mortality of cancer vary widely across race and ethnicity. This is attributed to an interplay of socioeconomic factors, environmental exposures, and genetic background. Cancer genomic studies have underrepresented minorities and individuals of non-European descent, thus limiting a comprehensive understanding of disparities in the diagnosis, prognosis, and treatment of cancer among these populations. Furthermore, the social constructs of race and ethnicity are far from precise categories to understand the biological underpinnings of such differences. In this study, we use a large real-world data (RWD) patient cohort to examine associations of genetic ancestry with somatic alterations in known cancer driver genes. Methods: We inferred genetic ancestry from approximately 50,000 de-identified records from cancer patients of diverse histology who underwent tumor genomic profiling with the Tempus xT next-generation sequencing (NGS) assay. Our cohort includes patients with brain, breast, colorectal, hematopoietic, lung, and ovarian cancers, among others. We used 654 ancestry informative markers selected to overlap the target regions of the 648-gene Tempus xT NGS assay to infer global ancestry proportions at the continental level: Africa (AFR), America (AMR), Europe (EUR), East Asia (EAS), and South Asia (SAS). We imputed race/ethnicity categories using ancestry proportions on subjects lacking such metadata. Results: Most patients were of European descent (72%), however, continental genetic ancestry inference identified 4.7 and 3.8-fold more patients with substantial (> 50%) AFR and AMR ancestry, correspondingly, compared with TCGA. We observed higher percentages of AFR ancestry patients with prostate, breast, and colorectal cancer (1.8-3.1%) and AMR ancestry patients with colorectal cancer (2.4%) compared to the overall cohort-level distributions (p < 0.05). Using imputation, we identified 60% and 121% more patients as likely Black and Hispanic/Latino, respectively. We observed several associations between genetic ancestry with tumor mutation burden (TMB), e.g., a reduction in median TMB in Asian breast cancer patients (Asian TMB mean = 2.3 m/Mb vs 4.4 for Black, 3.3 for Hispanic, and 4.2 for White; p < 0.0001), in paired tumor/normal sequencing data. Furthermore, we found associations between ancestry and nonsynonymous somatic mutations in cancer genes, e.g. in CTNNB1 with EAS ancestry (OR = 1.18) and EGFR with EAS (OR = 1.24), AMR (OR = 1.30), and EUR (OR = 0.89) ancestries (all p < 0.001) in lung cancer patients. Conclusions: Our results support the use of genetic ancestry inference on RWD to improve upon the social constructs of race and ethnicity, allowing us to better understand the impact of shared germline genetic or exposure backgrounds into cancer mutational processes that influence incidence, progression, and outcomes.
Scenery of multilocus inherited neoplasia alleles syndrome (MINAS) in a single Brazilian institution.
Authors: Murad Andre Marcio , Casali-da-Rocha José Claudio , Carneiro Juliana Garcia
Published: June 2022

10598

Background: Genetic testing of hereditary cancer using comprehensive gene panels can identify patients with more than one pathogenic mutation in high and/or moderate-risk-associated cancer genes. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS), which has been potentially linked to more severe clinical manifestations.To determine the prevalence and clinical features of MINAS in a large cohort of adult patients with hereditary cancer homogeneously tested with the same gene panel. Methods: A cohort of 1,234 unrelated patients with suspicion of hereditary cancer was screened using a validated NGS panel including 20 genes associated with hereditary cancer. Results: One hundred and forty two (8.7%) patients harbouring probably pathogenic or pathogenic mutatations and 9 harbouring two pathogenic mutations in dominant cancer-predisposing genes were identified, representing 6.3% (9/142) of patients with pathogenic mutations. All (9/9) of these cases presented clinical manifestations associated with only one of the mutations identified. One case showed mutations in MEN1 and MLH1 and developed tumours associated with both cancer syndromes. Interestingly, three of the double mutants had a young age of onset or severe breast cancer phenotype and carried mutations in moderate to low-risk DNA damage repair-associated genes; two of them presented biallelic inactivation of CHEK2. We included these two patients for the sake of their clinical interest although we are aware that they do not exactly fulfil the definition of MINAS since both mutations are in the same gene. Conclusions: Genetic analysis of a broad cancer gene panel identified the largest series of patients with MINAS described in a single study. Overall, our data do not support the existence of more severe manifestations in double mutants at the time of diagnosis although they do confirm previous evidence of severe phenotype in biallelic CHEK2 and other DNA repair cancer-predisposing genes.
Hereditary cancer screening at an urban safety net hospital.
Authors: Brehany Sydney , Colton Meryl D. , Duarte Cassandra , Baliton Michael , Okuyama Sasaki Sonia
Published: June 2022

10604

Background: Individuals with hereditary cancer syndromes (HCS) have a high lifetime risk of developing cancer. However, the rate at which at-risk individuals undergo genetic evaluation is low, particularly for individuals that belong to populations that are historically underserved. We sought to characterize the demographic factors that may be associated with receipt of recommended HCS evaluation and follow-up. Methods: All patients with pathologically confirmed breast, ovarian, or fallopian tube cancers and qualifying for hereditary breast and ovarian cancer (HBOC) testing based on NCCN guidelines from 2016 to 2021 at an urban safety-net hospital were included in this analysis. Institutional review board approval was obtained. Demographic and oncologic data, as well as HBOC genetic testing outcomes were collected through retrospective chart review using a standardized data collection tool. Univariate logistic regression models were constructed to test the association of variables with receiving hereditary cancer genetic testing. Results: A total of 312 patients were included in the analysis, 90% of which had breast cancer. Forty percent were non-English speaking, 31% were non-White, and 25% were uninsured. Overall, 70% of patients were referred for genetic counseling and 65% underwent testing. Our analysis showed higher association of genetic testing uptake with Spanish language [odds ratio (95% confidence interval)] [1.74 (1.04, 2.93)], stage II disease [2.15 (1.11, 4.16)], and having a referral to genetic counseling [9.21 (5.32, 15.96)]. A lower rate of genetic testing was associated with patients identifying as Black [0.36 (1.87, 0.70)], having Medicare insurance [0.29 (0.14, 0.61)], a higher Charlson Comorbidity Index [0.31 (0.13, 0.73)], and older age [0.94 (0.92, 0.96)]. Uninsured patients had a similar association with genetic testing uptake as patients with Medicaid. Variables seeming to have no association with genetic testing uptake include family history of cancer, type of cancer, performance status, substance use, and Latinx ethnicity. A pathologic variant was found in 13% of our population. A variant of unknown significance (VUS) was found in 33% of Hispanic or Latinx patients and in 46% of non-Hispanic or Latinx patients who received testing, for a combined VUS prevalence of 39%. Conclusions: Our analysis shows that genetic testing rates for patients meeting HBOC syndrome criteria at an urban, safety-net institution were higher than expected, particularly for Spanish speaking patients and those with Medicaid or no insurance. We hypothesize this may be due to the emphasis our institution places on the care of uninsured patients through programs to make services accessible, as well as strong engagement with the Spanish speaking community. These results can help guide future interventions to target patient groups with lower rates of genetic testing, as well as maintain the successes seen among our diverse population.
Challenges faced by female oncologists in sub-Saharan Africa.
Authors: Mutebi Miriam Claire , Aryeetey Naa Adorkor , Carson Laura M. , Mwanzi Sitna Ali , Lombe Dorothy Chilambe , Woldetsadik Edom Seife , Msadabwe Susan Citonje , Lasebikan Nwamaka , Mohamed Zainab , Ramogola-Masire Doreen , Alemu Haimanot Kasahun , Jalink Matthew , Jagsi Reshma , Vanderpuye Verna D. , Hammad Nazik
Published: June 2022

11001

Background: Recent articles by ASCO and ESMO have identified challenges facing female oncologists in western contexts. The challenges female oncologists face in sub-Saharan Africa (SSA) have yet to be explored. This study was launched by the AORTIC Education and Training Committee to determine the most common and substantial challenges faced by female oncologists in SSA and identify potential solutions. Methods: A diverse panel of 32 female oncologists from 20 countries in SSA was recruited through professional and personal networks. Following an initial meeting to review terminology, a modified three-round Delphi process took place. Participants iteratively reviewed a list of previously identified challenges facing women in oncology in SSA and identified new challenges. The survey was conducted via REDCap, a secure-web-based software platform. Participants reflected on personal experiences or those of colleagues, and were asked to indicate their agreement with each listed challenge, as well as propose solutions. Descriptive statistics identified the most common challenges. Following the third survey, a focus group was held to enrich study data. A thematic analysis is being conducted on the focus group transcript to identify key themes, and a subsequent modified Delphi process is being executed to build consensus around potential solutions to identified challenges. Results: Response rates for the 3 modified Delphi rounds were 66%, 66%, and 53%. The challenge with the greatest agreement was, “pressure to maintain a work-family life balance and meet social obligations”. These were felt to be unique to women in SSA due to an extended family network with several responsibilities beyond the nuclear family. The next two top-scored challenges were “lack of female support and networks”, and “micro-aggressions” (Table). Conclusions: Female oncologists in SSA experience many of the challenges that have been previously identified by similar studies in other regions, with different degrees of perceived importance. Some challenges have a different lived experience for female oncologists in SSA. The second part of this study will include thematic analysis of the recent focus group and explore potential solutions to mitigate these challenges, which will add insight and potential paths forward to optimizing a diverse workforce in SSA.[Table: see text]
Seeking racial equity in hematology and oncology: A fellow-led educational series to promote reflection and action.
Authors: Stein Jacob Newton , Gaddy Jacquelyne Janean , Sorah Jonathan D , Wooten Melissa , Gibson Keisha , Collichio Frances A.
Published: June 2022

11004

Background: With the murder of George Floyd and health disparities laid bare by the COVID pandemic, the US is reckoning with racial injustice. Across medicine and oncology, institutions are grappling with how to address systemic racism and improve care for patients of color. At the University of North Carolina (UNC), trainees developed an educational curriculum to raise awareness of implicit bias and introduce methods to address racial inequities. We present our findings on feasibility and acceptability of a fellow-led course on racism in medicine at a major academic medical center. Methods: UNC oncology fellows adapted a curriculum on implicit bias and racism in medicine in spring 2021. Our aims were 1) to improve knowledge and awareness about implicit bias and systemic racism and 2) introduce methods to address racial inequities. We used lived experiences and collated materials from scientific literature and lay media to illustrate key points. Sessions were: 1) Introduction and Implicit Bias, 2) Implicit Bias in Action: A Case Study, 3) Race-Based Metrics: Journal Club, 4) Career Perspective on Equity in Oncology. Videos, journal articles, and group discussion were employed to appeal to many learning styles. Results: Four sessions were held virtually for the Divisions of Oncology and Hematology. Attendance ranged from 28 to 35 per session. A post curriculum survey assessed perception of racial inequality in medicine and the series’ effects using a Likert scale. Twenty-nine participants completed the survey, 12 of whom were fellows. Of all participants, 71% reported that the course improved knowledge or awareness of racial inequities "some" or "a great deal" and 61% reported that it improved their comfort level addressing racial inequities "some" or "a great deal." All participants endorsed at least “some” racial inequity in medicine. Notably, over 75% of participants indicated interest in further sessions. Conclusions: Formulation of an educational curriculum by fellows and delivered in a division wide setting was feasible and well received by participants with robust discussion and interest in further work. Fundamental to this series’ effectiveness was creating a space for discussion and reflection among colleagues. The goals of improving knowledge and introducing methods to address racial inequities were met. Importantly, our course was integrated alongside institutional efforts on DEI. We were limited by a lack of pre-course survey results due to a technical error. Given the current groundswell of interest and focus in improving racial equity in our society, we encourage other institutions to take similar steps to highlight issues of systemic racism and continue to move our field in the right direction.
Global oncology and cancer disparities education.
Authors: Forbes Victoria , Buteau Anne Christine , Hoxha Ilir , Ademi Islami Dafina , Palmer John P. , Chamberlin Mary D.
Published: June 2022

11006

Background: Comprehensive patient care requires an understanding of medical guidelines and the intersectional context of the patient’s identity and experiences. Hematology/Oncology programs must explicitly teach topics addressing various disparities of care to prepare trainees for informed care. We have developed a Global Oncology and Disparities of Cancer Program to address this gap. Methods: The telementoring program was piloted in 2019 at Dartmouth and has evolved to include didactics, discussion, and evaluations. Participants from across the globe include medical students, residents, Hematology/Oncology Fellows, Faculty, Global Health Scholars, and cancer clinicians. US Hematology/Oncology trainees from Dartmouth and the University of Connecticut consistently participate in the international program. Monthly sessions from September 2021-June 2022 include: Esophageal and GI Cancers in Rwanda, HCC and Cholangiocarcinomas, Gastric Cancer, ASCO International, Global Med ED in Haiti, Breast Cancer in Kosovo, Breast Cancer Risk Factor Prediction Tools Research, Shared Decision Making in Breast Cancer, Hemoglobinopathies, and Health Disparities and Capacity-Building in Rwanda. A pre-course survey was sent to identify participant’s demographics, barriers, and expectations. We will administer a post-course survey. Results: We have preliminary data for our ongoing project. However, we anticipate complete data collection and analysis before the ASCO Meeting. 24 participants were enrolled. 12 (52%) of the participants were located outside of the US in locations such as Haiti, Kosovo, and France. Using a 5-point Likert scale, 11 (46%) participants were “not at all” or only “slightly” aware of obstacles faced by Oncology patients and caregivers in seeking access to healthcare in the US. 7 (29%) participants answered similarly regarding those in low- and middle-income countries. Meanwhile, participants rated ‘’gaining different perspectives’’ as their most important reason for attending with 19 (79%) rating this as “very important” or above. For anticipated improvement from the course, understanding risk factors and cancer biology internationally and recognizing disparities in healthcare between domestic and international settings were the highest rated with 18 (75%) expecting an improvement to a “large degree” or higher. Conclusions: We developed a virtual educational experience to enhance participants’ ability to address disparities of care through challenging Global Oncology topics. Our course is ongoing however initial surveys show a need and desire for this content from participants. We intend to analyze the course surveys to shape future courses. This program can serve as a model for Hematology-Oncology programs to address unmet needs in the curriculum and prepare trainees to provide more complete care to improve cancer outcomes.
Mapping global oncology priorities: A survey of the directors of the NCI-designated cancer centers.
Authors: Prakash Laura , Estes Taylor , Garton Elise M. , Eldridge Linsey , Cira Mishka K. , Duncan Kalina , Gopal Satish , He Min , Ciolino Henry , Loehrer Patrick J.
Published: June 2022

11008

Background: By 2040, an estimated 69% of all cancer deaths globally will occur in LMICs. Recognizing this, ASCO formed the Academic Global Oncology Task Force in 2017 to help formalize the global oncology (GO) field. Their recommendations included: better engagement with the National Cancer Institute (NCI) Center for Global Health (CGH), increased funding, and development of forums to highlight global cancer research and control activities. To further clarify how GO programs are defined and to better understand the perspectives and needs of cancer research leaders, CGH conducted a survey of the 71 Directors at the NCI-Designated Cancer Centers (NDCC). Methods: A 19-question survey was designed using Microsoft Forms and sent to the NDCC Directors via email. Responses were collected from July to September 2021. Two coders reviewed the qualitative responses to categorize the data into thematic areas. Analyses were conducted in Microsoft Excel. Results: Seventy of 71 (99%) NDCC Directors responded to the survey. 41 NDCCs (59%) reported dedicated GO programs or plans to create such a program within 5 years. Additionally, 16 Directors reported GO activities without a dedicated program, while 13 reported no GO activities. The Directors described GO as having high/extremely high (39%) or moderate (50%) importance relative to other priorities, across all types of NDCCs (basic, clinical, or comprehensive). Eight NDCCs (11%) described GO as a low priority or non-priority. 31 NDCCs (44%) reported dedicated funding for GO activities. Directors estimated interest in GO to be higher among junior faculty and trainees than senior and mid-career faculty. Future goals for established or developing GO programs included: recruitment of leadership, formalizing a strategic vision, establishing partnerships, and increasing the number of activities with international collaborations. Barriers noted were limited funding, limited capacity and expertise, and prioritizing the needs in domestic NDCC catchment areas. Conclusions: Despite variation across NDCCs, GO interest is strong as expressed by Center Directors. Strategic planning, increased funding, and improved collaboration within and between NDCCs were reported as necessary to strengthen GO at NDCCs. Continued leadership from ASCO, the NCI, and other international organizations can help facilitate dialogue and increase the prioritization of GO activities at NDCCs.
Online scaffolds: A constructivist approach to oncology fellow learning.
Authors: Brondfield Sam , Schwede Matthew , Johnson Tyler Paul , Arora Shagun
Published: June 2022

11010

Background: Oncology is a vast and fast-paced field. Fellows must expend significant effort to learn and stay updated. Up-to-date learning tools covering core oncology content in a digestible manner are lacking. Additionally, passive lectures are common in oncology, while constructivist approaches that may improve learning are rare. Therefore, we piloted updatable online modules (“scaffolds”) as a learning tool for oncology fellows. Methods: Author SB, a University of California, San Francisco (UCSF) solid-tumor oncologist, designed 12 scaffolds (breast, non-small cell lung, small cell lung, head/neck, salivary/thyroid, upper gastrointestinal, lower gastrointestinal, germ cell, bladder/renal/adrenal, prostate, melanoma, and sarcoma) using Google Slides between 12/2018 and 6/2019. The scaffolds included bullet points and tables/figures synthesized from the ASCO self-evaluation program textbook’s solid tumor chapters and the National Comprehensive Cancer Network (NCCN) guidelines. We emailed scaffold links to all UCSF and Stanford oncology fellows in 2019-2020, including instructions for fellows to update the scaffolds without exceeding 20 slides per scaffold, 5 lines per slide, or 7 words per line. The scaffolds were reintroduced to new fellows at the beginning of each academic year. SB audited to ensure no erroneous information was added. In December 2021 we reviewed updates tracked in Google Slides and conducted one UCSF and one Stanford focus group with four 1st-3rd year fellows each. Results: Between 7/2019 and 12/2021, fellows made 60 updates to the scaffolds, with a mean of 5 updates per scaffold ranging from new trials to changes in management. During the same period, the auditor made 9 updates and found no erroneous fellow updates. Fellow updates occasionally exceeded specified limits, requiring correction. Content analysis revealed that fellows considered the scaffolds to be accessible and succinct learning tools that 1) addressed a dearth of similar resources, 2) served as effective preparation for clinical work and examinations, 3) provided structured information for rapid review, and 4) made subsequent interactions with complex resources such as NCCN guidelines easier. Barriers to fellows updating the scaffolds included lack of ownership and low confidence in judgment regarding appropriate updates. Conclusions: In this two-institution pilot, oncology fellows used and subsequently updated online scaffolds in a constructivist fashion. This model has the potential to fill a crucial gap in available learning resources and can be applied to other specialties. Assigning scaffolds to fellows with faculty mentorship may facilitate ownership and bolster fellow confidence in updating these tools. Individual institutions may update their own versions of the scaffolds to align with institution-specific needs.
Impact of social media on the emotional health and burnout of pediatric and adult oncology professionals: A SWOG and COG survey.
Authors: Moerdler Scott , Barry Maura Meredith , Henry Elizabeth , Lucas Tiffany Lin , Marshall Ariela Lucy , Dizon Don S. ,   Collaboration for Outcomes using Social Media in Oncology (COSMO)
Published: June 2022

11013

Background: Social media (SoMe) engagement is common in oncology, especially for patients and support groups, allowing for education and support. However the impact on oncology professionals remains unknown. The purpose of this study was to evaluate professional SoMe use and its potential associations with wellbeing and burnout. Methods: An electronic survey was developed and piloted by pediatric and adult oncologists. Questions included demographics, details of SoMe use, and emotional health assessments including a 2-item burnout questionnaire. The survey was distributed to all members of SWOG Cancer Research Network and Children’s Oncology Group via Qualtrics. Data was analyzed as of 2/6/2022. Results: The initial survey demographic and emotional health questions were completed by 1558 individuals. Of these, 1069 (68%) reported not using SoMe professionally, while 489 (31%) did. SoMe engagers were primarily female, born 1976–1984, attendings, from academic institutions, and balanced across adult and pediatrics (Table). Among those who use SoMe professionally, 54% (267/489) reported burnout, compared to 66% (701/1069) in the non-SoMe group (p = 0.0001). Remaining emotional health outcomes were similar between groups: choosing this job/career again, time for personal/family life, and career satisfaction (p > 0.1 for all). An additional section on the impact of SoMe on emotional health was completed by 473 SoMe engagers. While 49% (233/473) reported that SoMe has no impact on burnout, 18% (86/473) felt that SoMe helps alleviate burnout. SoMe use was reported to have somewhat/extremely positive impact on wellness (defined as physical, mental, emotional, spiritual wellness) by 28% (131/473). Networking and recognized shared experiences were the top areas of SoMe that improved wellness. Close to half (208/473, 44%) responded that SoMe does not negatively impact wellness. Professional anxiety, amount of time spent online, and keeping up to maintain an online presence were the most frequently noted aspects that negatively impact wellness. Nearly half (232/473, 49%) somewhat/strongly agree that SoMe provides a sense of community. One limitation includes distribution to engaged cooperative group members which may impact results. Conclusions: This analysis suggests that social media engagement might help provide a positive impact on the wellness and reduce burnout among oncology professionals. We hope to further explore themes with qualitative interviews to better understand the impact of SoMe on our emotional health. Our goal is to develop educational interventions based on these salient positive and negative factors. [Table: see text]
A multiple center, open-label, single-arm, phase II clinical trial of MRG002, an HER2-targeted antibody-drug conjugate, in patients with HER2-low expressing advanced or metastatic breast cancer.
Authors: Jiang Zefei , Sun Tao , Wang Xiaojia , Liu Qiang , Yan Min , Tong Zhongsheng , Geng Cuizhi , Tang Jinhai , Yin Yongmei , Yu Guohua , Wang Jingfen , Su Wuyun , Wang Shusen , Pan Yueyin , Yang Hua
Published: June 2022

1102

Background: MRG002 is a novel HER2-targeted ADC, composed of a sugar-modified trastuzumab, MMAE payload and a cleavable vc-linker. MRG002 was effective in HER2-low expressing breast cancer in preclinical studies. Hence, we conducted the phase II study to evaluate the safety and anti-tumor efficacy of MRG002 in HER-low breast cancer. Methods: HER2 low tumor expression was determined by a central lab and had to be immunohistochemistry (IHC)1+ or 2+/ISH-. Eligible patients had advanced/metastatic HER2-low expressing breast cancer that failed standard therapies. MRG002 was administered intravenously once every 3 weeks at the dose of 2.6 mg/kg, until disease progression or unacceptable toxicity which ever occurred first. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC). The secondary endpoints were progression-free survival (PFS), disease control rate (DCR), and safety. Results: A total of 56 female patients with HER2-low advanced or metastatic breast cancer were enrolled at the time of data cut-off (Dec 31, 2021) and had received at least one cycle of MRG002. The median age was 55 (30-72) years. Most patients were HER2 IHC1+ (83.9%), hormone receptor positive (HR+) (85.7%), and with a ECOG PS of 1 (57.1%). Twenty-eight patients (50.0%) had received at least 2 lines of chemotherapy and the median treatment was 3. Forty-one patients (73.2%) had visceral metastasis and 31 patients (55.4%) had bone metastasis. The ORR and DCR in 49 evaluable patients were 34.7% and 75.5%, with 17 PR, 20 SD and 12 PD. Subgroup analysis indicated that the ORR was 39.5% (15/38) and DCR was 76.3% (29/38) among the evaluable patients with visceral metastasis. The tumor responses were similar in both the HER2 IHC 1+ and IHC 2+ subgroups, as is 34.1% and 37.5% respectively, which might be attributed to fewer IHC 2+ enrollment in this trial. Although only 8 HR- subjects enrolled in our study, the ORR (37.5%) and DCR (62.5%) is promising in these triple negative BC patients post to ≥2 line therapies. Most common treatment related adverse events (TRAEs) were grade 1 or 2. The most common TRAEs (≥20%) were neutrophil count decreased (53.6%), white blood cell count decreased (48.2%), AST increased (46.4%), alopecia and ALT increased (39.3%), blood lactate dehydrogenase increased(33.9%), GGT increased (32.1%), nausea (32.1%), vomiting (23.2%), constipation (23.2%), diarrhea(23.2%) and hyperglycemia (21.4%). Most common grade ≥3 TRAE(≥10%) was neutrophil count decreased(14.3%). No patients died due to MRG002. Conclusions: MRG002 shows promising efficacyand well tolerated in patients with HER2-low breast cancer. Further evaluation is underway. Clinical trial information: NCT04742153.