bluuebunny/crossref_metadata_2025 huggingface dataset:
Germline mutations and the presence of clonal hematopoiesis of indeterminate potential (CHIP) in 20,963 patients with BRCA-associated cancers.
Authors: Marshall Catherine Handy , Gondek Lukasz , Mauer Elizabeth , Chao Calvin Y. , Luo Jun , Antonarakis Emmanuel S.
Published: June 2023

10522

Background: The contribution of germline genetics on the emergence of CHIP in patients with solid tumor malignancies is not well understood. We hypothesized that those with germline (g) alterations in homologous recombination repair genes (gHRR) and BRCA-associated cancers (breast, ovarian, prostate, pancreas) would have different rates of CHIP than those without. Methods: We analyzed a large real-world Tempus multimodal database of paired germline and somatic DNA sequencing results. CHIP was calculated based on the presence of pathogenic or likely pathogenic alterations in any one of 16 CHIP-associated genes ( ASXL1, BCOR, BCORL1, CBL, CREBBP, CUX1, DNMT3A, GNB1, JAK2, PPM1D, PRPF8, SETDB1, SF3B1, SRSF2, TET2, U2AF1) with a variant allele frequency of at least 2%. Patients with g alterations in BRCA1, BRCA2, ATM, CHEK2, and PALB2 were compared to those without gHRR alterations (sporadic). Results: In breast cancer, patients with g BRCA1 (n = 104) mutations were younger (med 43 yrs) at diagnosis compared to sporadic cases (n = 6,546 med 56yrs) but had similar rates of CHIP (3% vs 5%). Those with gPALB2 (n = 42 med age 55) had the highest rate of CHIP (14%). gBRCA2 (n = 148; med age 52), gATM (n = 57 med age 52), and gCHEK2 (n = 57 med age 53) and similar rates of CHIP (3%, 4%, 7%). In ovarian cancer, patients with gBRCA1 (n = 137 med age 53) were younger at diagnosis than sporadic cases (n = 3,979 med age 63) with similar rates of CHIP (4% vs 3%). Those with gBRCA2 (n = 83 med age 61) were similar (4%) and gPALB2 (n = 11 med age 68) had the highest rate of 9%. CHIP was not detected among patients with g ATM (n = 23 med age 61) or g CHEK2 mutations (n = 9, med age 59). In prostate cancer, 4% of patients with sporadic cases had CHIP (n = 4,183 med age 66) compared to 4% in gBRCA2 (n = 109 med age 63) and 5% in gATM (n = 44 med age 66). gCHEK2 had 17% prevalence of CHIP (n = 12 med age 66) followed by gPALB2 (n = 12 med age 69). There were no CHIP mutations found among those with g BRCA1 (n = 16 med age 64). In pancreatic cancer, patients with g BRCA2 (n = 89 med age 64) and PALB2 (n = 20 med age 62) were younger at diagnosis, compared to sporadic cases (n = 5,176 med age 67) with lower rates of CHIP (1% gBRCA2, 0 PALB2, 5% sporadic). The highest proportion was in gBRCA1 patients (n = 20 med age 63) with 10%, gCHEK2 (n = 16 med age 68) with 6% and gATM (n = 60 med age 66) with 5%. Conclusions: Despite younger age at diagnosis, patients with g BRCA1 had similar or higher rates of CHIP within breast and ovarian cancer. Women with g PALB2 alterations and breast and ovarian cancer, as well as men with g CHEK2 mutations and prostate cancer, had higher rates of CHIP. These data suggest that gHRR mutations may influence the prevalence of CHIP among patients with BRCA-associated cancers and more research is needed.
Twenty-year patterns in area deprivation index and risk of metastatic prostate cancer at initial diagnosis among men in Ohio.
Authors: Cullen Jennifer , Payne Julia Yang , Rhodes Stephen Paul , Shoag Jonathan Evan
Published: June 2023

10526

Background: Men diagnosed with prostate cancer (PCa) have a 5-year overall survival (OS) rate of 98%. However, this rate plummets to approximately 30% for men diagnosed with metastatic PCa. Furthermore, PCa exerts a greater burden on African American men with a higher incidence and a higher mortality rate than other races. These disparities have been contributed to a result of interactions among genes, health behaviors, and access to care. In our study, we examined Social Determinants of Health (SDoH) – social risk factors that contribute to disparities in cancer mortality. Area deprivation index (ADI) is one of the assessments used to measure these social risk factors. ADI can assess a geographic area’s level of socioeconomic deprivation and is associated with health outcomes on the census block level. Variables used in ADI are grouped into 4 domains – education, income, employment, and housing quality. Most of the communities will fall between a standardized score of 40 to 160. In this study, we used a large population-based cancer database to examine the impact of ADI on risk of metastatic PCa at diagnosis in Ohio. Methods: The Ohio Cancer Incidence Surveillance System (OCISS) data were examined for the period 1996 to 2016 to predict the odds of distant stage at diagnosis. Generalized additive models were constructed with age and year of cancer diagnosis, area deprivation index, race, and Hispanic ethnicity as predictors. The relationship between continuous variables and odds of distant diagnosis was modeled via penalized cubic splines. Odds ratios were calculated for race and Hispanic ethnicity. To summarize the results for variables modeled via splines, predicted probabilities were calculated with other variables held at their average or reference values. Results: We identified 112,023 men with PCa in OCISS database. The median age was 67 (IQR 61-67) years old. Subjects were 85.3% White, 13.8% Black, and 0.9% other races. Only 0.6% of men were Hispanic. By stage, 84.6% (N=94753) had localized PCa, 10.4% (N=11640) had regional PCa, and 5.0% (N=5571) had distant PCa. The median ADI was 93.9 (IQR 83.6-106.5). Our analysis showed that Black men had 41.8% higher odds of having metastatic PCa at diagnosis than White men. Furthermore, our analysis showed similar risk of metastatic PCa at diagnosis in lower ADI values but higher risk at higher ADI values (Table). Conclusions: Higher ADI values were associated with higher risk of metastatic PCa at diagnosis. Interventions should target populations with socioeconomic deprivation and aim to improve patient access to prostate cancer prevention, screening, and treatment services. [Table: see text]
Examining the potential for lead-time bias by estimating stage-specific proportions of deaths due to diagnosed cancer.
Authors: Chang Ellen T. , Clarke Christina A. , Colditz Graham A. , Gomez Scarlett L. , Kurian Allison W. , Hubbell Earl A.
Published: June 2023

10535

Background: Lead-time bias occurs when cancer is detected earlier in time, but with no change in lifespan. Cause of death is not susceptible to lead-time bias; therefore, stratifying cause of death by cancer stage informs the potential for lead-time bias in early detection across cancer types. Methods: Using recent data from 17 US Surveillance, Epidemiology, and End Results (SEER) cancer registries for 1 152 610 first incident primary cancers among patients aged 50–84 years at diagnosis in 2006–2010, we evaluated proportional causes of death by cancer type and uniformly classified stage at diagnosis (American Joint Committee on Cancer, 6th edition), following or extrapolating all patients until death. Results: A minority of cancer patients diagnosed at stages I–II (27%) went on to die from their index cancer, whereas most stage IV cancer patients (85%) did. For patients diagnosed with stage I cancer at all sites combined, an estimated 26% of deaths were due to the index cancer, 61% due to non-cancer causes, and 12% due to a subsequent primary (non-index) cancer. At stage II, 27% of deaths were due to the index cancer, 60% due to non-cancer causes, and 13% due to a non-index cancer. In contrast, at stage IV, 85% of deaths were attributed to the index cancer, with 13% non-cancer and 2% non-index-cancer deaths. Index cancer mortality from stages I–II cancer was proportionally lowest for thyroid, melanoma, uterus, prostate, and breast, and highest for pancreas, liver, esophagus, lung, and stomach. Leading causes of non-index cancer death (lung, pancreas, and colorectal) and non-cancer death (heart disease and COPD) at each stage were similar to those in the general US population. Non-White racial/ethnic groups, including Hispanics and non-Hispanic Blacks, Asian Americans/Pacific Islanders, and American Indians/Alaska Natives, experienced a higher percentage of deaths from stages I–II cancer than non-Hispanic Whites. Conclusions: Across all cancer types, the percentage of patients who went on to die from their cancer was three times greater at stage IV than at stages I–II. As mortality patterns are not influenced by lead-time bias, these data suggest that earlier stage at diagnosis is broadly, if not uniformly, associated with substantially reduced risk of cause-specific death from cancer; therefore, early detection is likely to improve outcomes across cancer types, including those currently unscreened. [Table: see text]
Incomplete HPV vaccination among individuals aged 27-45 years in the United States: A mixed effect analysis of individual and contextual factors.
Authors: Adekanmbi Victor , Guo Fangjian , Hsu Christine , Kuo Yong-Fang , Berenson Abbey
Published: June 2023

10546

Background: In the United States, the Human papillomavirus (HPV) vaccine is approved for use up to age 45. Incomplete HPV vaccination rates among those over age 26, however, remain high. The aim of this study was to examine the independent effects of individual- and neighborhood-level factors on incomplete HPV vaccine series in the United States (US) among those aged 27-45 years. Methods: This retrospective cohort study used administrative data from Optum’s Clinformatics DataMart Database to identify individuals aged 27-45 years who received 1 or more doses of HPV vaccine between July 2019 and June 2022. Multilevel multivariable logistic regression models were applied to the data on 7,662 individuals aged 27-45 years who were fully vaccinated against HPV or not, nested within 3839 neighborhoods across the US. Results: More than half of the participants in this study (52.93%) were not completely vaccinated against HPV. About 64% of the eligible participants aged 27-30 years did not complete their HPV vaccine series. After adjusting for all other covariates in the final model, being older than 30 years old decreased the odds of incomplete HPV vaccine series. Participants living in neighborhoods of South region of the US had enhanced odds of incomplete HPV vaccine series compared to those residing in Northeast region (aOR 1.21; 95% CrI 1.03–1.42). There was significant clustering of incomplete HPV vaccine series at the neighborhood level. Conclusions: This study revealed that individual- and neighborhood-level factors significantly influence HPV vaccination incompleteness in the US. Interventions to improve HPV vaccination uptake and completion should take into consideration both individual- and contextual-level characteristics during design, planning and implementation of policies and programs to improve HPV vaccination coverage and completion in the US and other similar countries. Acknowledgement Dr. Adekanmbi is supported by a research career development award (K12HD052023: Building Interdisciplinary Research Careers in Women’s Health Program-BIRCWH; Berenson, PI) from the National Institutes of Health/Office of the Director (OD), National Institute of Allergy and Infectious Diseases (NIAID), and Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD). Dr. Guo is currently supported by an award (K07CA222343) from the National Institutes of Health, National Cancer Institute (NIH/NCI). Dr. Berenson is supported by an award (PP200048) from the Cancer Prevention and Research Institute of Texas (CPRIT). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or CPRIT. Conflict of Interest: All authors report no conflicts of interest.
Sex differences in cancer incidence rates by race and ethnicity: Results from the surveillance, epidemiology, and end results (SEER) Registry (2000-2019).
Authors: Tosakoon Sararat , Lawrence Wayne R. , Shiels Meredith S. , Jackson Sarah S.
Published: June 2023

10547

Background: Sex differences in cancer incidence are pronounced, with men having 2-3 times the rate of most non-reproductive cancers than women. However, whether the male predominance is due to differences in biological factors or behavior remains not well understood. This study investigated sex differences in cancer incidence by race and ethnicity to provide a greater understanding of whether differences are driven by biological factors or environmental exposures. Methods: Cancer incidence data from the Surveillance, Epidemiology and End Result (SEER) program (2000-2019) was used to calculate male-to-female incidence rate ratios (MF IRR) for each cancer site and histological subtype, stratified by race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian/Pacific Islander, American Indian/Alaskan Native, and Hispanic), and age-standardized to the 2000 U.S. population for individuals ages ≥20 years. Results: Most non-reproductive cancers had a male predominance across race and ethnicity, with the largest MF IRR seen for cancers of the tonsil, hypopharynx, larynx, and Kaposi sarcoma (MF IRR > 4). Three cancers, gallbladder; peritoneum, omentum, mesenter; and thyroid, were more common among females than males across all race and ethnicity. Females had a higher incidence of anal cancer than males for all racial and ethnic groups except for non-Hispanic Black individuals where the MF IRR was >1. Cancers of the stomach, skin (excluding basal and squamous cell), melanoma skin, and other non-epithelial, and myeloma had greater MF IRR among non-Hispanic White adults than all other racial and ethnic groups. Non-Hispanic Black individuals had higher MF IRR of cancers of the liver and lung and bronchus, compared to other racial and ethnic group. Non-Hispanic White males had the highest MF IRRs for esophagus adenocarcinoma and gastric cardia adenocarcinoma and the lowest MF IRR for esophagus SCC compared to other races and ethnicity. Conclusions: The MF IRR for most cancers in this study did not differ by race and ethnicity, suggesting the influence of biological factors. Differences in the MF IRR across race and ethnicity may indicate carcinogenic exposure differences leading to the development of non-sex-specific cancers. Further research is needed to identify biological drivers of cancer incidence for most non-reproductive cancers. Funding: Intramural Research Program of the Division of Cancer Epidemiology and Genetics in the National Cancer Institute, National Institutes of Health.
Polygenic risk scores in assessing lung cancer susceptibility in non-Hispanic White and Black populations.
Authors: Trendowski Matthew R , Lusk Chrissy , Wenzlaff Angie , Neslund-Dudas Christine , Gadgeel Shirish M. , Soubani Ayman , Schwartz Ann G.
Published: June 2023

10548

Background: Polygenic risk scores (PRS) have become an increasingly popular approach to evaluate cancer susceptibility, but have not adequately represented Black patients in model development. We used previously identified single nucleotide polymorphisms (SNPs) and annotated SNPs in associated gene regions to develop PRS in non-Hispanic Whites and Blacks using the INHALE dataset. Methods: Using the Multi-Ethnic Genotype Array, 1,204 SNPs for non-Hispanic Whites and 1,515 SNPs for Blacks were evaluated for their association with lung cancer risk adjusting for age, sex, total pack-years, family history of lung cancer, history of COPD and the top five PCs for genetic ancestry. Gene region-specific significant SNPs (p < 0.05) were used to develop race-specific PRS. Results: The race-specific PRS included different sets of significant SNPs and were highly associated with lung cancer risk in both non-Hispanic Whites (OR = 1.07, 95% CI: 1.05-1.09, p = 3.44x10-9) and Blacks (OR = 1.12, 95% CI: 1.08-1.17, p = 9.14x10-8). These models remained significant for both Whites (OR = 1.05, 95% CI: 1.03-1.09, p = 0.0004) and Blacks (OR = 1.08, 95% CI: 1.01-1.15, p = 0.01) who currently do not meet USPSTF screening guidelines. AUC analysis demonstrated the Black-specific model (AUC = 0.68) outperformed the White-specific model (AUC = 0.57) (p = 0.03) when examined exclusively in the Black cohort. Conclusions: Using previously validated SNPs and gene regions, we developed race-specific PRS in non-Hispanic White and Black INHALE participants. Further validation of PRS could enable the incorporation of genetic risk modeling into lung cancer screening to identify patients who do not have traditional risk factors for lung cancer, as well as stratify patients into different levels of risk based on their genetic profile. Through the development of a reliable genetic risk factor prediction model, clinicians will have another method by which to evaluate lung cancer susceptibility, potentially leading to earlier diagnoses that portend more favorable treatment outcomes.
Impact of race and age on intrinsic subtype distribution and treatment decisions in metastatic breast cancer: Preliminary analysis of HARMONY (LCCC1829).
Authors: Ivory Joannie M. , Rashid Naim , Zagami Paola , Perou Charles M. , Reeder-Hayes Katherine Elizabeth , Carey Lisa A.
Published: June 2023

1055

Background: Gene expression profiling (GEP) is used to classify breast cancer (BC) into four intrinsic subtypes: Luminal A (LumA), Luminal B (LumB), HER2-Enriched, and Basal-like. Non-LumA subtypes are associated with poorer outcomes. Studies in early BC show that hormone receptor-positive (HR+)/HER2-negative (HER2-) tumors have a higher frequency of non-LumA subtypes in Black and younger (<50) women. Similarly, triple negative BC, which carries the poorest prognosis and is mostly Basal-like, are overrepresented in Black and younger women. These variations in intrinsic subtype contribute to outcomes disparities. The extent to which these racial and age differences in subtypes and mortality occur in metastatic breast cancer (MBC) is unknown. Methods: HARMONY (NCT03769415) is a prospective clinical trial in patients with newly diagnosed MBC. Bulk tumor GEP (PAM50 intrinsic subtyping) is performed on primary and metastatic tumors. A primary objective is to determine the extent and treatment implications of molecular discordance (defined a priori as treatment differences by intrinsic subtype compared to clinical subtype); other endpoints to be reported later include GEP comparisons between primary and metastatic samples. Here we examine differences in a) intrinsic subtype and b) treatment patterns in MBC by race and age. Results: At the time of analysis, the study had accrued 220 participants. Mean age was 58, 24% were Black women. Sixty-five percent had HR+/HER2- MBC, 14% HER2-positive, and 21% triple negative. Unlike in early BC, LumB exceeded LumA (LumA 27%, LumB 35%, HER2-Enriched 12%, Basal-like 25%). Similar to early BC, subtype varied by race and age with more non-LumA subtypes in young and Black women. Discordance between intrinsic and clinical subtype was seen in 24% of Black, 20% of White women, in 29% of younger and 18% of older women. Treatment patterns also differed by race and age, where a higher percentage of younger Black women received first-line chemotherapy compared to younger White women overall (45% vs. 10%, p=0.0025), and in HR+/HER2- disease (33% vs 8.7%, p=>0.05). No difference was seen in older women (24% vs 17%, p=0.44). Median progression free survival was worst in younger Black women compared to all other participants (5.4 vs 19.5 months, p=0.027), which may be driven by clinical subtype. Conclusions: Intrinsic subtype of tumors in a metastatic population has a different distribution by race and age than early BC, with more poor-prognosis non-LumA subtypes, and approximately 1 in 5 have discordance between clinical and molecular subtype, which may be therapeutically relevant. Clinical trial information: NCT03769415 . [Table: see text]
Disparities in germline genetic testing results from a cohort of 493,515 black and white patients.
Authors: Wyatt Rachel , Nielsen Sarah M. , Chen Elaine , Heald Brandie , Esplin Edward D. , Tomlinson Gail Elizabeth
Published: June 2023

10550

Background: When undergoing germline genetic testing (GGT), Black patients (pts) are more likely than non-Hispanic White (NHW) pts to receive uncertain results and less likely to receive definitive molecular diagnoses as the Black genome is less well-characterized. As GGT is increasingly pertinent to cancer care, it is important to explore the scope of these disparities. Methods: A retrospective cohort of clinician-reported Black and NHW pts who underwent GGT (43-84 genes) from 2015-2022 was evaluated. Frequencies of pathogenic/likely pathogenic (P/LP) and variant of uncertain significance (VUS) results were compared between Black and NHW pts. Rate and type of VUS reclassifications were also compared. Differences in proportions were determined using Chi-square test and significance was set at 0.05. Results: The cohort consisted of 493,515 pts (48,684 [10%] Black and 444,831 [90%] NHW). VUS results were significantly more frequent and P/LP results significantly less frequent for Black compared to NHW pts (46% vs. 32% and 9 vs.13%, respectively). This was also true for pts who reported a history of cancer, across all common hereditary cancer types (Table). Comparing Black to NHW pts, there were more unique instances of VUS reclassifications over time (13% of 13,629 vs. 9% of 53,195 unique VUS), including 12% vs. 8% downgraded to benign/likely benign and 0.9% vs. 1.3% upgraded to P/LP. Conclusions: Lower rates of actionable results limit risk-reducing interventions for Black pts and their families. However, VUS rates continue to decline, particularly in Black pts, as more individuals (of any race or ethnicity) are sequenced. Clinicians can be reassured that most (but not all) VUS that are reclassified are downgraded to benign. [Table: see text]
African American women who carry the BRCA1/2 mutation: Clinical characteristics and prevention strategies.
Authors: Karki Ujjwal , Ghimire Bipin , Shrotriya Shiva , Rangarajan Tara , Zakalik Dana
Published: June 2023

10554

Background: Carriers of pathogenic variants (PV) in BRCA1/2 have an increased risk of breast, ovarian, and other cancers . The clinical characteristics and uptake of risk-reducing interventions in African American(AA) women with BRCA1/2 PVs are less well studied. Methods: After IRB approval, we performed a retrospective chart review on African American women seen at Nancy and James Grosfeld Cancer Genetics Center at Beaumont Health from January 1, 2006, to December 31, 2021, who tested positive for a BRCA 1/2 mutation. We analyzed demographics, cancer characteristics, outcomes, and prevention strategies. Results: Of 238 African American(AA) women who underwent genetic testing, 69 patients (29%) were identified to be a carrier of BRCA1/2 PVs or likely pathogenic variants (LPVs). The median age at testing was 49 years (range: 24-87). Forty-six women (67%) had a cancer diagnosis, with a median age at diagnosis of 52 years. Four women had two, and one had three cancers, for a total of 52 cancers. Breast cancer was the most common type of cancer (40; 77%), with a median age at diagnosis of 48 years (range 24-73) and a majority (26; 65%) being BRCA2 carriers. Most were invasive ductal carcinoma (87.8%), high-grade (80%), ER-positive (52%), PR-negative (68%), HER2-negative (94%) and stage I or II disease (63%). Fifteen (38%) were triple-negative. Most patients (87%) received adjuvant systemic chemotherapy or endocrine therapy, 31% received neoadjuvant chemotherapy, and 39% received adjuvant radiation. The 3- and 5-year survival was 94% and 91%, respectively, with a median follow-up of 103 months. Three patients (all BRCA2 carriers ) developed contralateral breast cancer (median time to recurrence: 201 months); 3 (all BRCA2) developed local recurrence (median time to recurrence: 60 months), and 4(2 BRCA1, 2 BRCA2) developed metastatic recurrence (median time to recurrence: 34 months). Other cancers observed were ovarian (n = 6; 4 BRCA2, 2 BRCA1), uterine (2), lung (2), kidney (1), and glioblastoma (1). Compared to AA carriers without cancer, those with cancer were more likely to undergo risk-reducing mastectomy (RRM; 68% vs. 23%) and risk-reducing salpingo-oophorectomy (RRSO; 72% vs. 55%). In the non-cancer group, significantly fewer patients elected RRM (23%) compared to RRSO (55%). Conclusions: Our study outlines the characteristics of AA women who carry BRCA1/2 PVs, revealing that most had high-grade invasive ductal breast cancer with excellent survival. Patients without a cancer diagnosis were less likely to undergo risk-reducing surgery, highlighting the importance of effective counseling focusing on primary prevention in these high-risk patients. Further research is needed to better characterize cancer risk and address potential barriers to uptake of risk-reducing interventions in this population.
Racial disparities in aging-related comorbidity among breast cancer survivors.
Authors: Nguyen Kirsten , Wang Cong , De Vis Jill , Alford Mason , Rafat Marjan , Chakravarthy Anuradha Bapsi , Shu Xiao-Ou
Published: June 2023

10555

Background: Black breast cancer (BC) patients have a higher mortality rate than their white counterparts, potentially due to age acceleration caused by cancer and its treatments. However, epidemiological evidence is limited. Methods: Our study includes 1885 BC patients and 1224 cancer free women (controls) recruited at Vanderbilt University Medical Center from 2004 to 2021. Patient demographics and aging-related outcomes were extracted from the tumor registry or electronic health records. Aging-related outcomes included 28 comorbidities and the Charlson Comorbidity Index (CCI) at baseline (biopsy) and follow-up (latest clinical visit). The associations of BC status with CCI and specific comorbidities were evaluated by linear and logistic regression models, respectively. The associations of race with aging-related outcomes were evaluated among cases. All analyses were adjusted for age, and follow-up outcomes were adjusted for baseline information. Results: The median follow-up time is 10 years. BC patients had a higher mean CCI at baseline (1.32 vs 0.59, p<0.01) and follow-up (beta=1.04, 95% CI=0.94-1.14) than controls. Results from individual comorbidities showed that BC survivors had a higher risk of developing cardiovascular disease, liver disease, hypertension, hyperlipidemia, gastroesophageal reflux disease (GERD), and depression. Among BC patients, Black women were diagnosed at a younger age (52.0 vs 55.8, p<0.01), but had a higher baseline and follow-up CCI than Whites. Black BC survivors were more likely to develop peptic ulcer disease, diabetes, second malignancy, hypertension, and GERD than White BC survivors, even after adjustment for baseline comorbidities. [Table: see text]
Sleep health and quality of life in African American cancer survivors: The Detroit ROCS Cohort.
Authors: Beebe-Dimmer Jennifer Lynn , Trendowski Matthew R , Ruterbusch Julie J. , Martin Jennifer , Baird Tara , Schwartz Ann G. , Badr Safwan
Published: June 2023

10556

Background: Sleep disturbances are particularly prevalent among cancer survivors, likely attributed in part to anxiety over prognosis, treatment, and associated financial concerns. We know little about prevalence, patterns and predictors of poor sleep health in African American (AA) cancer survivors. Sleep problems may contribute in part to the observed disparities in outcomes in this high-risk population and represents a modifiable target to improve quality of life and longer-term health problems. Methods: The Detroit Research on Cancer Survivors (ROCS) study is a large cohort of AA cancer survivors diagnosed with female breast, prostate, colorectal, endometrial, lung or any other early onset cancer on or after 01/01/2013 in Metropolitan Detroit. We have enrolled 5,073 survivors into the study, each completing a baseline survey with annual follow-up to update medical history, health related quality of life (QoL), and other prognostic factors. In 2021, a supplemental sleep survey was administered to all eligible survivors. The current investigation analyzes sleep, QoL (measured using the Functional Assessment of Cancer Therapy - General (FACT-G) survey), and relevant health behavior data from 716 survivors who completed the sleep survey. Sleep health was measured using the Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). Block regression was used to estimate the contribution of clustered factors to QoL. Five blocks were evaluated: sleep health, demographics, cancer characteristics, comorbidities, and health behaviors. Results: Nearly 60% of AA cancer survivors in the study reported symptoms indicative of poor sleep quality (PSQI score 6-21) with 17% reporting excessive daytime sleepiness (ESS score 11-24) and 11% reporting moderate to severe insomnia (ISI score ≥ 15). Sleep disturbances and poor quality of sleep were associated with clinically meaningful declines in QoL, where survivors with ISI scores in the clinical range reported adjusted FACT-G scores 19 points lower than those with ISI score below the clinical range (95% CI -14.7, -22.6). Sleep health accounted for the largest proportion of variability in FACT-G scores (R2= 0.28) and accounted for an additional 19% of the variance over and above the other 4 blocks. Finally, AA survivors reporting regular physical activity also reported better sleep quality in all 3 sleep scales (p < 0.001). Conclusions: A substantial proportion of AA cancer survivors reported poor sleep quality which impacted their QoL. Understanding the determinants of sleep health in this population will lead to the development of interventions aimed at improving quality of life and downstream health consequences in AA cancer survivors.
Prevalence of and racial/ethnic distribution of full-body skin examination among sexual and gender minority patients.
Authors: Freeman Jincong Q. , Verghese Michelle , Connor Brian W. , Hazra Aniruddha , Romero Iris , Fisher Andrew R. , Rosenblatt Adena E.
Published: June 2023

10557

Background: Skin cancer disproportionately affects sexual and gender minorities in the United States. A full-body skin examination (FBSE) can help detect early signs of skin cancer and is an important prevention method. However, there are no national guidelines of routine FBSE for skin cancer. Further, data on FBSE participation among lesbian, gay, bisexual, transgender, and/or queer (LGBTQ+) patients are lacking, and little is known about the racial/ethnic distribution of FBSE in this patient population. Methods: Cross-sectional survey data on FBSE participation and key characteristics were collected from patients who were recruited at clinics and community centers or via social media from August 2022 to January 2023. Eligibility criteria included being at least 18 years old and self-identifying as LGBTQ+. Receipt of an FBSE, assessed by asking patients whether they had ever received an FBSE in the past, was dichotomized as yes and no. Descriptive statistics, i.e., mean (SD) and count (%), were calculated, with distribution comparisons using Student’s t, Pearson’s Chi-square, or Fisher’s exact tests as appropriate. Results: A total of 124 LGBTQ+ patients responded to the survey. The mean age was 32.4 (SD = 12.1) years. Overall, 41.5% of the patients reported ever having received an FBSE in the past. By race/ethnicity, 62.5% of Non-Hispanic Black patients reported ever having received an FBSE, followed by 52.1% of Non-Hispanic White, 28.6% of Hispanic or Latino, 28.6% of multiple races, and 10.5% of Asian ( p= 0.005). By gender identity, 61.5% of transgender male patients reported receipt of an FBSE in the past, followed by 57.1% of transgender female, 39.3% of cisgender female, 35.4% of cisgender male, and 35.0% of genderqueer, non-binary, or gender non-conforming. Comparing patients who reported ever having received an FBSE, those who did not were more likely to not be employed (47.9% vs. 26.0%, p= 0.046), to be on Medicaid (18.5% vs. 6.1%, p= 0.074), to not have visited a dermatologist in the past (41.7% vs. 7.8%, p< 0.001), and to not have been told at an increased risk for skin cancer (87.3% vs. 43.2%, p< 0.001). No significant differences in educational attainment or sexual orientation were observed between patients who reported ever having received an FBSE and those who did not. Conclusions: The prevalence of FBSE was higher among Non-Hispanic Black or Non-Hispanic White LGBTQ+ patients than among those who are Hispanic or Latino, multiracial, or Asian. In addition, our findings suggest that low socioeconomic status and health care utilization may influence FBSE access or participation in LGBTQ+ patients. Strategies for improving equitable access to FBSE among LGBTQ+ patients, particularly among those with ethnic minority background or low socioeconomic status and health care utilization, may be needed.
Vitamin D deficiency as a risk factor for breast cancer development.
Authors: Mackey James David , Young Peter , Zimmerer Rene , Miles Brittany
Published: June 2023

10559

Background: Previous studies and meta-analyses have suggested that women with low levels of vitamin D may be at increased risk of breast cancer development and recurrence. The relationship is suspected to be inverse, nonlinear, and predominantly present in postmenopausal women. The purpose of this study was to use the TriNetX platform to determine the magnitude of breast cancer risk increase for women with significant vitamin D deficiency and evaluate the significance of menopause on vitamin D-associated breast cancer risk. Methods: The TriNetX platform was used to generate patient cohorts via International Classification of Disease-10 (ICD-10) codes. All patients were females over 40, had no prior history of breast cancer (C50), and had been diagnosed with menopause (Z78.0). One cohort had less than 20 ng/mL of vitamin D while the other had greater than 30 ng/mL. The cohorts were balanced for age, race, and ethnicity, resulting in 73,659 patients in each arm. They were then evaluated for the future development of breast cancer (C50). Two additional cohorts were created of premenopausal patients aged 40-55 using the same vitamin D parameters and cohort balancing. Results: Postmenopausal women with vitamin D levels below 20 ng/mL had a 45% greater risk of developing breast cancer (risk ratio 1.45, 95% CI (1.38,1.52), p-value <0.0001). (Table) Deficient premenopausal women were also found to be at significantly increased risk although the absolute risk difference was small (relative risk 1.18, 95% CI (1.10,1.27), p-value <0.0001). Conclusions: These results confirm and also quantify the previously-suspected increased breast cancer risk for women who are deficient in vitamin D. The impact of low vitamin D levels on breast cancer risk in premenopausal patients was statistically significant but small in magnitude, while postmenopausal women were found to have approximately 45% higher risk as compared to women who were not deficient. Vitamin D supplementation for all deficient postmenopausal women should be considered. [Table: see text]
A nationwide population based primary CNS lymphoma (PCNSL) analysis: Do Hispanics have better outcomes?
Authors: Orellana Ysaith , Lucero Kana , Liu Qianqian , Michalek Joel , Diaz Duque Adolfo Enrique
Published: June 2023

10560

Background: Over the last decade, overall survival (OS) of PCNSL patients has increased from 12.5 months to 26 months (N. Oncol, PMID 30418592). One study examined the incidence of PCNSL in the Hispanic (HI) population in Texas (Cureus, PMID: 33042676), but a national study is needed to understand ethnic disparities, as many HI face barriers to health care access (Natl Cance Inst Monogr, PMIDL 8562207). This study aims to understand demographics, treatment patterns, and outcomes of HI and Non-Hispanic (NH) patients with PCNSL nationally. Methods: Data analyzed on PCNSL patients in the United States (US) was reported to the Surveillance, Epidemiology, End Results (SEER) 18 database between 2000 and 2018. Racial groups analyzed included NH whites, HI whites, Blacks, and Asian/Pacific Islanders (PI). Patient characteristics, age-adjusted incidence rate, and survival rate were compared across ethnic groups (HI vs. NH). Stratification by age, gender, and stage at diagnosis was considered. Data was stratified using Kaplan-Meier and Cox regression analyses to compare OS between HI and NH. Multivariate analysis and propensity score matching was performed with adjustment for age, stage, and B-symptoms. Results: Of 5819 PCNSL patients, 15% were HI, and 85% NH. 57% were male compared to 51% of NH. As compared to NH at diagnosis, HI patients were younger, 59 years vs. 66 years(y) (p<0.001); the majority of HI (42%) were diagnosed in the age bracket of 60-80y (p<0.001). Approximately 30% of HI were diagnosed in 2015-2018, while most of NH (29%) were diagnosed in 2010-2014 (p=0.054). With 52% of HI being diagnosed at <60y, only 32% in NH. As for race, most of HI and NH were White (97% vs. 79%), followed by Black (1% vs. 8%). On survival analysis, the survival probability at 2, 5, and 10y of HI vs. NH were (0.507 vs. 0.441), (0.395 vs. 0.322), and (0.237 vs. 0.225), respectively. The median survival time was 2.1y for HI vs. 1.2y for NH. There was an OS difference favoring HI (p=0.0009). On multivariate analysis, when adjusted for age, patients with PCNSL between 60-80y and above have 3.4 times more likely to die from disease after diagnosis with HR 3.4 (95% CI:2.9-4) and 1.7 (95% CI: 1.6-1.9). Conclusions: Our study demonstrates statistically longer median survival and OS favoring the HI population. The younger age of diagnosis in HI patients could be a factor in their survival probability for PCNSL, given that both HI and NH received similar treatment and had a similar staging. However, additional studies would be needed to validate this observation and determine other biological or socioeconomic factors that may play a role. [Table: see text]
Elevated cancer risk among individuals with combinations of cancer-related risk factors: A large claims database analysis.
Authors: Cong Ze , Ye Xiangyang , Kurian Allison W.
Published: June 2023

10561

Background: Besides age, many risk factors have been associated with elevated cancer risk. Understanding cancer incidence rates among patients with single or multiple risk factors can help inform cancer prevention and detection efforts. Methods: A retrospective observational analysis was conducted on individuals aged 50-79 in 2020 using Optum’s de-identified Clinformatics Data Mart Database which includes Medicare Advantage (MA) (vast majority aged 65+) and commercially insured members (mostly below 65 and employed). Patients with no prior cancer diagnosis (continuously enrolled with no cancer claims for one year) and with cancer risk factors were identified using ICD-10-CM and CPT-4 codes, including autoimmune-related chronic inflammation (diabetes, inflammatory bowel disease, asthma, or rheumatoid arthritis) (INFLAM AUTO); non-autoimmune related chronic inflammation (fatty liver disease, obesity, or cirrhosis/chronic hepatitis B/C) (INFLAM NONAUTO); immunodeficiency (primary or secondary immunodeficiency, HIV, or status post organ transplant); and smoking. Cancer incidence rate ratios (IRR) were calculated by comparing one-year cancer incidence rate among the groups with risk factors versus the general population by insurance type (IRR>1 means elevated risk of cancer). Groups with evidence of any risk factor and combinations of risk factors were assessed. Statistical significance of IRRs was evaluated using logistic regression models adjusting for demographic characteristics. Results: Cancer incidence rates of 1.12% and 2.11% were observed among the approximately 1.3 and 2.4 million general population aged 50-79 in commercial and MA plans, respectively. Enrollees with any of the risk factors or combinations analyzed had statistically significantly elevated risk of cancer (IRRs>1.00, p<0.05). Commercially insured groups with highest risk included transplant (IRR=7.68, prevalence=0.02%), immunodeficient and smokers (IRR=3.66, prevalence=0.16%), cirrhosis/chronic hepatitis B/C (IRR=2.61, prevalence=0.41%), INFLAM AUTO and smokers (IRR=2.43, prevalence=3.56%), and smoker (IRR=2.33, prevalence=11.11%). Results in MA were generally consistent with the commercial plan (Table). Conclusions: Patients in both commercial and MA plans with any risk factor experienced significantly elevated cancer risk. Cancer prevention and screening strategies can be informed by risk levels among different patient subgroups to optimize resource allocation. [Table: see text]
The impact of extending CRC screening to the older population: Results from CRC-AIM microsimulation model.
Authors: Ebner Derek W. , Kisiel John B. , Estes Chris , Vahdat Vahab , Limburg Paul J.
Published: June 2023

10567

Background: Average-risk screening for colorectal cancer (CRC) is effective and recommended. The U.S. Preventive Services Task Force issued grade A and B recommendations for screening ages 50-75 and 45-49, respectively, however the recommendation for the older population (ages 76-85) is grade C (moderate certainty that the net benefit is small). With emerging blood-based CRC screening, we evaluated the benefits of screening the older population with continued multi-target stool DNA (mt-sDNA) or FIT strategies and/or with a modality shift to blood-based tests after age 75. Methods: Using the validated CRC-AIM microsimulation model, triennial mt-sDNA and annual FIT screening (ages 45-75) followed by four strategies for ages 76-85 (no screening, continued mt-sDNA/FIT, or a modality shift to blood-based screening using either CMS criteria [CMS] or recently reported blood test data from the ECLIPSE study1 [BT; Guardant Health, Inc.] were considered. For CMS criteria and BT, CRC sensitivity were set at 74% and 83%; and adenoma sensitivity was set to 20%, and 13%; and CRC specificity was set to 90% for both tests. Real-world (RWE) adherence for initial screening was set to 80% (CMS, BT), 65.6% (mt-sDNA), and 42.6% (FIT). Adherence for follow-up colonoscopy was set to 72.1% (mt-sDNA, CMS, BT) and 46.0% (FIT). Results: Screening among the population aged 45-85 resulted in 281 life years gained (LYG) with continued mt-sDNA as compared to 193 with continued FIT. Furthermore, mt-sDNA reduced CRC mortality by 70% as compared to 49% by FIT (Table). When screening modality was shifted to CMS (76-85 year olds), mt-sDNA/CMS resulted in 279 LYG as compared to 196 for FIT/CMS. CRC incidence was reduced by 59% (mt-sDNA/CMS) as compared to 38% (FIT/CMS), and mortality declined by 69% (mt-sDNA/CMS) as compared to 51% (FIT/CMS). Reductions in disease burden were lower when modality was switched to BT after age 75 due to reduced test performance. Conclusions: Extending CRC screening to the older population with continued mt-sDNA demonstrated the best health outcomes compared to other modalities. A modality shift after age 75 to blood-based testing resulted in greater LYG as compared to no screening, with performance at CMS criteria yielding better results than BT. Therefore, despite inferior performance, blood-based tests may offer a CRC screening option for older patients who are unable to complete stool testing. [Table: see text]
LungFlag, a machine-learning (ML) personalized tool for assessing lung cancer risk in a community setting, to evaluate performance in flagging non-small cell lung cancer (NSCLC) regardless of sex or race.
Authors: Morgenstern David , Choman Eran Netanel
Published: June 2023

10570

Background: Application of ML-based risk prediction models to lung cancer screening cohorts have been shown to increase screening efficiency. However, ML-based models may be vulnerable to sexual and racial bias arising from historical bias in health care access as well as biased training data. Demonstrating fairness in the predictions of ML-based models is a prerequisite to their acceptance by clinicians and patients. We assessed the clinical performance of LungFlag based on sex and race, two key demographic subgroups at risk for disparate outcomes due to bias. Methods: The LungFlag machine learning model is a retrospectively validated ML model intended to identify individuals who are at elevated risk for lung cancer and should be counseled regarding lung cancer screening. LungFlag uses existing routine outpatient lab measurements, smoking history, comorbidities, and demographic data to flag high-risk individuals. We compare performance of LungFlag between sexes and between races and calculate the sensitivity at the overall positivity rate of 3%. We chose a case-control design based on a large US-based community and outpatient dataset including 39,135 case patients with NSCLC and 212,454 contemporaneous NSCLC-free controls. We included ever-smokers, ages 45-80, with available lab measurements from 3-12 months before diagnosis, and minimal follow-up of 24 months. Sub-populations with less than 1% representation from the total population were excluded. Results: The comparison between the sub-populations presented by sensitivity and specificity indexes is detailed in the table. No statistically significant difference was demonstrated in the sensitivity of the model to flag individuals that were diagnosed with NSCLC on multiple sub-populations. Conclusions: The LungFlag model demonstrated fairness with respect to sex and race based on similar clinical sensitivity in a large, community-based retrospective dataset. Further assessment in prospective studies and in additional racial sub-populations is recommended to support this conclusion. [Table: see text]
Incidence, landscape and survival outcome of de novo malignancy after double lung transplantation.
Authors: Chung Liam Il-Young , Lee Jeeyeon , Yang Won Jun , Kim Hye Sung , Lee Yunjoo , Yu Jisang , Bharat Ankit , Chae Young Kwang
Published: June 2023

10574

Background: Organ transplant recipients are at greater risk of developing malignancies due to their immunosuppressive management. However, the incidence of post-transplant malignancy after double lung transplantation (DLT) has not been studied. This study investigated the incidence, trends, and most common types of post-transplant malignancy following DLT. Methods: Data extracted from the Organ Procurement Transplantation Network (OPTN) registry after DLT for non-cancerous disease. We evaluated the incidence of post-transplant malignancy, and assessed the annual and cumulative risk of each malignancy after DLT. And the overall survival (OS) of recipients with or without post-transplant malignancy was analyzed by Kaplan-Meire survival method. Results: A total of 23,935 cases were identified and analyzed from the OPTN database (13,768; 57.5% male, 10,167; 42.5% female). 5,629 cases (23.5%) were found to have post-transplant malignancy and 18,306 cases (76.5%) had no post-transplant malignancy. Among patients with post-transplant malignancy 3,785 (67.2%) were male and 1844 (32.8%) were female. Those with post-transplant malignancy had a longer OS compared to those without post-transplant malignancy (P < 0.001). While the median OS was 97.2 months and 5-year survival rate was 83.6% in recipients with post-transplant malignancy, the median OS was 36.7 months and 5-year survival rate was 67.3% in For those without post-transplant malignancy. The risk for post-transplant malignancy was greatest during the first 3-5 years post-transplantation. The most common types of post-transplant malignancies were squamous cell skin cancer (n = 2711, 48.2%), basal cell skin cancer (n = 965, 17.1%), lymphoma (n = 570, 10.1%), lung cancer (n = 187, 3.3%), colorectal cancer (n = 184, 3.3%). Conclusions: The lifetime incidence of post-transplant malignancy following DLT was identified to be 20.1% and those with post-transplant malignancy had a longer OS compared to those without post-transplant malignancy. Further studies are needed to investigate the underlying mechanism for the increased risk of malignancy following DLT and its association with OS.