tbuckley/cabot-search huggingface dataset:
Geographic and sociodemographic variations in disease burden, epidemiological trends, and risk factors of early-onset lung cancer: A global analysis.
Authors: Wang-Zhong Li, Xianhua Gui, Hengrui Liang, Wei Wang, Wenhua Liang, Jianxing He
Journal: Journal of Clinical Oncology (2024)

11169 Background: Exploring the emerging trend of early-onset lung cancer (EOLC) burden is pivotal for guiding the implementation of preventive strategies among young adults. We aimed to provide a comprehensive examination of the geographic and sociodemographic variations in the disease burden, along with epidemiological trends and risk factors associated with EOLC over the past three decades. Methods: EOLC refers to lung cancer diagnosed in individuals aged 20-49 years. Utilizing the GBD 2019 data, we estimated the age-standardised incidence, mortality, and disability-adjusted life years (DALYs) rates for EOLC by sex, socio-demographic index (SDI) quintiles, and geographical location for the period from 1990 to 2019. We investigated the relationships between concomitant risk factors and EOLC incidence at national level, and calculated the DALYs attributable to risk factors. The relative contribution of population growth, population ageing, and epidemiological changes to the variations in burden of EOLC over study period was measured using the decomposition analysis. Incidence was forecast to 2040 using the Bayesian age-period-cohort model. Results: A total of 135,704 EOLC cases, equating to a age-standardised incidence rate of 4.0 (95% UI 3.6 to 4.3) per 100,000, were estimated in 2019 worldwide and was the second leading cause of cancer death among young adults, with higher disease burden occurred in males and those from middle and high-middle SDI regions. An overall decreasing trend in burden of EOLC was observed globally; such trends were more pronounced among males and followed a gradient across SDI levels, with the greater decrease observed in high and high-middle SDI regions. Sex, tobacco smoking prevalence, per capita cigarette-equivalent estimates, average age of smoking initiation, ambient ozone pollution, and GDP per capita were independently and significantly associated with EOLC incidence at the population level. Smoking remained the top contributor to burden of EOLC, with the exception of Andean Latin America, North Africa, and the low SDI regions, where ambient particulate matter pollution and household air pollution from solid fuels ranked as the foremost attributable risk factors. Population growth was the primary driver behind the global increase in EOLC cases in low and low-middle SDI regions, while epidemiological changes accounted for the most substantial reduction in EOLC cases across most regions. The global incidental cases of EOLC was projected to increase by 31.1% in 2040, with a more pronounced increase in females and those from high-middle and middle SDI locations. Conclusions: Our findings underscore significant geographic and sociodemographic disparities in the epidemiological burden of EOLC, emphasizing the necessity for policymakers to devise and apply region-specific, evidence-driven preventive strategies.
CGP-based IO biomarker assessment and treatment utilization across a major US health system.
Authors: Alexa K. Dowdell, Ryan Meng, Roshanthi K. Weerasinghe, Ann Vita, Bela Bapat, Douglas Hanes, Brock Schroeder, Maude Champagne, John Leonard Fox, Cliff Wong, Hoifung Poon, Carlo B. Bifulco, Brian Piening
Journal: Journal of Clinical Oncology (2024)

e23109 Background: Immune checkpoint inhibitors (IO) have become a powerful precision therapy option to treat advanced stage cancer with biomarkers such as PD-L1, tumor mutational burden (TMB), and microsatellite instability (MSI) associated with improved patient response rates. Despite this, many patients do not receive genomic testing for all IO biomarkers. Providence, a large US community health system, developed a pathologist-directed testing protocol where comprehensive genomic profiling (CGP) was routinely used at time of diagnosis for advanced cancer patients. Methods: Advanced cancer patients who received CGP (ProvSeq 523) and IHC testing for PD-L1 between 2019-2023 were included in the study. Patients were required to be treated at Providence and were assessed for presence of IO biomarkers and subsequent therapy selection. Real world data were curated from patient charts and genomic laboratory data by employing a novel natural-language processing (NLP) approach to accelerate abstraction. Results: The study included 2,502 patients (53% female, median age 68y, 83% white). Top 3 tumor types tested were lung (40%), colorectal (9%), and breast (8%). Overall, 58% (N = 1,455) of patients had presence of ≥1 IO biomarker, with 46% (N = 1,155) being PD-L1 positive, and 27% (N = 682) being TMB-H. In PD-L1 negative patients (N = 1,347; 54%), 300 (22%) were TMB-H and 18 (1%) were MSI-H. 53% (N = 767) of patients who harbored an actionable IO biomarker received IO-based therapy. Fewer patients with an IO biomarker received chemotherapy compared to patients without an IO biomarker (23% vs 35%, p &lt; 0.001). Patients who possessed ≥2 IO biomarkers received an IO precision therapy 68% of the time vs 47% in patients with 1 IO biomarker (p &lt; 0.001). In PD-L1 negative patients, 26% (N = 78) of TMB-H patients received IO monotherapy compared to 5% (N = 49) of TMB-L patients. Conclusions: IO biomarker presence is associated with increased precision therapy use. CGP identified many TMB-H patients for IO monotherapy that would have been missed with PD-L1 testing alone. More than half of patients eligible for IO therapy don’t receive it; ongoing analyses will evaluate the impact of pathology-directed reflex testing on IO as well as targeted therapy approaches. [Table: see text]
Origin associated with heterogeneity amongst Hispanic patients with breast cancer in the United States.
Authors: Anahi McIntyre, Nadeem Bilani, Amy Tiersten
Journal: Journal of Clinical Oncology (2024)

e23077 Background: There are over 50 million self-identifying Hispanics in the United States. This, however, represents a heterogenous population variably affected by an array of determinants of health, including race and insurance status. We used a national registry to investigate for significant differences in outcomes of Hispanic patients with breast cancer in the United States by country of origin. Methods: We identified a cohort of Hispanic patients in the United States with breast cancer for which origin was documented using the 2004-2019 National Cancer Database (NCDB) dataset. The NCDB delineates the following specific origins: Puerto Rico, Mexico, Cuba, South or Central America (excluding Brazil), or the Dominican Republic. We performed multivariate logistic regression modeling to identify whether origin was a significant predictor of advanced cancer staging at diagnosis (AJCC stage III or IV), adjusting for age, race, receptor subtype, histology, grade, insurance status, and facility type. Consequently, we used Cox Regression survival modeling to investigate whether overall survival (OS) differed by Hispanic origin after adjusting for stage at diagnosis and other confounders of survival: age, race, stage at diagnosis, receptor subtype, and systemic therapy received. Results: Of the identified n = 60,438 Hispanic patients with breast cancer in the United States: n = 26,800 (44.3%) had Mexican, n = 9,792 (16.2%) had Puerto Rican, n = 5,283 (8.8%) had Cuban, n = 14,381 (23.8%) had South/Central American, and n = 4,172 (6.9%) had Dominican Republic origins. After adjusting for the aforementioned covariates, we found that origin was a significant predictor of staging at diagnosis (p &lt; 0.001). Patients originally from Mexico were more likely to be diagnosed at advanced stages compared to patients from Puerto Rico (OR 1.31; 95% CI, 1.18-1.46; p &lt; 0.001). We also identified that origin was a significant predictor of overall survival in this cohort even when controlling for various confounders, including stage at diagnosis. Compared to patients from Puerto Rico, patients from Central/South America (HR 0.78, 95% CI 0.70-0.88, p &lt; 0.001) and patients from the Dominican Republic (HR 0.77, 95% CI 0.65-0.92, p = 0.003) exhibited significantly improved overall survival. There was no statistically-significant survival difference between patients from Mexico and patients from Puerto Rico. Conclusions: This real-world analysis showed that, for Hispanic individuals living in the US with breast cancer, origin is significantly associated with outcomes even after accounting for other known determinants of health. We suggest that region of origin should be studied further as a potential determinant of outcomes in patients with cancer.
Assessing secular trends in lung cancer stage in the United States community oncology setting from 2013 to 2023.
Authors: Lisa Herms, Zhaohui Su, Nicholas J Robert, Amy K. O'Sullivan, Jessica K Paulus
Journal: Journal of Clinical Oncology (2024)

11178 Background: Detecting disease at an early stage is critical to improving lung cancer (LC) survival, as reflected in guidelines recommending screening with low dose computed tomography for individuals at high risk by clinical societies including the NCCN (2011) and US Preventive Services Task Force (2013, updated 2021). Presenting stage distribution may also be impacted by healthcare utilization changes following the COVID-19 pandemic. Real-world data (RWD)-based investigations are important complements to national cancer registries to provide insight into this potentially changing diagnostic landscape, especially given utilization, practice and referral patterns unique to community settings. We thus assessed LC stage from 2013-23 in a large, nationally representative sample of community oncology practices leveraging RWD. Methods: This is a retrospective observational cohort study of patients within The US Oncology Network and non-Network practices, which include a nationally representative network of over 3,700 providers and more than 1 million patients seen annually in community-based oncology practices. All adult (≥18 years) patients diagnosed with non-small cell LC (NSCLC) or small-cell LC (SCLC) who had a first observed stage available in the community oncology setting within 2013 to 2023 were included. Demographics and medical history data were sourced from structured data fields in iKnowMed, an oncology-specific electronic health record system. Time trends of patient diagnosis and characteristics were descriptively evaluated. Results: The analysis included 98,806 patients with LC (84,023 [85.0%] NSCLC and 14,783 [15.0%] SCLC). Approximately half were female (49.7% and 50.3% in each disease), three-fourths were White (72.7% and 77.0%, respectively), and mean ages at diagnosis were 69.9 and 68.1 years. From 2013 to 2023, there was an increase in the total number of patients observed in the database with a documented stage, from 7,159 to 9,115 (27.3% increase) for NSCLC and from 1,162 to 1,595 (37.3% increase) for SCLC. This was largely driven by an absolute increase in advanced stage diagnoses. The proportion of patients diagnosed with Stage IV NSCLC increased from 43.3% in 2013 to 49.3% in 2023, while the proportions of Stage 0/I and II diagnoses decreased. A similar trend was observed for SCLC, with 60.3% of patients diagnosed with Stage IV in 2013 compared to 68.2% in 2023. The proportion of Stage IV NSCLC cancers increased in the pandemic period, from 48.0% in 2019 to 51.6% in 2020 and 50.6% in 2021. Conclusions: Over the last decade, the proportion of advanced stage LC cases has increased, possibly reflecting changes in referral patterns and utilization specific to the community setting, including those related to the COVID-19 pandemic. The burden of advanced disease highlights the need for continuous investment in advanced-stage treatments as well as early detection efforts.
Patient navigation as an effective way to increase breast, cervical, and colorectal cancer screening among immigrants in the US: A systematic review.
Authors: Katherine Mann, Kennedy Sun, Jeffrey Jang, Aneka Khilnani, Emmalee Barrett, Thomas Harrod, Serena Phillips
Journal: Journal of Clinical Oncology (2024)

e22501 Background: Immigrants undergo recommended cervical, breast, and colorectal cancer screening at a lower frequency than U.S.-born patients and face unique language, educational, and cultural barriers. The delay or lack of screening has known implications in the presentation of breast, cervical, and colorectal malignancies, including worse staging at diagnosis. To address the disparity in cancer screening that immigrants experience, various interventions have been studied, including patient navigation (PN) programs. This systematic review aims to determine whether PN increases cervical, breast, and colorectal cancer screening in immigrant populations. Methods: A systematic literature search was conducted using PubMed, Scopus, and Web of Science to identify English-language articles published from January 2000 to November 2023 examining the role of patient navigators in encouraging routine breast, colorectal, and cervical cancer screening among immigrant populations in the United States. For the articles that met the inclusion criteria, details of patient navigation programs and uptake or change in cancer screening behaviors were extracted. Results: We screened 2196 articles, 53 of which met criteria for review, and 18 articles were ultimately included in the analysis. PN programs increased breast, cervical, or colorectal screening within immigrant populations compared to the control or alternative intervention in all 18 studies. In 7 out of 18 (38.9%) studies, the PN intervention group achieved screening rates similar to or above Non-Hispanic White national average screening rates. Two of those studies occurred in the outpatient setting, which resulted in higher screening rates than community-based settings. Two of those 7 studies that matched the Non-Hispanic White screening rates also had a longer duration of over 4 years. The majority of PN programs included educational sessions or materials and screening appointment scheduling assistance delivered from members of the same cultural group. Other services included identification and assistance with overcoming barriers, insurance assistance, reminders, transportation, and accompaniment to screening appointments. Of the 18 studies included, rural areas were underrepresented, and the training of patient navigators was not always described. Conclusions: Our review suggests that PN programs are effective at increasing cancer screening rates among immigrant populations, and certain aspects of PN programs, including outpatient settings and longer navigation duration, may help to further increase screening rates.
Long-term cardiovascular outcomes in survivors of 20 adult solid tumors: Large population-based matched cohort study.
Authors: Arunkumar Krishnan, Kunal C. Kadakia, Declan Walsh, Saleh A Alqahtani
Journal: Journal of Clinical Oncology (2024)

11177 Background: The past few decades have seen notable advancements in how cancer is diagnosed and treated, with improvements in cancer survival. Cardiovascular diseases (CVDs) are the major life-limiting comorbidity among cancer survivors. Evidence is scarce on the risks of specific CVDs in survivors of a wide range of solid tumors, hindering informed strategies for prevention and management. Thus, we evaluated a large population-based U.S. electronic health records database. Methods: This large retrospective cohort study was conducted by using the TriNetX dataset between January 2008 and December 2022. All adult patients (&gt;18 years) with a diagnosis of 20 most common solid tumors alive 12 months after diagnosis were matched with controls without a cancer history in a 1:1 ratio with these a priori identified potential confounders: demographics, BMI, nicotine dependence, comorbidities, labs, and medications. The primary outcome was the first incidence of CVD like heart failure (HF), major adverse cardiovascular events (MACE; unstable angina, myocardial infarction, or coronary artery intervention), or venous thromboembolism (VT), and cerebrovascular events (CVE; stroke, transient ischemic attack, cerebral infarction, carotid intervention). Hazard ratios (HR) were calculated to assess the outcomes. Results: 890126 individuals with a solid tumor of interest followed up at least 1 year later were identified and matched to 1787244 controls. The VT risk was higher among survivors of 18 out of 20 specific solid cancer types than controls. HRs ranged from HR 3.68( 95% CI 3.48-3.89) for kidney cancer and HR 1.27 (95% CI 1.21–1.35) in patients after pancreatic cancer. HRs for VT were more prominent without prior CVDs. Higher risks of CVDs were the most common immuno -and chemotherapy. Higher risk of HF was observed in lung (HR 1.46, 95% CI 1.32–1.89), liver (HR 1.22, 95% CI 1.18–1.26), and ovarian (HR 2.01, 95% CI 1.64–2.45) cancers and in patients younger than 55 years. Pericarditis and arrhythmia were common in lung, bile duct, and stomach cancers. A greater risk of arrhythmia was also observed in lung, kidney, and thyroid cancers, whereas CVE was observed in CNS cancers. Conclusions: Survivors of site-specific solid tumors are at a higher medium to long-term risk of one or more CVDs than the general population. Notably, substantial variations in risk were observed across different cancer primary sites. The outcomes underscore the importance of heightened monitoring for CVDs after a cancer diagnosis.
Association of higher baseline stress and pain with clinical outcomes: Secondary analysis from Alliance A011502.
Authors: Shipra Gandhi, Karla V. Ballman, Michelle D. Holmes, Kala Visvanathan, Banu Symington, Margaret Carvan, Carol Matyka, Anna Weiss, Eric P. Winer, Wajeeha Razaq, Lisa A. Carey, Ann H. Partridge, Wendy Y. Chen
Journal: Journal of Clinical Oncology (2024)

11016 Background: A011502 is a phase 3 randomized double-blind clinical trial that enrolled high-risk nonmetastatic breast cancer (BC) patients (pts) and randomized pts to aspirin 300 mg daily vs. placebo. There was no significant difference in invasive disease-free survival (iDFS) between the two arms. A secondary objective was to determine the association of inflammation-affiliated factors (stress, depression, poor sleep quality and pain) with iDFS and overall survival (OS). We hypothesized that these baseline factors are associated with worse clinical outcomes. Methods: At baseline, 2735, 2720, 2422 and 2610 pts completed Perceived Stress Scale (PSS), Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI) and Center for Epidemiologic Studies Depression Scale Revised (CESD-R) respectively. Stress was categorized with PSS scores: low (0-13), moderate (14-26) or high stress (27-40). Pain was categorized with BPI scores: none/mild (0-3) or moderate/severe (≥4). Sleep quality was categorized with PSQI scores: good (0-5) or poor ( &gt; 5).Depression was categorized with CESD-R scores: no depression (0-15) or depression (≥16). Associations between the measures of interest and outcomes were performed with multivariable Cox models controlling for age, body mass index, time since diagnosis, race, ethnicity, hormone receptor status and treatment arm. Results: Median follow up was 35 months. The associations from multivariable Cox model are shown in Table 1. Pts who reported high PSS had significantly worse iDFS and (non-significant) worse OS. Moderate/severe average (avg) pain was significantly associated with worse iDFS and OS. Poor sleep quality and depression were associated with worse iDFS and OS but not statistically significant. Conclusions: Pts reporting higher stress and pain at baseline had worse outcomes. We acknowledge that both pain and stress may be related to other non-cancer issues (chronic comorbidities). Our study highlights the need for clinical trials to consider including questionnaires to assess pt-reported outcomes. Future studies are warranted to determine if measures to decrease pain and stress would improve BC outcomes. U10CA180821, U10CA180882, UG1CA233196; https://acknowledgments.alliancefound.org . NCT02927249: Clinical trial information: NCT02927249 . [Table: see text]
Co-occurrence of germline pathogenic variants in a Brazilian cohort of patients with breast cancer.
Authors: Andreza Karine de Barros Almeida Souto, Thaiana Aragao Santana, Leandro Jonata Carvalho Oliveira, Marcela Lima Bulcao, João Paulo Gonzaga de Farias, Carolina de Bustamante Fernandes, Fernanda Christtanini Koyama, Daniela Tiaki Uehara, Fernanda Orpinelli Ramos do Rego, Layla Testa Galindo, Bruno Lemos Ferrari, Max S. Mano, Rodrigo Dienstmann, Mariano Zalis, Bernardo Garicochea
Journal: Journal of Clinical Oncology (2024)

e22532 Background: The estimated prevalence of germline pathogenic variants (PV) or likely pathogenic variants (LPV) in high and moderate penetrance genes is around 7-10% among women with breast cancer (BC). The emergence of next-generation sequencing (NGS) technology allowed multi-gene panel testing (MGPT) analysis at a lower cost. However, the detection of incidental findings with unknown significance (VUS) and challenges with variant interpretation increase substantially with MGPT. The effect of co-existing PV/LPV in two or more genes is still understudied. Here, we present the prevalence of concurrent germline LPV/PV in a cohort of Brazilian women with BC who underwent a MGPT in a single reference laboratory. Methods: Retrospective observational study using a laboratory cohort (Oncoclínicas Precision Medicine). This study includes women with BC who performed a germline MGPT (able to call SNVs, indels and CNVs) from 2019 to 2023. All patients were tested in a single reference laboratory (OC Precision Medicine) and originated from several Brazilian centers within the Oncoclínicas network. Two distinct germline NGS assays were used: breast and ovarian cancer (BOC) panel (36 genes) and a pan-cancer (PC) panel (105 genes). Results: In the overall cohort, 2,651 women with BC were included in this analysis. The median age at genetic testing was 51 years. 1,867 pts (70.4%) underwent a PC panel testing and the remaining 784 pts (29.6%) a BOC panel.Overall, 314 (12%) pts carrier of LP/PV in high- and/or moderate-penetrance genes. Two or more heterozygous LP/PV were found in 35 pts (1.32%), including 8 pts (1.02%) in the BOC panel and 27 pts (1.44%) in the PC panel subgroups. There were no differences in age of onset of BC in single vs co-occurring double mutants. The most frequent co-existing PV/LPV were found in BRCA2 (11) / BRCA1 (8) / PALB2 (4) / TP53 (3) and MUTYH (7) / CHEK2 (3) in the high and moderate penetrance genes, respectively. Six pts (0.23%) had a double heterozygous involving high and/or moderate penetrance genes. Interestingly, there was a case with four heterozygous variants in TP53, MUTYH, MUTYH and APC. Conclusions: In times of rapid incorporation of MGPT in the clinical practice, our real-world data showed that a small proportion of BC patients could be carriers of two or more germline heterozygous LP/PV in cancer genes. However, this represents a challenging scenario for patient and family management, especially in a co-occurrence of high and moderate penetrance genes.