tbuckley/cabot-search huggingface dataset:
Risk of secondary leukemias in patients with germline PALB2 pathogenic variants after chemotherapy exposure.
Authors: Hatem Ellaithy, Lauren Bear, Kathleen Steinberg, Douglas Scott Micalizzi, Andrew Mark Brunner, Arushi Saini
Journal: Journal of Clinical Oncology (2024)

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

10542 Background: Several susceptibility loci have been identified in genome-wide association studies (GWAS) of single nucleotide polymorphisms (SNPs) that are associated with ovarian cancers. Polygenic risk scores (PRS) combining certain loci have shown limited performance at predicting ovarian cancer risk. However, the utilization of PRS with ovarian cancer screening tests, like transvaginal ultrasound (TVU), warrants further evaluation. This study investigated the association between a polygenic risk score and ovarian cancer risk and abnormal TVU screening in a large-scale randomized controlled ovarian cancer screening trial. Methods: A polygenic risk score was constructed using weighted sums of risk alleles of 15 ovarian cancer SNPs identified in previous GWAS to evaluate the association with abnormal TVU screening results and ovarian cancer outcomes in female participants of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Complete genotyping information, TVU results, and ovarian cancer outcomes were available for 15722 females (mean age 62.2 years +/- 5.3) with European ancestry, including 116 ovarian cancer cases. Abnormal TVU was defined as ovarian volume or cyst volume &gt; 10 cm 3 , any solid/cystic component within a cystic ovarian tumor, or any solid area or papillary projection extending into the cavity of a cystic ovarian tumor. Polygenic risk scores were categorized as quartiles and odds ratios (OR) were calculated to assess risk of ovarian cancer or abnormal TVU result using the lowest PRS quartile as reference category. Results: TVU screening results were abnormal for 732 (732/15722, 4.66%) participants and normal for 14990 (14990/15722, 95.3%) participants at trial baseline. PRS within the fourth quartile demonstrated increased risk of ovarian cancer with reference to the lowest quartile (OR 1.77, 95% confidence interval: 1.04-3.08). Similarly, women in the highest quartile of the PRS had increased odds of an abnormal TVU screening result (OR 1.46, 95% confidence interval: 1.17-1.83) compared to women in the lowest PRS quartile. Conclusions: A polygenic risk score including 15 loci previously shown to be associated with ovarian cancer risk showed an association with increased ovarian cancer risk in the PLCO trial. Furthermore, the PRS was also associated with abnormal ultrasound results. Our findings support further evaluation of polygenic risk scores and transvaginal ultrasound for ovarian cancer risk stratification and screening approaches.
Burden of gastrointestinal luminal tract cancer (GLC) from 2000 to 2019 in low SDI countries.
Authors: Sakditad Saowapa, Natchaya Polpichai, Chalothorn Wannaphut, Manasawee Tanariyakul, Phuuwadith Wattanachayakul, Pharit Siladech, Diego Alonso Olavarria Bernal, Lukman Aderoju Tijani
Journal: Journal of Clinical Oncology (2024)

10558 Background: In regions with low social and economic development, gastrointestinal luminal cancer (GLC) poses a significant burden, and disparities in care are prevalent, leading to adverse disease outcomes but remain poorly studied. This study aims to assess the epidemiology of GLC in low Socio-demographic Index (SDI) regions. Methods: We analyzed temporal trends in the burden of GLC (Colorectal cancer, Esophageal cancer, Stomach cancer) using data from 2000 to 2019 from the Global Burden of Disease Study 2019. We conducted a comprehensive analysis of annual frequencies, age-standardized rates (ASRs), age-specific death rate (ASDR), and annual percentage change (APC) of luminal GI cancer incidence, death, and disability-adjusted life-years (DALYs) by sex, country, and cancer type. Results: In 2019, the frequency of incident cases due to colon cancer, esophageal cancer, and stomach cancer was 39,045, 28,132, and 43,188 respectively, with a male predominance. The number of death cases and DALYs is highest in stomach cancer, with 43,876 deaths and 1,233,251 DALYs, respectively. During 2000 to 2019, the ASDRs increased significantly for colon cancer (APC: 0.78% (0.71 to 0.84), while they decreased significantly for esophageal cancer (APC: -0.57% (-0.65 to -0.48)) and stomach cancer (APC: -1.1% (-1.26 to -0.96)). The highest ASDRs in colorectal cancer were noted in 2019 in Uganda (11.55 (9.24 - 13.75)), while the highest increase in APC in colorectal cancer was noted in Burkina Faso (APC: 1.27% (1.12 to 1.42)). Conclusions: In the preceding decade, the epidemiological landscape of GLC in low SDI countries has undergone dynamic shifts, demonstrating a heavier shift towards colorectal cancer. These findings warrant heightened awareness and strategic interventions to combat the disease.
Differences in shared decision-making and prostate cancer screening by sexual orientation and race/ethnicity.
Authors: Kirsten Nguyen, Gilbert Gonzales
Journal: Journal of Clinical Oncology (2024)

10525 Background: There are well-documented disparities among racial and sexual minorities in prostate cancer screening uptake and shared-decision making (SDM) conversations. However, it is unclear how racial/ethnic identity and sexual orientation interact to affect prostate-specific antigen (PSA) testing uptake. Methods: Data came from the 2018-2022 Behavioral Risk Factor Surveillance Survey (BRFSS). Outcomes were survey responses to questions about engagement in SDM and PSA testing uptake. The sample included 88,365 heterosexual (HS) men and 2,562 sexual minority (SM) men ages 55 to 69. Data were stratified by race/ethnicity and survey-weighted logistic regression models analyzed the association between sexual orientation and outcomes. Models controlled for age, relationship status, education, household income, insurance status, having a usual source of care, and region. Results: White SM men were more likely to have discussed disadvantages of PSA testing with their healthcare provider [odds ratio (OR)=1.407; p&lt;0.001] and to have undergone PSA testing [OR=1.320; p&lt;0.001] compared to White HS men. Asian SM men were more likely to have had discussions about PSA testing [OR=4.470; p&lt;0.05]; to have discussed advantages [OR=4.596; p&lt;0.05]; to have been recommended PSA testing [OR=4.836; p&lt;0.05] and to have undergone PSA testing [OR=4.401; p&lt;0.001] compared to Asian HS men. Black SM men were more likely to undergo screening because of an issue or a reason besides routine screening [OR=1.073, p&lt;0.05] compared with Black HS men. Hispanic SM men were more likely to have undergone screening as part of a routine checkup [OR=4.2, p&lt;0.001] compared with Hispanic HS men. There were no sexual orientation differences in PSA screening or SDM among American Indian or Native Alaskans. Conclusions: Differences in PSA testing uptake and SDM by sexual orientation vary by race/ethnicity. Further research is needed to study the factors affecting PSA testing uptake and SDM among sexual minority men of different racial/ethnic groups. [Table: see text]
Efficacy and safety of dinutuximab in the management of high-risk neuroblastoma: A systematic review and meta-analysis.
Authors: Malik Waleed Zeb Khan, Muhammad Ahmad, Muhammad Maaz Bin Zahid, Salman Khan, Dawood Shehzad, Jibran Ikram, Meekoo Dhar
Journal: Journal of Clinical Oncology (2024)

e22000 Background: Neuroblastoma (NB) is a malignant tumor of the sympathetic nervous system that usually occurs in children below 5 years of age. High-risk neuroblastoma (HR-NB) has a poor prognosis despite a number of treatment strategies. Dinutuximab, an anti-GD2 monoclonal antibody, has been recently added to the standard of care due to its improved prognosis. We aimed to systematically assess the outcomes of HR-NB patients treated with dinutuximab and compare them with those on other treatment regimens. Methods: A comprehensive search strategy was used to search PubMed and the Cochrane Library for articles investigating the effect of dinutuximab on the outcomes of patients with HR-NB. Eligibility criteria included: 1) Diagnosis of HR-NB based on INRG and INSS staging and MYCN status 2) Dinutuximab as the primary agent used in the intervention group 3) Mean/median follow-up time greater than 6 months. Three investigators independently reviewed and extracted relevant articles. Any disagreements were addressed through consultation with other authors. The risk of bias assessment of the selected articles was conducted using the Cochrane Risk of Bias Tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa scale for observational studies. Review Manager software was used to obtain and display the meta-analysis estimates in forest plots. Random effects models were used to calculate the mean difference and overall estimated effects for continuous variables. The primary outcomes were all-cause mortality and 5-year event-free survival (5-year-EFS). Results: Five studies, including two RCTs, two secondary analyses of clinical trials, and one retrospective cohort study, comprising 1,393 participants, were included in the analysis. 686 of the patients received dinutuximab, while the remaining 707 patients were assigned to other therapies as controls. Dinutuximab was associated with lower all-cause mortality as compared to control [pooled RR, 0.41; 95% CI, 0.22-0.75, P = 0.004, I2 = 31%]. 5-year-EFS was also greater for patients treated with dinutuximab [MD: 0.12; 95% CI, 0.09-0.16; P &lt; 0.001, I 2 = 98%]. Conclusions: Our findings suggest that dinutuximab is linked to a significant reduction in overall mortality and a noteworthy improvement in the 5-Year-EFS for patients with HR-NB, when compared to other treatment options.
Cancer burden in South Asians in the United States: Epidemiologic report using Surveillance, Epidemiology, and End Results (SEER) program.
Authors: Jasmin Hundal, Yanwen Chen, Moaath Khader Mustafa Ali, Akriti Gupta Jain, Anjali S. Advani, Aaron Thomas Gerds, Sophia Balderman, John C. Molina, Hetty E Carraway, Sudipto Mukherjee, Abhay Singh
Journal: Journal of Clinical Oncology (2024)

10574 Background: Studying racial-ethnic disparities in cancer risk can help in identifying underlying factors and developing targeted screening and education strategies. South Asian Americans (SAA), Asian Indians and Pakistanis, are a fast-growing ethnic group in the US, but there is limited research on their cancer risks. This study examines cancer prevalence patterns in the SAA population compared to Whites in the US. Methods: We analyzed cancer prevalence in 5,120,423 patients diagnosed with 23 different types of cancer between 2000 and 2018, using data from 18 SEER cancer registries. We compared cancer prevalence between SAA and Whites and examined factors such as cancer types, demographics, socioeconomic status, and urban vs. rural residency. Χ 2 test was used to determine statistical significance (p&lt;0.001). Results: Our analysis revealed higher prevalence of breast (19.0% vs. 14.6%) and thyroid (5.9% vs. 2.8%) cancers among SAAs compared to Whites, but lower rates of lung (6.5% vs. 12.0%), colorectal (5.9% vs. 7.4%), and melanoma (0.8% vs. 5.4%) cancers; p&lt;0.001. Demographically, a significantly larger proportion of younger individuals (22.3% vs. 10.0%, ages 00-44) were found in the SAA cohort. The SAA survivor cohort also had a significantly higher percentage of females (50.8% vs. 48.6%) and married individuals than their White counterparts (69.3% vs 55.3%). Lastly, there were significant state-based variances in cancer prevalence. In California, SAAs had a lower cancer prevalence (23%) compared to Whites (38.5%), while in New Jersey, SAAs had a higher cancer prevalence (36.7%) than Whites (12.3%). Conclusions: Our analysis shows a disparity, highlighting the need for culturally attuned healthcare policies to enhance cancer education and screening among diverse groups. The higher prevalence of breast cancer in SAAs suggest possible effective screening, while lower rates of colorectal and lung cancers point to potential awareness gaps or cultural barriers. Addressing these, alongside researching genetic, environmental, and lifestyle influences—particularly given the younger SAA cancer population—is prudent. A focused approach, emphasizing targeted public health initiatives and further research, is necessary to enhance cancer outcomes and ensure health equity.
Pediatric cancer registry in Turkey 2002-2023: 22 years of achievement (TPOG &amp; TPHD).
Authors: M. Tezer Kutluk, Akif Yeşilipek
Journal: Journal of Clinical Oncology (2024)

10051 Background: The survival rates for childhood cancer have seen significant improvements in high-income countries over the past few decades. However, in low- and middle-income countries, it remains a substantial challenge. Access to care remains a significant barrier to improving survival rates in low- and middle-income countries (LMICs). The pediatric cancer registry is a crucial component of pediatric cancer control efforts. In this context, we present the findings from 22 years of the pediatric cancer registry in Turkey. Methods: The present pediatric cancer registry was established by Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association in 2002. The childhood cancer cases registered between 2002-2023 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 22 years from 2002 to 2023, 50887 cases were registered. For all cases, median age was 6.5 year (0-19; M/F 28641/22233, 6 hermaphrodite, 7 unknown). Age distribution was 0-4 yrs, 41.1%; 5-9 yrs, 24.7%; 10-14 yrs, 23.1%; 15-19 yrs, 11.0%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (14633, 28.8%, 5.6, 8510/6123); Lymphoma &amp; other RES tumors (8958, 17.6%, 9.2, 5956/3000, 2 unknown); CNS [brain &amp; spinal] (7299, 14.3%, 7.0, 4066/3232, 1 unkown); Sympathetic system (3783, 7.4%, 2.4, 1951/1831, 1 hermaphrodite); Retinoblastoma (1444, 2.8%, 1.5, 752/692); Renal (2310, 4.5%, 3.1, 1140/1168, 1 hermaphrodite &amp; 1 unknown); Liver (732, 1.4%, 2.1, 428/304); Malignant bone (3122, 6.1%, 12.5, 1747/1375); Soft tissue sarcomas (3675, 7.2%, 7.3, 2047/1628); Germ cell (2933, 5.8%, 8.9, 1077/1849, 4 hermaphrodite, 3 unknown); Carcinoma &amp; other malignant epithelial (1628, 3.2%, 13.1, 783/845); Other/non-specific malignant (370, 0.7%, 7.8, 184/186). Five-year survival rate was found as 71.1%. Conclusions: The survival rates for children and adolescents have improved to 70%, a figure comparable to that of other middle-income countries and reflective of the quality of pediatric cancer care in Turkey. This represents a successful pediatric cancer registry from a middle-income country, covering a period of over 20 years. It has become a valuable resource for stakeholders at both the national and international levels.
Comparative risk of obesity-related cancer with glucagon-like protein-1 receptor agonists vs. bariatric surgery in patients with BMI ≥ 35.
Authors: Cindy (Hsin-Ti) Lin, Benjamin Liu, Hannah Hill, Jiasheng Wang, Xiaonan Han, Scot C. Remick, William Tse, Gengqing Song
Journal: Journal of Clinical Oncology (2024)

10508 Background: Bariatric surgery is suggested to reduce the risk of obesity-related cancers, prompting us to explore whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) offers a similar association. Methods: We queried TriNetX, a global healthcare database to identify patients with BMI of ≥ 35. Three pair-wise propensity score-matched (PSM) comparisons were created: 1) GLP-1 RA vs. Bariatric Surgery, 2) GLP-1 RA vs. No Intervention, 3) Bariatric Surgery vs. No Intervention. Cohorts were exclusive and no intervention was defined as an ambulatory visit. Patients required a minimum of 1 year of continuous GLP-1 RA therapy or follow-up, extended to 3 and 5 years in sensitivity analyses. Exclusions included a history of cancer or in situ neoplasms, as well as factors that significantly impact cancer risk and/or mortality including alcohol use disorder, organ transplantation, HIV, decompensated cirrhosis, peptic ulcer disease, dialysis dependency, left ventricular ejection fraction ≤ 20%, or other weight loss medication exposure. PSM utilized obesity therapy indications, Elixhauser and Charlson Comorbidity indices, prior follow-up, and demographics. Follow-up extended to 15 years, assessing 13 obesity-related cancers after intervention using Kaplan Meier (KM) and Cox-proportional Hazards Models (HR). Secondary outcomes included the risk of all-cause mortality and precancerous lesions. Results: After PSM, we identified 20,009, 3,229, and 11,104 patients in Comparison 1, 2, and 3, respectively. For Comparison 1, at 15 years, 273 (KM event rate 8.75%) patients on GLP-1 RA therapy and 397 (6.58%) with bariatric surgery developed an obesity-associated cancer, respectively (HR 0.99; 95% CI 0.87 - 1.13). Patients who received GLP-1 RA (HR 0.61; 95% CI 0.46 - 0.81) and bariatric surgery (HR 0.78; 95% CI 0.67 - 0.91) had a reduced risk of obesity-related cancer compared to no intervention. Among 20,009 patients, 40 (0.353%) and 61 (0.876%) of patients developed thyroid cancer in the GLP-1 RA and bariatric surgery groups, respectively (HR: 0.837; CI: 0.558 - 1.254). Patients lost significantly more weight after bariatric surgery as compared to GLP-1 RA at 1-2 years (BMI change -5.31 ± 6.05 vs. -1.57 ± 5.12 kg/m 2 ; p &lt; 0.0001). GLP-1 RA initiation was associated with lower all-cause mortality compared to control (HR 0.5; 95% CI 0.40 - 0.62) and bariatric surgery (HR 0.859; 95% CI 0.77 - 0.96). Neither GLP-1 RA nor bariatric surgery was associated with precancerous lesions compared to control. Sensitivity analyses supported the above outcomes. Conclusions: GLP-1 RA was associated with a lower risk of obesity-related cancer comparable to bariatric surgery in patients with BMI ≥ 35. GLP-1 RA has superior all-cause mortality benefits despite inferior weight loss compared to bariatric surgery.
Racial disparities in pediatric patients with acute myeloid leukemia.
Authors: Ashley Becker, Anjali Mishra, Maya Mathews, Peter T. Silberstein, Michelle Swedek
Journal: Journal of Clinical Oncology (2024)

10031 Background: Leukemia is a cancer of the blood and bone marrow characterized by the rapid and uncontrolled production of abnormal white blood cells. Acute myeloid leukemia (AML) makes up 15–20% of all childhood acute leukemias (1). The purpose of this study is to use the National Cancer Database (NCDB) to provide an updated investigation of racial disparities in survival in pediatric patients with AML. Investigating the different factors associated with poor outcomes provides valuable information when allocating resources and understanding where policies will be useful to improve patient outcomes. Methods: Pediatric (0-19 years old) AML patients were identified in this retrospective cohort study via the 2004-2020 NCDB. Chi square analysis, Fischer's exact test, and t-tests were used to analyze demographic variables. Kaplan Meier survival analysis was used to compare mean survival across race categories which was repeated with demographic variables of interest using a multivariate Cox regression. Results: A total of 4765 patients were identified in this study. Most patients were male (53.5%), White (73.0%), held private insurance (52.3%), and resided in metropolitan areas (82.0%). The mean age at diagnosis was 8.1 years old. There was no significant difference in age at diagnosis and time to treatment start across racial categories. Black patients had lower mean survival compared to White patients (131 vs 148 months, p&lt;0.001). When controlling for age, sex, metropolitan status, comorbidity status, income, education, and insurance status as covariates, Black race independently portended a poorer prognosis compared to White race (hazard ratio: 1.174, 95% confidence interval: 1.003-1.376, p=0.046). Black patients were more likely to be uninsured (4.1%) compared to White patients (2.8%) (p&lt;0.001). Black patients were more likely to reside in zip codes with lower incomes (36.0% vs 17.6%, p&lt;0.001) and lower education attainment (38.7% vs 27.8%, p&lt;0.001) compared to White patients. Black patients were more likely to have comorbidities with a Charlson-Deyo score of &gt;1 than White patients (11.2% vs 6.2%, p&lt;0.001). Black patients were also more likely to be from metropolitan areas than White patients (90.5% compared to 83.9%, p&lt;0.001). Conclusions: This study indicates that Black AML patients experience lower survival rates and are subject to more predictors of poor outcomes. Black patients were more likely to be uninsured, have comorbidities, live in zip codes with lower incomes and lower education attainment. 1. Morais, R. V. de et al (2021). J De Pediatria, 97(2), 204–210. https://doi.org/10.1016/j.jped.2020.02.003.