tbuckley/cabot-search huggingface dataset:
Risk of stroke in patients with atrial fibrillation and chronic lymphocytic leukemia.
Authors: Ekrem Yetiskul, Taqi Rizvi, Shahkar Khan, Salman Khan, Omer Alomari, Alaukika Agarwal, Samer Asmar, Sajan Sah, Georges Khattar, Yisroel Grabie, Fares Saliba, Amanda Marie Matra, Asmaa Mokhtar, Meekoo Dhar, Alexander Bershadskiy, Danyal F. Khan, Ahmad Mustafa, Jonathan Spagnola, Valay K. Parikh
Journal: Journal of Clinical Oncology (2024)

e19030 Background: There has been a noticeable increase in the incidence of Atrial Fibrillation (AF) in patients with Chronic lymphocytic leukemia (CLL), especially patients treated with first-line therapy medications such as ibrutinib. However, these patients' risk of thromboembolic events is not well defined. Methods: Data for hospitalized patients with AF was obtained from The National Inpatient Sample (NIS) database from 2016-2018. Baseline risk factors were identified using ICD-10 codes. Patients who were already on anticoagulation were excluded. A logistic regression model was used to establish the relationship between variables and to adjust for underlying risk factors. The primary outcome was ischemic stroke between CLL and non-CLL patient cohorts. Results: The total number of patients was 1784456, out of which 1171644 patients were included in the study. There were 1165283 patients without CLL and 6361 with CLL. AF patients with CLL had more males (62.5% vs. 37.5%; P&lt;.001), were older (74.6 vs. 78.82; P&lt;.001), and had a lower prevalence of diabetes, hypertension, coronary artery disease, and hyperlipidemia. Pre-match analysis showed a lower rate of stroke in patients with AF and CLL compared to those without CLL (2.7% vs 4.2%; p&lt;0.001). Post-match analysis revealed similar results with a lower risk of strokes in patients with CLL (4% vs 2.7%; p&lt;0.001). Binary logistic regression analysis for primary and secondary outcomes revealed similar results pre-match and post-match. Patients who have AF and CLL had lower rates of stroke compared to those without CLL (OR: 0.647(0.530–0.790); p&lt;0.001). Conclusions: AF patients with CLL were associated with a lower risk of ischemic stroke compared to those without CLL despite a higher risk profile as assessed by traditional risk factors. These findings should be considered while making decisions for therapies for the prevention of thromboembolic events.
Real-world treatment switching and sequencing to next line of therapy of zanubrutinib, acalabrutinib, and ibrutinib in CLL/SLL.
Authors: Javier Pinilla-Ibarz, Mei Xue, Elizabeth Wu, Kaitlyn Esselman, Wesley Furnback, Swetha Challagulla, Keri Yang
Journal: Journal of Clinical Oncology (2024)

e19022 Background: Evaluating use of Bruton tyrosine kinase inhibitors (BTKis) for the treatment of CLL/SLL is crucial to understand real-world outcomes of these therapies in diverse populations. The objective of this study was to evaluate real-world switching and sequencing to next line of therapy in patients (pts) initiating BTKis as first-line (1L) or second-line (2L) CLL/SLL treatment. Methods: A retrospective study was conducted using IntegraConnect PrecisionQ to identify adult pts with ≥1 diagnosis for CLL/SLL initiating zanubrutinib (zanu), acalabrutinib (acala), or ibrutinib (ibru) in 1L or 2L between 1/1/2020-2/28/2023 (index period). Index date was defined as date of BTKi initiation. Pts were required to be continuously enrolled for ≥30 days pre- and post-index date. Treatment switching was measured as pts initiating another treatment within same line or advancing to next line of therapy within 90 days. Sequencing to next line of therapy was calculated from time to next treatment Kaplan-Meier curve, censoring patients at end of follow-up, and reported as proportion of pts receiving next line of therapy at 180 days. Results: 2,816 pts initiated a 1L BTKi (zanu=157; acala=1,238; ibru=1,421) and 1,253 initiated a 2L BTKi (zanu=107; acala=672; ibru=474). No major differences were observed in baseline demographic and clinical characteristics among 1L and 2L BTKi cohorts. Median follow-up in 1L was 123 days for zanu, 406 days for acala, and 637 days for ibru. Regardless of line of therapy, switching rate at ≤60 days and 61-89 days was statistically significantly lower for pts receiving zanu vs acala and ibru (P&lt;0.0001, both 1L and 2L) (Table). Proportion of pts receiving next line of therapy at 180 days was lower for zanu vs acala and ibru (1L P=0.2958; 2L P&lt;0.0001) (Table). Conclusions: Zanu pts had significantly lower switching rate within 90 days and lower proportion of pts receiving next line of therapy at 180 days when compared with acala and ibru in 1L and 2L. Longer follow-up and larger zanu sample size are required for a comprehensive assessment of treatment outcomes associated with use of BTKis in CLL/SLL. [Table: see text]
A cross-sectional study of synchronous liver metastasis in patients with gastric cancer.
Authors: Haijun Zhang, Tingya Wang
Journal: Journal of Clinical Oncology (2024)

e16015 Background: The specific organ microenvironment can promote the colonization of tumor cells. However, lack of research shed light on the liver microenvironment in synchronous liver metastasis in patients with gastric cancer (synGCLM). With the epidemic of hepatitis B virus (HBV) infection in China, we aim to explore the influence of hepatitis B surface antigen (HBsAg) on the risk of synGCLM. Methods: It was a cross-sectional study that enrolled 858 cases of newly diagnosed gastric cancer (GC). SynGCLM confirmed by biopsy or imaging evaluation reported by two senior radiologists. HBsAg-positive was defined as the detection of serum HBsAg more than 10 IU/mL. The prevalence of synGCLM was compared between patients with HBsAg (HBsAg + ) and those without HBsAg (HBsAg - ). The risk factors for synGCLM were analyzed by univariate and multivariate logistic regression analyses. Especially in the HBsAg + GC patients, aspartate aminotransferase to platelet ratio index (APRI), liver fibrosis-4 index (FIB-4) levels and hepatitis B e antigen (HBeAg) status were further analyzed. Results: The prevalence of synGCLM of the HBsAg + group was 16.7%, higher compared to 7.0% of the HBsAg - group, which was of statistical significance (p = 0.014). Multivariate logistic regression analysis demonstrated that HBsAg (Odds ratio (OR) = 3.359, p = 0.008), the elevated level of carcinoembryonic antigen (CEA) (OR = 3.775, p &lt; 0.001), alpha-fetoprotein (AFP) (OR = 6.204, p &lt; 0.001), γ-glutamyltransferase (GGT) (OR = 5.081, p &lt; 0.001), alkaline phosphatase (ALP) (OR = 3.968, p = 0.002) and age (OR = 1.028, p = 0.033) were risk factors for synGCLM. Among the HBsAg + patients, both ARPI and FIB-4 were statistically higher in the patients with synGCLM (synGCLM + ) compared to those without synGCLM (synGCLM - ) (ARPI: p = 0.045; FIB-4: p = 0.047); HBeAg positivity was detected in 20.0% of synGCLM + patients compared to 6.0% of synGCLM - patients, but the difference was of no significance (p = 0.190). Conclusions: HBV infection is a risk factor for synGCLM whereas elevated ARPI and FIB-4 may be pro-metastatic especially among the HBsAg + GC patients. Age, preoperative CEA, AFP, GGT and ALP levels are associated with increased risk of synGCLM.
Advanced signet ring cell type gastroesophageal cancers in Latin American patients age 40 and below: A summary of one tertiary care center's experience and a review of the literature.
Authors: Timothy Lewis Cannon, Jamie Randall, Whitney Rose Swain, Haresh Mani, Raymond Couric Wadlow, Jasmine Huynh, Arthur Winer
Journal: Journal of Clinical Oncology (2024)

e16069 Background: Gastric Cancer mortality rates in Latin American countries of Central and South America (LA) are among the highest in the world. After observing multiple cases of advanced gastric adenocarcinoma (GA) with signet ring cell differentiation in young immigrants from LA, we sought to understand the prevalence and demographics of young-onset gastric cancer at our institution. Methods: We used the Inova Fairfax Hospital cancer registry to perform a retrospective cohort study by identifying all patients ≤ 40 from 2013-2022 with 1) GA, and 2) all cancers, and comparing the percentage of LA patients in each group. We noted a trend towards high rates of GC in young immigrants of LA six years ago, and now provide an updated analysis. We then reviewed phenotypic characteristics of each tumor, including signet ring cell differentiation, Her-2/Neu overexpression, and H. Pylori status and the time interval between diagnosis and death. Results: From 2013-2022, 21/37 patients (56.8%) ≤ 40 with GA were from LA (Table 1), with the majority from El Salvador. 95% (20/21) of LA patients had tumors with signet ring cell morphology, 88% (14/16) of non-LA patients had tumors with signet ring cell morphology. In comparison, patients that self-identified as “Hispanic/Spanish” made up 8.1% of subjects ≤ 40 with all cancers during the same time period. Conclusions: At our tertiary care center, Stage IV signet ring cell gastric cancer is highly prevalent in young patients from Latin America. Further exploration of epidemiological risk factors is warranted. [Table: see text]
Hodgkin’s lymphoma, lymphocyte-depleted, reticular: An NCDB analysis of demographic and socioeconomic factors of diagnosed patients.
Authors: Frances Nowlen, Kat Chin, Po Jung Huang, Anas Halloum, Peter T. Silberstein, Craig Heise, Beau Hsia
Journal: Journal of Clinical Oncology (2024)

e19033 Background: Lymphocyte-depleted Hodgkin's lymphoma (LDHL) is an aggressive, rare form of Hodgkin’s lymphoma (HL). The LDHL reticular subtype (LDHL-R) is characterized by a scant invasion of lymphocytes without an increase in collagen fibers by fibroblasts. Patient demographics and clinical features of LDHL-R are poorly understood, causing it to frequently be misdiagnosed as other variants of HL. At diagnosis, patients have often already progressed to late disease staging. The demographic and socioeconomic factors of patients diagnosed with LDHL-R within the National Cancer Database (NCDB) were analyzed to better understand its epidemiology. Methods: A retrospective cohort analysis was performed using data from the 2004-2020 NCDB of the 51 cases of LDHL-R (ICD-O-3 9655). Demographic and socioeconomic factors such as age, sex, race, Hispanic status, treatment facility type, Charles-Deyo score, and 90-day mortality were examined using descriptive statistics. Diagnostic trends were quantified through regression analysis. Results: A total of 51 patients were diagnosed with Hodgkin lymphoma, lymphocyte depletion, reticular subtype within the NCDB. The most common primary site of diagnosis was within lymph nodes of multiple regions (41%). The majority of patients were males (65%), White (72%), and non-Hispanic (74%). Patients tended to have residence in metropolitan counties with populations greater than 1 million (71%) and were enrolled in academic/research programs (36%). Most of the patients were privately insured (41%) followed by those insured by Medicare (29%). A higher percentage of patients were in the top quartile of income earners (31%) than those in the second, third, or fourth quartiles. The incidence rate of diagnosis remained constant from 2004 to 2020 (R² = 0.02). The mean age of diagnosis was 51 years (SD=21, Range=14–90). Using the AJCC System, patients tended to be classified as Stage IV (41%) at diagnosis and had a Charlson-Deyo comorbidity score of 0 (71%). Primary treatment methods involved chemotherapy (84%) and radiation therapy (20%). Surgical intervention was given to 14 patients, and post-surgery survival rates were 93% after 90 days. Conclusions: To the best of our knowledge, this is the first NCDB analysis of the demographic factors of patients diagnosed with LDHL-R. Consistent with previous studies about the aggressiveness of this subtype of Hodgkin’s Lymphoma, most patients received a Stage IV diagnosis. Understanding LDHL-R’s epidemiology could result in significantly earlier diagnoses and improved prognosis. Patients tended to be male, White, and non-Hispanic with a residence in metropolitan counties. To improve understanding of the impact of demographic and socioeconomic factors of the diagnosis, treatment, and survival of patients with LDHL-R, more research is recommended.
The clinical significance and expression of MAGE-A3 in patients with esophageal squamous cell carcinoma.
Authors: Lan Wang, Jing Zuo, Yudong Wang, Li Feng, Zhisong Fan, Long Wang, Jing Han, Xue Zhang, Jiayin Liu, Dan Li, Hui Jin
Journal: Journal of Clinical Oncology (2024)

e16065 Background: More than half of esophageal cancer patients are diagnosed as advanced, and although immunotherapy has shown strong anti-tumor activity in esophageal cancer patients, the survival benefits are limited. Melanoma-associated antigen 3 (MAGE-A3) is a cancer testis antigen that is almost not expressed in normal tissues, but highly expressed in various malignant tumors, including esophageal cancer. MAGE-A3 has restrictive expression and good immunogenicity, making it an ideal immunotherapy target. This study aims to explore the expression and clinical significance of MAGE-A3 in esophageal squamous cell (ESCC) . Methods: 103 ESCC tissues and 77 adjacent cancerous tissues were collected, and the expression of MAGE-A3 was detected using immunohistochemistry. Furthermore, the relationship between MAGE-A3 and clinical pathological features was analyzed, and the prognostic significance of MAGE-A3 for ESCC patients was analyzed with overall survival (OS) as the endpoint. Results: The positive expression rate of MAGE-A3 in ESCC tissue was 68.0% (70/103), and the positive expression rate in adjacent tissues was 7.8% (6/77). The positive expression in ESCC was significantly higher than that in adjacent tissues. In ESCC, the expression of MAGE-A3 is associated with age, pathological grade, TNM staging, and lymph node metastasis. Both univariate and multivariate analyses showed that the expression of MAGE-A3 is an independent risk factor affecting the prognosis of ESCC patients. The high expression of MAGE-A3 predicted poor OS for ESCC patients. Conclusions: MAGE-A3 is highly expressed in ESCC and is associated with poor prognosis, and could be a potential prognostic marker and therapeutic target.
Survival outcomes in patients with stage IV gastric cancer with Krukenberg tumors: A systematic review and meta-analysis.
Authors: Junaid Anwar, Ahmed Abdelhakeem, Muhammad Shariq Khan, Hafiz Muhammad Arslan, Zouina Sarfraz, Anwaar Saeed
Journal: Journal of Clinical Oncology (2024)

e16020 Background: Stage IV gastric cancer patients with Krukenberg tumors tend to have poor survival outcomes, usually less than 2 years. The management of such tumor groups remains unstandardized, and whether oophorectomy improves survival is unknown. In this study, we systematically analyze the survival outcomes in gastric cancer patients with ovarian metastases who received either standard chemotherapy, surgical resection of ovarian metastases, or combined chemotherapy and surgery. Methods: We synthesized randomized controlled trials and observational studies, which were retrieved by systematically searching MEDLINE (PubMed), Embase, and the Cochrane Library through January 25, 2024, using the Boolean logic. Participants included individuals with pathologically and radiologically confirmed ovarian metastasis or clinically symptomatic cases with imaging evidence. Statistical analyses were conducted using R (v.4.3.2., Vienna) (PROSPERO ID-CRD42023488373). Results: A total of 1502 patients from 17 retrospective studies were pooled for differential overall survival (OS) outcomes ( Table). The OS in the standard chemotherapy cohort using the random effects model was 6.708 months (95% CI: 3.867 to 9.548). Heterogeneity was non-significant (P = 0.3854) with I2 of 5.5%. In the surgical resection cohort, OS was 12.786 months (95% CI: 6.9 to 18.671). I2 was 0%, and heterogeneity was low (P = 0.6013). In the combined chemotherapy and surgical resection cohort, OS was 16.228 months (95% CI: 12.254 to 20.202). I2 was 0%, and heterogeneity was insignificant (P = 0.9632). Conclusions: This meta-analysis provides novel insights into survival outcomes associated with distinct therapeutic modalities in gastric cancer with krukenberg metastases, contributing valuable evidence for clinical decision-making and future research directions. While the combined approach of chemotherapy and surgery demonstrates the highest effect size for OS, judicious consideration of patient-centric approaches is imperative in the oncological care landscape. [Table: see text]
Effect of two enteral immunonutrition formulas on immune function in Chinese patients with gastrointestinal cancers undergoing surgery: A secondary analysis of a randomized clinical trial.
Authors: Xuan Xu, Yan Liu, Gang Xiao, Yanbing Zhou, Bin Liang, Baogui Wang, Weiming Kang, Yingjiang Ye, Han Liang, Guole Lin, Jianchun Yu, Wei Chen
Journal: Journal of Clinical Oncology (2024)

e16019 Background: Immunomodulating nutrition is believed to reduce systemic inflammation and postoperative complications in surgical patients.This study aimed to evaluate the impact of two enteral immunonutrition formulas (immune-enhanced formula and immune-modulating formula) on the immune function of Chinese patients following gastrointestinal cancer surgery. Methods: We conducted a secondary analysis of immune function in perioperative enteral immunonutrition. Between October 2018 and September 2020, 308 patients undergoing resection and gastrointestinal reconstruction for gastrointestinal cancer received preoperative 5-day and postoperative 7-day feeding. They were randomly assigned in a double-blinded manner to either the immune-enhanced formula (intervention) or immune-modulating formula group (control). . The primary endpoints were the levels of CD4 + and CD8 + T cells and CD4 + /CD8 + ratio. Secondary endpoints included inflammatory markers, such as C-reactive protein (CRP) and IL-6 levels. Results: Of the 308 patients included, 193 (62.7%) exhibited adequate compliance ( &gt; 75%). Patients in the immune-enhanced formula group did not demonstrate significant differences in CD4 + T cells, CD8 + T cells, CRP, and IL-6 levels compared with the immune-modulating formula group. However, among patients with low prealbumin levels, the median difference in CD4 + /CD8 + ratio on postoperative day 7 was 1.845 in the immune-enhanced formula group and 1.68 in the immune-modulating formula group ( P = 0·036). Conclusions: This study suggests that immunonutrition may significantly enhance immune function in patients with gastrointestinal tumors. In particular, our data indicate that immune-enhanced formula may be more effective in ameliorating immune responses in patients with compromised nutritional status, making them more responsive to immunonutrition. Clinical trial information: NCT03665714 .
Comparison of zanubrutinib (zanu) and acalabrutinib (acala) in B-cell malignancies: An adverse event (AE)-based analysis.
Authors: Tahla Munir, Yucai Wang, Leyla Mohseninejad, Tushar Srivastava, Anurag Gupta, Raju Gautam, Swetha Challagulla, Mei Xue, Keri Yang, Rhys Williams, Vincent Levy, Shouhao Zhou
Journal: Journal of Clinical Oncology (2024)

e19049 Background: Acala and zanu are 2 nd generation Bruton tyrosine kinase inhibitors (BTKis) that have demonstrated improved safety profiles vs 1 st generation BTKi ibrutinib in clinical trials. While head-to-head comparison of zanu vs acala is lacking, a recent meta-analysis of clinical trials provided a comprehensive, indirect comparison of the AE profiles in B-cell malignancies (Hwang, Hemasphere. 2023;7(S3):1134). This study aims to evaluate costs and impacts on quality of life (QoL) for zanu vs acala using their AE profiles. Methods: A health economic model was developed to determine cost and QoL associated with AE management for zanu and acala. The incidence rates ( IRs) of all grade and grade ≥3 AEs of interest (n=21, including bleeding events, hypertension, atrial fibrillation, cytopenias, infections, headache, arthralgia, diarrhea) were taken from the meta-analysis. Additional model inputs, such as disutility, average duration of AE, and unit cost of each AE were sourced from published literature and publicly available cost databases in consultation with clinical experts. The model was developed from the US perspective, considering Medicare costs, inflated to 2023 USD. Model outcomes were AE management cost (= IR * unit cost) and quality-adjusted life years (QALYs) lost due to AE (= IR * Disutility * Duration/365.25). Results: In the base-case scenario (considering all AEs), treating a hypothetical cohort of 1000 patients (pts) with zanu instead of acala yielded cost savings of $124K and 3.7 QALY gains (i.e., 3.7 years extra in full health). Subgroup analysis for severe (grade ≥3) and non-severe AEs (grade 1-2) demonstrated similar trends. A sensitivity analysis limited to AEs significantly different between zanu and acala (n=13) yielded consistent results. Additionally, a probabilistic sensitivity analysis, conducted with 1000 iterations to account for uncertainty in model parameters, confirmed robustness of the model, indicating stable conclusions across a wide range of parameter uncertainties. Conclusions: This analysis suggested that zanu is cost-saving and associated with added health benefits compared to acala in terms of AE management in pts with B-cell malignancies. Should these results derived from meta-analysis of clinical trial data be applicable to real-world pt populations across different indications, the potential cost savings could be considerable. These results could be further improved if the differences in efficacy of zanu vs acala are also incorporated. [Table: see text]