tbuckley/cabot-search huggingface dataset:
A randomized phase II trial of systemic chemotherapy with or without trastuzumab followed by surgery in HER2 positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: 3-year follow-up data of the Japan Clinical Oncology Group study JCOG1301C (Trigger study).
Authors: Masaki Aizawa, Masanori Tokunaga, Nozomu Machida, Riku Kajikawa, Noriko Mitome, Motohiro Hirao, Masato Nishida, Takahiro Kinoshita, Atsushi Yasuda, Tomono Kawase, Mikihiro Kano, Yukinori Kurokawa, Narikazu Boku, Takaki Yoshikawa, Masanori Terashima
Journal: Journal of Clinical Oncology (2025)

393 Background: We previously reported better objective and pathological response with the addition of trastuzumab to preoperative chemotherapy in the randomized phase II trial comparing the efficacy of systemic chemotherapy with or without trastuzumab followed by surgery in HER2 positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis. Here, we report 3-year follow-up data. Methods: Eligible patients with HER2-positive gastric cancer having extensive lymph node metastasis were randomized to receive preoperative chemotherapy with S-1/cisplatin (SP: S-1 80–120 mg/body on days 1–14, and cisplatin 60 mg/m2 on day 1, q21 days, 3-4 courses) in arm A or SP plus trastuzumab (first course 8 mg/kg followed by 6 mg/kg, day 1 on each course) in arm B. After gastrectomy, adjuvant chemotherapy with S-1 was added for 1 year in both arms. The primary endpoint was overall survival (OS), and the sample size was planned to be 130 patients in total, expecting a 10% increase in the 3-year OS (70% vs 80%) with a 1-sided alpha of 0.2, a power of 0.75. Results: The study was terminated in March 2021 due to slow patient accrual. In total, 46 patients were randomized to either arm A (22 patients) or arm B (24 patients). Patient characteristics were well balanced between the arms. Planned preoperative chemotherapy was completed in 20 patients (90.9%) in arm A and in 23 patients (95.8%) in arm B. Objective response rate tended to be higher in arm B (66.7% [16/24]) than in arm A (36.4% [8/22], p=0.08), and R0 resection was achieved in 20 patients (90.9%) in arm A and 22 patients (91.7%) in arm B. The adjuvant chemotherapy was completed in 54.6% (12/22) in arm A and in 54.2% (13/24) in arm B. With the median observation period of 4.1 years, the 3-year OS was 68.2% in arm A and was 78.9% in arm B with a hazard ratio of 0.698 (95% confidence interval (CI), 0.221-2.209). The 3-year progression-free survival of arm A and arm B was 39.3% and 62.3%, respectively, with a hazard ration of 0.562 (95% CI, 0.229-1.377). Conclusions: Preoperative chemotherapy with SP plus trastuzumab was feasible, and tended to improve the objective response rate, OS and progression-free survival. An integrated analysis with other clinical trials evaluating perioperative trastuzumab is being planned. Clinical trial information: s031180006.
Development and validation of machine learning model for mortality after curative gastrectomy for gastric cancer.
Authors: Ki Bum Park
Journal: Journal of Clinical Oncology (2025)

386 Background: The risk for postoperative complications can significantly impact perioperative planning. The aim of this study is to develop and validate a model based on various machine learning techniques to predict postoperative mortality (PM) after curative radical gastrectomy for gastric cancer. Methods: Data from a nationwide survey led by the Korean Gastric Cancer Association was used for the development set, which included 12,722 patients who underwent gastrectomy in 2019 across 68 institutions in South Korea. The validation set comprised 4,887 patients from 8 institutions between 2009 and 2017. PM was defined as all-cause death within 30 days after surgery or in-hospital death beyond 30 days. Five machine learning models (CatBoost, Gradient Boosting, Light GBM, Random Forest, XGBoost) were evaluated using perioperative clinical characteristics. Model performance was assessed using the area under the receiver operation characteristic curve (AUROC) with 5-fold cross-validation. Results: The PM rates were 0.83% and 1.04% in the development and validation set, respectively. In the development set, the Random Forest model demonstrated the highest discrimination capacity with an AUROC of 0.772, followed by Gradient Boosting at 0.767, CatBoost at 0.742, XGBoost at 0.732, and LightGBM at 0.717. However, in the validation set, CaBoost showed the highest AUROC at 0.747, while the AUROC for Random Forest decreased to 0.688. Conclusions: The CatBoost model demonstrated robust and consistent performance in predicting PM risk across both development and validation datasets. To further enhance the performance of the model and ensure stable clinical application, future research should focus on developing methods for quantitative measurement of perioperative factors such as surgical techniques.
A phase I trial of intraperitoneal (IP) mesothelin (MSLN)-targeted CAR T-cell therapy in patients with MSLN-positive esophagogastric cancer (EGC) with peritoneal carcinomatosis.
Authors: Joan Choo, Jasmeen Saini, Adrian Gonzalez - Aguirre, Parastoo Dahi, Sophie Hieronymi, Stacy Fernstedt, Kay See Tan, Prasad S. Adusumilli, Geoffrey Yuyat Ku
Journal: Journal of Clinical Oncology (2025)

TPS513 Background: Outcomes for patients with advanced EGC remain poor. The peritoneum is an immune-privileged niche and a common site of metastases occurring in up to 40% of patients with metastatic EGC; this is characterised by poor survival because of resistance to immunotherapy and a lack of measurable disease, which excludes trial participation. MSLN was selected as a target for CAR T cell therapy as it is overexpressed in up to 60% of EGC, is associated with aggressive disease biology and has low levels of expression in normal tissues. In pre-clinical in vivo models of peritoneal carcinomatosis, improved efficacy was observed with regional administration of IP CAR T cells, compared with systemic CAR T cells. No significant toxicity was observed at clinically relevant doses of IP administered CAR T-cells. M28z1XXPD1DNR CAR T-cells are a next-generation MSLN-targeted CAR, equipped with a modified CD3z (1XX), and a PD-1 dominant negative receptor (PD1DNR) that provides T-cell intrinsic checkpoint blockade. Methods: This is a single-arm phase I study assessing the safety, maximum tolerated dose (MTD) and preliminary efficacy of IP administered M28zXXPD1DNR CAR T cells in patients with MSLN-positive (IHC ≥ 25%) EGC with evidence of peritoneal carcinomatosis (imaging and/or cytology). Patients with concomitant extraperitoneal disease are eligible. Patients must have received at least one prior line of treatment for advanced or metastatic disease and have at least one measurable or evaluable lesion per RECIST 1.1. A minimum of 4 patients and maximum of 18 patients will be treated with 4 escalating doses (with 1 “fallback” dose) of CAR T cells to a maximum of 3 x 10 7 cells/kg administered via peritoneal catheter (Table). Lymphodepletion with fludarabine 30mg/m 2 /day and cyclophosphamide 300mg/m 2 /day is given for 3 days prior to the CAR T cell infusion. Adverse events, response rates (RECIST 1.1), survival outcomes and immuno-monitoring (immune cell phenotyping and serum/peritoneal fluid cytokine analysis) will be assessed. The trial is currently enrolling patients. Clinical trial information: Will be registered before ASCO GI. Dose-escalation scheme based on the continuous reassessment method. Dose Level Dose (cells/kg) 1 1 x 10 6 2 (Starting dose) 3 x 10 6 3 6 x 10 6 4 1 x 10 7 5 3 x 10 7
A phase II double window of opportunity trial evaluating the oral TGF-beta receptor I inhibitor vactosertib in patients undergoing standard of care preoperative therapy for locally advanced esophageal adenocarcinoma.
Authors: Kanchi Patell, Lauren E. Henke, Jennifer Anne Dorth, Melissa Amy Lumish, Madison Conces, AMR Mohamed, Sakti Chakrabarti, Amit Mahipal, David L. Bajor, Andrew Blum, Kishore Guda, J. Eva Selfridge
Journal: Journal of Clinical Oncology (2025)

TPS516 Background: Esophageal adenocarcinoma (EAC) is the seventh most common cancer globally and ranks sixth in overall mortality. Despite improvements in pre-operative therapy, EAC has a high recurrence rate, especially among patients whose tumors do not achieve pathologic complete response (pCR), thus there is a critical need to enhance pCR rate and improve long-term outcomes. We recently discovered that a subset of EACs are driven by tumor-intrinsic oncogenic TGFβ signaling and have identified two potential biomarkers to predict response to anti-TGFβ therapy. One of these biomarkers is enriched in poorly differentiated EAC. We hypothesize that TGFβ signaling blockade will exert a tumor-inhibitory effect in patients with EAC and propose a double window-of-opportunity trial to test if TGFβ receptor I inhibitor vactosertib can improve pCR and induce tumor metabolic response in patients undergoing neoadjuvant therapy for localized EAC. Methods: This phase II double window of opportunity study assesses the efficacy and pharmacodynamics of the oral TGFβ Receptor I inhibitor vactosertib in patients with locally advanced esophageal adenocarcinoma (EAC). Patients will be treated with single-agent vactosertib in two windows of opportunity: the first will be prior to initiation of standard of care neoadjuvant therapy and the second after completion of neoadjuvant therapy prior to surgery. Patients will be eligible if they have poorly differentiated EAC and are appropriate for neoadjuvant therapy followed by resection as per standard of care. The primary objectives are improvement in pCR compared to historical controls and metabolic response (decrease in fluorodeoxyglucose uptake by PET CT) in the primary tumor after the first window. Secondary objectives will evaluate biomarkers of response identified in preclinical studies. Pre- and post-first window of opportunity treatment biopsies will be obtained for correlative and exploratory analyses. Clinical trial information: NCT06044311 .
The impact of nutritional status on recurrence-free survival (RFS) in patients with locally advanced oesophagogastric adenocarcinoma (LA-OGA) treated with FLOT therapy.
Authors: Keiji Sugiyama, Sacheen Kumar, M. Asif Chaudry, Nikhil Patel, Pranav Patel, David Cunningham, Naureen Starling, Sheela Rao, Charlotte Victoria Fribbens, Ian Chau
Journal: Journal of Clinical Oncology (2025)

388 Background: Malnutrition and weight loss were reported as poor prognostic factors in operable OGA. This study examines the relationship between oncological outcomes and nutritional status in LA-OGA patients under the current standard of care, perioperative FLOT therapy. Methods: From 2017 to 2023, 423 patients who had radical resection at Royal Marsden Hospital were screened. Inclusion criteria included LA-OGA (cT2≤ and Nany or Tany and N+), at least one cycle of neoadjuvant chemotherapy (NAC), and ECOG PS 0–2. Nutritional status was assessed by body weight and prognostic nutritional index (PNI), with significant weight loss defined as a 5% loss within six months before diagnosis or during NAC. PNI was calculated as serum albumin (g/L) + 0.005 × lymphocyte count /μL, with categories of severe (&lt;45), mild to moderate (45–49.9), and normal (≥50). The primary endpoint was 3-year recurrence-free survival (3y-RFS). Restricted mean survival time (RMST) at 36 months was calculated to analyze survival time. Multivariate analyses were performed to identify prognostic factors for RFS. The pathological response was assessed using tumour regression grade (TRG) (Mandard criteria). Results: Of the 423 patients, 210 met the inclusion criteria. Primary tumour sites were the oesophagus (52.4%), the oesophagogastric junction (18.1%), and the stomach (29.5%). The median follow-up was 26.5 months. Weight loss at baseline and after NAC, as well as PNI, did not significantly impact RFS (p=0.13, p=0.91, p=0.69, p=0.45). However, a PNI decrease from baseline was associated with significantly shorter 3y-RFS (46% vs. 69%, p&lt;0.001), and the RMST difference was 5.46 months (p&lt;0.001). Multivariable analyses showed ypN positivity (p&lt;0.001), R1 resection (p&lt;0.001), and PNI decrease (p=0.03) as negative prognostic factors for RFS. Pathological response did not differ regardless of PNI change (28.2% vs. 30.4%, p=0.75). Conclusions: A decrease of PNI is a significant poor prognostic factor for RFS in LA-OGA patients undergoing FLOT, suggesting that maintaining nutritional status during NAC could enhance survival outcomes.
Effects of neighborhood deprivation index on survival in gastric cancers.
Authors: Sawyer Bawek, Mrinalini Ramesh, Kayla Catalfamo, Kristopher Attwood, Sarbajit Mukherjee
Journal: Journal of Clinical Oncology (2025)

336 Background: Previous studies have shown that living in disadvantaged neighborhoods resulted in poor outcomes in several malignancies. Neighborhood Deprivation Index (NDI) identifies key variables from 13 measures, including the following dimensions of socioeconomic (SES) status: wealth and income, education, occupation, and housing conditions. In this study, we aimed to investigate the effect of NDI among patients with gastric cancer (GC). Methods: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database from 1996-2015. NDI was divided into two groups: less disadvantaged areas (NDI &lt;60) and highly disadvantaged areas (NDI &gt;60), respectively. Demographic and clinical characteristics were summarized by NDI groups. All associations were compared using Kruskal-Wallis and Chi-Square tests, respectively. Kaplan Meier curves were summarized by the NDI group for overall survival (OS) and disease-specific survival (DSS). All associations were compared using a log-rank test. Cox multivariate regression was performed to measure the association between NDI and OS/DSS. All analyses were conducted in RStudio v4.2.3 at a significance level of ≤ 0.05. Results: A total of 19,205 GC (11,137 patients with NDI&lt;60 and 8,068 NDI&gt;60) patients were analyzed. Disadvantaged areas (NDI&gt;60) had a higher proportion of Black and Hispanic, single, uninsured, rural patients with later disease stage as compared to NDI &lt;60. Median OS was 10.0 months for patients with NDI &lt;60 versus 9.0 months for those with NDI &gt;60 (p=0.0007). Median DSS was 12.0 months for NDI &lt;60 and 10.0 months for NDI &gt;60 (p=0.010). Multivariate analysis revealed that factors associated with worse OS included NDI &gt;60 [HR 1.044, p=0.009], age (&gt;60) [HR 1.28, p&lt;0.001], male sex [HR 1.082, p&lt;0.001], single marital status [HR 1.21, p&lt;0.001], uninsured status [HR 1.13], p &lt;0.001], advanced disease stage (III/IV) [HR 2.05, p&lt;0.001], and higher grade [HR 1.32, p&lt;0.001]. On the other hand, non-Hispanic Black [HR 0.98] and Hispanic [HR 0.94] race and urban location [HR 0.91, p&lt;0.001] were associated with improved OS. Factors associated with inferior DSS included NDI &gt;60 [HR 1.037, p=0.038], age (p&lt;0.001), male sex [HR 1.05, p=0.005], single marital status [HR 1.15, p&lt;0.001], advanced disease stage (III/IV) [HR 2.375, p&lt;0.001], and advanced grade (III/IV) [HR 1.40, p&lt;0.001). In contrast, Hispanic [HR 0.94], non-Hispanic Black [0.96], and urban location [HR 0.90, p&lt;0.001] were associated with improved DSS. Conclusions: Patients from areas with higher NDI had worse OS and DSS for GC. Tailored healthcare policies that aim to improve healthcare delivery to areas with high deprivation may help improve GC outcomes.
Genetic differences in colorectal cancer across race and ethnicity.
Authors: Carrie Sha, Zhengming Chen, Fatima Qadri, John-William Sidhom, Erika Hissong, Jini Hyun, Uqba Khan, Manish A. Shah
Journal: Journal of Clinical Oncology (2025)

28 Background: Colorectal cancer (CRC) is the fourth most common cause of cancer death and cancer-related mortality is expected to increase exponentially. Ethnic minorities, in particular African Americans, have increased mortality from CRC. Although multifactorial, differences in somatic gene mutations could contribute to these racial discrepancies. Mutations in the critical oncogene KRAS are associated with worse prognosis in CRC. Recent literature suggests that in CRC patients, KRAS mutations are more frequently found in African Americans compared to Caucasians. This finding led to our hypothesis that molecular alterations across multiple races/ethnicities could explain differences in patient outcomes. This project will also inform a larger analysis using artificial intelligence learning models to predict race from tumor-specific genetic variants, as a tool to identify genetic drivers of race-specific patient outcome. Methods: We examined the molecular alterations in 304 patients diagnosed with CRC who had genetic testing between June 2021 and April 2023 at NYP Queens, NYP Brooklyn, and NYP Cornell. Race and ethnicity, genetic mutations, mortality, tumor location, and age, stage, and the presence of metastasis at diagnosis was collected. Patients self-identified as Non-Hispanic Black (NHB), White (NHW), Asian (NHA), American Indian (NHAI), or Hispanic, Other, or Declined. Median and interquartile range were used to summarize continuous variables, and frequency and proportion were used to summarize categorical variables. The significance of difference across ethnicity groups was tested using Kruskal-Wallis rank sum test for continuous variables and Fisher’s exact test for categorical variables. Mutational correlates of race using a multiple-instance learning artificial intelligence approach (i.e. Anaya et al., Nature Biomedical Engineering, 2023), will be presented. This method will predict race from patients' tumor-specific genetic variants, allowing us to identify specific variants and patterns predictive of race, and potential drivers of patient outcome. Results: Amongst the 304 CRC patients, we identified 116 NHW, 51 NHA, 40 NHB, 35 Hispanic and 1 NHAI, for a total population of 243. BRAF mutations were almost absent in NHB (2.5%) and NHA (3.9%), compared to NHW (13.8%; p=0.02). KRAS mutations were also more prevalent in underserved populations; 65.7% Hispanic, 57.5% NHB, compared with 44.8% NHW (p=0.14). We further identified substantial differences in KRAS mutations when dividing the Asian population into East Asian (62.9%) and South Asian (37.5%). Conclusions: We identified significant differences in key molecular drivers between ethnicities. Our findings suggest that genomic and tumor specific differences across ethnicities could in part explain differences in patient survival across these groups. Mutational correlates of race and survival using natural language processing will be presented.
Evaluation of the Effects of a Cardiac Rehabilitation program with Combined Training on Left Ventricular mass in Patients with Heart Failure
Authors: Lara-Vargas Jorge A
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Background and Aim: Heart failure (HF) is a chronic, multisystemic, heterogeneous, and progressive syndrome where sustained activation of compensatory neurohormonal mechanisms leads to maladaptive left ventricular remodeling. There is evidence that regular exercise stimulates physiological cardiac growth, increases mitochondrial biogenesis, mitophagy, and improves mitochondrial dynamics in healthy hearts. However, its effects on left ventricular mass and the relationship with peak VO2 gains, specifically with combined training in HF patients, have not been elucidated. Therefore, the aim of the study is to assess whether a cardiac rehabilitation program (CRP) with combined training can increase left ventricular mass and thereby peak oxygen consumption (VO2p) in patients with HF. Materials and Methods: A quasi-experimental, non-controlled study was conducted in chronic HF patients who completed the supervised phase 2 of the CRP. Participants underwent transthoracic echocardiography and a cardiopulmonary exercise test with gas analysis (CPET) where echocardiographic variables such as mass, end-diastolic volume, posterior wall thickness and interventricular septal thickness of the left ventricle were measured, as well as cardiopulmonary exercise variables such as VO2p, VT1, VAT, VT2, FATmax and crossover, at admission and discharge. Results: A total of 50 patients diagnosed with HF were included, 70% men, with a mean age of 63.9 ± 11.7 years. In the inferential analysis between baseline parameters and after completing the CRP, significant differences were found in LVEF (p &lt;0.001), end diastolic volume (p &lt;0.001), left ventricular mass indexed to total body surface area (p &lt;0.001), oxygen pulse (p &lt;0.001), Mets-C (p &lt;0.001), VT1 (p = 0.013), VAT (p = 0.002), VT2 (p &lt;0.001), FATmax (p = 0.003), and crossover (p &lt;0.001). VO2 peak behavior was analyzed in patients who had an increase in ventricular mass (n=17) compared to those who had a decrease in ventricular mass (n=33), finding both groups had statistically significant changes in VO2 peak (p = 0.04). Conclusions: CRPs based on combined physical training are effective and safe in patients with chronic HF, improving peak VO2 in clinically stable patients regardless of changes in left ventricular geometry measured through left ventricular mass. While the most frequently presented adaptation at the end of the intervention was reverse remodeling, this condition does not contravene the gains in cardiorespiratory fitness, as this ventricular mass could generate greater fitness and aerobic power.
Fetal Complete Heart Block. A Successful Surgical Permanent Pacemaker Implantation in a Small for Gestational Age Baby (2.4 Kg): A Case report and Mini Review
Authors: Vishnu Datt
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

Congenital complete heart block (CCHB) without structural cardiac anomalies is a rare disease with an incidence of 1 in 15 000 – 20000 live births. CCHB is associated with high intrauterine and post-natal mortality. Maternal autoimmune diseases are often the predisposing factors for the isolated CCHB. Antibodies cross the placenta and cross-react with the developing conduction system, leading to injury and CCHB. Prenatal detection using intrauterine foetal echocardiography at the time of the obstetrics scan, and management with steroids, as well as appropriate delivery planning, and urgent permanent pacemaker implantation (PPI) in the newborn may improve the outcomes in CCHB. However, PPI in neonates can be challenging due to their small size, small vascular and ventricular sizes, and even leadless pacemakers and transvenous implantation in the neonates remain unsuitable. We describe a rare case of CCHB diagnosed at 19th week of pregnancy onwards in 25 yrs old mother, who was a known case of SLE for the last 5 yrs. The CCHB in the small -for -gestational -age (2.4 kg) male, newborn was refractory to the infusion of dobutamine, isoprenaline and dexamethasone. A detailed informed consent was obtained from the parents, and the CCHB was successfully managed with surgical LV epicardial PPI and using a VVI pacing mode at 120 bpm on the first day of life. Only few cases have been reported on the surgical LV epicardial PPI where both leads are attached to the LV and device has been fixed in the left thoracic cavity.