tbuckley/cabot-search huggingface dataset:
Demographic and socioeconomic factors of enterochromaffin cell carcinoid.
Authors: Simardeep Cheema, Elizabeth Rizk, Angel Joseph, Mark Moroz, Jasika Grover, Abhigna Reddy, Sukhmani Kaur Gill, Frances Nowlen, Peter T. Silberstein, Daniel Lee, Michael Demangone, Anthony Rossi, Craig Heise, Beau Hsia
Journal: Journal of Clinical Oncology (2024)

e16288 Background: Gastric carcinoid tumors, previously known as neuroendocrine neoplasms, are derived from enterochromaffin cells and show an increasing incidence globally. Neuroendocrine tumors often result in hormonal syndromes due to the production of exogenous hormonal peptides by the tumor. Current treatment options include surgical resection and somatostatin pharmacotherapy to blunt tumor growth. A gastric carcinoid malignancy that requires more investigation is enterochromaffin cell carcinoid (ECC). Considering the increasing incidence of gastric carcinoids, a retrospective investigation of demographic data involving enterochromaffin cell carcinoids was performed using the National Cancer Database (NCDB). Methods: The 2004-2019 NCDB was explored to perform a retrospective cohort analysis of patients diagnosed with ECC. 200 patients with a histologically confirmed diagnosis (ICD-O-3 code 8241/3) were identified. Descriptive statistics were used to analyze the following demographic data of patients in this study: race, sex, age, income quartile, facility type, Hispanic status, and Chales/Deyo score. Regression analysis was used to interpret incidence trends. Results: The NCDB identified 200 patients diagnosed with ECC from 2004-2019 with incidence rates varying over this time (R² = 0.0001). The mean age at diagnosis was 55 years (SD = 19.7, range = 14-90). Women (62%) were more likely to be diagnosed than men. The majority of patients were White (86%) and non-Hispanic (80%). Most patients (99.9%) received treatment for the remission of the cancer, predominantly through surgical means (86.5%). More patients were treated in an Comprehensive Community Cancer program (34.5%) than in an academic/research program (26.0%). The majority of individuals lived in metropolitan counties with a population greater than 1 million (54%) than in other metropolitan counties (22%). Most patients were in the fourth quartile of income earners (32.1%). The top primary site was the appendix (40.5%), and most individuals (79.5%) had Charles/Deyo comorbidity scores of 0. Conclusions: To the best of our understanding, this is the first NCDB investigation of Enterochromaffin Cell Carcinoid (ECC) and therefore addresses a meaningful educational disparity on the topic. Most ECC patients tend to be White, non-Hispanic individuals with a primary diagnosis site of the appendix, consistent with previous studies. Upon analyzing the socioeconomic factors of ECC patients, it was found that they often fall into the top income quartile, live in densely populated metropolitan counties, and receive treatment from a comprehensive community cancer program. Due to the significance of these demographic and socioeconomic factors, more research is needed to understand their impact on the diagnosis and treatment of ECC.
Alliance A022106: A phase II/III trial of NABPLAGEM vs nab-paclitaxel/gemcitabine as second-line treatment for <i>BRCA1/2</i> or <i>PALB2</i> mutant metastatic pancreatic ductal adenocarcinoma (PLATINUM).
Authors: Erica S Tsang, Qian Shi, Kenneth P. Olive, Eric Andrew Collisson, Jesse G. Dixon, Mike Cusnir, Rafael Winograd, Gregory P. Botta, Raymond Couric Wadlow, Ardaman Shergill, Jeffrey A. Meyerhardt, Eileen M. O'Reilly, Andrew H. Ko
Journal: Journal of Clinical Oncology (2024)

TPS4205 Background: Multiple lines of evidence support the use of platinum-based chemotherapy for patients with homologous recombination deficiency-associated pancreatic adenocarcinoma (HRD PDAC; 15-20%). However, the impact of the specific platinum agent used remains uncertain. Mechanistically, oxaliplatin and cisplatin act distinctly on cancer cells, reflected in disparate toxicity profiles and target disease indications; furthermore, preclinical studies have shown that BRCA2-deficient cell lines and mice demonstrate significantly greater sensitivity to cisplatin compared to oxaliplatin. While oxaliplatin, part of the FOLFIRINOX regimen, represents the most commonly used platinum analogue for PDAC, clinical data shows that cisplatin (in combination with gemcitabine) can produce robust response rates (~70%) specifically in patients with germline BRCA/PALB2-mutated metastatic PDAC. We therefore designed a randomized clinical trial (PLATINUM) through the Alliance for Clinical Trials in Oncology cooperative group to assess the optimal chemotherapy regimen in patients with HRD-associated metastatic PDAC following front-line FOLFIRINOX and to test the hypothesis that a platinum switch strategy will be beneficial. Methods: The study consists of a seamless phase II/III design, with the primary endpoint of the phase III component being overall survival. Eligible patients will have metastatic PDAC, a confirmed pathogenic BRCA1/2 or PALB2 mutation (somatic or germline), and demonstrated disease progression on front-line FOLFIRINOX, with or without subsequent PARP inhibitor maintenance. Patients will be randomized 1:1 to receive (1) the de facto standard of gemcitabine plus nab-paclitaxel; or (2) the experimental 3-drug combination of gemcitabine, nab-paclitaxel, and cisplatin (NABPLAGEM), which has been previously studied in non-biomarker-selected patients with advanced biliary tract cancer (SWOG1815) and metastatic PDAC. Both treatment arms will use a once every other week dosing schedule. A total of 100 patients will be enrolled, which provides 90% power to detect an effect size of hazard ratio 0.5 (median OS of 18 vs 9 months) at a one-sided alpha of 0.05. Reports containing efficacy, adverse events, and administrative information will be provided to the Alliance DSMB every 6 months. Planned correlatives include ctDNA analysis for BRCA reversion mutations in all patients, as well as whole genome and transcriptome sequencing in an optional biopsy cohort. This study was activated in December 2023. Clinical trial information: NCT06115499 .
Nodular number as a prognostic indicator in hepatic resection for intermediate-stage hepatocellular carcinoma: An international multicenter observational study.
Authors: Han Liu, Zhong-Qi Fan, Ming-Da Wang, Matteo Serenari, Myron Schwartz, Zhong Chen, Ya-Hao Zhou, Xian-Ming Wang, Ting-Hao Chen, Jie Li, Cheng-Wu Zhang, Hong Wang, Wei-Min Gu, Ying-Jian Liang, Matteo Cescon, Guo-Yue Lv, Tian Yang
Journal: Journal of Clinical Oncology (2024)

e16271 Background: The role of hepatic resection in treating Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) is a subject of ongoing debate. This study aims to assess the prognostic significance of the number of nodular HCC in patients undergoing hepatic resection for intermediate-stage (BCLC stage B) HCC. Methods: An analysis was conducted using data from a multicenter database of patients who underwent curative-intent resection for BCLC intermediate-stage HCC. Patients were classified into binodular and tri(+)nodular (≥ 3 nodules) groups based on the number of tumor nodules. Long-term overall survival (OS) and recurrence-free survival (RFS) were compared between these groups. Univariate and multivariate Cox-regression analyses identified risk factors for OS and RFS. Additional comparisons were made with outcomes in patients with uninodular large HCC (single nodule &gt; 5 cm; BCLC stage A). Results: Of the 338 patients with BCLC intermediate-stage HCC, 187 (55.3%) had binodular and 151 (44.7%) had tri(+)nodular disease. Patients with binodular HCC showed significantly better median OS (49.6 months) and RFS (22.2 months) compared to those with tri(+)nodular HCC (33.5 and 13.7 months, P = 0.036 and 0.009, respectively), and outcomes comparable to those with uninodular large HCC (59.8 and 26.8 months, P = 0.144 and 0.311, respectively). Multivariate analyses indicated that binodular HCC was independently associated with improved OS and RFS following hepatic resection in BCLC intermediate-stage HCC. Conclusions: Patients with binodular HCC exhibit more favorable survival outcomes post-resection of BCLC intermediate-stage HCC compared to those with tri(+)nodular HCC, akin to outcomes observed in BCLC early-stage uninodular large HCC. These findings highlight the prognostic relevance of nodular number in stratifying and guiding surgical decisions for intermediate-stage HCC. [Table: see text]
Tislelizumab plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy for elderly patients with inoperable locally advanced esophageal squamous cell carcinoma: A multicenter, randomized, parallel-controlled, phase II clinical trial.
Authors: Wencheng Zhang, Ke Zhang, Qifeng Wang, Jianzhong Cao, Chengcheng Fan, Wenbin Shen, Qin Xiao, Xiaolin Ge, Xiao Liu, Tian Zhang, Xi Chen, Jie Dong, Zewei Li, Zhunhao Zheng, Cihui Yan, Qingsong Pang, Ping Wang
Journal: Journal of Clinical Oncology (2024)

TPS4183 Background: There is few high-level prospective randomized studies and international consensus guideline on treatment in elderly patients with inoperable locally advanced esophageal squamous cell carcinoma (LAESCC). Double-agent intravenous chemotherapy concurrent with radiotherapy is the standard of care for LAESCC. However, it’s based on clinical trials that only enrolled patients ≤ 75 years old and infeasible in elderly patients. Oral S-1 plus concurrent radiotherapy for elderly ESCC showed tolerable toxicity and survival benefit compared with radiotherapy alone. While, the 3-year overall survival (OS) rate is limited about 40%. Therefore, it urgently needs find new treatment strategies to further improve the efficacy in elderly ESCC patients. Tislelizumab, the antii-PD-1 antibody, has recently been proved in the first- and second-line standard treatment for advanced ESCC. It shows mild toxicities and might be well-tolerated in the elderly. Here, we conducted the first clinical trial to assess the efficacy and safety of tislelizumab plus concurrent chemotherapy (CCRT) versus CCRT for elderly patients with inoperable LAESCC. Methods: The study is an open label, multicenter, parallel-controlled, investigator-initiated phase II clinical trial in elderly patients with inoperable LAESCC. We plan to enroll 136 elderly patients with LAESCC who will be randomly divided into two groups: tislelizumab combined with CCRT group (tislelizumab + radiotherapy + S-1) and CCRT group (radiotherapy + S-1). Tislelizumab is given intravenously on the first day of CCRT at the dose of 200 mg once every 3 weeks (Q3W). Radiotherapy is delivered at 50.4 Gy/1.8 Gy/28 fraction (5 times per week). S-1 is orally given at the dose of 40-60 mg from day1 to day14 and day 22 to 35. We will evaluate the efficacy and safety during the treatment and follow-up period until disease progression, death or the end of the trial. Considering the median progression free survival (PFS) is 16 months in elder receiving CCRT in history studies, we expect the median PFS would be 28 months at the hazard ratio of 0.57. The final sample size consists in 136 patients by 1:1 randomized in the two groups with 80% power and one-sided alpha and calculating for a 10% dropout rate. The primary endpoint is PFS. Secondary endpoints include OS, objective response rate, duration of objective response and severity of adverse events. Fresh or archival tumor tissues and peripheral blood samples will be used in the exploratory studies. This trial started on October 10, 2023 and has enrolled 19 patients till February 1, 2024. Clinical trial information: NCT06061146 .
Genomic and biomarker analysis of immunotherapy combined with chemotherapy treated for patients with metastatic BTC cancer: A real world study.
Authors: Miaomiao Gou, Guanghai Dai, Zhi-Kuan Wang
Journal: Journal of Clinical Oncology (2024)

e16373 Background: Biliary tract cancer (BTC) is a heterogeneous group of diseases with dismal prognosis. The TOPAZ-1 phase III trial and KENOTE 966 reported a survival benefit with the immune checkpoint inhibitor (ICI) plus chemotherapy (GemCis,GC) in patients with advanced BTC. Consequently, immunotherapy plus chemotherapy has become a new standard care for advanced BTC. Understanding the association between genomic alterations and immunotherapy outcomes of BTC could further improve the clinical benefits. Therefore, we conducted this real-world study in China. Methods: This study included 47 patients with metastatic BTC treated with PD-1/PD-L1(ICI) antibodies in combination with chemotherapy from January 2019 to January 2023 in Medical Oncology department of Chinese PLA General Hospital. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall response rate (ORR), disease control rate (DCR). The exploration endpoint was genomic and biomarker analysis. Genomic tumor DNA was isolated from 30 patients and used for targeted next-generation sequencing genes to identify the genomic profiles. Results: 47 patients received immune checkpoint inhibitor (ICI) plus with chemotherapy in first line were enrolled in this study. The median PFS were 5.4m (95%CI,4.4-6.3), ORR and DCR was 21.3% and 83.0%, respectively. Patients were grouped into two group:AS+PD1(n=34) group and GC+ICI(n=13) group. In the AS(Albumin paclitaxel+S1)+PD1 group, mPFS was 5.0m (95%CI 3.8-6.1), ORR were 20.6% and DCR were 79.4% as we reported previously. In the GC+ ICI, mPFS was 7.9m (95%CI 4.7-11.1), ORR was 23.1% and DCR was 92.3%. There was no difference in terms of PFS, ORR and DCR between two groups. With regard to biomarker analysis, PD-L1 expression positive were 16 patients, which of mPFS were 4.2m and ORR were 18.8%, otherwise 12 patients were PDL1 expression negative, of whom mPFS were 9.1m and 33.3% as unexpected. Average TMB were 4.5mt/MB for MSS type patients. There is no difference of PFS between TMB high(&gt;4.5mt/MB) or low(&lt;4.5mt/MB). As for genomic analysis, the most common gene alterations were TP53(N=13, 43%))KRAS(N=8, 26.7%), NTRK1\2\3(N=8, 26.7%), IDH1/2(N=6, 20%), PIK3CA(N=6, 20%), BRCA2(N=5, 16.7%). MDM2(N=5,16.7%), BRAF(N=4,13.3%). The mutations are mainly concentrated in the DDR (20) pathway followed by the RTK-RAS (16), TP53 (13), CPF (9), FA (9), HRR (9), and PI3K (8) pathways. Compared between long term survival(PFS&gt;5.4m)and short term survival(PFS&lt;5.4m), MDM2 was only predictor for short survival(p&lt;0.05). Conclusions: Compared to AS+pd-1, patients received GP+ ICI numerically had better outcomes. It seems PD-L1 and TMB were not good predictors to select patients who can more benefit from immunotherapy plus chemotherapy. MDM2 mutation suggest patients tend to less active to immunotherapy-based modality.
Incidence and demographics of bile duct cystadenocarcinoma from the National Cancer Database.
Authors: Michael Demangone, Karam Rabih Abi Karam, Daniel Lee, Dylan Langland, Beau Hsia, Anthony Rossi, Craig Heise, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2024)

e16231 Background: Bile duct cystadenocarcinoma, a rare tumor of the biliary tree, manifests itself within both multilocular and unilocular cysts composed of mucous-secreting, cytologically malignant epithelial cell populations. While similar in presentation to other biliary tree malignancies, bile duct cystadenocarcinoma has unique morphological variations between sexes. This contrast in disease manifestation based on sex could potentially impact diagnostic imaging, testing approaches, and treatment strategies for both female and male patients. The potential impact of demographics on the prognosis of bile duct cystadenocarcinoma, along with limited literature on the subject, make it a compelling subject for hypothesis generating epidemiological inquiry. The National Cancer Database will be used to illuminate the demographic intricacies. In this pursuit, we aim to provide a demographic and incidence background to prompt future research dedicated to the understanding of bile duct cystadenocarcinoma. Methods: The National Cancer Database (NCDB) was used to complete a retrospective cohort analysis of all patients diagnosed with histologically confirmed bile duct cystadenocarcinoma from the years 2004 to 2020. Demographic factors were subjected to descriptive statistical techniques, while a comprehensive regression analysis was employed to analyze the patterns in disease incidence. Results: Between 2004 and 2020, 64 patients were diagnosed with bile duct cystadenocarcinoma in the NCDB. There was a decline of incidence per year (R2 = 0.0392). The majority of those diagnosed with this disease were female (70%). Most of the patients were from Caucasian ethnicity (73%). The average age of diagnosis was 65 years old ( SD = 12.5, range = 33-88). The highest percentage of patients were on Medicare (55%). The primary site of the cancer was in the intrahepatic bile duct (63%). 70% of patients had a Charlson-Deyo Score of 0. Stage 1 was the most detected stage (42%). The average size of the tumor when detected was 65 mm (SD = 35.5, range = 9-144 mm). Most patients (72%) received surgical treatment and the remainder received radiation or chemotherapy alone. Regarding margins post-surgery, most of the patients (56%) had no residual tumor. Almost all patients (92%) received treatment designed for cure/remission. Mean survival after diagnosis was 8 years. Conclusions: Consistent with a vast majority of case reports, our results demonstrated that the majority of cases of bile duct cystadenocarcinoma were found in women (70%). Moreover, given that a significant proportion of patients affected by this disease are covered by Medicare (55%), we contend that investigating the precise influence of demographic factors and social determinants of health in this context presents a compelling avenue for future research.
Influence on surgical approach in hepatocholangiocarcinoma: A demographic and socioeconomic analysis.
Authors: Mohammed Al Kurnas, Ashley Becker, Xinxin Wu, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2024)

e16280 Background: Hepatocholangiocarcinoma (HCC-CC) is a rare and aggressive malignancy of the liver that contains histopathological features of both hepatocellular carcinoma and cholangiocarcinoma. Surgery is the mainstay of treatment, and the surgical approaches used include radical hepatic resection, laparoscopic, and robotic surgery. There has yet to be a study that explores the impact of demographic features on the choice of surgical modality in patients with HCC-CC. The National Cancer Database (NCDB) was analyzed to determine the effects of demographic features on surgical modality and overall survival. Methods: A retrospective cohort analysis utilizing the NCDB included 2,449 patients diagnosed with HCC-CC (ICD-8180/3) between 2004-2020. Surgical modality was categorized into either open or minimally invasive by the preliminary treatment. Minimally invasive techniques included robotic-assisted and minimally invasive. Race, sex, age at diagnosis, income level, insurance used, distance from the facility, and the status of the facility as an academic center on the surgical modality were compared using Pearson Chi-squared tests or independent samples t-test as pertinent. Multivariate analysis with binary logistic regression was used to analyze the following categorical variables in relation to choice of surgical modality: race, sex, income, insurance, sex, and facility type. Surgical treatment modality on overall survival was analyzed by the Kaplan-Meier method. Exclusion criteria included missing data. Results: Most cases analyzed were White (75.8%), male (67.5%), and had government insurance as the primary payor at diagnosis (60.6%). Of the cases analyzed, 625 underwent surgery (25.5%). Patients who underwent minimally invasive surgery were more likely to be government-insured than patients who underwent open surgery (69.8% vs. 55.6%, P &lt; 0.05). Patients who underwent open surgery were younger on average (61.4 vs. 66.0 years, P &lt; 0.05). There was no significant difference in distance from residence to the treatment facility between the two surgical approaches. Multivariate analysis showed that patients treated at academic centers were less likely to receive minimally invasive surgery (28.1%) over open surgery (71.9%; P = 0.041, 95% CI 0.469-0.985) without statistical significance for race, sex, income, or insurance. The average survival time was significantly longer in open vs minimally invasive surgery (67.9 vs. 55.3 months, P &lt; 0.05). Conclusions: We identified that patients who underwent open surgery had significantly better overall survival with an average difference of 12.6 months. Even after accounting for other factors, the choice of surgical modality was significantly influenced by treatment at an academic institution. Patients receiving care at an academic facility are more likely to receive open surgery leading to overall increased survival.
Impact of acute ischemic stroke on mortality in gastrointestinal malignancies: A nationwide analysis.
Authors: Natchaya Polpichai, Sakditad Saowapa, Phuuwadith Wattanachayakul, Pojsakorn Danpanichkul, Panisara Fangsaard, Shu-Yen Chan, Nattanicha Chaisrimaneepan, Ekaphop Sirachainan
Journal: Journal of Clinical Oncology (2024)

e16372 Background: Acute ischemic stroke, marked by a sudden loss of brain blood supply, carries potential life-threatening consequences. The impact on individuals with pre-existing gastrointestinal (GI) malignancies, coupled with ensuing complex medical complications affecting morbidity and mortality, remains inadequately understood. This study aims to assess the influence of acute ischemic stroke on in-hospital mortality in GI cancer patients in the United States. Methods: This retrospective analysis utilized the 2016-2020 National Inpatient Survey (NIS) database. Adults aged 18 and above with esophageal, gastric, colon, cholangiocarcinoma, hepatocellular carcinoma, and pancreatic cancers were identified using the International Classification of Disease-10 (ICD-10) code. The cohort was stratified into patients with and without acute ischemic stroke. Hospital mortality was analyzed using STATA 18, adjusted for age, gender, race, insurance, Charlson’s index, baseline hospital characteristics, and comorbidities. Multivariate logistic regression analysis was performed, with all P values ≤ 0.05 considered statistically significant. Results: Among 2,133,465 adults with GI malignancies, 28,394 were hospitalized with acute ischemic stroke. Patients with acute ischemic stroke were older (mean age 71.19 vs. 67.01 years; P &lt; 0.001), more likely to be male (55.47%, P = 0.002), Caucasian (67.96%, P &lt; 0.001), from urban teaching hospitals (76.83%, P = 0.011), and had Medicare insurance (70.50%, P &lt; 0.001). Acute ischemic stroke was most associated with pancreatic cancer (39.81%), colon cancer (30.13%), and esophageal cancer (9.86%). Within the cohort of patients with acute ischemic stroke, esophageal cancer patients had the highest mortality rates of 20%. After adjusting for potential confounders, patients with colon cancer, esophageal cancer, gastric cancer, pancreatic cancer, cholangiocarcinoma, and hepatocellular carcinoma had significantly higher odds of in-hospital mortality of 2.91, 2.50, 2.31, 2.22, 1.65, and 1.51, respectively. Conclusions: This study reveals an association between outcomes in hospitalized GI cancer patients and acute ischemic stroke, leading to increased mortality despite adjusting for potential confounders. The impact of anticancer therapies on the vascular system may influence the risk and severity of ischemic events. Further studies are needed to develop tailored prevention, diagnosis, and management strategies to reduce disease complications and the overall healthcare burden of cerebrovascular events.