tbuckley/cabot-search huggingface dataset:
The factors associated with all-cause in-hospital mortality in patients with malignant well-differentiated gastroenteropancreatic neuroendocrine tumors: A retrospective analysis of National Inpatient Survey (NIS) 2020 dataset.
Authors: Elvis Obomanu, Tarfa Verinumbe, Hilary Elom
Journal: Journal of Clinical Oncology (2024)

e16292 Background: Neuroendocrine tumors (NET) affect less than 200,000 (52 per 100,000) of the US population, with malignant well-differentiated gastroenteropancreatic (GEP) NETs accounting for about 65% of the cases. Owing to its rarity, the evidence on factors associated with all-cause mortality is limited. To address this gap, this study aims to identify socio-demographic and clinical factors associated with all-cause in-hospital mortality for patients with malignant well-differentiated GEP NET. Methods: We analyzed data from 2020 Nationwide Inpatient Sample survey on patients hospitalized with malignant well-differentiated GEP NET. Using ICD10 code, we identified patients hospitalized with any diagnosis of malignant well-differentiated GEP NET. In-hospital mortality was assessed based on the patient final disposition on discharge and dichotomized. Exposure variables analyzed included age, sex, tumor site, history of essential hypertension, COVID-19, hyperlipidemia, insurance status, length of hospital stay, and number of comorbidities present on the patients record. Multivariable logistic regression was used to assess for factors associated with mortality. Results: Of the 956 patients in this study, most were white (73.43%), male (48.28%) and mean age was 65 years (SD 13.59). Affected sites include small intestine (57.25%), pancreas (13.56%), colon (8.47%), appendix (8.26%), stomach (8.68%) and rectum (3.51%). Our results revealed that females were less likely to die in the hospital compared to their male counterpart hospitalized with malignant well-differentiated GEP NET (aOR = 0.42; 95% CI: 0.19 - 0.95). The presence of hyperlipidemia was significantly associated with in-hospital mortality (aOR = 0.24; 95% CI: 0.08 - 0.75). For every unit increase in the number of comorbidities, there is 12% increased risk of mortality (aOR = 1.12; 95% CI: 1.05 -1.19). The associations of age, race, tumor site, history of hypertension, insurance status or length of stay with in-hospital mortality were not statistically significant. Conclusions: Our study found significant associations of sex, hyperlipidemia, number of comorbidities and in-hospital mortality among patients with malignant well-differentiated GEP NET. Findings from this study highlight that factors such as sex, hyperlipidemia and number of comorbidities may be critical when developing prognostic tools that can be used to determine the risk of mortality among hospitalized patients hospitalized with these tumors.
Discovering urinary protein biomarkers for hepatocellular carcinoma in the population of patients with chronic hepatitis B: A single-center case-control study.
Authors: Yuke Zhang, Yongfa Huang, Jiali Xing, Yuxin Wang, Bao Jin, Runze Xue, Ye Guo, Xiaoyan Chang, Mei Guan, Xiao Liu, Xueshuai Wan, Hong Zhao, Zhixian Hong, Haifeng Xu, Jianqiang Wu, Yilei Mao, Shunda Du
Journal: Journal of Clinical Oncology (2024)

e16230 Background: Chronic hepatitis B (CHB) can result in hepatocellular carcinoma (HCC) imposing a substantial health and economic burden worldwide. Early detection of hepatitis B virus-related HCC (HBV-HCC) in CHB with potential biomarkers has emerged as an urgent and challenging task. Recent progression of urinary proteomics provides a promising method for HBV-HCC biomarker discovery. Methods: This single-center case-control study, conducted at Peking Union Medical College Hospital, enrolled 33 patients with HBV-HCC, 26 patients with CHB, 30 healthy controls, and 33 controls with other types of cancer. Urine proteomes were analyzed using liquid chromatography with tandem mass spectrometry by data-dependent acquisition or parallel reaction monitoring, respectively. Differential analysis was carried out with limma package in R software, and the origin of selected proteins was confirmed with immunohistochemistry of surgical specimens. The diagnostic performance of the biomarker panel was evaluated with area under receiver operator curves (AUROC). Results: 21 urinary proteins were significantly upregulated in HBV-HCC compared with CHB samples, playing key roles in vesicular transportation, cytoskeleton-extracellular matrix interaction, and tumor development according to enrichment analysis. Immunohistochemistry validated the differential expression of 4 urinary proteins (4UP: HNRNPM, ADGRG1, APOC1, and RALA) across cancerous and adjacent normal liver tissues. These proteins were specifically found in HBV-HCC but not in CHB, healthy control, or other cancer controls. The AUROCs of 4UP individually (0.642 for APOC1, 0.780 for HNRNPM, 0.755 for ADGRG1, 0.729 for RALA) were no worse than that of serum α-fetoprotein (AUROC = 0.751), and the 4UP panel unified via logistic regression showed an AUROC of 0.828. Conclusions: Urinary proteomics revealed HNRNPM, ADGRG1, APOC1, and RALA as biomarkers to distinguish HBV-HCC from CHB. The 4UP could be traced back to HBV-HCC tumor cells, shedding light on pathogenesis of HBV-HCC. [Table: see text]
Avelumab first-line maintenance (1LM) for advanced urothelial carcinoma (aUC): Long-term outcomes from JAVELIN Bladder 100 in patients (pts) with low tumor burden.
Authors: Joaquim Bellmunt, Thomas Powles, Se Hoon Park, Eric Voog, Begoña Pérez Valderrama, Howard Gurney, Anders Ullén, Yohann Loriot, Srikala S. Sridhar, Norihiko Tsuchiya, Cora N. Sternberg, Jeanny B. Aragon-Ching, Daniel P. Petrylak, Miguel A. Climent Duran, Karin Tyroller, Jason Hoffman, Natalia Jacob, Petros Grivas, Shilpa Gupta
Journal: Journal of Clinical Oncology (2024)

4566 Background: In the JAVELIN Bladder 100 phase 3 trial, avelumab 1LM + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in pts with aUC that had not progressed with 1L platinum-based chemotherapy (PBC). Results led to the incorporation of avelumab 1LM into international guidelines. Prior analyses have shown that low tumor burden (eg, nonvisceral metastases or lymph node [LN]-only disease) is associated with better outcomes in pts with aUC receiving immune checkpoint inhibitors. We report post hoc analyses of efficacy and safety in subsets of pts with low tumor burden from JAVELIN Bladder 100. Methods: Eligible pts with unresectable locally advanced (LA) or metastatic UC without progression after 1L PBC were randomized 1:1 to receive avelumab + BSC (n=350) or BSC alone (n=350). The primary endpoint was OS measured from randomization; secondary endpoints included PFS and safety. In this post hoc analysis, pts with nonvisceral metastases included those with LA disease or only nonvisceral disease, including bone metastasis, at randomization. Results: In the avelumab + BSC and BSC alone arms, 159 and 159 pts had nonvisceral metastases and 51 and 51 pts had LN-only disease, of whom 42 and 35 pts had LN-only disease in the pelvic/retroperitoneal area. At the efficacy data cutoff (June 4, 2021), median follow-up was ≥38 mo in both arms (≥2 y in all pts). In all subgroups, OS and PFS were prolonged with avelumab + BSC vs BSC alone (Table). Incidence of treatment-related adverse events (TRAEs) with avelumab were similar across subgroups. In the avelumab + BSC and BSC alone arms, subsequent anticancer drug treatment was received by 90 (56.6%) vs 119 pts (74.8%) with nonvisceral metastases, 27 (52.9%) vs 39 pts (76.5%) with LN-only disease, and 22 (52.4%) vs 27 pts (77.1%) with pelvic/retroperitoneal LN-only disease. Conclusions: Exploratory analyses suggest that avelumab 1LM has pronounced efficacy and manageable toxicity in pts with aUC who have low tumor burden, supporting its use as a standard of care in this setting. Clinical trial information: NCT02603432 . [Table: see text]
Differential IDH1 and IDH2 mutation-related landscape in intrahepatic cholangiocarcinoma.
Authors: Shuaishuai Xu, Wenxin Qu, Yifei Shen, Jian Ruan
Journal: Journal of Clinical Oncology (2024)

e16224 Background: Patients with intrahepatic cholangiocarcinoma (ICC) are prone to recurrence and poor survival. Targeted therapy related to isocitrate dehydrogenase (IDH) is an extremely important treatment. IDH1 and IDH2 mutations are generally thought to have similar effects on the tumor landscape. However, it is doubtful whether these two mutations have exactly the same effects on tumor cells and the tumor microenvironment. Methods: All collected tumor samples were subjected to simultaneous whole-exon sequencing and proteome sequencing. Results: IDH1 mutations accounted for 12.2%, and IDH2 mutations accounted for 5.5%, all missense mutations. Tumors with IDH mutations had lower proportions of KRAS and TP53 mutations. Mutated genes were obviously enriched in the kinase pathway in the tumors with IDH2 mutations. The signaling pathways were mainly enriched in the activation of cellular metabolic activities and an increase of inhibitory immune cells in the tumors with IDH mutations. Moreover, tumors had unique enrichment in DNA repair in IDH1 mutants and secretion of biological molecules in IDH2 mutants. Inhibitory immune cells might be more prominent in IDH2 mutants, and the expression of immune checkpoints PVR and HLA-DQB1 were more prominent in IDH1 mutants. IDH mutations were more related to metabolism-related and inflammation-immune response clusters, and some belonged to the DNA replication cluster. Conclusions: These results revealed the differential IDH1 and IDH2 mutation-related landscapes, and we have provided an important reference database to guide ICC treatment.
Predictors of malignancy and survival in patients with pheochromocytoma and paraganglioma.
Authors: Hector Raul Gonzalez-Sanchez, Alejandro Aranda-Gutierrez, Andres Meraz-Brenez, Haydee Cristina Verduzco-Aguirre, Roberto De la Peña-Lopez
Journal: Journal of Clinical Oncology (2024)

e16289 Background: Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors for which the definitive diagnosis of malignancy hinges on the detection of metastatic disease, rather than histological features, making prognostication particularly challenging. Consequently, identifying reliable clinical predictors for both malignancy and survival is of utmost importance. Methods: We retrospectively analyzed records of patients with biopsy-proven PCC or PGL treated at a single center in Mexico City from 2008 to 2022. Patients with follow-up &gt; =12 months were eligible. Data was collected from electronic medical records. Independent-samples T-test and X 2 and Fisher’s exact tests were used to evaluate associations between variables. We used the Kaplan-Meier method to calculate disease-free survival (DFS) and overall survival (OS) rates, and utilized the log-rank test to compare these outcomes across clinicopathological features. Cox regression analysis was used to determine survival hazard ratios (HR). Results: Among 60 patients, the mean age at diagnosis was 41 years, 37 (62%) had PCC, and 12 (20%) had malignant disease (6 distant recurrences and 6 de novo metastatic cases). Clinicopathological features according to disease type (i.e. benign or malignant) are shown in Table 1. Patients with malignant disease were more likely to have PGL (67% vs. 31%, p = 0.024) and have a body mass index of &gt; =30 kg/m 2 at diagnosis (67% vs. 8%, p &lt; 0.01). With a median follow-up of 42 months (95% CI 35-49), 8 recurrences (2 local and 6 distant) and 6 deaths were recorded, yielding 3-year DFS and OS rates of 92% and 91%, respectively. In a multivariate analysis including factors associated with DFS and OS in univariate analyses (i.e. obesity status and hypertension at diagnosis), only obesity (HR 4.93, 95% CI 1.02 - 23.79; p = 0.047) remained associated with a worse DFS, with no influence on OS. Conclusions: This study highlights obesity as a significant predictor of malignancy and recurrence in patients with PCC and PGL, marking a novel finding in the literature on these tumors. Further research is warranted to explore the underlying mechanisms linking obesity with more aggressive disease in PCC and PGL. [Table: see text]
Apatinib and camrelizumab plus hepatic arterial infusion with oxaliplatin and 5-fluorouracil vs. apatinib and camrelizumab as the first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A randomized multi-center clinical trial.
Authors: MinKe He, Zefeng Du, Zhicheng Lai, Anna Kan, Ming Shi
Journal: Journal of Clinical Oncology (2024)

TPS4194 Background: The combination of immune checkpoint inhibitors and antiangiogenic drugs has been approved as the first-line treatment for advanced hepatocellular carcinoma (HCC). However, the survival benefit is still limited, especially in patients with high-risk features (Vp4, and/or bile duct invasion and/or tumor occupancy of ≥50% of the liver). Hepatic arterial infusion chemotherapy (HAIC) plus apatinib (an antiangiogenic drug) and camrelizumab (a PD-1 antibody) showed encouraging antitumor activity for these patients in a previous phase 2 study. Herein, we investigated the efficacy and safety of apatinib and camrelizumab plus HAIC compared with apatinib and camrelizumab as the first-line treatment for HCC with portal vein tumor thrombus (PVTT). Methods: In this randomized, open-label, phase 3 trial, eligible patients are ≥18 years with HCC confirmed by radiology, histology, or cytology. Other eligibility criteria were as follows: with PVTT, ECOG PS 0/1, no history of systemic therapy, not amenable to curative treatment approach, Child-Pugh A class liver score, and ≥1 measurable lesion by RECIST v1.1. A total of 214 patients (anticipated) will be randomized (1:1) to receive apatinib (250mg orally once daily) and camrelizumab (200 mg IV Q2W) plus HAIC with FOLFOX (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 , 5-fluorouracil bolus 400 mg/m 2 on day 1, and 5-fluorouracil infusion 2400 mg/m 2 for 20 hours via hepatic artery Q4W) or apatinib (250mg orally once daily) and camrelizumab (200 mg IV Q2W) until disease progression or intolerable toxicity. Stratification will be by patients with or without high-risk features. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, objective response rate per RECIST 1.1 and mRECIST, disease control rate per RECIST 1.1 and mRECIST, time to progression, duration of response, time to response, and safety. Whole-Exome Sequencing and RNA Sequencing of tumor biopsy samples were performed for predictive biomarker exploration. Clinical trial information: NCT05198609 .
VIRAGE: A phase IIb, open-label, randomized study of nab-paclitaxel and gemcitabine plus/minus VCN-01 in patients with metastatic pancreatic cancer.
Authors: Rocio Garcia-Carbonero, Roberto Pazo Cid, Teresa Macarulla, Alana Nguyen, Edward Kim, Berta Laquente, Tara Elisabeth Seery, Mireya Cazorla, Carmen Guillen-Ponce, Eva Martinez De Castro, Beatriz Anton-Pascual, Andrés J. Muñoz Martín, Miriam Lobo, Ignacio Garrido-Laguna, Charles Le, Michael Kaleko, Mary Ann Shallcross, Carmen Blasco, Manel Cascallo, Manuel Hidalgo
Journal: Journal of Clinical Oncology (2024)

TPS4210 Background: VCN-01 is a modified oncolytic adenovirus type 5 (Ad5) designed to replicate selectively in cancer cells with a dysfunctional RB1-E2F pathway and express hyaluronidase to enhance virus intratumoral spread and facilitate chemotherapy and immune cells extravasation into the tumor. Results obtained in a previous phase I trial in patients with solid tumors, including metastatic pancreatic cancer, showed that a single systemic administration of VCN-01 is feasible and has an acceptable safety profile alone or when combined with standard of care chemotherapy (SoC) nab-paclitaxel plus gemcitabine (NCT02045602). VCN-01 reached and replicated in tumors and encouraging biological and clinical activity was observed when administered in combination with SoC to patients with metastatic pancreatic adenocarcinoma (mPDAC). Based on the promising phase I results, a phase IIb, open-label, randomized study was initiated to evaluate treatment with two doses of VCN-01 in combination with nab-paclitaxel and gemcitabine in patients with mPDAC. Methods: VIRAGE is a multi-center, open label, randomized, 2-parallel arm, phase IIb trial that evaluates the safety, tolerability and efficacy of two separate VCN-01 intravenous administrations (1x10 13 vp/dose) in combination with SoC (nab-paclitaxel at 125mg/m 2 and gemcitabine at 1000mg/m 2 ) as first line treatment in chemonaïve mPDAC patients. A total of 92 subjects in North America and European Union will be recruited and randomized (1:1) to receive either SoC nab-paclitaxel and gemcitabine (on days 1, 8 and 15 of each 28-day cycle) (Arm I), or doses of VCN-01 administered 1 week prior to SoC nab-paclitaxel and gemcitabine in each of cycle 1 (week 1) and cycle 4 (week 14) (Arm II). Cycles 1 and 4 of Arm II will be 35-day cycles to accommodate VCN-01 dosing, while all other SoC cycles will be 28 days. Patients will continue study treatment until progressive disease (PD), unacceptable toxicity or patient’s/investigator’s decision. The primary endpoint is overall survival (OS) and the assessment of safety and tolerability of two intravenous doses of VCN-01 added to SoC. The secondary objectives include time-to-progression (TTP), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), duration of the response (DoR), 1-year OS and PFS rates, and serial changes in tumor markers (Ca19.9). At 31 Jan 2024, the enrollment is ongoing in US and Spanish sites. Clinical trial information: NCT05673811 .
A single-center retrospective analysis of allergies and survival outcomes in pancreatic adenocarcinoma.
Authors: Peter Chi-Win Li, Amethyst Saldia, Sara Olson
Journal: Journal of Clinical Oncology (2024)

e16299 Background: Survival from pancreatic adenocarcinoma (PDAC) remains poor, with a 5 year survival of 12.5%. A prior 2010 epidemiological study done at Memorial Sloan Kettering Cancer Center (MSKCC) found an association between self-reported allergies and improved survival in PDAC patients. In this retrospective study, we analyzed self-reported allergies and outcomes in both resected and unresected PDAC patients. Methods: Data including allergy status and clinical information were collected from an ongoing PDAC registry study at MSKCC. 1389 eligible PDAC patients were approached and 917 were enrolled between April 2004 and November 2017. 874 patients were included in our overall survival (OS) analysis using Kaplan-Meier methods. 43 patients were excluded due insufficient data or loss to follow up. Cox proportional hazards models were used to adjust for covariates. Results: Of the 874 patients analyzed, mean age at diagnosis was 63.5 years (standard deviation: 11.4), 52% were male, and race was 87% white, 6% black, 4% Asian, and 3% other race. 32.3% had surgery and 85% received chemotherapy. Median overall survival (OS) was 32.8 vs. 27.7 months [Hazard Ratio (HR) 0.95, p = 0.73] and 12.5 vs. 11.2 months [HR 1.04, p = 0.66] in for PDAC patients with allergies compared to those without in the resected and unresected cohorts, respectively. Advanced stage was associated with worse outcomes in both groups. Chemotherapy was significantly associated with improved survival only in the unresected group (HR 0.48, 95% CI 0.30-0.78, p = 0.030). Other established PDAC risk factors were also analyzed. Smoking history, diabetes, and family history were not associated with survival. Only obesity was significantly associated with worse outcomes in the unresected group (HR 1.3, 95% CI 1.01-1.67, p = 0.04). Conclusions: Contrary to previous findings, self-reported allergies were not significantly associated with improved survival in PDAC. In atopic patients, T helper type 2 cells are upregulated with allergen exposure and produce more IgE. Tumor-specific IgE has shown protective benefits in preclinical models but can be downregulated in the tumor microenvironment in PDAC. Further studies are needed to explore the relationship between allergies and PDAC and understand potential aspects of the immune system that can be harnessed to improve outcomes. One study limitation was that allergies were self-reported and not confirmed with allergy testing. We were also able to redemonstrate worse outcomes with more advanced stages and the benefit of chemo in the advanced setting. Further studies are needed to explore the mechanisms behind obesity and PDAC. [Table: see text]
TACE combined with tislelizumab and lenvatinib in the treatment of advanced liver cancer: A real world study.
Authors: Bo Li, Xiaoli Yang, Hao Tang, Shu Qin, Fangyi Peng, Song Su
Journal: Journal of Clinical Oncology (2024)

e16270 Background: The combination of transcatheter arterial chemoembolization (TACE) plus Lenvatinib prolonged progression-free survival (PFS) and overall survival (OS) than Lenvatinib or TACE monotherapy for patients with hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of Lenvatinib plus monoclonal antibody against programmed cell death 1 (anti-PD1) and TACE for patients with advanced HCC. Methods: Pts with advanced HCC who treated with Lenvatinib plus anti-PD1 and TACE were enrolled. Objective response rate (ORR), PFS, disease control rate (DCR) and OS were calculated to assess the antitumor response and the treatment-related adverse events to the safety. Consecutive pts were identified from September 2021 to August 2023.The Patients were included based on the following chief eligibility criteria. After signing the informed consent form, patients received sequential treatment with TACE in combination with Lenvatinib and tislelizumab. The anti-PD1 were recommended to be used continually every 3 weeks until disease progression, or intolerable toxicity. Lenvatinib was recommended to be used continually every day until disease progression, or intolerable toxicity. Follow up TACE should be given according to the patient's condition, no more than 3 times. Results: Between Sep. 2021 to Aug. 2023, 45 were enrolled. All pts received at least one dose of study treatment. The median age was 56 years(range34,73), 4 of the pts are BCLC-B stage, 41 of the pts are BCLC-C stage.Progression occurred in 8 of 45 patients and 14 patients died. The median PFS was 13.4 months (95% CI: 10.9-15.8 months) and the median OS was 20 months (95% CI: 9.8-30.4months). Of the 45 patients, a total of 3 (6.7%) patients achieved complete response (CR), and these 3 patients were treated with surgical resection. Partial Response (PR) was achieved in 12 patients (20%), Stable Disease (SD) in 22 pts (33.3%), Progressive Disease (PD) in 8 pts (17.8%), and Objective Response Rate (ORR) in patients. The Objective Response Rate (ORR) was 33.3% and the Disease Control Rate (DCR) was 82.2%.Treatment-related adverse events included increased AST 44.4%(20/45), increased ALT 51.1%(23), increased total bilirubin 42.2%(19/45), rash 44.4%(20/45), pruritus 42.2%(19/45), gastrointestinal reaction 33.3%(15/45), abdominal pain 24.4%(11/45), sensory abnormality 20%(9/45), and arthralgias 4.4%(2/45), etc., and Grade 3 Adverse events were increased ALT 2.2%(1/45), increased AST 4.4%(2/45), increased total bilirubin 2.2%(1/45), rash 2.2%(1/45), and gastrointestinal reaction 2.2%(1/45).No grade 4 or above adverse events occurred. Conclusions: In this study, TACE plus anti-PD1 and targeted therapies showed favorable efficacy and manageability in patients with advanced HCC. Toxicity was manageable with a low incidence of grade 3-4 adverse events. There were no unexpected safety signals.