tbuckley/cabot-search huggingface dataset:
Short-term and long-term outcomes of transduodenal ampullectomy for patients with early ampullary cancer.
Authors: Ryoichi Miyamoto
Journal: Journal of Clinical Oncology (2024)

e16244 Background: Transduodenal ampullectomy (TDA) has been attempted in early ampullary cancer. However, the indication and extent of TDA with curative intent remain controversial. Here, we address the perioperative and long-term outcomes of patients with early ampullary cancer who underwent TDA. Methods: Ten early ampullary cancer patients who underwent TDA and 11 early ampullary cancer patients who underwent subtotal stomach-preserving pancreatoduodenectomy (SSPPD) at this institute were respectively enrolled. Among this cohort, we analyzed the perioperative outcomes and long-term outcomes. Results: In terms of the perioperative outcomes between the TDA and SSPPD groups, the TDA group exhibited a shorter operating time (244 minutes vs. 390 minutes, p = 0.003), less intraoperative blood loss (67.5 grams vs. 774 grams, p = 0.006) and shorter length of postoperative hospital stay (15 days vs. 33 days). With respect to the postoperative nutrition status, the TDA group exhibited less postoperative weight loss (0.67% vs. 8.95%, p = 0.021), a better CONUT score (1.0 vs. 2.1, p = 0.011) and a better PNI score (42.9 vs. 40.9, p = 0.018). The 5-year survival rate in the adenoma with high-grade dysplasia (HGD) and T1a (M) groups was 100%, while the median survival time in the T1a (OD) group was 20.7 months (p = 0.0028). Conclusions: TDA is assumed to be a feasible and effective surgical procedure for the treatment of selected patients with early ampullary cancer, including patients with adenoma with HGD or T1a (M) ampullary cancer.
Peritumoral HLJ1-STAT3 pathway investigation in carcinogen-induced hepatocellular carcinoma.
Authors: Wei-Jia Luo, Min-Hui Chien, Sung-Liang Yu, Pan-Chyr Yang, Kang-Yi Su
Journal: Journal of Clinical Oncology (2024)

e16251 Background: Hepatocellular carcinoma (HCC) is a major global health issue and its treatment options have been limited. Therefore, it is urgent to develop cancer biomarkers for defining cancer risk, diagnosis, prognosis, and even finding new therapeutic targets. Human Liver DnaJ-Like Protein (HLJ1), which belongs to DnaJ heat shock protein family (HSP40) member B4 (DNAJB4), has been identified as a tumor suppressor in various cancers including lung cancer and colorectal cancer. Though the biological function of HLJ1 in either cancer or the liver has emerged in recent years, the precise role of HLJ1 in HCC carcinogenesis is still unclear. Methods: Samples for gene expression cDNA microarray were from 6-8 weeks wild-type (WT) and HLJ1 knockout (HLJ1 -/- ) mice liver. For the long-term carcinogenesis study, both mice are injected with 20 mg/kgbw diethylnitrosamine (DEN) at postnatal day 15. After that, 50 mg/kgbw DEN was administrated weekly to mice between the ages of 4 to 12 weeks. Mice were sacrificed at ages 30 and 36 weeks to assess the tumor count and size. For the short-term DEN study, 6-8-week-old mice were injected with 100 mg/kg DEN, and 24 and 48 hours after administration the liver tissues were frozen and fixed for western blotting and IHC analysis. Cancer cell transplantation was performed by intrasplenic injection of HLJ1-wildtype LLC and B16F1 cells into both genotypes. Clinical information of 362 liver cancer patients from the TCGA database was analyzed for the correlation between HLJ1 expression and survival. Results: In cDNA microarray analysis, We demonstrated that HLJ1 deficiency led to HCC gene signatures associated with activated IL-6/STAT3 signaling pathways. We used the DEN as a carcinogen and found STAT3 and H2AX phosphorylation induced by short-term DEN treatment was amplified in HLJ1-deficient mice. In long-term DEN experiments, HLJ1 deletion promoted tumor initiation and proliferation at the early and late stages of HCC progression accompanied by pronounced STAT3 phosphorylation in the normal part instead of the tumor part. Furthermore, transplantation of HLJ1-wildtype B16F1 and LLC cell lines into HLJ1-deficient mice led to more tumorigenic phenotype than into wildtype mice. Clinical information of 362 liver cancer patients from the TCGA database exhibited that higher expression of HLJ1 in the tumor part is correlated to a lower disease-specific survival rate. Conclusions: In summary, HLJ1 protects against DEN-induced HCC hepatocarcinogenesis through the regulation of STAT3 signaling in the peritumoral normal cells. Hence, HLJ1 can be a prognostic biomarker for liver cancer and a promising therapeutic target for HCC in the future.
Pandemic Stringency Measures and Hospital Admissions for Eating Disorders
Authors: Nadia Roumeliotis, Matthew Carwana, Katia Charland, Ofélie Trudeau, Mike Benigeri, Mamadou Diop, Holly Agostino, Kate Zinszer, Isra Amsdr, Baudoin Forgeot d’Arc, Sylvana Côté, Nicole E. Basta, Patricia Fontela, Soren Gantt, Terry P. Klassen, Caroline Quach, Quynh Doan, Sarah Ahira, Samina Ali, Upton Allen, Krista Baerg, Megan Bale-Nick, Ananya Banerjee, Michelle Barton, Darcy Beer, Simon Berthelot, Julie Bettinger, Maala Bhatt, Melanie Buba, Francine Buchanan, Jared Bullard, Brett Burstein, Catherine Burton, Rahul Chanchlani, Michaël Chassé, Karen Choong, Evelyn Constantin, Cora Constantinescu, Carrie Costello, Sylvana Côté, Tammie Dewan, Tanya Di Genova, Olivier Drouin, Karen Dryden-Palmer, Geneviève Du Pont- Thibodeau, Marc-André Dugas, Raven Dumont-Maurice, Guillaume Emeriaud, Jason Emsley, Mark Ferro, Karen Forbes, Isabel Fortier, Jennifer Foster, Jessica Foulds, Stephen Freedman, Gabrielle Freire, Eleni Galanis, Peter Gill, Jocelyn Gravel, Emily Gruenwoldt, Gonzalo Guerra, Astrid Guttman, Betty Jean Hancock, Robyn Harrison, Joanna Holland, Ari Joffe, Fatima Kakkar, April Kam, James D. Kellner, Lisa Knisley, Thierry Lacaze-Masmonteil, Saptharishi Lalgudi Ganesan, Marc- André Langlois, Nicole Le Saux, Laurie Lee, Kirk Leifso, Patricia Li, Andrea Linares, Sanjay Mahant, Isabelle Marc, Ahmed Mater, James McNally, Garth Meckler, Shaun Morris, Haifa Mtaweh, Srin Murthy, Fiona Muttalib, Leigh- Anne Newhook, Jessica Nicoll, Nathalie Orr-Gaucher, Joseph Pagano, Anna Pangilinan, Jesse Papenburg, Jeffrey Pernica, Naveen Poonai, Elodie Portales-Casamar, Robert Porter, Rupeena Purewal, Paula Robeson, Joan Robinson, Manish Sadarangani, Marina Salvadori, Susan Samuel, Shannon Scott, Anupam Sehgal, Archna Shah, Tatiana Sotindjo, Carla Southward, Taylor Stoesz, Robert Strang, Shazeen Suleman, Peter Szatmari, Sepi Taheri, Jennifer Tam, Roseline Thibeault, Karina Top, Krystel Toulouse, Sze-Man Tse, Anupma Wadhwa, Gita Wahi, Sam Wong, Bruce Wright, Rae Yeung
Journal: JAMA Pediatrics (2024)

Hospitalizations for eating disorders rose dramatically during the COVID-19 pandemic. Public health restrictions, or stringency, are believed to have played a role in exacerbating eating disorders. Few studies of eating disorders during the pandemic have extended to the period when public health stringency restrictions were lifted.
Utility of an amplicon-based ctDNA platform for advanced cholangiocarcinomas (CCA) in Asia.
Authors: Gin Wai Kwok, Jonathan Poh, Chae Yin Cher, Pannapa Pinweha
Journal: Journal of Clinical Oncology (2024)

e16206 Background: Cholangiocarcinoma represents a major cause of cancer mortality in Asia. While clinical outcomes have improved with the addition of anti-PD1/PDL1 agents to standard-of-care chemotherapy for advanced disease, recent data suggests that novel agents against IDH1 mutations, FGFR2 and NTRK rearrangements, BRAF V600E mutations, and microsatellite instability (MSI) are effective. Tumor-based next generation sequencing (NGS) is routinely recommended by guidelines but is limited by tissue availability and quality in patients with unresectable disease. A comprehensive circulating tumor DNA-based (ctDNA) NGS platform offers an acceptable alternative, but its clinical utility and pickup rate for oncogenic drivers remain unknown. Methods: In our multi-national cohort of advanced CCA across 5 countries, we explored the utility of Lucence LiquidHALLMARK (LHM), a Medicare-reimbursed, amplicon-based NGS ctDNA platform targeting 80 cancer related genes, 10 fusions, and MSI. Performance of LHM has been previously reported. Data was retrieved in-house by a de-identified centralized database and pooled for analysis. Here, we report the demographic and genomic findings of our cohort and highlight the impact of testing on actionable molecular alteration discovery. Results: Between Jan 2020 and Dec 2023, 60 samples from 56 patients (62.5% male) with advanced CCA in Hong Kong SAR (50.0%), Singapore (41.1%), Thailand (3.6%), Philippines (3.6%), and Malaysia (1.8%) underwent LHM testing. Metastatic disease accounted for 83.9% and 8.9% had locally advanced disease. Median age was 67 years (range 33-88), with 34% and 30% of tests obtained during first-line therapy and at diagnosis respectively. Only 6 cases had available tissue NGS results. Analysis on 56 baseline samples showed an 80.4% discovery rate (45/56 patients) for ≥1 molecular alterations. A median of 2 variants (mean 3.27) was detected per sample, with variant allele fraction ranging from 0.05% to 66.5%. Importantly, 8.9% (5/56) of patients harbored ≥1 actionable variants, including 3 with FGFR2 rearrangements ( FGFR2- WAC, FGFR2- ACTR1A, FGFR2- CAMK2D) and 2 with BRAF V600E drivers. A further 3 patients had potentially druggable variants in IDH2 and FGFR3 and 12 harbored BRCA1/2 variants, of which 4 were deleterious. None of the samples had MSI. Top 10 mutated genes were TP53 (48%), KRAS (21%), BRCA2 (18%), PIK3CA (11%), TERT (9%), CDKN2A (9%), SMAD4 (9%), FGFR2 (7%), BRAF (7%), and CDK6 (5%). Limited histopathological and treatment outcomes are available in the current dataset. Conclusions: Our advanced cholangiocarcinoma cohort of 56 patients from 5 Asian countries showed that an amplicon based ctDNA liquid biopsy platform overcomes the tissue-related challenges of genomic profiling specific to unresectable biliary tumors. We showed an 80.4% discovery rate for any molecular alterations and a 8.9% pickup rate for variants with strong actionability.
Role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte-ratio (PLR) in unresectable hepatocellular carcinoma (uHCC): Subgroup analysis of patients treated with camrelizumab (cam) + rivoceranib (rivo) in the CARES-310 trial.
Authors: Adam Burgoyne, Ahmed Omar Kaseb, Wei Shi, Laura Alexander, Xianzhang Meng, Kristin Ryan, Chris Galloway, Will Neubach, Arndt Vogel, Stephen Lam Chan
Journal: Journal of Clinical Oncology (2024)

e16197 Background: CARES-310 (NCT03764293) evaluated the combination of the PD-1 inhibitor, cam, and the VEGFR-2 tyrosine kinase inhibitor, rivo, compared to sorafenib (sor) for the treatment of 543 patients (pts) with uHCC. Cam + rivo significantly improved mOS (22.1 months [mo] [95% CI 19.1-27.2] vs 15.2 mo [13.0-18.5] HR 0.62 [95% CI 0.49-0.80]; one-sided p &lt; 0.0001) and mPFS (5.6 mo [95% CI 5.5-6.3] vs 3.7 mo [2.8-3.7]; HR 0.54 [95% CI 0.44-0.67]; one-sided p &lt; 0.0001) compared to sor. The most common (≥20%) grade ≥3 treatment-related adverse events (TRAEs) for cam + rivo were hypertension (37.5%) and increased AST (16.5%) vs palmar-plantar erythrodysesthesia syndrome (15.2%) for sor. An elevated level of inflammation, including NLR and PLR, have been associated with poor survival outcomes in pts with HCC (Lin S, et al. Trans Cancer Res. 2021). Here, we present a subgroup analysis of the CARES-310 trial evaluating the impact of baseline (BL) NLR and PLR status on pt outcomes. Methods: The subgroup of pts treated with cam+rivo and BL NLR &lt; 5 or ≥5 and PLR &lt; 300 or ≥300 were evaluated for mOS, mPFS, overall response rate (ORR), disease control rate (DCR), and safety. Results: Of 272 pts treated with cam+rivo, 64.3% of pts had extrahepatic spread, median AFP was 84.1 ng/mL, 86.8% were Child-Pugh (CP) class A5, 13.2% were CP class A6, 73.5% were ALBI grade 1, 26.5% were ALBI grade 2. Additionally, 249 pts had NLR &lt; 5, 10 pts had NLR ≥5, 252 pts had PLR &lt; 300, and 7 pts had PLR ≥300. Pts with BL NLR &lt; 5 and PLR &lt; 300 demonstrated improved outcomes in mOS, mPFS, ORR, and DCR vs pts with BL NLR ≥5 and PLR ≥300 (Table). Rates of any grade TRAEs and grade ≥ 3 TRAEs were comparable between pts with BL NLR &lt; 5 and ≥5 and PLR &lt; 300 and ≥300 (Table). Conclusions: These results suggest that NLR and PLR may serve as a prognostic marker in patients with uHCC, but larger studies are needed to validate these findings. Clinical trial information: NCT03764293 . [Table: see text]
Outcomes of patients with intrahepatic cholangiocarcinoma with a focus on the interaction between tumor stage and age on mortality over the past decade.
Authors: Ayrton Bangolo, Vignesh Nagesh, Shraboni Dey, Hadrian Tran, Daniel Elias, Charlene Mansour, Izage Kianifar Aguilar, Aman Siddiqui, Nikita Wadhwani, Simcha Weissman, Pierre Fwelo
Journal: Journal of Clinical Oncology (2024)

e16201 Background: Intrahepatic cholangiocarcinoma(iCCA) is the second most prevalent liver tumor and originates from the epithelial cells of the bile duct . The purpose of this study is to assess to the extent independent prognostic factors influence mortality in iCCA. We also investigated the clinical characteristics and survival outcomes of patients with iCCA between 2010 and 2017. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database provided information on 5083 iCCA patients in the USA, between 2010 and 2017. Demographics, clinical features, overall mortality (OM), cancer-specific mortality (CSM), and the interaction between age and tumor stage were analyzed. Variables with p &lt; 0.1 in univariate Cox regression were included in the multivariate model, with a hazard ratio (HR) &gt; 1 indicating adverse prognostic factors. Results: Multivariate Cox proportional hazard regression analyses showed higher OM in males (HR = 1.19), metropolitan counties with 250,000 population (HR = 1.15), and lower in the age groups 40-59 (HR = 0.58) and 60-79 (HR = 0.65). Patients who underwent radiation therapy (HR = 0.78), chemotherapy (HR = 0.54), and surgery (HR = 0.29) had lower OM. Similarly, CSM was higher in males (HR = 1.17) and metropolitan counties (HR = 1.18), but lower in age groups 40-59 (HR = 0.52) and 60-79 (HR = 0.57). Interaction analysis revealed higher OM in stage III tumors with lymph node involvement aged 40-59 (HR = 2.30). CSM was higher in ages 40-59 with stage III iCCA (HR = 2.60) and stage IV (HR = 2.81), as well as in 60-79 with stage III (HR = 2.24) and stage IV tumors (HR = 2.93). OM and CSM were higher in all age groups &gt; 40 compared to the younger population. Conclusions: In this large retrospective study using the SEER database, we unfolded an aspect of iCCA mortality that has not been previously studied. We found a significant interaction between two independent prognostic factors that enhance mortality. This data may assist treating oncologists in selecting patients that would benefit from early aggressive treatment modalities which proved to be beneficial as seen in our study. This study paves the way for future prospective randomized clinical trials to further understand the impact of such interactions in patients with iCCA, especially in the era of precision oncology.
Circulating tumor DNA for recurrence monitoring following resection for pancreas adenocarcinoma.
Authors: Neda Amini, Shruti Koti, BENJAMIN ASCHERMAN, Daniel King
Journal: Journal of Clinical Oncology (2024)

e16365 Background: Detecting early recurrence among patients with resected pancreatic cancer may facilitate earlier treatment and better outcomes for patients with resected pancreatic ductal adenocarcinoma (PDAC). Circulating tumor DNA (ctDNA) has shown promise as a tumor-specific biomarker for PDAC but has not yet entered routine clinical use. This study aims to conduct analytical and clinical validation of Signatera ctDNA profiling to predict recurrence in patients with PDAC. Methods: A retrospective IRB-approved protocol evaluating the use of Signatera ctDNA testing among patients who underwent resection at Northwell Health during 2019-2023. The utility of ctDNA status to predict PDAC recurrence during follow-up was assessed using cox regression. Results: There were 91 ctDNA tests among 24 patients. With a median follow-up of 15 months, recurrence was observed in 38% (9/24) of patients and 8 patients died. Among patients with recurrence, most of them had positive ctDNA before showing signs of recurrence on the imaging (6/9, 66.7%) with mean lead time of 116 days, while 2 of them had positive ctDNA after recurrence and one patient never had positive ctDNA. At the time of recurrence, eight patients had elevated CA19-9, while two patients with normal CA19-9 had positive ctDNA. The median recurrence-free survival (RFS) was 23 months (95% CI, 11-not reached). Patients with detectable preoperative ctDNA had significantly decreased median RFS (14 months; 7 of 10 (70%) recurred) when compared with patients negative for ctDNA [not reached; 2/14 (14.3%) recurred; P= 0.005). In multivariable Cox model after adjusting for potential risk factors, detection of ctDNA was associated with RFS. (table). Conclusions: Signatera ctDNA profiling identified relapse earlier than imaging for most patients. These results suggest the potential for a prospective trial evaluating early treatment interventions in this deadly disease to improve survival rates. [Table: see text]
Survival outcomes in patients with advanced intrahepatic cholangiocarcinoma in United States: A nationwide analysis.
Authors: Diya Jayram, Nouman Aziz, Hamza Naeem, Shahzaib Ahmad, Muhammad Ahsan Hanif Chaudhary, Shreyas S. Bellur, Mohammad Arfat Ganiyani, Fathima Shehnaz Ayoobkhan, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2024)

e16211 Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy after hepatocellular carcinoma. Anecdotal evidence shows that chemotherapy and radiotherapy after surgical resection confer better survival outcomes in patients with advanced disease. This study aims to demonstrate outcomes of different therapeutic options in patients with stage 4 ICC. Methods: We queried the National Cancer Database from 2004 to 2020 to identify patients with stage 4 ICC. The study compared median overall survival (mOS) using Kaplan-Meier methodology and pair-wise log-rank test among different therapeutic groups, including surgery (Sx) alone, chemotherapy (CT) alone, radiotherapy (RT) alone, surgery + chemotherapy (Sx+CT), surgery + chemoradiation (Sx+CRT), and chemoradiation (CRT). The results of the study were reported in concordance with STROBE guidelines. Results: Among 13,735 patients with stage 4 ICC, the median age was 64 years (range: 17-90+ years), 51.0% were male, 83.6% were White, 9.1% Black and 4.0 % Asian. 342 (2.5%) underwent Sx, 10061 (73.3%) CT alone, 427 (3.1%) underwent RT alone, 744 (5.4%) Sx+CT, 314 (2.3%) Sx+CRT, and 1847 (13.5%) underwent CRT. Patients who underwent Sx+CRT had better mOS (23.8 months, 95% CI 20.5-24.1) than all other modalities, including Sx (11.1 months, 95% CI 8.2-13.4), CT (8.6 months, 95% CI 8.4-8.9), RT (4.7 months, 95% CI 3.8-5.2), Sx+CT (21.9 months, 95% CI 20.0-24.1) and CRT (11.7 months, 95% CI 11.1-12.3) p &lt; 0.01. Conclusions: Unlike other gastrointestinal malignancies, multimodal therapy i.e., chemoradiation after surgical resection of primary tumor improves survival in advanced ICC. However, prospective studies affirming these findings are warranted.[Table: see text]
Surgical resection versus thermal ablation: Comparison of sequential options after successful TACE downstaging therapy for unresectable hepatocellular carcinoma—A long-term multi-institutional study.
Authors: Chao An, Pei-Hong Wu, Jin-Hua Huang
Journal: Journal of Clinical Oncology (2024)

e16258 Background: Transarterial chemoembolization (TACE) is an effective and safe treatment for unresectable hepatocellular carcinoma (uHCC). However, the selection of sequential therapeutic modalities after TACE downstaging therapy is still controversial. The aim of this study is to compare the efficacy and safety of surgical resection (SR) and thermal ablation (TA) after successful TACE downstaging therapy for uHCC. Methods: In this real-world multi-institutional study from June 2008 to October 2022, 8,219 consecutive patients with HCC underwent conventional TACE at 12 hospitals. Patients underwent successful TACE downstaging therapy for uHCC beyond Milan criteria, who were assigned into SR group and TA group. The propensity score matching (PSM) was applied to reduce selection bias between groups. Cumulative overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan‒Meier method with the log-rank test. A comparison analysis of major complications was performed using the c 2 test. Results: 609 (7.4%) patients received SR or TA after TACE. After PSM 1:1, 185 patients in the SR group were matched with 185 in the TA group. After 4.5 years of median follow-up time, the cumulative 1-, 3-, 5- and 10-year OS rates were 98.8%, 89.3%, 82.9% and 64.4% in the SR group and 99.5%, 88.4%, 75.3% and 53.9% in the TA group, respectively, showing no significant difference ( P = .381). The cumulative 1-, 3-, 5- and 10-year PFS rates were 88.5%, 69.2%, 58.8% and 32.2% in the SR group and 90.6%, 71.4%, 53.1% and 32.0% in the TA group, respectively, showing no significant difference ( P = .855). The incidences of major complications were 6.5% in the SR group and 7.6% in the TA group, showing no significant difference ( P = .684). Conclusions: For uHCC patients beyond the Milan criteria received TACE downstaging therapy, TA might be acceptable as an alternative to SR in first-line sequential treatment scheme.