tbuckley/cabot-search huggingface dataset:
The effect of obesity in hospitalized patients with hepatocellular carcinoma: A nationwide analysis.
Authors: Ekrem Turk, Ayobami Gbenga Olafimihan, Muhammad Bilal Ibrahim, Alejandro Nieto Dominguez, Vaishali Deenadayalan
Journal: Journal of Clinical Oncology (2024)

569 Background: Obesity, a prominent issue in global health, is known to increase the risk factors associated with a variety of cancers, including hepatocellular carcinoma (HCC), the most common type of primary liver cancer. While existing research affirms the heightened risk of developing HCC in individuals with obesity, there remains a significant gap in understanding the specific influences of obesity on the outcomes of patients admitted with primary HCC diagnosis during their index hospital admission. This study explores the mortality rate, length of stay (LOS), and healthcare utilization in HCC patients with and without obesity. Methods: Nationwide Inpatient Sample (NIS) was queried to determine adult hospitalized patients with a primary diagnosis of HCC using ICD-10 codes. The primary outcome was defined as the effect of obesity on inpatient mortality in those patients. Secondary outcomes included LOS, total hospital charge, health care utilization, ICU admission. We evaluated the baseline characteristics using the t-test and chi-square test. Multivariable logistic regression analysis was performed to assess the association of HCC with obesity and inpatient mortality adjusted by age, gender, race, Charlson index, insurance, and household income. Results: A total of 62,050 HCC patients were identified, and 10.9% of these patients had obesity. HCC patients with obesity were younger (64.7 vs. 65 years, p=0.220), more likely to be female (32.2% vs. 24%, p &lt; 0.001), White (59.8% vs. 50.2% p &lt; 0.001), and more likely to have no insurance (28.8% vs. 23.3%, p &lt; 0.001) compared to HCC patients without obesity. HCC with obesity had higher mean Charlson Comorbidity index 5.9 vs. 5.5, p &lt; 0.001). The overall inpatient mortality rate was 8.2% for all patients who are admitted for HCC; lower in HCC with obesity (5.6%) vs HCC without obesity (8.5%) (p &lt; 0.001). Charlson index, Male gender, African–American race, Hospital teaching status, insurance status found to be associated with inpatient mortality among HCC hospitalizations. HCC with obesity had a lower odds ratio with decreased all-cause mortality of 25% compared to HCC without obesity (aOR 0.75, 95% CI 0.58-0.96, p = 0.023). In addition, HCC with obesity was associated with increased LOS mean 6.3 vs. 5.7 days (adjusted difference: 0.6 p &lt; 0.001), and total hospital charges (mean $112,687 vs $88,481, adjusted difference: $21122 p &lt; 0.0001). Also; ICU transfer rate and AKI development were found more in obese cohort and this different was statistically significant. Conclusions: Our study revealed that HCC patients with obesity had a lower inpatient mortality rate compared to those without obesity, despite longer hospital stays and higher costs. These findings hint at a complex interplay between obesity and HCC outcomes, necessitating further in-depth research.
Biweekly gemcitabine plus nab-paclitaxel as first-line therapy for older adult patients with unresectable pancreatic cancer: A prospective study.
Authors: Kenji Ikezawa, Toshihiro Imai, Ryoji Takada, Takuo Yamai, Nobuyasu Fukutake, Kazuyoshi Ohkawa
Journal: Journal of Clinical Oncology (2024)

672 Background: Although the number of older adult patients (aged ≥ 75 years) with pancreatic cancer (PC) is increasing, there are still limited data regarding chemotherapy for these patients, who experience adverse events more frequently than younger patients with PC. In this study, we evaluated the efficacy and safety of biweekly gemcitabine plus nab-paclitaxel (GnP) as first-line therapy for older adult patients with unresectable PC. Methods: We conducted a single-center prospective study. Patients aged ≥ 75 years with pathologically proven unresectable pancreatic adenocarcinoma were enrolled after obtaining written informed consent. Patients were treated with a modified regimen of gemcitabine (1000 mg/m 2 ) and nab-paclitaxel (125 mg/m 2 ) on days 1, 15 of every 28-day cycle. The primary endpoint was the overall response rate. Secondary endpoints included disease control rate, overall survival, progression-free survival, 1-year survival rate, 2-year survival rate, and adverse events. Results: From August 2018 to March 2021, 17 patients were enrolled (locally advanced 4; metastatic 13). Five patients (29.4%) were men, and the median age was 77 years (range: 75-81). The median Geriatric 8 score was 13 points (range 6-17). Biliary drainage was performed in three patients. The overall response rate was 47.1% (8/17). Disease control rate was 82.4% (14/17). Median overall survival was 16.8 months (95% confidence interval (CI) 5.9-24.6) and median progression-free survival was 8.3 months (95% CI: 4.9-10.1), respectively. The 1-year survival rate and 2-year survival rates were 58.8% and 29.4%, respectively. Grade 3 or 4 hematologic adverse events and non-hematologic adverse events were observed in 17.6% (3/17) and 29.4% (5/17), respectively. No deaths was observed in association with biweekly GnP regimen. Conclusions: Biweekly GnP as first-line therapy can provide favorable treatment outcomes with tolerable toxicity in older adult patients with unresectable PC. Clinical trial information: jRCTs051190038 .
Annals Graphic Medicine - Dr. Mom: Dr. Mom of a Tween
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2024)

Web Exclusives23 January 2024Annals Graphic Medicine - Dr. Mom: Dr. Mom of a TweenFREEGrace E. Farris, MDGrace E. Farris, MDUniversity of Texas, Austin, Texas (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G23-0061 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Author, Article, and Disclosure InformationAuthors: Grace E. Farris, MDAffiliations: University of Texas, Austin, Texas (G.E.F.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G23-0061.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Dell Medical School at the University of Texas in Austin, Texas. You can view her work at her website: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears quarterly in Annals Graphic Medicine at Annals.org.This article was published at Annals.org on 23 January 2024. Nextarticle Advertisement FiguresReferencesRelatedDetails Metrics Latest ePublished: 23 January 2024 Copyright & PermissionsCopyright © 2024 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
FOLFIRINOX plus high intensity focused ultrasound for locally advanced/borderline resectable pancreatic ductal adenocarcinoma: A prospective single arm phase II trial.
Authors: Dong Ho Lee, Jae Young Lee, Sang Hyub Lee, Jin-Young Jang
Journal: Journal of Clinical Oncology (2024)

670 Background: FOLFIRINOX has been the standard regimen for locally advanced pancreatic cancer (LAPC) for palliation and borderline resectable pancreatic cancer (BRPC) for neoadjuvant treatment. According to the results of animal studies, concurrent use of high intensity focused ultrasound (HIFU) and chemotherapy can enhance the drug delivery to the target tissue. In this phase II trial, we aimed to evaluate the safety and therapeutic efficacy of FOLFIRINOX plus HIFU for patients with LAPC or BRPC. Methods: This study was designed as a prospective single center phase II trial (Study identifier: NCT05262452). We prospectively enrolled 60 patients (M:F=35:25; median age, 67.0 years old) with LAPC (n=23) or BRPC (n=37). The median tumor size was 4.0 cm (Interquartile range, 2.7-4.6). All patients were treated by FOLFIRINOX (oxaliplatin, 85mg/m 2 of body-surface area; irinotecan, 180mg/m 2 ; leucovorin, 400 mg/m 2 ; and fluorouracil, 400 mg/m 2 given as a bolus followed by 2400 mg/m 2 given as a 46-hour continuous infusion) every 2 weeks until disease progression. HIFU was combined in the first 4 cycles of chemotherapy with following parameters: intensity of 2.0 kw/cm 2 , duty cycle of 1%, exposure time of 3 seconds and PRF of 10Hz. Follow-up contrast enhanced CT was taken every 4 cycles for the response evaluation using response evaluation criteria for solid tumor 1.1. Overall survival (OS) and progression-free survival were estimated using Kaplan-Meier method. All analyses were intention-to-treat. Results: Two patients withdrew the consent, and two patients could not complete planned 4 cycles of FOLFIRINOX plus HIFU treatment owing to sepsis from severe neutropenia related to chemotherapy. Among 56 patients who completed the 4 cycle of FOLFIRINOX plus HIFU and continued chemotherapy, partial response was achieved in 36 patients (60.0%, 36/60), and stable disease in 20 patients. Regarding the adverse effect (AE), 32 of 60 patients experienced grade 3 (n=22) or grade 4 (n=10) AE, all of them were related to FOLFIRINOX chemotherapy. No AE related to HIFU was observed. The estimated OS was 94.8%, 75.9% and 67.6% at 6-, 12- and 18 months, respectively. Regarding the PFS, the 6-, 12- and 18-month PFS was 91.9%, 70.3% and 56.2%, respectively. Conclusions: FOLFIRINOX plus HIFU was safe and effective treatment for LAPC/BRPC, providing 60.0% of partial response rate without any additional AE to chemotherapy. Clinical trial information: NCT05262452 .
Extrahepatic cholangiocarcinoma: Genomic variables associated with anatomical location and outcome.
Authors: William A Preston, Esther N. Drill, Thomas Boerner, James J. Harding, Andrea Cercek, Eileen Mary O'Reilly, Ghassan K. Abou-Alfa, Wungki Park, Vinod P. Balachandran, Jeffrey A. Drebin, Kevin Soares, Alice Chia-Chi Wei, T. Peter Kingham, Michael Ian D'Angelica, William R. Jarnagin
Journal: Journal of Clinical Oncology (2024)

554 Background: Genomic determinants of outcome in intrahepatic cholangiocarcinoma have become clear but remain ill-defined in extrahepatic cholangiocarcinoma (ECA). We aimed to clarify the genomic alterations that define ECA, analyze differences between perihilar (PCA) and distal (DCA) disease, and determine clinicopathologic and genomic factors associated with survival. Methods: Patients with EHC with tissue available for targeted next-generation sequencing at Memorial Sloan Kettering Cancer Center were identified. Differences between PCA and DCA were compared, stratified by disease extent and treatment. Associations between genomic alterations and clinicopathologic features and outcomes were analyzed. Univariable and then multivariable cox proportional hazards regression were used to compare survival, which was reported from operation in resected patients and from diagnosis in non-resected patients. Results: Two-hundred-twenty-four patients (n=127 PCA, n=97 DCA, 2006-2022) met inclusion criteria. Median survival was 29 months (IQR [25, 35]; 43 months [35, 48] resection, 17 months [13, 19] without). Compared to PCA, DCA was enriched in TP53mut (67 [69%] vs. 42 [33%]), Q&lt;0.01) and epigenetic pathway alterations (44 [45%] vs. 37 [29%], Q=0.041) and had more altered pathways (3 vs. 2, Q&lt;0.01). KRASmut was similar between PCA (46 [36%]) and DCA (36 [37%]); however, PCA was enriched in KRAS G12V (16 [13%] vs. 4 [4%]) and Q61H (11 [9%] vs. 3 [3%], P=0.002). No other clinicopathologic or genomic variables distinguished PCA from DCA (Table). MDM2mut occurred in 19/141 (13%) patients with nodal/metastatic disease compared to 1/83 (1%) patients with local disease ( Q=0.03), but conferred no survival disadvantage. In resected patients, survival was similar between PCA and DCA and no genomic alterations were associated with outcome. By contrast, in patients without surgery, CDKN2Adel (HR 2.59, 95% CI [1.48, 4.52]) and APCmut (HR 5.11, 95% CI [1.96, 13.3]) were associated with survival disadvantages. Lack of resection (HR 3.13, 95% CI [2.25, 4.36]), CDKN2Amut (HR 1.80 [95% CI 1.80, 2.68), and APCmut (HR 2.00 [95% CI 1.04, 3.87]) were associated with poor survival in the entire cohort. Conclusions: In this study, aside from a higher incidence of TP53mut in DCA and some differences in KRAS subtype alteration patterns, genomic alterations were comparable between PCA and DCA. CDKN2Amut and APCmut were associated with poor survival in all patients but no biomarkers provided significant prognostic information when tumors were resected. [Table: see text]
SWOG S2107: Randomized phase II trial of encorafenib and cetuximab with or without nivolumab for patients with previously treated, microsatellite stable, <i>BRAF<sup>V600E</sup></i> metastatic and/or unresectable colorectal cancer.
Authors: Van K. Morris, Katherine A. Guthrie, Scott Kopetz, Rimini Breakstone, Thomas Benjamin Karasic, Zishuo Ian Hu, Sarah Colby, Marwan Fakih, Sepideh Gholami, Philip Jordan Gold, Philip A. Philip
Journal: Journal of Clinical Oncology (2024)

TPS234 Background: Patients with microsatellite stable (MSS), BRAF V600E metastatic colorectal cancer (mCRC) experience poor survival outcomes. Treatment with the BRAF inhibitor encorafenib (E) and anti-EGFR antibody cetuximab (C) is an approved treatment combination, with a reported overall response rate (ORR) of 20% and median progression-free survival (PFS) of 4.1 months. Anti-PD-1 antibodies like nivolumab (N) are ineffective as monotherapy for patients with MSS, BRAF V600E mCRC. In preclinical models of MSS, BRAF V600E CRC, inhibition of BRAF and EGFR induces a loss of expression of mismatch repairs genes and promotes a microsatellite instability-high phenotype, which may prime these tumors for response to immunotherapy. In support of these findings, a single-institution clinical trial of E + C + N for 26 participants with MSS, BRAF V600E mCRC reported an ORR of 50% and median PFS of 7.2 months. We hypothesize that the addition of N to E + C will improve PFS for participants with MSS, BRAF V600E mCRC. Methods: In this prospective phase II clinical trial (N=75), participants with previously treated MSS, BRAF V600E mCRC will be randomized 2:1 into 2 arms, respectively: experimental treatment (E + C + N) or standard treatment (E + C). No prior BRAF, EGFR, or immunotherapy agents are allowed. All participants will receive E (300 mg PO daily) and C (500 mg/m 2 IV every 14 days), and participants in the experimental arm will receive N (480 mg IV every 28 days). The primary endpoint is PFS. Secondary endpoints include overall survival, best overall response, duration of response, and safety/tolerability. Using a one-sided α= .10 and power 80%, we target an improvement in median PFS from 4.2 to 7.3 months and a hazard ratio of 0.57. Additional participants specimens will be collected for exploratory correlative research. As of 9/2023, 37 of 75 planned participants have been enrolled. Clinical trial information: NCT05308446 .
A first-in-human, open-label, phase I trial of daily oral zelenirstat, an NMT inhibitor, in patients with relapsed/refractory advanced cancer including gastrointestinal cancers.
Authors: Jennifer L. Spratlin, Randeep S. Sangha, Rahima Jamal, Erwan Beauchamp, Luc G. Berthiaume, John Robert Mackey
Journal: Journal of Clinical Oncology (2024)

129 Background: Myristoylation catalyzed by N-myristoyltransferases (NMT) 1 and 2 regulates membrane-bound signaling important in cancer, including Src and Src-family tyrosine kinases. Zelenirstat is a potent oral small molecule pan-NMT inhibitor. Transcriptomic analysis of zelenirstat treated cell lines identified an expression signature that predicts cancers most likely to be responsive to NMT inhibition; high sensitivity scores were seen in colorectal carcinomas and diffuse large B-cell lymphoma. The objectives of this phase I study were to determine the safety, tolerability, and maximum tolerated dose (MTD) of zelenirstat monotherapy in patients (pts) with refractory cancers. Methods: Pts with advanced solid malignancies or relapsed/refractory B-cell lymphomas were dose escalated with daily oral zelenirstat in 28-day cycles until progressive disease or dose-limiting toxicity (DLT). Results: Between September 2021 and July 2023, pts received 28-day cycles of zelenirstat ranging from 20 mg/d to 280 mg/d. In 21 evaluable patients, DLT was not observed up to and including the 210 mg/d cohort. Gastrointestinal DLTs were seen in the 280 mg/d cohort, establishing 210 mg/d to be the MTD. In doses up to and including 210 mg/d, gastrointestinal adverse events were the most common, reported in 29% of pts; these were primarily Gr 1 or 2 diarrhea, nausea or vomiting. Transient Gr 2 thrombocytopenia was seen in 3 pts. Zelenirstat did not induce neuropathy, alopecia, or prolong QT intervals. Plasma concentrations peaked between 1h and 4 h, terminal half-lives were 6.7 to 12 h, and steady state was achieved by day 8. Proton pump inhibitors lowered exposure and were prohibited in the higher dose cohorts. At 100 mg/d and higher, trough plasma concentrations exceeded the levels predicted to be therapeutic. Stable disease as best response was seen in 5 (30%) of 17 evaluable pts, including 1 patient with advanced refractory colon cancer who received 6 cycles of therapy at 140 mg daily dosing prior to PD. Another colon cancer patient with 5 prior lines of therapy continues 210 mg/d dosing after &gt; 5 cycles of therapy, with non-RECIST criteria reductions of approximately 50% in CEA and tumor volumes. Conclusions: Zelenirstat was well-tolerated on a continuous daily oral schedule at doses as high as 210 mg/d, establishing the MTD to be 210 mg. The absence of severe toxicities, attainment of plasma concentrations highly active in preclinical models, and early evidence of clinical benefit in patients with refractory colon cancer warrant further trials. Updated data will be presented. Clinical trial information: NCT04836195 .
Nivolumab (NIVO) plus (+) chemotherapy (chemo) or ipilimumab (IPI) vs chemo as 1L treatment for advanced esophageal squamous cell carcinoma (ESCC): First comprehensive biomarker analyses from CheckMate 648.
Authors: Ming Lei, Yuichiro Doki, Yuko Kitagawa, Ken Kato, Ian Chau, Jin Yao, Jianming Xu, Lucjan S. Wyrwicz, Satoru Motoyama, Takashi Ogata, Hisato Kawakami, Chih-Hung Hsu, Antoine Adenis, Farid El Hajbi, Maria Di Bartolomeo, Maria Ignez Braghiroli, Eva Holtved, Mariela A. Blum Murphy, Ruslan Novosiadly, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2024)

252 Background: NIVO + chemo and NIVO + IPI demonstrated superior overall survival (OS) vs chemo in previously untreated patients with advanced ESCC in CheckMate 648 (NCT03143153), resulting in approvals in many countries. We present first comprehensive exploratory biomarker analysis results from this trial. Methods: Whole exome sequencing (WES) of baseline tumor tissue and matching blood was performed to assess tumor mutational burden (TMB) and select gene alterations. TMB-high tumors were defined as ≥ 199 mutations/exome. RNA sequencing of baseline tumor tissue was used to assess gene expression signatures (GES). GES subgroups were defined by signature score tertiles. Results: In total, 60% (191/321) of patients receiving NIVO + chemo were both WES- and GES-evaluable; 62% (200/325) and 58% (188/325) of patients receiving NIVO + IPI and 59% (190/324) and 59% (192/324) receiving chemo were WES- and GES-evaluable, respectively. In the NIVO + chemo arm, patients with TMB-high tumors had numerically longer median OS (mOS) compared with TMB-low tumors, whereas mOS was similar between TMB subgroups treated with NIVO + IPI, although the number of patients with TMB-high tumors was small (Table). Higher inflammation and lower β-catenin GES scores were associated with improved OS benefit of NIVO + chemo or IPI vs chemo (Table). Lower fibroblast GES scores were associated with improved OS benefit of NIVO + IPI vs chemo (Table). Additional biomarker analyses, including select gene alterations and GES in tumor cell PD-L1 subgroups, will be presented. Conclusions: These results further support the clinical efficacy of NIVO + chemo and NIVO + IPI in 1L ESCC and suggest enhanced OS benefit in multiple biomarker subgroups. The clinical utility of these biomarkers should be validated in future trials. Clinical trial information: NCT03143153 . [Table: see text]
Impact of early tumor shrinkage and depth of response in patients with <i>BRAF</i> V600E-mutant metastatic colorectal cancer.
Authors: Shohei Udagawa, Hiroki Osumi, Akira Ooki, Takeru Wakatsuki, Shota Fukuoka, Koichiro Yoshino, Mikako Tamba, Mariko Ogura, Daisuke Takahari, Keisho Chin, Kensei Yamaguchi, Eiji Shinozaki
Journal: Journal of Clinical Oncology (2024)

142 Background: Early tumor shrinkage (ETS) and the depth of response (DpR) are early on-treatment surrogate markers for survival in patients with metastatic colorectal cancer (mCRC) receiving anti-epidermal growth factor receptor (EGFR) monoclonal antibody. However, the utility of ETS and DpR for BRAF V600E mutant (MT) mCRC which has a poor prognosis remains unclear. The aim of this study is to evaluate the association between ETS and DpR and clinical outcomes in BRAF V600E MT mCRC. Methods: mCRC patients who were diagnosed BRAF V600E MT and treated with 1 st line chemotherapy from June 2011 to March 2023 at single cancer institute were enrolled. We analyzed the association between ETS and DpR and clinical outcome in patients who had at least one target lesion. Subgroup analysis of clinical factors related to progression free survival (PFS) and overall survival (OS) was performed using multivariate analysis. ETS was defined as the relative change in the sum of the longest diameters of RECIST target lesions at first follow-up CT scan compared to baseline and DpR was defined as the relative change in the sum of the longest diameters of RECIST target lesions at the nadir in the absence of new lesions or progression of non-target lesions compared to baseline. Results: In total, 54 patients of BRAF V600E MT mCRC had at least one target lesion. In total of StageI-IV CRC patients, the incidence of BRAF V600E MT was 6.3% (233/3705). Patients with ETS ≥ 20% and DpR ≥ 25% (median value) were 24 (44.4%) and 27 (50%) respectively. PFS was 7.5 months (95% confidence interval (CI), 5.0-9.9) and OS was 17.1 months (95% CI, 11.7-20.2). Patients with ETS ≥ 20% had longer PFS and tended to have longer OS than those with non-ETS, with a median PFS of 9.8 months vs. 4.8 months (P Log-rank = 0.048, hazard ratio (HR), 0.55; 95% CI, 0.30-1.00), and a median OS of 22.6 months vs. 11.6 months (P Log-rank = 0.18, HR, 0.67; 95% CI, 0.37-1.21). Patients with DpR ≥ 25% had also longer PFS and OS than those with non-DpR, with a median PFS of 11.0 vs. 4.3 months (P Log-rank &lt; 0.01, HR, 0.36; 95% CI, 0.20-0.66) and a median OS of 22.6 vs. 10.1 months (P Log-rank = 0.047, HR, 0.55; 95% CI, 0.31-1.00). Median time to DpR was 3.05 months. In multivariate analysis, DpR was significantly associated with both longer PFS (HR: 0.27, 95% CI: 0.14–0.55, P &lt; 0.01) and OS (HR: 0.52, 95% CI: 0.29–0.96, P = 0.04). Conclusions: ETS and DpR may be early surrogate markers for clinical outcome in BRAF V600E MT mCRC who were treated with 1 st line chemotherapy.