bluuebunny/crossref_metadata_2025_split huggingface dataset:
The value of pretreatment 18F-FDG PET/CT to predict the pathological treatment response of hepatocellular carcinoma patients treated with PD-1 inhibitors and lenvatinib as a conversion therapy in BCLC stage C.
Authors: Wang Guanyun , Ma Guangyu , Zhang Wenwen , Xu Baixuan , Lu Shichun , Chen Jiaxin , Luan Xiaohui , Wang Zhanbo , Xu Xiaodan , Guan Zhiwei , Tong Shuang 
Published: June 2022

e16130 Background: Current systemic therapy for patients with hepatocellular carcinoma (HCC) in BCLC stage C consists of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). This study aimed to assess the parameters of pretreatment 18F-FDG PET/CT as a predictor of the pathological treatment response (PTR) of HCC patients treated with PD-1 inhibitors and lenvatinib as a conversion therapy in BCLC stage C. Methods: We retrospective analyzed 20 consecutive patients with HCC in BCLC stage C. All patients underwent pretreatment 18F-FDG PET/CT and treated with PD-1 inhibitors and lenvatinib as a conversion therapy and surgery. Patients were categorized into responders (n=9) and non-responders (n=11) according to PTR. The PTR was classified based on the primary tumor cellularity (responder, defined as <10% cellularity). The parameters of PET/CT including lesion size, SUVmax (max standardized uptake value), SUVmean (mean standard uptake value), MTV2.5 (metabolic tumor volume2.5), TLG2.5 (total lesion glycolysis2.5), SUVpeak (peak standard uptake value), and TLR (tumor-to-normal liver standardized uptake value ratio, SUVmax of the tumor/SUVmean of the normal liver parenchyma) were calculated and compared between two groups. The diagnostic efficacy was evaluated by ROC. PTR was compared with pretreatment 18F-FDG PET/CT parameters by using Spearman correlation analysis. The prognosis was followed up. Results: TLR (5.59±1.90 vs. 2.84±1.70, respectively; P=0.003) showed significant difference in responders and non-responders and the largest area under the curve (sensitivity: 1.000, specificity: 0.727, positive predictive value: 0.750, negative predictive value: 1.000, AUC=0.899, 95%CI: 0.759-1.000), and optimal diagnostic threshold of 3.09. The relationship between 18F-FDG PET/CT parameters and PTR showed TLR had moderate positive correlation with pathological treatment response, with correlation coefficients (rs) of 0.69 ( P＜0.05). During the follow-up, no patients died, and 1 patient (11.1%) showed tumor recurrence in responders. In all 11 non-responders, 5 patients (45.5%) had tumor recurrence and 4 patients (36.4%) died. Conclusions: The TLR may be a powerful marker to predict the PTR of HCC patients with BCLC stage C who treated with PD-1 inhibitors and lenvatinib as a conversion therapy.[Table: see text]
Role of metformin in the treatment of cholangiocarcinoma: A systematic review.
Authors: Adigun Aisha Olanike , Naeem Aleena , Poladi Keerthi , Moorthy Vivek Soorya Sathya , Fatima Farwah , Ahmad Muhammad , Zamani Zarlakhta , Haider Mobeen Zaka , Zamani Nilofar , Mushtaq Muhammad Umair 
Published: June 2022

e16132 Background: Non-cancer medications and their potential anti-cancer activity have attracted significant interest in recent years. The aim of this research is to conduct a systematic assessment of the existing evidence on the usefulness of metformin in the treatment of cholangiocarcinoma. Methods: We conducted literature search using PubMed, Clinicaltrials.gov, Embase, and Cochrane to retrieve studies evaluating the role of Metformin in the treatment of Cholangiocarcinoma. Three studies were finalized after careful screening. Results: We analyzed 3 studies. The total population was 638. The types of Cholangiocarcinoma varied from intrahepatic cholangiocarcinoma found in 293, to extrahepatic Cholangiocarcinoma in 365 and gallbladder carcinoma in 149 patients. Patients were in different stages of treatment such as undergoing chemotherapy, surgery or post- resection and/or post chemotherapy. The mean survival rate was significantly increased to 30.4 months and 13.2 months in patients using Metformin vs. 23.48 months and 10.3 months among patients not using Metformin (p < 0.0005) after resection of the tumor. An increase in the mean survival rate was reported among patients using Metformin vs. non-users after the administration of chemotherapy, i.e., 25.9 months vs. 10.6 months (p = 0.0016), respectively. Metformin in combination with Chloroquine showed favorable results regarding adverse events, however, no clinical activity was reported against IDH-1 mutated intrahepatic cholangiocarcinoma. Conclusions: Our analysis concludes while the use of Metformin is associated with significantly improved post-operative survival, it does not show any significant clinical activity against IDH-1 mutated intrahepatic cholangiocarcinoma. Metformin also showed significant improvement in patients taking chemotherapy. Studies, including trials to evaluate the effectiveness of Metformin alone or used in combination with non-cancer medications or chemotherapeutic agents could provide more definitive recommendations for the treatment of Cholangiocarcinoma.[Table: see text]
Frequency of loco-regional complications and their IMPACT on hospitalization outcomes in patients with cholangiocarcinoma.
Authors: Shah Mihir , Kumi Dennis Danso , Deenadayalan Vaishali , Ferreira de Araujo Litvin Rafaella , Dasgupta Mona , Turk Ekrem , Gupta Shweta 
Published: June 2022

e16135 Background: Cholangiocarcinomas, based on their anatomic location are prone to a myriad of local and regional complications. This study aims to explore if the outlook of patients differs based on what type of loco-regional complications they are admitted with. Methods: The National Inpatient Sample (NIS) was queried to identify adult patients with underlying cholangiocarcinoma between 2016-2018. Relative frequency and diagnosis of locoregional complications as principal diagnosis in these patients were identified and top 5 loco-regional complications were studied and compared for all-cause mortality, mean length of stay (LOS), mean total hospital charges (THC). Statistics were performed using t-test, univariate and multinomial logistic regression. Results: There were 26,410 hospitalizations in patients with cholangiocarcinoma. Upper gastrointestinal bleed (UGIB) represented the most frequent loco-regional complication (9.2%), followed by acute liver failure and cancer pain admission (6.7% each). Mortality rate of all admissions was 5.84%; all complications except failure to thrive were associated with significantly increased odds of mortality, the highest in acute liver failure (AOR- 3.72). Except admissions for cancer associated pain, all complications were associated with statistically significant increased LOS, highest in UGIB (Adjusted mean difference of 5 days). Similarly, admission with UGIB was associated with the highest THC while cancer pain admission had a much lower cost. Conclusions: Among the loco-regional complications of cholangiocarcinoma that were studied, UGIB was the most frequent, associated with longest hospital LOS (5 extra days) and highest THC. Admission with acute hepatic failure was associated with the highest odds of mortality while cancer associated pain and failure to thrive were associated with the shortest length of stay and lowest mean charges. Further efforts are needed to improve outpatient pain management to prevent these admissions and identify ways to improve outcomes in patients with UGIB. [Table: see text]
Regorafenib (REGO) ± PD-1 inhibitor in second-line setting for unresectable hepatocellular carcinoma (uHCC) in real-world practice.
Authors: Bi Huaqiang , Pei Jun , Ma Kuansheng , Zhang Yanling , Xia Feng 
Published: June 2022

e16148 Background: No response and resistance occurred for the most uHCC patients with the treatment of molecular targeted agents and\or anti-PD-1 inhibitors. And the second-line therapies are still unmet the ideal clinical outcome. A pilot study that assessed the effectiveness of the combination therapy of REGO + PD-1 inhibitor in second-line setting for pts with advance uHCC showed promising result. Methods: This single-center, retrospective, real-world study was conducted between Jan 2019 to Jul 2021. All patients with uHCC, who were treated with second-line REGO + PD-1 inhibitor or REGO monotherapy were evaluated. The progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), overall survival (OS) were observed. Results: Forty-six patients with uHCC were included in the study, and most had received previous systemic treatment including targeted therapy and immunotherapy. In all pts, median treatment duration of regorafenib was 152.5 days. Median follow-up was 9.0 months. Tumor response was evaluated in 25 and 21 pts in REGO + PD-1 inhibitor and REGO monotherapy group respectively, ORR was 40% and 19.0% respectively; DCR was 88% and 71.4% respectively. Median OS was not reached in either group; the median PFS of the REGO + PD-1 inhibitor group was 11.5 months, which was significantly higher than that of the REGO monotherapy group (5.1 months) (C2=3.867; P=0.049). The most common AE grade ≥3 was diarrhea (4.3%), and was solely observed in REGO monotherapy group. Conclusions: Our preliminary findings suggested that the striking improvement in PFS and ORR were compelling in the REGO + PD-1 inhibitor group, and regardless of previous treatment, regorafenib was clinically effective for uHCC pts in second-line treatment whether in combination with PD-1 inhibitor or not in Chinese patients. And there was a trend to increased efficacy with no increased toxicity in combination therapy. Further analysis in a real-world study with a large sample size is crucial to substantiate our results.
Comparison of immune checkpoint inhibitor monotherapy versus Sorafenib in unresectable hepatocellular carcinoma.
Authors: Chan Abigail Sy , Rout Amit , Kumar Rohit 
Published: June 2022

e16160 Background: Combination immune checkpoint inhibitors (ICI) or with a vascular endothelial growth factor receptor (VEGFR) agent is now the standard 1st line (1L) therapy in patients with advanced/unresectable hepatocellular carcinoma (uHCC). Currently, there is a paucity of data on the use of ICI monotherapy when combination ICI/VEGFR is contraindicated. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety outcomes of ICI monotherapy versus sorafenib in patients with uHCC in the 1L setting. Methods: A systematic search of electronic databases was conducted for randomized controlled trials comparing ICI versus sorafenib in the treatment of uHCC. Efficacy endpoints were overall survival (OS), objective response rates (ORR), and progression free survival (PFS). Safety endpoints of interests were any adverse events (AE) and > grade 3 AEs. We performed random effects meta-analysis to estimate odds ratio (OR) with 95% confidence intervals for individual endpoints. Results: A total of 2 studies with 1521 patients were included in the final analysis. Compared to sorafenib, ICIs were associated with improved OS [OR 0.75; 95% confidence interval (CI) 0.6-0.94]. Similarly, ICI had increased odds of ORR [OR 2.99; 95% CI 1.93-4.62] and PFS [OR 1.41; 95% CI 1.07-1.85] compared to the sorafenib arm. In the safety analyses, ICIs were associated with reduced risk of > grade 3 AE [OR 0.40; 95% CI 0.22-0.72] and any AEs [OR 0.25; 95% CI 0.12-0.55] when compared to sorafenib. Conclusions: Our meta-analysis suggests that ICI monotherapy has improved OS, PFS, ORR, and better safety profile in 1L uHCC compared to sorafenib.
Development of hand-food skin reaction correlates with prognosis of patients with HCC who were treated with sorafenib.
Authors: Lee Young-Sun , Lee Yoonseok , Oh Sang Cheul , Kim Ji Hoon 
Published: June 2022

e16171 Background: Sorafenib is one of the effective systemic therapy in patient with advanced hepatocellular carcinoma (HCC). However, there are few prospective studies that have examined prognostic factors of sorafenib response. In this study, we analyzed prognostic factors of HCC patients who were treated with sorafenib. Methods: Between May 2016 and May 2018, 288 advanced HCC patients treated with sorafenib were enrolled at 13 hospitals. We analyzed possible prognostic factors of sorafenib response (overall survival and progression free survival) using Univariate and Multivariate analyses with Cox proportional hazards regression model. Results: Among the 288 patients, chronic hepatitis B (68.4%) was main cause in development of HCC. 85.4% of patients were in the advanced stage of Barcelona Clinic Liver Cancer. Hand-foot skin reactions (HFSR) were observed in 142 patients (49.2%). The univariate analysis identified presence of ascites, serum albumin level and creatinine level, presence of HFSR as potential prognostic factors for overall survival (OS). In multivariate analysis for OS, presence of HFSR (HR 0.144; 95% CI: 0.063-0.330, p 0.002), albumin level (HR ratio 0.283; 95% CI: 0.148-0.544, p < 0.001), creatinine level (HR 1.395; 95% CI 1.133-1.717, p 0.002) were significant factors of OS. In univariate and multivariate analysis, presence of HFSR (HR 0.212; 95% CI: 0.091-0.495, p < 0.001), and serum albumin level (HR 0.30, 95% CI: 0.158-0.568, p < 0.001) were show significant correlation with progression free survival. Conclusions: Developing HFSR from sorafenib therapy and high serum albumin level were associated with improved OS and PFS. Developing HFSR have been suggested as possible predictor of good sorafenib response. Clinical trial information: NCT03212625.
Clinical impact of the changes of muscle volume during various systemic therapies in patients with unresectable hepatocellular carcinoma.
Authors: Matsumoto Hiroaki , Tsuchiya Kaoru , Hayakawa Yuka , Tanaka Yuki , Ishido Shun , Inada Kento , Kirino Sakura , Yamashita Koji , Nobusawa Tsubasa , Kakegawa Tatsuya , Higuchi Mayu , Takaura Kenta , Tanaka Shohei , Maeyashiki Chiaki , Kaneko Shun , Tamaki Nobuharu , Yasui Yutaka , Nakanishi Hiroyuki , Kurosaki Masayuki , Izumi Namiki 
Published: June 2022

e16177 Background: Sarcopenia is associated with clinical outcomes in cirrhosis and hepatocellular carcinoma (HCC). However, the clinical impact of muscle volume during systemic therapy is unknown. We investigated the changes in muscle volume during various systemic therapies for HCC. Methods: The patients with unresectable HCC (u-HCC) treated with a molecular targeted agent as initial systemic therapy were included. The skeletal muscle mass index (SMI) was calculated from the skeletal muscle area at the L3 level of the lumbar vertebrae using computed tomography. Sarcopenia was defined as an L3 SMI value≦42 cm2/m2 for men and 38 cm2/m2 for women. ΔSMI was defined as the difference between baseline and 6-14 weeks after the administration of the agent. Results: A total of 174 patients was analyzed. The 1st-line agent was sorafenib (SOR) (n = 89), lenvatinib (LEN)(n = 58), and atezolizumab plus bevacizumab (ATE+BEV) (n = 27). In three groups, ATE+BEV group had significantly fewer discontinuation due to adverse events. (ATE+BEV 6 cases, LEN 31 cases, SOR 32 cases, p = 0.014). The median PFS was 4.1, 3.0, and 6.1 months in SOR, LEN, and ATE+BEV. The median Δ In patients treated with ATE+BEV, pretreatment sarcopenia was not associated with OS and PFS, while the patients with a SMI decrease (at 6-14W, n = 12) had significantly shorter PFS than the patients without a SMI decrease (n = 15) (p = 0.026). The best radiological response based on RECIST ver1.1 in ATE+BEV was CR (n = 2), PR(n = 6), SD(n = 15), and PD (n = 3). The patients without a SMI decrease tended to have better disease control rate than patients with a SMI decrease (100% vs. 75%, p = 0.08). There were no significant differences in age, etiology, ALBI score, BCLC stage, and pretreatment AFP between the patients with and without a SMI decrease. The significant factor associated with PFS after the administration of ATE+BEV as 1st-line was a decrease of SMI (HR9.44, 95% CI 1.04-85.6, p = 0.046). In patients treated with SOR and LEN, pretreatment sarcopenia and SMI decrease were not significantly associated with OS and PFS. Conclusions: The decrease of muscle volume at 6-14W was significantly associated with PFS in patients treated with ATE+BEV, while pretreatment sarcopenia was not a significant factor. Monitoring muscle volume during immunotherapy would be useful in clinical practice.
Genomic determinants and clinical relevance of cancer-associated thrombosis in biliary tract cancers.
Authors: Nichetti Federico , Provenzano Leonardo , Miliziano Daniela , Sposetti Caterina , Pircher Chiara , Bini Marta , Franza Andrea , Massa Giacomo , Niger Monica , Di Bartolomeo Maria , De Braud Filippo G. 
Published: June 2022

e16179 Background: Biliary tract cancers (BTCs) are a group of rare tumors with a dismal prognosis and a complex molecular landscape. In this setting, the incidence and clinical relevance of cancer-associated thrombosis (CAT) is unknown, thus BTCs are not included in common thrombotic risk scores (e.g. Khorana Score). Moreover, retrospective studies highlighted associations between thromboembolic events and some genetic alterations, such as KRAS in lung and colorectal cancer, ALK/ROS1 in lung cancer and IDH1 mutations in glioma. Nevertheless, the impact of different genomic alterations on CAT risk in BTCs patients has never been investigated. The aim of this study was to investigate for the first time the incidence and the clinical relevance of CAT in a cohort of BTC patients. In addition, we investigated the association between tumor genomics and CAT in this patients’ population. Methods: Clinical and genomic data of consecutive BTC patients who underwent extensive molecular profiling with the FoundationOneCDx panel at Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy, were collected. The association between genomic alterations and CAT incidence was investigated with the Fisher exact test, considering alterations occurring in at least 5% of patients. Cox regression was used to analyze the impact of CAT, considered as a time-dependent covariate, on overall survival (OS). Results: 140 patients were included in the analysis, mostly represented by cases of intrahepatic cholangiocarcinoma (77%). CAT occurred in 18 (13%) patients, the majority being pulmonary embolism (28%) and visceral thrombosis (44%). Pathogenic KRAS and BRCA1 mutations were found in 33% and 11% of patients with CAT, resulting significantly associated with an increased risk of thrombosis ( p = 0.041 for both). Patients who experienced CAT showed a significantly poorer OS (HR 3.29, p = < 0.001). Conclusions: This is the first report describing a non-negligible incidence and significant prognostic impact of CAT in BTC patients. Future studies investigating the clinical and molecular risk factors for CAT in this population are needed to tailor thromboprophylaxis in this rare population.
Pemigatinib in Chinese patients with advanced/metastatic or surgically unresectable cholangiocarcinoma including FGFR2 fusion or rearrangement: Updated data from an open-label, single-arm, multicenter phase II study (CIBI375A201 study).
Authors: Shi Guoming , Huang Xiaoyong , Wen Tianfu , Song Tianqiang , Kuang Ming , Mou Haibo , Bao Lequn , Zhao Hai-Tao , Zhao Hong , Feng Xielin , Zhang Bixiang , Peng Tao , Zhang Yubao , Li Xiangcheng , Yu Hongsheng , Cao Yu , Luo Yang , Chen Mingxia , Fan Jia , Zhou Jian 
Published: June 2022

e16183 Background: Pemigatinib is a selective FGFR inhibitor that showed effectiveness and tolerability in patients with cholangiocarcinoma with FGFR2 fusion or rearrangement. However, pemigatinib has not been investigated in Chinese population with cholangiocarcinoma (CCA). Initial efficacy and safety data were previously presented (G-M. Shi et al. ESMO 2021; NCT04256980). Here, we report updated follow-up results from the phase II study. Methods: Patients aged 18 years or older with recurrent or metastatic CCA that failed at least one prior systemic therapy were enrolled. In Part 1, 3 subjects were enrolled regardless of the FGFR2 status and were treated at 9 mg pemigatinib. The other 31 subjects with documented FGFR2 fusion or rearrangement were enrolled in Part 2 and received 13.5 mg pemigatinib. From 2/26/2020 to 12/20/2021, all the subjects in both parts were orally given pemigatinib QD on a 2 weeks on/1 week off schedule until disease progression, unacceptable toxicity, withdrawal of consent, or physician decision. The primary efficacy end point was ORR assessed by independent radiological review committee (IRRC) per RECIST V1.1 in 31 patients enrolled in Part 2. Results: As of the data cutoff date (Dec 20th, 2021), with a median follow up of 12.6 (11.8, 14.2) months, among 30 efficacy evaluable subjects with 1 participant excluded due to inadequate FGFR2 aberrant frequency, the updated confirmed objective response rate (ORR) was 60% (95% CI: 42.5%, 77.5%) per RECIST 1.1. The median DOR was 8.3 months (95% CI: 6.5, 11.2), and with 8 pts still maintaining tumor control of partial response. The updated median PFS was 9.1 months (95% CI: 7.8, 11.0). The DCR was also 100% (95% CI: 100%, 100%). All 34 subjects were included for safety analysis. As of data cutoff the safety profile was consistent with the primary analysis, with no new safety signals or concerns identified. With the longer follow up time, the frequency of grade 3 or higher TRAEs was increased to 26.5%. One patient experienced TRAE leading to treatment discontinuation, while no TRAE leading to death was observed or reported. TEAEs leading to dose interruption or dose reduction occurred in 23.5% and 14.7% of patients, respectively. Conclusions: Pemigatinib was high response rate and manageable tolerability in Chinese patients with recurrent or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangement. Editorial acknowledgement: Guoming Shi and Xiaoyong Huang contributed equally to this work. Clinical trial information: NCT04256980.