bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical feasibility of curative surgery after nab-paclitaxel plus gemcitabine-cisplatin chemotherapy in patients with locally advanced cholangiocarcinoma.
Authors: Choi Sung Hoon , Kang Beodeul , Cheon Jaekyung , Chon Hongjae , Kim Dae Jung , Kwon Chang-Il , Ko Kwang Hyun 
Published: January 2022

387 Background: In a recent phase II trial, nab-paclitaxel plus gemcitabine-cisplatin (Gem/Cis/nab-P) demonstrated prolonged survival and unprecedentedly high response rate in patients with advanced cholangiocarcinoma following treatment. We aimed to evaluate the clinical feasibility of this triplet chemotherapy as induction chemotherapy in patients with locally advanced cholangiocarcinoma. Methods: We retrospectively reviewed patients with locally advanced cholangiocarcinoma who were treated with Gem/Cis/nab-P between October 2019 to December 2020. Resectability after induction chemotherapy was evaluated by a multidisciplinary team. Treatment response and surgical pathology were reviewed. Results: Of the 85 patients were included in this study. 46 (54.1%) had measurable lesions. The objective response rate (ORR) and disease control rate in patients with measurable disease were 51.1% and 85.1%, respectively. Fifty-two (61.2%) patients were determined as resectable. Four patients that were judged to be resectable did not undergo surgery due to patient refusal or poor performance status after chemotherapy. Finally, 48 out of 85 patients (56.5%) underwent subsequent curative surgery after induction chemotherapy. There were six complete remission cases (12.5%) in the final pathology, which all reported patients with extrahepatic cholangiocarcinoma. R0 resection was achieved in 46 out of the 48 patients (95.8%). Despite the initial locally advanced cholangiocarcinoma, a pathologic T stage of less than T2 was reported in 44 (95.7%) patients. Lymph node metastasis was confirmed in 13 (27.1%) patients. The overall survival rates in patients who had chemotherapy followed by surgery was better than in those treated with chemotherapy alone ( P = 0.009). Conclusions: Gem/Cis/nab-P as induction chemotherapy showed promising efficacy and clinical feasibility before curative surgery in patients with locally advanced cholangiocarcinoma. This study showed that triplet chemotherapy using Gem/Cis/nab-P has a clear down-staging effect through a high response rate in patients with cholangiocarcinoma
Treatment patterns and clinical outcomes among patients with biliary tract cancers in a large commercially insured US population.
Authors: Valderrama Adriana , Singhal Mukul , Wang Liya , Nepal Bal , Kamble Shital , Grabner Michael , Malhotra Usha , Javle Milind M. 
Published: January 2022

398 Background: The American Cancer Society estimates 11,980 new cases of biliary tract cancers (BTCs), including gall bladder and nearby large bile ducts, to occur in the US in 2021. BTCs are characterized by poor prognosis and limited treatment choices. Gemcitabine (GEM) plus platinum chemotherapy is the standard of care. However, there are limited data regarding real-world treatment patterns and clinical outcomes for BTCs patients receiving systemic treatments (ST). Methods: A retrospective cohort study of BTCs patients who received first line (1L) ST, using US private payer Cancer Care Quality Program (CCQP) data and administrative claims from the HealthCore Integrated Research Database (HIRD) between 07/01/2014 - 03/31/2021, was performed. Index date was defined as first claim of ST within 60 days of documented 1L therapy in the CCQP from 01/01/2015 - 09/30/2020. Adult BTCs patients with ≥6 months pre-index enrollment were included. Patients with ampullary cancer, brain/ CNS metastases, other primary cancer before BTCs diagnosis were excluded. Treatment patterns and clinical outcomes were examined. Results: A total of 413 patients [Stage IV (n=315), III (n=44), II/I (n=54)] were identified. The mean (SD) age was 61 (10) years, 55% were female, and there were 67% intrahepatic, 22% gall bladder, and 11% extrahepatic BTCs. There were 150 (36%), 203 (49%), 27 (7%) patients with baseline ECOG scores of 0, 1, 2+, respectively. At pre-index, frequently observed conditions included non-alcoholic liver diseases (75%), hypertension (65%), dyslipidemia (48%), mental health conditions (47%), gallstones (41%), gastrointestinal disorders (39%), and obesity (32%). GEM was commonly used as monotherapy (6%) or in combinations (85%): GEM + Cisplatin (64%), GEM + Oxaliplatin (6%), GEM + Capecitabine (5%), GEM + others (10%). Median overall survival was 11.5 months. The table summarizes clinical outcomes by stage. Conclusions: Most patients with BTCs received 1L GEM-based therapies, experienced poor survival and had high hospitalization rates. These data indicate need for future innovative approaches for management of BTC.[Table: see text]
Pattern and clinical significance of lymph node metastasis from hepatocellular carcinoma.
Authors: Lee Byung min , Choi Jin-Young , Seong Jinsil 
Published: January 2022

431 Background: We investigated clinical features and prognostic significance as well as the significance of local treatment on LN metastasis from HCC. Methods: The patients diagnosed of HCC with LN metastasis from 2001 to 2019 were evaluated. The HCC was diagnosed using image study and serum tumor marker based on Korean Liver Cancer Study Group guideline. The LN metastasis was diagnosed in accordance to diagnosis criteria in imaging study. The pattern of LN metastasis was evaluated based on imaging study and stratified by 3 groups: group A, regional LN metastasis group, group B, beyond regional intra-abdomen LN metastasis and group C, extra-abdomen LN metastasis group. Results: A total of 852 patients were included. The local treatment of either resection or RT were performed in 265 patients (31.1%). The OS between 3 groups was significantly different; the 1-year OS was 39.8%, 25.5% and 22.2% for group A, B and C, respectively ( p<0.001). The local treatment group presented favorable features involving better liver function, controlled primary cancer and lesser extra-nodal metastasis than no local treatment group (CP-A: 72.5% vs. 54.2%, control of primary cancer: 44.9% vs. 8.7%, extra-nodal metastasis: 85.3% vs. 52.1%, p<0.001). After propensity score matching (PSM), the features were well balanced between the two groups. The OS was significantly better in the local treatment group even after PSM (1-year OS: 51.8% vs. 26.6%, p<0.001). Local treatment showed superior OS in both LN only metastasis and LN plus extra-nodal metastasis (62.3% vs. 31.6% vs. 45.0% vs. 23.4%, p<0.001). In LN only metastasis patients, the dynamics of disease progression showed no difference between two groups ( p=0.651). Conclusions: This study showed that the survival and pattern of failure were significantly different depending on the location of LN metastasis. In patients with regional LN metastasis, active local treatment would enhance the survival of patients.
Toripalimab plus bevacizumab as first-line treatment for advanced hepatocellular carcinoma: A single-arm phase II study.
Authors: Hao Chunyi , Du Chengyou , Peng Baogang , Zhang Wu , Shan Yunfeng , Lv Ang , Wu Jianhui , Shang Changzhen , Luo Xuan , Wei Jinxing , Xiao Heng , Qiu Jianguo , Hua Yunpeng , Shen Shunli , Wang Ting , Dai Shengjie , Chen Xiang , Yan Shican , Hao Chunyi 
Published: January 2022

435 Background: Anti-PD-1/PD-L1 combining with antiangiogenic agents has showed encouraging anti-tumor efficacy for treating advanced hepatocellular carcinoma (HCC). Toripalimab, a humanized monoclonal antibody against PD-1, has already been approved for melanoma, nasopharyngeal carcinoma and urothelial carcinoma in China. Therefore, we aimed to assess the safety and efficacy of toripalimab plus bevacizumab as a first-line treatment for unresectable HCC. Methods: This is a multicenter, single-arm, open-label, phase II study. Patients with unresectable locally advanced or metastatic HCC, BCLC stage C or B, Child-Pugh stage A, ECOG PS ≤ 1, at least one measurable lesion, no prior systemic therapy, were enrolled and treated with toripalimab (240mg, IV, D1) plus bevacizumab (15 mg/kg, IV, D1) every 3 weeks as first-line treatment until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoints were tolerability and objective response rate (ORR, per RECIST 1.1 by investigators). The secondary endpoints included the ORR (per mRECIST by independent review committee), the disease control rate (DCR) and progressive free survival (PFS), DoR, time-to-progression (TTP), time-to-response (TTR) and OS. Tumor response was assessed every 6 weeks. Results: As the data cut-off dateofJune 23, 2021,54 pts were enrolled (males 48; median age 54 years [range 26-68]; ECOG PS 0-1; 87.0% with HBV infection; 74.1% in BCLC stage C; 74.1% had received previous local treatment). All pts received at least one cycle of toripalimab plus bevacizumab treatment with median cycles 10 [range 1-18]. Among 52 evaluable patients, per RECIST v1.1, ORR was 32.7% (17/52) with 1 CR and 16 PR, and DCR was 78.8% (41/52); per mRECIST, ORR was 46.2% (95% CI: 32.2-60.5%) and DCR was 94.2% (95% CI: 84.1-98.8%). The median PFS was 9.9 months (95%CI: 5.5-11.0) and median OS has not reached. Most treatment related adverse events (TRAEs) were grade 1-2. Grade ≥3 TRAEs occurred in 25.9% pts, SAEs occurred in 27.8% pts, and grade ≥3 irAEs occurred in 11.1% pts. No treatment-emergent adverse event (TEAE) leading to death occurred in the study. Conclusions: Toripalimab in combination with bevacizumab as first-line treatment showed promising antitumor activity in patients with advanced HCC, and a manageable safety profile. A randomized phase 3 trial of toripalimab plus bevacizumab versus sorafenib (NCT04723004) are ongoing to further validate the efficacy of combination as first-line treatment in advanced HCC patients. Clinical trial information: NCT04605796.
A retrospective single centre study exploring the efficacy of sequential tyrosine kinase inhibitors (TKI) in patients with hepatocellular cancer.
Authors: Roberts Catherine , Kaina Phillipa , Propper David , Diamantis Nikolaos , Delderfield Rachael , Karuri Alice , Reyes Marilyn , Nijjar Rajinder , Slater Sarah 
Published: January 2022

443 A retrospective single centre study exploring the efficacy of sequential tyrosine-kinase inhibitors (TKI) for patients with hepatocellular carcinoma. Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality. In the UK patients with advanced or intermediate disease despite locoregional treatments are offered a tyrosine-kinase inhibitor (TKI). Sorafenib (SOR) remains the approved first-line choice, with lenvatinib (LEN) and regorafenib (REG) used as either alternative first line or second line therapies, respectively. Previous studies have shown increased overall survival when comparing a single drug to placebo; however few have studied outcomes for patients treated with one or more TKIs. Methods: Data was collected from patients who received TKI therapy for HCC between January, 2016 and September, 2020, within the Barts Health NHS Trust, London. The Electronic Medical Record system was used to gather information pertaining to treatment. The non-parametric Pearson correlation coefficient was calculated using IBM SPSS software to explore the duration of TKI therapy and overall survival. Results: 64 patients were included in the cohort, 17% (n=11) female, 83% (n=53) were male. Median age was 68 years (range 38 - 92 years) and median survival from diagnosis was 18 months (range 4 - 106 months). 51 patients received one TKI, 12 patients received two and 1 patient received three sequential TKIs There was no significant correlation between the number of cycles of SOR or LEN received and overall survival ( p = 0.387), but there was a statistically significant correlation in the group of patients who received SOR and then REG (rs = 0.973, p = 0.000). There was also a statistically significant correlation (rs = 0.360, p = 0.004) between the cumulative number of cycles of TKI treatment and overall survival for all patients (i.e. SOR only, LEN only and those who received more than one TKI). Conclusions: Our analysis suggests that across the cohort, a longer duration of TKI treatment (measured in cycles) may be associated with increased overall survival for patients with advanced HCC. Further data is required to explore the impact on quality of life during therapy. [Table: see text]
Association of early alpha-fetoprotein response with survival in patients with HBV-related hepatocellular carcinoma receiving lenvatinib.
Authors: Wang Nanya , Shi Jiyu , Liu Bo 
Published: January 2022

448 Background: Lenvatinib is a standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). We assessed the value of early alpha-fetoprotein (AFP) response for predicting clinical outcomes to lenvatinib treatment in patients with HBV-related uHCC and elevated AFP levels. Methods: This was a retrospective analysis of the medical records of consecutive patients with HBV-related uHCC and baseline AFP levels ≥20 ng/ml who received lenvatinib for > 1 month at The First Hospital of Jilin University between November 2018 and May 2021. Early AFP response was defined as a > 20% decrease in AFP serum level from baseline after 4 weeks of lenvatinib treatment. We evaluated radiological response using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as well as progression-free survival (PFS), and overall survival (OS) in AFP responders and non-responders. Potential prognostic factors for PFS and OS were assessed using univariate and multivariate Cox proportional hazards models. Intergroup differences were compared using a Mann–Whitney U test for continuous variables, a Fisher’s exact test for categorical variables and a log–rank test for survival data. Results: Medical records from 79 patients were screened and a total of 46 patients were included in the analysis; 84.4% had received lenvatinib in first-line, 63% were Child-Pugh class A, 56.4% had extrahepatic metastases, 35.6% had portal vein thrombosis and 10.3% and 87.2% had BCLC stage B and C disease, respectively. Of the 46 patients, 65.2% (n = 30) were early AFP responders and 34.8% (n = 16) were AFP non-responders. Baseline characteristics were balanced between early AFP responders and non-responders, except for age (≥60 years: 43.3% vs. 12.5%; p = 0.0366) and presence of portal vein thrombosis (46.7% vs. 13.3%; p = 0.0277). The median follow-up time was 18.0 (IQR, 3-29) months. Early AFP responders versus non-responders had a significantly higher objective response rate (34.5% vs 6.3%, p = 0.0349), disease control rate (82.8% vs 50.0%; p = 0.0203) and a longer median PFS (13.0 vs 7.0 months; HR, 0.464; 95% CI, 0.222-0.967; p = 0.028). Multivariate analysis confirmed that early AFP response (HR, 0.366; 95% CI, 0.169-0.795; p = 0.0110), ECOG PS of 0 (HR, 0.497; 95% CI, 0.323-0.877; p = 0.0326) and ALBI grade 1 (HR, 0.411; 95% CI, 0.277-0.863; p = 0.0283) were independent prognostic factors for longer PFS. Conclusions: AFP is an important prognostic factor and a predictive biomarker of survival benefit for patients with HBV-related uHCC receiving treatment with lenvatinib.
Final clinical outcome and biomarker analysis of sintilimab plus a bevacizumab biosimilar (IBI305) for advanced hepatocellular carcinoma: A phase Ib clinical trial.
Authors: Zhang Wen , Gong Caifeng , Bi Xinyu , Xuenan Peng , SUN Yongkun , Wang Yan , Zhou Hui , Zhao Hong , Cai Jianqiang , Zhou Ai-Ping 
Published: January 2022

455 Background: The combination of immune checkpoint inhibitors (ICI) and vascular endothelial growth factor (VEGF) antibodies manifested high efficacy in advanced hepatocellular carcinoma (HCC), which still needs to be further verified. We aimed to evaluate the safety and activity of this strategy with different doses, as well as to explore potential predictive biomarkers. Methods: In this two-part phase Ib study, patients with advanced or metastatic HCC were enrolled. Part 1 was dose escalation trial with sintilimab plus bevacizumab biosimilar (IBI305) 7.5 mg/kg (initial dose) or 15 mg/kg (escalated dose). Part 2 was extension in each tolerable dose group. Peripheral blood samples and tumor tissue specimens were collected before treatment to detect serum cytokines and tumor immune microenvironment (TiME) by multiplexed bead immunoassays and multicolor immunofluorescence. Results: Fifty patients were enrolled in final analysis. Among all, IBI305 7.5 mg/kg was administered in 29 patients and 21 patients with 15 mg/kg. The most common adverse event suspected to be treatment-related was hypertension (32%), proteinuria (26%) and fever (26%). The incidence of the grade 3-5 adverse events in group 15 mg/kg was 28.6%, while 13.8% in 7.5 mg/kg group. Overall, the ORR was 34% (17/50) and the DCR reached to 78% (39/50). The median PFS was 10.5 months (95%CI, 8.4-12.7) and the median OS was 20.2 months (95%CI, 16.1 -24.3). The ORR for 7.5 mg/kg and 15 mg/kg were 31% and 38%, respectively. Further analysis showed that responder patients (CR+PR+SD≥12 weeks) had significantly higher level of serum CD137 than those with non-responder group (PD+SD≥12weeks) (median, 32.8 versus 19.8 pg/mL, P = 0.034). Patients with a high level of CD137 ≥ 31.8 pg/mL had longer PFS (mPFS:14.2 vs. 4.1months, P = 0.001) and OS (mOS: NR vs.15.6months, P = 0.023). In addition, the TiME analysis demonstrated that the density of M1 macrophages (CD68+CD163-) in stroma was related to efficacy (P = 0.033), longer PFS (P = 0. 024) and OS (P = 0.046). Conclusions: The sintilimab plus IBI305 is well tolerated and effective, IBI305 of 7.5 mg/kg could be also optional to some patients. The serum CD137 and M1 macrophages are potential predicting biomarkers for the combination therapy Clinical trial information: NCT04072679.
Early experience of combining immune checkpoint inhibitor and radiotherapy in heavily pretreated hepatobiliary cancer.
Authors: Kim Yong Tae , Lee Byung Min , Seong Jinsil 
Published: January 2022

457 Background: Promising therapeutic results of immune checkpoint inhibitor (ICI) have been reported in various solid tumors. Radiotherapy (RT) is known to enhance the immunogenic effect. The immunogenic effect of RT is expected to improve the therapeutic effect of ICI. In this study, we aimed to investigate the efficacy and toxicity of combining ICI and RT in hepatobiliary cancer. Methods: Patients who received RT and ICI combination therapy for hepatobiliary cancer from January 2020 to April 2021 were retrospectively reviewed. Baseline patient characteristics such as age at diagnosis, stage, previous treatment, radiation dose, tumor volume, and lymphocyte count were recorded. The primary endpoints were in-field and out-field control rate. The secondary endpoint was treatment-related toxicities. Overall survival and progression-free survival were also evaluated. The disease control rate and survival were assessed using the Kaplan-Meier method. Results: In total, 17 patients and 35 treated lesions were included for analysis. The median follow up period was 5.5 months (range 2.4 – 19.8 months). Of the 17 patients, 14 were diagnosed hepatocellular carcinoma (82.4%). Twelve patients had distant metastasis (70.6%). Various treatments were administered to the patients prior to ICI and RT combination treatment. The 6-month overall survival and progression-free survival was 62.7% and 26.5%, respectively. The 6-month in-field control rate was 67.4% and 6-month out-field control rate was 26.6%. Higher BED (≥ 90 Gy) was a significant prognostic factor for both in-field and out-field control, and lymphopenia (≤ 800 /μL) at the time of RT start was a poor prognostic factor for outfield control. Fractional dose of less than 5 Gy showed improved in-field and out-field control. Treatment related toxicity occurred in 10 patients (58.8%). The most frequent adverse event was GI disorders such as esophagitis (n = 3) and epigastric pain (n = 3). Patients who experienced treatment-related toxicity were well recovered after conservative care. There was no grade 3 or 4 toxicity. Conclusions: The combination of ICI and RT showed substantial efficacy with acceptable toxicity in heavily pretreated advanced hepatobiliary cancer patients. Dose per fraction of less than 5 Gy may be appropriate for better efficacy in future study of combining ICI and RT. The results of this study provides a basis for future prospective study in hepatobiliary cancer.
Safety and dose-escalation study of a targeted oncolytic adenovirus, suratadenoturev (OBP-301), in patients with refractory advanced liver cancer: Phase I clinical trial.
Authors: Heo Jeong , Liang Ja-Der , Kim Chang Won , Woo Hyun Young , Shih I-Lun , Su Tung-Hung , Lin Zhong-Zhe , Chang Stanley , Urata Yasuo , Chen Pei-Jer 
Published: January 2022

459 Background: Suratadenoturev (OBP-301) is an oncolytic adenovirus that harbors a promoter of human telomerase reverse transcriptase ( hTERT) and is genetically modified to selectively replicate within and then lyse cancer cells. The aim of this study was to assess the safety and optimal dosage for intratumoral (IT) injection of OBP-301 in patients with advanced hepatocellular carcinoma (HCC). Methods: An open-label, non-comparative, phase I dose-escalation trial was performed in 20 patients who had refractory advanced HCC. OBP-301 was administered to the primary tumor using ultrasound guidance. A single IT injection of 1010 virus particles (VP) was administered to patients in the initial cohort (Cohort-1), and the subsequent single-dose cohorts received 1011 VP (Cohort-2), 1012 VP (Cohort-3), and 3×1012 VP (Cohort-4). A multiple dose cohort (Cohort-5) received 2×1012 VP × 3 times every 2 weeks. Each of the single-dose cohorts had 3 patients and there was a single escalating dose of OBP-301 from 1010 to 3×1012 VP. The multiple-dose cohort had 8 patients, and 6 of them received multiple escalating doses of 2×1012 VP ×3 times every 2 weeks. Results: There were 18 males and 2 females, and the median age was 59.39 years (range: 48.4–65.9). Patients had good tolerance of the single dose and multiple-dose regimens, and the maximum tolerated dose (MTD) was more than 6×1012 VP/patient. There was no evidence of toxicity with increasing dose, but there was a greater frequency of treatment-emergent adverse events (TEAEs) in Cohorts 4–5 than in Cohorts 1–3. The most common TEAEs related to OBP-301 were influenza-like illness (30%), pyrexia (15%), and fatigue, decreased platelet count, abdominal distension, and anemia (10% each). The overall intrahepatic mRECIST response occurred in 7 patients (39%) with confirmed stable disease (SD) and 11 (61%) with progressive disease (PD). The best target response occurred in 14 patients (78%) and 4 (22%) of them had PD. There was evidence of OBP-301 replication-dependent dissemination in the blood. Cohorts 4–5 had about 50% greater levels of CD8+ T cells in peripheral blood after OBP-301 injection. Conclusions: Multiple IT injections of OBP-301 are well-tolerated in advanced HCC. Although antitumor activity of the study medication alone would not be demonstrated obviously, SD observed as best local response was higher than as overall response. Improved anti-tumor efficacy can be achieved with adjusting viral injection volume to the target sites as well as with adopting the combination therapy with another immunothrapeutics in further study (JRCT ID: jRCT2033200223). Clinical trial information: NCT02293850.