bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regorafenib second-line therapy for surgical recurrent hepatocellular carcinoma: An exploration of continuing regorafenib therapy after tumor progression—A single-center retrospective analysis of 90 cases.
Authors: Wu Liqun , Rao Wei , Guan Ge , Xin Yang , Niu Qinghui , Fan Ning , Guo Yuan , Li Zixiang , Wang Song , Cai Jinzhen 
Published: June 2023

e16164 Background: To explore the prognosis of patients with continuing regorafenib therapy after the HCC progression of second-line regorafenib therapy. Methods: The HCC patients with second treatment by regorafenib from Dec. 2017 to Dec. 2021 were collected from His system of the hospital. The inclusion criteria included surgical treatment with hepatectomy or liver transplantation, the HCC diagnosis by pathological confirmed, Child-Pugh A-B and ECOG PS≤2 when taking regorafenib, exposure time ≥21 days. Efficacy was evaluated according to RECIST v1.1 (solid tumor efficacy Evaluation Criteria). Results: By Dec. 31, 2022, the median follow-up time was 17.6 months since taking regorafenib. The median overall survival (OS) time was 26.0 months (95%CI 19.75-32.25 months) in 110 patients with second-line regorafenib treatment for recurrent HCC after surgical treatment, and the median OS time of first-line sequential regorafenib was 37.6 months (95%CI 30.23-44.97 months). In 100 cases of regorafenib progression, 10 cases received only palliative therapy after progression. The ninety cases continued the antitumor therapy, the median OS time after progression was 18.0 months (95%CI 12.93-23.07). There were 56 patients (62.2%) who continued to take regorafenib and 34 patients (37.8%) who took other targeted drugs. The median OS time after progression in the two groups was 18.0 and 19.8 months, respectively (P=0.614). In 56 patients who continued regorafenib, Kaplan-Meier analysis and Cox regression risk model analysis showed that NLR≥4.0, liver tumor load larger and without combination therapy were independent risk factors for survival after progression in patients with continued regorafenib. Conclusions: The overall survival time 18.0 months was found in patients with HCC progression after second-line regorafenib therapy, these patients with recurrent HCC underwent surgical treatment (resection or liver transplantation). There was no significant difference in OS time between those who continued regorafenib therapy and those who selected other targeted agents after HCC progression with the regorafenib. The NLR≥4.0, liver tumor load lager, and without combination therapy were independent risk factors for survival after progression in patients who continued regorafenib.
Gemcitabine, cisplatin, nab-paclitaxel: The effectiveness of this regimen for gall bladder cancer.
Authors: Chaugule Deepali , Bhargava Prabhat Ghanshyam , Ostwal Vikas S. , Srinivas Sujay , Patil Rajshree Nivrutti , Ghadi Aayushi , Vadodaria Divya , Munot Pritesh Naresh , Joarder Ritam , Vaidyanathan Arvind , Goel Mahesh , Patkar Shraddha , Ramaswamy Anant 
Published: June 2023

e16168 Background: Locally Advanced inoperable/metastatic Gallbladder Cancers (GBC) are treated with either GC, GO, or single-agent Gemcitabine based on physician discretion. However, based on about 50% response rates (ORR) and prolonged survival in the phase II trial of biliary tract patients, were treated with Gemcitabine - Cisplatin - Nab-Paclitaxel (GCNP). Methods: Consecutive series of patients diagnosed with locally advanced (liver infiltration > 5 cm, large nodes at porta, abutting duodenum), inoperable and metastatic biliary tract patients between January 2018 to August 2022 were evaluated for first-line chemotherapy GCNP, in the Multidisciplinary Joint Clinic (MDJC). The primary endpoint was ORR and the secondary endpoints were survival and tolerance. Results: A total of 142 patients received GCNP during the specified time period. The median age of the cohort was 52 years (range: 21- 79), the majority were females (61.3%), and the majority were GB (81.7%). Response rates were available in 137 patients. CR, PR, and SD were seen in 9 (6.3%), 87 (61.3%), and 24 (16.9%) respectively, for a RR of 67.6% and CBR of 84.5%. Median EFS was 9.92 (95% CI, 7.69- 12.14) months. Of the 52 patients in whom GCNP was given with NACT intent for locally advanced GBC, 17 patients underwent surgery (34%). Conclusions: Our study indicates that GCNP leads to better response rates, better chances of unresectable disease being surgically feasible at a later date, and possibly offers better survival in the GBC cohort.
Real-world efficacy and safety of donafenib-based therapies in patients with unresectable hepatocellular carcinoma: A retrospective study.
Authors: Shang Changzhen , Luo Xuan , Zhong Jinyi , Zhang Jianlong , Li Huilong , Tan Wenliang , Lei Zhang , Chen Yajin 
Published: June 2023

e16169 Background: According to the results of phase III ZGDH3 study, donafenib has significantly improved overall survival (OS) versus sorafenib in first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC). The present study aimed to evaluate the efficacy and safety of donafenib-based therapies in patients with uHCC regardless of first- or later-line systemic therapy. Methods: This single-center retrospective study involved 30 patients with histopathologically/cytologically or clinically confirmed uHCC at Sun Yat-sen Memorial Hospital, Sun Yat-sen University between August 2021 and February 2022. Eligible patients underwent donafenib-based therapies until disease progression, death, or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included OS, objective response rate (ORR), disease control rate (DCR), and safety. Tumor response was determined according to the RECIST v1.1 and modified (m)RECIST. Results: Of these eligible 30 patients, the median age was 55 years (range, 27–73), 93% were male, 93% with HBV and 63% were BCLC C. Donafenib was commonly used as a monotherapy (17%) or in combination with immune checkpoint inhibitors (ICIs), transarterial therapy, both, or other treatments. Twenty (67%) patients underwent donafenib-based therapies as a first-line treatment, of which 15 (75%) underwent a triple combination of donafenib, ICIs, and transarterial therapy. By the cutoff date of January 2023, the median PFS and OS were not yet reached; the 6-month PFS and OS rates were 70.0% and 90.0%, respectively, and the 12-month PFS and OS rates were 66.5% and 86.5%, respectively. The ORR and DCR for all patients were 43.3% and 73.3%, respectively, based on both RECIST v1.1 (CR 4 [13.3%], PR 9 [30.0%], SD 9 [30.0%]) and mRECIST (CR 5 [16.7%], PR 8 [26.7%], SD 9 [30.0%]). Among the 20 patients who underwent donafenib-based first-line systemic therapy, the ORRs according to RECIST v1.1 and mRECIST were both 55.0%, and higher ORRs (73.3% per RECIST v1.1 and mRECIST) were observed in 15 patients who underwent donafenib, ICIs, and transarterial therapy. Overall, 15 (50.0%) patients had more than one treatment-related adverse event (TRAEs) and the most common AEs were hand-foot skin reaction (26.7%), rash (10.0%), and gingival bleeding (10.0%). Grade 3 AEs occurred in 16.7% of patients. No TRAE led to death in the study. Conclusions: This study indicated that donafenib-based therapies, particularly donafenib in combination with ICIs plus transarterial therapy, show promising antitumor activity in patients with uHCC, and no new safety signals were observed in real-world settings. Clinical trial information: ChiCTR2200063822 .
The clinical efficacy and safety of sintilimab plus anlotinib for unresectable intrahepatic cholangiocarcinoma (ICC): A prospective, single-arm phase II study.
Authors: Cheng Jian-Wen , Yang Xin-Rong , Xu Yang , Huang Xiao-Wu , Qiu Shuang-Jian , Sun Hui-Chuan , Fan Jia , Zhou Jian 
Published: June 2023

e16170 Background: Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy. Immunotherapy plus chemotherapy regimen (such as TOP-AZ study) had demonstrated important therapeutic advantages in ICC, but the severe AEs reaction to chemotherapy might deteriorate treatment compliance, performance status and quality of life, and even subsequent treatment eligibility. Hence there is an unmet need for a more tolerable regimen with comparable efficacy for patients with unresectable ICC. The clinical benefits of combining Sintilimab and Anlotinib have been reported in a variety of clinical studies of solid tumors, such as non-small cell lung cancer and hepatocellular carcinoma. This trial aims to explore the safety and efficacy of Sintilimab plus Anlotinib in unresectable ICC. Methods: This is a prospective, single-arm, open-label exploratory, phase II study (ChiCTR2000035901). Eligible unresectable ICC patients received Sintilimab (200 mg, iv, d1) and Anlotinib (12 mg, po, d1-14) every 3 weeks till disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) assessed by RECIST v1.1 and secondary endpoints included progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), overall survival (OS), surgical conversion rate, as well as safety and tolerability. Results: Up to the end of January 2023, 18 patients were enrolled with a median age of 60.4 years (range 36-73), 61.1% were male, and all patients were classified into Child-Pugh A. 12 of 18 patients (66.7%) presented with TNM stage IV and 8 (8/18, 44.4%) patients had distant metastasis. All patients were efficacy evaluable, confirmed ORR was 33.3% and DCR was 83.3%. Of these, 16.7% (3/18) patients achieved complete response (CR), and 16.7% (3/18) patients achieved partial response (PR). Median PFS was 7.49 months (95% CI: 3.12-13.2). Among those, 3 (16.7%) patients further received surgical resection and 2 of 3 them were still disease-free survival till last follow-up. Treatment-related AEs (TRAEs) occurred in 12/18 pts (66.7%), while the most commonly reported TRAEs were hypertension in 29.6%. Grade 3 TRAEs occurred in 6/18 pts (33.3%) and there was no grade 4-5 TRAEs. Conclusions: In view of its encouraging efficacy and safety profile, Sintilimab plus Anlotinib might represents a viable and safe chemotherapy-free regimen in unresectable ICC treatment. Enrollment and further follow-up are ongoing. Clinical trial information: ChiCTR2000035901 .
The impact of DNA damage repair gene mutations on therapeutic response among Chinese patients diagnosed with advanced biliary tract cancer.
Authors: Gou Hongfeng 
Published: June 2023

e16190 Background: Biliary tract cancer (BTC) is a fatal disease characterized by molecular heterogeneity, which results in variations in biological behavior. Despite this, the knowledge of pathogenic alterations in the Chinese BTC population using next-generation sequencing (NGS) profiles remains limited. Therefore, we performed a retrospective investigation to assess the predictive significance of DNA damage repair (DDR) mutations in facilitating precision medicine for this disease. Methods: NGS profiling was carried out on resected tissues obtained from Chinese patients diagnosed with advanced BTC. In addition, baseline clinical and genetic characteristics were collected, along with data on their survival outcomes. Results: A total of 68 Chinese patients with BTC who received ﬁrst-line platinum-containing chemotherapies were enrolled in this study [intrahepatic cholangiocarcinoma (ICC), 33; extrahepatic cholangiocarcinoma (ECC), 13; gallbladder carcinoma (GBC), 22]. Genetic alterations were observed in 67 patients (98.5%), with TP53 (50.0%), KRAS (26.8%), ARID1A (16.2%), and CDKN2A (16.2%) being the most commonly mutated genes. Patients with TP53 mutations demonstrated a trend towards reduced median OS (16.6 vs. 20.1 months, P=0.145). Mutations in DDR genes were identified in 29 (42.6%) of overall patients, primarily involving ATM (11.8%) and BAP1 genes (8.8%), and were signiﬁcantly associated with longer mPFS (6.4 vs. 4.8 months, P=0.022) and mOS (21.2 vs. 14.3 months, P=0.011) in patients who received ﬁrst-line platinum-containing chemotherapies. DDR-mutated patients treated with PD-1 blockades showed a tendency towards improved overall survival compared to the DDR-naive group (20.8 vs. 14.3 months, P=0.297). Furthermore, tumor mutational burden (TMB) could be estimated in 63 cases and was signiﬁcantly higher in those with DDR mutations (P=0.029). Conclusions: Genetic information can aid in identifying a subgroup of BTC patients who may benefit from targeted therapy, this retrospective study demonstrated the predictive significance of DDR mutations for platinum-based chemotherapy efficacy in Chinese patients. Nonetheless, additional research is necessary to explore the potential of DDR mutations in predicting sensitivity to PD-1 blockade.
Incidence of metachronous peritoneal metastases for intrahepatic cholangiocarcinoma after curative resection: A single center cohort analysis.
Authors: Gül-Klein Safak , Schöning Wenzel , Lurje Georg , Keshi Eriselda , Kuzinska Matylda Zofia , Nathanael Raschzok , Krenzien Felix , Alberto Vilchez Miguel Enrique , Ramackers Wolf , Thuss-Patience Peter C. , Pratschke Johann , Rau Beate , Pelzer Uwe 
Published: June 2023

e16199 Background: The impact of metachronous peritoneal metastases (m-pm) on survival after curative resection for intrahepatic cholangiocarcinoma (iCCA) is poorly understood, while there is some knowledge to the occurrence of pulmonary and hepatic metastases. Studies are needed to analyze the impact of advanced metastatic disease for m-pm for iCCA after curative resection. Methods: At the Charité - Universitätsmedizin Berlin, a total of 1979 patients with the general diagnosis of cholangiocellular carcinoma were discussed in interdisciplinary tumor conferences from 2010 to 2022. Results: At the Charité - Universitätsmedizin Berlin, a total of 1979 patients with the general diagnosis of cholangiocellular carcinoma were discussed in interdisciplinary tumor conferences from 2010 to 2022. iCCA was present in 269 cases and proven histopathological results were documented at our hospital in 227 patients. Out of these, 209 patients underwent curative resection, while no advanced tumor disease leading to termination of the indicated operation were found. Two patients presented limited synchronous peritoneal metastases (s-pm) intraoperatively. The postoperative histopathological result presented N0-status in 113 patients and N+-status in 96 patients. Metachronous metastases were diagnosed in 17 patients after 103 months on average with a mean overall survival (OS) of 108 months. Regarding postoperative complications >3b Clavien-Dindo after the initial surgery one patient died in the early postoperative follow-up within the first 30 days. Complete radical resection (R0) was achieved in 133 patients, while R1-status was recorded in 28 patients. Furthermore seven m-pm patients additionally presented hepatic metastases, five m-pm patients pulmonary metastases, while one m-pm patient showed simultaneous hepatic and pulmonal metastases and one other m-pm patient developed even hepatic, pulmonal and osseous metastases. Neoadjuvant oncologic therapy was performed in two patients, adjuvant therapy was applied in six patients prior to the diagnosis of m-pm. Again, a total of five patients received palliative therapy after diagnosis of m-pm. Nevertheless, one patient underwent pulmonary metastectomy. Conclusions: The primary aim regarding the two s-pm patients was immediate postoperative surgical outcome without complications (>3a according to Clavien-Dindo) and was feasible, regarding the prognostic impact of s-pm for surgical resectability; curative resection seems to be an option. The primary aim for m-pm was OS, while promising outcomes were shown in this study.
The safety and efficacy of donafenib combined with anti-PD-1 antibody as adjuvant therapy for patients (pts) with hepatocellular carcinoma (HCC): Updated results of a phase 2 study.
Authors: Chen Yiwen , Shen Yan , Zhang Min , Wu Jian , Gao Shunliang , Que Risheng , Yu Jun , Tang Xiaofeng , Bai Xueli , Liang Tingbo 
Published: June 2023

e16202 Background: Adjuvant therapy may have an important role in decreasing recurrence rates and improve survival in selected pts with HCC following surgical resection. However, there is no standard treatment options or strategies. This study aimed to investigate the safety and efficacy of donafenib combined with anti-PD-1 antibody as adjuvant therapy for HCC pts with high risks of recurrence. Methods: This prospective, open-label, single-arm study planned to enroll 30 pts who had undergone radical surgery and were diagnosed as HCC confirmed by histology or cytology with any of the following risk factors: a) Microvascular invasion (MVI); b) Satellite nodules in specimens; c) >3 tumor nodules; d) Portal vein tumor thrombosis (excluded main portal vein invasion). Donafenib combined with anti-PD-1 antibody was initiated at 4 to 8 weeks after surgical resection and continued for up to six months. The primary endpoint was the cumulative 1-year recurrence-free survival rate (RFSR). The secondary endpoints were recurrence-free survival (RFS), overall survival, and safety. Results: As of December 31st, 2022, a total of 23 pts received donafenib plus anti-PD-1 antibody (toripalimab) with a mean follow-up of 7.6 months (safety set). The most common risk factor was MVI (91%). 20 pts were included in efficacy set (three pts were excluded due to ineligibility), of whom 16 pts had one risk factor and four had two. Intrahepatic recurrence occurred in 3 pts (15%) and no extrahepatic metastasis or death was reported. The RFSR at one year was 83.0% (90%CI, 61.6%-93.1%) in all the pts from efficacy set, 81.9% (90%CI, 59.6%-92.6%) and 92.3% (90%CI, 66.0%-98.5%) in pts with MVI and MVI-low risk, and 85.1% (90%CI, 59.6%-95.1%) in pts with only one risk factor. The median RFS was not reached. The incidence of grade 3 adverse events related to donafenib and/or toripalimab was 52.2% (12/23). No pts had grade 4/5 adverse events. Adverse events leading to withdrawal of any and both treatments occurred in six (26.1%) and one (4.3%) pts, respectively. The most common grade 3 treatment-related adverse events (occurred in more than one patient) were palmar-plantar erythrodysesthesia syndrome (17.4%), rash (17.4%), alanine aminotransferase increased (13.0%), and aspartate aminotransferase increased (8.7%). Conclusions: These results were consistent with earlier reports. The combination of donafenib and toripalimab may be a promising adjuvant therapy for pts with MVI, satellite nodules or multiple tumor after hepatectomy. No safety issues were noted. Clinical trial information: NCT04418401 . [Table: see text]
Transcatheter arterial chemoembolization using CalliSpheres beads loaded with arsenic trioxide for unresectable large or huge hepatocellular carcinoma: A prospective study.
Authors: Duan Xuhuan , Li Hao , Chen Pengfei , Sun Tao , Kuang Donglin , Lu Huibin , Qiao Bingbing , Fan Zhengjun , Ren Jianzhuang , Han Xinwei 
Published: June 2023

e16204 Background: To determine the safety and efficacy of transcatheter arterial chemoembolization with CalliSpheres beads loaded with arsenic trioxide (CBATO-TACE) in the first-line treatment of patients with large (5 cm ≤ maximum diameter＜10 cm) or huge (maximum diameter ≥10 cm) hepatocellular carcinoma (HCC). Methods: Patients were randomly allocated to the CBATO-TACE group and the cTACE group. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall survival (OS), treatment response, and treatment- related adverse events (TRAEs). The extrahepatic collateral arteries, liver function, and liver fibrosis after the first TACE were also evaluated. Results: From September 2018 to September 2020, a total of 207 patients underwent TACE were consecutively enrolled in this study. The median PFS was 9.5 months (range: 8.0-11.0) in the CBATO group, which was significantly longer than that in the cTACE group (6.0 months, range: 4.0-6.0) ( P< 0.0001). Patients in the CBATO group had a median OS of 22 months (range: 20.0-27.0) compared with 16 months (range:15.0-20.0）in the cTACE group ( P= 0.0084). The most common TRAEs were fever ( P= 0.043), nausea and vomiting ( P= 0.002), which were more observed in the cTACE group. In addition, the progressive disease time, pulmonary metastasis rate ( P= 0.01), the mean number of EHC arteries ( P= 0.01) and average number of TACE sessions ( P= 0.025) were significantly decreased in the CBATO group. Conclusions: CBATO-TACE achieved better therapeutic outcomes and similar safety profile compared to cTACE in large or huge HCC patients. Furthermore, CBATO-TACE was able to reduce extrahepatic collateral arteries production and extrahepatic lung metastasis. Clinical trial information: ChiCTR1800018418 .
Donafenib combined with anti-PD-1 antibody as adjuvant treatment in patients with hepatocellular carcinoma at high risk of recurrence after radical resection: A retrospective analysis.
Authors: Li Chenggang , Shen Hanchuan , Zhang Hangyu 
Published: June 2023

e16209 Background: Surgical resection is one of the most effective treatments for HCC. However, the recurrence rate after hepatectomy is still very high with the 5-year recurrence rate of 60~70%, which is even higher in patients with high-risk recurrence factors. There is no globally recognized standard adjuvant therapy for HCC after radical resection. Here, we evaluated the safety and efficacy of donafenib combined with anti-PD-1 antibody as adjuvant therapy for HCC patients with high risks of recurrence. Methods: We retrospectively analyzed the patients who were diagnosed as hepatocellular carcinoma and underwent R0 resection in Chinese PLA general hospital from June 2021 to Nov 2022, and were confirmed by pathological examination to have any one of the following high-risk factors: the number of tumors ≥ 2, the maximum diameter of tumors ≥ 5cm, portal vein tumor thrombus, microvascular invasion (MVI) and satellite lesions. These patients would receive donafenib combined with anti-PD-1 antibody as adjuvant therapy up to 1 year. The primary endpoint was recurrence free survival (RFS). Secondary endpoints included 1 and 2 year RFS rate, overall survival (OS) and safety. Results: 32 patients were included in this analysis, all of them received donafenib 100mg bid plus anti-PD-1 antibody as adjuvant therapy. Pts were classified as BCLC stage A (50.0%), B (15.6%) and stage C (34.4%). The study population was predominantly HBV-positive (87.5%). 17/32 (53.1%) pts had microvascular invasion, 8/32 (25%) had satellite nodules and 2/32 (6.3%) had portal vein tumor thrombus. 17/32 (53.1%) pts had tumor size ≥5 cm, the median tumor size was 5.00 cm (range 2.0 to 12.5) based on pathological findings and 8/32 (25%) had tumor number≥2. Seven pts (21.9%) underwent secondary surgery after tumor recurrence, the rate of tumor rupture and incomplete capsules were 9.4% and 18.8% respectively. 1 patient (3.1%) had bile duct tumor thrombus. The median duration of follow up was 7.34 months, three pts experienced recurrence and one patient died of liver failure. The 1-year recurrence-free survival rate was 80.1%. The median RFS was 18.62 months (95%CI, 7.33 to 29.91). The median OS was not reached. Among all the pts who received adjuvant therapy, 27 (84.4%) pts had at least one treatment-related AE (TRAE). Grade 3 TRAEs occurred in 4 (12.5%) pts, no grades 4 or 5 were reported. 1 (3.1%) patient discontinued treatment because of high risk of upper gastrointestinal bleeding. Common TRAEs included hand-foot syndrome (28.1%), platelet count decreased (25.0%), aspartate aminotransferase increased (21.9%), rash (18.7%) and blood bilirubin increased (15.6%). Conclusions: The combination of donafenib and anti-PD-1 antibody as adjuvant therapy demonstrated promising efficacy and was well tolerated in HCC patients with high risks of recurrence.