bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Anticoagulation for portal vein thrombosis in patients with hepatocellular carcinoma: A retrospective observational study.
Authors: Antonios Kais , Antonios Bana , Al-Banaa Kadhim , Chisti Mohammad Muhsin
Published: June 2023

e16212

Background: Portal vein thrombosis (PVT) occurs in 10-40% of patients with hepatocellular carcinoma (HCC). Advanced imaging modalities, such as MRI, can differentiate between bland PVT and tumor thrombus, and help determine the need for anticoagulation (AC). Our study aims to assess the use of AC in patients with HCC and concomitant PVT. Methods: We conducted a retrospective observational study at eight hospitals in a community healthcare system in southeast Michigan. Patients with a combined diagnosis of HCC and PVT were identified between August 2016 and September 2022. Demographics, clinical characteristics, use of AC, type of thrombus, and median survival were collected through chart review. Results: A total of 122 patients were diagnosed with HCC and PVT (17 patients were lost to follow-up). The median age at diagnosis was 72.7 years and 77.1% of patients were male. Majority (66.6%) of patients were white. Underlying cirrhosis was present in 85.7% of patients, of which 41% was due to HCV infection. Around half of the patients had a Child-Pugh Class-B at diagnosis. AC was started in 46% of patients, with apixaban being the most commonly used agent (56%). Imaging results in the AC group confirmed that 52% of patients had a tumor thrombus. Of all the patients started on AC, 25% had bleeding complications. Overall, death occurred in 52.1% of patients in the AC group compared to 57.9% of patients who did not receive AC. Median survival was 6 months in both groups (p=0.7). Using cox-proportional hazards model, there was no difference observed in overall survival between patients who received AC and patients who did not (HR 0.91, 95% CI 0.54-1.53, p=0.72). Conclusions: In this retrospective review of patients with HCC and PVT, no difference in survival was observed between patients who received AC and patients who did not receive AC. Further randomized prospective data are needed to guide management in this high-risk patient group. [Table: see text]
The efficacy and safety of donafenib-containing regimens as postoperative adjuvant therapy for hepatocellular carcinoma (HCC): A multicenter retrospective study.
Authors: Rao Jianhua , Zhu Xinhua , Zhang Hongwei , Wei Xin , Xu Yonghua , Zhang Long , Zhang Feng , Li Xiangcheng , Cheng Feng
Published: June 2023

e16213

Background: Hepatectomy is a key treatment for long-term survival in patients (pts) with HCC, but a high recurrence rate seriously affects the prognosis. Currently, there is no standard treatment for adjuvant therapy, transarterial chemoembolization (TACE), anti-angiogenic therapy, immune checkpoint inhibitor (ICI) therapy, or combination strategies being evaluated. Donafenib as first-line systemic therapy is recommended in advanced HCC, but this as adjuvant therapy is still explored. This study evaluated the efficacy and safety of donafenib-containing regimens as postoperative adjuvant therapies in HCC. Methods: We retrospectively reviewed the data of pts who had received donafenib monotherapy (D) or a combined regimen (D+TACE, D+ICI, or D+TACE+ICI) as adjuvant therapy in 5 Chinese centers from June 2021 to December 2022. Recurrence was assessed using imaging. A high-risk (HR) subpopulation was defined as pts with any of the following conditions: [i] single lesion >5 cm or multiple lesions of any size; [ii] lesion(s) complicated by tumor thrombus (TT); and [iii] microvascular invasion (MVI) grade ≥1. We analyzed the median relapse-free survival (mRFS) and one-year cumulative recurrence-free survival rate (1y-RFS) of the overall population and HR subpopulation, and safety (CTCAE5.0) of the overall population. Results: This study included 102 pts. At the data cut-off, mRFS had not yet been achieved, with a 1y-RFS rate of 78.2%; 12 pts (11.8%) experienced recurrence. In the HR subpopulation (N=80), the 1y-RFS rate was 79.4%, based on different treatment regimens, the 1y-RFS rates of the D (n=20), D+TACE (n=26), D+ICI (n=23), and D+TACE+ICI (n=11) groups were 87.5%, 87.7%, 72.4%, and 74.1%, respectively, and mRFS had not yet been reached; based on different clinical stages, the 1y-RFS rates of pts with China liver cancer staging stage Ib (n=35) and IIa (n=15) were 93.3% and 71.6%, respectively, with stage Ⅰa (n=12) and Ⅱb (n=7) were not reached, mRFS with IIIa (n=11) was 8.9 months (95% CI: 2.9–15.0 months). Among the overall population, 68 pts (66.7%) had treatment-related adverse events (TRAE) of any grade, and the incidence of grade 3 TRAE was 8.8% (9/102). None of the pts experienced grade 4 or 5 TRAE. Conclusions: These results preliminarily showed that donafenib-containing regimens as postoperative adjuvant therapies were safe and effective for HCC. [Table: see text]
Real world impact of hepatocellular carcinoma stage and hepatic function on health-related quality of life.
Authors: Gupta Amol , Zorzi Jane , Ho Won Jin , Baretti Marina , Azad Nilofer Saba , Griffith Paige , Dao Doan , Kim Amy K. , Philosophe Benjamin , Georgiades Christos , Kamel Ihab R. , Burkhart Richard , Liddell Robert , Hong Kelvin , Shubert Christopher , Lafaro Kelly , Meyer Jeffrey , Anders Robert A. , Burns William , Yarchoan Mark
Published: June 2023

e16215

Background: Health-Related Quality of Life (HRQoL) is an important prognostic indicator and clinical endpoint for patients with hepatocellular carcinoma (HCC). The relationship between cancer stage, liver function, performance status, and HRQoL in HCC in a real-world clinical setting is not well defined. Methods: A retrospective chart review was undertaken of consecutive patients with HCC treated at our institution's liver multidisciplinary clinic between February 2020 and August 2022. We examined the relationship between Barcelona Clinic Liver Cancer (BCLC) stage, Child Pugh (CP) score, and Eastern Cooperative Oncology Group (ECOG) performance status on HRQoL at diagnosis. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. Results: Fifty-one patients met our inclusion criteria. The median age was 69 and the mean FACT-Hep score was 130.3 ± 20.3. FACT-Hep total and subscales showed no significant association with BCLC stages A, B, and C (p =0.224), except in the Emotional Well Being (EWB) subscale (p =0.001). There was no impact of ECOG performance status on the FACT-Hep scores, except for the Functional Well Being (FWB) subscale (p=0.006). Patients with a CP B had significantly more impairment in FACT-Hep than patients with CP A, including FACT-Hep total score (118.5 ±27.3 versus 134.3 ±23.8; p =0.021) and subscales including the Physical Well Being (p =0.018), FWB (p =0.030), Hepatobiliary Cancer Subscale (p <0.001), and FACT-Hep Trial Outcome Index score (p =0.003). Conclusions: Cancer stage poorly correlates with HRQoL at diagnosis in HCC patients. Impaired liver function reduces overall quality of life in HCC patients. Further large-scale prospective studies should be undertaken which incorporate validated HRQoL tools in the routine assessment of HCC patients. [Table: see text]
A retrospective study exploring the safety and efficacy of hepatic arterial infusion chemotherapy and sequential transarterial embolization combined with lenvatinib and tislelizumab in unresectable hepatocellular carcinoma.
Authors: Zhong Jian-Hong , Chen Zu-Shun , Qi Lu-Nan , Zhang Zhi-Ming , Xiang Bang-De , Ma Liang
Published: June 2023

e16219

Background: Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) and lenvatinib with or without immune checkpoint inhibitors (ICIs) are first-line treatment in unresectable hepatocellular carcinoma (HCC). However, the objective response rate (ORR) under HAIC plus lenvatinib and ICIs is not satisfactory. Hereby, we retrospectively explore the efficacy and safety of the combination therapy of HAIC sequential transarterial embolization (TAE) combined with lenvatinib and tislelizumab as a first-line treatment in patients with unresectable HCC. Methods: A retrospective analysis of related clinical data of 35 unresectable HCC patients who received HAIC-TAE combined with lenvatinib and tislelizumab were performed. All patients received at least once HAIC sequential TAE combined with lenvatinib and tislelizumab. The primary end-point was the progression-free survival (PFS) rate per mRECIST at six months. The secondary endpoints included safety, objective response rate (ORR), overall survival (OS), surgical conversion rate and disease control rate. Results: Thirty-five patients (65.7% with BCLC C stage while 22.9% with BCLC B stage disease) were enrolled. The primary end-point of PFS rate was 77.1% at six months. However, the median overall survival was not reached at February 10, 2023. The ORR per RECIST 1.1 was 36.4%, and per mRECIST was 63.6% after twice HAIC sequential TAE. Progressive disease was found in 1 patient in each course of HAIC sequential TAE. Eight patients (22.9%) with 12 tumors received curative hepatic resection. Among these eight patients, two patients (25%) and five tumors (41.7%) were with pathological complete response. Six patients (75%) and ten tumors (83.3%) were with tumor necrosis more than 90%. The rate of tumor necrosis more than 50% was 100%. Four patients with partial response received radiotherapy (n=3) or radiofrequency ablation (n=1). The most common adverse events were elevation of alanine aminotransferase, fever and abdominal pain, and no treatment-related death was reported. Conclusions: FOLFOX-HAIC sequential TAE combined with lenvatinib and tislelizumab showed safe and encouraging antitumor activity for unresectable HCC. Based on the data from this study, a prospective, single-arm Phase II trial is planned. Clinical trial information: NCT05532319 .
Sintilimab combined with bevacizumab biosimilar as a conversion therapy in potentially resectable intermediate-stage hepatocellular carcinoma (HCC): Updated results of a phase II trial.
Authors: Sun Huichuan , Zhu Xiaodong , Gao Qiang , Qiu Shuang-Jian , Shi Ying-Hong , Wang Xiao-Ying , Huang Xiao-Wu , Yang Xin-Rong , Ji Yuan , Pang Yanrui , He Yi-Feng , Xu Yong-Feng , Liu Jie , Sun Mingquan , Li Mei-Ling , Zhu Jin-Jin , Shen Ying-Hao , Huang Cheng , Zhou Jian , Fan Jia
Published: June 2023

e16220

Background: The combination of Sintilimab (a PD-1 antibody) and bevacizumab (bev) biosimilar improved progression-free survival and overall survival in unresectable or advanced HCC as compared with sorafenib in ORIENT-32 study and was approved as first-line treatment for unresectable HCC in China. We assessed the efficacy and safety of the combination therapy as conversion therapy for potentially resectable intermediate-stage HCC. Methods: Treatment-naïve patients (pts) with potentially resectable intermediate stage (BCLC stage B) HCC were enrolled in this phase II trial (NCT04843943). Eligible pts received sintilimab (200 mg, IV, D1) and bev (15 mg/kg, IV, D1) per 3 weeks. Tumor response and resectability were assessed every 6 weeks per RECIST v1.1. Pts with evaluations of partial response (PR) or at least two consecutive stable disease (SD) and eligible for R0 resection were referred for hepatectomy, then continued with sintilimab/bev for at most 12 months. Primary endpoints were event-free survival (EFS) (time from study enrollment to tumor progression, disease recurrence after surgery, or death from any cause) and treatment safety. Secondary endpoints included R0 resection rate, pathologic response, objective response rate (ORR), and disease control rate (DCR). Results: At data cutoff on Feb 7, 2023, 30 pts with BCLC-B stage HCC were enrolled. Of them, 25 pts (83.3%) were up-to-7 criteria out. The median follow-up time was 15.3 months (interquartile range [IQR] 13.8-17.6). ORR and DCR were 26.7% and 90.0% (8 PR and 19 SD). 17 pts (56.7%) met the pre-designated criteria for hepatectomy and received liver resection, including 7 pts were evaluated as PR and 10 as SD before surgery. The median time from initiation of sintilimab/bev to liver resection was 4.3 months (IQR 2.3-5.6). No postoperative mortality was observed. 2 pts had a pathological complete response. Median EFS was 13.8 months (95%CI, 10.3-17.3), and the 6-month and 12-month EFS rates were 76% and 60%, respectively. 3 pts died, and OS data was not mature. Most treatment-related AEs (TRAE) were grade 1-2, and grade 3/4 TRAEs occurred in 7 pts (23.3%). 9 serious adverse events occurred, and 3 of them were treatment associated. Conclusions: For pts with potentially resectable intermediate-stage HCC, sintilimab/bev in combination with liver resection was safe and may improve long-term survival. Clinical trial information: NCT04843943 .
Updated results from ALTER-H004 trial: Anlotinib combined with TACE as adjuvant therapy for patients with hepatocellular carcinoma at high risk of recurrence after surgery—A single arm, multi-center, phase II clinical trial.
Authors: Wu Zheng , Wang Zheng , Zhang Lei , Song Xiaojing
Published: June 2023

e16222

Background: Hepatectomy is deemed as a curative treatment for patients (pts) with hepatocellular carcinoma (HCC). Unfortunately, high recurrent risk after curative resection compromised the long-term survival of HCC significantly. Transarterial chemoembolization (TACE) as adjuvant therapy was proved to improve therapeutic outcomes for pts with high recurrent risk after hepatectomy. However, the survival benefit of TACE remained unsatisfactory. ALTER-H004 trial was designed to identify the efficacy and safety of anlotinib as maintenance adjuvant treatment following TACE in pts with HCC. The preliminary results of ALTER-H004 had been reported at 2022 ASCO (e16120). Here we reported the results at the data cutoff of January 15, 2023. Methods: Pts with one of the following high risk factors after hepatectomy were eligible: ≥5cm and <10cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus (Cheng's classification I/II). Eligible pts received conventional TACE treatment within 1-2 months after hepatectomy, and on the 4th day after TACE treatment, oral anlotinib (12mg, qd, 2 weeks on 1 week off) was given until disease recurrence or unacceptable toxicity. The predefined sample size was 30. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: At January 15, 2023, 29 pts were enrolled and 28 pts were available for prognostic assessment, among whom, 11 pts were still on treatment and 9 relapsed, 3 withdrew the consent, 5 discontinued own to intolerable adverse reactions. The longest duration of treatment is 27.83 months. The median DFS has not reached yet and the 1-year DFS rate was 76.46% (95% CI: 54.83~88.70) and 2-year DFS rate was 65.41% (95% CI: 41.70~81.39). Safety profile indicated that 18 pts (64.3%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs were detected in 5 pts (17.9%) including hypertension (7.1%), leukocytopenia (7.1%) and ascites (3.6%). No grade 4 or 5 TRAEs were observed. Conclusions: Anlotinib combined with TACE as adjuvant therapy in pts with HCC at high recurrent risk exhibited promising prognosis and tolerable safety profile preliminarily, and the conclusion needed to be confirmed in large-scale clinical trials subsequently. Clinical trial information: NCT04213118 .
Real-world (RW) treatment and surveillance patterns in patients with hepatocellular carcinoma (HCC) after resection (R) or ablation (A): Evidence from commercial and Medicare populations.
Authors: Tan Amie , Schuldt Robert , Ogale Sarika , Hernandez Painter Sairy
Published: June 2023

e16223

Background: Prognosis of early HCC after curative resection (R) or ablation (A) remains poor due to lack of approved standard of care for adjuvant therapy. Guidelines recommend that patients (pt) receive surveillance imaging every 3 to 6 months for the first 2 years after R or A. RW data on treatment and surveillance patterns after curative intent therapy in the US can provide insights into how novel therapies may be integrated into the treatment paradigm. Methods: We conducted two retrospective, population-based studies of newly diagnosed HCC pts who underwent R or A as the first HCC therapy using data from Pharmetrics Plus commercial claims (2018 - 2021) and SEER-Medicare data (2010 - 2019), respectively. Continuous enrollment in health plans ≥6 months prior to diagnosis (Dx) date and ≥3 months after R or A, and no transplant during study period, was required. Treatments received within 3 months following R or A were defined as adjuvant therapy. Results: Among 705 eligible HCC pts with commercial insurance coverage, the majority were male (73%) and mean (SD) age at Dx was 61(9) years. Among them, 56% received A, 32% received R, and 12% had both R and A after Dx. 126/705 (18%) pts received adjuvant therapy. Most commonly used treatments were systemic therapy (44%) followed by transarterial chemoembolization (TACE) or transarterial embolization (TAE) (41%). Only 20% of pts received surveillance imaging in the first 2 years following R or A (Table). A total of 2,005 Medicare beneficiaries with HCC were identified from SEER-Medicare (male: 67%; White: 68%; Black: 11%; Asian: 19%). Mean (SD) age at Dx was 70(8) years. Among them, 54% received A, 36% received R, and 10% received both as the initial therapy for HCC. 238/2,005 (12%) pts received adjuvant therapy. Most commonly used treatments were TACE/TAE (61%) followed by systemic therapy (29%). Unlike the commercial insurance cohort, the majority of pts in the Medicare cohort (78%) received surveillance imaging within 2 years following R or A. Conclusions: Despite lack of clinical evidence and approved adjuvant therapy in the US, notable use of treatment in RW practice were observed. Types of adjuvant therapy used and utilization of surveillance varied by payers. A significant proportion of pts did not receive ongoing surveillance imaging despite guideline recommendations. These findings highlight the desire and unmet need for clinical evidence of treatments in pts with early HCC following curative intent therapy. [Table: see text]
Impact of surgical treatment on overall survival in cholangiocarcinoma of the gallbladder: An NCDB study.
Authors: Al Kurnas Mohammed , Silberstein Peter T. , Wu Xinxin
Published: June 2023

e16224

Background: Cholangiocarcinoma (CCA) is a malignancy of the epithelial cells of the biliary tree. Surgical treatment is the preferred treatment option for all subtypes, but 5-year survival rates remain low. The surgical approaches used in the treatment of CCA include radical hepatic resection, laparoscopic, and robotic surgery. Although CCA can arise from the intrahepatic bile duct or extrahepatic bile duct, there exists a subtype with the gallbladder as the primary site. While there have been studies comparing outcomes among surgical procedures, there has yet to be a study that explores the impact of surgery on CCA of the gallbladder. The National Cancer Database (NCDB) was analyzed to determine the effects of surgical modality on overall survival. Methods: A retrospective cohort analysis utilizing the NCDB included 1,880 patients diagnosed with CCA (ICD-8160-3) affecting the gallbladder (topography code C23.9) between 2010 and 2020. Surgical modalities included robotic-assisted, minimally invasive, open, or no surgery. Approaches were categorized by the definitive treatment and open surgeries included procedures converted to open and unspecified. Facility structures were categorized as academic facilities versus non-academic facilities and facility type influence on surgical treatment was compared using Pearson Chi-squared tests. Surgical treatment and facility type on overall survival was analyzed by the Kaplan-Meier method. Results: The majority of the cases analyzed were White (74.7%), female (62.4%), and had Medicare as the primary payor at diagnosis (54.9%). The mean age at diagnosis was 68.4 years (min = 24, max = 90, std. deviation = 11.9) with an average Charlson-Deyo score of 0.5. Of the 1,880 patients analyzed, only 328 underwent surgery (17.4%). There was a statistically significant increase in the overall survival of those who underwent surgery (mean = 33.4 months) over those who did not (mean = 14.7 months, p < 0.001). Those at academic facilities had better overall survival than those at non-academic facilities (p < 0.001), but facility type was not statistically significant for whether patients received surgery. However, those at an academic facility were more likely to have open versus minimally invasive surgery (70.0%) compared to those at a non-academic facility (50.%, p < 0.002). Conclusions: We identified that patients who underwent surgery had significantly better overall survival than those who did not with an average difference of 18.7 months. While there was no difference in the likelihood of having surgery at academic vs. non-academic facilities, the overall survival for those at academic facilities was greater and we found that these patients were more likely to have open surgery over minimally invasive surgery. Further study is needed to determine what other biomedical or socioeconomic factors may account for the difference in overall survival at academic facilities.
Recurrence rate-based strategy to tailor surveillance scheduling in single hepatocellular carcinoma ≤2 cm after curative therapy: Analysis of 6,105 global patients.
Authors: Chen Qi-Feng , Lyu Ning , Zhao Ming
Published: June 2023

e16225

Background: For initially diagnosed very early-stage hepatocellular carcinoma (HCC, VEH, i.e. single Hepatocellular Carcinoma ≤2 cm), surveillance after surgical resection (SR) or radiofrequency ablation (RFA) remains largely unclear. We conducted this multicenter study to explore optimal surveillance strategies and evaluate the current surveillance strategies for initially diagnosed VEH after SR/RFA to support the clinical follow-up schedule. Methods: A total of 6,105 initially diagnosed VEH patients who received SR/RFA from global centers were included. After the measurement of the recurrence rate of each month, delayed detection times for tumor recurrence of various follow-up strategies were calculated. The candidate strategies were evaluated according to the delayed detection times and the tumor volume doubling time (TVDT), and a preferable surveillance strategy was recommended. Results: The cumulative 1-, 2-, 3-, 4-, and 5-year recurrence probabilities were 12.7%, 25.9%, 35.7%, 43.7%, and 49.3%, respectively. Based on the monthly recurrence rate, programing surveillance schedules were tailored, which were more effective than current surveillance strategies under the same visits. When patients were followed up every 6 months, the delayed recurrence detection after curative treatment was expected to be 2.35 to 2.57 months. Given that 93.3% of patients did not have >TVDT with a rapid growth subtype when recurrent nodules were detected, a surveillance strategy with a 6-month interval was recommended. Conclusions: Six months of interval surveillance was conservatively supported in patients with VEH after curative therapy.
Comparison of T cell infiltration in hepatocellular carcinoma between whole exome and transcriptome sequencing data.
Authors: Lv Xing , Dong Wei , Zhang Zunyi , Li Jian , Wang Wenqiang , Dong Linfeng , Yang Zuoquan , Zhou Yanqing , Zhao Shuhua , Chen Shifu , Zhang Erlei
Published: June 2023

e16226

Background: Immunotherapy is one of the most promising therapeutics for hepatocellular carcinoma (HCC), and the immune infiltration status in tumors could be used as a biomarker for immunotherapy. However, evaluation of immune infiltration is usually based on RNA-Seq (transcriptome sequencing), which is limited in clinical practice due to the difficulty of handling RNA. On the other hand, WES (whole exome sequencing) is frequently performed to detect tumor mutations in cancer clinic. Therefore, we try to compare T cell infiltration in hepatocellular carcinoma obtained from WES data and RNA-Seq data, evaluate the potential of T cell infiltration from WES data as a biomarker for immunotherapy. Besides, we also evaluated the association of T cell fraction obtained from WES data and other clinical information. Methods: Seventy pairs of HCC tumor and matched normal tissue samples underwent both WES and RNA-Seq. T cell ExTRECT score and mcpCounter score were used to represent the immune infiltration status, and they were generated from WES data and RNA-Seq data respectively. Tumor mutational burden (TMB) score and some characteristics (tumor size, blood pressure, etc.) were also calculated for correlation analysis. Results: T cell ExTRECT score was positively correlated with mcpCounter score (Spearman correlation coefficient: 0.54). While TMB score showed no correlation with T cell ExTRECT score (Spearman correlation coefficient: -0.06) and mcpCounter score (Spearman correlation coefficient: -0.09). Besides, T cell ExTRECT score was negatively associated with main tumor size (Spearman correlation coefficient: -0.38) and High Blood Pressure (Spearman correlation coefficient: -0.37). Conclusions: These results suggest that T cell ExTRECT score obtained from WES and mcpCounter score generated by RNA-seq data is highly correlated, and neither of them is associated with TMB score. T cell ExTRECT score could be used to evaluate immune infiltration in hepatocellular carcinoma, and may serve as a biomarker for immunotherapy regardless of TMB score. Further investigation is still needed to evaluate the clinical outcome of immunotherapy for hepatocellular carcinoma with T cell ExTRECT score.
An observational study of donafenib as adjuvant therapy to prevent hepatocellular carcinoma recurrence after curative surgery.
Authors: Shang Changzhen , Zhong Jinyi , Luo Xuan , Zhang Jianlong , Li Huilong , Hua Yonglin , Tan Wenliang , Lei Zhang , Chen Yajin
Published: June 2023

e16227

Background: The five-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection is as high as 70% and remains a major clinical challenge. Many investigators have suggested adjuvant therapy to prevent HCC recurrence, and several promising outcomes have been reported. Donafenib has been approved as a standard treatment for patients with unresectable HCC in China. Here, we describe our preliminary results regarding the efficacy and safety of donafenib as an adjuvant therapy for patients with HCC after hepatectomy. Methods: This was an observational study of patients with HCC following hepatectomy treated with donafenib in routine practice at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. The enrolled patients were 75 years or younger, had been diagnosed with HCC, showed no evidence of recurrence at radiological follow-up within one month after hepatectomy, and had at least one high recurrence risk factor, such as tumor diameter ≥5 cm, tumor number ≥2, microvascular invasion, or serum a-fetoprotein level before surgery ≥400 ng/mL. All of the patients had adequate hematologic, hepatic, and renal functions. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints included 6- and 12-month RFS rates, overall survival, and adverse events. Results: Seventeen patients were enrolled in this study. The median age was 56 years (range, 40–72), 88.2% were males, 82.4% with HBV, 17.6% had preoperative serum a-fetoprotein levels ≥400 ng/mL, 35.3% had tumor diameters ≥5 cm, 29.4% had tumor numbers ≥2, and 29.4% had microvascular invasion. The median follow-up time for the entire patient cohort was 16 months (95% confidence interval [CI], 11.9–20.1), and 5 of 17 patients relapsed, with a recurrence rate of 29.4%. The median RFS was not reached; the 6- and 12-month RFS rates were 88.2% and 70.1%, respectively. Treatment-related adverse events (TRAEs) occurred in 82.4% of the patients, most of which were grades 1–2. Grade 3 TRAEs, including hand-foot skin reaction and rash, were observed in three (16.4%) patients. No grade 4 or 5 TRAEs occurred. Conclusions: The findings of the present study suggest that donafenib as adjuvant therapy may be a potentially effective way to prevent HCC recurrence after curative surgery. Our findings should be validated in a larger, prospectively evaluated sample. Clinical trial information: ChiCTR2200064030 .