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Purpose: To assess the activity and toxicity of hepatic arterial infusion chemotherapy (HAIC)+tislelizumab+lenvatinib (HAIC+tisle+len) in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) type IV (Vp4 hCC) in a real-world context. Methods: Fifty-five patients, with Vp4 hCC receiving HAIC+tisle+len therapy from April 2021 to December 2022, were analyzed retrospectively. Data on patient characteristics, adverse events (AEs), treatment, and survival were collected. Outcomes were disease control rate (DCR), overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and treatment-related AEs (TRAEs). Results: As of December 20, 2023, the median follow-up was 17.5 months (95% confidence interval [CI]: 14.7– 22.5). The ORR was 52.7% (3 complete response [CR], 26 partial response [PR]) as per RECIST v1.1 and 65.5% (12 CR, 24 PR) as per mRECIST. The DCR was 94.5% using both RECIST v1.1 and mRECIST. The median PFS and the median OS were 8.0 months (95% CI: 6.2– 12.3) and 16.7 months (95% CI: 12.0-not reached), respectively. Additionally, PFS was independently predicted only by the best tumor response. In patients with the best tumor response (PR or CR), the median PFS was 11.7 months (95% CI: 8.02-not reached) by mRECIST and 15.4 months (95% CI: 7.39-not reached) by RECIST v1.1. Hypertension (14.5%), decreased albumin levels (10.9%) and anorexia (9.1%) were the most frequently observed grade 3– 4 TRAEs. Conclusion: HAIC+tisle+len regimen demonstrated a promising efficacy and favorable safety for patients with HCC and Vp4, providing valuable real-world evidence to complement the trial data for Vp4 hCC. [ABSTRACT FROM AUTHOR]

Background and Aim: Shipixiaoji granules (SPXJ) is traditional Chinese medicine that treats hepatocellular carcinoma (HCC). However, its efficacy in HCC is still unknown. This prospective study assessed the outcomes of using SPXJ combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the management of patients with unresectable HCC. Methods: This study was conducted as a single-arm phase II clinical trial. We recruited patients diagnosed with CNLC stage Ⅱ to Ⅲ HCC. The treatment regimen included oral lenvatinib (12 mg for patients weighing ≥60 kg; 8 mg for those weighing <60 kg) once daily, intravenous tislelizumab (200 mg) every 3 weeks, and SPXJ twice daily. The primary endpoint was defined as progression-free survival (PFS) in accordance with RECIST 1.1 criteria. Results: Fifty-four patients were enrolled in this study. The primary endpoint was achieved, with a median PFS of 12.7 months. The objective response rate (ORR) was recorded at 55.6%. The disease control rate (DCR) was observed at 98.1%. Additionally, we compared PFS based on the participants' sleep behavior. The results indicated that patients with a morning chronotype had a median PFS of 14.1 months, while those with a night chronotype had a median PFS of 9.85 months (95% CI: 1.366-6.853, P <.05). Treatment-related adverse events were reported in 96.3% (n = 52) of patients. Conclusions: The combination of SPXJ, lenvatinib, and tislelizumab demonstrated substantial safety and anti-tumor efficacy as first-line treatment for unresectable HCC. Moreover, patients' sleep behavior significantly influences treatment efficacy. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to explore the curative effects of hepatic arterial infusion chemotherapy (HAIC) combined with Tislelizumab and Lenvatinib on unresectable hepatocellular carcinoma (HCC). Patients and methods: From September 2021 to September 2023, 42 patients with unresectable HCC who were treated in the First Affiliated Hospital of Chongqing Medical University were enrolled in this retrospective single-arm study. They received HAIC combined with Tislelizumab and lenvatinib. Baseline characteristics, laboratory indicators before and after treatment, and imaging findings were collected from medical records. The primary endpoint was objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and safety indicators. Results: A total of 199 HAIC treatments were performed, with a median of 5.5 times (3.75–6.0 times). Based on the mRECIST and RECIST1.1 criterion, the ORR was 71.4% and 57.1%, the DCR was 92.9% and 92.9%. Up to the follow-up date of October 1, 2024, the median PFS was 14.0 months (95% CI, 11.6–16.4 months), and the median OS was 26.0 months.The incidence of any grade of adverse events was 97.6%. The most commonly reported treatment-related grade 3–4 adverse events included thrombocytopenia (28.6%), elevated total bilirubin (19%), and abdominal pain (16.7%). There was no treatment-related death. Conclusion: For unresectable HCC, HAIC combined with tirelizumab and lenvatinib has good anti-tumor efficacy and acceptable adverse reactions. [ABSTRACT FROM AUTHOR]

Background: Older patients with advanced cholangiocarcinoma lack systemic therapy standards. These people have a high risk of chemotherapy, accompanied by adverse reactions and even discontinuation of treatment. Case presentation: We report a 78-year-old female subject with advanced intrahepatic cholangiocarcinoma presenting with unresectable lesions involving the hepatic veins, along with extensive metastatic lymph nodes. After the geriatric assessment, capecitabine was utilized for only one cycle owing to adverse events (AEs). Next, a combination of low-dose lenvatinib and tislelizumab was administrated as a second-line treatment, which resulted in remarkable early tumor shrinkage. The following individual lenvatinib taper enabled a manageable safety profile and durable deep response. A near-complete response was achieved, with the primary tumor significantly reducing from 5.6 cm × 4.7 cm to nearly complete disappearance, accompanied by complete regression of lymph nodes, and both progression-free survival and overall survival exceeding 24 months. Conclusion: The case provides valuable insights that could influence future treatment strategies for older patients with advanced cholangiocarcinoma who are unsuitable for chemotherapy. The dose-individualized chemotherapy-free regime of lenvatinib and tislelizumab might be used in similar cases to improve their outcomes. [ABSTRACT FROM AUTHOR]

Objective: Comparing the efficacy of transarterial chemoembolization (TACE) combined with lenvatinib plus tislelizumab (TLT) with TACE combined with lenvatinib (TL) for unresectable hepatocellular carcinoma, particularly in determining which patients can benefit more from the TLT treatment. Methods: From March 2021 to September 2023, a total of 169 patients from three centers were included in this study, with 103 patients receiving TLT and 66 patients receiving TL. The Kaplan-Meier method was utilized to evaluate the cumulative overall survival (OS) and progression-free survival (PFS) between the two groups and were assessed using the log-rank test. Subgroup analysis on tumor number, maximum tumor diameter, presence of portal vein thrombosis, AFP level, and Child-Pugh class were conducted. Results: The median OS was 26 months in the TLT group, and 20 months in the TL group. The median PFS was 14 months in the TLT group and 9 months in the TL group. The Kaplan-Meier curve demonstrated a significantly superior OS and PFS in the TLT group compared to the TL group. Subgroup analysis showed that for patients with a maximum tumor diameter greater than 7 cm, AFP > 400 ng/ml and accompanied by portal vein tumor thrombus, and Child-Pugh class A, there was a statistically significant difference in OS between TLT and TL groups. Conclusions: OS and PFS were significantly improved in patients who received TLT compared to those who received TL, patients with a largest tumor diameter greater than 7 cm, AFP > 400 ng/ml, Child-Pugh class A and PVTT appeared to derive more benefit. [ABSTRACT FROM AUTHOR]

Background: Older patients with advanced cholangiocarcinoma lack systemic therapy standards. These people have a high risk of chemotherapy, accompanied by adverse reactions and even discontinuation of treatment. Case presentation: We report a 78-year-old female subject with advanced intrahepatic cholangiocarcinoma presenting with unresectable lesions involving the hepatic veins, along with extensive metastatic lymph nodes. After the geriatric assessment, capecitabine was utilized for only one cycle owing to adverse events (AEs). Next, a combination of low-dose lenvatinib and tislelizumab was administrated as a second-line treatment, which resulted in remarkable early tumor shrinkage. The following individual lenvatinib taper enabled a manageable safety profile and durable deep response. A near-complete response was achieved, with the primary tumor significantly reducing from 5.6 cm × 4.7 cm to nearly complete disappearance, accompanied by complete regression of lymph nodes, and both progression-free survival and overall survival exceeding 24 months. Conclusion: The case provides valuable insights that could influence future treatment strategies for older patients with advanced cholangiocarcinoma who are unsuitable for chemotherapy. The dose-individualized chemotherapy-free regime of lenvatinib and tislelizumab might be used in similar cases to improve their outcomes. [ABSTRACT FROM AUTHOR]

The combination therapy of Tislelizumab plus Lenvatinib has recently emerged as the new standard of care for unresectable hepatocellular carcinoma (HCC). This treatment has demonstrated a significant reduction in tumor burden, raising the possibility of conversion therapy. However, the full safety and efficacy of this combination in real-world settings are not yet fully understood. We recently reported the case of a 36-year-old man with initially unresectable massive HCC, for whom radical surgery (RS) was contraindicated. After receiving Tislelizumab/Lenvatinib plus transarterial chemoembolization (TACE), the patient achieved complete pathological remission and subsequently underwent RS. The patient did not experience postoperative severe complications, and there was no recurrence during the follow-up period. Tislelizumab/Lenvatinib plus TACE therapy may lead to a complete pathological response in advanced HCC. Nevertheless, the safety of prolonged treatment needs to be assessed. [ABSTRACT FROM AUTHOR]

Jiayun Jiang,1 Hui Zhang,1 Jiejuan Lai,1 Shiyu Zhang,1 Yanjiao Ou,1 Yu Fu,2,&ast; Leida Zhang1,&ast; 1Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leida Zhang, Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email 2518569931@qq.com Yu Fu, Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, Beibei District, Chongqing, 400715, People’s Republic of China, Email fuyu2020@swu.edu.cnPurpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib and tislelizumab (TACE-Len-T) versus TACE plus lenvatinib (TACE-Len) as the first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).Patients and Methods: This retrospective study included 136 uHCC patients treated with TACE-Len-T or TACE-Len from January 1, 2021, to June 30, 2023. Clinical outcomes including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs) were compared between the two groups. The risk factors affecting OS and PFS were also analyzed.Results: The median OS and PFS of the TACE-Len-T group were significantly longer than those of the TACE-Len group (Median OS: not reached vs 13.8 months, P< 0.001; Median PFS: 13.0 months vs 2.7 months, P< 0.001). The best overall objective response rate (ORR) was also better with TACE-Len-T treatment (ORR: 72.1% vs 29.4%, P< 0.001), and the disease control rate (DCR) significantly increased in the TACE-Len-T group (88.2% vs 48.5%, P< 0.001). Multivariate analyses revealed that TACE-Len treatment, tumor number > 3, and cTACE were independent risk factors for OS, whereas TACE-Len treatment was the only independent risk factor for PFS. The frequency and severity of AEs in the TACE-Len-T group were comparable to those in the TACE-Len group (any grade: 92.6% vs 91.2%, P=0.753; grade 3 or 4: 33.8% vs 32.3%, P=0.855).Conclusion: TACE-Len-T treatment significantly improved OS, PFS, ORR, and DCR over TACE-Len treatment, with a manageable safety profile in uHCC.Keywords: unresectable hepatocellular carcinoma, transarterial chemoembolization, lenvatinib, tislelizumab, immunotherapy

Background Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the beneft of its combination with immunotherapy needs to be verifed. This study evaluated the efcacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. Methods In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight≥60 kg: 12 mg;<60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon’s two-stage design,>6 responders were needed in stage 1 (n=30) to continue the study, and≥18 responders were needed by the end of stage 2 (n=60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. Results Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p=0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the frst 60 patients of the efcacy evaluable analysis set (n=62). After a median follow-up of 15.7 months, confrmed ORR and disease control rate were 38.7% (24/62, 95% confdence interval [CI], 26.6–51.9) and 90.3% (56/62, 95% CI, 80.1–96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8–not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7–94.4). Grade≥3 treatment-related adverse events occurred in 18 (28.1%) patients. Conclusions Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as frst-line therapy for patients with uHCC. [ABSTRACT FROM AUTHOR]

Song Chen,1 Feng Shi,2 Zhiqiang Wu,3 Liguang Wang,4 Hongjie Cai,3 Ping Ma,5 Yuanmin Zhou,5 Qicong Mai,2 Fan Wang,3 Shuangyan Tang,3 Wenquan Zhuang,3 Jiaming Lai,6 Xiaoming Chen,2 Huanwei Chen,4 Wenbo Guo3 1Department of Minimally Invasive Interventional Therapy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Interventional Radiology, Guangdong Provincial People’s Hospital, Guangzhou, People’s Republic of China; 3Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Hepatopancreatic Surgery, the First People’s Hospital of Foshan, Foshan, People’s Republic of China; 5Department of Oncology, the Twelfth People’s Hospital of Guangzhou, Guangzhou, People’s Republic of China; 6Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Huanwei Chen, Department of Hepatopancreatic Surgery, the First People’s Hospital of Foshan, Foshan, People’s Republic of China, Email chwei_fsyyy@163.com Wenbo Guo, Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China, Email guowenbo@mail.sysu.edu.cnPurpose: The current therapeutic strategies for high-risk, unresectable hepatocellular carcinoma (HCC) patients demonstrate suboptimal outcomes. This study aimed to assess the clinical efficacy of the combined approach of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and tislelizumab, either with or without transhepatic arterial embolization (TAE), in managing HCC patients with portal vein tumor thrombus (PVTT) and significant tumor load.Patients and Methods: In this multicenter retrospective study, we analyzed patients diagnosed with primary, unresectable HCC presenting with PVTT and substantial tumor load who had undergone treatment with HAIC, lenvatinib, and tislelizumab, with or without TAE (referred to as the THLP or HLP group), between January 2019 and February 2022 across four medical centers in China. The outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS).Results: The study cohort comprised 100 patients, 50 each in the THLP and HLP groups. The THLP group demonstrated a significantly superior ORR (72% vs 52%, P=0.039). However, both groups exhibited comparable DCR (88% vs 76%, P=0.118), as assessed by the modified response evaluation criteria in solid tumors. The median OS and PFS for the entire cohort were 12.5 months (95% CI, 10.9– 14.8) and 5.0 months (95% CI, 4.2– 5.4), respectively. The THLP group exhibited a significantly extended OS (median, 14.1 vs 11.3 months, P=0.041) and PFS (median, 5.6 vs 4.4 months, P=0.037) in comparison to the HLP group. The most frequently reported treatment-related adverse events included abdominal pain and nausea, both reported by 59% of patients.Conclusion: The combination of HAIC, lenvatinib, tislelizumab, and TAE was feasible in HCC patients with PVTT and high tumor burden, with tolerable safety.Keywords: hepatocellular carcinoma, transhepatic arterial embolization, hepatic arterial infusion chemotherapy, lenvatinib, tislelizumab