Efficacy of Lenvatinib Combined with Anti-PD-1 Antibodies plus Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective, Multicenter Study.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti-PD-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07-34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The two-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion: Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

A new species and a replacement name in Cynanchum (Apocynaceae, Asclepiadeae) from China.

Cynanchumpingtaoi S.Jin Zeng, G.D.Tang & Miao Liao, sp. nov. (Apocynaceae) from Yunnan Province, China, is described and illustrated based on morphological and molecular evidence. Its deeply cordate to reniform leaves and campanulate, large flowers show that it is a member of former Raphistemma Wall., which has been included in Cynanchum L.. It is different from all former Raphistemma species by the broadly ovate corolla lobes, purple-red corolla and connivent corona tip slightly exceeding the corolla throat. Meanwhile, Cynanchumlonghushanense G.D.Tang & Miao Liao, nom. nov. is proposed as replacement name for Raphistemmabrevipedunculatum Y.Wan, which was considered a synonym of Cynanchumhooperianum (Blume) Liede & Khanum but is here reinstated as a distinct species because of significant morphological differences.

Long-term surgical outcomes of bile duct tumor thrombus versus portal vein tumor thrombus for hepatocellular carcinoma: a propensity score matching analysis.

Background: Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT). Methods: The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts. Results: Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively). Conclusion: Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT.

A new scoring system for predicting the outcome of hepatocellular carcinoma patients without microvascular invasion-a large-scale multicentre study.

BACKGROUND: The prognosis of HCC patients without MVI (so called M0) is highly heterogeneous and the need for adjuvant therapy is still controversial. METHODS: Patients with HCC with M0 who underwent liver resection (LR) or liver transplantation (LT) as an initial therapy were included. The Eastern Hepatobiliary Surgery Hospital (EHBH)-M0 score was developed from a retrospective cohort to form the training cohort. The classification which was developed using multivariate cox regression analysis was externally validated. RESULTS: The score was developed using the following factors: α-fetoprotein level, tumour diameter, liver cirrhosis, total bilirubin, albumin and aspartate aminotransferase. The score differentiated two groups of M0 patients (≤3, >3 points) with distinct long-term prognoses outcomes (median overall survival (OS), 98.0 vs. 46.0 months; p < 0.001). The predictive accuracy of the score was greater than the other commonly used staging systems for HCC. And for M0 patients with a higher score underwent LR. Adjuvant transcatheter arterial chemoembolization (TACE) was effective to prolong OS. CONCLUSIONS: The EHBH M0 scoring system was more accurate in predicting the prognosis of HCC patients with M0 after LR or LT. Adjuvant therapy is recommended for HCC patients who have a higher score.

Salvage Surgery for Initially Unresectable HCC With PVTT Converted by Locoregional Treatment Plus Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody.

BACKGROUND: This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies. METHODS: The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT. RESULTS: Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (P = .370 and .334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS. CONCLUSIONS: For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT.

Effect of transcatheter arterial chemoembolization combined with lenvatinib plus anti-PD-1 antibodies in patients with unresectable hepatocellular carcinoma: A treatment with Chinese characteristics.

Therapies for patients with unresectable hepatocellular carcinoma (uHCC) are currently popular. Current first-line standard-of-care treatments for uHCC are systematic therapies. However, treatments that combine locoregional therapy with systemic therapy are widely accepted in China and have demonstrated high rates of tumor response and conversion to resection with manageable toxicity. A literature review was performed by searching published literature in PubMed and Web of Science up to December 2023 for relevant articles on the use of triple therapy (transarterial chemoembolization combined with lenvatinib and anti-PD-1 antibodies) in uHCC. This review concentrates on the efficacy and safety of triple therapy with Chinese characteristics in patients with uHCC and describes the outcome of conversion surgery, degree of pathological necrosis, and effect prediction. This article will contribute to a comprehensive understanding of the role of triple therapy with Chinese characteristics in patients with uHCC.

Outcomes of Salvage Surgery Versus Non-Salvage Surgery for Initially Unresectable Hepatocellular Carcinoma After Conversion Therapy with Transcatheter Arterial Chemoembolization Combined with Lenvatinib Plus Anti-PD-1 Antibody: A Multicenter Retrospective Study.

BACKGROUND: Combination treatment with transcatheter arterial chemoembolization (TACE), lenvatinib, and anti-programmed death-1 (anti-PD-1) antibodies (triple therapy) has a high rate of tumor response and converted resection for initially unresectable hepatocellular carcinoma (uHCC) patients. This study aimed to assess the outcomes of salvage surgery in uHCC patients after conversion therapy with triple therapy. METHODS: uHCC patients who met the criteria for hepatectomy after receiving triple therapy as first-line treatment were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) rates in patients who received salvage surgery (SR group) and those who did not (non-SR group) were compared. RESULTS: Of the 144 patients assessed, 91 patients underwent salvage surgery and 53 did not. The OS rates in the SR group were significantly better than those in the non-SR group. The 1- and 2-year OS rates in the SR group were 92.0% and 79.9%, respectively, whereas those in the non-SR group were 85.5% and 39.6 %, respectively (p = 0.007); however, there was no significant difference in the PFS rates. Upon further stratification, OS and PFS were significantly better in the SR group than in the non-SR group in patients who were assessed as partial responses (PR), while there was no significant difference in patients who were assessed as complete response (CR). CONCLUSIONS: Salvage surgery is recommended and is associated with a favorable prognosis for uHCC patients who were assessed as PR after conversion therapy, however it may not be necessary for uHCC if CR was achieved.

Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial.

Hepatocellular carcinoma (HCC), particularly when accompanied by microvascular invasion (MVI), has a markedly high risk of recurrence after liver resection. Adjuvant immunotherapy is considered a promising avenue. This multicenter, open-label, randomized, controlled, phase 2 trial was conducted at six hospitals in China to assess the efficacy and safety of adjuvant sintilimab, a programmed cell death protein 1 inhibitor, in these patients. Eligible patients with HCC with MVI were randomized (1:1) into the sintilimab or active surveillance group. The sintilimab group received intravenous injections every 3 weeks for a total of eight cycles. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat population. Key secondary endpoints included overall survival (OS) and safety. From September 1, 2020, to April 23, 2022, a total of 198 eligible patients were randomly allocated to receive adjuvant sintilimab (n = 99) or undergo active surveillance (n = 99). After a median follow-up of 23.3 months, the trial met the prespecified endpoints. Sintilimab significantly prolonged RFS compared to active surveillance (median RFS, 27.7 versus 15.5 months; hazard ratio 0.534, 95% confidence interval 0.360-0.792; P = 0.002). Further follow-up is needed to confirm the difference in OS. In the sintilimab group, 12.4% of patients experienced grade 3 or 4 treatment-related adverse events, the most common of which were elevated alanine aminotransferase levels (5.2%) and anemia (4.1%). These findings support the potential of immune checkpoint inhibitors as effective adjuvant therapy for these high-risk patients. Chinese Clinical Trial Registry identifier: ChiCTR2000037655 .

Cyclic loading changes the taproot's tensile properties and reinforces the soil via the shrub's taproot in semi-arid areas, China.

This study aimed to reveal the soil reinforcement by shrub root systems after repeated stress from external forces, such as high winds and runoff, for extended periods in the wind-hydraulic compound erosion zone. Using the widely distributed Shandong mine area soil and water-conserving plant species, Caragana microphylla, Hippophae rhamnoides, and Artemisia ordosica, cyclic loading tests were conducted on taproots of the three plant species (1-5 mm diameter) via a TY8000 servo-type machine to investigate the taproots' tensile properties response to repeated loading-unloading using simulated high wind pulling and runoff scouring. Our study revealed that the tensile force was positively correlated with the root diameter but the tensile strength was negatively correlated under monotonic and cyclic loading of the three plants' taproots. However, after cyclic loading, the three plant species' taproots significantly enhanced the tensile force and strength more than monotonic loading (P < 0.05). The taproot force-displacement hysteresis curves of the three plant species revealed obvious cyclic characteristics. Structural equation modeling analysis revealed that root diameter and damage method directly affected the taproots' survival rate, reflecting their sustainable soil reinforcement capacity. The damage method significantly influenced the soil reinforcement more than the root diameter. Our findings reveal that the plant species' taproots can adapt more to the external environment and enhance their resistance to erosion after natural low perimeter erosion damage, effectively inducing soil reinforcement. Particularly, the taproots of Caragana microphylla have superior soil-fixing ability and can be used for ecological restoration.

Transcatheter arterial chemoembolisation combined with lenvatinib plus camrelizumab as conversion therapy for unresectable hepatocellular carcinoma: a single-arm, multicentre, prospective study.

Background: The synergistic effect of locoregional therapy in combination with systemic therapy as a conversion therapy for unresectable hepatocellular carcinoma (uHCC) is unclear. The purpose of this study was to evaluate the efficacy and safety of transcatheter arterial chemoembolisation (TACE) combined with lenvatinib and camrelizumab (TACE + LEN + CAM) as conversion therapy for uHCC. Methods: This single-arm, multicentre, prospective study was conducted at nine hospitals in China. Patients (aged 18-75 years) diagnosed with uHCC, an Eastern Cooperative Oncology Group performance score (ECOG-PS) of 0-1 and Child-Pugh class A received camrelizumab (200 mg, every 3 weeks) and lenvatinib (bodyweight ≥60 kg: 12 mg/day; <60 kg: 8 mg/day) after TACE treatment. Surgery was performed after tumour was assessed as meeting the criteria for resection. Patients who did not meet the criteria for surgery continued to receive triple therapy until disease progression or intolerable toxicity. Primary endpoints were objective response rate (ORR) according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and safety. Secondary endpoints included the surgical conversion rate, radical (R0) resection rate, and disease control rate (DCR). This study was registered with Chinese Clinical Trial Registry (ChiCTR2100050410). Findings: Between Oct 25, 2021, and July 20, 2022, 55 patients were enrolled. As of the data cutoff on June 1, 2023, the median follow-up was 13.3 months (IQR 10.6-15.9 months). The best tumour response to triple therapy was complete response (CR) in 9 (16.4%) patients, partial response (PR) in 33 (60.0%) patients, stable disease (SD) in 5 (9.1%) patients, or progressive disease (PD) in 7 (12.7%) patients. The ORR was 76.4% (42/55, 95% CI, 65.2-87.6%), and the DCR was 85.5% (47/55, 95% CI, 76.2-94.8%) per mRECIST. Twenty-four (43.6%) of the 55 patients suffered from grade 3-4 treatment-related adverse events (TRAEs). No grade 5 TRAEs occurred. A total of 30 (30/55, 54.5%) patients were converted to resectable HCC and 29 (29/55, 52.7%) patients underwent resection. The R0 resection rate was 96.6% (28/29). The major pathologic response (MPR) and pathologic complete response (pCR) rates in the surgery population were 65.5% (19/29) and 20.7% (6/29), respectively. Only one patient developed a Clavien-Dindo IIIa complication (abdominal infection). No Clavien-Dindo IIIb-V complications occurred. The median OS and median PFS were not reached. Interpretation: The triple therapy (TACE + LEN + CAM) is promising active for uHCC with a manageable safety. Moreover, triple therapy has good conversion efficiency and the surgery after conversion therapy is feasible and safe. To elucidate whether patients with uHCC accepting surgical treatment after the triple therapy can achieve better survival benefits than those who receive triple therapy only, well-designed randomised controlled trials are needed. Funding: This study was funded by the Natural Science Foundation of Fujian Province, China (2022J01691) and the Youth Foundation of Fujian Province Health Science and Technology Project, China (2022QNA035).

The TAE score predicts prognosis of unresectable HCC patients treated with TACE plus lenvatinib with PD-1 inhibitors.

BACKGROUND AND AIMS: Transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) exhibits promising efficacy for unresectable hepatocellular carcinoma (uHCC). We aimed to evaluate the prognosis of patients with uHCC who received triple therapy and develop a prognostic scoring model to identify patients who benefit the most from triple therapy. METHODS: A total of 246 patients with uHCC who received triple therapy at eight centers were included and assigned to the training and validation cohorts. Prognosis was evaluated by the Kaplan-Meier curves. The prognostic model was developed by utilizing predictors of overall survival (OS), which were identified through the Cox proportional hazards model. RESULTS: In the training cohort, the 3-year OS was 52.0%, with a corresponding progression-free survival (PFS) of 30.6%. The median PFS was 13.2 months [95% confidence interval, 9.7-16.7]. Three variables (total bilirubin ≥ 17 µmol/L, alpha-fetoprotein ≥ 400 ng/mL, and extrahepatic metastasis) were predictors of poor survival and were used for developing a prognostic model (TAE score). The 2-year OS rates in the favorable (0 points), intermediate (1 point), and dismal groups (2-3 points) were 96.9%, 61.4%, and 11.4%, respectively (p < 0.001). The PFS was also stratified according to the TAE score. These findings were confirmed in an external validation cohort. CONCLUSIONS: Triple therapy showed encouraging clinical outcomes, and the TAE score aids in identifying patients who would benefit the most from triple therapy.

Short-term and long-term outcomes after robotic versus open hepatectomy in patients with large hepatocellular carcinoma: a multicenter study.

BACKGROUND: Robotic hepatectomy (RH) is currently widely accepted and it is associated with some benefits when compared to open hepatectomy (OH). However, whether such benefits can still be achieved for patients with large hepatocellular carcinoma (HCC) remain unclear. This study aimed to evaluate the short-term and long-term outcomes of patients undergoing RH or OH. METHODS: Perioperative and survival data from patients with large HCC who underwent RH or OH between January 2010 and December 2020 were collected from eight centres. Propensity score matching (PSM) was performed to minimise potential biases. RESULTS: Using predefined inclusion criteria, 797 patients who underwent OH and 309 patients who underwent RH were enroled in this study. After PSM, 280 patients in the robotic group had shorter operative time (median 181 vs. 201 min, P <0.001), lower estimated blood loss (median 200 vs. 400 ml, P <0.001), and shorter postoperative length of stay (median 6 vs. 9 days, P <0.001) than 465 patients in the open group. There were no significant differences between the two groups in overall survival and recurrence-free survival. Cox analysis showed AFP greater than 400 ng/ml, tumour size greater than 10 cm, and microvascular invasion were independent risk factors for overall survival and recurrence-free survival. After PSM, subgroup analysis showed that patients with a huge HCC (diameter >10 cm) who underwent RH had significantly lower estimated blood loss (median 200.0 vs. 500.0 min, P <0.001), and shorter length of stay (median 7 vs. 10 days, P <0.001) than those who underwent OH. CONCLUSION: Safety and feasibility of RH and OH for patients with large HCC were comparable. RH resulted in similar long-term survival outcomes as OH.

Clinical Complete Response After Conversion Therapy for Unresectable Hepatocellular Carcinoma: Is Salvage Hepatectomy Necessary?

Background: This study aimed to determine whether salvage hepatectomy offers prognostic advantages for unresectable hepatocellular carcinoma (uHCC) patients with clinical complete response (cCR) after conversion therapy. Methods: A total of 74 consecutive uHCC patients with cCR after conversion therapy at seven major cancer centers in China between October 2018 and December 2021 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Disease-free survival (DFS) and overall survival (OS) rates were compared between the surgical group and the non-surgical group. Results: Before PSM, 45 patients received salvage hepatectomy, and 29 patients received nonsurgical treatment. The 1-, 2-, and 3-year DFS rates were 77.8%, 61.5%, and 61.5% in the surgical group and 81.2%, 60.9%, and 60.9% in the non-surgical group, respectively. The 1-, 2-, and 3-year OS rates were 92.9%, 92.9%, and 69.7% in the surgical group and 100%, 70%, and 70% in the non-surgical group, respectively. There were no statistical differences in DFS and OS between groups [hazard ratio (HR)=0.715, 95% confidence interval (CI): 0.250-2.043, p=0.531; HR=0.980, 95% CI: 0.177-5.418, p=0.982, respectively]. After PSM, 26 pairs of patents were selected; there remained no significant differences in DFS and OS between these two groups (HR=1.547, 95% CI: 0.512-4.669, p=0.439; HR=1.024, 95% CI: 0.168-6.242, p=0.979, respectively). Conclusion: Through the study, it tend to show that salvage hepatectomy may be not essential for uHCC patients with cCR, especially for patients with a high risk of surgical complications. Prospective trials with long term follow-up are warranted to evaluate this treatment option.

Surgical outcomes of hepatocellular carcinoma with extrahepatic bile duct tumor thrombus: a multicenter study.

Background: The long-term prognosis after surgery of patients with hepatocellular carcinoma (HCC) and extrahepatic bile duct tumor thrombus (Ex-BDTT) remains unknown. We aimed to identify the surgical outcomes of patients with HCC and Ex-BDTT. Methods: A total of 138 patients with Ex-BDTT who underwent hepatectomy with preservation of the extrahepatic bile duct from five large hospitals in China between January 2009 and December 2017 were included. The Cox proportional hazards model was used to analyze overall survival (OS) and recurrence-free survival (RFS). Results: With a median follow-up of 60 months (range, 1-127.8 months), the median OS and RFS of the patients were 28.6 and 8.9 months, respectively. The 1-, 3-, and 5-year OS rates of HCC patients with Ex-BDTT were 71.7%, 41.2%, and 33.5%, respectively, and the corresponding RFS rates were 43.5%, 21.7%, and 20.0%, respectively. Multivariate analysis identified that major hepatectomy, R0 resection, and major vascular invasion were independent prognostic factors for OS and RFS. In addition, preoperative serum total bilirubin ≥ 4.2 mg/dL was an independent prognostic factor for RFS. Conclusion: Major hepatectomy with preservation of the extrahepatic bile duct can provide favorable long-term survival for HCC patients with Ex-BDTT.

Transarterial Chemoembolization Plus Lenvatinib and PD-1 Inhibitors for Hepatocellular Carcinoma with Main Trunk Portal Vein Tumor Thrombus: A Multicenter Retrospective Study.

Purpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4). Patients and Methods: This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan-Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: Median follow-up duration was 18 (4.0-26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8-30.5) months, whereas the median PFS was 14.5 (range, 1.3-27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred. Conclusion: TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.

Early Tumor Marker Response Predicts Treatment Outcomes in Patients with Unresectable Hepatocellular Carcinoma Receiving Combined Lenvatinib, Immune Checkpoint Inhibitors, and Transcatheter Arterial Chemoembolization Therapy.

Purpose: Few reliable biomarkers for predicting the efficacy of triple therapy (lenvatinib + immune checkpoint inhibitors + transarterial chemoembolization) exist for patients with unresectable hepatocellular carcinoma (uHCC). This study explored the prognostic role of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels in patients with uHCC receiving triple therapy. Patients and Methods: This retrospective study included 93 patients with uHCC who received triple therapy at Fujian Provincial Hospital between August 2020 and November 2022. Depending on the respective baseline levels, the patients were divided into high-AFP and high-DCP groups. An early response was defined as an AFP or DCP concentration >50% less than the baseline concentration after 6 weeks of triple therapy. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: After 6 weeks of triple therapy, 75.3% (58/77) and 78.9% (60/76) of patients in the high-AFP and high-DCP groups achieved an objective response. Early AFP and DCP responses were positively associated with ORR (high-AFP group: odds ratio [OR]: 13.542; 95% confidence interval [CI]: 3.991-45.950, p<0.001; high-DCP group: OR: 17.853; 95% CI: 4.478-71.179, p<0.001). In the high-AFP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the AFP responders than those in the non-responders (PFS: 66.4%, 59.6%, 48.2% vs 42.3%, 19.3%, 0%, p<0.001; OS: 94.5%, 90.4%, 77.3% vs 75.6%, 66.2%, 49.6%, p=0.006). In the high-DCP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the DCP responders than those in the non-responders (PFS: 67.4%, 57.7%, 39.0% vs 38.9%, 8.1%, 0%, p<0.001; OS: 94.7%, 94.7%, 83.3% vs 77.0%, 53.9%, 36.0%, p<0.001). Conclusion: After 6 weeks of triple therapy, an AFP or DCP reduction of >50% predicts better treatment outcomes in uHCC patients.

Outcomes of Salvage Surgery for Initially Unresectable Hepatocellular Carcinoma Converted by Transcatheter Arterial Chemoembolization Combined with Lenvatinib plus Anti-PD-1 Antibodies: A Multicenter Retrospective Study.

Introduction: The actual rate of conversion surgery and its prognostic advantages remain unclear. This study aimed to assess the outcomes of salvage surgery after conversion therapy with triple therapy (transcatheter arterial chemoembolization [TACE] combined with lenvatinib plus anti-PD-1 antibodies) in patients with initially unresectable hepatocellular carcinoma (uHCC). Methods: Patients with initially uHCC who received at least one cycle of first-line triple therapy and salvage surgery at five major cancer centers in China were included. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) rates after salvage surgery. The secondary endpoints were perioperative complications, 90-day mortality, and pathological tumor response. Results: Between June 2018 and December 2021, 70 patients diagnosed with uHCC who underwent triple therapy and salvage surgery were analyzed: 39 with Barcelona Clinic Liver Cancer (BCLC) stage C, 22 with BCLC stage B, and 9 with BCLC stage A disease. The median interval between the start of triple therapy and salvage surgery was 4.3 months (range, 1.7-14.2 months). Pathological complete response and major pathological response were observed in 29 (41.4%) and 59 (84.3%) patients, respectively. There were 2 cases of perioperative mortality (4.3%) and 5 cases of severe perioperative complications (7.1%). With a median follow-up of 12.9 months after surgery (range, 0.3-36.8 months), the median OS and RFS were not reached. The 1- and 2-year OS rates were 97.1% and 94.4%, respectively, and the corresponding RFS rates were 68.9% and 54.4%, respectively. Conclusion: First-line combination of TACE, lenvatinib, and anti-PD-1 antibodies provides a better chance of conversion therapy in patients with initially uHCC. Furthermore, salvage surgery after conversion therapy is effective and safe and has the potential to provide excellent long-term survival benefits.

Effect of different PD-1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma.

BACKGROUND: Immune checkpoint inhibitor (ICI) combination therapy offers a new option for treatment of unresectable intrahepatic cholangiocarcinoma (uICC). AIM: To compare the effect of different anti-PD-1 combination therapies as the first-line treatments for uICC. METHODS: This study included 318 patients who received chemotherapy alone (Chemo), anti-PD-1 plus chemotherapy (ICI-chemo), anti-PD-1 plus targeted therapy (ICI-target) or anti-PD-1 plus targeted therapy and chemotherapy (ICI-target-chemo) as first line for uICC from 22 centres in China. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. RESULTS: Patients with ICI-chemo (median PFS [mPFS], 6.3 months; HR: 0.61, 95% CI: 0.42-0.88; p = 0.008; median OS [mOS], 10.7 months; HR: 0.61, 95% CI: 0.39-0.94; p = 0.026), ICI-target (7.2 months; HR: 0.54, 95% CI: 0.36-0.80; p = 0.002; 15.8 months; HR: 0.54, 95% CI: 0.35-0.84; p = 0.006) or ICI-target-chemo (6.9 months; HR: 0.65, 95% CI: 0.47-0.90; p = 0.009; 14.4 months; HR: 0.47, 95% CI: 0.31-0.70; p < 0.001) achieved better clinical outcomes than those with Chemo (3.8 months; 9.3 months). ICI-target was not inferior to ICI-chemo in survival outcomes (HR for PFS: 0.88, 95% CI: 0.55-1.42; p = 0.614; HR for OS: 0.89, 95% CI: 0.51-1.55; p = 0.680). ICI-target-chemo yielded similar prognoses as ICI-chemo (HR for PFS: 1.07, 95% CI: 0.70-1.62; p = 0.764; HR for OS: 0.77, 95% CI: 0.45-1.31; p = 0.328) and ICI-target (HR for PFS: 1.20, 95% CI: 0.77-1.88; p = 0.413; HR for OS: 0.86, 95% CI: 0.51-1.47; p = 0.583) but resulted in more adverse events (p < 0.001; p = 0.010). Multivariable and propensity score analyses supported these findings. CONCLUSIONS: Among patients with uICC, ICI-chemo or ICI-target provided more survival benefits than Chemo while achieving comparable prognoses and fewer adverse events than ICI-target-chemo.