BACKGROUND Real-world data remain limited on the effectiveness of magnesium isoglycyrrhizinate (MgIG) for post hepatectomy liver injury. We hypothesize that perioperative MgIG is effective as a management strategy against hepatic injury in patients undergoing hepatectomy. AIM To evaluate the prophylactic and therapeutic effectiveness of MgIG for hepatic injury in patients undergoing hepatectomy in a real-world setting. METHODS We retrospectively reviewed the clinical data of consecutive Chinese patients who underwent hepatectomy between March 2020 and March 2023 at two tertiary care hospitals in China. The cohorts were balanced using propensity score matching (PSM). The primary outcome was the prevalence of postoperative liver injury, defined as >= 3 & times; upper limit of normal of the serum levels of alanine aminotransferase (ALT) or aspartate aminotransferase. RESULTS The rate of postoperative liver injury was 76.9% among 1711 eligible patients. After PSM, patients who received perioperative MgIG had a significantly greater reduction in the prevalence of liver injuries than those who only received postoperative MgIG on postoperative day (POD) 3 (53.3% vs 69.1%; P = 0.006) and POD 7 (14.2% vs 23.6%; P = 0.027). The proportions of patients with >= 50% reduction in ALT were significantly higher in patients treated with MgIG plus other liver protectants than those treated with other liver protectants on POD 3 and 7, and upon hospital discharge. Multivariable analysis indicated an independent protective role of prophylactic MgIG in postoperative liver injury. CONCLUSION This study indicates that the addition of preoperative prophylaxis to postoperative treatment with MgIG can mitigate of the rise of aminotransferases and enhance postoperative liver function recovery, conferring benefits on more surgical patients.

PURPOSE:Nonmetastatic tumor-draining lymph nodes (TDLNs-) are central to initiating and sustaining antitumor immunity. The impact of their surgical removal on immunotherapy efficacy in recurrent biliary tract cancer remains unclear. We investigated the effect of TDLNs- dissection extent on treatment outcomes in this population. EXPERIMENTAL DESIGN:This real-world study retrospectively analyzed clinical and survival data from 101 patients with recurrent biliary tract cancer who received immunotherapy across five Chinese hospitals (2018-2023). Patients were stratified by extent of TDLNs- dissection (≤6 vs. >6). Multiplex immunofluorescence (mIF) analysis of lymph node immune microenvironments was performed in a representative subset of patients (n = 20) from Sun Yat-sen Memorial Hospital. RESULTS:Patients with ≤6 TDLNs- dissected (n = 59) achieved significantly longer progression-free survival (PFS) than those with >6 dissected (n = 42; HR, 0.48; 95% confidence interval, 0.31-0.73; P = 0.001), although there was no statistical difference in overall survival. The mIF staining analysis revealed that TDLNs- contained higher densities of TCF-1+PD-1-CD8+ tumor-specific memory T cells and CD11c+ conventional dendritic cells and lower proportions of FOXP3+CD4+ regulatory T cells and TCF-1-PD-1+CD69+CD8+ terminally exhausted T cells compared with metastatic TDLNs (TDLNs+). Among immunotherapy responders, TDLNs- exhibited greater TCF-1+PD-1-CD8+ T-cell and CD11c+ cell densities than those in nonresponders. Importantly, a higher proportion of TCF-1+PD-1-CD8+ T cells in TDLNs- correlated with improved PFS, whereas extensive dissection of TDLNs- diminished this benefit. CONCLUSIONS:Excessive removal of TDLNs- compromises the efficacy of immunotherapy in recurrent biliary tract cancer. A selective lymphadenectomy approach that prioritizes clearance of TDLNs+ while preserving TDLNs- may optimize outcomes for patients receiving postoperative immunotherapy. See related commentary by Vonderheide, p. 2326.

e16171 Background: Triple therapy combining transarterial therapy, tyrosine kinase inhibitors (TKIs), and programmed death-1 (PD-1) inhibitors represents a promising therapeutic strategy for unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the efficacy and safety of transarterial therapy combined with donafenib (a TKI) and PD-1 inhibitors as first-line treatment in a real-world uHCC cohort. Methods: This was a multicenter, retrospective study conducted across five medical centers in China. We analyzed patients diagnosed with uHCC who had received at least one cycle of triple combination therapy comprising transarterial therapy (hepatic arterial infusion chemotherapy [HAIC] and/or transarterial chemoembolization [TACE]), donafenib, and PD-1 inhibitors. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), surgical conversion rate, and safety. Tumor responses were assessed according to both the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1. Results: After screening, 70 patients were included in the analysis. Key baseline characteristics were as follows: median age 55 years; 92.9% male; 87.1% with HBV infection; 60.0% at BCLC stage C. Additionally, 48.6% of patients had macrovascular invasion, 22.9% had extrahepatic metastasis, and 74.2% presented with multiple tumors, with a median maximum tumor diameter of 86.5 mm. The PD-1 inhibitors administered included tislelizumab (41.4%), camrelizumab (37.1%), sintilimab (18.6%), toripalimab (2.9%). Transarterial therapy regimens consisted of TACE plus HAIC (38.6%), HAIC alone (34.3%), and TACE alone (27.1%). After a median follow-up of 27.5 months, the median PFS was 12.7 months (95% CI, 8.4-23.8) per both mRECIST and RECIST v1.1. The median OS was 29.3 months (95% CI, 22.4-NA) with 12- and 24-month OS rates of 81.7% and 57.2%, respectively. The ORR was 67.1% per mRECIST and 52.9% per RECIST v1.1, and the DCR was 87.1% by both criteria. The surgical conversion rate was 22.9%. Treatment-related adverse events (TRAEs) occurred in 87.1% of patients, with grade 3-4 events in 37.1%. The most common TRAEs included liver dysfunction (51.4%), hand-foot skin reaction (47.1%), decreased platelet count (18.6%), and decreased white blood cell count (17.1%). Conclusions: This real-world study demonstrates that transarterial therapy combined with donafenib and PD-1 inhibitors provides encouraging survival outcomes and a manageable safety profile for uHCC patients. Clinical trial information: ChiCTR2200063822.

Pancreaticobiliary maljunction (PBM) is a recognized congenital risk factor for gallbladder cancer (GBC), but its prognostic significance after GBC diagnosis remains unclear. This single-center retrospective cohort study included 229 patients with pathologically confirmed GBC treated between 2015 and 2025, comprising 75 with PBM and 154 with non-PBM (NPBM). The primary analysis was predefined in the surgery without hepaticojejunostomy (HJ) group to assess the prognostic association of PBM under a relatively homogeneous surgical strategy, with secondary analyses among all surgically resected patients and palliative/nonsurgical patients. Overlap weighting was used to improve baseline comparability, and survival outcomes were evaluated using complementary Cox regression models. Patients with PBM were younger and less likely to have cholelithiasis than patients with NPBM. PBM tumors more frequently showed high Ki-67 expression and aberrant p53 immunostaining patterns. PBM was associated with worse overall survival (OS) in the palliative/nonsurgical group (hazard ratio [HR] 3.10, 95

Representativeness of study participants.

Background: Immunotherapy has revolutionized hepatocellular carcinoma (HCC) treatment, increasingly being incorporated into various stages of treatment, including preoperative therapy. However, preoperative immunotherapy alters both physiological status and tumor biology, potentially impacting the perioperative risk. We aimed to explore the association between the implementation details of preoperative immunotherapy and perioperative risk. Methods: This study retrospectively enrolled HCC patients who received immune checkpoint inhibitor (ICI)-based immunotherapy prior to radical surgery. A comprehensive dataset encompassing baseline characteristics and immunotherapy-specific parameters was collected. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors, followed by validation through machine learning algorithms to evaluate the predictive performance of the derived determinants. Results: This multicenter retrospective study enrolled 303 HCC patients who received preoperative immunotherapy across 26 participating centers. Based on specified perioperative risk stratification criteria, 182 patients (60.07%) were stratified into the low-risk cohort, while 121 patients (39.93%) constituted the high-risk cohort. Multivariate logistic regression analysis identified several independent risk factors of elevated perioperative risk: ICI duration exceeding four cycles [odds ratio (OR), 2.00; 95% confidence interval (CI) 1.20-3.32]; the occurrence of grade >= 3 immune-related adverse events (irAEs) (OR, 2.36; 95% CI: 1.13-4.92); the presence of major vein thrombus (OR, 2.05; 95% CI: 1.25-3.38); multiple tumor nodules (OR, 1.74; 95% CI: 1.02-2.98); and maximal tumor diameter >5 cm (OR, 2.02; 95% CI: 1.10-3.73). Subgroup analyses consistently demonstrated these associations. Machine learning algorithms quantified feature importance for perioperative risk predictors, with extended ICIs duration (mean importance rank =2.88) and grade >= 3 irAEs (mean importance rank =2.38) emerging as top-ranked variables. Conclusions: This multicenter retrospective study reveals ICIs duration and high-grade irAEs were associated with elevated perioperative risk in HCC patients undergoing preoperative immunotherapy, providing actionable insights for optimizing perioperative management protocols.

Immunotherapy efficacy in patients with recurrent BTC.

e16297 Background: Patients (pts) in BCLC stage A/B HCC beyond Milan criteria have a high recurrence rate after radical surgery. However, the standardized perioperative treatment strategy has not been established. This study aimed to investigate to efficacy and safety of systemic chemotherapy with mFOLFOX7 regimen combined with camrelizumab (CAM, anti-PD-1 antibody) plus apatinib (APA, anti-angiogenesis) as conversion therapy for potentially resectable HCC. Methods: In this prospective, single arm, phase II study, treatment-naive adult pts with BCLC stage A/B HCC beyond Milan criteria (assessed by MDT as unsuitable for radical resection surgery) were included. The enrolled pts received CAM (200 mg, q3w), APA (250 mg, qd), and mFOLFOX7 (oxaliplatin 85 mg/m 2 , leucovorin 200 mg/m 2 , 5-fluorouracil bolus 400 mg/m 2 on day 1, and 5-fluorouracil infusion 2400 mg/m 2 for 46 hours; q3w; up to 6 cycles). The surgical feasibility of pts was evaluated every 2 cycles. Sequential therapy began 2 weeks after surgery. CAM and APA were given for up to 12 months or approximately 17 cycles. The primary endpoint was major pathological reactions (MPR), defined as viable tumor cells in less than 50% of tumor bed. Secondary endpoints were complete pathological reactions (pCR), objective response rate (ORR, by RECIST v1.1 and mRECIST), disease-free survival (DFS), overall survival (OS), and safety. Exploratory endpoint is presence of microvascular invasion (MVI), defined as postoperative histologically confirmed MVI. Results: At the data cut-off (Jan. 25, 2025), a total 14 patients were screened. Among these, 12 pts were enrolled (3 woman and 9 men; median age, 61.5 years; range, 38 - 73 years) and received neoadjuvant therapy. The median tumor size was 82.5 mm (range, 44 - 147). 12 pts had HBV infection and 3 (25%) pts had more than 1 tumors. With a median follow-up of 7.2 months (95% CI: 0.6 - 13.7), no progression or death event occurred. Out of 12 patients, 7(58.3%) were in follow-up/ finished treatment, while 5 (41.7%) patients were still receiving CAM plus APA. After a median of 3 (2-4) treatment cycles, 1 pts achieved PR but refused surgery, 11 pts underwent hepatic resection. R0 resection rate was 100%, 7 (63.6%) pts achieved MPR. Among pts with MVI, M0 was found in 81.8% (9/11) pts, M1 was found in 18.2% (2/11) pts. The most common AEs included increased alanine aminotransferase (58.3%), decreased neutrophil count (41.6%) and diarrhea (41.6%); and Grade 3-4 AEs occurred in 1 of 12 patients. None of them had Serious Adverse Drug Reactions (SADRs). Conclusions: Neoadjuvant mFOLFOX7 combined with Camrelizumab and Apatinib is effective and tolerable in pts with BCLC stage A/B HCC beyond Milan criteria. Preoperative neoadjuvant therapy has reduced the rate of MVI. More data would be further analyzed and reported. Clinical trial information: NCT06670107 .

e16202 Background: Immune checkpoint inhibitor combined with chemotherapy have shown improved prognosis compared with chemotherapy alone in patients with advanced intrahepatic cholangiocarcinoma (ICC). However, whether adding tyrosine kinase inhibitor (TKI) could further provide more survival benefits remains unclear. This study aims to evaluate the efficacy and safety of apatinib (a VEGFR2-targeted TKI) combined with adebrelimab (PD-L1 inhibitor) and GEMOX chemotherapy as first-line treatment for advanced ICC. Methods: This study (ACADEMY) enrolled adults aged ≤75 years with pathologically confirmed advanced ICC. All patients received apatinib (250 mg daily) combined with adebrelimab (1200 mg, day 1) and GEMOX chemotherapy (Gemcitabine 1000 mg/m 2 , day 1 and day 8; Oxaliplatin 85 mg/m 2 , day 1) per 21-day cycle. Tumor response was assessed using both RECIST 1.1 and mRECIST criteria. Survival outcomes were analyzed using Kaplan-Meier methods. The primary endpoint was objective response rate (ORR) accessed by RECIST 1.1 criteria. The secondary endpoints included progression free survival (PFS), overall survival (OS), disease control rate (DCR) and treatment-related adverse events (TRAEs). A Simon’s two -stage Optimum design was adopted in this study. If a response is observed in over 3 out of the initial 13 evaluated patients during the first phase, an additional 21 patients would be recruited for the study. Results: As of January 4, 2026, a total of 22 patients were recruited (median age 58.9 years; 59.1% female; 27.2% HBV-positive), with 19 included in efficacy analysis. Baseline characteristics: median tumor size 7.2 cm, median tumor number 3.5, 95.5% with TNM stage III-IV, 45.5% with macrovascular invasion. The ORR was 31.6% (RECIST 1.1) and 63.2% (mRECIST), and DCR was 100% (RECIST 1.1 and mRECIST criteria). With a median follow-up time of 7.9 months, the estimated median PFS was 6.2 months (95% CI: 5.4-NR), the 6-month OS rate was 100%, and the median OS was not reached. 21.1% (4/19) patients underwent radical surgical resection after tumor downstaging. In the respect of safety evaluation, TRAEs were observed in all enrolled patients, 50.0% with grade 3-4, and no grade 5 TRAE occurred. The most frequent AEs were hypoalbuminemia (68.2%), fatigue (59.1%) and liver damage (36.4%). Conclusions: Apatinib combined with adebrelimab and GEMOX regimen demonstrates promising efficacy and acceptable safety profile as first-line treatment for advanced ICC, supporting its potential as a preferred therapeutic option. Clinical trial information: NCT06925516 .

Many cases of hepatocellular carcinoma (HCC) are initially considered unresectable. Advances in conversion therapy have enabled some of these patients to subsequently undergo curative resection. However, an insufficient future liver remnant (FLR) prevents HCC patients with HCC undergoing conversion therapy from obtaining the opportunity for surgical resection. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been shown to be effective in promoting FLR hypertrophy in patients with HCC. Nevertheless, the safety and feasibility of ALPPS in patients with HCC who have an insufficient FLR after conversion therapy have rarely been reported. Here, we report the first case in which salvage robotic ALPPS enabled a patient with HCC and insufficient FLR after conversion therapy to undergo radical resection. This 56-year-old man was diagnosed with initially unresectable HCC and received five cycles of lenvatinib plus pembrolizumab. Although a partial response was achieved on oncological evaluation, the patient was not eligible for surgical resection because the FLR remained insufficient at 35.5% of the standard liver volume. To promote FLR hypertrophy and achieve radical resection, we performed a two-stage robotic ALPPS after the fifth cycle of systemic therapy. The FLR increased from 35.5% to 49.4% 1 month after the first stage of ALPPS (robotic cholecystectomy, right portal vein ligation, and liver partition), and subsequent robotic right hemihepatectomy was successfully performed. The patient recovered uneventfully after the two-stage procedure, and no recurrence was observed at the 3-month postoperative follow-up. This case demonstrates that total robotic ALPPS is a feasible bridge to curative resection for selected patients with insufficient FLR after successful conversion therapy. Building upon the concept of salvage ALPPS, this report further highlights the technical advantages of a total robotic platform in facilitating precise, minimally invasive staged hepatectomy.

Proportional hazards assumptions checked by schoenfeld residuals.

Baseline characteristics of the entire cohort.

Bootstrap distribution of the optimal cutoff value for dissected TDLNs−.

BACKGROUND:Lenvatinib is utilized as a first-line therapy for hepatocellular carcinoma (HCC); however, the emergence of resistance significantly impairs its clinical efficacy. Ferroptosis, a newly recognized form of cell death, has been implicated in tumor progression and treatment resistance. This study investigates the interaction between ferroptosis and lenvatinib resistance in HCC and explores the underlying mechanisms. METHODS:A lenvatinib-resistant cell line was established, combined with multiplex transcriptome sequencing and external bioinformatics analysis to identify key resistance genes. The biological functions of lenvatinib resistance were validated through assays of cell viability, colony formation, apoptosis, and xenograft models. Ferroptosis effects were analyzed using assays such as transmission electron microscopy (TEM), C11-BODIPY staining, malondialdehyde (MDA) measurement, and Fe2+ detection. Furthermore, KEGG pathway enrichment analysis, Western blotting, immunofluorescence colocalization, and immunohistochemistry were conducted to explore the underlying mechanisms. RESULTS:Transcriptome sequencing combined with in vitro and in vivo experiments revealed that AKR1B10 was significantly downregulated following short-term lenvatinib treatment, but was upregulated with the induction of resistance. Knockdown of AKR1B10 markedly reversed acquired resistance to lenvatinib. Furthermore, we found that the upregulation of AKR1B10 substantially inhibited lenvatinib-induced ferroptosis. Mechanistically, the NQO1/GPX4 axis was identified as the downstream signaling pathway through which AKR1B10 regulates ferroptosis. Notably, overexpression of NQO1 effectively restored both ferroptosis and sensitization to lenvatinib induced by AKR1B10 knockdown. CONCLUSIONS:This study reveals that AKR1B10 inhibits ferroptosis in HCC through the NQO1/GPX4 axis, promoting acquired resistance to lenvatinib. These findings suggest that AKR1B10 could be a novel therapeutic target for overcoming lenvatinib resistance.

BACKGROUND:Hepatocellular carcinoma with portal vein tumor thrombus (HCC-PVTT) is correlated with poor prognosis.1 Recent advances in first-line therapies have enabled some patients with HCC-PVTT to become candidates for curative resection.2,3 However, over 50% of patients experience disease progression during initial treatment,4 and subsequent second-line options remain limited. Furthermore, reports on radical resection in patients with HCC-PVTT after second-line therapy are scarce. Herein, this case highlights the successful downstaging of HCC-PVTT with second-line therapy, followed by laparoscopic hepatectomy and portal vein thrombectomy. METHODS:A 56-year-old patient with HCC-PVTT involving the main and left portal veins initially received camrelizumab, apatinib, and systemic FOLFOX (oxaliplatin, fluorouracil, leucovorin).5 After 3 cycles, the PVTT progressed to the right portal vein. The multidisciplinary team recommended switching to second-line therapy with regorafenib, adebrelimab, and hepatic arterial infusion chemotherapy. RESULTS:The patient experienced progression after first-line therapy (tumor enlargement, PVTT extension), and second-line therapy achieved notable shrinkage of both the tumor and the PVTT. After 5 cycles, surgical resection was feasible. Laparoscopic extended left hepatectomy with portal vein thrombectomy was completed in 340 minutes, with 100 mL blood loss. Pathology revealed HCC with extensive necrosis. Postoperative regorafenib and adebrelimab was administered for 3 cycles, and the patient remains recurrence free to date. CONCLUSION:This case report highlights that, for patients with HCC-PVTT with first-line therapy resistance, actively applying second-line therapy can still yield an opportunity for radical resection. It also suggests the feasibility of laparoscopic extended hepatectomy with thrombectomy, emphasizing the value of individualized, multidisciplinary strategies for improving outcomes in complex HCC cases.

TPS4257 Background: The combination of camrelizumab (an anti-PD-1 IgG4 monoclonal antibody) and rivoceranib (a VEGFR2-TKI) is a standard of care, first-line (1L) therapy for advanced hepatocellular carcinoma (HCC). However, immune therapy resistance leads to ineffective initial treatment and difficulty in maintaining long-term efficacy in some patients. Several studies have shown that oxaliplatin and fluorouracil can induce immunogenic cell death in tumor cells and induce antitumor immune response in the body. Intravenous FOLFOX chemotherapy may regulate the liver tumor microenvironment and improve clinical benefit, a hypothesis supported by positive efficacy signals in the Phase II VIC-TRIPLETS study (NCT05412589). Here we present the design of a phase III randomized controlled study. Methods: This investigator-initiated, phase III, randomized, open-label, multicenter trial (NCT06280508) aims to compare the efficacy and safety of camrelizumab and rivoceranib combined with (CAREFOL) or without intravenous FOLFOX chemotherapy (CARE) as first-line treatment for unresectable HCC. Eligible patients are aged at least 18 years, with unresectable or metastatic HCC, no previous systemic treatment, with BCLC stage B or C disease (which is not amenable to or had progressed after surgical or locoregional therapy), at least one measurable lesion per RECIST 1.1 criteria, Child-Pugh class A liver function, an ECOG performance status of 0 or 1, and adequate organ function. Approximately 326 Participants will be randomly assigned (1:1) using a centralized interactive response system. Randomization is stratified by presence of extrahepatic metastasis (yes vs no), macrovascular invasion (Vp0-3 vs Vp4), and baseline α-fetoprotein level ( < 400 ng/mL vs ≥400 ng/mL). The experimental group consisted of camrelizumab 200 mg intravenously every 3 weeks plus rivoceranib 250 mg orally once daily combined with 21-day cycles of intravenous FOLFOX chemotherapy (oxaliplatin 85 mg/m 2 , levofolinate 200 mg/m 2 , 5-fluorouracil bolus 400 mg/m 2 on day 1, and 5-fluorouracil infusion 2400 mg/m 2 for 46 hours; up to 6 cycles). The control group is camrelizumab plus rivoceranib (same as experimental group). The dual primary endpoints are investigator-assessed progression-free survival per RECIST v1.1 and overall survival. Secondary endpoints include objective response rate, disease control rate, duration of response, surgical conversion rate, time-to-treatment failure, safety. The trial is currently screening eligible patients. Clinical trial information: NCT07267806 .

Reagents and antibodies used in the study.

4118 Background: China bears a high biliary tract cancer (BTC) burden, with cholangiocarcinoma rising incidence ( > 6/100,000 vs 0.3–6/100,000 globally) and high mortality ( > 4/100,000). Over 60% of BTC patients are diagnosed at advanced stage (stage III/IV), and nearly two-thirds are unresectable. GEMOX regimen is a widely recognized standard of care in China, favored for its reduced renal toxicity and better tolerability compared with GemCis. Envafolimab is the world's first subcutaneously (SC) injectable anti-PD-L1 monoclonal antibody approved by China's NMPA. We report the final analysis of this pivotal trial, the first global phase III study initiated to evaluate immunotherapy plus chemotherapy in this setting. Methods: In this multicenter, open-label, phase III study in China, eligible patients (pts) with previously untreated, unresectable locally advanced/metastatic BTC were randomized 1:1 to envafolimab (2.5 mg/kg SC weekly) + GEMOX (gemcitabine 1000 mg/m² d1, 8; oxaliplatin 85 mg/m² d1, Q3W) or GEMOX chemotherapy alone. Chemotherapy was limited to 6 cycles in both arms. Stratification factors: primary site, disease stage, prior therapy, and ECOG PS. Primary endpoint: OS. Secondary endpoints: PFS, ORR (RECIST v1.1 by BICR), and safety. Results: 472 pts were randomized; 462 treated (envafolimab+GEMOX n = 232; GEMOX n = 230). At the final analysis, the primary endpoint was met well. Envafolimab+GEMOX significantly improved OS vs GEMOX (HR 0.723; 95% CI 0.585–0.880; P = 0.0016). Median OS was 10.9 months vs 8.6 months; 36-mo OS rates were 12.5% vs 7.7%. OS benefit was observed across subgroups, notably in intrahepatic cholangiocarcinoma (HR 0.705) and metastatic disease (HR 0.704). Median PFS (BICR) was 4.8 vs 4.6 months (HR 0.899; 95% CI 0.713–1.132); notably, the gallbladder cancer subgroup showed more favorable PFS benefit (HR 0.628). ORR was 27.6% vs 20.9%. Grade 3–4 TEAEs occurred in 69.4% (combination) vs 56.1% (chemo). irAEs occurred in 20.7%. Conclusions: This study demonstrates that adding subcutaneously administered envafolimab to GEMOX significantly improves OS with a manageable safety profile in advanced BTC. Compared with other regimens, the combination showed robust efficacy with a low rate of irAEs. Those findings establish envafolimab, the world's first SC PD-L1 inhibitor, combined with GEMOX as a new, effective, and convenient standard of care for this population. Clinical trial information: NCT03478488 .

Validation of the prognostic threshold for TDLNs− and assessment of the model robustness.