ABSTRACT
BACKGROUND: This study aims to analyze the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) blockade plus chemotherapy in real-world applications. Additionally, we report survival outcomes with a median follow-up of 40.1 months. METHODS: From January 2018 to October 2022, we retrospectively recruited patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after receiving PD-1 blockade (immunotherapy) plus chemotherapy at Jiangsu Cancer Hospital. RESULTS: A total of 132 eligible ESCC patients were included, and R0 resection was achieved in 131 cases (99.2 %). A complete pathological response rate (ypT0N0) was observed in 32 patients (24.2 %), and the objective response rate was 59.1 %. The most common grade 3-4 treatment-related adverse events (TRAEs) were leukopenia (18.2 %) and neutropenia (15.9 %). Three cases (2.3 %) of grade 3 immune-related AEs were observed, including increased ALT (0.8 %), rash (0.8 %), and encephalitis (0.8 %). The 1-year disease-free survival (DFS) and overall survival (OS) rates were 68.2 % and 89.4 %, respectively, and the 2-year DFS and OS rates were 55.1 % and 78.6 %, respectively. The pathological responses of 103 cases (94.5 % of 109) of the index lymph node (ILN) were categorized as the worst regression subgroup. In these cases, using the pathological response of the ILN to indicate the status of other lymph nodes would not result to a missed therapeutic lymph node dissection. CONCLUSIONS: Neoadjuvant immunotherapy plus chemotherapy is safe and effective for ESCC, with observable survival benefits. The pathological response of the ILN after neoadjuvant therapy may have important value in guiding therapeutic lymph node dissection.
ABSTRACT
BACKGROUND: The triple combination of hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitors (ICIs) is expected to have a synergistic anticancer effect in HCC. We conducted this meta-analysis to evaluate the efficacy and safety of the triple combination treatment in advanced HCC patients. METHODS: PubMed, Embase, Cochrane Library, Web of Science databases were systematically searched for relevant studies from the inception of each database to May 10, 2023. All articles focusing the triple combination treatment of HAIC-FO plus TKI and ICIs for advanced HCC were eligible. The meta-analysis was conducted following the PRISMA guidelines. The risk of bias was assessed using the Joanna Briggs Institute (JBI) for case series and Newcastle-Ottawa Scale (NOS) for cohort studies. The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). The secondary results were adverse events. Further meta-analysis of control studies demonstrated the superiority of the triple combination modality to TKI plus ICIs, and TKI alone. RESULTS: Nine articles (four cohort studies and five one-arm studies) involving 777 advanced HCC patients were included in this meta-analysis. In terms of survival analysis, the pooled median PFS was 11 months (95% CI: 10.1-12.0 months) with low heterogeneity (I2 = 0%, p = 0.97). With regard to tumor response, the pooled ORR and DCR was 61.6% (I2=0%, p = 0.71) and 87.9% (I2 = 13%, p = 0.33) with low heterogeneity, respectively. As compared with TKIs plus ICIs, and TKIs alone, the triple combination thrapy was associated with improved median OS (HR=0.51, 95%CI 0.41-0.62) with low heterogeneity across studies (I2 = 0%, p = 0.47), median PFS (HR=0.51, 95%CI 0.41-0.64) with low heterogeneity across studies (I2 = 0%, p = 0.41), ORR (RR = 0.56, 95% CI: 0.42-0.74) with high heterogeneity across studies (I2 = 69%, p = 0.02), and DCR (RR = 0.38, 95%CI 0.27-0.54) with low heterogeneity across studies (I2 = 14%, p = 0.32). The most common 3/4 AEs were elevated ALT and AST, thrombocytopenia, hypertension, nausea and vomiting in this meta-analysis. CONCLUSIONS: The triple combination therapy of HAIC-FO plus TKI and ICIs showed promising efficacy and safety in patients with advanced HCC. REGISTRATION: The protocol was registered with PROSPERO (ID:CRD42023424281).
Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Antineoplastic Agents/therapeutic use , Immune Checkpoint Inhibitors/therapeutic use , Liver Neoplasms/pathology , Protein Kinase Inhibitors/therapeutic useABSTRACT
Objective: The aim of this study is to investigate the feasibility and effectiveness of endovascular brachytherapy with iodine-125 (I-125) seed strand for the treatment of extensive portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients. Methods: A total of 40 HCC patients complicated by extensive PVTT who received I-125 seed strand implantation from January 2015 to December 2022 in our center were analyzed retrospectively. Endpoints included technical success rate, concurrent therapies, overall survival time, and complications. Multivariate and subgroup analyses were conducted for overall survival. Results: The successful rate of operation was 100%, and there was no operation-related death. A total of 37 patients received single I-125 seed strand implantation, and three patients received double I-125 seed strand implantation. A total of 23 patients received a concurrent therapy: transarterial chemoembolization (TACE) combined with systematic treatment (n = 6), TACE alone (n = 10), and systematic treatment alone (n = 9). At a median follow-up of 3.5 (interquartile range (IQR), 2~8.5) months, the median overall survival (OS) of all patients was 92 days (95% confidence interval (CI): 77~108). In the subgroup analysis, the median OS was 128 days (95% CI: 101~155 days) in the I-125 seed strand implantation plus systematic treatment group and was longer than that (75 days (95% CI: 36~114) of the I-125 seed strand alone group (p = 0.037). Multivariate analysis revealed that no systematic treatment was an independent risk factor affecting the prognosis in this study. Six patients died of upper gastrointestinal bleeding: four patients in the I-125 seed strand alone group and two patients in the combination of I-125 seed strand with systematic treatment group. Conclusions: The study shows that endovascular brachytherapy with I-125 seed strand implantation is a safe and effective treatment method for extensive PVTT in HCC patients. The combination of I-125 seed strand implantation and systematic treatment can prolong the survival time.
