Adjuvant immune checkpoint inhibitors associated with higher recurrence-free survival in postoperative hepatocellular carcinoma (PREVENT): a prospective, multicentric cohort study.

BACKGROUND: Adjuvant therapy may improve survival of patients with hepatocellular carcinoma (HCC) after curative resection. This study compared safety and efficacy outcomes between patients at high risk of recurrence who received different types of adjuvant therapy or no such therapy after hepatic resection for HCC. METHODS: Recurrence-free survival (RFS), overall survival, and adverse events were compared among patients who received adjuvant immune checkpoint inhibitors (ICIs) alone, ICIs with tyrosine kinase inhibitors (TKIs), or no adjuvant therapy between 13 March 2019 and 19 March 2022. This study was registered on ClinicalTrials.gov (NCT05221398). RESULTS: Of the 517 patients in final analysis, 432 (83.6%) received no adjuvant therapy, 53 (10.2%) received ICIs alone, and 32 (6.2%) received adjuvant ICIs and TKIs. During median follow-up of 34.0 months (IQR 27.8 to 41.6 months), RFS was significantly longer among patients who received either type of adjuvant therapy (25.2 months, 95%CI 16.4-34.0) than among those who received none (16.1 months, 95%CI 12.9-19.4), and this difference remained significant after propensity score matching (HR 0.52, 95%CI 0.35-0.76, P = 0.004). Overall survival was unaffected by either type of adjuvant therapy, while significant difference was observed between patients who received adjuvant therapy or not after propensity score matching (HR 0.31, 95%CI 0.17-0.59, P = 0.005). The rate of grade 3 or 4 adverse events was similar between the two types of adjuvant therapy. CONCLUSIONS: ICIs alone or with TKIs may improve RFS of patients at high risk of HCC recurrence after curative resection.

Second-line treatment options for hepatocellular carcinoma: current state and challenges for the future.

INTRODUCTION: Since the approval of sorafenib for systemic treatment of advanced hepatocellular carcinoma (HCC), many tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have shown efficacy and tolerability as first-line treatments. On the other hand, these first-line therapies are associated with low objective response and drug resistance. Many drugs have been successfully tested for second-line treatment of advanced HCC. While the rapid proliferation of second-line treatments for advanced HCC brings hope to patients, it also complicates clinical decision-making. AREAS COVERED: This review aims to facilitate decisions by summarizing the latest guidelines for second-line treatment of HCC in various countries or regions. We then review existing second-line treatment options and discuss challenges that should be addressed in the future. A literature search was conducted in April 2022 of PubMed/Medline, Cochrane library, and abstracts of international cancer meetings. EXPERT OPINION: There is no standard second-line treatment, especially for the case of sequential treatment after atezolizumab plus bevacizumab (atezo+bev) and further studies focused on sequential treatment are warranted in this setting. The design of clinical trials, different etiologies, and complications or quality of life (QoL) are interesting issues in the second-line setting.

Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer.

BACKGROUND: Pituitary tumor transforming gene-1 (PTTG1) transcription factor is identified as carcinogenic and associated with tumor invasiveness, but its role in bladder cancer (BLCA) remains obscure. This research is intended to analyze the aberrant expression and clinical significance of PTTG1 in BLCA, explore the relationship between PTTG1 and tumor microenvironment characteristics and predict its potential transcriptional activity in BLCA tissue. METHODS: We compared the expression discrepancy of PTTG1 mRNA in BLCA and normal bladder tissue, using the BLCA transcriptomic datasets from GEO, ArrayExpress, TCGA, and GTEx. In-house immunohistochemical staining was implemented to determine the PTTG1 protein intensity. The prognostic value of PTTG1 was evaluated using the Kaplan-Meier Plotter. CRISPR screen data was utilized to estimate the effect PTTG1 interference has on BLCA cell lines. We predicted the abundance of the immune cells in the BLCA tumor microenvironment using the microenvironment cell populations-counter and ESTIMATE algorithms. Single-cell RNA sequencing data was applied to identify the major cell types in BLCA, and the dynamics of BLCA progression were revealed using pseudotime analysis. PTTG1 target genes were predicted by CistromeDB. RESULTS: The elevated expression level of PTTG1 was confirmed in 1037 BLCA samples compared with 127 non-BLCA samples, with a standardized mean difference value of 1.04. Higher PTTG1 expression status exhibited a poorer BLCA prognosis. Moreover, the PTTG1 Chronos genetic effect scores were negative, indicating that PTTG1 silence may inhibit the proliferation and survival of BLCA cells. With PTTG1 mRNA expression level increasing, higher natural killer, cytotoxic lymphocyte, and monocyte lineage cell infiltration levels were observed. A total of four candidate targets containing CHEK2, OCIAD2, UBE2L3, and ZNF367 were determined ultimately. CONCLUSIONS: PTTG1 mRNA over-expression may become a potential biomarker for BLCA prognosis. Additionally, PTTG1 may correlate with the BLCA tumor microenvironment and exert transcriptional activity by targeting CHEK2, OCIAD2, UBE2L3, and ZNF367 in BLCA tissue.