ABSTRACT
BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs), trans-arterial chemoembolization (TACE), and radiotherapy to treat hepatocellular carcinoma (HCC) has not been well-defined. We performed a meta-analysis to characterize tumor response and survival associated with multimodal treatment of HCC. METHODS: PubMed, Embase, Medline, Scopus, and CINAHL databases were searched (1990-2022). Random-effect meta-analysis was conducted to compare efficacy of treatment modalities. Odds ratios (OR) and standardized mean difference (SMD) were reported. RESULTS: Thirty studies (4170 patients) met inclusion criteria. Triple therapy regimen (ICI + TKI + TACE) had the highest overall disease control rate (DCR) (87%, 95% CI 83-91), while ICI + radiotherapy had the highest objective response rate (ORR) (72%, 95% CI 54%-89%). Triple therapy had a higher DCR than ICI + TACE (OR 4.49, 95% CI 2.09-9.63), ICI + TKI (OR 3.08, 95% CI 1.63-5.82), and TKI + TACE (OR 2.90, 95% CI 1.61-5.20). Triple therapy demonstrated improved overall survival versus ICI + TKI (SMD 0.72, 95% CI 0.37-1.07) and TKI + TACE (SMD 1.13, 95% CI 0.70-1.48) (both p < 0.05). Triple therapy had a greater incidence of adverse events (AEs) compared with ICI + TKI (OR 0.59, 95% CI 0.29-0.91; p = 0.02), but no difference in AEs versus ICI + TACE or TKI + TACE (both p > 0.05). CONCLUSION: The combination of ICIs, TKIs and TACE demonstrated superior tumor response and survival and should be considered for select patients with advanced HCC.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Immune Checkpoint Inhibitors , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/therapy , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Combined Modality Therapy , Treatment Outcome , Male , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/adverse effectsABSTRACT
BACKGROUND: With the growing number of adults requiring operations for CHD, prolonged length of stay adds an additional burden on healthcare systems, especially in developing countries. This study aimed to identify factors associated with prolonged length of stay in adult patients undergoing operations for CHD. METHODS: This retrospective study included all adult patients (≥18 years) who underwent cardiac surgery with cardiopulmonary bypass for their CHD from 2011 to 2016 at a tertiary-care private hospital in Pakistan. Prolonged length of stay was defined as hospital stay >75th percentile of the overall cohort (>8 days). RESULTS: This study included 166 patients (53.6% males) with a mean age of 32.05 ± 12.11 years. Comorbid disease was present in 59.0% of patients. Most patients underwent atrial septal defect repair (42.2%). A total of 38 (22.9%) patients had a prolonged length of stay. Post-operative complications occurred in 38.6% of patients. Multivariable analysis showed that pre-operative body mass index (odds ratio: 0.779; 95% confidence interval: 0.620-0.980), intraoperative aortic cross-clamp time (odds ratio: 1.035; 95% confidence interval: 1.009-1.062), and post-operative acute kidney injury (odds ratio: 7.392; 95% confidence interval: 1.036-52.755) were associated with prolonged length of stay. CONCLUSION: Predictors of prolonged length of stay include lower body mass index, longer aortic cross-clamp time, and development of post-operative acute kidney injury. Shorter operations, improved pre-operative nutritional optimisation, and timely management of post-operative complications could help prevent prolonged length of stay in patients undergoing operations for adult CHD.
