AimTo evaluate the feasibility of computed tomography (CT) - derived measurements of body composition parameters to predict the risk factor of non-objective response (non-OR) in patients with hepatocellular carcinoma (HCC) undergoing anti-PD-1 immunotherapy and hepatic artery infusion chemotherapy (immune-HAIC).MethodsPatients with histologically confirmed HCC and treated with the immune-HAIC were retrospectively recruited between June 30, 2019, and July 31, 2021. CT-based estimations of body composition parameters were acquired from the baseline unenhanced abdominal CT images at the level of the third lumbar vertebra (L3) and were applied to develop models predicting the probability of OR. A myosteatosis nomogram was built using the multivariate logistic regression incorporating both myosteatosis measurements and clinical variables. Receiver operating characteristic (ROC) curves assessed the performance of prediction models, including the area under the curve (AUC). The nomogram’s performance was assessed by the calibration, discrimination, and decision curve analyses. Associations among predictors and gene mutations were also examined by correlation matrix analysis.ResultsFifty-two patients were recruited to this study cohort, with 30 patients having a OR status after immune-HAIC treatment. Estimations of myosteatosis parameters, like SM-RA (skeletal muscle radiation attenuation), were significantly associated with the probability of predicting OR (P=0.007). The SM-RA combined nomogram model, including serum red blood cell, hemoglobin, creatinine, and the mean CT value of visceral fat (VFmean) improved the prediction probability for OR disease with an AUC of 0.713 (95% CI, 0.75 to 0.95) than the clinical model nomogram with AUC of 0.62 using a 5-fold cross-validation methodology. Favorable clinical potentials were observed in the decision curve analysis.ConclusionsThe CT-based estimations of myosteatosis could be used as an indicator to predict a higher risk of transition to the Non-OR disease state in HCC patients treated with immune-HAIC therapy. This study demonstrated the therapeutic relevance of skeletal muscle composition assessments in the overall prediction of treatment response and prognosis in HCC patients.
Purpose: To assess the safety and efficacy of local ablation plus PD-1 inhibitor toripalimab in previously treated unresectable hepatocellular carcinoma (HCC). Patients and Methods: In the multicenter, two-stage, and randomized phase 1/2 trial, patients were randomly assigned to receive toripalimab alone (240mg, every 3 weeks), subtotal local ablation followed by toripalimab starting on post-ablation day 3 (Schedule D3) or on post-ablation day 14 (Schedule D14). The first endpoint of stage 1 was to determine which combination schedule could continue and progression-free survival (PFS) as the primary endpoint for stage 1/2. Results: A total of 146 patients were recruited. During stage 1, Schedule D3 achieved numerically higher objective response rate than Schedule D14 for non-ablation lesions (37.5% versus 31.3%), and was chosen for stage 2 evaluation. For the entire cohort of both stages, patients with Schedule D3 had a significantly higher objective response rate than with toripalimab alone (33.8% versus 16.9%, P = 0.027). Moreover, patients with Schedule D3 had improved median PFS (7.1 months versus 3.8 months, P ﹤0.001) and median overall survival (18.4 months versus 13.2 months, P = 0.005), as compared with toripalimab alone. In addition, six (9%) patients with toripalimab, 8 (12%) with Schedule D3, and 4 (25%) with Schedule D14 developed grade 3 or 4 adverse events, and one patient (2%) with Schedule D3 manifested grade 5 treatment-related pneumonitis. Conclusions: In patients with previously treated unresectable HCC, subtotal ablation plus toripalimab improved the clinical efficacy as compared with toripalimab alone with an acceptable safety profile.
BackgroundCDK1 is critical for cell viability and plays an important role in biological events. MiR-195 is pivotal in pathogenesis and development of hepatocellular carcinoma (HCC). But the association between CDK1 and miR-195 in HCC is underexplored. MethodsGene expression was assayed via qRT-PCR, and corresponding protein levels were assessed via Western blot. Cell cycle was assayed through ow cytometry. DNA replication was detected by EDU staining. Cell proliferation was determined via plate colony formation assay. Targeting relationship between miR-195-5p and CDK1 was analyzed by bioinformatics analysis and dual-luciferase gene assay. DNA damage was marked by immuno uorescence staining. ResultsCDK1 was overexpressed in HCC tissues and cells. Silencing CDK1 modulated cell cycle of HCC cells and inhibited DNA replication and proliferation. In HCC cells, miR-195-5p reduced CDK1 level, inhibited the G1 phase-to-S phase transition, induced DNA damage response, and inhibited DNA replication and proliferation. ConclusionMiR-195-5p targeted CDK1 and repressed synthesis of new DNA in HCC cells, thus restraining HCC cell proliferation.
Background CDK1 is critical for cell viability and plays an important role in biological events. MiR-195 is pivotal in pathogenesis and development of hepatocellular carcinoma (HCC). But the association between CDK1 and miR-195 in HCC is underexplored. Methods Gene expression was assayed via qRT-PCR, and corresponding protein levels were assessed via Western blot. Cell cycle was assayed through flow cytometry. DNA replication was detected by EDU staining. Cell proliferation was determined via plate colony formation assay. Targeting relationship between miR-195-5p and CDK1 was analyzed by bioinformatics analysis and dual-luciferase gene assay. DNA damage was marked by immunofluorescence staining. Results CDK1 was overexpressed in HCC tissues and cells. Silencing CDK1 modulated cell cycle of HCC cells and inhibited DNA replication and proliferation. In HCC cells, miR-195-5p reduced CDK1 level, inhibited the G1 phase-to-S phase transition, induced DNA damage response, and inhibited DNA replication and proliferation. Conclusion MiR-195-5p targeted CDK1 and repressed synthesis of new DNA in HCC cells, thus restraining HCC cell proliferation.
<p>Supplementary Fig. 3 A. Progression-free survival by CD8+ TIL density. B. Overall survival by CD8+ TIL density. Dot marks indicate censored data.</p>
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