Neoadjuvant immune checkpoint blockade in resectable hepatocellular carcinoma: A systematic review and meta-analyisis.
Bibliographic record
Abstract
590 Background: Hepatocellular carcinoma (HCC) presents a significant therapeutic challenge due to its high recurrence rates after curative-intent resection. Neoadjuvant immune checkpoint blockade (ICB) has emerged as a promising strategy to improve tumor control by modulating the immune microenvironment prior to surgery. This systematic review and meta-analysis aim to assess the safety and efficacy of neoadjuvant ICB in improving clinical outcomes for patients with resectable HCC. Methods: A systematic search of PubMed, EMBASE, and Cochrane databases was conducted to identify clinical trials examining neoadjuvant ICB in resectable HCC. Primary endpoints included pathological complete response (pCR), major pathological response (mPR), overall response rate (ORR), and grade 3-4 treatment-related adverse events (TRAE). Prespecified subgroup analyses were conducted for studies combining ICB with tyrosine kinase inhibitors (TKIs) or dual ICB therapies. Pooled proportions were calculated using a random-effects model via the R package "meta." Inter-study heterogeneity was assessed using the I² statistic and test for subgroup differences were conducted. Results: Out of 1,321 studies screened, 14 clinical trials involving 252 patients with resectable HCC were included. Most studies were phase II trials (57%), and patient median age ranged from 57.5 to 68.0 years, with 88.3% of patients being male. The pooled prevalence of mPR was 32% (95% CI, 24–42%; I² = 9%)while pCR was achieved in 24% (95% CI, 17–34%; I² = 29%)of patients. The ORR was 27% (95% CI, 18–39%; I² = 49%), and severe adverse events (grade 3-4 TRAE) had a pooled prevalence of 24% (95% CI, 17–34%; I² = 16%). Subgroup analysis of trials combining ICB with TKIs showed an ORR 34% (95% CI, 20–55%; I² = 60%), an mPR rate of 27% (95% CI, 19–40%; I² = 0%), and a pCR rate of 20% (95% CI, 14–30%; I² = 0%). Dual ICB therapies demonstrated a higher mPR rate of 42% (95% CI, 26–67%; I² = 16%) and a pCR rate of 41% (95% CI, 29–59%; I² = 29%), but were associated with a higher incidence of severe TRAE (41%; 95% CI, 29–60%; I² = 0%). Conclusions: Neoadjuvant ICB demonstrates promising efficacy in resectable HCC, particularly when combined with TKIs or dual ICB therapies. While dual ICB enhances pathological response rates, it is associated with higher rates of severe TRAE. These results highlight the need of further studies to optimize combination strategies that balance efficacy and safety for patients with resectable HCC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.017 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.014 | 0.031 |
| Bibliometrics | 0.007 | 0.008 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".