ArticleInternational journal of surgery (London, England)2026
Comparative predictive value of immunotherapy biomarkers: a systematic review and network meta-analysis.
Article in International journal of surgery (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
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7 authors.
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Abstract
backgroundImmunotherapy efficacy remains limited in over 60% of cancer patients, necessitating reliable predictive biomarkers. This network meta-analysis (NMA) compared the performance of 13 biomarkers to identify optimal predictors.
methodsWe searched PubMed, OVID, Embase, Cochrane Trials, Web of Science, and trial registries (ClinicalTrials.gov, WHO ICTRP) from inception to 1 September 2025, for a comprehensive NMA evaluating 13 biomarkers (circulating tumor DNA [ctDNA], programmed cell death ligand 1 [PD-L1; at varying thresholds], tumor mutational burden [TMB], et al.). Subgroup analyses were performed for various cancers. Heterogeneity and publication bias were assessed.
resultsThis analysis included 54 634 patients from 194 clinical studies worldwide. ctDNA demonstrated the highest sensitivity (0.82, 95% CI: 0.72-0.89) and overall discriminative ability (DOR = 9.75, 95% CI: 5.20-16.73; AUC = 0.769). PD-L1 exhibited threshold-dependent performance: the ≥ 50% cutoff showed the highest specificity (0.78, 95% CI: 0.73-0.81) and diagnostic accuracy (DOR = 2.60, 95% CI: 1.86-3.52; AUC = 0.661) but the lowest sensitivity (0.42, 95% CI: 0.36-0.49), while the ≥ 1% cutoff achieved the highest sensitivity (0.68, 95% CI: 0.65-0.71) at the cost of the lowest specificity (0.48, 95% CI: 0.45-0.51). TMB provided a moderate balance of sensitivity (0.56, 95% CI: 0.50-0.60) and specificity (0.69, 95% CI: 0.65-0.73). MSI demonstrated the highest specificity overall (0.89, 95% CI: 0.85-0.93), but had limited sensitivity (0.36, 95% CI: 0.27-0.46). irAEs displayed relatively higher sensitivity (0.69, 95% CI: 0.60-0.77) with moderate specificity (0.59, 95% CI: 0.50-0.67). Among inflammatory markers, PLR (AUC = 0.623) showed slightly better predictive power than NLR (AUC = 0.613), while LIPI and LDH exhibited the least overall effectiveness (AUC = 0.585 and 0.544, respectively).
conclusionBiomarker performance varies by cancer type and clinical context. ctDNA, PD-L1 (high thresholds, as ≥50%), and TMB are leading predictors, with combinations potentially optimizing performance. Future research must address heterogeneity and standardization to refine individualized immunotherapy strategies.
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