ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026
Ultra-rare TP53 and KRAS variants predict survival in ICI-treated solid tumours.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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- Erratum issued
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5 authors.
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Abstract
backgroundThe prognostic relevance of ultra-rare TP53 and KRAS variants in advanced solid tumours treated with immune-checkpoint inhibitors (ICI) is unclear.
methodsWe performed a retrospective cohort study using the Memorial Sloan Kettering Cancer Center MSK-IMPACT clinical-genomic dataset (cBioPortal study ID: tmb_mskcc_2018). TP53 and KRAS alterations were stratified by rarity (ultra-rare vs common) and analysed for overall survival (OS). Kaplan-Meier analyses and multivariable Cox proportional hazards models were fitted, adjusting for tumour type, tumour mutational burden (TMB), tumour purity, histology, age and sex.
resultsIn the overall cohort, 51.4% of tumours harboured TP53 or KRAS mutations. Ultra-rare variants were independently associated with worse OS (HR 1.34, 95% CI 1.14-1.56; p < 0.001), with a median OS of 14.0 months versus 22.0 months in common/wild-type patients. Tumour-specific analyses suggested heterogeneity: non-small-cell lung cancer showed shorter OS for ultra-rare variants (approximately 10-13 months vs 17 months for wild type), whereas melanoma showed improved outcomes (HR 0.59, 95% CI 0.44-0.78; p < 0.001).
conclusionUltra-rare TP53 and KRAS variants provide prognostic information in ICI-treated advanced solid tumours, but the direction and magnitude of effect vary by tumour type. These findings support tumour-specific interpretation and motivate mechanistic and therapeutic studies in this underserved molecular subgroup.
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