| Sumario: | Key Points: Question: Is tumor-infiltrating clonal hematopoiesis (TI-CH) associated with clinical factors and overall survival in patients with solid tumors? Findings: In this cohort study of 10 571 patients with solid tumors, TI-CH was identified in 1943 patients (18.38%). Older age and prior cytotoxic chemotherapy were significantly associated with an increased likelihood of TI-CH; furthermore, there was a significant association between TI-CH and worse overall survival, particularly in patients with breast cancer. Meaning: These findings suggest that TI-CH may serve as a prognostic biomarker in solid tumors, highlighting the importance of risk stratification, particularly for older patients or those with a history of cytotoxic chemotherapy. Importance: Tumor-infiltrating clonal hematopoiesis (TI-CH) indicates the infiltration of somatically mutated hematopoietic cells into the tumor microenvironment. While clonal hematopoiesis is a known prognostic factor in hematologic malignant neoplasms, the clinical relevance of TI-CH in solid tumors remains poorly understood. Objective: To characterize the prevalence of TI-CH in solid tumors and evaluate its association with clinical factors and overall survival (OS). Design, Setting, and Participants: This retrospective cohort study analyzed whole-genome sequencing data of a large cohort of patients with solid tumors from the Genomics England 100 000 Genomes Project between 2015 and 2019. The data analysis was conducted from June to November 2025. Main Outcomes and Measures: The primary outcome was the prevalence of TI-CH, defined by somatic variants in 74 driver genes (variant allele frequency 2% to 30%) in tumor tissue. Secondary outcomes included associations of TI-CH with clinical factors (age, cytotoxic chemotherapy) and OS, assessed using Cox proportional hazards models. Results: Among 10 571 patients with solid tumors (mean [SD] age, 64.68 [12.18] years; 6430 [60.83%] female), TI-CH was detected in 1943 patients (18.38%), with the highest frequency observed in patients with TET2 variants (212 patients [10.91%]) and in patients with endometrial cancer (251 patients [32%]). TI-CH was more common with older age (odds ratio [OR], 1.15 [95% CI, 1.10-1.19]) and cytotoxic chemotherapy (OR, 1.24 [95% CI, 1.06-1.44]). TI-CH was significantly associated with worse pan-cancer OS (hazard ratio [HR], 1.13 [95% CI, 1.02-1.25]), particularly breast cancer OS (HR, 1.95 [95% CI, 1.54-2.48]). At the gene level, worse pan-cancer OS was significantly associated with GATA2 variants (HR, 3.00 [95% CI, 1.61-5.59]), and worse breast cancer OS was significantly associated with TET2 variants (HR, 2.92 [95% CI, 1.59-5.37]). Conclusions and Relevance: In this cohort study, older age and cytotoxic chemotherapy were associated with higher odds of TI-CH. TI-CH was associated with worse survival in patients with solid tumors, specifically implicating GATA2 (pan-cancers) and TET2 (breast cancer) variants. These findings suggest TI-CH may serve as a prognostic biomarker in patients with solid tumors. This cohort study investigates tumor-infiltrating clonal hematopoiesis in solid tumors and evaluates its association with clinical factors and overall survival.
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