Clonal Hematopoiesis of Indeterminate Potential and its Association with Treatment Outcomes and Adverse Events in Patients with Solid Tumors
Bibliographic record
Abstract
ABSTRACT: Clonal hematopoiesis of indeterminate potential (CHIP) is the clonal expansion of hematopoietic stem cells from somatic mutations. It is a common incidental finding in cell-free DNA (cfDNA). We investigated the incidence of CHIP in cfDNA from patients with solid tumors and explored its association with treatment outcomes and adverse events. We reviewed cfDNA results from a local prospective solid tumor cohort (PREDiCT-l) and two randomized trials: Canadian Cancer Trials Group CO.26 [durvalumab + tremelimumab (D + T) or best supportive care in metastatic colorectal cancer] and Canadian Cancer Trials Group PA.7 (gemcitabine and nab-paclitaxel ± D + T in metastatic pancreatic adenocarcinoma). CHIP+ was defined as any mutation in DNMT3A, TET2, or ASXL1 with a variant allele frequency ≥2%. Presumed germline variants (variant allele frequency >40%) were removed. The first line of treatment after cfDNA was reviewed for grade ≥3 and dose-limiting toxicities. The prevalence of CHIP in the 465 included patients was 10% to 30%, and it was more common as age increased (P = 0.003). DNMT3A was the gene most frequently mutated in all cohorts. Patients with CHIP in PA.7 treated with immunotherapy showed an improved progression-free survival versus CHIP− [HR = 0.55 (0.28–1.07); P = 0.079, P-interaction = 0.098 (multivariable)]. However, patients with CHIP treated with chemotherapy in PREDiCT-l showed a trend toward worse progression-free survival [HR = 1.82 (0.98–3.38); P = 0.059]. There was no difference in adverse event rates between CHIP ± groups for those treated with chemotherapy or immunotherapy. CHIP is common in patients with solid tumors. Although not appearing to affect rates of adverse events, CHIP may affect outcomes from immunotherapy or chemotherapy. SIGNIFICANCE: Liquid biopsy is increasingly being used in oncology for tumor molecular characterization. CHIP is a common incidental finding in cfDNA, and its prevalence increases with age. This study builds on growing evidence of common CHIP variants in patients with solid tumors. The results suggest a possible clinical impact of CHIP on treatment outcomes from immunotherapy or chemotherapy. This may have implications for treatment selection for patients with solid tumors.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".