Clinical importance of clonal hematopoiesis in metastatic gastrointestinal tract cancers Journal Article
| Authors: | Diplas, B. H.; Ptashkin, R.; Chou, J. F.; Sabwa, S.; Foote, M. B.; Rousseau, B.; Argilés, G.; White, J. R.; Stewart, C. M.; Bolton, K.; Chalasani, S. B.; Desai, A. M.; Goldberg, Z.; Gu, P.; Li, J.; Shcherba, M.; Zervoudakis, A.; Cercek, A.; Yaeger, R.; Segal, N. H.; Ilson, D. H.; Ku, G. Y.; Zehir, A.; Capanu, M.; Janjigian, Y. Y.; Diaz, L. A. Jr; Maron, S. B. |
| Article Title: | Clinical importance of clonal hematopoiesis in metastatic gastrointestinal tract cancers |
| Abstract: | Importance: Clonal hematopoiesis (CH) has been associated with development of atherosclerosis and leukemia and worse survival among patients with cancer; however, the association with cancer therapy efficacy, in particular immune checkpoint blockade (ICB), and toxicity has not yet been established. Given the widespread use of ICB and the critical role hematopoietic stem cell-derived lymphocytes play in mediating antitumor responses, CH may be associated with therapeutic efficacy and hematologic toxicity. Objective: To determine the association between CH and outcomes, hematologic toxicity, and therapeutic efficacy in patients with metastatic gastrointestinal tract cancers being treated with systemic therapy, both in the first-line metastatic treatment setting and in ICB. Design, Setting, and Participants: This retrospective cohort study included 633 patients with stage IV colorectal (CRC) and esophagogastric (EGC) cancer who were treated with first-line chemotherapy and/or ICB at Memorial Sloan Kettering Cancer Center. Patients underwent matched tumor and peripheral blood DNA sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets next-generation sequencing assay between January 1, 2006, and December 31, 2020. Exposures: Clonal hematopoiesis-related genetic alterations were identified by next-generation sequencing of patients' tumor and normal blood buffy coat samples, with a subset of these CH alterations annotated as likely putative drivers (CH-PD) based upon previously established criteria. Main Outcomes and Measures: Patients with CH and CH-PD in peripheral blood samples were identified, and these findings were correlated with survival outcomes (progression-free survival [PFS] and overall survival [OS]) during first-line chemotherapy and ICB, as well as baseline white blood cell levels and the need for granulocyte colony-stimulating factor (G-CSF) support. Results: Among the 633 patients included in the study (390 men [61.6%]; median age, 58 [IQR, 48-66] years), the median age was 52 (IQR, 45-63) years in the CRC group and 61 (IQR, 53-69) years in the EGC group. In the CRC group, 161 of 301 patients (53.5%) were men, compared with 229 of 332 patients (69.0%) in the EGC group. Overall, 62 patients (9.8%) were Asian, 45 (7.1%) were Black or African American, 482 (76.1%) were White, and 44 (7.0%) were of unknown race or ethnicity. Presence of CH was identified in 115 patients with EGC (34.6%) and 83 with CRC (27.6%), with approximately half of these patients harboring CH-PD (CRC group, 44 of 83 [53.0%]; EGC group, 55 of 115 [47.8%]). Patients with EGC and CH-PD exhibited a significantly worse median OS of 16.0 (95% CI, 11.6-22.3) months compared with 21.6 (95% CI, 19.6-24.3) months for those without CH-PD (P =.01). For patients with CRC and EGC, CH and CH-PD were not associated with PFS differences in patients undergoing ICB or first-line chemotherapy. Neither CH nor CH-PD were correlated with baseline leukocyte levels or increased need for G-CSF support. Conclusions and Relevance: These findings suggest CH and CH-PD are not directly associated with the treatment course of patients with metastatic gastrointestinal tract cancer receiving cancer-directed therapy. © 2023 American Medical Association. All rights reserved. |
| Keywords: | adult; cancer chemotherapy; cancer survival; controlled study; middle aged; leukemia; retrospective studies; major clinical study; overall survival; genetics; fluorouracil; systemic therapy; antineoplastic agent; colorectal cancer; progression free survival; blood toxicity; cohort analysis; retrospective study; docetaxel; irinotecan; gastrointestinal neoplasms; survival time; blood sampling; folinic acid; stomach cancer; clinical effectiveness; leukocyte count; oxaliplatin; esophagus cancer; granulocyte colony stimulating factor; african american; caucasian; filgrastim; asian; gastrointestinal tumor; clinical outcome; pegfilgrastim; first-line treatment; clonal hematopoiesis; immune checkpoint inhibitor; high throughput sequencing; clinical relevance; dna sequencing; humans; human; male; female; article; black person; blood buffy coat |
| Journal Title: | JAMA Network Open |
| Volume: | 6 |
| Issue: | 2 |
| ISSN: | 2574-3805 |
| Publisher: | American Medical Association |
| Date Published: | 2023-02-01 |
| Start Page: | e2254221 |
| Language: | English |
| DOI: | 10.1001/jamanetworkopen.2022.54221 |
| PUBMED: | 36729457 |
| PROVIDER: | scopus |
| PMCID: | PMC9896303 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding authors are Steven Maron and Luis Diaz Jr -- Export Date: 1 March 2023 -- Source: Scopus |
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