Background: Oligo-metastatic disease (OMD) in colon cancer patients exhibits distinct clinical behavior compared to poly-metastatic disease (PMD), with a more responsive and indolent course. This study aims to identify clinical and biological factors uniquely associated with oligo-metastatic behavior. Methods: Metastatic colon cancer patients from an academic center underwent genetic characterization. OMD was defined as <= 3 lesions per organ, each with a total diameter <70 mm and none exceeding 25 mm. Tumor DNA sequencing by NGS utilized the TruSight Oncology 500 kit. Overall survival (OS) was determined from metastasis diagnosis until death using Kaplan-Meier analysis. Multivariate Cox regression examined prognostic links between clinicopathological and genetic factors. Associations with metastatic patterns were evaluated using Chi-square. Results: The analysis involved 104 patients (44 with OMD, 60 with PMD). OMD was more prevalent in males (P = 0.0299) and with single organ involvement (P = 0.0226). Multivariate analysis adjusted for age (>70 vs. <70 years), gender (male vs. female), tumor side (right vs. left), metastatic involvement (more than one site vs. one site), response to first-line therapy (disease control vs. no disease control), and RAS/BRAF variants (wild-type vs. mutated) identified OMD vs. PMD as the strongest independent predictor of survival (HR: 0.14; 95 % CI: 0.060.33; P <0.0001). OMD patients exhibited distinct molecular characteristics, including lower frequencies of BRAF p.V600E (P=0.0315) and KRAS mutations (P=0.0456), as well as a higher frequency of high tumor mutational burden (P=0.0127). Additionally, by integrating data from public datasets and our case study, we hypothesize that some gene alterations (i.e.: BRAF, SMAD4, RAFT, and mTOR) may prevent OMD occurrence. Conclusion: OMD, characterized by male predominance, single-site involvement, and distinct molecular features in colon cancer, suggests the need for tailored management strategies.
Clinical and genetic drivers of oligo-metastatic disease in colon cancer
Sirica R.;Ianniello M.;Castiello R.;Cascella M.;Mercadante E.;Tathode M.;Cossu A. M.;Bocchetti M.;Caraglia M.;Nasti G.;
2025
Abstract
Background: Oligo-metastatic disease (OMD) in colon cancer patients exhibits distinct clinical behavior compared to poly-metastatic disease (PMD), with a more responsive and indolent course. This study aims to identify clinical and biological factors uniquely associated with oligo-metastatic behavior. Methods: Metastatic colon cancer patients from an academic center underwent genetic characterization. OMD was defined as <= 3 lesions per organ, each with a total diameter <70 mm and none exceeding 25 mm. Tumor DNA sequencing by NGS utilized the TruSight Oncology 500 kit. Overall survival (OS) was determined from metastasis diagnosis until death using Kaplan-Meier analysis. Multivariate Cox regression examined prognostic links between clinicopathological and genetic factors. Associations with metastatic patterns were evaluated using Chi-square. Results: The analysis involved 104 patients (44 with OMD, 60 with PMD). OMD was more prevalent in males (P = 0.0299) and with single organ involvement (P = 0.0226). Multivariate analysis adjusted for age (>70 vs. <70 years), gender (male vs. female), tumor side (right vs. left), metastatic involvement (more than one site vs. one site), response to first-line therapy (disease control vs. no disease control), and RAS/BRAF variants (wild-type vs. mutated) identified OMD vs. PMD as the strongest independent predictor of survival (HR: 0.14; 95 % CI: 0.060.33; P <0.0001). OMD patients exhibited distinct molecular characteristics, including lower frequencies of BRAF p.V600E (P=0.0315) and KRAS mutations (P=0.0456), as well as a higher frequency of high tumor mutational burden (P=0.0127). Additionally, by integrating data from public datasets and our case study, we hypothesize that some gene alterations (i.e.: BRAF, SMAD4, RAFT, and mTOR) may prevent OMD occurrence. Conclusion: OMD, characterized by male predominance, single-site involvement, and distinct molecular features in colon cancer, suggests the need for tailored management strategies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
