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: 0.06-0.33; 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, RAF1, 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
Francesco Sabbatino;Marco Cascella;
2024-01-01
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: 0.06-0.33; 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, RAF1, 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.
