Clinical and genetic drivers of oligo-metastatic disease in colon cancer
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 behavio...
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Elsevier
2025-02-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558624001520 |
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| author | Alessandro Ottaiano Mariachiara Santorsola Roberto Sirica Annabella Di Mauro Antonella Di Carlo Monica Ianniello Francesco Sabbatino Rosa Castiello Francesca Del Peschio Marco Cascella Francesco Perri Maurizio Capuozzo Nicola Martucci Edoardo Mercadante Valentina Borzillo Rossella Di Franco Francesco Izzo Vincenza Granata Carmine Picone Antonella Petrillo Massimiliano Berretta Salvatore Stilo Luca Tarotto Anna Chiara Carratù Gerardo Ferrara Madhura Tathode Alessia Maria Cossu Marco Bocchetti Michele Caraglia Guglielmo Nasti Giovanni Savarese |
| author_facet | Alessandro Ottaiano Mariachiara Santorsola Roberto Sirica Annabella Di Mauro Antonella Di Carlo Monica Ianniello Francesco Sabbatino Rosa Castiello Francesca Del Peschio Marco Cascella Francesco Perri Maurizio Capuozzo Nicola Martucci Edoardo Mercadante Valentina Borzillo Rossella Di Franco Francesco Izzo Vincenza Granata Carmine Picone Antonella Petrillo Massimiliano Berretta Salvatore Stilo Luca Tarotto Anna Chiara Carratù Gerardo Ferrara Madhura Tathode Alessia Maria Cossu Marco Bocchetti Michele Caraglia Guglielmo Nasti Giovanni Savarese |
| author_sort | Alessandro Ottaiano |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c73aac76188d44bebeadefe3765d8747 |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-c73aac76188d44bebeadefe3765d87472025-02-03T04:16:34ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-02-0160101111Clinical and genetic drivers of oligo-metastatic disease in colon cancerAlessandro Ottaiano0Mariachiara Santorsola1Roberto Sirica2Annabella Di Mauro3Antonella Di Carlo4Monica Ianniello5Francesco Sabbatino6Rosa Castiello7Francesca Del Peschio8Marco Cascella9Francesco Perri10Maurizio Capuozzo11Nicola Martucci12Edoardo Mercadante13Valentina Borzillo14Rossella Di Franco15Francesco Izzo16Vincenza Granata17Carmine Picone18Antonella Petrillo19Massimiliano Berretta20Salvatore Stilo21Luca Tarotto22Anna Chiara Carratù23Gerardo Ferrara24Madhura Tathode25Alessia Maria Cossu26Marco Bocchetti27Michele Caraglia28Guglielmo Nasti29Giovanni Savarese30SSD-Innovative Therapies for Abdominal Metastases, IRCCS ''G. Pascale'', Istituto Nazionale Tumori di Napoli, Via M. Semmola, Naples 80131, Italy; Corresponding author.SSD-Innovative Therapies for Abdominal Metastases, IRCCS ''G. Pascale'', Istituto Nazionale Tumori di Napoli, Via M. Semmola, Naples 80131, ItalyAMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, Casalnuovo Di Napoli 80013, ItalyUnit of Pathology, IRCCS ''G. Pascale'', Istituto Nazionale Tumori di Napoli, Via M. Semmola, Naples 80131, ItalyAMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, Casalnuovo Di Napoli 80013, ItalyAMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, Casalnuovo Di Napoli 80013, ItalyMedical Oncology, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi 84081, ItalyAMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, Casalnuovo Di Napoli 80013, ItalyAMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, Casalnuovo Di Napoli 80013, ItalyUnit of Anesthesia and Pain Medicine, Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi 84081, ItalyMedical and Experimental Head and Neck Oncology Unit, IRCCS ''G. Pascale'', Istituto Nazionale Tumori di Napoli, Via M. Semmola, Naples 80131, ItalyCoordinamento Farmaceutico, ASL-Naples-3, Ercolano 80056, ItalyUnit of Thoracic Surgery, Istituto Nazionale Tumori di Napoli, IRCCS ''G. Pascale'', Via M. Semmola, Naples 80131, ItalyUnit of Thoracic Surgery, Istituto Nazionale Tumori di Napoli, IRCCS ''G. Pascale'', Via M. Semmola, Naples 80131, ItalyDepartment of Radiation Oncology, IRCCS ''G. Pascale'', Istituto Nazionale Tumori di Napoli, Via M. Semmola, Naples 80131, ItalyDepartment of Radiation Oncology, IRCCS ''G. Pascale'', Istituto Nazionale Tumori di Napoli, Via M. Semmola, Naples 80131, ItalyUnit of Epato-Biliary Surgery, Istituto Nazionale Tumori di Napoli, IRCCS ''G. Pascale'', Via M. Semmola, Naples 80131, ItalyUnit of Radiology, Istituto Nazionale Tumori di Napoli, IRCCS ''G. Pascale'', Via M. Semmola, Naples 80131, ItalyUnit of Radiology, Istituto Nazionale Tumori di Napoli, IRCCS ''G. Pascale'', Via M. Semmola, Naples 80131, ItalyUnit of Radiology, Istituto Nazionale Tumori di Napoli, IRCCS ''G. Pascale'', Via M. Semmola, Naples 80131, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, Messina 98122, ItalyInterventional Radiology Unit, Istituto Nazionale Tumori di Napoli, IRCCS ''G. Pascale'', Via M. Semmola, Naples 80131, ItalyInterventional Radiology Unit, Istituto Nazionale Tumori di Napoli, IRCCS ''G. Pascale'', Via M. Semmola, Naples 80131, ItalySSD-Innovative Therapies for Abdominal Metastases, IRCCS ''G. Pascale'', Istituto Nazionale Tumori di Napoli, Via M. Semmola, Naples 80131, ItalyUnit of Pathology, IRCCS ''G. Pascale'', Istituto Nazionale Tumori di Napoli, Via M. Semmola, Naples 80131, ItalyDepartment of Precision Medicine, University of Campania ''L. Vanvitelli'', Via Luigi De Crecchio 7, Naples 80138, Italy; Laboratory of Precision and Molecular Oncology, Biogem Scarl IRGS, Ariano Irpino, ItalyDepartment of Precision Medicine, University of Campania ''L. Vanvitelli'', Via Luigi De Crecchio 7, Naples 80138, Italy; Laboratory of Precision and Molecular Oncology, Biogem Scarl IRGS, Ariano Irpino, ItalyDepartment of Precision Medicine, University of Campania ''L. Vanvitelli'', Via Luigi De Crecchio 7, Naples 80138, Italy; Laboratory of Precision and Molecular Oncology, Biogem Scarl IRGS, Ariano Irpino, ItalyDepartment of Precision Medicine, University of Campania ''L. Vanvitelli'', Via Luigi De Crecchio 7, Naples 80138, Italy; Laboratory of Precision and Molecular Oncology, Biogem Scarl IRGS, Ariano Irpino, ItalySSD-Innovative Therapies for Abdominal Metastases, IRCCS ''G. Pascale'', Istituto Nazionale Tumori di Napoli, Via M. Semmola, Naples 80131, ItalyAMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, Casalnuovo Di Napoli 80013, ItalyBackground: 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.http://www.sciencedirect.com/science/article/pii/S1476558624001520Oligo-metastatic diseaseNext generations sequencingPrognosisBRAFKRASTumor mutational burden |
| spellingShingle | Alessandro Ottaiano Mariachiara Santorsola Roberto Sirica Annabella Di Mauro Antonella Di Carlo Monica Ianniello Francesco Sabbatino Rosa Castiello Francesca Del Peschio Marco Cascella Francesco Perri Maurizio Capuozzo Nicola Martucci Edoardo Mercadante Valentina Borzillo Rossella Di Franco Francesco Izzo Vincenza Granata Carmine Picone Antonella Petrillo Massimiliano Berretta Salvatore Stilo Luca Tarotto Anna Chiara Carratù Gerardo Ferrara Madhura Tathode Alessia Maria Cossu Marco Bocchetti Michele Caraglia Guglielmo Nasti Giovanni Savarese Clinical and genetic drivers of oligo-metastatic disease in colon cancer Neoplasia: An International Journal for Oncology Research Oligo-metastatic disease Next generations sequencing Prognosis BRAF KRAS Tumor mutational burden |
| title | Clinical and genetic drivers of oligo-metastatic disease in colon cancer |
| title_full | Clinical and genetic drivers of oligo-metastatic disease in colon cancer |
| title_fullStr | Clinical and genetic drivers of oligo-metastatic disease in colon cancer |
| title_full_unstemmed | Clinical and genetic drivers of oligo-metastatic disease in colon cancer |
| title_short | Clinical and genetic drivers of oligo-metastatic disease in colon cancer |
| title_sort | clinical and genetic drivers of oligo metastatic disease in colon cancer |
| topic | Oligo-metastatic disease Next generations sequencing Prognosis BRAF KRAS Tumor mutational burden |
| url | http://www.sciencedirect.com/science/article/pii/S1476558624001520 |
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