Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status
Importance: We know of no data on the prognostic value of primary tumor location (PTL) according to BRAF, RAS, and microsatellite instability (MSI) status in patients who have undergone resection for colon cancer (CC) and have been treated with current standard adjuvant chemotherapy. Objective: To d...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2018 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/172459 |
| Online Access: | https://hdl.handle.net/2445/172459 |
| Access Level: | Open access |
| Keyword: | Càncer colorectal Pronòstic mèdic Colorectal cancer Prognosis |
| _version_ | 1878740953671401472 |
|---|---|
| author | Taieb, Julien |
| author2 | Kourie, Hampig Raphael Emile, Jean-François Malicot, Karine Le Balogoun, Ralyath Tabernero Caturla, Josep Mini, Enrico Folprecht, Gunnar Van Laethem, Jean-Luc Mulot, Claire Bouché, Olivier Aparicio, Thomas Michel, Pierre Thaler, Josef Bridgewater, John Van Cutsem, Eric Perkins, Géraldine Lepage, Come Salazar Soler, Ramón Laurent-Puig, Pierre Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 Investigators. |
| author2_role | author author author author author author author author author author author author author author author author author author author author |
| author_browse | Aparicio, Thomas Balogoun, Ralyath Bouché, Olivier Bridgewater, John Emile, Jean-François Folprecht, Gunnar Kourie, Hampig Raphael Laurent-Puig, Pierre Lepage, Come Malicot, Karine Le Michel, Pierre Mini, Enrico Mulot, Claire Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 Investigators. Perkins, Géraldine Salazar Soler, Ramón Tabernero Caturla, Josep Taieb, Julien Thaler, Josef Van Cutsem, Eric Van Laethem, Jean-Luc |
| author_facet | Taieb, Julien Kourie, Hampig Raphael Emile, Jean-François Malicot, Karine Le Balogoun, Ralyath Tabernero Caturla, Josep Mini, Enrico Folprecht, Gunnar Van Laethem, Jean-Luc Mulot, Claire Bouché, Olivier Aparicio, Thomas Michel, Pierre Thaler, Josef Bridgewater, John Van Cutsem, Eric Perkins, Géraldine Lepage, Come Salazar Soler, Ramón Laurent-Puig, Pierre Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 Investigators. |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| description | Importance: We know of no data on the prognostic value of primary tumor location (PTL) according to BRAF, RAS, and microsatellite instability (MSI) status in patients who have undergone resection for colon cancer (CC) and have been treated with current standard adjuvant chemotherapy. Objective: To determine the prognostic and predictive value of PTL according to BRAF, RAS, and MSI status in patients with stage III CC receiving adjuvant treatment with FOLFOX (folinic acid [leucovorin calcium], fluorouracil, and oxaliplatin) with or without cetuximab. Design, Setting, and Participants: This post hoc analysis included patients with available tumor blocks of resected stage III colon adenocarcinoma who participated in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 phase 3 randomized trial. Among the 2559 patients who underwent randomization, 1900 were screened by next-generation sequencing, which showed that 1869 had full information concerning PTL. We categorized primary tumor site as located proximal (right) or distal (left) to the splenic flexure. Main Outcomes and Measures: The associations between PTL (right- vs left-sided) and disease-free survival (DFS), survival after relapse (SAR), and overall survival (OS) were assessed by Cox models and adjusted for clinical and pathological features, treatment, and MSI, BRAF, and RAS status. Results: Among the 1869 patients (1056 [57%] male; mean [SD] age, 59.4 [9.5] years) with full molecular data analyzed, 755 (40%) had a right-sided tumor, 164 (10%) had MSI, 942 (50%) had RAS mutations, and 212 (11%) had BRAF mutations. Right-sided tumor location was not prognostic for DFS in the whole population but was associated with a shorter SAR (hazard ratio [HR], 1.54; 95% CI, 1.23-1.93; P = .001) and OS (HR, 1.25; 95% CI, 1.02-1.54; P = .03). When looking at DFS in the different molecular subgroups, we found similar results for microsatellite-stable tumors and tumors with MSI; a better DFS in right-sided vs left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P = .046); and a worse DFS in right-sided vs left-sided tumors in patients with RAS and BRAF double wild type (HR, 1.39; 95% CI, 1.01-1.92; P = .04). These results were found independently of the treatment received, and no beneficial effect of cetuximab on DFS or OS was observed in left-sided tumors. Conclusions and Relevance: Although right-sided tumor location is associated with poor survival in patients with metastatic CC as previously reported, the association with disease recurrence appears to vary for patients with stage III CC and RAS or BRAF mutations vs those with double wild type. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_dc67f82f65615a8ca07d30dbc42e7166 |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/172459 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | American Medical Association |
| publisherStr | American Medical Association |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status Taieb, Julien Kourie, Hampig Raphael Emile, Jean-François Malicot, Karine Le Balogoun, Ralyath Tabernero Caturla, Josep Mini, Enrico Folprecht, Gunnar Van Laethem, Jean-Luc Mulot, Claire Bouché, Olivier Aparicio, Thomas Michel, Pierre Thaler, Josef Bridgewater, John Van Cutsem, Eric Perkins, Géraldine Lepage, Come Salazar Soler, Ramón Laurent-Puig, Pierre Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 Investigators. Càncer colorectal Pronòstic mèdic Colorectal cancer Prognosis Importance: We know of no data on the prognostic value of primary tumor location (PTL) according to BRAF, RAS, and microsatellite instability (MSI) status in patients who have undergone resection for colon cancer (CC) and have been treated with current standard adjuvant chemotherapy. Objective: To determine the prognostic and predictive value of PTL according to BRAF, RAS, and MSI status in patients with stage III CC receiving adjuvant treatment with FOLFOX (folinic acid [leucovorin calcium], fluorouracil, and oxaliplatin) with or without cetuximab. Design, Setting, and Participants: This post hoc analysis included patients with available tumor blocks of resected stage III colon adenocarcinoma who participated in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 phase 3 randomized trial. Among the 2559 patients who underwent randomization, 1900 were screened by next-generation sequencing, which showed that 1869 had full information concerning PTL. We categorized primary tumor site as located proximal (right) or distal (left) to the splenic flexure. Main Outcomes and Measures: The associations between PTL (right- vs left-sided) and disease-free survival (DFS), survival after relapse (SAR), and overall survival (OS) were assessed by Cox models and adjusted for clinical and pathological features, treatment, and MSI, BRAF, and RAS status. Results: Among the 1869 patients (1056 [57%] male; mean [SD] age, 59.4 [9.5] years) with full molecular data analyzed, 755 (40%) had a right-sided tumor, 164 (10%) had MSI, 942 (50%) had RAS mutations, and 212 (11%) had BRAF mutations. Right-sided tumor location was not prognostic for DFS in the whole population but was associated with a shorter SAR (hazard ratio [HR], 1.54; 95% CI, 1.23-1.93; P = .001) and OS (HR, 1.25; 95% CI, 1.02-1.54; P = .03). When looking at DFS in the different molecular subgroups, we found similar results for microsatellite-stable tumors and tumors with MSI; a better DFS in right-sided vs left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P = .046); and a worse DFS in right-sided vs left-sided tumors in patients with RAS and BRAF double wild type (HR, 1.39; 95% CI, 1.01-1.92; P = .04). These results were found independently of the treatment received, and no beneficial effect of cetuximab on DFS or OS was observed in left-sided tumors. Conclusions and Relevance: Although right-sided tumor location is associated with poor survival in patients with metastatic CC as previously reported, the association with disease recurrence appears to vary for patients with stage III CC and RAS or BRAF mutations vs those with double wild type. American Medical Association https://hdl.handle.net/2445/172459 |
| spellingShingle | Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status Taieb, Julien Càncer colorectal Pronòstic mèdic Colorectal cancer Prognosis |
| status_str | publishedVersion |
| title | Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status |
| title_full | Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status |
| title_fullStr | Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status |
| title_full_unstemmed | Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status |
| title_short | Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status |
| title_sort | Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status |
| topic | Càncer colorectal Pronòstic mèdic Colorectal cancer Prognosis |
| topic_facet | Càncer colorectal Pronòstic mèdic Colorectal cancer Prognosis |
| url | https://hdl.handle.net/2445/172459 |