Alison Dormieux1, Laura Mezquita2, Paul Henry Cournede3, Jordi Remon4, Melodie Tazdait1, Ludovic Lacroix5, Etienne Rouleau5, Julien Adam6, Maria-Virginia Bluthgen2, Francesco Facchinetti7, Lambros Tselikas1, Frank Aboubakar2, Charles Naltet2, Pernelle Lavaud2, Anas Gazzah2, Cécile Le Pechoux8, Nathalie Lassau1,9, Corinne Balleyguier1,9, David Planchard2, Benjamin Besse2, Caroline Caramella10,11,12. 1. Imaging Department, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France. 2. Cancer Medicine Department, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France. 3. MICS laboratory, CentraleSupélec, Université Paris-Saclay, Gif-sur-Yvette, France. 4. Medical Oncology Department, Centro Integral Oncología Clara Campal Bacelona, HM-Delfos, Barcelona, Spain. 5. Molecular Biology Department, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France. 6. Pathology Department, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France. 7. Research Department (U981), Gustave Roussy Cancer Campus, Université Paris-Saclay, F-94805, Villejuif, France. 8. Radiation Therapy Department, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France. 9. IR4M, UMR 8081, CNRS, Université Paris-Saclay, F-91400, Orsay, France. 10. Imaging Department, Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France. caroline.caramella@gustaveroussy.fr. 11. IR4M, UMR 8081, CNRS, Université Paris-Saclay, F-91400, Orsay, France. caroline.caramella@gustaveroussy.fr. 12. Radiology Department, Gustave Roussy, 114 Rue Édouard-Vaillant, 94805, Villejuif Cedex, France. caroline.caramella@gustaveroussy.fr.
Abstract
OBJECTIVES: The aim of our study was to investigate the association between driver oncogene alterations and metastatic patterns on imaging assessment, in a large cohort of metastatic lung adenocarcinoma patients. METHODS: From January 2010 to May 2017, 550 patients with stage IV lung adenocarcinoma with molecular analysis were studied retrospectively including 135 EGFR-mutated, 81 ALK-rearrangement, 47 BRAF-mutated, 141 KRAS-mutated, and 146 negative tumors for these 4 mutations (4N). After review of the complete imaging report by two radiologists (junior and senior) to identify metastatic sites, univariate correlation analyzes were performed. RESULTS: We found differences in metastatic tropism depending on the molecular alteration type when compared with the non-mutated 4N group: in the EGFR group, pleural metastases were more frequent (32% versus 20%; p = 0.021), and adrenal and node metastases less common (6% versus 23%; p < 0.001 and 11% versus 23%; p = 0.011). In the ALK group, there were more brain and lung metastases (respectively 42% versus 29%; p = 0.043 and 37% versus 24%; p = 0.037). In the BRAF group, pleural and pericardial metastases were more common (respectively 47% versus 20%; p < 0.001 and 11% versus 3%; p = 0.04) and bone metastases were rarer (21% versus 42%; p = 0.011). Lymphangitis was more frequent in EGFR, ALK, and BRAF groups (respectively 6%, 7%, and 15% versus 1%); p = 0.016; p = 0.009; and p < 0.001. CONCLUSION: The application of these correlations between molecular status and metastatic tropism in clinical practice may lead to earlier and more accurate identification of patients for targeted therapy. KEY POINTS: • Bone and brain metastasis are the most common organs involved in lung adenocarcinoma but the relative incidence of each metastatic site depends on the molecular alteration. • EGFR-mutated tumors preferentially spread to the pleura and less commonly to adrenals, ALK-rearrangement tumors usually spread to the brain and the lungs, whereas BRAF-mutated tumors are unlikely to spread to bones and have a serous (pericardial ad pleural) tropism. • These correlations could help in the clinical management of patients with metastatic lung adenocarcinoma.
OBJECTIVES: The aim of our study was to investigate the association between driver oncogene alterations and metastatic patterns on imaging assessment, in a large cohort of metastatic lung adenocarcinomapatients. METHODS: From January 2010 to May 2017, 550 patients with stage IV lung adenocarcinoma with molecular analysis were studied retrospectively including 135 EGFR-mutated, 81 ALK-rearrangement, 47 BRAF-mutated, 141 KRAS-mutated, and 146 negative tumors for these 4 mutations (4N). After review of the complete imaging report by two radiologists (junior and senior) to identify metastatic sites, univariate correlation analyzes were performed. RESULTS: We found differences in metastatic tropism depending on the molecular alteration type when compared with the non-mutated 4N group: in the EGFR group, pleural metastases were more frequent (32% versus 20%; p = 0.021), and adrenal and node metastases less common (6% versus 23%; p < 0.001 and 11% versus 23%; p = 0.011). In the ALK group, there were more brain and lung metastases (respectively 42% versus 29%; p = 0.043 and 37% versus 24%; p = 0.037). In the BRAF group, pleural and pericardial metastases were more common (respectively 47% versus 20%; p < 0.001 and 11% versus 3%; p = 0.04) and bone metastases were rarer (21% versus 42%; p = 0.011). Lymphangitis was more frequent in EGFR, ALK, and BRAF groups (respectively 6%, 7%, and 15% versus 1%); p = 0.016; p = 0.009; and p < 0.001. CONCLUSION: The application of these correlations between molecular status and metastatic tropism in clinical practice may lead to earlier and more accurate identification of patients for targeted therapy. KEY POINTS: • Bone and brain metastasis are the most common organs involved in lung adenocarcinoma but the relative incidence of each metastatic site depends on the molecular alteration. • EGFR-mutated tumors preferentially spread to the pleura and less commonly to adrenals, ALK-rearrangement tumors usually spread to the brain and the lungs, whereas BRAF-mutated tumors are unlikely to spread to bones and have a serous (pericardial ad pleural) tropism. • These correlations could help in the clinical management of patients with metastatic lung adenocarcinoma.
Entities:
Keywords:
Adenocarcinoma of lung; Multimodal imaging; Mutation; Neoplasm metastasis
Authors: Vincent Fallet; Lise Matton; Antoine Schernberg; Anthony Canellas; François H Cornelis; Jacques Cadranel Journal: Transl Lung Cancer Res Date: 2021-07