Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: Analysis from the ProfiLER 01 trial
Background: Advanced sarcoma is a group of heterogeneous disease with poor prognosis and poor efficacy of medical treatment. They represent a promising group of tumors to assess molecular-based therapy (MBT) strategy. Patients and methods: Genomic profiles of patients with advanced sarcoma included...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-12-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523320303624 |
| _version_ | 1818199025928634368 |
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| author | Patrick Arnaud-Coffin Mehdi Brahmi Hélène Vanacker Lauriane Eberst Olivier Tredan Valery Attignon Daniel Pissaloux Emilie Sohier Philippe Cassier Gwenaelle Garin David Pérol Jean-Yves Blay Armelle Dufresne |
| author_facet | Patrick Arnaud-Coffin Mehdi Brahmi Hélène Vanacker Lauriane Eberst Olivier Tredan Valery Attignon Daniel Pissaloux Emilie Sohier Philippe Cassier Gwenaelle Garin David Pérol Jean-Yves Blay Armelle Dufresne |
| author_sort | Patrick Arnaud-Coffin |
| collection | DOAJ |
| description | Background: Advanced sarcoma is a group of heterogeneous disease with poor prognosis and poor efficacy of medical treatment. They represent a promising group of tumors to assess molecular-based therapy (MBT) strategy. Patients and methods: Genomic profiles of patients with advanced sarcoma included in the ProfiLER program were established by NGS using a 69 genes panel and CGH array. A weekly molecular board reviewed genomic reports to select relevant genomic alterations and propose recommendations for MBT. Results: A genomic profile was available for 158 of 164 patients. At least 1 relevant genomic alteration was reported for 106 patients (67%), with frequent multiple alterations (68%). In total, 289 relevant genomic alterations were identified in 143 different genes; 139 homozygous deletions, 86 gene amplifications and 64 somatic mutations. The most frequently impacted genes were TP53, Rb1, CDKN2A, CDK4, MDM2, and PTEN. MBT was recommended for 47 patients and initiated for 13 patients.One objective response was observed for an angiosarcoma treated with pazopanib for FLT4 amplification; 4 patients had a stable disease, including a long-lasting 33 months stabilization. Conclusion: Genomic profiling for advanced sarcoma is feasible, even for bone sarcoma. A small proportion of patients are eventually treated with MBT, similar to other tumor types. We could not demonstrate this strategy to be beneficial to patients. Our data suggest that molecular profiling should not be used in routine practice but warrants further exploration in clinical trials, focusing on sarcoma with complex genomic, and adding transcriptomic analysis to the copy number and mutational analyses. |
| first_indexed | 2024-12-12T02:15:13Z |
| format | Article |
| id | doaj.art-ffc501a49bf846bd911d361813418c43 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-12T02:15:13Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-ffc501a49bf846bd911d361813418c432022-12-22T00:41:49ZengElsevierTranslational Oncology1936-52332020-12-011312100870Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: Analysis from the ProfiLER 01 trialPatrick Arnaud-Coffin0Mehdi Brahmi1Hélène Vanacker2Lauriane Eberst3Olivier Tredan4Valery Attignon5Daniel Pissaloux6Emilie Sohier7Philippe Cassier8Gwenaelle Garin9David Pérol10Jean-Yves Blay11Armelle Dufresne12Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France; University Claude Bernard, Léon Bérard Cancer Center, Lyon, FranceDepartment of Medical Oncology, Léon Bérard Cancer Center, Lyon, France; University Claude Bernard, Léon Bérard Cancer Center, Lyon, FranceDepartment of Medical Oncology, Léon Bérard Cancer Center, Lyon, FranceDepartment of Medical Oncology, Léon Bérard Cancer Center, Lyon, FranceDepartment of Medical Oncology, Léon Bérard Cancer Center, Lyon, FranceDepartment of Translational Research and Innovation, Léon Bérard Cancer Center, Lyon, FranceDepartment of Translational Research and Innovation, Léon Bérard Cancer Center, Lyon, FranceDepartment of Translational Research and Innovation, Léon Bérard Cancer Center, Lyon, FranceDepartment of Medical Oncology, Léon Bérard Cancer Center, Lyon, FranceDepartment of Clinical Research and Innovation, Léon Bérard Cancer Center, Lyon, FranceDepartment of Clinical Research and Innovation, Léon Bérard Cancer Center, Lyon, FranceDepartment of Medical Oncology, Léon Bérard Cancer Center, Lyon, France; University Claude Bernard, Léon Bérard Cancer Center, Lyon, FranceDepartment of Medical Oncology, Léon Bérard Cancer Center, Lyon, France; Corresponding author at: Department of Medical Oncology, Léon Bérard Cancer Center, 28 Rue Laennec, 69008 Lyon, France.Background: Advanced sarcoma is a group of heterogeneous disease with poor prognosis and poor efficacy of medical treatment. They represent a promising group of tumors to assess molecular-based therapy (MBT) strategy. Patients and methods: Genomic profiles of patients with advanced sarcoma included in the ProfiLER program were established by NGS using a 69 genes panel and CGH array. A weekly molecular board reviewed genomic reports to select relevant genomic alterations and propose recommendations for MBT. Results: A genomic profile was available for 158 of 164 patients. At least 1 relevant genomic alteration was reported for 106 patients (67%), with frequent multiple alterations (68%). In total, 289 relevant genomic alterations were identified in 143 different genes; 139 homozygous deletions, 86 gene amplifications and 64 somatic mutations. The most frequently impacted genes were TP53, Rb1, CDKN2A, CDK4, MDM2, and PTEN. MBT was recommended for 47 patients and initiated for 13 patients.One objective response was observed for an angiosarcoma treated with pazopanib for FLT4 amplification; 4 patients had a stable disease, including a long-lasting 33 months stabilization. Conclusion: Genomic profiling for advanced sarcoma is feasible, even for bone sarcoma. A small proportion of patients are eventually treated with MBT, similar to other tumor types. We could not demonstrate this strategy to be beneficial to patients. Our data suggest that molecular profiling should not be used in routine practice but warrants further exploration in clinical trials, focusing on sarcoma with complex genomic, and adding transcriptomic analysis to the copy number and mutational analyses.http://www.sciencedirect.com/science/article/pii/S1936523320303624Molecular profilingSarcomaPrecision medicineMolecular-targeted therapyAdvanced cancer |
| spellingShingle | Patrick Arnaud-Coffin Mehdi Brahmi Hélène Vanacker Lauriane Eberst Olivier Tredan Valery Attignon Daniel Pissaloux Emilie Sohier Philippe Cassier Gwenaelle Garin David Pérol Jean-Yves Blay Armelle Dufresne Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: Analysis from the ProfiLER 01 trial Translational Oncology Molecular profiling Sarcoma Precision medicine Molecular-targeted therapy Advanced cancer |
| title | Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: Analysis from the ProfiLER 01 trial |
| title_full | Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: Analysis from the ProfiLER 01 trial |
| title_fullStr | Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: Analysis from the ProfiLER 01 trial |
| title_full_unstemmed | Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: Analysis from the ProfiLER 01 trial |
| title_short | Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: Analysis from the ProfiLER 01 trial |
| title_sort | therapeutic relevance of molecular screening program in patients with metastatic sarcoma analysis from the profiler 01 trial |
| topic | Molecular profiling Sarcoma Precision medicine Molecular-targeted therapy Advanced cancer |
| url | http://www.sciencedirect.com/science/article/pii/S1936523320303624 |
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