Modeling the Prognostic Impact of Circulating Tumor Cells Enumeration in Metastatic Breast Cancer for Clinical Trial Design Simulation
| العنوان: | Modeling the Prognostic Impact of Circulating Tumor Cells Enumeration in Metastatic Breast Cancer for Clinical Trial Design Simulation |
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| المؤلفون: | Lorenzo Gerratana, Jean-Yves Pierga, James M Reuben, Andrew A Davis, Firas H Wehbe, Luc Dirix, Tanja Fehm, Franco Nolé, Rafael Gisbert-Criado, Dimitrios Mavroudis, Salvatore Grisanti, Jose A Garcia-Saenz, Justin Stebbing, Carlos Caldas, Paola Gazzaniga, Luis Manso, Rita Zamarchi, Marta Bonotto, Angela Fernandez de Lascoiti, Leticia De Mattos-Arruda, Michail Ignatiadis, Maria-Teresa Sandri, Daniele Generali, Carmine De Angelis, Sarah-Jane Dawson, Wolfgang Janni, Vicente Carañana, Sabine Riethdorf, Erich-Franz Solomayer, Fabio Puglisi, Mario Giuliano, Klaus Pantel, François-Clément Bidard, Massimo Cristofanilli |
| المساهمون: | Gerratana, Lorenzo, Pierga, Jean-Yve, Reuben, James M, Davis, Andrew A, Wehbe, Firas H, Dirix, Luc, Fehm, Tanja, Nolé, Franco, Gisbert-Criado, Rafael, Mavroudis, Dimitrio, Grisanti, Salvatore, Garcia-Saenz, Jose A, Stebbing, Justin, Caldas, Carlo, Gazzaniga, Paola, Manso, Lui, Zamarchi, Rita, Bonotto, Marta, Fernandez de Lascoiti, Angela, De Mattos-Arruda, Leticia, Ignatiadis, Michail, Sandri, Maria-Teresa, Generali, Daniele, De Angelis, Carmine, Dawson, Sarah-Jane, Janni, Wolfgang, Carañana, Vicente, Riethdorf, Sabine, Solomayer, Erich-Franz, Puglisi, Fabio, Giuliano, Mario, Pantel, Klau, Bidard, François-Clément, Cristofanilli, Massimo, Institut Català de la Salut, [Gerratana L] Department of Medical Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano (PN), Italy. [Pierga JY] Department of Medical Oncology, Institut Curie, Paris & Saint-Cloud, Paris University, Paris, France. [Reuben JM] Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. [Davis AA] Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Department of Medicine, Division of Oncology, Washington University School of Medicine in St. Louis, MO, USA. [Wehbe FH] Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. [Dirix L] Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Antwerp, Belgium. [De Mattos-Arruda L] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Mama - Càncer - Prognosi, K-nearest neighbor, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Neoplasms::Neoplastic Processes::Neoplasm Metastasis::Neoplastic Cells, Circulating [DISEASES], biomarker, clinical trial model, liquid biopsy, machine learning, Breast Neoplasms, Information Science::Computing Methodologies::Computer Simulation [INFORMATION SCIENCE], Simulació per ordinador, Ciencias de la información::metodologías computacionales::simulación por ordenador [CIENCIA DE LA INFORMACIÓN], Biomarkers, Tumor, Humans, Computer Simulation, Retrospective Studies, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Clinical Trials as Topic, Liver Neoplasms, Neoplastic Cells, Circulating, Prognosis, Oncology, neoplasias::procesos neoplásicos::metástasis neoplásica::células neoplásicas circulantes [ENFERMEDADES], Cèl·lules canceroses, Female |
| الوصف: | Biomarker; Liquid biopsy; Machine learning Biomarcadores; Biopsia líquida; Aprendizaje automático Biomarcadors; Biòpsia líquida; Aprenentatge automàtic Despite the strong prognostic stratification of circulating tumor cells (CTCs) enumeration in metastatic breast cancer (MBC), current clinical trials usually do not include a baseline CTCs in their design. This study aimed to generate a classifier for CTCs prognostic simulation in existing datasets for hypothesis generation in patients with MBC. A K-nearest neighbor machine learning algorithm was trained on a pooled dataset comprising 2436 individual MBC patients from the European Pooled Analysis Consortium and the MD Anderson Cancer Center to identify patients likely to have CTCs ≥ 5/7 mL blood (StageIVaggressive vs StageIVindolent). The model had a 65.1% accuracy and its prognostic impact resulted in a hazard ratio (HR) of 1.89 (Simulatedaggressive vs SimulatedindolentP < .001), similar to patients with actual CTCs enumeration (HR 2.76; P < .001). The classifier’s performance was then tested on an independent retrospective database comprising 446 consecutive hormone receptor (HR)-positive HER2-negative MBC patients. The model further stratified clinical subgroups usually considered prognostically homogeneous such as patients with bone-only or liver metastases. Bone-only disease classified as Simulatedaggressive had a significantly worse overall survival (OS; P < .0001), while patients with liver metastases classified as Simulatedindolent had a significantly better prognosis (P < .0001). Consistent results were observed for patients who had undergone CTCs enumeration in the pooled population. The differential prognostic impact of endocrine- (ET) and chemotherapy (CT) was explored across the simulated subgroups. No significant differences were observed between ET and CT in the overall population, both in terms of progression-free survival (PFS) and OS. In contrast, a statistically significant difference, favoring CT over ET was observed among Simulatedaggressive patients (HR: 0.62; P = .030 and HR: 0.60; P = .037, respectively, for PFS and OS). The study was supported by Lynn Sage Cancer Research Foundation and the the CRO Aviano 5x1000 2014 per la Ricerca Sanitaria, Cancer Specific Intramural Grant. The funding sources had no role in the study design, data collection, data analysis, interpretation, or writing of the manuscript. |
| وصف الملف: | ELETTRONICO; application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd28e762c51263f622c8e7d064b07334 http://hdl.handle.net/11368/3017431 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fd28e762c51263f622c8e7d064b07334 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |