1. Modeling the Prognostic Impact of Circulating Tumor Cells Enumeration in Metastatic Breast Cancer for Clinical Trial Design Simulation.
- Author
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Gerratana, Lorenzo, Pierga, Jean-Yves, Reuben, James M, Davis, Andrew A, Wehbe, Firas H, Dirix, Luc, Fehm, Tanja, Nolé, Franco, Gisbert-Criado, Rafael, Mavroudis, Dimitrios, Grisanti, Salvatore, Garcia-Saenz, Jose A, Stebbing, Justin, Caldas, Carlos, Gazzaniga, Paola, Manso, Luis, Zamarchi, Rita, Bonotto, Marta, Lascoiti, Angela Fernandez de, and Mattos-Arruda, Leticia De
- Subjects
BIOMARKERS ,CLINICAL trials ,RESEARCH methodology ,METASTASIS ,MACHINE learning ,MANN Whitney U Test ,SURVIVAL analysis (Biometry) ,DESCRIPTIVE statistics ,CELL lines ,BODY fluid examination ,BREAST tumors - Abstract
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 (StageIV
aggressive vs StageIVindolent ). The model had a 65.1% accuracy and its prognostic impact resulted in a hazard ratio (HR) of 1.89 (Simulatedaggressive vs Simulatedindolent P <.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). [ABSTRACT FROM AUTHOR]- Published
- 2022
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