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- Title
Modeling the Prognostic Impact of Circulating Tumor Cells Enumeration in Metastatic Breast Cancer for Clinical Trial Design Simulation.
- Authors
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; Mattos-Arruda, Leticia De
- 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 (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 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).
- 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
- Publication
Oncologist, 2022, Vol 27, Issue 7, pe561
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1093/oncolo/oyac045