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Modeling the Prognostic Impact of Circulating Tumor Cells Enumeration in Metastatic Breast Cancer for Clinical Trial Design Simulation.
- Source :
- Oncologist; Jul2022, Vol. 27 Issue 7, pe561-e570, 10p, 2 Charts, 5 Graphs
- Publication Year :
- 2022
-
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<superscript>aggressive</superscript> vs StageIV<superscript>indolent</superscript>). The model had a 65.1% accuracy and its prognostic impact resulted in a hazard ratio (HR) of 1.89 (Simulated<superscript>aggressive</superscript> vs Simulated<superscript>indolent</superscript> 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 Simulated<superscript>aggressive</superscript> had a significantly worse overall survival (OS; P <.0001), while patients with liver metastases classified as Simulated<superscript>indolent</superscript> 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 Simulated<superscript>aggressive</superscript> patients (HR: 0.62; P =. 030 and HR: 0.60; P =. 037, respectively, for PFS and OS). [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10837159
- Volume :
- 27
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Oncologist
- Publication Type :
- Academic Journal
- Accession number :
- 158429041
- Full Text :
- https://doi.org/10.1093/oncolo/oyac045