TY - JOUR
T1 - Modeling the Prognostic Impact of CirculatingTumor Cells Enumeration in Metastatic Breast Cancer for ClinicalTrial Design Simulation
AU - Gerratana, Lorenzo
AU - Pierga, Jean Yves
AU - Reuben, James M.
AU - Davis, Andrew A.
AU - Wehbe, Firas H.
AU - Dirix, Luc
AU - Fehm, Tanja
AU - Nolé, Franco
AU - Gisbert-Criado, Rafael
AU - Mavroudis, Dimitrios
AU - Grisanti, Salvatore
AU - Garcia-Saenz, Jose A.
AU - Stebbing, Justin
AU - Caldas, Carlos
AU - Gazzaniga, Paola
AU - Manso, Luis
AU - Zamarchi, Rita
AU - Bonotto, Marta
AU - de Lascoiti, Angela Fernandez
AU - De Mattos-Arruda, Leticia
AU - Ignatiadis, Michail
AU - Sandri, Maria Teresa
AU - Generali, Daniele
AU - De Angelis, Carmine
AU - Dawson, Sarah Jane
AU - Janni, Wolfgang
AU - Carañana, Vicente
AU - Riethdorf, Sabine
AU - Solomayer, Erich Franz
AU - Puglisi, Fabio
AU - Giuliano, Mario
AU - Pantel, Klaus
AU - Bidard, François Clément
AU - Cristofanilli, Massimo
N1 - Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press.
PY - 2022/6
Y1 - 2022/6
N2 - 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).
AB - 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).
KW - K-nearest neighbor
KW - biomarker
KW - clinical trial model
KW - liquid biopsy
KW - machine learning
UR - http://www.scopus.com/inward/record.url?scp=85130980801&partnerID=8YFLogxK
U2 - 10.1093/oncolo/oyac045
DO - 10.1093/oncolo/oyac045
M3 - Article
C2 - 35278078
AN - SCOPUS:85130980801
SN - 1083-7159
VL - 27
SP - E561-E570
JO - Oncologist
JF - Oncologist
IS - 7
ER -