Pretreatment ¹⁸F-FDG Uptake Heterogeneity Predicts Treatment Outcome of First-Line Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer

Background: Intratumoral heterogeneity of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) uptake in primary tumor has proven to be a surrogate marker for predicting treatment outcome in various tumors. However, the value of intraindividual heterogeneity in metastatic diseases remains unknown. The aim of this study was to evaluate pretreatment positron emission tomography/computed tomography (PET/CT) ¹⁸F-FDG-based heterogeneity for the prediction of first-line treatment outcome in metastatic triple-negative breast cancer (mTNBC).

Materials and methods: mTNBC patients from three clinical trials (NCT00601159, NCT01287624, and NCT02341911) with whole-body ¹⁸F-FDG PET/CT scan before first-line gemcitabine/platinum were included. Heterogeneity index (HI) and the maximum of FDG uptake (MAX) across total metastatic lesions (-T) on baseline PET/CT scans were assessed. HI was measured by MAX divided by the minimum FDG uptake across metastatic lesions. Optimal cutoffs were determined by time-dependent receiver operator characteristics (ROC) analysis. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.

Results: A total of 42 mTNBC patients were included in this study. The median PFS of patients with high HI-T (>1.9) and high MAX-T (>10.5) was significantly shorter than patients with low HI-T (<1.9; p = .049) and low MAX-T (<10.5; p = .001). In terms of OS, only high MAX-T was significant for poorer outcome (p = .013). ROC curve analysis confirmed the predictive value of MAX and HI in mTNBC patients. Area under the ROC curve for MAX-T and HI-T was 0.75 and 0.65, indicating a higher predictive accuracy than conventional clinical risk factors.

Conclusion: HI and MAX measured among metastatic lesions on pretreatment ¹⁸F-FDG PET/CT scans could be potential predicators for first-line treatment outcome in patients with mTNBC.

Implications for practice: Intratumoral heterogeneity of ¹⁸F-fluorodeoxyglucose (FDG) uptake in primary tumor has proven to be a robust surrogate predictive marker. A novel positron emission tomography/computed tomography (PET/CT) parameter-heterogeneity index (HI) to quantify the heterogeneous characteristics of metastatic disease is proposed. Triple-negative breast cancer (TNBC) is a highly heterogeneous disease and remains a clinical challenge. The predictive performance of HI, along with the maximum FDG uptake (MAX), measured on pretreatment PET/CT scans in patients with metastatic TNBC was evaluated. Results indicate that HI and MAX may serve as applicable imaging predicators for treatment outcome of metastatic TNBC in clinical practice.