Early Prediction of Tumor Response to Neoadjuvant Chemotherapy and Clinical Outcome in Breast Cancer Using a Novel FDG-PET Parameter for Cancer Stem Cell Metabolism

Chanwoo Kim, Sang-Ah Han, Kyu Yeoun Won, Il Ki Hong, Deog Yoon Kim, Chanwoo Kim, Sang-Ah Han, Kyu Yeoun Won, Il Ki Hong, Deog Yoon Kim

Abstract

Cancer stem cells (CSCs) contribute to chemoresistance and tumor relapse. By using the distinct metabolic phenotype of CSC, we designed novel PET parameters for CSC metabolism and investigated their clinical values. Patients with breast cancer who underwent 18F-FDG PET/CT before neoadjuvant chemotherapy (NAC) were retrospectively included. We developed a method to measure CSC metabolism using standardized uptake value histogram data. The predictive value of novel CSC metabolic parameters for pathologic complete response (pCR) was assessed with multivariable logistic regression. The association between the CSC parameter and disease-free survival (DFS) was also determined. We identified 82 patients with HER2-positive/triple-negative subtypes and 38 patients with luminal tumors. After multivariable analysis, only metabolic tumor volume for CSC (MTVcsc) among metabolic parameters remained the independent predictor of pCR (OR, 0.12; p = 0.022). MTVcsc successfully predicted pathologic tumor response to NAC in HER2-positive/triple-negative subtypes (accuracy, 74%) but not in the luminal subtype (accuracy, 29%). MTVcsc was also predictive of DFS, with a 3-year DFS of 90% in the lower MTVcsc group (<1.75 cm3) versus 72% in the higher group (>1.75 cm3). A novel data-driven PET parameter for CSC metabolism provides early prediction of pCR after NAC and DFS in HER2-positive and triple-negative subtypes.

Keywords: FDG PET/CT; breast cancer; cancer stem cell metabolism; neoadjuvant chemotherapy.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Workflow of measuring novel PET parameters for cancer stem cell metabolism.
Figure 2
Figure 2
Representative cases of a patient with pCR and a patient with the residual tumor. (A) A patient with the triple negative subtype (cT2N1) achieved pCR after receiving AC + T #8. (B) A patient with the triple negative subtype (cT2N1) failed to achieve pCR after receiving AC + T #8. pCR: pathologic complete response; AC + T: doxorubicin and cyclophosphamide followed by paclitaxel; MTVcsc: metabolic tumor volume for cancer stem cell; TLGcsc: total lesion glycolysis for cancer stem cell.
Figure 3
Figure 3
Patient flow. NAC: neoadjuvant chemotherapy; VOI: volume of interest; SUVmax: maximum standardized uptake value.
Figure 4
Figure 4
Kaplan-Meier plot for DFS according to MTVcsc in HER2-positive and TN subtypes. DFS: disease-free survival.

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