Heterogeneity of targeted lung lesion predicts platinum-based first-line therapy outcomes and overall survival for metastatic triple-negative breast cancer patients with lung metastasis: a “PET biopsy” method

: Background: Platinum-based chemotherapy is widely used as first-line therapy for metastatic triple-negative breast cancer (mTNBC). Intratumor heterogeneity derived from fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is a potential predictor of treatment outcomes and the prognosis of breast cancer. However, the presence of multiple lesions and complex calculation methods leads to difficulties in the clinical use of this parameter for metastatic breast cancer. The aim of this study is to provide a convenient and effective measurement of intratumor heterogeneity to predict treatment outcomes for mTNBC patients with lung metastasis. Patients and methods: We enrolled mTNBC patients with lung metastasis who underwent 18F-FDG PET/CT scans before first-line therapy from three clinical trials (NCT01287624, NCT02341911 and NCT02546934). Apart from the regular FDG parameters, including standard uptake value (SUV), total lesion glycolysis (TLG) and metabolic tumor volume (MTV), we defined the lung index as the SUVmean divided by the difference between the SUVmax and SUVmean for the targeted lung lesion. The MTV was automatically exported from the manual delineation using software based on an adaptive threshold of SUV intensity >2.5 within the contouring margin. The TLG was calculated using the following formula: TLG=SUVmean×MTV. Progression-free survival (PFS) and overall survival were estimated by the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazard model. Results: The data from 31 patients were available for analysis. The median PFS of low-lung index (LI) patients was 8.1 months, which was significantly longer than that of high-LI patients (HR=3.3, 95% CI 1.5-7.3, p=0.003). Patients with low TLG had a significantly better PFS than those with high TLG (HR=2.6, 95% CI 1.2-5.8, p=0.014). Patients with low TLG had significantly longer overall survival than those with high TLG (31.2 months vs 13.9 months, HR=3.1, 95% CI 1.2-8.6, p=0.029). Multivariate analysis confirmed the predictive value of LI and TLG. Conclusions: This study proposed a new "PET biopsy" method to evaluate the intratumor heterogeneity of mTNBC on pretreatment 18F-FDG PET/CT scans and indicated the predictive value of LI and TLG for first-line platinum-based treatment outcomes and overall survival. These findings could help clinicians recognize patients who are likely to not only have a favorable response to platinum-based therapy but also a good prognosis.