Prospective assessment of the association between circulating tumor cells and control of brain disease after focal radiotherapy of breast cancer brain metastases

ABSTRACT Introduction Predicting the risk of early distant brain failure (DBF) is in demand for management decisions in patients who are candidates to local treatment of brain metastases. This study aims to analyze the association between circulating tumor cells (CTC) and brain disease control after stereotactic radiotherapy/radiosurgery (SRT) for breast cancer brain metastasis (BCBM). Methods Prospective assessment of CTC before (CTC1) and 4–5 weeks after (CTC2) SRT and its relations with the number of new lesions suggestive of BCBM before SRT (NL). CTC were quantified and analyzed by immunocytochemistry to evaluate the expression of the proteins COX2, EGFR, ST6GALNAC5, NOTCH1 and HER2. Distant brain failure-free survival (DBFFS), the primay endpoint, diffuse distant brain failure-free survival (D-DBFFS) and overall survival (OS) were estimated. Analysis for DBF within 6 months, with death as competing risk, was performed. Results Patients were included between 2016 and 2018. CTC were detected in all 39 patients before and in 34 of 35 patients after SRT. After median follow-up of 16.6 months, median DBFFS, D-DBFFS and OS were 15.3, 14.1 and 19.5 months, respectively. DBF at 6 months was 40% with CTC1 ≤ 0.5 and 8.82% with CTC1 > 0.5 CTC/mL (P = .007) and of D-DBF at 6 months was 40% with CTC1 ≤ 0.5 and 0 with CTC1 > 0.5 CTC/mL (P = .005) and 25% with NL/CTC1 > 6.8 and 2.65% with NL/CTC1 ≤ 6.8 (P = .063). On multivariate analysis, DBFFS was inferior with CTC1 ≤ 0.5 (HR 8.27, 95% CI, 2.12–32.3; P = .002) and D-DBFFS was inferior with CTC1 ≤ 0.5 (HR 10.22, 95% CI, 1.99–52.41; P = .005). Protein expression was not associated with outcomes. Conclusions These data suggest that CTC1 and NL/CTC1 may have a role as a biomarker of early diffuse DBF and subsequent guide between focal or whole-brain radiotherapy in patients with BCBM.