In Reply We thank Drs Tsoutsou and Vozenin for their insightful comments regarding our recent article detailing the potential for using circulating tumor cell (CTC) status as a predictive biomarker for benefit of radiotherapy among patients with early-stage breast cancer.1
While radiotherapy was associated with longer locoregional recurrence-free survival, disease-free survival, and overall survival specifically for patients with CTC-positive disease, the mechanism underlying this finding remains unclear. Tsoutsou and Vozenin hypothesize that radiotherapy, via the local release of immunogenic factors, may lead to enhanced systemic antitumor immune activity that is able to eradicate subclinical micrometastatic disease. Patients with CTC-positive disease may therefore derive an abscopal benefit from radiotherapy via activation of the immune system beyond locoregional control. Alternatively, CTC status may be a surrogate for residual local disease or associated with endocrine resistance. Radiotherapy may therefore benefit patients with a CTC-positive status via more conventional principles. Further study is needed to clarify the clinical potential of CTC status as a predictive biomarker as well as to shed light on the underlying mechanisms of radiotherapeutic benefit in patients with a CTC-positive status.