Local control by radiotherapy: is that all there is?

Abstract

Radiotherapy is a local treatment modality employed in breast cancer to reduce local recurrence following surgery. The observed association of optimal local control with improved survival was not expected in a disease characterized by early systemic spread. The underlying mechanisms whereby the application of ionizing radiation to the primary tumor site can have systemic effects remain unclear and are the subject of much debate. In the present article we discuss the hypothesis that radiotherapy has unique biological effects and that, in addition to killing residual neoplastic cells after surgery is performed, it might favorably alter the microenvironment at the primary tumor site during the process of wound healing and the development of antitumor immune responses.

Figure 1

Enhanced expression of the chemokine CXCL16 following irradiation of human breast cancer cells. HTB20 cells, derived from a primary human breast cancer [45], were harvested 48 hours after mock treatment (-) or after irradiation with a dose of 12 Gy (+) and a cell block was prepared as previously described [46]. Sections (8 μm) were stained with H&E or with goat polyclonal antiserum against human CXCL16 (R&D Systems, Minneapolis, MN, USA) or with normal goat serum as a control, followed by peroxidase-conjugated secondary antibody, were visualized with 3,3-diaminobenzidine (DAB Substrate Kit; BD Pharmingen, San Diego, CA, USA), and were counterstained with hematoxylin. Magnification ×400.

Figure 2

The surgical cavity and its microenvironment. (a) Process of epithelial to mesenchymal transition. (b) Digital radiograph of the lumpectomy cavity targeted by a radiation boost field, limited by a multileaf collimator. Increased density characterizes the persistent fluid at the surgical wound site. (c) Schematic representation of some of the effects radiation has on the immunological microenvironment of the tumor. DC, dendritic cell; ICAM, intracellular adhesion molecule; MHC, major histocompatibility complex; RT, radiation therapy.