Neoadjuvant Stereotactic Ablative Radiotherapy To Treat Early Stage Breast Cancer Patients: The Role Of DCE-MRI
Abstract
The current standard of breast conserving therapy is lumpectomy followed by whole breast radiotherapy which is prohibitively long for many patients (4-6 weeks). In addition, the need for treating the whole breast has been questioned. The London Regional Cancer Program is enrolling early stage breast cancer patients in a prospective Phase I/II clinical trial (SIGNAL) to assess the safety/efficacy of neoadjuvant stereotactic ablative radiotherapy (SABR) to the tumour alone to reduce treatment times. This provides a unique opportunity to assess tumour response to SABR using non-invasive imaging. Patients received a pre-SABR dynamic contrast-enhanced (DCE)-MRI to guide target volume delineation. A subset also received post-SABR DCE-MRI to facilitate response assessment.
Recent safety concerns of long-term retention of gadolinium-based contrast agents (GBCA) in brain and bone led us to reduce the dose of GBCA to half the clinical dose part way through SIGNAL. Chapter 2 presents an investigation of the impact of this reduction on the inter- and intra-observer variability for target volume delineation and we found no significant decreases. These results are important for any context that requires repeated administrations of GBCAs to patients.
Chapter 3 presents an investigation of the impact of intra-session image registration on the voxel-by-voxel application of the Tofts model. Image registration led to significant reductions in the uncertainty in model parameter estimates and unphysical parameter estimates. Also, we showed that computation time could be reduced by a factor of two without affecting these results.
Chapter 4 presents an investigation of DCE-MRI based assessment of treatment response to SABR in early stage breast cancer. The analysis included two time delays post-SABR (6-7 or 16-19 days) and two SABR fractionation schemes (21Gy/1fraction or 30Gy/3fractions). DCE-MRI response assessment one-week post-SABR was confounded by acute inflammatory effects whereas 2.5 weeks appeared sufficiently long to minimize these effects. Kinetic parameters measured 2.5 weeks post-SABR in both fractionation groups were indicative of response, but only the single fraction led to enhancement in tissue surrounding the tumour. Such metrics will be valuable in adapting treatment to patients and in future studies that will investigate higher ablative doses with the potential to eliminate surgery.