Novel Surrogate Markers as Predictors of Radiation Toxicity in Breast Cancer Patients Undergoing Helical Tomotherapy Compared to Standard Radiation Therapy

Overview

Radiotherapy is standard treatment for breast cancer after lumpectomy. Although this treatment showed substantial patient benefits and decrease of local recurrence and deaths from breast cancer, it also results in some severe late side-effects, such as skin fibrosis and cardiac failure. It's possible to offer breast irradiation (RT) and minimizing toxicities radiation dose to skin, lung and heart. This will be achieved with highly conformal RT delivery using Tomotherapy. We plan to evaluate this approach in clinical study. We plan also to evaluate the value of genomic, cellular and functional imaging endpoints as predictive markers of toxicity in our breast cancer population. This program is expected to prospectively validate that Tomotherapy for breast RT can decrease skin, lung and heart toxicities and maintaining excellent cancer control after lumpectomy.

Radiotherapy is standard treatment after conservative surgery for early-stage breast cancer. Although this approach substantially improves local control and reduces deaths from breast cancer, it also results in some severe late side-effects, including skin fibrosis, deaths from radiation-induced cardiac disease and lung cancer. We will undertake a novel approach to the evaluation of radiation-induced toxicity during and after whole breast irradiation (RT) following breast-conserving surgery, with the long-term strategic goal of minimizing RT toxicity in early breast cancer. Theoretically, it is possible to achieve this goal through very highly conformal RT delivery and avoidance of RT in toxicity-prone individuals where possible. We plan to evaluate the utility of genomic analysis, cellular DNA repair competence, and functional imaging endpoints as predictive markers of toxicity in our breast cancer population. This program is expected to (a) prospectively validate that HT for breast RT can decrease acute toxicity whilst maintaining excellent cancer control after BCS; (b) demonstrate that novel surrogate markers will aid in the prediction of acute and/or late normal tissue toxicity with a view to identify toxicity-prone (or conversely, robust) individuals from amongst the breast cancer population.

Conditions