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Intensity Modulated Breast Irradiation Under the Guidance of PET/CT Imaging
Whole-breast radiation therapy is part of standard treatment for women with early-stage breast cancer. Clinically, a number of complications and undesired radiation side effects have been associated with the treatment. Accelerated partial-breast irradiation using brachytherapy and conformal radiation therapy has been proposed based on the clinical observation that majority of the ipsilateral breast recurrences after radiation therapy are in the close proximity to the tumor bed. While the approach has several advantages, there exist considerable uncertainty in the target definition. The same problem also occurs in the definition of the boost volume in conventional whole-breast irradiation. The objective of this project is to establish a novel paradigm of molecular image guided breast IMRT and to demonstrate its advantage in enhancing tumor control while reducing complications and side effects. Our working hypotheses are 1) the use of positron emission tomography/computed tomography (PET/CT) with fluorothymidine (FLT) tracer and the elimination of breathing motion blurring effect will greatly enhance the sensitivity and specificity of breast imaging and allow to accurately delineate breast lesions; and 2) the development and integration of the state-of-art inverse planning technique will improve the sub-optimal performance of the existing planning techniques and provide us with highly conformal 3D dose distribution. The specific aims are to: 1) develop techniques to eliminate the blurring effect of breathing motion in PET/CT imaging and evaluate the efficacy of FLT PET/CT for breast radiotherapy; 2) establish an inverse planning system to optimize breast IMRT treatment; and 3) evaluate the potential of PET-guided partial-breast treatment by comparing with the existing techniques. Effective integration of the PET/CT with consideration of various uncertainties affords a significant opportunity to improve current breast radiotherapy and to enhance the success of the treatment. With the increased accuracy in tumor target definition and better dose coverage, the proposed technique should yield significantly improved treatment outcome while greatly reducing the radiation side effects. The development will also lay the technical foundation for the next generation breast radiation therapy (i.e., biologically conformal radiation therapy), in which the biology distribution derived from biological images is incorporated to truly individualize patient treatment.
Despite of the fact that radiotherapy has been a standard treatment for breast cancer, it has not been clear how much tissue surrounding the tumor bed needs to be irradiated and whole-breast irradiation strategy has been employed clinically, which is associated with a number of instances of moderate or even severe acute and chronic toxicity. Partial-breast irradiation targeting the tumor site rather than the whole breast has recently been proposed and early studies show promising results in preventing cancer from returning in selected patients. Because of the reduced treatment volume, the sensitive organs are better spared and side effects are reduced. In addition, a higher daily dose can be delivered to the tumor to accelerate the treatment course, which reduces the health care cost and is more convenient for patients.
While the new technique has several advantages and may substantially improve breast cancer management, the appropriate volume for irradiation has been a subject of considerable debate. Currently available imaging modalities are based on the detection of physical properties, which may not be consistent with the biological changes of the breast tissue. These methods are neither comprehensive nor infallible, especially in women with radiographically dense breasts. Biological imaging that improves breast cancer detection, localization, evaluation of therapy, and its effective integration in radiotherapy is highly desirable. This project is directed at establishing a novel paradigm of molecular imaging guided IMRT breast treatment and to demonstrate its advantage in enhancing tumor control while reducing treatment complications and side effects. Toward this goal, we will 1) develop techniques to eliminate the blurring effect of breathing motion in positron emission tomography/computed tomography (PET/CT) imaging and evaluate the efficacy of FLT PET/CT for breast radiotherapy; 2) establish an inverse planning system to optimize breast IMRT treatment; and 3) evaluate the potential of PET-guided partial-breast treatment by comparing with the existing techniques. The successful completion of the project will provide the radiation oncology discipline an effective means to accurately define the breast tumor target volume. Effective integration of the PET/CT with consideration of various uncertainties affords a significant opportunity to improve current breast radiotherapy and to enhance the success of the treatment. Normal structure avoidance will also improve the quality of life of breast cancer survivors.