Research Project
2097428
Advances in the radiotherapeutic treatment of malignancies have often been the consequence of technical innovation. Application of new technology, however, can produce radiobiological consequences that differ from that with conventional methods. Such is the case with a method termed "pulse simulated" low dose rate irradiation (PSLDR). The new method, PSLDR, utilizes a single, high activity, radioactive source which scans through a tumor volume periodically during the treatment time. This is in contrast to the traditional continuous low dose rate irradiation (CLDR) where there are numerous radioactive sources in fixed positions within a tumor for the entire treatment. From a biological standpoint, the primary difference in PSLDR irradiation is the concentration of dose accumulation into short periods of time, and the repetition of these dose fractions at specific intervals. This is in contrast to CLDR where the dose accumulates uniformly throughout the entire treatment time. The possible extra toxicity to normal tissue from PSLDR could detract from the technical advantages of this modality. If PSLDR radiation parameters can be selected which do not increase normal tissue toxicity compared to CLDR, this new scanning source technique would have several advantages. The advantages include: 1] superior dose distribution; 2] precise control over the average dose rate which would make clinical treatment conditions more reproducible; and 3] radiation exposure and safety conditions for patients and hospital personnel will be greatly improved. In the radiotherapeutic treatment of pelvic malignancies such as prostate, cervix, uterine, and vaginal cancer, rectal toxicity is one of the major dose limiting factors. We therefore are proposing to utilize female Wistar rats to determine whether rectal toxicities from PSLDR are greater than those from CLDR. In particular, our goal is to determine the upper limit of dose fraction size for the PSLDR technique which will result in acceptable late rectal toxicity to CLDR. Five different PSLDR fraction sizes will be compared with CLDR when the overall dose rate is 0.75 Gy/h for each condition. Radiation toxicity will be analyzed both in terms of functional endpoints, such as bowel obstruction and weight loss, and histological alterations. These data will lead us to a greater understanding of the range of dose fraction sizes that will result in PSLDR toxicity which is equivalent to CLDR. The knowledge gained will aid us in the application of this new methodology to clinical treatment and thus hopefully improve tumor cure rates while reducing toxicities.
