International Journal of Radiation Oncology*Biology*Physics
Clinical investigation: prostateAssociation of rectal toxicity with thermal dose parameters in treatment of locally advanced prostate cancer with radiation and hyperthermia☆
Introduction
A primary concern in the treatment of clinically localized prostate cancer is the impact that any given treatment has on quality of life. Even in the setting of locally advanced disease, where more effective treatments beyond the current standard of combination of external beam radiation and androgen suppression are needed, the impact of more aggressive therapy has to be weighed against the potential toxicities of added therapy. Although many men with locally advanced disease eventually die of prostate cancer, death due to disease does not typically occur for several years. Therefore, the onset of side effects near term to treatment may have a very significant impact on quality of life.
Hyperthermia has been demonstrated to improve clinical outcomes, including survival, in several Phase III trials for a variety of malignancies 1, 2, 3, 4, 5. The role of hyperthermia in treatment of prostate cancer, however, remains to be fully defined. The favorable long-term safety profile of transrectal ultrasound hyperthermia for treatment of prostate cancer was previously reported in a Phase I series (6). This report indicated that hyperthermia could be safely administered with radiation. However, the association of temperature with treatment toxicity was not assessed. Because rectal toxicity is a primary concern with radiation therapy and potentially may be exacerbated by hyperthermia, definition of the association of thermal dose parameters with rectal toxicity should further the goal of delivery of hyperthermia in a maximally effective yet safe manner.
Despite the use of hyperthermia for over two decades in the treatment of pelvic tumors, to date little is known about the potential impact of heat on increased rectal toxicity. In this report, we define for the first time the association of thermal dose parameters with increased rectal toxicity in the setting of combined treatment of prostate cancer with hyperthermia and radiation.
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Methods and materials
All patients, including men with clinical stage T2b-T3b disease by 4th edition American Joint Committee On Cancer criteria, were enrolled in a Phase II study at the Dana-Farber Cancer Institute. All patients received 6660 cGy ± 5% normalized to 95% with two hyperthermia treatments administered at least 1 week apart during the first 4 weeks of radiation. Radiation therapy was administered with a four-field technique with ≥6-MV photons. After accrual of the first three patients, an amendment was
Results
Thirty patients received a total of 58 hyperthermia treatments between September 1997 and December 2000 on the Dana-Farber Cancer Institute Phase II hyperthermia trial. Median follow-up was 13 months (range: 4–36 months), and median age was 65 years (range: 45–78 years); 1992 American Joint Committee on Cancer clinical stages were represented as follows: T2b, 14; T2c, 8; T3a, 4; and T3b, 4 patients. Median Gleason score was 7 (range: 6–9), and median PSA was 11.9 ng/nL (range: 2.5–65 ng/nL).
Discussion
There are limited published findings on the impact of hyperthermia directed to the pelvis on rectal toxicity. Reports describing the relationship of thermal parameters with rectal toxicity have used tumor or generalized normal tissue temperature profiles. To date, the association of tissue-specific parameters for rectal wall temperature with increased rectal toxicity has not been defined.
In a final report of the Phase I trial using the transrectal ultrasound device used in our Phase II study,
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This work was supported by NCI Grant No. P-01 CA 31303.