Combination external beam radiation and brachytherapy boost with androgen suppression for treatment of intermediate-risk prostate cancer: an initial report of CALGB 99809.

PURPOSE: Transperineal prostate brachytherapy (TPPB) can be used with external beam radiation therapy (EBRT) to provide a high-dose conformal boost to the prostate. The results of a multicenter Phase II trial assessing safety of combination of EBRT and TPPB boost with androgen suppression (AST) in treatment of intermediate-risk prostate cancer are present here. MATERIALS AND METHODS: Patients had intermediate-risk prostate cancer. Six months of AST was administered. EBRT to the prostate and seminal vesicles was administered to 45Gy followed by TPPB using either (125)I or (103)Pd to deliver an additional 100Gy or 90Gy. Toxicity was graded using the National Cancer Institute CTC version 2 and the Radiation Therapy Oncology Group late radiation morbidity scoring systems. RESULTS: Sixty-three patients were enrolled. Median follow-up was 38 months. Side effects of AST including sexual dysfunction and vasomotor symptoms were commonly observed. Apart from erectile dysfunction, short-term Grade 2 and 3 toxicity was noted in 21% and 7%, primarily genitourinary related. Long-term Grade 2 and 3 toxicities were noted in 13% and 3%. Two patients had Grade 3 dysuria that resolved with longer follow-up. The most common Grade 2 long-term toxicity was urinary frequency (5%). No biochemical or clinical evidence of progression was noted for the entire cohort. CONCLUSIONS: In a cooperative group setting, combination EBRT and TPPB boost with 6 months of AST was generally well tolerated with expected genitourinary and gastrointestinal toxicities. Further follow-up will be required to fully assess long-term toxicity and cancer control.

Pelvic radiotherapy, sex hormones, and breast cancer.

Radiotherapy for malignant and benign gynecologic disease in middle age has been found to be associated inversely with the risk of breast cancer in several published studies. The ovaries received substantial doses of radiation from such treatments, in the tens of Gray (Gy) from radiotherapy for cervical cancer and one to 10 Gy from radiotherapy for benign gynecologic disease (BGD). The relative risk of breast cancer incidence or mortality decreased with increasing radiation dose to the ovaries between zero to six Gy but varied little with further increases in dose. Evidence of a protective effect even among women irradiated past the age of 50 suggests a mechanism other than that associated with induction of an early menopause. An inverse association with radiotherapy among women over age 50 was seen only for women with ovarian doses exceeding about four to five Gy, namely, those treated for cervical cancer or with external beam X-rays for BGD. Ovarian doses of two to three Gy from intrauterine radium (226Ra) treatments for BGD were not associated with an appreciably reduced risk of breast cancer, even though the treatments had the intended effect of inducing menopause in women in their mid-40s. The relevant target cells in the ovaries for radiologic menopause likely are those involved in estrogen production. Although the postmenopausal ovary has largely stopped producing estrogens, it continues to secrete androgens. Serum hormone measurements on a small sample of cervical cancer patients indicate that high-dose pelvic radiotherapy eliminates or greatly reduces this residual androgen-producing activity in ovaries of postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)