CLINICAL INVESTIGATION Prostate A PHASE II STUDY OF HIGH-DOSE-RATE AFTERLOADING BRACHYTHERAPYAS MONOTHERAPY FORTHE TREATMENT OF LOCALIZED PROSTATE CANCER CARIE CORNER, F.R.C.R., ANA MARIA ROJAS,PH.D., LINDA BRYANT, D.C.R.(T.), PETER OSTLER, F.R.C.R., AND PETER HOSKIN, M.D., F.R.C.R. Mount Vernon Cancer Centre, Mount Vernon Hospital, Northwood, Middlesex, UK Purpose: A Phase II dose escalation study has been undertaken to evaluate high-dose-rate brachytherapy (HDRBT) monotherapy for prostate cancer. Methods and Materials: A total of 110 patients have been entered, all with locally advanced cancer. Three dose levels have been used; 34 Gy in four fractions, 36 Gy in four fractions, and 31.5 Gy in three fractions. These equate to 226Gy 1.5, 252Gy 1.5 , and 252Gy 1.5 , respectively. Thirty patients have received 34 Gy, 25 received 36 Gy, and 55 patients received 31.5 Gy. Acute and late toxicity was analyzed using the International Prostate Symptom Score, and urologic and rectal events were scored using the Radiation Therapy Oncology Group/Common Terminology Criteria scoring systems. Results: Seven patients required urethral catheterization at 2 weeks; 3 receiving 34 Gy, 1 receiving 36 Gy, and 3 receiving 31.5 Gy. Only 3 patients remained catheterized at 12 weeks. Radiation Therapy Oncology Group 1 and 2 gastrointestinal toxicity at 2 weeks was seen in 61%, 68%, and 77%, respectively. Grade 3 bladder toxicity was seen in 2 patients at 6 months, 1 each from the 36 Gy and 31.5 Gy arms. One patient from the 31.5-Gy cohort reported Grade 2 bowel toxicity at 6 months. Prostate-specific antigen (PSA), stratified for androgen deprivation therapy (ADT) and no-ADT patients ranged from 16.1–22.9 mg/L and 11.1–12.5 mg/L, respectively. This fell at 12 months to 0.2–0.6 mg/L and 0.5–1.4 mg/L, respectively. No PSA relapses have yet been seen with a median follow-up of 30 months (34 Gy), 18 months (36 Gy), and 11.8 months (31.5 Gy). Conclusions: Early results suggest an excellent biochemical response with no differences seen in acute and late tox- icity between doses of 34 Gy/four fractions, 36 Gy/four fractions, or 31.5 Gy/three fractions. Ó 2008 Elsevier Inc. Phase II study, Dose escalation, High-dose-rate monotherapy, Afterloading brachytherapy, Localized prostate cancer. INTRODUCTION There is now established evidence that dose escalating exter- nal beam radiotherapy (>70 Gy) in the treatment of localized prostate cancer improves biochemical disease control (1). Dose escalation, however, is often at the expense of an in- crease in genitourinary and gastrointestinal toxicity (2). Brachytherapy delivers a high localized dose to the tumor while minimizing normal tissue toxicity. The techniques available to deliver interstitial brachytherapy use either per- manent low-dose-rate (LDR) seeds or high-dose-rate (HDR) afterloading. Numerous studies have reported excellent bio- chemical disease control in favorable risk disease using io- dine-125 seeds with a prescription dose of 145 Gy (3–5) or using LDR palladium-103 seeds (6, 7). HDR brachytherapy for prostate cancer has been predominantly used as a boost af- ter external beam radiation therapy in unfavorable risk disease (8–11). In recent years, HDR monotherapy has been explored as an alternative to seed monotherapy in favorable risk pros- tate cancer (12). From the published data on the radiobiology of prostate cancer, it is believed to be a tumor with a low alpha beta (a/b) ratio 1.5 Gy (13–15). A recent overview of the liter- ature supports lower a/b values for prostate tumor than for rectum or bladder (16, 17). As a result, prostate cancers will be significantly more sensitive to radiation fraction size, which means that a small number of larger fractions will exploit this radiobiologic advantage and achieve bio- logic dose escalation. Reprint requests to: Carie Corner, F.R.C.R., Mount Vernon Can- cer Centre, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, UK. Tel: (+44) 1923 844533; Fax: (+44) 1923 844167; E-mail: cariecorner@yahoo.com Presented in part at the Groupe Europeen de Curitherapie–Euro- pean Society for Therapeutic Radiology and Oncology–International Society of Intraoperative Radiotherapy-Europe (GEC-ESTRO-ISO- IORT Europe) joint meeting, 2007, Montpellier, France, May 12, 2007. Conflict of interest: none. Acknowledgments—We are grateful to Mr. Y. Tsang for assistance with the statistical analyses. Received Oct 5, 2007, and in revised form Dec 16, 2007. Accepted for publication Dec 17, 2007. 441 Int. J. Radiation Oncology Biol. Phys., Vol. 72, No. 2, pp. 441–446, 2008 Copyright Ó 2008 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/08/$–see front matter doi:10.1016/j.ijrobp.2007.12.026