doi:10.1016/j.ijrobp.2007.02.034 CLINICAL INVESTIGATION Prostate TRANSPERINEAL INJECTION OF HYALURONIC ACID IN ANTERIOR PERIRECTAL FAT TO DECREASE RECTAL TOXICITY FROM RADIATION DELIVERED WITH INTENSITY MODULATED BRACHYTHERAPY OR EBRT FOR PROSTATE CANCER PATIENTS PEDRO J. PRADA, M.D.,* JOSÉ FERNÁNDEZ, M.D., PH.D.,* ALVARO A. MARTINEZ, M.D., † ÁNGELES DE LA RÚA, M.D.,* JOSE M. GONZALEZ, M.D.,* JOSE M. FERNANDEZ, M.D., ‡ AND GERMAN JUAN, M.D.* Departments of *Radiation Oncology and ‡ Radiology, Hospital Central de Asturias, Oviedo, Spain; † Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI. Purpose: Rectal toxicity remains a serious complication affecting quality of life for prostate cancer patients treated with radiotherapy. We began an investigational trial injecting hyaluronic acid (HA) in the perirectal fat to increase the distance between the prostate and the anterior rectal wall. This is the first report using HA injection in oncology. Methods and Materials: This is a trial of external beam radiation therapy with HDR brachytherapy boosts in prostate cancer. During the two high-dose-rate (HDR) fractions, thermoluminescent dosimeter dosimeters were placed in the urethra and in the rectum. Before the second HDR fraction, 3–7 mL (mean, 6 mL) of HA was injected under transrectal ultrasound guidance in the perirectal fat to systematically create a 1.5-cm space. Urethral and rectal HDR doses were calculated and measured. Computed tomography and magnetic resonance imaging were used to assess the stability of the new space. Results: Twenty-seven patients enrolled in the study. No toxicity was produced from the HA or the injection. In follow-up computed tomography and magnetic resonance imaging, the HA injection did not migrate or change in mass/shape for close to 1 year. The mean distance between rectum and prostate was 2.0 cm along the entire length of the prostate. The median measured rectal dose, when normalized to the median urethral dose, demonstrated a decrease in dose from 47.1% to 39.2% (p < 0.001) with or without injection. For an HDR boost dose of 1150 cGy, the rectum mean Dmax reduction was from 708 cGy to 507 cGy, p < 0.001, and the rectum mean Dmean drop was from 608 to 442 cGy, p < 0.001 post-HA injection. Conclusion: The new 2-cm distance derived from the HA injection significantly decreased rectal dose in HDR brachytherapy. Because of the several-month duration of stability, the same distance was maintained during the course of external beam radiation therapy. © 2007 Elsevier Inc. Prostate cancer, Brachytherapy, External radiation, Rectal protection and toxicity, Hyaluronic acid. INTRODUCTION During the last decade, high-dose-rate (HDR) and low- dose-rate (LDR) prostate brachytherapy have appreciated worldwide renaissance as prostate cancer treatments. This has been documented in the urology (1) and radiotherapy literature (2). It has been used as monotherapy for favorably staged patients (3–5) or as a boost to external beam radia- tion therapy (EBRT) for intermediate- and high-risk patients (6 –12). They are considered within the standard of care for prostate cancer patients (13–19). Although prostatectomy in any of its forms remains a highly accepted therapy, the shorter recovery time from brachytherapy and the significant decrease in toxicity from brachytherapy has made this treatment more acceptable to patients. In particular, the extremely low rates of urinary incontinence and decreased frequency of erectile dysfunc- tion make brachytherapy a more appealing treatment for prostate cancer patients (5, 13, 20). The main complications of radiotherapy are related to genitourinary dysfunction or rectal damage. Although tech- niques to decrease toxicity (e.g., peripheral loading, intra- operative real time dosimetry, and others) have been de- scribed, they are predominantly with the intention to decrease urethral damage (21–23). However, attempts to decrease rectal toxicity have been less successful (24, 25). The majority of publications are in agreement that, re- Reprint requests to: Pedro Prada, M.D., Department of Radia- tion Oncology, Hospital Central de Asturias, C/ Julian Claveria s/n Oviedo 33006 (Asturias), Spain. Tel: (+34) 985-271539; Fax: (+34) 985-271539; E-mail: pprada@telecable.es Conflict of interest: none. Received March 24, 2006, and in revised form Jan 31, 2007. Accepted for publication Feb 18, 2007. Int. J. Radiation Oncology Biol. Phys., Vol. 69, No. 1, pp. 95–102, 2007 Copyright © 2007 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/07/$–see front matter 95