CLINICAL INVESTIGATION Prostate
A PHASE II STUDY OF HIGH-DOSE-RATE AFTERLOADING BRACHYTHERAPY AS
MONOTHERAPY FOR THE TREATMENT OF LOCALIZED PROSTATE CANCER
, F.R.C.R., A
, 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
, and 252Gy
, 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
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 $1.5 Gy (13–15). A recent overview of the liter-
ature supports lower a/b values for prostate tumor than for
rectum or bladder (16, 17). As a result, prostate cancers
will be signiﬁcantly more sensitive to radiation fraction
size, which means that a small number of larger fractions
will exploit this radiobiologic advantage and achieve bio-
logic dose escalation.
Reprint requests to: Carie Corner, F.R.C.R., Mount Vernon Can-
cer Centre, Mount Vernon Hospital, Northwood, Middlesex HA6
2RN, UK. Tel: (+44) 1923 844533; Fax: (+44) 1923 844167;
Presented in part at the Groupe Europeen de Curitherapie–Euro-
pean Society for Therapeutic Radiology and Oncology–International
Society of Intraoperative Radiotherapy-Europe (GEC-ESTRO-ISO-
IORT Europe) joint meeting, 2007, Montpellier, France, May 12,
Conﬂict of interest: none.
Acknowledgments—We are grateful to Mr. Y. Tsang for assistance
with the statistical analyses.
Received Oct 5, 2007, and in revised form Dec 16, 2007.
Accepted for publication Dec 17, 2007.
Int. J. Radiation Oncology Biol. Phys., Vol. 72, No. 2, pp. 441–446, 2008
Copyright Ó 2008 Elsevier Inc.
Printed in the USA. All rights reserved
0360-3016/08/$–see front matter