Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial

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• 作者：Prof David Dearnaley ; FRCR^a ; ^b ; ^{david.dearnaley@icr.ac.uk} ; Isabel Syndikus ; FRCR^c ; Georges Sumo ; MSc^b ; Margaret Bidmead ; MSc^a ; David Bloomfield ; FRCR^d ; Catharine Clark ; PhD^e ; Annie Gao ; MSc^b ; Shama Hassan ; MSc^b ; Prof Alan Horwich ; FRCR^a ; ^b ; Robert Huddart ; FRCR^a ; ^b ; Vincent Khoo ; MD^a ; ^b ; Peter Kirkbride ; FRCR^j ; Helen Mayles ; MSc^c ; Philip Mayles ; PhD^c ; Olivia Naismith ; MSc^a ; Chris Parker ; FRCR^a ; Helen Patterson ; FRCR^f ; Martin Russell ; FRCP^g ; Christopher Scrase ; FRCR^h ; Chris South ; MSc^a ; John Staffurth ; MDⁱ ; Emma Hall ; PhD^b
• 刊名：Lancet Oncology
• 出版年：2012
• 出版时间：January 2012
• 年：2012
• 卷：13
• 期：1
• 页码：43-54
• 全文大小：461 K

文摘

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Summary

Background

Prostate cancer might have high radiation-fraction sensitivity, implying a therapeutic advantage of hypofractionated treatment. We present a pre-planned preliminary safety analysis of side-effects in stages 1 and 2 of a randomised trial comparing standard and hypofractionated radiotherapy.

Methods

We did a multicentre, randomised study and recruited men with localised prostate cancer between Oct 18, 2002, and Aug 12, 2006, at 11 UK centres. Patients were randomly assigned in a 1:1:1 ratio to receive conventional or hypofractionated high-dose intensity-modulated radiotherapy, and all were given with 3-6 months of neoadjuvant androgen suppression. Computer-generated random permuted blocks were used, with risk of seminal vesicle involvement and radiotherapy-treatment centre as stratification factors. The conventional schedule was 37 fractions of 2 Gy to a total of 74 Gy. The two hypofractionated schedules involved 3 Gy treatments given in either 20 fractions to a total of 60 Gy, or 19 fractions to a total of 57 Gy. The primary endpoint was proportion of patients with grade 2 or worse toxicity at 2 years on the Radiation Therapy Oncology Group (RTOG) scale. The primary analysis included all patients who had received at least one fraction of radiotherapy and completed a 2 year assessment. Treatment allocation was not masked and clinicians were not blinded. Stage 3 of this trial completed the planned recruitment in June, 2011. This study is registered, number ISRCTN97182923.

Findings

153 men recruited to stages 1 and 2 were randomly assigned to receive conventional treatment of 74 Gy, 153 to receive 60 Gy, and 151 to receive 57 Gy. With 50¡¤5 months median follow-up (IQR 43¡¤5-61¡¤3), six (4¡¤3 % ; 95 % CI 1¡¤6-9¡¤2) of 138 men in the 74 Gy group had bowel toxicity of grade 2 or worse on the RTOG scale at 2 years, as did five (3¡¤6 % ; 1¡¤2-8¡¤3) of 137 men in the 60 Gy group, and two (1¡¤4 % ; 0¡¤2-5¡¤0) of 143 men in the 57 Gy group. For bladder toxicities, three (2¡¤2 % ; 0¡¤5-6¡¤2) of 138 men, three (2¡¤2 % ; 0¡¤5-6¡¤3) of 137, and none (0¡¤0 % ; 97¡¤5 % CI 0¡¤0-2¡¤6) of 143 had scores of grade 2 or worse on the RTOG scale at 2 years.

Interpretation

Hypofractionated high-dose radiotherapy seems equally well tolerated as conventionally fractionated treatment at 2 years.

Funding

Stage 1 was funded by the Academic Radiotherapy Unit, Cancer Research UK programme grant; stage 2 was funded by the Department of Health and Cancer Research UK.