ESTRO38 Congress Report

Brachytherapy

2. Single dose high-dose rate (HDR) brachytherapy as monotherapy for localised prostate cancer (E38-0833) H Tharmalingam 1,2,3 , Y Tsang 1 , PJ Hoskin 1,2,3 (on behalf of the National UK HDR Prostate Brachytherapy Database)

1 Mount Vernon Cancer Centre, Northwood, UK, 2 The Christie Hospital NHS Trust, Manchester, UK, 3 University of Manchester

Context of the study For patients with localised prostate cancer, radical radiotherapy can be delivered as either external beam radiotherapy (EBRT) or as brachytherapy (BT), the latter offering higher local dose delivery. Low-dose rate (LDR) BT using permanent implantation of radioactive seeds is established as monotherapy for patients with low- and intermediate-risk prostate cancer. High-dose rate (HDR) brachytherapy (BT) using an afterloader which passes an iridium source along catheters temporarily implanted into the prostate is an attractive alternative offering several potential advantages over LDR treatment. The low α/β ratio of prostate cancer makes it more sensitive to radiotherapy delivered in larger doses per fraction with HDR BT and HDR therapy is not subject to the same dosimetric inconsistencies as LDRwhere changes in prostate volume and seedmigration post implant impact on dose delivery over the 6 months of active delivery from I125 seeds. For the patient LDR BT is associated with more prolonged urinary symptoms following treatment compared to HDR. Overview of abstract Several series have confirmed the safety and efficacy of multi- fraction (four to six) HDR BT schedules as monotherapy for localized prostate cancer. Tomitigate the logistic challenges of multi-fraction regimes, efforts have beenmade to reduce the number of fractions. Favourable biochemical control and low toxicity rates have been reported with two and three fraction protocols. The role of a more cost-effective and convenient single fraction regime is developing with conflicting efficacy results to date. We report outcomes fromamulticentre national UK database of patients treated in a unifying protocol with a single 19Gy dose of HDR BT. What were the three main findings of your research? A total of 441 patients were recruited to the study. Median follow-up was 26 months. The 3-year biochemical progression-free survival (bPFS) rate was 88% for all patients; 100%, 90% and 79% for low-, intermediate- and high-risk patients respectively (p=0.055) (Figure 1). Sites of relapse were identified radiologically in 21 of the 27 biochemical failures. Of these, 14 had a local recurrence in the prostate. Acute grade 2 GU and GI toxicity peaked at 1 month post- implant; prevalence rates of 12% and 3% respectively. No grade 3 or 4 acute toxicity was reported. Two patients developed late grade 3 GU toxicity, both surgically-managed urethral strictures. Two patients developed late grade 3 GI toxicity, both rectal fistulae requiring colostomy.

What impact could your research have? The results for low risk patients are comparable with other treatment modalities; The use of 19Gy single dose HDR brachytherapy can be considered alongside LDR BT, EBRT, active surveillance and radical prostatectomy in this group of patients, the low toxicity profile making HDR BT particularly attractive. The biochemical control rates seen in intermediate and high-risk patients are lower than those reported withmulti- fractionated HDR BT. They are also lower than those seen in equivalent populations treated with LDR brachytherapy, conventional or hypofractionated EBRT and combined EBRT and BT boost, suggesting that 19Gy delivered in a single HDR BT dose is suboptimal in these risk groups. Where biochemical failure occurred, isolated intra-prostatic relapse predominated supporting the rationale for dose intensificationwhich should be feasible given the low toxicity of the regime. Dose escalation should be explored in future single dose HDR protocols using either increased dose to the whole gland or a focal boost to a dominant lesion. Is this research indicative of a bigger trend in oncology? A number of treatment options are available in the armamentarium for patients with localised prostate cancer including active surveillance, surgery, dose-escalated EBRT and brachytherapy. For those receiving radiotherapy, hypofractionated radiotherapy schedules will predominate with external beam stereotactic protocols now being evaluated in large-scale randomised controlled trials. HDR BT offers an alternative means of intense dose delivery and ultra-hypofractionation which, when given in a single dose has added financial and logistical benefits. In low- risk patients, single dose 19Gy HDR BT can be considered alongside other options with high rates of biochemical control and a low toxicity profile. Further investigation of single dose HDR protocols in less favourable subgroups will define the optimal dose and the role of subvolume dose escalation to allow single dose HDR BT to take its place in these patients also.

BRACHYTHERAPY | Congress report

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