Original ArticleSpaceOAR Hydrogel in Dose-escalated Prostate Cancer Radiotherapy: Rectal Dosimetry and Late Toxicity
Introduction
The evidence supporting dose escalation in prostate cancer is well established. Multiple studies have reported improved biochemical outcomes, local control and disease-free survival with doses above 70 Gy, with some reporting a dose response beyond 80 Gy [1], [2], [3], [4]. The potential trade-off for dose escalation is an increased risk of normal tissue damage, particularly to the bladder and bowel. Rectal toxicity occurs as a result of radiation-related inflammation, fibrosis, microvascular damage and oedema within the bowel wall and mucosa [5], [6]. Late rectal effects may include bleeding, urgency and incontinence, all of which affect quality of life [7]. Rectal dose–volume histogram parameters predictive of late grade 2 gastrointestinal toxicity have been identified from previous reports, including V40, V55–65 and V70 [8], [9], [10], [11].
In comparison with three-dimensional conformal techniques, the use of intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT) results in significant sparing of the organs at risk [12], [13]. However, despite these advances, minimising the dose to the anterior rectum can be challenging due to the proximity of the anterior rectum to the posterior prostate. At least part of the rectum will inevitably lie within the high dose planning target volume (PTV).
Increasing the space between the rectum and prostate is a simple but potentially very effective method of reducing rectal radiation dose. Various methods of producing such a separation have been reported, including the injection of collagen or hyaluronic acid, or the use of a biodegradable rectal spacer balloon [14], [15], [16]. The use of collagen is limited by the potential for immune reactions, and concerns exist with respect to hyaluronic acid, which has been shown to persist in tissues up to 12 months after injection [17]. Hydrogel is biologically inert, with no reported immune-related side-effects. These hydrogels (which are >90% water by weight) are thin liquids when injected, but then polymerise in situ to form a soft hydrogel after the two precursor solutions mix.
In 2012, the Northern Sydney Cancer Centre (NSCC) initiated a prospective trial to evaluate the use of SpaceOAR hydrogel (Augmenix, Waltham, MA, USA) in patients receiving dose-escalated IMRT for prostate cancer. Outcomes for the first 10 patients have previously been reported [18]. Here we describe the dosimetric outcomes, acute and late toxicity for the completed study with a minimum follow-up duration of 2 years.
Section snippets
Materials and Methods
Approval for this phase I/II trial was granted by the Local Health District Human Research Ethics Committee. Eligible patients had histologically proven T1-3 prostate cancer and were fit for dose-escalated prostate radiotherapy. The primary end points of the study were: (i) comparison of the rectal volume receiving from 30–82 Gy and (ii) postoperative toxicity; the secondary end points were acute and late toxicity.
Results
Thirty patients were recruited to the study between March 2012 and July 2013, with the last patient completing treatment in September 2013 (median follow-up 28 months, range 24–38). Patient and tumour characteristics are outlined in Table 1. The median age was 72 years (range 58–84 years). Most patients reported normal bowel function at baseline. Seven patients had a history of haemorrhoids; only one reported any recent rectal bleeding.
Five patients had T3 disease, including four with seminal
Discussion
In this study, the use of hydrogel resulted in significant reductions in key rectal dose volume parameters. This dosimetric advantage is due to the physical distance created between the posterior prostate and the rectum by the spacer, which lead to a mean difference in prostate–rectal separation of 10.5 mm in our patients when the pre- and post-hydrogel computed tomography scans were compared. Based on our experience, we would expect this separation to be maintained throughout the treatment
Conclusion
The procedure was well tolerated with no documented peri-operative complications. SpaceOAR hydrogel significantly reduced the dose to the rectum from V30–82 Gy, with the greatest difference observed at higher rectal doses (V65 to V82). Late grade 1 gastrointestinal toxicity was significantly lower than that seen in the control cohort.
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