Elsevier

Clinical Oncology

Volume 28, Issue 10, October 2016, Pages e148-e154
Clinical Oncology

Original Article
SpaceOAR Hydrogel in Dose-escalated Prostate Cancer Radiotherapy: Rectal Dosimetry and Late Toxicity

https://doi.org/10.1016/j.clon.2016.05.005Get rights and content

Highlights

  • 30 patients with prostate cancer were treated with hydrogel in situ on a prospective trial.

  • Patients received 80 Gy in 40 fractions using an IMRT technique.

  • Plans pre- and post-hydrogel insertion showed significant reductions in rectal doses with hydrogel.

  • Patients had a minimum follow-up of 2 years (median = 28 months).

  • Late grade 1 rectal toxicity was reduced in the hydrogel group compared to a cohort treated without.

Abstract

Aim

To investigate the feasibility, dosimetric benefits and late toxicity of a temporary hydrogel spacer between the rectum and the prostate for prostate intensity-modulated radiotherapy.

Materials and methods

Thirty patients with prostate cancer were enrolled on a phase I/II study. All patients underwent magnetic resonance imaging before and after placement of 10 cm3 of hydrogel. The first 10 patients had an additional magnetic resonance imaging after the completion of radiation treatment. SpaceOAR hydrogel was injected under general anaesthetic using a transperineal approach with transrectal ultrasound guidance. Primary end points were perioperative toxicity and comparison of rectal dosimetry. Secondary end points included cute and late radiation toxicity. All patients were planned on both pre- and post-hydrogel scans to a D95 of 80 Gy in 40 fractions. A contemporary control group of 110 prostate cancer patients treated with the same prescription was identified for comparison.

Results

There were no perioperative complications. Rectal doses were significantly lower for the post-hydrogel plans, especially above 65 Gy (V82 = 0.2% versus 1.3%; V80 = 0.8% versus 5.3%; V75 = 2.2% versus 9.5%; V70 = 3.7% versus 12.3%; V65 = 5.4% versus 14.7%; V40 = 22.9% versus 32% and V30 = 42.7% versus 49.4%). There was no significant difference in acute grade 1 and 2 gastrointestinal toxicity, which was 43% versus 51% and 0% versus 4.5% in the hydrogel and control groups, respectively. Late grade 1 was significantly less frequent in the hydrogel group (16.6% versus 41.8%, P = 0.04).

Conclusion

SpaceOAR hydrogel was inserted with minimal side-effects. Dosimetric benefits were greatest at higher rectal doses (V65 to V82). Late grade 1 gastrointestinal toxicity was significantly lower than that seen in patients treated without hydrogel.

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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