Space creation, maintenance and absorption of a polyethylene glycol based prostate – rectum spacer

Study Objective. To evaluate the space creation, maintenance and absorption of an absorbable hydrogel injected into the perirectal space of patients prior to undergoing prostate radiotherapy. Design. CT or MR imaging performed before hydrogel application (Baseline), one week after hydrogel application, following 8 weeks of IMRT (78Gy total) and then again 6 months following implantation. Setting. University hospital Patients. Twenty one prostate cancer patients with clinical stage T1 or T2 pathology Interventions. Transperineal hydrogel injection into the perirectal space prior to IMRT Measurements and Main Results. Measurement of space between the prostate and rectum in each patient at each time point. Results. Hydrogel injection resulted in the creation of 11.5 + 6.6 mm space (measured space – baseline). Space following IMRT and at six months was 12.3 + 5.1 and 3.0 + 2.8 mm, respectively (mean + SD). Conclusion. Hydrogel spacer injection into the perirectal space resulted in > 1 cm additional space between the prostate and rectum that was maintained throughout radiotherapy. The hydrogel was substantially absorbed within 6 months. Rectal toxicity due to unintended rectal radiation in prostate cancer patients is largely a function of the close proximity of those two structures. Thus, to reduce the amount of rectal radiation, researchers have evaluated different biomaterials as temporary spacers between the prostate and rectum in patients undergoing prostate radiation therapy. Prada and colleagues were able to create an additional 1.5 cm of space between the prostate and rectum following the injection of hyaluronic acid (HA) into the perirectal space (Prada 2007). Similarly, also using HA Wilder was able to create 8-18 mm space (Wilder 2010), and more recently Noyes and colleagues evaluated the use of human collagen for the same purpose, resulting in 1.3 cm of space (Noyes 2011). While promising, issues related to HA radiation sensitivity (Daar 2010) and the potential of viral transmission from human derived products have resulted in considerable interest in synthetic polyethylene glycol (PEG) based materials used elsewhere in the body. DuraSeal Dural Sealant (Covidien, Mansfield, MA) and Mynx Vascular Closure Device (AccessClosure, Mountain View, CA) are both absorbable PEG based hydrogels widely used in neurosurgery and interventional procedures, respectively. The safety profile of those products, in conjunction with the improved toxicity profile of PEGylated drugs (Jain 2010), suggests that PEG hydrogels may be ideal for use as prostate – rectum spacers. Recently a PEG based hydrogel has been developed specifically as a prostate – rectum spacer for rectal sparing in prostate cancer patients undergoing radiation therapy. SpaceOARTM System (Augmenix Inc, Waltham, MA) is injected into the perirectal space as a liquid via the transperineal route, where it opens the prostate rectum potential space and then polymerizes into a soft hydrogel (Figure 1). This created space can then reduce rectal radiation due to patient set up errors and to prostate / rectum movement during treatment. However, in order to function properly this created space must be dimensionally stable and last throughout radiotherapy (typically 3 months). Dimensional stability throughout the course of radiotherapy is essential since radiation is delivered per a dose plan generated before the start of treatment, and gross changes in shape or space during treatment may lead to dosing errors. This paper outlines the results of SpaceOAR hydrogel space creation, maintenance and absorption following application in 21 patients in our facility over an 18 month period. Figure 1: The SpaceOAR applicator allows for simultaneous precursor injection through an 18G needle into the perirectal space. Once injected the precursors polymerizes to form an absorbable hydrogel. Materials and Methods A total of 21 patients were enrolled in a PEG – based hydrogel spacer evaluation initiated in October 2009, following Ethics Committee approval in our institution. Subjects with prostates < 80 cc, PSA ≤ 20 ng/mL, Gleason Score ≤ 7 (grade 3 predominant pattern) and clinical stage T1 or T2 pathology were considered eligible. Subjects with metastatic disease, prior prostate surgery or radiotherapy, or a history of inflammatory bowel disease were excluded from the study. Prior to hydrogel spacer treatment all patients were imaged (CT or MRI) for the measurement of baseline prostate – rectum spacing. Using local anesthesia, an 18 G needle was used to inject the hydrogel precursors into the perirectal space, where they lifted the prostate and then solidified. Approximately one week following hydrogel spacer treatment patients were again imaged to measure the space created due to hydrogel injection. Patient dose plans for subsequent radiation delivery were then created using the post-implantation CT scan. Following delivery of radiation (200 cGy x 39 fractions) patients were again imaged for measurement of hydrogel persistence throughout radiation. Finally, six months following implantation patients were again imaged to determine the extent of hydrogel absorption. Baseline, post hydrogel application, post IMRT and 6 month images were reviewed by an independent Radiation Oncologist who measured the mid gland space between the prostate and rectal lumen for every patient. Space resulting from hydrogel application was calculated by subtracting the baseline space from the space measured at each subsequent time point. Results The space resulting from hydrogel implantation, along with the space remaining after radiation therapy, and at 6 months following implantation was 11.5 + 6.6, 12.3 + 5.1 and 3.0 + 2.8 mm, respectively (mean + SD, Figure 2). Figure 2: Hydrogel space created as measured one week following implantation (Dose planning), at completion of radiotherapy (End IMRT) and at six months following implantation (End Acute Phase). As seen in Figure 3, the hydrogel appearance is more conspicuous under T2 MR imaging than under CT. Nonetheless, the similarity in prostate – rectum space and gel morphology at both the post hydrogel and post IMRT time points is clearly evident. Figure 3: CT and MR images from one patient within one week of implantation (Left, Post Hydrogel), at completion of radiotherapy (Middle, Post IMRT) and six months post implantation (Right, Six Months). Similarities in hydrogel and prostate morphology demonstrate gel stability during radiotherapy, with hydrogel absorption at six months. Post Hydrogel (CT) Post IMRT (T2 MRI) Six Months (T2 MRI)