SpaceOAR Hydrogel Placement in Patients Undergoing Proton Therapy and Low-Dose-Rate Brachytherapy
*Eric Chung, Nicholas DAmico, Bryan J. Traughber, Rodney Ellis
Department of Radiation Oncology, Case Western Reserve University School of Medicine, Ohio, USA
*Corresponding Authour: Eric M Chung, Department of Radiation Oncology Case Western Reserve University School of Medicine, Cleveland, USA. E-mail: email@example.com
Citation: Chung EM, D’Amico N, Ellis R (2018) SpaceOAR Hydrogel Placement in Patients Undergoing Proton Therapy and Low-Dose-Rate Brachytherapy. J Interv Radiol Nucl Med 2018: 53-57. doi: https://doi.org/10.29199/2637-7152/IRNM-103024
Received Date: 10 October 2018; Accepted Date: 20 October 2018; Published Date:11 November 2018
Dose escalation in prostate cancer has been shown to improve biochemical control in patients treated with definitive radiotherapy. Despite advances in radiation therapy techniques including intensity-modulated radiotherapy, volumetric arc therapy and proton therapy, rectal toxicity continues to be a concern. One method of reducing rectal dose and limiting subsequent toxicity is insertion of a biodegradeable hydrogel (SpaceOAR) to increase the distance between the rectum and prostate, thus decreasing the radiation dose received by the rectal wall. This device has been used in a variety of clinical scenarios in the treatment of prostate cancer, including external beam radiation therapy (EBRT), stereotactic body radiation therapy (SBRT) and brachytherapy. However, there have been no reported cases of a SpaceOAR hydrogel being placed prior to proton therapy that is later followed by a low dose-rate (LDR) prostate brachytherapy boost. We present a case report of SpaceOAR placement in a man who presented with intermediate risk prostate cancer who received combined modality therapy using androgen deprivation therapy (ADT) and proton therapy followed by an LDR brachytherapy boost. We report that SpaceOAR hydrogel was stable with no signs of radiation degradation post-EBRT. Additionally, placement of LDR seeds was feasible several months after rectal spacer implant and following a 5-week course of proton therapy with no dosimetric consequences. In conclusion, placement of an absorbable hydrogel spacer material can increase separation between the rectum and prostate and appears stable throughout proton therapy. The absorbable hydrogel is clearly visualized after proton therapy and appears safe for administration of LDR brachytherapy as a boost.
Keywords: Brachytherapy; Prostate Cancer; Proton Therapy; LDR, Hydrogel; SpaceOAR; LDR - Low Dose Rate
Dose escalation has been shown to improve biochemical control in patients treated with definitive radiation therapy for prostate cancer. Despite the advancement of radiation therapy techniques such as intensity-modulated radiation therapy, volumetric arc therapy and proton therapy, rectal toxicity remains a significant concern. Recent studies have shown that Grade 2 or higher acute and long-term rectal toxicities occur in approximately <10-4% and 6.4-24%, respectively, for prostate cancer patients treated with radiation. [1-3] Additionally, it has been well documented that areas of the rectal wall receiving doses of 70 Gy or higher have an even greater chance of developing rectal toxicity. [4,5].
One method of reducing rectal dose and limiting subsequent toxicity is insertion of a biodegradable hydrogel (SpaceOAR). This device is a synthetic polyethylene glycol hydrogen that is injected into space between the prostate and the rectum, thereby distancing the rectum from the prostate. This increased distance results in decreased radiation dose to the anterior rectal wall and has been shown to reduce the risk of rectal toxicity.[6-8] The device has shown to remain stable for three months, after which it liquefies by hydrolysis, and is absorbed and cleared in the patient’s urine in about six months. This device has subsequently been used in a variety of clinical scenarios in the treatment of prostate cancer, including external beam radiation therapy (EBRT), stereotactic body radiation therapy (SBRT) and brachytherapy. However, to the best of our knowledge, this is the first report of a SpaceOAR hydrogel being placed prior to proton therapy that is later followed by a low dose-rate (LDR) prostate brachytherapy boost.
Our patient is a 65-year old male who initially presented with a rising prostate specific antigen (PSA) of 6.9 ng/mL compared to 2.9 ng/mL the year prior. The patient was asymptomatic at the time of presentation, and digital rectal examination was negative. A prostate biopsy was performed and demonstrated Gleason 8 (4+4) prostate adenocarcinoma in the left median lobe, Gleason 7 (4+3) in the left lateral prostate and Gleason 7 (3+4) in the left apex. His Sexual Health Inventory for Men (SHIM) and American Urological Association (AUA) scores at the time were 5 and 5, respectively. The patient declined surgical resection of the prostate gland and was treated with a combined modality therapy using ADT and proton therapy followed by a Palladium-103 LDR brachytherapy boost. He began ADT approximately 2 months prior to initiation of proton therapy.
MRI scan of the prostate was performed following the biopsy results (Figure 1). This demonstrated a minimal fat pad between the mid prostate and apex of the prostate and the anterior rectal wall. There was no MRI evidence of extracapsular extension, seminal vesicle invasion or pelvic lymphadenopathy. In order to decrease rectal toxicity with planned radiation therapy a polyethylene glycol (PEG) hydrogel spacer (SpaceOAR) device was placed between the rectum and prostate. This was performed under conscious sedation following the placement of four gold fiducial markers that were used for image guidance with proton therapy. The hydrogel spacer was injected using a transperineal approach with transrectal ultrasound guidance according to the standard protocol and device instructions. The dimensions of the device were then measured using ultrasound. The measured height was 11.7 mm and the measured length was 40.2 mm.
One week following SpaceOAR and fiducial marker placement, the patient underwent CT simulation and repeat MRI scan of the prostate (Figure 2). MRI sequences were fused to planning of CT in order to plan proton therapy. These images also confirmed accurate placement of the SpaceOAR device. The patient then underwent proton radiation therapy 2 months after initiation of hormonal therapy to a total dose of 45 GyE in 25 fractions. The prostate and seminal vesicles were treated using an opposed lateral technique. The patient tolerated treatment well with no acute toxicity aside from minimal increased urinary frequency.
20 days following the completion of proton therapy, the patient underwent prostate seed implant boost. The time interval between original placement of the device and prostate seed implant was 63 days. 100 Gy was prescribed to the mean peripheral dose with the use of Pd-103. The pre-treatment MRI that was attained following SpaceOAR placement was used to generate an MRI pre-plan (Figure 3a, Table 1). Institutional standards were followed in order to prepare the patient for LDR brachytherapy, which included placement of a rectal probe for ultrasound guidance. At the time of the implant, the patient’s prostate volume was calculated to be 19.25 cc. The ultrasound image was then aligned to the preplanned MRI and intraoperative treatment planning was performed (Figure 3b, Table 2). After review of the fused images, the implant was performed utilizing a total of 22 needles that were inserted into the prostate with position verified by ultrasound and/or fluoroscopy. Real-time dosimetry was used to track seed placement and ensure adequate coverage. Approximately 3 seeds per needle were inserted for a total of 70 palladium-103 seeds. Mean activity per seed was 1.346 mCi and total activity used was 94.2 mCi. Importantly, the SpaceOAR device was able to be clearly visualized without any visible structural deformities or signs of radiation degradation on ultrasound at the time of seed placement. Additionally, the SpaceOAR device had no impact on seed placement or visualization allowing for excellent intra-operative dosimetry.
The patient tolerated the seed implant well and there was minimal bleeding from the procedure. A post-operative CT scan was performed in order to calculate post-operative dosimetry (Figure 4). The patient’s foley catheter was then removed and he did not have any acute urinary retention. He was given a prescription for ciprofloxacin and instructed to complete a standard, week long course of prophylactic antibiotics. He was given standard precautions following all prostate seed implants that are performed at our institution. Final post-operative dosimetry revealed a D90 of 115.8 Gy. The prostate V100, V150 and V200 were 98.2%, 63.1% and 33.4% respectively. The urethra V150 was 14.9%. D2cc to the rectum was 15.3 Gy. The patient has been seen for 1 month follow up and continues to do well. He has occasional dysuria that does not interfere with his daily activities or require medical therapy. He has no urinary urgency or frequency and is not currently using Flomax. The patient reports no diarrhea, hematochezia or changes in bowel habits.
Progress in radiation therapy techniques in recent years has allowed dose escalation that has improved treatment outcomes. Considerable attention is now focused on reducing treatment toxicity. Due to the rapid dose fall off with intensity-modulated radiation therapy (IMRT), proton therapy and LDR brachytherapy, we have seen that even a small increase in the distance between rectum and prostate can result in significant decreases in radiation dose received by the rectum. Several previous reports have shown that absorbable hydrogel implant between the prostate and rectum can result in decreased acute and long-term toxicity in patients receiving IMRT and brachytherapy treatment. A previous report by Susil et al. showed that the use of a hydrogel implant reduced the rectal wall V70 in IMRT plans from 19.9% to 4.5% . Additionally, a phase II study including 48 patients reported that hydrogel placement was able to increase the space between the rectum and prostate by over 7.5 mm, resulting in at least a 25% reduction of V70 in 95.7% of patients. Furthermore, variability between gel thickness mid-gland, mean gel thickness, gel symmetry and % length of planning target volume with gel contact had no impact on results, suggesting a benefit to hydrogel implant regardless of hydrogel placement variability.
Although the rapid dose fall off in interstitial brachytherapy possesses certain dosimetry advantages, rectal toxicity remains a concern, particularly when used as boost following external beam radiation. The current American Brachytherapy Society guidelines for LDR brachytherapy strongly recommends limiting the rectal volume receiving the prescription dose or higher to under 1 cm3 and 1.3 cm3 on day 1 and 30, respectively.  To date, there have been few studies that describe the benefit of SpaceOAR in patients undergoing LDR brachytherapy. Beydoun et al. first reported the use of SpaceOAR implant in 5 patients undergoing I-125 seed LDR brachytherapy. SpaceOAR hydrogel was placed on average at 35 days post-implantation and resulted in 1.25 cm prostate-rectal separation, and mean RV100 decreased from 3.04 to 0.06 cm.3,  The hydrogel contains material that polymerize within seconds after injection to form a firm gel that maintains separation between the prostate and rectum for at least 3 months and is completely resorbed by the end of 6 months.
To date, there have been no case reports of hydrogel spacer implant followed by EBRT and subsequent LDR brachytherapy to our knowledge. As PEG hydrogels begin to resorb, it can have dosimetric consequences due to changes in the physical separation between the prostate and rectum. Furthermore, EBRT combined with LDR brachytherapy has an increased risk for rectal toxicity. In our case report, PEG hydrogel was used to create a space between the rectum and prostate that did not change considerably during proton therapy. Additionally, the SpaceOAR hydrogel was able to be clearly visualized on ultrasound and post-procedure CT scan at the time of Pd-103 seed implant. In our single institutional experience, 9 patients have had SpaceOAR hydrogel implants placed preoperatively before LDR brachytherapy, 8 had protons with a brachytherapy boost and 1 had IMRT with a brachytherapy boost. The only precaution noted from this experience was that placement of SpaceOAR hydrogel preoperatively before LDR brachytherapy can cause pubic arch interference to be more notable by raising the prostate gland anteriorly. However, this did not prevent proper hydrogel implantation or loss of visualization of the prostate by ultrasound during LDR brachytherapy. Overall, the spacer was stable and showed no signs of radiation degradation and there were no procedure-related complications or adverse events. Consequently, we report that placement of seeds was feasible several months after rectal spacer implant and following a 5-week course of proton therapy.
Acute and late rectal toxicity remains a serious concern during the administration of EBRT and brachytherapy for prostate cancer. Absorbable hydrogel spacers have demonstrated promise in numerous reports to decrease dose to the rectum and reduce acute and late rectal toxicities and may allow for safer administration of brachytherapy. SpaceOAR hydrogel remains stable throughout proton therapy and is clearly visualized when performing LDR brachytherapy as a boost. Hydrogel spacer implant has potential to reduce rectal toxicity when used in patients treated with combination EBRT and LDR brachytherapy.
Figure 1: Magnetic resonance images of prostate pre-SpaceOAR placement. (A) Sagittal image, (B) Axial image.
Figure 2: Magnetic resonance images of spacer post-application. (A) Sagittal image, (B) Axial image.
Figure 3: (A) Axial magnetic resonance image of pre-LDR brachytherapy plan, (B) Axial image of ultrasound intra-op plan
Table 1: Dosimetry Table of Pre-Op Plan
Table 2: Dosimetry Table of Intra-Op Plan
Figure 4: CT axial image of post-op plan