Dr Richard Foster (Radiation Oncology Institute) Reduction in Rectal Toxicity with SpaceOARTM Hyrdogel during Prostate Cancer Radiotherapy. Dr Amy YM Teh (Radiation Oncology Institute & Sydney Adventist Hospital Clinical School –University of Sydney) Dr Richard Foster (Radiation Oncology Institute) A Prof Henry Woo (Sydney Adventist Hospital Clinical School –University of Sydney) QF022 Rev 1

Conflicts of Interest Nil conflicts of interest.

Introduction Due to proximity of rectum to the prostate, curative radiotherapy for prostate cancer leads to irradiation of the anterior rectal wall, resulting in rectal toxicity. Rectum is one of the main dose-limiting structures in Prostate Radiotherapy.

SpaceOARTM Hydrogel Synthetic polyethylene glycol based hydrogel. Injected between prostate and rectum. Creating distance between prostate and rectum, thereby reducing rectal irradiation.

SpaceOARTM Hydrogel

Objective To report on our early experience using SpaceOARTM Hydrogel during prostate radiotherapy: Implantation experience Distance created between prostate & rectum Dosimetry Clinical outcome

Methods Rectal symptoms assessed at baseline, weekly during radiotherapy, 6 weeks, 3 months and 6 months after radiotherapy. Rectal symptoms monitored using: NCI CTCAE v3.0 during treatment. EORTC QOL-C30 version 3 after treatment.

Results Between Oct 2011 to Mar 2013, SpaceOARTM Hydrogel inserted into 15 patients: 4 EBRT with IMRT/daily IGRT to 76-78Gy. 5 HDR (18Gy) + EBRT (50Gy). 6 LDR I-125 seeds (145Gy)

Patient & Tumour Characteristics Age: Median 70yr (64 – 80yr) PSA: Median 6.2ug/L (0.7 – 22ug/L) Gleason: One G6; nine G7; one G8; four G9. Stage: T1c-T4 N0M0 (Nine T1c; four T2a/b; one T4) Prostate size: 36.6cc (15.5 - 89.6cc)

Implantation Experience 14 General Anaesthetic 1 Local Prostatic Block. Insertions at time of fiducial seed insertion before EBRT. Insertions after HDR catheter/LDR seed implantation with brachytherapy.

Implantation Experience

Implantation Experience

Implantation Experience Hydro-dissection with 10mL saline to create space. Lesson learnt: Lower trans-rectal probe. 2 Y-adaptor blockage. Lesson learnt: Tilt head up. Spare Y-adaptor.

Distance Created: Prostate to Rectum Base: 1.1cm (0-1.9cm) Mid: 0.8cm (0.4-1.5cm) Apex: 0.7cm (0.4-2.3cm) Prostate SpaceOARTM Rectum

Distance Created: Prostate to Rectum Base: 1.1cm (0-1.9cm) Mid: 0.8cm (0.4-1.5cm) Apex: 0.7cm (0.4-2.3cm) Prostate SpaceOARTM Rectum

Rectal Dosimetry: External Beam Radiotherapy Achieved Rectal Constraints Target Rectal Constraints V40Gy 39% (23-49%) <60% V60Gy 13% (8-18%) <40% V75Gy 3% (0-5%) <5%

Rectal Dosimetry: HDR Brachytherapy Achieved Rectal Constraints Target Rectal Constraints D1cc 68.1% (52.1 – 72.9%) <75% D2cc 61.5% (47.1 – 68.7%) <70% V100% V100% dose: 0cc (0cc) <0.5cc

Rectal Dosimetry: LDR Brachytherapy Planned (before SpaceOARTM) Median (range) Achieved (after SpaceOARTM) D0.1cc (%) 96.1 (75.4 – 100.3) 60.1 (46.2 – 107.0) D1cc (%) 75.6 (63.2 – 79.7) 46.1 (29.8 – 76.9) D2cc (%) 65.9 (55.2 – 71.0) 39.6 (25.7 – 65.6) V100% (cc) 0.1 (0.0 – 0.1) 0.0 (0.0 – 0.2)

Clinical Outcome: Acute Rectal Toxicity 66% reported no change to rectal habits. 2 constipation initially (HDR and LDR). 2 flatulence, urgency, mucus starting Week 3 EBRT til 6 weeks after EBRT, settled by 6 months. (Buscopan/Imodium PRN CTCAE v3 N (%) G0 12 (80%) G1-2 2 (13.3%) G3 1 (7%)

Clinical Outcome Follow up: 25 (13 to 37 months) No biochemical failure. No change in bowel habits reported compared to pre-treatment baseline. No change in BO/day compared to pre-treatment baseline in all patients.

Clinical Outcome One patient PR bleed and mucus discharge one week post-LDR. Ulcer proven on sigmoidoscopy. Settled 3 month post-LDR.

Possible mechanisms of rectal injury: Infection. Mechanical injury: Piercing of rectal wall by insertion needle. Ischaemic injury: Excessive tension at anterior rectal wall. Radiation injury: Ineffective placement.

Possible solutions: Avoid infection: Sterile environment, antibiotics cover. Adequate imaging: TRUS-guidance on sagittal imaging with adequate bowel preparation. Appropriate needle positioning: Remove LDR template to optimize manoeuvrability, insert needle bevel positioned away from the rectum. Tilt bed “head up” to reduce downward angling of needle and delivery system. Allow space to be created: Reduce pressure of TRUS probe against anterior rectal wall, and hydro-dissect with normal saline first. Avoid ischaemia: Limit amount injected to 10mL and stop when resistance is felt.

Conclusion SpaceOARTM Hydrogel is a promising technology that allows rectal sparing during prostate radiotherapy. Care and consideration should be taken during its insertion so that SpaceOARTM Hydrogel itself would not compromise treatment or cause further complication. Look forward to long term follow-up data.

Brachytherapy Team Especially Nick Collett Rebecca Dwyer Sam Redfern Acknowledgement Brachytherapy Team Especially Nick Collett Rebecca Dwyer Sam Redfern