A Phase 1/2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer With a Simultaneous Integrated Boost to MRI-Identified Regions of High Tumor Volume (NCT02470897)

Abstract

Stereotactic body radiation therapy (SBRT) is a promising treatment option for low- and intermediate- risk prostate carcinoma. Dose escalation beyond currently standard SBRT regimens may further improve outcomes, particularly for bulkier tumors, but could be limited by adjacent organ dose constraints. However, selective dose escalation to identified regions of high tumor burden may offer a safer approach than uniform dose escalation. Therefore, this ongoing prospective study seeks to test the planning and delivery feasibilities and the tolerability of treating patients with a modest dose escalation to the entire prostate and a simultaneous integrated boost (SIB) to MRI-identified lesions. Low- or intermediate- risk prostate cancer patients (Gleason score ≤ 7, PSA ≤20, T stage ≤2b) are eligible and treated based on ability to undergo pre-treatment pelvic MRI. Patients enrolled to date undergoing MRI (n=10) received LINAC-based prostate SBRT (5 x 8.0 Gy delivered every other day) with urethral, anterior rectal wall and bladder base doses constrained to 7.25 Gy/fraction. MRI-identified PI-RADS 4 or 5 lesions received a SIB to 8.5 - 9.0 Gy/fraction. Patients not undergoing MRI imaging (n=6) received a uniform SBRT dose (5 x 7.5 Gy) with the same normal tissue constraints. Intra-fractional shifts were monitored with a repeat alignment scan after half of the fractional dose was delivered. Acute bowel and bladder toxicity was assessed using RTOG toxicity scales and the IPSS. Urinary, bowel and sexual quality of life will be assessed at regular intervals using the expanded prostate cancer index composite (EPIC-26) questionnaire. Median follow up was 8 months with a range of 2-16 months. Dosimetric evaluation of planned and delivered dose indicates that prostate SBRT including both a dose constraint applied to the urethra, anterior rectum and bladder base as well as a SIB to MRI-identified tumor subvolumes can be reproducibly planned and delivered. There were no grade 3 or 4 acute or late GI or GU toxicities and only two patients reported acute grade 2 urinary symptoms (2/16 or 12.5%). Average IPSS scores increased only modestly from pretreatment baseline scores of 8.2 to 6 week scores of 10.4 (p=0.02). This ongoing trial employs a simultaneous integrated boost to MRI-detected lesions during SBRT while constraining doses to immediately bordering normal organ subvolumes. Results to date indicate that this approach is dosimetrically feasible and deliverable, while preliminary outcomes find it to be well tolerated acutely. Additional accrual and follow up for this ongoing trial will be required to assess longer term conventional and patient reported toxicity outcomes as well as tumor control.