Magnetic resonance imaging-guided contouring in stereotactic body radiation therapy in localized disease prostate cancer: Preliminary results of a phase-II study

Background/Aim: Magnetic resonance imaging (MRI)-guided stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for prostate cancer. The goal of prostate SBRT is to treat the entire prostate and proximal seminal vesicles, while limiting radiation dose to the adjacent critical structures, including the bladder, rectum, and membranous urethra. Since the prostate apex is commonly involved with cancer, under-dosing this region would likely increase the risk of recurrence. MRI imaging better defines the prostate and reduces the overall target volume compared to Computed Tomography (CT) imaging. In addition, the prostatic-rectal and prostatic-bladder interfaces are better defined by MRI than by CT imaging. Furthermore, the more accurate delineation of the prostatic apex allows for dose reduction to the genitourinary diaphragm (GUD). A phase-II study of SBRT for localized prostate cancer at low-/intermediate- risk (according to NCCN score) and risk of lymph node involvement <17% (Roach Index) was carried out between November 2015 and July 2017. In this report, the preliminary results in terms of acute toxicity are documented. Materials and Methods: This is a prospective analysis of 30 patients treated with SBRT using volumetric modulated arc therapy (VMAT) technique. The plans were created by the Eclipse™ Treatment Planning System (ver. 10, Varian Medical Systems). Dose distributions were calculated using a 6-MV beam and the AAA dose calculation algorithm. The SBRT-VMAT plans were set up with two full arc arrangements. The prescription dose was 36.25 Gy, administered in 5 fractions; assuming α/β 1.5 Gy, it corresponded to a biologically effective dose (BED) to the prostate equal to 211.5 Gy. The gross tumor volume (GTV) (prostate with the 1/3 proximal seminal vesicles) was delineated using the MRI T2-weighted (T2w) and FLAIR images, co-registered with planning-CT images. Our local rigid registration method employed the 3 intraprostatic gold fiducial markers (GFM) as landmarks. The GTV was delineated also on CT-images and compared to MR-based GTV, by using the DICE metric. All patients were contoured under the supervision of the same physician (AM). For the planning, an isotropic margin of 6 mm around the MR-based GTV is added to obtain the planning tumor volume (PTV). To study the potential association to the bladder trigone on long-term urinary function, the bladder trigone was MRbased contoured too. An indwelling catheter was inserted to aid in the delineation of the urethra. The request for prescription dose was (V100%)>95% of the PTV. According to our internal protocol, minimum dose (98%) to PTV > 97%, and maximum dose (2%) <110% of the prescribed dose were recommended. The rectal dose- volume goals were V50% <50%, V80% <20%, V90 <10%, V100% <5%. The bladder dose-limits were V50% <40%, V92.4% <12.7%, and V100% <10%. Concerning the urethra and the trigone, the constraints for the maximum dose (Dmax) were Dmax<39.9 Gy and Dmax<38.9 Gy, respectively. The image-guided radiotherapy protocol was based on 3 intraprostatic fiducial markers, with daily online checks by cone beam computed tomography. The acute toxicity gastrointestinal (GI) and genitourinary (GU) were recorded using the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer scale. Additional data are collected by means of International Prostate Symptom Score (I-PSS) and International Index of Erectile Function (IIEF-5) questionnaires. Results: Between November 2015 and July 2017, 30 patients were enrolled in this prospective study; the median follow-up duration was 6 months (range, 3-18 months). The median age was 74 years (range=60-81). The mean target registration error was 0.05±0.02 mm (SD). The CT-contoured prostate resulted on average 35% larger that the true gland (MR-based volume) with a mean DICE coefficient of 0.79 (range=0.61-0.90), such that posterior portions were always missed and anterior normal tissue always included. The requests for coverage of the PTV were accomplished for all the VMAT plans; dose constraints for each organ at risk were largely fulfilled. Acute GU and GE toxicity of grade 2 were observed in 26% and 10% patients respectively. The patients presented with urinary obstructive symptoms before radiation treatment had a slight increase in the severity of their symptoms, with the complete recovery at 3 months from the end of the radiotherapy. Conclusion: The present study showed an important reduction in volume of MR-guided prostate, in agreement with literature data. These reductions are primarily due to reduced variation at the superior and inferior extent of the prostate, and translate into reductions in delivered dose to the rectum. This improved soft tissue visualization on MRI has also been shown to reduce interobserver variation in prostate contouring. The dosimetric data of these first 30 patients are favorable for both target coverage and organs at risk dose limits, indicating that SBRTVMAT planning in conjunction with MRI-based prostate is safe for localized prostate cancer patients at low- or intermediate-risk. Our preliminary moderate acute toxicity results were consistent with these dosimetric data. Finally, despite these encouraging results, longer follow-up periods are necessary to confirm them.