Faculty Bibliography

BACKGROUND:Studies using stereotactic body radiotherapy (SBRT) dose escalation in in low- and intermediate-risk prostate cancer patients have indicated favorable outcomes. OBJECTIVE:To evaluate tolerance and tumor control outcomes in low- and intermediate-risk prostate cancer patients treated with high-dose SBRT following our phase 1 trial. DESIGN, SETTING, AND PARTICIPANTS:A total of 551 patients with low- or intermediate-risk prostate cancer were treated with SBRT. INTERVENTION:Treatment with 37.5-40Gy SBRT in five fractions directed to the prostate and seminal vesicles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Outcome measurements included acute toxicities (<3 mo after radiotherapy [RT]) and late toxicities (>3 mo after RT) and tumor control evaluation (prostate-specific antigen [PSA] levels at 3-6-mo intervals and post-treatment prostate biopsy at 2yr). RESULTS AND LIMITATIONS:Acute grade 2 gastrointestinal (GI) toxicities occurred in 1.8% of patients, and late grade 2 and 3 GI toxicities were observed in 3.4% and 0.4% of patients, respectively. Acute grade 2 genitourinary (GU) toxicities occurred in 10% of patients, and grade 3 acute GU toxicities were observed in 0.7% of patients. Late grade 2 and 3 GU toxicities were observed in 21.1% and 2.5% of patients, respectively. The use of a hydrogel rectal spacer was significantly associated with reduced late GI toxicity and lower odds of developing late GU toxicity. The median follow-up was 17 mo, and 53% of those with at least 2yr of follow-up (103/193) had a biopsy performed. The 5-yr cumulative incidence of PSA failure was 2.1%, and the incidence of a positive 2-yr treatment biopsy was 12%. Limitations to this report include its retrospective nature and short follow-up time. CONCLUSIONS:Favorable short-term outcomes were achieved with high-dose SBRT for low- and intermediate-risk disease. Severe late toxicities were observed and favorable tumor control was found. PATIENT SUMMARY:We utilized stereotactic body radiotherapy, a form of external beam radiotherapy that delivers highly targeted high-dose treatment to the prostate, to treat over 500 localized prostate cancer patients in five sessions over 1.5 wk. Treatments were well tolerated without significant urinary or rectal side effects. Nearly 90% of those who underwent biopsies after treatment did not demonstrate residual active disease.

Our purpose was to evaluate the performance of ¹¹C-choline PET/CT in detecting biochemically recurrent prostate cancer (PCa) in a large non-European cohort (in the context of emerging evidence for prostate-specific membrane antigen PET in this setting) and to map patterns of PCa recurrence. Methods: We retrospectively analyzed ¹¹C-choline PET/CT scans from 287 patients who were enrolled in an imaging protocol based on rising prostate-specific antigen (PSA) levels (mean, 3.43 ng/mL; median, 0.94 ng/mL; range, 0.15-89.91 ng/mL) and suspected recurrent PCa. A total of 187 patients had undergone primary radical prostatectomy (RP) (79/187 had secondary radiotherapy), 30 had undergone primary radiotherapy, and 70 had a persistent PSA elevation after receiving initial treatment (69 after RP, 1 after radiotherapy). The level of suspicion for recurrence on ¹¹C-choline PET/CT was scored (0, negative; 1, equivocal; 2, positive) by 2 readers. The correlation between ¹¹C-choline PET/CT positivity and initial treatment, Gleason score, National Comprehensive Cancer Network stage, PSA level, PSA doubling time, PSA velocity, and time between initial treatment and PET imaging was evaluated. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were used to map ¹¹C-choline recurrence patterns. Results: Considering scores 1 and 2 as positives, consensus between the 2 readers deemed 66% of the ¹¹C-choline PET/CT scans as positive. When sorted by PSA level, 45% of patients with a PSA of less than 0.5 ng/mL, 56% of patients with a PSA of 0.5-0.99 ng/mL, 70% of patients with a PSA of 1.0-1.99 ng/mL, and 90% of patients with a PSA of at least 2.0 ng/mL scored either 1 or 2 on ¹¹C-choline PET/CT scans. When considering scores of 2 only, ¹¹C-choline PET/CT positivity was 54% (28%, 46%, 62%, and 81%, respectively, for patients with PSA < 0.5 ng/mL, 0.5-0.99 ng/mL, 1.0-1.99 ng/mL, and ≥ 2.0 ng/mL). In multivariate analysis, only PSA level was significantly associated with scan positivity. Pattern analysis showed that pelvic lymph nodes were the most common site of recurrence, and 28% of patients had ¹¹C-choline-positive suspected recurrences outside the initial treatment field. Conclusion:

BACKGROUND:To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences. METHODS:Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to maintain a full bladder and empty rectum prior to simulation and each treatment. A single reviewer delineated organs at risk (OARs) on the simulation (Sim-CT) and Cone Beam CTs (CBCT) for analyses. RESULTS:Bladder and rectum volume reductions were observed throughout the course of SBRT, with largest mean reductions of 86.9 mL (19.0%) for bladder and 6.4 mL (8.7%) for rectum noted at fraction #5 compared to Sim-CT (P < 0.01). Higher initial Sim-CT bladder volumes were predictive for greater reduction in absolute bladder volume during treatment (ρ = - 0.69; P < 0.01). Over the course of SBRT, there was a small but significant increase in bladder mean dose (+ 4.5 ± 12.8%; P < 0.01) but no significant change in the D2cc (+ 0.8 ± 4.0%; P = 0.28). The mean bladder trigone displacement was in the anterior direction (+ 4.02 ± 6.59 mm) with a corresponding decrease in mean trigone dose (- 3.6 ± 9.6%; P < 0.01) and D2cc (- 6.2 ± 15.6%; P < 0.01). There was a small but significant increase in mean rectal dose (+ 7.0 ± 12.9%, P < 0.01) but a decrease in rectal D2cc (- 2.2 ± 10.1%; P = 0.04). No significant correlations were found between relative bladder volume changes, bladder trigone displacements, or rectum volume changes with rates of genitourinary or rectal toxicities. CONCLUSIONS:Despite smaller than expected bladder and rectal volumes at the time of treatment compared to the planning scans, dosimetric impact was minimal and not predictive of detrimental clinical outcomes. These results cast doubt on the need for excessively strict bladder filling and rectal emptying protocols in the context of image guided prostate SBRT and prospective studies are needed to determine its necessity.

PURPOSE/OBJECTIVE:To determine the impact of using fiducial match for daily image-guidance on pelvic lymph node (PLN) coverage for prostate cancer patients receiving stereotactic body radiation therapy (SBRT). METHODS:Thirty patients underwent SBRT treatment to the prostate and PLN from 2014 to 2016. Each patient received either 800cGy × 5 or 500cGy × 5 to the prostate and 500cGy × 5 to the PLN. A 5 mm clinical target volume (CTV)-to-planning target volume (PTV) margin around the PLN was used for planning. Two registrations with planning computed tomography (PCT) for each of the daily cone beam CTs (CBCTs) were performed: a rigid registration to fiducials and to the bony anatomy. The average translational difference between fiducial and bony match as well as percentage of fractions with differences > 5mm were calculated. Changes in bladder and rectal volume as well as center-of-mass (COM) position from simulation parameters, and their correlation with translational difference were also evaluated. The dosimetric impact of the translational differences was calculated by shifting the plan isocenter. RESULTS:The average translational difference between fiducial and bony match was 0.06 ± 0.82, 2.1 ± 4.1, -2.8 ± 4.3, and 5.5 ± 4.2 mm for lateral, vertical, longitudinal, and vector directions. The average change in bladder and rectal volume from simulation was -67.2 ± 163.04 cc (-12 ± 52%) and -1.6 ± 18.75 (-2 ± 30%) cc. The average change in COM of bladder from the simulation position was 0.34 ± 2.49, 4.4 ± 8.1, and -3.9 ± 7.5 mm along the LR, AP, and SI directions. The corresponding COM change for the rectum was 0.17 ± 1.9, 1.34 ± 3.5, and -0.6 ± 5.2 mm. CONCLUSIONS:The 5 mm margin covered ~75% of fractions receiving PLN irradiation with SBRT, daily CBCT and fiducial-guided setup. The dosimetric impact on PLN coverage was significant in 19% of fractions or 25% of patients. A larger translational shift was due to variation in rectal volume and changes in COM position of the bladder and rectum. A consistent bladder positioning and/or rectum filling compared with presimulation volume were essential for adequate coverage of PLN in a hypofractionated treatment regime.

BACKGROUND AND PURPOSE:To identify early biochemical predictors of survival in intermediate- and high-risk prostate cancer patients with a pre-treatment PSA <20 ng/mL following definitive radiation therapy (RT) and androgen deprivation therapy (ADT). MATERIALS AND METHODS:A single-institution review of 2566 intermediate and high-risk prostate cancer patients treated with definitive RT and neoadjuvant and concurrent ADT from 1990 to 2012 was performed. The first prostate-specific antigen (PSA) value within three months of ADT initiation (post-ADT PSA) and the first PSA within three months after RT completion (post-RT PSA) were recorded. 1275 had baseline PSA <20 ng/mL and either post-ADT or post-RT PSA available. Median follow-up was 7.6 years. The relationship between post-treatment PSA kinetics and biochemical relapse (BR), distant metastasis (DM), prostate cancer specific death (PCSD) and overall survival (OS) was modeled using Cox regression univariate and multivariate analysis (MVA). RESULTS:MVA demonstrated a strong association between a post-RT PSA ≥0.09 ng/mL and a significantly higher risk of BR (HR: 1.93; 95% CI: 1.45-2.57; p < 0.001), DM (HR: 2.97; 95% CI: 2.01-4.39; p < 0.001), PCSD (HR: 2.99; 95% CI: 1.73-5.15; p < 0.001) and OS (HR: 1.49; 95% CI: 1.18-1.86; p < 0.001). Post-RT PSA reduction of ≥95% relative to the baseline PSA was associated with a significantly lower risk of BR (MVA HR: 0.58; 95% CI: 0.41-0.83; p = 0.003) and DM (MVA HR: 0.47; 95% CI: 0.30-0.76; p = 0.002). CONCLUSION:A PSA value ≥0.09 ng/mL early after RT completion is associated with significantly worse prognosis across all clinical outcomes, and an early PSA reduction of ≥95% is associated with reduced risk of BR and DM. These findings may identify patients who require early aggressive systemic management for high-risk disease.

PURPOSE/OBJECTIVE:To develop an Eclipse plug-in (MLC_MODIFIER) that automatically modifies control points to expose fiducials obscured by MLC during VMAT, thereby facilitating tracking using periodic MV/kV imaging. METHOD/METHODS:Three-dimensional fiducial tracking was performed during VMAT by pairing short-arc (3°) MV digital tomosynthesis (DTS) images to triggered kV images. To evaluate MLC_MODIFIER efficacy, two cohorts of patients were considered. For first 12 patients, plans were manually edited to expose one fiducial marker. Next for 15 patients, plans were modified using MLC_MODIFIER script. MLC_MODIFIER evaluated MLC apertures at appropriate angles for marker visibility. Angles subtended by control points were compressed and low-dose "imaging" control points were inserted and exposed one marker with 1 cm margin. Patient's images were retrospectively reviewed to determine rate of MV registration failures. Failure categories were poor DTS image quality, MLC blockage of fiducials, or unknown reasons. Dosimetric differences in rectum, bladder, and urethra D1 cc, PTV maximum dose, and PTV dose homogeneity (PTV HI) were evaluated. Statistical significance was evaluated using Fisher's exact and Student's t test. RESULT/RESULTS:Overall MV registration failures, failures due to poor image quality, MLC blockage, and unknown reasons were 33% versus 8.9% (P < 0.0001), 8% versus 6.4% (P < 0.05), 13.6% versus 0.1% (P < 0.0001), and 7.6% versus 2.4% (P < 0.0001) for manually edited and MLC_MODIFIER plans, respectively. PTV maximum and HI increased on average from unmodified plans by 2.1% and 0.3% (P < 0.004) and 22.0% and 3.3% (P < 0.004) for manually edited and MLC_MODIFIED plans, respectively. Changes in bladder, rectum, and urethra D1CC were similar for each method and less than 0.7%. CONCLUSION/CONCLUSIONS:Increasing fiducial visibility via an automated process comprised of angular compression of control points and insertion of additional "imaging" control points is feasible. Degradation of plan quality is minimal. Fiducial detection and registration success rates are significantly improved compared to manually edited apertures.

BACKGROUND AND PURPOSE/OBJECTIVE:Magnetic resonance (MR) only radiation therapy for prostate treatment provides superior contrast for defining targets and organs-at-risk (OARs). This study aims to develop a deep learning model to leverage this advantage to automate the contouring process. MATERIALS AND METHODS/METHODS:Six structures (bladder, rectum, urethra, penile bulb, rectal spacer, prostate and seminal vesicles) were contoured and reviewed by a radiation oncologist on axial T2-weighted MR image sets from 50 patients, which constituted expert delineations. The data was split into a 40/10 training and validation set to train a two-dimensional fully convolutional neural network, DeepLabV3+, using transfer learning. The T2-weighted image sets were pre-processed to 2D false color images to leverage pre-trained (from natural images) convolutional layers' weights. Independent testing was performed on an additional 50 patient's MR scans. Performance comparison was done against a U-Net deep learning method. Algorithms were evaluated using volumetric Dice similarity coefficient (VDSC) and surface Dice similarity coefficient (SDSC). RESULTS:< 0.001). Average VDSC was 0.93 ± 0.04 (bladder), 0.83 ± 0.06 (prostate and seminal vesicles [CTV]), 0.74 ± 0.13 (penile bulb), 0.82 ± 0.05 (rectum), 0.69 ± 0.10 (urethra), and 0.81 ± 0.1 (rectal spacer). Average SDSC was 0.92 ± 0.1 (bladder), 0.85 ± 0.11 (prostate and seminal vesicles [CTV]), 0.80 ± 0.22 (penile bulb), 0.87 ± 0.07 (rectum), 0.85 ± 0.25 (urethra), and 0.83 ± 0.26 (rectal spacer). CONCLUSION/CONCLUSIONS:A deep learning-based model produced contours that show promise to streamline an MR-only planning workflow in treating prostate cancer.