Intact Prostate Cancer Research Articles

Online Correction of Intrafraction Motion during Volumetric Modulated Arc Therapy for Prostate Radiotherapy: A Cohort Study Quantifying the Frequency of Shifts and Analysis of Men at Highest Risk.

We have previously described our early experience using fiducial markers to correct for intrafraction motion during radiation therapy (RT) to the prostate using the TrueBeam Advanced imaging package. We sought to further characterize the utility of this approach in a larger cohort, and analyze factors associated with intrafraction motion. A total of 132 men with fiducial markers treated with RT for intact prostate cancer at a single center were treated with a VMAT technique using 2-3 arcs. All patients underwent planning CT after a rectal enema and same day placement of 3 fiducial markers (Gold Anchor). Triggered kV images were acquired every 10 seconds using an onboard imaging system. Intrafraction motion correction was considered if any two fiducial markers were observed beyond a 3 mm tolerance margin. A manual 2D-3D match was performed using the fiducial markers from the single triggered kV image to obtain a couch shift. Shift data were extracted from the record and verify system and expressed as a single 3-dimensional translation. Shift percent was defined as the number of instances of a >3 mm intrafraction correction divided by the total number of fractions for a given patient. Clinical variables were evaluated, including body mass index, hormone therapy (ADT), prostate, rectal bladder volumes, and rectal width (transverse dimension of rectum at the mid-gland of prostate on simulation CT). Across 2659 fractions, intrafraction motion correction was performed 582 times, in 463 fractions (17%). 101/132 patients (77%) had at least one shift during their treatment course, and 48/132 patients (36%) had shifts with an average magnitude of at least 5 mm. The median shift was 3.6 mm (range, 0-2.4 cm; IQR, 1.5-5.4 mm). 25% of men had a shift percent >20% (SP>20%). Univariate analysis revealed that only larger rectal volume or width, smaller prostate size, and use of ADT were associated with SP>20% (p<0.05). Men with rectal width in the top quartile (>3.6 cm) were more likely to have intrafraction motion corrected with SP>20% (47% vs 18%, p = 0.0016), and similarly men with rectal volume in the top quartile (>112 cc) were more likely to have SP>20% (44% vs 19%, p = 0.0067). On multivariate analysis, only rectal parameters (e.g., top quartile rectal width, HR 3.9, p = 0.0024) were correlated with a higher frequency of intrafraction motion. Intrafraction motion occurs in a significant percentage of men undergoing prostate RT with VMAT, and is correctable utilizing a common feature. On multivariate analysis, rectal volume and width were associated with larger shift percent. Treatment approaches which do not account for intrafraction motion should consider including methods of immobilization, or larger PTV margins in order to avoid marginal miss of the prostate.

Does a Dominant Intraprostatic Lesion Boost Require Daily Adaptation when Treated with Stereotactic Online Adaptive MR-Guided Therapy?

Multiple trials have demonstrated a dose-response relationship for radiation therapy in the treatment of localized prostate cancer. Recent data has also demonstrated a benefit with whole gland stereotactic radiation therapy (SBRT) in conjunction with a simultaneous integrated boost to the dominant intraprostatic lesion (DIL). SBRT with a DIL boost can often increase dose to nearby organs at risk such as the rectum and online adaptive MR guided radiation therapy (MGgRT) may offer a dosimetric and toxicity benefit. A prospective database of MRgRT patients was queried for intact prostate cancer patients who received SBRT with a SIB to the DIL. The guideline for adaptation for coverage was to ensure the PTV-prostate coverage at 95% of prescribed dose was greater than 92% or by discretion of the treating physician. Adaptions for organs at risk were made to meet prescription constraints. The number of fractions requiring adaptation to meet organs at risk constraints and/or adequate coverage were reviewed. A total of 26 patients were treated with SBRT with a DIL boost using stereotactic online adaptive MRgRT from 2020 to 2022. 10 of 26 patients were treated for re-irradiation of intact prostate. Out of the 130 fractions delivered, 107 fractions required adaptation (82.3%). 59 fractions were adapted for urethra (45.2%), 48 fractions were adapted for bladder (36.9%), 36 fractions were adapted for rectum (27.7%), 23 fractions were adapted for bladder neck (17.7%), and 19 fractions were adapted for coverage (14.6%). For 53 fractions (40.8 %), adaptation was required for more than one organ at risk. A total of 82.3% of fractions required adaptation for patients treated with SBRT with a DIL boost using stereotactic online adaptive MRgRT. Adaptation occurred most frequently for urethral (45.2%), bladder (36.9%), and rectal constraints (27.7%). Further studies are needed to elucidate if daily adaptive online MRgRT translates to reduced patient toxicity and improved quality of life.

Does Stereotactic Online Adaptive MRgRT to the Prostate Preclude the Need for Rectal Spacer

Historical prospective trials have shown that hydrogel rectal spacers can be very effective at decreasing rectal wall dose, and in turn rectal toxicity, in patients undergoing curative intent fractionated courses of radiotherapy for prostate cancer. However, in the modern era of stereotactic online adaptive MR guided radiation (MRgRT), it's not yet determined if rectal spacers improve the potential daily need for plan adaptation. A prospective database of MRgRT patients were queried for intact prostate cancer patients who received stereotactic online adaptive MR guided radiation. Patients were reviewed for the presence of a hydrogel rectal spacer present on the planning images. The number of adaptive fractions as well as the organs at risk out of tolerance were noted for each patient. Comparisons between number of fractions adapted as well as the number of fractions adapted for rectal constraints, were noted. For each case within this patient group that required plan adaptation, pre-specified dose constraints were finally met prior to treatment delivery. A total of 27 patients were treated with stereotactic online adaptive MRgRT from 2020 to 2022. 8 patients had a hydrogel rectal spacer placed prior to treatment. Out of the 95 fractions delivered to non-hydrogel patients, 78 were adapted, with 52 for urethra, 31 for bladder, 5 for bladder neck, and 35 for rectum. Of the 40 fractions delivered to patients with a hydrogel spacer, 20 were adapted. The corresponding reasons for adaptation in this group were 14 times for the urethra, 19 times for the bladder, 8 times for the bladder neck, and 8 times for the rectum. It was common for multiple at-risk organs to require adaptation for a single fraction within both cohorts. Although the percentage of patients requiring adaptation for rectal constraints was greater in the non-hydrogel patients (36.8% vs. 20%), this was not found to be statistically significant; p value greater than 0.1. The presence of a rectal spacer did not significantly reduce the need for online plan adaptation of the rectum for stereotactic online adaptive MRgRT. Furthermore, patients with a rectal spacer continued to often require adaptation to meet other prescription constraints. Further work is necessary to better select patients who would benefit from hydrogel spacers in the setting of online adaptive MRgRT. Additionally, longer follow-up of this patient population coupled with a larger patient cohort overall remains needed to increase the power of this analysis and to further explore the clinical outcomes of this patient group.

Dosimetrically Correlating the Acute Effect of Bone Radiation on Anemia in Men with Intact Prostate Cancer

<h3>Purpose/Objective(s)</h3> Published data evaluating the effect of radiation (RT) on pelvic bone marrow is mainly based on women with gynecological cancers receiving concurrent chemotherapy. The effect of RT on bone marrow in men with prostate cancer (PC) is less clear, where chemotherapy is not routinely delivered. This study aimed to determine if there is a dosimetric correlation between the volume of pelvic bone irradiated when treating PC and reduced hemoglobin (Hgb) values. Impaired marrow function affects patient quality of life and future systemic therapy. The a priori hypothesis was that volume of pelvic bone receiving at least 4 Gy (V4Gycc) would correlate significantly with marrow toxicity, given that 4Gy is the LD50 dose for a total body exposure. <h3>Materials/Methods</h3> A prospective database of PC patients treated at one institution was utilized. Non-metastatic patients treated between 2008 and 2021 with definitive RT were selected. Patients were included if they had at least one Hgb value within two years prior to their RT start date and at least one Hgb value within three years of RT completion. Patients with confounding diagnoses were excluded and were censored at the time of a second oncologic treatment course or confounding event known to lower Hgb levels. All patient charts were individually audited for accuracy. Pelvic bone (L3/L4 interface through ischial tuberosities) was contoured, and the dose to this structure was calculated. Doses were converted to 2 Gy equivalent doses (EQD2) using an α/β of 10. Exploratory analysis suggested dichotomizing into low volume exposures (LVE; V4Gycc <=1000cc) and high-volume exposures (HVE, V4Gycc >1000cc). Non-parametric kernel regressions evaluating the effects of time, V4Gycc, and androgen deprivation therapy (ADT) use on Hgb values was performed. Percent reduction in Hgb from baseline was evaluated. <h3>Results</h3> 222 patients were included in final analysis. Median starting Hgb was 15.0 g/dL (IQR 14.2-15.9). The mean V4Gycc was 1283cc (IQR 1740-2044). Hgb nadir occurred around day 90 post-RT start. Both HVE and LVE groups had significantly lower Hgb as a percentage of baseline at day 90 (HVE= 85.4%, p < 0.001; LVE=94.8%, p < 0.001). HVE resulted in significantly lower Hgb levels compared to LVE at day 90 (95% confidence intervals; 80.3% - 88.9% vs 90.9% - 98.3%, p < 0.001). ADT use had no effect on Hgb levels (p = 0.45). Kernel-weighted local polynomial smoothing implies HVE also have impaired marrow recovery compared to V4Gycc < 1000. <h3>Conclusion</h3> In prostate cancer treatment, a V4Gycc of bone marrow >1000 results in significantly lower Hgb nadir as a percentage of baseline than patients who received V4Gycc < 1000. Our model predicts that if a patient receives V4Gycc to pelvic bone marrow >1000, they will become mildly anemic with a baseline Hgb of 15.2, moderately anemic with a baseline Hgb of 12.8, and severely anemic with a baseline Hgb of 9.3. Limiting pelvic bone marrow to <1000cc receiving ≥4Gy EQD2 is a proposed dose constraint to limit acute marrow toxicity.

Magnetic Resonance Imaging-Guided vs. Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer (MIRAGE): Primary Endpoint Analysis of a Phase III Randomized Trial

<h3>Purpose/Objective(s)</h3> Magnetic resonance imaging (MRI) guidance offers multiple potential advantages over computed tomography (CT) guidance in the context of stereotactic body radiotherapy (SBRT) for intact prostate cancer. Herein we report the outcomes of a phase III randomized trial comparing acute grade ≥2 genitourinary (GU) toxicity after MRI- vs. CT-guided prostate SBRT. <h3>Materials/Methods</h3> Following stratification based on IPSS (≤15 or >15) and prostate volume (≤50 or >50 mL), patients were randomized to receive SBRT with CT- vs. MRI-guidance. Planning margins of 4 mm (CT-arm) and 2 mm (MRI-arm) were placed around the prostate and proximal seminal vesicles, and this volume received 40 Gy in five fractions. Elective nodal radiotherapy and rectal spacers were allowed per physician discretion. The primary endpoint was the incidence of acute (i.e., within 90 days of SBRT completion) grade ≥2 GU physician-reported toxicity (by CTCAE version 4.03). The trial had a superiority design, hypothesizing that 154 patients would provide 89% power to detect a 14% reduction in acute grade ≥2 GU toxicity with MRI-guidance with a one-sided significance level of 0.025. Changes in patient-reported outcomes were compared using a chi-square test with the same significance level. <h3>Results</h3> Between May 2020 and October 2021, 156 patients (n=77 CT and n=79 MRI) were randomized. 81% of patients had NCCN unfavorable intermediate-, high, or very high-risk disease, 44% had placement of a spacer and 27% had nodal radiation. Rates of acute grade ≥2 GU toxicity were significantly lower with MRI- vs. CT-guidance (24.4% [95%CI 15.4-35.4%] vs. 43.4% [95%CI 32.1-55.3%], p=0.01). Rates of acute grade ≥2 GI toxicity were also significantly lower with MRI-guidance (0.0% [95% CI 0-4.6%] vs. 10.5% [4.7-19.7%], p=0.003). On multivariable analysis adjusting for trial arm, age, IPSS, gland volume, spacer use, lymph node radiation, and use of a simultaneous integrated boost dose to gross disease, trial arm remained associated with a 60% reduction in odds of grade ≥2 GU toxicity (odds ratio 0.40 [95%CI 0.19-0.84], p=0.02). MRI-guidance was associated with a significantly smaller proportion of patients with a ≥15-point increase in IPSS approached (6.8% vs. 19.4%, p=0.011). MRI-guidance was associated with a significantly reduced proportion of patients with a clinically significant (>12 point) significant decrease in EPIC-26 bowel scores (25.0% vs. 50.0%, p=0.0013). <h3>Conclusion</h3> MRI-guidance significantly reduced acute grade ≥2 GU and GI toxicity. Patient-reported outcomes were also improved at 1 month with MRI-guidance, and trial arm was a significant predictor of lower odds of moderate GU toxicity after adjusting for other important covariates. Differences in late toxicity will take years to manifest, but in the interim, these data strongly suggest that MRI-guided prostate SBRT affords significantly reduced toxicity compared with CT-guided SBRT.

Density Overrides that Best Predict Bowel Changes during Pencil Beam Scanning Proton Radiotherapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> Changes in patient anatomy during pencil beam scanning proton radiotherapy (PBSPT) can result in substantial differences in dose distribution. In patients with prostate cancer receiving elective nodal irradiation (ENI), interfraction variability in bowel position or bowel filling can highlight this uncertainty. Such changes are often managed by assessing the plan on CT dataset copies with the bowel contour overridden to other densities. The ideal Hounsfield Unit (HU) overrides remain unclear, but extremes (HU=0 water and HU=-1000 air) are often utilized. The aim of the present study is to determine the bowel density overrides that are most predictive of bowel changes during a course of PBSPT. <h3>Materials/Methods</h3> Consecutive patients, from a single institution, receiving PBSPT with ENI for intact prostate cancer were retrospectively reviewed for the period between 10/2020-12/2021. Proton radiotherapy consisted of 50.4 Gy in 28 fractions to the pelvic lymph node stations with a simultaneous integrated boost to 70 Gy in 28 fractions to the prostate. Individually contoured loops of small bowel, large bowel, and rectum were overridden to HU of 0 to -1000 in 100 HU intervals. A bowel evaluation structure, consisting of a bowel bag cropped 3 cm away from the high-risk volume, was created; its dose volume histogram was reviewed; and values for the maximum point dose (Dmax), V105%, V45Gy, V20Gy were recorded for each plan. The dosimetry of bowel override plans were compared to the patient's Quality Assurance CT (QACT) scans. The bowel override plan which most closely matched the dosimetry of each QACT for each dosimetric parameter was determined, and the prevalence of closest prediction for each override value was tabulated. <h3>Results</h3> A total of 32 QACTs from 12 patients were included. For Dmax, HU=0, HU=-100, and HU=-700 predicted most accurately with 10 (31.3%), 5 (15.6%), and 4 (12.5%) closest predictions, respectively. For V105%, HU=-700 and HU=-1000 performed best with 6 (18.8%) and 7 (21.9%), respectively. For V45, HU=0 and HU=-500 predicted best with 13 (40.6%) and 5 (15.6%), respectively. For V20, HU=0, HU=-200, and HU=-600 predicted best with 18 (56.3%), 4 (12.5%), and 3 (9.4%), respectively. Overall, HU=0, -100, -600, -700, and -1000 predicted best with 42 (32.8%), 11 (8.6%), 10 (7.8%), 12 (9.4%), and 12 (9.4%) out of the 128 total dose metrics, respectively. This created a relative bimodal distribution with peaks in the 0 to -100 and -600 to -700 ranges. The nominal plan predicted best in 13 scenarios. <h3>Conclusion</h3> Bowel density override plans remain an important tool for assessment of PBSPT robustness to bowel filling changes throughout the course of therapy as the nominal CT relatively poorly predicts QACT dosimetry. The relatively bimodal distribution of accurate predictions in this study would suggest that the most predictive overrides would be HU∼0 and HU∼-650. Future investigation into multidataset robust optimization with these overrides to improve plan robustness is planned.

Magnetic resonance imaging-guided versus computed tomography-guided stereotactic body radiotherapy for prostate cancer (MIRAGE): Interim analysis of a phase III randomized trial.

255 Background: Magnetic resonance imaging (MRI) guidance offers several theoretical advantages over computed tomography (CT) guidance in the context of stereotactic body radiotherapy (SBRT) for intact prostate cancer. Here we report the results of an interim analysis of the phase III MIRAGE trial, which directly compared MRI- and CT-guidance with a pragmatic primary endpoint of acute grade ≥2 genitourinary (GU) toxicity. Methods: MIRAGE is a single center, randomized phase 3 trial. Men undergoing SBRT for localized prostate cancer were randomly assigned to either CT-guidance or MRI-guidance. Planning margins of 4 mm (CT-arm) and 2 mm (MRI-arm) were placed around the prostate and proximal seminal vesicles, and this volume received 40 Gy in five fractions. Elective nodal radiotherapy and rectal spacers were allowed per physician discretion. The primary outcome was the incidence of acute (i.e., within 90 days of SBRT) grade ≥2 GU physician-reported toxicity (by CTCAE version 4.03). Secondary outcomes of interest included the incidence of acute grade ≥2 GU physician-reported toxicity, changes in IPSS scores at 1 and 3 months, and changes in EPIC-26 bowel domain summary scores at 1 and 3 months. A pre-specified efficacy analysis was planned once the 100th patient was eligible for evaluation of the primary endpoint. Results: On 9/1/2021, 100 patients became eligible for evaluation for the interim analysis (51 CT arm, 49 MRI arm). Acute grade ≥2 GU toxicity was significantly reduced in men receiving MRI-guided SBRT (incidence of 24 (47.1%) vs. 11 (22.4%), p = 0.01). Acute grade ≥2 GI toxicity was also significantly reduced in men receiving MRI-guided SBRT (incidence of 7 (13.7%) vs. 0 (0%), p = 0.01.). The increase in IPSS scores from baseline was significantly higher in men receiving CT-guided SBRT at 1 month post-SBRT (median change of 10 vs. 6, p = 0.03), but not at 3 months (median change of 3 vs. 2, p = 0.3). The decrement in EPIC-26 bowel domain scores was significantly greater at 1 month in men receiving CT-guided SBRT (median change of -8.3 vs. 0, p = 0.03), but not at 3 months (median change of -2.3 vs. 0, p = 0.4). Given the large primary endpoint signal seen, our protocol was amended to reduce the projected sample size to 154 while still maintaining 89% power to detect a difference. Conclusions: This interim analysis demonstrates a statistically significant reduction in acute grade ≥2 GU toxicity with MRI-guidance versus CT-guidance in the context of prostate SBRT. Patient-reported urinary and bowel function metrics are also better preserved at the 1 month time point with MRI-guidance, though this difference dissipates (potentially due to side-effect management) at the 3 month time point. Accrual has been completed as of October 2021 and a final analysis for the primary endpoint is anticipated in early 2022. Clinical trial information: NCT04384770.

Estimating Proton Stopping Power Ratio of a Novel Iodinated Rectal Hydrogel Spacer Using Dual Energy Computed Tomography

A novel iodinated rectal hydrogel spacer (I-RS) has been developed to make the gel radiopaque on CT compared to the standard rectal hydrogel spacers (S-RS). As the iodine in I-RS strongly absorbs kV photons, the accuracy of currently employed CT calibration built into a single energy CT (SECT) becomes inaccurate to determine the proton stopping power ratio (PSR) of the injected gel. Direct measurements of PSR mediated by I-RS with proton beams has been reported; however, those measurements were conducted under ideal conditions without fully accounting for density heterogeneity mediated by air bubbles co-injected with the gel during placement. This study used dual-energy CT (DECT) to estimate I-RS PSR in patients undergoing CT simulation for prostate cancer (PCa) radiotherapy (RT).Sequential scans at 90 and 140 kVp were acquired for 7 intact PCa (I-RS n = 5, S-RS n = 2) on a Philips Brilliance scanner. PSR was reconstructed following the method proposed by Torikoshi and improved by Yang, and compared to similar measurements when I-RS was replaced with S-RS. A pre-calculated table correlating effective atomic number with all possible Hounsfield Unit (HU) combinations from two sequential scans was implemented to accelerate reconstruction. PSRs were compared between DECT and SECT, and between I-RS and S-RS.In gel, HU measurements were heterogeneous (range -372 - +358). The mean PSR on reconstruction when using DECT was 0.966 (0.940-0.980) for I-RS. Replacement of I-RS with S-RS HU density resulted in a mean PSR of 0.937 (0.926-0.941) by DECT. PSR for I-RS on SECT was 1.107, and 1.014 for S-RS. The estimated difference between PSR in I-RS and S-RS on DECT vs. SECT were 14% and 8%, respectively.These data demonstrate that the use of I-RS in proton RT treatment planning could overestimate proton range due to underestimating PSR when CT simulation is performed using standard SECT. Notably, PSR absolute value reported here is different compared to previously reported in vitro data under ideal conditions and may be related to differences in gel heterogeneity in vivo. Heterogeneity is highlighted by the wide range of gel HU measurements. Direct measurements of PSR will be obtained in a planned future experiment. These data suggest that PSR overestimation due to I-RS should be considered when planning PCa treatment using proton therapy for patients who get I-RS to reduce treatment toxicity.

Five-Year Development and Usage Outcomes of eContour, a Web-Based Interactive Contouring Atlas

<h3>Purpose/Objective(s)</h3> The delivery of safe and effective radiation therapy relies on accurate target delineation, particularly in the era of highly conformal treatment techniques. Contouring resources can improve accuracy but are fragmented and underused. We report the 5-year development and usage outcomes of a free, online, easily accessible web-based interactive contouring atlas. <h3>Materials/Methods</h3> <b>eContour</b> (https://econtour.org) was developed using modern web technologies, including HTML5, Python, and an interpreted computer programming language, to interactively display images and contours from real patient cases. The viewer has standard tools for image manipulation, contour display, image overlays, and radiation dose distribution. Information from evidence-based guidelines and clinical pearls are summarized and presented next to each case. Mixpanel software was used to collect web usage statistics, including user demographics, geography, and case views. <h3>Results</h3> In the first 5 years of operation (February 1, 2016 to February 1, 2021), a total of 22,889 users registered on eContour. Users represented a total of 146 countries, with the largest cohort from the United States (7,096, 31%). Other countries with > 700 registered users included Spain, India, Brazil, China, and Russia. The majority of registered users (58%) reported their profession as physicians, including 10,869 practicing radiation oncologists (47%) and 2,583 resident physicians (11%). There are 3,107 users who identified as physicians and were geographically within the US. The remaining users identified as radiation therapists (10%), dosimetrists (10%), medical physicists (8.7%), and medical students (6.6%). As of February 2021, a total of 65 cases have been developed covering 9 disease sites. The most commonly viewed disease site was head and neck (23% of all case views), followed by gynecological, gastrointestinal, and breast cancer. The most commonly viewed cases include pre-operative rectal cancer, head and neck organs-at-risk, and intact prostate cancer. Over 5 years, usage of <b>eContour</b> has increased both in terms of total users and case views. Total users have grown > 600% since 2017; 3,613 (2017), to 12,248 (2019), to 22,889 cumulative total users (2021). In the fourth quarter of 2020, <b>eContour</b> averaged 1,018 case views per weekday. Since the onset of the COVID pandemic, usage of <b>eContour</b> has accelerated. Annual case views increased 56% year-over-year from 2019 to 2020 (147,846 to 230,304 views) as compared to essentially stable from 2018 to 2019 (144,769 to 147,846). <h3>Conclusion</h3> With approximately 5,000 radiation oncologists in the US, we estimate 60% of US radiation oncologists are registered users. Growth in users and web site traffic over the first 5 years of <b>eContour</b> show its strong potential to increase the use of evidence-based contouring information at the point of care.

Long-term Clinical Outcomes in Favorable Risk Prostate Cancer Patients Receiving Proton Beam Therapy.

PurposeLong-term data regarding the disease control outcomes of proton beam therapy (PBT) for patients with favorable risk intact prostate cancer (PC) are limited. Herein, we report our institution's long-term disease control outcomes in PC patients with clinically localized disease who received PBT as primary treatment.MethodsOne hundred sixty-six favorable risk PC patients who received definitive PBT to the prostate gland at our institution from 2010 to 2012 were retrospectively assessed. The outcomes studied were biochemical failure-free survival (BFFS), biochemical failure, local failure, regional failure, distant failure, PC-specific survival, and overall survival. Patterns of failure were also analyzed. Multivariate Cox proportional hazards modeling was used to estimate independent predictors of BFFS.ResultsThe median length of follow-up was 8.3 years (range, 1.2–10.5 years). The majority of patients had low-risk disease (58%, n = 96), with a median age of 64 years at the onset of treatment. Of 166 treated men, 13 (7.8%), 8 (4.8%), 2 (1.2%) patient(s) experienced biochemical failure, local failure, regional failure, respectively. Regional failure was seen in an obturator lymph node in 1 patient and the external iliac lymph nodes in the other. None of the patients experienced distant failure. There were 5 (3.0%) deaths, none of which were due to PC. The 5- and 8-year BFFS rate were 97% and 92%, respectively. None of the clinical disease characteristics or treatment-related factors assessed were associated with BFFS on multivariate Cox proportional hazards modeling (all P > .05).ConclusionDisease control rates reported in our assessment of PBT were similar to those reported in previous clinically localized intact PC analyses, which used intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, or radical prostatectomy as definitive therapy. In addition, BFFS rates were similar, if not improved, to previous PBT studies.

Characterization of an Iodinated Rectal Spacer for Prostate Photon and Proton Radiation Therapy

PurposeConventional rectal spacers (nonI-SPs) are low-contrast on computed tomography (CT), often necessitating magnetic resonance imaging for accurate delineation. A new formulation of spacers (I-SPs) incorporates iodine to improve radiopacity and CT visualization. We characterized placement, stability, and plan quality of I-SPs compared to nonI-SPs. Methods and MaterialsPatients with intact prostate cancer (n = 50) treated with I-SPs and photons were compared to randomly selected patients (n = 50) with nonI-SPs (photon or proton therapy). The I-SP was contoured on the planning CT and cone beam CTs at 3 timepoints: first, middle, and final treatment (n = 200 scans). I-SPs Hounsfield units (HU), volume, surface area (SA), centroid position relative to prostate centroid, and distance between prostate/rectum centroids were compared on the planning CTs between each cohort. I-SP changes were evaluated on cone beam CTs over courses of treatment. Dosimetric evaluations of plan quality and robustness were performed. I-SP was tested in a phantom to characterize its relative linear stopping power for protons. ResultsI-SPs yielded a distinct visible contrast on planning CTs compared to nonI-SPs (HU 138 vs 12, P < .001), allowing delineation on CT alone. The delineated volume and SA of I-SPs were smaller than nonI-SPs (volume 8.9 vs 10.6 mL, P < .001; SA 28 vs 35 cm2, P < .001), yet relative spacer position and prostate-rectal separation were similar (P = .79). No significant change in HU, volume, SA, or relative position of the I-SPs hydrogel occurred over courses of treatment (all P > .1). Dosimetric analysis concluded there were no significant changes in plan quality or robustness for I-SPs compared to nonI-SPs. The I-SP relative linear stopping power was 1.018, necessitating HU override for proton planning. ConclusionsI-SPs provide a manifest CT contrast, allowing for delineation on planning CT alone with no magnetic resonance imaging necessary. I-SPs radiopacity, size, and relative position remained stable over courses of treatment from 28 to 44 fractions. No changes in plan quality or robustness were seen comparing I-SPs and nonI-SPs.

ARPM-net: A novel CNN-based adversarial method with Markov random field enhancement for prostate and organs at risk segmentation in pelvic CT images.

The research is to develop a novel CNN-based adversarial deep learning method to improve and expedite the multi-organ semantic segmentation of CT images and to generate accurate contours on pelvic CT images. Planning CT and structure datasets for 120 patients with intact prostate cancer were retrospectively selected and divided for tenfold cross-validation. The proposed adversarial multi-residual multi-scale pooling Markov random field (MRF) enhanced network (ARPM-net) implements an adversarial training scheme. A segmentation network and a discriminator network were trained jointly, and only the segmentation network was used for prediction. The segmentation network integrates a newly designed MRF block into a variation of multi-residual U-net. The discriminator takes the product of the original CT and the prediction/ground-truth as input and classifies the input into fake/real. The segmentation network and discriminator network can be trained jointly as a whole, or the discriminator can be used for fine-tuning after the segmentation network is coarsely trained. Multi-scale pooling layers were introduced to preserve spatial resolution during pooling using less memory compared to atrous convolution layers. An adaptive loss function was proposed to enhance the training on small or low contrast organs. The accuracy of modeled contours was measured with the dice similarity coefficient (DSC), average Hausdorff distance (AHD), average surface Hausdorff distance (ASHD), and relative volume difference (VD) using clinical contours as references to the ground-truth. The proposed ARPM-net method was compared to several state-of-the-art deep learning methods. ARPM-net outperformed several existing deep learning approaches and MRF methods and achieved state-of-the-art performance on a testing dataset. On the test set with 20 cases, the average DSC on the prostate, bladder, rectum, left femur, and right femur were 0.88 ( 0.11), 0.97 ( 0.07), 0.86 ( 0.12), 0.97 ( 0.01), and 0.97 ( 0.01), respectively. The average HD (mm) on these organs were 1.58 ( 1.77), 1.91 ( 1.29), 3.14 ( 2.39), 1.76 ( 1.57), and 1.92 ( 1.01). The average surface HD (mm) on these organs are 2.11 ( 2.03), 2.36 ( 2.43), 3.05 ( 2.11), 1.99 ( 1.66), and 2.00 ( 2.07). ARPM-net was designed for the automatic segmentation of pelvic CT images. With adversarial fine-tuning, ARPM-net produces state-of-the-art accurate contouring of multiple organs on CT images and has the potential to facilitate routine pelvic cancer radiation therapy planning process.

Neurologically asymptomatic cerebral oligometastatic prostate carcinoma metastasis identified on [Ga]Ga-THP-PSMA PET/CT

BackgroundBrain metastases from prostate cancer are rare and usually only occur in the context of widespread systemic disease. This is the first case report of a solitary brain oligometastasis, in a neurologically intact prostate cancer patient with no other systemic disease, detected using [68Ga]Ga-THP-PSMA PET/CT and only the second one using a PSMA-based radiopharmaceutical.Case presentationWe report the case of a prostate cancer patient presenting 5 years after robot-assisted laparoscopic prostatectomy with biochemical recurrence, no neurological symptoms, and in the absence of metastatic lesions in the body on conventional imaging. A solitary cerebral metastasis was detected using [68Ga]Ga-THP-PSMA PET/CT, surgically resected, leading to a drop in serum PSA and a good recovery.ConclusionIn this case, [68Ga]Ga-THP-PSMA PET/CT resulted in a major change in clinical management and avoided additional morbidity associated with delayed diagnosis and treatment. This report demonstrates the importance of considering the presence of metastatic disease outside the conventional locations of prostate cancer spread, as well as the importance of ensuring comprehensive [68Ga]Ga-PSMA PET/CT coverage from vertex to upper thighs.

Risk of erectile dysfunction after modern radiotherapy for intact prostate cancer.

Erectile dysfunction (ED) is a prevalent side effect of prostate cancer treatment. We hypothesized that the previously reported rates of ED may have improved with the advent of modern technology. The purpose of this project was to evaluate modern external beam radiotherapy and brachytherapy techniques to determine the incidence of radiotherapy (RT) induced ED. A systematic review of the literature published between January 2002 and December 2018 was performed to obtain patient reported rates of ED after definitive external beam radiotherapy, ultrafractionated stereotactic radiotherapy, and brachytherapy (BT) to the prostate in men who were potent prior to RT. Univariate and multivariate analyses of radiation dose, treatment strategy, and length of follow-up were analyzed to ascertain their relationship with RT-induced ED. Of 890 articles reviewed, 24 met inclusion criteria, providing data from 2714 patients. Diminished erectile function status post RT was common and similar across all studies. The median increase in men reporting ED was 17%, 26%, 23%, and 23%, 3DCRT, IMRT, low dose rate BT, and SBRT, respectively, at 2-year median follow-up. ED is a common side effect of RT. Risk of post-RT ED is similar for both LDR brachytherapy and external beam RT with advanced prostate targeting and penile-bulb sparing techniques utilized in modern RT techniques.

Obesity and Acute Urinary and Bowel Quality of Life (QOL) during Prostate Radiation Therapy

Obesity has been associated with increased risk of complications for men undergoing radical prostatectomy; however, the impact of obesity on toxicity and QOL with external beam radiotherapy (RT) is unclear. We examined acute changes in urinary and bowel QOL among obese men compared to non-obese men receiving RT for prostate cancer. All patients receiving definitive RT (>70 Gy) for intact prostate cancer at a single institution from 2010 to 2016 prospectively completed QOL surveys using the validated Prostate Cancer Symptom Index (PCSI) at baseline and weekly during treatment. Urinary Obstructive/Irritative and Bowel domains scores were calculated, ranging from 0 (best QOL) to 100 (worst). QOL scores were compared among patients who were non-obese (body mass index <30) vs obese (body mass index≥30) using parametric statistical tests. We further compared each individual urinary and bowel item among obese and non-obese patients, and a worsening of ≥2 points on a 4-5 point Likert scale in any item during RT was defined as a clinically meaningful change in the PCSI. Logistic regression assessed whether obesity was associated with clinically significant worsening of specific symptoms, adjusting for age, baseline symptoms, and androgen deprivation therapy use. Two hundred eleven patients were included and 39% were obese; 90% received concurrent androgen deprivation therapy. At baseline, overall bowel and urinary domain scores were not significantly different among obese and non-obese patients. Bowel and urinary scores worsened from baseline to end of RT for both obese and non-obese patients. On multivariable analysis, obesity was not significantly associated with worsening of any individual urinary or bowel symptom. Our results showed no evidence that obesity increased acute patient-reported urinary or bowel QOL changes overall, or for any individual symptom, during RT. These findings help inform patients and physicians during the treatment decision-making process.Tabled 1Abstract TU_42_3734; Table 1BaselineWeek 1-2Week 3-4Week 5-6Week 7-9Bowel scoreNon-obese4.65.56.88.110.1Obese6.66.710.58.99.5Difference2.01.23.70.8-0.6Urinary scoreNon-obese24.128.221.337.737.8Obese27.129.525.637.539.4Difference3.01.34.3-0.21.6 Open table in a new tab

Permanent prostate brachytherapy monotherapy with I-125 for low- and intermediate-risk prostate cancer: Outcomes in 974 patients

PurposeTo report outcomes of patients undergoing low-dose-rate (LDR) brachytherapy and investigate factors associated with biochemical failure and survival. MethodsConsecutive patients undergoing LDR with I-125 at our institution between 1998 through 2013 for primary intact prostate cancer were examined. Those with low- and intermediate-risk disease receiving LDR with a minimum of 2 years followup and at least one post-LDR prostate-specific antigen (PSA) were included. ResultsAbout 974 patients satisfied inclusion criteria. With median followup of 72 months, biochemical failure occurred in 45 patients. Freedom from biochemical failure as defined by the Phoenix criterion was 96% and 88% at 5 and 10 years, worse for intermediate risk as compared with low risk, with 10-year freedom from biochemical failure of 76% versus 92% (hazard ratio [HR] = 3.7, p < 0.001), respectively. On multivariable analysis, increased prebiopsy PSA, Gleason 4 + 3, and no androgen deprivation therapy were associated with biochemical failure. Gleason 4 + 3 was the factor most strongly associated with biochemical failure (HR = 7.01, p < 0.001). No examined factors were associated with local failure. Gleason 4 + 3 disease increased the likelihood of distant metastasis (HR = 12.4, p = 0.003) and prostate cancer–specific death (HR = 13.2, p < 0.001). No difference in outcomes between patients with Gleason 3 + 3 versus 3 + 4 was observed. ConclusionsLDR brachytherapy provided excellent outcomes in this large series of patients treated for localized organ-confined prostate cancer. Local recurrence at 10 years was low at 2.1%. Primary Gleason 4 + 3, higher pretreatment PSA, and no receipt of androgen deprivation therapy were the only factors associated with biochemical failure. Primary Gleason 4 disease was also predictive of distant metastases and decreased prostate cancer–specific survival.

Abstract B024: Family history of prostate cancer and the incidence of ERG- and PTEN-defined prostate cancer

Abstract Introduction: Family history is among the strongest known risk factors for prostate cancer. Emerging data suggest unique molecular subtypes of disease, including common somatic genetic aberrations: fusions of androgen-regulated promoters with ERG and, separately, PTEN loss. We examined associations between family history and incidence of these subtypes under the hypothesis that family history could be differentially associated with their occurrence. Methods: We studied 47,115 men in the prospective Health Professionals Follow-up Study from 1986 to 2009. ERG and PTEN status were assessed with immunohistochemistry. Multivariable competing risk models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between self-reported family history of prostate cancer and disease defined by molecular subtypes. Results: During a median follow-up of 22.3 years, 5,606 prostate cancer cases were diagnosed. Among them, 889 and 711 were assayed for ERG status (48% ERG+) and PTEN loss (14% PTEN null), respectively. Prostate cancer family history was positively associated with both ERG+ (HR=1.85; 95% CI: 1.47-2.33) and ERG- (HR=2.20; 95% CI: 1.78-2.72) disease (P-heterogeneity=0.29). High-grade ERG+ disease suggested a pronounced association (HR=2.58; 95% CI: 1.85-3.61; P-heterogeneity versus high-grade ERG-: 0.08). Family history was also positively associated with PTEN null (HR=2.39; 95% CI: 1.53-3.71) and PTEN intact (HR=1.88; 95% CI: 1.54-2.28) prostate cancer (P-heterogeneity=0.34). Conclusion: Prostate cancer family history is positively associated with prostate cancer defined by ERG and PTEN, suggesting a similar role of genetic susceptibility for these subtypes. It is possible that high-grade ERG+ disease could be uniquely associated with positive family history. Citation Format: Dana Hashim, Amparo G. Gonzalez-Feliciano, Thomas U. Ahearn, Andreas Pettersson, Lauren Barber, Claire H. Pernar, Ericka M. Ebot, Stephen Finn, Edward L. Giovannucci, Rosina T. Lis, Massimo Loda, Giovanni Parmigiani, Kathryn L. Penney, Tamara Lotan, Philip W. Kantoff, Lorelei A. Mucci, Rebecca E. Graff. Family history of prostate cancer and the incidence of ERG- and PTEN-defined prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B024.

CHD1 deletion is an independent predictor of poor prognosis by increased metastasis in both PTEN-deficient and -intact prostate cancer

CHD1 deletion is an independent predictor of poor prognosis by increased metastasis in both PTEN-deficient and -intact prostate cancer

Magnetic resonance image-guided radiation therapy (MR-IGRT) for the treatment of prostate cancer: Initial clinical experience and patient selection.

156 Background: Magnetic resonance image-guided radiation therapy (MR-IGRT) has been implemented at our institution since 2014. We report on the initial clinical experience and patient selection in treating prostate cancer utilizing the first commercially-implemented MR-IGRT system. Methods: A total of 13 patients with prostate cancer have been treated with intensity-modulated radiation therapy (IMRT) using an MR-IGRT system. Of those treated, 6 patients received definitive radiation therapy (RT) for low, intermediate or high risk prostate cancer, 5 patients were treated with salvage RT after biochemical failure following surgery, and 1 patient was treated for the boost portion of definitive RT. Results: Patients were selected for MR-IGRT based on various clinical decisions. Four patients had co-morbidities requiring anticoagulation for which fiducial marker placement was contraindicated and soft tissue visualization via MR imaging was thought to be beneficial for daily set-up. Three patients were referred from outside institutions with concerns of radiation dose to the small bowel, and daily MR monitoring of bowel anatomy could be performed with plans for treatment adaptation if anatomy changed. One patient had received prior RT for rectal cancer and dose to organs at risk was of concern. The remainder of patients were post-operative salvage cases selected based on physician concern of accurate and reproducible daily localization with fiducial markers alone. Daily volumetric MR was monitored with the ability for treatment adaptation should small bowel dose increase, and no treatment changes were required. For all cases, onboard sagittal cine MR was visually monitored for bladder and target motion, and qualitative evaluation demonstrated no significant intra-fraction motion. Conclusions: MR-IGRT provides unique advantages when fiducial markers are contraindicated or when daily visualization of dose to the small bowel or other organs at risk is required to monitor and potentially prevent normal tissue toxicity. Clinical trials are in development to formally evaluate MR-IGRT for the treatment of intact and salvage prostate cancer.

Health-Related Quality of Life and Efficacy Outcomes of Cs-131 Brachytherapy in Combination With External Beam Radiation Therapy in Patients With Intermediate- and High-Risk Prostate Cancer

Results: Four year freedom from (FF) G2+ GI and GU toxicity were both 91%. GI and GU toxicity included 50% diarrhea, 50% hemorrhage, and 8% proctitis (nZ12), and 46% frequency, 13% obstructive, 20% cystitis, and 33% incontinence (nZ15), respectively. RTOG 0534 rectum and bladder goals were not achieved in 65% and 41% of cases, while institutional goals were not achieved in 21% and 25% of cases, respectively. However, none of these proposed goals were associated with late toxicity (P>.1). Median trigone V70 Gy was 23%. Dose to the bladder trigone was not associated with GU toxicity, although V70 Gy <25% trended toward an association (4 year FFG2+ GU toxicity, 94% vs 87%, PZ.2). Meanwhile, dose to the bladder-CTV was not associated with GU toxicity at various dose levels. Univariate analysis for age, pelvic RT, RT dose, anticoagulation use, ADT, time from RP to RT, and tobacco history were not associated with toxicity. Conclusion: No tested tissue parameters were associated with post-RP RT late toxicity, perhaps influenced by the low rate of toxicity. In the absence of any established DVH relationships in the post-RP setting, it is reasonable to use normal tissue sparing guidelines for intact prostate cancer. Dose to the trigone requires further study and may be more meaningful than dose to the bladder or bladder-CTV. Author Disclosure: A. Parekh: None. C. Son: None. J.M. Melotek: None. C. Pelizzari: None. G. Hubert: None. S. Liauw: None.