Prostate Planning Target Volume Research Articles

Microboost dose escalation for localized prostate cancer within a statewide radiation oncology quality consortium.

298 Background: The phase III FLAME trial demonstrated that in localized prostate cancer, an external beam radiotherapy (EBRT) simultaneous integrated microboost to an MRI-defined dominant intraprostatic lesion improves biochemical control without affecting toxicity and quality of life. Given the complexity required to deliver high microboost doses, we hypothesized that practice patterns are variable in clinical practice. We aimed to characterize microboost utilization and evaluate dosimetric parameters within the statewide Michigan Radiation Oncology Quality Consortium (MROQC). Methods: Men with intermediate or high-risk prostate adenocarcinoma treated with curative intent radiotherapy for intact disease were included. Data was prospectively collected, including T/N-category, Gleason score, prostate-specific antigen, and percent positive biopsy cores. Full DICOM files were available for dosimetric data. Multivariable analyses (MVA) were used to evaluate associations between receipt of microboost, known prognostic factors, and fiducial marker and rectal spacer placement (advanced image guided radiation therapy (IGRT)). Results: From 10/26/20 to 06/26/23, 741 patients across 26 centers were enrolled, 71% (n=528) with intermediate-risk and 29% (n=213) with high-risk disease. Androgen deprivation therapy was planned in 61%. EBRT + whole-gland brachytherapy boost was utilized in 29% (n=217/741) of patients. Of those treated with EBRT (71%, n=524/741), 10% received a microboost (n = 53/524). Brachytherapy boost and microboost were used in 9 and 7 centers, respectively. Most patients received either conventional fractionation or moderate hypofractionation- 11% and 66% in EBRT without microboost and 21% and 60% with microboost, respectively. Microboost treatment was associated with use of a planning MRI (91% vs. 62%, p <0.0001) as well as fiducial marker and rectal spacer placement (76% vs. 45%, p <0.0001). Median prostate planning target volume (PTV) was smaller in microboost patients (127 cc vs. 91 cc, p = 0.002); median boost volume was 21 cc. Median boost dose (D0.1cc) was 117% (IQR 115% – 119%) of the PTV prescription. Microboost patients had significantly higher mean bladder D1cc[%] (105.7% vs. 103.4%, p = 0.002) and numerically lower rectal D1cc[%] (90.7% vs. 94.1%, p = 0.065). On MVA, receipt of microboost was significantly associated with grade group 4 or 5 disease, planning MRI use, and fiducial and rectal spacer use. Conclusions: Within a large, diverse prospective cohort of men with prostate cancer treated in both academic and community settings, a microboost was utilized in 10% of EBRT cases. Microboost use was associated with higher grade group, MRI planning, and advanced IGRT. EBRT microboost is an emerging dose escalation strategy and further studies confirming safety and improved clinically meaningful outcomes may increase uptake in routine practice.

Empowering Vision Transformer by Network Hyper-Parameter Selection for Whole Pelvis Prostate Planning Target Volume Auto-Segmentation

U-Net, based on a deep convolutional network (CNN), has been clinically used to auto-segment normal organs, while still being limited to the planning target volume (PTV) segmentation. This work aims to address the problems in two aspects: 1) apply one of the newest network architectures such as vision transformers other than the CNN-based networks, and 2) find an appropriate combination of network hyper-parameters with reference to recently proposed nnU-Net (“no-new-Net”). VT U-Net was adopted for auto-segmenting the whole pelvis prostate PTV as it consisted of fully transformer architecture. The upgraded version (v.2) applied the nnU-Net-like hyper-parameter optimizations, which did not fully cover the transformer-oriented hyper-parameters. Thus, we tried to find a suitable combination of two key hyper-parameters (patch size and embedded dimension) for 140 CT scans throughout 4-fold cross validation. The VT U-Net v.2 with hyper-parameter tuning yielded the highest dice similarity coefficient (DSC) of 82.5 and the lowest 95% Haussdorff distance (HD95) of 3.5 on average among the seven recently proposed deep learning networks. Importantly, the nnU-Net with hyper-parameter optimization achieved competitive performance, although this was based on the convolution layers. The network hyper-parameter tuning was demonstrated to be necessary even for the newly developed architecture of vision transformers.

Adaptive Ultra-Hypofractionated Whole-Pelvic Radiotherapy in High-Risk and Very High-Risk Prostate Cancer on 1.5-1.5 MR Linac: The Estimated Delivered Dose and Early Toxicity Results

To study the feasibility and safety for patients with high-risk (HR) and very high-risk (VHR) prostate cancer treated with adaptive ultra-hypofractionated whole-pelvic radiotherapy (UHF-WPRT) on 1.5 magnetic resonance (MR)-Linac. Sevenpatients with clinical stage T3a-4N0-1M0-1c consecutively treated with UHF-WPRT on a 1.5-T MR-Linac were recruited prospectively in a phase II trial (NCT05183074, ChiCTR2000033382). A 36.25 Gy dose in five fractions was delivered every other day with a boost of 40 Gy to the whole prostate, as well as 25 Gy to whole pelvic nodal area with a concomitant boost of 35 Gy to metastatic regional nodes. To estimate the delivered dose, we collected data by 3D-MR for the following stages: pre-MR, position verification-MR (PV-MR) in the Adapt-To-Shape (ATS) workflow, and 3D-MR during the beam-on phase (Bn-MR) and at the end of RT (post-MR). The target and organ-at-risk contours in the PV-MR, Bn-MR, and post-MR stages were projected from the pre-MR data by deformable image registration and manually adapted by the physician, followed by dose recalculation for the ATS plan. The cumulative acute genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated as per NCI-CTCAE 5.0 criteria. The primary endpoints were acute ≥grade 3 genitourinary (GU) and gastrointestinal (GI) toxicities during the first 3 months. Overall, 133 MR scans were collected (35 pre-MR, 35 PV-MR, 31 Bn-MR and 32 post-MR scans). With a median on-couch time of 61 minutes, the mean prostate and pelvic planning target volume (PTV)-V95% of all scans was 96.98 ± 3.06% and 96.44 ± 2.85%, respectively. The corresponding mean prostate clinical target volume (CTV)-V100% was 99.89 ± 0.32%, 98.71 ± 1.90%, 97.77 ± 2.89%, and 98.56 ± 1.72%, and the mean pelvic CTV-V100% was 97.57% ± 3.70%, 96.54 ± 3.80%, 95.43 ± 4.31%, and 94.39 ± 4.47% on pre-MR, PV-MR, Bn-MR and post-MR scans, respectively. For the 4 patients with positive nodes, the mean V100% of metastatic regional nodes was 99.89 ± 0.81%. The median V29 Gy change in the rectal wall was -1% (-18%-20%). The V29 Gy of the rectal wall increased by >15% was observed in one scan. A slight increase in the high dose of bladder wall was noted due to gradual bladder growth during the workflow. With median follow-up time of 7.3 (4.6-12.2) months, all patients were followed-up for more than 3 months. No patient was observed with acute CTCAE grade 2 or more severe GU or GI toxicities (0%). UHF-RT to prostate and pelvic with ATS workflow is well tolerated by patients with HR and VHR prostate cancer, with only mild GU and GI toxicities. The 3D-MR-based dosimetry analysis demonstrated clinically acceptable estimated dose coverage of target volumes during the beam-on period.

Dosimetry Validation of MR-Only Treatment Planning Based upon the Synthetic MRCAT Pelvis with Continuous Hounsfield Units in Prostate Cancer

MR-based radiotherapy delivery systems are increasingly encouraging treatment planning based upon an AI generated synthetic CT created from an MR image. Concerns remain concerning the dosimetric accuracy of this approach. to evaluate and compare the feasibilities and dosimetry of magnetic resonance (MR) image-based planning using pelvic synthetic computed tomography (sCT) versus conventional computed tomography (cCT) based planning. We used the new MRCAT pelvis MRI-SIM (1.5T) with continuous Hounsfield units for dose calculation. The hypothesis was that planning based upon sCT vs cCT would not lead to a difference in dose delivery. A total of 10 consecutive patients with prostate cancer representing a range of treatment regimens underwent both a conventional CT based 3d simulation and also an MR simulation from which an MRI-simulation procedure for calculating attenuation (MRCAT) image was generated. A VMAT plan was generated based upon the cCT, and then applied to the sCT without re-optimization. Delivered dose was recalculated on the sCT plan using the fixed monitor units previously optimized for the cCT. Dose volume histograms (DVHs) were calculated for targets and organs at risk (OAR) and compared with those achieved with the cCT. In addition, dose values from 10 different point-coordinates and dose distributions volumes (i.e., volume receiving 80%, 50%, 30% prescribe dose etc.) were compared. All patients were receiving definitive RT to prostate: 2 prostate and seminal vesicles and 8 prostate with lymph nodes were treated. Median prostate volume was 34.3 cc (range 29 cc-84 cc), median number of fractions was 12 (range 5 fr-26 fr), median prescription dose was 51.6 Gy (range 40 Gy-70.2 Gy). The mean dose to the prostate planning target volume and six different OAR were calculated on sCT and cCT, differed by 0.7% ± 1.3% (p = 0.02). Three dose distribution line volume between 30%-80% of prescribed dose, differed by 1.8%±3% (p = 0.02). Ten point-coordinate dose values from different tissues including bone, fat, air and muscle around the planning treatment volume differed by 0.4% ±0.7% (p = 0.03). There was a very small (∼ 1%), but clinically insignificant, difference in the dose distribution results obtained using sCT from MRCAT compared with those obtained with cCT. The Philips pelvic MRCAT, even in the absence of a cCT, is suitable for clinical treatment planning in prostate radiotherapy.

Analytical dosimetric study of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for prostate cancer

PurposeThe study aimed to compare the dosimetric results and treatment delivery efficiency among four techniques to explore the preferred technique in prostate treatment.Materials and methods7 IMRT, 9 IMRT, 1 ARC, and 2 ARC plans were created for 30 prostate cancer patients using the Eclipse™ treatment planning system (Varian Medical Systems). All the plans were designed to deliver 80.0 Gy in 40 fractions to the prostate planning target volume (PTV). Target coverage, organs at risk (OARs), number of monitor units, homogeneity, and conformity were compared across the four techniques to assess the quality of the plans.ResultsThe study revealed better Planning Target Volume (PTV) dose coverage in the VMAT-2A than in the other plans. At the same time, VMAT-2A plans were found to be significantly lower in terms of Bladder and rectum doses than other techniques. In addition, VMAT has the advantage of considerably reducing the number of monitor units and treatment time.ConclusionFor prostate cancer, VMAT may offer a favorable dose gradient profile, conformity, and MU and treatment time compared to IMRT.

Effect of Large Prostate Volume on Efficacy and Toxicity of Moderately Hypofractionated Radiation Therapy in Patients With Prostate Cancer

PurposeTo evaluate the effect of prostate volume on outcomes after moderately hypofractionated radiation therapy (mHFRT) for prostate cancer. Methods and MaterialsProstate cancer patients treated with mHFRT at a Veteran's Affairs Medical Center from August 20, 2008, to January 31, 2018, were identified. Patients were placed into a large prostate planning target volume (LPTV) cohort if their prostate PTV was in the highest quartile. Acute/late genitourinary (GU) and gastrointestinal toxicity events among patients with and without LPTV were compared. Multivariable analyses estimated the effect of factors on toxicity. Overall survival, biochemical recurrence-free survival, and freedom from late GU/gastrointestinal toxicity of patients with and without LPTV were estimated via Kaplan-Meier. ResultsFour hundred and seventy-two patients were included. Ninety-three percent received 70 Gy in 2.5 Gy fractions; 75% received androgen deprivation therapy. Median follow-up was 69 months. Patients with LPTV (PTV >138.4 cm3) had a higher late 2 + GU toxicity compared with those without (59% vs 48%, P = .03). Earlier time to late 2 + GU toxicity was associated with LPTV (hazard ratio 1.36; 95% confidence interval [CI], 1.00-1.86; P = .047), androgen deprivation therapy use (hazard ratio 1.60; 95% CI, 1.13-2.27; P = .01), and higher baseline American Urologic Association symptom score (odds ratio 1.03; 95% CI, 1.02-1.05; P < .001). At 2 years, freedom from late 2 + GU toxicity was 46% (95% CI, 47%-54%) for those with LPTV versus 61% (95% CI, 55%-65%) for those without (P = .04). Late grade 3 GU toxicity was 7% for those with LPTV and 4% for those without. No differences in overall survival or biochemical recurrence-free survival were observed between patients with or without LPTV. ConclusionsLPTV did not affect efficacy of mHFRT for prostate cancer; however, it was associated with increased risk and earlier onset of late grade 2 + GU toxicity.

A comparative study of prostate PTV margins for patients using hydrogel spacer or rectal balloon in proton therapy.

To compare the planning target volume (PTV) margins needed for prostate patients who have used hydrogel spacer or rectal balloon during proton treatments. Total of 190 prostate patients treated with proton therapy during 2017 were selected for this study. Of these patients, 96 had hydrogel spacer injection and 94 patients had only rectal balloons insertion. All patients had implanted gold markers inside the prostate for daily target alignment. Post-treatment radigraphs were obtained to evaluate prostate intrafraction motion. The systematic and random components of patient setup residual error and prostate intrafraction motion error were obtained. PTV margins were calculated using the van Herk formula for both patient groups. For setup residual error, the mean values in the superior-inferior (SI) direction and the variances in the left-right (LR) direction were statistically different between the two groups. For intrafraction motion, there were significant differences of the mean values in the SI direction and of the variances in both LR and anterior-posterior (AP) directions. The population PTV margins for hydrogel spacer group were 2.6mm, 3.3mm, and 1.6mm in LR, SI, AP directions, respectively. For the rectal balloon group, the PTV margins were 2.1mm, 3.1mm, and 2.0mm in LR, SI, AP directions, respectively. Statistically significant differences were observed in the patient setup and prostate intrafraction motion errors of the two patient groups. However, under the current protocol of bladder preparation and daily marker-based x-ray image-guidance, population PTV margins were comparable between the two patient groups.

A deep learning framework for prostate localization in cone beam CT-guided radiotherapy.

To develop a deep learning-based model for prostate planning target volume (PTV) localization on cone beam computed tomography (CBCT) to improve the workflow of CBCT-guided patient setup. A two-step task-based residual network (T2 RN) is proposed to automatically identify inherent landmarks in prostate PTV. The input to the T2 RN is the pretreatment CBCT images of the patient, and the output is the deep learning-identified landmarks in the PTV. To ensure robust PTV localization, the T2 RN model is trained by using over thousand sets of CT images with labeled landmarks, each of the CTs corresponds to a different scenario of patient position and/or anatomy distribution generated by synthetically changing the planning CT (pCT) image. The changes, including translation, rotation, and deformation, represent vast possible clinical situations of anatomy variations during a course of radiation therapy (RT). The trained patient-specific T2 RN model is tested by using 240 CBCTs from six patients. The testing CBCTs consists of 120 original CBCTs and 120 synthetic CBCTs. The synthetic CBCTs are generated by applying rotation/translation transformations to each of the original CBCT. The systematic/random setup errors between the model prediction and the reference are found to be <0.25/2.46mm and 0.14/1.41° in translation and rotation dimensions, respectively. Pearson's correlation coefficient between model prediction and the reference is higher than 0.94 in translation and rotation dimensions. The Bland-Altman plots show good agreement between the two techniques. A novel T2 RN deep learning technique is established to localize the prostate PTV for RT patient setup. Our results show that highly accurate marker-less prostate setup is achievable by leveraging the state-of-the-art deep learning strategy.

Evaluation of PTV margins in IMRT for head and neck cancer and prostate cancer

AbstractPurpose:The aim of this study was to evaluate planning target volume (PTV) margins for two different locations using an electronic portal imaging device (EPID) to ensure that the correct radiation dose is delivered to the tumour when using intensity-modulated radiation therapy (IMRT).Materials and methods:Setup data were collected from 40 patients treated with IMRT for head and neck cancer (HN) (20 patients) and prostate cancer (20 patients). Setup errors from 720 registration images were analysed to evaluate systematic and random errors. Thereafter, optimal PTV margins were calculated based on International Commission on Radiation Units and Measurements 62 (ICRU), Stroom and Parker formulas compared with the Van Herk’s recipe.Results:To calculate the margins around the PTV, several different formulas have been used. Setup margins ranged between 2–4·3, 2·2–4·6 and 2·1–4·7 mm in X, Y and Z directions, respectively, for HN cases. Similarly, for the prostate site, setup margins ranged between 3·7–8·3, 3·2–6·8 and 3·3–8·2 mm in X, Y and Z directions.Conclusion:To ensure better coverage of target volume, we adopted a PTV margin of 5 mm for HN PTVs and 10 mm for prostate PTVs in our department.

A cone beam CT-based study on fiducial seed migration and planning target volume margin in prostate radiotherapy

AbstractAim:This study attempts to investigate fiducial marker (FM) migration and calculate the prostate planning target volume (PTV) margin considering the setup errors after translation corrections alone (T) and translation plus rotational corrections (T+R) and anatomy variation with respect to the corrected fiducial position, analysed on cone beam computed tomography (CBCT) images.Methods and materials:CBCT images from 25 patients are analysed for FM movements, setup error and anatomy variation with respect to the seed match positions. Systematic and random components of setup error and prostate movements are used to calculate the PTV margin for CBCT-based FM localisation in two scenarios, translation corrections only and translation plus rotational correction. MTNW887825 soft tissue gold markers (Civco, Orange City, FL, USA) were used with the department-specific immobilisation system and rectal and bladder filling protocols.Results:The average directional inter-marker distance variation is −0·05 ± 0·90 mm. The systematic setup errors for T+R are 0·40, 0·63 and 0·80 mm in right–left (RL), anterior–posterior (AP) and superior–inferior (SI), respectively. The corresponding values for T only are 0·54, 0·69 and 0·90 mm. The systematic prostate movement from T+R corrected FM positions are 0·65, 1·27 and 1·32 mm in the RL, AP and SI directions.Findings:Minimal FM movements are noted from the study. The PTV margins to incorporate the daily T+R corrected setup error and prostate deformation are found to be 2·5, 4·5 and 5·2 mm in the RL, AP and SI directions, respectively. The corresponding margins for T only corrected scenario are found to be 2·8, 4·8 and 5·7 mm.

Comparison of Deep Learning-Based and Patch-Based Methods for Pseudo-CT Generation in MRI-Based Prostate Dose Planning

Deep learning methods (DLMs) have recently been proposed to generate pseudo-CT (pCT) for magnetic resonance imaging (MRI) based dose planning. This study aims to evaluate and compare DLMs (U-Net and generative adversarial network [GAN]) using various loss functions (L2, single-scale perceptual loss [PL], multiscale PL, weighted multiscale PL) and a patch-based method (PBM). Thirty-nine patients received a volumetric modulated arc therapy for prostate cancer (78 Gy). T2-weighted MRIs were acquired in addition to planning CTs. The pCTs were generated from the MRIs using 7 configurations: 4 GANs (L2, single-scale PL, multiscale PL, weighted multiscale PL), 2 U-Net (L2and single-scale PL), and the PBM. The imaging endpoints were mean absolute error and mean error, in Hounsfield units, between the reference CT (CTref) and the pCT. Dose uncertainties were quantified as mean absolute differences between the dose volume histograms (DVHs) calculated from the CTref and pCT obtained by each method. Three-dimensional gamma indexes were analyzed. Considering the image uncertainties in the whole pelvis, GAN L2 and U-Net L2 showed the lowest mean absolute error (≤34.4 Hounsfield units). The mean errors were not different than 0 (P ≤ .05). The PBM provided the highest uncertainties. Very few DVH points differed when comparing GAN L2 or U-Net L2 DVHs and CTref DVHs (P ≤ .05). Their dose uncertainties were ≤0.6% for the prostate planning target Volume V95%, ≤0.5% for the rectum V70Gy, and ≤0.1% for the bladder V50Gy. The PBM, U-Net PL, and GAN PL presented the highest systematic dose uncertainties. The gamma pass rates were >99% for all DLMs. The mean calculation time to generate 1 pCT was 15 s for the DLMs and 62 min for the PBM. Generating pCT for MRI dose planning with DLMs and PBM provided low-dose uncertainties. In particular, the GAN L2 and U-Net L2 provided the lowest dose uncertainties together with a low computation time.

Pseudo-CT Generation for MRI-Only Radiation Therapy Treatment Planning: Comparison Among Patch-Based, Atlas-Based, and Bulk Density Methods

Methods have been recently developed to generate pseudo-computed tomography (pCT) for dose calculation in magnetic resonance imaging (MRI)-only radiation therapy. This study aimed to propose an original nonlocal mean patch-based method (PBM) and to compare this PBM to an atlas-based method (ABM) and to a bulk density method (BDM) for prostate MRI-only radiation therapy. Thirty-nine patients received a volumetric modulated arc therapy for prostate cancer. In addition to the planning computed tomography (CT) scans, T2-weighted MRI scans were acquired. pCTs were generated from MRIs using 3 methods: an original nonlocal mean PBM, ABM, and BDM. The PBM was performed using feature extraction and approximate nearest neighbor search in a training cohort. The PBM accuracy was evaluated in a validation cohort by using imaging and dosimetric endpoints. Imaging endpoints included mean absolute error and mean error between Hounsfield units of the pCT and the reference CT (CTref). Dosimetric endpoints were based on dose-volume histograms calculated from the CTref and the pCTs for various volumes of interest and on 3-dimensional gamma analyses. The PBM uncertainties were compared with those of the ABM and BDM. The mean absolute error and mean error obtained from the PBM were 41.1 and -1.1 Hounsfield units. The PBM dose-volume histogram differences were 0.7% for prostate planning target volume V95%, 0.5% for rectum V70Gy, and 0.2% for bladder V50Gy. Compared with ABM and BDM, PBM provided significantly lower dose uncertainties for the prostate planning target volume (70-78Gy), the rectum (8.5-29Gy, 40-48Gy, and 61-73Gy), and the bladder (12-78Gy). The PBM mean gamma pass rate (99.5%) was significantly higher than that of ABM (94.9%) or BDM (96.1%). The proposed PBM provides low uncertainties with dose planned on CTref. These uncertainties were smaller than those of ABM and BDM and are unlikely to be clinically significant.

Clinical outcome and toxicity evaluation of simultaneous integrated boost pelvic IMRT/VMAT at different dose levels combined with androgen deprivation therapy in prostate cancer patients.

BackgroundThe role of dose escalation in patients receiving long-term androgen deprivation therapy (ADT) is still a controversial issue. The aim of the current study was to evaluate whether dose escalation for ≥76–80 Gy had any advantage in terms of biochemical disease-free survival (BDFS), distant metastasis-free survival (DMFS), or overall survival outcomes over the dose levels from 70 to <76 Gy.Patients and methodsThe study included a cohort of 24 patients classified with high- and intermediate-risk localized prostate cancer. All patients received ADT, starting at 4–6 months before radiation therapy and continued for a total period of 12–24 months in high-risk patients. The treatment plan was given in two phases. In the first phase, the nodal planning target volume (PTV) and the prostate PTV received 48.6 and 54 Gy, respectively, over 27 fractions. The treatment was applied through intensity-modulated radiation therapy or volumetric modulated arc therapy with a simultaneous integrated boost technique.ResultsMore than half of the patients were in T3–T4 stage, 79.1% of the patients were in the high-risk category, and all patients received ADT. The rate of acute grade II gastrointestinal and genitourinary toxicities in all patients were 41.7% and 62.5%, respectively. The rate of freedom from grade II rectal toxicity at 2 years was 89% and 83% for patients treated with dose levels <76 and ≥76 Gy, respectively. The rate of BDFS at 2 years was 90% and 85% for doses <76 and ≥76 Gy, respectively. The DMFS at 2 years was 100% and 76% for dose levels <76 and ≥76 Gy, respectively.ConclusionIn the current study, there were no significant differences in the BDFS and DMFS between patients treated with a dose of <76 and ≥76 Gy, including elective pelvic lymph nodes irradiation combined with ADT.

Geographical miss of the prostate during image-guided radiotherapy with a 6-mm posterior expansion margin

IntroductionOur department commonly uses a planning target volume (PTV) expansion of 6 mm posterior and 1 cm in all other directions when treating prostate cancer patients with image‐guided radiotherapy (IGRT). This study aimed to test the adequacy of this PTV expansion by assessing geographical miss of the prostate on post‐treatment cone‐beam CT (CBCT) and identify those at risk of geographical miss.MethodsTwenty‐two prostate cancer patients receiving IGRT with implanted fiducial markers underwent daily pre‐treatment orthogonal kV imaging followed by a post‐treatment CBCT for a total of 432 fractions. The prostate was outlined on all CBCTs. For each imaging set, the volume of geographic miss was measured by subtracting the PTV from the planning CT and prostate volume on the post‐treatment CBCT.ResultsThe prostate volume moved outside the PTV by >0.01 cc in 9% of fractions (39/432). This occurred in 13 (59%) of 22 patients. Large prostates >40 cc and >50 cc had significantly more geographical miss events (both P < 0.001). Changes in rectal filling appear to be responsible for prostate motion/deformation in 82% (32/39) of fractions.ConclusionsOur analysis suggests that, despite IGRT, prostate PTV margins are not adequate in some patients, particularly those with large prostates. PTV margins may be reduced in some other patients. Prostate rotation and deformation play an important role in setting margins and may not always be represented accurately by fiducial marker displacements. Individualised and adaptive margins for prostate cancer patients should be a priority for future research.

Effect of External Targeted Radiotherapy on Dosimetry Due to Rapid Clearance of Gold Nanoparticles

Progress in the application of gold nanoparticles (GNPs) in the biomedical research of small animals has substantially advanced in recent years. Studies suggest a high potential of applying nanoparticle technology to the targeted drug delivery and sensitization system for external beam radiotherapy. Therefore, a scenario of integrated cancer therapy is highly expected, in which patients are treated with administration of GNP media and external beam radiotherapy simultaneously. However, a possible problem is that GNPs may be rapidly transported through the circulatory system to the kidneys, accumulating in the bladder. As a consequence, dosimetric variations could occur as GNP media are absent in the treatment planning, but present in the bladder at a high density during treatment delivery. This study investigates the effect of the rapid clearance of GNPs on dosimetric variations and biological consequences. A prostate phantom and five clinical cases are included. Intensity-modulated radiation therapy (IMRT) and RapidArc are used as the treatment techniques. Dose-volume histograms show that the amounts of dose delivered to the prostate planning target volume (PTV), bladder, and rectum decrease. Linear correlations between the concentration of GNP media in the bladder and the corresponding percentage changes of mean dose at the PTV are formulated. For biological consequences, high-dose regions in the mucosal areas of the bladder and rectum are identified. To manage a dosimetric variation of less than 3 % for the prostate PTV, the phantom study results suggest an upper threshold of 97.48 mg-Au/mL with IMRT and 168.22 mg-Au/mL with RapidArc, whereas the clinical study suggests 131.58 mg-Au/mL with RapidArc.

SU-E-T-284: Dose Plan Optimization When Using Hydrogel Prostate-Rectum Spacer: A Single Institution Experience

Purpose: To describe rectal dose reduction achieved and techniques used to take advantage of the increased peri-rectal spacing provided by injected polyethylene-glycol. Methods: Thirty prostate cancer patents were 2:1 randomized during a clinical trial to evaluate the effectiveness of injected poly-ethylene glycol hydrogel (SpaceOAR System) in creating space between the prostate and the anterior rectal wall. All patients received a baseline CT/MR scan and baseline IMRT treatment plan. Patients were randomized to receive hydrogel injection (n=20) or Control (n=10), followed by another CT/MR scan and treatment plan (single arc VMAT, 6 MV photons, 79.2 Gy, 44 fractions). Additional optimization structures were employed to constrain the dose to the rectum; specifically an avoidance structure to limit V75 <15%, and a control structure to limit the maximum relative dose <105% in the interface region of the anterior rectal wall and the prostate planning target volume. Dose volumetric data was analyzed for rectal volumes receiving 60 through 80 Gy. Results: Rectal dose reduction was observed in all patients who received the hydrogel. Volumetric analysis indicates a median rectal volume and (reduction from baseline plan) following spacer application of 4.9% (8.9%) at V60Gy, 3.8% (8.1%) at V65Gy, 2.5% (7.2%) at V70Gy, 1.6% (5.8%) at V75Gy, and 0.5% (2.5%) at V80Gy. Conclusion: Relative to planning without spacers, rectal dose constraints of 5%, 4%, 3%, 2%, 1% for V60, V65, V70, V75, and V80, should be obtainable when peri-rectal spacers are used. The combined effect of increased peri-rectal space provided by the hydrogel, with strict optimization objectives, resulted in reduced dose to the rectum. To maximize benefit, strict optimization objectives and reduced rectal dose constraints should be employed when creating plans for patients with perirectal spacers. Clinical Trial for SpaceOAR product conducted by Augmenix,Inc. The research site was paid to be a participating site.

SU‐E‐T‐448: Heightened Apical Positivity of 2‐Year Post‐Radiotherapy Biopsies Is Not Related to Suboptimal Dosimetry

Purpose:Previous research has demonstrated that following radiation therapy for prostate cancer, there is a relative increase in positive biopsies in the apex versus the rest of the prostate. The increase could be due to: 1) Inter‐fraction apex motion or deformation, 2) Intra‐fraction apex motion or deformation, 3) Suboptimal dose coverage in the apex, 4) Tissue composition in the apex and/or 5) Prostate size. In this initial study, the potential for suboptimal dose coverage in the apex was assessed by splitting the prostate planning target volume into the apex (inferior third) and remainder.Methods:69 patients were selected from 303 patients treated on a clinical radiotherapy trial for prostate cancer. These patients were selected as they had both a localized (sextant template) 2‐year post‐treatment biopsy and 3D dose information. Of these patients, 10 had positive biopsies in the apex, 8 in the remainder and 11 in both locations. For all patients, the following dosimetric data was acquired from the apex dose volume histogram: Dmean, Dmax, Dmin, D95% and V100%. Unpaired, one‐tailed t‐tests were used to test for statistical significance (p &lt; 0.05) between all dosimetric parameters for patients with positive versus negative apical biopsies. Additionally, D95% for the apex was plotted against D95% of the remainder.Results:There was no statistical difference for the selected apical dosimetric parameters for patients with positive versus negative biopsies (p‐values &gt; 0.05). No correlation was found between D95% (normalized to the prescription dose) for the apex and remainder (R2 = 0.0116).Conclusion:No correlation was found between positive apical biopsy and suboptimal dosimetric coverage. Current research is looking into inter‐fraction apex motion and deformation as a potential source of the increased apical failure using daily CBCT images.

SU‐E‐P‐42: Benefit of Equivalent Uniform Dose in Prostate IMRT Planning to Reduce Bladder Toxicity

Purpose:To assess the benefit of bladder wall sub‐volume equivalent uniform dose (EUD) constrains in prostate cancer IMRT planningMethods:The bladder wall was defined by the volume between the external manually delineated wall and a contraction of 7 mm from this external wall. This bladder wall was then separated into two parts: the internal‐bladder wall (bla‐in) represented by the portion of the bladder wall that intersected with the planning target volume (PTV) plus 5 mm extension; the external‐bladder wall (bla‐ex) represented by the remaining part of the bladder wall. Two IMRT plans, with and without using EUD constraints, were generated and compared for 53 prostate cancer patients, to deliver 80Gy to the prostate PTV (V95&gt;95%). In the plan with EUD constraints, the values of the “a” parameter of the EUD models were: 10.0 for bla‐in and 2.3 for bla‐ex., and 5 for the rectum.Results:The use of bladder EUD objectives increased significantly the conformal index (0.73±0.04 vs. 0.93±0.02) and decreased both the doses in the bladder wall (V70: 22.66% vs. 18.88%, Dmean: 39.40Gy vs. 35.04Gy) and the bladder wall NTCP values (NTCP at 3 years bladder toxicity &gt;= LENT/SOMA Grade2: 16.68% vs. 14.48%, NTCP at 3 years bladder bleeding: 7.16% vs. 5.88%, NTCP at 5 years bladder toxicity &gt;= LENT/SOMA Grade2: 20.15% vs. 17.75%, NTCP at 5 years bladder bleeding: 10.38% vs. 8.36%). The use of bladder EUD objectives, although slightly decreasing the dose to the rectum wall (Dmax: 75.19Gy vs. 75.05Gy, V72: 12.95Gy vs. 12.72Gy) as well, increased however the dose in the femoral heads (V55‐femoral head left: 0.06% vs. 0.30%, V55‐femoral head right: 0.04% vs. 0.21%).Conclusion:Separating bladder wall into two parts with appropriate bladder EUD objectives may reduce bladder toxicity, while keeping high dose to the prostate.

Prostate Stereotactic Ablative Radiation Therapy Using Volumetric Modulated Arc Therapy to Dominant Intraprostatic Lesions

PurposeTo investigate boosting dominant intraprostatic lesions (DILs) in the context of stereotactic ablative radiation therapy (SABR) and to examine the impact on tumor control probability (TCP) and normal tissue complication probability (NTCP).Methods and MaterialsTen prostate datasets were selected. DILs were defined using T2-weighted, dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Four plans were produced for each dataset: (1) no boost to DILs; (2) boost to DILs, no seminal vesicles in prescription; (3) boost to DILs, proximal seminal vesicles (proxSV) prescribed intermediate dose; and (4) boost to DILs, proxSV prescribed higher dose. The prostate planning target volume (PTV) prescription was 42.7 Gy in 7 fractions. DILs were initially prescribed 115% of the PTVProstate prescription, and PTVDIL prescriptions were increased in 5% increments until organ-at-risk constraints were reached. TCP and NTCP calculations used the LQ-Poisson Marsden, and Lyman-Kutcher-Burman models respectively.ResultsWhen treating the prostate alone, the median PTVDIL prescription was 125% (range: 110%-140%) of the PTVProstate prescription. Median PTVDIL D50% was 55.1 Gy (range: 49.6-62.6 Gy). The same PTVDIL prescriptions and similar PTVDIL median doses were possible when including the proxSV within the prescription. TCP depended on prostate α/β ratio and was highest with an α/β ratio = 1.5 Gy, where the additional TCP benefit of DIL boosting was least. Rectal NTCP increased with DIL boosting and was considered unacceptably high in 5 cases, which, when replanned with an emphasis on reducing maximum dose to 0.5 cm3 of rectum (Dmax0.5cc), as well as meeting existing constraints, resulted in considerable rectal NTCP reductions.ConclusionsBoosting DILs in the context of SABR is technically feasible but should be approached with caution. If this therapy is adopted, strict rectal constraints are required including Dmax0.5cc. If the α/β ratio of prostate cancer is 1.5 Gy or less, then high TCP and low NTCP can be achieved by prescribing SABR to the whole prostate, without the need for DIL boosting.

Feasibility of prostate robotic radiation therapy on conventional C-arm linacs

PurposeSignificant dosimetric improvement for radiation therapy using optimized noncoplanar fields has been previously demonstrated. The purpose here is to study the feasibility of optimized robotic noncoplanar radiation therapy, termed 4π therapy, for prostate cancer treatments on a conventional C-arm linac. Methods and materialsTwelve low-risk prostate cancer patients previously treated by 2-arc volumetric modulated arc therapy (VMAT) were selected. Forty gray in 5 fractions were prescribed to cover 95% of the prostate planning target volume (PTV). To replan by 4π therapy, a column generation method was used to optimize beam orientations and fluence. A total of 30 beams were selected for each patient. ResultsBoth planning methods provided adequate PTV coverage. Compared against VMAT plans, the 4π plan reduced the rectum V50%, V80%, V90%, D1cc, and the penile bulb maximum doses by 50%, 28%, 19% 11%, and 9% (P < .005), respectively, and the mean body dose was reduced from 2.07 Gy to 1.75 Gy (P = .0001). The bladder dose was only slightly reduced. ConclusionsBy optimizing beam angles and fluences in the noncoplanar solution space, superior prostate treatment plan quality was achieved compared against state of the art VMAT plans. The dosimetric potential for 4π therapy is established on an existing C-arm linac platform.