Reducing PTV margins for prostate SBRT with motion compensation and gating techniques.

The purpose of this study is to investigate the dosimetric accuracy of prostate SBRT when motion is considered. To account for target movement, motion compensation and gating techniques were investigated with PTV margins reduced to 2 mm. To allow for dosimetric measurements a Delta4 phantom, Gafchromic film, and Hexamotion motion platform were utilized. Four motion files were utilized that represent a range of motions. Analysis of measured prostate motions for fifteen patients was performed to ensure detected motions were similar to those previously reported and motion files utilized were suitable. Five patient plans were utilized to allow for the effects of MLC and target motion interplay to be investigated. For both motion compensation and gating techniques, plans were delivered to the stationary phantom and for each of four motion types with/without compensation/gating enabled. Using a 3%, 2 mm and 80% threshold gamma criteria, film measurements had an average pass rate of 80.5% for uncorrected deliveries versus 96.0% for motion compensated deliveries. For gated techniques average pass rates increased from 89.9% for uncorrected to 94.8% with gating enabled. Measurements with the Delta4 arrays were analyzed with a 3%, 2 mm and 10% threshold dose. An average pass rate of 83.8% was measured for uncorrected motions versus 94.8% with motion compensation. For the gated technique an average pass rate of 87.2% was found for uncorrected motions versus 96.9% with gating enabled. These results show that very high gamma pass rates are achievable when motion compensation or gating techniques are applied. When target motion is not accounted for shifts up to 5 mm in planned versus delivered isodose distributions were found. However, when motion compensation, or gated techniques were applied, much smaller differences between planned and delivered isodose distributions were found. With these techniques dose delivery accuracy is greatly improved, allowing for PTV margins to be reduced.

Contour similarity and its implication on inverse prostate SBRT treatment planning.

PURPOSE: Success of auto-segmentation is measured by the similarity between auto and manual contours that is often quantified by Dice coefficient (DC). The dosimetric impact of contour variability on inverse planning has been rarely reported. The main aim of this study is to investigate whether automatically generated organs-at-risk (OARs) could be used in inverse prostate stereotactic body radiation therapy (SBRT) planning and whether the dosimetric parameters are still clinically acceptable after radiation oncologists modify the OARs. METHODS AND MATERIALS: Planning computed tomography images from 10 patients treated with SBRT for prostate cancer were selected and automatically segmented by commercially available atlas-based software. The automatically generated OAR contours were compared with the manually drawn contours. Two volumetric modulated arc therapy (VMAT) plans, autoRec-VMAT (where only automatically generated rectums were used in optimization) and autoAll-VMAT (where automatically generated OARs were used in inverse optimization) were generated. Dosimetric parameters based on the manually drawn PTV and OARs were compared with the clinically approved plans. RESULTS: The DCs for the rectum contours varied from 0.55 to 0.74 with a mean value of 0.665. Differences of D95 of the PTV between autoRec-VMAT and manu-VMAT plans varied from 0.03% to -2.85% with a mean value of -0.64%. Differences of D0.03cc of manual rectum between the two plans varied from -0.86% to 9.94% with a mean value of 2.71%. D95 of PTV between autoAll-VMAT and manu-VMAT plans varied from 0.28% to -2.9% with a mean value -0.83%. Differences of D0.03cc of manual rectum between the two plans varied from -0.76% to 6.72% with a mean value of 2.62%. CONCLUSION: Our study implies that it is possible to use unedited automatically generated OARs to perform initial inverse prostate SBRT planning. After radiation oncologists modify/approve the OARs, the plan qualities based on the manually drawn OARs are still clinically acceptable, and a re-optimization may not be needed.

The use of a thin guide-wire for urethral definition in prostate SBRT treatments with Cyberknife.

PURPOSE: To study and analyze the effect of the use of a thin guide-wire instead of a Foley catheter for urethral definition in prostate stereotactic body radiation therapy (SBRT) treatments and to compare treatment parameters in both situations. MATERIAL AND METHODS: Thirty-seven prostate SBRT patients were employed in this study. A Foley catheter was employed in nine of them, and a guide-wire was employed in the other 28 patients. For each of the 28 patients in which the guide-wire was employed, a comparison between urethral positions in both situations was performed, allowing for a margin definition of the urethra when a Foley catheter was employed. Displacements of the prostate during treatment were obtained, allowing for an analysis of prostate positions in both situations. Also, different treatment parameters such as the number of treatment interruptions, couch movements performed, and x-rays needed were gathered. RESULTS: Large differences between urethral positions can be found in the anterior-posterior (AP) directions compared to those in the lateral (LAT) direction. Differences are also larger in areas closer to the base of the prostate, where margins applied in the case of using a Foley catheter are 16 mm with a mean displacement of 6 mm in the posterior direction. No differences in the treatment parameters were found during treatment in both situations. The difference found in absolute prostate pitch rotations suggests that the Foley catheter provokes a shift of the prostate position, which does not occur when employing the guide-wire. CONCLUSIONS: Foley catheters shift the urethral position, making them a wrong surrogate of the urethra when no catheters are present. The margins needed to assess uncertainties introduced by the use of a Foley catheter are larger than those usually applied. The use of a Foley catheter did not present any additional difficulty during treatment delivery in terms of images employed or interruptions produced.

The effect of integrating knowledge-based planning with multicriteria optimization in treatment planning for prostate SBRT.

Knowledge-based planning (KBP) and multicriteria optimization (MCO) are two powerful tools to assist treatment planners in achieving optimal target coverage and organ-at-risk (OAR) sparing. The purpose of this work is to investigate if integrating MCO with conventional KBP can further improve treatment plan quality for prostate cancer stereotactic body radiation therapy (SBRT). A two-phase study was designed to investigate the impact of MCO and KBP in prostate SBRT treatment planning. The first phase involved the creation of a KBP model based on thirty clinical SBRT plans, generated by manual optimization (KBP_M). A ten-patient validation cohort was used to compare manual, MCO, and KBP_M optimization techniques. The next phase involved replanning the original model cohort with additional tradeoff optimization via MCO to create a second model, KBP_MCO. Plans were then generated using linear integration (KBP_M+MCO), non-linear integration (KBP_MCO), and a combination of integration methods (KBP_MCO+MCO). All plans were analyzed for planning target volume (PTV) coverage, OAR constraints, and plan quality metrics. Comparisons were generated to evaluate plan and model quality. Phase 1 highlighted the necessity of KBP and MCO in treatment planning, as both optimization methods improved plan quality metrics (Conformity and Heterogeneity Indices) and reduced mean rectal dose by 2 Gy, as compared to manual planning. Integrating MCO with KBP did not further improve plan quality, as little significance was seen over KBP or MCO alone. Principal component score (PCS) fitting showed KBP_MCO improved bladder and rectum estimated and modeled dose correlation by 5% and 22%, respectively; however, model improvements did not significantly impact plan quality. KBP and MCO have shown to reduce OAR dose while maintaining desired PTV coverage in this study. Further integration of KBP and MCO did not show marked improvements in treatment plan quality while requiring increased time in model generation and optimization time.

Transperineal ultrasound is a good alternative for intra-fraction motion monitoring for prostate stereotactic body radiotherapy.

PURPOSES: To report our experience in a prospective study of implementing a transperineal ultrasound system to monitor intra-fractional prostate motion for prostate stereotactic body radiotherapy (SBRT). MATERIAL AND METHODS: This IRB-approved prospective study included 23 prostate SBRT patients treated between 04/2016 and 11/2019 at our institution. The prescription doses were 36.25 Gy to the Low-Dose planning target volume (LD-PTV) and 40 Gy to the High-Dose PTV (HD-PTV) in five fractions with 3 mm planning margins. The transperineal ultrasound system was successfully used in 110 of the 115 fractions. For intra-fraction prostate motion, the real-time prostate displacements measured by ultrasound were exported for analysis. The percentage of time prostate movement exceeded a 2 mm threshold was calculated for each fraction of all patients. T-test was used for all statistical comparisons. RESULTS: Ultrasound image quality was adequate for prostate delineation and prostate motion tracking. The setup time for each fraction under ultrasound-guided prostate SBRT was 15.0 ± 4.9 min and the total treatment time per fraction was 31.8 ± 10.5 min. The presence of an ultrasound probe did not compromise the contouring of targets or critical structures. For intra-fraction motion, prostate movement exceeded 2 mm tolerance in 23 of 110 fractions for 11 of 23 patients. For all fractions, the mean percentage of time when the prostate moved more than 2 mm in any direction during each fraction was 7%, ranging from 0% to 62% of a fraction. CONCLUSION: Ultrasound-guided prostate SBRT is a good option for intra-fraction motion monitoring with clinically acceptable efficiency.

Retrospective analysis of MV-kV imaging-based fiducial tracking in prostate SBRT treatment.

PURPOSE: Motion management is critical for prostate stereotactic body radiotherapy (SBRT) due to its high fractional dose and proximity to organs at risk. This study seeks to quantify the advantages of MV-kV tracking over kV imaging alone through a retrospective analysis of over 300 patients who underwent prostate SBRT treatment using MV-kV tracking. METHODS: An MV-kV imaging-based fiducial tracking technique has been developed at our institute and become a standard clinical practice. This technique calculates three-dimensional (3D) fiducial displacement in real time from orthogonal kV and MV images acquired simultaneously. The patient will be repositioned if for two consecutive MV-kV data points, the motion is larger than a tolerance of 1.5 mm in any of the lateral, superior-inferior, and/or anterior-posterior directions. This study retrospectively analyzed detected 3D motions using an MV-kV approach of 324 patients who recently underwent prostate SBRT treatments. An algorithm was developed to recover the 2D motion components as if they were detected by kV or MV imaging alone. RESULTS: Our results indicated that out-of-tolerance motions were primarily limited to the range of 1.5-3 mm (>95%). The motions are primarily anterior-posterior and superior-inferior, with less than 14.8% of the occurrences in the lateral direction. Compared to out-of-tolerance occurrences detected by MV-kV approach, kV alone caught 46.6% of motions in all three directions, and MV alone caught 46.7%. kV alone shows an overall missing rate of 45.8% for superior-inferior motions and 38.6% for lateral motions. It is also demonstrated that the detectability of motion in specific directions greatly depends on gantry angles, as does the missing rate. CONCLUSIONS: Our study demonstrated that MV-kV imaging-based intrafraction motion tracking is superior to single kV imaging for prostate SBRT in clinical practice.

Prostate SBRT using O-Ring Halcyon Linac - Plan quality, delivery efficiency, and accuracy.

Cone beam CT-guided prostate stereotactic body radiotherapy (SBRT) treatment on the recently installed novel O-ring coplanar geometry Halcyon Linac with a single energy 6MV-flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a fast, safe, and feasible treatment modality for early stage low- and intermediate-risk prostate cancer patients. Following the RTOG-0938 compliance criteria and utilizing two-full arc geometry, VMAT prostate SBRT plans were generated for ten consecutive patients using advanced Acuros-based algorithm for heterogeneity corrections with Halcyon couch insert. Halcyon VMAT plans with the stacked and staggered multileaf collimators (MLC) produced highly conformal SBRT dose distributions to the prostate, lower intermediate dose spillage and similar dose to adjacent organs-at-risks (OARs) compared to SBRT-dedicated Truebeam VMAT plans. Due to lower monitor units per fraction and less MLC modulation through the target, the Halcyon VMAT plan can deliver prostate SBRT fractions in and overall treatment time of less than 10 minutes (for 36.25 Gy in five fractions), significantly improving patient compliance and clinic workflow. Pretreatment quality assurance results were similar to Truebeam VMAT plans. We have implemented Halcyon Linac for prostate SBRT treatment in our institution. We recommend that others use Halcyon for prostate SBRT treatments to expand the access of curative hypofractionated treatments to other clinics only equipped with a Halcyon Linac. Clinical follow-up results for patients who underwent prostate SBRT treatment on our Halcyon Linac is underway.

Urethra contouring on computed tomography urethrogram versus magnetic resonance imaging for stereotactic body radiotherapy in prostate cancer.

Accurate urethra contouring is critical in prostate SBRT. We compared urethra contouring on CT-urethrogram and T2-weighted MRI. The dice similarity coefficient, Jaccard index, Hausdorff distance and mean distance to agreement were evaluated. All four metrics indicate better agreement and less variability in urethra contouring on CT-urethrogram, compared to T2-weighted MRI.

Per-fraction planning to enhance optimization degrees of freedom compared to the conventional single-plan approach.

Objective. In conventional radiotherapy, a single treatment plan is generated pre-treatment, and delivered in daily fractions. In this study, we propose to generate different treatment plans for all fractions ('Per-fraction' planning) to reduce cumulative organs at risk (OAR) doses. Per-fraction planning was compared to the 'Conventional' single-plan approach for non-coplanar 4 × 9.5 Gy prostate stereotactic body radiation therapy (SBRT).Approach. An in-house application for fully automated, non-coplanar multi-criterial treatment planning with integrated beam angle and fluence optimization was used for plan generations. For the Conventional approach, a single 12-beam non-coplanar IMRT plan with individualized beam angles was generated for each of the 20 included patients. In Per-fraction planning, four fraction plans were generated for each patient. For each fraction, a different set of patient-specific 12-beam configurations could be automatically selected. Per-fraction plans were sequentially generated by adding dose to already generated fraction plan(s). For each fraction, the cumulative- and fraction dose were simultaneously optimized, allowing some minor constraint violations in fraction doses, but not in cumulative.Main results. In the Per-fraction approach, on average 32.9 ± 3.1 [29;39] unique beams per patient were used. PTV doses in the separate Per-fraction plans were acceptable and highly similar to those in Conventional plans, while also fulfilling all OAR hard constraints. When comparing total cumulative doses, Per-fraction planning showed improved bladder sparing for all patients with reductions in Dmean of 22.6% (p= 0.0001) and in D1cc of 2.0% (p= 0.0001), reductions in patient volumes receiving 30% and 50% of the prescribed dose of 54.7% and 6.3%, respectively, and a 3.1% lower rectum Dmean (p= 0.007). Rectum D1cc was 4.1% higher (p= 0.0001) and Urethra dose was similar.Significance. In this proof-of-concept paper, Per-fraction planning resulted in several dose improvements in healthy tissues compared to the Conventional single-plan approach, for similar PTV dose. By keeping the number of beams per fraction the same as in Conventional planning, reported dosimetric improvements could be obtained without increase in fraction durations. Further research is needed to explore the full potential of the Per-fraction planning approach.

Simulating an intra-fraction adaptive workflow to enable PTV margin reduction in MRIgART volumetric modulated arc therapy for prostate SBRT.

Purpose: This study simulates a novel prostate SBRT intra-fraction re-optimization workflow in MRIgART to account for prostate intra-fraction motion and evaluates the dosimetric benefit of reducing PTV margins. Materials and methods: VMAT prostate SBRT treatment plans were created for 10 patients using two different PTV margins, one with a 5 mm margin except 3 mm posteriorly (standard) and another using uniform 2 mm margins (reduced). All plans were prescribed to 36.25 Gy in 5 fractions and adapted onto each daily MRI dataset. An intra-fraction adaptive workflow was simulated for the reduced margin group by synchronizing the radiation delivery with target position from cine MRI imaging. Intra-fraction delivered dose was reconstructed and prostate DVH metrics were evaluated under three conditions for the reduced margin plans: Without motion compensation (no-adapt), with a single adapt prior to treatment (ATP), and lastly for intra-fraction re-optimization during delivery (intra). Bladder and rectum DVH metrics were compared between the standard and reduced margin plans. Results: As expected, rectum V18 Gy was reduced by 4.4 ± 3.9%, D1cc was reduced by 12.2 ± 6.8% (3.4 ± 2.3 Gy), while bladder reductions were 7.8 ± 5.6% for V18 Gy, and 9.6 ± 7.3% (3.4 ± 2.5 Gy) for D1cc for the reduced margin reference plans compared to the standard PTV margin. For the intrafraction replanning approach, average intra-fraction optimization times were 40.0 ± 2.9 seconds, less than the time to deliver one of the four VMAT arcs (104.4 ± 9.3 seconds) used for treatment delivery. When accounting for intra-fraction motion, prostate V36.25 Gy was on average 96.5 ± 4.0%, 99.1 ± 1.3%, and 99.6 ± 0.4 for the non-adapt, ATP, and intra-adapt groups, respectively. The minimum dose received by the prostate was less than 95% of the prescription dose in 84%, 36%, and 10% of fractions, for the non-adapt, ATP, and intra-adapt groups, respectively. Conclusions: Intra-fraction re-optimization improves prostate coverage, specifically the minimum dose to the prostate, and enables PTV margin reduction and subsequent OAR sparing. Fast re-optimizations enable uninterrupted treatment delivery.

Dosimetric comparison of MR-guided adaptive IMRT versus 3DOF-VMAT for prostate stereotactic radiotherapy.

INTRODUCTION: To compare the dosimetry of prostate stereotactic radiotherapy (SBRT) delivered by adaptive intensity modulated radiotherapy (A-IMRT) and 3 degree of freedom volumetric modulated arc therapy (3DOF-VMAT). METHODS & MATERIALS: Twenty-five prostate patients treated with High Dose Rate (HDR) brachytherapy followed by SBRT were included (fifteen with hydrogel spacer in place for treatment). Interfraction changes in the volume of prostate, rectum and bladder were measured. Fractional dose to these structures was estimated for A-IMRT and 3DOF-VMAT for comparison against the corresponding reference dose and between each other. RESULTS: Clinically acceptable dose was delivered to prostate in all 125 fractions through A-IMRT and 3DOF-VMAT. A-IMRT was better than 3DOF-VMAT in reducing dose to 1 cm3 of rectum. Conversely, 3DOF-VMAT was superior in sparing 50% and 20% of rectum. When comparing the reference and delivered dose, there was no significant difference for Bladder D5cm3 for either technique. However, rectum in the high dose region benefited more from A-IMRT by being irradiated to a lower than reference dose in more fractions than 3DOF-VMAT. Hydrogel spacer reduced the rectal dose and was associated with a smaller deviation from reference dose for rectum D50% for A-IMRT. CONCLUSIONS: Despite the presence of large interfraction organ volumes changes, clinically acceptable dose was delivered to the prostate by both systems. A-IMRT facilitated a greater rectal sparing from the high dose region than 3DOF-VMAT. Further reduction in rectal dose could be achieved by hydrogel spacer to displace the rectum, or by adaptation delivered by VMAT.

Impact of intrafraction changes in delivered dose of the day for prostate cancer patients treated with stereotactic body radiotherapy via MR-Linac.

Purpose: The purpose of this study is to evaluate the impact of intrafraction pelvic motion by comparing the adapted plan dose (APD) and the computed delivered dose of the day (DDOTD) for patients with prostate cancer (PCa) treated with SBRT on the MR-Linac. Methods: Twenty patients with PCa treated with MR-guided adaptive SBRT were included. A 9-field IMRT distribution was adapted based on the anatomy of the day to deliver a total prescription dose of 3000 cGy in 5 fractions to the prostate plus a 5 mm isotropic margin. Prostate, bladder, and rectum were re-contoured on the MR-image acquired during treatment delivery (MRBO). DDOTD was computed by propagating the dose from the daily adapted plan generated during treatment onto the MRBO. Results: Target coverage was met for all fractions, however, computed DDOTD was significantly less than the APD (p < 0.05). During an average treatment of 53 min, mean bladder volume increased by 116%, which led to a significant decrease in the DDOTD bladder D40% (p < 0.001). However, DDOTD to bladder 5 cc was significantly higher (p < 0.001) than APD. Rectum intrafraction changes were observed based on a volume change of -20% to 83% and presence of significant dose changes from APD to DDOTD for rectum D20% (p < 0.05) and D1cc (p < 0.0001). Conclusions: Intrafraction motion observed during prostate SBRT treatment on the MR-Linac have dosimetric impacts on both the target and organs at risk. Post-treatment computation using DDOTD may inform adaptation beyond anatomic changes in subsequent treatment fractions to best capitalize on MR-Linac technology and widen the therapeutic index of SBRT for PCa.

Assessment of HDR brachytherapy-replicating prostate radiotherapy planning for tomotherapy, cyberknife and VMAT.

A dosimetric study was undertaken to assess the ability of Cyberknife (CK), Volumetric Modulated Arc Therapy (VMAT), and TomoTherapy (Tomo) to generate treatment plans that mimic the dosimetry of high dose-rate brachytherapy (HDR BT) for prostate cancer. The project aimed to assess the potential of using stereotactic body radiotherapy (SBRT) for boost treatment of high-risk prostate cancer patients where HDR BT in combination with conformal external beam radiotherapy (EBRT) is the standard of care. The datasets of 6 prostate patients previously treated with HDR BT were collated. VMAT, CK, and TomoTherapy treatment plans were generated for each dataset using the target and organ-at-risk structures as defined by the Radiation Oncologist during the HDR BT treatment process. The HDR BT plan isodoses were also converted into planning structures to assist the other modalities to achieve a HDR BT-like dose distribution. CK plans were created using both the iris collimator (IC) and a multileaf collimator (MLC). Comparison of the techniques was made based on dose-volume indices. Each plan was created at centres experienced using the respective treatment planning systems (TPS). Planning target volume (PTV V100%), i.e., the volume of the planning target volume (PTV) receiving 100% of the relative dose, in VMAT and TomoTherapy SBRT plans was higher than HDR BT plans. PTV V150% and V200%, i.e., volume of the PTV receiving 150% and 200% of the relative dose, were approached on all the CK MLC and TomoTherapy SBRT plans. However, it is not presently achievable for "virtual brachytherapy" SBRT to replicate the same high intraprostatic doses as HDR BT while meeting the constraints on the organs-at-risk (OARs). Half of the CK IC plans achieved PTV V150% but this was at the expense of high rectal dose. TomoTherapy and CK MLC plans achieved PTV V150% and V200% but the bladder dose was higher compared to CK IC plans. VMAT exhibited excellent PTV coverage based on V100 and OAR sparing, but without any ability to achieve the high intra-prostatic doses of HDR (V150% and V200%). SBRT techniques can be used to deliver hypofractionated radiotherapy to the PTV V100%. Based on the comparison of "physical" dose distributions, SBRT cannot presently achieve the same high intraprostatic doses as HDR BT while respecting the OAR constraints. SBRT still remains an attractive treatment option for delivering hypofractionated treatments for prostate cancer compared to HDR BT, in particular as it is less invasive and less resource intensive. Long-term outcomes of clinical trials comparing HDR BT and SBRT "prostate boosts" may show whether the high intraprostatic doses are clinically significant and correlate with outcomes.

Intrafractional stability of MR-guided online adaptive SBRT for prostate cancer.

BACKGROUND: MR-guided online adaptive stereotactic body radiation therapy (SBRT) for prostate cancer aims to reduce toxicity by full compensation of interfractional uncertainties. However, the process of online adaptation currently takes approximately 45 min during which intrafractional movements remain unaccounted for. This study aims to analyze the dosimetric benefit of online adaptation and to evaluate its robustness over the duration of one treatment fraction. METHODS: Baseline MR-scans at a MR-linear accelerator were acquired for ten healthy male volunteers for generation of mock-prostate SBRT plans with a dose prescription of 5 × 7.25 Gy. On a separate day, online MR-guided adaptation (ViewRay® MRIdian) was performed, and thereafter MR images were acquired every 15 min for 1 h to assess the stability of the adapted plan. RESULTS: A dosimetric benefit of online MR-guided adaptive re-planning was observed in 90% of volunteers. The median D95CTV- and D95PTV-coverage was improved from 34.8 to 35.5 Gy and from 30.7 to 34.6 Gy, respectively. Improved target coverage was not associated with higher dose to the organs at risk, most importantly the rectum (median D1ccrectum baseline plan vs. adapted plan 33.3 Gy vs. 32.3 Gy). The benefit of online adaptation remained stable over 45 min for all volunteers. However, at 60 min, CTV-coverage was below a threshold of 32.5 Gy in 30% of volunteers (30.6 Gy, 32.0 Gy, 32.3 Gy). CONCLUSION: The dosimetric benefit of MR-guided online adaptation for prostate SBRT was robust over 45 min in all volunteers. However, intrafractional uncertainties became dosimetrically relevant at 60 min and we therefore recommend verification imaging before delivery of MR-guided online adapted SBRT.

Complementing Prostate SBRT VMAT With a Two-Beam Non-Coplanar IMRT Class Solution to Enhance Rectum and Bladder Sparing With Minimum Increase in Treatment Time.

PURPOSE: Enhance rectum and bladder sparing in prostate SBRT with minimum increase in treatment time by complementing dual-arc coplanar VMAT with a two-beam non-coplanar IMRT class solution (CS). METHODS: For twenty patients, an optimizer for automated multi-criterial planning with integrated beam angle optimization (BAO) was used to generate dual-arc VMAT plans, supplemented with five non-coplanar IMRT beams with individually optimized orientations (VMAT+5). In all plan generations, reduction of high rectum dose had the highest priority after obtaining adequate PTV coverage. A CS with two most preferred directions in VMAT+5 and largest rectum dose reductions compared to dual-arc VMAT was then selected to define VMAT+CS. VMAT+CS was compared with automatically generated i) dual-arc coplanar VMAT plans (VMAT), ii) VMAT+5 plans, and iii) IMRT plans with 30 patient-specific non-coplanar beam orientations (30-NCP). Plans were generated for a 4 x 9.5 Gy fractionation scheme. Differences in PTV doses, healthy tissue sparing, and computation and treatment delivery times were quantified. RESULTS: For equal PTV coverage, VMAT+CS, consisting of dual-arc VMAT supplemented with two fixed, non-coplanar IMRT beams with fixed Gantry/Couch angles of 65°/30° and 295°/-30°, significantly reduced OAR doses and the dose bath, compared to dual-arc VMAT. Mean relative differences in rectum Dmean, D1cc, V40GyEq and V60GyEq were 19.4 ± 10.6%, 4.2 ± 2.7%, 34.9 ± 20.3%, and 39.7 ± 23.2%, respectively (all p<0.001). There was no difference in bladder D1cc, while bladder Dmean reduced by 17.9 ± 11.0% (p<0.001). Also, the clinically evaluated urethra D5%, D10%, and D50% showed small, but statistically significant improvements. All patient VX with X = 2, 5, 10, 20, and 30 Gy were reduced with VMAT+CS, with a maximum relative reduction for V10Gy of 19.0 ± 7.3% (p<0.001). Total delivery times with VMAT+CS only increased by 1.9 ± 0.7 min compared to VMAT (9.1 ± 0.7 min). The dosimetric quality of VMAT+CS plans was equivalent to VMAT+5, while optimization times were reduced by a factor of 25 due to avoidance of individualized BAO. Compared to VMAT+CS, the 30-NCP plans were only favorable in terms of dose bath, at the cost of much enhanced optimization and delivery times. CONCLUSIONS: The proposed two-beam non-coplanar class solution to complement coplanar dual-arc VMAT resulted in substantial plan quality improvements for OARs (especially rectum) and reduced irradiated patient volumes with minor increases in treatment delivery times.

Fully automated treatment planning for MLC-based robotic radiotherapy.

PURPOSE: To propose and validate a fully automated multicriterial treatment planning solution for a CyberKnife® equipped with an InCiseTM 2 multileaf collimator. METHODS: The AUTO BAO plans are generated using fully automated prioritized multicriterial optimization (AUTO MCO) of pencil-beam fluence maps with integrated noncoplanar beam angle optimization (BAO), followed by MLC segment generation. Both the AUTO MCO and segmentation algorithms have been developed in-house. AUTO MCO generates for each patient a single, high-quality Pareto-optimal IMRT plan. The segmentation algorithm then accurately mimics the AUTO MCO 3D dose distribution, while considering all candidate beams simultaneously, rather than replicating the fluence maps. Pencil-beams, segment dose depositions, and final dose calculations are performed with a stand-alone version of the clinical dose calculation engine. For validation, AUTO BAO plans were generated for 33 prostate SBRT patients and compared to reference plans (REF) that were manually generated with the commercial treatment planning system (TPS), in absence of time pressure. REF plans were also compared to AUTO RB plans, for which fluence map optimization was performed for the beam angle configuration used in the REF plan, and the segmentation could use all these beams or only a subset, depending on the dosimetry. RESULTS: AUTO BAO plans were clinically acceptable and dosimetrically similar to REF plans, but had on average reduced numbers of beams ((beams in AUTO BAO)/(beams in REF) (relative improvement): 24.7/48.3 (-49%)), segments (59.5/98.9 (-40%)), and delivery times (17.1/22.3 min. (-23%)). Dosimetry of AUTO RB and REF were also similar, but AUTO RB used on average fewer beams (38.0/48.3 (-21%)) and had on average shorter delivery times (18.6/22.3 min. (-17%)). Delivered Monitor Units (MU) were similar for all three planning approaches. CONCLUSIONS: A new, vendor-independent optimization workflow for fully automated generation of deliverable high-quality CyberKnife® plans was proposed, including BAO. Compared to manual planning with the commercial TPS, fraction delivery times were reduced by 5.3 min. (-23%) due to large reductions in beam and segment numbers.

Rationale for Involved Field Stereotactic Body Radiation Therapy-Enhanced Intermittent Androgen Deprivation Therapy in Hormone-Sensitive Nodal Oligo-Recurrent Prostate Cancer Following Prostate Stereotactic Body Radiation Therapy.

Lymph node recurrent prostate cancer is a common clinical scenario that is likely to increase significantly with the widespread adoption of novel positron emission tomography (PET) agents. Despite increasing evidence that localized therapy is disease modifying, most men with lymph node recurrent prostate cancer receive only systemic therapy with androgen deprivation therapy (ADT). For men who receive localized therapy the intent is often to delay receipt of systemic therapy. Little evidence exists on the optimal combination of local and systemic therapy in this patient population. In this hypothesis generating review, we will outline the rationale and propose a framework for combining involved field SBRT with risk adapted intermittent ADT for hormone sensitive nodal recurrent prostate cancer. In patients with a limited number of nodal metastases, involved field stereotactic body radiation therapy (SBRT) may have a role in eliminating castrate-resistant clones and possibly prolonging the response to intermittent ADT. We hypothesize that in a small percentage of patients, such a treatment approach may lead to long term remission or cure.

Favorable Biochemical Freedom From Recurrence With Stereotactic Body Radiation Therapy for Intermediate and High-Risk Prostate Cancer: A Single Institutional Experience With Long-Term Follow-Up.

Purpose/Objective(s): The current study reports long-term overall survival (OS) and biochemical freedom from recurrence (BFFR) after stereotactic body radiation therapy (SBRT) for men with intermediate and high-risk prostate cancer in a single community hospital setting with early adoption. Materials/Methods: Ninety-seven consecutive men with intermediate and high-risk prostate cancer treated with SBRT between 2007 and 2015 were retrospectively studied. Categorical variables for analysis included National Comprehensive Cancer Network risk group, race, Gleason grade group, T stage, use of androgen deprivation therapy, and planning target volume dose. Continuous variables for analysis included pretreatment prostate-specific antigen (PSA), percent cores positive, age at diagnosis, PSA nadir, prostate volume, percent prostate that received 40 Gy, and minimum dose to 0.03 cc of prostate (Dmin). BFFR was assessed using the Phoenix nadir +2 definition. OS and BFFR were estimated using Kaplan-Meier (KM) methodology with comparisons accomplished using log-rank statistics. Multivariable analysis (MVA) was accomplished with a backwards selection Cox proportional-hazards model with statistical significance taken at the p < 0.05 level. Results: Median FU is 78.4 months. Five- and ten-year OS KM estimates are 90.9 and 73.2%, respectively, with 19 deaths recorded. MVA reveals pretreatment PSA (p = 0.032), percent prostate 40 Gy (p = 0.003), and race (p = 0.031) were predictive of OS. Five- and nine-year BFFR KM estimates are 92.1 and 87.5%, respectively, with 10 biochemical failures recorded. MVA revealed PSA nadir (p < 0.001) was the only factor predictive of BFFR. Specifically, for every one-unit increase in PSA nadir, there was a 4.2-fold increased odds of biochemical failure (HR = 4.248). No significant differences in BFFR were found between favorable intermediate, unfavorable intermediate, and high-risk prostate cancer (p = 0.054) with 7-year KM estimates of 96.6, 81.0, and 85.7%, respectively. Conclusions: Favorable OS and BFFR can be expected after SBRT for intermediate and high-risk prostate cancer with non-significant differences seen for BFFR between favorable intermediate, unfavorable intermediate, and high-risk groups. Our 5-year BFFR compares favorably with the HYPO-RT-PC trial of 84%. PSA nadir was predictive of biochemical failure. This study is ultimately limited by the small absolute number of high-risk patients included.

Adaptive SBRT by 1.5 T MR-linac for prostate cancer: On the accuracy of dose delivery in view of the prolonged session time.

PURPOSE: Adaptive Stereotactic Body Radiotherapy (SBRT) of prostate cancer (PC) by online 1.5 T MRi-guidance prolongs session-time, due to contouring and planning tasks, thus increasing the risk of prostate motion. Hence, the interest to verify the adequacy of the delivered dose. MATERIAL AND METHODS: For twenty PC patients treated by 35 Gy (Dp) in five fractions, daily pre- and post- delivery MRi scans were respectively used for adapt-to-shape (ATS) optimization, and re-computation of the delivered irradiation (Drec). Two expansion recipes, from Clinical (CTV) to Planning target volume (PTV), which slightly differed in the posterior margin were used for groups I and II, of ten patients each. Plans had to assure D95% ≥ 95%Dp to PTV, and D1cc ≤ Dp to rectum, bladder, penile bulb, and urethral planning-risk-volume (urethral-PRV). The adequacy of the delivered dose was estimated by inter-fraction average (ifa) of dose-volume metrics computed from Drec. A cumulative dose (Dsum) was calculated from the five daily Drec deformed onto the simulation MRi. RESULTS: For each patient, CTV coverage resulted in D95% > 95%Dp when estimated as ifa by Drec. No significant difference for D95% and D99% metrics to CTV resulted between groups I and II. D1cc was < Dp for rectum, urethral-PRV, and penile bulb, whereas < 103.5%Dp for the bladder. Significant correlations resulted between metrics computed by Dsum and as ifa by Drec, by both linear-correlation analysis, and Receiver-Operating-Characteristic curve analysis. CONCLUSIONS: Our results for PC-SBRT confirm the adequacy of the delivered dose by ATS with 1.5 T MR-linac, and the consistency between dose-volume metrics computed by Drec and Dsum.

Stereotactic Ablative Radiotherapy for Prostate Cancer-The Treatment Results of 500 Patients and Analysis of Failures.

OBJECTIVE: Stereotactic ablative radiotherapy is a very promising approach for the treatment of patients with prostate cancer. The aim of this study was to evaluate the clinical tolerance, effectiveness, patterns of failure, and attempt to define predictive factors based on our experience. METHODS: The cohort consists of 264 low-risk and 236 intermediate-risk consecutive patients treated at one institution. Prostate-specific antigen (PSA), adverse effects, and androgen deprivation therapy (ADT) usage were noted. RESULTS: Median follow-up was 31.3 months. Over 90% of the patients reported no gastrointestinal toxicity. There were 4 occurrences of G3+ sequelae. 75% patients had no genitourinary toxicity at first month, and up to 90% during the rest of follow-up, with only 1 case of G3 adverse event. The toxicity was more pronounced in patients with higher PSA concentrations. Prior to stereotactic ablative radiotherapy, the mean PSA was 7.59 and 277 patients used ADT. The PSA decreased for up to 20 months before reaching a plateau. The decline was slower, and PSA levels were higher in patients without ADT. A total of 15 treatment failures occured in a median time of 19.9 months. Higher PSA concentrations were connected with higher failure rates, even in the first month and prior to reaching Phoenix criterion. CONCLUSION: CyberKnife-based stereotactic ablative radiotherapy of low-risk and intermediate-risk prostate cancer patients is an effective and well-tolerated modality of treatment. PSA is the most important predictive factor. The evolution of PSA concentration in a particular subgroup of patients suggests that ADT in intermediate-risk cases could improve long-term results.