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This study reports clinical experience and feasibility of using a 2-dimensional (2D)-kV image system with online intervention in the ultrafractionated stereotactic body radiation treatment (UF-SBRT) of prostate cancer.Fifteen patients with prostate cancer who had a low- to intermediate-risk marker implanted received UF-SBRT with online 2D-kV image tracking and a manual beam interruption strategy with a 2-mm motion threshold. A total of 180 kV paired setup images and 1272 intrabeam 2D-kV images were analyzed to evaluate the setup deviation and intratreatment target deviation. Correlation of expected treatment interruptions with a set of parameters (eg, image and treatment time; direction of deviation) was performed (Spearman test). A subset of the data from 22 fractions was re-evaluated to check the differences in analysis results between using the planning position and using the pretreatment setup position as a reference. Margins based on the derived system and random errors were calculated to evaluate the feasibility of the workflow in ensuring prostate coverage during treatment.Mean target motion in 3D propagated from 1.0 mm (setup at 0 minutes) to 2.0 mm (beam on at 7 minutes) to 2.4 mm (end at 13.5 minutes). Out of 75 fractions, 50 were found to require beam interruption. Interruption had a strong correlation with prostate motion along the longitudinal direction and had moderate correlation with prostate motion along the vertical direction and the prostate's treatment starting position along vertical and longitudinal directions. Using the pretreatment position as a reference for intrabeam monitoring, the magnitude of motion deviation from the reference position was reduced by 0.3 mm at a vertical direction and 0.4 mm at lateral and longitudinal directions. The calculated 3D margin to ensure target coverage was 3.7 mm, 4.6 mm, and 5.0 mm in lateral, vertical, and longitudinal directions, respectively.Prostate motion propagated over time. It is feasible to use a 2D-kV online intrabeam monitoring system with a proper intervention scheme to perform UF-SBRT for prostate cancer.

PURPOSE: To investigate predictors associated with post-treatment biopsy outcomes after stereotactic body radiotherapy (SBRT) for localized prostate cancer. MATERIALS AND METHODS: 257 patients treated with prostate SBRT to dose levels of 32.5 Gy to ≥40 Gy in 5–6 fractions underwent a post-treatment biopsy performed approximately two years after treatment to evaluate local control status. 73 had% intermediate-risk disease (n=187) and the remaining 17% (n=43) and 10% (n=27) had low-risk and high-risk disease, respectively. RESULTS: The incidence of positive, negative, and treatment-effect post-treatment biopsies were 15.6%, 57.6%, and 26.8%, respectively. The incidence of a positive biopsy according to dose was 37.5% (n=9/24), 21.4% (n=6/28), 19.4% (n=6/31), and 10.9% (n=19/174) for 32.5 Gy, 35 Gy, 37.5 Gy, and ≥40 Gy, respectively. In a multivariable model, patients treated with SBRT doses of

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

Background and purpose Magnetic Resonance (MR)-only planning has been implemented clinically for radiotherapy of prostate cancer. However, fewer studies exist regarding the overall success rate of MR-only workflows. We report on successes and challenges of implementing MR-only workflows for prostate. Materials and methods A total of 585 patients with prostate cancer underwent an MR-only simulation and planning between 06/2016 – 06/2018. MR simulation included images for contouring, synthetic-CT generation and fiducial identification. Workflow interruptions occurred that required a backup CT, a re-simulation or an update to our current quality assurance (QA) process. The challenges were prospectively evaluated and classified into synthetic-CT generation, motion/artifacts in the MRs, fiducial QA and bowel preparation guidelines. Results MR-only simulation was successful in 544 (93.2%) patients. In seventeen patients (2.9%), reconstruction of synthetic-CT failed due to patient size, femur angulation, or failure to determine the body contour. Twenty-four patients (4.1%) underwent a repeat/backup CT scan because of artifacts on the MR such as image blur due to patient motion or biopsy/surgical artifacts that hampered identification of the implanted fiducial markers. In patients requiring large coverage due to nodal involvement, inhomogeneity artifacts were resolved by using a two-stack acquisition and adaptive inhomogeneity correction. Bowel preparation guidelines were modified to address frequent rectum/gas issues due to longer MR scan time. Conclusions MR-only simulation has been successfully implemented for a majority of patients in the clinic. However, MR-CT or CT-only pathway may still be needed for patients where MR-only solution fails or patients with MR contraindications.

Purpose This study reports clinical experience using a linear accelerator-based MV-kV imaging system for intrafraction motion management during prostate stereotactic body radiation therapy (SBRT). Methods and Materials From June 2016 to August 2018, 193 prostate SBRT patients were treated using MV-kV motion management (median dose 40 Gy in 5 fractions). Patients had 3 fiducials implanted then simulated and treated with a full bladder and empty rectum. Pretreatment orthogonal kVs and cone beam computed tomography were used to position patients and evaluate internal anatomy. Motion was tracked during volumetric modulated arc therapy delivery using simultaneously acquired kV and MV images from standard on-board systems. Treatment was interrupted to reposition patients when motion >1.5-2 mm was detected. Motion traces were analyzed and compared with Calypso traces from a previously treated similar patient cohort. To evaluate “natural motion” (ie, if we had not interrupted treatment and repositioned), intrafraction couch corrections were removed from all traces. Clinical effectiveness of the MV-kV system was explored by evaluating toxicity (Common Terminology Criteria for Adverse Events v3.0) and biochemical recurrence rates (nadir + 2 ng/mL). Results Median number of interruptions for patient repositioning was 1 per fraction (range, 0-9). Median overall treatment time was 8.2 minutes (range, 4.2-44.8 minutes). Predominant motion was inferior and posterior, and probability of motion increased with time. Natural motion >3 mm and >5 mm in any direction was observed in 32.3% and 10.2% of fractions, respectively. Calypso monitoring (n = 50) demonstrated similar motion results. In the 151 MV-kV patients with ≥3-month follow-up (median, 9.5 months; range, 3-26.5 months), grade ≥2 acute genitourinary/gastrointestinal and late genitourinary/gastrointestinal toxicity was observed in 9.9%/2.0% and 11.9%/2.7%, respectively. Biochemical control was 99.3% with a single failure in a high-risk patient. Conclusions The MV-kV system is an effective method to manage intrafraction prostate motion during SBRT, offering the opportunity to correct for prostate clinical target volume displacements that would have otherwise extended beyond typical planning target volume margins.

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.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.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.Our study demonstrated that MV-kV imaging-based intrafraction motion tracking is superior to single kV imaging for prostate SBRT in clinical practice.

PURPOSE: To report toxicity outcomes, prostate-specific antigen (PSA) relapse, and cumulative incidence posttreatment biopsy results among patients treated on a prospective dose escalation study using ultra-hypofractionated stereotactic body radiation therapy (SBRT) for patients with low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: A total of 136 patients were enrolled in a phase 1 dose-escalation study to determine the tolerance of escalating radiation dose levels of SBRT for the treatment of localized prostate cancer. The initial dose level was 32.5 Gy in 5 fractions, and doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy. Eligibility criteria included only patients with low and intermediate risk, and the maximum prostate volume was 60 cm(3). Patients treated with neoadjuvant androgen deprivation were excluded. The median follow-up in survivors for the 4 dose levels was 5.9, 5.4, 4.1, and 3.5 years, respectively. RESULTS: The incidence of acute grade 2 rectal toxicities for dose levels 1 to 4 were 0%, 2.9%, 2.8%, and 11.4% respectively. No grade 3 or 4 acute rectal toxicities were observed. The incidence of acute grade 2 urinary toxicities for dose levels 1 to 4 were 16.7%, 22.9%, 8.3%, and 17.1%, respectively. No grade 3 or 4 acute urinary toxicities were observed. No grade 2 or higher rectal toxicities were observed. The incidence of late grade 2 urinary toxicities for dose levels 1 to 4 was 23.3%, 25.7%, 27.8%, and 31.4%, respectively. Only 1 late grade 3 urinary toxicity (urethral stricture) developed in the 40-Gy dose arm; the stricture was corrected with transurethral resection. No grade 4 late urinary toxicity was observed. The 5-year cumulative incidence of prostate-specific antigen failure for dose levels 1 to 4 was 15%, 6%, 0%, and 0%. The incidence of a 2-year positive posttreatment biopsy was 47.6%, 19.2%, 16.7%, and 7.7%, respectively for the 4 dose arms (P = .013). CONCLUSIONS: SBRT doses ranging from 32.5 to 40 Gy in 5 fractions were well tolerated without severe urinary or rectal toxicities. Biopsy outcomes suggest improved rates of tumor clearance observed with higher doses. © 2019 Elsevier Inc. All rights reserved.

Purpose This study aimed to evaluate the toxicity of prostate and pelvic lymph node stereotactic body radiation therapy (SBRT) for high-risk prostate cancer. Methods and Materials Twenty-three patients with high-risk or lymph node-positive prostate cancer were treated with SBRT that delivered 37.5 to 40 Gy in 5 fractions to the prostate and seminal vesicles, with concomitant treatment of the pelvic nodes to 25 Gy. In general, patients received neoadjuvant, concurrent, and adjuvant androgen deprivation therapy for a duration of 18 months. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events, version 3.0. The median follow-up was 19 months (range, 3-48 months). Results Acute grade 1 gastrointestinal (GI) toxicities were noted in 2 patients (9.1%). No patient experienced acute grade ≥2 GI toxicity. Acute genitourinary (GU) grade 1, 2, and 3 toxicities were observed in 7 patients (31.8%), 8 patients (36.4%), and 1 patient (4.5%), respectively. Late grade 2 GI and GU toxicities were observed in 2 patients (9.1%) and 6 patients (27.3%), respectively. No late grade ≥3 GI toxicity was noted. Late grade ≥3 GU (hemorrhagic cystitis) was noted in 1 patient (4.5%), which responded to laser fulguration. Conclusions SBRT with pelvic lymph node radiation therapy was feasible and well tolerated. The incidence of grade ≥3 GU and GI toxicities was uncommon. Continued follow-up will be required to determine the long-term safety and efficacy of this approach for high-risk patients.

PURPOSE/OBJECTIVE(S) The purpose of this study was to evaluate if a minimum bladder reference contour could help reduce treatment delays and imaging needed for pre-treatment setup in patients undergoing prostate stereotactic body radiation therapy (SBRT). MATERIALS/METHODS 20 patients undergoing 5-fraction SBRT to the prostate and seminal vesicles were included in this pilot study. Patients were simulated with a full bladder (1 cup, 45min prior). The simulated bladder was contoured and then a script automatically generated four possible "min reference contours as a contraction by 1, 2, 3, and 4 cm from the superior bladder border. The smallest reference contour that still met our bladder dose constraints was selected as the min_bladder to be used to guide pre-treatment setup. Radiation therapists and treating physicians were instructed to consider bladder filling sufficient if the volume on the cone-beam CT (CBCT) upon visual inspection appeared larger than the min_bladder reference even if smaller than the simulated bladder. Approved CBCTs were used to evaluate bladder and bowel dosimetry. Treatment time (first kV image to beam-off) and number of CBCTs were compared to 66 consecutive patients treated prior to introducing the min-bladder reference contour. RESULTS The average simulated bladder, min_bladder, and treated bladder sizes were 398 ± 139cc, 157 ± 54cc and 300 ± 150cc, respectively. There was 1 of 100 total fractions where bladder constraints were exceeded, however the approved CBCT bladder volume was less than the min_bladder reference and the total cumulative bladder dose for this patient was within constraints. Average cumulative max bowel dose was 14.5 Gy in 5 fractions with a maximum cumulative max bowel dose 32.5 Gy in 5 fractions. Compared to our historical average treatment time of 31.5 ± 20 min/fraction, the pilot study average was 26 ± 15 min/fraction (P = 0.003). Average number of CBCTs/fraction also decreased from 1.38 ± 0.69 to 1.24 ± 0.60 (P = 0.048). Based on our annual SBRT treatment volume, we estimate that use of this reference contour will save > 150 hours and > 260 CBCTs per year in our department. CONCLUSION Our results suggest that the reference contour accurately predicted the minimum bladder volume needed to avoid exceeding bladder constraints, did not inadvertently overexpose bowel, and significantly reduced treatment time and number of pre-treatment CBCTs. A similar reference contour is now being developed for other prostate definitive and post-op regimens at our institution.

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

Purpose Localizing lung tumors during treatment delivery is critical for managing respiratory motion, ensuring tumor coverage, and reducing toxicities. The purpose of this project is to develop a real-time system that performs markerless tracking of lung tumors using simultaneously acquired MV and kV images during radiotherapy of lung cancer with volumetric modulated arc therapy. Method Continuous MV/kV images were simultaneously acquired during dose delivery. In the subsequent analysis, a gantry angle-specific region of interest was defined according to the treatment aperture. After removing imaging artifacts, processed MV/kV images were directly registered to the corresponding daily setup cone-beam CT (CBCT) projections that served as reference images. The registration objective function consisted of a sum of normalized cross-correlation, weighted by the contrast-to-noise ratio of each MV and kV image. The calculated 3D shifts of the tumor were corrected by the displacements between the CBCT projections and the planning respiratory correlated CT (RCCT) to generate motion traces referred to a specific respiratory phase. The accuracy of the algorithm was evaluated on both anthropomorphic phantom and patient studies. The phantom consisted of localizing a 3D printed tumor, embedded in a thorax phantom, in an arc delivery. In an IRB-approved study, data were obtained from VMAT treatments of two lung cancer patients with three electromagnetic (Calypso) beacon transponders implanted in airways near the lung tumor. Result In the phantom study, the root mean square error (RMSE) between the registered and actual (programmed couch movement) target position was 1.2 mm measured by the MV/kV imaging system, which was smaller compared to the MV or kV alone, of 4.1 and 1.3 mm, respectively. In the patient study, the mean and standard deviation discrepancy between electromagnetic-based tumor position and the MV/KV-markerless approach was -0.2 ± 0.6 mm, 0.2 ± 1.0 mm, and -1.2 ± 1.5 mm along the superior-inferior, anterior-posterior, and left-right directions, respectively; resulting in a 3D displacement discrepancy of 2.0 ± 1.1 mm. Poor contrast around the tumor was the main contribution to registration uncertainties. Conclusion The combined MV/kV imaging system can provide real-time 3D localization of lung tumor, with comparable accuracy to the electromagnetic-based system when features of tumors are detectable. Careful design of a registration algorithm and a VMAT plan that maximizes the tumor visibility are key elements for a successful MV/KV localization strategy.

Background and Purpose This study summarizes the cranial stereotactic radiosurgery (SRS) volumetric modulated arc therapy (VMAT) procedure at our institution. Materials and Methods Volumetric modulated arc therapy plans were generated for 40 patients with 188 lesions (range 2–8, median 5) in Eclipse and treated on a TrueBeam STx. Limitations of the custom beam model outside the central 2.5 mm leaves necessitated more than one isocenter pending the spatial distribution of lesions. Two to nine arcs were used per isocenter. Conformity index (CI), gradient index (GI) and target dose heterogeneity index (HI) were determined for each lesion. Dose to critical structures and treatment times are reported. Results Lesion size ranged 0.05–17.74 cm3 (median 0.77 cm3), and total tumor volume per case ranged 1.09–26.95 cm3 (median 7.11 cm3). For each lesion, HI ranged 1.2–1.5 (median 1.3), CI ranged 1.0–2.9 (median 1.2), and GI ranged 2.5–8.4 (median 4.4). By correlating GI to PTV volume a predicted GI = 4/PTV0.2 was determined and implemented in a script in Eclipse and used for plan evaluation. Brain volume receiving 7 Gy (V 7 Gy) ranged 10–136 cm3 (median 42 cm3). Total treatment time ranged 24–138 min (median 61 min). Conclusions Volumetric modulated arc therapy provide plans with steep dose gradients around the targets and low dose to critical structures, and VMAT treatment is delivered in a shorter time than conventional methods using one isocenter per lesion. To further improve VMAT planning for multiple cranial metastases, better tools to shorten planning time are needed. The most significant improvement would come from better dose modeling in Eclipse, possibly by allowing for customizing the dynamic leaf gap (DLG) for a special SRS model and not limit to one DLG per energy per treatment machine and thereby remove the limitation on the Y‐jaw and allow planning with a single isocenter.

PURPOSE/OBJECTIVE(S) Automated marker detection allows real time image guidance for treatment setup in 6D and intra-beam monitoring in 3D on a standard linear accelerator. This study retrospectively assessed the accuracy and efficiency of automated marker registration vs. manual match from a group of treated prostate SBRT patients. MATERIALS/METHODS An automated marker detection scheme was developed by reconstructing a 3D marker model from orthogonal paired images for pre-treatment setup alignment using iterative closest point (ICP). The 3D marker model was back-projected to monoscopic x-ray images acquired during treatment. 3D marker motion was estimated from the consecutive (40o gantry angle apart) monoscopic x-ray images. Standard treatment was 2 arc Volumetric-modulated arc therapy (VMAT) plan prescribed to 8 Gy per fraction (x5). From 9 SBRT prostate patients, 135 paired images and 810 monoscopic x-ray images were analyzed using the automated scheme by comparing to the 3D marker model of planning image. A subgroup of the data set (5 patients, 12 fractions, 235 monoscopic images) were re-aligned to 3D marker position of setup images from the automated program to compare marker motion without realignment, which had minor residual setup error after manual match. Paired sample Wilcoxon ranked test was run to evaluate the improvement of using automated alignment, P-value < 0.05 was considered significant. RESULTS Using automated marker match as reference, the residual setup error after manual match of the entire group (135 paired images) was (0.3 ± 0.6) mm, (0.1 ± 0.7) mm, (0.2 ± 0.8) mm in lateral (Lat), longitudinal (Long), vertical (Vert) directions, and (-2.6 ± 5.0)o, (-0.1 ± 2.8)o, (-1.3 ± 3.0)o in pitch, yaw, roll directions, respectively. The centroid of the marker position had an error of (0.2 ± 1.2) mm, (-0.6 ± 1.3) mm, (0.7 ± 1.4) mm in Lat, Long, Vert directions, respectively, during treatment (from 810 images). Treatment error at Lat, Long, Vert directions had stronger correlation with setup error in Lat & roll (-0.57 & -0.18), in Long & yaw (-0.49 & -0.25), and in Vert & roll (0.48 & 0.31), respectively. The magnitude of the improvement for individual fraction of the subgroup (235 images) using automated setup correction was 0.4 mm, 0.4 mm, 0.4 mm in Lat (P < 0.01), Long (P = 0.04), Vert (P = 0.39). The fraction of the treatment time that the marker centroid had a positional error of more than 2mm (a tolerance which triggered treatment interruption) was 9.5%, 18.5%, 12% in Lat, Long, Vert directions, respectively, using manual setup match, and 2.5%, 8.5%, 0.5% using automated setup match. CONCLUSION This study demonstrated the ability of automated marker match to improve the accuracy and efficiency of prostate SBRT during treatment using monoscopic x-ray image. The improvement of treatment accuracy was 0.4 mm in each (X, Y, and Z) dimension. The improvement treatment efficiency was 50% reduction of treatment interruption which needs re-imaging. In addition, auto-registration saves manual markers alignment time.

Purpose To develop an Eclipse plug‐in (MLC_MODIFIER) that automatically modifies control points to expose fiducials obscured by MLC during VMAT, thereby facilitating tracking using periodic MV/kV imaging. Method Three‐dimensional fiducial tracking was performed during VMAT by pairing short‐arc (3°) MV digital tomosynthesis (DTS) images to triggered kV images. To evaluate MLC_MODIFIER efficacy, two cohorts of patients were considered. For first 12 patients, plans were manually edited to expose one fiducial marker. Next for 15 patients, plans were modified using MLC_MODIFIER script. MLC_MODIFIER evaluated MLC apertures at appropriate angles for marker visibility. Angles subtended by control points were compressed and low‐dose “imaging” control points were inserted and exposed one marker with 1 cm margin. Patient's images were retrospectively reviewed to determine rate of MV registration failures. Failure categories were poor DTS image quality, MLC blockage of fiducials, or unknown reasons. Dosimetric differences in rectum, bladder, and urethra D1 cc, PTV maximum dose, and PTV dose homogeneity (PTV HI) were evaluated. Statistical significance was evaluated using Fisher's exact and Student's t test. Result Overall MV registration failures, failures due to poor image quality, MLC blockage, and unknown reasons were 33% versus 8.9% (P

Purpose To develop personalized multivariate dose-response models for late dysphagia in patients with head and neck cancer treated in the modern era of combined chemotherapy with intensity-modulated radiation therapy. Patients and Methods The analysis included 424 patients (oropharyngeal cancer [n = 295] and nasopharyngeal, hypopharyngeal, or laryngeal cancer [n = 129]) who received definitive chemoradiation between January 2004 and April 2009. The superior, middle, and inferior pharyngeal constrictor muscles were contoured. We calculated generalized equivalent uniform dose (gEUD) for each and the total constrictor muscle volume, with the volume effect parameter a varying from log10 a = −1 to +1 in steps of 0.1. We used the National Cancer Institute Common Toxicity Criteria for Adverse Events (version 3.0) to grade late dysphagia and logistic regression to evaluate the correlation of gEUD( a) with grade 2 or higher (≥ G2) and grade 3 or higher (≥ G3) late dysphagia at each value of a. Results Median follow-up was 33.3 months (range, 6 to 69 months). There were 41 cases (10%) of ≥ G2 dysphagia and 22 cases (5%) of ≥ G3 dysphagia. Mean doses to the total constrictor ranged from 30.1 to 85.7 Gy (median, 61.2 Gy). The predicted rate of ≥ G2 dysphagia increased by approximately 3.4% per Gy at the mean dose, for which the probability of ≥ G2 dysphagia is 50%. The threshold mean total constrictor doses that limited rates of ≥ G2 and ≥ G3 dysphagia to < 5% were < 58 Gy and < 61 Gy, respectively. Other significant factors in the multivariate predictive model included disease site, mean dose to total constrictor muscle, and patient age. Conclusion Incidences of both ≥ G2 and ≥ G3 dysphagia were dependent on the mean radiation dose to the total constrictor muscle volume, disease site, and patient age. Limiting the total volume of constrictor muscle to < 58 Gy could keep the predicted rate of ≥ G2 dysphagia to < 5%.

Purpose: Robust detection of implanted fiducials is essential for monitoring intrafractional motion during hypofractionated treatment. The authors developed a plan optimization strategy to ensure clear visibility of implanted fiducials and facilitate 3D localization during volumetric modulated arc therapy (VMAT). Methods: Periodic kilovoltage (kV) images were acquired at 20° gantry intervals and paired with simultaneously acquired 4.4° short arc megavoltage digital tomosynthesis (MV-DTS) to localize three fiducials during VMAT delivery for hypofractionated prostate cancer treatment. Beginning with the original optimized plan, control point segments where fiducials were consistently blocked by multileaf collimator(MLC) within each 4.4° MV-DTS interval were first identified. For each segment, MLC apertures were edited to expose the fiducial that led to the least increase in the cost function. Subsequently, MLC apertures of all control points not involved with fiducial visualization were reoptimized to compensate for plan quality losses and match the original dose–volume histogram. MV dose for each MV-DTS was also kept above 0.4 MU to ensure acceptable image quality. Different imaging (gantry) intervals and visibility margins around fiducials were also evaluated. Results: Fiducials were consistently blocked by the MLC for, on average, 36% of the imagingcontrol points for five hypofractionated prostate VMAT plans but properly exposed after reoptimization. Reoptimization resulted in negligible dosimetric differences compared with original plans and outperformed simple aperture editing: on average, PTV D98 recovered from 87% to 94% of prescription, and PTV dose homogeneity improved from 9% to 7%. Without violating plan objectives and compromising delivery efficiency, the highest imaging frequency and largest margin that can be achieved are a 10° gantry interval, and 15 mm, respectively. Conclusions: VMAT plans can be made to accommodate MV-kV imaging of fiducials. Fiducial visualization rate and workflow efficiency are significantly improved with an automatic modification and reoptimization approach.

Prostate position is affected by the varying filling of the bladder and rectum, and so may move at any time during dose delivery. In the setting of SBRT then, a single image guided setup prior to treatment may be inadequate, possibly resulting in dose coverage to the target being less than, and dose to the rectal wall or bladder being higher than that planned. In this chapter, reports on the dosimetric benefits of intra-fractional monitoring and correction are discussed. Various approaches taken to achieve this, both those commercially available, and in clinical development are surveyed. The importance of bowel preparation and the use of other interventions are also discussed.

PURPOSE: Until now, real-time 3D image guided radiotherapy (IGRT) has been the domain of dedicated cancer radiotherapy systems. However, the tipping point to the broad adoption of real-time IGRT is the availability of this technology on standard-equipped radiotherapy systems. The purpose of this work is to review real-time 3D IGRT on standard-equipped cancer radiotherapy systems, focusing on clinically implemented solutions. METHOD: Three groups in three continents have clinically implemented novel real-time 3DIGRT solutions on standard-equipped linear accelerators. These technologies encompass kilovoltage, combined megavoltage-kilovoltage and combined kilovoltage-optical imaging. The cancer sites treated span pelvic and abdominal tumors where respiratory motion is present. For each method the 3D-measured motion during treatment is reported. Post-treatment, dose reconstruction was used to assess the treatment quality in the presence of motion with and without real-time 3D IGRT. The geometric accuracy was quantified through phantom experiments. A literature search was conducted to identify additional real-time 3D IGRT methods that could be clinically implemented in the near future. RESULTS: The real-time 3D IGRT methods were successfully clinically implemented and have been used to treat over 200 patients. Systematic target position shifts were observed using all three methods. Dose reconstruction demonstrated that the delivered dose is closer to the planned dose with real-time 3D IGRT than without real-time 3D IGRT. In addition, compromised target dose coverage and variable normal tissue doses were found without real-time 3D IGRT. The geometric accuracy results with real-time 3D IGRT had a mean error of

To investigate the influence of treatment plan data and image guidance (IG) on positioning uncertainty during prostate cancer (PCa) radiotherapy (RT).Body mass index (BMI), planning target volume (PTV), bladder volume (BV), and rectal cross section area (RCS) were collected for 267 consecutive PCa patients undergoing daily IGRT. Radiographic isocenter corrections to intra-prostatic fiducials for 12,490 treatment fractions were used to derive random (RE) and systematic (SE) inter-fraction uncertainties for the cardinal axes. These data were used to simulate RE and SE for weekly IG and Action Level (AL)-IG treatment protocols.SE and RE were 2-5 and 3-4mm in the cardinal axes, respectively, during simulation of no IG. Without IG, positive correlations (p0.01) were noted for (1) anterior-posterior RE vs. RCS and BV and (2) cranio-caudal RE vs. RCS, BV and BMI. The RE increase was 3mm for the highest quartile of RCS, BV and BMI. Daily IGRT eliminated this relationship. 3D IG corrections of 1cm or more occured in 27% of treatment fractions and in 97% of patients.PCa patients with elevated pre-treatment BV, RCS and BMI have increased inter-fractionation positioning uncertainty and appear the primary candidates for daily IGRT.

Background We examined patterns of failure in pediatric patients with thoracic sarcoma and pulmonary metastases treated with intensity-modulated radiation therapy with dose-painting (DP-IMRT). Procedure Eleven pediatric patients, five with Ewing sarcoma family tumors (ESFT) and six with rhabdomyosarcoma (RMS), with primary thoracic tumors and pulmonary metastases underwent DP-IMRT with chemotherapy for definitive treatment. Eight patients also underwent surgery. Median time to RT was 21 (15–31) weeks. Nine patients received 45–50.4–Gy in 1.8 Gy fractions to the primary tumor (n = 3) or post-operative tumor bed (n = 6). Two patients ≤4 years received 12 Gy intraoperative radiation therapy and 30.6–36 Gy IMRT postoperatively to the tumor bed. All patients received 14–16.8 Gy in 0.54–0.88 Gy fractions to the whole lungs (n = 6) or hemithorax (n = 5) using dose-painting technique. A representative case was re-planned with IMRT plus standard AP/PA whole lung irradiation (WLI) for dosimetric comparison. Results With 27-month median follow-up, 3-year pulmonary relapse-free survival in all patients was 61%: 80% for RMS and 40% for ESFT. Five patients (4 ESFT and 1 RMS) experienced pulmonary relapse at median 16 (9–41) months. There were no local failures. Our representative case demonstrated more homogeneous target volume coverage of the whole lungs and decreased mean dose to esophagus (15%), heart (31%), spinal cord (15%), and liver (19%) with DP-IMRT. Conclusions The treatment of children with a primary thoracic tumor and pulmonary metastases poses a significant challenge. DP-IMRT is one solution to this technical problem. Initial data from this small series suggest DP-IMRT is feasible and produces superior sparing of critical normal tissues. Pediatr Blood Cancer 2013;60:1616–1620. © 2013 Wiley Periodicals, Inc.

To evaluate the incidence and predictors of hip toxicity postradiotherapy for localized prostate cancer.4067 prostate cancer patients were treated with external beam radiotherapy (EBRT; n=2569; 63%) or brachytherapy with or without supplemental EBRT (n=1508; 27%). 43% (n=1738) were treated with neo-adjuvant and concurrent ADT and 57% (n=2329) with radiotherapy alone. Hip toxicity was defined as moderate or severe pain upon ambulation with or without the need for hip-revision surgery. Median follow-up was 7years (range, 3-21years).One hundred twenty-one (2.7%) patients developed moderate-to-severe hip pain after radiotherapy affecting ambulation. Of these, 73 (60%) required hip replacement secondary to persistent hip pain. Among patients with baseline degenerative joint disease (DJD) changes on scans, 10-year incidence of hip-related toxicity was 11% versus 3% for those without such changes (P.001). The only variables on multivariate analysis associated with hip-related toxicity post-radiotherapy were baseline DJD on imaging (P.0001) and prolonged ADT for salvage therapy (P.0001).Prostate EBRT or brachytherapy is associated with low incidence of long-term hip-related toxicity. The only variables identified associated with hip toxicity posttherapy was the presence of baseline DJD and prolonged salvage ADT posttreatment for patients developing recurrence.

Robust detection of implanted fiducials is essential for monitoring intrafractional motion during hypofractionated treatment. The authors developed a plan optimization strategy to ensure clear visibility of implanted fiducials and facilitate 3D localization during volumetric modulated arc therapy (VMAT).Periodic kilovoltage (kV) images were acquired at 20° gantry intervals and paired with simultaneously acquired 4.4° short arc megavoltage digital tomosynthesis (MV-DTS) to localize three fiducials during VMAT delivery for hypofractionated prostate cancer treatment. Beginning with the original optimized plan, control point segments where fiducials were consistently blocked by multileaf collimator (MLC) within each 4.4° MV-DTS interval were first identified. For each segment, MLC apertures were edited to expose the fiducial that led to the least increase in the cost function. Subsequently, MLC apertures of all control points not involved with fiducial visualization were reoptimized to compensate for plan quality losses and match the original dose-volume histogram. MV dose for each MV-DTS was also kept above 0.4 MU to ensure acceptable image quality. Different imaging (gantry) intervals and visibility margins around fiducials were also evaluated.Fiducials were consistently blocked by the MLC for, on average, 36% of the imaging control points for five hypofractionated prostate VMAT plans but properly exposed after reoptimization. Reoptimization resulted in negligible dosimetric differences compared with original plans and outperformed simple aperture editing: on average, PTV D98 recovered from 87% to 94% of prescription, and PTV dose homogeneity improved from 9% to 7%. Without violating plan objectives and compromising delivery efficiency, the highest imaging frequency and largest margin that can be achieved are a 10° gantry interval, and 15 mm, respectively.VMAT plans can be made to accommodate MV-kV imaging of fiducials. Fiducial visualization rate and workflow efficiency are significantly improved with an automatic modification and reoptimization approach.

Purpose To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged ≤7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% ( P =.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.

PURPOSE: Periodic MV/KV radiographs taken during volumetric modulated arc therapy (VMAT) for hypofractionated treatment provide guidance in intrafractional motion management. The choice of imaging frequency and timing are key components in delivering the desired dose while reducing associated overhead such as imaging dose, preparation, and processing time. In this project the authors propose a paradigm with imaging timing and frequency based on the spatial and temporal dose patterns of the treatment plan. METHODS: A number of control points are used in treatment planning to model VMAT delivery. For each control point, the sensitivity of individual target or organ‐at‐risk dose to motion can be calculated as the summation of dose degradations given the organ displacements along a number of possible motion directions. Instead of acquiring radiographs at uniform time intervals, MV/KV image pairs are acquired indexed to motion sensitivity. Five prostate patients treated via hypofractionated VMAT are included in this study. Intrafractional prostate motion traces from the database of an electromagnetic tracking system are used to retrospectively simulate the VMAT delivery and motion management. During VMAT delivery simulation patient position is corrected based on the radiographic findings via couch movement if target deviation violates a patient‐specific 3D threshold. The violation rate calculated as the percentage of traces failing the clinical dose objectives after motion correction is used to evaluate the efficacy of this approach. RESULTS: Imaging indexed to a 10 s equitime interval and correcting patient position accordingly reduces the violation rate to 19.5% with intervention from 44.5% without intervention. Imaging indexed to the motion sensitivity further reduces the violation rate to 12.1% with the same number of images. To achieve the same 5% violation rate, the imaging incidence can be reduced by 40% by imaging indexed to motion sensitivity instead of time. CONCLUSIONS: The simulation results suggest that image scheduling according to the characteristics of the treatment plan can improve the efficiency of intrafractional motion management. Using such a technique, the accuracy of delivered dose during image‐guided hypofractionated VMAT treatment can be improved.

Purpose: Hypofractionated prostate radiotherapy may benefit from both volumetric modulated arc therapy (VMAT) due to shortened treatment time and intrafraction real-time monitoring provided by implanted radiofrequency(RF) transponders. The authors investigate dosimetrically driven action thresholds (whether treatment needs to be interrupted and patient repositioned) in VMAT treatment with electromagnetic (EM) tracking. Methods: VMAT plans for five patients are generated for prescription doses of 32.5 and 42.5 Gy in five fractions. Planning target volume (PTV) encloses the clinical target volume (CTV) with a 3 mm margin at the prostate-rectal interface and 5 mm elsewhere. The VMAT delivery is modeled using 180 equi-spaced static beams. Intrafraction prostate motion is simulated in the plan by displacing the beam isocenter at each beam assuming rigid organ motion according to a previously recorded trajectory of the transponder centroid. The cumulative dose delivered in each fraction is summed over all beams. Two sets of 57 prostate motion trajectories were randomly selected to form a learning and a testing dataset. Dosimetric end points including CTV D95%, rectum wall D1cc, bladder wall D1cc, and urethra Dmax, are analyzed against motion characteristics including the maximum amplitude of the anterior-posterior (AP), superior-inferior (SI), and left-right components. Action thresholds are triggered whenmore » intrafraction motion causes any violations of dose constraints to target and organs at risk (OAR), so that treatment is interrupted and patient is repositioned. Results: Intrafraction motion has a little effect on CTV D95%, indicating PTV margins are adequate. Tight posterior and inferior action thresholds around 1 mm need to be set in a patient specific manner to spare organs at risk, especially when the prescription dose is 42.5 Gy. Advantages of setting patient specific action thresholds are to reduce false positive alarms by 25% when prescription dose is low, and increase the sensitivity of detecting dose limits violations by 30% when prescription dose is high, compared to a generic 2 mm action box. The sensitivity and specificity calculated from the testing dataset are consistent to the learning set, which indicates that the patient specific approach is reliable and reproducible within the scope of the prostate database. Conclusions: This work introduces a formalism for ensuring a VMAT delivery meets the most clinically important dose requirements by using patient specific and dosimetric-driven action thresholds to hold the beam and reposition the patient when necessary. Such methods can provide improved sensitivity and specificity compared to conventional methods, which assume directionally symmetric action thresholds.« less

Purpose To develop a collimator trajectory optimization paradigm for volumetric modulated arc therapy (VMAT) and evaluate this technique in paraspinal stereotactic body radiation therapy (SBRT). Method and Materials We propose a novel VMAT paradigm, Coll-VMAT, which integrates collimator rotation with synchronized gantry rotation, multileaf collimator (MLC) motion, and dose-rate modulation. At each gantry angle a principal component analysis (PCA) is applied to calculate the primary cord orientation. The collimator angle is then aligned so that MLC travel is parallel to the PCA-derived direction. An in-house VMAT optimization follows the geometry-based collimator trajectory optimization to obtain the optimal MLC position and monitor units (MU) at each gantry angle. A treatment planning study of five paraspinal SBRT patients compared Coll-VMAT to standard VMAT (fixed collimator angle) and static field IMRT plans. Plan evaluation statistics included planning target volume (PTV) V95%, PTV-D95%, cord-D05%, and total beam-on time. Results Variation of collimator angle in Coll-VMAT plans ranges from 26° to 54°, with a median of 40°. Patient-averaged PTV V95% (94.6% Coll-VMAT vs. 92.1% VMAT and 93.3% IMRT) and D95% (22.5 Gy vs. 21.4 Gy and 22.0 Gy, respectively) are highest with Coll-VMAT, and cord D05% (9.8 Gy vs. 10.0 Gy and 11.7 Gy) is lowest. Total beam-on time with Coll-VMAT (5,164 MU) is comparable to standard VMAT (4,868 MU) and substantially lower than IMRT (13,283 MU). Conclusion Collimator trajectory optimization-based VMAT provides an additional degree of freedom that can improve target coverage and cord sparing of paraspinal SBRT plans compared with standard VMAT and IMRT approaches.

Purpose To develop an optimization method using volumetric modulated arc therapy (VMAT) and evaluate VMAT plans relative to the standard intensity-modulated radiotherapy (IMRT) approach in prostate cancer. Methods and Materials A single gantry rotation was modeled using 177 equispaced beams. Multileaf collimator apertures and dose rates were optimized with respect to gantry angle subject to dose-volume–based objectives. Our VMAT implementation used conjugate gradient descent to optimize dose rate, and stochastic sampling to find optimal multileaf collimator leaf positions. A treatment planning study of 11 prostate cancer patients with a prescription dose of 86.4 Gy was performed to compare VMAT with a standard five-field IMRT approach. Plan evaluation statistics included the percentage of planning target volume (PTV) receiving 95% of prescribed dose (V95), dose to 95% of PTV (D95), mean PTV dose, tumor control probability, and dosimetric endpoints of normal organs, whereas monitor unit (MU) and delivery time were used to assess delivery efficiency. Results Patient-averaged PTV V95, D95, mean dose, and tumor control probability in VMAT plans were 96%, 82.6 Gy, 88.5 Gy, and 0.920, respectively, vs. 97%, 84.0 Gy, 88.9 Gy, and 0.929 in IMRT plans. All critical structure dose requirements were met. The VMAT plans presented better rectal wall sparing, with a reduction of 1.5% in normal tissue complication probability. An advantage of VMAT plans was that the average number of MUs (290 MU) was less than for IMRT plans (642 MU). Conclusion The VMAT technique can reduce beam on time by up to 55% while maintaining dosimetric quality comparable to that of the standard IMRT approach.

Intensity-modulated radiotherapy (IMRT) has become an effective tool for cancer treatment with radiation. However, even expert radiation planners still need to spend a substantial amount of time manually adjusting IMRT optimization parameters such as dose limits and costlet weights in order to obtain a clinically acceptable plan. In this paper, we describe two main advances that simplify the parameter adjustment process for five-field prostate IMRT planning. First, we report the results of a sensitivity analysis that quantifies the effect of each hand-tunable parameter of the IMRT cost function on each clinical objective and the overall quality of the resulting plan. Second, we show that a recursive random search over the six most sensitive parameters as an outer loop in IMRT planning can quickly and automatically determine parameters for the cost function that lead to a plan meeting the clinical requirements. Our experiments on a ten-patient dataset show that for 70% of the cases, we can automatically determine a plan in 10 min (on the average) that is either clinically acceptable or requires only minor adjustment by the planner. The outer-loop optimization can be easily integrated into a traditional IMRT planning system.

Purpose The combination of permanent low-dose-rate interstitial implantation (LDR-BRT) and external beam radiotherapy (EBRT) has been used in the treatment of clinically localized prostate cancer. While a high radiation dose is delivered to the prostate in this setting, the actual biologic dose equivalence compared to monotherapy is not commonly invoked. We describe methodology for obtaining the fused dosimetry of this combined treatment and assigning a dose equivalence which in turn can be used to develop desired normal tissue and target constraints for biologic-based treatment planning. Methods and materials Patients treated with this regimen initially receive an I-125 implant prescribed to 110 Gy followed, 2 months later, by 50.4 Gy in 28 fractions using intensity-modulated external beam radiotherapy. Ab initio methodology is described, using clinically derived biologic parameters (α, β, potential doubling time for prostate cancer cells [T pot ], cell loss factor), for calculating tumor control probability isoeffective doses for the combined LDR and conventional fraction EBRT treatment regimen. As no such formalism exists for assessing rectal or urethral toxicity, we make use of semi-empirical expressions proposed for describing urethral and rectal complication probabilities for specific treatment situations (LDR and fractionation, respectively) and utilize the notion of isoeffective dose to extend these results to combined LDR-EBRT regimens. Results The application to treatment planning of the methodology described in this study is illustrated with real-patient data. We evaluate the effect of changing LDR and EBRT prescription doses (in a manner that remains isoeffective with 81 Gy EBRT alone or with 144 Gy LDR monotherapy) on rectal and urethral complication probabilities, and suggest that it should be possible to improve the therapeutic ratio by exploiting joint LDR-EBRT planning. Conclusions We describe new methodology for biologically based treatment planning for patients who receive combined low-dose-rate brachytherapy and external beam radiotherapy for prostate cancer. Using relevant mathematical tools, we demonstrate the feasibility of fusing dose distributions from each treatment for this combined regimen, which can then be expressed as isoeffective dose distributions. Based on this information, dose constraints for the rectum and urethra are described which could be used for planning such combination regimens.

Purpose: Cranial SRS VMAT plans must have steep dose gradient around each target to reduce dose to normal brain. This study reports on the correlation between gradient index (GI=V50%/V100%), target size and target dose heterogeneity index (HI=PTV Dmax/prescription dose) for multi-lesion cranial SRS VMAT plans. Methods: VMAT plans for 10 cranial cases with 3 to 6 lesions (total 39 lesions) generated in Varian Eclipse V11.0.47 with a fine-tuned AAA beam model and 0.125 cm dose grid were analyzed. One or two iso centers were used depending on the spatial distribution of lesions. Two to nine coplanar and non-coplanar arcs were used per isocenter. Conformity index (CI= V100%/VPTV), HI, and GI were determined for each lesion. Dose to critical structures were recorded. Results: Lesion size ranged from 0.05–11.00 cm3. HI ranged from 1.2–1.4, CI ranged from 1.0–2.8 and GI from 3.1–8.4. Maximum dose to brainstem, chiasm, lenses, optic nerves and eyes ranged from 120–1946 cGy, 47–463 cGy, 9–121 cGy, 14–512 cGy, and 17–294 cGy, respectively. Brain minus PTV (Brain-PTV) V7Gy was in the range 1.1–6.5%, and Brain-PTV Dmean was in the range 94–324 cGy. Conclusion: This work shows that a GI 0.4cc. For smaller lesions, GI increases rapidly. GI is lower when HI is increased. Based on this study, recommend HI is 1.4, and recommended GI is for volumes 1.0cc GI

Purpose: To assess the patterns of failure for patients with medulloblastoma receiving a conformal tumor bed boost rather than a boost to the entire posterior fossa. Patients and Methods: From 1994 to 2002, 32 consecutive patients with newly diagnosed medulloblastoma treated at Memorial Sloan-Kettering Cancer Center (New York, NY) received a conformal boost to the tumor bed in conjunction with craniospinal radiation therapy. Twenty-eight patients also received chemotherapy. The median age was 9 years (range, 3 to 34 years), and the male to female ratio was 3:1. Twenty-seven patients had standard-risk disease, and five patients had high-risk disease. Craniospinal doses ranged from 23.4 to 39.6 Gy, and total tumor bed doses ranged from 54 to 59.4 Gy. Results: With a median follow-up of 56 months, six patients have relapsed; five relapsed outside of the posterior fossa, and one failed within the posterior fossa, outside of the high-dose boost volume. Five-year actuarial disease-free and overall survival rates were 84% and 85%, respectively. Freedom from posterior fossa failure was 100% and 86% at 5 and 10 years, respectively. Freedom from distant failure was 84% at 5 years, with a trend for improvement when full-dose craniospinal radiation (36 to 39.6 Gy) was used compared with a reduced dose (23.4 Gy) of radiation (100% v 63%, respectively; P = .06). No other predictive variables were identified. Conclusion: Conformal treatment to the tumor bed allows for significant sparing of critical structures. The posterior fossa failure rate in this series is similar to that reported when the entire posterior fossa is treated. This approach should be investigated further in a phase III trial.

Background and purpose : To assess the effect of internal organ motion on the dose distributions and biological indices for the target and non-target organs for three different conformal prostate treatment techniques. Materials and methods : We examined three types of treatment plans in 20 patients: (1) a six field plan, with a prescribed dose of 75.6 Gy; (2) the same six field plan to 72 Gy followed by a boost to 81 Gy; and (3) a five field plan with intensity modulated beams delivering 81 Gy. Treatment plans were designed using an initial CT data set (planning) and applied to three subsequent CT scans (treatment). The treatment CT contours were used to represent patient specific organ displacement; in addition, the dose distribution was convolved with a Gaussian distribution to model random setup error. Dose–volume histograms were calculated using an organ deformation model in which the movement between scans of individual points interior to the organs was tracked and the dose accumulated. The tumor control probability (TCP) for the prostate and proximal half of seminal vesicles (clinical target volume, CTV), normal tissue complication probability (NTCP) for the rectum and the percent volume of bladder wall receiving at least 75 Gy were calculated. Results : The patient averaged increase in the planned TCP between plan types 2 and 1 and types 3 and 1 was 9.8% (range 4.9–12.5%) for both, whereas the corresponding increases in treatment TCP were 9.0% (1.3–16%) and 8.1% (−1.3–13.8%). In all patients, plans 2 and 3 (81 Gy) exhibited equal or higher treatment TCP than plan 1 (75.6 Gy). The maximum treatment NTCP for rectum never exceeded the planning constraint and percent volume of bladder wall receiving at least 75 Gy was similar in the planning and treatment scans for all three plans. Conclusion : For plans that deliver a uniform prescribed dose to the planning target volume (PTV) (plan 1), current margins are adequate. In plans that further escalate the dose to part of the PTV (plans 2 and 3), in a fraction of the cases the CTV dose increase is less than planned, yet in all cases the TCP values are higher relative to the uniform dose PTV (plan 1). Doses to critical organs remain within the planning criteria.

Purpose To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analyses were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum ( P =.006), the V90 of the trigone ( P =.006), and the maximal dose to the trigone ( P =.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum ( P =.009) and increased maximal dose to the trigone ( P =.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 ( P =.001; odds ratio 5.19). Conclusions The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone seems to be associated with a reduction in late GU toxicity.

To determine the extent and predictors for prostatic motion in a large number of patients evaluated with multiple CT scans during radiotherapy, and evaluate the implications of these data on the design of appropriate treatment margins for patients receiving high-dose three-dimensional conformal radiotherapy.Fifty patients underwent four serial computerized tomography (CT) scans, consisting of an initial planning scan and subsequent scans at the beginning, middle, and end of the treatment course. Each scan was performed with the patient in the prone treatment position within an immobilization device used during therapy. Contours of the prostate and seminal vesicles were drawn on the axial CT slices of each scan, and the scans were matched by alignment of the pelvic bones with a chamfer matching algorithm. Using the contour information, distributions of the displacement of the organ center of mass and organ border from the planning position were determined separately for the prostate and seminal vesicles in each of the three principle directions: anterior-posterior (AP), superior-inferior (SI) and left-right (LR). Each distribution was fitted to a normal (Gaussian) distribution to determine confidence limits in the center of mass and border displacements and thereby evaluate for the optimal margins needed to contain target motion.The most common directions of displacement of the prostate center of mass (COM) were in the AP and SI directions and were significantly larger than any LR movement. The mean prostate COM displacement (+/- 1 standard deviation, SD) for the entire population was -1.2 +/- 2.9 mm, -0.5 +/- 3.3 mm and -0.6 +/- 0.8 mm in the, AP and SI and LR directions respectively (negative values indicate posterior, inferior or left displacement). The mean (+/- 1 SD) seminal vesicle COM displacement for the entire population was - 1.4 +/- 4.9 mm, 1.3 +/- 5.5 mm and -0.8 +/- 3.1 mm in the AP and SI and LR directions, respectively. The data indicate a tendency for the population towards posterior displacements of the prostate from the planning position and both posterior and superior displacements of the seminal vesicles. AP movement of both the prostate and seminal vesicles were correlated with changes in rectal volume (P = 0.0014 and0.0001, respectively) more than with changes in bladder volume (P = 0.030 for seminal vesicles and 0.19 for prostate). A logistic regression analysis identified the combination of rectal volume60 cm3 and bladder volumes40 cm3 as the only predictor of large (3 mm) systematic deviations for the prostate and seminal vesicles (P = 0.05) defined for each patient as the difference between organ position in the planning scan and mean position as calculated from the three subsequent scans.Prostatic displacement during a course of radiotherapy is more pronounced among patients with initial planning scans with large rectal and bladder volumes. Such patients may require more generous margins around the CTV to assure its enclosure within the prescription dose region. Identification and correction of patients with large systematic errors will minimize the extent of the margin required and decrease the volume of normal tissue exposed to higher radiation doses.

Purpose: To prospectively assess the effect of supine vs. prone treatment position on the dose to normal tissues in prostate cancer patients treated with the three-dimensional conformal technique. Methods and Materials: Twenty-six patients underwent three-dimensional treatment planning in both the supine and prone treatment positions. The planning target volume and normal tissue structures were outlined on each CAT scan slice, and treatment plans were compared to assess the effect of treatment position on the volume of rectum, bladder, and bowel exposed to the high doses of irradiation. Results: The average dose to the rectal wall and the V95 (volume of rectal wall receiving at least 95% of the prescription dose) for the prone position were 64 and 24% of the prescription dose, respectively, compared to 72 and 29%, respectively, for the supine position (p < 0.05). When the average rectal wall dose was used as an endpoint, 14 of the 26 patients (54%) had an advantage for the prone position compared to 1 (4%) who demonstrated and advantage for the supine position (p < 0.0002). Similarly, when V95 of the rectal wall was used as a measure of comparison, 15 patients (58%) had an advantage for the prone position compared to 1 (4%) who demonstrated an advantage for the supine position (p < 0.0002). In 13 patients (50%), a change from spine to the prone position was associated with reduction of the V95 to levels < 30% of the prescription dose compared to 3 patients (11%) in whom such an advantage resulted from change of the prone to the supine position (p < 0.005). The effect of treatment position on the rectal wall dose was most pronounced in the region of the seminal vesicles. An increased volume of bowel was also noted in the supine position. The treatment position, however, had no significant impact on the dose to the bladder wall. Conclusions: Three-dimensional conformal radiotherapy for prostate cancer in the prone position is associated with significant reduction of the dose to the rectum and bowel resulting in an improvement in the therapeutic ratio.

To develop an optimization algorithm for volumetric modulated arc therapy which incorporates an electromagnetic tracking (EMT) guided gating strategy and is robust to residual intra-fractional motion uncertainties. In a computer simulation, intra-fractional motion traces from prior treatments with EMT were converted to a probability distribution function (PDF), truncated using a patient specific action volume that encloses allowed deviations from the planned position, and renormalized to yield a new PDF with EMT-gated interventions. In lieu of a conventional planning target volume (PTV), multiple instances of clinical target volume (CTV) and organs at risk (OARs) were replicated and displaced to extreme positions inside the action volume representing possible delivery scenarios. When optimizing the volumetric modulated arc therapy plan, doses to the CTV and OARs were calculated as a sum of doses to the replicas weighted by the PDF to account for motion. A treatment plan meeting the clinical constraints was produced and compared to the counterpart conventional margin (PTV) plan. EMT traces from a separate testing database served to simulate motion during gated delivery. Dosimetric end points extracted from dose accumulations for each motion trace were utilized to evaluate potential clinical benefit. Five prostate cases from a hypofractionated protocol (42.5 Gy in 5 fractions) were retrospectively investigated. The patient specific gating window resulted in tight anterior and inferior action levels (~1 mm) to protect rectal wall and bladder wall, and resulted in an average of four beam interruptions per fraction in the simulation. The robust-optimized plans achieved the same average CTV D95 coverage of 40.5 Gy as the PTV-optimized plans, but with reduced patient-averaged rectum wall D1cc by 2.2 Gy (range 0.7 to 4.7 Gy) and bladder wall mean dose by 2.9 Gy (range 2.0 to 3.4 Gy). Integration of an intra-fractional motion management strategy into the robust optimization process is feasible and may yield improved OAR sparing compared to the standard margin approach.

Purpose: evaluate a commercial synthetic CT (syn-CT) software for use in prostate radiotherapy Methods: Twenty prostate patients underwent CT and MR simulation scans in treatment position on a 3T Philips scanner. The MR protocol consisted of a T2w turbo spin-echo for soft tissue contrast, a 2D balanced-fast field echo (b-FFE) for fiducial identification, a dual-echo 3D FFE B0 map for distortion analysis and a 3D mDIXON FFE sequence to generate syn-CT. Two echoes are acquired during mDIXON scan, allowing water, fat, and in-phase images to be derived using the frequency shift of the fat and water protons. Tissues were classified as: air, adipose, water, trabecular/spongy bone and compact/cortical bone and assigned specific bulk HU values. Bone structures are segmented based on a pelvis bone atlas. Accuracy of syn-CT for patient treatment planning was analyzed by transferring the original plan and structures from the CT to syn-CT via rigid registration and recalculating dose. In addition, new IMRT plans were generated on the syn-CT using structures contoured on MR and transferred to the syn-CT. Accuracy of fiducial-based localization at the treatment machine performed using syn-CT or DRRs generated from syn-CT was assessed by comparing to orthogonal kV radiographs or CBCT. Results: Dosimetric comparison between CT and syn-CT was within 0.5% for all structures. The de-novo optimized plans generated on the syn-CT met our institutional clinical objectives for target and normal structures. Patient-induced susceptibility distortion based on B0 maps was within 1mm and 0.4 mm in the body and prostate. The rectal and bladder outlines on the syn-CT were deemed sufficient for assessing rectal and bladder filling on the CBCT at the time of treatment. CBCT localization showed a median error of < ±1 mm in LR, AP and SI direction. Conclusion: MRI derived syn-CT can be used clinically in MR-alone planning and treatment process for prostate. Drs. Deasy, Hunt and Tyagi have Master research agreement with Philips healthcare.

Purpose: To commission a custom 6MV-SRS-AAA Eclipse beam model for VMAT multiple lesions cranial SRS treatment on a Varian TrueBeam STx. Methods: Six clinical plans were created using a customized beam model with dosimetric-leaf-gap(DLG) optimized for clinical treatments. Each plan had 4–6 non-isocentric targets with size from 0.2 to 7.1cc. All fields were measured with EBT3 film in the coronal plane in a solid water phantom and with an AS1000 EPID using gantry rotation. In addition, an end-to-end test was performed with coronal and sagittal films in an anthropomorphic phantom verifying dosimetry and localization accuracy. Portal dose distributions were generated with a custom portal dosimetry algorithm(PDIP). Measured dose distributions were compared with calculations using average dose difference (DD), and gamma function, γ. Using a 1.25mm grid, the γ criteria, local DD ≤ 3% and 2mm distance-to-agreement, were applied in regions with dose 50% of maximum. Results: The respective DD and γ for all films were 94.2%. The portal dose γ scores for all the plans were >94.9%. However, local regions with underdose >10%, were observed when targets were treated with the 5mm leaves. The same plans re-optimized with two isocenters such that all lesions were under the 2.5mm leaves did not show this effect. The DD and localization error of the end-to-end test were within 3.4% and 1.0mm respectively. Conclusion: The custom AAA beam model is capable of calculating acceptable dosimetry for targets using only the 2.5 mm leaves. This restricts lesions to within ±4cm of isocenter. The observed underdose beneath the 5mm leaves is attributed to a limitation in Eclipse that uses a single DLG representing the DLG's of both 2.5mm and 5mm leaves. If lesions are >4cm from isocenter, a multiple isocenter technique should be considered to allow the use of only the 2.5mm leaves.

Purpose: Segmentation of prostate CBCT images is an essential step towards real-time adaptive radiotherapy. It is challenging For Calypso patients, as more artifacts are generated by the beacon transponders. We herein propose a novel wavelet-based segmentation algorithm for rectum, bladder, and prostate of CBCT images with implanted Calypso transponders. Methods: Five hypofractionated prostate patients with daily CBCT were studied. Each patient had 3 Calypso transponder beacons implanted, and the patients were setup and treated with Calypso tracking system. Two sets of CBCT images from each patient were studied. The structures (i.e. rectum, bladder, and prostate) were contoured by a trained expert, and these served as ground truth. For a given CBCT, the moving window-based Double Haar transformation is applied first to obtain the wavelet coefficients. Based on a user defined point in the object of interest, a cluster algorithm based adaptive thresholding is applied to the low frequency components of the wavelet coefficients, and a Lee filter theory based adaptive thresholding is applied to the high frequency components. For the next step, the wavelet reconstruction is applied to the thresholded wavelet coefficients. A binary/segmented image of the object of interest is therefore obtained. DICE, sensitivity, inclusiveness and ΔV were used to evaluate the segmentation result. Results: Considering all patients, the bladder has the DICE, sensitivity, inclusiveness, and ΔV ranges of [0.81–0.95], [0.76–0.99], [0.83–0.94], [0.02–0.21]. For prostate, the ranges are [0.77–0.93], [0.84–0.97], [0.68–0.92], [0.1–0.46]. For rectum, the ranges are [0.72–0.93], [0.57–0.99], [0.73–0.98], [0.03–0.42]. Conclusion: The proposed algorithm appeared effective segmenting prostate CBCT images with the present of the Calypso artifacts. However, it is not robust in two scenarios: 1) rectum with significant amount of gas; 2) prostate with very low contrast. Model based algorithm might improve the segmentation in these two scenarios.

Purpose: To quantify and compare the dosimetric impact of motion management correction strategies during VMAT and IMRT for hypofractionated prostate treatment. Methods: Two arc VMAT and 9 field IMRT plans were generated for two prostate cancer patients undergoing hypofractionated radiotherapy (7.5Gy × 5 and 8Gy × 5). 212 motion traces were retrospectively extracted from treatment records of prostate cancer patients with implanted Calypso beacons. Dose to the CTV and normal tissues was reconstructed for each trace and plan taking into account the actual treatment delivery time. Following motion correction scenarios were simulated: (1) VMAT plan – (a) No correction, (b) correction between arcs, (c) correction every 20 degrees of gantry rotation and (2) IMRT plan - (a) No correction,(b) correction between fields. Two mm action threshold for position correction was assumed. The 5–95% confidence interval (CI) range was extracted from the family of DVHs for each correction scenario. Results: Treatment duration for 8Gy plan (VMAT vs IMRT) was 3 vs 12 mins and for 7.5Gy plan was 3 vs 9 mins. In the absence of correction, the VMAT 5–−95% CI dose spread was, on average, less than the IMRT dose spread by 2% for CTVD95, 9% for rectalwall (RW) D1cc and 9% for bladderwall (BW) D53. Further, VMAT b/w arcs correction strategy reduced the spread about the planned value compared to IMRT b/w fields correction by: 1% for CTVD95, 2.6% for RW1cc and 2% for BWD53. VMAT 20 degree strategy led to greater reduction in dose spread compared to IMRT by: 2% for CTVD95, 4.5% for RW1cc and 6.7% for BWD53. Conclusion: In the absence of a correction strategy, the limited motion during VMAT’s shorter delivery times translates into less motion-induced dosimetric degradation than IMRT. Performing limited periodic motion correction during VMAT can yield excellent conformity to planned values that is superior to IMRT. This work was partially supported by Varian Medical Systems

Purpose Stereotactic body radiotherapy (SBRT) is being used with increasing frequency as definitive treatment of early stage prostate cancer. Much of the justification for its adoption was derived from earlier clinical results using high-dose-rate (HDR) brachytherapy. We determine whether HDR's dosimetry can be achieved by virtual SBRT. Methods and Materials Patients with intermediate-risk prostate cancer on a prospective trial evaluating the efficacy of HDR monotherapy treated to dose of 9.5 Gy × 4 fractions were used for this study. A total of 5 patients were used in this analysis. Virtual SBRT plans were developed to reproduce the planning target volume (PTV) HDR dose distributions. Both normal tissue– and PTV-prioritized plans were generated. Results From the normal tissue–prioritized plan, HDR and virtual SBRT achieved similar PTV V 100 (93.8% vs. 93.1%, p = 0.20) and V 150 (40.3% vs. 42.9%, p = 0.69) coverage. However, the PTV V 200 was not attainable with SBRT (15.2% vs. 0.0%, p D max was significantly lower with HDR (94.2% vs. 99.42%, p = 0.05). The rectal D 2 cc was also lower (60.8% vs. 71.1%, p = 0.07). Difference in D 1 cc urethral dose was not significantly different (87.7% vs. 75.2%, p = 0.33). Comparing the PTV-prioritized plans, the rectal D max (94.2% vs. 111.1%, p = 0.05) and mean dose (27.1% vs. 33.3%, p = 0.03) were significantly higher using SBRT, and the rectal D 2 cc was higher using SBRT (60.8% vs. 81.8%, p = 0.07). Conclusions HDR achieves significantly higher intraprostatic doses while achieving a lower maximum rectal dose compared with our virtual SBRT treatment planning. Future studies should compare clinical outcomes and toxicity between these modalities.