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Background and purpose Positional verification during single fraction lung SBRT could increase confidence and reduce the chance of geographic miss. As planar 2DkV imaging during VMAT irradiation is already available on current linear accelerators, markerless tracking based on these images could offer widely available and low-cost verification. We evaluated treatment delivery data and template matching and triangulation for 3D-positional verification during free-breathing, single fraction (34 Gy), 10 MV flattening-filter-free VMAT lung SBRT. Methods and materials Tumor tracking based on kV imaging at 7 frames/second was performed during irradiation in 6 consecutive patients (7 lesions). Tumor characteristics, tracking ability, comparison of tracking displacements with CBCT-based shifts, tumor position relative to the PTV margin, and treatment times are reported. Results For all 7 lesions combined, 3D tumor position could be determined for, on average, 71% (51–84%) of the total irradiation time. Visually estimated tracked and automated match +/− manually-corrected CBCT-derived displacements generally agreed within 1 mm. During the tracked period, the longitudinal, lateral and vertical position of the tumor was within a 5 mm/3 mm PTV margin 95.5/85.3% of the time. The PTV was derived from the ITV including all tumor motion. The total time from first set-up imaging to end of the last arc was 18.3–31.4 min (mean = 23.4, SD = 4.1). Conclusion 3D positional verification during irradiation of small lung targets with limited motion, was feasible. However, tumor position could not be determined for on average 29% of the time. Improvements are needed. Margin reduction may be feasible. Imaging and delivery of a single 34 Gy fraction was fast.

Purpose Accurate verification of tumor position during irradiation could reduce the probability of target miss. We investigated whether a commercial gantry-mounted 2-dimensional (2D) kilo-voltage (kV) imaging system could be used for real-time 3D tumor tracking during volumetric modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT). Markerless tumor tracking on kV fluoroscopic images was validated using a life-like moving thorax phantom and subsequently performed on kV images continuously acquired before and during free-breathing VMAT lung SBRT. Methods and Materials The 3D-printed/molded phantom containing 3 lung tumors was moved in 3D in TrueBeam developer mode, using simulated regular/irregular breathing patterns. Planar kV images were acquired at 7 frames/s during 11 Gy/fraction 10 MV flattening filter free VMAT. 2D reference templates were created for each gantry angle using the planning 4D computed tomography inspiration phase. kV images and templates were matched using normalized cross correlation to determine 2D tumor position, and triangulation of 2D matched projections determined the third dimension. 3D target tracking performed on cone beam computed tomography projection data from 18 patients (20 tumors) and real-time online tracking data from 2 of the 18 patients who underwent free-breathing VMAT lung SBRT are presented. Results For target 1 and 2 of the phantom (upper lung and middle/medial lung, mean density –130 Hounsfield units), 3D results within 2 mm of the known position were present in 92% and 96% of the kV projections, respectively. For target 3 (inferior lung, mean density –478 Hounsfield units) this dropped to 80%. Benchmarking against the respiratory signal, 13/20 (65%) tumors (10.5 ± 11.1 cm3) were considered successfully tracked on the cone beam computed tomography data. Tracking was less successful (≤50% of the time) in 7/20 (1.2 ± 1.5 cm3). Successful online tracking during lung SBRT was demonstrated. Conclusions 3D markerless tumor tracking on a standard linear accelerator using template matching and triangulation of free-breathing kV fluoroscopic images was possible in 65% of small lung tumors. The smallest tumors were most challenging.

Purpose: Organ-at-risk (OAR) delineation is a key step in treatment planning but can be time consuming, resource intensive, subject to variability, and dependent on anatomical knowledge. We studied deep learning (DL) for automated delineation of multiple OARs; in addition to geometric evaluation, the dosimetric impact of using DL contours for treatment planning was investigated. Methods and Materials: The following OARs were delineated with DL developed in-house: both submandibular and parotid glands, larynx, cricopharynx, pharyngeal constrictor muscle (PCM), upper esophageal sphincter, brain stem, oral cavity, and esophagus. DL contours were benchmarked against the manual delineation (MD) clinical contours using the Sørensen-Dice similarity coefficient. Automated knowledge-based treatment plans were used. The mean dose to the manually delineated OAR structures was reported for the MD and DL plans. Results: DL delineation of all OARs took 2 Gy higher and >2 Gy lower, respectively, in the DL plans. Conclusions: DL-based segmentation for head and neck OARs is fast; for most organs and most patients, it performs sufficiently well for treatment-planning purposes. It has the potential to increase efficiency and facilitate online adaptive radiation therapy.

Transmission beam (TB) proton therapy (PT) uses single, high energy beams with Bragg-peak behind the target, sharp penumbras and simplified planning/delivery. TB facilitates ultra-high dose-rates (UHDRs, e.g., ≥40 Gy/s), which is a requirement for the FLASH-effect. We investigated (1) plan quality for conventionally-fractionated head-and-neck cancer treatment using spot-scanning proton TBs, intensity-modulated PT (IMPT) and photon volumetric-modulated arc therapy (VMAT), (2) UHDR-metrics. VMAT, 3-field IMPT and 10-field TB-plans, delivering 70/54.25 Gy in 35 fractions to boost/elective volumes, were compared (n = 10 patients). To increase spot peak dose-rates (SPDRs), TB-plans were split into three subplans, with varying spot monitor units and different gantry currents. Average TB-plan organs-at-risk (OAR) sparing was comparable to IMPT: mean oral cavity/body dose were 4.1/2.5 Gy higher (9.3/2.0 Gy lower than VMAT), most other OAR mean doses differed by &lt, 2 Gy. Average percentage of dose delivered at UHDRs was 46%/12% for split/non-split TB-plans and mean dose-averaged dose-rate 46/21 Gy/s. Average total beam-on irradiation time was 1.9/3.8 s for split/non-split plans and overall time including scanning 8.9/7.6 s. Conventionally-fractionated proton TB-plans achieved comparable OAR-sparing to IMPT and better than VMAT, with total beam-on irradiation times &lt, 10s. If a FLASH-effect can be demonstrated at conventional dose/fraction, this would further improve plan quality and TB-protons would be a suitable delivery system.

Purpose: To present the radiation therapy quality assurance results from a prospective multicenter phase 2 randomized trial of short versus protracted urethra-sparing stereotactic body radiation therapy (SBRT) for localized prostate cancer. Methods and Materials: Between 2012 and 2015, 165 patients with prostate cancer from 9 centers were randomized and treated with SBRT delivered either every other day (arm A, n = 82) or once a week (arm B, n = 83); 36.25 Gy in 5 fractions were prescribed to the prostate with (n = 92) or without (n = 73) inclusion of the seminal vesicles (SV), and the urethra planning-risk volume received 32.5 Gy. Patients were treated either with volumetric modulated arc therapy (VMAT; n = 112) or with intensity modulated radiation therapy (IMRT; n = 53). Deviations from protocol dose constraints, planning target volume (PTV) homogeneity index, PTV Dice similarity coefficient, and number of monitor units for each treatment plan were retrospectively analyzed. Dosimetric results of VMAT versus IMRT and treatment plans with versus without inclusion of SV were compared. Results: At least 1 major protocol deviation occurred in 51 patients (31%), whereas none was observed in 41. Protocol violations were more frequent in the IMRT group (P 98% (31.1 vs 30.8 Gy, P 2% (37.9 vs 38.7 Gy, P 50% (24.5% vs 33.5%, P =.0001). To achieve its goals volumetric modulated arc therapy required fewer monitor units than IMRT (2275 vs 3378, P 90% (9.1% vs 10.4%, P =.0003) and V80% (13.2% vs 15.7%, P =.0003). Conclusions: Protocol deviations with potential impact on tumor control or toxicity occurred in 31% of patients in this prospective clinical trial. Protocol deviations were more frequent with IMRT. Prospective radiation therapy quality assurance protocols should be strongly recommended for SBRT trials to minimize potential protocol deviations.

Background and purpose Patient selection for proton therapy by comparing proton/photon treatment plans is time-consuming and prone to bias. RapidPlan™, a knowledge-based-planning solution, uses plan-libraries to model and predict organ-at-risk (OAR) dose-volume-histograms (DVHs). We investigated whether RapidPlan, utilizing an algorithm based only on photon beam characteristics, could generate proton DVH-predictions and whether these could correctly identify patients for proton therapy. Material and methods ModelPROT and ModelPHOT comprised 30 head-and-neck cancer proton and photon plans, respectively. Proton and photon knowledge-based-plans (KBPs) were made for ten evaluation-patients. DVH-prediction accuracy was analyzed by comparing predicted-vs-achieved mean OAR doses. KBPs and manual plans were compared using salivary gland and swallowing muscle mean doses. For illustration, patients were selected for protons if predicted ModelPHOT mean dose minus predicted ModelPROT mean dose (ΔPrediction) for combined OARs was ≥6 Gy, and benchmarked using achieved KBP doses. Results Achieved and predicted ModelPROT/ModelPHOT mean dose R2 was 0.95/0.98. Generally, achieved mean dose for ModelPHOT/ModelPROT KBPs was respectively lower/higher than predicted. Comparing ModelPROT/ModelPHOT KBPs with manual plans, salivary and swallowing mean doses increased/decreased by

Purpose To investigate changes in head-and-neck cancer (HNC) plan quality following the introduction of new technologies and planning techniques in the last decade. Methods and materials Thirty plans were selected from each of four successive periods (P). P1: 7-field static intensity-modulated radiotherapy (IMRT) with parotid gland sparing; P2: dual-arc volumetric-modulated arc therapy (VMAT, similar to P3-P4), including submandibular gland sparing; P3: inclusion of individual swallowing muscles and attempts to further reduce parotid and oral cavity doses through manual interactive optimization; P4: containing the same organs-at-risk (OARs) as P3, but automatically interactively optimized. Plan benchmarking included mean salivary gland/swallowing muscle/oral cavity (D sal /D swal /D oc ) doses. Differences in mean doses between the periods were analyzed by an ANCOVA, taking geometric differences across periods into account. Results Compared to P1, P2 plans improved D sal by 3.4Gy on average. P3 improved D sal /D swal /D oc by 6.9/11.5/7.2Gy over P2, showing that D swal and D sal could be improved simultaneously. In P4, D oc /D swal slightly improved over P3 by 1.7/3.8Gy. Improved OAR sparing in P3/P4 did not come at the cost of increased dose deposition elsewhere and planning target volume (PTV) dose homogeneity was similar. Conclusions New technologies and planning techniques were successfully implemented into routine clinical care and resulting in improved HNC plan quality.

Purpose: Interactive optimization during treatment planning requires intermittent adjustment of organ-at-risk (OAR) objectives relative to the dose–volume histogram line. This is a labor-intensive process and the resulting plans are prone to variations in quality. The authors’ in-house developed approach to automated interactive optimization (AIO) automatically moves the mouse cursor to adjust the position of on-screen optimization objectives. This allows for the use of more objectives per OAR and results in a more frequent and consistent adjustment of these objectives during optimization. The authors report a detailed evaluation of AIO performance in support of its implementation for routine head and neck cancer (HNC) planning and an evaluation for locally advanced lungcancer (LC) planning which requires a different optimization strategy. Methods: Volumetric modulated arc therapy AIO plans (APs) were created for 70 HNC patients with a simultaneously integrated boost and 20 LC patients and benchmarked against their respective manually interactively optimized plans (MPs). The same set of optimization objectives and priorities was used for all APs, although planning target volume (PTV) optimization priorities could be increased manually in a subsequent “continue previous optimization” calculation. HNC plans were benchmarked using mean dose to individual and composite OARs and elective/boost PTV (PTVE/PTVB) volumes receiving 95% and 107% of the prescription dose (V95% and V107%, respectively). A clinician performed blinded comparison of 20 APs and respective MPs. LC plans were compared using PTV V95%/V107%, contralateral lung (CL) volume receiving 5 Gy (V5Gy), total lung (TL)-PTV V5Gy/V20Gy, and esophagus and heart V40Gy/V60Gy/mean doses. Results: For HNC, statistically significant improvements in sparing of all OARs, except for the ipsilateral submandibular gland and trachea, were obtained in the APs compared to MPs. Average mean dose to oral cavity, composite salivary, and swallowing structures were 25.4/23.8, 24.2/23.2, and 29.5/25.5 Gy, respectively, for the MPs/APs. PTV heterogeneity was similar: in the APs, PTVB V95% was 0.2% higher while PTV B/PTV E V107% was 0.4%/1.0% lower. In 19 out of 20 HNC patients, the clinician preferred the AP, mainly because of better OAR sparing and PTV dose homogeneity. For LC, APs had a significantly lower CL V5Gy (6.1%), heart mean dose/V60Gy (0.9 Gy/1.2%) and esophagus mean dose/V60Gy (0.9 Gy/2.8%), a nonsignificantly higher TL V20Gy (1.4%), and a slight, but significantly higher dose deposition to the body. PTV dose coverage and homogeneity were similar in the APs and MPs. AIO was considered sufficiently robust for clinical use in LC. Conclusions: HNC and LC APs were at least as good as, and often of improved quality over MPs. To date, AIO has been clinically implemented for HNC planning.

Purpose The purpose was to report our initial experience with online markerless 3-dimensional (3D) spine position monitoring. We used template matching plus triangulation of fluoroscopic kilovoltage images acquired with the gantry-mounted imager during flattening filter-free volumetric modulated arc spine stereotactic body radiation therapy delivery on a conventional linear accelerator. Methods and Materials Kilovoltage images were acquired at 7 frames per second and streamed to a stand-alone computer. Two-dimensional templates (1/°) containing the clinical target volume were generated from planning computed tomography (CT) data before the first fraction and matched to the (prefiltered) kilovoltage images during treatment. Each 2-dimensional registration was triangulated with multiple previous registrations, resulting in the 3D spine position offset from the planned position in real time during treatment. If the offset was more than a certain threshold, the treatment was manually stopped and a cone beam CT scan was acquired to reposition the patient. Results During irradiation of 10 fractions in 3 patients, images were analyzed at an average rate of 1.0 to 1.3 frames per second; all other frames were excluded from the analysis because of limitations in processing speed. As a result of the start-up period of triangulation and poorer image quality at the start of treatment (lateral imaging angles), the first 3D position was determined after an average of 4.9 seconds. On the basis of the position results, we interrupted the treatment beam 2 times for different patients. In all cases the spine position results corresponded well with the CT–cone beam CT match values used for subsequent repositioning. Conclusions For the first time, we have determined the spine position during stereotactic body radiation therapy delivery on a standard linear accelerator using the gantry-mounted kilovoltage imager. This has the potential to increase confidence in the treatment, and the need for 2 treatment interruptions demonstrates the benefit of monitoring during irradiation. However, software improvements are needed to increase processing speed.

Background This is a dosimetric comparative study intended to establish appropriate low-to-intermediate dose-constraints for the rectal wall (Rwall) in the context of a randomized phase-II trial on urethra-sparing stereotactic body radiotherapy (SBRT) for prostate cancer. The effect of plan optimization on low-to-intermediate Rwall dose and the potential benefit of an endorectal balloon (ERB) are investigated. Methods Ten prostate cancer patients, simulated with and without an ERB, were planned to receive 36.25Gy (7.25Gyx5) to the planning treatment volume (PTV) and 32.5Gy to the urethral planning risk volume (uPRV). Reference plans with and without the ERB, optimized with respect to PTV and uPRV coverage objectives and the organs at risk dose constraints, were further optimized using a standardized stepwise approach to push down dose constraints to the Rwall in the low to intermediate range in five sequential steps to obtain paired plans with and without ERB (Vm1 to Vm5). Homogeneity index for the PTV and the uPRV, and the Dice similarity coefficient (DSC) for the PTV were analyzed. Dosimetric parameters for Rwall including the median dose and the dose received by 10 to 60% of the Rwall, bladder wall (Bwall) and femoral heads (FHeads) were compared. The monitor units (MU) per plan were recorded. Results Vm4 reduced by half D30%, D40%, D50%, and Dmed for Rwall and decreased by a third D60% while HIPTV, HIuPRV and DSC remained stable with and without ERB compared to Vmref. HIPTV worsened at Vm5 both with and without ERB. No statistical differences were observed between paired plans on Rwall, Bwall except a higher D2% for Fheads with and without an ERB. Conclusions Further optimization to the Rwall in the context of urethra sparing prostate SBRT is feasible without compromising the dose homogeneity to the target. Independent of the use or not of an ERB, low-to-intermediate doses to the Rwall can be significantly reduced using a four-step sequential optimization approach.

Background and purpose Central lung stereotactic body radiotherapy (SBRT) can cause proximal bronchial tree (PBT) toxicity. Information on PBT position relative to the high-dose could aid risk management. We investigated template matching + triangulation for high-frequency markerless 3D PBT position monitoring. Materials and methods Kilovoltage projections of a moving phantom (full-fan cone-beam CT [CBCT, 15 frames/second] without MV irradiation: 889 images/dataset + CBCT and 7 frames/second fluoroscopy with MV irradiation) and ten patients undergoing free-breathing stereotactic/hypofractionated lung irradiation (full-fan CBCT without MV irradiation, 470–500 images/dataset) were retrospectively analyzed. 2D PBT reference templates (1 filtered digitally reconstructed radiograph/°) were created from planning CT data. Using normalized cross-correlation, templates were matched to projection images for 2D position. Multiple registrations were triangulated for 3D position. Results For the phantom, 2D right/left PBT position could be determined in 86.6/75.1% of the CBCT dataset without MV irradiation, and 3D position (excluding first 20° due to the minimum triangulation angle) in 84.7/72.7%. With MV irradiation, this was up to 2% less. For right/left PBT, root-mean-square errors of measured versus “known” position were 0.5/0.8, 0.4–0.5/0.7, and 0.4/0.5–0.6 mm for left–right, superior–inferior, and anterior–posterior directions, respectively. 2D PBT position was determined in, on average, 89.8% of each patient dataset (range: 79.4–99.2%), and 3D position (excluding first 20°) in 85.1% (range: 67.9–99.6%). Motion was mainly superior–inferior (range: 4.5–13.6 mm, average: 8.5 mm). Conclusions High-frequency 3D PBT position verification during free-breathing is technically feasible using markerless template matching + triangulation of kilovoltage projection images acquired during gantry rotation. Applications include organ-at-risk position monitoring during central lung SBRT.

Not all clinics have breath‐hold radiotherapy available for left‐breast irradiation. However intensity‐modulated radiotherapy (IMRT) has also been advocated as a means of lowering heart doses. There is currently no large‐scale, long‐term follow‐up data after breast IMRT and, since dose distributions may differ from classic tangent‐based radiotherapy, caution is needed to avoid unexpected worsening of the late toxicity profile. We compared four IMRT techniques for free‐breathing left‐breast irradiation. Consistent with the aforementioned concerns, our goal in planning was to prioritize organ at risk (OAR) sparing in a way that mimicked tangent‐based radiotherapy. Ten simultaneous integrated boost treatment plans (PTVelective=15×2.67 Gy;PTVboost=15×3.35 Gy) were created using 1) hybrid‐IMRT (H‐IMRT), 2) full IMRT (F‐IMRT), and 3) volumetric‐modulated arc therapy with two partial arcs (2ARC) and 4) six partial arcs (6ARC). Reduction in OAR mean and low dose was prioritized. End‐points included OAR sparing (e.g., heart, left anterior descending artery [LAD+3 mm], lungs, and contralateral breast) and PTV coverage/dose homogeneity. Under these conditions we found the following: 1) H‐IMRT provided the best mean and low dose OAR sparing, PTVelective coverage (mean V95%=98%),PTVboost coverage (V95%=98%), and PTV homogeneity. However, it delivered most intermediate–high dose to the heart, LAD+3 mm and ipsilateral lung; 2) 6ARC had the best intermediate–high dose sparing, followed by F‐IMRT, but this was at the expense of more dose in the contralateral lung and breast and worse PTV coverage (PTVelective mean V95%=96%/97% and PTVboost mean V95%=91%/96% for 6ARC/F‐IMRT). When trying to spare mean and low dose to OARs, the preferred IMRT technique for left‐breast irradiation without breath‐hold was H‐IMRT. This is currently the standard solution in our institution for left‐breast radiotherapy under free‐breathing and breath‐hold conditions. PACS numbers: 87.53kn, 87.53Jw, 87.55.D‐, 87.55.de, 87.55.dk

Purpose: (1) To validate retrospective markerless tracking software for small lung tumors by comparing tracked motion in 4-dimensional planning computed tomography (4DCT) derived kV projection images and known tumor motion in the same 4DCT. (2) To evaluate variability of tumor motion using kV projection images from cone-beam computed tomography (CBCT) scans acquired on different days. Methods: Nonclinical tumor tracking software (TTS) used a normalized cross correlation algorithm to track the tumor on enhanced kV projection images (e.g., from a CBCT scan). The reference dataset consisted of digitally reconstructed radiographs (DRRs) from one phase of a planning 4DCT. TTS matches two in-plane coordinates and obtains the out-of-plane coordinate by triangulating with match results from other projections. (1) To validate TTS, tracking results were compared with known 4DCT tumor motion for two patients (A and B). Projection images (1 image/1°) were digitally reconstructed for each 4DCT phase. From these, kV projection series were composed simulating full breathing cycles every 20° of gantry rotation [breathing period = 20°/(6°/s) = 3.33 s]. Reference templates were 360 “tumor enhanced” DRRs from the 4DCT expiration phase. TTS-derived tumor motion was compared to known tumor motion on 4DCT. (2) For five patients, TTS-assessed motion during clinical CBCT acquisition was compared with motion on the planning 4DCT, and the motion component in the Y (cranio–caudal)-direction was compared with the motion of an external marker box (RPM, real-time position management). Results: (1) Validation results: TTS for case A (tumor 6.2 cm3, 32 mm axial diameter) over 360° showed mean motion X (medial–lateral) = 3.4, Y = 11.5, and Z (ventral–dorsal) = 4.9 mm (1 SD < 1.0 mm). Corresponding 4DCT motion was X = 3.1, Y = 11.3, and Z = 5.1 mm. Correlation coefficients between TTS tumor motion and displacement of the tumor’s center of mass (CoM) on 4DCT were 0.64, 0.96, and 0.82 (X, Y, and Z, respectively). For case B (4.1 cm3, 20 mm diameter), due to temporarily decreased tumor visibility preventing TTS from resolving the tumor, robust tracking data were only available between angles 300°–40° and 120°–220°. Mean motion according to TTS was X = 2.0, Y = 7.7, and Z = 8.2 mm (1 SD 2.0 mm (1 SD) in four of five patients. In addition, clinical tumor motion amplitude differed from that seen on planning 4DCT. Internal and external structures that create abrupt density change (e.g., table-top edge, interface between lung/mediastinum and lung/heart) were observed to prevent 360° tracking of the tumor. Correlation coefficients between TTS motion in the Y-direction and the RPM signal (22 observations) ranged from 0.78 to 0.96. In 2D, 241 TTS matches at end-inspiration and end-expiration were visually validated: mean difference was 0.8 mm (SD = 0.7) for both. Conclusions: TTS can track small lung tumors if these are visible in kV projections. A 4DCT dataset can be used to validate kV tracking of moving targets. TTS and 4DCT displacement agreed to within 2 mm. TTS and RPM motion were closely associated but tumor motion during CBCT can vary from the planning 4DCT.

BACKGROUND AND PURPOSE: Proof of tumor position during stereotactic body radiotherapy (SBRT) delivery is desirable. We investigated if cone-beam CT (CBCT) scans reconstructed from (collimated) fluoroscopic kV images acquired during irradiation could show the dominant tumor position.MATERIALS AND METHODS: Full-arc CBCT scans were reconstructed using FDK filtered back projection from 38kV fluoroscopy datasets (16 patients) continuously acquired during volumetric modulated spine SBRT. CBCT-CT match values were compared to the average spine offset values found using template matching+triangulation of the individual kV images. Multiple limited-arc CBCTs were reconstructed from fluoroscopic images acquired during lung SBRT of an anthropomorphic thorax phantom using 20-180° arc lengths and for 3 breath-hold lung SBRT patients.RESULTS: Differences between 3D CBCT-CT match results and average spine offsets found using template matching+triangulation were 0.1±0.1mm for all directions (range: 0.0-0.5mm). For limited-arc CBCTs of the thorax phantom, the automatic 3D CBCT-CT match results for arc lengths of 80-180° were ≤1mm. 20° CBCT reconstruction still allowed for positional verification in 2D.CONCLUSIONS: (Limited-arc) CBCT reconstructions of kV images acquired during irradiation can identify the dominant position of the tumor during treatment delivery.

Introduction Stereotactic ablative radiotherapy (SABR) is currently not the guideline-recommended treatment for lung tumors measuring more than 5 cm. However, improvements in radiotherapy techniques have led to increasing use of SABR for larger tumors. Methods We analyzed the clinical outcomes in patients with a primary or recurrent NSCLC measuring more than 5 cm and treated with five or eight fractions of SABR at our center. Patients who had prior thoracic radiotherapy were excluded. Results A total of 63 consecutive patients with a median tumor diameter of 5.8 cm (range 5.1–10.4) were identified; 81% had T2N0 disease and 18% had T3N0 disease. The median Charlson comorbidity index was 2 (range 0–6). After a median follow-up of 54.7 months, median survival was 28.3 months. Disease-free survival at 2 years was 82.1%, and the local, regional, and distant control rates at 2 years were 95.8%, 93.7%, and 83.6%, respectively. An out-of-field distant recurrence at one or more sites was the most common pattern of failure (10%). Grade 3 or higher toxicity was recorded in 30% of patients, with radiation pneumonitis being the most common toxicity (19%). A likely (n = 4) or possible (n = 8) treatment-related death was scored in 19% of patients. There was preexisting interstitial lung disease in eight patients (13%), with fatal toxicity developing in five of them (63%). Conclusions Lung SABR in tumors larger than 5 cm resulted in high local control rates and acceptable survival outcomes in a patient population with appreciable comorbidity. Patients with interstitial lung disease should be considered a very high-risk population for SABR.

Background: Volumetric-modulated arc therapy (VMAT) delivery for stereotactic ablative radiotherapy (SABR) of multiple lung tumors allows for faster treatments. We report on clinical outcomes and describe a general approach for treatment planning. Material and methods: Patients undergoing multi iso-center VMAT-based SABR for ≥2 lung lesions between 2009 and 2014 were identified from the VU University Medical Center and London Health Sciences Centre. Patients were eligible if the start date of the SABR treatment for the different lesions was within a time range of 30 days. SABR was delivered using separate iso-centers for lesions at a substantial distance from each other. Tumors were either treated with a single fraction of 34 Gy, or using three risk-adapted dose-fractionation schemes, namely three fractions of 18 Gy, five fractions of 11 Gy, or eight fractions of 7.5 Gy, depending on the tumor size and the location. Multivariable analysis was performed to assess factors predictive of clinical outcomes. Results: Of 84 patients (188 lesions) identified, 46% were treated for multiple metastases and 54% for multiple primary NSCLC. About 97% were treated for two or three lesions, and 56% had bilateral disease. After a median follow-up of 28 months, median overall survival (OS) for primary tumors was 27.6 months, and not reached for metastatic lesions (p = .028). Grade ≥3 toxicity was observed in 2% of patients. Multivariable analysis showed that grade 2 or higher radiation pneumonitis (n = 9) was best predicted by a total lung V35Gy of ≥6.5% (in 2Gy/fraction equivalent) (p = .007). Conclusion: Severe toxicity was uncommon following SABR using VMAT for up to three lung tumors. Further investigations of planning parameters are needed in patients presenting with more lesions.

Background and purpose Different planning protocols may define varying planning target volume (PTV) dose criteria. We investigated the hypothesis that this could result in differences in organ-at-risk (OAR) sparing. Material and methods Volumetric modulated arc therapy plans were created for ten locally advanced head and neck cancer patients following PTV criteria specified by the RTOG, EORTC and institutional (VUmc) protocols. Resulting plans were evaluated on the basis of the homogeneity index, calculated for the boost/elective PTVs as HIB/HIE = 100% * (D2% − D98%)/D50% and mean dose to individual and composite salivary (compsal) and swallowing (compswal) OARs. Results RTOG plans were the most homogeneous, with mean HIB of 8.2 ± 0.9%, compared to 9.5 ± 1.0%/11.6 ± 1.5% for the VUmc/EORTC plans. EORTC plans provided most OAR sparing, with compsal/compswal doses of 24.6 ± 7.7/22.9 ± 4.2 Gy, compared to 32.2 ± 9.7/29.9 ± 4.2 Gy and 28.4 ± 8.1/24.7 ± 5.3 Gy for RTOG and VUmc, respectively. EORTC provided 7.2/7.7 Gy mean dose reductions to the contra/ipsilateral parotid glands compared to RTOG. Conclusions Different planning protocols resulted in different levels of PTV dose homogeneity. We observed differences of up to ⩾7 Gy in composite and individual mean OAR doses. This could influence rates of toxicity and should be taken into account when comparing clinical studies. A consensus should be reached between major trial groups on appropriate PTV parameters.

Purpose To identify dosimetric factors that predict development of radiation pneumonitis (RP) following stereotactic or hypofractionated radiotherapy for lung tumors. Methods Seventy-nine consecutive patients with either a planning target volume (PTV)>100cm 3 ( n =69) or prior pneumonectomy or bi-lobectomy ( n =13) were identified. Radiation doses (range: 5–50Gy, with 5Gy increments) were converted to equivalent doses (EQD 2Gy ) ( α / β =3). Total lung (TL), ipsilateral (IL) and contralateral lung (CL) volumes minus PTV, receiving 5Gy (V5) up to 50Gy (V50) and mean lung dose (MLD) were analyzed. Predictors of grade ⩾3 RP (CTCAEv4.03) were identified with concordance-statistics (C-statistic) and p -values used to quantify the performance of the model. Factors found to be significant were entered into a recursive partitioning analysis (RPA). Results Median PTV was 150cm 3 . Grade ⩾3 RP was observed in 8 patients (10%). In univariable analysis, CL-MLD, CL-V5-15, TL-MLD, TL-V5-V10 and ITV size were predictive of RP ( p p =.007) and ITV ( p =.063) were the strongest predictors of grade ⩾3 RP, with excellent discrimination ( C -statistic: 0.868). Conclusion Contralateral MLD and ITV size are both strong predictors of grade ⩾3 RP post treatment. Planning constraints should aim to keep contralateral MLD below 3.6Gy.

Purpose On-line tumor matching for SABR lung setup requires margins for inaccuracies due to intra-fraction variability of breathing-averaged tumor position (BATP), and CBCT image guidance. We studied intra-fraction variability during SABR delivery using VMAT, corrected these for measurement inaccuracies and quantified the CBCT image-guidance uncertainties. Materials and Methods For 193 fractions in 38 patients positioned without immobilization devices, CBCT scans were acquired before and after 2 arcs of a RapidArc treatment. A hidden-marker test was performed to determine the accuracy of the CBCT system and an inter-observer test was performed to measure registration accuracy. Intra-fraction variability was calculated after correction for these components of variance, and the prediction interval for setup inaccuracies was determined. Results Correction for measurement inaccuracies reduced the intra-fraction variability of the BATP from 1.9 to1.6 mm in AP, from 1.7 to1.4 mm in SI and from 1.5 to1.1 mm in LR direction (1SD). Intra-fraction variability in bony anatomy after correction was ≤ 1 mm (1 SD). The 95% prediction interval to account for CBCT image-guidance uncertainties and intra-fraction variability was determined, and was found to be within our institutional PTV margins of 5mm. Conclusions Our findings show that it is essential to account for measurement and system inaccuracies when obtaining data for validating PTV margins from on-line CBCT image guidance. This article is protected by copyright. All rights reserved.

Stereotactic body radiotherapy (SBRT) often gives a high radiation dose in one or a few fractions to the planning target volume (PTV) and has been used to treat tumors at a variety of locations inc...

Purpose In large stage III lung tumors, planning delivery of doses exceeding 60 Gy can be challenging and time consuming. Intensity modulated radiation therapy (IMRT) can improve target coverage but may increase volumes receiving low-dose irradiation. We clinically implemented a novel hybrid IMRT (h-IMRT) technique that allowed plans to be produced quickly, and compared these plans with 4 other techniques. Methods and Materials h-IMRT was used to treat 14 consecutive patients with planning target volumes (PTVs) exceeding 500 cm 3 (average, 779 cm 3 ) with concurrent chemo-radiation therapy to 66 Gy. h-IMRT plans consisted of 2 components: an anterior-posterior/posterior-anterior/posterior-anterior (AP-PA-PA) oblique, open-field technique delivering an average dose of 58 Gy, plus a 3-field IMRT component optimized to achieve a final homogeneous dose of 66 Gy. Total lung V 20 and contralateral lung V 5 were kept as low as possible but preferably less than 35% and less than 50%, respectively. All plans were retrospectively replanned using a 5- to 9-field 3-dimensional conformal technique, full RapidArc, 6-field full IMRT, and a hybrid RapidArc (h-RapidArc) technique similar to the h-IMRT. Results The h-IMRT, h-RapidArc, and full RapidArc plans could be generated in less than 2 h, with the first 2 plans achieving the lowest V 5 (36%) and V 20 (30%) values together with the smallest hot spots. Both the 3-dimensional conformal and full IMRT plans occasionally led to unacceptable hot spots outside the PTV. Full RapidArc plans were fast and achieved comparable V 20 values but led to slightly higher V 5 values. Conclusions Both h-IMRT and h-RapidArc permitted delivery of 66 Gy to large stage III lung tumors, and both were superior to either full IMRT or RapidArc plans for reducing lung doses. The clinical significance of small increases in V 5 during chemo-radiation therapy delivery are unknown, but the present study suggests that h-IMRT and h-RapidArc are preferable for treatment of large tumors.

PURPOSE To investigate the impact of the calculation resolution of the anisotropic analytical algorithms (AAA) for a variety of small fields in homogeneous and heterogeneous media and for RapidArc plans. METHODS Dose distributions calculated using AAA version 8.6.15 (AAA8) and 10.0.25 (AAA10) were compared to measurements performed with GafChromic EBT film, using phantoms made of polystyrene or a combination of polystyrene and cork. The accuracy of the algorithms calculated using grid resolutions of 2.5 and 1.0 mm was investigated for different field sizes, and for a limited selection of RapidArc plans (head and neck, small meningioma, and lung). Additional plans were optimized to create excessive multileaf collimator modulation and measured on a homogenous phantom. Gamma evaluation criterion of 3% dose difference and 2- or 1-mm distance to agreement (DTA) were applied to evaluate the accuracy of the algorithms. RESULTS For fields < or = 3 x 3 cm2, both versions of AAA predicted lower peak doses and broader penumbra widths than the measurements. However, AAA10 and a finer calculation grid improved the agreement. For RapidArc plans with many small multileaf collimator (MLC) segments and relatively high number of monitor units (MU), AAA8 failed to identify small dose peaks within the target. Both versions performed better in polystyrene than in cork. In homogeneous cork layers, AAA8 underestimated the average target dose for a clinical lung plan. This was improved with AAA10 calculated using a 1 mm grid. CONCLUSIONS AAA10 improves the accuracy of dose calculations, and calculation grid of 1.0 mm is superior to using 2.5 mm, although calculation times increased by factor of 5. A suitable upper MU constraint should be assigned during optimization to avoid plans with high modulation. For plans with a relative high number of monitor units, calculations using 1 mm grid resolution are recommended. For planning target volume (PTV) which contains relatively large area of low density tissue, users should be aware of possible dose underestimation in the low density region and recalculation with AAA10 grid 1.0 mm is recommended.

Purpose Volumetric modulated arc therapy (RapidArc, Varian Medical Systems) permits the delivery of highly conformal dose distributions. We studied planning and delivery in patients who underwent RapidArc for locally advanced head-and-neck cancer (HNC). Methods and Materials A total of 35 consecutive patients who completed RapidArc with concurrent chemotherapy for Stages III-IV tumors of the oro- and hypopharynx/larynx in our center were identified. All underwent bilateral neck irradiation and 21 patients had at least N2 disease. A simultaneous integrated boost (SIB) delivered 70 Gy (in 2 Gy/fraction) to the planning target volume (PTV) boost and elective nodal regions (PTV elect ) received 57.75 Gy. A standard planning constraint set was used and constraints for parotid glands were individually adapted. Treatments were delivered using two arcs after all plans were verified in a solid water phantom using GafChromic External Beam Therapy films. Results RapidArc planning generally took 1.5–2 h, which was faster than with our previous seven-field intensity-modulated radiotherapy sliding window technique. Film dosimetry revealed that 0.6% of films exceeded a combination of dose differences ≥3% or distance to agreement ≥2 mm. More than 99% of both PTVs received ≥95% of the prescription dose. Average plan conformity index was 1.13 and mean dose to ipsilateral and contralateral parotid glands were 31.4 Gy and 26.1 Gy, respectively. The mean beam-on time was Conclusions RapidArc achieved excellent target coverage and normal tissue sparing, with delivery completed in less than 3 min. RA is currently our standard intensity-modulated radiotherapy approach for advanced HNC.

Purpose Radiologic lung density changes are observed in more than 50% of patients after stereotactic body radiotherapy (SBRT) for lung cancer. We studied the relationship between SBRT dose and posttreatment computed tomography (CT) density changes, a surrogate for lung injury. Methods and Materials The SBRT fractionation schemes used to treat Stage I lung cancer with RapidArc were three fractions of 18 Gy, five fractions of 11 Gy, or eight fractions of 7.5 Gy, prescribed at the 80% isodose. Follow-up CT scans performed at less than 6 months ( n = 50) and between 6 and 9 months ( n = 30) after SBRT were reviewed. Posttreatment scans were coregistered with baseline scans using a B-spline deformable registration algorithm. Voxel-Hounsfield unit histograms were created for doses between 0.5 and 50 Gy. Linear mixed effects models were used to assess the effects of SBRT dose on CT density, and the influence of possible confounders was tested. Results Increased CT density was associated with higher dose, increasing planning target volume size, and increasing time after SBRT (all p 6 Gy, were most prominent in areas receiving >20 Gy, and seemed to plateau above 40 Gy. In regions receiving >36 Gy, the reduction in air-filled fraction of lung after treatment was up to 18%. No increase in CT density was observed in the contralateral lung receiving ≥3 Gy. Conclusions A dose–response relationship exists for quantitative CT density changes after SBRT. A threshold of effect is seen at low doses, and a plateau at highest doses.

Purpose To determine the accuracy of frameless stereotactic radiosurgery using the BrainLAB ExacTrac system and robotic couch by measuring the individual contributions such as the accuracy of the imaging and couch correction system, the linkage between this system and the linac isocenter and the possible intrafraction motion of the patient in the frameless mask. Materials and methods An Alderson head phantom with hidden marker was randomly positioned 31 times. Automated 6D couch shifts were performed according to ExacTrac and the deviation with respect to the linac isocenter was measured using the hidden marker. ExacTrac-based set-up was performed for 46 patients undergoing hypofractionated stereotactic radiotherapy for 135 fractions, followed by verification X-rays. Forty-three of these patients received post-treatment X-ray verification for 79 fractions to determine the intrafraction motion. Results The hidden target test revealed a systematic error of 1.5 mm in one direction, which was corrected after replacement of the system calibration phantom. The accuracy of the ExacTrac positioning is approximately 0.3 mm in each direction, 1 standard deviation. The intrafraction motion was 0.35 ± 0.21 mm, maximum 1.15 mm. Conclusion Intrafraction motion in the BrainLAB frameless mask is very small. Users are strongly advised to perform an independent verification of the ExacTrac isocenter in order to avoid systematic deviations.

Volumetric modulated arc therapy (RapidArc) allows for fast delivery of stereotactic body radiotherapy (SBRT) delivery in stage I lung tumors. We compared dose distributions and delivery times between RapidArc and common delivery techniques in small tumors.In 18 patients who completed RapidArc SBRT for tumors measuring70 cm(3), new treatment plans were generated using non-coplanar 3D conformal fields (conf-SBRT) and dynamic conformal arc radiotherapy (DCA). For 9 patients with tumors adjacent to the chest wall, co-planar intensity-modulated radiotherapy (IMRT) plans were also generated. PTV dose coverage, organs at risk (OAR) doses and treatment delivery times were assessed.RapidArc plans achieved a superior conformity index (CI) and lower V(45 Gy) to chest wall (p0.05) compared to all other techniques. RapidArc led to a small increase in V(5 Gy) to contralateral lung compared to conf-SBRT (4.4±4% versus 1.2±1.8%, p=0.011). For other OAR, RapidArc and conf-SBRT plans were comparable, and both were superior to DCA plans. Delivery of a 7.5 Gy-fraction required 3.9 min (RapidArc), 11.6 min (conf-SBRT), and 12 min (IMRT).In stage I lung tumors measuring70 cm(3), RapidArc plans achieved both the highest dose conformity and shortest delivery times.

Purpose An internal target volume (ITV) is often used for incorporating tumor motion into radiotherapy planning but it overestimates the margins necessary for breathing motion. We describe a pragmatic approach using maximum- and minimum-intensity projections (MIP and Min-IP) only, for reducing ITVs in stereotactic radiotherapy by using dosimetric margins that compensate for motion-induced dose blurring. Patients and method We studied tumor motion characteristics from 26 repeat 4DCT scans derived from 10 patients. These were used to calculate the shift in cranio-caudal direction of the 80% isodose due to dose blurring of the time-averaged dose distribution caused by respiratory motion. The dosimetric margins necessary to compensate for dose blurring were calculated relative to the ITV, which can be determined efficiently using the MIP. Peak-to-peak motion amplitude was determined using the MIP and Min-IP. A programmable respiratory motion phantom was used to investigate imaging artifacts in determining the ITV for realistic motion patterns. Dose profiles were both calculated and measured in lung- and water-equivalent tissue. Results Using margins for the 80% dose level permitted the use of smaller target volumes relative to the use of ITV-based volumes, with (i) greater reductions seen at the end-inspiration edge than at expiration side due to asymmetric breathing motion patterns and (ii) a linear relationship seen with breathing amplitude. The average reduction of the ITV at a 95% confidence level is given by 0.2× A pp −1.3mm at expiration side, where A pp is the peak-to-peak breathing amplitude, and 0.3× A pp −2.2mm at inspiration side. Dosimetric margins did not differ significantly between water-equivalent and lung tissue for 80% isodose. Conclusion A simple margin recipe for breathing motion linear with breathing amplitude can be used to calculate the ITV reductions achievable for stereotactic radiotherapy of lung tumors.

Purpose Volumetric intensity-modulated arc therapy (RA) allows for rapid delivery of highly conformal dose distributions. In this study, planning and dosimetry of RA were compared with conventional intensity-modulated radiation therapy (IMRT) plans of head-and-neck cancer patients. Materials and Methods Computed tomography scans of 12 patients who had completed IMRT for advanced tumors of the naso-, oro- and hypopharynx were replanned using RA using either one or two arcs. Calculated doses to planning target volume (PTV) and organs at risk (OAR) were compared between IMRT and RA plans. Dose distributions for single arc ( n = 8) and double arc ( n = 4) plans were verified using film dosimetry in three to five coronal planes using a quality assurance phantom. Results RA plans allowed for a mean reduction in number of monitor units (MU) by nearly 60%, relative to seven field sliding window IMRT plans. RA plans achieved similar sparing of all OAR as IMRT. Double arc RA provided the best dose homogeneity to PTV with a lower standard deviation of PTV dose (1.4 Gy), vs. single arc plans (2.0 Gy) and IMRT (1.7 Gy). Film measurements showed good correspondence with calculated doses; the mean gamma value was 0.30 (double arc) and area of the film with a gamma exceeding 1 was 0.82%. Conclusions RA is a fast, safe, and accurate technique that uses lower MUs than conventional IMRT. Double arc plans provided at least similar sparing of OAR and better PTV dose homogeneity than single arc or IMRT.

Purpose: Proton radiotherapy for head-and-neck cancer (HNC) aims to improve organ-at-risk (OAR) sparing over photon radiotherapy. However, it may be less robust for setup and range uncertainties. The authors investigated OAR sparing and plan robustness for spot-scanning proton planning techniques and compared these with volumetric modulated arc therapy (VMAT) photon plans. Methods: Ten HNC patients were replanned using two arc VMAT (RapidArc) and spot-scanning proton techniques. OARs to be spared included the contra- and ipsilateral parotid and submandibular glands and individual swallowing muscles. Proton plans were made using Multifield Optimization (MFO, using three, five, and seven fields) and Single-field Optimization (SFO, using three fields). OAR sparing was evaluated using mean dose to composite salivary glands (CompSal) and composite swallowing muscles (CompSwal). Plan robustness was determined for setup and range uncertainties (±3 mm for setup, ±3% HU) evaluating V95% and V107% for clinical target volumes. Results: Averaged over all patients CompSal/CompSwal mean doses were lower for the three-field MFO plans (14.6/16.4 Gy) compared to the three-field SFO plans (20.0/23.7 Gy) and VMAT plans (23.0/25.3 Gy). Using more than three fields resulted in differences in OAR sparing of less than 1.5 Gy between plans. SFO plans were significantly more robust than MFO plans. VMAT plans were the most robust. Conclusions: MFO plans had improved OAR sparing but were less robust than SFO and VMAT plans, while SFO plans were more robust than MFO plans but resulted in less OAR sparing. Robustness of the MFO plans did not increase with more fields.

Purpose Automated and knowledge-based planning techniques aim to reduce variations in plan quality. RapidPlan uses a library consisting of different patient plans to make a model that can predict achievable dose-volume histograms (DVHs) for new patients and uses those models for setting optimization objectives. We benchmarked RapidPlan versus clinical plans for 2 patient groups, using 3 different libraries. Methods and Materials Volumetric modulated arc therapy plans of 60 recent head and neck cancer patients that included sparing of the salivary glands, swallowing muscles, and oral cavity were evenly divided between 2 models, Model 30A and Model 30B , and were combined in a third model, Model 60 . Knowledge-based plans were created for 2 evaluation groups: evaluation group 1 (EG1), consisting of 15 recent patients, and evaluation group 2 (EG2), consisting of 15 older patients in whom only the salivary glands were spared. RapidPlan results were compared with clinical plans (CP) for boost and/or elective planning target volume homogeneity index, using HI B /HI E = 100 × (D2% − D98%)/D50%, and mean dose to composite salivary glands, swallowing muscles, and oral cavity (D sal , D swal , and D oc , respectively). Results For EG1, RapidPlan improved HI B and HI E values compared with CP by 1.0% to 1.3% and 1.0% to 0.6%, respectively. Comparable D sal and D swal values were seen in Model 30A , Model 30B , and Model 60 , decreasing by an average of 0.1, 1.0, and 0.8 Gy and 4.8, 3.7, and 4.4 Gy, respectively. However, differences were noted between individual organs at risk (OARs), with Model 30B increasing D oc by 0.1, 3.2, and 2.8 Gy compared with CP, Model 30A , and Model 60 . Plan quality was less consistent when the patient was flagged as an outlier. For EG2, RapidPlan decreased D sal by 4.1 to 4.9 Gy on average, whereas HI B and HI E decreased by 1.1% to 1.5% and 2.3% to 1.9%, respectively. Conclusions RapidPlan knowledge-based treatment plans were comparable to CP if the patient's OAR-planning target volume geometry was within the range of those included in the models. EG2 results showed that a model including swallowing-muscle and oral-cavity sparing can be applied to patients with only salivary gland sparing. This may allow model library sharing between institutes. Optimal detection of inadequate plans and population of model libraries requires further investigation.

Background and purpose Central lung SABR is less established due to toxicity concerns. We describe plan quality and clinical outcomes for patients treated with VMAT SABR using 8×7.5Gy. Materials and methods We studied 80 consecutive patients with primary NSCLC and PTV ⩽2cm from the proximal bronchial tree (PBT), treated between 2008 and 2013. Dosimetric data were compared with institutional guidelines and study protocols, and long-term clinical outcomes were analyzed. Results PTV V 95% was 60Gy in 96% of patients. Dmax was ⩾60Gy in 40% of patients for PBT, 26.3% for aorta, 55% for heart, and 1.3% for trachea. Esophageal maximum Dmax was 58Gy. Mean lung V 5Gy / V 20Gy was 21/8%. 54 patients (68%) exceeded RTOG0813 Dmax for ⩾1 organ-at-risk (OAR), with 27 exceeding PBT Dmax. 5 of 78 patients (6.4%) with adequate follow-up information had grade 3 toxicity. Grade 4 toxicity was not observed. Treatment-related death was considered possible ( n =3) or likely ( n =3) in 6 patients (7.5%). With median follow-up of 47months, 3-year survival was 53%, compared with 57% for 252 peripheral tumors treated with 3/5-fractions SABR in the same period ( p =0.369). Conclusions Although a substantial proportion of central SABR patients received ⩾60Gy to OARs, the 3-year survival was no different from peripheral SABR.

Spine stereotactic radiotherapy (SBRT) requires intrafraction motion1-2mm. We evaluated the accuracy and precision of digital tomosynthesis (DTS) in combination with triangulation for spine position tracking.Single-slice DTS images were generated from kV cone beam CT (CBCT) projection images. They were registered to reference DTS images reconstructed from the planning CT-scan to determine 2D shifts between actual patient position and treatment plan position. 3D spine position was obtained by triangulation of each registration with a previous registration, for every 1° of data. For 7 patients who underwent spine SBRT, the standard deviation (SD) of DTS+triangulation over one entire dataset was evaluated for different DTS angles (2-16°) and triangulation angles (1-46°). For 32 CBCT datasets, acquired before or after treatment of the 7 patients, using 4° DTS and 18° triangulation angle, SDs were determined and average positions were compared to clinically performed CBCT registrations.Mean SDs were 0.29±0.10mm for lateral (range 0.1-0.55mm), 0.14±0.08 for longitudinal (0.05-0.39) and 0.24±0.10 for the vertical direction (0.10-0.57). Lateral and vertical SDs for thoracic spine were higher than for lumbar spine. Differences between clinical CBCT registration and DTS+triangulation were 0.1±0.26, 0.02±0.33 and -0.07±0.21mm.The combination of DTS and triangulation allows for monitoring spine position with sub-mm accuracy and precision.

To the Editor, Intensity-modulated radiation therapy (IMRT) is particularly useful for treating irregularly shaped planning target volumes (PTVs) whilst minimizing doses to organs at risk (OARs). V...

Purpose: Gamma-ray spectroscopic scans to measure boron concentrations in the irradiated volume were performed during treatment of 5 patients suffering from brain tumors with boron neutron capture therapy (BNCT). In BNCT, the dose that is meant to be targeted primarily to the tumor is the dose coming from the reaction 10 B(n,α) 7 Li, which is determined by the boron concentration in tissue and the thermal neutron fluence rate. The boron distribution throughout the head of the patient during the treatment is therefore of major interest. The detection of the boron distribution during the irradiation was until now not possible. Methods and Materials: Five patients suffering from glioblastoma multiforme and treated with BNCT in a dose escalation study were administered the boron compound, boron sulfhydryl (BSH; Na 2 B 12 H 11 SH). Boron concentrations were reconstructed from measurements performed with the gamma-ray telescope which detects locally the specific gamma rays produced by neutron capture in 10 B and 1 H. Results: For all patients, at a 10 B concentration in blood of 30 ppm, the boron concentration in nonoperated areas of the brain was very low, between 1 and 2.5 ppm. In the target volume, which included the area where the tumor had been removed and where remaining tumor cells have to be assumed, much higher boron concentrations were measured with large variations from one patient to another. Superficial tissue contained a higher concentration of 10 B than the nonoperated areas of the brain, ranging between 8 and 15 ppm. Conclusions: The measured results correspond with previous tissue uptake studies, confirming that normal brain tissue hardly absorbs the boron compound BSH. Gamma-ray telescope measurements seem to be a promising method to provide information on the biodistribution of boron during therapy. Furthermore, it also opens the possibility of in vivo dosimetry.

Purpose Use of stereotactic ablative radiation therapy (SABR) for subcentimeter lung tumors is controversial. We report our outcomes for tumors with diameter ≤1 cm and their visibility on cone beam computed tomography (CBCT) scans and retrospectively evaluate the planned dose using a deterministic dose calculation algorithm (Acuros XB [AXB]). Methods and Materials We identified subcentimeter tumors from our institutional SABR database. Tumor size was remeasured on an artifact-free phase of the planning 4-dimensional (4D)-CT. Clinical plan doses were generated using either a pencil beam convolution or an anisotropic analytic algorithm (AAA). All AAA plans were recalculated using AXB, and differences among D95 and mean dose for internal target volume (ITV) and planning target volume (PTV) on the average intensity CT dataset, as well as for gross tumor volume (GTV) on the end respiratory phases were reported. For all AAA patients, CBCT scans acquired during each treatment fraction were evaluated for target visibility. Progression-free and overall survival rates were calculated using the Kaplan-Meier method. Results Thirty-five patients with 37 subcentimeter tumors were eligible for analysis. For the 22 AAA plans recalculated using AXB, Mean D95 ± SD values were 2.2 ± 4.4% (ITV) and 2.5 ± 4.8% (PTV) lower using AXB; whereas mean doses were 2.9 ± 4.9% (ITV) and 3.7 ± 5.1% (PTV) lower. Calculated AXB doses were significantly lower in one patient (difference in mean ITV and PTV doses, as well as in mean ITV and PTV D95 ranged from 22%-24%). However, the end respiratory phase GTV received at least 95% of the prescription dose. Review of 92 CBCT scans from all AAA patients revealed that the tumor was visualized in 82 images, and its position could be inferred in other images. The 2-year local progression-free survival was 100%. Conclusions Patients with subcentimeter lung tumors are good candidates for SABR, given the dosimetry, ability to localize tumors with image guidance, and excellent local control.

The delivery of high dose conventional stereotactic body radiotherapy (SBRT) for patients with stage I lung tumors generally takes 30–45 min per fraction. The novel volumetric intensity-modulated arc therapy (RA) for planning and delivery enabled much faster treatment for three patients with different fractionation schemes. This reduces the risk of intrafraction motion and is more patient friendly. In addition, in comparison to the conventional plans using 10 static non-coplanar fields, RA plans achieved superior dose conformity around the PTV and reduced chest wall doses.

Monitoring the stability of patient position is essential during high-precision radiotherapy such as spine stereotactic body radiotherapy (SBRT). We evaluated the combination of digital tomosynthesis (DTS) and triangulation for spine position detection, using non-clinical DTS software and an anthropomorphic pelvic phantom that includes a bone-like spine structure. Kilovoltage cone beam CT projection images over 2-16° gantry rotation were used to generate single slice DTS images. Each DTS slice was registered to a digitally reconstructed DTS derived from the planning CT scan to determine 2D shifts between actual phantom and treatment plan position. Two or more DTS registrations, central axes 4-22° apart, were triangulated to determine the 3D phantom position. Using sequentially generated DTS images, the phantom position can be updated every degree with a small latency of DTS and triangulation angle. The precision of position determination was investigated as function of DTS and triangulation angle. To mimic the scenario of spine SBRT, the effect on the standard deviation of megavoltage radiation delivery during kV image acquisition was tested. In addition, the ability of the system to detect different types of movement was investigated for a variety of small sudden and gradual movements during kV image acquisition.

Investigation of clonogenic cell survival and cell proliferation following single dose and fractionated delivery of high dose rate flattening filter free (FFF) irradiation compared to conventional dose rates.The human astrocytoma D384, glioma T98 and lung carcinoma SW1573 cell lines were irradiated using either a single dose (0-12 Gy) or a fractionated protocol of 5 daily fractions of 2 Gy (D384) or 3 Gy (SW1573). Cells were irradiated inside a phantom using fixed gantry beams of a linear accelerator. A sliding window technique created homogeneous dose distributions over the surface of the cell cultures. Irradiations using standard beams (6 MV, 600 MU/min.) and high dose rate FFF beams (10 MV, 2400 MU/min.) were compared. Cell survival was determined by clonogenic assay. In the fractionated irradiation set-up, the number of clonogenic cells was estimated by including tumor cell proliferation during the overall treatment time in the analysis.All cell lines showed equal cell survival following irradiation using either the FFF beams or conventional flattened (FF) beams. This was observed after single dose exposure (0-12 Gy) as well as after fractionated irradiation (p = 0.08 for D384 and 0.20 for SW1373 cell lines).FFF irradiation with a dose rate of 2400 MU/min and four times higher dose per pulse compared to irradiation with FF beams did not change cell survival for three human cancer cell lines up to a fraction dose of 12 Gy compared to irradiation using FF beams.

Purpose Flattening filter free (FFF) beams offer the potential for a higher dose rate, shorter treatment time, and lower peripheral dose. To investigate their role in large-field treatments, this study compared flattened and FFF beams for breast irradiation. Methods and Materials Ten left breast clinical plans comprising 2 tangential beams and a medially located 3-field simultaneous integrated boost (SIB) were replanned. Full intensity modulated radiotherapy (IMRT), hybrid IMRT, electronic tissue compensator (ETC), and multiple static field treatment plans were created for the elective breast volume using flattened and FFF beams, in combination with a 3-field IMRT SIB. Plan quality was assessed and delivery times were measured for all plans for 1 patient. Out-of-field doses were measured using an ionization chamber for an IMRT plan optimized on a corner of simple cubic phantom for both flattened and FFF beams. Results For each technique, mean target volume metrics (planning target volume coverage, homogeneity, conformity) were typically within 3% for flattened and FFF beams. Larger mean differences in boost conformity favoring flattened hybrid (7.2%) and full IMRT (5.5%) plans may have reflected limitations in plan normalization. Calculated heart and ipsilateral lung doses were comparable; however, both flattened and FFF low-dose phantom measurements were substantially higher than calculated values, rendering the comparison of low dose in the contralateral breast uncertain. Beam delivery times were on average 31% less for FFF. Conclusions In general, target volume metrics for flattened and FFF plans were comparable. The planning system did not seem to allow for accurate peripheral dose evaluation. FFF was associated with a potentially shorter treatment time. All 4 IMRT techniques allowed FFF beams to generate acceptable plans for breast IMRT.

We investigated the dosimetric impact of the interplay effect during RapidArc stereotactic body radiation therapy for lung tumors using flattening filter-free (FFF) beams with different dose rates.Seven tumors with motion ≤20 mm, treated with 10-MV FFF RapidArc, were analyzed. A programmable phantom with sinusoidal longitudinal motion (30-mm diameter "tumor" insert; period = 5 s; individualized amplitude from planning 4-dimensional computed tomography) was used for dynamic dose measurements. Measurements were made with GafChromic EBT III films. Plans delivered the prescribed dose to 95% of the planning target volume, created by a 5-mm expansion of the internal target volume. They comprised 2 arcs and maximum dose rates of 400 and 2400 MU/min. For 2400 MU/min plans, measurements were repeated at 3 different initial breathing phases to model interplay over 2 to 3 fractions. For 3 cases, 2 extra plans were created using 1 full rotational arc (with contralateral lung avoidance sector) and 1 partial arc of 224° to 244°. Dynamic and convolved static measurements were compared by use of gamma analysis of 3% dose difference and 1 mm distance-to-agreement.For 2-arc 2400 MU/min plans, maximum dose deviation of 9.4% was found in a single arc; 7.4% for 2 arcs (single fraction) and5% and 3% when measurements made at 2 and 3 different initial breathing phases were combined, simulating 2 or 3 fractions. For all 7 cases,99% of the area within the region of interest passed the gamma criteria when all 3 measurements with different initial phases were combined. Single-fraction single-arc plans showed higher dose deviations, which diminished when dose distributions were summed over 2 fractions. All 400 MU/min plans showed good agreement in a single fraction measurement.Under phantom conditions, single-arc and single-fraction 2400 MU/min FFF RapidArc lung stereotactic body radiation therapy is susceptible to interplay. Two arcs and ≥2 fractions reduced the effect to a level that appeared unlikely to be clinically significant.

Purpose To study the dosimetric impact of relatively short-duration intrafraction shifts during a single fraction of RapidArc delivery for vertebral stereotactic body radiation therapy (SBRT) using flattened (FF) and flattening filter-free (FFF) beams. Methods and Materials The RapidArc plans, each with 2 to 3 arcs, were generated for 9 patients using 6-MV FF and 10-MV FFF beams with maximum dose rates of 1000 and 2400 MU/min, respectively. A total of 1272 plans were created to estimate the dosimetric consequences in target and spinal cord volumes caused by intrafraction shifts during one of the arcs. Shifts of 1, 2, and 3 mm for periods of 5, 10, and 30 seconds, and 5 mm for 5 and 10 seconds, were modelled during a part of the arc associated with high doses and steep dose gradients. Results For FFF plans, shifts of 2 mm over 10 seconds and 30 seconds could increase spinal cord D max by up to 6.5% and 13%, respectively. Dosimetric deviations in FFF plans were approximately 2-fold greater than in FF plans. Reduction in target coverage was Conclusion Even short-duration intrafraction shifts can cause significant dosimetric deviations during vertebral SBRT delivery, especially when using very high dose rate FFF beams and when the shift occurs in that part of the arc delivering high doses and steep gradients. The impact is greatest on the spinal cord and its planning-at-risk volume. Accurate and stable patient positioning is therefore required for vertebral SBRT.

Purpose Flattening filter–free (FFF) beams with higher dose rates and faster delivery are now clinically available. The purpose of this planning study was to compare optimized non-FFF and FFF RapidArc plans for stereotactic body radiotherapy (SBRT) and to validate the accuracy of fast arc delivery. Methods and Material Ten patients with peripheral lung tumors and 10 with vertebral metastases were planned using RapidArc with a flattened 6-MV photon beam and a 10-MV FFF beam for fraction doses of 7.5–18 Gy. Dosimetry of the target and organs at risk (OAR), number of monitor units (MU), and beam delivery times were assessed. GafChromic EBT2 film measurements of FFF plans were performed to compare calculated and delivered dose distributions. Results No major dosimetric differences were seen between the two delivery techniques. For lung SBRT plans, conformity indices and OAR doses were similar, although the average MU required were higher with FFF plans. For vertebral SBRT, FFF plans provided comparable PTV coverage, with no significant differences in OAR doses. Average beam delivery times were reduced by a factor of up to 2.5, with all FFF fractions deliverable within 4 min. Measured FFF plans showed high agreement with calculated plans, with more than 99% of the area within the region of interest fulfilling the acceptance criterion. Conclusion The higher dose rate of FFF RapidArc reduces delivery times significantly, without compromising plan quality or accuracy of dose delivery.

Background and purpose Intra-fraction patient motion is incompletely understood and the optimum amount of support or immobilization during stereotactic body radiotherapy (SBRT) is unclear. Rigid immobilization is often advocated, but motion still occurs. In contrast, we deliver the vast majority of SBRT using simple supporting devices, simultaneously emphasizing comfort, frequent position checks and progressive reduction in treatment times. We report spine stability during lung SBRT. Materials and methods Patients lie on a thin mattress with arms supported above their head and below-knee support. Stereoscopic spine X-rays before and after fraction delivery identified motion in three translational and three rotational directions. Results Images from 109 fractions in 30 patients resulted in 327 translational and 327 rotational pre- and post-fraction comparisons. Mean RapidArc® delivery time for variable fraction dose was 4.2 min (SD = 1.4). 92% and 97% of translational and rotational differences were ⩽1 mm and ⩽1° in any direction and 98% of translational differences were ⩽1.5 mm. Mean vertical, longitudinal and lateral motion was 0 mm (SD = 0.4), 0 mm (0.6) and 0 mm (0.6). 84% and 94% of the 109 fractions were delivered with ⩽1 and ⩽1.5 mm translation in all three directions and 93% with ⩽1° of rotation. Two patients accounted for 10/17 fractions with >1 mm translational motion. Conclusions Based on pre and post-fraction X-ray imaging during fast lung SBRT, simple support devices can result in spine stability that is comparable to that reported with rigid external immobilization.

Background Salivary gland function decreases after radiation doses of 39 Gy or higher. Currently, submandibular glands are not routinely spared. We implemented a technique for sparing contralateral submandibular glands (CLSM) during contralateral elective neck irradiation without compromising PTV coverage. Methods Volumetric modulated arc therapy (RapidArc™) plans were applied in 31 patients with stage II-IV HNC without contralateral neck metastases, all of whom received elective treatment to contralateral nodal levels II-IV. Group 1 consisted of 21 patients undergoing concurrent chemo-radiotherapy, with elective nodal doses of 57.75 Gy (PTVelect) and 70 Gy to tumor and pathological nodes (PTVboost) in 7 weeks. Group 2 consisted of 10 patients treated with radiotherapy to 54.45 Gy to PTVelect and 70 Gy to PTVboost in 6 weeks. All clinical plans spared the CLSM using individually adapted constraints. For each patient, a second plan was retrospectively generated without CLSM constraints ('non-sparing plan'). Results PTV coverage was similar for both plans, with 98.7% of PTVelect and 99.2% of PTVboost receiving ≥95% of the prescription dose. The mean CLSM dose in group 1 was 33.2 Gy for clinical plans, versus 50.6 Gy in 'non-sparing plans' (p < 0.001). In group 2, mean CLSM dose was 34.4 Gy for clinical plans, and 46.8 Gy for non-sparing plans (p = 0.002). Conclusions Elective radiotherapy to contralateral nodal levels II-IV using RapidArc consistently limited CLSM doses well below 39 Gy, without compromising PTV-coverage. Future studies will reveal if this extent of dose reduction can reduce patient symptoms.

Background and purpose Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiation therapy (SBRT). As target geometry is complex, we compared SBRT plans using volumetric modulated arc radiotherapy (RapidArc®, RA) and conventional intensity-modulated radiotherapy (IMRT). Materials and methods RA and IMRT plans to deliver a fraction of 16Gy to at least 90% of planning target volume (PTV) were compared for PTV coverage, normal organ sparing and estimated delivery times. Group 1 consisted of PTVs to only vertebral body ( n =3), while group 2 had PTVs encompassing the entire vertebra ( n =4). Finally, RA delivery parameters in four patients were assessed. Results Both techniques delivered 16Gy to a mean of 95% and 85% of the PTV in groups 1 and 2, respectively. Spinal cord sparing was comparable; mean V 10-partial cord for RA and IMRT in group 1 was 3.6%, and was 9.4% versus 11.5%, respectively, in group 2. Estimated mean treatment times for RA with 2–3 arcs and IMRT were comparable. Clinical RA beam-on times ranged from 11 to 15.4min. Conclusions Both RA and conventional IMRT plans deliver high quality vertebral SBRT, but plan quality was poorer when the PTV consisted of the entire vertebra.

Purpose Volumetric modulated arc therapy (RapidArc; Varian Medical Systems, Palo Alto, CA) allows fast delivery of stereotactic radiotherapy for Stage I lung tumors. We investigated discrepancies between the calculated and delivered dose distributions, as well as the dosimetric impact of leaf interplay with breathing-induced tumor motion. Methods and Materials In 20 consecutive patients with Stage I lung cancer who completed RapidArc delivery, 15 had tumor motion exceeding 5 mm on four-dimensional computed tomography scan. Static and dynamic measurements were performed with Gafchromic EBT film (International Specialty Products Inc., Wayne, NJ) in a Quasar motion phantom (Modus Medical Devices, London, Ontario, Canada). Static measurements were compared with calculated dose distributions, and dynamic measurements were compared with the convolution of static measurements with sinusoidal motion patterns. Besides clinical treatment plans, additional cases were optimized to create excessive multileaf collimator modulation and delivered on the phantom with peak-to-peak motions of up to 25 mm. γ Analysis with a 3% dose difference and 2- or 1-mm distance to agreement was used to evaluate the accuracy of delivery and the dosimetric impact of the interplay effect. Results In static mode film dosimetry of the two-arc delivery in the phantom showed that, on average, fewer than 3% of measurements had γ greater than 1. Dynamic measurements of clinical plans showed a high degree of agreement with the convolutions: for double-arc plans, 99.5% met the γ criterion. The degree of agreement was 98.5% for the plans with excessive multileaf collimator modulations and 25 mm of motion. Conclusions Film dosimetry shows that RapidArc accurately delivers the calculated dose distribution and that interplay between leaves and tumor motion is not significant for single-fraction treatments when RapidArc is delivered with two different arcs.