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• Small improvements by adding iterations do not outweigh longer optimization time. • Dose restoration results depend critically on the prior treatment plan. • Adapted plans may be improved by advanced tuning of optimization parameters. • Only a small number of new spots is needed to yield adequate target coverage. Intensity-modulated proton therapy is highly sensitive to anatomical variations. A dose restoration method and a full plan adaptation method have been developed earlier, both requiring several parameter settings. This study evaluates the validity of the previously selected settings by systematically comparing them to alternatives. The dose restoration method takes a prior plan and uses an energy-adaptation followed by a spot-intensity re-optimization to restore the plan to its initial state. The full adaptation method uses an energy-adaptation followed by the addition of new spots and a spot-intensity optimization to fit the new anatomy. We varied: 1) The margins and robustness settings of the prior plan, 2) the spot-addition sample size, i.e. the number of added spots, 3) the spot-addition stopping criterion, and 4) the spot-intensity optimization approach. The last three were evaluated only for the full plan adaptation. Evaluations were done on 88 CT scans of 11 prostate cancer patients. Dose was prescribed as 55 Gy(RBE) to the lymph nodes and seminal vesicles with a boost to 74 Gy(RBE) to the prostate. For the dose restoration method, changing the applied CTV-to-PTV margins and plan robustness in the prior plans yielded insufficient target coverage or increased OAR doses. For the full plan adaptation, more spot-addition iterations and using a different optimization approach resulted in lower OAR doses compared to the default settings while maintaining target coverage. However, the calculation times increased by up to 20 times, making these variations infeasible for online-adaptation. We recommend maintaining the default setting for the dose restoration approach. For the full plan adaptation we recommend to focus on fine-tuning the optimization-parameters, and apart from this using the default settings. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) for lung tumours has been gaining wide acceptance in lung cancer. Here, we review the technological evolution of SBRT delivery in lung cancer, from the first treatments using the stereotactic body frame in the 1990’s to modern developments in image guidance and motion management. Finally, we discuss the impact of current technological approaches on the requirements for quality assurance as well as future technological developments. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To quantify the impact of uncorrected or partially corrected pelvis rotation and spine bending on region-specific residual setup errors in prone-treated cervical cancer patients. Methods and materials: Fifteen patients received an in-room CBCT scan twice a week. CBCT scans were registered to the planning CT-scan using a pelvic clip box and considering both translations and rotations. For daily correction of the detected translational pelvis setup errors by couch shifts, residual setup errors were determined for L5, L4 and seven other points of interest (POIs). The same was done for a procedure with translational corrections and limited rotational correction (±3°) by a 6D positioning device. Results: With translational correction only, residual setup errors were large especially for L5/L4 in AP direction (Σ =5.1/5.5mm). For the 7 POIs the residual setup errors ranged from 1.8 to 5.6mm (AP). Using the 6D positioning device, the errors were substantially smaller (for L5/L4 in AP direction Σ =2.7/2.2mm). Using this device, the percentage of fractions with a residual AP displacement for L4>5mm reduced from 47% to 9%. Conclusions: Setup variations caused by pelvis rotations are large and cannot be ignored in prone treatment of cervical cancer patients. Corrections with a 6D positioning device may considerably reduce resulting setup errors, but the residual setup errors should still be accounted for by appropriate CTV-to-PTV margins. [Copyright &y& Elsevier]

Purpose: Compared with many small circular beams used in CyberKnife treatments, beam’s eye view-shaped fields are generally more time-efficient for dose delivery. However, beam’s eye view-shaping devices, such as a mini-multileaf collimator (mMLC), are not presently available for CyberKnife, although a variable-aperture collimator (Iris, 12 field diameters; 5–60 mm) is available. We investigated whether the Iris can mimic noncoplanar mMLC treatments using a limited set of principal beam orientations (nodes) to produce time-efficient treatment plans. Methods and Materials: The data from 10 lung cancer patients and the beam-orientation optimization algorithm “Cycle” were used to generate stereotactic treatment plans (3 × 20 Gy) for a CyberKnife virtually equipped with a mMLC. Typically, 10–16 favorable beam orientations were selected from 117 available robot node positions using beam’s eye view-shaped fields with uniform fluence. Second, intensity-modulated Iris plans were generated by inverse optimization of nonisocentric circular candidate beams targeted from the same nodes selected in the mMLC plans. The plans were evaluated using the mean lung dose, lung volume receiving ≥20 Gy, conformality index, number of nodes, beams, and monitor units, and estimated treatment time. Results: The mMLC plans contained an average of 12 nodes and 11,690 monitor units. For a comparable mean lung dose, the Iris plans contained 12 nodes, 64 beams, and 21,990 monitor units. The estimated fraction duration was 12.2 min (range, 10.8–13.5) for the mMLC plans and 18.4 min (range, 12.9–28.5) for the Iris plans. In contrast to the mMLC plans, the treatment time for the Iris plans increased with an increasing target volume. The Iris plans were, on average, 40% longer than the corresponding mMLC plans for small targets (<80 cm3) and ≤121% longer for larger targets. For a comparable conformality index, similar results were obtained. Conclusion: For stereotactic lung irradiation, time-efficient and high-quality plans were obtained for robotic-controlled noncoplanar treatments using a mMLC. Iris is a time-efficient alternative for small targets, with similar or better plan quality. [Copyright &y& Elsevier]

Purpose: To develop and evaluate a method for adding dose distributions of combined external beam radiotherapy (EBRT) and brachytherapy (BT) for oropharyngeal patients. Methods and Materials: Two computed tomography (CT) scans were used for 5 patients: the EBRT CT, used for EBRT planning, and the BT CT, acquired after catheter implantation. For each scan, the salivary glands and the chewing and swallowing muscles were contoured, and a dose distribution was calculated. A nonrigid transformation was obtained by registering the organs’ surfaces. Then the BT dose distribution was mapped onto the EBRT dose distribution by applying the transformation obtained. To account for differences in fractionation, the physical doses were converted to equivalent dose in 2 Gy (EQD 2), and the total dose was found by adding dose voxel by voxel. The robustness of the dose addition was investigated by varying delineations and input parameters of the registration method and by varying the α/β parameter for EQD 2. The effect of the perturbations was quantified using dose–volume histograms (DVH) and gamma analyses (distance-to-agreement/dose-difference = 1 mm/1 Gy). Results: The variations in input parameters and delineations caused only small perturbations in the DVH of the added dose distributions. For most organs the gamma index was low, and it was moderately elevated for organs lying in areas with a steep gradient (median gamma index ≤2.3 for constrictor muscles, ≤0.7 for all other organs). Conclusions: The presented method allows adding dose distributions of combined EBRT and BT for oropharyngeal patients. In general, the method is reliable and robust with respect to uncertainties in organ delineation, perturbations in input parameters of the method, and α/β values. [ABSTRACT FROM AUTHOR]

Abstract: Background and Purpose: To design and evaluate a 3D patient-specific model to predict the cervix–uterus shape and position. Methods and Materials: For 13 patients lying in prone position, 10 variable bladder filling CT-scans were acquired, 5 at planning and 5 after 40Gy. The delineated cervix–uterus volumes in 2–5 pre-treatment CT-scans were used to generate patient-specific models that predict the cervix–uterus geometry by bladder volume. Model predictions were compared to delineations, excluding those used for model construction. The prediction error was quantified by the margin required around the predicted volumes to accommodate 95% of the delineated volume and by the predicted-to-delineated surface distance. Results: The prediction margin was significantly smaller (average 50%) than the margin encompassing the cervix–uterus motion. The prediction margin could be decreased (from 7 to 5mm at planning and from 10 to 8mm after 40Gy) by increasing (from 2 to 5) the number of CT-scans used for the model construction. Conclusion: For most patients, even with a model based on only two CT-scans, the prediction error was well below the margin encompassing the cervix–uterus motion. The described approach could be used to create prior to treatment, an individualized treatment strategy. [Copyright &y& Elsevier]

Abstract: Purpose: To investigate application of pre-treatment established correlations between bladder-filling changes and cervix–uterus displacements in adaptive therapy. Materials and methods: Thirteen cervical cancer patients participated in this prospective study. Pre-treatment, and after delivery of 40Gy, a full bladder CT-scan was acquired, followed by voiding the bladder and acquisition of 4 other 3D scans in a 1h period with a naturally filling bladder (variable bladder filling CT-scans, VBF-scans). For the pre-treatment VBF-scans, linear correlations between bladder volume change and displacements of the tip of the uterus (ToU) and the center of mass (CoM) of markers implanted in the fornices of the vagina relative to the full bladder planning scan were established. Prediction accuracy of these correlation models was assessed by comparison with actual displacements in CT-scans, both pre-treatment and after 40Gy. Inter-fraction ToU and marker-CoM displacements were derived from the established correlations and twice-weekly performed in-room bladder volume measurements, using a 3D ultrasound scanner. Results: Target displacement in VBF-scans ranged from up to 65mm in a single direction to almost 0mm, depending on the patient. For pre-treatment VBF-scans, the linear correlation models predicted the mean 3D position change for the ToU of 26.1mm±10.8 with a residual of only 2.2mm±1.7. For the marker-CoM, the 8.4mm±5.3 mean positioning error was predicted with a residual of 0.9mm±0.7. After 40Gy, the mean ToU displacement was 26.8mm±15.8, while prediction based on the pre-treatment correlation models yielded a mean residual error of 9.0mm±3.7. Target positioning errors in the fractioned treatments were very large, especially for the ToU (−18.5mm±11.2 for systematic errors in SI-direction). Conclusions: Pre-treatment acquired VBF-scans may be used to substantially enhance treatment precision of cervical cancer patients. Application in adaptive therapy is promising and warrants further investigation. For highly conformal (IMRT) treatments, the use of a full bladder drinking protocol results in unacceptably large systematic set-up errors. [Copyright &y& Elsevier]

Abstract: Purpose: To provide a prescription dose for Monte Carlo (MC) treatment planning in patients with non-small-cell lung cancer according to tumor size and location. Methods: Fifty-three stereotactic radiotherapy plans designed using the equivalent path-length (EPL) algorithm were re-calculated using MC. Plans were compared by the minimum dose to 95% of the PTV (D95), the heterogeneity index (HI) and the mean dose to organs at risk (OARs). Based on changes in D95, the prescription dose was converted from EPL to MC. Based on changes in HI, we examined the feasibility of MC prescription to plans re-calculated but not re-optimized with MC. Results: The MC fraction dose for peripheral tumors is 16–18Gy depending on tumor size. For central tumors the MC dose was reduced less than for peripheral tumors. The HI decreased on average by 4–9% in peripheral tumors and 3–5% in central tumors. The mean dose to OARs was lower for MC than EPL, and correlated strongly (R 2 =0.98–0.99). Conclusion: For the conversion from EPL to MC we recommend a separate prescription dose according to tumor size. MC optimization is not required if a HI⩾70% is accepted. Dose constraints to OARs can be easily converted due to the high EPL–MC correlation. [Copyright &y& Elsevier]

Purpose: To quantify the clinical accuracy of the respiratory motion tracking system of the CyberKnife treatment device. Methods and Materials: Data in log files of 44 lung cancer patients treated with tumor tracking were analyzed. Errors in the correlation model, which relates the internal target motion with the external breathing motion, were quantified. The correlation model error was compared with the geometric error obtained when no respiratory tracking was used. Errors in the prediction method were calculated by subtracting the predicted position from the actual measured position after 192.5 ms (the time lag to prediction in our current system). The prediction error was also measured for a time lag of 115 ms and a new prediction method. Results: The mean correlation model errors were less than 0.3 mm. Standard deviations describing intrafraction variations around the whole-fraction mean error were 0.2 to 1.9 mm for cranio–caudal, 0.1 to 1.9 mm for left–right, and 0.2 to 2.5 mm for anterior–posterior directions. Without the use of respiratory tracking, these variations would have been 0.2 to 8.1 mm, 0.2 to 5.5 mm, and 0.2 to 4.4 mm. The overall mean prediction error was small (0.0 ± 0.0 mm) for all directions. The intrafraction standard deviation ranged from 0.0 to 2.9 mm for a time delay of 192.5 ms but was halved by using the new prediction method. Conclusions: Analyses of the log files of real clinical cases have shown that the geometric error caused by respiratory motion is substantially reduced by the application of respiratory motion tracking. [Copyright &y& Elsevier]

Abstract: Background and Purpose: For cervical cancer patients, bladder filling variations may result in inadequate EBRT target coverage, unless large safety margins are used. For a group of patients who received full bladder instructions, inter-fraction variations and time trends in bladder volume were quantified, and a 3D ultrasound (US) scanner was tested for on-line bladder volume measurements. Methods and materials: For 24 patients, the bladder volume was measured with US at the time of the planning CT scan, and twice weekly during the course of RT. Comparisons of US with planning CT were used to assess the bladder scanner accuracy. Patients were treated in prone on a belly board, EPID images were acquired to correlate set-up errors with bladder filling variations. Results: Measured US and CT bladder volumes were strongly correlated (R =0.97, slope 1.1± 0.1). The population mean bladder volume at planning of 378±209ml (1SD) reduced to 109±88ml (1SD) in week 6, a reduction by 71% (average reduction 46ml/week), revealing a large inter-fraction time trend. Intra-patient variation in bladder volume during RT was 168ml (1SD) (range 70–266ml). Rotation around the LR axis was significantly correlated with bladder volume changes. Conclusions: Despite a full bladder instruction, bladder volumes reduced dramatically during treatment, implying large time trends in target position of these patients. The portable US scanner provides a quick and reliable measurement of the bladder volume, which might assist future online treatment adaptation. [Copyright &y& Elsevier]