Anders Bertelsen

Single Arc Volumetric Modulated Arc Therapy of head and neck cancer

BACKGROUND The quality of Volumetric Modulated Arc Therapy (VMAT) plans is highly dependent on the performance of the optimization algorithm used. Recently new algorithms have become available which are capable of generating VMAT plans for Elekta accelerators. The VMAT algorithm in Pinnacle is named SmartArc and its capability to generate treatment plans for head and neck cancer was tested. METHODS Twenty-five patients with oropharyngeal or hypopharyngeal carcinoma, previously treated with IMRT by means of Pinnacle and Elekta accelerators, were replanned with single arc VMAT. The VMAT planning objectives were to achieve clinical target coverage and sparing of the organs at risk (OAR). Comparison with the original clinically used IMRT was made by evaluating (1) dose-volume histograms (DVHs) for PTVs, (2) DVHs for OARs, (3) delivery time and monitor units (MU), and (4) treatment accuracy. RESULTS Equivalent or superior target coverage and sparing of OARs were achieved with VMAT compared to IMRT. Volumes in the healthy tissues receiving between 17.3 Gy and 49.4 Gy were significantly reduced and the conformity (CI(95%)) of the elective PTV was improved from 1.7 with IMRT to 1.6 with VMAT. Compared to step-and-shoot IMRT, VMAT reduced the number of MUs by 8.5% to 460+/-63 MUs per fraction, and delivered on an Elekta Synergy accelerator, the treatment time was on average reduced by 35% to 241 +/- 16s. In Delta4 measurements of the VMAT treatments, 99.6 +/- 0.5% of the detector points passed a 3 mm and 3% gamma criterion, identical to the results of IMRT. CONCLUSIONS The target coverages obtained in the IMRT and VMAT plans were found to be very similar. SmartArc generated single arc VMAT plans with equivalent or better target coverage and sparing of OARs compared to IMRT, while both delivery time and MUs were decreased. Very good dose accuracy results were obtained delivering the plans on an Elekta accelerator.

Locoregional Control of Non-Small Cell Lung Cancer in Relation to Automated Early Assessment of Tumor Regression on Cone Beam Computed Tomography

PURPOSE Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its potential use in response adapted personalized radiation therapy is evaluated empirically. METHODS AND MATERIALS Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearsons correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2 groups having volume regressions below or above the population median value. Kaplan-Meier plots of locoregional disease-free rate and overall survival in the 2 groups were used to evaluate the predictive value of tumor regression during treatment. Cox proportional hazards model was used to adjust for other clinical characteristics. RESULTS Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearsons correlation coefficient between manual and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could be quantified early into the treatment course. Interestingly, patients with pronounced volume regression had worse locoregional tumor control and overall survival. This was significant on patient with non-adenocarcinoma histology. CONCLUSIONS Evaluation of routinely acquired CBCT images during radiation therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy.

Automatic planning of head and neck treatment plans

Treatment planning is time-consuming and the outcome depends on the person performing the optimization. A system that automates treatment planning could potentially reduce the manual time required for optimization and could also provide a method to reduce the variation between persons performing radiation dose planning (dosimetrist) and potentially improve the overall plan quality. This study evaluates the performance of the Auto-Planning module that has recently become clinically available in the Pinnacle3 radiation therapy treatment planning system. Twenty-six clinically delivered head and neck treatment plans were reoptimized with the Auto-Planning module. Comparison of the two types of treatment plans were performed using DVH metrics and a blinded clinical evaluation by two senior radiation oncologists using a scale from one to six. Both evaluations investigated dose coverage of target and dose to healthy tissues. Auto-Planning was able to produce clinically acceptable treatment plans in all 26 cases. Target coverages in the two types of plans were similar, but automatically generated plans had less irradiation of healthy tissue. In 94% of the evaluations, the autoplans scored at least as high as the previously delivered clinical plans. For all patients, the Auto-Planning tool produced clinically acceptable head and neck treatment plans without any manual intervention, except for the initial target and OAR delineations. The main benefit of the method is the likely improvement in the overall treatment quality since consistent, high-quality plans are generated which even can be further optimized, if necessary. This makes it possible for the dosimetrist to focus more time on difficult dose planning goals and to spend less time on the more tedious parts of the planning process. PACS number: 87.55.de.Treatment planning is time‐consuming and the outcome depends on the person performing the optimization. A system that automates treatment planning could potentially reduce the manual time required for optimization and could also provide a method to reduce the variation between persons performing radiation dose planning (dosimetrist) and potentially improve the overall plan quality. This study evaluates the performance of the Auto‐Planning module that has recently become clinically available in the Pinnacle3 radiation therapy treatment planning system. Twenty‐six clinically delivered head and neck treatment plans were reoptimized with the Auto‐Planning module. Comparison of the two types of treatment plans were performed using DVH metrics and a blinded clinical evaluation by two senior radiation oncologists using a scale from one to six. Both evaluations investigated dose coverage of target and dose to healthy tissues. Auto‐Planning was able to produce clinically acceptable treatment plans in all 26 cases. Target coverages in the two types of plans were similar, but automatically generated plans had less irradiation of healthy tissue. In 94% of the evaluations, the autoplans scored at least as high as the previously delivered clinical plans. For all patients, the Auto‐Planning tool produced clinically acceptable head and neck treatment plans without any manual intervention, except for the initial target and OAR delineations. The main benefit of the method is the likely improvement in the overall treatment quality since consistent, high‐quality plans are generated which even can be further optimized, if necessary. This makes it possible for the dosimetrist to focus more time on difficult dose planning goals and to spend less time on the more tedious parts of the planning process. PACS number: 87.55.de

Radiation dose response of normal lung assessed by Cone Beam CT – A potential tool for biologically adaptive radiation therapy

BACKGROUND Density changes of healthy lung tissue during radiotherapy as observed by Cone Beam CT (CBCT) might be an early indicator of patient specific lung toxicity. This study investigates the time course of CBCT density changes and tests for a possible correlation with locally delivered dose. METHODS A total of 665 CBCTs in 65 lung cancer patients treated with IMRT/VMAT to 60 or 66 Gy in 2 Gy fractions were analyzed. For each patient, CBCT lung density changes during the treatment course were related to the locally delivered dose. RESULTS A dose response is observed for the patient population at the end of the treatment course. However, the observed dose response is highly variable among patients. Density changes at 10th and 20th fraction are clearly correlated to those observed at the end of the treatment course. CONCLUSIONS CBCT density changes in healthy lung tissue during radiotherapy correlate with the locally delivered dose and can be detected relatively early during the treatment. If these density changes are correlated to subsequent clinical toxicity this assay could form the basis for biological adaptive radiotherapy.

Set-up errors in patients undergoing image guided radiation treatment. Relationship to body mass index and weight loss

Background. The purpose of this study was to quantify the set-up errors of patient positioning during IGRT and to correlate set-up errors to patient-specific factors such as weight, height, BMI, and weight loss. Patients and methods. Thirty four consecutively treated head-and-neck cancer patients (H&N) and 20 lung cancer patients were investigated. Patients were positioned using customized immobilization devices consisting of vacuum cushions and thermoplastic shells. Treatment was given on an Elekta Synergy accelerator. Cone-beam acquisitions were obtained according to a standardized Action Limit protocol and compared to pre-treatment CT images. The average 3D deviation from three initial cone beam scans was compared to deviations at the 10th and 20th treatment session and correlated by linear regression analysis to height, weight, and BMI, and in H&N to weight loss as expressed by the relative weight change over time. Results. The SD of the translational and rotational random set-up errors during the first three sessions for H&N were 0.9mm (Left-Right), 1.1mm (Anterior-Posterior), 0.7mm (Cranio-Caudal) and 0.7° (LR-axis), 0.5° (AP-axis), and 0.7° (CC-axis). The equivalent data for lung cancer patients were 1.1mm (LR), 1.1mm (AP), 1.5 mm (CC) and 0.5° (LR-axis), 0.6° (AP-axis), and 0.4° (CC-axis). The median BMI for H&N and lung was 25.8 (17.6–39.7) and 23.7 (17.4–38.8), respectively. The median weekly weight change for H&N was −0.3% (−2.0 to 1.1%). With H&N and lung cancer analyzed separately, no statistically significant correlation was observed between set-up errors and height, weight, BMI, or weight change during treatment, irrespectively whether the 3D deviations from the initial three cone beam scans or scans from the 10th or 20th treatment sessions were used. Conclusion. This IGRT study did not support the hypothesis that set-up errors during radiotherapy are correlated to patient height, weight, BMI, or weight loss.

Validation of a new control system for Elekta accelerators facilitating continuously variable dose rate

PURPOSE Elekta accelerators controlled by the current clinically used accelerator control system, Desktop 7.01 (D7), uses binned variable dose rate (BVDR) for volumetric modulated arc therapy (VMAT). The next version of the treatment control system (Integrity) supports continuously variable dose rate (CVDR) as well as BVDR. Using CVDR opposed to BVDR for VMAT has the potential of reducing the treatment time but may lead to lower dosimetric accuracy due to faster moving accelerator parts. Using D7 and a test version of Integrity, differences in ability to control the accelerator, treatment efficiency, and dosimetric accuracy between the two systems were investigated. METHODS Single parameter tests were designed to expose differences in the way the two systems control the movements of the accelerator. In these tests, either the jaws, multi leaf collimators (MLCs), or gantry moved at constant speed while the dose rate was changed in discrete steps. The positional errors of the moving component and dose rate were recorded using the control systems with a sampling frequency of 4 Hz. The clinical applicability of Integrity was tested using 15 clinically used VMAT plans (5 prostate, 5 H&N, and 5 lung) generated by the SmartArc algorithm in PINNACLE. The treatment time was measured from beam-on to beam-off and the accuracy of the dose delivery was assessed by comparing DELTA4 measurements and PINNACLE calculated doses using gamma evaluation. RESULTS The single parameter tests showed that Integrity had an improved feedback between gantry motion and dose rate at the slight expense of MLC control compared to D7. The single parameter test did not reveal any significant differences in the control of either jaws or backup jaws between the two systems. These differences in gantry and MLC control together with the use of CVDR gives a smoother Integrity VMAT delivery compared to D7 with less abrupt changes in accelerator motion. Gamma evaluation (2% of 2 Gy and 2 mm) of the calculated doses and DELTA4 measured doses corrected for systematic errors showed an average pass rate of more than 97.8% for both D7, Integrity BVDR, and Integrity CVDR deliveries. Direct comparisons between the measured doses using strict gamma criteria of 0.5% and 0.5 mm showed excellent agreement between D7 and Integrity delivered doses with average pass rates above 95.7%. Finally, the Integrity control system resulted in a significant 35% (55 +/- 13 s) reduction in treatment time, on average. CONCLUSIONS Single parameter tests showed that the two control systems differed in their feedbac loops between MLC, gantry, and dose rate. These differences made the VMAT deliveries more smooth using the new Integrity treatment control system, compared to the current Desktop 7.01. Together with the use of CVDR, which results in less abrupt changes in dose rate, this further increases the smoothness of the delivery. The use of CVDR for VMAT with the Integrity desktop results in a significant reduction in treatment time compared to BVDR with an average reduction of 35%. This decrease in delivery time was achieved without compromising the dosimetric accuracy.

Automatic treatment planning improves the clinical quality of head and neck cancer treatment plans

Highlights • Autoplan can produce clinically better VMAT radiotherapy plans for H&N cancer.• Autoplan plans have similar target coverage with significant sparing of OAR.• With a template the TPS can automatically create better plans than manually created plans.

Prediction of lung density changes after radiotherapy by cone beam computed tomography response markers and pre-treatment factors for non-small cell lung cancer patients.

BACKGROUND AND PURPOSE This study investigates the ability of pre-treatment factors and response markers extracted from standard cone-beam computed tomography (CBCT) images to predict the lung density changes induced by radiotherapy for non-small cell lung cancer (NSCLC) patients. METHODS AND MATERIALS Density changes in follow-up computed tomography scans were evaluated for 135 NSCLC patients treated with radiotherapy. Early response markers were obtained by analysing changes in lung density in CBCT images acquired during the treatment course. The ability of pre-treatment factors and CBCT markers to predict lung density changes induced by radiotherapy was investigated. RESULTS Age and CBCT markers extracted at 10th, 20th, and 30th treatment fraction significantly predicted lung density changes in a multivariable analysis, and a set of response models based on these parameters were established. The correlation coefficient for the models was 0.35, 0.35, and 0.39, when based on the markers obtained at the 10th, 20th, and 30th fraction, respectively. CONCLUSIONS The study indicates that younger patients without lung tissue reactions early into their treatment course may have minimal radiation induced lung density increase at follow-up. Further investigations are needed to examine the ability of the models to identify patients with low risk of symptomatic toxicity.

Time evolution of regional CT density changes in normal lung after IMRT for NSCLC

PURPOSE This study investigates the clinical radiobiology of radiation induced lung disease in terms of regional computed tomography (CT) density changes following intensity modulated radiotherapy (IMRT) for non-small-cell lung cancer (NSCLC). METHODS A total of 387 follow-up CT scans in 131 NSCLC patients receiving IMRT to a prescribed dose of 60 or 66 Gy in 2 Gy fractions were analyzed. The dose-dependent temporal evolution of the density change was analyzed using a two-component model, a superposition of an early, transient component and a late, persistent component. RESULTS The CT density of healthy lung tissue was observed to increase significantly (p<0.0001) for all dose levels after IMRT. The time evolution and the size of the density signal depend on the local delivered dose. The transient component of the density signal was found to peak in the range of 3-4 months, while the density tends to stabilize at times >12 months. CONCLUSIONS The radiobiology of lung injury may be analyzed in terms of CT density change. The initial transient change in density is consistent with radiation pneumonitis, while the subsequent stabilization of the density is consistent with pulmonary fibrosis.

Does VMAT for treatment of NSCLC patients increase the risk of pneumonitis compared to IMRT ? - A planning study

Abstract Background. Volumetric modulated arc therapy (VMAT) for treatment of non-small cell lung cancer (NSCLC) patients potentially changes the risk of radiation-induced pneumonitis (RP) compared to intensity modulated radiation therapy (IMRT) if the dose to the healthy lung is changed significantly. In this study, clinical IMRT plans were used as starting point for VMAT optimization and differences in risk estimates of RP between the two plan types were evaluated. Material and methods. Fifteen NSCLC patients prescribed 66 Gy in 2 Gy fractions were planned with IMRT and subsequently with single arc VMAT. Dose metrics were evaluated for target and lung together with population averaged dose volume histograms. The risk of RP was calculated using normal tissue complication probability (NTCP) models. Finally, applicability of the plans was tested through delivery on an Elekta accelerator. Results. When changing from IMRT to VMAT only modest differences were observed in the dose to the lung and target volume. On average, fractions of lung irradiated to doses between 18 Gy and 48 Gy were statistically significant reduced using VMAT compared to IMRT. For the fraction of lung receiving more than 20 Gy the reduction was 1.2% percentage points: (range –0.6 –2.6%). The evaluated toxicity were smaller with VMAT compared to IMRT, however only modest differences were observed in the NTCP values. The plans were delivered without any problems. The average beam on time with VMAT was 83 s. This was a reduction of 141 s (ranging from 37 s to 216 s) compared to IMRT. Conclusions. Using IMRT as reference for the VMAT optimization it was possible to implement VMAT in the clinic with no increase in estimated risk of RP. Thus, toxicity is not expected to be a hindrance to using VMAT and will profit from the shorter delivery time with VMAT compared to IMRT.