Clinical pilot study for EPID-based in vivo dosimetry using EPIgray™ for head and neck VMAT.

This work details the clinical pilot study methodology used at Wellington Blood and Cancer Centre (WBCC) before the clinical release of in vivo dosimetry (IVD) system EPIgray™ for head and neck (H&N) volumetric modulated arc therapy (VMAT) treatments. Clinical pilot studies make it possible to select appropriate, department-specific tolerance ranges for the treatment type and site under investigation. An IVD clinical pilot study of H&N VMAT treatments was conducted over 3 months at WBCC using EPIgray™ dose reconstruction software and included 12 patients and 32 individual treatment fractions. Statistical analysis of the dose deviations between the treatment planning system (TPS) dose and EPIgray™ reconstructed dose confirmed that a deviation tolerance range of ± 7.0% was an appropriate choice for H&N VMAT at WBCC.

Dose accumulation to assess the validity of treatment plans with reduced margins in radiotherapy of head and neck cancer.

BACKGROUND AND PURPOSE: Literature has reported reduced treatment toxicity in head-and-neck radiotherapy (HNRT) when reducing the planning target volume (PTV) margin from 5 to 3 mm but loco-regional control was not always preserved. This study used deformable image registration (DIR)-facilitated dose accumulation to assess clinical target volume (CTV) coverage in the presence of anatomical changes. MATERIALS AND METHODS: VMAT plans for 12 patients were optimized using 3 or 5 mm PTV and planning risk volume (PRV) margins. The planning computed tomography (pCT) scan was registered to each daily cone beam CT (CBCT) using DIR. The inverse registration was used to reconstruct and accumulate dose ( D acc ). CTV coverage was assessed using the dose-volume histogram (DVH) metric D 99 % acc and by individual voxel analysis. Both approaches included an uncertainty estimate using the 95% level of confidence. RESULTS: D 99 % acc was less than 95% of the prescribed dose D presc for three cases including only one case where this was at the 95% level of confidence. However for many patients, the accumulated dose included a substantial volume of voxels receiving less than 95% D presc independent of margin expansion, which predominantly occurred in the subdermal region. Loss in target coverage was very patient specific but tightness of target volume coverage at planning was a common factor leading to underdosage. CONCLUSION: This study agrees with previous literature that PTV/PRV margin reduction did not significantly reduce CTV coverage during treatment, but also highlighted that tight coverage of target volumes at planning increases the risk of clinically unacceptable dose delivery. Patient-specific verification of dose delivery to assess the dose delivered to each voxel is recommended.

Quantifying the dose accumulation uncertainty after deformable image registration in head-and-neck radiotherapy.

BACKGROUND AND PURPOSE: Deformable image registration (DIR) facilitated dose reconstruction and accumulation can be applied to assess delivered dose and verify the validity of the treatment plan during treatment. This retrospective study used in silico deformations based on clinically observed anatomical changes as ground truth to investigate the uncertainty of reconstructed and accumulated dose in head-and-neck radiotherapy (HNRT). MATERIALS AND METHODS: A planning CT (pCT), cone beam CT (CBCT) from week one of treatment and three later CBCTs were selected for 12 HNRT patients. These images were used to generate in silico reference CBCTs and deformation vector fields (DVFs) as ground truth with B-spline DIR. Inverse consistency (IC) of voxels was assessed by determining their net displacement after successive application of the forward and backward DVF. The reconstructed dose based on demons DIR was compared to the ground truth to assess the structure-specific uncertainties of this DIR algorithm for inverse consistent and inverse inconsistent voxels. RESULTS: Overall, 98.5% of voxels were inverse consistent with the 95% level of confidence range for dose reconstruction of a single fraction equal to [-2.3%; +2.1%], [-10.2%; +15.2%] and [-9.5%; +12.5%] relative to their planned dose for target structures, critical organs at risk (OARs) and non-critical OARs, respectively. Inverse inconsistent voxels generally showed a higher level of uncertainty. CONCLUSION: The uncertainty in accumulated dose using DIR can be accurately quantified and incorporated in dose-volume histograms (DVHs). This method can be used to prospectively assess the adequacy of target coverage during treatment in an objective manner.

Off-line setup corrections only marginally reduce the number of on-line corrections for prostate radiotherapy using implanted gold markers.

PURPOSE: To evaluate the efficiency of combining on-line and off-line corrections for the positioning of patients receiving external beam radiotherapy for prostate cancer. MATERIALS AND METHODS: Daily portal images were acquired during the treatment of 102 patients to verify and correct the position of the prostatic gland using implanted gold markers. In addition to an existing off-line procedure, on-line corrections were applied in the anterior-posterior (AP) direction only, to limit the increase in daily workload. The possible increase in workload of the combined correction procedure for on-line corrections in either two or three directions was further investigated by simulating the required position corrections for 500 treatments. RESULTS: The combined correction procedure in AP-direction resulted in a systematic dispersion and random variation of 0.3mm (1 SD) and 1.0mm (1 SD), respectively. Application of off-line corrections during pre-treatment setup reduced the number of required on-line corrections from 22+/-4 (1 SD) to 17+/-4 (1 SD), at the cost of 1.4+/-1.0 (1 SD) off-line corrections. For on-line corrections in two or three directions, application of a combined on-line/off-line procedure did not noticeably reduce the number of setup corrections. CONCLUSIONS: The on-line procedure is feasible and significantly improves both systematic and random errors to below 1 mm with a limited impact on the workload and treatment time. The application of off-line setup corrections during pre-treatment patient positioning only marginally reduces the number of on-line setup corrections.

Monitoring anatomical changes of individual patients using statistical process control during head-and-neck radiotherapy.

BACKGROUND AND PURPOSE: Reduced toxicity while maintaining loco-regional control rates have been reported after reducing planning target volume (PTV) margins for head-and-neck radiotherapy (HNRT). In this context, quantifying anatomical changes to monitor patient treatment is preferred. This retrospective feasibility study investigated the application of deformable image registration (DIR) and Exponentially Weighted Moving Average (EWMA) Statistical Process Control (SPC) charts for this purpose. MATERIALS AND METHODS: DIR between the computed tomography for treatment planning (pCT) images of twelve patients and their daily on-treatment cone beam computed tomography (CBCT) images quantified anatomical changes during treatment. EWMA charts investigated corresponding trends. Uncertainty analysis provided 90% confidence limits which were used to confirm whether a trend previously breached a threshold. RESULTS: Trends in patient positioning reproducibility occurred before the end of treatment week four in 54% of cases. Using SPC process limits, only 24% of these were confirmed at a 90% confidence level before the end of treatment. Using an a priori clinical limit of 2 mm, absolute changes in patient pose were detected in 39% of cases, of which 82% were confirmed. Soft tissue trends outside SPC process limits occurring before the end of treatment week four were confirmed in 90% of cases. CONCLUSION: Structure specific action thresholds enabled detection of systematic anatomical changes during the first four weeks of treatment. Investigation of the dosimetric impact of the observed deviations is needed to show the efficacy of SPC to timely indicate required treatment adaptation and provide a safety net for PTV margin reduction.

Review of the patient positioning reproducibility in head-and-neck radiotherapy using Statistical Process Control.

BACKGROUND AND PURPOSE: A remarkable improvement in patient positioning was observed after the implementation of various process changes aiming to increase the consistency of patient positioning throughout the radiotherapy treatment chain. However, no tool was available to describe these changes over time in a standardised way. This study reports on the feasibility of Statistical Process Control (SPC) to highlight changes in patient positioning accuracy and facilitate correlation of these changes with the underlying process changes. MATERIALS AND METHODS: Metrics were designed to quantify the systematic and random patient deformation as input for the SPC charts. These metrics were based on data obtained from multiple local ROI matches for 191 patients who were treated for head-and-neck cancer during the period 2011-2016. RESULTS: SPC highlighted a significant improvement in patient positioning that coincided with multiple intentional process changes. The observed improvements could be described as a combination of a reduction in outliers and a systematic improvement in the patient positioning accuracy of all patients. CONCLUSION: SPC is able to track changes in the reproducibility of patient positioning in head-and-neck radiation oncology, and distinguish between systematic and random process changes. Identification of process changes underlying these trends requires additional statistical analysis and seems only possible when the changes do not overlap in time.

Sensitivity and specificity of time resolved point dose measurements for patient specific quality assurance.

This study aimed to quantify the sensitivity and specificity of time-resolved point dose measurements. Criteria were defined to assess whether errors would cause a clinically relevant dose deviation during patient treatment. The sensitivity and specificity were determined based on verification measurements of five error-free plans and 84 intentional error plans. Receiver operator characteristic analysis was conducted to quantify the efficiency of the method. In addition, the specificity of the method was investigated in more detail by assessing its ability to identify different error modes. For measurements made at planning target volume locations, a moderate sensitivity (65% ± 13%), specificity (76% ± 12%), and an area under the curve (AUC) equal to 0.77 were obtained for a quality control (QC) acceptance criterion of 2%. Measurements made at organ at risk (OAR) locations had high sensitivity (80% ± 20%), but low specificity (54% ± 13%), and an AUC equal to 0.70. The low specificity for OAR locations could be traced to the impact of a small couch tilt on measurement locations at larger distances from the isocentre, resulting in increased shielding by multi-leaf collimator (MLC) leaves. Further analysis showed that output errors and errors affecting the penumbra region can be resolved on a per measurement basis with moderate to high sensitivity (100% and 67% for errors in output, and in the penumbra region, respectively) and high specificity (77% and 85% for errors in output, and in the penumbra region, respectively). This can potentially result in saving time investigating failing QC measurements.

Accurate two-dimensional IMRT verification using a back-projection EPID dosimetry method.

The use of electronic portal imaging devices (EPIDs) is a promising method for the dosimetric verification of external beam, megavoltage radiation therapy-both pretreatment and in vivo. In this study, a previously developed EPID back-projection algorithm was modified for IMRT techniques and applied to an amorphous silicon EPID. By using this back-projection algorithm, two-dimensional dose distributions inside a phantom or patient are reconstructed from portal images. The model requires the primary dose component at the position of the EPID. A parametrized description of the lateral scatter within the imager was obtained from measurements with an ionization chamber in a miniphantom. In addition to point dose measurements on the central axis of square fields of different size, we also used dose profiles of those fields as reference input data for our model. This yielded a better description of the lateral scatter within the EPID, which resulted in a higher accuracy in the back-projected, two-dimensional dose distributions. The accuracy of our approach was tested for pretreatment verification of a five-field IMRT plan for the treatment of prostate cancer. Each field had between six and eight segments and was evaluated by comparing the back-projected, two-dimensional EPID dose distribution with a film measurement inside a homogeneous slab phantom. For this purpose, the y-evaluation method was used with a dose-difference criterion of 2% of dose maximum and a distance-to-agreement criterion of 2 mm. Excellent agreement was found between EPID and film measurements for each field, both in the central part of the beam and in the penumbra and low-dose regions. It can be concluded that our modified algorithm is able to accurately predict the dose in the midplane of a homogeneous slab phantom. For pretreatment IMRT plan verification, EPID dosimetry is a reliable and potentially fast tool to check the absolute dose in two dimensions inside a phantom for individual IMRT fields. Film measurements inside a phantom can therefore be replaced by EPID measurements.

Time-resolved dosimetry using a pinpoint ionization chamber as quality assurance for IMRT and VMAT.

PURPOSE: To develop a method to verify the dose delivery in relation to the individual control points of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) using an ionization chamber. In addition to more effective problem solving during patient-specific quality assurance (QA), the aim is to eventually map out the limitations in the treatment chain and enable a targeted improvement of the treatment technique in an efficient way. METHODS: Pretreatment verification was carried out for 255 treatment plans that included a broad range of treatment indications in two departments using the equipment of different vendors. In-house developed software was used to enable calculation of the dose delivery for the individual beamlets in the treatment planning system (TPS), for data acquisition, and for analysis of the data. The observed deviations were related to various delivery and measurement parameters such as gantry angle, field size, and the position of the detector with respect to the field edge to distinguish between error sources. RESULTS: The average deviation of the integral fraction dose during pretreatment verification of the planning target volume dose was -2.1% ± 2.2% (1 SD), -1.7% ± 1.7% (1 SD), and 0.0% ± 1.3% (1 SD) for IMRT at the Radboud University Medical Center (RUMC), VMAT (RUMC), and VMAT at the Wellington Blood and Cancer Centre, respectively. Verification of the dose to organs at risk gave very similar results but was generally subject to a larger measurement uncertainty due to the position of the detector at a high dose gradient. The observed deviations could be related to limitations of the TPS beam models, attenuation of the treatment couch, as well as measurement errors. The apparent systematic error of about -2% in the average deviation of the integral fraction dose in the RUMC results could be explained by the limitations of the TPS beam model in the calculation of the beam penumbra. CONCLUSIONS: This study showed that time-resolved dosimetry using an ionization chamber is feasible and can be largely automated which limits the required additional time compared to integrated dose measurements. It provides a unique QA method which enables identification and quantification of the contribution of various error sources during IMRT and VMAT delivery.

Validation of Varian's SmartAdapt® deformable image registration algorithm for clinical application.

BACKGROUND: Re-contouring of structures on consecutive planning computed tomography (CT) images for patients that exhibit anatomical changes is elaborate and may negatively impact the turn-around time if this is required for many patients. This study was therefore initiated to validate the accuracy and usefulness of automatic contour propagation for head and neck cancer patients using SmartAdapt® which is the deformable image registration (DIR) application in Varian's Eclipse™ treatment planning system. METHODS: CT images of eight head and neck cancer patients with multiple planning CTs were registered using SmartAdapt®. The contoured structures of target volumes and OARs of the primary planning CT were deformed accordingly and subsequently compared with a reference structure set being either: 1) a structure set independently contoured by the treating Radiation Oncologist (RO), or 2) the DIR-generated structure set after being reviewed and modified by the RO. RESULTS: Application of DIR offered a considerable time saving for ROs in delineation of structures on CTs that were acquired mid-treatment. Quantitative analysis showed that 84% of the volume of the DIR-generated structures overlapped with the independently re-contoured structures, while 94% of the volume overlapped with the DIR-generated structures after review by the RO. This apparent intra-observer variation was further investigated resulting in the identification of several causes. Qualitative analysis showed that 92% of the DIR-generated structures either need no or only minor modification during RO reviews. CONCLUSIONS: SmartAdapt is a powerful tool with sufficient accuracy that saves considerable time in re-contouring structures on re-CTs. However, careful review of the DIR-generated structures is mandatory, in particular in areas where tumour regression plays a role.

An endorectal balloon reduces intrafraction prostate motion during radiotherapy.

PURPOSE: To investigate the effect of endorectal balloons (ERBs) on intrafraction and interfraction prostate motion during radiotherapy. METHODS AND MATERIALS: Thirty patients were treated with intensity-modulated radiotherapy, to a total dose of 80 Gy in 40 fractions. In 15 patients, a daily-inserted air-filled ERB was applied. Prostate motion was tracked, in real-time, using an electromagnetic tracking system. Interfraction displacements, measured before each treatment, were quantified by calculating the systematic and random deviations of the center of mass of the implanted transponders. Intrafraction motion was analyzed in timeframes of 150 s, and displacements >1 mm, >3 mm, >5 mm, and >7 mm were determined in the anteroposterior, left-right, and superoinferior direction, and for the three-dimensional (3D) vector. Manual table corrections, made during treatment sessions, were retrospectively undone. RESULTS: A total of 576 and 567 tracks have been analyzed in the no-ERB group and ERB group, respectively. Interfraction variation was not significantly different between both groups. After 600 s, 95% and 98% of the treatments were completed in the respective groups. Significantly fewer table corrections were performed during treatment fractions with ERB: 88 vs. 207 (p = 0.02). Intrafraction motion was significantly reduced with ERB. During the first 150 s, only negligible deviations were observed, but after 150 s, intrafraction deviations increased with time. This resulted in cumulative percentages of 3D-vector deviations >1 mm, >3 mm, >5 mm, and >7 mm that were 57.7%, 7.0%, 0.7%, and 0.3% in the ERB-group vs. 70.2%, 18.1%, 4.6%, and 1.4% in the no-ERB group after 600 s. The largest reductions in the ERB group were observed in the AP direction. These data suggest that a 5 mm CTV-to-PTV margin is sufficient to correct for intrafraction prostate movements when using an ERB. CONCLUSIONS: ERB significantly reduces intrafraction prostate motion, but not interfraction variation, and may in particular be beneficial for treatment sessions longer than 150 s.

Reduction of treatment volume and radiation doses to surrounding tissues with intraprostatic gold markers in prostate cancer radiotherapy.

BACKGROUND: High-precision radiotherapy with gold marker implantation is a standard technique for prostate cancer treatment. To provide insight into the beneficial effect of gold markers, the influence on treatment volume and radiation doses to healthy tissues was investigated. PATIENTS AND METHODS: Three consecutive treatment margins were constructed, for 10 patients with localized prostate cancer, to show the reduction of planning target volume (PTV): PTV 10 mm (no markers), PTV 7 mm (markers), and PTV 7/5 mm (markers and online correction). On planning computed tomography (CT) scan, the prostate, bladder, rectal wall, and anal canal were contoured. The treatment volume and radiation doses to surrounding organs were calculated. In 65 patients, with the online protocol and gold markers, late toxicity was evaluated. RESULTS: With gold markers a significant PTV reduction of 27% was achieved (P < .001). Subsequently, radiation dose reductions to the mean of 17% (± 4.5%) to the bladder, 19% (± 4.7%) to the anal canal, and 12% (± 3%) to the rectal wall, respectively were seen (P < .001). With 5-mm posterior margins an additional PTV reduction of 3.7% (P < .001) and total radiation dose reduction to the mean of 24% (± 4%), and 16% (± 4.5%) to anal canal and rectal wall, respectively were seen (P < .001). Late Grade 1-2 genitourinary and gastrointestinal toxicity was seen in 32%, and 33%, respectively. Grade 3 toxicity was less than 10%. CONCLUSIONS: This study showed a significant reduction of treatment volume and radiation doses to healthy tissues with intraprostatic gold markers.