J. Stroom

Inclusion of geometrical uncertainties in radiotherapy treatment planning by means of coverage probability

PURPOSE Following the ICRU-50 recommendations, geometrical uncertainties in tumor position during radiotherapy treatments are generally included in the treatment planning by adding a margin to the clinical target volume (CTV) to yield the planning target volume (PTV). We have developed a method for automatic calculation of this margin. METHODS AND MATERIALS Geometrical uncertainties of a specific patient group can normally be characterized by the standard deviation of the distribution of systematic deviations in the patient group (Sigma) and by the average standard deviation of the distribution of random deviations (sigma). The CTV of a patient to be planned can be represented in a 3D matrix in the treatment room coordinate system with voxel values one inside and zero outside the CTV. Convolution of this matrix with the appropriate probability distributions for translations and rotations yields a matrix with coverage probabilities (CPs) which is defined as the probability for each point to be covered by the CTV. The PTV can then be chosen as a volume corresponding to a certain iso-probability level. Separate calculations are performed for systematic and random deviations. Iso-probability volumes are selected in such a way that a high percentage of the CTV volume (on average > 99%) receives a high dose (> 95%). The consequences of systematic deviations on the dose distribution in the CTV can be estimated by calculation of dose histograms of the CP matrix for systematic deviations, resulting in a so-called dose probability histogram (DPH). A DPH represents the average dose volume histogram (DVH) for all systematic deviations in the patient group. The consequences of random deviations can be calculated by convolution of the dose distribution with the probability distributions for random deviations. Using the convolved dose matrix in the DPH calculation yields full information about the influence of geometrical uncertainties on the dose in the CTV. RESULTS The model is demonstrated to be fast and accurate for a prostate, cervix, and lung cancer case. A CTV-to-PTV margin size which ensures at least 95% dose to (on average) 99% of the CTV, appears to be equal to about 2Sigma + 0.7sigma for three all cases. Because rotational deviations are included, the resulting margins can be anisotropic, as shown for the prostate cancer case. CONCLUSION A method has been developed for calculation of CTV-to-PTV margins based on the assumption that the CTV should be adequately irradiated with a high probability.

Acute morbidity reduction using 3DCRT for prostate carcinoma : A randomized study

PURPOSE To study the effects on gastrointestinal and urological acute morbidity, a randomized toxicity study, comparing conventional and three-dimensional conformal radiotherapy (3DCRT) for prostate carcinoma was performed. To reveal possible volume effects, related to the observed toxicity, dose-volume histograms (DVHs) were used. METHODS AND MATERIALS From June 1994 to March 1996, 266 patients with prostate carcinoma, stage T1-4N0M0 were enrolled in the study. All patients were treated to a dose of 66 Gy (ICRU), using the same planning procedure, treatment technique, linear accelerator, and portal imaging procedure. However, patients in the conventional treatment arm were treated with rectangular, open fields, whereas conformal radiotherapy was performed with conformally shaped fields using a multileaf collimator. All treatment plans were made with a 3D planning system. The planning target volume (PTV) was defined to be the gross target volume (GTV) + 15 mm. Acute toxicity was evaluated using the EORTC/RTOG morbidity scoring system. RESULTS Patient and tumor characteristics were equally distributed between both study groups. The maximum toxicity was 57% grade 1 and 26% grade 2 gastrointestinal toxicity; 47% grade 1, 17% grade 2, and 2% grade > 2 urological toxicity. Comparing both study arms, a reduction in gastrointestinal toxicity was observed (32% and 19% grade 2 toxicity for conformal and conventional radiotherapy, respectively; p = 0.02). Further analysis revealed a marked reduction in medication for anal symptoms: this accounts for a large part of the statistical difference in gastrointestinal toxicity (18% vs. 14% [p = ns] grade 2 rectum/sigmoid toxicity and 16% vs. 8% [p < 0.0001] grade 2 anal toxicity for conventional and conformal radiotherapy, respectively). A strong correlation between exposure of the anus and anal toxicity was found, which explained the difference in anal toxicity between both study arms. No difference in urological toxicity between both treatment arms was found, despite a relatively large difference in bladder DVHs. CONCLUSIONS The reduction in gastrointestinal morbidity was mainly accounted for by reduced toxicity for anal symptoms using 3DCRT. The study did not show a statistically significant reduction in acute rectum/sigmoid and bladder toxicity.

Catching errors with in vivo EPID dosimetry

The potential for detrimental incidents and the ever increasing complexity of patient treatments emphasize the need for accurate dosimetric verification in radiotherapy. For this reason, all curative treatments are verified, either pretreatment or in vivo, by electronic portal imaging device (EPID) dosimetry in the Radiation Oncology Department of the Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands. Since the clinical introduction of the method in January 2005 until August 2009, treatment plans of 4337 patients have been verified. Among these plans, 17 serious errors were detected that led to intervention. Due to their origin, nine of these errors would not have been detected with pretreatment verification. The method is illustrated in detail by the case of a plan transfer error detected in a 5×5Gy intensity-modulated radiotherapy (IMRT) rectum treatment. The EPID reconstructed dose at the isocenter was 6.3% below the planned value. Investigation of the plan transfer chain revealed that due to a network transfer error, the plan was corrupted. 3D analysis of the acquired EPID data revealed serious underdosage of the planning target volume: On average 11.6%, locally up to 20%. This report shows the importance of in vivo (EPID) dosimetry for all treatment plans as well as the ability of the method to assess the dosimetric impact of deviations found.

Clinical experience with EPID dosimetry for prostate IMRT pre-treatment dose verification

The aim of this study was to demonstrate how dosimetry with an amorphous silicon electronic portal imaging device (a-Si EPID) replaced film and ionization chamber measurements for routine pre-treatment dosimetry in our clinic. Furthermore, we described how EPID dosimetry was used to solve a clinical problem. IMRT prostate plans were delivered to a homogeneous slab phantom. EPID transit images were acquired for each segment. A previously developed in-house back-projection algorithm was used to reconstruct the dose distribution in the phantom mid-plane (intersecting the isocenter). Segment dose images were summed to obtain an EPID mid-plane dose image for each field. Fields were compared using profiles and in two dimensions with the y evaluation (criteria: 3%/3 mm). To quantify results, the average gamma (gamma avg), maximum gamma (gamma max), and the percentage of points with gamma < 1(P gamma < 1) were calculated within the 20% isodose line of each field. For 10 patient plans, all fields were measured with EPID and film at gantry set to 0 degrees. The film was located in the phantom coronal mid-plane (10 cm depth), and compared with the back-projected EPID mid-plane absolute dose. EPID and film measurements agreed well for all 50 fields, with (gamma avg) =0.16, (gamma max)=1.00, and (P gamma < 1)= 100%. Based on these results, film measurements were discontinued for verification of prostate IMRT plans. For 20 patient plans, the dose distribution was re-calculated with the phantom CT scan and delivered to the phantom with the original gantry angles. The planned isocenter dose (plan(iso)) was verified with the EPID (EPID(iso)) and an ionization chamber (IC(iso)). The average ratio, (EPID(iso)/IC(iso)), was 1.00 (0.01 SD). Both measurements were systematically lower than planned, with (EPID(iso)/plan(iso)) and (IC(iso)/plan(iso))=0.99 (0.01 SD). EPID mid-plane dose images for each field were also compared with the corresponding plane derived from the three dimensional (3D) dose grid calculated with the phantom CT scan. Comparisons of 100 fields yielded (gamma avg)=0.39, gamma max=2.52, and (P gamma < 1)=98.7%. Seven plans revealed under-dosage in individual fields ranging from 5% to 16%, occurring at small regions of overlapping segments or along the junction of abutting segments (tongue-and-groove side). Test fields were designed to simulate errors and gave similar results. The agreement was improved after adjusting an incorrectly set tongue-and-groove width parameter in the treatment planning system (TPS), reducing (gamma max) from 2.19 to 0.80 for the test field. Mid-plane dose distributions determined with the EPID were consistent with film measurements in a slab phantom for all IMRT fields. Isocenter doses of the total plan measured with an EPID and an ionization chamber also agreed. The EPID can therefore replace these dosimetry devices for field-by-field and isocenter IMRT pre-treatment verification. Systematic errors were detected using EPID dosimetry, resulting in the adjustment of a TPS parameter and alteration of two clinical patient plans. One set of EPID measurements (i.e., one open and transit image acquired for each segment of the plan) is sufficient to check each IMRT plan field-by-field and at the isocenter, making it a useful, efficient, and accurate dosimetric tool.

On-line set-up corrections during radiotherapy of patients with gynecologic tumors

PURPOSE Positioning of patients with gynecologic tumors for radiotherapy has proven to be relatively inaccurate. To improve the accuracy and reduce the margins from clinical target volume (CTV) to planning target volume (PTV), on-line set-up corrections were investigated. METHODS AND MATERIALS Anterior-posterior portal images of 14 patients were acquired using the first six monitor units (MU) of each irradiation fraction. The set-up deviation was established by matching three user-defined landmarks in portal and simulator image. If the two-dimensional deviation exceeded 4 mm, the table position was corrected. A second portal image was acquired using 30 MU of the remaining dose. This image was analyzed off-line using a semiautomatic contour match to obtain the final set-up accuracy. To verify the landmark match accuracy, the contour match was retrospectively performed on the six MU images as well. RESULTS The standard deviation (SD) of the distribution of systematic set-up deviations after correction was < 1 mm in left-right and cranio-caudal directions. The average random deviation was < 2 mm in these directions (1 SD). Before correction, all standard deviations were 2 to 3 mm. The landmark match procedure was sufficiently accurate and added on average 3 min to the treatment time. The application of on-line corrections justifies a CTV-to-PTV margin reduction to about 5 mm. CONCLUSIONS On-line set-up corrections significantly improve the positioning accuracy. The procedure increases treatment time but might be used effectively in combination with off-line corrections.

Comparison of prostate cancer treatment in two institutions: a quality control study

PURPOSE To minimize differences in the treatment planning procedure between two institutions within the context of a radiotherapy prostate cancer trial. PATIENTS AND METHODS Twenty-two patients with N0 M0 prostate cancer underwent a computed tomography (CT) scan for radiotherapy treatment planning. For all patients, the tumor and organs at risk were delineated, and a treatment plan was generated for a three-field technique giving a dose of 78 Gy to the target volume. Ten of the 22 cases were delineated and planned in the other institution as well. The delineated volumes and dose distributions were compared. RESULTS All treatments fulfilled the trial criteria. The mean volume ratio of the gross tumor volumes (GTVs) in both institutions was 1.01, while the mean volume ratio of the planning target volumes (PTVs) was 0.88. The three-dimensional (3D) PTV difference was 3 mm at the prostate apex and 6-8 mm at the seminal vesicles. This PTV difference was mainly caused by a difference in the method of 3D expansion, and disappeared when applying an improved algorithm in one institution. The treated volume (dose > or =95% of isocenter dose) reflects the size of the PTV and the conformity of the treatment technique. This volume was on average 66 cm3 smaller in institution A than in institution B; the effect of the PTV difference was 31 cm3 and the difference in technique accounted for 36 cm3. The mean delineated rectal volume including filling was 112 cm3 and 125 cm3 for institution A and B, respectively. This difference had a significant impact on the relative dose volume histogram (DVH) of the rectum. CONCLUSION Differences in GTV delineation were small and comparable to earlier quantified differences between observers in one institution. Different expansion methods for generation of the PTV significantly influenced the amount of irradiated tissue. Strict definitions of target and normal structures are mandatory for reliable trial results.

Microscopic disease extension in three dimensions for non-small-cell lung cancer: development of a prediction model using pathology-validated positron emission tomography and computed tomography features.

PURPOSE One major uncertainty in radiotherapy planning of non-small-cell lung cancer concerns the definition of the clinical target volume (CTV), meant to cover potential microscopic disease extension (MDE) around the macroscopically visible tumor. The primary aim of this study was to establish pretreatment risk factors for the presence of MDE. The secondary aim was to establish the impact of these factors on the accuracy of positron emission tomography (PET) and computed tomography (CT) to assess the total tumor-bearing region at pathologic examination (CTV(path)). METHODS AND MATERIALS 34 patients with non-small-cell lung cancer who underwent CT and PET before lobectomy were included. Specimens were examined microscopically for MDE. The gross tumor volume (GTV) on CT and PET (GTV(CT) and GTV(PET), respectively) was compared with the GTV and the CTV at pathologic examination, tissue deformations being taken into account. Using multivariate logistic regression, image-based risk factors for the presence of MDE were identified, and a prediction model was developed based on these factors. RESULTS MDE was found in 17 of 34 patients (50%). The MDE did not exceed 26 mm in 90% of patients. In multivariate analysis, two parameters (mean CT tumor density and GTV(CT)) were significantly associated with MDE. The area under the curve of the two-parameter prediction model was 0.86. Thirteen tumors (38%, 95% CI: 24-55%) were identified as low risk for MDE, being potential candidates for reduced-intensity therapy around the GTV. In the low-risk group, the effective diameter of the GTV(CT/PET) accurately represented the CTV(path). In the high-risk group, GTV(CT/PET) underestimated the CTV(path) with, on average, 19.2 and 26.7 mm, respectively. CONCLUSIONS CT features have potential to predict the presence of MDE. Tumors identified as low risk of MDE show lower rates of disease around the GTV than do high-risk tumors. Both CT and PET accurately visualize the CTV(path) in low-risk tumors but underestimate it in high-risk tumors.

Field margin reduction using intensity-modulated x-ray beams formed with a multileaf collimator

PURPOSE In axial, coplanar treatments with multiple fields, the superior and inferior ends of a planning target volume (PTV) are at risk to get underdosed due to the overlapping penumbras of all treatment fields. We have investigated a technique using intensity modulated x-ray beams that allows the use of small margins for definition of the superior and inferior field borders while still reaching a minimum PTV-dose of 95% of the isocenter dose. METHODS AND MATERIALS The applied intensity modulated beams, generated with a multileaf collimator, include narrow (1.1-1.6 cm) boost fields to increase the dose in the superior and inferior ends of the PTV. The benefits of this technique have been assessed using 3D treatment plans for 10 prostate cancer patients. Treatment planning was performed with the Cadplan 3D planning system (Varian-Dosetek). Dose calculations for the narrow boost fields have been compared with measurements. The application of the boost fields has been tested on the MM50 Racetrack Microtron (Scanditronix Medical AB), which allows fully computer-controlled setup of all involved treatment fields. RESULTS Compared to our standard technique, the superior-inferior field length can be reduced by 1.6 cm, generally yielding smaller volumes of rectum and bladder in the high dose region. For the narrow boost fields, calculated relative dose distributions agree within 2% or 0.2 cm with measured dose distributions. For accurate monitor unit calculations, the phantom scatter table used in the Cadplan system had to be modified using measured data for square fields smaller than 4 x 4 cm2. The extra time needed at the MM50 for the setup and delivery of the boost fields is usually about 1 min. CONCLUSION The proposed use of intensity modulated beams yields improved conformal dose distributions for treatment of prostate cancer patients with a superior-inferior field size reduction of 1.6 cm. Treatments of other tumor sites can also benefit from the application of the boost fields.

Using histopathology breast cancer data to reduce clinical target volume margins at radiotherapy

PURPOSE This study aimed to quantify the incidence and extension of microscopic disease around primary breast tumors in patients undergoing breast-conserving therapy (BCT), focusing on a potential application to reduce radiotherapy boost volumes. METHODS AND MATERIALS An extensive pathology tumor-distribution study was performed using 38 wide local excision specimens of BCT patients. Specimen orientation was recorded and microscopic findings reconstructed to assess the incidence of microscopic disease around the macroscopic tumor. A model of disease spread was built, showing probability of disease extension outside a treated volume (P(out,vol)). The model was applied in 10 new BCT patients. Taking asymmetry of tumor excision into account, new asymmetric margins for the clinical target volume of the boost (CTV(boost)) were evaluated that minimize the volume without increasing P(out,TTV) (TTV being total treated volume: V(surgery) + CTV(boost)). Potential reductions in CTV(boost) and TTV were evaluated. RESULTS Microscopic disease beyond the tumor boundary occurred isotropically at distances > 1 cm (intended surgical margin) and > 1.5 cm (intended TTV margin) in 53% and 36% of the excision specimens, respectively. In the 10 prospective patients, the average P(out,TTV) was, however, only 16% due to larger surgical margins than intended in some directions. Asymmetric CTV(boost) margins reduced the CTV(boost) and TTV by 27% (20 cc) and 12% (21 cc) on average, without compromising tumor coverage. CONCLUSIONS Microscopic disease extension may occur beyond the current CTV(boost) in approximately one sixth of patients. An asymmetric CTV(boost) that corrects for asymmetry of the surgical excision has the potential to reduce boost volumes while maintaining tumor coverage.

In aqua vivo EPID dosimetry

PURPOSE At the Netherlands Cancer Institute--Antoni van Leeuwenhoek Hospital in vivo dosimetry using an electronic portal imaging device (EPID) has been implemented for almost all high-energy photon treatments of cancer with curative intent. Lung cancer treatments were initially excluded, because the original back-projection dose-reconstruction algorithm uses water-based scatter-correction kernels and therefore does not account for tissue inhomogeneities accurately. The aim of this study was to test a new method, in aqua vivo EPID dosimetry, for fast dose verification of lung cancer irradiations during actual patient treatment. METHODS The key feature of our method is the dose reconstruction in the patient from EPID images, obtained during the actual treatment, whereby the images have been converted to a situation as if the patient consisted entirely of water; hence, the method is termed in aqua vivo. This is done by multiplying the measured in vivo EPID image with the ratio of two digitally reconstructed transmission images for the unit-density and inhomogeneous tissue situation. For dose verification, a comparison is made with the calculated dose distribution with the inhomogeneity correction switched off. IMRT treatment verification is performed for each beam in 2D using a 2D γ evaluation, while for the verification of volumetric-modulated arc therapy (VMAT) treatments in 3D a 3D γ evaluation is applied using the same parameters (3%, 3 mm). The method was tested using two inhomogeneous phantoms simulating a tumor in lung and measuring its sensitivity for patient positioning errors. Subsequently five IMRT and five VMAT clinical lung cancer treatments were investigated, using both the conventional back-projection algorithm and the in aqua vivo method. The verification results of the in aqua vivo method were statistically analyzed for 751 lung cancer patients treated with IMRT and 50 lung cancer patients treated with VMAT. RESULTS The improvements by applying the in aqua vivo approach are considerable. The percentage of γ values ≤1 increased on average from 66.2% to 93.1% and from 43.6% to 97.5% for the IMRT and VMAT cases, respectively. The corresponding mean γ value decreased from 0.99 to 0.43 for the IMRT cases and from 1.71 to 0.40 for the VMAT cases, which is similar to the accepted clinical values for the verification of IMRT treatments of prostate, rectum, and head-and-neck cancers. The deviation between the reconstructed and planned dose at the isocenter diminished on average from 5.3% to 0.5% for the VMAT patients and was almost the same, within 1%, for the IMRT cases. The in aqua vivo verification results for IMRT and VMAT treatments of a large group of patients had a mean γ of approximately 0.5, a percentage of γ values ≤1 larger than 89%, and a difference of the isocenter dose value less than 1%. CONCLUSIONS With the in aqua vivo approach for the verification of lung cancer treatments (IMRT and VMAT), we can achieve results with the same accuracy as obtained during in vivo EPID dosimetry of sites without large inhomogeneities.