[en] Purpose: To quantify in three dimensions the geometric uncertainties of bladder irradiation (i.e., uncertainties in target delineation, organ motion, and patient setup). Methods and Materials: Pelvic CT images were obtained for 10 male bladder cancer patients. Apart from the initial planning CT scan, three follow-up scans were made for each of the patients. The bladder volumes in the planning CT scan were outlined by seven radiation oncologists. One observer also delineated the bladder volumes in the follow-up scans. Two-dimensional scalar maps of the interobserver variation and organ motion of the bladder surfaces were constructed. The setup errors were derived from the portal imaging results of the pooled group of bladder and prostate patients. Results: All bladder volumes were consistently outlined by all observers. Generally small variations occurred (1.5-3 mm, 1 SD), although in 50% of the patients, larger discrepancies were observed in discriminating the bladder from the base of the prostate. Analysis of the portal imaging data showed setup errors of up to 3 mm (1 SD). Organ motion is the predominant geometric uncertainty in the radiotherapy process (5 mm, 1 SD, at the cranial side of the bladder), although 9 of 10 patients were able to preserve a fairly reproducible bladder volume during the complete treatment course. Conclusion: Anisotropic margins between the clinical target volume and planning target volume are needed in conformal radiotherapy of the bladder. Especially at the cranial side of the bladder, larger margins are needed because of the impact of bladder shape variation

[en] Purpose: To define margins for systematic rotations and translations, based on known statistical distributions of these deviations. Methods and Materials: The confidence interval-based expansion method for translations, known as the ''rolling ball algorithm,'' was extended to include rotations. This new method, which we call the Rotational and Translational Confidence Limit (RTCL) method, is exact for a point with arbitrary rotations and translations or for a finite shape with rotations only. The method was compared with two existing expansion methods: a rolling ball algorithm without rotations, and a convolution (blurring) method which included rotations. On the basis of these methods, planning target volumes (PTVs, expanded clinical target volumes [CTVs]) were constructed for a number of shapes (a sphere, a sphere with an extension, and three prostate cases), and evaluated in several ways by means of a Monte Carlo method. The accuracy of each method was measured by determining the probability of finding the CTV completely inside the PTV (P_CTVinPTV), using parameters that yield a 90% probability for a sphere-shaped CTV without rotations. Furthermore, with the expansion parameters adjusted to give an equal P_CTVinPTV for all methods, PTV volumes were compared. Results: With the expansion algorithm parameters chosen to yield P_CTVinPTV = 90% for a sphere, an average P_CTVinPTV of 84%, 57%, and 46% was obtained for the other shapes, using the RTCL method, coverage probability, and rolling ball, respectively. With the parameters adjusted to yield an equal P_CTVinPTV for all methods, the PTV volume was on average 8% larger for the coverage probability method and 15% larger for the rolling ball algorithm compared to the RTCL method. Conclusion: The RTCL method provides an accurate way to include the effects of systematic rotations in the margin. Compared to other algorithms, the method is less sensitive to the shape of the CTV, and, given a fixed probability of finding the CTV inside the PTV, a smaller PTV volume can be obtained

[en] Purpose: To provide an analytical description of the effect of random and systematic geometrical deviations on the target dose in radiotherapy and to derive margin rules. Methods and Materials: The cumulative dose distribution delivered to the clinical target volume (CTV) is expressed analytically. Geometrical deviations are separated into treatment execution (random) and treatment preparation (systematic) variations. The analysis relates each possible preparation (systematic) error to the dose distribution over the CTV and allows computation of the probability distribution of, for instance, the minimum dose delivered to the CTV. Results: The probability distributions of the cumulative dose over a population of patients are called dose-population histograms in short. Large execution (random) variations lead to CTV underdosage for a large number of patients, while the same level of preparation (systematic) errors leads to a much larger underdosage for some of the patients. A single point on the histogram gives a simple ''margin recipe.'' For example, to ensure a minimum dose to the CTV of 95% for 90% of the patients, a margin between CTV and planning target volume (PTV) is required of 2.5 times the total standard deviation (SD) of preparation (systematic) errors (Σ) plus 1.64 times the total SD of execution (random) errors (σ') combined with the penumbra width, minus 1.64 times the SD describing the penumbra width (σ_p). For a σ_p of 3.2 mm, this recipe can be simplified to 2.5 Σ + 0.7 σ'. Because this margin excludes rotational errors and shape deviations, it must be considered as a lower limit for safe radiotherapy. Conclusion: Dose-population histograms provide insight into the effects of geometrical deviations on a population of patients. Using a dose-probability based approach, simple algorithms for choosing margins were derived

[en] Purpose: To determine, in three-dimensions, the difference between prostate delineation in magnetic resonance (MR) and computer tomography (CT) images for radiotherapy treatment planning. Patients and Methods: Three radiation oncologists, considered experts in the field, outlined the prostate without seminal vesicles both on CT, and axial, coronal, and sagittal MR images for 18 patients. To compare the resulting delineated prostates, the CT and MR scans were matched in three-dimensions using chamfer matching on bony structures. The volumes were measured and the interscan and interobserver variation was determined. The spatial difference between delineation in CT and MR (interscan variation) as well as the interobserver variation were quantified and mapped three-dimensionally (3D) using polar coordinates. A urethrogram was performed and the location of the tip of the dye column was compared with the apex delineated in CT and MR images. Results: Interscan variation: CT volumes were larger than the axial MR volumes in 52 of 54 delineations. The average ratio between the CT and MR volumes was 1.4 (standard error of mean, SE: 0.04) which was significantly different from 1 (p < 0.005). Only small differences were observed between the volumes outlined in the various MR scans, although the coronal MR volumes were smallest. The CT derived prostate was 8 mm (standard deviation, SD: 6 mm) larger at the base of the seminal vesicles and 6 mm (SD 4 mm) larger at the apex of the prostate than the axial MRI. Similar figures were obtained for the CT and the other MRI scans. Interobserver variation: The average ratio between the volume derived by one observer for a particular scan and patient and the average volume was 0.95, 0.97, and 1.08 (SE 0.01) for the three observers, respectively. The 3D pattern of the overall observer variation (1 SD) for CT and axial MRI was similar and equal to 3.5 to 2.8 mm at the base of the seminal vesicles and 3 mm at the apex. Conclusion: CT-derived prostate volumes are larger than MR derived volumes, especially toward the seminal vesicles and the apex of the prostate. This interscan variation was found to be larger than the interobserver variation. Using MRI for delineation of the prostate reduces the amount of irradiated rectal wall, and could reduce rectal and urological complications

[en] Purpose: To determine the influence of observer variation and treatment planner variation on the dose delivered to the target and normal structures when irradiating paranasal sinus carcinomas. Patients and Methods: Nine patients with paranasal sinus tumors underwent debulking surgery and subsequent radiation therapy. Two observers from two different institutions delineated the clinical target volumes (CTVs) for the elective and the boost volumes. These volumes were expanded in three dimensions with a 5-mm margin. At both institutions, a three-dimensional conformal treatment plan of 46 Gy to the elective volumes, plus 20 Gy to the boost target volumes, was designed. The delineated volumes and treatment plans were compared. Results: The mean volume ratio between institutions of the elective CTVs was 0.9 (standard error = 0.05). The differences were located mainly at the bottom of the nasal cavity and at the frontal border of the target areas. The differences in boost CTVs were large; the mean volume ratio was 2.6 (standard error = 0.58). After expansion of the CTV, the mean distance between the planning target volume (PTV) and the chiasm differed by 0.5 cm between the two institutions. Cases with smaller distances between the PTV and the chiasm had more underdosage to the PTV. This effect was less pronounced for institution A (1 vol.%/cm) than for institution B (10 vol.%/cm) treatment plans, which were less conformal. When the treatment plan was designed for the PTV of institution B, 23 volume % of the PTV of institution A received <95% of the prescribed dose. If the treatment plan was designed for the (on average larger) PTV of institution A, the underdosed volume of PTV at institution B was 17%. The relative underdosage to the 'other' PTV was larger when the original treatment plan was more conformal. Conclusion: In the irradiation of paranasal sinus cancer, both the treatment planner and the observer have a significant influence on the dose to the target and organs at risk. Both effects are similar in magnitude. The observer effect increases with more conformal treatment plans. Minimizing the observer variation is important for adequate irradiation of paranasal sinus cancer

[en] Background and purpose: To compare intensity-modulated treatment plans of patients with head and neck cancer generated by forward and inverse planning. Materials and methods: Ten intensity-modulated treatment plans, planned and treated with a step and shoot technique using a forward planning approach, were retrospectively re-planned with an inverse planning algorithm. For this purpose, two strategies were applied. First, inverse planning was performed with the same beam directions as forward planning. In addition, nine equidistant, coplanar incidences were used. The main objective of the optimisation process was the sparing of the parotid glands beside an adequate treatment of the planning target volume (PTV). Inverse planning was performed both with pencil beam and Monte Carlo dose computation to investigate the influence of dose computation on the result of the optimisation. Results: In most cases, both inverse planning strategies managed to improve the treatment plans distinctly due to a better target coverage, a better sparing of the parotid glands or both. A reduction of the mean dose by 3-11 Gy for at least one of the parotid glands could be achieved for most of the patients. For three patients, inverse planning allowed to spare a parotid gland that had to be sacrificed by forward planning. Inverse planning increased the number of segments compared to forward planning by a factor of about 3; from 9-15 to 27-46. No significant differences for PTV and parotid glands between both inverse planning approaches were found. Also, the use of Monte Carlo instead of pencil beam dose computation did not influence the results significantly. Conclusion: The results demonstrate the potential of inverse planning to improve intensity-modulated treatment plans for head and neck cases compared to forward planning while retaining clinical utility in terms of treatment time and quality assurance

[en] Background and purpose: To develop and validate an adaptive intervention strategy for radiotherapy of head-and-neck cancer that accounts for systematic deformations by modifying the planning-CT (pCT) to the average misalignments in daily cone beam CT (CBCT) measured with deformable registration (DR). Methods and materials: Daily CBCT scans (808 scans) for 25 patients were retrospectively registered to the pCT with B-spline DR. The average deformation vector field (< DVF>) was used to deform the pCT for adaptive intervention. Two strategies were simulated: single intervention after 10 fractions and weekly intervention with an < DVF> from the previous week. The model was geometrically validated with the residual misalignment of anatomical landmarks both on bony-anatomy (BA; automatically generated) and soft-tissue (ST; manually identified). Results: Systematic deformations were 2.5/3.4 mm vector length (BA/ST). Single intervention reduced deformations to 1.5/2.7 mm (BA/ST). Weekly intervention resulted in 1.0/2.2 mm (BA/ST) and accounted better for progressive changes. 15 patients had average systematic deformations >2 mm (BA): reductions were 1.1/1.9 mm (single/weekly BA). ST improvements were underestimated due to observer and registration variability. Conclusions: Adaptive intervention with a pCT modified to the average anatomy during treatment successfully reduces systematic deformations. The improved accuracy could possibly be exploited in margin reduction and/or dose escalation

[en] Background and purpose: Concomitant chemoradiation is more and more used for advanced head and neck cancer. It improves local control and survival compared to radiotherapy alone, but goes along with serious toxicity. This study was set up to determine the relationship between patient-, tumour- and treatment-related factors and acute/late toxicity after concomitant chemoradiation. Patients and methods: One hundred and twenty-five consecutive patients with newly diagnosed inoperable stage III and IV head and neck cancer were enrolled for intra-arterial chemoradiation. There were 28 women (22%) and 97 men (78%) and the mean age was 55 years (range 30-80). One hundred and nine patients had stage IV disease (87%), 16 patients (13%) had stage III disease. Statistical analyses were performed to identify an association between factors and acute/late toxicity. Results: There were eight treatment-related deaths (6%). Severe acute toxicity (grade 3-4), mainly mucositis and dysphagia as categorized by the RTOG toxicity criteria, was recorded in 51% of the patients. Leucopenia (grade 3-4) occurred in 39% and aspiration pneumonia in 20% of patients. Tracheotomy was necessary in 15 (12%) patients. Neurological complications during treatment occurred in 3 (2%) patients. Severe late toxicity occurred in 34% of the patients. The most important of these were pneumonia (14%), osteoradionecrosis (9%) and swallowing problems with permanent percutaneous gastrostomy (20%). Statistical analysis did show a significant association between site and severe acute mucositis (p = 0.007), site and osteoradionecrosis (p = 0.014) and age and xerostomia (p = 0.004). Conclusions: Chemoradiation is frequently associated with serious toxicity. Oral cavity tumours and older age are related to acute mucositis/osteoradionecrosis and xerostomia, respectively

[en] 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 ≥ 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

[en] Purpose: To study the potential impact of the combined use of CT and MRI scans on the Gross Tumor Volume (GTV) estimation and interobserver variation. Methods and Materials: Four observers outlined the GTV in six patients with advanced head and neck cancer on CT, axial MRI, and coronal or sagittal MRI. The MRI scans were subsequently matched to the CT scan. The interobserver and interscan set variation were assessed in three dimensions. Results: The mean CT derived volume was a factor of 1.3 larger than the mean axial MRI volume. The range in volumes was larger for the CT than for the axial MRI volumes in five of the six cases. The ratio of the scan set common (i.e., the volume common to all GTVs) and the scan set encompassing volume (i.e., the smallest volume encompassing all GTVs) was closer to one in MRI (0.3-0.6) than in CT (0.1-0.5). The rest volumes (i.e., the volume defined by one observer as GTV in one data set but not in the other data set) were never zero for CT vs. MRI nor for MRI vs. CT. In two cases the craniocaudal border was poorly recognized on the axial MRI but could be delineated with a good agreement between the observers in the coronal/sagittal MRI. Conclusions: MRI-derived GTVs are smaller and have less interobserver variation than CT-derived GTVs. CT and MRI are complementary in delineating the GTV. A coronal or sagittal MRI adds to a better GTV definition in the craniocaudal direction