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Purpose: To investigate the applicability of 3-dimensional (3D) surface imaging for image guidance in deep-inspiration breath-hold radiation therapy (DIBH-RT) for patients with left-sided breast cancer. For this purpose, setup data based on captured 3D surfaces was compared with setup data based on cone beam computed tomography (CBCT)., Methods and Materials: Twenty patients treated with DIBH-RT after breast-conserving surgery (BCS) were included. Before the start of treatment, each patient underwent a breath-hold CT scan for planning purposes. During treatment, dose delivery was preceded by setup verification using CBCT of the left breast. 3D surfaces were captured by a surface imaging system concurrently with the CBCT scan. Retrospectively, surface registrations were performed for CBCT to CT and for a captured 3D surface to CT. The resulting setup errors were compared with linear regression analysis. For the differences between setup errors, group mean, systematic error, random error, and 95% limits of agreement were calculated. Furthermore, receiver operating characteristic (ROC) analysis was performed., Results: Good correlation between setup errors was found: R(2)=0.70, 0.90, 0.82 in left-right, craniocaudal, and anterior-posterior directions, respectively. Systematic errors were ≤0.17 cm in all directions. Random errors were ≤0.15 cm. The limits of agreement were -0.34-0.48, -0.42-0.39, and -0.52-0.23 cm in left-right, craniocaudal, and anterior-posterior directions, respectively. ROC analysis showed that a threshold between 0.4 and 0.8 cm corresponds to promising true positive rates (0.78-0.95) and false positive rates (0.12-0.28)., Conclusions: The results support the application of 3D surface imaging for image guidance in DIBH-RT after BCS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To determine the use of surgical clips as a surrogate for localization of the excision cavity and to quantify the stability of the clips' positions during the course of external beam radiotherapy for breast cancer patients, using cone beam computed tomography (CBCT) scans., Methods and Materials: Twenty-one breast cancer patients with surgical clips placed in the breast excision cavity were treated in a supine position with 28 daily fractions. CBCT scans were regularly acquired for a setup correction protocol. Retrospectively, the CBCT scans were registered to the planning CT scans, using gray-value registration of the excision cavity region and chamfer matching of the clips. Subsequently, residual setup errors (systematic [Σ] and random [σ]) of the excision cavity were estimated relative to the clips' registration. Finally, the stability of the clips' positions were quantified as the movement of each separate clip according to the center of gravity of the excision cavity., Results: When clips were used for online setup corrections, the residual errors of the excision cavity were Σ(left-right) = 1.2, σ(left-right) = 1.0; Σ(cranial-caudal)  = 1.3, σ(cranial-caudal) = 1.2; and Σ(anterior-posterior)  = 0.7, σ(anterior-posterior) = 0.9 mm. Furthermore, the average distance (over all patients) between the clips and centers of gravity of the excision cavities was 18.8 mm (on the planning CT) and was reduced to 17.4 mm (measured on the last CBCT scan)., Conclusion: Clips move in the direction of the center of gravity of the excision cavity, on average, 1.4 mm. The clips are good surrogates for locating the excision cavity and providing small residual errors., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the feasibility, cardiac dose reduction, and the influence of the setup error on the delivered dose for fluoroscopy-guided deep inspiration breath hold (DIBH) irradiation using a cone-beam CT for irradiation of left-sided breast cancer patients., Methods and Materials: Nineteen patients treated according to the DIBH protocol were evaluated regarding dose to the ipsilateral breast (or thoracic wall), heart, (left ventricle [LV] and left anterior descending artery [LAD]), and lung. The DIBH treatment plan was compared to the free-breathing (FB) treatment planning and to the dose data in which setup error was taken into account (i.e., actual delivered dose)., Results: The largest setup variability was observed in the direction perpendicular to the RT field (μ = -0.8 mm, Σ = 2.9 mm, σ = 2.0 mm). The mean (D(mean)) and maximum (D(max)) doses of the DIBH treatment plan was significantly lower compared with the FB treatment plan for the heart (34% and 25%, p < 0.001), LV (71% and 28%, p < 0.001), and LAD (52% and 39.8%, p < 0.001). For some patients, large differences were observed between the heart D(max) according to the DIBH treatment plan and the actual delivered dose (up to 71%), although D(max) was always smaller than the planned FB dose (mean group reduction = 29%, p < 0.001)., Conclusion: The image-guided DIBH treatment protocol is a feasible irradiation method with small setup variability that significantly reduces the dose to the heart, LV, and LAD., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To quantify the differences in setup errors measured with the cone-beam computed tomography (CBCT) and electronic portal image devices (EPID) in breast cancer patients., Methods and Materials: Repeat CBCT scan were acquired for routine offline setup verification in 20 breast cancer patients. During the CBCT imaging fractions, EPID images of the treatment beams were recorded. Registrations of the bony anatomy for CBCT to planning CT and EPID to digitally reconstructed-radiographs (DRRs) were compared. In addition, similar measurements of an anthropomorphic thorax phantom were acquired. Bland-Altman and linear regression analysis were performed for clinical and phantom registrations. Systematic and random setup errors were quantified for CBCT and EPID-driven correction protocols in the EPID coordinate system (U, V), with V parallel to the cranial-caudal axis and U perpendicular to V and the central beam axis., Results: Bland-Altman analysis of clinical EPID and CBCT registrations yielded 4 to 6-mm limits of agreement, indicating that both methods were not compatible. The EPID-based setup errors were smaller than the CBCT-based setup errors. Phantom measurements showed that CBCT accurately measures setup error whereas EPID underestimates setup errors in the cranial-caudal direction. In the clinical measurements, the residual bony anatomy setup errors after offline CBCT-based corrections were Σ(U) = 1.4 mm, Σ(V) = 1.7 mm, and σ(U) = 2.6 mm, σ(V) = 3.1 mm. Residual setup errors of EPID driven corrections corrected for underestimation were estimated at Σ(U) = 2.2mm, Σ(V) = 3.3 mm, and σ(U) = 2.9 mm, σ(V) = 2.9 mm., Conclusion: EPID registration underestimated the actual bony anatomy setup error in breast cancer patients by 20% to 50%. Using CBCT decreased setup uncertainties significantly., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To investigate the stability of a novel type of markers used in partial bladder tumor irradiation and tumor deformation as indicated by the markers., Materials and Methods: In 15 patients with solitary bladder cancer, lipiodol was injected in the bladder wall during flexible cystoscopy to identify the tumor. A planning CT scan was made, followed by daily cone-beam CT (CBCT) scans during treatment. To study the accuracy of using these markers for image guidance, uncertainties U1 and U2 were calculated, which were defined as the difference between submask registration (covering single marker) and the average of all submask registrations and the difference between the submask registration and the general mask registration (including all markers), respectively. Finally, to study tumor deformation, the relative movement of each marker pair was correlated with the relative bladder volume (RBV)., Results: The analyzed patients had 2.3 marker injections on average. The lipiodol spot size was 0.72 +/- 1.1 cm(3). The intensity of spots in both CT and CBCT was significantly higher than the surrounding bladder tissue. The uncertainties U1 and U2 were comparable, and the uncertainties in left-right direction (0.14-0.19 cm) were smaller than those in cranial-caudal and anterior-posterior directions (0.19-0.32 cm). The relative marker movement of within-zone marker pairs was much smaller (and has less dependence on the RBV) than across-zones marker pairs., Conclusions: Lipiodol markers are a feasible method to track bladder tumor by using online CBCT. Tumor deformation is observed, especially for tumors that cross the defined bladder zones.

Purpose: To quantify the interfraction position variability of the excision cavity (EC) and to compare the rib and breast surface as surrogates for the cavity. Additionally, we sought to determine the required margin for on-line, off-line and no correction protocols in external beam radiotherapy., Methods and Materials: A total of 20 patients were studied who had been treated in the supine position for 28 daily fractions. Cone-beam computed tomography scans were regularly acquired according to a shrinking action level setup correction protocol based on bony anatomy registration of the ribs and sternum. The position of the excision area was retrospectively analyzed by gray value cone-beam computed tomography-to-computed tomography registration. Subsequently, three setup correction strategies (on-line, off-line, and no corrections) were applied, according to the rib and breast surface registrations, to estimate the residual setup errors (systematic [Sigma] and random [sigma]) of the excision area. The required margins were calculated using a margin recipe., Results: The image quality of the cone-beam computed tomography scans was sufficient for localization of the EC. The margins required for the investigated setup correction protocols and the setup errors for the left-right, craniocaudal and anteroposterior directions were 8.3 mm (Sigma = 3.0, sigma = 2.6), 10.6 mm (Sigma = 3.8, sigma = 3.2), and 7.7 mm (Sigma = 2.7, sigma = 2.9) for the no correction strategy; 5.6 mm (Sigma = 2.0, Sigma = 1.8), 6.5 mm (Sigma = 2.3, sigma = 2.3), and 4.5 mm (Sigma = 1.5, sigma = 1.9) for the on-line rib strategy; and 5.1 mm (Sigma = 1.8, sigma = 1.7), 4.8 mm (Sigma = 1.7, sigma = 1.6), and 3.3 mm (Sigma = 1.1, sigma = 1.6) for the on-line surface strategy, respectively., Conclusion: Considerable geometric uncertainties in the position of the EC relative to the bony anatomy and breast surface have been observed. By using registration of the breast surface, instead of the rib, the uncertainties in the position of the EC area were reduced.

Purpose: To evaluate the first clinical results of an off-line adaptive radiotherapy (ART) protocol for prostate cancer using kilovoltage cone-beam computed tomography (CBCT) in combination with a diet and mild laxatives., Methods and Materials: Twenty-three patients began treatment with a planning target volume (PTV) margin of 10 mm. The CBCT scans acquired during the first six fractions were used to generate an average prostate clinical target volume (AV-CTV), and average rectum (AV-Rect). Using these structures, a new treatment plan was generated with a 7-mm PTV margin. Weekly CBCT scans were used to monitor the CTV coverage. A diet and mild laxatives were introduced to improve image quality and reduce prostate motion., Results: Twenty patients were treated with conform ART protocol. For these patients, 91% of the CBCT scans could be used to calculate the AV-CTV and AV-Rect. In 96% of the follow-up CBCT scans, the CTV was located within the average PTV. In the remaining 4%, the prostate extended the PTV by a maximum of 1 mm. Systematic and random errors for organ motion were reduced by a factor of two compared with historical data without diet and laxatives. An average PTV reduction of 29% was achieved. The volume of the AV-Rect that received >65 Gy was reduced by 19%. The mean dose to the anal wall was reduced on average by 4.8 Gy., Conclusions: We safely reduced the high-dose region by 29%. The reduction in irradiated volume led to a significant reduction in the dose to the rectum. The diet and laxatives improved the image quality and tended to reduce prostate motion.

Purpose: Kilovoltage cone-beam computed tomography (CBCT) has been developed to provide accurate soft-tissue and bony setup information. We evaluated clinical CBCT setup data and compared CBCT measurements with electronic portal imaging device (EPID) images for lung cancer patients., Methods and Materials: The setup error for CBCT scans at the treatment unit relative to the planning CT was measured for 62 patients (524 scans). For 19 of these patients (172 scans) portal images were also made. The mean, systematic setup error (Sigma), and random setup error (sigma) were calculated for the CBCT and the EPID. The differences between CBCT and EPID and the rotational setup error derived from the CBCT were also evaluated. An offline shrinking action level correction protocol, based on the CBCT measurements, was used to reduce systematic setup errors and the impact of this protocol was evaluated., Results: The CBCT setup errors were significantly larger than the EPID setup errors for the cranial-caudal and anterior-posterior directions (p < 0.05). The mean overall setup errors after correction measured with the CBCT were 0.2 mm (Sigma = 1.6 mm, sigma = 2.9 mm) in the left-right, -0.8 mm (Sigma = 1.7 mm, sigma = 4.0 mm) in cranial-caudal and 0.0 mm (Sigma = 1.5 mm, sigma = 2.0 mm) in the anterior-posterior direction. Using our correction protocol only 2 patients had mean setup errors larger than 5 mm, without this correction protocol 51% of the patients would have had a setup error larger than 5 mm., Conclusion: Use of CBCT scans provided more accurate information concerning the setup of lung cancer patients than did portal imaging.

Purpose: To determine the planning target volume (PTV) margin for an adaptive radiotherapy procedure that uses five computed tomography (CT) scans to calculate an average prostate position and rectum shape. To evaluate alternative methods to determine an average rectum based on a single delineation., Methods and Materials: Repeat CT scans (8-13) of 19 patients were used. The contoured prostates of the first four scans were matched on the planning CT (pCT) prostate contours. With the resulting translations and rotations the average prostate position was determined. An average rectum was obtained by either averaging the coordinates of corresponding points on the rectal walls or by selecting the "best" rectum or transforming the pCT rectum. Dose distributions were calculated for various expanded average prostates. The remaining CT scans were used to determine the dose received by prostate and rectum during treatment., Results: For the prostate of the pCT scan and a 10-mm margin, all patients received more than 95% of the prescribed dose to 95% of the prostate. For the average prostate, a margin of 7 mm was needed to obtain a similar result (average PTV reduction 30%). The average rectum overestimated the mean dose to the rectum by 0.4 +/- 1.6 Gy, which was better than the pCT rectum (2.1 +/- 3.0 Gy) and the alternative average rectums (1.0 +/- 2.6 Gy and 1.4 +/- 3.2 Gy)., Conclusions: Our adaptive procedure allows for reduction of the PTV margin to 7 mm without decreasing prostate coverage during treatment. For accurate estimation of the rectum dose, rectums need to be delineated and averaged over multiple scans.

Purpose: First, to quantify bladder-tumor motion in 3 dimensions during a 4-week to 5-week course of external radiotherapy. Second, to relate the motion to the tumor location on the bladder wall. Third, to extensively evaluate gross tumor volume (GTV) shape and volume changes during the course of the treatment., Methods and Materials: Multiple repeat computed tomography (CT) images were obtained for 21 bladder cancer patients. These scans were matched to the rigid bony anatomy. For each patient, the main direction and magnitude of the tumor movement was determined by use of principle-component analysis. To study GTV shape changes, all GTVs were registered to the GTV in the planning CT scan, and the residual shape errors were determined by measurement of edge variations perpendicular to the median surface., Results: Gross tumor volume translations were largest in cranial-caudal and anterior-posterior direction (SD, 0.1 to approximately 0.9 cm). The translations were strongly correlated with the tumor location on the bladder wall. The average value of the local standard deviations of the GTV shape ranged from 0.1 to approximately 0.35 cm., Conclusions: Despite large differences in bladder filling, variations in GTV shape were small compared with variations in GTV position. Geometric uncertainties in the GTV position depended strongly on the tumor location on the bladder wall.

Purpose: To evaluate the feasibility of adaptive radiotherapy (ART) in combination with a partial bladder irradiation., Methods and Materials: Twenty-one patients with solitary T1-T4 N0M0 bladder cancer were treated to the bladder tumor + 2 cm margin planning target volume (PTV(CONV)). During the first treatment week, five daily computed tomography (CT) scans were made immediately before or after treatment. In the second week, a volume was constructed encompassing the gross tumor volumes (GTVs) on the planning scan and the five CT scans (GTV(ART)). The GTV(ART) was expanded with a 1 cm margin for the construction of a PTV(ART). Starting in the third week, patients were treated to PTV(ART). Repeat CT scans were used to evaluate treatment accuracy., Results: On 5 of 91 repeat CT scans (5%), the GTV was not adequately covered by the PTV(ART). On treatment planning, there was only one scan in which the GTV was not adequately covered by the 95% isodose. On average, the treatment volumes were reduced by 40% when comparing PTV(ART) with PTV(CONV) (p < 0.0001)., Conclusion: The adaptive strategy for bladder cancer is an effective way to deal with treatment errors caused by variations in bladder tumor position and leads to a substantial reduction in treatment volumes.

Purpose: To evaluate the impact of different tabletops with or without a knee support on the position of the rectum, prostate, and bulb of the penis; and to evaluate the effect of these patient-positioning devices on treatment planning., Methods and Materials: For 10 male volunteers, five MRI scans were made in four different positions: on a flat tabletop with knee support, on a flat tabletop without knee support, on a rounded tabletop with knee support, and on a rounded tabletop without knee support. The fifth scan was in the same position as the first. With image registration, the position differences of the rectum, prostate, and bulb of the penis were measured at several points in a sagittal plane through the central axis of the prostate. A planning target volume was generated from the delineated prostates with a margin of 10 mm in three dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each planning target volume. Dose-volume histograms were calculated for all rectal walls., Results: The shape of the tabletop did not affect the rectum and prostate position. Addition of a knee support shifted the anterior and posterior rectal walls dorsally. For the anterior rectal wall, the maximum dorsal shift was 9.9 mm (standard error of the mean [SEM] 1.7 mm) at the top of the prostate. For the posterior rectal wall, the maximum dorsal shift was 10.2 mm (SEM 1.5 mm) at the middle of the prostate. Therefore, the rectal filling was pushed caudally when a knee support was added. The knee support caused a rotation of the prostate around the left-right axis at the apex (i.e., a dorsal rotation) by 5.6 degrees (SEM 0.8 degrees ) and shifts in the caudal and dorsal directions of 2.6 mm (SEM 0.4 cm) and 1.4 mm (SEM 0.6 mm), respectively. The position of the bulb of the penis was not influenced by the use of a knee support or rounded tabletop. The volume of the rectal wall receiving the same dose range (e.g., 40-75 Gy) was reduced by 3.5% (SEM 0.9%) when a knee support was added. No significant differences were observed between the first and fifth scan (flat tabletop with knee support) for all measured points, thereby excluding time trends., Conclusions: The rectum and prostate were significantly shifted dorsally by the use of a knee support. The rectum shifted more than the prostate, resulting in a dose benefit compared with irradiation without knee support. The shape of the tabletop did not influence the rectum or prostate position.

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.

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.

Purpose: To correctly evaluate realistic treatment plans in terms of absorbed dose to the clinical target volume (CTV), equivalent uniform dose (EUD), and tumor control probability (TCP) in the presence of execution (random) and preparation (systematic) geometric errors., Materials and Methods: The dose matrix is blurred with all execution errors to estimate the total dose distribution of all fractions. To include preparation errors, the CTV is randomly displaced (and optionally rotated) many times with respect to its planned position while computing the dose, EUD, and TCP for the CTV using the blurred dose matrix. Probability distributions of these parameters are computed by combining the results with the probability of each particular preparation error. We verified the method by comparing it with an analytic solution. Next, idealized and realistic prostate plans were tested with varying margins and varying execution and preparation error levels., Results: Probability levels for the minimum dose, computed with the new method, are within 1% of the analytic solution. The impact of rotations depends strongly on the CTV shape. A margin of 10 mm between the CTV and planning target volume is adequate for three-field prostate treatments given the accuracy level in our department; i.e., the TCP in a population of patients, TCP(pop), is reduced by less than 1% due to geometric errors. When reducing the margin to 6 mm, the dose must be increased from 80 to 87 Gy to maintain the same TCP(pop). Only in regions with a high-dose gradient does such a margin reduction lead to a decrease in normal tissue dose for the same TCP(pop). Based on a rough correspondence of 84% minimum dose with 98% EUD, a margin recipe was defined. To give 90% of patients at least 98% EUD, the planning target volume margin must be approximately 2.5 Sigma + 0.7 sigma - 3 mm, where Sigma and sigma are the combined standard deviations of the preparation and execution errors. This recipe corresponds accurately with 1% TCP(pop) loss for prostate plans with clinically reasonable values of Sigma and sigma., Conclusion: The new method computes in a few minutes the influence of geometric errors on the statistics of target dose and TCP(pop) in clinical treatment plans. Too small margins lead to a significant loss of TCP(pop) that is difficult to compensate for by dose escalation.

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.

Purpose: With the mean lung dose (MLD) as an estimator for the normal tissue complication probability (NTCP) of the lung, we assessed whether the probability of tumor control of lung tumors might be increased by dose escalation in combination with a reduction of field sizes, thus increasing target dose inhomogeneity while maintaining a constant MLD., Methods and Materials: An 8-MV AP-PA irradiation of a lung tumor, located in a cylindrically symmetric lung-equivalent phantom, was modeled using numerical simulation. Movement of the clinical target volume (CTV) due to patient breathing and setup errors was simulated. The probability of tumor control, expressed as the equivalent uniform dose (EUD) of the CTV, was assessed as a function of field size, under the constraint of a constant MLD. The approach was tested for a treatment of a non-small cell lung cancer (NSCLC) patient using the beam directions of the clinically applied treatment plan., Results: In the phantom simulation it was shown that by choosing field sizes that ensured a minimum dose of 95% in the CTV ("conventional" plan) taking into account setup errors and tumor motion, an EUD of the CTV of 43.8 Gy can be obtained for a prescribed dose of 44.2 Gy. By reducing the field size and thus shifting the 95% isodose surface inwards, the EUD increases to a maximum of 68.3 Gy with a minimum dose in the CTV of 55.2 Gy. This increase in EUD is caused by the fact that field size reduction enables escalation of the prescribed dose while maintaining a constant MLD. Further reduction of the field size results in decrease of the EUD because the minimum dose in the CTV becomes so low that it has a predominant effect on the EUD, despite further escalation of the prescribed dose. For the NSCLC patient, the EUD could be increased from an initial 62.2 Gy for the conventional plan, to 83.2 Gy at maximum. In this maximum, the prescribed dose is 88.1 Gy, and the minimum dose in the CTV is 67.4 Gy. In this case, the 95% isodose surface is conformed closely to the "static" CTV during treatment planning., Conclusions: Iso-NTCP escalation of the probability of tumor control is possible for lung tumors by reducing field sizes and allowing a larger dose inhomogeneity in the CTV. Optimum field sizes can be derived, having the highest EUD and highest minimum dose in the CTV under condition of a constant NTCP of the lungs. We conclude that the concept of homogeneous dose in the target volume is not the best approach to reach the highest probability of tumor control for lung tumors.

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 (Sigma) plus 1.64 times the total SD of execution (random) errors (sigma') combined with the penumbra width, minus 1.64 times the SD describing the penumbra width (sigma(p)). For a sigma(p) of 3.2 mm, this recipe can be simplified to 2.5 Sigma + 0.7 sigma'. 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.

Purpose: To investigate the clinical importance and feasibility of a 3-D portal image analysis method in comparison with a standard 2-D portal image analysis method for pelvic irradiation techniques., Methods and Materials: In this study, images of 30 patients who were treated for prostate cancer were used. A total of 837 imaged fields were analyzed by a single technologist, using automatic 2-D and 3-D techniques independently. Standard deviations (SDs) of the random, systematic, and overall variations, and the overall mean were calculated for the resulting data sets (2-D and 3-D), in the three principal directions (left-right [L-R], cranial-caudal [C-C], anterior-posterior [A-P]). The 3-D analysis included rotations as well. For the translational differences between the three data sets, the overall SD and overall mean were computed. The influence of out-of-plane rotations on the 2-D registration accuracy was determined by analyzing the difference between the 2-D and 3-D translation data as function of rotations. To assess the reliability of the 2-D and 3-D methods, the number of times the automatic match was manually adjusted was counted. Finally, an estimate of the workload was made., Results: The SDs of the random and systematic components of the rotations around the three orthogonal axes were 1. 1 (L-R), 0.6 (C-C), 0.5 (A-P) and 0.9 (L-R), 0.6 (C-C), 0.8 (A-P) degrees, respectively. The overall mean rotation around the L-R axis was 0.7 degrees, which deviated significantly from zero. Translational setup errors were comparable for 2-D and 3-D analysis (ranging from 1.4 to 2.2 mm SD and from 1.5 to 2.5 mm SD, respectively). The variation of the difference between the 2-D and 3-D translation data increased from 1.1 mm (SD) for zero rotations to 2.7 mm (SD) for out-of-plane rotations of 3 degrees, due to a reduced 2-D registration accuracy for large rotations. The number of times the analysis was not considered acceptable and was manually adjusted was 44% for the 2-D analysis, and 6% for the 3-D analysis., Conclusion: True 3-D analysis of setup errors for a group of 30 patients with prostate cancer demonstrated that setup rotations are rather small. The deformation of the projected anatomy in portal images caused by out-of-plane rotations leads to a reduced 2-D registration accuracy. For rotations larger than 3 degrees this effect can be quite pronounced, making 3-D registration the preferred method. Furthermore, the automatic 3-D registration has a higher success rate, most likely because this technique uses more information compared to the 2-D method.

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.

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.