BACKGROUND:: Stereotactic body radiation therapy (SBRT) is a treatment option for colorectal liver metastases. Local control, patient survival and toxicity were assessed in an experience of SBRT for colorectal liver metastases. METHODS:: SBRT was delivered with curative intent to 20 consecutively treated patients with colorectal hepatic metastases who were candidates for neither resection nor radiofrequency ablation (RFA). The median number of metastases was 1 (range 1-3) and median size was 2.3 (range 0.7-6.2) cm. Toxicity was scored according to the Common Toxicity Criteria version 3.0. Local control rates were derived on tumour-based analysis. RESULTS:: Median follow-up was 26 (range 6-57) months. Local failure was observed in nine of 31 lesions after a median interval of 22 (range 12-52) months. Actuarial 2-year local control and survival rates were 74 and 83 per cent respectively. Hepatic toxicity grade 2 or less was reported in 18 patients. Two patients had an episode of hepatic toxicity grade 3. CONCLUSION:: SBRT is a treatment option for patients with colorectal liver metastases who are not candidates for resection or RFA. Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Several methods can be used to achieve multi-criteria optimization of radiation therapy treatment planning, which strive for Pareto-optimality. The property of the solution being Pareto optimal is desired, because it guarantees that no criteria can be improved without deteriorating another criteria. The most widely used methods are the weighted-sum method, in which the different treatment objectives are weighted, and constrained optimization methods, in which treatment goals are set and the algorithm has to find the best plan fulfilling these goals. The constrained method used in this paper, the 2pc (2-phase -constraint) method is based on the -constraint method, which generates Pareto-optimal solutions. Both approaches are uniquely related to each other. In this paper, we will show that it is possible to switch from the constrained method to the weighted-sum method by using the Lagrange multipliers from the constrained optimization problem, and vice versa by setting the appropriate constraints. In general, the theory presented in this paper can be useful in cases where a new situation is slightly different from the original situation, e.g. in online treatment planning, with deformations of the volumes of interest, or in automated treatment planning, where changes to the automated plan have to be made. An example of the latter is given where the planner is not satisfied with the result from the constrained method and wishes to decrease the dose in a structure. By using the Lagrange multipliers, a weighted-sum optimization problem is constructed, which generates a Pareto-optimal solution in the neighbourhood of the original plan, but fulfills the new treatment objectives.

Technical improvements in planning and dose delivery and in verification of patient positioning have substantially widened the therapeutic window for radiation treatment of cancer. However, changes in patient anatomy during the treatment limit the exploitation of these new techniques. To further improve radiation treatments, anatomical changes need to be modeled and accounted for Nonrigid registration can be used for this purpose. This article describes the design, the implementation, and the validation of a new framework for nonrigid registration for radiotherapy applications. The core of this framework is an improved version of the thin plate spline robust point matching (TPS-RPM) algorithm. The TPS-RPM algorithm estimates a global correspondence and a transformation between the points that represent organs of interest belonging to two image sets. However, the algorithm does not allow for the inclusion of prior knowledge on the correspondence of subset of points, and therefore, it can lead to inconsistent anatomical solutions. In this article TPS-RPM was improved by employing a novel correspondence filter that supports simultaneous registration of multiple structures. The improved method allows for coherent organ registration and for the inclusion of user-defined landmarks, lines, and surfaces inside and outside of structures of interest. A procedure to generate control points from segmented organs is described. The framework parameters r and lambda, which control the number of points and the nonrigidness of the transformation, respectively, were optimized for three sites with different degrees of deformation (head and neck, prostate, and cervix) using two cases per site. For the head and neck cases, the salivary glands were manually contoured on CT scans, for the prostate cases the prostate and the vesicles, and for the cervix cases the cervix uterus, the bladder, and the rectum. The transformation error obtained using the best set of parameters was below 1 mm for all the studied cases. The lengths of the deformation vectors were on average (+/- 1 standard deviation) 5.8 +/- 2.5 and 2.6 +/- 1.1 mm for the head and neck cases, 7.2 +/- 4.5 and 8.6 +/- 1.9 mm for the prostate cases, and 19.0 +/- 11.6 and 14.5 +/- 9.3 mm for the cervix cases. Distinguishable anatomical features were identified for each case and were used to validate the registration by calculating residual distances after transformation: 1.5 +/- 0.8, 2.3 +/- 1.0, and 6.3 +/- 2.9 mm for the head and neck, prostate, and cervix sites, respectively. Finally, the authors demonstrated how the inclusion of these anatomical features in the registration process reduced the residual distances to 0.8 +/- 0.5, 0.6 +/- 0.5, and 1.3 +/- 0.7 mm for the head and neck, prostate, and cervix sites, respectively. The inclusion of additional anatomical features produced more anatomically coherent transformations without compromising the transformation error. The authors concluded that the presented nonrigid registration framework is a powerful tool to simultaneously register multiple segmented organs with very different complexities.

BACKGROUND AND PURPOSE: We are developing a technique for highly focused vocal cord irradiation in early glottic carcinoma to optimally treat a target volume confined to a single cord. This technique, in contrast with the conventional methods, aims at sparing the healthy vocal cord. As such a technique requires sub-mm daily targeting accuracy to be effective, we investigate the accuracy achievable with on-line kV-cone beam CT (CBCT) corrections. MATERIALS AND METHODS: CBCT scans were obtained in 10 early glottic cancer patients in each treatment fraction. The grey value registration available in X-ray volume imaging (XVI) software (Elekta, Synergy) was applied to a volume of interest encompassing the thyroid cartilage. After application of the thus derived corrections, residue displacements with respect to the planning CT scan were measured at clearly identifiable relevant landmarks. The intra- and inter-observer variations were also measured. RESULTS: While before correction the systematic displacements of the vocal cords were as large as 2.4+/-3.3mm (cranial-caudal population mean+/-SD Sigma), daily CBCT registration and correction reduced these values to less than 0.2+/-0.5mm in all directions. Random positioning errors (SD sigma) were reduced to less than 1mm. Correcting only for translations and not for rotations did not appreciably affect this accuracy. The residue random displacements partly stem from intra-observer variations (SD=0.2-0.6mm). CONCLUSION: The use of CBCT for daily image guidance in combination with standard mask fixation reduced systematic and random set-up errors of the vocal cords to <1mm prior to the delivery of each fraction dose. Thus, this facilitates the high targeting precision required for a single vocal cord irradiation.

PURPOSE: To assess day-to-day differences between planned and delivered target volume (TV) and organ-at-risk (OAR) dose distributions in liver stereotactic body radiation therapy (SBRT), and to investigate the dosimetric impact of setup corrections. METHODS AND MATERIALS: For 14 patients previously treated with SBRT, the planning CT scan and three treatment scans (one for each fraction) were included in this study. For each treatment scan, two dose distributions were calculated: one using the planned setup for the body frame (no correction), and one using the clinically applied (corrected) setup derived from measured tumor displacements. Per scan, the two dose distributions were mutually compared, and the clinically delivered distribution was compared with planning. Doses were recalculated in equivalent 2-Gy fraction doses. Statistical analysis was performed with the linear mixed model. RESULTS: With setup corrections, the mean loss in TV coverage relative to planning was 1.7%, compared with 6.8% without corrections. For calculated equivalent uniform doses, these figures were 2.3% and 15.5%, respectively. As for the TV, mean deviations of delivered OAR doses from planning were small (between -0.4 and +0.3 Gy), but the spread was much larger for the OARs. In contrast to the TV, the mean impact of setup corrections on realized OAR doses was close to zero, with large positive and negative exceptions. CONCLUSIONS: Daily correction of the treatment setup is required to obtain adequate TV coverage. Because of day-to-day patient anatomy changes, large deviations in OAR doses from planning did occur. On average, setup corrections had no impact on these doses. Development of new procedures for image guidance and adaptive protocols is warranted.

A high dosimetric accuracy is required for radiotherapy treatments where IMRT in combination with narrow treatment margins is applied to achieve optimally conformal dose distributions. In order to routinely verify the in vivo fluence delivery (i.e., during the actual patient treatment), our method for predicting portal dose images with a patient in the beam was validated. A unique feature of this method is that it is fully based on calibration measurements with an EPID. The portal dose image (PDI) behind a patient is dependent on the transmission of primary radiation through the patient and a contribution of scattered radiation from the patient. To derive both components, the patient geometry as observed in the planning CT scan is converted into an equivalent homogeneous phantom. A limited set of EPID measurements is required to derive the input parameters of this model. The accuracy of the in vivo PDI prediction was verified using measurements behind phantoms and four prostate cancer patients treated with IMRT. Behind homogeneous slab phantoms, the local differences between measured and predicted PDIs were within 2% inside the field, while behind a lung and a pelvic phantom, the agreement was within 3% or within 3 mm in regions with steep gradients. Outside the fields, the PDIs agreed within 2% of the global dose maximum. Evaluation of the in vivo PDI measurements behind patients showed that, on average, 87% of the pixels inside the field fulfilled the 3% local dose and 3 mm distance-to-agreement criteria. For half of the failing pixels the differences occurred due to changes in patient geometry with respect to the planning CT or due to beam attenuation by the treatment couch that was not accounted for. A fully EPID-based method for predicting portal dose images using the planning CT scan has been implemented and validated for phantoms and clinical patients.

PURPOSE: To quantify the clinical accuracy of the respiratory motion tracking system of the CyberKnife treatment device. METHODS AND MATERIALS: Data in log files of 44 lung cancer patients treated with tumor tracking were analyzed. Errors in the correlation model, which relates the internal target motion with the external breathing motion, were quantified. The correlation model error was compared with the geometric error obtained when no respiratory tracking was used. Errors in the prediction method were calculated by subtracting the predicted position from the actual measured position after 192.5 ms (the time lag to prediction in our current system). The prediction error was also measured for a time lag of 115 ms and a new prediction method. RESULTS: The mean correlation model errors were less than 0.3 mm. Standard deviations describing intrafraction variations around the whole-fraction mean error were 0.2 to 1.9 mm for cranio-caudal, 0.1 to 1.9 mm for left-right, and 0.2 to 2.5 mm for anterior-posterior directions. Without the use of respiratory tracking, these variations would have been 0.2 to 8.1 mm, 0.2 to 5.5 mm, and 0.2 to 4.4 mm. The overall mean prediction error was small (0.0 +/- 0.0 mm) for all directions. The intrafraction standard deviation ranged from 0.0 to 2.9 mm for a time delay of 192.5 ms but was halved by using the new prediction method. CONCLUSIONS: Analyses of the log files of real clinical cases have shown that the geometric error caused by respiratory motion is substantially reduced by the application of respiratory motion tracking.

PURPOSE: In dose escalation trial, for prostate cancer patients, zero CTV-PTV margins towards the rectum are often applied in the boost phase in order to avoid excessive dose delivery to the rectum. In this study, the dosimetric impact of non-exclusion of the rectum from the boost PTV is evaluated. Treatment plans created according to the protocol used in our institute for patients in a Dutch hypofractionated trial (HYPO), where the rectum is excluded from the boost PTV, were compared to plans designed with a modified version of this protocol (HYPO-exp) for which the rectal exclusion was not performed. Differences in target coverage and rectum dose were quantified. METHODS AND MATERIALS: Treatment plans were generated for 36 prostate cancer patients. In the HYPO plans, the CTV-PTV margins around the prostate were 6mm (7.5mm at the caudal side) and 10mm around the seminal vesicles (PTV1). For the boost phase, these margins were reduced to 5mm, but no margin was taken at the overlap with the rectum (PTV2). The margin prescription for HYPO-exp was identical to that for HYPO, except that the zero CTV-PTV margin towards the rectum was omitted. For the HYPO and HYPO-exp plans, a simultaneous integrated boost technique using IMRT was applied to deliver 72.2Gy to PTV1 and 78Gy to PTV2. For all plans, the dose to the rectum was compared using V(50), V(60), V(70), the equivalent uniform dose (EUD), considering alpha=9 and 1, respectively, and normal tissue complication probabilities (NTCPs). In addition, the dose coverage of PTV1 and PTV2 and the minimum dose in those volumes were quantified. To assess the clinical impact of differences in dose delivery to the rectum, both IMRT plans were also compared to a plan (DESC) based on the treatment protocol applied in our institute in a former national dose escalation trial, which in the meantime has a median follow-up of six years. RESULTS: Compared to HYPO, V(70) and the rectal EUD calculated with alpha=9 were slightly higher for HYPO-exp, but the differences were not statistically significant. V(50), V(60) and the rectal EUD calculated with alpha=1 were similar for both the IMRT plans. In contrast, each of these parameters was significantly lower compared to DESC (p<0.001). The coverage of the boost PTV, used in HYPO-exp, by at least 95% of the prescribed dose was significantly better for HYPO-exp than for HYPO (p<0.001). In the overlap of this volume with the rectum, the minimum dose increased by 1.1+/-1.2Gy for HYPO-exp (p=0.002) and the mean dose by 1.2+/-1.5Gy (p=0.001). CONCLUSION: By omitting the zero margin towards the rectum, underdosages in the target volume are reduced significantly, while a clinically relevant increase in rectum exposure is not observed.

PURPOSE: To quantify the residual geometric uncertainties after on-line corrections with intraprostatic fiducial markers, this study analyzed the deformation of the prostate and, in particular, the seminal vesicles relative to such markers. PATIENTS AND METHODS: A planning computed tomography (CT) scan and three repeat CT scans were obtained for 21 prostate cancer patients who had had three to four cylindrical gold markers placed. The prostate and whole seminal vesicles (clinical target volume [CTV]) were delineated on each scan at a slice thickness of 1.5 mm. Rigid body transformations (translation and rotation) mapping the markers onto the planning scan positions were obtained. The translation only (T(only)) or both translation and rotation were applied to the delineated CTVs. Next, the residue CTV surface displacements were determined using nonrigid registration of the delineated contours. For translation and rotation of the CTV, the residues represented deformation; for T(only), the residues stemmed from deformation and rotation. T(only) represented the residues for most currently applied on-line protocols. The patient and population statistics of the CTV surface displacements were calculated. The intraobserver delineation variation was similarly quantified using repeat delineations for all patients and corrected for. RESULTS: The largest CTV deformations were observed at the anterior and posterior side of the seminal vesicles (population average standard deviation </=3 mm). Prostate deformation was small (standard deviation </=1 mm). The increase in these deviations when neglecting rotation (T(only)) was small. CONCLUSION: Although prostate deformation with respect to implanted fiducial markers was small, the corresponding deformation of the seminal vesicles was considerable. Adding marker-based rotational corrections to on-line translation corrections provided a limited reduction in the estimated planning margins.

BACKGROUND AND PURPOSE: The aim of this study is to investigate whether surgical clips in the lumpectomy cavity are representative for position verification of both the tumour bed and the whole breast in simultaneously integrated boost (SIB) treatments. MATERIALS AND METHODS: For a group of 30 patients treated with a SIB technique, kV and MV planar images were acquired throughout the course of the fractionated treatment. The 3D set-up error for the tumour bed was derived by matching the surgical clips (3-8 per patient) in two almost orthogonal planar kV images. By projecting the 3D set-up error derived from the planar kV images to the (u, v)-plane of the tangential beams, the correlation with the 2D set-up error for the whole breast, derived from the MV EPID images, was determined. The stability of relative clip positions during the fractionated treatment was investigated. In addition, for a subgroup of 15 patients, the impact of breathing was determined from fluoroscopic movies acquired at the linac. RESULTS: The clip configurations were stable over the course of radiotherapy, showing an inter-fraction variation (1 SD) of 0.5mm on average. Between the start and the end of the treatment, the mean distance between the clips and their center of mass was reduced by 0.9mm. A decrease larger than 2mm was observed in eight patients (17 clips). The top-top excursion of the clips due to breathing was generally less than 2.5mm in all directions. The population averages of the difference (+/-1 SD) between kV and MV matches in the (u, v)-plane were 0.2+/-1.8mm and 0.9+/-1.5mm, respectively. In 30% of the patients, time trends larger than 3mm were present over the course of the treatment in either or in both kV and MV match results. Application of the NAL protocol based on the clips reduced the population mean systematic error to less than 2mm in all directions, both for the tumour bed and the whole breast. Due to the observed time trends, these systematic errors can be further reduced to about 1mm by using an eNAL protocol instead. CONCLUSIONS: The relative positions of implanted surgical clips in the lumpectomy cavity after breast-conserving surgery remain stable during the course of radiotherapy treatment. Application of a NAL or eNAL set-up correction protocol based on surgical clips allows for adequate treatment of both the tumour bed and the whole breast with tight CTV-PTV margins.