Impact of magnetic resonance-guided versus conventional radiotherapy workflows on organ at risk doses in stereotactic body radiotherapy for lymph node oligometastases

Background and purpose: Magnetic resonance (MR)-linac delivery is expected to improve organ at risk (OAR) sparing. In this study, OAR doses were compared for online adaptive MR-linac treatments and conventional cone beam computed tomography (CBCT)-linac radiotherapy, taking into account differences in clinical workflows, especially longer session times for MR-linac delivery. Materials and methods: For 25 patients with pelvic/abdominal lymph node oligometastases, OAR doses were calculated for clinical pre-treatment and daily optimized 1.5 T MR-linac treatment plans (5 × 7 Gy) and compared with simulated CBCT-linac plans for the pre-treatment and online anatomical situation. Bowelbag and duodenum were re-contoured on MR-imaging acquired before, during and after each treatment session. OAR hard constraint violations, D 0.5cc and D 10cc values were evaluated, focusing on bowelbag and duodenum. Results: Overall, hard constraints for all OAR were violated less often in daily online MR-linac treatment plans compared with CBCT-linac: in 5% versus 22% of fractions, respectively. D 0.5cc and D 10cc values did not differ significantly. When taking treatment duration and intrafraction motion into account, estimated delivered doses to bowelbag and duodenum were lower with CBCT-linac if identical planning target volume (PTV) margins were used for both modalities. When reduced PTV margins were achievable with MR-linac treatment, bowelbag doses were lower compared with CBCT-linac. Conclusions: Compared with CBCT-linac treatments, the online adaptive MR-linac approach resulted in fewer hard planning constraint violations compared with single-plan CBCT-linac delivery. With respect to other bowelbag/duodenum dose-volume parameters, the longer duration of MR-linac treatment sessions negatively impacts the potential dosimetric benefit of daily adaptive treatment planning

Online adaptive MR-guided radiotherapy: Conformity of contour adaptation for prostate cancer, rectal cancer and lymph node oligometastases among radiation therapists and radiation oncologists

Background and purpose: Online adaptive MR-guided treatment planning workflows facilitate daily contour adaptation to the actual anatomy. Allocating contour adaptation to radiation therapists (RTTs) instead of radiation oncologists (ROs) might allow for increasing workflow efficiency. This study investigates conformity of adapted target contours provided by dedicated RTTs and ROs. Materials and methods: In a simulated online procedure, 6 RTTs and 6 ROs recontoured targets and organs at risk (OAR) in prostate cancer (n = 2), rectal cancer (n = 2) and lymph node-oligometastases (n = 2) cases. RTTs gained contouring competence beforehand by following a specific in-house training program. For all target contours and the reference delineations volumetric differences were determined and Dice similarity coefficient (DSC), conformity index (CI) and generalized CI were calculated. Delineation time and -confidence were registered for targets and OAR. Impact of contour adaptation on treatment plan quality was investigated. Results: Delineation conformity was generally high with DSC, CI and generalized CI values in the range of 0.81-0.94, 0.87-0.95 and 0.63-0.85 for prostate cancer, rectal cancer and LN-oligometastasis, respectively. Target volumes were comparable for both, RTTs and ROs. Time needed and confidence in contour adaptation was comparable as well. Treatment plans derived with adapted contours did not violate dose volume constrains as used in clinical routine. Conclusion: After tumor site specific training, daily contour adaptations as needed in adaptive online radiotherapy workflows can be accurately performed by RTTs. Conformity of the derived contours is high and comparable to contours as provided by ROs

Single blind randomized Phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a randomized controlled trial

Background: The treatment results of external beam radiotherapy for intermediate and high risk prostate cancer patients are insufficient with five-year biochemical relapse rates of approximately 35%. Several randomized trials have shown that dose escalation to the entire prostate improves biochemical disease free survival. However, further dose escalation to the whole gland is limited due to an unacceptable high risk of acute and late toxicity. Moreover, local recurrences often originate at the location of the macroscopic tumor, so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control. A reduction of distant metastases and improved survival can be expected by reducing local failure. The aim of this study is to investigate the benefit of an ablative microboost to the macroscopic tumor within the prostate in patients treated with external beam radiotherapy for prostate cancer.Methods/Design: The FLAME-trial (Focal Lesion Ablative Microboost in prostatE cancer) is a single blind randomized controlled phase III trial. We aim to include 566 patients (283 per treatment arm) with intermediate or high risk adenocarcinoma of the prostate who are scheduled for external beam radiotherapy using fiducial markers for position verification. With this number of patients, the expected increase in five-year freedom from biochemical failure rate of 10% can be detected with a power of 80%. Patients allocated to the standard arm receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in the experimental arm receive 77 Gy to the entire prostate and an additional integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions. The secondary outcome measures include treatment-related toxicity, quality of life and disease-specific survival. Furthermore, by localizing the recurrent tumors within the prostate during follow-up and correlating this with the delivered dose, we can obtain accurate dose-effect information for both the macroscopic tumor and subclinical disease in prostate cancer. The rationale, study design and the first 50 patients included are described.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Effect of translational and rotational errors on complex dose distributions with off-line and on-line position verification

PURPOSE: To investigate the influence of translational and rotational errors on prostate intensity-modulated radiotherapy (IMRT) with an integrated boost to the tumor and to evaluate the effect of the use of an on-line correction protocol. METHODS AND MATERIALS: For 19 patients, who had been treated with prostate IMRT and fiducial marker-based position verification, highly inhomogeneous IMRT plans, including an integrated tumor boost, were made using varying margins (2, 4, 6, and 8 mm). The measured translational and rotational errors were used to calculate the dose using two positioning strategies: an off-line and an on-line protocol to correct the translational shifts. The estimated dose to the targets and the organs at risk was compared with the intended dose. RESULTS: Residual deviations after off-line correction led to statistically significant, but very small, reductions in dose coverage. Even when a 2-mm margin was used, the average reduction in dose to 99% of the volume was 1.4 +/- 1.9 Gy for the tumor, 1.5 +/- 1.5 Gy for the prostate without seminal vesicles (boost volume), and 4.3 +/- 4.6 Gy, including the seminal vesicles (clinical target volume). Patients with large systematic rotational errors demonstrated a substantial decrease in dose, especially for the clinical target volume. If an on-line correction protocol was used, the average mean dose and dose to 99% of the volume of the targets improved. However, the extensive dose reduction for patients with large rotational errors barely recovered with on-line correction. CONCLUSION: For complex prostate IMRT with an integrated tumor boost, the use of an on-line correction protocol yields little improvement without the correction of rotational error

Intrafraction motion of the prostate during external-beam radiation therapy:Analysis of 427 patients with implanted fiducial markers

Purpose: To analyze the intrafraction motion of the prostate during external-beam radiation therapy of patients with prostate cancer. Methods and Materials: Between August 2001-December 2005, 427 patients with Stage T3Nx/0Mx/0 prostate carcinoma received intensity-modulated radiation therapy treatment combined with position verification with fiducial gold markers. For a total of 11,426 treatment fractions (average, 27 per patient), portal images were taken of the first segment of all five beams. The irradiation time of the technique varied between 5-7 min. From these data, the location of gold markers could be established within every treatment beam under the assumption of minimal marker movement. Results: In 66% of treatment fractions, a motion outside a range of 2 mm was observed, with 28% outside a range of 3 mm. The intrafraction marker movements showed that motion directions were often reversed. However, the effect was small. Even with perfect online position-correction at the start of irradiation, intrafraction motion caused position uncertainty, but systematic errors (Sigma) were limited to <0.6 mm, and random errors (sigma) to <0.9 mm. This would result in a lower limit of 2 mm for margins, in the absence of any other uncertainties. Conclusions: Intrafraction motion of the prostate occurs frequently during external-beam irradiation on a time scale of 5-7 min. Margins of 2 mm account for these intrafraction motions. However, larger margins are required in practice to accommodate other uncertainties in the treatment. (c) 2007 Elsevier Inc

Probabilistic treatment planning for pancreatic cancer treatment: prospective incorporation of respiratory motion shows only limited dosimetric benefit

<p><b>Background:</b> We introduced a probabilistic treatment planning approach that prospectively incorporates respiratory-induced motion in the treatment plan optimization. The aim of this study was to determine the potential dosimetric benefit by comparing this approach to the use of an internal target volume (ITV).</p> <p><b>Material and method:</b> We retrospectively compared the probabilistic respiratory motion-incorporated (RMI) approach to the ITV approach for 18 pancreatic cancer patients, for seven simulated respiratory amplitudes from 5 to 50 mm in the superior-inferior (SI) direction. For each plan, we assessed the target coverage (required: D_98%≥95% of 50 Gy prescribed dose). For the RMI plans, we investigated whether target coverage was robust against daily variations in respiratory amplitude. We determined the distance between the clinical target volume and the 30 Gy isodose line (i.e. dose gradient steepness) in the SI direction. To investigate the clinical benefit of the RMI approach, we created for each patient an ITV and RMI treatment plan for the three-dimensional (3D) respiratory amplitudes observed on their pretreatment 4D computed tomography (4DCT). We determined D_mean, V_30Gy, V_40Gy and V_50Gy for the duodenum.</p> <p><b>Results:</b> All treatment plans yielded good target coverage. The RMI plans were robust against respiratory amplitude variations up to 10 mm, as D_98% remained ≥95%. We observed steeper dose gradients compared to the ITV approach, with a mean decrease from 25.9 to 19.2 mm for a motion amplitude of 50 mm. For the 4DCT motion amplitudes, the RMI approach resulted in a mean decrease of 0.43 Gy, 1.1 cm³, 1.4 cm³ and 0.9 cm³ for the D_mean, V_30Gy, V_40Gy and V_50Gy of the duodenum, respectively.</p> <p><b>Conclusion:</b> The probabilistic treatment planning approach yielded significantly steeper dose gradients and therefore significantly lower dose to surrounding healthy tissues than the ITV approach. However, the observed dosimetric gain for clinically observed respiratory motion amplitudes for this patient group was limited.</p

Full-Thickness Closure in Breast-Conserving Surgery: The Impact on Radiotherapy Target Definition for Boost and Partial Breast Irradiation. A Multimodality Image Evaluation

Background: During breast-conserving surgery (BCS), surgeons increasingly perform full-thickness closure (FTC) to prevent seroma formation. This could potentially impair precision of target definition for boost and accelerated partial breast irradiation (APBI). The purpose of this study was to investigate the precision of target volume definition following BCS with FTC among radiation oncologists, using various imaging modalities

Contouring of prostate tumors on multiparametric MRI : Evaluation of clinical delineations in a multicenter radiotherapy trial

PURPOSE: To date no guidelines are available for contouring prostate cancer inside the gland, as visible on multiparametric (mp-) MRI. We assessed inter-institutional differences in interpretation of mp-MRI in the multicenter phase III FLAME trial. METHODS: We analyzed clinical delineations on mp-MRI and clinical characteristics from 260 patients across three institutes. We performed a logistic regression analysis to examine each institute's weighting of T2w, ADC and Ktrans intensity maps in the delineation of the cancer. As reviewing of all delineations by an expert panel is not feasible, we made a selection based on discrepancies between a published tumor probability (TP) model and each institute's clinical delineations using Areas Under the ROC Curve (AUC) analysis. RESULTS: Regression coefficients for the three institutes were -0.07, -0.27 and -0.11 for T2w, -1.96, -0.53 and -0.65 for ADC and 0.15, 0.20 and 0.62 for Ktrans, with significant differences between institutes for ADC and Ktrans. AUC analysis showed median AUC values of 0.92, 0.80 and 0.79. Five patients with lowest AUC values were reviewed by a uroradiologist. CONCLUSION: Regression coefficients revealed considerably different interpretations of mp-MRI in tumor contouring between institutes and demonstrated the need for contouring guidelines. Based on AUC values outlying delineations could efficiently be identified for review

Multiatlas-based segmentation with preregistration atlas selection

Purpose: Automatic, atlas-based segmentation of medical images benefits from using multiple atlases, mainly in terms of robustness. However, a large disadvantage of using multiple atlases is the large computation time that is involved in registering atlas images to the target image. This paper aims to reduce the computation load of multiatlas-based segmentation by heuristically selecting atlases before registration. Methods: To be able to select atlases, pairwise registrations are performed for all atlas combinations. Based on the results of these registrations, atlases are clustered, such that each cluster contains atlas that registers well to each other. This can all be done in a preprocessing step. Then, the representatives of each cluster are registered to the target image. The quality of the result of this registration is estimated for each of the representatives and used to decide which clusters to fully register to the target image. Finally, the segmentations of the registered images are combined into a single segmentation in a label fusion procedure. Results: The authors perform multiatlas segmentation once with postregistration atlas selection and once with the proposed preregistration method, using a set of 182 segmented atlases of prostate cancer patients. The authors performed the full set of 182 leave-one-out experiments and in each experiment compared the result of the atlas-based segmentation procedure to the known segmentation of the atlas that was chosen as a target image. The results show that preregistration atlas selection is slightly less accurate than postregistration atlas selection, but this is not statistically significant. Conclusions: Based on the results the authors conclude that the proposed method is able to reduce the number of atlases that have to be registered to the target image with 80% on average, without compromising segmentation accuracy. © 2013 American Association of Physicists in Medicine