Publications by authors named "Reynaert Nick"

38 Publications

Unintended dose to the lower axilla in adjuvant radiotherapy for breast cancer: Differences between tangential beam and VMAT.

Radiother Oncol 2021 Oct 11;164:282-288. Epub 2021 Oct 11.

Department of Radiation Oncology, Breast Working Group, Institut Jules Bordet, Université libre de Bruxelles, Brussels, Belgium. Electronic address:

Background And Purpose: To evaluate dosimetric differences in unintended dose to the lower axilla between 3D-standard (3DCRT), tangential beam forward intensity modulated radiotherapy (F-IMRT) and volumetric modulated arc therapy (VMAT). The objective is to evaluate whether results of clinical trials, such as the ACOSOG-Z011 trial, that evaluated omission of axillary clearance can be extrapolated towards more conformal techniques like VMAT.

Materials And Methods: Twenty-five consecutive patients treated with whole breast radiotherapy alone (WBRT) using a F-IMRT technique were identified. Three additional plans were created for every patient: one plan using a single 270° arc (VMAT 1x270°), another using two small ≤90° opposing arcs (VMAT 2x < 90°) and thirdly a 3DCRT plan without F-IMRT. Axillary levels I-II were contoured after the treatment plans were made.

Results: The volume of the axilla level I that was covered by the 50% isodose (V50%) was significantly higher for VMAT 2x < 90° (71.3 cm, 84% of structure volume, p < 0.001) and VMAT 1x270° (68.8 cm, 81%, p < 0.01) compared to 3DCRT (60.3 cm, 71%) and F-IMRT (60.8 cm, 72%). The V50% to the axilla level II, however, was low for all techniques: 12.3 cm (12%); 8.9 cm (9%); 4.3 cm (4%); 4.4 cm (4%) for VMAT 2x < 90°, VMAT 1x270°, 3DCRT, F-IMRT, respectively. For the higher doses (V90% and above), no clinically relevant differences were seen between the different modalities.

Conclusion: WBRT treatments with VMAT do not lead to a significant reduction of the unintended axillary dose in comparison with a tangential beam setup. Hence, concerning tumor control, VMAT can be applied to clinical situations similar to the Z0011 trial. The intermediate axillary dose is higher with VMAT, but the clinical consequence of this difference on toxicity is unknown.
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http://dx.doi.org/10.1016/j.radonc.2021.10.005DOI Listing
October 2021

Dose calculation validation of a convolution algorithm in a solid water phantom.

Phys Med 2021 Sep 13;89:193-199. Epub 2021 Aug 13.

Medical Physics Department, Centre Bordet, Brussels, Belgium.

Purpose: The dose calculated using a convolution algorithm should be validated in a simple homogeneous water-equivalent phantom before clinical use. The dose calculation accuracy within a solid water phantom was investigated.

Methods: The specific Gamma knife design requires a dose rate calibration within a spherical solid water phantom. The TMR10 algorithm, which approximates the phantom material as liquid water, correctly computes the absolute dose in water. The convolution algorithm, which considers electron density miscalculates the dose in water as the phantom Hounsfield units were converted into higher electron density when the original CT calibration curve was used. To address this issue, the electron density of liquid water was affected by modifying the CT calibration curve. The absolute dose calculated using the convolution algorithm was compared with that computed by the TMR10. The measured depth dose profiles were also compared to those computed by the convolution and TMR10 algorithms. A patient treatment was recalculated in the solid-water phantom and the delivery quality assurance was checked.

Results: The convolution algorithm and the TMR10 calculate an absolute dose within 1% when using the modified CT calibration curve. The dose depth profile calculated using the convolution algorithms was superimposed on the TMR10 and measured dose profiles when the modified CT calibration curve was applied. The Gamma index was better than 93%.

Conclusions: Dose calculation algorithms, which consider electron density, require a CT calibration curve adapted to the phantom material to correctly compute the dose in water.
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http://dx.doi.org/10.1016/j.ejmp.2021.08.003DOI Listing
September 2021

Artificial Intelligence in magnetic Resonance guided Radiotherapy: Medical and physical considerations on state of art and future perspectives.

Phys Med 2021 May 19;85:175-191. Epub 2021 May 19.

Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.

Over the last years, technological innovation in Radiotherapy (RT) led to the introduction of Magnetic Resonance-guided RT (MRgRT) systems. Due to the higher soft tissue contrast compared to on-board CT-based systems, MRgRT is expected to significantly improve the treatment in many situations. MRgRT systems may extend the management of inter- and intra-fraction anatomical changes, offering the possibility of online adaptation of the dose distribution according to daily patient anatomy and to directly monitor tumor motion during treatment delivery by means of a continuous cine MR acquisition. Online adaptive treatments require a multidisciplinary and well-trained team, able to perform a series of operations in a safe, precise and fast manner while the patient is waiting on the treatment couch. Artificial Intelligence (AI) is expected to rapidly contribute to MRgRT, primarily by safely and efficiently automatising the various manual operations characterizing online adaptive treatments. Furthermore, AI is finding relevant applications in MRgRT in the fields of image segmentation, synthetic CT reconstruction, automatic (on-line) planning and the development of predictive models based on daily MRI. This review provides a comprehensive overview of the current AI integration in MRgRT from a medical physicist's perspective. Medical physicists are expected to be major actors in solving new tasks and in taking new responsibilities: their traditional role of guardians of the new technology implementation will change with increasing emphasis on the managing of AI tools, processes and advanced systems for imaging and data analysis, gradually replacing many repetitive manual tasks.
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http://dx.doi.org/10.1016/j.ejmp.2021.05.010DOI Listing
May 2021

Split-VMAT technique to control the deep inspiration breath hold time for breast cancer radiotherapy.

Radiat Oncol 2021 Apr 20;16(1):77. Epub 2021 Apr 20.

Medical Physics Department, Institut Jules Bordet - Université Libre de Bruxelles, Brussels, Belgium.

Background: To improve split-VMAT technique by optimizing treatment delivery time for deep-inspiration breath hold (DIBH) radiotherapy in left-sided breast cancer patients, when automatic beam-interruption devices are not available.

Methods: Ten consecutive patients were treated with an eight partial arcs (8paVMAT) plan, standard of care in our center. A four partial arcs (4paVMAT) plan was also created and actual LINAC outputs were measured, to evaluate whether there was a dosimetric difference between both techniques and potential impact on the delivered dose. Subsequently, ten other patients were consecutively treated with a 4paVMAT plan to compare the actual treatment delivery time between both techniques. The prescribed dose was 40.05 Gy/15 fractions on the PTV breast (breast or thoracic wall), lymph nodes (LN) and intramammary lymph node chain (IMN). Treatment delivery time, PTVs coverage, conformity index (CI), organs at risk (OAR) dose, monitor units (MU), and gamma index were compared.

Results: Both split-VMAT techniques resulted in similar dose coverage for the PTV Breast and LN, and similar CI. For PTV IMN we observed a 5% increased coverage for the volume receiving ≥ 36 Gy with 4paVMAT, with an identical volume receiving ≥ 32 Gy. There was no difference for the OAR sparing, with the exception of the contralateral organs: there was a 0.6 Gy decrease for contralateral breast mean (p ≤ 0.01) and 1% decrease for the volume of right lung receiving ≥ 5 Gy (p = 0.024). Overall, these results indicate a modest clinical benefit of using 4paVMAT in comparison to 8paVMAT. An increase in the number of MU per arc was observed for the 4paVMAT technique, as expected, while the total number of MU remained comparable for both techniques. All the plans were measured with the Delta phantom and passed the gamma index criteria with no significant differences. Finally, the main difference was seen for the treatment delivery time: there was a significant decrease from 8.9 to 5.4 min for the 4paVMAT plans (p < .05).

Conclusions: This study is mainly of interest for centers who are implementing the DIBH technique without automatic beam-holding devices and who therefore may require to manually switch the beam on and off during breast DIBH treatment. Split-VMAT technique with 4 partial arcs significantly reduces the treatment delivery time compared to 8 partial arcs, without compromising the target coverage and the OAR sparing. The technique decreases the number of breath holds per fraction, resulting in a shorter treatment session.
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http://dx.doi.org/10.1186/s13014-021-01800-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056647PMC
April 2021

Improving generalization in MR-to-CT synthesis in radiotherapy by using an augmented cycle generative adversarial network with unpaired data.

Med Phys 2021 Jun 24;48(6):3003-3010. Epub 2021 Apr 24.

Univ. Lille, CNRS, Centrale Lille, UMR 9189 CRIStAL, Lille, F-59000, France.

Purpose: MR-to-CT synthesis is one of the first steps in the establishment of an MRI-only workflow in radiotherapy. Current MR-to-CT synthesis methods in deep learning use unpaired MR and CT training images with a cycle generative adversarial network (CycleGAN) to minimize the effect of misalignment between paired images. However, this approach critically assumes that the underlying interdomain mapping is approximately deterministic and one-to-one. In the current study, we use an Augmented CycleGAN (AugCGAN) model to create a robust model that can be applied to different scanners and sequences using unpaired data.

Materials And Methods: This study included T2-weighted MR and CT pelvic images of 38 patients in treatment position from five different centers. The AugCGAN was trained on 2D transverse slices of 19 patients from three different sites. The network was then used to generate synthetic CT (sCT) images of 19 patients from the two other sites. Mean absolute errors (MAEs) for each patient were evaluated between real and synthetic CT images. Original treatment plans of nine patients were recalculated using sCT images to assess the dose distribution in terms of voxel-wise dose difference, gamma, and dose-volume histogram analysis.

Results: The mean MAEs were Hounsfield units ( ) and 65.8 HU for the first and second test sites, respectively. The maximum dose difference to the target was with a gamma pass rate using the 3%, 3 mm criteria above 99%. The average time required to generate a complete sCT image for a patient on our GPU was 8.5 s.

Conclusion: This study suggests that our unpaired approach achieves good performance in generalization with respect to sCT image generation.
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http://dx.doi.org/10.1002/mp.14866DOI Listing
June 2021

Monte Carlo as quality control tool of stereotactic body radiation therapy treatment plans.

Phys Med 2021 Apr 23;84:205-213. Epub 2021 Mar 23.

Radiotherapy Department, Institute Jules Bordet, Brussels, Belgium. Electronic address:

Purpose/objective: The objective of this study was to verify the accuracy of treatment plans of stereotactic body radiation therapy (SBRT) and to verify the feasibility of the use of Monte Carlo (MC) as quality control (QC) on a daily basis.

Material/methods: Using EGSnrc, a MC model of Agility™ linear accelerator was created. Various measurements (Percentage depth dose (PDD), Profiles and Output factors) were done for different fields sizes from 1x1 up to 40x40 (cm). An iterative model optimization was performed to achieve adequate parameters of MC simulation. 40 SBRT patient's dosimetry plans were calculated by Monaco™ 3.1.1. CT images, RT-STRUCT and RT-PLAN files from Monaco™ being used as input for Moderato MC code. Finally, dose volume histogram (DVH) and paired t-tests for each contour were used for dosimetry comparison of the Monaco™ and MC.

Results: Validation of MC model was successful, as <2% difference comparing to measurements for all field's sizes. The main energy of electron source incident on the target was 5.8 MeV, and the full width at half maximum (FWHM) of Gaussian electron source were 0.09 and 0.2 (cm) in X and Y directions, respectively. For 40 treatment plan comparisons, the minimum absolute difference of mean dose of planning treatment planning (PTV) was 0.1% while the maximum was 6.3%. The minimum absolute difference of Max dose of PTV was 0.2% while the maximum was 8.1%.

Conclusion: SBRT treatment plans of Monaco agreed with MC results. It possible to use MC for treatment plans verifications as independent QC tool.
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http://dx.doi.org/10.1016/j.ejmp.2021.02.025DOI Listing
April 2021

Report dose-to-medium in clinical trials where available; a consensus from the Global Harmonisation Group to maximize consistency.

Radiother Oncol 2021 06 17;159:106-111. Epub 2021 Mar 17.

Trans Tasman Radiation Oncology Group (TROG), Newcastle, Australia; Radiation Oncology Department, Calvary Mater Newcastle, Australia; School of Mathematical and Physical Sciences, University of Newcastle, Australia; Institute of Medical Physics, University of Sydney, Australia.

Purpose: To promote consistency in clinical trials by recommending a uniform framework as it relates to radiation transport and dose calculation in water versus in medium.

Methods: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group (GHG; www.rtqaharmonization.org) compared the differences between dose to water in water (D), dose to water in medium (D), and dose to medium in medium (D). This was done based on a review of historical frameworks, existing literature and standards, clinical issues in the context of clinical trials, and the trajectory of radiation dose calculations. Based on these factors, recommendations were developed.

Results: No framework was found to be ideal or perfect given the history, complexity, and current status of radiation therapy. Nevertheless, based on the evidence available, the GHG established a recommendation preferring dose to medium in medium (D).

Conclusions: Dose to medium in medium (D) is the preferred dose calculation and reporting framework. If an institution's planning system can only calculate dose to water in water (D), this is acceptable.
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http://dx.doi.org/10.1016/j.radonc.2021.03.006DOI Listing
June 2021

Combined quality and dose-volume histograms for assessing the predictive value of Tc-MAA SPECT/CT simulation for personalizing radioembolization treatment in liver metastatic colorectal cancer.

EJNMMI Phys 2020 Dec 14;7(1):75. Epub 2020 Dec 14.

Medical Physics Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 Rue Héger-Bordet, B-1000, Brussels, Belgium.

Background: The relationship between the mean absorbed dose delivered to the tumour and the outcome in liver metastases from colorectal cancer patients treated with radioembolization has already been presented in several studies. The optimization of the personalized therapeutic activity to be administered is still an open challenge. In this context, how well the Tc-MAA SPECT/CT predicts the absorbed dose delivered by radioembolization is essential. This work aimed to analyse the differences between predictive Tc-MAA-SPECT/CT and post-treatment Y-microsphere PET/CT dosimetry at different levels. Dose heterogeneity was compared voxel-to-voxel using the quality-volume histograms, subsequently used to demonstrate how it could be used to identify potential clinical parameters that are responsible for quantitative discrepancies between predictive and post-treatment dosimetry.

Results: We analysed 130 lesions delineated in twenty-six patients. Dose-volume histograms were computed from predictive and post-treatment dosimetry for all volumes: individual lesion, whole tumoural liver (TL) and non-tumoural liver (NTL). For all dose-volume histograms, the following indices were extracted: D, D, D, D and D. The results showed mostly no statistical differences between predictive and post-treatment dosimetries across all volumes and for all indices. Notably, the analysis showed no difference in terms of D, confirming the results from previous studies. Quality factors representing the spread of the quality-volume histogram (QVH) curve around 0 (ideal QF = 0) were determined for lesions, TL and NTL. QVHs were classified into good (QF < 0.18), acceptable (0.18 ≤ QF < 0.3) and poor (QF ≥ 0.3) correspondence. For lesions and TL, dose- and quality-volume histograms are mostly concordant: 69% of lesions had a QF within good/acceptable categories (40% good) and 65% of TL had a QF within good/acceptable categories (23% good). For NTL, the results showed mixed results with 48% QF within the poor concordance category. Finally, it was demonstrated how QVH analysis could be used to define the parameters that predict the significant differences between predictive and post-treatment dose distributions.

Conclusion: It was shown that the use of the QVH is feasible in assessing the predictive value of Tc-MAA SPECT/CT dosimetry and in estimating the absorbed dose delivered to liver metastases from colorectal cancer via Y-microspheres. QVH analyses could be used in combination with DVH to enhance the predictive value of Tc-MAA SPECT/CT dosimetry and to assist personalized activity prescription.
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http://dx.doi.org/10.1186/s40658-020-00345-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736450PMC
December 2020

Development of staffing, workload and infrastructure in member departments of the European Organisation for Research and Treatment of Cancer (EORTC) radiation oncology group.

Radiother Oncol 2021 02 17;155:226-231. Epub 2020 Nov 17.

Department of Radiation Oncology, University Hospital Zurich, 8091 Zurich, Switzerland.

Purpose: The EORTC Radiation Oncology Group uses a Facility Questionnaire (FQ) to collect information from its member radiation oncology departments. We analysed the FQ database for patient-related workload, staffing levels and infrastructure to determine developments in radiation oncology departments in the clinical trials community.

Materials & Methods: We exported the FQ database in August 2019. Departments were included if their FQ was created or updated within the two preceding years. Observations were compared with previous evaluations of the FQ database.

Results: In total, 161 departments from 24 mostly European countries were analysed. The average number of patients per department increased by 3.0% to 2,453 (2013: 2,381). The annual number of patients decreased by 7.4% to 225 per radiation oncologist (2013: 243) and by 7.9% to 326 per medical physicist (2013: 354). In contrast, the number of patients increased by 23.3% to 106 per radiation therapist (RTT) (2013: 86) and per treatment unit by 3.9 % to 485 (2013: 467). In a pairwise comparison of departments that were available in 2013 and 2019, the number of patients per radiation oncologist (p = 0.02) and per physicist (p = 0.0003) decreased significantly. The number of departments that own a dedicated PET-CT scanner more than doubled (2013: 4%; 2019: 9%) and the availability of stereotactic body radiation therapy (SBRT) increased by 31.8% to 85.7% of the departments (2013: 65%).

Conclusion: The case-related workload per radiation oncologist and per physicist continues to decrease but increases per RTT and treatment unit. This is likely driven by an increased use of complex techniques, multimodality imaging and the implementation of automation in radiation oncology departments.
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http://dx.doi.org/10.1016/j.radonc.2020.11.009DOI Listing
February 2021

MR to CT synthesis with multicenter data in the pelvic area using a conditional generative adversarial network.

Phys Med Biol 2020 04 2;65(7):075002. Epub 2020 Apr 2.

Department of Medical Physics, Centre Oscar Lambret, Lille, France. University Lille, CNRS, Centrale Lille, UMR 9189 - CRIStAL, Lille, France. Author to whom any correspondence should be addressed.

The establishment of an MRI-only workflow in radiotherapy depends on the ability to generate an accurate synthetic CT (sCT) for dose calculation. Previously proposed methods have used a Generative Adversarial Network (GAN) for fast sCT generation in order to simplify the clinical workflow and reduces uncertainties. In the current paper we use a conditional Generative Adversarial Network (cGAN) framework called pix2pixHD to create a robust model prone to multicenter data. This study included T2-weighted MR and CT images of 19 patients in treatment position from 3 different sites. The cGAN was trained on 2D transverse slices of 11 patients from 2 different sites. Once trained, the network was used to generate sCT images of 8 patients coming from a third site. The Mean Absolute Errors (MAE) for each patient were evaluated between real and synthetic CTs. A radiotherapy plan was optimized on the sCT series and re-calculated on CTs to assess the dose distribution in terms of voxel-wise dose difference and Dose Volume Histograms (DVH) analysis. It takes on average of [Formula: see text] to generate a complete sCT (88 slices) for a patient on our GPU. The average MAE in HU between the sCT and actual patient CT (within the body contour) is 48.5 ± 6 HU with our method. The maximum dose difference to the target is 1.3%. This study demonstrates that an sCT can be generated in a multicentric context, with fewer pre-processing steps while being fast and accurate.
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http://dx.doi.org/10.1088/1361-6560/ab7633DOI Listing
April 2020

Personalised radioembolization improves outcomes in refractory intra-hepatic cholangiocarcinoma: a multicenter study.

Eur J Nucl Med Mol Imaging 2019 Oct 19;46(11):2270-2279. Epub 2019 Jul 19.

Nuclear Medicine Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium.

Purpose: Reported outcomes of patients with intra-hepatic cholangiocarcinoma (IH-CCA) treated with radioembolization are highly variable, which indicates differences in included patients' characteristics and/or procedure-related variables. This study aimed to identify patient- and treatment-related variables predictive for radioembolization outcome.

Methods: This retrospective multicenter study enrolled 58 patients with unresectable and chemorefractory IH-CCA treated with resin Y-microspheres. Clinicopathologic data were collected from patient records. Metabolic parameters of liver tumor(s) and presence of lymph node metastasis were measured on baseline F-FDG-PET/CT. Tc-MAA tumor to liver uptake ratio (TLR) was computed for each lesion on the SPECT-CT. Activity prescription using body-surface-area (BSA) or more personalized partition-model was recorded. The study endpoint was overall survival (OS) starting from date of radioembolization. Statistical analysis was performed by the log-rank test and multivariate Cox's proportional hazards model.

Results: Median OS (mOS) post-radioembolization of the entire cohort was 10.3 months. Variables associated with significant differences in terms of OS were serum albumin (hazard ratio (HR) = 2.78, 95%CI:1.29-5.98, p = 0.002), total bilirubin (HR = 2.17, 95%CI:1.14-4.12, p = 0.009), aspartate aminotransferase (HR = 2.96, 95%CI:1.50-5.84, p < 0.001), alanine aminotransferase (HR = 2.02, 95%CI:1.05-3.90, p = 0.01) and γ-GT (HR = 2.61, 95%CI:1.31-5.22, p < 0.001). The presence of lymph node metastasis as well as a TLR < 1.9 were associated with shorter mOS: HR = 2.35, 95%CI:1.08-5.11, p = 0.008 and HR = 2.92, 95%CI:1.01-8.44, p = 0.009, respectively. Finally, mOS was significantly shorter in patients treated according to the BSA method compared to the partition-model: mOS of 5.5 vs 14.9 months (HR = 2.52, 95%CI:1.23-5.16, p < 0.001). Multivariate analysis indicated that the only variable that increased outcome prediction above the clinical variables was the activity prescription method with HR of 2.26 (95%CI:1.09-4.70, p = 0.03). The average mean radiation dose to tumors was significantly higher with the partition-model (86Gy) versus BSA (38Gy).

Conclusion: Radioembolization efficacy in patients with unresectable recurrent and/or chemorefractory IH-CCA strongly depends on the tumor radiation dose. Personalized activity prescription should be performed.
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http://dx.doi.org/10.1007/s00259-019-04427-zDOI Listing
October 2019

3D Monte Carlo dosimetry of intraoperative electron radiation therapy (IOERT).

Phys Med 2019 Jan 15;57:207-214. Epub 2019 Jan 15.

Nuclear Metrology, Ecole Polytechnique, Université Libre de Bruxelles, Bruxelles, Belgium; Radiothérapy Department, Institut Jules Bordet, Bruxelles, Belgium.

Purpose: This paper studies the feasibility of using Monte Carlo (MC) for treatment planning of intraoperative electron radiation therapy (IOERT) procedure to get 3D dose by using patient's CT images.

Methods: The IOERT treatment planning was performed using the following successive steps: I) The Mobetron 1000® machine was modelled with the EGSnrc MC codes. II) The MC model was validated with measurements of percentage depth doses and profiles for three energies (12, 9, 6) MeV. III) CT images were imported as DICOM files. IV) Contouring of the planning target volume (PTV) and the organs at risk was done by the radiation oncologist. V) The medical physicist with the radiation oncologist, had chosen the same parameters of IOERT procedures like energy, applicator (type, size) and using or not bolus. VI) Finally, dose calculation and analysis of 3D maps was carried out.

Results: The tuning process of the MC model provides good results, as the maximum value of the root mean square deviation (RMSD) was less than 3% between the MC simulated PDDs and the measured PDDs. The contouring and dose analysis review were easy to conduct for the classical treatment planning system. The radiation oncologist had many tools for dose analysis such as DVH and color wash for all the slides. Summation of the 3D dose of IOERT with other radiotherapy plans is possible and helpful for total dose estimation. Archiving and documentation is as good as treatment planning system (TPS).

Conclusions: The method displayed in this paper provides a step forward for IOERT Dosimetry and allows to obtain accurate dosimetry of treated volumes.
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http://dx.doi.org/10.1016/j.ejmp.2018.12.037DOI Listing
January 2019

A dosimetry procedure for organs-at-risk in Lu peptide receptor radionuclide therapy of patients with neuroendocrine tumours.

Phys Med 2018 Dec 22;56:41-49. Epub 2018 Nov 22.

Department of Nuclear Medicine, Institut Jules Bordet-Université Libre de Bruxelles (ULB), 121 boulevard de Waterloo, 1000 Brussels, Belgium. Electronic address:

Purpose: Peptide receptor radionuclide therapy with Lu-DOTATATE has become a standard treatment modality in neuroendocrine tumours (NETs). No consensus has yet been reached however regarding the absorbed dose threshold for lesion response, the absorbed dose limit to organs-at-risk, and the optimal fractionation and activity to be administered. This is partly due to a lack of uniform and comparable dosimetry protocols. The present article details the development of an organ-at-risk dosimetry procedure, which could be implemented and used routinely in a clinical context.

Methods: Forty-seven patients with NETs underwent Lu-DOTATATE therapy. Three SPECT/CT images were acquired at 4, 24 and 144-192 h post-injection. Three blood samples were obtained together with the SPECT/CT acquisitions and 2 additional samples were obtained around 30 min and 1 h post-injection. A bi-exponential fit was used to compute the source organ time-integrated activity coefficients. Coefficients were introduced into OLINDA/EXM software to compute organ-at-risk absorbed doses. Median values for all patients were computed for absorbed dose coefficient D/A and for late effective half-life T for kidneys, spleen and red marrow.

Results: Dosimetry resulted in a median[interquartile range] of 0.78[0.35], 1.07[0.58] and 0.028[0.010] Gy/GBq for D/A and of 55[9], 71[9] and 52[18] h for T for kidneys, spleen and red marrow respectively.

Conclusions: A dosimetry procedure for organs-at-risk in Lu-DOTATATE therapy based on serial SPECT/CT images and blood samples can be implemented routinely in a clinical context with limited patient burden. The results obtained were in accordance with those of other centres.
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http://dx.doi.org/10.1016/j.ejmp.2018.11.001DOI Listing
December 2018

Shielding disk position in intra-operative electron radiotherapy (IOERT): A Monte Carlo study.

Phys Med 2018 Jul 15;51:1-6. Epub 2018 Jun 15.

Radiotherapy Department, Institute Jules Bordet, Belgium. Electronic address:

Purpose: In IOERT breast treatments, a shielding disk is frequently used to protect the underlying healthy structures. The disk is usually composed of two materials, a low-Z material intended to be oriented towards the beam and a high-Z material. As tissues are repositioned around the shield before treatment, the disk is no longer visible and its correct alignment with respect to the beam is guaranteed. This paper studies the dosimetric characteristics of four possible clinical positioning scenarios of the shielding disk. A new alignment method for the shielding disk in the beam is introduced. Finally, it suggests a new design for the shielding disk.

Methods: As the first step, the IOERT machine "Mobetron 1000" was modeled by using Monte Carlo simulation, tuning the MC model until an excellent match with the measured PDDs and profiles was achieved. Four possible shielding disk positioning scenarios were considered, determining the dosimetric impact. Furthermore, in our center, to prevent beam misalignment, we have developed a shielding disk equipped with guiding rods. Having ascertained a correct alignment between the disk and the beam, we can propose a new internal design of the shielding disk that can improve the dose distribution with a better coverage of the treated area.

Results: All MC simulations were performed with a 12 MeV beam, the maximum energy of Mobetron 1000 and a 5.5 cm diameter flat tip applicator, this applicator being the most clinically used. The simulations were compared with measurements performed in a water phantom and showed good results within 2.2% of root mean square difference (RMSD). The misplacement positions of the shielding disk have dosimetric impacts in the treatment volume and a small translation could have a significant influence on healthy tissues. The D-scenario is the worst which could happens when the shielding disk is flipped upside down, giving up to 144% dose instead of 90% at the surface of the Pb/Al shielding disk. A new shielding design used, together with our alignment tool, is able to give a more homogeneous dose in the target area.

Conclusions: The accuracy of shielding disk position can still be problematic in IOERT dosimetry. Any method that can ascertain the good alignment between the shielding disk and the beam is beneficial for the dose distribution and is a prerequisite for an optimized shield internal design that could improve the coverage of the treated area and the protection of healthy tissues.
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http://dx.doi.org/10.1016/j.ejmp.2018.05.023DOI Listing
July 2018

Y-PET/CT-based dosimetry after selective internal radiation therapy predicts outcome in patients with liver metastases from colorectal cancer.

EJNMMI Res 2018 Jul 13;8(1):60. Epub 2018 Jul 13.

Department of Nuclear Medicine, Jules Bordet Institute, Université Libre de Bruxelles, Rue Héger-Bordet 1, B-1000, Brussels, Belgium.

Background: The aim of this work was to confirm that post-selective internal radiation therapy (SIRT) Y-PET/CT-based dosimetry correlates with lesion metabolic response and to determine its correlation with overall survival (OS) in liver-only metastases from colorectal cancer (mCRC) patients treated with SIRT. Twenty-four mCRC patients underwent pre/post-SIRT FDG-PET/CT and post-SIRT Y-PET/CT. Lesions delineated on pre/post-SIRT FDG-PET/CT were classified as non-metabolic responders (total lesion glycolysis (TLG)-decrease < 15%) and high-metabolic responders (TLG-decrease ≥ 50%). Lesion delineations were projected on the anatomically registered Y-PET/CT. Voxel-based 3D dosimetrywas performed on the Y-PET/CT and lesions' mean absorbed dose (Dmean) was measured. The coefficient of correlation between Dmean and TLG-decrease was calculated. The ability of lesion Dmean to predict non-metabolic response and high-metabolic response was tested and two cutoff values (Dmean-under-treated and Dmean-well-treated) were determined using ROC analysis. Patients were dichotomised in the "treated" group (all the lesions received a Dmean > Dmean-under-treated) and in the "under-treated" group (at least one lesion received a Dmean < Dmean-under-treated). Kaplan-Meier product limit method was used to describe OS curves.

Results: Fifty-seven evaluable mCRC lesions were included. The coefficient of correlation between Dmean and TLG-decrease was 0.82. Two lesion Dmean cutoffs of 39 Gy (sensitivity 80%, specificity 95%, predictive-positive-value 86% and negative-predictive-value 92%) and 60 Gy (sensitivity 70%, specificity 95%, predictive positive-value 96% and negative-predictive-value 63%) were defined to predict non-metabolic response and high-metabolic response respectively. Patients with all lesions Dmean> 39 Gy had a significantly longer OS (13 months) than patients with at least one lesion Dmean < 39 Gy (OS = 5 months) (p = 0.012;hazard-ratio, 2.6 (95% CI 0.98-7.00)).

Conclusions: In chemorefractory mCRC patients treated with SIRT, lesion Dmean determined on post-SIRT Y-PET/CT correlates with metabolic response and higher lesion Dmean is associated with prolonged OS.
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http://dx.doi.org/10.1186/s13550-018-0419-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045565PMC
July 2018

Diffusion weighted MRI as an early predictor of tumor response to hypofractionated stereotactic boost for prostate cancer.

Sci Rep 2018 Jul 10;8(1):10407. Epub 2018 Jul 10.

INSERM, U1171, University of Lille, Lille, France.

We evaluated the feasibility of using the kinetic of diffusion-weighted MRI (DWI) and the normalized apparent coefficient diffusion (ADC) map value as an early biomarker in patients treated by external beam radiotherapy (EBRT). Twelve patients were included within the frame of a multicenter phase II trial and treated for intermediate risk prostate cancer (PCa). Multiparametric MRI was performed before treatment (M0) and every 6 months until M24. Association between nADC and PSA or PSA kinetic was evaluated using the test of nullity of the Spearman correlation coefficient. The median rates of PSA at the time of diagnosis, two years and four years after EBRT were 9.29 ng/ml (range from 5.26 to 17.67), 0.68 ng/ml (0.07-2.7), 0.47 ng/ml (0.09-1.39), respectively. Median nADC increased from 1.14 × 10 mm/s to 1.59 × 10 mm/s between M0 and M24. Only one patient presented a decrease of nADC (1.35 × 10 mm/s and 1.11 × 10 mm/s at M0 and M12 respectively). The increase in nADC at M6 was correlated with PSA decrease at M18, M24 and M30 (p < 0.05). The increase in nADc at M12 was correlated with PSA decrease at M36 (p = 0.019). Early nADC variation were correlated with late PSA decrease for patients with PCa treated by EBRT.
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http://dx.doi.org/10.1038/s41598-018-28817-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039515PMC
July 2018

On the conversion of dose to bone to dose to water in radiotherapy treatment planning systems.

Phys Imaging Radiat Oncol 2018 Jan 9;5:26-30. Epub 2018 Feb 9.

National Physics Laboratory, Acoustics and Ionising Radiation Division, Teddington, TW 11 0LW, UK.

Background And Purpose: Conversion factors between dose to medium (D) and dose to water (D) provided by treatment planning systems that model the patient as water with variable electron density are currently based on stopping power ratios. In the current paper it will be illustrated that this conversion method is not correct.

Materials And Methods: Monte Carlo calculations were performed in a phantom consisting of a 2 cm bone layer surrounded by water. D was obtained by modelling the bone layer as water with the electron density of bone. Conversion factors between D and D were obtained and compared to stopping power ratios and ratios of mass-energy absorption coefficients in regions of electronic equilibrium and interfaces. Calculations were performed for 6 MV and 20 MV photon beams.

Results: In the region of electronic equilibrium the stopping power ratio of water to bone (1.11) largely overestimates the conversion obtained using the Monte Carlo calculations (1.06). In that region the MC dose conversion corresponds to the ratio of mass energy absorption coefficients. Near the water to bone interface, the MC ratio cannot be determined from stopping powers or mass energy absorption coefficients.

Conclusion: Stopping power ratios cannot be used for conversion from D to D provided by treatment planning systems that model the patient as water with variable electron density, either in regions of electronic equilibrium or near interfaces. In regions of electronic equilibrium mass energy absorption coefficient ratios should be used. Conversions at interfaces require detailed MC calculations.
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http://dx.doi.org/10.1016/j.phro.2018.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807555PMC
January 2018

Abstract ID: 222 Clinical implementation of a Monte Carlo based QA platform for validation of Tomotherapy and Cyberknife treatment plans.

Phys Med 2018 Jan;45 Suppl 1:S3-S4

Centre Oscar Lambret, Medical Physics Department - Academic Department of Radiation Oncology, Lille, France; Institut Jules Bordet - Université Libre de Bruxelles, Medical Physics Department, Brussels, Belgium.

Introduction: This work describes the clinical implementation of a Monte Carlo based platform for treatment plan validation for Tomotherapy and Cyberknife, including a semi-automatic plan evaluation module based on dose constraints for organs-at-risk (OAR).

Methods: The Monte Carlo-based platform Moderato [1] is based on BEAMnrc/DOSXYZnrc and allows for automated re-calculation of doses planned with Tomotherapy and Cyberknife techniques. The Prescription/Validation module generates a set of dose constraints based on the anatomical region and fractionation scheme considered. Upon achievement of the planning, dose results are displayed with visual warnings in case of constraint violation. The system was tested on 83 patient cases in order to evaluate the influence of difference in calculation algorithms on OAR constraints.

Results: The first results with the Tomotherapy plans allowed for detecting and correcting a problem with the CT Hounsfield units when using a large reconstruction diameter (a CT artifact that lead to air voxels with an overestimated density). The Cyberknife results also showed some dose differences associated with different energy thresholds between Moderato and the Monte Carlo algorithm used in the Treatment Planning Station. Regarding OAR constraints, re-calculation generated few violations in thoracic, pelvic and abdominal cases. However, in spinal and head cases, significant differences can appear (-11% to +6%) on optic pathways and spinal cord, leading to doses above the limits.

Conclusions: The Moderato platform constitutes a promising tool for the validation of plan quality, offering both dose re-calculation and OAR constraints evaluation. First results show the importance of this verification for some specific regions. Further work is ongoing to optimize the quantity and relevance of the information displayed, before fully introducing the system in clinical routine.
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http://dx.doi.org/10.1016/j.ejmp.2017.11.030DOI Listing
January 2018

Dosimetric characterization of MRI-only treatment planning for brain tumors in atlas-based pseudo-CT images generated from standard T1-weighted MR images.

Med Phys 2016 Dec;43(12):6557

Department of Radiotherapy, Centre Oscar Lambret, Lille 59000, France.

Purpose: Magnetic resonance imaging (MRI)-only radiotherapy treatment planning requires accurate pseudo-CT (pCT) images for precise dose calculation. The current work introduced an atlas-based method combined with MR intensity information. pCT analyses and Monte Carlo dose calculations for intracranial stereotactic treatments were performed.

Methods: Twenty-two patients, representing 35 tumor targets, were scanned using a 3D T1-weighted MRI sequence according to the clinical protocol. The MR atlas image was registered to the MR patient image using a deformable algorithm, and the deformation was then applied to the atlas CT. Two methods were applied. The first method (MRdef) was based on deformations only, while the second (MRint) also used the actual MR intensities. pCT analysis was performed using the mean (absolute) error, as well as an in-house tool based on a gamma index. Dose differences between pCT and true CT were analyzed using dose-volume histogram (DVH) parameters, statistical tests, the gamma index, and probability density functions. An unusual case, where the patient underwent an operation (part of the skull bone was removed), was studied in detail.

Results: Soft tissues presented a mean error inferior to 50 HUs, while low-density tissues and bones presented discrepancies up to 600 HUs for hard bone. The MRdef method led to significant dose differences compared with the true CT (p-value < 0.05; Wilcoxon-signed-rank test). The MRint method performed better. The DVH parameter differences compared with CT were between -2.9% and 3.1%, except for two cases where the tumors were located within the sphenoid bone. For these cases, the dose errors were up to 6.6% and 5.4% (D and D). Furthermore, for 85% of the tested patients, the mean dose to the planning target volume agreed within 2% with the calculation using the actual CT. Fictitious bone was generated in the unusual case using atlas-based methods.

Conclusions: Generally, the atlas-based method led to acceptable dose distributions. The use of common T1 sequences allows the implementation of this method in clinical routine. However, unusual patient anatomy may produce large dose calculation errors. The detection of large anatomic discrepancies using MR image subtraction can be realized, but an alternative way to produce synthetic CT numbers in these regions is still required.
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http://dx.doi.org/10.1118/1.4967480DOI Listing
December 2016

Accelerated partial breast irradiation using robotic radiotherapy: a dosimetric comparison with tomotherapy and three-dimensional conformal radiotherapy.

Radiat Oncol 2016 Feb 27;11:29. Epub 2016 Feb 27.

Academic Department of Radiation Oncology, Centre Oscar Lambret, 3 rue Frédéric Combemale, BP 307, 59020, LILLE Cedex, France.

Background: Accelerated partial breast irradiation (APBI) is a new breast treatment modality aiming to reduce treatment time using hypo fractionation. Compared to conventional whole breast irradiation that takes 5 to 6 weeks, APBI is reported to induce worse cosmetic outcomes both when using three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT). These late normal tissue effects may be attributed to the dose volume effect because a large portion of the non-target breast tissue volume (NTBTV) receives a high dose. In the context of APBI, non-coplanar beams could spare the NTBTV more efficiently. This study evaluates the dosimetric benefit of using the Cyberknife (CK) for APBI in comparison to IMRT (Tomotherapy) and three dimensional conformal radiotherapy (3D-CRT).

Methods: The possibility of using surgical clips, implanted during surgery, to track target movements is investigated first. A phantom of a female thorax was designed in-house using the measurements of 20 patients. Surgical clips of different sizes were inserted inside the breast. A treatment plan was delivered to the mobile and immobile phantom. The motion compensation accuracy was evaluated using three radiochromic films inserted inside the breast. Three dimensional conformal radiotherapy (3D-CRT), Tomotherapy (TOMO) and CK treatment plans were calculated for 10 consecutive patients who received APBI in Lille. To ensure a fair comparison of the three techniques, margins applied to the CTV were set to 10 mm. However, a second CK plan was prepared using 3 mm margins to evaluate the benefits of motion compensation.

Results: Only the larger clips (VITALITEC Medium-Large) could be tracked inside the larger breast (all gamma indices below 1 for 1 % of the maximum dose and 1 mm). All techniques meet the guidelines defined in the NSABP/RTOG and SHARE protocols. As the applied dose volume constraints are very strong, insignificant dosimetric differences exist between techniques regarding the PTV coverage and the sparing of the lung and heart. However, the CK may be used to reduce high doses received by the NTBTV more efficiently.

Conclusions: Robotic stereotactic radiotherapy may be used for APBI to more efficiently spare the NTBTV and improve cosmetic results of APBI.
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http://dx.doi.org/10.1186/s13014-016-0607-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769549PMC
February 2016

Monte Carlo calculation based on hydrogen composition of the tissue for MV photon radiotherapy.

J Appl Clin Med Phys 2015 09 8;16(5):117–130. Epub 2015 Sep 8.

Centre Oscar Lambret; AQUILAB SAS; UMR CNRS 8520.

The purpose of this study was to demonstrate that Monte Carlo treatment planning systems require tissue characterization (density and composition) as a function of CT number. A discrete set of tissue classes with a specific composition is introduced. In the current work we demonstrate that, for megavoltage photon radiotherapy, only the hydrogen content of the different tissues is of interest. This conclusion might have an impact on MRI-based dose calculations and on MVCT calibration using tissue substitutes. A stoichiometric calibration was performed, grouping tissues with similar atomic composition into 15 dosimetrically equivalent subsets. To demonstrate the importance of hydrogen, a new scheme was derived, with correct hydrogen content, complemented by oxygen (all elements differing from hydrogen are replaced by oxygen). Mass attenuation coefficients and mass stopping powers for this scheme were calculated and compared to the original scheme. Twenty-five CyberKnife treatment plans were recalculated by an in-house developed Monte Carlo system using tissue density and hydrogen content derived from the CT images. The results were compared to Monte Carlo simulations using the original stoichiometric calibration. Between 300 keV and 3 MeV, the relative difference of mass attenuation coefficients is under 1% within all subsets. Between 10 keV and 20 MeV, the relative difference of mass stopping powers goes up to 5% in hard bone and remains below 2% for all other tissue subsets. Dose-volume histograms (DVHs) of the treatment plans present no visual difference between the two schemes. Relative differences of dose indexes D98, D95, D50, D05, D02, and Dmean were analyzed and a distribution centered around zero and of standard deviation below 2% (3 σ) was established. On the other hand, once the hydrogen content is slightly modified, important dose differences are obtained. Monte Carlo dose planning in the field of megavoltage photon radiotherapy is fully achievable using only hydrogen content of tissues, a conclusion that might impact MRI dose calculation, but can also help selecting the optimal tissue substitutes when calibrating MVCT devices.
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http://dx.doi.org/10.1120/jacmp.v16i5.5586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690166PMC
September 2015

Adapted Prescription Dose for Monte Carlo Algorithm in Lung SBRT: Clinical Outcome on 205 Patients.

PLoS One 2015 24;10(7):e0133617. Epub 2015 Jul 24.

Academic Radiation Oncology Department, Oscar Lambret Comprehensive Cancer Center, 3 rue Frédéric Combemale, Lille, France; Faculty of Medicine, University Lille 2, Lille, France; ONCOLille, maison régionale de la recherche Clinique, Lille, France.

Purpose: SBRT is the standard of care for inoperable patients with early-stage lung cancer without lymph node involvement. Excellent local control rates have been reported in a large number of series. However, prescription doses and calculation algorithms vary to a great extent between studies, even if most teams prescribe to the D95 of the PTV. Type A algorithms are known to produce dosimetric discrepancies in heterogeneous tissues such as lungs. This study was performed to present a Monte Carlo (MC) prescription dose for NSCLC adapted to lesion size and location and compare the clinical outcomes of two cohorts of patients treated with a standard prescription dose calculated by a type A algorithm or the proposed MC protocol.

Patients And Methods: Patients were treated from January 2011 to April 2013 with a type B algorithm (MC) prescription with 54 Gy in three fractions for peripheral lesions with a diameter under 30 mm, 60 Gy in 3 fractions for lesions with a diameter over 30 mm, and 55 Gy in five fractions for central lesions. Clinical outcome was compared to a series of 121 patients treated with a type A algorithm (TA) with three fractions of 20 Gy for peripheral lesions and 60 Gy in five fractions for central lesions prescribed to the PTV D95 until January 2011. All treatment plans were recalculated with both algorithms for this study. Spearman's rank correlation coefficient was calculated for GTV and PTV. Local control, overall survival and toxicity were compared between the two groups.

Results: 205 patients with 214 lesions were included in the study. Among these, 93 lesions were treated with MC and 121 were treated with TA. Overall survival rates were 86% and 94% at one and two years, respectively. Local control rates were 79% and 93% at one and two years respectively. There was no significant difference between the two groups for overall survival (p = 0.785) or local control (p = 0.934). Fifty-six patients (27%) developed grade I lung fibrosis without clinical consequences. GTV size was a prognostic factor for overall survival (HR = 1.026, IC95% [1.01-1.041], p<0.001) and total dose was a prognostic factor for local control (HR = 0.924, IC95% [0.870-0.982], p = 0.011). D50 of the GTV calculated with MC correlated poorly with the D95 of the PTV calculated with TA (r = 0.116) for lesions with a diameter of 20 mm or less. For lesions larger than 20 mm, spearman correlation was higher (r = 0.618), but still insufficient.

Conclusion: No difference in local control or overall survival was found between patients treated with a type A or a type B algorithm in our cohort. A size and location adapted GTV-based prescription method could be used with a type B algorithm. External validation of these results is warranted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133617PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514775PMC
May 2016

Registration by interactive inverse simulation: application for adaptive radiotherapy.

Int J Comput Assist Radiol Surg 2015 Aug 7;10(8):1193-200. Epub 2015 Apr 7.

Oscar Lambret Hospital, Lille, France,

Purpose: This paper introduces a new methodology for semi-automatic registration of anatomical structure deformations. The contribution is to use an interactive inverse simulation of physics-based deformable model, computed in real time.

Methods: The method relies on nonlinear finite element method (FEM) within a constraint-based framework. Given a set of few registered points provided by the user, a real-time optimization adapts the boundary conditions and(/or) some parameters of the FEM in order to obtain the adequate geometrical deformations. To dramatically fasten the process, the method relies on a projection of the model in the space of the optimization variables. In this reduced space, a quadratic programming problem is formulated and solved very quickly. The method is validated with numerical examples for retrieving some unknown parameters such as the Young's modulus and some pressures on the boundaries of the model.

Results: The approach is employed in the context of radiotherapy of the neck where weight loss during the 7 weeks of the therapy modifies the volume of the anatomical structures and induces large deformations. Indeed, sensitive structures such as the parotid glands may cross the target volume due to these deformations which leads to adverse effects for the patient. We thus apply the approach for the registration of the parotid glands during the radiotherapy of the head and neck cancer.

Conclusions: The results show how the method could be used in a clinical routine and be employed in the planning in order to limit the radiations of these glands.
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http://dx.doi.org/10.1007/s11548-015-1175-4DOI Listing
August 2015

What is the normal tissues morbidity following Helical Intensity Modulated Radiation Treatment for cervical cancer?

Radiother Oncol 2015 Jun 4;115(3):386-91. Epub 2015 Mar 4.

Centre Oscar Lambret, Université Lille 2 and ONCOLille Consortium, France.

Background And Purpose: To report on normal tissues morbidity following IMRT for cervix cancer.

Material And Methods: The first 61 patients of a prospective series were included. 50 Gy to the PTV 1(pelvis) and 60 Gy to the PTV 2 (centro-pelvic disease and GTV nodes) were delivered concomitantly in 28 fractions, followed by a brachytherapy boost. For the small bowel, 50 Gy was the maximal dose, while V45 and V40 had to be <50 cc and 200 cc, respectively. For the bladder, rectum and sigmoid structures, 60 Gy was the maximal dose, and V45 and V40 had to be <20% and <50%. Acute and late toxicity data were prospectively collected.

Results: The median follow-up period was 40 months (range: 23-60). 30% and 90% of acute and moderate late side effects were reported respectively. Considering the AUC data of the organs at risk (OAR) DVH, late morbidity and doses were significantly linked (p⩽0.03), predominantly between 10 Gy and 40 Gy, considering the small bowel and sigmoid colon. The high dose regions exhibited no significant impact.

Conclusion: The moderate dose volumes represent the predominant cause of morbidity after IMRT. Prospective trials are thus required to investigate new ways of dose distribution within the OAR.
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http://dx.doi.org/10.1016/j.radonc.2015.02.010DOI Listing
June 2015

Introducing interactive inverse FEM simulation and its application for adaptive radiotherapy.

Med Image Comput Comput Assist Interv 2014 ;17(Pt 2):81-8

We introduce a new methodology for semi-automatic deformable registration of anatomical structures, using interactive inverse simulations. The method relies on non-linear real-time Finite Element Method (FEM) within a constraint-based framework. Given a set of few registered points provided by the user, a real-time optimization adapts the boundary conditions and(/or) some parameters of the FEM in order to obtain the adequate geometrical deformations. To dramatically fasten the process, the method relies on a projection of the model in the space of the optimization variables. In this reduced space, a quadratic programming problem is formulated and solved very quickly. The method is validated with numerical examples for retrieving Young's modulus and some pressures on the boundaries. Then, we apply the approach for the registration of the parotid glands during the radiotherapy of the head and neck cancer. Radiotherapy treatment induces weight loss that modifies the shape and the positions of these structures and they eventually intersect the target volume. We show how we could adapt the planning to limit the radiation of these glands.
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http://dx.doi.org/10.1007/978-3-319-10470-6_11DOI Listing
January 2015

GTV-based prescription in SBRT for lung lesions using advanced dose calculation algorithms.

Radiat Oncol 2014 Oct 16;9:223. Epub 2014 Oct 16.

Service de Physique Médicale, Centre Oscar Lambret, Lille, France.

Background: The aim of current study was to investigate the way dose is prescribed to lung lesions during SBRT using advanced dose calculation algorithms that take into account electron transport (type B algorithms). As type A algorithms do not take into account secondary electron transport, they overestimate the dose to lung lesions. Type B algorithms are more accurate but still no consensus is reached regarding dose prescription. The positive clinical results obtained using type A algorithms should be used as a starting point.

Methods: In current work a dose-calculation experiment is performed, presenting different prescription methods. Three cases with three different sizes of peripheral lung lesions were planned using three different treatment platforms. For each individual case 60 Gy to the PTV was prescribed using a type A algorithm and the dose distribution was recalculated using a type B algorithm in order to evaluate the impact of the secondary electron transport. Secondly, for each case a type B algorithm was used to prescribe 48 Gy to the PTV, and the resulting doses to the GTV were analyzed. Finally, prescriptions based on specific GTV dose volumes were evaluated.

Results: When using a type A algorithm to prescribe the same dose to the PTV, the differences regarding median GTV doses among platforms and cases were always less than 10% of the prescription dose. The prescription to the PTV based on type B algorithms, leads to a more important variability of the median GTV dose among cases and among platforms, (respectively 24%, and 28%). However, when 54 Gy was prescribed as median GTV dose, using a type B algorithm, the variability observed was minimal.

Conclusion: Normalizing the prescription dose to the median GTV dose for lung lesions avoids variability among different cases and treatment platforms of SBRT when type B algorithms are used to calculate the dose. The combination of using a type A algorithm to optimize a homogeneous dose in the PTV and using a type B algorithm to prescribe the median GTV dose provides a very robust method for treating lung lesions.
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http://dx.doi.org/10.1186/s13014-014-0223-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205279PMC
October 2014

Characterization of recombination effects in a liquid ionization chamber used for the dosimetry of a radiosurgical accelerator.

J Vis Exp 2014 May 9(87). Epub 2014 May 9.

Department of Medical Physics, Centre Oscar Lambret.

Most modern radiation therapy devices allow the use of very small fields, either through beamlets in Intensity-Modulated Radiation Therapy (IMRT) or via stereotactic radiotherapy where positioning accuracy allows delivering very high doses per fraction in a small volume of the patient. Dosimetric measurements on medical accelerators are conventionally realized using air-filled ionization chambers. However, in small beams these are subject to nonnegligible perturbation effects. This study focuses on liquid ionization chambers, which offer advantages in terms of spatial resolution and low fluence perturbation. Ion recombination effects are investigated for the microLion detector (PTW) used with the Cyberknife system (Accuray). The method consists of performing a series of water tank measurements at different source-surface distances, and applying corrections to the liquid detector readings based on simultaneous gaseous detector measurements. This approach facilitates isolating the recombination effects arising from the high density of the liquid sensitive medium and obtaining correction factors to apply to the detector readings. The main difficulty resides in achieving a sufficient level of accuracy in the setup to be able to detect small changes in the chamber response.
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http://dx.doi.org/10.3791/51296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174048PMC
May 2014

Improving dose calculations on tomotherapy MVCT images.

J Appl Clin Med Phys 2012 Sep 6;13(6):3986. Epub 2012 Sep 6.

Department of Medical Physics, Centre Oscar Lambret, 3, Rue Frédéric Combémale, 59020 Lille, France.

The purpose of this investigation was the creation of a new protocol allowing more precise dose calculations on megavoltage CT (MVCT) images for tomotherapy, both for adaptive and StatRT planning. Daily MVCT images offer, next to positioning purposes, the possibility for daily dose check and adaptive planning. Dose calculations use the image value to density table (IVDT) to calculate physical densities from Hounsfield Units (HUs). These measured HUs change over time, leading to a dose calculation error. We noticed dose calculation variations due to IVDT changes of: 0.2% dose during a day, up to 1.6% dose from long-term variations, and up to 1.5% dose due to technical interventions. An analysis was performed applying the general methodology of a calibration problem. A model HU = bρc - 1020 was obtained using a weighted least squares inverse prediction method (HU as function of density) taking into account the heteroscedasticity. The b parameter is the major variable and depends also on the dose rate (DR). We demonstrate the correction for DR variations and the constance of the c parameter. Instead of scanning the whole tissue characterization phantom daily, we propose a simplified daily protocol: (a) morning airscan-like procedure with only two inserts on the table (defining b and thus the IVDT curve), (b) DR variations throughout the day can be corrected for using the DR model. A patient-specific protocol for which two inserts next to the patient are scanned could also be used, but results in equal uncertainties and is less practical. Therefore we recommend the morning procedure with dose rate variation correction. Applying the proposed transformations and the model, the correct IVDT of the moment can be reconstructed, with a simple measurement in the morning, and corrected with DR changes during the day. This corresponds with a linear mapping in time of the proposed IVDT function. The dosimetric variation is hereby reduced from up to 3% to 0.4 % for the tested pelvic and head-and-neck cases. In practice, several IVDT curves corresponding to "b" values can be entered. The correct IVDT curve of that moment can then be chosen from the list. Instead of the two high-density inserts on table, any calibrated single density phantom could be used in order to create the IVDT curve of the day, but it should have a larger size than the current inserts.
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http://dx.doi.org/10.1120/jacmp.v13i6.3986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718528PMC
September 2012

Dosimetric comparison of different treatment modalities for stereotactic radiosurgery of arteriovenous malformations and acoustic neuromas.

Radiother Oncol 2013 Feb 10;106(2):192-7. Epub 2012 Aug 10.

Department of Radiotherapy, Universitair Ziekenhuis Brussel, Brussel, Belgium.

Purpose: We investigated the influence of beam modulation on treatment planning by comparing four available stereotactic radiosurgery (SRS) modalities: Gamma-Knife-Perfexion, Novalis-Tx Dynamic-Conformal-Arc (DCA) and Dynamic-Multileaf-Collimation-Intensity-Modulated-radiotherapy (DMLC-IMRT), and Cyberknife.

Material And Methods: Patients with arteriovenous malformation (n = 10) or acoustic neuromas (n = 5) were planned with different treatment modalities. Paddick conformity index (CI), dose heterogeneity (DH), gradient index (GI) and beam-on time were used as dosimetric indices.

Results: Gamma-Knife-Perfexion can achieve high degree of conformity (CI = 0.77 ± 0.04) with limited low-doses (GI = 2.59 ± 0.10) surrounding the inhomogeneous dose distribution (D(H) = 0.84 ± 0.05) at the cost of treatment time (68.1 min ± 27.5). Novalis-Tx-DCA improved this inhomogeneity (D(H) = 0.30 ± 0.03) and treatment time (16.8 min ± 2.2) at the cost of conformity (CI = 0.66 ± 0.04) and Novalis-TX-DMLC-IMRT improved the DCA CI (CI = 0.68 ± 0.04) and inhomogeneity (D(H) = 0.18 ± 0.05) at the cost of low-doses (GI = 3.94 ± 0.92) and treatment time (21.7 min ± 3.4) (p<0.01). Cyberknife achieved comparable conformity (CI = 0.77 ± 0.06) at the cost of low-doses (GI = 3.48 ± 0.47) surrounding the homogeneous (D(H) = 0.22 ± 0.02) dose distribution and treatment time (28.4min±8.1) (p<0.01).

Conclusions: Gamma-Knife-Perfexion will comply with all SRS constraints (high conformity while minimizing low-dose spread). Multiple focal entries (Gamma-Knife-Perfexion and Cyberknife) will achieve better conformity than High-Definition-MLC of Novalis-Tx at the cost of treatment time. Non-isocentric beams (Cyberknife) or IMRT-beams (Novalis-Tx-DMLC-IMRT) will spread more low-dose than multiple isocenters (Gamma-Knife-Perfexion) or dynamic arcs (Novalis-Tx-DCA). Inverse planning and modulated fluences (Novalis-Tx-DMLC-IMRT and CyberKnife) will deliver the most homogeneous treatment. Furthermore, Linac-based systems (Novalis and Cyberknife) can perform image verification at the time of treatment delivery.
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http://dx.doi.org/10.1016/j.radonc.2012.07.002DOI Listing
February 2013
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