Evaluation of stereotactic VMAT lung treatment plans for small moving targets.

PURPOSE: The aim of this study is to perform patient quality controls and end-to-end tests for stereotactic VMAT lung treatment plans and to investigate the influence of various parameters on the results. METHOD: 18 plans were defined by an experimental design methodology to cover a large variety of stereotactic VMAT lung treatments including different doses per fraction, target diameters, target movements and respiratory parameters. Plans were first controlled using portal dosimetry and a homogeneous static cylindrical phantom. End-to-end tests were then performed in a dynamic respiratory thorax phantom. Measurements were conducted with ionization chamber and films. Calculations were performed with the AcurosXB and AAA algorithms in 6 FFF. RESULTS: Portal dosimetry gave excellent gamma pass rates (greater than 97.1 %) and dose deviations between measurement and calculations in a homogeneous static phantom were smaller than 2 %. The methodology followed for comparing calculated and measured doses in a moving target was validated in static fields (largest deviation smaller than  2 %). End-to-end tests showed mean deviations of 1.9 %, 3.3 % and 6.6 % for the 3, 2 and 1 cm diameter's target respectively. Deviations increased for larger movements for the 1 cm lesion. CONCLUSION: End-to-end tests revealed that stereotactic VMAT lung treatment plans for moving targets can be delivered within 5 % for 3 and 2 cm diameter targets and amplitudes up to 1.5 cm. The AcurosXB and AAA algorithms however tend to underestimate the dose to the target. Even with satisfactory patient quality controls like portal dosimetry, extra care should be taken for GTV lesions smaller than 2 cm.

Evaluation of a commercial synthetic computed tomography generation solution for magnetic resonance imaging-only radiotherapy.

PURPOSE: To evaluate the Siemens solution generating Synthetic computed tomography (sCT) for magnetic resonance imaging (MRI)-only radiotherapy (RT). METHOD: A retrospective study was conducted on 47 patients treated with external beam RT for brain or prostate cancer who underwent both MRI and CT for treatment planning. sCT images were generated from MRI using automatic bulk densities segmentation. The geometric accuracy of the sCT was assessed by comparing the Hounsfield Units (HU) difference between sCT and CT for bone structures, soft-tissue, and full body contour. VMAT plans were computed on the CT for treatment preparation and then copied and recalculated with the same monitor units on the sCT using the AcurosXB algorithm. A 1%-1mm gamma analysis was performed and DVH metrics for the Planning Target Volume (PTV) like the Dmean  and the D98% were compared. In addition, we evaluate the usability of sCT for daily position verification with cone beam computed tomography (CBCT) for 14 prostate patients by comparing sCT/CBCT registration results to CT/CBCT. RESULTS: Mean HU differences were small except for the skull (207 HU) and right femoral head of four patients where significant aberrations were found. The mean gamma pass rate was 73.2% for the brain and 84.7% for the prostate and Dmean were smaller than 0.5%. Large differences for the D98% of the prostate group could be correlated to low Dice index of the PTV. The mean difference of translations and rotations were inferior to 3.5 mm and 0.2° in all directions with a major difference in the anterior-posterior direction. CONCLUSION: The performances of the software were shown to be similar to other sCT generation algorithms in terms of HU difference, dose comparison and daily image localization.

Comparison of five dose calculation algorithms in a heterogeneous media using design of experiment.

PURPOSE: Design of experiments (DoE) provides a methodology to reveal the influence of input values on the measured output with a limited number of trials. The purpose of this study was to describe how DoE can be used to evaluate the performances of several dose calculation systems in heterogeneous media, including algorithms like Pencil Beam (PB), Anisotropic Analytical Algorithm (AAA), Acuros XB (AXB), Monte Carlo (MC) and Collapsed Cone Volume (CCV). METHOD: This study was carried out using a CIRS Model 002LFC IMRT Thorax Phantom customized with a water-equivalent heterogeneity inside the lung. The calculated dose distributions were compared to Gafchromic® EBT3 film measurements. The beam configurations were selected using DoE to study the influence of five parameters simultaneously (energy, collimator angulation, gantry angulation, X and Y jaws) and to optimize the number of experiments. An analysis of variance was performed over the entire irradiation field and over various regions of interest (tumour, shadow of tumour and lungs). RESULTS: DoE enabled to quantify and determine the statistically significant factors, leading to an evaluation of the dose calculation systems in the lung case. The resulting scoring could be as follow (from best to worst): AXB_Dm, CCV, AXB_Dw, XVMC_Dm, XVMC_Dw, AAA and last PB. Differences between the algorithms were specially observed in the tumour and the shadow regions. CONCLUSION: DoE is a robust statistical method to compare several dose calculation systems. The various analyses lead to the conclusion that AXB handled more accurately most of the situations investigated in heterogeneous media.

Design of experiments in medical physics: Application to the AAA beam model validation.

PURPOSE: The purpose of this study is to evaluate the usefulness of the design of experiments in the analysis of multiparametric problems related to the quality assurance in radiotherapy. The main motivation is to use this statistical method to optimize the quality assurance processes in the validation of beam models. METHOD: Considering the Varian Eclipse system, eight parameters with several levels were selected: energy, MLC, depth, X, Y1 and Y2 jaw dimensions, wedge and wedge jaw. A Taguchi table was used to define 72 validation tests. Measurements were conducted in water using a CC04 on a TrueBeam STx, a TrueBeam Tx, a Trilogy and a 2300IX accelerator matched by the vendor. Dose was computed using the AAA algorithm. The same raw data was used for all accelerators during the beam modelling. RESULTS: The mean difference between computed and measured doses was 0.1±0.5% for all beams and all accelerators with a maximum difference of 2.4% (under the 3% tolerance level). For all beams, the measured doses were within 0.6% for all accelerators. The energy was found to be an influencing parameter but the deviations observed were smaller than 1% and not considered clinically significant. CONCLUSION: Designs of experiment can help define the optimal measurement set to validate a beam model. The proposed method can be used to identify the prognostic factors of dose accuracy. The beam models were validated for the 4 accelerators which were found dosimetrically equivalent even though the accelerator characteristics differ.

[Spinal stereotactic body radiotherapy: French assessment in 2016]. / État des lieux de la radiothérapie en conditions stéréotaxiques vertébrale en France en 2016.

PURPOSE: Stereotactic body radiotherapy to vertebral column remains uncommon practice and only relevant in selected group of patients. The main objective of the study was to describe the current state of medical practices of stereotactic body radiotherapy to vertebral column in France in 2016 and to assess the diversity of practices to identify areas for improvement and establish a common database set for this technique. MATERIALS AND METHODS: A questionnaire was written with contribution of a medical physicist, a radiation oncologist, an information technologist and a radiotherapy resident. The questionnaire was distributed online to a radiation oncologists and a medical physicists partner of selected French radiotherapy specialized centres that provide stereotactic body radiotherapy to vertebral metastasis from April to June 2016. The questionnaire surveyed the following topics: patients' selection, simulation, targeted volume and organs at risk delineation, prescription, dosimetric implementation and image guidance. RESULTS: A total of 31 centres were surveyed. Seventy eight per cent of centres (n=21) completed the questionnaire. The "ideal" patient for spine stereotactic radiotherapy according to these institutions has a good performance status, a long life expectancy, controlled primary tumour with oligometastatic spread. The most prescribed protocol was 30Gy in three fractions. For clinical target volume delineation, about two thirds of centres used the International Spine Radiosurgery Consortium (ISRC) recommendations (Noël G et al.,2006). CONCLUSION: This study identified some consistency of practices in some aspects despite the lack of consensus guidelines. Nevertheless, further studies are needed to establish consensus of planning and treatment.

[Recurrence sites following definitive intensity-modulated conformational radiotherapy of squamous-cell carcinomas of the upper aerodigestive tract]. / Sites de récidive après radiothérapie conformationnelle avec modulation d'intensité des carcinomes épidermoïdes des voies aérodigestives supérieures.

PURPOSE: The implementation of intensity-modulated radiotherapy (IMRT) in a centre requires regular critical review of medical practices and feedback to optimize the subsequent management of patients. PATIENTS AND METHODS: We reviewed and determined through a retrospective single-centre study recurrence sites of 167 consecutive patients treated for head and neck squamous cell carcinoma excluding skin or sinuses. Patients had mostly stage III or IV locally advanced cancer (n=123). RESULTS: Locoregional control rates at 1 and 2 years were respectively 87.9% (95% confidence interval [95%CI]: 81.6%-92.1%) and 77.6% (95%CI: 70.1%-83.5). Among 55 relapses, 20 patients (36.4%) had treatment failures. Patients treated with 70 Gy relapsed mainly in high risk volume (78%). Those treated with 66 Gy recurred regionally outside the irradiated volume (n=4) or in the irradiated high risk volume (n=3) or had isolated metastatic failure (n=3). Those irradiated with 50 Gy had regional relapse outside the irradiated volume (n=2) or isolated metastatic relapse (n=2). We noticed respectively 5.4%, 10.2% and 4.2% isolated metastatic, local, cervical lymph node relapse. CONCLUSION: Our results are consistent with data from the literature. Corrective actions were performed to enhance our practices.

Silencing of miR-21 by locked nucleic acid-lipid nanocapsule complexes sensitize human glioblastoma cells to radiation-induced cell death.

The recent discovery of microRNA (miRNA) as major post-transcriptional repressors prompt the interest of developing novel approaches to target miRNA pathways to improve therapy. In this context, although the most significant barrier to their widespread clinical use remains delivery, nuclease-resistant locked nucleic acid (LNA) that bind specifically and irreversibly to miRNA represent interesting weapons. Thus, by focusing on oncongenic miR-21 miRNA, which participate to cancer cell resistance to apoptotic signals, the aim of the present study was to investigate the possibility of silencing miRNA by LNA conjugated to lipid nanocapsules (LNCs) as miRNA-targeted nanomedicines in U87MG glioblastoma (GBM) cells. After synthesis of an amphiphilic lipopeptide affine for nucleic acids, a post-insertion procedure during the LNC phase inversion formulation process allowed to construct peptide-conjugated LNCs. Peptide-conjugated LNCs were then incubated with LNAs to allow the formation of complexes characterized in gel retardation assays and by their physicochemical properties. U87MG cell treatment by LNA-LNC complexes resulted in a marked reduction of miR-21 expression as assessed by RTqPCR. In addition, exposure of U87MG cells to LNA-LNC complexes followed by external beam radiation demonstrated a significant improvement of cell sensitivity to treatment and emphasizes the interest to investigate further this miRNA-targeted strategy.

[Adjuvant treatment of keloid scars: electrons or brachytherapy?]. / Traitement postopératoire des cicatrices chéloïdes : électrons ou irradiation interstitielle ?

PURPOSE: Evaluation of perioperative treatment of keloid scars with electron beam therapy or iridium 192 low dose rate brachytherapy. PATIENTS AND METHODS: From 1994 to 2010, 95 patients with 142 keloid scars have been treated by immediate perioperative irradiation and retrospectively reviewed in our institute: 116 scars were treated by electrontherapy and 26 by brachytherapy. RESULTS: In the electrontherapy group treated locations were: earlobe (n=88, 76%), thorax (n=14, 12%), neck (n=9, 8%), limbs (n=5, 4%). The median size of lesions was 3cm (range [R]: 0.5-18cm). In 95.6% of cases, a dose of 15Gy was delivered in five fractions of 3Gy. The median follow-up was 70 months (R: 7-161 months). The 2-year and 5-year local control were respectively 69% (95% confidence interval [95% CI]: 59-76%) and 55% (95% CI: 45-64%). In the brachytherapy group treated locations were: neck (n=3, 11%), earlobe (n=8, 32%), abdomen (n=3, 11%), thorax (n=2, 8%), limbs (n=10, 38%). The median size of lesions was 6.6cm (R: 1.7-28cm). The median dose delivered at 5mm from the source was 20Gy (R: 15-20.69). The median follow-up was 113 months (R: 21-219 months). The 2-year and 5-year local control were respectively 84.6% (95% CI: 64-94%) and 73.5% (95% CI: 49-87%). So far, no radiation-induced cancer has occurred. A trend to a better local control with brachytherapy was noted (compared to electrontherapy, 2-year relapse is halved with brachytherapy) though this difference did not reach the significance (P=0.0991), probably due to the reduced number of patients in the brachytherapy group. CONCLUSION: Brachytherapy seems to provide better local control compared to electrontherapy, and should be proposed as first line treatment. However, electrontherapy is an interesting alternative in case of difficulty to realize brachytherapy. There is probably a dose effect: according to published data, 25 to 30Gy should at least be proposed.

[Are there any dosimetric advantages in using VMAT for treatment of locally advanced non-small cell lung cancer?]. / La radiothérapie avec modulation d'intensité rotationnelle apporte-t-elle un avantage dosimétrique dans le traitement du cancer bronchique localement évolué ?

PURPOSE: To analyse the dosimetric differences between the conventional conformal radiation therapy (CR) and the volumetric modulated arc therapy (VMAT) for non-small-cell locally advanced lung cancer (NSCLC). PATIENTS AND METHODS: Two plans (CR and VMAT) were calculated for ten NSCLC patients. Dose to PTV, organs at risk and external contours (body), conformity index (PTV volume/volume of the 95% reference isodose) and homogeneity index ([maximal dose-minimal dose]/dose prescription) were compared. RESULTS: Doses delivered to PTV (homogeneity index, maximal, minimal and mean dose) are similar with both techniques but conformity index is improved by 60% with VMAT: from 0.55±0.07 with CR to 0.89±0.07 with VMAT (P=0.002). Pulmonary protection is improved with VMAT: with CR and VMAT, respectively, the mean lung dose is 14.1±5.2Gy and 12.2±4.5Gy, the lung volume which receives at least 30Gy (V30) is 20±8% and 14±5%, and the V20 is 24±11% and 20±10% (P=0.002). The mean dose received by the body is also 9% lower (P=0.004) and V5 is 13% higher (P=0.004) with VMAT. V10 and V15 were similar with both modalities. From 20Gy and higher, irradiated body volume is larger with CR than with VMAT. The relative difference increases with the dose: from 10% for 20Gy (P=0.014) up to 39% for 62.7Gy (P=0.002). CONCLUSION: Compared to CR, VMAT greatly improves conformity and reduces mean dose and dose delivered from 20Gy and higher to the lungs and the body.

[Dosimetric study of the different techniques to deal with respiratory motion for lung stereotactic radiotherapy]. / Étude dosimétrique des différentes techniques de gestion du mouvement respiratoire pour l'irradiation thoracique en conditions stéréotaxiques.

PURPOSE: To evaluate the different respiratory movement management techniques during irradiation of lung tumours. PATIENTS AND METHODS: Seven patients with one or more primary or secondary lung lesions less than 5 cm (11 tumours in total) had three computed tomographies (CT): free-breathing, deep-inspiration breath-hold using a spirometer, and 4-dimensional (4D). From these three acquisitions, five treatment plans were performed: free-breathing (reference method), deep-inspiration breath-hold, and three from the 4D CT: two breathing synchronized treatments (inspiration and expiration) and one treatment taking into account all the tumour motions (definition of the internal target volume [ITV]). Planning target volume (PTV) size and dose delivered to the lungs were compared. RESULTS: Mean PTV with the free-breathing modality was 83 ± 28 cm(3), which was significantly greater than any of the other techniques (P<0.0001). Compared to the free-breathing PTV, PTV defined with the ITV was reduced by one quarter (63 ± 31 cm(3)), and PTV with the deep-inspiration breath-hold, breathing synchronized inspiration and breathing synchronized expiration techniques were reduced by one third (50 to 54 ± 24 to 26 cm(3)). Deep-inspiration led to significantly increase the healthy lung volume compared to other methods (mean volume of 5500 ± 1500 cm(3) versus 3540 to 3920 cm(3), respectively, P<0.0001). The volume of healthy lungs receiving at least 5 and 20 Gy (V5 and V5) were significantly higher with the free-breathing method than any of the other methods (P<0.0001). The deep-inspiration breath-hold modality led to the lowest lung V5 and V20. CONCLUSION: Deep-inspiration breath-hold technique provides the most significant dosimetric advantages: small PTV and large lung volume. However, patients must be able to hold 20 seconds of apnea. Respiratory gating also reduces the PTV, but its application often requires the implantation of fiducial, which limit its use. A 4-dimensional CT allows for a personalized and reduced PTV compared to free-breathing CT.

GATE: a simulation toolkit for PET and SPECT.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.