Optimization of the Eclipse TPS beam configuration parameters for small field dosimetry using Monte Carlo simulations and experimental measurements.

PURPOSE: To evaluate the impact of tuning the beam configurations parameters on the Analytical Anisotropic Algorithm (AAA) and the Acuros XB (AXB) algorithm for small fields using Monte Carlo simulations and measurements. METHODS: The TrueBeam STx with the high-definition 120 multi-leaf collimator (HD120-MLC) was modeled with Geant4 application for emission tomography (GATE) Monte Carlo platform and validated against measurements. The impact of varying the effective spot size (ESS) and dosimetric leaf gap (DLG) on AAA and AXB calculations was carried out for small MLC-fields ranging from 0.5×0.5 cm2 to 3 × 3 cm2. Beam penumbras, field sizes and output factors calculated by AAA and AXB were compared to GATE calculations and measurements. RESULTS: The beam penumbra comparisons showed that the best ESS value for AXB was about 1.0 mm in the crossplane direction and 0.5 mm in the inplane direction. By optimizing the ESS values, AXB could provide output factor results almost within 2% of GATE calculations and measurements for fields down to 0.5×0.5 cm2. For AAA, significant output factor differences were observed for all ESS values and tuning the DLG in addition to the ESS optimization resulted in an absorbed dose difference of less than 2.5% for MLC-fields down to 1 × 1 cm2. CONCLUSION: By optimizing the ESS values, AXB can achieve accurate output factors in the case of small MLC-fields without the need of DLG tuning. Nevertheless, compromises between the output factor, DLG and ESS values were found necessary for AAA calculations. A MLC model improvement would allow to avoid the complexity related to tuning the configuration parameters.

Helical tomotherapy for post-mastectomy radiation therapy with or without breast implant: a single institution experience.

Introduction: We report on our experience of using Helical Tomotherapy (HT) in the context of post-mastectomy radiation therapy (PMRT) with or without immediate implant-based breast Reconstruction (IBR). Material and methods: The study included a total of 173 patients who underwent PMRT with HT between 2013 and 2015 in our institution (87 immediate breast reconstructions with retropectoral implants (IBR + ), 86 without reconstructions (IBR-)). The chest wall target volume included subcutaneous tissue and pectoralis muscle and excluded the posterior region of the implant as well as the ribs. Results: Median time to initiation of the first adjuvant treatment from mastectomy was similar between the two groups (p = 0.134). Dose coverage to the chest wall was significantly improved for the IBR + group (V95% = 95.1 % versus 92.0 %; p < 0.0001). The irradiated volume of the ipsilateral lung was significantly decreased in the IBR + group with a median V20Gy of 11.6 %, compared to 15.2 % for the control group (p < 0.0001). The median heart V15Gy was also significantly lower in the IBR + group than in the control group (1.7 vs 2.5 %; p = 0.0280). The reconstruction failure rate was 14.9% (n = 13). After a median follow-up of 65 months, loco regional recurrence rate was low in both groups: 3 patients (3.4%) in the IBR + group and 5 patients (5.8%) in the control group, without any local recurrence in the posterior part of the implant. Conclusions: The presence of a breast implant reduces cardiac and pulmonary doses during Tomotherapy irradiation, without compromising oncological outcomes.

Field output correction factors and electron fluence perturbation of the microSilicon and microSilicon X detectors.

Objective.The aim of this study was to determine field output correction factorskQclin,Qreffclin,frefand electron fluence perturbation for new PTW unshielded microSilicon and shielded microSilicon X detectors.Approach.kQclin,Qreffclin,freffactors were calculated for 6 and 10 MV with and without flattening filter beams delivered by a TrueBeam STx. Correction factors were determined for field sizes ranging from 0.5 × 0.5 cm2to 3 × 3 cm2using both experimental and numerical methods. To better understand the underlying physics of their response, total electron (+positron) fluence spectra were scored in the sensitive volume considering the various component-dependent perturbations.Main results.The microSilicon and microSilicon X detectors can be used down to the smallest studied field size by applying corrections factors fulfilling the tolerance of 5% recommended by the IAEA TRS483. Electron fluence perturbation in both microSilicon detectors was greater than that in water but to a lesser extent than their predecessors. The main contribution of the overall perturbation of the detectors comes from the materials surrounding their sensitive volume, especially the epoxy in the case of unshielded diodes and the shielding for shielded diodes. This work demonstrated that the decrease in the density of the epoxy for the microSilicon led to a decrease in the electron fluence perturbation.Significance.A real improvement was observed regarding the design of the microSilicon and microSilicon X detectors compared to their predecessors.

Technical note: GAMMORA, a free, open-source, and validated GATE-based model for Monte-Carlo simulations of the Varian TrueBeam.

PURPOSE: Monte Carlo (MC) is the reference computation method for medical physics. In radiotherapy, MC computations are necessary for some issues (such as assessing figures of merit, double checks, and dose conversions). A tool based on GATE is proposed to easily create full MC simulations of the Varian TrueBeam STx. METHODS: GAMMORA is a package that contains photon phase spaces as a pre-trained generative adversarial network (GAN) and the TrueBeam's full geometry. It allows users to easily create MC simulations for simple or complex radiotherapy plans such as VMAT. To validate the model, the characteristics of generated photons are first compared to those provided by Varian (IAEA format). Simulated data are also compared to measurements in water and heterogeneous media. Simulations of 8 SBRT plans are compared to measurements (in a phantom). Two examples of applications (a second check and interplay effect assessment) are presented. RESULTS: The simulated photons generated by the GAN have the same characteristics (energy, position, and direction) as the IAEA data. Computed dose distributions of simple cases (in water) and complex plans delivered in a phantom are compared to measurements, and the Gamma index (3%/3mm) was always superior to 98%. The feasibility of both clinical applications is shown. CONCLUSIONS: This model is now shared as a free and open-source tool that generates radiotherapy MC simulations. It has been validated and used for five years. Several applications can be envisaged for research and clinical purposes.

A study of the interplay effect in radiation therapy using a Monte-Carlo model.

PURPOSE: In modulated radiotherapy, breathing motion can lead to Interplay (IE) and Blurring (BE) effects that can modify the delivered dose. The aim of this work is to present the implementation, the validation and the use of an open-source Monte-Carlo (MC) model that computes the delivered dose including these motion effects. METHODS: The MC model of the Varian TrueBeam was implemented using GATE. The dose delivered by different modulated plans is computed for several breathing patterns. A validation of these MC predictions is achieved by a comparison with measurements performed using a dedicated programmable motion platform, carrying a quality assurance phantom. A specific methodology was used to separate the IE and the BE. The influence of different motion parameters (period, amplitude, shape) and plan parameters (volume margin, dose per fraction) was also analyzed. RESULTS: The MC model was validated against measurement performed with motion with a mean 3D global gamma index pass rate of 97.5% (3%/3 mm). A significant correlation is found between the IE and the period and the antero-posterior amplitude of the motion but not between the IE and the CTV margin or the shape of motion. The results showed that the IE increases D2% and decreases the D98% of CTV with mean values of +6.9% and -3.3% respectively. CONCLUSIONS: We validated the feasibility to assess the IE using a MC model. We found that the most important parameter is the number of breathing cycles that must be greater than 20 for one arc to limit the IE.

Towards the standardization of the absorbed dose report mode in high energy photon beams.

The benefits of using an algorithm that reports absorbed dose-to-medium have been jeopardized by the clinical experience and the experimental protocols that have mainly relied on absorbed dose-to-water. The aim of the present work was to investigate the physical aspects that govern the dosimetry in heterogeneous media using Monte Carlo method and to introduce a formalism for the experimental validation of absorbed dose-to-medium reporting algorithms. Particle fluence spectra computed within the sensitive volume of two simulated detectors (T31016 Pinpoint 3D ionization chamber and EBT3 radiochromic film) placed in different media (water, RW3, lung and bone) were compared to those in the undisturbed media for 6 MV photon beams. A heterogeneity correction factor that takes into account the difference between the detector perturbation in medium and under reference conditions as well as the stopping-power ratios was then derived for all media using cema calculations. Furthermore, the different conversion approaches and Eclipse treatment planning system algorithms were compared against the Monte Carlo absorbed dose reports. The detectors electron fluence perturbation in RW3 and lung media were close to that in water (≤1.5%). However, the perturbation was greater in bone (∼4%) and impacted the spectral shape. It was emphasized that detectors readings should be corrected by the heterogeneity correction factor that ranged from 0.932 in bone to 0.985 in lung. Significant discrepancies were observed between all the absorbed dose reports and conversions, especially in bone (exceeding 10%) and to a lesser extent in RW3. Given the ongoing advances in dose calculation algorithms, it is essential to standardize the absorbed dose report mode with absorbed dose-to-medium as a favoured choice. It was concluded that a retrospective conversion should be avoided and switching from absorbed dose-to-water to absorbed dose-to-medium reporting algorithm should be carried out by a direct comparison of both algorithms.

A study of the interplay effect for VMAT SBRT using a four-axes motion phantom.

PURPOSE: To assess the accuracy of volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) when treating moving targets (such as lung or liver lesions), focusing on the impact of the interplay effect in the event of complex breathing motion and when a gating window is used. METHODS: A dedicated programmable motion platform was implemented. This platform can carry large quality assurance (QA) phantoms and achieve complex three-dimensional (3D) motion. Volumetric modulated arc therapy SBRT plans were delivered with TrueBeam linac to this moving setup and the measured dose was compared to the computed one. Several parameters were assessed such as breathing period, dose rate, dose prescription, shape of the breathing pattern, the use of a planning target volume (PTV) margin, and the use of a gating window. RESULTS: Loss of dose coverage (D95%) was acceptable in most situations. The doses received by 95% of the CTV, D95% ( C T V m ) ranged from 94 to 101% (mean 98%) and the doses received by 2% of the CTV D2% ( C T V m ) ranged from 94% to 110% of the prescribed dose. A visible interplay effect was observed when no margin was used or when the number of breathing cycles during the treatment delivery was lower than 20. CONCLUSIONS: In our clinical context, treating lung and liver lesions using VMAT SBRT is reasonable. The interplay effect was moderated and acceptable in all simulated situations.

Gene flow prevents mitonuclear co-adaptation: A comparative portrait of sympatric wild types and cybrids in the fish Chrosomus eos.

Allospecific mtDNA can occasionally be beneficial for the fitness of populations. It is, however, difficult to assess the effect of mtDNA in natural conditions due to genetic and/or environmental interactions. In the fish Chrosomus eos, the transfer of C. neogaeus mitochondria occurs in a single generation and results in natural cybrids. For a few lakes in Quebec, C. eos can harbor either a C. eos mtDNA (wild types) or a C. neogaeus mtDNA (cybrids). Moreover, mtDNA of cybrids originated either from Mississippian or Atlantic glacial refuges. Such diversity provides a useful system for in situ assessment of allospecific mtDNA effects. We determined genetic, epigenetic and transcriptomic variation as well as mitochondrial enzymatic activity (complex IV) changes among wild types and cybrids either in sympatry or allopatry. Wild types and cybrids did not segregate spatially within a lake. Moreover, no significant genetic differentiation was detected among wild types and cybrids indicating sustained gene flow. Mitochondrial complex IV activity was higher for cybrids in both sympatry and allopatry while no difference was detected among cybrid haplotypes. Epigenetic and transcriptomic analyses revealed only subtle differences between sympatric wild types and cybrids compared to differences between sites. Altogether, these results indicate a limited influence of allospecific mtDNA in nuclear gene expression when controlling for genetic and environmental effects. The absence of a reproductive barrier between wild types and cybrids results in random association of either C. eos or C. neogaeus mtDNA with C. eos nDNA at each generation, and prevents mitonuclear co-adaptation in sympatry.

Virtual bolus for total body irradiation treated with helical tomotherapy.

Intensity-modulated radiation therapy (IMRT) for total body irradiation (TBI) is practiced in several centers using the TomoTherapy System. In this context the planning target volume (PTV) is the entire body including the skin. A safety margin in the air surrounding the body should be added to take into account setup errors. But using inverse planning, over-fluence peak could be generated in the skin region to insure dose homogeneity. This work proposes to study the performance of the use of a virtual bolus (VB). A VB is a material placed on the skin surface during planning, but absent for the real treatment. The optimal VB that compensates large setup errors without introducing a high-dose increase or hot spots for small setup errors was determined. For two cylindrical phantoms, 20VBs with different densities, thicknesses or designs were tested. Dose coverage of the PTV (V95%) in the presence of simulated setup errors was computed to assess the VB performance. A measure of the dose increase in the phantom center due to the absence of the VB during treatment was also achieved. Finally, the fluence peak at the phantom edge was measured in complete buildup conditions using a large phantom and a detector matrix. Using these VBs, simulated setup errors were compensated to a minimum value of 2.6 and 2.1 cm for small and large phantom, respectively (and only 1.2 and 1.7 cm with no VB). An optimal double-layer VB was found with a density of 0.4 kg.m(-3) and a total thickness of 8mm; an inner layer of 5 mm was declared as the target for the treatment planning system and an additional layer of 3 mm was added to avoid the over-fluence peak. Using this VB, setup errors were compensated up to 2.9 cm. The dose increase was measured to be only +1.5% at the phantom center and over-fluence peak was strongly decreased.

Integration method of 3D MR spectroscopy into treatment planning system for glioblastoma IMRT dose painting with integrated simultaneous boost.

BACKGROUND: To integrate 3D MR spectroscopy imaging (MRSI) in the treatment planning system (TPS) for glioblastoma dose painting to guide simultaneous integrated boost (SIB) in intensity-modulated radiation therapy (IMRT). METHODS: For sixteen glioblastoma patients, we have simulated three types of dosimetry plans, one conventional plan of 60-Gy in 3D conformational radiotherapy (3D-CRT), one 60-Gy plan in IMRT and one 72-Gy plan in SIB-IMRT. All sixteen MRSI metabolic maps were integrated into TPS, using normalization with color-space conversion and threshold-based segmentation. The fusion between the metabolic maps and the planning CT scans were assessed. Dosimetry comparisons were performed between the different plans of 60-Gy 3D-CRT, 60-Gy IMRT and 72-Gy SIB-IMRT, the last plan was targeted on MRSI abnormalities and contrast enhancement (CE). RESULTS: Fusion assessment was performed for 160 transformations. It resulted in maximum differences <1.00 mm for translation parameters and ≤1.15° for rotation. Dosimetry plans of 72-Gy SIB-IMRT and 60-Gy IMRT showed a significantly decreased maximum dose to the brainstem (44.00 and 44.30 vs. 57.01 Gy) and decreased high dose-volumes to normal brain (19 and 20 vs. 23% and 7 and 7 vs. 12%) compared to 60-Gy 3D-CRT (p < 0.05). CONCLUSIONS: Delivering standard doses to conventional target and higher doses to new target volumes characterized by MRSI and CE is now possible and does not increase dose to organs at risk. MRSI and CE abnormalities are now integrated for glioblastoma SIB-IMRT, concomitant with temozolomide, in an ongoing multi-institutional phase-III clinical trial. Our method of MR spectroscopy maps integration to TPS is robust and reliable; integration to neuronavigation systems with this method could also improve glioblastoma resection or guide biopsies.

[Clinical prediction rule for diagnosing deep vein thrombosis in primary care]. / Réalisation d'un score clinique de prédiction de thrombose veineuse profonde des membres inférieurs spécifique à la médecine générale.

Patients with suspected deep vein thrombosis (DVT) are often managed on an outpatient basis by primary care physicians. International guidelines recommend anticoagulant treatment for patients with suspected DVT when diagnostic testing is delayed or when clinical probability is high. Our goal was to build a clinical prediction rule specifically for easy use in primary care to help decide about starting anticoagulant therapy while awaiting ultrasound examination. Between January and December 2006, 276 patients with clinically suspected DVT were included in this study by 189 general practitioners from Brittany, France. All patients underwent a standardized clinical assessment and were then referred for ultrasonography. The diagnosis of DVT was confirmed in 103 (37%) patients. The final clinical prediction rule comprises four risk factors for DVT (personal history of venous thromboembolism +1, immobilization in previous month +1, estrogen contraceptive +2, active malignancy +3), one clinical sign (swelling of the calf +1), and the presence of an alternative diagnosis more likely than that of DVT (-3). The proportion of confirmed DVT was 26% in patients classified as at low risk, with a score less than 2 points, and 63% in patients classified at high risk, that is, with a score of 2 points or more. This clinical prediction rule is based on simple history and clinical factors that are routinely collected by GPs from patients with suspected DVT. It could help to decide about the immediate prescription of anticoagulation pending ultrasound. This rule should be externally validated before its use in clinical practice can be recommended.

Initial evaluation of a four-dimensional computed tomography system using a programmable motor.

A dynamic lung tumor phantom was used to investigate the geometric reconstruction accuracy of a commercial four-dimensional computed tomography (4D-CT) system. A ball filled with resin, embedded in a cork cube, was placed on a moving platform. Various realistic antero-posterior (AP) motions were programmed to reproduce the respiratory motion of a lung tumor. Several three-dimensional (3D) CT and 4D-CT images of this moving object were acquired and compared using different acquisition parameters. Apparent volume and diameter of the ball were measured and compared to the real values. The position of two points (the AP limits of the ball) during the motion in the coordinate system of the CT scanner were also compared with the expected values. Volume error was shown to increase with object speed. However, although the volume error was associated with intraslice artifacts, it did not reflect large interslice inconstancies in object position and should not be used as an indicator of image accuracy. The 3D-CT gave a random position of the tumor along the phantom excursion; accuracy in the assessment of position by 4D-CT ranged from 0.4 mm to 2.6 mm during extreme phases of breathing. We used average projection (AVE) and maximum intensity projection (MIP) algorithms available on the commercial software to create internal target volumes (ITVs) by merging gross tumor volume (GTV) images at various respiratory phases. The ITVs were compared to a theoretical value computed from the programmed ball excursion. The ITVs created from the MIP algorithm were closer to the theoretical value (within 12%) than were those created from the AVE algorithm (within 40%).

Lung volume assessment for a cross-comparison of two breathing-adapted techniques in radiotherapy.

PURPOSE: To assess the validity of gated radiotherapy of lung by using a cross-check methodology based on four-dimensional (4D)-computed tomography (CT) exams. Variations of volume of a breathing phantom was used as an indicator. METHODS AND MATERIALS: A balloon was periodically inflated and deflated by a medical ventilator. The volume variation (DeltaV) of the balloon was measured simultaneously by a spirometer, taken as reference, and by contouring 4D-CT series (10 phases) acquired by the real-time position management system (RPM). Similar cross-comparison was performed for 2 lung patients, 1 with free breathing (FB), the other with deep-inspiration breath-hold (DIBH) technique. RESULTS: During FB, DeltaV measured by the spirometer and from 4D-CT were in good agreement: the mean differences for all phases were 8.1 mL for the balloon and 10.5 mL for a patient-test. End-inspiration lung volume has been shown to be slightly underestimated by the 4D-CT. The discrepancy for DeltaV between DIBH and end-expiration, measured from CT and from spirometer, respectively, was less than 3%. CONCLUSIONS: Provided that each slice series is correctly associated with the proper breathing phase, 4D-CT allows an accurate assessment of lung volume during the whole breathing cycle (DeltaV error <3% compared with the spirometer signal). Taking the lung volume variation into account is a central issue in the evaluation and control of the toxicity for lung radiation treatments.

[Respiratory gated radiotherapy: the 4D radiotherapy]. / La radiothérapie asservie à la respiration: la radiothérapie 4D.

Respiration-gated radiotherapy offers a significant potential for improvement in the irradiation of tumor sites affected by respiratory motion such as lung, breast and liver tumors. An increased conformality of irradiation fields leading to decreased complications rates of organs at risk (lung, heart...) is expected. Respiratory gating is in line with the need for improved precision required by radiotherapy techniques such as 3D conformal radiotherapy or intensity modulated radiotherapy. Reduction of respiratory motion can be achieved by using either breath hold techniques or respiration synchronized gating techniques. Breath hold techniques can be achieved with active, in which airflow of the patient is temporarily blocked by a valve, or passive techniques, in which the patient voluntarily breath-hold. Synchronized gating techniques use external devices (CCD camera for the GEMS/Varian system tested at Curie Institute) to predict the phase of the respiration cycle while the patient breaths freely. A new strategy is currently developed: the 4D Respiration correlated CT. It consists of retrospectively reconstruct CT slices at different phases of the breathing cycle allowing to measure residual movements and to choose the optimal patient's breathing phase where tumor movements are lower. These techniques presently investigated in several medical centers worldwide. The first results are very promising.