Multicriteria optimization of radiation therapy: Towards empowerment and standardization of reverse planning for head and neck squamous cell carcinoma.

PURPOSE: The purpose of this study was to assess if multicriteria optimization could limit interoperator variability in radiation therapy planning and assess if this method could contribute to target volume coverage and sparing of organ at risk for intensity-modulated curative radiation therapy of head and neck cancers. MATERIAL AND METHODS: We performed a retrospective analysis on 20 patients treated for an oropharyngeal or oral cavity squamous cell carcinoma. We carried out a comparative dosimetric study of manual plans produced with Precision® software, compared with the plans proposed using the multicriteria optimization method (RayStation®). We assessed interoperator reproducibility on the first six patients, and dosimetric contribution in sparing organs at risk using the multicriteria optimization method. RESULTS: Median age was 69 years, most lesions were oropharyngeal carcinoma (65%), and 35% lesions were stage T3. First, we obtained a high degree of similarity between the four operator measurements for each patient at the level of each organ. Intraclass correlation coefficients were greater than 0.85. Second, we observed a significant dosimetric benefit for contralateral parotid gland, homolateral and contralateral masseter muscles, homolateral and contralateral pterygoid muscles and for the larynx (P<0.05). For the contralateral parotid gland, the mean dose difference between the multicriteria optimization and manual plans was -2.0Gy (P=0.01). Regarding the larynx, the mean dose difference between the two plans was -4.6Gy (P<0.001). CONCLUSION: Multicriteria optimization is a reproducible technique and faster than manual optimization. It allows dosimetric advantages on organs at risk, especially for those not usually taken into consideration in manual dosimetry. This may lead to improved quality of life.

Recommendations for stereotactic body radiation therapy for spine and non-spine bone metastases. A GETUG (French society of urological radiation oncolgists) consensus using a national two-round modified Delphi survey.

Background and purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two. Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines. Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials.

Management of metallic implants in radiotherapy.

The number of patients with metallic implant and treated with radiotherapy is constantly increasing. These hardware are responsible for the deterioration in the quality of the CT images used at each stage of the radiation therapy, during delineation, dosimetry and dose delivery. We present the update of the recommendations of the French society of oncological radiotherapy on the pros and cons of the different methods, existing and under evaluation, which limit the impact of metallic implants on the quality and safety of radiation treatments.

Radiotherapy for patient with cardiac implantable electronic device, consensus from French radiation oncology society.

Radiotherapy in patients with cardiac implantable electronic device such as pacemakers or defibrillators, is a clinical situation that is becoming increasingly common. There is a risk of interaction between the magnetic field induced by accelerators and the cardiac implantable electronic device, but also a risk of device dysfunction due to direct and/or indirect irradiation if the cardiac implantable electronic device is in the field of treatment. The risk can be dose-dependent, but it is most often independent of the total dose and occurs randomly in case of neutron production (stochastic effect). The presence of this type of device is therefore described as a contraindication for radiotherapy by the French national agency for the safety of medicines and health products (Agence nationale de sécurité du médicament et des produits de santé, ANSM). Nevertheless, since radiotherapy is often possible, it is advisable to respect the recommendations of good practice, in particular the eligibility criteria, the monitoring modalities before, during and after irradiation according to the type of treatment, the dose and the characteristics of the cardiac implantable electronic device. It is sometimes necessary to discuss repositioning the device and/or modifying the treatment plan to minimize the risk of cardiac implantable electronic device dysfunction. We present the update of the recommendations of the French society of oncological radiotherapy on in patients with cardiac implantable electronic device.

Prevention of radiation-induced cancers.

The issue of radiation-induced cancers must be taken into consideration during therapeutic irradiations. Risk factors for radiation-induced cancer include: the age of the patients, the volumes irradiated, the presence of risk cofactors and the exposure of critical organs. Those should be part of the therapeutic decision, in terms of indication, as well as choice of the radiotherapy technique (including repositioning systems). We present the update of the recommendations of the French society for radiation oncology on the modalities for preventing radiation-induced cancers.

[Radiotherapy for patients with early-stage glottic squamous cell carcinoma of the larynx: Interest of hypofractionation?] / Radiothérapie du carcinome épidermoïde du larynx de stade précoce, étage glottique : intérêt de l'hypofractionnement ?

Hypofractionated radiotherapy of early-stage squamous cell carcinoma of the glottic larynx is a promising treatment option. This can be divided into radiotherapy with moderate hypofractionation (up to 2.5Gy per fraction), more intense hypofractionation (between 2.5 and 4.5Gy per fraction) and stereotactic radiotherapy (above 4.5Gy per fraction). Most studies evaluating moderate hypofractionation show a local control rate between 85 and 95%. Acute laryngeal toxicity is superior to conventional treatment, but only for grades 1 and 2, with no significant difference reported for severe toxicity. Stereotactic radiotherapy in this pathology is also an emerging entity, but some authors have reported significant toxicity. There are currently no standardized guidelines for treatment and management regimen. We conducted a systemic review of published prospective and retrospective trials to evaluate efficacy, toxicity, and discuss future directions.

[Stereotactic body radiotherapy for locally advanced pancreatic cancer: A systemic review]. / Radiothérapie stéréotaxique dans le cancer du pancréas localement avancé : revue de la littérature.

Stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) is an emerging treatment option. Most studies showed local control of approximately 75% with no evidence of improved overall survival. Gastrointestinal toxicities could be significant, ranging up to 22% for acute toxicities≥grade 3+ and 44% for late toxicities≥grade 3+. Currently, no standardized guidelines for treatment and management scheme. We conducted a systemic review of published prospective and retrospective trials to evaluate the efficacy, safety, technical data, and discuss future directions.

[Place and modalities of postoperative radiotherapy in the management of cerebral metastases]. / Place et modalités de l'irradiation postopératoire dans la prise en charge des métastases cérébrales.

Metastases are the most common brain tumors. After surgery, stereotactic radiotherapy (SRT) of the resection cavity is the standard of care. Data from two randomized trials indicate that SRT to the surgical bed is an effective treatment in reducing local failure as compared with observation, while reducing the risk of cognitive deterioration and maintaining quality of life as compared with whole brain radiation therapy. Local control appears higher after hypofractionated SRT compared to single-fraction SRT. Several questions such as target volumes, the optimal regimen in particular for large tumor bed, strategies to reduce the risk of lepto-meningeal recurrence, and the treatment sequence still need to be answered.

Time of PTV is ending, robust optimization comes next.

Continuous improvements have been made in the way to prescribe, record and report dose distributions since the therapeutic use of ionizing radiations. The international commission for radiation units and measurement (ICRU) has provided a common language for physicians and physicists to plan and evaluate their treatments. The PTV concept has been used for more than two decades but is becoming obsolete as the CTV-to-PTV margin creates a static dose cloud that does not properly recapitulate all planning vs. delivery uncertainties. The robust optimization concept has recently emerged to overcome the limitations of the PTV concept. This concept is integrated in the inverse planning process and minimizes deviations to planned dose distribution through integration of uncertainties in the planning objectives. It appears critical to account for the uncertainties that are specific to protons and should be accounted for to better exploit the clinical potential of proton therapy. It may also improve treatment quality particularly in hypofractionated photon plans of mobile tumors and more widely to photon radiotherapy. However, in contrast to the PTV concept, a posteriori evaluation of plan quality, called robust evaluation, using error-based scenarios is still warranted. Robust optimization metrics are warranted. These metrics are necessary to compare PTV-based photon and robustly optimized proton plans in general and in model-based NTCP approaches. Assessment of computational demand and approximations of robust optimization algorithms along with metrics to evaluate plan quality are needed but a step further to better prescribe radiotherapy may has been achieved.

Integration of the M6 Cyberknife in the Moderato Monte Carlo platform and prediction of beam parameters using machine learning.

PURPOSE: This work describes the integration of the M6 Cyberknife in the Moderato Monte Carlo platform, and introduces a machine learning method to accelerate the modelling of a linac. METHODS: The MLC-equipped M6 Cyberknife was modelled and integrated in Moderato, our in-house platform offering independent verification of radiotherapy dose distributions. The model was validated by comparing TPS dose distributions with Moderato and by film measurements. Using this model, a machine learning algorithm was trained to find electron beam parameters for other M6 devices, by simulating dose curves with varying spot size and energy. The algorithm was optimized using cross-validation and tested with measurements from other institutions equipped with a M6 Cyberknife. RESULTS: Optimal agreement in the Monte Carlo model was reached for a monoenergetic electron beam of 6.75 MeV with Gaussian spatial distribution of 2.4 mm FWHM. Clinical plan dose distributions from Moderato agreed within 2% with the TPS, and film measurements confirmed the accuracy of the model. Cross-validation of the prediction algorithm produced mean absolute errors of 0.1 MeV and 0.3 mm for beam energy and spot size respectively. Prediction-based simulated dose curves for other centres agreed within 3% with measurements, except for one device where differences up to 6% were detected. CONCLUSIONS: The M6 Cyberknife was integrated in Moderato and validated through dose re-calculations and film measurements. The prediction algorithm was successfully applied to obtain electron beam parameters for other M6 devices. This method would prove useful to speed up modelling of new machines in Monte Carlo systems.

[Stereotactic body radiotherapy. How to better protect normal tissues?] / Radiothérapie stéréotaxique extra crânienne. Comment mieux protéger les tissus sains ?

The use of stereotactic body radiotherapy (SBRT) has increased rapidly over the past decade. Optimal preservation of normal tissues is a major issue because of their high sensitivity to high doses per session. Extreme hypofractionation can convert random errors into systematic errors. Optimal preservation of organs at risk requires first of all a rigorous implementation of this technique according to published guidelines. The robustness of the imaging modalities used for planning, and training medical and paramedical staff are an integral part of these guidelines too. The choice of SBRT indications, dose fractionation, dose heterogeneity, ballistics, are also means of optimizing the protection of normal tissues. Non-coplanarity and tracking of moving targets allow dosimetric improvement in some clinical settings. Automatic planning could also improve normal tissue protection. Adaptive SBRT, with new image guided radiotherapy modalities such as MRI, could further reduce the risk of toxicity.

[RadioTransNet, the French network for preclinical research in oncological radiotherapy]. / RadioTransNet, le réseau national de radiothérapie oncologique préclinique.

The ambition of the RADIOTRANSNET network, launched by the INCa at the end of 2018, is to create a French research consortium dedicated to preclinical radiotherapy to foster scientific and clinical interactions at the interface of radiotherapy and radiobiology, and to identify research priorities dedicated to innovation in radiotherapy. The activities of the network are organized around four major axes that are target definition, normal tissue, combined treatments and dose modelling. Under the supervision of the Scientific Council, headed by a coordinator designated by the SFRO and a co-coordinator designated by the SFPM, three leaders coordinate each axis: a radiation-oncologist, a medical physicist and a biologist, who are responsible for organizing a scientific meeting based on the consensus conference methodology to identify priority issues. The selected themes will be the basis for the establishment of a strategic research agenda and a roadmap to help coordinate national basic and translational research efforts in oncological radiotherapy. This work will be published and will be transmitted to the funding institutions and bodies with the aim of opening dedicated calls to finance the necessary human and technical resources. Structuration of a preclinical research network will allow coordinating the efforts of all the actors in the field and thus promoting innovation in radiotherapy.

[Radiotherapy treatment planning of prostate cancer using magnetic resonance imaging]. / Planification de la radiothérapie du cancer de la prostate par l'imagerie par résonance magnétique.

PURPOSE: Magnetic resonance imaging (MRI) plays an increasing role in radiotherapy dose planning. Indeed, MRI offers superior soft tissue contrast compared to computerized tomography (CT) and therefore could provide a better delineation of target volumes and organs at risk than CT for radiotherapy. Furthermore, an MRI-only radiotherapy workflow would suppress registration errors inherent to the registration of MRI with CT. However, the estimation of the electronic density of tissues using MRI images is still a challenging issue. The purpose of this work was to design and evaluate a pseudo-CT generation method for prostate cancer treatments. MATERIALS AND METHODS: A pseudo-CT was generated for ten prostate cancer patients using an elastic deformation based method. For each patient, dose delivered to the patient was calculated using both the planning CT and the pseudo-CT. Dose differences between CT and pseudo-CT were investigated. RESULTS: Mean dose relative difference in the planning target volume is 0.9% on average and ranges from 0.1% to 1.7%. In organs at risks, this value is 1.8%, 0.8%, 0.8% and 1% on average in the rectum, the right and left femoral heads, and the bladder respectively. CONCLUSION: The dose calculated using the pseudo-CT is very close to the dose calculated using the CT for both organs at risk and PTV. These results confirm that pseudo-CT images generated using the proposed method could be used to calculate radiotherapy treatment doses on MRI images.

[Reference bases of radiotherapy under stereotaxic conditions for bronchopulmonary, hepatic, prostatic, upper aero-digestive, cerebral and bone tumors or metastases]. / Bases référentielles de la radiothérapie en conditions stéréotaxiques pour les tumeurs ou métastases bronchopulmonaires, hépatiques, prostatiques, des voies aérodigestives supérieures, cérébrales et osseuses.

Since decades, stereotactic radiotherapy has spread out worldwide. Published results are very numerous. To clarify obviousness among all the publications, this recommendation review was written. Voluntarily, authors limited analysis of international best evidence literature on malignant tumors of lung, liver, prostate, head and neck, and metastasis of bone and brain. These data could be used to advance standardization and quality improvement of treatments performed in the nationwide radiotherapy departments and can provide useful guidance for centers worldwide.

Hypofractionated Stereotactic Radiotherapy for Patients with Intracranial Meningiomas: impact of radiotherapy regimen on local control.

We evaluated efficacy and tolerance of hypofractionated stereotactic radiation treatment (hFSRT) in the management of intracranial meningiomas. Between December 2008 and June 2016, 126 patients with 136 intracranial meningiomas were treated with robotic hFSRT. hFSRT was performed as primary irradiation and as a salvage option for the local recurrence after prior radiotherapy. The median prescription dose was 25 Gy (12-40) with a median number of fractions of 5 (3-10). After a median follow-up of 20.3 months (range 1-77 months), the 24-months local control (LC) rate was 81% in the primary hFSRT group and 39% after hFSRT in the re-irradiation group (p=0.002). The clinical control rate of symptoms in the overall population was 95% (95% CI: 89-98%). Progression-free survival (PFS) in the overall population at 24 months was 70% (95% CI: 60%-79%). In the primary hFSRT group, PFS was significantly lower with the most hypofractionated schedules of 21-23 Gy in 3 fractions vs. 25-40 Gy in 5-10 fractions: 62% vs. 92% (p = 0.0006). The incidence of radionecrosis at 24 months was significantly lower in the primary hFSRT group, at 2% vs. 20% in the re-irradiation hFSRT group (p = 0.002).

[Stereotactic body radiation therapy for hepatic malignancies: Organs at risk, uncertainties margins, doses]. / Radiothérapie stéréotaxique hépatique : organes à risque, marges d'incertitudes, doses.

Stereotactic body radiation therapy for primary and metastatic hepatic malignancies can be performed in association and/or as an alternative to surgery and radiofrequency. The consequences of the great number of techniques available are heterogeneity in contouring, dose prescription and in determination of dose constraints for organs at risk. The objective of this paper is to improve the quality and safety and to help the diffusion of this technique for a majority of patients. In 2016, the French Society of Radiation Oncology (SFRO) published guidelines for external radiotherapy and brachytherapy ("Recorad"). This paper is an update of these recommendations considering recent publications.

About the non-consistency of PTV-based prescription in lung.

PURPOSE: The goal of this study is to show that the PTV concept is inconsistent for prescribing lung treatments when using type B algorithms, which take into account lateral electron transport. It is well known that type A dose calculation algorithms are not capable of calculating dose in lung correctly. Dose calculations should be based on type B algorithms. However, the combination of a type B algorithm with the PTV concept leads to prescription inconsistencies. METHODS: A spherical isocentric setup has been simulated, using multiple realistic values for lung density, tumor density and collimator size. Different prescription methods are investigated using Dose-Volume-Histograms (DVH), Dose-Mass-Histograms (DMH), generalized Equivalent Uniform Dose (gEUD) and surrounding isodose percentage. RESULTS: Isodose percentages on the PTV drop down to 50% for small tumors and low lung density. When applying the same PTV prescription to different patients with different lung characteristics, the effective mean dose to the GTV is very different, with factors up to 1.4. The most consistent prescription method seems to be the D50%DMH (PTV) DMH point, but is also limited to tumors with size over 1cm. CONCLUSIONS: Even when using the different prescription methods, the prescription to the PTV is not consistent for type B-algorithm based dose calculations if clinical studies should produce coherent data. This combination leads to patients' GTV with low lung density possibly receiving very high dose compared to patients with higher lung density. The only solution seems to remove the classical PTV concept for type B dose calculations in lung.

[Intraprostatic fiducials in stereotactic radiotherapy for prostate cancer]. / Fiduciels intraprostatiques dans le cadre de la radiothérapie stéréotaxique du cancer de la prostate.

PURPOSE: Image-guided radiotherapy for prostate cancer is widely used in radiotherapy departments. Intraprostatic gold fiducial markers are used to visualize prostate position and motion before and during treatment. The aim of this report is to describe our experience of implanting intraprostatic fiducial markers under local anesthesia before hypofractionated stereotactic radiotherapy for prostate cancer and to assess its tolerance and reproducibility. PATIENTS AND METHODS: Over a 6 and a half year period, 226 patients with prostate cancer received a stereotactic radiotherapy using the CyberKnife® system (Accuray) in our institution. Eighteen patients were treated for recurrence after prostatectomy; these patients were excluded from the study. Among the 208 remaining patients, 94 patients (45.2%) received stereotactic radiotherapy as a boost after external beam radiotherapy (three fractions of 6Gy); 36 patients (17.3%) were had a re-irradiation (six fractions of 6Gy) and 78 patients (37.5%) had a exclusive stereotactic radiotherapy (68 patients received five fractions of 7.25Gy and 11 patients five fractions of 6.25Gy). Four markers were implanted in all patients using transrectal ultrasound; the procedure was performed under local anesthesia, using transperineal access. The four fiducial markers were implanted in two strands with two fiducial each one, 1cm apart. In order to follow the recommendations of the image-guided radiotherapy system, the two strands of the two markers were located on the same plane in the middle of the prostate, at least 2cm apart from the midline. After insertion, correct positioning of fiducials markers was verified by X-ray. Dosimetry scanning was performed after the implantation procedure; prostate position tracking was possible before and during treatment through the kilovoltage incorporated system of the robotic accelerator. Clinical data, X-ray verification and dosimetry scanner have been retrospectively reviewed for all patients. RESULTS: The tolerance to procedure was excellent; only four patients (1.8%) described pain related to implant. No urinary side effects were reported. Median time from fiducial implantation to dosimetry scanner was 16 days (4-113 days). Four fiducials were found within the prostate at dosimetry scanner in 181 patients and three in 27 remaining patients. All intraprostatic fiducials were used to track the prostate gland before and during treatment. CONCLUSIONS: Intraprostatic fiducial markers implantation is a safe and reproducible procedure that allows us to have reliable prostate information before and during stereotactic radiotherapy.

Clinical implementation of a Monte Carlo based treatment plan QA platform for validation of Cyberknife and Tomotherapy treatments.

PURPOSE: The main focus of the current paper is the clinical implementation of a Monte Carlo based platform for treatment plan validation for Tomotherapy and Cyberknife, without adding additional tasks to the dosimetry department. METHODS: The Monte Carlo platform consists of C++ classes for the actual functionality and a web based GUI that allows accessing the system using a web browser. Calculations are based on BEAMnrc/DOSXYZnrc and/or GATE and are performed automatically after exporting the dicom data from the treatment planning system. For Cyberknife treatments of moving targets, the log files saved during the treatment (position of robot, internal fiducials and external markers) can be used in combination with the 4D planning CT to reconstruct the actually delivered dose. The Monte Carlo platform is also used for calculation on MRI images, using pseudo-CT conversion. RESULTS: For Tomotherapy treatments we obtain an excellent agreement (within 2%) for almost all cases. However, we have been able to detect a problem regarding the CT Hounsfield units definition of the Toshiba Large Bore CT when using a large reconstruction diameter. For Cyberknife treatments we obtain an excellent agreement with the Monte Carlo algorithm of the treatment planning system. For some extreme cases, when treating small lung lesions in low density lung tissue, small differences are obtained due to the different cut-off energy of the secondary electrons. CONCLUSIONS: A Monte Carlo based treatment plan validation tool has successfully been implemented in clinical routine and is used to systematically validate all Cyberknife and Tomotherapy plans.

[Stereotactic body radiation therapy for spinal metastases]. / Radiothérapie stéréotaxique des métastases osseuses vertébrales.

After the liver and lungs, bones are the third most common sites of cancer metastasis. Palliative radiotherapy for secondary bone tumours helps relieve pain, improve the quality of life and reduce the risk of fractures. Stereotactic body radiotherapy can deliver high radiation doses with very tight margins, which has significant advantages when treating tumours close to the spinal cord. Strict quality control is essential as dose gradient at the edge of the spinal cord is important. Optimal schedule is not defined. A range of dose-fractionation schedules have been used. Pain relief and local control are seen in over 80%. Toxicity rates are low, although vertebral fracture may occur. Ongoing prospective studies will help clarify its role in the management of oligometastatic patients.