Acceptance, commissioning and quality assurance of the MRIdian®: Site experience and three years follow-up.

PURPOSE: This study presents the methodology and results of the acceptance and periodical quality controls on the MRIdian®. MATERIALS AND METHODS: The impact of the magnetic field on other machines was investigated by controlling nearby linacs dose profiles. The image quality of the 0.345T MR scanner was evaluated, also assessing the integrated linear accelerator influence. The photon beams lateral and depth dose profiles were measured in motorized water tanks, along dose rate and output factors, and compared to Monte Carlo (MC) calculations. The isocenter position, gantry angles and multi-leaf collimator (MLC) position were controlled using film dosimetry. Gating latency and dosimetric accuracy were controlled with a dynamic phantom. RESULTS: The magnetic field had no significant impact on other nearby linacs. Image quality was within tolerances and did not vary over time. Dose profiles measured showed good agreement with MC data, with maximum differences of 1.3% in-field. Output factors were within 0.8% of calculated values. Imaging and radiative isocenter matched within 0.9±0.4mm over all monthly controls. Gantry rotation was precise within -0.1±0.2°, with an isocenter variation of 1.4±0.3mm diameter. The average MLC position was within 0.4±0.1mm of theoretical value. Finally, the gating latency was 0.14±0.07sec and the gated dose within 0.3% of base value. CONCLUSION: All results are within the tolerances fixed by ViewRay® and show low variations over 2 years, comforting the use of small margins and gating for high-dose adaptive treatments.

Comprehensive commissioning and quality assurance validation of Ethos™ therapy.

PURPOSE: Adaptive radiotherapy with the Ethos® therapy Varian system has been recently implemented at the Montpellier Cancer Institute, France. This article details the commissioning performed before the implementation of this new treatment planning system (TPS). MATERIAL AND METHODS: To validate the golden beam data of the machine (Halcyon linear accelerator), percentage depth doses (PDD) and profiles were measured for several field sizes and at different depths with a microdiamond chamber. The final doses calculated for different plan types with the Ethos Acuros XB algorithm and the Halcyon Eclipse Analytic Anisotropic Algorithm were compared using the gamma index method. Lastly, for the patient quality assurance (QA) process, the patient treatment plan results obtained with the Mobius3D QA platform (Varian) were compared with the portal dosimetry results obtained with Epiqa (Epidos). RESULTS: Minor differences were observed for the PDD and profile curves (mean difference of 0.2% and 2%, respectively). The χ index pass rate was above 98% for all measures using the 1%/1mm and 2%/2mm criteria for PDD and profile evaluations. The Ethos AXB algorithm was validated for every configuration (fixed fields, standard IMRT and VMAT fields, and clinical plans) with 2D/3D gamma index values>99%. Seventy-three 3-arcs-VMAT QA plans and 27 9-fields-IMRT QA plans were evaluated. Both showed excellent agreement with the TPS calculations (mean gamma pass rate higher than 99%). No difference was observed between IMRT and VMAT. CONCLUSION: The beam delivery, the Ethos AXB algorithm, and the patient QA were comprehensively validated using independent tools.

[Treatment of oligometastatic or oligoprogression cancer]. / Traitement des oligometastases et oligoprogression.

We propose in this short review to report the impact of stereotactic body radiation therapy (SBRT) in oligometastatic or oligoprogressive cancer patients in terms of metastatic progression-free and global survival, and to identify the place of SBRT in patient's pathway.

[Predictive assays for responses of tumors and normal tissues in radiation oncology]. / Outils pour la prédiction de la réponse tumorale et des tissus sains en oncologie radiothérapie.

The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the target volume. Tumor sensitivity to radiotherapy may be particularly inconstant depending on location, histology, somatic genetic parameters and the capacity of the immune system to infiltrate the tumor. In addition, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. In a same population treated in one center with the same technique, it appears that individual radiosensitivity clearly exists, namely in terms of late side effects that are in principle non-reversible. This review details the different radiobiological approaches that have been developed to better predict the tumor response but also the radiation-induced late effects.

[Liver stereotactic body radiotherapy: Clinical features and technical consequences, results. Which treatment machine in which situation?] / Radiothérapie stéréotaxique hépatique : particularités cliniques et implications techniques, résultats. Quelle machine pour quelle situation ?

Liver stereotactic body radiotherapy is a developing technique for the treatment of primary tumours and metastases. Its implementation is complex because of the particularities of the treated organ and the comorbidities of the patients. However, this technique is a treatment opportunity for patients otherwise in therapeutic impasse. The scientific evidence of liver stereotactic body radiotherapy has been considered by the French health authority as insufficient for its widespread use outside specialized and experienced centers, despite a growing and important number of retrospective and prospective studies, but few comparative data. This article focuses on the specific features of stereotactic body radiotherapy for liver treatments and the results of published studies of liver stereotactic body radiotherapy performed with classic linear accelerators and dedicated radiosurgery units.

[Individual modification of the dose, volume and fractionation of breast radiotherapy]. / Personnalisation de la dose, du volume et du fractionnement de la radiothérapie du sein.

Randomized trials demonstrated similar overall survival between mastectomy and breast-conservative surgery followed by adjuvant radiation therapy. Breast-conservative surgery, with adjuvant radiation therapy, with or without neoadjuvant systemic therapy has become the standard of care for women with early or locally advanced breast cancer. Nevertheless, certain cardiac, lung or cutaneous toxicities may alter the long-term body image and the quality of life of a limited number of patients who consider having had "overtreatment" or treatment outside the best knowledge of science. In case of low-risk breast cancer, several trials have evaluated the carcinologic outcome in absence of radiation therapy after breast-conservative surgery. Local recurrences increased in case of breast-conservative surgery alone but without impact on overall survival. Multiple debates have emerged in order to select the most appropriate evaluation criteria. Finally, a large consensus has considered that reducing local recurrences is important but with modern technologies and after identifying patients of individual radiosensitivity. Indeed, in case of a low absolute risk of local recurrence, radiation therapy techniques have been developed to allow a focal treatment especially for patients with high risk of developing late effects. This kind of compromise takes into account the reduction risk of local recurrences but also the probability of developing radiation-induced cutaneous sequelae. In the same way, for patients considered at high risk of recurrence, the huge volumes need specific techniques to better cover the targets while protecting the surrounding critic organs such as heart and lung. Intensity-modulated radiation therapy and the local high boost may help to decrease local recurrences of these more extended and aggressive diseases while considering the individual radiosensitivity that paves the way of long-term sequelae. In this article, we detail a personalized approach of breast radiation therapy considering the absolute risk of local recurrences and the probability of radiation-induced toxicity appearance.

[Modalities and advantages of image guided radiation therapy of breast cancer in adjuvant setting]. / Modalités et intérêt de radiothérapie guidée par l'image pour les cancers du sein en situation adjuvante.

In adjuvant setting, breast cancer radiotherapy volumes include whole mammary gland or chest wall, and when indicated, nodal area such as axilla, supraclavicular, and internal mammary chain. An accurate patients positioning is required due to some geometric complexity of target volumes closed to organs at risk as heart and lung. Image guided radiation therapy allows such accuracy. Here we propose a review on image guided radiotherapy for breast cancer.

[The major debate: Micrometastases and breast cancer - To be for nodal irradiation]. / Le grand débat : cancers du sein pN1mi ­ pour l'irradiation des aires ganglionnaires.

Standard of care in breast cancer management is well-defined. However, some gray zones still exist, in particular adjuvant radiotherapy indications in case of pN1mi breast cancer. Here we propose to define their prognosis, to underpin the benefit of adjuvant treatments in such patients' management and to define lymphedema risk, which is the most common late side effect of locoregional treatments.

Prospective medical analysis of radiation therapist image repositioning during image-guided radiotherapy.

PURPOSE: Radiation oncologists are responsible for deciding which day-to-day variations are acceptable or not in the treatment setup. However, properly qualified and trained radiation therapists might be capable to perform image registration. We evaluated in our centre the capability and accuracy of radiation therapists to validate positioning images in a prospective study. METHODS AND PATIENTS: A total of 84 patients treated for prostate, head and neck, lung or breast cancer was prospectively and randomly included from July 2011 to July 2013 in radiotherapy unit of our institution. For each patient, three positioning images were randomly analysed. Two radiation oncologists analysed all positioning images and shifts decided by the radiation therapists in an independent and blinded way. The radiation oncologists had to decide whether to validate or not this shift and give a corresponding additional shift, if any. A theoretical disagreement rate less than 5% between radiation therapists and radiation oncologists was planned. RESULTS: A total of 240 images were analysed (head and neck: 15.0%; prostate: 14.2%; breast: 55.0%; lung: 15.8%). The global disagreement between radiation oncologists and radiation therapists for all the images analysed was 2.5% 95% confidence interval (95% CI) [1.0-5.0], corresponding to six images out of 240. A 100% agreement was reached for prostate and lung images, a 97.2% agreement for head and neck images and a 96.2% agreement for breast images. CONCLUSIONS: The radiation therapist validation for repositioning images seemed accurate for image-guided radiotherapy in our institution. Periodic evaluation and in-house training are warranted when routine delegation of image registration to radiation therapists is considered.

[Modalities of breast cancer irradiation in 2016: Aims and indications of intensity modulated radiation therapy]. / Techniques d'irradiation du cancer du sein en 2016 : intérêt et indications de la radiothérapie conformationnelle avec modulation d'intensité.

Irradiation techniques for breast cancer (arctherapy, tomotherapy) are evolving and intensity-modulated radiation therapy is being increasingly considered for the management of these tumours. Here, we propose a review of intensity-modulated radiation therapy planning issues, clinical toxicities and indications for breast cancer.

[Radiotherapy for soft tissue sarcomas: Technical evolution and impact on clinical benefit]. / Radiothérapie des sarcomes des tissus mous des membres : évolution technique et impact sur le bénéfice clinique.

The standard treatment for extremity soft tissue sarcomas is based on the association of surgery and radiotherapy. This strategy allows local control improvement with the risk of increased toxicity. There is therefore a growing interest to identify those patients who will benefit from radiotherapy and those who will have the same local control with surgery alone. Furthermore, the development of toxicity has been correlated with the extension of the irradiated volume and the volume receiving high doses. Technological development as intensity modulated radiotherapy and image-guided radiotherapy allows limited irradiated volume improving the protection of the organs at risk leading to clinical benefit improvement. Moreover, efforts are being done to improve local control for the patients at high risk of local relapse. In this paper, we discuss all these mentioned aspects.

[Radiotherapy of bladder cancer]. / Radiothérapie des cancers de vessie.

Surgery (radical cystectomy) is the standard treatment of muscle-invasive bladder cancer. Radiochemotherapy has risen as an alternative treatment option to surgery as part as organ-sparing combined modality treatment or for patients unfit for surgery. Radiochemotherapy achieves 5-year bladder intact survival of 40 to 65% and 5-year overall survival of 40 to 50% with excellent quality of life. This article introduces the French recommendations for radiotherapy of bladder cancer: indications, exams, technique, dosimetry, delivery and image guidance.

Twin machines validation for VMAT treatments using electronic portal-imaging device: a multicenter study.

PURPOSE: To verify the accuracy of volumetric arc therapy (VMAT) using the RapidArc™ device when switching patients from one single linear accelerator (linac) to a paired energy and mechanics "twin" linac without reoptimization of the original treatment plan. PATIENTS AND METHODS: Four centers using 8 linacs were involved in this study. Seventy-four patients previously treated with the 6MV photon RapidArc™ technique were selected for analysis, using 242 measurements. In each institution, all patients were planned on linac A, and their plans were verified both on linac A and on the twin linac B. Verifications were done using the amorphous silicium electronic portal imager (EPID) of the linacs and were analyzed with the EpiQa software (Epidos, Bratislavia, Slovakia). The gamma index formalism was used for validation with a double threshold of 3 % and 3 mm with a measurement resolution of 0.39 mm/pixel, and a smoothed resolution of approximately 2.5 mm. RESULTS: The number of points passing the gamma criteria between the measured and computed doses was 94.79 ± 2.57 % for linac A and 94.61 ± 2.46 % for linac B. Concerning the smoothed measurement analysis, 98.67 ± 1.26 % and 98.59 ± 1.20 % points passing the threshold were obtained for linacs A and B, respectively. The difference between the 2 dose matrices acquired on the EPID was very small, with 99.92 ± 0.06 % of the points passing the criteria. CONCLUSION: For linacs sharing the same mechanical and energy parameters, this study tends to indicate that patients may be safely switched from treatment with one linac to treatment with its twin linac using the same VMAT plan.

Concurrent or sequential letrozole with adjuvant breast radiotherapy: final results of the CO-HO-RT phase II randomized trial.

BACKGROUND: We present here final clinical results of the COHORT trial and both translational sub-studies aiming at identifying patients at risk of radiation-induced subcutaneous fibrosis (RISF): (i) radiation-induced lymphocyte apoptosis (RILA) and (ii) candidates of certain single-nucleotide polymorphisms (SNPs). PATIENTS AND METHODS: Post-menopausal patients with stage I-II breast cancer (n = 150) were enrolled and assigned to either concurrent (arm A) or sequential radiotherapy (RT)-letrozole (arm B). Among them, 121 were eligible for RILA and SNP assays. Grade ≥2 RISF were the primary end point. Secondary end points were lung and heart events and carcinologic outcome. RILA was performed to predict differences in RISF between individuals. A genome-wide association study was performed to identify SNPs associated with RILA and RISF. Analyses were done by intention to treat. RESULTS: After a median follow-up of 74 months, 5 patients developed a grade ≥2 RISF. No significant difference was observed between arms A and B. Neither grade ≥2 lung nor symptomatic cardiac toxicity was observed. Median RILA value of the five patients who had grade ≥2 RISF was significantly lower compared with those who developed grade ≤1 RISF (6.9% versus 13%, P = 0.02). Two SNPs were identified as being significantly associated with RILA: rs1182531 (P = 4.2 × 10(-9)) and rs1182532 (P = 3.6 × 10(-8)); both located within the PHACTR3 gene on chromosome 20q13.33. CONCLUSIONS: With long-term follow-up, letrozole can safely be delivered concomitantly with adjuvant breast RT. Translational sub-studies showed that high RILA values were correlated with patients who did not develop RISF. REGISTERED CLINICAL TRIAL: NCT00208273.

[Radiomics: Definition and clinical development]. / Définition et applications cliniques des radiomics.

The ultimate goal in radiation oncology is to offer a personalized treatment to all patients indicated for radiotherapy. Radiomics is a tool that reinforces a deep analysis of tumors at the molecular aspect taking into account intrinsic susceptibility in a long-term follow-up. Radiomics allow qualitative and quantitative performance analyses with high throughput extraction of numeric radiologic data to obtain predictive or prognostic information from patients treated for cancer. A second approach is to define biological or constitutional that could change the practice. This technique included normal tissue individual susceptibility but also potential response of tumors under ionizing radiation treatment. These "omics" are biological and technical techniques leading to simultaneous novel identification and exploration a set of genes, lipids, proteins.

[Does nodal irradiation (clavicular and internal mammary chains) increase the toxicity of adjuvant breast radiotherapy?]. / L'irradiation des aires ganglionnaires (sus-claviculaire et mammaire interne) augmente-t-elle la toxicité de la radiothérapie adjuvante mammaire?

Treatment volume is a major risk factor of radiation-induced toxicity. As nodal irradiation increases treatment volume, radiation toxicity should be greater. Nevertheless, scientific randomised data do not support this fact. However, a radiation-induced toxicity is possible outside tangential fields in the nodal volumes not related to breast-only treatment. Treatment should not be adapted only to the disease but personalized to the individual risk of toxicity for each patient.

[Impact of intensity-modulated radiotherapy on node irradiation for breast cancer]. / Impact de la modulation d'intensité dans l'irradiation des aires ganglionnaires du cancer du sein.

Irradiation of node areas is still a complex challenge in external radiotherapy for breast cancer. Acceptable target coverage is always balanced by protection of organs at risk and patient morphology. Intensity-modulated radiotherapy increases the quality of dose distribution on the planning target volume, but modifies dramatically the irradiation coverage of critical structures in a different way compared to 3D treatment. In this paper we analyze this new technique in breast treatment with node regions, its expected gain and potential risks.

[Management of locally advanced anal canal carcinoma with modulated arctherapy and concurrent chemotherapy]. / Place de l'arcthérapie modulée et de la chimiothérapie concomitante dans la prise en charge des cancers du canal anal localement évolués.

The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45 Gy in 1.8 Gy per fraction in the prophylactic planning target volume and additional 14 to 20 Gy in the boost planning target volume (5 days per week) with a possibility of 15 days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment break that increases risk of local failure. These techniques also allow a reduction in late gastrointestinal and skin toxicities of grade 3 or above, as well as better functional conservation of anorectal sphincter. The technical achievements (simulation, contouring, prescription dose, treatment planning, control quality) of volumetric modulated arctherapy are discussed.

[New external radiotherapy technologies for breast cancer]. / Nouvelles techniques de radiothérapie externe : exemple de prise en charge dans les cancers du sein.

The purpose of new radiotherapy techniques is to better deliver dose conformation in the tumour volume while diminishing organs at risk exposition. Their development is soaring in the breast cancer field in the adjuvant setting with intensity-modulated radiation therapy but also in cerebral and extracerebral oligometastastic presentation. Their usage is still being debated for breast cancer care. The objective of this narrative review is to list and discuss clinical data at our disposal for these news technologies.

[Stereotactic body radiation therapy and oligometastases]. / Radiothérapie stéréotaxique extracrânienne et oligométastases.

In stage IV cancers, locoregional management of primitive tumours as surgery and/or radiotherapy improved both progression-free survival and overall survival. Among metastatic cancer patients, some of them are considered as oligometastatic stage as they present few metastatic sites associated with low tumor aggressiveness. For those patients, metastatic local control, and therefore prolonged time to progression should be reached through local treatments as surgery and/or radiofrequency ablation and/or stereotactic radiotherapy. Here we propose a review of oligometastatic stage and results from extracranial stereotactic radiotherapy in terms of efficacy and tolerance.