Innovations en radiothérapie

Radiotherapy is a major treatment for cancer curability. During recent years, radiotherapy has gained in precision and reproducibility using major technological advances. Three-dimensional conformal radiotherapy has been implemented into routine practice with the delineation of tumor volumes and organs at risk and the use of dosimetry (integrating dose constraints and dose-volume histograms). Intensity-modulated radiation therapy (IMRT) can ??sculpt?? the dose around treatment volumes to spare normal tissues more efficiently. Image-guided radiation therapy is now widely used to control the position of the target during a treatment course. Dynamic arctherapy is a way to optimize IMRT using arctherapy, an old concept that makes IMRT delivery quicker and accessible for a larger patient load. Concepts in radiotherapy are strong and will be deployed on all radiotherapy units. Radiation oncology is probably only at its dawn. These innovations open a promising future for improvements in the cure of cancer.     

Asservissement respiratoire en radiothérapie mammaire

Postoperative radiotherapy is a cornerstone of the local treatment in breast cancer. It has been proved with high level of evidence that it decreases local relapse and improves survival of patients. However, radiotherapy comes with healthy tissue toxicity, heart and lung in particular. With constant improvement of radiation techniques, several methods have been developed to decrease the dose to the heart and the lungs. Sometimes, respiratory maneuvers can help, due to patient's anatomy: the radiotherapy is gated with patient's breath. The Deep Inspiration Breath Hold technique is the most popular and there are several ways to perform it. This note will describe the different systems with published data in order to help the radiation oncologist in the daily practice.     

L’imagerie en radiothérapie

The goal of radiation therapy is to deliver a high-dose of radiation to the tumour or target region to improve local control of disease and a low-dose to normal soft tissues to limit side effects. Conformal radiation therapy, intensity modulated radiotherapy (IMRT), brachytherapy and stereotactic radiosurgery have been developed to achieve the desired dose distribution. They require precise imaging of internal anatomy so that it is well adapted to the tumour and organs at risk. Indeed, morphological imaging such as computed tomography is already recommended for radiotherapy planning. But radiation oncologists are also considering other imaging modalities for treatment planning and imaging tools capable of controlling patient motion during treatment. The aim of this article is to present and illustrate the place of imaging during treatment planning and delivery via techniques such as: 4D computed tomography, morphological and functional MRI, positron emission tomography, and imaging devices mounted on accelerators.     

Innovations et recherche en radiothérapie en France

Significant advances in radiation therapy have recently been observed. Important technological advances allow for greater precision in defining target volumes and organs at risk, which will certainly impact the risk/benefit ratio for cancer care, particularly in the new setting of therapeutic associations using new drugs. Despite the major role of radiation therapy in the multidisciplinary management of several cancers, pharmaceutical industry support for radiation therapy trials that do not involve drugs remains nil. Thus, grant applications for radiotherapy studies are mainly oriented towards institutional clinical research. At the same time, research in radiation therapy has changed considerably. In France, since the beginning of the year 2000, the Cancer Institute (INCa) has considered radiation oncology modernisation as one of the health priorities. In their programs, substantial grants have been allocated to the evaluation of innovative techniques, including financial issues and their potential generalisation throughout the country. Funding for clinical research programs has also been allocated to significant projects that will impact future clinical practice. In this article, we aim to describe the various plans for restructuring radiation therapy in France, and make an inventory of the innovative projects in clinical and technology research that involve public and private institutions.     

Immunothérapie et radiothérapie

Radiotherapy, primarily known for its cytotoxic effect on the tumor cells, via the induction of DNA damages, has the ability to induce a systemic antitumoral response. By an immunologic cell death, tumor cells exposed to radiation release a large amount of neoantigenes and pro-inflammatory mediators, acting as an in situ vaccine, resulting in an tumor regression within the primary irradiated site, but also in the distant “out of field” secondary tumors. However, this phenomenon is extremly rare with radiotherapy alone, suggesting that the radiation-induced antitumor immunity is not sufficient for overcoming the tumor's and its microenvironnement immunosuppressing effect. Over the last years, many scientific data and preclinical studies have demonstrated that the combination of local irradiation with immune therapy has a synergistic action in inducing an antitumoral immunity, thus enhancing an abscopal effect. In this article, we summarize the main mechanisms cancer harnesses to evade the control of the immune system and how ionising radiations can induce an antitumor immunity. A focus reports then on recent preclinical and clinical research built on this background of combined radiation and immune therapy, which bear the great potential to further improve anticancer therapies.     

Doses dans les organes à risque en radiothérapie conformationnelle et en radiothérapie en conditions stéréotaxiques : la vessie

Bladder dose constraints in case of conformational radiotherapy/intensity-modulated radiotherapy and stereotactic radiotherapy are reported from the literature, in particular from the French radiotherapy society RECORAD recommendations, according to the treated pelvic tumor sites. The dose–volume effect on urinary toxicity is not clearly demonstrated, making difficult to establish absolute dose constraints for the bladder. In case of high-dose prostate cancer radiotherapy, the bladder dose constraints are: V60 Gy < 50% and maximum dose < 80 Gy for standard fractionation and V60 Gy < 5%, V48 Gy < 25% and  V41Gy < 50% for moderate hypofractionation (20 fractions of 3 Gy). In case of prostate stereotactic radiotherapy (five fractions of 7.25 Gy), the most frequent dose constraints in the literature are V37 Gy < 10 cm³ and V18 Gy < 40%. In case of conformational radiotherapy of cervix cancer, postoperative endometrium, anal canal and rectum, the recommendations are V40 Gy < 40% and D2% lower than the prescribed dose.     

Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie stéréotaxique : les poumons

Radiation-induced lung disease (RILD) is common after radiation therapy and represents cornerstone toxicities after treatment of thoracic malignancies. From a review of literature, the objective of this article was to summarize clinical and non-clinical parameters associated with the risk of RILD in the settings of normo-fractionated radiotherapy and stereotactic body radiation therapy (SBRT). For the treatment of lung cancers with a normo-fractionated treatment, the mean lung dose (MLD) should be below 15–20 Gy. For a thoracic SBRT, V20 Gy < 10% and MLD < 6 Gy are recommended. One should pay attention to central tumors and respect specific dose constraints to the bronchial tree. The recent technological improvements may represent an encouraging way to decrease lung toxicities. Finally, our team developed a calculator in order to predict the risk of radiation pneumonitis.     

Marges en radiothérapie du cancer de la vessie

Radical cystectomy is the gold standard treatment of invasive bladder carcinoma, but conservative treatment is a serious option for selected patients. It comprises a transurethral resection, as complete as possible, before a radiation therapy of the whole bladder and pelvis, with a concomitant chemotherapy. Bladder wall movements during the treatment course lead to the use of wide margins to cover the clinical target volume. Planning target volume margins must be anisotropic to correspond to the mobility of each bladder zone: 10 mm in the inferior portion, 15 mm in lateral directions, and 20 to 25 mm in anterior and superior directions. The development of image-guided radiotherapy and adaptative radiotherapy should lead to a reduction of these margins. Besides, partial bladder radiotherapy is showing encouraging results, by reducing the clinical target volume in well-selected patients.     

Doses dans les organes à risque en radiothérapie conformationnelle et en radiothérapie en conditions stéréotaxiques : os et moelle osseuse

In patients undergoing external radiation therapy, bone marrow and cortical bone structures are all often neglected as organs at risk. Still, from increased febrile neutropenia risk in patients undergoing chemoradiation for a pelvic tumour to increased risk of vertebral fracture when undergoing hypofractioned stereotactic radiotherapy of a spinal metastasis, adverse effects are frequent and sometimes serious. This literature review first defines the rules for contouring these structures, then the dose constraints currently recommended. This article focuses first on conventional irradiation or intensity modulation radiotherapy considering classical fractionation. Secondly, it focuses on stereotactic radiotherapy. The considered organs will be haematopoietic structures, and bone cortical structures. Current recommendations are summarised in a table.     

Le contrôle de la respiration en radiothérapie

Background and purpose

The use of centimetric margins to cover the target movements influenced by the breathing create an important irradiation. Some radiotherapies may be improved applying a breathing control.

Material and methods

Breathing control essentially involves any of three techniques and two methods. Breath hold or synchronization have to be implemented regarding to the expected improvements.

Clinical objectives

Lung, liver and breast sites have specific constraints. Lung radiotherapy is optimized when sparing healthy parenchyma with inspiration. Left breast radiotherapy often needs to protect the heart pushed out of the irradiation fields with inspiration. The liver is the most complex site where all methods have the same low precision.

Conclusions

Breathing control during radiotherapy brings important dosimetric improvements. The results of current clinical trials will help to confirm the potential benefit.     

Utilisation de l’imagerie multimodalité en radiothérapie

The quality of treatment that one can realize today in conformai radiotherapy, can be reached only if one has access to 3D imaging allowing a precise determination of the volume of the organs at risk and of the GTV. For this reason, one has access to anatomical imaging, CT or MRI, and functional and metabolic imaging, PET or SPECT imaging. CT gives the electronic density of the tissus, which is essential to ensure a very precise calculation of dose distribution. Its insufficiency in the visualization of the tumor and some anatomical structures makes necessary the registration of these images with MRI of which distorsions are sufficiently weak to be usable in radiotherapy. The registration will be usable only if images of each modality are realized with the patient in treatment position, except for brain, where only CT, on which is based the registration, must be done in treatment position. At least, if one wants to visualize the active parts of a tumor or to make the difference between fibrosis and tumor left or recurrence after radiotherapy or chemetherapy, it is necessary to use PET or SPECT. To define correctly the CTV using these images, one must realize the anatomical localization of the metabolic abnormalities, which they highlight with a registration based on CT or MRI. The difficulties to obtain the registration of these images led the manufacturer to propose mixed machines allowing to realize, at the same time, a CT imaging and a PET or a SPECT imaging with the patient in treatment position.     

Innovations thérapeutiques en radiothérapie du cancer de la prostate localisé

Intensity-modulated radiation therapy, image-guided radiation therapy with fiducial markers and prostate brachytherapy allow the delivery of dose escalation for localized prostate cancer with very low rates of long-term toxicity and sequelae. Nowadays, modern radiotherapy techniques make it possible to shorten treatment time with hypofractionation, to better protect surrounding healthy tissues and to escalate the dose even further. Advances in radiotherapy are closely linked to advances in magnetic resonance imaging (MRI) and/or PET imaging. Functional imaging makes it possible to deliver personalised pelvic nodal radiotherapy, targeting the nodal areas at higher risk of microscopic involvement. In patients with an index lesion at baseline or at failure, MR-based focal therapy or focal dose escalation with brachytherapy or stereotactic body radiation therapy is also currently investigated. MR-based adaptive radiotherapy, which makes it possible to track prostate shifts during radiation delivery, is another step forward in the integration of MR imaging in radiation delivery.     

Logothérapie,groupe de paroles et analyse existentielle en cours de radiothérapie : expérience pilote d’un centre parisien de radiothérapie

Objective

A pilot study has been carried out to assess the benefit of a pilot support group based on existential analysis and logotherapy (therapy centred on the sense of existentialism), alongside the medical treatment of breast cancer.

Materials and Methods

A group of women under the care of the Hartmann Oncology Institute in the final phase of treatment for breast cancer were selected to take part in the support group during this very specific transition period between being ill and resuming a “normal” life.

Results

Between December 2015 and June 2016, eight women participated in the support group. Results taken from an assessment session and a satisfaction survey completed by all participants demonstrate the importance of talking, the relationships created session after session within the group and the support provided by the synergy between the group and its leaders in order to assert a new lifestyle dynamic — a noodynamic according to the terminology of Viktor Frankl (1905–1997), the psychiatrist who created logotherapy — and to give a new purpose to their life.

Conclusions

The results from the support groups on the quality of life of patients treated for breast cancer are encouraging, and establishing these groups alongside logotherapy would be advantageous for a larger number of patients.

     

La radiothérapie en conditions stéréotaxiques des métastases cérébrales en situation complexe

Stereotactic radiation therapy of brain metastases is a treatment recognized as effective, well tolerated, applicable for therapeutic indications codified and validated by national and international guidelines. However, the effectiveness of this irradiation, the evolution of patient care and the technical improvements enabling its implementation make it possible to consider it in more complex situations: proximity of brain metastases to organs at risk; large, cystic, haemorrhagic or multiple brain metastases, combination with targeted therapies and immunotherapy, stereotactic radiotherapy in patients with a pacemaker. This article aims to put forward the arguments available to date in the literature and those resulting from clinical practice to provide decision support for the radiation oncologists.     

Les big data,généralités et intégration en radiothérapie

The many advances in data collection computing systems (data collection, database, storage), diagnostic and therapeutic possibilities are responsible for an increase and a diversification of available data. Big data offers the capacities, in the field of health, to accelerate the discoveries and to optimize the management of patients by combining a large volume of data and the creation of therapeutic models. In radiotherapy, the development of big data is attractive because data are very numerous et heterogeneous (demographics, radiomics, genomics, radiogenomics, etc.). The expectation would be to predict the effectiveness and tolerance of radiation therapy. With these new concepts, still at the preliminary stage, it is possible to create a personalized medicine which is always more secure and reliable.