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.     

Anesthésie générale en radiothérapie pédiatrique

BackgroundThe majority of children under 3 years require anesthesia for radiotherapy.MethodsThis work reports the experience of Paul-Strauss Center over a 4-year period on 15 children and covering 386 general anesthesia.Results and conclusionThe rate of anesthesia-related complications was low (0.5%) subject to the experience of the anesthesiologists and follow-up recommendations.     

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.     

Les carcinomes du nasopharynx Les modalités de la radiothérapie et les associations de la radiothérapie et de la chimiothérapie: état actuel et perspectives

Nasopharyngeal carcinoma (NPC) is a highly radiosensitive and chemosensitive. In the patient with locally advanced Humours, the results of conventional radiotherapy are unsatisfactory with significant rates of both local recurrences and distant metastases. The aim of this review is to report the innovative strategies for treatment of the nasopharyngeal carcinoma. Altered fractionation techniques can improve local control. The impact of the innovative techniques, including conformai radiation, stereotactic radiation and IMRT, on survival, must be evaluated in randomised trials. The encouraging early results obtained with concurrent (more than sequential) chemotherapy and radiotherapy must be confirmed in prospective randomized trial in endemic areas.     

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.     

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.     

Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie stéréotaxique : le foie

The liver is an essential organ that ensures many vital functions such as metabolism of bilirubin, glucose, lipids, synthesis of coagulation factors, destruction of many toxins, etc. The hepatic parenchyma can be irradiated during the management of digestive tumors, right basithoracic, esophagus, abdomen in toto or TBI. In addition, radiotherapy of the hepatic area, which is mainly stereotactic, now occupies a central place in the management of primary or secondary hepatic tumors. Irradiation of the whole liver, or part of it, may be complicated by radiation-induced hepatitis. It is therefore necessary to respect strict dosimetric constraints both in stereotactic and in conformational irradiation in order to limit the undesired irradiation of the hepatic parenchyma which may vary according to the treatment techniques, the basic hepatic function or the lesion size. The liver is an organ with a parallel architecture, so the average tolerable dose in the whole liver should be considered rather than the maximum tolerable dose at one point. The purpose of this article is to propose a development of dose recommendations during conformation or stereotactic radiotherapy of the liver.     

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.     

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.     

Inhibiteurs de PARP et radiothérapie

PARP inhibition is a promising therapeutic approach for solid cancers that present defects in DNA double-strand break repair. It could also serve as a clinically meaningful aid to radiotherapy. This article presents an overview of mechanistic, pre-clinical and clinical data that substantiate this hypothesis but also could help determine its potential pitfalls.     

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.     

Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie en conditions stéréotaxiques : le cœur

Radiation therapy of breast cancer, Hodgkin lymphoma, lung cancer and others thoracic irradiations induce an ionizing radiation dose to the heart. Irradiation of the heart, associated with patient cardiovascular risk and cancer treatment-induced cardiotoxicity, increase cardiovascular mortality. The long survival after breast or Hodgkin lymphoma irradiation requires watching carefully late treatment toxicity. The over-risk of cardiac events is related to the dose received by the heart and the irradiated cardiac volume. The limitation of cardiac irradiation should be a priority in the planning of thoracic irradiations. Practices have to be modified, using modern techniques to approach of the primary objective of radiotherapy which is to optimize the dose to the target volume, sparing healthy tissues, in this case the heart. We have reviewed the literature on cardiac toxicity induced by conformational tridimensional radiation therapy, intensity-modulated radiation therapy or stereotactic body radiation therapy, in order to evaluate the possibilities to limit cardiotoxicity. Finally, we summarise the recommendations on dose constraints to the heart and coronary arteries.     

Érythropoïétine et radiothérapie

Erythropoietin (EPO) is a glycoprotein hormone. This hormone is a growth factor for red blood cells precursors in the bone marrow. The decrease of oxygen partial pressure, a reduced number of erythrocytes caused by bleeding or excessive destruction, or increased tissues oxygen requirements lead to increased secretion of EPO. Its action takes place on bone marrow erythroblastic cells through specific receptors. EPO stimulates the proliferation of red cell precursors stem cells in the bone marrow, thus increasing their production in one to two weeks. The effectiveness of EPO at increasing haemoglobin and improving patients’ quality of life has been demonstrated by several studies. However, its use in radiotherapy remains controversial. While tumour hypoxia caused by anaemia is a factor of radio resistance and thus a source of local failure, tumour expression of EPO receptors presents a significant risk for tumour progression and neo-angiogenesis, which would be increased during the administration of EPO. The purpose of this article is to answer the question: is there a place for EPO in combination with radiotherapy in the management of cancer?