Radiothérapie stéréotaxique par accélérateurs adaptés ou dédiés

Stereotactic radiation therapy, consisting in irradiating the tumor with a high dose per fraction, has a therapeutic potential because of excellent local control. This technique requires a high accuracy level in order to minimize the risk of normal tissue toxicity. Initially used for cerebral localization, the stereotactic radiation therapy can be used for lung and liver tumors thanks to personalized immobilization devices, time resolved tomodensitometry for tumor deformation, collimators with small size leaves, advanced dose distribution calculation algorithms and 3D imaging for patient set-up. This article will review the different clinical applications and the different aspects (mechanical, dosimetric and biological) to evaluate before implementing this complex irradiation technique using adapted or dedicated linear accelerators.     

Radiothérapie intracérébrale en conditions stéréotaxiques

Stereotactic radiosurgery is used for treating several brain diseases. Radiosurgery is a non-invasive alternative to surgery for brain metastases, and randomized trials are on going to assess the role of radiosurgery. Radiosurgery has been advocated for patients with small benign meningioma or with vestibular schwannoma, but there is no proof of efficacy and safety of radiosurgery in comparison with other treatments. Radiosurgery can obliterate 80-90% of small arteriovenous malformations, but no information exists on the survival of treated compared with untreated patients. The limited information available suggests that radiosurgery should be fully evaluated in well-designed prospective studies.     

Radiothérapie stéréotaxique hypofractionnée des métastases surrénaliennes

Adrenal glands are a common site for metastatic spread since they represent the fourth metastatic site of solid tumors. Interest in local ablative treatments of oligometastases is growing since literature suggests better progression-free survival, quality of life and potentially overall survival in selected patients. Surgery remains the first treatment of adrenal oligometastases because results are good, with a long enough follow-up. However, stereotactic radiotherapy appears to be comparable to surgery and could be proposed to elderly, unfit, inoperable patients, or even to patients whose systemic treatment should not be suspended for too long. This article aims to present a review of published studies to date on stereotactic radiotherapy of adrenal metastases and to propose a treatment protocol.     

Radiothérapie stéréotaxique des métastases osseuses du squelette périphérique

PurposeStereotaxic radiotherapy is performed regularly for the irradiation of non-spine bone metastases, but its place is not well understood.Materials and methodsThis article in stereotaxic radiotherapy of non-spine bones oligometastases presents the current scientific data relating to the indications, to virtual simulation, to the delineation of target volumes, to the total dose and fractionation, to the efficacy and tolerance.ResultsOligometastatic patients are classified into 4 categories: oligorecurrences, oligometastasis, oligopersistence, oligoprogression. The prognosis will be evaluated according to the following characteristics: primary tumor, quantitative characteristics, kinetics, qualitative characteristics. The delineation of GTV includes extensions to the soft tissue and bone marrow with the aid of MRI and PET. The CTV corresponds to a margin of 2 to 5 mm and the PTV to a margin of 2 mm. The most widely used irradiation schemes are: 1 single fraction of 18 to 24 Gy/1 fr; 24 Gy/2 fr; 27 to 30 Gy/3 fr; 30 to 35 Gy/5 fr. Stereotaxis provides 90% local control at 1 year and good pain control. The side effects are not very marked.ConclusionStereotaxic radiotherapy is feasible, non-invasive, minimally toxic and effective with good local control and good pain relief. The main issue remains selecting the patients most likely to benefit from it.     

Radiothérapie stéréotaxique hypofractionnée des métastases osseuses

Hypofractionated stereotactic radiotherapy can deliver high doses of bone metastases while sparing adjacent healthy tissue not only for a decompressive or analgesic purpose, but also to improve the local control of the irradiated region. Various phases I or II studies showed the feasibility of such an approach at the cost of limited toxicity, including during re-irradiation. Hypofractionated stereotactic radiotherapy to oligometastases may also improve the long-term control of metastatic disease.     

Épidémiologie des lésions métastatiques cérébrales

The most frequent intracranial brain tumours are brain metastases. All types of cancer can develop brain metastases but two thirds of brain metastases occurring in adult patients are secondary to one of these three cancers: lung cancer, breast cancer and melanoma. In accordance with these data, this review is focusing on the epidemiology of these three types of cancer. We report here the incidence, risk factors, median time of brain metastases occurrence after diagnosis of the primary cancer, prognosis and median survival for these three types of cancer. We also discuss the clinical implications of these data. The second part of this review is focusing on the Graded Prognostic Assessment scores in all types of primary cancer with brain metastases, how they can be applied in clinical research for a better stratification of patients, and to some extent in clinical practice to guide decisions for personalized treatments. These scores provide a better understanding of the different profiles of clinical evolution that can be observed amongst patients suffering from brain metastases according to the type of primary cancer. We highlighted the most remarkable and useful clinical implications of these data.     

Épidémiologie des métastases cérébrales et tropisme cérébral

Recent progresses in chemotherapies and targeted therapies have improved survival in cancer patients. In this context of better-controlled systemic disease, brain metastases (BM) are emerging as a new challenge for the oncologist. However, BM epidemiology and biology remain largely unclear. Incidence of BM is increasing. This trend could be explained by improvement in the quality of neuro-imaging (MRI) and increased survival. Primary cancers associated with BM patients are mainly: lung, breast, renal, colorectal cancers and melanoma. Prevalence of BM is estimated at 9% although this figure is probably underestimated. Time from initial to BM diagnoses is increasing and BM is occurring more frequently in individuals with advanced-stage disease. Biology of BM remains poorly known. Interactions between circulated tumoral cells (CTC) and blood-brain-barrier (BBB) cells are required. Some cytokines may act as CTC attractants and promote BM formation. BM development also involves several steps (extravasations through non-fenestrated capillaries, local proliferation, neoangiogenesis…), which represent potential therapeutic targets.     

Radiothérapie stéréotaxique hypofractionnée des métastases cérébrales : bénéfice de l’irradiation encéphalique totale ?

Purpose

To study overall survival, risk of neurological death, local recurrence and development of new brain metastasis in patients treated for brain oligometastases with hypofractionated stereotactic radiotherapy with CyberKnife^®, according to the association or not with an additional whole brain irradiation.

Délinéation du lit opératoire des métastases cérébrales opérées traitées par irradiation en conditions stéréotaxiques adjuvante : revue de la littérature

Stereotactic radiotherapy of the surgical bed of brain metastases is a technique that comes supplant indications of adjuvant whole brain radiotherapy after surgery. After a growing number of retrospective studies, a phase III trial has been presented and validated this indication. However, several criteria such as the dose, the fractionation, the use of a margin and definition of volumes remain to be defined. Our study consisted in making a literature review in order to provide a guideline of delineation of surgical beds of brain metastases, as well as the different modalities of their implementation process.     

Radiochirurgie stéréotaxique des malformations artérioveineuses cérébrales

Radiosurgery as treatment for arteriovenous malformations has shown a good efficacy in reducing intracranial bleeding due to rupture. The choice of therapeutic modalities is based on evolutive risk and arteriovenous malformations volume, patient profile and risks stratification following therapeutic techniques (microsurgery, radiosurgery, embolization). Nidus size, arteriovenous malformations anatomical localization, prior embolization or bleeding, distributed dose are predictive factors for radiosurgery's good results and tolerance. This review article will highlight arteriovenous malformations radiosurgery indications and discuss recent irradiation alternatives for large arteriovenous malformation volumes.     

Diagnostic différentiel entre récidive tumorale et radionécrose après radiothérapie stéréotaxique d’une métastase cérébrale

Magnetic resonance imaging (MRI) is a method of choice for follow-up of irradiated brain metastasis. It is difficult to differentiate local tumour recurrences from radiation induced-changes in case of suspicious contrast enhancement. New advanced MRI techniques (perfusion and spectrometry) and amino acid positron-emission tomography (PET) allow to be more accurate and could avoid a stereotactic biopsy for histological assessment, the only reliable but invasive method. We report the case of a patient who underwent surgery for a single, left frontal brain metastasis of a breast carcinoma, followed by adjuvant stereotactic radiotherapy in the operative bed. Seven months after, she presented a local change in the irradiated area on the perfusion-weighted MRI, for which the differentiation between a local tumour recurrence and radionecrosis was not possible. PET with 2-deoxy-(¹⁸F)-fluoro-D-glucose (FDG) revealed a hypermetabolic lesion. After surgical resection, the histological assessment has mainly recovered radionecrosis with few carcinoma cells. The multimodal MRI has greatly contributed to refine the differential diagnosis between tumour recurrence and radionecrosis, which remains difficult. The FDG PET is helpful, in favour of the diagnosis of local tumour recurrence when a hypermetabolic lesion is found. Others tracers (such as carbon 11 or a fluoride isotope) deserve interest but are not available in all centres. Stereotactic biopsy should be discussed if any doubt remains.     

Radiothérapie en conditions stéréotaxiques en pédiatrie

Stereotactic radiotherapy is a very high precision procedure, which has been limited to radiosurgery for a long time. Technological improvements allowed the development of radiotherapy in stereotactic conditions, leading to a lot of innovations. Previously indicated for cerebral pathologies, this procedure is now developed for extracerebral locations. In paediatrics, stereotactic radiotherapy is still limited, delivered precociously, due to the possibility of long-term late effects that needs to be addressed. This review reports the different useful conditions, technical evolutions, and the current validated paediatric indications, with differences from adults, and future directions.     

Traitement systémique des métastases cérébrales de mélanome

Melanomas have a high rate of brain metastases. Both the functional prognosis and the overall survival are poor in these patients. Until now, surgery and radiotherapy represented the two main modalities of treatment. Nevertheless, due to the improvement in the management of the extracerebral melanoma, the systemic treatment may be an option in patients with brain metastases. Immunotherapy with anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) – ipilimumab – or BRAF (serine/threonine-protein kinase B-raf) inhibitors – vemurafenib, dabrafenib – has shown efficacy in the management of brain metastases in a- or pauci-symptomatic patients. Studies are ongoing with anti-PD1 (programmed cell death 1) and combinations of targeted therapies associating anti-RAF (raf proto-oncogene, serine/threonine kinase) and anti-MEK (mitogen-activated protein kinase kinase).     

Risque de radionécrose après radiothérapie hypofractionnée en conditions stéréotaxiques du lit opératoire de métastases cérébrales

Purpose

To investigate the factors that potentially lead to brain radionecrosis after hypofractionated stereotactic radiotherapy targeting the postoperative resection cavity of brain metastases.

Les leucémies myélomonocytaires juvéniles

Juvenile myelomonocytic leukemias (JMML) are rare but severe myelodysplastic and myeloproliferative neoplasms of infancy. They represent about 10 new cases per year in France and preferentially affect males. JMML are all stem cell diseases the common denominator of which is RAS pathway dysregulation, due to mutations in RAS (NRAS, KRAS) or RAS regulatory components (PTPN11, NF1 or CBL). This leads to an hypersensivity of myeloid progenitors to GM-CSF (granulo-macrophagic colony stimulating factor) which induces in turn excessive monocytic and macrophagic proliferation in blood and bone marrow. All organs can be infiltrated by this monocytic proliferation leading to multisystemic failure. Blast crisis with transformation into acute myeloid leukemia occurs in one third of patients. A salient feature of JMML is their frequent association with predisposition syndromes such as Noonan syndrome, neurofibromatosis and CBL syndrome, which are developmental diseases associated with a constitutional RAS pathway deregulation, now grouped under the name RASopathies. Clinical heterogeneity makes JMML diagnosis difficult. Splenomagaly is the most constant sign. Palor, adenopathy, respiratory or cutaneous symptoms can also be present. Blood smear shows monocytosis (>1×10⁹/L) presence of myeloid progenitors and abnormal basophils. The demonstration of an endogeneous in vitro growth of myeloid progenitors although not very specific can help JMML diagnosis. Nowadays, genetic typing has to be included in the workup of JMML diagnosis and allows to evidence a mutation in more than 90% of cases. JMML have a poor prognosis. The only curative treatment is bone marrow transplantation but approximately 35% of patients relapse. JMML clinical course is highly heterogeneous and unpredictable. Some rare patients have an indolent evolution or even spontaneous remission. Age over two years, thrombopenia below 33×10⁹/L and high foetal hemoglobin (HbF) level for age are poor prognosis criteria but hardly predict individual outcome. Several research directions are currently being explored to improve prognosis prediction and provide more effective targeted treatments.     

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.