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.     

Pharmacogénétique—pharmacogénomie, quelle est la différence?

Sans résumé     

Les médecins généralistes et la détection précoce des cancers de la peau

Introduction

One of the goals of the French Cancer Plan 2009–2013 is to strengthen the role of the general practitioner at each stage of the patient’s care. As part of its mission in informing health professionals on prevention, the French National Cancer Institute, INCa, implements a barometric survey to better assess the knowledge and practices of GPs on the early detection of skin cancer.

Method

This survey was achieved in two steps, in October 2009 and 2011, by phoning a sample of 600 representative GPs, constructed according to the quota method.

Results

A large majority of the GPs believe they have the necessary knowledge on the prevention and early detection of these cancers (81%) and thus feel comfortable answering questions from patients (87%). However a further analysis reveals that they consider their knowledge to be in need of upgrading. They express a strong demand for information and training. In terms of practice, if the examination of the patient’s skin is usual, it is not always fully carried out by the GP. Self-examination for patients identified at risk is not systematically demonstrated (57%). GPs are especially attentive to the color (83%) or the evolution of a nevus (60%), less to other elements of the ABCDE rule. In case of doubt, when noticing a suspicious skin lesion, the GP addresses his patient to the dermatologist (96%). The care management of patients, as established by the French National Health Insurance, was well accepted and did not change the GPs’ practices.

Conclusions

The results of the 2009 survey are comparable with those of 2011. Current actions, carried out in partnership with GPs on this topic, would benefit from a reinforcement of concerted information actions and continuing education.     

Les métastases cérébrales des cancers du sein : qui,quand, et comment les opérer ?

Questions about both the place and the role of surgery on brain metastasis from breast cancer are arising more and more frequently in practice due to the increase of brain metastasis in patients suffering from a form of cancer recognized as one of the most recurrent cancers in adults but also one of the most sensitive to general treatments of the systemic disease. With improvements in anaesthesia, in surgical instruments, and in global care, neurosurgery has taken advantage of new techniques such as pre- and even per-operative imagery and also neuronavigation. These techniques enable radical and effective surgical intervention with a high level of safety for the patient, making neurosurgery perfectly competitive with other therapeutic modalities, particularly on functional grounds. As for symptomatic treatments or other anti-metastasis treatments, most situations allow a reflection on the global therapeutic strategy which can be adapted to individual cases depending on the patient's general prognosis. In developing this global therapeutic strategy, surgical treatment is still as relevant as ever.     

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.     

Les syndromes paranéoplasiques neurologiques

Paraneoplastic neurological disorders (PND) are defined by the occurrence of a neurological syndrome without other aetiology in patients suffering from cancer. A panel of onconeural antibodies has been described in association with PND and is a major key to the diagnosis of such syndromes. PND are rare but precede the diagnosis of a tumour in more than 60% of patients suffering from such syndromes. The identification of neurological symptoms as paraneoplastic could subsequently lead to the early diagnosis and treatment of the related cancer. Despite various neurological presentations that are not specific to PND, some so-called “classical” syndromes are very reminiscent of PND, including progressive cerebellar degeneration, limbic encephalitis, encephalomyelitis, opsoclonus-myoclonus, subacute sensory neuronopathy, Lambert-Eaton myasthenic syndrome, dermatomyositis, dysautonomia and cancer-associated retinopathy. Recognition of such syndromes will guide the physician to look for a possible cancer. As the tumours are frequently small at this stage, FDG PET imaging may well be necessary. Sometimes, it may be necessary to consider surgical exploration in patients with specific onconeural antibodies if other examinations are negative.     

Les micrométastases : entité biologique et réalité clinique ?

Micrometastases or sub-micrometastases can be detected by standard histopathological method sometimes associated with immunohistochemistry in lymph nodes, bone marrow and blood. The consequence of these small size involvement may be prognostic and therapeutic. Two factors are necessary to assess this kind of involvement: the rate of involvement of non-sentinel lymph node after axillary lymph node dissection and significative difference of survivals. The rate of involvement of non-sentinel lymph node in case of micrometastases or sub-micrometastases is different from the rate of involvement in case of no lymph node metastases (7 to 8%) or in case of macrometases (30 to 50%). Micrometastase is an important factor to determine the rate of involvement of non-sentinel lymph node, the overall or disease free survival and to assess the need of radiotherapy and chemotherapy. In conclusion, micrometastases and sub-micrometastases have a clinical impact even if complementary axillary lymph node dissection is still discussed.     

Programme Général

Programme Général

Programme Général     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

Les tumeurs gliales et glioneuronales de l'adulte et de l'enfant : principales altérations génétiques et classification histomoléculaire

Glial and glioneuronal tumors in children and adult demonstrate distinctive clinical, neuroradiological and molecular features depending on the pathological subtype and within a same subgroup according to the age. In children, gliomas are mainly located in the infratentorial part of the brain. They are most often benign and circumscribed but infiltrative tumors with dismal prognosis are recorded within the pons (DIGP) or the thalamus. Glioblastomas are very rare in children. In contrast, gliomas in adult mainly occur in the cerebral hemispheres and the most frequent subtype is glioblastoma. Glioneuronal tumors mainly occurred in children and young adults. In addition, although pilocytic astrocytomas, pleomorphic xanthoastrocytomas and gangliogliomas are classified into different subgroups according to the WHO 2007 classification, these tumors demonstrate similar neuroradiological findings: they are cystic with contrast enhancement of a mural nodule. Major advances have been made these last five years in the discovery of some master genes that are involved in gliomagenesis and point out differences between children and adults. In adults, infiltrative gliomas can be classified into two major subgroups depending on the existence or not of IDH mutations. IDH-dependent gliomagenesis encompasses diffuse grade II and grade III (they can also show additional molecular alterations such as TP53 mutation or 1p19q codeletion) and secondary glioblastomas. IDH-independent gliomagenesis include triple negative grade II gliomas, gliomatosis cerebri (grade III) and de novo glioblastomas. Pilocytic astrocytomas, pleomorphic xanthoastrocytomas and gangliogliomas share in common BRAF alterations. However, KIAA1549-BRAF fusion characterizes pilocytic astrocytomas whereas V600E BRAF mutation is mainly recorded in pleomorphic xanthoastrocytomas and gangliogliomas.     

Les cancers du cavum juvéniles : aspects anatomocliniques,biologiques, thérapeutiques et évolutifs

Nasopharyngeal carcinoma (NPC) represents one of the most frequent epithelial tumours of the child in intermediate risk regions. In the Maghreb, it represents the first cancer of teenagers of 15-20 years old. The Epstein Barr virus (EBV) is the most important etiologic factor. Its role in the pathogeneses of NPC has been confirmed by several studies. Young NPCs are characterized by a low rate of EBV antibodies and a high level of LMP1 cell expression than in adult’s NPC. The undifferentiated carcinoma nasopharyngeal type (UCNT) represents the most frequent histological type. Immunohistochimical analyses of North Africa early onset NPC is characterized by a weak expression of bcl-2 and p53 and a strong expression of LMP1 and c-kit what makes them different from the adult’s NPC. Clinically, cervical node involvement is constantly present. Juvenile NPC is characterized by a very important locoregional extension as well as a high rate of distant metastases. More than 15% of patients had metastases at diagnosis. Radiotherapy is still the standard therapy of NPC. Only some retrospectives studies have been published to determine the benefit, the type and the timing of the chemotherapy in the treatment of juvenile NPC. Metastatic relapses constitute the main cause of death at these youngpatients. An improvement of the prognosis canbewaited with concomitant chemotherapy and intensity modulated radiotherapy. However, randomized multi institutional studies are necessary to standardize the treatment of the NPC in childhood.     

Les récidives des tumeurs des voies aérodigestives supérieures

Recurrences of tumours of the upper aerodigestive tract are frequent despite the improvement of the primary treatment and they limit the rate of survival long-term. They occur in patients with multiple co-morbidities, often associated with sequelae or side effects of earlier treatments. The salvage treatment will add a cumulative toxicity and therapeutic options are limited. The choice will go from curator to palliative treatment. The report benefit-risk must be assessed in each case depending on the terrain and prognostic factors that have been identified, such as performance status, the time between initial disease and the recurrence, the site and the stratification of the recurrence. In operable non-metastatic recurrence surgery remains the treatment of choice. Multimodal treatment involving surgery, radiation therapy and chemotherapy in this context is being evaluated. Non-operable tumors have long been considered only in a palliative context. The evaluation of detailed irradiation as bifractionnated radiotherapy combined with chemotherapy helped establish protocols allowing long-term survivals and consider these treatments as potentially curators. However, the toxicity of these treatments is important. That is why the technical innovations of the radiation and the development of new chemotherapeutic agents today offer opportunities remaining to assess. The use of irradiation targeted by intensity-modulated radiation therapy (IMRT), and stereotactic radiotherapy by decreasing the irradiated volume should decrease the toxicity. Generally better tolerated than conventional chemotherapy agents, targeted therapies also took their places associated with radiotherapy in the treatment of these patients already treated. Cetuximab was the first agent obtaining an indication. Other agents are being evaluated in metastatic recurrent tumors, including exploring the possibilities of radiopotentialisation nanoparticles and the inhibitors of apoptosis proteins.