GENETIC COUNSELING AND PARP INHIBITORS PRESCRIPTION: Upon the availability of the PARP inhibitors in relapsed ovarian carcinoma, the pathways of the oncogenetic counseling were modified. Any research for a constitutional alteration of the BRCA1 and BRCA2 genes must be accompanied by an oncogenetic counseling. BRCA testing is recommended from the diagnosis to every woman with an ovarian or fallopian tube or peritoneum of high grade adenocarcinoma, whatever the age at the diagnosis and her family history. In case of sensitive relapse or potential inclusion in a clinical trial and in the absence of preliminary constitutional research, the oncogenetic counseling is organized according to a fast track pathway and a somatic analysis can be realized in parallel. Today, olaparib is indicated for patients with a high grade serous ovarian or fallopian tube or peritoneum adenocarcinoma, with deleterious mutation of BRCA genes (constitutional or somatic), and in sensitive platinum relapse, and in maintenance therapy after a response to chemotherapy including platinum. The indication of a treatment with olaparib can be discussed in multidisciplinary staff for the other non-serous high grade ovarian carcinoma if all other criteria are gathered. Olaparib is prescribed in monotherapy, to start at the latest 8 weeks after the last chemotherapy cycle, under narrow surveillance, because of its gastrointestinal and hematologic toxicities.

UPDATED 2016 RECOMMENDATIONS FOR THE CLINICAL PRACTICE OF NICE/SAINT-PAUL-DE-VENCE IN OVARIAN CANCER AND ADVANCED CERVICAL CANCER: Since the first edition of the 2012-2013 Clinical Practice Recommendations Nice-Saint-Paul for gynecological cancers, the management of ovarian cancer has become more complex with a better definition of histological subtypes of ovarian cancers, the update of the anatomo-clinical classifications, the evolution of the recommended quality criteria for surgery. In addition, the integration of new medical options, such as PARP inhibitors, requires us to review our management of ovarian cnacer patients (including early systematic oncogenetic research of homologous recombination pathway deficiency). Similarly, medical treatment has evolved in advanced cervical cancer with the new option of bévacizumab therapy. On behalf of the GINECO group, we have updated the guidelines for ovarian epithelial cancer (excepted rare tumors) and advanced cervical cancer in order to allow rapid dissemination of the latest advances to the medical community in order to adjust the daily practice.

The implementation of an internal quality control is mandatory to guarantee the accuracy of HER2 status in invasive breast cancers.

Forward thinking does not seek to predict the future, to unveil it as if it were already in existence, rather, its aim is to help us to construct it. Although today's epidemiological and therapeutic situations for urogenital tumours can evolve over the next 10 years, diagnostic and therapeutic methods, as well as the treatment and implementation of innovations, are already rapidly changing. Rather than reducing our prospective thinking to the therapeutic treatment of cancer only, we will aim at proposing a global sanitary vision that includes diagnosis, therapies, prevention, routine utilisation of technomedicine, genomics and even nanomedicine. This journey into the near future of tomorrow's cancerology holds the promise of being better adapted to the evolution of the medical thinking process. Imagining the way we will be treating renal, prostatic and urothelial tumours in 10 years' time is as much an introspection into our present day treatment system as a projection into its hoped for future evolution.

Urothelial carcinomas are the fourth leading cause of cancer in humans. Their incidence is increasing by more than 50% in 25 years. The superficial forms (70% cases) require a close active surveillance to identify frequent recurrences and progression to invasive stage. Our main goal was to identify prognostic molecular markers for bladder cancer that could be used alone or in combination in routine clinical practice. In this aim, we evaluated the capability of the BCA-oligo test based on a CGH array to correctly classify tumoral grade/stage.

The acute lymphoblastic leukemia (ALL) is one of the first cancer for which emerged the particularity of the adolescent and young adult population. After decades of poorly concerted approaches, adult and pediatric haematologists found out that adolescents treated according to pediatric approaches had a better outcome than those treated in adult protocols. Therefore, pediatric-inspired therapies have been successfully implemented in the young adult population, leading to decreased criteria for allogeneic stem cell transplantation. More recently, a high prevalence of Philadelphia-like ALL has been identified in the AYA population, which opens the door to the combination of target therapy similar to Philadelphia-positive ALL. AYA patients require specific care programs including fertility counselling, adhesion evaluation, and long-term survivor follow-up. They are to be optimally treated by multidisciplinary teams, exploring their personal needs and determining the best management of the "whole patient".

Cabozantinib is an oral multiple tyrosine kinase receptor inhibitor (ITK): VEGFR2, c-MET and RET. Inhibition of VEGFR and c-MET decrease resistance of VEGFR inhibitor via c-MET axis. Cabozantinib improve progression-free survival (PFS) in progressive metastatic medullary thyroid cancer (MTC): 4 months in the placebo group and 11.2 months in the cabozantinib group (P<0.001) in all patient subgroups including those with or without prior ITK and RET mutation status. Cabozantinib increased overall survival (OS) compared with everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR ITK treatment: 21.4 months in cabozantinib group and 16.5 months in everolimus group (P<0.0003). Cabozantinib obtained the AMM for the treatment of progressive metastatic MTC and advanced renal cell carcinoma. Cabozantinib is a new option in the treatment of MTC by inclusion in therapeutic trials (no payment in this indication) and advanced renal cell carcinoma (hospital delivery). Its tolerance is similar to anti-angiogenic therapies and justifies an optimal management of the secondary effect.

Ground-glass opacities nodules are frequently detected with the advances of radiological imaging. These can be preinvasive lesions such as atypical adenomatous hyperplasia but also invasive lesions. It leads to question in patients with lung cancer about treatment strategy and follow up.

The search for mutations epidermal growth factor receptor (EGFR) has changed the therapeutic approach and prognosis of non-small cell lung cancer (NSCLC). The effectiveness of tyrosine kinase inhibitors (TKI) has been demonstrated orally in patients with EGFR mutation. We report the case of a patient for whom treatment with TKI was started effectively in a Critical Care Unit.

Epithelial ovarian cancer (EOC) affects 4500 women a year in France, with a survival of 30% at 5 years. Treatment is based on extensive surgery and chemotherapy. Around 15% of EOCs are due to genetic mutation predisposition essentially with mutated BRCA1 and BRCA2 genes. Four histological subtypes are described (serous, endometrioid, and mucinous cells to clear), corresponding to different carcinogenesis and distinct molecular mutations. High-grade serous EOCs have a mutation of the BRCA genes in 20-30% of cases. This mutation causes a deficit of repair by homologous recombination of DNA in case of double strand break, allowing greater sensitivity to platinum salts and the use of PARP inhibitors, a protein involved in the repair of single-strand breaks of DNA. PARP inhibitors have shown efficacy in patients mutated BRCA but this effectiveness remains to be demonstrated in patients without congenital mutation, but with acquired BRCAness profile EOC. The BRCAness profile is defined by a tumor having a defect in DNA repair counterpart (not limited to BRCA mutation). Molecular definition of BRCAness is still not consensual but is necessary for the use of PARP inhibitors. Gene expression analyses have identified four subgroups of high-grade serous CEO: mesenchymal, proliferative, differentiated and immunoreactive. These four subtypes, not mutually exclusive, although correlated with prognosis, are not yet used in clinical routine.

The syndrome of Familial Non Medullary Thyroid Carcinoma (FNMTC) includes two or more patients with an isolated non-medullary thyroid cancer (papillary, follicular, anaplastic) within the same family. To diagnose FNMTC, the clinician must exclude a syndromic presentation such as the syndromes of Cowden, Gardner or Werner, and the Carney Complex. Up to now, a hundred families with FNMTC have been genetically studied, including forms with (Ch19p13.2) or without oxyphilia (Ch2q21), in association with a multinodular goiter (Ch14q32), or with a renal cancer (Ch1q21). Several candidate genes of susceptibility have been proposed: SRGAP1, NKX2-1, FOXE1 and HABP2. So far, it is considered that familial cases represent less than 5 % of thyroid cancers. Although rare, these cases represent a unique opportunity to improve our understanding of thyroid cancer. The identification of candidate genes will enrich our knowledge of thyroid cancer pathophysiology. Based on the literature and our experience of the follow-up of eight families with FNMTC, we discuss epidemiological, clinical, pathological and genetic aspects of FNMTC with a view to improve the diagnosis and treatment of this disease.

Lynch syndrome (LS) is a syndrome that carries a genetic predisposition to certain cancers associating, either in a single individual or in a family, a visceral tumour, mainly colorectal, with a high risk of other synchronous or metachronous cancers. LS is linked with mutations in the genes coding for proteins in the DNA repair system. Phenotypic variants of SL exist, including Muir-Torre syndrome (MTS) and Turcot syndrome (TS), both of which predispose to colorectal cancer. They may be distinguished by the presence of benign or malignant sebaceous tumours in MTS, and tumours of the central nervous system in TS.

ROS1 fusions are rare mutations that preferentially concern young and non-smoker women. The ROS1-rearranged protein conserves an intact tyrosine kinase domain, leading to the constitutive activation of the ROS1 tyrosine kinase function and of its downstream pathways, that are known to be involved in tumorigenesis. These molecular abnormalities have shown their oncogenic potential in animals' models and in human, with an early effect on carcinogenesis. Several partners have been identified. Patients with non-small cell lung cancers (NSCLC) harbouring ROS1 alterations can receive specific targeted therapies. Indeed, crizotinib has recently been approved in France in advanced ROS1-rearranged NSCLC. We propose a review of the oncogenic role of ROS1 rearrangements, the different methods for its diagnosis, and the available treatments.

Immune-checkpoint inhibitors represent potent new therapies for most lymphomas, particularly for refractory diseases. Contrasting with solid tumors the majority of lymphoma are sensitive to conventional therapies and immunotherapies such as anti-CD20 or anti-CD30. But relapsing lymphoma or refractory disease have a very poor prognosis and new drugs are mandatory. Immune-checkpoint inhibitors targeting CTLA4, PD-1 et PD-L1 demonstrated efficiency with prolonged survivals even after bone marrow allograft for aggressive disease. Lymphomas differ from solid tumors as tumor cells belong to the immune compartment and therefore molecules targeting immune cells may act on both immune environment and tumor cells. Furthermore, PD-L1 expression in most lymphomas is related to tumor cell molecular alterations such as PD-L1 gene amplification or mutation. PD-L1 protein expression on tumor cells and immune cells, particularly it frequency and distribution vary according to different lymphoma subtype and it may help to assess diagnosis as it may predict therapeutical response.

Theileria are obligate eukaryotic intracellular parasites of cattle. The diseases they cause, Tropical theileriosis and East Coast Fever, cause huge economic loss in East African, Mediterranean and central and South-East Asian countries. These apicomplexan parasites are the only intracellular eukaryotic parasites known to transform their host cell and represent a unique model to study host-parasite interactions and mechanisms of cancer onset.Here, we review how Theileria parasites induce transformation of their leukocyte host cell and discuss similarities with tumorigenesis. We describe how genomic innovation, epigenetic changes and hijacking of signal transductions enable a eukaryotic parasite to transform its host cell.

The remarkable efficacy of PD-1/PD-L1 and CTLA4 immune checkpoint inhibitors has led to numerous approvals in melanoma, non-small cell lung cancer, kidney cancer and several other cancers. Nevertheless, a response is observed in a variable proportion of patients, emphasizing the need for predictive biomarkers of efficacy of immune checkpoint inhibitors effectiveness. Several predictive biomarkers of efficacy are of interest: companion tests such PD-L1 immunohistochemistry, the mutational load, the immune status of the tumor and its molecular profile. They do not allow a perfect selection of the patients, but standardization procedures for certain techniques are ongoing. Moreover the emergence of new approaches, such as the multiplex in situ techniques and the microbiote analysis, may offer the opportunity to better select patients who really benefit from immunotherapy. The goal of this article is to discuss available and promising predictive biomarkers of efficacy for immunotherapy strategies.