CONS: Therapeutic de-escalation in breast cancer surgery is not recommanded for all patients. Concerning the axillary management, there are still some contraindications for practicing sentinel node, and avoiding axillary dissection is not safe for more than 3 positive sentinel nodes and in the absence of adjuvant treatment. Mastectomy can also be preferred by patients rather than conservative surgery, especially in case of genetic mutation, or for oncological reasons. Larger glandular resections, known as oncoplasties, should also be chosen in case of associated ductal carcinoma in situ and risky subgroups of local recurrence after neoadjuvant therapy. Finally, all patients will not benefit from ambulatory surgery.

A surgical therapeutic de-escalation is going to continue but necessarily has to design in a progressive careful way and especially arranged with the other practitioners and therapeutic methods. These strategies concern as well the surgery of the breast as that of the axillary basin.

EXAMPLE OF SARCOMAS IN FRANCE: Sarcomas are rare and heterogeneous tumours, and improvement of knowledge and of patient management need to gather and share data and biological material. The French sarcoma database stores in a warehouse clinical, pathological, molecular, therapeutic and follow-up data as well as data on samples and medical practices. This database and the national structured networks constitute major tools for the French Sarcoma Group.

HOW A BIOMARKER CAN BECOME AN ACCEPTABLE SUBSTITUTION CRITERIA ?: Numerous biomarkers of the treatment activity are now available as a result of the fascinating progresses in biology and biotechnology. Together with the rapidly growing understanding of the mechanisms of action of new agents, these biomarkers provide promising tools to evaluate early the effect of treatments against cancer. It is tempting to use these new markers of activity as primary endpoints to evaluate new treatments in the context of randomized clinical trials. Nevertheless, a mandatory preliminary step is to demonstrate that the two endpoints carry the same information in order to validate whether the biomarker is a surrogate of the final endpoint. We illustrate on several examples in prostate, gastric and early breast cancer that it is important to distinguish two levels of information: the individual level that allows to monitor a patient to anticipate treatment failure, and the trial level that enables to predict the treatment effect on the final endpoint based on the treatment effect measured on the surrogate endpoint. In several cases, the formal validation turned out to be disappointing despite strong biological rational.

WHY PATHOLOGY REMAINS (AND WILL REMAIN) MANDATORY?: Numerous techniques are now available for the molecular evaluation of a tissular or cellular sample in the context of metastatic disease. They include in situ molecular techniques, such as immunohistochemistry for the study of proteins and peptides, in situ hybridization for the study of nucleic acids and in situ cytogenetics (FISH and its variants) for the demonstration of chromosome alterations. They also include all the techniques of molecular biology, which can now be applied to frozen as well as fixed tissue samples. The combination of all these techniques makes it possible an integrated and coherent approach, not limited to the description of DNA abnormalities, but able to correlate genomic alterations with functional, and even structural changes. A second major interest of the analysis of tissue samples is that they make it possible to analyzing not only tumor cells, but also their environment, formed by the stroma and its populations. The study of stroma and of stromal cells, in particular of immune cells, is now of paramount importance for providing new prognostic and predictive biomarkers, especially for anti-angiogenic strategies and for cancer immunotherapy. Tissue analysis is therefore the only way to perform a « total », « phenogenomic » characterization of the tumor as an organ : this is particularly important in the moment in which descriptive genomics is substituted by functional genomics and integrated biology.

Oligometastic progression (or solitary metastases) can justify ablative treatment for metastatic treatment. When such a strategy is discussed, it is important to notice that definition of oligometastases is not consensual both in terms of clinical presentation than on the biological basis. Does a specific biological background truly exist and are there markers that could predict for additional occult disease and its oligo or polymetastatic profile in individuals with demonstrated oligometastasis. This article provides a summary of the state of the art in this field and highlights some current areas of controversies.

ANTI-PD1 ROLE IN TREATMENT OF CUTANEOUS MELANOMA: The treatment of metastatic melanoma dramatically changed over the last years. Two therapeutic revolutions emerged in parallel, targeted anti-BRAF and anti-MEK therapies, for patients BRAFV600 mutated and immunotherapy with immune checkpoint blockers using anti-CTLA-4 then anti-PD1 monoclonal antibodies. Indeed, melanoma immunotherapy was a golden objective for many years but in spite of important efforts using cytokines (interferon, interleukin) and different vaccine approaches no objective improvement of patients 'prognosis was obtained. Ipilimumab, authorized in 2011, was the first drug which showed a benefit of overall survival in patients with metastatic melanoma in spite a low response rate (10-15) and the occurrence of about 25% of serious toxicity. Anti-PD1 appear as a new generation of immune checkpoint blockade with response rates between 30 to 40% of the patients, a proven overall survival benefit as compared with chemotherapy or ipilimumab and less toxicity than ipilimumab. Two molecules, pembrolizumab and nivolumab were recently approved in monotherapy, for metastatic melanoma. Several questions remain unresolved: the respective indications of anti-PD1 and targeted therapies in first line therapy in patients with BRAF mutant melanoma, the benefit of combining immunotherapy with radiotherapy or with targeted therapies, the optimal treatment duration, and the benefit of the anti-PD1 in the adjuvant setting. The combination of ipilimumab and nivolumab, recently approved by the FDA but not yet in Europ, shows an improvement of the objective response rates (50-57%) and progression free survival compared with nivolumab but is associated with an higer incidence of serious adverse events (more than 50%).

Metastatic process is described as a "dissemination of neoplastic cells in a distant secondary site, in which cells proliferate to develop a mass of cells partially differentiated". The vast majority of death in solid cancers is the consequence of metastasis development which lead to vital organ dysfunction. In the present review, either recent discoveries or controversial subjects associated with metastasis process will be discussed. Indeed epithelia-mesenchymal transition (EMT), circulating tumor cells, tumor dormancy, colonization in distant organ and cancer stem cells are tackled.

REFLEXIONS ABOUT NEW STRATEGIES OF RADIOTHERAPY FOR EARLY BREAST CANCER: Radiotherapy (RT) remains a major treatment element in early breast cancer, with a major impact on local control and survival. For ductal carcinoma in situ (DCIS), RT reduces local recurrence (LR) rates by 50 to 60 % after conservative surgery (both in situ and invasive). This was confirmed by four randomized trials and one meta-analysis. For infiltrating breast cancers (IBC), RT also reduces LR rates by 65 to 75 % after conservative surgery. Boost allows an additional reduction of LR. RT is efficient in all age categories, but hypofractionated schemes are particularly adapted to elderly women. Partial breast irrradiation techniques are very much heterogeneous and lack follow-up. They should be used in LR low-risk patients only and in the frame of controlled studies. Locoregional RT for high-risk patients (especially in pN+) remains essential to reduce the locoregional recurrence rate and to increase survival, as confirmed in several meta-analyses. Four studies showed a survival benefit (2-3 %), thanks to internal mammary chain irradiation in LR high-risk patients. Moreover, axillary RT seems to be a likely valuable alternative to axillary dissection in case of sentinel node invasion. Finally, with the modern techniques and dosimetric optimization, RT toxicity was reduced, or even cancelled, arousing hope for a better increased benefit for the patients in the future.

Inflammatory myofibroblastic tumors (IMT) are rare tumors. They were originally described in the lung, but they have been now observed in many others locations, mainly abdominal and pelvic. These tumors are usually benign but their recurrent nature and the presence of an abnormality of chromosome band 2p23 in some of them, suggest that some lesions form a true tumor entity. Surgical excision as complete as possible is the gold standard treatment. We report the case of a 38 years old female, who presented a recurrent metastasizing inflammatory myofibroblastic tumor causing lactic acidosis and other biological abnormalities such as hypercalcemia, hypoalbuminemia, hypoglycemia, disseminated intravascular coagulation and inflammatory syndrome.

Treatment of patients with locally advanced rectal cancer remains challenging. Preoperative imaging with pelvic MRI allows to identify patients for multimodal treatment including induction chemothe- rapy or neoadjuvant radio-chemotherapy and an extended surgical resection. With multidisciplinary approach and an experienced team, excellent oncologic results may be achieved, as well as a good function and quality of life, even with preservation of the anus in the majority of patients.

Cancer is a leading cause of venous thromboembolism (VTE) and vice versa. Pulmonary embolism is the second cause of death in cancer patients. Tumor progression is associated with coagulation activation. The pathogenesis of thrombosis during cancer is particularly complex stemming from multiple connections of this disease with both systems of inflammation and hemostasis. The risk of VTE depends on cancer type and the stage of the disease, the anticancer treatments and the time since cancer diagnosis as well as on the presence of patient-related risk factors (i.e. age, obesity, previous history of VTE, underlying diseases…). The presence of other precipitating factors and the duration of the exposure to them are also key elements in the assessment of such a thrombotic risk. It is therefore important to identify all the VTE risk factors to identify patients at high vascular risk and to determine the period during which this risk is significantly increased. The integration of biomarkers of hypercoagulability in proposed risk assessment models for VTE will improve their capacity to identify patients eligible for pharmacological thromboprophylaxis. In this review, we report the current status of knowledge on the connection between cancer and hypercoagulability, the numerous risk factors for VTE must be identified in cancer patients and the best methodology to build a more accurate assessment of this vascular risk in such a complex medical context.

Advanced pancreatic cancer (APC), one of the most aggressive tunors, was considered to be resistant to chemotherapy for decades. FOLFIRINOX (5-FU, leucovorin, iNinotecah and oxaliplatin) regimen showed an improvement of quality of life and overall sUrvival.ir APb patients with good performance status (ECOG < 2).

Before molecular analysis is performed, morphological control with an estimation of the tumour cell percentage (%TC) could have a major impact on mutation detection. Accreditation according to NF EN ISO 15189 commands an authorization through evaluation of skills. The objective of this work was to validate the empowerment of pathologists to estimate %TC in tissue sample prior to molecular analysis. The accreditation technical guidance methods in Medical biology and histopathology were taken as references. %TC was the ratio of tumour cell nuclei on all nuclei within the area selected for the DNA extraction. External evaluations quality scores were used for accuracy. In order to assess the intermediate precision, 35 %TC estimation were performed 15 days apart in 4 samples (biopsies, transparietal biopsies or surgical specimen, either fixed or frozen) by 7 pathologists. Three other cases with interference (inflammation, mucus, necrosis) were evaluated. A result was satisfactory if %TC were within ±20 % of expected percentage obtained by the average of 35 estimates. The performances were satisfactory since no estimate was made more than 20 % of the expected percentage. Low interpathologists reproducibility has been reported in the literature and can have a consequence on molecular analysis in samples with low %TC, where the value reach the analytical sensitivity thresholds of molecular techniques. The current report is an example of a step of the accreditation process, which is a challenge for pathologists' activity in the future.

The 2007 World Health Organization (WHO) classification of tumors of the central nervous system distinguishes meningeal hemangiopericytomas (HPC) from solitary fibrous tumors (TFS). In the WHO classification of tumors of soft tissue and bone, those neoplasms are no longer separate entities since the discovery in 2013 of a common oncogenic event, i.e. the NAB2-STAT6 gene fusion. A shared histopronostic grading system, called "Marseille grading system", was recently proposed, based on hypercellularity, mitotic count and necrosis. We evaluated the immunophenotype and histoprognosis in a retrospective cohort of intracranial HPC and TFS.

The most important criterion for optimal cancer treatment is a correct classification of the tumour. During the last three years, several very important progresses have been made with a better definition of urothelial carcinoma (UC), especially from a molecular point of view. We start having a global understanding of UC, although many details are still not completely understood.