Endometrial cancer is the most prevalent genital tract cancer in occident and the third most common cancer among women in Tunisia. It is dominated by carcinoma. The identification of prognostic factors allows a better understanding of its outcome and guides its therapeutic approach. We propose to describe the clinicopathological features and identify the histoprognostic factors of this cancer. It is a retrospective analysis of a series of 62 total hysterectomy specimens with bilateral salpingo-oophorectomy from women with primary carcinoma of the endometrium, colligated in Anatomy Laboratory and Pathology Salah Azaiz Institute of Tunis over a period of 5 years, from January 2003 to December 2007. The median age was 60 years. At the time of diagnosis, 25% of patients were nulliparous and 86% were menopaused. The endometrioid adenocarcinoma was the most common, accounting for 84% of cases (5% of them were grade 3). A myometrial invasion superior or equal to 50% was observed in 40% of cases. 42% of cases were classified as stage IA, 14% in stage IB, 16% in stage II, 18% stage III and 10% in stage IV. 22% of patients had nodal involvement. Overall survival at 5 years was 81%. In multivariate analysis, stage IV, nodal involvement and brachytherapy have influenced this rate. Event-free survival at 5 years was 71%. It was directly related to stage and nodal involvement. Stage, histological type, tumor grade, invasion of more than half of the myometrium and lymph node involvement were the most important adverse prognostic factors, dictating an appropriate management of these tumors.

Treatments for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin are currently limited. Atezolizumab (Tecentriq®) is a monoclonal antibody targeting PD-L1. The first of IMVIGOR 210 phase II trial (NCT02951767) investigated atezolizumab as front line treatment among 119 patients with metastatic urothelial cancer unfit for cisplatin. Response rate was 23% and median overall survival 15.9 months. The second cohort (NCT02108652) included 310 patients whose tumors were progressing after first line platinum-based chemotherapy. Response rate was 15% and median overall survival 7.9 months. Among patients with high PD-L1 expression on infiltrating immune cells (ICs), response rate was 26% and median overall survival 11 months. Atezolizumab was well-tolerated in both cohorts with 66% of treatment-related toxicities including 12% (cohort 1) and 7% (cohort 2) of grade 3-4 adverse events. These results led to an approval by the FDA in United States and the EMA in Europe. In France, atezolizumab was available through an early access agreement by the French National Agency for Medicines and Health Products (ANSM) for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin. So far, its avaibility in France within the EMA approval is pending its pricing.

Immunotherapy as a treatment of solid malignancy is based on the activation of the immune system against tumor cells. Since 1976, intravesical instillation of Bacillus Calmette-Guérin (BCG) has been used widely for the treatment of non muscle invasive bladder cancer and is nowadays recommended by all scientific guidelines. New targeted systemic immunotherapies and particularly checkpoints inhibitors are now widely used in several different cancers and notably in onco-urology. Immune checkpoint molecule inhibitors have opened the possibility of treatments for cancers and there are already phase 2 and 3 trials running with or without BCG in localized, muscle invasive and metastatic bladder cancer.

Tumor cells can be recognized by the immune system and in particular by cytotoxic CD8+T cells. From this observation was derived the concept that vaccination targeting these tumor-associated molecules was feasible. Preventive cancer vaccines targeting oncogenic papillomavirus or hepatitis B virus do exist and are efficient. They aim at preventing the introduction into the body of viruses that play a role in oncogenesis. To date, in the case of an already grown cancer, the anti-tumor vaccines have had no impact on the care of patients. These vaccines are gaining renewed interest, as new antigenic targets have emerged and have been incorporated into the design of vaccines, such as mutated antigens which appeared to be more immunogenic. Less editing cells than tumor cells in the tumor microenvironment, such as protumor endothelial cells or fibroblasts, could also be eliminated by cancer vaccines. New vaccine efficacy criteria have been identified, such as the need to induce intratumoral resident T lymphocytes thanks to the development of mucosal vaccination to amplify them. Finally, because of the immunosuppression of the tumor microenvironment and the expression of inhibitory receptors on CD8+T cells in the tumor, various therapeutic association strategies between the anti-cancer vaccines and molecules supporting these inhibitions are currently used in clinical development. Especially, the efficacy of antibodies against costimulatory inhibitory molecules (PD-1, PD-L1…) relies on the presence of pre-existing CD8+T cells occurring in 25-30% of cancer patients. For the 70% resistant patients, cancer vaccine may reprogram this tumor environment via the induction of intratumoral CD8+T cells which will very likely counteract this resistance to anti-PD-1/PD-L1 antibodies.

The aim of this study is to measure the monitoring and the incidence of renovascular effects of angiogenesis inhibitors in real population.

Antiresorptives and antiangiogenics are treatments that have proven effective in oncology and the treatment of osteoporosis and they are increasingly prescribed. The care of these patients requires collaboration between the prescriber and the oral health professional to establish an optimized treatment plan. Therapeutic education of the patient is essential for him to understand the issues of good oral health and the adverse effects that can be caused by these treatments. The management is essentially based on the individual benefit/risk balance resulting from the general, local and inherent of the molecule risk factors. Management of drug-related osteonecrosis of the jaw should be as early as possible.

Recent progress in biology has made the study of the medical treatment of cancer more effective, but it has also revealed the large complexity of carcinogenesis and cell signaling. For many types of cancer, several therapeutic targets are known and in some cases drugs against these targets exist. Unfortunately, the target proteins often work in networks, resulting in functional adaptation and the development of resilience/resistance to medical treatment. The use of mathematical modeling makes it possible to carry out system-level analyses for improved study of therapeutic targeting in solid tumours. We present the main types of mathematical models used in cancer research and we provide examples illustrating the relevance of these approaches in molecular oncobiology.

Granuloma annulare as a granulomatous cutaneous reaction may be drug-induced. Immune checkpoint inhibitors including programmed death-1 (PD-1) inhibitors show remarkable antitumor activity and are approved for melanoma and other cancers. Different immune-related adverse effects have been described. We report herein a rare adverse effect of anti-PD1 therapy given for metastatic melanoma : granuloma annulare.

Actinomycosis is a chronic and extensive granulomatous, bacterial infection. Revelation by oral ulceration is rare.

Programmed death receptor 1 (PD1) checkpoint inhibitors are known for immune mediated toxicities such as colitis, endocrinopathies and pneumonitis. However, other rare adverse effects are reported in the literature. Nivolumab is an anti-PD1 immunotherapy used in the second line of non-small cell lung cancer (NSCLC). We report two cases of rare toxicities occurring under nivolumab in patients without a history of dysimmunity. A 79-year-old patient with a large-cell carcinoma showed a muscle weakness after the second course, revealing myositis with a CPK grade IV elevation as well as symptoms of myasthenia. The diagnosis of myositis was confirmed by a muscle biopsy. An 82-year-old patient followed for bronchial adenocarcinoma with EGFR mutation, presented with nivolumab shoulder and hip pain with extreme fatigue. After further investigations, the diagnosis of systemic erythematosus lupus was retained. Investigations led to the diagnosis of systemic lupus erythematosus. For both patients treatment was interrupted and systemic corticosteroid therapy was initiated permitting resolution of symptoms. The occurrence of symptoms of dysimmunity should attract the attention of the clinician, leading to discontinuation of anti-PD1 therapy and corticosteroid therapy. Retreatment after symptoms resolution must be collegially discussed if no alternative therapeutic is available.

Treatment of acute lymphoblastic leukemia requires high-dose systemic and/or intrathecal methotrexate to prevent and/or treat central nervous system disorders. Acute neurotoxicity of methotrexate, of unknown etiopathogenesis, is characterized by the polymorphism of clinical manifestations, responsible for a potentially harmful diagnostic delay in these immunosuppressed patients. We describe five episodes of transient acute leukoencephalopathy mimicking a stroke, reported in the literature as "pseudo-stroke syndrome". Neurologic symptoms occurred 3-10 days after IV or IT methotrexate and manifested as aphasia and alternating sensorimotor deficit. The fluctuating symptomatology regressed completely within a few days. Brain MRI, which is essential for diagnosis, demonstrated early white matter diffusion restriction in the affected cerebral area. These anomalies disappeared in one week, while hyperintense T2 FLAIR signals developed in the corresponding brain areas. The long-term progression of these pseudo-stroke patients was favorable, without any therapeutic modification. Nevertheless, the involvement of transient acute leukoencephalopathy episodes in the progressive onset of neuro-cognitive disorders is discussed.

Maintaining the genetic integrity is a key process in cell viability and is enabled by a wide network of repair pathways. When this system is defective, it generates genomic instability and results in an accumulation of chromosomal aberrations and mutations that may be responsible for various clinical phenotypes, including susceptibility to develop cancer. Indeed, these defects can promote not only the initiation of cancer, but also allow the tumor cells to rapidly acquire mutations during their evolution. Several genes are involved in these damage repair systems and particular polymorphisms are predictive of the onset of cancer, the best described of them being BRCA. In addition to its impact on carcinogenesis, the DNA damage repair system is now considered as a therapeutic target of choice for cancer treatment, as monotherapy or in combination with other cytotoxic therapies, such as chemotherapies or radiotherapy. PARP inhibitors are nowadays the best known, but other agents are emerging in the field of clinical research. The enthusiasm in this area is coupled with promising results and a successful collaboration between clinicians and biologists would allow to optimize treatment plans in order to take full advantage of the DNA repair system modulation.

The transmission of an intact and stable genetic code at each cell division relies on different DNA repair systems. Germline mutations of some of these genes cause cancer predisposition, whereas somatic mutations are frequently found in various cancer types, generating genomic instability. As a consequence, cancer cell becomes more susceptible to additional DNA damage. Pharmacological inhibition of DNA repair pathways exploits this frailty: it triggers more damages than cancer cell can tolerate, finally leading to apoptosis. The success of PARP (poly-ADP-ribose polymerase) inhibitors in BRCA1/2-mutated ovarian cancer shows the clinical relevance of this strategy. Herein, we explain the functioning of different DNA-repair pathways, describe the implicated proteins, and their close relation with cell-cycle checkpoints. We focus on novel therapeutic agents targeting DNA repair, their clinical results, and discuss challenges of combination therapies.

Patients with chronic hepatitis B infection are at risk of viral reactivation when treated by immuno- or chemotherapy, with potentially serious or even fatal consequences. This article proposes an overview on screening strategies and antiviral treatment recommendations for oncology patients. We have learned in hematology that reactivations are commun with rituximab and prophylactic treatment is recommanded for any patient who has been in contact with the virus. The risk appears to be lower with cytotoxics but has been far less studied. The recommandations are not formally consensual and upcoming studies will help to establish clearer practice guidelines.

The demonstration of frequent defects in the DNA damage response in high grade ovarian cancer has paved the way for a new therapeutic approach aimed at exploiting this unique vulnerability. The efficacy of poly (ADP) ribose polymerase inhibitors (PARPi) in patients with homologous recombination (HR) DNA repair deficient ovarian cancer (OC) resulting from a BRCA1/2 mutation has provided the proof of concept for synthetic lethality. Thus, olaparib is now approved by the EMA as maintenance therapy after response to a platinum regimen for patients with recurrent, platinum-sensitive, high-grade serous, BRCA1/2-mutated ovarian cancer. Furthermore, several recent trials in OC have demonstrated that the benefit of PARPi may not be limited to patients with BRCA mutations. These data, combined with genomic studies suggesting that a significant proportion of OC may harbor somatic and germline alterations in other HR genes open huge perspectives for exploiting DNA repair as a therapeutic strategy. The current priorities are to (i) determine whether new biomarkers of homologous recombination deficiency may identify the BRCA wild-type subset likely to derive benefit from PARPi; (ii) to determine whether the efficacy of PARPi can be improved by combinatorial strategies (with chemotherapy, radiotherapy, immunotherapy, anti-angiogenesis or DNA repair inhibitors) and (iii) to develop new approaches exploiting DNA repair deficiencies in ovarian and other gynecological tumors.

The arrival of new immunotherapies, called checkpoint inhibitors, is radically changing the world of oncology. Currently, there are some twenty different cancers which may respond to this type of therapy. It is therefore important that professionals involved in the care of elderly people with cancer are already made aware of these new treatments. This article explains how these checkpoint inhibitors work and describes their efficacy and their toxicity for elderly patients.