Myelodysplastic syndromes (MDS) are clonal stem cell diseases that primarily affect the elderly. They are classified into low- and high-risk MDS according to prognostic scoring systems. In high-risk patients, treatment should aim to modify the course of the disease by preventing progression to acute myeloid leukemia, and thus improve survival. Stem cell transplantation remains the only curative treatment when possible, but this concerns a small minority of patients. Treatment is mainly based on hypomethylating agents (HMA). Our understanding of the biology of MDS has led to the development of drugs targeting key cellular processes such as apoptosis or post-translational modifications of proteins, the microenvironment and genetic mutations. Currently, new drugs are mainly tested in combination with HMAs in several clinical trials and, although none has yet obtained marketing authorization, many molecules seem promising.

Interstitial lung disease (ILD) has been reported with many cancer drugs including some recent antibody-drug conjugates (ADCs). The mechanisms of ILD induced by many chemotherapy drugs, other drug classes and ADCs used in cancer, including breast cancer, are not clearly elucidated. In the absence of specific clinical or radiological signs, the diagnosis of drug-induced ILD is often a diagnosis of exclusion. When present, the most frequent symptoms are respiratory signs (cough, dyspnea, chest pain) and general signs (fatigue, fever). Any suspicion of ILD should be evaluated by imaging and, if in doubt, the CT scan should be evaluated by a pulmonologist and a radiologist. A network of multidisciplinary experts for proactive early management of ILD is important, including oncologist, radiologist, pulmonologist, infectious disease specialist and nurses. Patient education is essential to report new or exacerbated lung symptoms and prevent high-grade ILD. Study drug is discontinued temporarily or permanently according to ILD severity and type of ADC. For asymptomatic cases (Grade 1), the efficacy of corticosteroids is not clearly established; for higher grades, the benefit/risk balance of long-term corticosteroid therapy should be considered for the dose and treatment duration. Hospitalization and oxygen supplementation are required for severe cases (Grades 3-4). For patient follow-up, the expertise of a pulmonologist is necessary with repeated chest scans, spirometry and DLCO. Preventing ADC-induced ILDs and evolution to high grade rests on a network of multidisciplinary experts for assessment of individual risk factors, early management, close follow-up and patient education.

Electrolyte disorders (ED) are common in patients with cancer and in most cases, the etiologies do not differ from the general population. They may also be induced by the cancer, its therapy or paraneoplastic syndromes. ED are associated with poor outcomes, increased morbidity and mortality in this population. Hyponatremia is the most common disorder, often multifactorial, iatrogenic or secondary to the syndrome of inappropriate antidiuretic hormone secretion, usually due to small cell lung cancer. More rarely, hyponatremia may reveal adrenal insufficiency. Hypokalemia is generally multifactorial and associated with other ED. Cisplatin and ifosfamide induce proximal tubulopathies with hypokalemia and/or hypophosphatemia. Hypomagnesemia is often iatrogenic, related to cisplatin or cetuximab, but can be prevented by supplementation. Hypercalcemia can impair life quality and be life-threatening in the most severe cases. Hypocalcemia is less common and often of iatrogenic origin. Finally, the tumor lysis syndrome is a diagnostic and therapeutic emergency that affects the prognosis of patients. Its incidence tends to increase in solid oncology, related to the improvement of therapies. Prevention and early diagnosis of ED are essential to optimize the overall management of patients with underlying cancer and cancer therapy. The aim of this review is to synthesize most frequent ED and their management.

PARP inhibitors (PARPi) have established themselves as a class of essential anti-cancer drugs. They inhibit PARP proteins involved in DNA damage repair. Their anti-tumor action requires a concomitant abnormality in DNA damage repair, the homologous recombination deficiency (HRD). The genomic instability being too substantial, the tumor cell goes into apoptosis (concept of synthetic lethality). This last decade, the selection of patients benefiting from PARPi has been refined with convincing results for ovarian cancers, but also breast, prostate and pancreatic cancers. This article presents recent data that have impacted our clinical practice and the PARPi authorized in Switzerland.

High-grade serous ovarian carcinoma (HGSOC), the most frequent and aggressive form of epithelial ovarian cancer is characterized in half of cases by homologous recombination deficiency (HRD). This molecular alteration is defined by distinct causes and consequences. The main and most characterized cause is the presence of an alteration affecting BRCA1 and BRCA2 genes. Regarding consequences, a specific genomic instability leads to increased sensitivity to platinum salts and poly (ADP-ribose) polymerase (PARPi) inhibitors. This latter point enabled the advent of PARPi in first and second line maintenance. As such, the initial and rapid evaluation of HRD status with molecular tests is a key step in the management of HGSOC. Until recently, the range of tests offered proved to be very limited and suffered from technical and medical limitations. This has recently led to the development and validation of alternatives, including academic ones. This "state of the art" review will bring a synthesis concerning the assessment of HRD status in HGSOCs. After a brief introduction of HRD (including main causes and consequences) and of its predictive value regarding PARPi, we will discuss the limitations of current molecular tests and the existing alternatives. Finally, we will contextualize this to the situation in France, with special consideration concerning the positioning and the financial coverage of these tests, with the perspective of optimizing patient management .

The fear that the medical oncologist may have is that HIPEC integrated into a multidisciplinary care pathway will negatively impact the treatments that will follow. This fear is largely related to the side effects, which are themselves dependent on the medication used. Cisplatin, most frequently used for epithelial ovarian cancers, has essentially renal toxicity, which can be avoided by the use of sodium thiosulfate. Oxaliplatin induces more severe toxicities post surgery than mitomycin C in colorectal cancers. However, the data from randomized trials are reassuring for the medical oncologist concerning the course of postoperative treatment, as long as HIPEC is performed according to a standardized protocol, within trained teams, and after multidisciplinary discussion concerning its modalities.

Tripartite consultations with a coordination between hospital and community care givers were implemented within hospital center for patients who start an oral anticancer regimen.

Immune checkpoint inhibitors are now an integral part of the anti-cancer therapeutic arsenal. They have revolutionized the prognosis of certain cancers at the cost of a specific spectrum of dysimmune side effects that can affect the ophthalmological sphere. Patient education associated with increased vigilance of health care providers will allow faster detection and therefore optimal care to limit morbidity, maintain the best possible visual acuity and above all to be able to continue therapy prolonging survival. In this article, we describe the main ocular side effects as well as an outline of their management.

Nausea and vomiting induced by cancer treatment (CINV) remain one of the most common and feared side effects in children despite the use of new drugs to prevent them. The existing recommendations for the prophylaxis and treatment of CINV are based on adult patients in Anglo-Saxon societies. Based on a recent review of the literature, we focused on specific pediatric issues in order to offer recommendations validated by the supportive care committee of the French society for childhood cancer.

For therapeutic purposes, the development of new anti-cancer drugs requires their evaluation in terms of activity, cytotoxicity and pharmacokinetics. The candidate drugs are tested in vitro on cell lines and primary cells isolated from patients, and in vivo, often, using xenografts in immuno-compromised mice. In recent years, administrative constraints have become increasingly stringent and the 3R rule (reduce, refine, replace) requires the elaboration of alternative models capable to replace mouse models or at least to limit their use. Among them, xenograft on chick embryo chorioallantoic membrane (CAM assay) seems particularly efficient. It makes it possible to monitor and quantify tumor growth and tumor-associated parameters such as neoangiogenesis, invasion and migration. It allows the screening of drugs effective both on tumor cells and their microenvironment. Finally, the model seems adapted to the development of personalized medicine to which current research in cancerology is tending. In this context, this review focuses on the technique itself and its advantages.

Despite an increasing number of therapeutic indications, there are no specific recommendations regarding the management of PARP inhibitors other than what is specified in the SmPC of each substance. A Delphi French consensus was conducted to establish practical guidelines to meet the needs identified by healthcare professionals and patients.

Over the last decade, cancer mortality has decreased considerably, particularly in breast cancer thanks to better screening techniques and better therapeutic management. The significant increase in patient survival has led to the appearance of a certain number of events due to the side effects of the therapies used. Cardiovascular disease is the most frequently observed side effect in breast cancer, due to the direct toxicity of anti-cancer therapies but also due to traditional cardiovascular risk factors common to both of diseases. Anthracyclines, anti-HER2 therapies, chest radiotherapy and hormone therapy are the main causes of cardiotoxicity in breast cancer. It is important to know the rate of follow-up for cardiotoxicity screening and management.

Hypertension is a very common comorbidity in patients suffering from cancer, due to common risk factors. In addition, many oncology drugs, including the new tyrosine kinase-targeting drugs, may induce hypertension or unbalance a pre-existing hypertension. Severe hypertension may lead to cardiac, renal or vascular complications and require the discontinuation or modification of anticancer treatment. It is therefore necessary to be aware of the molecules at risk. The management of hypertension in cancer is the subject of expert consensus and is based on the usual antihypertensive drugs. Adequate cardiac monitoring should be organised before, during and after treatment to allow early management and avoid possible complications. The aim is to provide optimal oncological treatment and improve short-term survival, but also to reduce the long-term cardiovascular risk of cancer survivors.

Radiotherapy and targeted therapies play a major role in the management of cancers. Unfortunately, the toxicity and efficacy data regarding their association are tenuous and not centralized. Thus, we propose a literature review about the risks and opportunities of combining radiotherapy with targeted therapies.

Pegaspargase (Oncaspar®), a pegylated form of native Escherichia Coli-derived L-asparaginase is an essential component chemotherapy used in the treatment of acute lymphoblastic leukemia (ALL) in pediatric and adult patients. Its particular toxicity profile requires a specific management to improve safety and tolerability and optimize treatment outcome and therefore survival. Within the framework of workshops of practice harmonization of the French Society of Children and Adolescent Cancers, diagnostic and management of the most commonly occuring toxicities (excluding coagulation abnormalities) during Pegaspargase treatment were reviewed according to the analysis of published studies.

Dermatomyositis is an autoimmune disease mainly characterized by muscle and skin involvement. Its association with cancer is known but the term «paraneoplastic» remains debated. We report here the case of a 71-year-old woman with a new diagnosis of dermatomyositis with, at the same time, the discovery of a lung adenocarcinoma. Lung cancer was treated with pembrolizumab, an immune checkpoint inhibitor directed against the "Programmed cell Death protein 1" (PD-1) receptor. Three weeks later, the patient presented a severe flare of dermatomyositis. Administration of intravenous corticosteroids and infliximab were ineffective. Intravenous immunoglobulins were then administered, followed by subcutaneous methotrexate, with a progressive positive evolution. Flares of pre-existing autoimmune diseases are observed under immune check point inhibitors, even when the evolution of the cancer is favourable. These immune-related adverse events are often «mild to moderate» and severe immune related side effects are not more frequent when the patient has a pre-existing autoimmune disease. Treatment can be maintained in the majority of cases. However, as demonstrated in this clinical case, although immune checkpoint inhibitors are not contraindicated in autoimmune diseases, the presence of myositis requires special attention given the potential severity of flares.

Chemotherapy-induced neutropenia (FN) is the most common infectious complication in pediatric oncology. To our knowledge, no pediatric research has been published in Tunisia. The purpose of our study was to describe the features of FN among Tunisian children and to investigate factors correlated with FN. We conducted a prospective study of children with chemotherapy-induced FN at the Department of Pediatric Medicine A of the Tunis Children´s Hospital from July 2019 to December 2019. We recorded 50 episodes of FN in 32 patients whose mean age was 5.3 years (3 months-16 years). We included 26 patients with solid tumors (81%) and six patients with hemopathies (18.7%). The mean time between last treatment and fever onset was 10.67 days. Bacteriological investigation was contributory in 18% of cases and mainly showed gram positive cocci. Therapeutic protocol including 1st line empirical antibiotic therapy (3rd generation cephalosporin with aminoglycoside) was effective in 62% of cases. Mortality rate of patients with FN was 2%. The statistical study did not reveal any factor of correlation with late-onset neutropenia. In conclusion, our results are consistent with literature data on bacteriological documentation and mortality. Our 1st line treatment option based on 3rd generation cephalosporin associated with aminoglycoside was effective in 2/3 of the cases. In the future, oral antibiotics may be considered in patients at low risk for infection.

Tyrosine kinase inhibitors targeting the BCR-ABL1 oncoprotein represent an outstanding progress in chronic myeloid leukemia and long-term progression-free survival has become a reality for a majority of patients. However, tyrosine kinase inhibitors may at best chronicize rather than cure the disease thus current recommendation is to pursue treatment indefinitely. As a consequence, high quality treatment and care must integrate optimal disease control and treatment tolerability. Tyrosine kinase inhibitors have an overall favorable safety profile in clinical practice since most adverse events are mild to moderate in intensity. However, recent evidence has emerged that new generation tyrosine kinase inhibitors may sometimes damage vital organs and if not adequately managed, morbidity and mortality may increase. The 3rd generation tyrosine kinase inhibitor ponatinib is licensed for the treatment of chronic, accelerated or blast phase chronic myeloid leukaemia patients who are resistant to dasatinib or nilotinib; intolerant of dasatinib or nilotinib and for whom further treatment with imatinib is not clinically appropriate; or who express the T315I mutation. Ponatinib represents an important therapeutic option but it is associated with an increased risk of cardiovascular events. The purpose of this article by the France Intergroupe des Leucémies Myéloïdes Chroniques is to provide an overview of ponatinib efficacy and cardiovascular safety profile and to propose practical recommendations with the goal to minimize the risk and severity of cardiovascular events in ponatinib-treated patients.