Anticancer chemotherapy plays a key role in the treatment of cancer in children. Following its increased efficacy, three children out of four can now be cured. Nevertheless, given the fact that 25% of the children with cancer are not cured and chemotherapy-induced long-term side effects are numerous there is a need to keep developing new agents and new strategies to fight cancer. Moreover studies investigating off-patents drugs should be stimulated in paediatric oncology in order to improve our knowledge of "old" drugs. Here we will review the specificities of children as compared to adults in the context of clinical drug development and pharmacology research in paediatric oncology. Such a research is now encouraged and facilitated by a European regulation as well as by international consortia such as "Innovative Therapies for Children with Cancer" (ITCC).

Paediatric Hodgkin disease presents some particularities when compared to Hodgkin in adults. In this article, we focus on the paediatric particularities, especially in term of current treatment strategy. The aim is to decrease the important rate of late effects while keeping the excellent survival.

To develop a treatment strategy for peritoneal carcinomatosis using a combination of extended peritoneal resections, local destructive procedures and hyperthermic intraperitoneal chemotherapy creates great concern between healthcare workers involved in these procedures. New professional risks exist: risk of exposure to cytotoxic drugs, environmental risks (inhalation of smoke, aerosolization of chemotherapy agents). Information, education and training of healthcare workers is mandatory in order to ensure proper evaluation, prevention, and management of professional exposure risks in coordination with the occupational health office.

For the past two decades, significant developments have been made in supportive care for the management of chemotherapy-induced nausea and vomiting (CINV). A better understanding of the pathophysiology of vomiting and the introduction of two new classes of antiemetic agents with a high therapeutic index (serotonin type 3 receptor antagonists [anti-5HT3 or setrons] in the 1990s and neurokinin type 1 receptor antagonists [anti-NK1] in 2000), possibly combined with corticosteroids, have helped to improve the management of this distressing side effect, constantly feared by patients. It is essential to distinguish between the anticipatory, acute (first 24 hours) and delayed phases of CINV, to take into account the emetogenic potential of the different chemotherapy protocols (very low, low, moderate and high) together with individual risk factors. The authors would like to propose methodological and therapeutic recommendations for the primary and secondary prophylaxis of the acute and delayed phases of CINV, based on recent publications by international learned societies.

Medulloblastoma is the most frequent childhood brain tumor (30%) but account only for less than 1% of adult brain tumor. The overall survival increased significantly during the last two decades with 80% of long survivors at five years whatever the stage. Most children who survive have significant neurocognitive sequelae. All children are included in national and international prospective studies which propose risk-adapted radiation therapy and chemotherapy after surgery. Quality control of radiotherapy leads to reduce significantly the risk of recurrence and has an impact on survival. Risks of late toxicity should be taken into account at the time of the treatment. Due to the rarety in adult population, no prospective studies and few data about late effects are available. Adult medulloblastoma is a therapeutic challenge and their therapeutic strategies are similar to pediatric protocols. In order to improve the understanding of adult disease and to homogenize the treatment, National Cancer Institute (INCa) stimulated the creation of web conference to discuss each case prospectively and to propose a protocol of treatment. A better comprehension of biological processes and abnormal cellular signalling pathways involved in medulloblastoma pathogenesis had led toward a new prognostic classification to adapt the therapeutic strategy and gives hope of new therapeutic tools.

Evaluation of the fetus using prenatal ultrasound has resulted in increased detection of asymptomatic adnexal masses during pregnancy. Such masses are rarely malignant (1/10 000 to 1/50 000 pregnancies), but the possibility of borderline or cancer must be considered. It is a common assumption by both patients and physicians that if an ovarian cancer is diagnosed during pregnancy, treatment necessitates sacrificing the well-being of the fetus. However, in most cases, it is possible to offer appropriate treatment to the mother without placing the fetus at serious risk. The care of a pregnant woman with cancer involves evaluation of sometimes competing maternal and fetal risks and benefits. These recommendation approaches attempt to balance these risks and benefits; however, they should be considered advisory and should not replace specific interdisciplinary consultation with specialists in maternal-fetal medicine, gynecologic oncology, and pediatrics, as well as imaging and pathology, as needed. Second level ultrasound including Doppler is needed. MRI is not often necessary, and CA 125 is of low contribution. We suggest surgery be performed after 15 SA for ovarian masses which (1) persist into the second trimester, (2) are greater than 5 to 10 cm in diameter, or (3) have solid or mixed solid and cystic ultrasound characteristics. During antepartum surgical staging and debulking, homolateral salpingo-oophorectomy and peritoneal cytology and exploration are necessary. Women found to have advanced stage epithelial ovarian cancer should consider having completion of the debulking of the reproductive organs at the conclusion of the pregnancy. If chemotherapy is indicated, we recommend delaying administration, if possible, after the delivery or at least after 20 SA in order to minimize the potential fetal toxicity.

Since 10 years, the combination of chemoradiotherapy has become a standard of treatment of the advanced localized cervical cancer. Two systematic reviews of the literature (including the results of the different clinical trials) have already been published. The aim of this article is to present the results of the recent meta-analysis based on individual patient data and to discuss the perspectives. This meta-analysis was rigorously designed: trials selected had the same control arm with the same radiotherapy without concomitant chemotherapy, the definition of the primary outcome (overall survival) was homogeneous and analysis was made in intent to treat. The results confirm the advantage in overall survival in favor of the chemoradiotherapy with an absolute 5-year overall survival benefit of 6% (60-66%) and 8% of 5-year disease-free survival (50-58%). Interestingly, even if cisplatin seems to be the most active drug, a significant advantage is also observed with no platinum chemotherapy. A polychemotherapy is not more active than a monochemotherapy and there was a suggestion of a difference in the size of the survival benefit with tumor stage. Larger benefits were seen for the few trials in which additional chemotherapy was administered after chemoradiotherapy, but results have to be confirmed by other clinical trials. Late toxicity was not well evaluated and a long-term follow-up of the patients is important to assess the real incidence of long-term side effects of the chemoradiotherapy and the impact on quality of life. New strategies combining new chemotherapy protocols or targeted therapy with radiation are promising but have to be evaluated in comparative clinical trials before use in routine.

In oncogeriatric patients, severe malnutrition is associated with increased morbidity and mortality, nosocomial infections, radiotherapy or chemotherapy toxicities, and decreased of quality of life. Therefore, systematic screening and care of malnutrition is mandatory, in accordance with the French guidelines in 2007. Now, dietary counselling should be purposed systematically in malnourish patients and when radiotherapy or radiochemotherapy are considered. Oral supplementation by specific diet (immune-enhancing diets) should be used with cautions, and actually, reserved only in digestive neoplasms and surgery. In cases of severely malnourished patients or if dietary counselling suffers a setback, enteral nutrition should be recommended. In radiotherapy or chemotherapy, used parenteral nutrition is associated with an increase in infectious complications. Artificial nutrition should not be used when Karnofski index is lesser than 50% (or performance status greater than 2) and prognosis lesser at three months.

Hodgkin's disease, the most common cancer between 15 and 24 years, raises two problems in women in reproductive age: the preservation of fertility and the care during pregnancy. Chemotherapy and radiotherapy can destroy gonads and subsequently lead to a loss of fertility and premature ovarian failure. Many options are available today to maintain fertility in female patients treated for Hodgkin's disease, thanks to advances in assisted-reproduction technology. Chemotherapy and radiotherapy during the first trimester are associated with increased risk of congenital malformations and this risk diminishes as pregnancy advances. The management of this disease during pregnancy must be examined case by case.

A series of medical disciplines benefit from the emergence of diverse targeted therapies using monoclonal antibodies. Skin is affected by adverse events of such therapies primarily targeting internal cancers. As a unique event in medicine, some of the skin adverse effects are predictive markers of the therapeutic antineoplastic activity. This fact concerns the paroxismal acneiform eruption and the inflammatory flare-up of actinic keratoses. Such a situation is linked to the fact that these specific "unwanted" effects are not really side effects but rather represent the direct pharmacological consequence of the activity directed to the EGF receptors which are particularly abundant in the follicular ostium and in precursor lesions to skin carcinomas.

The goal of adjuvant endocrine therapy for early breast cancer is to prolong overall survival and improve the quality of life of patients. Studies on breast cancer show an early peak of recurrence at two years after surgery and distant recurrences that are responsible for a significant reduction in overall survival. Tamoxifen has been the standard of adjuvant endocrine therapy in breast cancer for years, however only about half of relapses are prevented and there is an early occurrence of serious adverse events due to agonistic estrogenic activity of tamoxifen, such as an increase in the risk of endometrial hyperplasia and venous thromboembolism. The use of aromatase inhibitors is changing this standard with studies covering various clinical settings. They have shown a benefit in many situations, such as an extension of endocrine therapy by tamoxifen, sequential hormonotherapy or up-front adjuvant therapy with aromatase inhibitors.

Being diagnosed with cancer and undergoing treatment can be a daunting experience. The side effects of treatment often influence a person's quality of life. One side effect that has been identified more recently is known as "chemobrain." Although attempts have been made to quantify and measure cognitive changes, little attention has been paid to describing the changes from the patient's viewpoint. This investigation was undertaken to understand the impact of cognitive changes on daily living and to identify the strategies patients used to cope with "chemobrain." Thirty-two individuals provided in-depth interviews about their experiences living with cognitive changes. Their descriptions provided clear evidence that the changes could effect daily living, social and work-related activities. About a quarter of the individuals expected the changes to be temporary while the rest were uncertain or expected the change to be permanent. The emotional distress people experienced was linked to whether or not the cognitive changes interfered with their doing something that was of importance to them. Overall, participants used a variety of strategies to cope with the changes. The most frequently identified strategy was "writing everything down." When asked what nurses could do to assist them in managing this side effect, participants emphasized how important it is for them to have information about the potential for cognitive change at the beginning of their treatment.

The surgeon must know the importance of angiogenesis in wound healing. He must also use anti-angiogenics to change the clinical situations and make curative a potentially ineffective surgery. However, these strategies require daily biological indicators able to quantify the tissue activity, that we do not possess yet, nor have we any indicator to predict tumour sensitivity to anti-angiogenics.

VEGF represents a model of gene expression regulation. RAS/RAF/MEK/ERK and PI3 Kinase pathways, activated in response to growth factors stimulation or by oncogenes, contribute to its expression by activating transcription factors or inactivating proteins implicated in degradation of its mRNA. These factors (Sp1/Sp3, HIF-1 and TTP) constitute molecular markers of tumor aggressiveness. VEGF is overexpressed in solid or hematologic tumors. Thus, numerous compounds regulating angiogenesis by targeting VEGF have been developed. However, their effects are not as spectacular as expected. The existence of anti-angiogenic isoforms of VEGF could be a cause of their less potent activity. These different points are discussed in this review article.

Angiogenesis is a basic process during development and in pathology as well. The molecular networks involved in angiogenesis are not totally understood. We have recently developed a new model for tumoral angiogenesis in the chicken embryo, which allows large scale studies. On the other hand we have uncovered a new induction pathway, which involves stress of the endoplasmic reticulum. These investigations open up novel prospects for the future.

Thoracic irradiation is a major weapon in the treatment of nonmetastatic primary lung cancer, in particular in patients presenting a locally advanced disease of the mediastinium. Acute radiation pneumonitis (ARP) is one of the main limiting toxicities. The purpose of this work is to sum up the current state of knowledge of the factors of risk of developing ARP. The incidence after conventional irradiation, in patients with non small cell lung cancer (NSCLC) is about 7 to 10% in the moderate although symptomatic forms of ARP and about 1 to 3% in the severe forms. The factors related to the patient, the tumour or treatments prior to the irradiation do not determine any specific risk of ARP besides an age of over 65 years that remains debatable. The validated predictive factors of ARP are mainly related to the irradiation factors (healthy lung volumes irradiated, average dose of irradiation, etc.). Nevertheless, in spite of the adjustment of these parameters, the individual susceptibility to the toxicity of thoracic radiotherapy remains significant, directing current research to the biological markers intrinsic to the patient. In particular, the involvement of early variations of certain cytokines (IL-6, IL-10, TGF-ss) in the occurrence of ARP during irradiation has been suggested and studies are under way to confirm their involvement and determine their role.

Radiation recall dermatitis is an inflammatory skin reaction occurring in a previously irradiated field following the delivery of a promoting agent. It has been described after a number of antineoplastic agents such as gemcitabine, taxanes, anthracyclines. We report the case of a 50-year-old man with metastatic prostate cancer who developed two consecutive radiation recall dermatitis episodes triggered by oral cyclophosphamide. They occurred 4 to 5 weeks after palliative radiotherapy on bone metastasis. Spontaneous resolution was observed within 6 weeks after discontinuation of cyclophosphamide and with local supportive care. To our knowledge this is the first reported case of radiation recall dermatitis after oral cyclophosphamide.