Chemotherapy and radiotherapy have increased the life expectancy of cancer patients but may cause premature ovarian failure and irreversible loss of fertility. In the context of childhood cancers, it is now acknowledged that possible negative effects of treatment on future reproductive autonomy are a major concern. While a few options are open to patients post-puberty, the only option currently open to prepubescent girls is cryopreservation of ovarian tissue and subsequent transplantation. Yet, this procedure raises ethical concerns related to its experimental nature and to risks involved in surgery and general anesthesia. In addition, the risk of malignant cells being reintroduced in the future following autologous transplantation of the ovarian tissue is still poorly evaluated. A number of ethical issues arise surrounding this procedure. While the girl's future reproductive autonomy is at stake, it is important to also consider risks associated with the procedure. Fertility preservation through cryopreservation of ovarian tissue thus raises a conflict between the principles of beneficence and non-maleficence. We argue that the ethical complexity surrounding fertility preservation for prepubescent girls should be resolved by applying the principle of "the child's right to an open future". We propose to consider 'beneficence' through the lens of the reproductive autonomy and her potentialin becoming a genetic parent.

Describe the process for designing and creating SimUPAC 360°, a virtual reality training in anti-cancer drug production units.

The incidence of oropharyngeal cancer induced by human papillomavirus (HPV) infection is steadily increasing in developed countries. These tumors are more chemoradiosensitive and have a better prognosis than HPV-negative one. In addition, they occur in younger and better-off patients with longer life expectancy. Current radiotherapy and chemotherapy protocols are currently being questioned as they may expose HPV-positive patients to excessive treatment and unnecessary toxic effects. Less intensive treatment regimens could possibly achieve similar efficacy with lower toxicity and improved quality of life. The aim of this work was to summarize the knowledge on these tumors and their implications for radiation oncologists. In this update, we will discuss ongoing de-escalation trials and highlight the issues raised by these studies. We will also comment on the results of recently published de-intensification studies. Three main strategies are analyzed in the present article: the de-escalation of the drug associated with radiotherapy, the de-escalation of the radiotherapy dose (in concomitant chemoradiotherapy, after induction chemotherapy, in a postoperative setting) and de-escalation of radiation target volumes. Our findings ultimately indicate that clinicians should not change the management of oropharyngeal cancer patients outside of clinical trials.

Proton pump inhibitors, a major progress in gastro-enterology, are globally among the most widely prescribed drugs. But, due to their strong gastric acid inhibition, they can be responsible for side effects, particularly in cancer patients. They are involved in renal function impairment, bone fractures, digestive bacterial overgrowth, particularlyclostridium difficile infections, anemia and hypomagnesemia. Long term use can increase the risks of gastric, pancreatic and liver cancers. They decrease absorption of weak bases drugs, particularly tyrosine kinase inhibitors and capecitabine and are responsible for a poorer prognosis if taken concomitantly with erlotinib, gefitinib and pazopanib. Modification of cyclin dependent kinases is also possible as well as decrease of efficacy of immune check point inhibitors (microbiome modifications). Absoption and efficacy of capecitabine seem also poorer with negative prognosis effect on treatment of gastric and colon cancer. Their long term use, particularly in cancer patients, should probably be avoided.

Objectives: the purpose of this study is to assess TAM safety in terms of side effects and hormonal status, the persistence of the treatment over a five years time-frame and to report the remote follow-up data.

Breast cancer affects about 3,000 new women of childbearing age each year. The desire for pregnancy is therefore a frequent issue in the management of breast cancer. We reviewed the current state of knowledge and recommendations in high-risk women, on the consideration of this desire for pregnancy in therapeutic management, the way to approach it, the preservation of fertility in the care process and finally on the outcomes of pregnancy after breast cancer. We evaluated the desire for pregnancy, qualitatively and quantitatively, after breast cancer through a literature review.

Over the past decades, progresses in oncology have improved the recovery rates after numerous malignant diseases, including breast cancer, that strike young adults in childbearing age. Quality of life of young cancer survivors has become a major issue. However, anticancer therapies can have a detrimental impact on fertility. It is now well-established that all patients should receive information about the fertility risks associated with their cancer treatment and the fertility preservation options available. These techniques aim to limit the negative impact of chemotherapy on the ovaries or to preserve gametes before treatment. Currently, oocyte or embryo freezing after controlled ovarian hyperstimulation represents the most effective method for preserving female fertility. Over the past years innovative protocols of ovarian stimulation have been developed to enable breast cancer patients to undergo oocyte or embryo cryopreservation irrespective of the phase of the cycle or without exogenous follicle-stimulating hormone related increase in serum estradiol levels. When controlled ovarian hyperstimualtion cannot be implemented, other techniques such as cryopreservation of ovarian cortex, in vitro maturation or the use of GnRH agonists may be proposed. However, it is important to inform patients that all these fertility preservation techniques do not represent a guarantee of pregnancy.

Despite proven survival benefits after breast cancer, long-trem compliance with adjuvant hormone therapy remains a major issue, partly due to the side effects of treatment. In young women treated for breast cancer, these treatments include tamoxifen, anti-aromatase and LH-RH analogues, with even more side effects when these treatments are combined, especially for younger patients with more aggressive disease. The management of the potential side effects requires first of all detailed and precise information at initiation of treatment, and preventive measures including patient education. Once the treatment has been initiated, clinicians should be able to propose to their patients appropriate measures to alleviate the potential of the side effects, which can be of various types: biological (dyslipidemia), physical (weight gain, hot flushes, vaginal dryness, sexual disorders with low libido, musculoskeletal symptoms…) or psychosocial (anxio-depressive disorders, poor body image, difficulties of professional reintegration). Management of these effects can combine various modalities: drugs (switching hormone therapy, anti-depressants, hormonal treatments of vaginal dryness in some cases, gabapentin), physical treatments (CO2 laser for vulvovaginal atrophy) or psycho-physical techniques (physical activity, mindfulness, acupuncture…). Eventually, the lenghth of these adjuvant hormonal treatments requires supportive measures to help young patients engage in new lifestyle measures, in particular in term of physical activity and diet. This will help them mitigate the symptoms related to these side-effects while reducing the long-term risks related to their disease and treatments.

Adjuvant endocrine therapy is highly effective and appropriate for all breast cancer patients with hormone receptor positive tumors, pre and post menopausal women. It's an oral daily pill for many years, after primary treatment. Although this medication dramatically reduces reccurrence rates and risk of death, many breast cancer survivors either fail to take pills with prescribed frequency (adherence) or discontinue therapy (persistence) or even never begin to take it. It's difficult to know exactly the prevalence of adherence and persistence but women age younger than 40 years had the highest risk of discontinuation. Medical literature of the last 15 years in this area has been carefully reviewed considering initiation treatment background, specificity of premenopausal young women population, healthcare provider and patient communication and respective views. It's highlighted that dedicated care, at first and after in follow up, is an essential part for better adherence. Guidelines processing are more and more complicated, expert medical assesment is required, shared decision must be provide. Patients need enhanced knowledge about mode of action, benefits but also potential side effects, and optimized patient provider relationship for empathy and better comprehension. Providers must believe in treatment relevance and convey their convictions.

Breast cancer in young women requires special vigilance because of the unique condition and complex management that is involved. The indication for chemotherapy should not be based on age alone but in association with the biological characteristics of the tumour. In addition, age is not considered as demonstrated predictor of chemosensitivity. The choice of adjuvant or neoadjuvant chemotherapy should be guided by the histological type of the tumour, the stage of the tumour and the patient's comorbidities. In this subgroup of patients, the recommendations for the use of molecular signatures follow those of the general population. This manuscript summarizes the main data and recommendations on the management of breast cancer in young women in term of chemotherapy.

Dermatological toxicities (affecting the skin, mucous membranes, nails or hair) are frequently associated with cancer treatments. They can represent a real burden for patients, with physical, social and psychological repercussions. These dermatological adverse events can also persist long after the treatment has ended, especially after treatment with cytotoxic chemotherapeutic agents such as taxanes. There is a clear need for the development of suitable supportive care measures to help manage these toxicities. The place of a hydrotherapy treatment in this context remains to be clarified. This article summarizes the main data available on the quality of life, and more specifically the dermatological quality of life, of patients for whom hydrotherapy was proposed after breast cancer. © 2020 Elsevier Masson SAS. All rights reserved.

Immune Checkpoint Inhibitor (ICI) therapy is now a standard of care in numerous cancers with very promising results. Nevertheless, adverse events, and especially immune-related adverse events (irAEs) not reported during clinical trials, are emerging and can be life-threatening.

The HIV infection remains a serious public health concern in France and around the world. Cancers are frequent among people living with HIV (PLWH) and have become the leading cause of mortality among this population in France. Certain non-AIDS-defining cancers are much more common among PLWH, such as anal carcinoma, Hodgkin lymphoma, hepatocellular carcinoma and lung cancer. The incidence of cancer among PLWH depending on various factors, virological control under combined antiretrovial therapies (cART), exposure prevention to oncogenic virus and toxics are of utmost importance, such as the implementation of specific screening programmes. Drug interactions between cART and oncologic treatments can lead to serious adverse effects or to a reduction in the therapeutic effects, therefore they require a close monitoring. The PLWH have been excluded from the oncologic clinical trials assessing the efficacy and toxicity profile of the immune checkpoints inhibitors (ICPi) because of an increased theoretical risk of inducing adverse events and a feared lack of efficacy in the immunocompromised population. However, the mostly retrospective clinical data reporting the use of ICPi among PLWH are somewhat reassuring with a safety and efficacy profile similar to what observed in HIV-negative patients. Regarding the "shock and kill" anti-HIV effects of ICPi, the preliminary clinical data available are still modest and relatively disappointing despite encouraging results obtained in vitro. HIV-associated cancers represent a particular care challenge due to the multiple comorbidities in the population and the high risk of drug interactions, thus the CANCERVIH national network is of particular interest within this context.

In the last classification of the World Health Organization (WHO) 2016, T-cell large granular lymphocyte (LGL) leukemia is a type of mature natural killer T (NKT) cell lymphatic hematologic disease. T-LGL leukemia is characterized by CD3+ T-cell phenotype and TCR gene rearrangement (T lymphocyte receptor). It is a rare disease, mainly affecting people living in the Western world. We report the case of a 60-year old Moroccan patient presenting with 1-month history of generalized jaundice with diffuse petechiae and impaired general condition. Initial clinical examination showed ascites of average abundance and hepatosplenomegaly; paraclinical examination objectified hepatocellular failure with neutropenia and thrombocytopenia. The diagnosis of T-LGL was retained based on cytological and immunophenotypic study of bone marrow blood as well as on the detection of TCR rearrangement using molecular test. The patient received cyclophosphamide associated with symptomatic treatment. The patient died within three months of the diagnosis due to septic shock with cachexia. T-LGL often has an indolent behavior and initial clinical status at diagnosis is generally moderate, with progressive onset but that was not so for our patient. Hepatocellular failure exceptionally results in T-cell large granular lymphocyte (LGL) leukemia.

Monoclonal antibodies are a therapeutic tool frequently used in oncology, as they allow the specific targeting of molecules expressed by cancer cells and, in most cases, induce minimal toxic effects on healthy tissues. Because monoclonal antibodies frequently lack significant toxicity and are not associated to a direct relationship between dose and effect, the methods of clinical development traditionally used for chemotherapy agents are scarcely useful for this class of drugs. In addition, no consensus exists on the definition of parameters different from toxicity that could assist the process of dose selection of monoclonal antibody in early clinical trials.

Many neurodegenerative or tumor brain pathologies should be able to benefit from the impressive medicinal advances that represent therapeutic antibodies. Unfortunately, many failures have been observed with antibodies whose targets are in the brain parenchyma due to their very low brain distribution. The blood-brain barrier (BBB) that exhibits extremely selective and restrictive properties is responsible for the low brain penetration of high-molecular mass molecules including therapeutic antibodies. The objective of this article is to present the properties of the BBB and the latest advances in the engineering of new antibody formats to possibly improve their brain distribution.

Monoclonal antibodies have revolutionized the treatment of many diseases, but their clinical effectiveness remains limited in some cases. Associations of antibodies binding to the same target (homo-combination) or to several different targets (hetero-combination), thereby mimicking a polyclonal humoral immune response, have demonstrated a therapeutic improvement in pre-clinical and clinical trials, mainly in the field of oncology and infectious diseases. The combinations increase the efficacy of the biological responses and override resistance mechanisms observed with antibody monotherapy. The most common method of formulating and administering antibody combinations is a separate formulation, with sequential injection of each antibody as individual drug substance. Alternatively, combined formulations are developed where the separately-produced antibodies are mixed before administration or produced simultaneously by a single cell line, or a mixture of cell lines as a polyclonal master cell bank. The regulation, the toxicity and the injection sequence of these oligoclonal antibody-based mixtures remain points to be clarified and optimized for a better therapeutic effect.