Sécurité en curiethérapie

No technique can now be used without previously considering the safety of patients, staff and public and risk management. This is the case for brachytherapy. The various aspects of brachytherapy are discussed for both the patient and the staff. For all, the risks must be minimized while achieving a treatment of quality. It is therefore necessary to establish a list as comprehensive as possible regardless of the type of brachytherapy (low, high, pulsed dose-rate). Then, their importance must be assessed with the help of their criticality. Radiation protection of personnel and public must take into account the many existing regulation texts. Four axes have been defined for the risk management for patients: organization, preparation, planning and implementation of treatment. For each axis, a review of risks is presented, as well as administrative, technical and medical dispositions for staff and the public.     

La Société médicale Balint

ASSOCIATIONS

La Société médicale Balint     

Obésité et irradiation : difficultés techniques,toxicité et efficacité

The number of obese patients has increased in France over the last two decades, which has had an impact on the incidence of numerous types of cancer. The treatment of cancer by radiotherapy is impacted by obesity as a result of the physical, technical and dosimetric constraints, the acute and late toxicity, local control and the survival of patients.     

Déterminants moléculaires et génétiques d’efficacité et de toxicité du 5-fluoro-uracile

At the present time, 5-FU remains the standard molecule in the treatment of a large number of solid tumours and is the first choice when it comes to gastrointestinal cancers. A large number of markers, indicators of response and safety, have been described for this molecule and its oral form, capecitabine. Although the number of markers with clinically validated relevance remains low, combining both genetic and molecular research at the patient’s bedside with these markers will provide personalised oncological medicine and aims to improve the efficacy/safety balance for these medicinal products. To this end, and at a time where multicentre studies presenting strong evidence are available, 5-Fluorouracil and other fluoropyrimidines should be seen as the molecules of choice, fully benefiting from the progress being made in the area of biomarker-based medicine.     

Avis du groupe de travail missionné par l’Autorité de sûreté nucléaire concernant la radiothérapie stéréotaxique

PurposeAt the request of the French nuclear safety authority (Autorité de Sûreté Nucléaire, ASN) a working party of multidisciplinary experts was initiated to elaborate a report regarding propositions for the clinical practice of stereotactic radiation therapy and the related medical physics.Material and methodsSeveral stereotactic radiation therapy experts were audited by the working party, especially neurosurgeons and neuroradiologists, as well as radiation oncologists, medical physicists and radiation technologists. An international survey was conducted looking at legal requirements and guidelines concerning stereotactic radiation therapy. A national survey was conducted in France among 29 departments performing stereotactic radiation therapy. The working party report was submitted for advice to the permanent group of medical experts of ASN.ResultsAmong the 13 countries who responded, very few have legal documents. Some of them are stating that stereotactic radiation therapy must be performed in a radiotherapy department and only by well-trained professionals. Guidelines describing the role of each participant have been published in the USA. In France, stereotactic radiation therapy is performed with dedicated machines or adapted linear accelerators. In 2009, within the 29 departments, 4247 patients were treated with stereotactic radiation therapy representing 4% of the patients treated with external beam radiation therapy. Intracranial lesions were: 3383 and extracranial: 864. The working party of multidisciplinary experts made 7 recommendations. The first one saying that stereotactic radiation therapy must be considered as a radiotherapy. The permanent group of medical experts is asking to modify the “décret du 19 mars 2007” regarding “radiosurgery”.ConclusionThe medical benefit of stereotactic radiation therapy is well admitted and it is an increasingly used technique. This work through practical guidelines and legal propositions intends to promote a well-controlled development of this radiotherapy technique.     

Fin de vie à domicile dans la dignité et la sérénité : contributions du médecin généraliste

A general practitioner is sometimes with a patient up to the end of their life, when this occurs at home. This is the case of a patient with pancreatic cancer, diagnosed with liver, bone and pulmonary metastases. She wished to die at home, with the support of her children and an old friend. Treatment was greatly facilitated through frank exchanges between all those concerned, and the few healthcare providers involved. The philosophy of life that the patient had shaped over the years, her hopes and her determination turned her death into a necessary passage, accepted with grace. The state of her body was less significant than her social and spiritual well being, which she was keen to preserve until the very last day. She remained lucid up to the very last moment of her life. We are analysing the different elements that facilitated this optimal care, from the perspective of the patient, her family and her treating physician. A discussion on the role of the healthcare providers allows the place of each of them to be determined, when dealing with a death at home. Should this social, philosophical and spiritual dimension of the dying be reserved for healthcare providers specialized in these fields? Can we direct patients towards a spirituality, a philosophy of life that makes death a less harsh reality? We will question the role society has to play in negating death.     

Précarité sociale, cancer et vulnérabilité psychique, lien direct ou indirect ?

The link between psychological vulnerability and cancer is not clearly established. However, there does appear to be a link between cancer and social marginality. Psychological fragility has been shown to be associated with tobacco addiction. Socially vulnerable people are at risk of undergoing screening less frequently and being treated less efficiently. These data could explain the deficit in terms of both monitoring of their pathologies and observed survival rates, compared with those relating to the general population. Such people do not refuse treatment or screening and are often well aware of screening methods and their usefulness, and wish to be treated if they are ill. The main problems relate to organisation and careprovision. Monitoring of such patients is not always possible and the notion of a “life-plan” is often nonexistent, thus preventing adequate management of the disease. Screening programs are not adapted for marginal and socially excluded populations. Solutions can be found but they depend on both social and health policies and the behaviour of every individual professional care-provider.     

Préservation de la fertilité masculine

The incidence of cancer increases and affects more and more young patients. On the other hand, survival rates also increase, but often at the price of infertility induced by the gonadal toxicity of many treatments and a risk of mutagenicity. The techniques of semen cryopreservation are easy and results obtained after utilization of cryopreserved semen for assisted reproduction (IUI, IVF, or intracytoplasmic sperm injection [ICSI]) are satisfactory. The information of a patient about the possibilities of cryopreservation of fertility prior to the use of potentially sterilizing treatment is a legal obligation for every physician. The improvement of quality of life after healing must encourage oncologists to propose fertility preservation to their patients, which offers a very reasonable chance of later paternity.     

Préservation de la fertilité féminine en oncologie

Physicians taking care of young women with cancer have two problems to solve: fight against the disease and improve the patient’s quality of life after cancer. To manage this “after cancer period,” they should consider preservation of fertility. This may influence the choice of oncologic treatments and also the specific use of techniques used in the field of assisted reproductive medicine. We describe here the main current techniques of conservation of the feminine fertility in oncology.     

Biosimilaires d’héparine de bas poids moléculaire: quel degré de similarité pour quel bénéfice clinique ?

The development of biosimilar versions of low molecular weight heparins (LMWHs) raises a real medical concern. To illustrate our concerns regarding biosimilars, we chose the example of the specific clinical setting associated to the antithrombotic management of the acute coronary syndromes (ACS). In this specific indication, the LMWH enoxaparin has consistently shown its superiority in terms of efficacy when compared to unfractionated heparin (UFH) and in some direct or indirect comparison to other LMWHs. This is because of these particular clinical evidences that enoxaparin was considered as the gold standard for anticoagulation in cardiology and became almost universally used in ACS management. We are concerned by the fact that some patients might be treated by a generic copy of enoxaparin, on the basis of simplified criteria which were shown not to be specific enough to enable differentiation among LMWHs, thus, are unable to differentiate between enoxaparin and a biosimilar, in particular. Without any evidence from clinical trials, especially in ACS indication, we believe it is hard to ensure that the benefitrisk ratio between enoxaparin and its copy be equivalent. Indeed along with efficacy, safety issues have to be taken into consideration: biosimilars consist of glycan chain mixtures that exhibit specific immunoallergic features. Furthermore, the contamination of raw material with other components or other glycans during molecule extraction may trigger potentially harmful immune reactions.     

Toxicité et qualité de vie comparées après curiethérapie par iode 125 et radiothérapie stéréotaxique des cancers prostatiques

Quality of life is a major issue for good prognostic prostate cancer, for which brachytherapy is one of the reference treatments. Stereotactic Body Radiotherapy (SBRT) is a recent alternative however not yet validated as a standard treatment. This review of the literature reports and compares the toxicities and the quality of life, either after exclusive brachytherapy with iodine 125 or after SBRT. The comparison is made with the limitations of the absence of randomized trial comparing the two treatment techniques. Acute toxicity appears to be lower after SBRT compared to brachytherapy (from 10 to 40 % versus 30 to 40 %, respectively). Conversely, acute and late gastrointestinal toxicity (from 0 to 21 % and from 0 to 10 % of grade 2, respectively) appears more frequent with SBRT. Late urinary toxicity seems identical between both techniques (from 20 to 30 % of grade 2), with a possible urinary flare syndrome. Both treatments have an impact on erectile dysfunction, although it is not possible to conclude that a technique is superior because of the limited data on SBRT. SBRT has better bowel and urinary (irritation or obstruction) quality of life scores than brachytherapy; while sexual and urinary incontinence remain the same. The absence of randomized trial comparing SBRT with brachytherapy for prostate cancers does not allow to conclude on the superiority of one technique over another, thus justifying a phase III medicoeconomic evaluation.     

Déterminants et facteurs prédictifs pour la radiosensibilité tumorale

Many predictive factors of tumor radiosensitivity have been described. Number of clonogenic cells, proliferation rate, hypoxia and intrinsic radiosensitivity are usually considered as the main parameters of tumor control. Intrinsic radiosensitivity is correlated in a first approach to the ability of the cell to detect and repair DNA damages, and so integrity of the different pathways involved in this function: PARP-1, XRCC1, ATM, p53, MRN complex or BRCA1… Genetic polymorphisms of some of these genes, found in normal lymphocytes, have been correlated to late toxicity of normal tissues. But, in tumors, because of the difficulty to obtain samplings and heterogeneity, accurate molecular analysis is not possible in many cases, and no valuable test of radiosensitivity exist at this moment. For example, TP53 gene has been evaluated in many studies and results regarding its potential as a predictive factor of tumor sensitivity are conflicting. Surviving fraction at 2 Gy (SF2) allowed a global evaluation of sensitivity, but the obtention of this parameter often takes a long time and failed in 20 to 40%. Evaluation of double-strand break repair capacity by immunochemistry quantification of phosphorylated forms of ATM, H2AX or MRE11 is an interesting topic. However, discovery of tumor stem cells in a number of epithelial tumors could revolutionize the understanding of radiosensitivity. Combination of genomic and functional techniques are probably essential to better predict this parameter.     

Le prix des médicaments anticancéreux est-il justifié ?

During the recent years, the price of drugs in general and more particularly of anti-cancer molecules have steadily risen and reached such a point that patient associations and health professionals have alerted public authorities to the risks generated by this inflation for the health system. After describing the methods currently used to determine drugs’ price in France, this article will analyze the reasons asserted by the pharmaceutical companies to justify these ever-rising costs and to compare the relative magnitude of benefits to patients and price incrementations, taking in account both survival and quality of life. Eventually, proposals for limiting this constant price expansion and therefore the hazards for the health system based on national solidarity will be stated.     

Étude QUALIOR : faisabilité et efficacité d’un programme d’activité physique adaptée standardisée et encadrée à domicile chez des patients bénéficiant d’une thérapie ciblée orale pour un cancer métastatique

The adverse effect most commonly reported by patients treated with oral targeted therapies for advanced cancer is the onset of fatigue, which may be a limiting factor in long-term tolerance of these treatments. Adapted physical activity (APA) has a demonstrated its beneficial effect on the level of fatigue experienced by patients treated for localised cancer and, under certain circumstances, has shown an improvement in survival. The majority of studies were conducted in the post-cancer period or during the treatment phase, with chemotherapy and/or radiotherapy. Very few studies have been carried out on patients treated with oral targeted therapies. APA programmes vary in quality in terms of their objectives and the ways in which they are carried out and assessed. Particularly for patients with fatigue who have an advanced illness, it is important to assess supervised, home-based APA programmes. The QUALIOR study, sponsored by Unicancer, is a phase II–III randomised study, with the aim of thoroughly assessing the implementation of a 3-month home-based APA programme for more than 300 patients treated with targeted therapy for an advanced cancer (including breast, kidney and lung cancer plus a diverse cohort) in improving fatigue and quality of life, as well as full-term treatment compliance. A secondary objective is to evaluate progression-free survival. This programme is also assessed for its medico-economic relevance. The feasibility of the APA programme, which has been designed with various intensity levels, is assessed during the phase II study, which will then be continued with a phase III study to measure the programme’s efficacy. The final objective is to provide access to supervised APA sessions, specifically aimed at patients treated with these new targeted therapies, within the framework of a supportive care activity.