Conséquences des traitements des cancers et préservation de la fertilité

Cancer prognosis has considerably improved over recent decades and increasing numbers of young adults live with the long-term consequences of their treatment. Their quality of life is often serious compromised by the inability to conceive a child. As such the recent and rapidly evolving practice of fertility preservation needs to become a standard option in cancer care. Embryos, oocytes, spermatozoa, and germinal tissue can be cryopreserved without damage until such time that the patient, freed from their illness can envisage starting a family. Fertility can be persevered prior to initiation of gonadotoxic treatments by different methods. Some options, in particular in prepubescent boys (and even in adolescents and young adults), though a high research priority and a source of great hope, remain highly experimental. Since the available options combine both validated and experimental methods, it is necessary that care teams are multidisciplinary and that they discuss these choices with the patient and (for children) their family. Even though some patients, through choice or otherwise, are not candidates for Fertility Preservation, their decision, taken in the light of complete, correct and understandable information about the available options, must be respected in accordance with their rights to determine their own reproductive future. The current situation in France needs improvement and multidisciplinary structures are forming where cancer specialists work closely with specialists in reproductive medicine and biology to provide rapid and coordinated patient care. The national cancer institute (INCA) with the Agence de la biomédecine have co-published a report that brings the knowledge of all involved in the care of these patients up to date and makes a series of propositions to improve the situation and notably to guarantee equitable access to quality care for all concerned persons. The principal areas of improvement are:

• — Equitably improve cancer patients’ access to fertility preservation across the country through the regional planning and establishment of multidisciplinary teams, supported by targeted funding and the authorisation of centres.
• — Publish and disseminate professional guidelines and verify that they are taken into account during multidisciplinary decision making.
• — Systematically inform patients and their families about the consequences of cancer therapy on reproductive function.
• — Set up longitudinal cohorts of patients.
• — Promote research into how to prevent or reduce the risk of the attenuation of fertility and into how to restore it.

     

Protonthérapie des carcinomes épidermoïdes des voies aérodigestives supérieures : de la physique à la clinique

Intensity-modulated radiation therapy (IMRT) is presently the recommended technique for the treatment of locally advanced head and neck carcinomas. Proton therapy would allow to reduce the volume of irradiated normal tissue and, thus, to decrease the risk of late dysphagia, xerostomia, dysgeusia and hypothyroidism. An exhaustive research was performed with the search engine PubMed by focusing on the papers about the physical difficulties that slow down use of proton therapy for head and neck carcinomas. Range uncertainties in proton therapy (±3 %) paradoxically limit the use of the steep dose gradient in distality. Calibration uncertainties can be important in the treatment of head and neck cancer in the presence of materials of uncertain stoichiometric composition (such as with metal implants, dental filling, etc.) and complex heterogeneities. Dental management for example may be different with IMRT or proton therapy. Some uncertainties can be somewhat minimized at the time of optimization. Inter- and intrafractional variations and uncertainties in Hounsfield units/stopping power can be integrated in a robust optimization process. Additional changes in patient's anatomy (tumour shrinkage, changes in skin folds in the beam patch, large weight loss or gain) require rescanning. Dosimetric and small clinical studies comparing photon and proton therapy have well shown the interest of proton therapy for head and neck cancers. Intensity-modulated proton therapy is a promising treatment as it can reduce the substantial toxicity burden of patients with head and neck squamous cell carcinoma compared to IMRT. Robust optimization will allow to perform an optimal treatment and to use proton therapy in current clinical practice.     

Pharmacogénétique des protéines de la famille MDR

Résumé: Les multidrug resistance proteins ou protéines MDR appartiennent à la super-famille des ATP-binding cassette proteins (protéines ABC). Ces protéines sont exprimées de manière constitutive au niveau de certains organes, où elles remplissent des fonctions de transport ou participent à la constitution de barrières physiologiques. Seules quelques-unes dentre elles sont capables dassurer le transport de médicaments et, par là-même, de jouer un rôle dans la biodistribution de ces molécules, avec des conséquences attendues sur la réponse thérapeutique. De nombreux polymorphismes génétiques ont été rapportés, susceptibles de modifier lexpression et/ou lactivité des protéines ABC. Ils pourraient ainsi constituer une source importante de variabilité de la biodistribution et de lefficacité thérapeutique dagents anticancéreux, notamment en cas dadministration par voie orale.     

Radiothérapie stéréotaxique des cancers de la prostate

Stereotactic radiotherapy is a new option in the treatment of prostate cancer. However, only retrospective series and a few prospective phase II trials are available at this moment, including a few thousands of patients with a short follow-up. Most of the protocols delivered 33 to 38 Gy in four or five fractions. Acute toxicity seems to be similar to the one observed after conventional radiotherapy. Late toxicity is less evaluable because of the short follow-up: the rate of radiation-induced proctitis seems low in the published series. Urinary toxicities are not properly evaluated: some series reported a high incidence of urinary complications grade or higher. Most of the patients belong to the D’Amico's favourable group: biochemical controls are equivalent to those observed after conventional irradiation, but the follow-up is often shorter than 5 years and no definitive conclusion could be made about the efficiency of the technique. Data for the intermediate and high risk groups are not mature. In conclusion, stereotactic radiotherapy could strongly modified the management of prostate cancer: some phase III trials have started to confirm the good results reported in preliminary series.     

Adaptation de la méthode HACCP à la prévention des risques en radiothérapie

HACCP method is used for quality insurance in the food industry for many years. It was adapted to radiotherapy to evaluate risk in the treatment process. This pragmatic approach led to the clear identification of different hazards along the process. It also allowed implementation of appropriate measures in order to reduce them.     

Facteurs pronostiques de la ré-irradiation des cancers des voies aérodigestives supérieures : revue de la littérature

Purpose

To specify the effectiveness of head and neck cancer reirradiation and make a synthesis of prognostic factors established by published series of patients.

Radiothérapie postopératoire des cancers de la prostate

After radical prostatectomy, the risk of biological recurrence at 5 years varies from 10 to 40 % and this natural evolution of the disease has led radiation therapy being proposed as a supplement to surgery. When the recurrence risk is essentially local, supplementary radiotherapy is justified in the aim of improving biological recurrence-free survival, local control, metastasis-free survival and specific and global survival, while respecting patient quality of life. Three recent studies, EORTC 22911, ARO 9602 and SWOG 8794 found a similar advantage for biological recurrence-free survival without higher major additional toxicity. However, only the SWOG 8794 study found a significant improvement for metastasis-free survival and global survival. In an adjuvant setting, the optimal moment to propose this postoperative radiotherapy remains uncertain: should it be proposed systematically to all pT3 R1 patients, running the risk of pointlessly treating patients who will never recur, or should it only be proposed at recurrence? The GETUG AFU 17 trial will provide answers to the question of the optimal moment for postoperative radiotherapy for pT3-4 R1 pN0 Nx patients with the objective of comparing an immediate treatment to a differed early treatment initiated at biological recurrence.     

Place de la chirurgie dans la prise en charge des métastases cérébrales

Surgical excision of brain metastases has been well evaluated in unique metastases. Two randomized phase III trial have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful. Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, to rule out a differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system or radionecrosis). Finally, the biological documentation of brain metastatic disease might be useful in situations where a specific targeted therapy can be proposed. Selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved overall survival of cancer patients partially due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to the local treatment of brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients.     

Les médecins généralistes et la détection précoce des cancers de la peau

Introduction

One of the goals of the French Cancer Plan 2009–2013 is to strengthen the role of the general practitioner at each stage of the patient’s care. As part of its mission in informing health professionals on prevention, the French National Cancer Institute, INCa, implements a barometric survey to better assess the knowledge and practices of GPs on the early detection of skin cancer.

Method

This survey was achieved in two steps, in October 2009 and 2011, by phoning a sample of 600 representative GPs, constructed according to the quota method.

Results

A large majority of the GPs believe they have the necessary knowledge on the prevention and early detection of these cancers (81%) and thus feel comfortable answering questions from patients (87%). However a further analysis reveals that they consider their knowledge to be in need of upgrading. They express a strong demand for information and training. In terms of practice, if the examination of the patient’s skin is usual, it is not always fully carried out by the GP. Self-examination for patients identified at risk is not systematically demonstrated (57%). GPs are especially attentive to the color (83%) or the evolution of a nevus (60%), less to other elements of the ABCDE rule. In case of doubt, when noticing a suspicious skin lesion, the GP addresses his patient to the dermatologist (96%). The care management of patients, as established by the French National Health Insurance, was well accepted and did not change the GPs’ practices.

Conclusions

The results of the 2009 survey are comparable with those of 2011. Current actions, carried out in partnership with GPs on this topic, would benefit from a reinforcement of concerted information actions and continuing education.     

Apport des analyses moléculaires à la classification anatomopathologique des sarcomes

Conventional histology and immunohistochemistry remain the basic tools for the diagnosis and classification of sarcomas. However, molecular biology can enrich the pathologists analysis: the identification of a specific molecular abnormality can confirm diagnosis, rule out a differential diagnosis, and sometimes provide prognostic information. About 15% of sarcomas bear a specific translocation, such as rearrangements of SS18 (SYT) [synovial sarcoma], DDIT3 (CHOP) [myxoid liposarcoma], FUS (TLS) [low-grade fibromyxoid sarcoma, myxoid liposarcoma], FOXO1 (FHKR) [alveolar rhabdomyosarcoma], PDGFB (dermatofibrosarcoma protuberans), and ALK (inflammatory myofibroblastic tumor). Rearrangements of the EWSR1 gene are less specific as found in many sarcomas (Ewing sarcoma, desmoplastic round cell tumor, clear cell sarcoma, myxoid liposarcoma, andmyoepithelioma). The search for an amplification of MDM2 gene is a sensitive and specific tool for the diagnosis of atypical lipomatous tumors/welldifferentiated liposarcomas and dedifferentiated liposarcomas (ALT/WDL). The same molecular abnormality can be observed in several tumor types, emphasizing the importance of integrating the results of any molecular study within clinical, morphological, and immunohistochemical context: ASPSCR1 (ASPL)-TFE3 translocation can be observed in alveolar soft tissue sarcoma but also in juvenile renal carcinomas, ETV6 (TEL)-NTRK3 (TRKC) translocation in infantile fibrosarcoma and secretory breast carcinoma, ALK rearrangements in inflammatory myofibroblastic tumors, anaplastic lymphomas, and lung adenocarcinomas. In some cases immunochemistry can highlight the consequence of a molecular abnormality: MDM2 overexpression in ALT/WDL, loss of INI1 expression in rhabdoid tumors and epithelioid sarcoma, and overexpression of ALK in inflammatory myofibroblastic tumors.     

Pharmaco-prévention et nutri-prévention des cancers de la prostate

In 2010, in France, 8,790 men died from prostate cancer despite a low and decreasing mortality rate. The individual risk/benefit ratio of prostate cancer screening is the focus of controversy and currently not in favor of a systematic screening program. Therefore, only prevention could reduce incidence, side effects of treatment and related mortality. Interestingly, prostate cancer prevention is also a field of controversy mainly about 5-alpha-reductase inhibitors. However, it could be expected that pharmaco- or diet-based prevention will be a huge tool for cancer control, even more for prostate cancer burden. This review comprehensively analyses which molecules or compounds could be used in preventive trials. With regard to pharmaco-prevention, three different kinds of drugs could be identified. First drugs, which aim at mainly or even solely reduce prostate cancer risk such as 5-alpha-reductase inhibitors and selective estrogen receptor modulators. Drugs, which aim at wider preventive impact such as: nonsteroidal anti-inflammatory drugs or difluoromethylornithine. Lastly, drugs for which reducing prostate cancer incidence is merely a side effect such as statins, metformin or histones desacetylase inhibitors. With regard to diet-based prevention, two main approaches could be identified: aliments and nutriments, on one hand, and vitamin and minerals, on the other. Interestingly if compounds reach experimental plausibility, natural foods or even global diet seem to have a higher impact. Lastly, besides assessment of efficacy, effectiveness required the critical step of compliance, which might actually be the weakest link of the prevention chain.     

Délinéation des volumes cibles anatomocliniques pour la radiothérapie des cancers du col utérin

Concurrent chemoradiation followed by brachytherapy is currently the standard treatment for locally advanced cervix carcinomas. Modern radiation techniques require planning based on 3D images, and therefore an accurate delineation of target volumes. The clinical target volume (CTV) used for the different phases of treatment are now well defined, but are not always easy to delineate on a CT scan which is currently the standard examination for simulation in radiotherapy. MRI and PET-CT are routinely performed at diagnosis, and can be used to improve the accuracy of the delineation. The objective of this review is to describe the definitions and recommendations of CTV in the treatment of cervical cancer.     

Place de la radiothérapie stéréotaxique dans la prise en charge des tumeurs hépatiques

Stereotactic radiotherapy is a high-precision technique based on the administration of high doses to a limited target volume. This treatment constitutes a therapeutic progress in the management of many tumours, especially hepatic ones. If surgery remains the standard local therapy, stereotactic radiotherapy is first dedicated to inoperable patients or unresectable tumours. Patients with moderately altered general status, preserved liver function and tumour lesions limited in number as in size are eligible to this technique. Results in terms of local control are satisfying, regarding primary tumours (notably hepatocellular carcinomas) as metastases stemming from various origins. If treatment protocols and follow-up modalities are not standardized to this day, iconographic acquisition using four-dimensional computed tomography, target volumes delineation based on morphological and/or metabolic data, and image-guided radiotherapy contribute to an oncologic efficacy and an improved sparing of the functional liver. The purpose of this literature review is to report the results of the main works having assessed stereotactic radiotherapy in the management of primary and secondary liver tumours. Technical particularities of this radiation modality will also be described.     

Place de la radiochirurgie et de la radiothérapie stéréotaxique hypofractionnée dans la prise en charge des métastases cérébrales

Brain metastases management is still controversial even though many trials are trying to define the respective roles of neurosurgery, whole-brain radiotherapy, single-dose stereotactic radiotherapy and fractionated stereotactic radiotherapy. In this article, we review data from trials that examine the role of radiosurgery and fractionated stereotactic radiotherapy in the management of brain metastases.     

Nouveautés dans la prise en charge des carcinomes nasopharyngés

Nasopharyngeal carcinoma is a rare condition, with less than 300 cases occurring per year in France. Its treatment can be difficult due to the importance of side effects, but tumor control is usually excellent following a well conducted chemoradiotherapy. This article summarizes the recent advances in nasopharyngeal cancer diagnosis, classification, treatment, surveillance and management of recurrences. Chemotherapy timing is discussed, along with arguments in favor of induction chemotherapy in locally advanced cases. As a survival advantage has been suggested for when patients are treated in high volume center it seems reasonable to refer these young patients for treatment to tertiary expert centers, especially given the low incidence of the disease.     

Place de la radiothérapie des cholangiocarcinomes intra- et extrahépatiques

Cholangiocarcinomas are digestive tumors whose incidence remains low and have poor prognosis. The benefits of adjuvant radiochemotherapy and radiotherapy have never been demonstrated in any phase III randomized controlled trial. Chemotherapy with capecitabine 6 months is the standard of care in adjuvant setting. Radiochemotherapy is validated in R1 patients. It is not recommended in neoadjuvant situations given the lack of evidence. Chemotherapy and radiochemotherapy are validated in adjuvant or locally advanced diseases. Stereotactic radiation therapy offers an interesting perspective, at the cost of significant digestive toxicities, requiring evaluation in randomized trials.