Évolution des cancers de l’œsophage : impact de la stratégie thérapeutique

PurposeTo assess the outcome of esophageal cancer according to therapeutic strategy.Patients and methodsOne-hundred and twenty patients with esophageal cancer treated by an association of radiotherapy and chemotherapy and possibly surgery, between 2004 and 2010, were retrospectively studied. The first site of relapse was classified as follows: local (tumour), locoregional (tumour and/or nodal: celiac, mediastinal, sus-clavicular) or metastatic.ResultsWith a 15.7-months (1.4–62) median follow-up, there were 89 deaths and 79 recurrences. Three types of treatments were performed: 50 Gy exclusive chemoradiotherapy (47 patients) or 50 to 65 Gy exclusive chemoradiotherapy (44 patients) or chemoradiotherapy followed by surgery (27 patients). The local first relapse was as much frequent as distant relapse (50 patients). With a-5 cm margin up and down to the tumour, there was only one nodal relapse. Two-year survival was 39.5% (95% confidence interval [IC]: 30.5–40.8) and relapse-free survival was 26.5% (CI: 18.6–35). Multivariate analysis revealed that treatment type and disease stage had a significant impact on survival, relapse-free survival and locoregional control. Compared to exclusive chemoradiotherapy, surgery improved locoregional control (40.2 versus 8.7 months, P = 0.0004) but in a younger population. Despite postoperative mortality, the gain was maintained for distance relapse-free survival (40.2 versus 10 months, P = 0.0147) and overall survival (29.3 versus 14.2 months, P = 0.0088). Compared to 50 Gy chemoradiotherapy, local control was improved if high dose chemoradiotherapy was performed (13.8 versus 7.5 months, P = 0.05) but not overall survival (14.0 versus 15.4 months, P = 0.24).ConclusionMore than one-third relapse is local. Locoregional control is better with high dose chemoradiotherapy. In this study, surgery performed in selected patients only, improved locoregional control, relapse-free disease and overall survival.     

Stratégie de prise en charge des métastases osseuses révélatrices

Résumé  Le diagnostic étiologique conditionne en grande partie la prise en charge des métastases osseuses révélatrices. Il suppose une démarche systématique clinique et un nombre limitéd’examens d’imagerie et d’examens biologiques. Si ces explorations sont négatives, il est inutile de poursuivre les investigations. La plupart des localisations osseuses peuvent faire l’objet de prélè vements cytohistologiques radioguidés. L’examen pathologique, avec étude immunohistochimique, voire moléculaire, apporte souvent des informations diagnostiquesdéterminantes et peut aider à lasélection du traitement.      

Impact de l’atteinte du ganglion sentinelle sur la stratégie thérapeutique des cancers du sein

The status of the axillary lymph nodes is the most important prognostic factor in breast cancer. Positive sentinel lymph node may be divided into two categories: metastatic, that is, pN1, and minimal lymph node involvement, that is, pN1mi and pN0i+. Postoperative management of pN1 patients following SNB (sentinel node biopsy) is same as pN1 patients following axillary lymph node dissection, whereas postoperative management of pN1mi and pN0i+ patients is still debated, with a trend to do a complementary axillary lymph node dissection because of the risk of positive-non-SNB. This risk is evaluated approximately 1015% (reclassifying in pN1) and can modify irradiation fields and adjuvant systemic therapy. Recent papers concerning the prognosis of these patients are published since 2008. The size of node metastasis seems to be correlated with 5-year distant free metastasis survival as well as the 10-year overall survival and has been described as a decisive factor for adjuvant systemic therapy. Analysis of lymphatic dissemination remains necessary in the management of breast cancer, and analysis of minimal lymph node involvement gives the surgeons an opportunity to play a role in optimizing the postoperative treatment and the prognosis of our patients.     

Stratégie de la prise en charge médicale dans les stades métastatiques

For a long time, advanced or metastatic renal carcinoma has presented a difficult therapeutic challenge in oncology practice. Only a few years ago, treatment mainly involved immunotherapy, which frequently led to stalemate. In just a few years, new therapies targeting vascular endothelial growth factors and their receptors (VEGF-R): sorafenib, sunitinib and bevacizumab, or the mammalian target of rapamycin (mTOR): temsirolimus and everolimus, have changed these patients’ prognosis and also their quality of life. With these new treatments, median overall survival is more than 26 months, when it was from 10 to 12 months with immunotherapy. Published trial data mean that in 2009 we have decision-making algorithms enabling us to offer patients optimal treatment. However, patients with distinctive characteristics (cerebral metastases, papillary or chromophobe histological subtype, older patients, etc) have rarely been evaluated with respect to the effect of these molecules. A few data are reported, often concerning small samples, in retrospective or not randomised trials. For these situations, tolerance and therapeutic impact of targeted therapies will be studied in future clinical trials.     

Comment traiter un cancer du rectum avec métastases hépatiques synchrones ? Une question de stratégie thérapeutique

The prognosis of patients with rectal cancer and synchronous liver metastasis has improved thanks to chemotherapy and rectal and liver surgery progresses. However, there is no consensus about optimal management and practices remain heterogeneous. A curative treatment may be considered for 20 to 30% of patients with complete resection of metastasis and primary tumor after induction chemotherapy. To this end, a primary optimal evaluation by a multidisciplinary board including hepatic and colorectal surgeons is crucial. The therapeutic strategy associates chemotherapy, radiotherapy, hepatic and rectal surgery. The most threatening site guides the sequence of treatments. If hepatic resectability is uncertain, a “liver first” strategy associating induction chemotherapy and hepatic surgery is preferred. In non-resectable metastatic cases, chemotherapies with targeted therapies might lead to secondary resection for 30% of patients (conversion). This has changed our practice and triggers reconsidering resectability after chemotherapy. When metastases remain non-resectable, additional treatment focusing on primary tumor should control pelvic symptoms otherwise hardly impacting quality of life. Rectal surgery, short-course radiotherapy (5 × 5 Gy), conformational long-course chemoradiotherapy or intensity-modulated radiation therapy with dose escalation are options discussed in this review.     

Bilan préthérapeutique des cancers de la jonction oesogastrique

Pretreatment assessment in patients with cancer of the gastroesophageal junction involves the evaluation of physiological status and tumor stage. Nutritional status is a prognostic and predictor factor of response to treatment; assessment involves the calculation of weight loss and the determination of serum albumin. Renal, cardiac, and pulmonary functions are evaluated (urea, creatinine, calculation of clearance, liver function tests, electrocardiogram, pulmonary function). The performance status (Karnofsky or WHO) is an important prognostic factor. The assessment of tumor stage involves the digestive endoscopy and endoscopic ultrasonography, CT thoraco-abdomino-pelvic injection, and PET-FDG. Laparoscopy is performed only when peritoneal involvement is suspected.     

La radiothérapie des cancers du rectum : stratégie thérapeutique et perspective

Standard treatment consisting of chemoradiotherapy followed by radical surgery with total mesorectal excision, resulting in good oncologic local control but high morbidity and poor functional results. The same treatment applied to all patients presenting with low or mid T3–4 rectal tumors could result in overtreatment of small tumors. However, it remains insufficient (or unsatisfactory?) for locally advanced tumors regarding metastatic recurrence rate. Treatment is decided by a multidisciplinary board on the basis of initial staging, including MRI which allows for resection margin prediction and post-treatment response evaluation. The therapeutic strategy is changing towards upfront chemotherapy and therapeutic desescalation omitting radiotherapy or surgery in a rectal preservation strategy. Moreover, tumor response leads to new multidisciplinary board discussion and treatment adaptation.     

Actualisation de la stratégie thérapeutique locorégionale dans les sarcomes des tissus mous et les tumeurs desmoïdes des membres

The treatment of soft tissue sarcomas of limbs should be discussed within an experienced multimodality team. Surgical resection remains the cornerstone of therapy for localized disease and achieves a five years overall survival around 75% and a local recurrence rate as low as 10% in the best series. In complex cases, neo-adjuvant treatments may be used such as systemic chemotherapy, isolated limb perfusion, or radiotherapy to achieve an optimal conservative approach. Molecular genetics of sarcomas and quality of margins are essential to guide diagnosis and therapeutic selection. In case of marginal or incomplete resection, a new enlarged surgical resection should always be discussed before administration of any adjuvant treatments. Many retrospective studies and two randomized studies (one of adjuvant brachytherapy and one of external beam radiotherapy) have shown that adjuvant radiotherapy after complete surgery significantly reduces the risk of local recurrence in extremity soft tissue sarcomas. A randomized study has compared pre- to postoperative radiotherapy. The results in terms of local control are similar in both arms. The risk of surgical complications is higher in the preoperative arm and the risk of late sequelae is higher in the postoperative arm. A randomized study within the French sarcoma group is ongoing evaluating the omission of postoperative radiotherapy in favourable cases. Presently, the role of systematic first-line invasive treatment (including surgery and/or radiotherapy) of desmoids is debated. It is becoming evident that up to 50% of patients with desmoids benefit from a front-line non-aggressive policy, because growth arrest is a common feature of this disease. Additional study of the molecular determinants of desmoid behaviour is needed to guide treatment.     

Place de la radiothérapie dans la prise en charge des lymphomes malins non hodgkiniens

The purpose of this review was to summarize recent data about lastest retrospective and prospective studies dealing with radiotherapy of non-Hodgkin lymphoma, in order to precise the schedule and the role of this treatment. A systematic review was done by searching studies on the website http://www.pubmed.gov (Medline) using the following keywords: radiotherapy, radiation therapy, non-Hodgkin lymphoma. The management of non-Hodgkin lymphoma varies a lot according to the histological type and stage. The dose of radiotherapy has been studied in only one randomized trial, which concluded that there was no difference between the low dose and the high dose arms. Radiotherapy is a very good option in follicular, cutaneous, digestive or orbital non-Hodgkin lymphoma. A recent post hoc analysis of randomized trials on radiotherapy for high-grade non-Hodgkin lymphoma strongly suggested a benefit of additional radiotherapy after chemotherapy in some situations. Radiotherapy of low-grade non-Hodgkin lymphoma is a very good option, while its use on high-grade non-Hodgkin lymphoma is sometimes recommended but further randomized trials are ongoing to better understand its role.     

Stratégie globale de prise en charge des métastases cérébrales : une approche multidisciplinaire

Brain metastases management has evolved over the last fifteen years and may use varying strategies, including more or less aggressive treatments, sometimes combined, leading to an improvement in patient's survival and quality of life. The therapeutic decision is subject to a multidisciplinary analysis, taking into account established prognostic factors including patient's general condition, extracerebral disease status and clinical and radiological presentation of lesions. In this article, we propose a management strategy based on the state of current knowledge and available therapeutic resources.     

éducation thérapeutique et cancer du sein

Therapeutic education in oncology is a recent phenomenon, and one which is likely to become more advertised and talked about in the months to come. We already understand the term well; however, all too often it is mixed in and combined with personal information. It was important for us to carefully go over the history of therapeutic education, the concept and its principles in relation to clearly identified chronic diseases, such as asthma, diabetes and renal failure. We also wanted to emphasise the different recommendations given by the French National Authority for Health (HAS) and the Hospital, Patient, Health and Territory Act promoting this concept in the in the field of oncology, and highlight that it is very beneficial and that it has already been introduced by oncology teams. All that is required is to structure and formalise the teaching and ongoing support of self-care or adjustment skills by the cancer patient, with the help of teams trained in ETP (therapeutic education). We have chosen to illustrate this concept through adjuvant breast cancer therapy (in the non-metastatic phase, because in this case the notion of chronic illness is obvious), as continuing with a physical activity or weight control become independent prognostic factors, which are just as important as the initial clinical or histological prognostic features.     

CXCR4 : nouvelle cible thérapeutique de la cellule leucémique ?

CXCR4, receptor of the chemokine SDF-1 (stromal cell-derived factor 1) plays a major role in the normal hematopoiesis but also in the biology of the leukaemic cell. This receptor is expressed on the surface of blasts and is a key molecule in “the anchoring” of the leukaemic stem cell (LSC) within the bone marrow niche. The interactions of the LSC with the bone marrow microenvironment promote survival signals and drug resistance. Recent flow cytometry analyses reported that CXCR4 expression levels have a major prognostic impact in acute myeloid leukaemia (AML). CXCR4 expression is associated with poor prognosis and can be useful to stratify patients, according to their phenotype, in order to establish risk-adapted strategies. Newly diagnosed AML are now routinely stratified according to molecular markers which guide prognosis and treatment. Many leukaemia are composed of multiples subclones with differential susceptibility to treatment and specific targeted therapies are missing. Despite therapeutic improvements for the treatment of AML, long term survival remains poor. Targeting CXCR4 is a novel promising approach of therapy. CXCR4 antagonists are used in combination with chemotherapy in preclinical and clinical studies. This review summarises our current knowledge regarding the key role of CXCR4 in AML and discusses how targeting this pathway could provide an interesting approach to eradicate the LSC.