Showing papers in "Bulletin Du Cancer in 2012"

SALTO: a randomized, multicenter study assessing octreotide LAR in inoperable bowel obstruction

Abstract: This phase II, multicenter, randomized, double-blind, non-comparative study assessed the efficacy and safety of immediate-release octreotide and octreotide LAR, in combination with corticosteroids and standard medical care, on the symptoms of inoperable malignant bowel obstruction (MBO) due to peritoneal carcinomatosis. The primary efficacy endpoint was “success” at day 14 defined as a composite endpoint including the absence of a nasogastric tube, and vomiting less than twice per day and no use of anticholinergic agents. Patients in the octreotide arm received octreotide LAR 30 mg intramuscular (im) on days 1, 29 and 57, as well as daily immediate-release octreotide 600 μg per day plus methylprednisolone on days 1 to 6. Placebo-treated patients received methylprednisolone and matched placebo instead of octreotide. Difficulties associated with enrolling patients at palliative-care stage meant only 64 patients (instead of the planned 102 patients) were randomized, 32 to octreotide and 32 to placebo. Despite randomization, more patients in the octreotide arm (46.4%) than in the placebo arm (21.9%) had a baseline Karnofsky score less than 50. An intention-to-treat analysis showed that in the octreotide and placebo arms, 12 (38%) and nine (28%), respectively, patients were successfully treated at day 14, which increased to 9/15 (60%) and 7/25 (28%), respectively, among patients with a baseline Karnofsky score greater or equal to 50. Octreotide-treated patients reported three drug-related adverse events (AEs), and no drug-related serious AEs or deaths. Octreotide LAR may have a key role in treating patients with a MBO due to peritoneal carcinomatosis, particularly in those with moderately severe disease.

Analyse coût-efficacité d’un test prédictif de la chimiothérapie dans le cancer du sein (Oncotype DX®) en France

Abstract: Resume Contexte. Dans le cancer du sein, la chimiotherapie adjuvante est souvent prescrite par precaution et donc parfois inutilement. Un test diagnostique du risque de recidive a dix ans chez les femmes avec un cancer du sein de stade precoce a ete developpe : Oncotype DX ® . Methode. Un modele de Markov a ete adapte afin d’evaluer les effets a long terme de ce test en termes de couts et d’annees de vie gagnees en France chez les patientes ayant un cancer du sein de stade precoce ER+, HER2- sans envahissement ganglionnaire. L’impact d’Oncotype DX ® sur les decisions de prescription de chimiotherapie a ete evalue par une meta-analyse d’etudes internationales. Les donnees de couts et epidemiologiques sont specifiques a la France. Resultats. Le test est associe a une diminution des couts par patiente de 570 € (1 600 € incluant la perte de productivite) et a un gain de 0,15 annees de vie par patiente, soit 0,14 quality-adjusted life-years (QALY). Conclusions. L’utilisation du test semble etre pertinente en pratique francaise. Ce test represente une opportunite d’optimisation du traitement en evitant des chimiotherapies inutiles et en prescrivant une chimiotherapie a des femmes qui ne l’auraient pas recue selon les criteres usuels.

Canaux cationiques TRP dans le cancer du sein : expression, rôle et corrélation avec des paramètres cliniques

Abstract: Breast cancer (BC) has the highest incidence rate in women in industrialized countries. Statistically, it is estimated that one out of 10 women will develop BC during her life. Evidence is accumulating for the role of ion channels in the development of cancer. Most studied ion channels in BC are K(+) channels, which are involved in cell proliferation, cell cycle progression and cell migration, and Na(+) channels, which correlate with invasiveness. Emerging studies demonstrated the role of Ca(2+) signaling in cancer cell proliferation, survival and migration. Recent findings demonstrated that the expression and/or activity of the transient receptor potential (TRP) channels are altered in several cancers. Among the TRP families, TRPC (canonical or classical), TRPM (melastatin) and TRPV (vanilloid) are related to malignant growth and cancer progression. Although these channels are frequently and abundantly expressed in many tumors, their specific expression, activity and roles in BC are still poorly understood. The expression of TRP channels has also been proposed as a tool for diagnosis, prognosis and/or therapeutic issues of several diseases. In cancer, TRPV6 and TRPM8 have been proposed as tumor progression markers of prostate cancer outcome and TRPC6 as a novel therapeutic target for esophageal carcinoma. Interestingly high levels of TRPC3 expression correlate with a favorable prognosis in patients with lung adenocarcinoma. Our team has recently reported the expression and role of TRPC1, TRPC6, TRPM7, TRPM8 and TRPV6 in BC cell lines and primary cultures. We have also investigated TRP expression and their clinical significance in human breast adenocarcinoma and we suggest that TRP channels are new potential BC markers. Indeed TRPC1 and TRPM8 may be considered as good prognosis markers of well-differentiated tumors, TRPM7 as a proliferative marker of poorly differentiated tumors and TRPV6 as a prognosis marker of aggressive cancers. In this review, we summarize the data reported to date regarding the changes in TRP expression associated with BC. We also discuss the importance of TRP channels in BC cells proliferation and migration and their interest as new BC markers.

Rôle de la voie PI3K-AKT-mTOR dans le cancer et les thérapeutiques antitumorales

Abstract: PI3K/AKT/mTOR pathway is an intracellular signalling pathway composed of different kinases. Many protein mutations are described in that pathway, and are responsible of dysregulation of cell growth, proliferation, survival and angiogenesis. Rapamycin is an antibiotic inhibiting mTOR. Different analogs of rapamycin are developed or being developed in antitumoral therapy, in which temsirolimus, everolimus and deforolimus, demonstrated antitumoral activity in renal cancer and mantle cell lymphoma, and many clinical trials are in progress in other tumors. In the future, predictive factors of response need to be identified; patient selection and associations with chemotherapy or with other targeted therapies should be explored.

Anatomopathologie des cancers de l’endomètre

Abstract: Endometrioid carcinoma is the third most frequent cancer among women in France. They are divided in two groups: type I and type II. This article describes anatomopathological and molecular features of this disease. Type I carcinoma, the most frequent, develops in a context of hyperoestrogenia. Endometrial glandular hyperplasia is the precursor lesion. The histological type is an endometrioid carcinoma. Its prognosis is good. Type II carcinoma is less frequent. It occurs on an atrophic mucosa. It is usually a more aggressive tumor like serous adenocarcinoma, clear cells carcinoma or carcinosarcoma with a poor prognosis. Type I and type II carcinoma also present different molecular pathways. PTEN inactivation, an early event in carcinogenesis, is the most frequent abnormality in type I carcinoma. An average of 28% of type I carcinoma also acquire PI3K mutations. On the contrary, P53 mutation is involved in 90% of type II carcinoma. Identifying and understanding these two types of endometrial carcinoma led to various therapeutic management.

Reconstruction with pasteurized autograft for primary malignant bone tumor of distal tibia

Abstract: Objective The aim of this study was to assess the specific protocol for the treatment of primary malignant bone tumors of distal tibiae in a group of patients for limb salvage, with wide “en bloc” intra-articular excision and reconstruction of the defect with recycled pasteurized autograft, which was stabilized using an internal fixator. Methods Between 1994 and 2009, ten patients (three females and seven males) at a mean age of 26.5 years old were treated for malignant bone tumors of the distal tibiae with “en bloc” intra-articular excision and ankle arthrodesis using recycled pasteurized autograft. Nine cases were histopathologically diagnosed as high-grade osteosarcoma, and one case as invasive osteoblastoma. All bone tumors were staged according to Enneking's criteria with two stages IIA cases, and eight stages IIB cases. Results At a mean follow-up of 81 months, the mean postoperative functional score was 74.3%. All the patients had bony union at the last follow-up. Six patients required secondary iliac crest cancellous bone grafting at the proximal end to achieve union. The mean time for graft union was 18.9 months, and the average union time of the proximal junctions was longer than that of the distal junctions. Superficial infection occurred in two patients (20.0%), which were resolved by changing dress. There was no deep infection or graft fracture during the entire procedure. Conclusions The use of pasteurized bone graft for primary malignant bone tumors of distal tibia indicated a satisfactory outcome, with regard to graft survival, complications, and functional results. A pasteurized auto-graft can be an easily accessible and economical alternative of high efficiency for the usual reconstruction modalities.

Routine administration of a single dose of cisplatin ≥ 75 mg/m2 after short hydration in an outpatient lung-cancer clinic.

Abstract: Background Cisplatin is a pivotal drug in combined chemotherapy for non-small cell and small-cell lung cancers (NSCLC or SCLC), but its renal toxicity limits its use. Current guidelines recommend 24 h hydration: thus hospitalization is required. The aim of this retrospective study was to confirm the safety of short hydration before giving an intermediate-to-high dose of cisplatin in an outpatient clinic. Patients and methods Patients eligible had NSCLC or SCLC and were being treated with a chemotherapy regimen that included cisplatin ≥ 75 mg/m 2 . They were given the same short hydration protocol for 1 day. Nephrotoxicity was defined as ≥ grade 1 according to NCIC common toxicity criteria. Predictive factors for nephrotoxicity were analyzed. Results Three hundred and fifty-seven consecutive patients (median age 58 years, range: 25-81) were reviewed. Twenty-one patients (6%) had ≥ grade 1 nephrotoxicity and all except one had grade 1 toxicity according to NCIC criteria for common toxicity (SC P = 0.002), initial serum creatinine ≥ 100 μmol/L (OR = 8.3 CI 95% [2.55-27.4] P = 0.0005), and dose cycle of cisplatin ≥ 100 mg/m 2 (OR = 10.8 CI 95% [3.6-32.5] P Conclusion Rapid outpatient administration of a single dose of cisplatin at ≥ 75 mg/m 2 is feasible without a high risk of nephrotoxicity.

Non-HIV Kaposi's sarcoma: a review and therapeutic perspectives

Abstract: "Classic" Kaposi's sarcoma (CKS) not related to HIV is a multifocal angioproliferative neoplasm that is linked to human herpesvirus. CKS is a cutaneous cancer frequently occurring with an indolent course. However, it can compromise the quality of life by causing pain, disfigurement and functional disability. For this reason, the main treatment goals are not only to reduce the cutaneous lesions but also to alleviate organ involvement and psychological stress by delaying disease progression and ultimately cure. This report summarizes systemic treatment options of CKS, including chemotherapy, immunotherapy and anti-HHV8 therapy. In addition, this review will focus on the recent understanding of carcinogenesis and consequently highlight potential "targeted" therapeutic interventions.

Multidisciplinarity and medical decision, impact for patients with cancer: sociological assessment of two tumour committees' organization.

Abstract: Purpose Medical practices in oncology are expected to be multidisciplinary, yet few articles studied how this may be concretely applied. In the present study, we evaluated the organization of two multidisciplinary committees, one for breast cancer and one for sarcoma, in a French Comprehensive Cancer Centre. Methods Both tumours were specifically chosen so as to emphasise substantial differences in relation with incidence, histological subtypes, management strategy, and scientific evidence. Between 2003 and 2004, 404 decision processes were observed, 210 for sarcoma (26 meetings) and 194 for breast cancer (10 meetings). The number of physicians who took part in the discussions and their medical specialties were systematically noted as well as the number of contradictory discussions, medical specialties represented in these contradictory discussions and the topics of contradiction. The last measured data was whether the final committee's decision was in conformity with the referent preferences or not. All these measures were related to the referent's medical speciality and working place, to the stage of the disease and to the disease management stage. Results Committees’ specificities concerned their organization, referent's medical specialties, the number of participants in discussions and their medical specialties. Discussions in the sarcoma committee tended to be more multidisciplinary, involving more specialties. Initial strategy proposal for one patient was modified during the discussions for 86 patients out of 210 (41%) and for 62 out of 194 (32%) respectively for sarcoma and breast cancer. However, there was no significant difference in the rate of contradictory discussions between breast cancer and sarcoma committees (32% versus 41% respectively; P = 0.08). The rates of contradictory discussions were similar for localized cancers, local relapse and metastasis disease (37%, 41% and 34% respectively; P = 0.86). Conclusions The present study reports more than 30% of changes concerning strategy for patient with cancer due to multidisciplinary discussions. This indicates that, providing tumour committees are adapted to the pathologies’ characteristics, they can promote a collective and multidisciplinary approach to oncology.

Facteurs de radiorésistance des cellules souches cancéreuses et perspectives de radiosensibilisation : l’exemple du glioblastome

Abstract: Les cellules souches cancereuses sont l'objet d'un interet croissant En particulier, plusieurs donnees suggerent leur implication dans les mecanismes de radioresistance tumorale, pouvant ainsi expliquer les echappements therapeutiques apres radiotherapie De par son pronostic pejoratif et son taux eleve de rechutes apres irradiation, le glioblastome constitue un modele tres souvent etudie dans la recherche de nouveaux radiosensiblisants Il existe plusieurs donnees precliniques suggerant que les cellules souches cancereuses pourraient constituer une cible therapeutique potentielle dans la perspective d'ameliorer l'efficacite biologique de l'irradiation A travers l'exemple du glioblastome, nous effectuons une revue des principales voies de signalisation intervenant dans les mecanismes de radioresistance des cellules souches cancereuses et pour lesquelles un ciblage pharmacologique laisse entrevoir des perspectives de radiosensibilisation

NM23, un exemple de gène suppresseur de métastase

Abstract: Metastasis suppressor genes - unlike tumor suppressor genes - are defined by their capacity to control metastatic dissemination in vivo without affecting growth of the primary tumor. The first of these metastasis suppressor genes, NM23, was identified in 1988. Since then, expression of NM23 has been studied widely in human tumor cohorts, often with contradictory results. Not only is NM23 overexpressed in most human solid tumors when compared to healthy tissues, but also low expression of NM23 correlates with metastasis and poor clinical prognosis in the advanced stages of a number of epithelial cancer types, including melanoma, breast, colon, and liver carcinoma. This does not hold true, however, for other cancer types such as neuroblastoma and hematological malignancies, in which high NM23 expression correlates with more aggressive disease. Genetic alterations in the NM23 gene - loss of heterozygosity, spontaneous mutations and polymorphisms - are rarely found in tumors; thus, the metastatic potential of tumor cells is probably affected by NM23 protein levels. Three lines of evidence demonstrate the anti-metastatic activity of NM23: first, overexpression of NM23 in metastatic cell lines reduces their metastatic potential in xenograft models; second, the incidence of lung metastases is elevated in NM23 knockout mice prone to develop hepatocellular carcinoma, and, third, silencing NM23 by RNA interference confers a "metastatic phenotype" on non-invasive human epithelial liver and colon cancer cell lines. It appears that NM23 is crucial for inhibiting invasive migration, so acting at early stages of metastatic dissemination. The mechanistic basis of the metastasis suppressor function of NM23 and its regulated expression still remains obscure, however. Reactivation of expression of the endogenous NM23 gene in tumor cells, or stimulation of the pathways it controls, constitutes a promising avenue for anti-metastatic therapy.

Cabazitaxel dans le cancer de la prostate métastatique résistant à la castration ayant progressé pendant ou après traitement par docétaxel : l’expérience française de l’essai TROPIC

Abstract: Resume En 2010, les resultats de l'etude TROPIC ont montre que le cabazitaxel, compare a la mitoxantrone, ameliore la survie globale mediane des patients atteints d'un cancer de la prostate metastatique resistant a la castration ayant progresse apres traitement par docetaxel. Nous rapportons ici les donnees d'efficacite et de tolerance observees dans le sous-groupe de patients inclus dans les centres francais. Dans cet essai de phase III randomise international, les patients recevaient de la prednisone associee soit au cabazitaxel 25 mg/m2, soit a la mitoxantrone 12 mg/m2, toutes les trois semaines. L'objectif principal etait la survie globale mediane. Les objectifs secondaires etaient la survie sans progression et la tolerance. Les analyses ont ete realisees en intention de traiter. Chez les 90 patients inclus en France, la survie globale etait de 18 mois avec le cabazitaxel contre 14,3 mois avec la mitoxantrone. La survie sans progression passait de 1,4 a 2,5 mois avec le cabazitaxel. Les toxicites observees etaient essentiellement hematologiques avec des neutropenies de grade 3 ou plus, le plus souvent non febriles, et digestives avec 4 % de diarrhees de grade 3 ou plus. Ces resultats sont comparables a ceux rapportes pour l'effectif total et le profil de tolerance global reste favorable sans aucun deces toxique dans le bras cabazitaxel.

Impact des complications tardives de la radiothérapie, de la dépression et de l’anxiété sur la qualité de vie à long terme dans le cancer du sein

Abstract: Resume Introduction Ce travail avait pour but d’evaluer l’impact des sequelles tardives de la radiotherapie, du type de traitement radiochimiotherapeutique (concomitant ou sequentiel), de la depression et de l’anxiete sur la qualite de vie (QV) globale, physique et emotionnelle des survivantes a long terme d’un cancer du sein. Patientes et methodes Nous avons evalue, chez 117 patientes (duree moyenne de suivi = 8,1 ans), la toxicite tardive de la radiotherapie (echelle LENT-SOMA), l’evaluation du resultat esthetique (par le medecin et la patiente), la QV (EORTC QLQ-C30) et la depression et l’anxiete (echelle HAD). Resultats En analyse univariee, plusieurs facteurs etaient associes a une alteration significative de QV: radiochimiotherapie sequentielle et moindre QV globale ( p = 0,002) et emotionnelle( p = 0,02); trouble depressif ou anxieux et moindre QV globale, physique et emotionnelle ( p ≤ 0,005); certaines complications tardives de la radiotherapie (douleurs et moindre QV physique, p = 0,01; fibrose et moindre QV emotionnelle, p = 0,04). En analyse multivariee, l’existence d’un trouble anxieux ou depressif etaient les predicteurs les plus forts d’alteration des trois dimensions de QV ( p ≤ 0,02). Conclusion Un meilleur depistage de la depression et de l’anxiete pourrait permettre une amelioration de la QV chez les patientes survivantes a long terme d’un cancer du sein.

Qualité de vie des femmes jeunes ayant un cancer du sein localisé et de leur partenaire : nécessité de développement de questionnaires spécifiques pour la patiente et le partenaire

Abstract: Purpose. To determine the feelings of young women with early breast cancer concomitantly with their partners at different treatment periods in order to create a specific quality of life (QOL) scale for this population. Materiel and methods. It was a prospective, multicentre, qualitative study, in patients younger than 45 years old at diagnosis and living with a partner for at least six months. Patients and partners were interviewed by a psychologist, from the diagnosis disclosure until follow up, using non-directing individual talks. Results. Sixty-nine couples were interviewed. Analyses of the interviews have highlighted the impact of disease on eight dimensions: psychological, physical, family, social, couple, sexuality, domestic, professional and economic dimensions. These impacts are mostly negative and are present in all periods and even after treatment for follow up. Discussion. A multidimensional profile of this specific population was established. A QOL scale dedicated to this population is being validated.

HLA class II susceptibility to cervical cancer among Tunisian women.

Abstract: The variability in host immunogenetic background, especially in human major histocompatibilty genes, has been shown to influence the susceptibility to human papillomavirus (HPV) infection and cervical neoplasia. Here, we conducted a case-control study in Tunisian women to examine the effect of genetic variation in HLA class II DRB1 and DQB1 genes on invasive cervical cancer (ICC) and squamous cell carcinoma (SCC). HLA genotyping was performed by PCR sequence-specific primers technique. The data revealed significant positive and negative associations, suggesting either predisposing or protective effects of these genes in the disease outcome. DRB1*15, alone or linked to DQB1*06, was associated with a 2.7- and 3.5-fold increase in risk for ICC, respectively. DRB1*13-DQB1*03 showed a similar 3.5 risk effect. Concerning SCC, we observed a relatively higher, about 1.2 times more, risk effect for these genetic markers. In contrast, only one haplotype – DRB1*13-DQB1*06 – provides evidence for a weak protection (about 0.3-fold reduction) of ICC and SCC. In conclusion, we suggest that HLA class II polymorphisms are involved in the genetic susceptibility to cervical cancer in Tunisian women.

Activité physique et survie après cancer

Abstract: Physical activity has been shown in large cohort studies to positively impact survival in cancer survivors. Existing randomized controlled trials showed a beneficial effect of physical activity on physical fitness, quality of life, anxiety and self-esteem; however, the small sample size, the short follow-up and the lack of standardization of physical activity intervention across studies impaired definite conclusion in terms of survival. Physical activity reduces adiposity and circulating estrogen levels and increases insulin sensitivity among other effects. A workshop was conducted at the International Agency for Research on Cancer in April 2011 to discuss the role of physical activity on cancer survival and the methodology to develop multicentre randomized intervention trials, including the type of physical activity to implement and its association with nutritional recommendations. The authors discuss the beneficial effect of physical activity on cancer survival with a main focus on breast cancer and report the conclusions from this workshop.

Consommation du dosage de l’antigène spécifique de la prostate (PSA) en France chez les hommes sans cancer de la prostate déclaré (2008-2010)

Abstract: Resume Cette etude a evalue la pratique du dosage de l’antigene specifique de la prostate (PSA) en France entre 2008 et 2010 chez les hommes de 40 ans et plus assures par le regime general, soit 10,9 millions de personnes, une fois exclus ceux qui avaient un cancer de la prostate declare. En 2010, 30,7 % des hommes de 40 ans et plus ont eu au moins un test de PSA, soit 12,3 % pour ceux de 40 a 54 ans, 47,7 % pour ceux de 55 a 74 ans et 47,6 % pour ceux de 75 ans et plus, avec une forte variabilite geographique. Les pourcentages d’hommes qui avaient eu au moins un dosage durant les trois ans etaient respectivement de 26,2 %, 77,3 % et 75,6 % pour les memes tranches d’âge. Parmi ces hommes de 40 ans et plus, 13 % ont eu plus de trois dosages du PSA en trois ans et specifiquement 21 % des 75 ans et plus. Pour les dosages de PSA realises en 2010, 88 % etaient prescrits par un generaliste liberal et 3,2 % par un urologue. A l’encontre des recommandations publiees concernant le dosage du PSA, les resultats observes demontrent l’existence d’un depistage de masse non organise du cancer de prostate, en particulier chez les hommes de 75 ans et plus.

Do anti-angiogenic therapies prevent brain metastases in advanced renal cell carcinoma?

Abstract: Background We analyzed renal cell carcinoma (RCC) brain metastasis (BM) risk factors and compared BM occurrence in metastatic RCC (mRCC) treated with or without anti-angiogenic agents (AA). Methods Data from all consecutive metastatic RCC patients (patients) treated in a french cancer center between 1995 and 2008 were reviewed. Patients had histologically confirmed advanced RCC without synchronous BM at the time of metastasis diagnosis. AA were sorafenib, sunitinib and bevacizumab. We also included patients treated with mTor inhibitors, temsirolimus and everolimus, as they also demonstrated anti-angiogenic activities. Characteristics of the two groups treated with or without AA were compared with a Fisher exact test. Impact of AA on overall survival (OS) and cumulative rate of brain metastasis (CRBM) was explored by Kaplan-Meier method. Results One hundred and ninety-nine patients with advanced RCC were identified, 51 treated with AA and 148 without AA. The median follow-up duration was 40 months. BM occurred in 35 patients. Characteristics between AA treated and non-AA treated groups were unbalanced and favoring better prognostic factors in AA treated group. Median OS was 24 months. AA treatment was not associated with a lower CRBM (HR=0.58 [0.26-1.30], P =0.187). Median survival free of BM was 11.8 months, CI95% (4.95-18.65) in the group without AA treatment and 28.9 months in the AA group, CI95% (18.64-39.16). Alkaline phosphatase (AP) was an independent prognostic factor for BM ( P =0.05). In multivariate Cox model, after adjustment to AP, AA did not improve the CRBM (aHR=0.53 [0.22-1.32]). Conclusion In this retrospective study, AA did not decrease significantly the CRBM. Elevated AP was a predictive factor for BM in mRCC.

Le parcours personnalisé de soins en oncosexologie : une nouvelle offre de soins au service des soignés et des soignants

Abstract: The sexual problematic linked to both cancers and their treatments remains underestimated by health carers especially since patients dare not speak about it. The oncosexology is a new offer of health care responding to an epidemiological reality, a strong demand, a care quality process and a societal demand of ethical, technical and humanist medicine. It aims at conciliating the oncological and quality of life objectives because sexual health belongs to oncological care and quality of life belongs to well-being for a majority of people/couple. By comparison to the pain situation of 20 years ago, a proactive politics is necessary to change the individual level to a collective one by modifying the attitudes of patients and… health carers, that is, by breaking the silence, by legitimating the demand and by allowing all the actors to be open about it. The optimal strategy for actualizing the "software" of physicians, who are the main factor of resistance, consists in simplifying and professionalizing the oncosexology by responding to the needs for information and offer visibility for all, and training for the most sensitized or involved carers. The term oncosexology should not shock. This new competence in supportive care corrects a real inequality of access to health care and fits in with a medical humanism by promoting a more personalized approach as much initially as in follow-up: a) to inform about sexual risks and sequels is an ethical and legal duty, b) the therapeutic strategy may be influenced by the iatrogenic sexual risk, which is frequently treatment-dependant, c) the impact and demand evolve throughout the health care process, d) multidisciplinary solutions exist according to the demand and its simple or complex nature, e) the impact is often positive for the patient/couple.

Place du médecin généraliste dans le traitement du cancer en Champagne-Ardenne

Abstract: Resume Introduction La loi HPST et le Plan cancer 2 insistent sur le role pivot du medecin generaliste (MG) dans la prise en charge (PEC) du patient atteint de cancer. Methode Une enquete d’opinion a ete menee en Champagne-Ardenne afin d’evaluer la satisfaction et les besoins de 1231MG dans la PEC des patients. Un questionnaire leur a ete envoye par la poste en mars et en avril 2011. Les donnees ont ete analysees avec le logiciel Sphinx. Resultats Le taux de participation etait de 33% ( n = 405/1231). Les participants etaient majoritairement des hommes ( n = 296; 73%), Âges en moyenne de 51,8ans (e.-t.: 9ans). Ils etaient majoritairement satisfaits ( n = 343; 85%) de la communication avec les cancerologues, du delai de reception du compte rendu de la reunion de concertation pluridisciplinaire ( n = 353; 88%) et du programme personnalise de soins ( n = 319; 81%). Mais, 69% ( n = 269) estimaient que leur communication avec les cancerologues restait a ameliorer. Enfin, deux tiers consideraient leur niveau de formation en cancerologie comme non satisfaisant ( n = 243; 64%). Conclusion Cette etude met en evidence des pistes d’amelioration pour renforcer la place du MG dans la PEC du patient atteint de cancer.

Sevrage tabagique, mise au point sur la prise en charge actuelle et ses résultats

Abstract: Tobacco prevention is the most effective prevention of cancer. Daily smoking promotes tumor progression, increases the risk of second cancer and decreases survival. The diagnosis of smoking and support for cessation and preventing recurrence is an integral part of cancer treatment. Smoking increases side effects of chemotherapy and surgery and reduces the effectiveness of radiotherapy and chemotherapy. Smokers with cancer do not smoke by life-style choice but because they are highly addicted and are suffering from a chronic relapsing disease: tobacco dependence, which justifies intensive medical management. The oncologist himself may perform this support or coordinate with other physicians in charge of the patient or with a tobacco cessation clinic, but patients are often unable to stop alone, as evidenced by the continued to use tobacco despite a cancer diagnosis. Treatment will always include a therapeutic education, compartmental behavioral therapy and medication. The patches and oral nicotine replacement or varenicline are the two most effective treatments that can be prescribed to smokers suffering of cancer, without including those with any motivation to quit. Smoking reducing occurred in a few days or weeks on treatment will allow them to reconsider the judgment. The full stop is always the goal for the doctor, even if it is not the patient initial goal. After stopping, the patient is not cured but still a patient with tobacco dependence who does not smoke. The risk of relapse in the year being 50%. The cancer patient management will use every visit to the point tobacco dependence and prevent relapse, alone or with assistance of a specialist. There is a lack of data on smoking cessation in cancer patients, but no item calls for a three-month quit rate of 50% as observed in the general population after an optimal management of tobacco cessation.

Biologie moléculaire des cancers épithéliaux de l’ovaire

Abstract: Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.

Tolérance et efficacité du bévacizumab en association aux taxanes en première ligne dans le cancer du sein métastatique : étude ATHENA-France

Abstract: The efficacy of the combination bevacizumab-chemotherapy in the first-line treatment of metastatic breast cancer (mBC) was demonstrated in several randomized clinical trials. However, limited safety data is available in daily medical practice. ATHENA is an international phase-IIIb study conducted in 2,251 patients with locally advanced or mBC, treated in first-line with bevacizumab combined with taxanes-based chemotherapy. The primary objective is safety assessment. In France, 365 patients were included. Their median age was 56 years (24-93 years) and ECOG performance status was 0 or 1 in 93.9% of patients. Bevacizumab was essentially combined with a taxanes monotherapy: docetaxel (37.3%) or paclitaxel (28.8%) or taxanes-based combination therapy (9.4%). The most frequent grade superior or equal to 3 adverse event (AE) was neutropenia (34.5%). Grade superior or equal to 3 AEs of special interest related to bevacizumab were arterial and venous thromboembolism (5.1%), high blood pressure (4.2%), proteinuria (2.3%) and hemorrhage (2%). Median time to progression was 9.5 months (95% CI: 8.8-10.4). The safety profile and the efficacy of the combination bevacizumab-taxanes in a population more representative of daily oncology practice in France are comparable to those reported in clinical trials in mBC.

Carcinomes sarcomatoïdes pulmonaires

Abstract: Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about 1 % of non-small cell lung carcinoma (NSCLC). In 2004, World Health Organization classification united under this name all the carcinomas with sarcomatous or sarcomatous-like component with spindle cell or giant cell appearance. There are five subtypes: spindle cell carcinoma, giant cell carcinoma, pleomorphic carcinoma, carcino-sarcoma and pulmonary blastoma. Clinical characteristics are not specific from the others subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastasis are frequent with atypical locations such as peritoneal or retroperitoneal sites. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here, we present a review of litterature in order to better describe these tumors.

Alerte sanitaire et implants mammaires PIP : expérience du centre régional de lutte contre le cancer de Lille

Abstract: Resume Introduction Le 30 mars 2010, l’Afssaps a publie une alerte sanitaire concernant les implants mammaires de la marque PIP, apres avoir identifie un taux de rupture plus important que pour d’autres fabricants. Cette alerte demandait le rappel de toutes les patientes concernees, avec en fonction de l’examen clinique, echographique et du souhait de la patiente la possibilite d’une explantation. Nous faisons le point sur les protheses PIP posees au centre Oscar-Lambret a Lille. Materiel et patientes etude retrospective concernant toutes les patientes porteuses d’une prothese mammaire PIP posee au centre Oscar-Lambret. Nous nous sommes interesses aux taux de patientes ayant choisi la surveillance clinique et echographique, aux taux d’explantation et de rupture prothetique. Resultats Trente-trois protheses (pour 31 patientes) de la marque PIP ont ete mises en place au centre entre le 2 mai 2006 et le 9 mars 2010. L’âge moyen des protheses etait de 15,35 mois. Nous avons realise huit explantations et constate trois ruptures intracapsulaires. Deux des trois ruptures etaient symptomatiques. Conclusion La majorite des patientes ont choisi la surveillance. Notre courte serie ne permet pas de donner une information precise sur leur risque de rupture prothetique, il faudrait etablir un registre national. La litterature illustre la faible sensibilite de l’echographie dans le diagnostic de rupture intracapsulaire et la superiorite de l’IRM. Dans le contexte d’une alerte sanitaire se pose la question de proposer, comme outil de surveillance prothetique, une IRM mammaire afin de reduire au minimum le taux de patientes porteuses d’une prothese rompue (faux negatif).

The expression and effects the CABYR-c transcript of CABYR gene in hepatocellular carcinoma.

Abstract: Background and aim CABYR, a calcium-binding tyrosine phosphorylation regulated fibrous sheath protein, was initially reported to be testis-specific and subsequently shown to be present in brain tumors, pancreas cancer and lung cancer. This study aimed to investigate the expression and effects of the CABYR-c transcript of CABYR gene in hepatocellular carcinoma. Methods mRNA and protein expression of CABYR-c was examined in 20 paired hepatocellular carcinoma tissues and adjacent non-cancerous tissues by real-time quantitative RT-polymerase chain reaction (PCR) and western blot analysis respectively. HepG2 cells were treated with the antisense oligodeoxynucleotides targeting CABYR-c mRNA (CABYR-c antisense oligonucleotides [AS ODNs]) for indicated times, the AS ODNs inhibition effect was evaluated by measuring the CABYR-c mRNA expression level of HepG2 cells after treatment using real-time quantitative RT-PCR, then cell proliferation was studied using MTT assay, and cell cycle distribution and apoptosis were detected by flow cytometry as well. Results CABYR-c mRNA levels in hepatocellular carcinoma tissues were significantly higher than that in the paired adjacent non-cancerous tissues (27.5 ± 1.2 versus 2.5 ± 0. 9, P P P P P Conclusion CABYR-c is highly expressed in hepatocellular carcinoma tissues and may play an oncogenic role in heptocarcinogenesis as well as its progression.

Lipoteichoic acid of Bifidobacterium in combination with 5-fluorouracil inhibit tumor growth and relieve the immunosuppression

Abstract: To investigate the therapeutic efficacy of lipoteichoic acid of Bifidobacterium (BLTA) in combination with 5-fluorouracil (5-FU) treatment on the mice bearing inoculated hepatoma-22 (H 22 ) cells and the effects of BLTA on immunological regulation of organism, and explore its mechanisms. Methods Tumor-bearing mice were treated with 5-FU alone, BLTA alone or BLTA in combination with 5-FU. The tumor size were observed and measured regularly. The growth inhibiting rate (IR) of tumor was detected. MTT assay was used to evaluate the proliferation of T lymphocytes and splenic NK cell and CTL activity. Enzyme linked immunosorbent assay (ELISA) was used to detect the change of IFN-Γ. FCM was used to detect T subgroup ratio of spleen cells of tumor-bearing mice. Expression change of mRNA and proteins of Foxp3 and TIM-3 were detected by Real-Time-PCR and Western blot in tumor-bearing mice tumor tissue. Results Both 5-FU and BLTA had inhibition effect on tumor-growth. While in the 5-FU + BLTA group, the inhibition of tumor growth was more significant, with increased T lymphocyte proliferation and IFN-Γproduction of spleen cells. Spleen cells of tumor-bearing mice had high CD4 + CD25 + regulatory T cell (CD4 + CD25 + T reg ) ratio and high mRNA and proteins expression of Foxp3 and TIM-3, but in the BLTA and 5-FU group, CD4 + CD25 + T reg ratio degraded, with down regulation mRNA and proteins expression of Foxp3 and TIM-3. But CD4 + T cells also decreased in spleen cells of tumor-bearing mice by alone 5-FU treated, splenic NK cell and CTL activity also degraded, while CD4 + T cells and splenic NK cell and CTL activity significantly increased by BLTA treated. BLTA in combination with 5-FU could also enhance the ratio of CD4 + T cells and splenic NK cell and CTL activity. Conclusion The present study suggested that BLTA in combination with 5-FU could enhance antitumor effect, with inhibiting TIM-3/TIM-3L pathway, cutting down immunosuppressive activity of CD4 + CD25 + T reg and enhancing cell-mediated immunity.

Toxicité rénale des produits de contraste chez le patient oncologique

Abstract: Resume Les patients oncologiques sont regulierement exposes a l’imagerie medicale lors du diagnostic mais aussi pour evaluer leurs reponses aux traitements. Ces patients sont egalement a fort risque d’insuffisance renale avant meme de regarder la potentielle nephrotoxicite de leur chimiotherapie. Dans ce contexte, connaitre les risques lies aux produits de contraste et les bonnes pratiques a adopter pour les eviter est indispensable. L’evaluation de la fonction renale y prend une place importante. La radiologie par rayons X utilisant les produits de contraste iodes (PCI) expose les patients a une insuffisance renale aigue. La nephropathie induite sera prevenue par une hydratation prealable a l’injection quand le debit de filtration glomerulaire du patient est inferieur a 60 mL/min/1,73 m 2 . Longtemps consideres comme une alternative securisante aux PCI car pratiquement non nephrotoxiques, les produits a base de gadolinium utilises en imagerie a resonance magnetique peuvent induire une fibrose nephrogenique systemique (FNS). Les recommandations europeennes et americaines des agences de sante se sont rapprochees recemment definissant des groupes a risque de FNS en fonction de leur niveau de fonction renale et du type de produits gadolines utilises. Comment evaluer la balance benefice-risque du patient oncologique pour lui choisir un examen radiologique informatif, efficace et sur ?

Existe-t-il un intérêt à poursuivre les frottis de dépistage du cancer du col utérin après 65 ans ? Ètude rétrospective sur 53 644 femmes

Abstract: Resume Contexte Un tiers des cancers du col uterin est decouvert apres 65 ans. Or, les recommandations francaises, concernant le depistage du cancer du col, sont d’exclure du depistage les femmes apres 65 ans ayant eu au moins deux frottis normaux consecutifs. Objectif Etudier la frequence des lesions cytologiques chez les femmes âgees de plus de 65 ans dont le rythme de suivi cytologique anterieur avait ete normal et suffisant, afin de determiner s’il existe un interet de poursuivre les frottis de depistage apres 65 ans. Patientes et methodes Etude retrospective multicentrique a partir des donnees de trois laboratoires de cytopathologie de la region Rhone-Alpes. Etude d’une population de 53 644 femmes de plus de 65 ans chez qui un frottis a ete realise entre 2004 et 2008. Resultats Des lesions precancereuses et cancereuses du col sont decouvertes apres 65 ans malgre un suivi anterieur suffisant. Le taux de frottis pathologique pour ce groupe de femmes est de 14,2 ‰ et il est de 1,4 ‰ pour les frottis evocateurs de cancer. Conclusion Il existe un interet a poursuivre les frottis de depistage apres 65 ans. Cette approche semble raisonnable tant du point de vue medical qu’economique.

French adaptation of a question prompt list for cancer patients and their carers in supportive and palliative care

Abstract: Allowing cancer patients to actively participate by asking questions during the medical consultation has demonstrated that it improves care provision. In order to ease this behaviour, an Australian team developed and validated a question-prompt list (QPL). Our purpose is to present the French adaptation of this tool. Independently translated by three translators, a first version in French was submitted to a committee of ten specialists, oncologists and psycho-oncologists. We submit that second version to a sample of 10 patients in supportive and palliative care unit, including a meeting with a psychologist. Clinicians and patients were invited to comment on the clarity, relevance and acceptability of the QPL. These findings suggest that French patients assessed this QPL to be comprehensive and helpful to express their concerns.