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Based on nationwide data from the French national cancer institute (INCa), we analyzed the evolution of cancer genetics consultations and testing over time, and the uptake of targeted tests in relatives of families with BRCA1/2 or MMR genes mutation. Genetic testing and consultations for familial high-risk individuals are exclusively funded and monitored by the INCa in France. All nationwide cancer genetics centers reported annually standardized parameters of activity from 2003 to 2011. The analysis included a total of 240,134 consultations and 134,652 genetic tests enabling to identify 32,494 mutation carriers. Referral for hereditary breast and ovarian cancer (HBOC) or colorectal cancer predisposition syndromes represented 59 % (141,639) and 23.2 % (55,698) consultations, respectively. From 2003 to 2011, we found a dramatic and steady increase of tests performed for BRCA1/2 (from 2,095 to 7,393 tests/year, P < 0.0001) but not for MMR genes (from 1,144 to 1,635/year, P = NS). The overall percentage of deleterious mutations identified in the probands tested was 13.8 and 20.9 % in HBOC and Lynch syndromes, respectively. Pooled analysis for BRCA1/2 and Lynch syndrome tests showed an inverse relationship between the percentage of mutation detected and the absolute number of tests performed over the time (overall Cochran-Armitage test for trend: P < 0.001). In families with BRCA1/2 or MMR identified mutations, there was an average number of 2.94 and 3.28 relatives performing targeted tests, respectively. This nationwide study shows a lack of referral and genetic testing in Lynch as compared to HBOC syndromes. Only a third of relatives of a proband with a predisposing mutation performed a targeted test. Enhanced information about benefit of genetic testing should be given to clinicians and patients for Lynch syndrome and relatives of a proband carrying an identified predisposing mutation.

Resume Cette etude preliminaire presente les resultats d’une demarche de validation d’un nouveau questionnaire du type d’interaction dans le jeu video (QTIJV), compose de 26 items. Cet instrument porte sur les deux types d’interaction : sensorimotrice et emotionnelle-narrative. Il a pour objet de distinguer un usage « normal » d’un usage « problematique » du jeu video. A cette fin, 313 adolescents âges de 11 a 18 ans, ont ete questionnes dans des etablissements scolaires d’Ile-de-France et d’Amiens. Les resultats attestent des bonnes qualites psychometriques de l’outil (structure factorielle, consistance interne, coefficient de correlation Bravais Pearson et de concordance test/retest sensibilite, validite interne et fidelite) avec une analyse factorielle confirmatoire proposant un nouveau modele theorique d’ajustement en sept facteurs.

In diesem Kapitel erfahren Sie mehr uber: Speiserohrenkrebs, Magenkrebs, Leberkrebs, primaren Leberkrebs (Hepatom oder hepatozellulares Karzinom, sekundaren (metastatischen) Leberkrebs, Gallenblasen- und Gallengangkrebs, Bauchspeicheldrusenkrebs, Dunndarmkrebs, Dickdarmkrebs (Kolon- und Rektumkarzinom), Analkrebs.

In diesem Kapitel erfahren Sie mehr uber Rauchen, Schutz vor Viren und Bakterien, genetischen Schutz, Hautkrebserkrankungen, Ernahrung – Magen-, Darm-, Brust-, Prostata- und Schilddrusenkrebs, Brustkrebs – sonstige potenziell praventive Masnahmen, berufsbedingte Krebserkrankungen, ionisierende Strahlung, Fruherkennung und fruhzeitige Behandlung pramaligner oder potenziell maligner Erkrankungen.

In diesem Kapitel erfahren Sie mehr uber Gebarmutterkrebs, Eierstockkrebs, Scheidenkrebs und Vulvakrebs.

In diesem Kapitel erfahren Sie mehr uber die Pravalenz von Krebs, benigne und maligne Tumoren, die Gefahren maligner Tumoren und die Ursachen einer malignen Erkrankung.

In diesem Kapitel erfahren Sie mehr uber Knoten, Geschwure, Schmerzen, Blutungen, Beeintrachtigungen von Gewebe- oder Organfunktionen, unerklarlichen Gewichtsverlust sowie Symptome der Metastasierung: Lymphknoten, Leber, Lunge, Knochen, Fett- und Muskelgewebe, Darm, Gehirn, CUP-Syndrom.

In diesem Kapitel erfahren Sie mehr uber Leukamien – akute Leukamien, chronische lymphozytare (lymphatische) Leukamie, chronische myeloische (granulozytare) Leukamie – und uber Lymphome – Hodgkin-Lymphom (vormals Morbus Hodgkin), Non-Hodgkin-Lymphome, multiples Myelom.

In diesem Kapitel erfahren Sie mehr uber die Bedeutung der Auswahl geeigneter Spezialisten fur die Patientenversorgung und des Aufbaus eines aufrichtigen und empathischen Verhaltnisses zwischen Arzt und Patient, uber die Fahigkeit, Patienten und ihren Angehorigen beunruhigende Nachrichten zu ubermitteln, sowie uber haufige Unterschiede zwischen Mannern und Frauen im Umgang mit Gesundheitsproblemen.

In diesem Kapitel erfahren Sie mehr uber Screening-Tests, bildgebende Verfahren zur Darstellung von Organen, Rontgenuntersuchung, Szintigraphie, Computertomographie (CT), Sonographie, Magnetresonanztomographie (MRT), Positronenemissionstomographie (PET), indirekte Anzeichen einer Krebserkrankung – Blut- und Serumanalysen – sowie direkte Anzeichen einer Krebserkrankung – Biopsie.

In diesem Kapitel erfahren Sie mehr uber Osteosarkom, Osteoklastom (zentraler Riesenzelltumor des Knochens), Ewing-Sarkom und Chondrosarkom.

In diesem Kapitel erfahren Sie mehr uber Knoten, Geschwure, Blutungen und Anzeichen von Blutverlust, vergroserte Lymphknoten, sonstige Schwellungen, Befunde der Allgemeinuntersuchung einschlieslich Mund, Rachen, Abdomen, Rektum und Anus sowie seltene und scheinbar in keinem Zusammenhang stehende Anzeichen einer Krebserkrankung.

In diesem Kapitel erfahren Sie mehr uber Typisierung, Bestimmung des Differenzierungsgrades und Stadieneinteilung maligner Tumoren, klinische Entscheidungen auf der Grundlage pathologischer Befunde.

In diesem Kapitel erfahren Sie mehr uber Lippenkrebs, Krebs im Mundraum, der vorderen Zunge und der Wangenschleimhaut, Zungengrund-, Tonsillen- und Pharynxkarzinom, Nasen-Rachen-Krebs, Kehlkopfkrebs, Speicheldrusenkrebs, Schilddrusenkrebs.

In diesem Kapitel erfahren Sie mehr uber Hirntumoren: klinische Zeichen, allgemeine Anzeichen, fokale Zeichen, pathologische Arten, Untersuchungen, Behandlung sowie uber Hirnmetastasen, Nervenzelltumoren und Retinoblastom.

Significant advances in the treatment of patients with breast cancer have been made in the past 10 years. The current systemic treatment of breast cancer is characterized by the discovery of multiple cancer targets leading to treatments that are more sophisticated and specific than conventional cytotoxic chemotherapy. Two classes of compounds that have helped improve clinical outcomes are small molecules and monoclonal antibodies targeting specific tyrosine kinase receptors. Many novel targets have been discovered, and parallel multiple approaches to anticancer therapy have recently emerged from the literature. One promising strategy is targeting the proangiogenic vascular endothelial growth factors (VEGFs), either by ligand sequestration (preventing VEGF receptor binding) or inhibiting downstream receptor signaling. Bevacizumab, a monoclonal antibody directed against VEGF, has been shown to improve the efficacy of taxanes in frontline treatment of patients with metastatic breast cancer. This review outlines the most promising breast cancer studies using bevacizumab combined with traditional cytotoxic agents in advanced breast cancer. In addition, we discuss the current indications reviewed by the Oncologic Drug Advisory Committee and define our vision of how the benefit of patient clinical trials should be measured.

Erythropoiesis-stimulating agents are indicated for the treatment of chemotherapy induced-anemia in cancer patients. Controlled clinical studies have shown that epoetin alfa consistently and significantly increases levels of hemoglobin (Hb), decreases the need for RBC transfusion, and improves the quality of life that is of such importance in cancer patients with a limited life expectancy. The rise achieved in Hb level correlates with an improvement in quality of life. Studies have also demonstrated that earlier initiation of epoetin therapy (i.e., starting treatment at an Hb level of 10–11 g/dl rather than waiting for Hb to fall to

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib and the cytotoxic agent docetaxel are both used for the second-line treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of gefitinib in combination with docetaxel within this disease setting, and to evaluate the predictive value of assessing pre-treatment levels of soluble serum EGFR and HER2. In this open-label, non-comparative, multicenter, phase II trial, patients with non-resectable advanced or metastatic NSCLC were treated with oral gefitinib (250 mg/day) in combination with docetaxel (75 mg/m2 IV every 3 weeks). Forty-eight patients were enrolled: 30 had progressed during or after platinum-based chemotherapy (Group A) and 18 were unsuitable for platinum-based chemotherapy (Group B). Anti-tumor activity was seen with objective response rates of 23.3% (Group A) and 11.8% (Group B). The most frequent adverse events considered to be gefitinib-related were diarrhea (57.4%) and skin-related events (dry-skin: 31.9%; rash: 29.8%; pruritus: 12.8%), and those considered to be docetaxel-related were alopecia (21.3%), nausea (19.1%), and diarrhea (17.0%). The addition of gefitinib did not seem to affect the hematological toxicity seen with docetaxel. Serum biomarker investigations revealed that patients who responded had lower serum EGFR levels than non-responders, although this association was not significant (p=0.07). In conclusion, the combination of gefitinib with docetaxel was feasible, generally well tolerated, and has activity for the treatment of advanced NSCLC. Soluble serum EGFR (and HER2 levels) did not appear to be predictive for response. Although this study confirms that the combination of gefinitib and docetaxel appears promisingly effective and tolerable, it should not be recommended as a standard option for second-line therapy in non-small cell lung cancer until results from phase III trials showing a significant superiority over docetaxel alone are available.

Resume Introduction Les inhibiteurs du recepteur du facteur de croissance epidermique (rEGF) representent une nouvelle strategie pour traiter certains cancers solides a des stades avances (colon et rectum, ovaire, pancreas...). Leurs effets secondaires cutanes commencent a etre decrits. Observations L’etude concernait 2 femmes et 2 hommes, sans antecedents d’acne, inclus dans un protocole therapeutique utilisant les inhibiteurs du rEGF. L’âge moyen etait de 52 ans. Les cancers primitifs etaient : cerebral, ovarien, mammaire et indetermine. Les inhibiteurs du rEGF etaient le gefitinib (ZD1839) (2 cas), le carnetinib (CI1033) et le cetuximab (IMC-C225). L’eruption a debute 7 jours apres l’initiation du traitement et etait faite de papulo-pustules folliculaires et de papules erythemateuses, monomorphes, predominant au visage, au decollete et au dos. Il n’y avait pas de comedons ni d’elements nodulaire ou kystique. La severite de l’eruption a conduit a l’arret du traitement chez 2 malades, suivi d’une regression complete des lesions cutanees. Chez un malade, la reduction des doses de gefitinib (IMC-C225) a conduit a la resolution progressive de l’eruption. L’examen anatomopathologique des papulo-pustules montrait une folliculite aigue suppuree. Chez les 2 malades preleves, l’ecouvillonnage d’une lesion pustuleuse et du nez a mis en evidence des colonies de staphylocoque dore coagulase positive. Un traitement associant une doxycycline (100 mg/j) et un peroxyde de benzoyle a ete prescrit pour une duree de 3 mois. L’evolution a ete favorable, en moyenne en 2 semaines. Discussion Les inhibiteurs du rEGF agissent en bloquant les mecanismes de la proliferation tumorale dans le traitement de certains cancers a des stades avances ou resistants aux autres therapeutiques. Notre serie de quatre malades se rapproche des cas publies, par la rapidite de survenue et le caractere monomorphe, papulopustuleux folliculaire, sans comedons, de l’eruption. Une reponse rapide aux cyclines et au peroxyde de benzoyle a egalement ete observee dans la litterature. Ce traitement doit etre rapidement mis en place et le malade prealablement informe des risques cutanes des inhibiteurs du rEGF. La physiopathologie de l’eruption reste inconnue. Les manifestations cutanees resulteraient probablement de l’interaction avec les fonctions des rEGF. Le mecanisme pourrait impliquer entre autres une surexpression des rEGF au niveau des keratinocytes et du follicule pileux.

The aim of the study was to measure taste thresholds among cancer patients under chemotherapy compared to controls. The study was performed with 110 cancer patients and 170 healthy subjects of similar age distribution were included in the study. The electrogustometric detection threshold was evaluated as the lowest current intensity perceived by the subject in three tongue sites independently with a constant current generator. Taste thresholds for all cancer patients demonstrated significantly higher values compared to controls. Cancer patients treated by chemotherapy demonstrated a temporary taste sensitivity deficit. Associated with the illness due to the treatment, this deficit explains the patients complaining of “abnormal or bad tastes”, which results in food aversion and has a negative impact on nutritional status and quality of life. In order to prevent the risk of anorexia and the enhanced morbidity related to this deficit, treatment should include relevant information to the subject for anticipating objective taste modifications and a psychological follow-up during the actual change of taste quality perceptions in everyday life.

El cancer representa la primera causa de mortalidad en los paises industrializados. Los esfuerzos terapeuticos hasta el momento no han logrado disminuir esta tendencia. Existen numerosas causas pero se pueden subrayar el aumento de la esperanza de vida, el tabaquismo y ciertos habitos alimentarios. Es por ello que la clave en la lucha contra el cancer se encuentra en la deteccion precoz y la prevencion. Se vera, sin embargo, que ello no es posible en todos los tipos de cancer: Para que la deteccion y la prevencion tengan exito se necesita la participacion activa de los poderes publicos, el personal medico y, sobre todo, de la poblacion. Por ultimo, se senalara la quimioprevencion como una de las posibles armas terapeuticas del futuro.

Summary Background Impaired regulation of apoptosis is known to be associated with the development of various cancers. Fas receptor (APO-1/CD95) binding to its ligand, Fas-ligand (Fas-L), has been shown to trigger apoptosis in various cell types. Objectives In this study, we examined CD95 and Fas-L expression on primary and metastatic melanoma cells from patients to investigate a potential correlation between these measures of apoptosis and different disease stages. Patients and methods Primary melanoma cells were obtained after surgical resection from 19 patients and metastatic cells from fine-needle aspiration of lymph nodes or palpable subcutaneous lesions in 25 patients. Normal skin cells were obtained at skin biopsy of 10 healthy donors. Results Flow cytometric analysis revealed that CD95 and Fas-L expression was detected in all the kinds of cell studied. In whole cell suspensions, CD95 expression was significantly higher (P , 0·0001) in normal skin cells than in melanoma cells, whatever the stage studied. By contrast, we observed an increase in Fas-L expression in melanoma cells compared with normal ones. Subsequently, using a double staining method, we studied these measures on HMB451 cells, a specific marker for melanoma cells, and found that CD95 expression was significantly higher (Pa 0·0005) in primary than in metastatic cells while Fas-L expression was significantly increased (Pa 0·0004) in metastatic compared with primary cells. Furthermore, a relationship was found between CD95 or Fas-L expression and Breslow thickness; as primary melanoma thickness progressively increased, the percentage of HMB451 CD951 cells decreased while that of HMB451 Fas-L1 cells concurrently increased. Conclusions These results suggest that downregulation of CD95 and upregulation of Fas-L in melanoma might be considered as concomitant with disease progression.

Fractionated cisplatin-containing regimens are routinely used for chemotherapy in certain types of cancer. Dolasetron has been shown to be effective in preventing acute emesis related to high-dose cisplatin chemotherapy over 24 h; its effectiveness has not been evaluated in fractionated cisplatin-containing chemotherapy. This trial was designed to assess the efficacy of dolasetron alone or dolasetron plus dexamethasone in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. The patients were 210 cancer in-patients, who were randomised to receive 100 mg dolasetron i.v. or 100 mg dolasetron i.v. plus 20 mg dexamethasone before chemotherapy primarily with cisplatin (15-50 mg/m2) infused overor =4 h for at least 2 but not more than 5 consecutive days. Dolasetron was administered to all patients 30 min before cisplatin. Dexamethasone was administered in double-blind fashion 5 min before cisplatin. Efficacy was measured at hour 24 of each study day using complete response (no vomiting and no rescue medication) and maximum severity of nausea, self-assessed by patients using a 100mm visual analogue scale. Most (198) of the patients completed the study and were evaluable. Overall complete response rates were significantly higher in the dolasetron plus dexamethasone group than in the dolasetron only group (72.9% vs. 40.8%, respectively; P0.0001). Complete response rates on each study day were also significantly higher with dolasetron plus dexamethasone than with dolasetron alone (P0.029), with an attenuated efficacy in the delayed phase in both groups. Chi-square test and logistic regression applied to daily response rates indicated a significant influence of treatment (day 1: P = 0.0002, day 2: P0.0001, day 3: P = 0.0007, day 4: P = 0.0007, day 5: P = 0.029). Treatment and duration of chemotherapy exerted the only statistically significant subgroup effects on complete response (P0.0001). Both treatments were administered safely. As seen with other 5-HT3 receptor antagonist antiemetics, the addition of dexamethasone to dolasetron significantly increases effectiveness in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. Both dolasetron and dolasetron plus dexamethasone were well tolerated.

Resume Introduction. — Les metastases osteocondensantes, ayant pour origine principale le cancer de la prostate, posent des problemes de diagnostic et de surveillance qui leur sont propres et moins bien connus que ceux des metastases lytiques. Nous analysons les differentes techniques d'imagerie et leur place respective. Actualites et points forts. — Les metastases osteocondensantes sont mises en evidence la plupart du temps par les radiographies standard. Au moindre doute diagnostique, le scanner est interessant par son etude de la topographie, de l'extension et des signes associes, ainsi que pour la surveillance. En complement, l'IRM donne des precisions sur le contenu lesionnel et le degre d'osteocondensation. Elle doit etre realisee apres les autres examens, mais devient un examen primordial pour le bilan rachidien complet en raison de son etude multiplanaire de la totalite du rachis. Perspectives et projets. — Les perspectives d'avenir sont constituees par le scanner helicoidal et l'etude du contenu et du volume lesionnel, notamment pour le suivi sous traitement, et l'IRM pour une meilleure analyse (IRM dynamique) de la composition lesionnelle.

Contexte Necitumumab (N), anticorps monoclonal humain IgG1 anti-EGFR, inhibe la liaison du ligand et l’activation du recepteur. L’EGFR est detecte dans la grande majorite des CBNPC-epi avances. Methodes Les points ayant un CBNPC-epi de stade IV ont ete randomises (1:1) entre GC + N (G = 1250 mg/m 2 iv, j1–j8 ; C = 75 mg/m 2 iv, j1 ; N = 800 mg iv, j1–j8) ou GC, tous les 21 j (6 cycles max). Les points GC + N controles ont poursuivi N seul jusqu’a progression ou toxicite inacceptable. Le critere principal de jugement etait la survie globale (SG). Les criteres secondaires incluaient la survie sans progression (SSP), le temps jusqu’a echec du traitement (TET), le taux de reponse objective (RO), et la tolerance. Resultats Mille quatre-vingt-treize points ont ete randomises (GC + N n = 545 ; GC n = 548). Les caracteristiques initiales, l’exposition a la chimiotherapie et les traitements a progression ont ete similaires dans les deux bras. L’adjonction de N a GC ameliore significativement la SG (HR = 0,84, p = 0,012) et la SSP (HR = 0,85, p = 0,020). La SG mediane est de 11,5 vs 9,9 m pour GC la SSP mediane est de 5,7 vs 5,5 m pour GC ; et le TET median de 4,3 vs 3,6 m pour GC. Le taux de RO est de 31 % vs 29 % pour GC ( p = 0,400), avec un taux de controle de la maladie (TCM) de 82 % vs 77 % pour GC ( p = 0,043). Les EIs de grade ≥ 3 avec GC + N augmentes de > 2 % par rapport a GC ont ete l’hypomagnesemie (8,7 % vs 1,1 %) et le rash cutane (3,7 % vs 0,2 %). Conclusions L’ajout de N a GC ameliore de maniere statistiquement significative la SG, la SSP, le TET et le TCM dans les cancers epidermoides de stade IV avec un profil de tolerance acceptable.

We have previously demonstrated that transfected hepatocellular carcinoma cells (Hepa1-6) with one copy (pAGO) and two copies (pYED) of the HSVtk gene, using liposomes, induced cell death of untransfected cells in the presence of ganciclovir (GCV). This phenomenon is called the 'bystander effect'. To determine whether an elevated level of connexin43 increases the bystander effect, we have cotransfected Hepa1-6 cells with a plasmid containing the HSVtk gene driven by the alpha-fetoprotein promoter (pFTK) or pAGO or pYED and connexin43. The results showed that, after GCV treatment, the percentage of growth inhibition was higher (25-30%) in cells cotransfected with HSVtk and connexin43 than in cells transfected only with HSVtk gene. The IC50 of GCV on cells transfected with pFTK/Connexin43 was 17.85-fold lower than cells transfected with pFTK alone. To improve these results, stable connexin43 transduced Hepa1-6 cells were transfected with pFTK followed by GCV treatment. In this case, the cell growth was markedly inhibited as compared with parental cells. Furthermore, we have studied the correlation between the expression of the HSVtk and the connexin43 proteins. Using flow cytometric analysis, scrape loading/dye transfer and immunoblotting assay we found that the cells transfected separately by pAGO, pYED, pFTK and pLTR-Cx43 showed an increase of connexin43 protein. This study indicates that transfecting Hepa1-6 cells with both connexin43 and HSVtk genes up-regulates connexin43 expression which enhances the bystander effect and subsequently tumor cell death.

Background: Controversies surrounding medical treatment in patients with unresectable hepatocellular carcinoma continue to persist. Aim: To perform a meta-analysis of therapeutic modalities which had been evaluated in two or more randomized trials. Methods: Fifty-two randomized trials were studied; only 30 were included. This overview identified seven therapeutic modalities which had been evaluated in two or more trials: adriamycin, 5-fluorouracil, interferon, percutaneous ethanol injection, transarterial chemotherapy, the combination of lipiodol with transarterial chemotherapy, and tamoxifen. Results: Comparisons of survival between control groups showed substantial heterogeneity. There was no survival benefit at 1 year with adriamycin (mean difference 4%), 5-fluorouracil (mean difference −3%), percutaneous ethanol injection (mean difference 6%) or transarterial chemotherapy (mean difference −2%). For interferon, the survival benefit was significant with the Der Simonian & Laird method (mean difference 9%, 95% CI = 1–18%, P = 0.04) but not with the Peto et al. method (2.4 mean odds ratio, 95% CI = O.9–6.8). The meta-analysis of tamoxifen showed a borderline survival benefit (mean difference 25%, 95% CI = 0–49%, P = 0.05). However, in sensitivity analyses, the survival benefit of tamoxifen was no longer significant. Conclusions: No treatment has clearly proven efficacy in survival. 5-Fluorouracil, adriamycin and transarterial chemotherapy were not associated with survival benefit at 1 year. The number of randomized controlled trials was insufficient to enable a conclusion to be reached for interferon and percutaneous ethanol injection. Controversy persists concerning tamoxifen efficacy. Interferon and tamoxifen require new randomized controlled trials on a larger population of patients.

The potent serotonin receptor (5-HT3) antagonists are new highly selective agents for the prevention and control of chemotherapy-induced nausea and vomiting that have been shown to be comparable to or more effective than traditional metoclopramide regimens. This study was designed to compare the antiemetic efficacy of dolasetron and metoclopramide in chemotherapy-naive and non-naive cancer patients receiving high-dose cisplatin-containing chemotherapy. This multicentre, double-blind, randomized trial compared the efficacy and safety of single i.v. doses of dolasetron mesilate salt (1.2 or 1.8 mg/kg) and metoclopramide (7 mg/kg) in 226 patients for the prevention of acute emesis and nausea associated with the administration of high-dose (or = 80 mg/m2) cisplatin. Efficacy and safety were evaluated for 24 h. Complete responses were achieved by 57%, 48%, and 35% of patients given dolasetron mesilate 1.8 mg/kg (P = 0.0009 vs metoclopramide), dolasetron mesilate 1.2 mg/kg (P = 0.0058 vs metoclopramide), and metoclopramide, respectively. Overall, dolasetron was significantly more effective than metoclopramide for time to first emetic episode, nausea, patient satisfaction, and investigator global assessment of efficacy. Males, chemotherapy-naive patients, and alcoholics had higher response rates. Dolasetron was well tolerated, with mild-to-moderate headache most commonly reported. Twelve percent of patients receiving metoclopramide reported extrapyramidal symptoms compared with 0% of patients receiving dolasetron. In conclusion, dolasetron mesilate was effective for the prevention of CINV with high-dose cisplatin. Single i.v. doses of dolasetron mesilate were more effective than 7 mg/kg metoclopramide in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, 1.8 mg/kg dolasetron mesilate consistently produced the highest response rates and appears to be the most effective dose for further clinical development.

The use of Helical CT significantly improves image quality of examinations in a number of clinical settings. It is particularly suited to the study of the tracheo-bronchial tree as a result of new ways of image processing (developed by GEMS research) which can produce virtual endoscopic images without the use of an endoscope. We present our initial anatamo-radiological findings and their educational value as well as our thoughts on potential future clinical applications.

Whether or not peripheral stem cells have an unlimited capacity for self renewal is debated. However, everyday haematopoietic requirements are met by progenitors ; and it seems that few 'real' stem cells are needed. Although we may not yet have identified these 'true' stem cells, for practical purposes the long term culture-initiating cells (LTC-ICs) are a close approximation. To date, experience in peripheral blood progenitor cell (PBPC) transplantation is largely confined to non-ablative regimens. It is therefore difficult to determine the number of PBPCs needed to effect long-term reconstitution. The number of tumour cells present among mobilised PBPCs can be reduced using the CD34 affinity column and by positive purging methods. The ex vivo expansion of CD34 cells also has the effect of diluting tumour cell concentration. In clinical use, PBPC transplantation has a proven role in support of high dose chemotherapy in certain haematological and oncological malignancies but the concept of dose intensification is not universally accepted. With the exception of leukaemia, lymphoma, myeloma or relapsed testicular cancer and possibly some subgroups of breast cancer ; high dose chemotherapy does not demonstrate a survival benefit. For patients with CML, autografting with Ph - cells appears to become a useful alternative to allogeneic BMT. Allogeneic PBPC transplantation may have potential, though work is preliminary. Cord blood transplantation between matched siblings is viable, but it is not yet clear whether this source will increase the donor pool for adults needing allogeneic transplantation. For gene therapy using haematopoietic cells to be effective, a greatly increased rate of transduction will be needed. Meeting in Paris in September 1995, a European School of Oncology Task Force considered a number of important questions relating to peripheral blood progenitor cell (PBPC) physiology and transplantation. This review is a brief account of their conclusions.

Resume La problematique des enjeux du cancer en France s’articule autour de dix points cles qui sont : une epidemiologie inquietante, une mortalite prematuree inacceptable, une prevention insuffisante, un depistage insuffisamment organise, un acces inegal aux soins et aux medicaments, un systeme de soins heterogene, des difficultes de reinsertion pour les malades, une recherche en manque d’optimisation et une absence ou une insuffisance de coordination des differents acteurs dans la lutte contre le cancer. Comme on le voit, ces points definissent une problematique complexe pour laquelle une mobilisation politique nationale vient d’etre mise en route par la declaration du 14 juillet 2002 du president de la Republique, monsieur Jacques Chirac, visant a considerer le cancer comme une priorite nationale. Avec 150 000 nouveaux cas en 1980 et 278 000 en 2000, l’incidence du cancer en France a augmente de plus de 60 % en 20 ans. De la meme maniere, la mortalite qui atteint aujourd’hui environ 150 000 morts par an montre une augmentation de plus de 25 000, du nombre de morts en 20 ans. Deux millions de personnes vivent aujourd’hui dans notre pays avec un cancer ou apres avoir eu un cancer, 700 000 sont en file active de traitement sans qu’il existe une veritable conscience collective de l’ampleur de ce fleau. Force est de constater que la France, au regard des donnees recentes de l’etude EUROCARE 2000, a le plus fort taux de mortalite de tous les pays d’Europe, avec un peu plus de 280 cas pour 100 000 habitants et par an, mais surtout la plus forte mortalite prematuree, c’est-a-dire mortalite avant 65 ans.

Fotemustine and dacarbazine constitute the most active single chemotherapeutic agents in the treatment of melanoma. In this phase II study we evaluated the activity and toxicity of a combination of fotemustine, dacarbazine and vindesine as a means of increasing response rate and survival time. Between September 1989 and November 1993, 43 patients with advanced melanoma were treated with a combination of 100 mg/m2 fotemustine on days 1 and 8, 250 mg/m2 dacarbazine on days 15 and 16 and 2 mg/m2 vindesine on days 15 and 16 as induction treatment. After a 5-week rest period, the patients exhibiting a response or stable disease received the same drugs administered once every 28 days as maintenance therapy until either progression or toxicity was observed. Among 41 evaluable patients, there were six complete responses and eight partial responses. The overall response rate was 32% (95% confidence interval: 18-46%), with 8 months median duration of response. Median survival time was 10 months. This regimen was well tolerated. From this large phase II study, we conclude that such a combination is active against advanced malignant melanoma and seems to be more effective than fotemustine or dacarbazine used alone, especially on visceral metastatic sites.

Background: Mutations in the promoter of the telomerase reverse transcriptase (TERT) and fibroblast growth factor receptor 3 (FGFR3) genes represent the most recurrent somatic alterations in urothelial carcinomas of the bladder. However, data regarding frequency and prognostic values of these alterations in upper-tumor urothelial carcinoma (UTUC) remain limited. Methods: DNA was extracted from 31 UTUC including 12 cases arising in the ureter and 19 in renal pelvis. Somatic mutations of TERT promoter and FGFR3 gene were assessed by Sanger sequencing. The generated sequences were analyzed by seqscape and mutational status of each of those genes were correlated with clinico-pathological tumor features. Disease-free survival and overall survival were estimated using the Kaplan-Meier method. Results: Median patient's age was 72 years (range: 41-83) with a male predominance (90.3%). Mutation status of TERT and FGFR3 were obtained in all tumors. Out of 31 UTUC, 81% were classified as high-grade including 56% which were muscle-invasive (≥pT2). TERT and FGFR3 mutations were detected in 19 (61%) and 14 (46%) tumors, respectively. Of note, 8 (26%) out of them harbored both mutations. In the TERT-mutated subgroup, we observed higher incidence of men as compared to TERT non-mutated subgroup (p = 0.04); in addition, we did not identify any other significant differences regarding other clinico-pathological features. This was also the case for FGFR3 mutations, although we observed a higher frequency in tumors arising in the ureter (66.6%) as compared to those located in renal pelvis (28.5%) (p = 0.11). Neither mutations of FGFR3 nor TERT were associated with progression-free survival and patient's overall survival. Conclusion: Our study identified a high rate of somatic mutations in FGFR3 and TERT which were similar between muscle-invasive and non-muscle invasive tumors as well as between tumors arising in the ureter or renal pelvis. As targeted inhibitors are being investigated in this setting, these results might have implications for patient's management. Citation Format: Roger Mouawad, Souheyla Bensalma, Xiaoping Su, Frederick Allanic, Eva Comperat, Morgan Rouprêt, JeanPhillipe Spano, Gabriel Malouf, David Khayat. Study of TERT promoter and FGFR3 mutations in upper-tumor urothelial carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 116.

Background: Upper-tumor urothelial carcinomas (UTUC) represent 5% among all urothelial tumors. The most frequent histological variant is transitional cell carcinomas (TCC). UTUC might arise within renal pelvis or ureters. Several studies suggested aggressive behavior of tumors arising within the ureter as compared to those which develop within renal pelvis. However, whether there is a biological basis of this difference remains unknown. Methods: We performed RNAsequencing on fourteen UTUC including 6 cases arising in the ureter and 8 in renal pelvis. Library prep followed by next-generation sequencing were done using Illumina Hiseq platform. Unsupervised clustering using differentially expressed genes was used to identify cancer subtypes. Identified subtypes were correlated with clinico-pathological features. Pathway analysis was performed using Gene Set Enrichment Analysis (GSEA). Results: Unsupervised clustering of gene expression revealed two clusters. Surprisingly, all tumors (n = 5/5) encompassing C1 were located in the ureters as compared to only one (n = 1/9) in C2 cluster (p = 0.003). No difference was observed between C1 and C2 clusters according to age, gender, grade, muscle-invasion status and stage. Using stringer cut-off (fold change ≥ or ≤-2 and FDR Conclusion: Our report suggests that transcriptional profiling of UTUC arising in the ureters and renal pelvis might be distinct. The observed difference might be related to immune response. Validation of these data in a larger independent cohort with analysis of the immune infiltrate is required. Citation Format: Gabriel Malouf, Roger Mouawad, Xiaoping Su, Hui Yao, Eva Comperat, Morgan Roupret, Jean-Philippe Spano, David Khayat. Transcriptionnal profiling of upper-tumor urothelial carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 106.

To evaluate the clinical and biologic safety of superparamagnetic iron oxide (SPIO) as a contrast agent in magnetic resonance (MR) imaging and to assess its efficacy in the detection of liver metastases.Twenty adults with liver metastases underwent MR imaging at 1.5 T before and 1 hour after infusion of SPIO. Four spin-echo (SE) sequences and one gradient-echo (GRE) sequence were used.There were no adverse reactions. Alterations in serum protein, serum iron, transferrin, and ferritin levels and transferrin saturation coefficient were statistically significant. The mean tumor-to-liver contrast-to-noise ratio (C/N) increased markedly with all sequences. The best postcontrast tumor-to-liver contrast was obtained with the GRE sequence (repetition time msec/echo time msec = 300/15). The mean number of apparent lesions detected after administration of SPIO increased by 12 with the proton-density-weighted SE sequences (800/30 and 2,500/30), four with the T2-weighted SE sequence (2,500/90), and seven with the GRE sequence (300/15).SPIO is safe, increases tumor-to-liver C/Ns with some sequences, and improves the detection of liver metastases.