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IF 11.855; International audience

Les cancers du colon atteignent principalement les patients âges. La prise en charge chirurgicale a fait des progres mais l’indication d’une chimiotherapie adjuvante reste controversee. Le choix du schema therapeutique et la selection des patients a traiter est un enjeu majeur. Des essais prospectifs specifiques a la population âgee sont necessaires.

La fragilite specifique des sujets âges les rend plus vulnerables aux differents stress entraines par la maladie cancereuse et ses traitements. Cette vulnerabilite, multifactorielle, rend plus complexe leur adaptation psychologique, d’autant plus que la maladie entraine une perte d’autonomie parfois non reversible. Les difficultes emotionnelles et les troubles cognitifs sont plus frequents, ce qui peut impacter les echanges d’information et les processus decisionnels et favoriser un risque de perte de chance oncologique. A l’occasion du 27e Congres de la Societe francaise de psycho-oncologie, dedie aux aspects psychologiques de la prise en charge des patients âges atteints de cancer, un groupe de travail multidisciplinaire compose d’experts dans le champ de la psychiatrie, de la neuropsychologie, de la geriatrie, de l’oncologie, de l’on-cogeriatrie, a travaille a ecrire les recommandations de prise en charge suivantes, discutees et validees ensuite lors d’une session specifique durant le congres. Elles preconisent de completer l’evaluation de la fragilite specifique du sujet âge, incluant les troubles cognitifs, par une evaluation de son etat emotionnel et de sa vulnerabilite psychiatrique eventuelle. L’identification des ressources de sante et des ressources sociales et familiales permettra a la fois de connaitre les soutiens possibles pour la personne, mais aussi de reperer d’eventuels besoins d’aide de l’entourage lui-meme. L’evaluation psycho-oncologique sera autant que possible realisee par un professionnel du soin psychique, et devrait etre systematique lors de la phase d’annonce, a chaque phase de modification therapeutique et a l’issue des traitements. Elle doit etre tracee dans le dossier medical. L’acces du patient âge a des prises en charge psycho-oncologiques de qualite doit etre assure, y compris par l’adaptation de ces prises en charge, psychotherapeutiques comme medicamenteuses. Une action d’education aux soins psychiques peut etre necessaire pour favoriser cette accessibilite. Un haut degre de collaboration avec les soignants est necessaire, tout comme une formation adequate de ceux-ci aux particularites psychiques de la prise en charge de ces patients. Enfin, des actions de recherche devront etre facilitees, dans les domaines de l’adaptation de l’evaluation et des prises en charge, comme sur la place de l’âge dans le systeme de soins oncologiques et sa prise en compte par les soignants ou le corps social.

Les cancers digestifs sont frequents chez les patients âges. Cependant, en dehors des cancers colorectaux, les etudes specifiques aux patients âges evaluant la prise en charge de ces cancers sont rares. Il apparait que chez des patients correctement selectionnes des traitements valides chez les patients plus jeunes sont applicables. L’adaptation du traitement a chaque cas doit faire l’objet d’une discussion pluridisciplinaire impliquant un geriatre.

Background In stage III colorectal cancer (CRC), adjuvant chemotherapy (CT) is usually prescribed within two months after curative surgery. Whether or not delaying initiation of CT affects survival is still debated. Material and methods We performed a meta-analysis (MA) of all published studies (full papers or abstracts) comparing delayed CT with standard care. Studies were obtained from a PubMed query (keywords: CRC, adjuvant treatment, delay of CT), a review (Chau et al., 2006), cross-checking references and abstracts from the proceedings of ASCO, ASCO GI and WCGI annual meetings. We chose a cutoff delay of 8 weeks. Risk Ratios (RRs) were calculated from the recorded events (deaths, relapses). We used EasyMA software (fixed-effect model). Results Fourteen studies (including four abstracts) were identified (17,645 patients; 5952 males, 5151 females, mean age 70 years). Of these, three could not be statistically analysed and three used another cutoff (4, 5 or 6 weeks), leaving 8 studies for main MA (13,158 patients; 3932 males, 3644 females, 5942 missing data; 5576 colon cancers, 6677 rectal, 1265 missing data). Delaying CT more than 8 weeks was associated to worse Overall Survival (OS) (RR: 1.20; 95% Confidence Interval (CI) 1.15–1.26). In the MA including all studies whatever their cutoff, longer delay was similarly associated to a worse OS but not a worse Relapse-Free Survival (RFS) (five studies). Conclusion Adjuvant chemotherapy should be started within 8 weeks after surgery. Delaying the initiation of adjuvant CT for more than 8 weeks after surgery significantly decreased OS but not RFS. This discrepancy might be due to factors not directly related to cancer (post-operative complications, social status) or to a more accurate appraisal of death.

Resume Objectif Nous rapportons un cas de cancer medullaire de la thyroide decouvert par TEP au 18 FDG. Patient et methodes Un homme de 73 ans opere d’un cancer du colon, avec ablation du sigmoide, a beneficie d’une tomographie par emission de positron au 18 fluorodeoxyglucose (TEP au 18 FDG), devant un taux eleve d’ACE et un nouvel episode d’occlusion, a la recherche de metastases a distance ou de recidive locoregionale. Les images obtenues ont montre une hyperfixation du FDG dans le lobe thyroidien droit. L’echographie thyroidienne a montre un nodule dans chaque lobe. Resultats Le resultat de la cytoponction etait suspect et le taux de calcitonine etait eleve. Le patient a ete opere d’une thyroidectomie sans curage. L’examen anatomopathologique a revele un cancer medullaire de la thyroide de 14 mm. Aucune mutation germinale du gene RET n’a ete retrouvee. Conclusions La TEP au 18 FDG peut detecter des cancers thyroidiens primitifs ou secondaires. Aussi, un incidentalome thyroidien decouvert sur une TEP au 18 FDG necessite une evaluation attentive.

Les medicaments anti-angiogeniques (medicaments anti-VEGF sur le marche: bevacizumab (Avastin®), sunitinib (Sutent®), sorafenib (Nexavar®) sont de plus en plus utilises dans le traitement de certains cancers (colon, sein, poumon, foie et rein). Leurs effets secondaires sont mal connus des medecins. L’hypertension arterielle (HTA) est l’effet indesirable le plus frequent. Son incidence depend de la definition de la molecule et de la dose. Elle est generalement controlable par les traitements antihypertenseurs et compromet rarement la poursuite du traitement. Plus rarement, elle peut avoir des consequences graves (HTA maligne, leucoencephalopathie posterieure reversible, accident vasculaire cerebral, etc.). Des atteintes renales sont moins frequentes: proteinurie moderee le plus souvent, reversible, et plus rarement, syndrome nephrotique, insuffisance renale aigue, glomerulopathie proliferative, nephrite interstitielle et microangiopathie thrombotique. Allongement de l’espace QT et insuffisance cardiaque ont ete observes avec des tinibs. Sur le plan therapeutique: 1) avant l’administration d’une premiere dose d’un traitement anti-angiogenique, il ne faut pas retarder l’administration d’une premiere dose ou administrer un traitement antihypertenseur en raison d’une pression arterielle (PA) elevee; 2) le bilan initial comporte unemesure de la PA realisee avec un appareil de mesure valide soit par le medecin traitant, soit au mieux en automesure tensionnelle (« regle des 3 », http://www.has-sante.fr), soit en mesure ambulatoire de la PA (appareil de mesure humeral valide (liste: http://afssaps.sante.fr); 3) la bandelette urinaire (et le cas echeant, quantification de la proteinurie), l’estimation de la fonction renale (formule de MDRD simplifiee plutot que Cockcroft et Gault) doivent etre faites avant traitement et au cours du suivi; 4) la prise en charge therapeutique se fait conformement aux recommandations (HAS HTA 2005: http://www.has-sante.fr); 5) la surveillance et la prise en charge therapeutique se feront au mieux dans le cadre d’un travail en reseau comprenant medecin generaliste, oncologue, cardiologue et nephrologue.

Arterial hypertension (HT) has been reported in all studies involving bevacizumab, an antiangiogenic agent designed to target vascular endothelial growth factor (VEGF). The mechanism underlying bevacizumab-related HT is not yet clearly understood. As far as endothelial dysfunction and microvascular rarefaction are hallmarks in all forms of HT, we tested the hypothesis that anti-VEGF therapy could alter the microcirculation in nontumor tissues and, thus, result in an increase in blood pressure (BP). We used intravital video microscopy to measure dermal capillary densities in the dorsum of the fingers. Microvascular endothelial function was assessed by laser Doppler flowmetry combined with iontophoresis of pilocarpine (acetylcholine analogue). All measurements were carried out in 18 patients before and after a 6-month treatment with bevacizumab (mean cumulative dose: 3.16 +/- 0.90 g). Mean BP was increased after 6 months of therapy compared with baseline, from 129 +/- 13/75 +/- 7 mmHg to 145 +/- 17/82 +/- 7 mmHg for systolic BP and diastolic BP, respectively (P < 0.0001). Compared with the baseline, mean dermal capillary density at 6 months was significantly lower (75 +/- 12 versus 83 +/- 13/mm(2); P < 0.0001), as well as pilocarpine-induced vasodilation (P < 0.05). Thus, bevacizumab treatment resulted in endothelial dysfunction and capillary rarefaction; both changes are closely associated and could be responsible for the rise in BP observed in most patients.

En 2008, les progres des connaissances en matiere de carcinogenese ont permis d’identifier des cibles moleculaires cles dans la genese de nombreuses tumeurs solides. Bien que non exhaustives encore, ces informations permettent l’utilisation de composes diriges contre les cibles moleculaires, specifiquement activees dans les cancers, donnant ainsi naissance au concept de therapie ciblee. Un des meilleurs modeles en oncologie est actuellement un sarcome digestif, le GIST ou la mutation d’un gene c-kit (correspondant a une tyrosine kinase) est a l’origine de la maladie. L’inhibition de cette tyrosine kinase permet le controle de la maladie dans plus de deux tiers des cas. Plusieurs anticorps ou molecules inhibitrices de tyrosine kinase sont deja commercialises. Ces traitements donnent parfois des taux de reponses limites en monotherapie, mais ont souvent une activite antitumorale additive avec la chimotherapie dans plusieurs types de tumeurs. Mais c’est aussi l’angiogenese a l’origine du developpement local et metastatique de la tumeur qui represente une cible efficace. Ainsi, dans les cancers digestifs, les progres recents ont ete saisissants puisque ces therapies ciblees sont associees tres frequemment aux chimotherapies dans les differentes lignes de traitements. Mais nous ne sommes qu’au debut du developpement de ces nouvelles classes therapeutiques. Cette revue pratique permet de faire le point sur l’utilisation de ces molecules en pratique quotidienne.

Aims: The Epidermal Growth Factor-Receptor (EGF-R) is frequently overexpressed in colorectal carcinoma (CRC) and patients can benefit from anti-EGF-R therapy. Yet, the relationship, within tumours, between EGF-R and the activity of downstream effectors such as the non-receptor tyrosine kinase p60c-src and the signal transducer and activator of transcription 3 (STAT3) has not been extensively analyzed. Methods and results: We evaluated EGF-R, tyrosine 416-phosphorylated p60c-src (P-p60c-src), STAT3 and tyrosine 705- phosphorylated STAT3 (P-STAT3) on Tissue Micro Array (TMA) from 126 patients with CRC. Composite immunohistochemistry scores based on the intensity of labelling and the percentage of positive cells were determined on TMA for EGF-R, P-p60c-src, STAT3 and P- STAT3. A high score was found in 56%, 61%, 62% and 27% of the cases for EGF-R, P-p60c-src, STAT3 and P-STAT3 respectively. There was a significant correlation between EGF-R and P-p60c-src (p =0 .006) and between P-p60c-src and P-STAT3 (p =0 .0009). STAT3 was significantly correlated with vascular emboli ( p =0 .03) and perineural invasion (p =0 .02). Conclusions: The correlations between EGF-R, P-p60-src and P-STAT3 and some stage-related pathological features point to a critical role for a EGF-R-connected p60c-src-kinase-mediated pathway involving STAT3 and contributing to cell survival and proliferation within CRC tumours.

Sur le plan etymologique, le mot de stomie vient du grec stoma, bouche. Une stomie est la communication artificielle, realisee par une operation chirurgicale, d’un organe creux a la peau. Une stomie, meme si elle n’est que temporaire, represente une contrainte et une atteinte a l’integrite physique du malade. Il apparait important de bien comprendre les indications, de donner une vision pratique importante a la dedramatisation, etant donne la frequence d’un tel geste. Si l’on comptabilise les 36 000 nouveaux cas de cancers colorectaux observes, plusieurs centaines de nouveaux patients seront stomises de facon temporaire ou definitive. Les progres dans la chirurgie du rectum ont permis ces dernieres annees de diminuer le nombre de colostomies definitives en raison du developpement de technique chirurgicale de preservation sphincterienne.

Sunitinib inhibits numerous tyrosine kinase receptors involved in tumor growth, angiogenesis, and metastatic invasion. It is indicated in case of metastatic renal carcinomas and gastrointestinal stromal tumors (GIST) resistant to imatinib. Prospective and retrospective studies have shown association between use of sunitinib and hypothyroidism affecting more than 50% of patients in some series. More amazing, was the non-visualisation of thyroid tissue evaluated with thyroid ultrasonography in two cases. Mechanisms of this side effect are not elucidated. Some studies have suggested destructive thyroiditis but no evidence of autoimmunity has been demonstrated. Anti angiogenic effect could be another hypothesis. Recently antithyroperoxidase activity of sunitinib has been demonstrated. Because hypothyroidism is easily accessible to treatment, screening of thyroid abnormalities is mandatory every three months to improve quality of life of these patients. This unique thyroid side effect of sunitinib with the non-visualisation of thyroid suggests a possible and promising antitumor activity in thyroid cancer.

We performed a meta-analysis of all published studies relating intratumoural microvessel density (MVD) (45 studies) or vascular endothelial growth factor (VEGF) expression (27 studies), both reflecting angiogenesis, to relapse free (RFS) and overall survival (OS) in colorectal cancer (CRC). For each study, MVD impact was measured by risk ratio between the two survival distributions with median MVD as cutoff. Eleven studies did not mention survival data or fit inclusion criteria, six were multiple publications of same series, leaving 32 independent studies for MVD (3496 patients) and 18 for VEGF (2050 patients). Microvessel density was assessed by immunohistochemistry, using antibodies against factor VIII (16 studies), CD31 (10 studies) or CD34 (seven studies). Vascular endothelial growth factor expression was mostly assessed by immunohistochemistry. Statistics were performed for MVD in 22 studies (the others lacking survival statistics) including nine studies (n = 957) for RFS and 18 for OS (n = 2383) and for VEGF in 17 studies, including nine studies for RFS (n = 1064) and 10 for OS (n = 1301). High MVD significantly predicted poor RFS (RR = 2.32 95% CI: 1.39-3.90; P0.001) and OS (RR = 1.44; 95% CI: 1.08-1.92; P = 0.01). Using CD31 or CD34, MVD was inversely related to survival, whereas it was not using factor VIII. Vascular endothelial growth factor expression significantly predicted poor RFS (RR = 2.84; 95% CI: 1.95-4.16) and OS (RR=1.65; 95% CI: 1.27-2.14). To strengthen our findings, future prospective studies should explore the relation between MVD or VEGF expression and survival or response to therapy (e.g. antiangiogenic therapy). Assessment of these angiogenic markers should be better standardised in future studies.

The area of biological and targeted therapies exploded in the late 1990s. After obtaining good results in hematological malignancies, cancer treatment is now being based on monoclonal antibodies. ASCO has integrated various areas of biological therapy into its scope of clinical activity. Trastuzumab (Heceptin) and bevacizumab (Avastin), antibodies targeting HER-2 and vascular endothelial growth factor, respectively, were approved by the United States Federal Drug Administration for first-line treatment of metastatic breast and colorectal cancer in combination with chemotherapy. Bevacizumab is the first approved agent to target tumor angiogenesis. This drug is now combined with chemotherapy to treat breast, lung, and colorectal cancer. In the past several years, significant advances in the underlying biological mechanisms of renal cell carcinoma, particularly the role of tumor angiogenesis, have made it possible to design molecularly targeted therapeutics. This meeting review is organized by tumor type and biotherapy modality.

La chirurgie a ete consideree comme le traitement standard du cancer bronchique non a petites cellules operable (CBNPC). Cependant, en depit d’une chirurgie optimale, la survie a 5 ans est mediocre, avec pres de la moitie des patients rechutant et decedant. La meta-analyse publiee en 1995 montrait un benefice pour les patients traites par une chimiotherapie a base de cisplatine, avec une reduction du risque de rechute de 13 %, non significative, une augmentation de survie de 5 %. Ceci permit de retrouver l’interet d’une chimiotherapie adjuvante. Ceci a permis d’inclure des milliers de patients dans des etudes randomisees, les patients recevant des traitements a base de cisplatine et des drogues recentes (paclitaxel ou vinorelbine). Au vu des donnees recentes, une chimiotherapie a base de cisplatine peut desormais etre consideree comme un standard chez les patients en bon etat general et operes de CBNPC.

Strategies for the treatment of metastatic colorectal cancer must take into account the contribution of monoclonal antibodies. A group of new efficient tools in oncology, these drugs target tumor antigens. Bevacizumab recognizes VEGF. Vascular endothelial growth factor (VEGF) is a key mediator in angiogenesis. This antibody combined with chemotherapy increases the survival of patients treated for metastatic colorectal cancer. Median survival of patients treated with antibodies and chemotherapy is 20 months, compared with only 15 months for patients treated with chemotherapy alone. Cetuximab is a monoclonal antibody that binds competitively and with high affinity to the EGF receptor. Cetuximab is currently approved for use in patients with pretreated colorectal cancer. EGF is a major cell growth factor. The side effects of these new biotherapies are different from chemotherapy: bevacizumab affects vascular elements and the most common side effect of anti-EGFR treatment is acneiform skin rash.

A microsatellite instability (MSI) phenotype is found in about 12% of colorectal cancers (CRCs) and is associated with a low recurrence rate after curative surgery. Several studies have identified clinical and pathological factors predictive of recurrence in resected CRC, but not in the MSI subgroup.This multicentre retrospective study included patients with stage I, II or III MSI CRCs. Disease-free survival (DFS) was calculated with the Kaplan-Meier method. Factors associated with DFS were identified in univariate and multivariate Cox analyses.We studied 521 patients with MSI CRC. Respectively 11%, 51% and 38% of patients were at stage I, II and III. Mean age was 68.7years and 36% of the patients received adjuvant chemotherapy. Median follow-up was 32.8months. The disease recurrence rates were 6% and 21% in stage II and III patients, respectively. The 3-year DFS rate was 77%. In univariate analysis, age, bowel obstruction, lymph node invasion, stage T4, vascular emboli, lymphatic invasion and perinervous invasion were associated with poorer DFS (P0.05). Three relevant independent predictors of poor DFS were identified in multivariate analysis, namely bowel obstruction (HR=2.46; 95%CI 1.31-4.62, P=0.005), vascular emboli (HR=2.79; 95%CI 1.74-4.47, P0.001) and stage T4 (HR=2.16; 95%CI 1.31-3.56, P=0.002).Bowel obstruction, vascular emboli and stage T4 are independently associated with MSI CRC recurrence, suggesting that screening for vascular emboli in routine clinical practice may assist with adjuvant chemotherapy decision-making.

Le cancer colorectal est un cancer frequent. Il s’agit du troisieme, par ordre de frequence chez l’homme, apres ceux du poumon et de la prostate, et le deuxieme chez la femme, apres le sein. On estimait en 2000 a 36 000 le nombre de nouveaux cas de cancers colorectaux. La survie des patients, comme dans tout cancer, depend du stade lors de sa decouverte. Elle varie a 5 ans de 90 % pour les stades initiaux (stade I) a 10% (stade IV). Ces deux raisons, importance du nombre et gravite de la maladie (si decouverte tardivement), justifient le principe du depistage. L’articulation entre une vision medicale et une vision chirurgicale reste la base du traitement de cette maladie, avec la resection notamment de la tumeur primitive. Actuellement, des biotherapies sont donnees en association a la chimiotherapie pour potentialiser leur efficacite reciproque, mais pourraient aussi etre utilisees en monotherapie pour maintenir l’efficacite et obtenir des taux de controle de la maladie plus eleves.

Resume Introduction Une meningite carcinomateuse est une complication majeure dans le CBNPC. Malgre le traitement par radiotherapie associee ou non a une chimiotherapie intra-thecale ou systemique, le pronostic reste tres reserve. Observations Nous rapportons l’observation d’une patiente non tabagique atteinte d’un adenocarcinome bronchique de type bronchiolo-alveolaire, presentant un meningite carcinomateuse compliquant l’evolution de sa maladie 3 ans apres le diagnostic de la tumeur primitive. Le traitement par gefitinib est initie apres une radiotherapie cerebrale devant la persistance d’un syndrome meninge. Ce traitement a permis une reponse clinique en moins de 3 semaines, et le maintien de cette reponse pendant 9 mois. Conclusion Le gefitinib peut entrainer une amelioration symptomatique sur la meningite carcinomateuse dans le CBNPC. Il merite d’etre evalue dans cette indication vu l’absence de toute therapeutique classique reellement active.

Resume Introduction En 2003 les nouvelles biotherapies faisaient une entree fracassante avec deux etudes majeures, celle d’Hurwitz avec l’Avastin® antiangiogenique (contre la micro-vascularisation tumorale) et l’etude connue sous le nom BOND avec l’anti-EGF, ou Erbitux®; (plus directement contre la proliferation tumorale). Ce dernier traitement est commercialise actuellement. Bien entendu les traitements chirurgicaux restent la premiere phase des traitements anticancereux, mais ils sont desormais secondes par des traitements qui s’affirment. Des etudes presentees paraissent importantes, d’abord dans le domaine des traitements adjuvants des cancers colorectaux, mais aussi celui des cancers metastatiques (nouvelles biotherapies). Enfin, de nouveaux traitements sont proposes dans les cancers plus rares et plus agressifs comme les cancers œsogastriques ou pancreatiques.

Incidence of colorectal cancers (CRCs) increases with age. The surgical and medical management of elderly patients needs to be improved. Until recently, these patients were not included into controlled clinical trials. Between 2004 and 2007, 88 patients (median age 79) had surgery for CRC in our hospital. In half the cases, patients had an emergency surgery (40/88). Twenty patients had dementia, with no relationships between dementia and emergency surgery (50% vs. 45% for patients without dementia), nor between dementia and median length of hospital stay (16 days vs. 22 days). In metastatic setting (20 patients), chemotherapy was omitted in 10 cases, usually patients with dementia (5 patients; p = 0.002) Standard therapy was hardly applicable because many patients were frail. In the future, usefulness of participation to the staffs of a geriatrist will be assessed prospectively.

Small bowel adenocarcinoma is a rare condition with poor prognosis. Like colorectal cancer, small bowel carcinoma may be a part of genetic syndromes with carcinogenetic pathways different from sporadic forms. We report a case of 41-year-old man with small bowel carcinoma revealing hereditary non polyposis colorectal cancer (HNPCC) syndrome. This report supports the systematic study of the MSI status in every patient with a small bowel carcinoma below 60-year-old of age in order to screen for HNPCC syndrome even in the absence of a family history of related cancers.

Every year in Europe and in USA, more than 60% of new cases of cancer are diagnosed at the patient's of more than 65 years with a mortality of more than 70%. Pain, is a major symptom which often accompanies cancer. It is always painful and intolerable, notably when pain is linked to bone metastases to elderly patients often poly pathological. In 1/3 of cases pain is present at the time of diagnosis of cancer and in 2/3 of cases at the advanced diseases. The bone metastases occupy the third place after the pulmonary and liver metastases. They are in order of frequency linked in breast cancer, the kidney and the prostate cancer. Bone metastases are at the origin of the loss of the elderly autonomy, with for consequence an impairment of quality of life. Validated tools are at now available to assess this pain. The different treatments offered in bone metastases pain are: the chemotherapy, the surgery, radiotherapy, bisphosphonates and analgesic treatment.

Colorectal cancer (CRC) is predominantly a disease of the elderly. The increase of life expectancy will no doubt lead to an increase of these cancers. Few studies have been specially designed for older patients treated for CRC. In general, publications consisted of small phase II studies or retrospective analyses of the subpopulation of elderly patients (from large phase III) -- patients over the age of 65 as compared with younger patients. Therefore we now need to offer specific treatment combining oncologist and geriatric physicians to better codify and adapt treatments to the physiological age of the patient. This is a review of the different stages of care for elderly patients with colorectal cancer in the light of recent publications.

Les tres nombreux travaux menes depuis les annees soixante sur le role de ľangiogenese dans les cancers ont permis ďaboutir a des traitements ciblant ce processus physiopathologique (1, 2).

Microsatelite instability (MSI) is the consequence of the inactivation of a mismatch repair gene and is observed in approximately 15% of colon cancer cases. Patients with MSI colon cancer do not benefit from 5-fluorouracil (5-FU)-based chemotherapy. A current treatment of reference for colon cancer is a combination of 5-FU and oxaliplatin (FOLFOX). The aim of this study was to determine the efficiency of the FOLFOX treatment in patients with metastatic MSI colon cancer.Tumour specimens were collected from patients with metastatic colon cancer treated with FOLFOX 4 modified or FOLFOX 6; these two regimens are based on 85 mg/m2 and 100 mg/m2 oxaliplatin, respectively. The MSI status was assessed by measuring the length of five monomorphic mononucleotide markers. The FOLFOX regimen was evaluated as a first-line treatment according to WHO criteria.Forty patients (22 men, 18 women), median age 63.5 years (27-83 years) were treated with FOLFOX 4 or 6. Nine patients had tumours exhibiting high MSI (MSI group) and 31 patients had tumours exhibiting microsatellite stability (MSS group). In the MSS group, 11 partial responses (36%) were observed, while there were only two in the MSI group (22%) (no significant difference). The two patients who were responders in the MSI group were treated with FOLFOX 6. The overall survival was not significantly different for MSI and MSS patients.No significant differences in the overall response rate or overall survival between the two groups of patients were observed. However, these results suggest that patients with MSI colon cancer are more sensitive to a higher dose of FOLFOX.

Sunitinib inhibits numerous tyrosine kinase receptors involved in tumor growth, angiogenesis, and metastatic invasion. It is indicated in case of metastatic renal carcinomas and gastrointestinal stromal tumors (GIST) resistant to imatinib. Prospective and retrospective studies have shown association between use of sunitinib and hypothyroidism affecting more than 50% of patients in some series. More amazing, was the non-visualisation of thyroid tissue evaluated with thyroid ultrasonography in two cases. Mechanisms of this side effect are not elucidated. Some studies have suggested destructive thyroiditis but no evidence of autoimmunity has been demonstrated. Anti angiogenic effect could be another hypothesis. Recently antithyroperoxidase activity of sunitinib has been demonstrated. Because hypothyroidism is easily accessible to treatment, screening of thyroid abnormalities is mandatory every three months to improve quality of life of these patients. This unique thyroid side effect of sunitinib with the non-visualisation of thyroid suggests a possible and promising antitumor activity in thyroid cancer.

Carcinomatous meningitis is a major complication in Non Small Cell Lung Cancer (NSCLC). Despite treatment with radiotherapy alone or in combination with intrathecal and systemic chemotherapy, its prognosis remains poor.We report a case of a female non-smoker with adenocarcinoma with bronchoalveolar features presenting with carcinomatous meningitis three years after the diagnosis of her primary tumour. Gefitinib treatment was proposed because of the persistence of meningitic symptoms despite cranial irradiation. Clinical response was observed within 3 weeks and lasted for 9 months.Gefitinib may be effective in treating carcinomatous meningitis complicating NSCLC and should be considered in this situation given the absence of effective alternatives.

Strategies for the treatment of metastatic colorectal cancer must take into account the contribution of monoclonal antibodies. A group of new efficient tools in oncology, these drugs target tumor antigens. Bevacizumab recognizes VEGF. Vascular endothelial growth factor (VEGF) is a key mediator in angiogenesis. This antibody combined with chemotherapy increases the survival of patients treated for metastatic colorectal cancer. Median survival of patients treated with antibodies and chemotherapy is 20 months, compared with only 15 months for patients treated with chemotherapy alone. Cetuximab is a monoclonal antibody that binds competitively and with high affinity to the EGF receptor. Cetuximab is currently approved for use in patients with pretreated colorectal cancer. EGF is a major cell growth factor. The side effects of these new biotherapies are different from chemotherapy: bevacizumab affects vascular elements and the most common side effect of anti-EGFR treatment is acneiform skin rash.

A 65-year-old man was treated initially for a localized rectal carcinoma in 1998. One year later, his serum carcinoembryonic antigen (CEA) level increased. Results of a colonoscopy and computed tomography (CT) of the lung were negative. Abdominal CT showed a right suprarenal mass, suggestive of a metastatic tumor. Fluorodeoxyglucose (FDG)-coincidence detection (CDET) imaging showed an isolated right suprarenal focus of uptake. Adrenalectomy confirmed the diagnosis. F-18 FDG can be used to determine whether tumors are resectable in patients with elevated CEA levels. The CT scan showed an isolated adrenal tumor, whereas FDG-CDET imaging characterized this enlargement as probably malignant with no other sites of pathologic uptake.

Background Tyrosine-Kinase Inhibitors (TKIs) markedly improve Progression Free Survival (PFS) of advanced NSCLC patients mutated for Epidermal Growth Factor Receptor (EGFR). Results on Overall Survival (OS) are more questionable. Therefore, we performed a publication-based meta-analysis to further assess this issue. Methods We did a PubMed query using keywords simultaneously (lung neoplasm, TKI, EGFR mutation, survival). We also searched for relevant abstracts in proceedings of ASCO, ESMO, WCLC annual meetings. We cross-checked all references from all articles. Only phase III randomized controlled trials comparing TKI and chemotherapy were included. We used EasyMA software. Results The 6 eligible studies included 2223 patients (516 males, 1688 females, mostly Asian, median age 60 years, 2155 adenocarcinomas (97 %), 996 mutated tumors, 389 stage IIIB, 1572 Stage IV (71 %), 1989 never smokers (89.5 %). Four studies assessed gefitinib, 2 erlotinib. Chemotherapies were doublets including a platinum salt. Four studies included only mutated patients. Compared to chemotherapy, EGFR TKIs significantly improved PFS (HR = 0.39, 95 % CI 0.28-0.53, random effect model). Conversely, OS was similar among patients who first received TKI or chemotherapy (HR = 1.00, CI 0.83-1.22, fixed effect model). PFS was significantly worse among non mutated patients in the 2 studies including both mutated and wild-type EGFR patients, whereas OS was unchanged. Concerning side-effects, rash, diarrhoea and interstitial lung disease were significantly more frequent after TKI (RRs 5.00; 2.40 and 6.07). As expected, fatigue (RR 0.41), nausea/vomiting (0.19) and haematological disorders were all significantly more frequent after chemotherapy (RRs for neutropenia, thrombocytopenia and anaemia 0.08; 0.18 and 0.26). Conclusions The major discrepancy between a markedly improved PFS and a similar OS after TKI compared with chemotherapy could be related to the high level of crossing-over between the 2 groups. We found no detrimental effect on OS of TKIs among wild-type patients. Disclosure All authors have declared no conflicts of interest.

Gastrointestinal stromal tumors (GISTs) are non differentiated sarcoma of the gastrointestinal tract and have for a long time been confused with well differentiated tumors and classified as leiomyosarcoma. These tumors are characterized immunohistochemically by CD 117 staining. This marker represents the expression of c-kit which is a receptor for growth factor with enzymatic activity (tyrosine kinase). Recent studies have found that an inhibitor of specific tyrosine kinase is effective in the treatment of GIST with an estimated response rate of more than 60%. This new drug could significantly improve the prognosis of these aggressive chemoresistant tumors.

Micrometastasis are defined by the existence of cells or groups of cells in target organs. In the particular cas of colon cancers, although lymph node involvement is frequent, metastatic medullary involvement (while rarely at the origin of identified metastasis) can also be observed. Furthermore, micrometastatics cells can be identified in the circulating blood. This research relies on recent technics of immunocytochemistry with image analysis or molecular biology technics (generally PCR or RT-PCR). It is essential to have a specific reliable marker of metastatic cells. The prognostic value of identifying micrometastasis in organs also remains to be defined.

Introduction: The prevalence of cancer increases with age, and pain is one of cancer's most frequent and disturbing symptoms. Numerous studies have evaluated various treatment approaches, but how pain and symptoms are assessed and managed in elderly people with cancer is unclear. Objectives: The purpose of this study was to estimate the prevalence of pain and to evaluate the adequacy of pain management in elderly patients with cancer. Methods: Using medical charts, we screened all patients with malignant disease, admitted to the geriatric oncology unit, and evaluated by means of CGA to determine the optimum treatment, between January 2011 and January 2013. Demographic data, characteristics of the cancer, reported pain, geriatric data, and analgesic treatment were collected for each patient. Results: 311 elderly patients with cancer were assessed. Median age was 84 ± 6.2 years [66–100]. Patients were predominantly female (60%). The most frequent locations of malignant disease were breast (24%), gastrointestinal (22%), lung (20%), and haematological (16%). Prevalence of reported pain was 44% (137 patients). The highest pain prevalence was observed in gastrointestinal cancer patients (48%). Metastatic patients have significantly more pain, (OR = 4.26, CI 95%: 2.61 – 6.96). 75% of patients with bone metastasis (n = 33/44) experienced pain, (OR = 6.31, CI 95%: 3.04–13.08). Among patients with low cognitive performance (n = 61), only 18% reported pain. Analgesics were prescribed in 197 patients (63%). Only 7% of overall patients received WHO level 3 drugs. Conclusion: This study clearly reports a high prevalence of pain and reduced drug prescribing and treatment among elderly patients with cancer. This issue appears to be most critical among people with severe dementia. Older individuals were less likely to receive any analgesia, especially morphine or another WHO level 3 drugs. The lack of prescription is probably linked to under assessment of pain and fear of adverse effects. Disclosure of interest: None declared.

The identification of factors associated with breast recurrence as first event (62 cases, 10%) following conservative surgery and radiation therapy are drawn out from a series++ of 618 mammary carcinomas of clinical size less than 40 mm, stage I and II (UICC), with a median follow up of 8 years. The most powerful predictive characteristic associated with the likelihood of breast recurrence is multiple foci of invasion (42.9% vs 8.9, P = 0.0001, relative risk [RR]: 6). After this rarely cited feature, young age, less than 40 years (20% vs 7.3%, P = 0.0001, RR: 2.8), extensive in situ carcinoma more than 25% (19.2% vs 8.7%, P = 0.003, RR: 2.5) were found also persistent in the Cox model, but not histologic size more than 25 mm (18.9% vs 9.1%, P = 0.01, RR: 2.3). The site of recurrence was studied on the 54 salvage mastectomy done. A high rate of recurrence at distance of the initial site was found: 37% whose more than half, 22%, were multicentric. No significant difference in the mean delay of appearance was noted between recurrence near or at distance of the initial cancer (mean delay 52 months vs 64 months). From the recurrence the evolution is not very favourable: excluding simultaneous metastases found at the preoperative investigation, ten cases, mammary recurrence is followed by a metastatic syndrome in 36% of cases against 17% without it (P = 0.01, RR: 1.9). Metastatic evolution is not significantly linked with the time, early or late, of the mammary recurrence (54.5% before 5 years vs 39% after) but with the association of a controlateral cancer (P = 0.03). Locally ten of the 54 mastectomy presented a thoracic recurrence, often in case of multicentric breast recurrence (P = 0.05) and not significantly when skin or areola were invaded by carcinoma.