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Pancreas 04/2013; 42(3):543-544. · 2.39 Impact Factor
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Sophie Gourgou-Bourgade,
Caroline Bascoul-Mollevi,
Françoise Desseigne,
Marc Ychou,
Olivier Bouché, Rosine Guimbaud,
Yves Bécouarn,
Antoine Adenis,
Jean-Luc Raoul,
Valérie Boige,
Jocelyne Bérille,
Thierry Conroy
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ABSTRACT: PURPOSETo compare the quality of life (QoL) of patients receiving oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) or gemcitabine as first-line chemotherapy and to assess whether pretreatment QoL predicts survival in patients with metastatic pancreatic cancer.Patients And methodsThree hundred forty-two patients with performance status 0 or 1 were randomly assigned to receive FOLFIRINOX (oxaliplatin, 85 mg/m(2); irinotecan, 180 mg/m(2); leucovorin, 400 mg/m(2); and fluorouracil, 400 mg/m(2) bolus followed by 2,400 mg/m(2) 46-hour continuous infusion, once every 2 weeks) or gemcitabine 1,000 mg/m(2) weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. QoL was assessed using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30 every 2 weeks.ResultsImprovement in global health status (GHS; P < .001) was observed in the FOLFIRINOX arm and improvement in emotional functioning (P < .001) was observed in both arms, along with a decrease in pain, insomnia, anorexia, and constipation in both arms. A significant increase in diarrhea was observed in the FOLFIRINOX arm during the first 2 months of chemotherapy. Time until definitive deterioration ≥ 20 points was significantly longer for FOLFIRINOX compared with gemcitabine for GHS, physical, role, cognitive, and social functioning, and six symptom domains (fatigue, nausea/vomiting, pain, dyspnea, anorexia, and constipation). Physical functioning, constipation, and dyspnea were independent significant prognostic factors for survival with treatment arm, age older than 65 years, and low serum albumin. CONCLUSIONFOLFIRINOX significantly reduces QoL impairment compared with gemcitabine in patients with metastatic pancreatic cancer. Furthermore, baseline QoL scores improved estimation of survival probability when added to baseline clinical and demographic variables.
Journal of Clinical Oncology 12/2012; · 18.37 Impact Factor
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Adrien Decorsière,
Christine Toulas,
Françoise Fouque,
Anne-Françoise Tilkin-Mariamé,
Janick Selves, Rosine Guimbaud,
Edith Chipoulet,
Caroline Delmas,
Jean-Marc Rey,
Pascal Pujol,
Gilles Favre,
Stefania Millevoi,
Stéphan Vagner
Cell cycle (Georgetown, Tex.) 07/2012; 11(13):2578-80. · 5.36 Impact Factor
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Delphine Bonnet,
Janick Selves,
Christine Toulas,
Marie Danjoux,
Jean Pierre Duffas,
Guillaume Portier,
Sylvain Kirzin,
Laurent Ghouti,
Nicolas Carrère,
Bertrand Suc,
Laurent Alric,
Karl Barange,
Louis Buscail,
Thierry Chaubard,
Kamran Imani, Rosine Guimbaud
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ABSTRACT: Recommended strategies to screen for Lynch syndrome in colorectal cancer are not applied in daily practice and most of Lynch cases remain undiagnosed.
We investigated in routine conditions a strategy that uses simplified clinical criteria plus detection of MisMatch Repair deficiency in tumours to identify Lynch carriers.
Colorectal cancer patients that met at least one of three clinical criteria were included: (1) colorectal cancer before 50 years, (2) personal history of colorectal or endometrial cancer, (3) first-degree relative history of colorectal or endometrial cancer. All tumours underwent an MisMatch Repair test combining microsatellite instability analysis and MisMatch Repair immunohistochemistry. Patients with an MisMatch Repair-deficient tumour were offered germline testing.
Of the 307 patients fulfilling the clinical criteria, 46 (15%) had a MisMatch Repair-deficient tumour. Amongst them 27 were identified as Lynch carriers (20 with germline mutation: 12 MLH1, 7 MSH2, 1 MSH6; 7 highly suspected cases despite failure of genetic testing). The simplified clinical criteria selected a population whose MisMatch Repair-deficient status was highly predictive (59%) of Lynch syndrome.
This bio-clinical strategy based on simplified clinical criteria combined with an MisMatch Repair test efficiently detected LS cases and is easy to use in clinical practice, outside expert centres.
Digestive and Liver Disease 04/2012; 44(6):515-22. · 3.05 Impact Factor
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Valérie Bonadona,
Bernard Bonaïti,
Sylviane Olschwang,
Sophie Grandjouan,
Laetitia Huiart,
Michel Longy, Rosine Guimbaud,
Bruno Buecher,
Yves-Jean Bignon,
Olivier Caron, [......],
Françoise Desseigne,
Jean-Christophe Saurin,
Pascaline Berthet,
Dominique Leroux,
Jacqueline Duffour,
Sylvie Manouvrier,
Thierry Frébourg,
Hagay Sobol,
Christine Lasset,
Catherine Bonaïti-Pellié
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ABSTRACT: Providing accurate estimates of cancer risks is a major challenge in the clinical management of Lynch syndrome.
To estimate the age-specific cumulative risks of developing various tumors using a large series of families with mutations of the MLH1, MSH2, and MSH6 genes.
Families with Lynch syndrome enrolled between January 1, 2006, and December 31, 2009, from 40 French cancer genetics clinics participating in the ERISCAM (Estimation des Risques de Cancer chez les porteurs de mutation des gènes MMR) study; 537 families with segregating mutated genes (248 with MLH1; 256 with MSH2; and 33 with MSH6) were analyzed.
Age-specific cumulative cancer risks estimated using the genotype restricted likelihood (GRL) method accounting for ascertainment bias.
Significant differences in estimated cumulative cancer risk were found between the 3 mutated genes (P = .01). The estimated cumulative risks of colorectal cancer by age 70 years were 41% (95% confidence intervals [CI], 25%-70%) for MLH1 mutation carriers, 48% (95% CI, 30%-77%) for MSH2, and 12% (95% CI, 8%-22%) for MSH6. For endometrial cancer, corresponding risks were 54% (95% CI, 20%-80%), 21% (95% CI, 8%-77%), and 16% (95% CI, 8%-32%). For ovarian cancer, they were 20% (95% CI, 1%-65%), 24% (95% CI, 3%-52%), and 1% (95% CI, 0%-3%). The estimated cumulative risks by age 40 years did not exceed 2% (95% CI, 0%-7%) for endometrial cancer nor 1% (95% CI, 0%-3%) for ovarian cancer, irrespective of the gene. The estimated lifetime risks for other tumor types did not exceed 3% with any of the gene mutations.
MSH6 mutations are associated with markedly lower cancer risks than MLH1 or MSH2 mutations. Lifetime ovarian and endometrial cancer risks associated with MLH1 or MSH2 mutations were high but do not increase appreciably until after the age of 40 years.
JAMA The Journal of the American Medical Association 06/2011; 305(22):2304-10. · 30.03 Impact Factor
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American Journal of Medical Genetics Part A 06/2011; 155A(6):1500-2. · 2.39 Impact Factor
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Bruno Landi,
Olivier Bouché, Rosine Guimbaud,
Thomas Aparicio,
Anne Berger,
Sylvie Bonvalot,
Bruno Buecher,
Jean-Yves Blay,
Christian Boustière,
Jean-Marie Coindre,
Jean-François Emile,
Marc Giovannini,
Thierry Lecomte,
Axel Le Cesne,
Geneviève Monges,
Bertrand Napoléon,
Laurent Palazzo,
Jean-Alain Chayvialle
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ABSTRACT: A number of guidelines on the management of gastro-intestinal stromal tumours (GISTs) have been published, mostly based on expert consensus. However, these guidelines have generally failed to address the specific problem of GISTs of limited size (i.e. those measuring a few centimetres in diameter) with which gastroenterologists are increasingly confronted. The aim of the present work was to draw up proposals for the diagnosis and treatment of GISTs measuring less than 5 cm in diameter. For this purpose, a number of practical questions were put to a panel of French experts.
Digestive and Liver Disease 05/2011; 43(12):935-9. · 3.05 Impact Factor
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Thierry Conroy,
Françoise Desseigne,
Marc Ychou,
Olivier Bouché, Rosine Guimbaud,
Yves Bécouarn,
Antoine Adenis,
Jean-Luc Raoul,
Sophie Gourgou-Bourgade,
Christelle de la Fouchardière,
Jaafar Bennouna,
Jean-Baptiste Bachet,
Faiza Khemissa-Akouz,
Denis Péré-Vergé,
Catherine Delbaldo,
Eric Assenat,
Bruno Chauffert,
Pierre Michel,
Christine Montoto-Grillot,
Michel Ducreux
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ABSTRACT: Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.
We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival.
The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001).
As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.).
New England Journal of Medicine 05/2011; 364(19):1817-25. · 53.30 Impact Factor
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Rosine Guimbaud
Annales de Pathologie 11/2010; 30(5 Suppl 1):77-9. · 0.25 Impact Factor
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Breast Cancer Research and Treatment 09/2009; 120(1):267-70. · 4.43 Impact Factor
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[show abstract]
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ABSTRACT: Well-differentiated metastatic endocrine carcinomas are difficult to manage because of variable disease outcome. New prognostic factors are required. These tumors overexpress somatostatin receptors (sst), implying the use of somatostatin analogs for tumor localization by somatostatin receptor scintigraphy using indium-111-pentetreotide ((111)In-pentetreotide) and for medical treatment. The aim of the present study was to evaluate the correlation between (111)In-pentetreotide scintigraphy, sst receptor expression, and prognosis.
Between 1994 and 2002, 48 consecutive patients with well-differentiated endocrine carcinomas and a negative (111)In-pentetreotide scintigraphy were retrospectively paired according to sex, age, and tumor localization with 50 patients with well-differentiated endocrine carcinomas and a positive tracer uptake at (111)In-pentetreotide scintigraphy. Overall survival and expression of sst1 to sst5 receptors by immunohistochemistry were assessed.
The lack of tracer uptake at the (111)In-pentetreotide scintigraphy seemed to be a poor prognostic factor (P = .007) for overall survival by Kaplan-Meier test and in multivariate analysis; age and absence of clinical secretory syndrome also seemed to be poor prognostic factors. The tracer uptake (positive (111)In-pentetreotide scintigraphy) correlated with the tumor expression of somatostatin receptor sst2 (P < .001) but not with that of sst1, sst3, sst4, or sst5. In a bivariate analysis, lack of sst2 expression also significantly correlated with poor prognosis.
We demonstrate the prognostic value of (111)In-pentetreotide scintigraphy in well-differentiated malignant endocrine tumors. In these tumors, sst2 somatostatin receptor expression correlates with both tracer uptake and a better prognosis.
Journal of Clinical Oncology 03/2008; 26(6):963-70. · 18.37 Impact Factor
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ABSTRACT: Local recurrence (LR) after curative surgery for rectal cancer occurs in 4 to 33% of cases especially if surgery is sub-optimal (without total excision of the mesorectum). In many cases, diagnosis of LR is made at a late stage because of the high rate of asymptomatic patients, 56% in the experience of the Mayo Clinic. MRI and PETscan are most effective for assessing local and general extension, with a high diagnostic accuracy. Surgical treatment alone or with radiation (preoperative and/or intraoperative) is the only curative treatment of LR with R0 resectability rates of 30% to 45%. Morbidity and mortality rates are high, especially for total exenteration and abdomino-sacral resection. After curative surgery, 5-year global survival is between 30% and 40%. Palliative resection of macroscopic residues is not recommended. Careful patient selection for curative surgery is the best way to optimize treatment in these cases.
Gastroentérologie Clinique et Biologique 02/2007; 31(1):55-67. · 0.80 Impact Factor
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Guillaume Portier,
Dominique Elias,
Olivier Bouche,
Philippe Rougier,
Jean-François Bosset,
Jean Saric,
Jacques Belghiti,
Pascal Piedbois, Rosine Guimbaud,
Bernard Nordlinger,
Roland Bugat,
Franck Lazorthes,
Laurent Bedenne
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ABSTRACT: Complete resection of liver metastases of colorectal origin is the only potentially curative treatment. In order to decrease recurrences, the use of adjuvant systemic chemotherapy after liver resection is controversial because no randomized study demonstrated its benefit.
In a multicenter trial, we randomly assigned 173 patients with completely resected (R0) hepatic metastases from colorectal cancer to surgery alone and observation (87 patients) or to surgery followed by 6 months of systemic adjuvant chemotherapy with a fluorouracil and folinic acid monthly regimen (86 patients). The main outcome criterion was disease-free survival. Secondary outcome measures were overall survival and treatment-related toxicity.
The intention-to-treat analysis was based on 171 patients, after a median follow-up of 87 months (SE = 5.8). The 5-year disease-free survival rate, after adjustment for major prognostic factors, was 33.5% for patients in the chemotherapy group and 26.7% for patients in the control group (Cox multivariate analysis: odds ratio for recurrence or death = 0.66; 95% CI, 0.46 to 0.96; P = .028). With regard to secondary outcome measures, a trend towards increased overall survival was observed but did not reach statistical significance (5-year overall survival: chemotherapy group, 51.1% v control group, 41.1%; odds ratio for death, 0.73; 95% CI, 0.48 to 1.10; P = .13).
Despite a suboptimal regimen, which was the standard at the beginning of the study, adjuvant intravenous systemic chemotherapy provided a significant disease-free survival benefit for patients with resected liver metastases from colorectal cancer.
Journal of Clinical Oncology 12/2006; 24(31):4976-82. · 18.37 Impact Factor
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ABSTRACT: The determination ofmicrosatellite instability (MSI) is an important step in the identification of familial colorectal cancer such as hereditary nonpolyposis colon cancer. It could also be of interest in the therapeutic management of sporadic cancer. International criteria for the determination of MSI have been published, recommending the use of microdissection. The aim of this work was to evaluate the impact of contaminant normal DNA in tumor samples for MSI assessment in colorectal cancer using a microdissection technique. We performed a comparative analysis of the microsatellite status between total DNA (DNA extracted from whole tumor samples) and microdissected DNA in 3 different regions from 23 cases of colorectal cancer. Six microsatellites were amplified using fluorescent polymerase chain reaction. We analyzed 9 cases with MSI and 14 cases without instability, with similar results between total DNA and microdissected DNA. Moreover, within a same tumor, the MSI phenotype was observed regardless of the region analyzed. Thus, this work shows the reproducibility of the MSI phenotype throughout a tumor. However, we observed a regional heterogeneity of the MSI profile, consisting of variations in the number and the size of unstable alleles within different regions. This result reflects the genetic heterogeneity of colorectal cancer with MSI. In the 14 cases without instability, we observed an increase of more than 60% in the loss of heterozygosity detection rate after microdissection. Thus, this work confirms the contribution of microdissection for loss of heterozygosity assessment.
Human Pathlogy 04/2006; 37(3):361-8. · 2.88 Impact Factor
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Gastroentérologie Clinique et Biologique 02/2006; 30(1):106-9. · 0.80 Impact Factor
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David J Hughes,
Sophie M Ginolhac,
Isabelle Coupier,
Laure Barjhoux,
Valérie Gaborieau,
Brigitte Bressac-de-Paillerets,
Agnès Chompret,
Yves-Jean Bignon,
Nancy Uhrhammer,
Christine Lasset, [......],
Michel Longy,
Christine Toulas, Rosine Guimbaud,
Drakoulis Yannoukakos,
Sylvie Mazoyer,
Henry T Lynch,
Gilbert M Lenoir,
David E Goldgar,
Dominique Stoppa-Lyonnet,
Olga M Sinilnikova
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ABSTRACT: Marked variation in phenotypic expression among BRCA1 and BRCA2 mutation carriers may be partly explained by modifier genes that influence mutation penetrance. Variation in CAG/CAA repeat lengths coding for stretches of glutamines in the C-terminus of the AIB1 protein (amplified in breast cancer 1, a steroid receptor coactivator) has been proposed to modify the breast cancer risk in women carrying germline BRCA1 mutations. We genotyped the AIB1 repeat length polymorphism from the genomic DNA of a group of 851 BRCA1 and 324 BRCA2 female germline mutation carriers to estimate an association with breast cancer risk modification. Hazard ratios (HR) were calculated using a Cox proportional hazards model. For BRCA1 and BRCA2 mutation carriers, analyzed separately and together, we found that women who carried alleles with 28 or more polyglutamine repeats had no increased risk of breast cancer compared to those who carried alleles with fewer repeats (HR for BRCA1/2 carriers = 0.88, 95% CI [confidence interval] = 0.75-1.04). Analyzing average repeat lengths as a continuous variable showed no excess risk of breast cancer (BC) in BRCA1 or BRCA2 mutation carriers (HR for average repeat length in BRCA1/2 carriers = 1.01, 95% CI = 0.92-1.11). These results strongly suggest that contrary to previous studies, there is no significant effect of AIB1 genetic variation on BC risk in BRCA1 mutation carriers and provide an indication that there is also no strong risk modification in BRCA2 carriers.
International Journal of Cancer 12/2005; 117(2):230-3. · 5.44 Impact Factor
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Rosine Guimbaud
Gastroentérologie Clinique et Biologique 11/2005; 29(10):1041-3. · 0.80 Impact Factor
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David J Hughes,
Sophie M Ginolhac,
Isabelle Coupier,
Marilys Corbex,
Brigitte Bressac-de-Paillerets,
Agnès Chompret,
Yves-Jean Bignon,
Nancy Uhrhammer,
Christine Lasset,
Sophie Giraud, [......],
Francine Durocher,
Anne-Marie Moisan,
Jacques Simard,
Sylvie Mazoyer,
Henry T Lynch,
Csilla Szabo,
Gilbert M Lenoir,
David E Goldgar,
Dominique Stoppa-Lyonnet,
Olga M Sinilnikova
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ABSTRACT: The HH genotype of the nonconservative amino acid substitution polymorphism N372H in the BRCA2 gene was reported to be associated with a 1.3- to 1.5-fold increase in risk of both breast and ovarian cancer. As these studies concerned sporadic cancer cases, we investigated whether N372H and another common variant located in the 5'-untranslated region (203G > A) of the BRCA2 gene modify breast or ovarian cancer risk in BRCA1 mutation carriers. The study includes 778 women carrying a BRCA1 germ-line mutation belonging to 403 families. The two BRCA2 variants were analyzed by the TaqMan allelic discrimination technique. Genotypes were analyzed by disease-free survival analysis using a Cox proportional hazards model. We found no evidence of a significant modification of breast cancer penetrance in BRCA1 mutation carriers by either polymorphism. In respect of ovarian cancer risk, we also saw no effect with the N372H variant but we did observe a borderline association with the 5'-untranslated region 203A allele (hazard ratio, 1.43; CI, 1.01-2.00). In contrast to the result of Healey et al. on newborn females and adult female controls, we found no departure from Hardy-Weinberg equilibrium in the distribution of N372H alleles for our female BRCA1 carriers. We conclude that if these single-nucleotide polymorphisms do modify the risk of cancer in BRCA1 mutation carriers, their effects are not significantly larger than that of N372H previously observed in the general population.
Cancer Epidemiology Biomarkers & Prevention 02/2005; 14(1):265-7. · 4.12 Impact Factor
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ABSTRACT: Although annexin l exerts extracellular anti-inflammatory properties, little is known about its release in inflammatory diseases. Here, we characterized annexin 1 secretion in ulcerative colitis (UC) patients. Annexin 1 was detected by immunoblotting, in tissue homogenates and supernatants of colonic biopsies incubated in culture media, and in luminal colonic perfusates of UC patients. Annexin 1 was released by inflamed colonic biopsies from patients having severe UC but not by biopsies from healthy colon of the same patient or by biopsies from non-UC patients or from patients with slight or moderate UC. Annexin 1 was detected in luminal colonic perfusates of patients having moderate or slight UC but not in perfusates from control patients. The level of annexin 1 expression and secretion was unrelated to long-term glucocorticoid treatment, but annexin 1 secretion in perfusates was induced, in some patients, by short-term glucocorticoid exposure. These results show that annexin 1 is secreted endogenously in the colon of patients with UC. This secretion, which occurs both in vitro and in vivo, depends on the severity of inflammation. Given the anti-inflammatory effects of annexin 1, this protein may serve to down-regulate the inflammatory response in the course of inflammatory bowel disease.
Inflammatory Bowel Diseases 10/2004; 10(5):584-92. · 4.86 Impact Factor
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Rosine Guimbaud
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ABSTRACT: Close to half of patients suffering from colorectal cancer develop metastases. Their natural prognosis is grim with a median survival of 6 to 7 months. Current treatment options rest on surgery and (or) chemotherapy. Complete surgical excision of the metastates is the treatment of choice as it permits cure rates and levels of long-term survival never attained with chemotherapy. It is only justified if it is complete; it must be systematically discussed with a specialised multidisciplinary team. However, it is possible only in a maximum of 10% of patients. More than half of the patients operated on finish by having a recurrence; post-operative chemotherapy seems to diminish this risk. Furthermore, so-called "palliative" chemotherapy consists of protocols that are by and large well tolerated, based on 5-FU-folic acid and more recent cytotoxics such as oxaliplatin and irinotecan. When a surgical solution cannot be offered (such is the case in the majority of patients), these active treatment plans permit an amelioration in survival (going from a median of 6 months to more that 20 months) without a deterioration in the quality of life. Thus, if the general state of the patient allows, and in the absence of serious organ failure, palliative chemotherapy is most often indicated. Several cycles can be given: tolerance and efficacity must be regularly evaluated so that it is only re-administered in cases of benefit. Sometimes the tumoral reduction is such that metastases that weren't initially resectable become so. The combination of the different therapeutic options has permited significant advances; multidisciplinary discussion of all cases of patients suffering from metastatic colorectal cancer is an indispensable pre-requisite for a well-adapted and efficacious management.
La Revue du praticien 02/2004; 54(2):167-76.
