Manuel Jorge Rodrigues
Curie Institute
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Featured researches published by Manuel Jorge Rodrigues.
European Journal of Cancer | 2010
Nadège Gruel; Carlo Lucchesi; Virginie Raynal; Manuel Jorge Rodrigues; Gaëlle Pierron; Rémi Goudefroye; Paul Cottu; Fabien Reyal; Xavier Sastre-Garau; A. Fourquet; Olivier Delattre; Anne Vincent-Salomon
In order to get insight into the molecular alterations of invasive lobular carcinoma (ILC), comparative genomic hybridisation array and transcriptomic analyses of a series of 62 oestrogens-positive (ER) invasive tumours [21 ILC and 41 invasive ductal carcinomas (IDC)] were performed. ILC and IDC shared highly recurrent regions of gains (1q12-q44(+) in more than 60% of the cases, 16pter-p11.2(+) in 45% and 63% of ILC and IDC, respectively) and losses (16q11.2-q24.2(-) in 84% of ILC and 67.5% of IDC and 17pter-p12(-) in 50% of ILC and IDC). However, ILC genomic signature was characterised by significantly more frequent losses of 13q21.33-q31.3 region (46.5%) and 22q11.23-q12.1 region (50%) whereas IDC showed significantly more frequent losses of 11q23.1-q23.2 region (in 44% of IDC). Nine different regions of high level amplifications were found in 38% of ILC (8/21 cases). Localised on chromosome 11 (11q13.2 region), the most frequent region of amplification encompassing the CCND1 and FGF3 genes was observed in five different ILC. Unsupervised hierarchical clustering of transcriptomic data showed that ILC and IDC clustered apart. Genes involved in cell adhesion, cell communication and trafficking, extra cellular matrix-interaction pathways or cell mobility contributed to this clustering. Despite these differences, the overall clinical outcome of ILC was identical to that of IDC. This molecular study highlights that lobular and oestrogens-positive ductal invasive carcinomas share common genomic alterations but that ILC present some specific molecular alterations. These molecular specificities should help with the identification of new therapeutic targets for ILC patients.
Annals of Oncology | 2013
Manuel Jorge Rodrigues; Julien Péron; J-S Frenel; Y.-A. Vano; J. Wassermann; Marc Debled; F. Picaud; Laurence Albiges; Anne Vincent-Salomon; P. Cottu
BACKGROUND Randomized clinical trials showed the benefit of adjuvant trastuzumab-based chemotherapy (ATBC) for node-positive and/or >1 cm HER2+ breast carcinomas. No efficacy data have been published on ATBC in large series of pT1abN0 HER2+ tumors. PATIENTS AND METHODS This retrospective study evaluated 276 cases of pT1abN0 HER2+ breast tumors in eight French cancer centers. Factors associated with prognosis and ATBC prescription were analyzed. RESULTS A total of 129 cases (47%) were treated with ATBC (ATBC+), 19 with chemotherapy alone, 5 with trastuzumab alone, and 123 (45%) with neither trastuzumab nor chemotherapy (ATBC-). ATBC use was associated with the date of diagnosis (before or after June 2005) and with poor prognostic features. At a median follow-up of 44 months, there were 13 recurrences in the ATBC- group and 2 in the ATBC+ group. ATBC was associated with a significant survival benefit (99% 40-month disease-free survival for ATBC+ versus 93% for ATBC- cases; P = 0.018). Lack of hormone receptors (HRs) and the presence of lymphovascular invasion (LVI) were significantly associated with a poor prognosis and a greater benefit of ATBC. CONCLUSIONS ATBC was associated with a significantly reduced risk of recurrence in pT1abN0 HER2+ tumors, and was more beneficial in HR- and/or LVI+ tumors.
British Journal of Ophthalmology | 2014
Nathalie Cassoux; Manuel Jorge Rodrigues; Corine Plancher; Bernard Asselain; Christine Levy-Gabriel; Livia Lumbroso-Le Rouic; Sophie Piperno-Neumann; Rémi Dendale; Xavier Sastre; Laurence Desjardins; Jérôme Couturier
Objective This study investigated the capacity of genetic analysis of uveal melanoma samples to identify high-risk patients and discusses its clinical implications. Methods Patients with posterior uveal melanoma were prospectively enrolled. Tumour samples were derived from enucleated globe, fine-needle aspirates or endoresection. Chromosome 3 and 8 status was determined by array comparative genomic hybridisation (array-CGH). Patients were followed after treatment to detect metastasis. Results Four groups were classified by array-CGH. Patients were divided into disomy 3 and normal chromosome 8 (D3/8nl), disomy 3 and 8q gain (D3/8g), monosomy 3 and normal chromosome 8 (M3/8nl) and monosomy 3 and 8 or 8q gain (M3/8g). Median follow-up was 28 months (range: 1–147 months). At the end of the study, 128 patients (33.7%) had developed metastasis and 96 patients had died. Univariate Cox proportional hazard analysis showed that factors associated with metastasis included basal tumour diameter p=0.0007, tumour thickness p=0.01, mixed/epithelioid cell type p=0.0009 and genomic data p<0.0001. High-risk profile was more strongly associated with metastasis than the other prognostic factors p<0.001. Multivariate Cox modelling analysis showed that the status of chromosomes 3 and 8 were the only two variables that independently contributed to prognosis: monosomy 3 alone p=0.001 and monosomy 3 and 8q gain p<0.0001. Conclusions Array-CGH allowed identification of three prognostic groups with low, intermediate and high risk of developing metastasis. Array-CGH is a reliable and inexpensive method for uveal melanoma prognosis. This method is now currently used in France.
Journal of Clinical Oncology | 2018
Richard D. Carvajal; Sophie Piperno-Neumann; Ellen Kapiteijn; Paul B. Chapman; Stephen Frank; Anthony M. Joshua; Josep M. Piulats; Pascal Wolter; Veronique Cocquyt; Bartosz Chmielowski; T.R. Jeffry Evans; Lauris Gastaud; Gerald P. Linette; Carola Berking; Jacob Schachter; Manuel Jorge Rodrigues; Alexander N. Shoushtari; Delyth Clemett; Dana Ghiorghiu; Gabriella Mariani; Shirley Spratt; Susan Lovick; Peter Barker; Elaine Kilgour; Zhongwu Lai; Gary K. Schwartz; Paul C. Nathan
Purpose Uveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal melanoma in a randomized phase II trial. Methods The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) study was a phase III, double-blind trial ( ClinicalTrial.gov identifier: NCT01974752) in which patients with metastatic uveal melanoma and no prior systemic therapy were randomly assigned (3:1) to selumetinib (75 mg twice daily) plus dacarbazine (1,000 mg/m2 intravenously on day 1 of every 21-day cycle) or placebo plus dacarbazine. The primary end point was progression-free survival (PFS) by blinded independent central radiologic review. Secondary end points included overall survival and objective response rate. Results A total of 129 patients were randomly assigned to receive selumetinib plus dacarbazine (n = 97) or placebo plus dacarbazine (n = 32). In the selumetinib plus dacarbazine group, 82 patients (85%) experienced a PFS event, compared with 24 (75%) in the placebo plus dacarbazine group (median, 2.8 v 1.8 months); the hazard ratio for PFS was 0.78 (95% CI, 0.48 to 1.27; two-sided P = .32). The objective response rate was 3% with selumetinib plus dacarbazine and 0% with placebo plus dacarbazine (two-sided P = .36). At 37% maturity (n = 48 deaths), analysis of overall survival gave a hazard ratio of 0.75 (95% CI, 0.39 to 1.46; two-sided P = .40). The most frequently reported adverse events (selumetinib plus dacarbazine v placebo plus dacarbazine) were nausea (62% v 19%), rash (57% v 6%), fatigue (44% v 47%), diarrhea (44% v 22%), and peripheral edema (43% v 6%). Conclusion In patients with metastatic uveal melanoma, the combination of selumetinib plus dacarbazine had a tolerable safety profile but did not significantly improve PFS compared with placebo plus dacarbazine.
Oncologist | 2016
Sophie Piperno-Neumann; Alhassane Diallo; Marie-Christine Etienne-Grimaldi; François-Clément Bidard; Manuel Jorge Rodrigues; Corine Plancher; Pascale Mariani; Nathalie Cassoux; Didier Decaudin; Bernard Asselain; Vincent Servois
Lessons Learned Trials dedicated to metastatic uveal melanoma are needed because of the poor prognosis of this rare cancer and because its biology is distinct from that of cutaneous melanoma. Agents targeting the MEK/ERK/MAP kinase pathways are being tested. Background. In experimental models, bevacizumab suppressed in vitro growth and in vivo hepatic metastasis of ocular melanoma cells. Additional preclinical data suggested a potential benefit when combining bevacizumab with dacarbazine. Methods. This noncomparative phase II study evaluated a combination of bevacizumab (10 mg/kg on days 8 and 22) with temozolomide (150 mg/m2 on days 1–7 and 15–21) in 36 patients with metastatic uveal melanoma (MUM). The primary endpoint was the progression-free rate (PFR) at 6 months. Using a modified 2-step Fleming plan, at least 10 of 35 patients were required to support a predefined PFR at 6 months of 40%. Secondary objectives were progression-free survival (PFS), overall survival (OS), and safety; liver perfusion computed tomography (CT) for response imaging; and impact of VEGF-A gene polymorphisms on bevacizumab pharmacodynamics. Results. First- and second-step analyses revealed nonprogression at 6 months in 3 of 17 and 8 of 35 patients, respectively. Finally, the 6-month PFR was 23% (95% confidence interval [CI]: 10–39), with long-lasting stable disease in 5 patients (14%). Median PFS and OS were 12 weeks and 10 months, respectively. No unexpected toxicity occurred. Liver perfusion CT imaging was not useful in assessing tumor response, and VEGF-A gene polymorphisms were not correlated with toxicity or survival. Conclusion. In patients with MUM, a combination of bevacizumab plus temozolomide achieved a 6-month PFR of 23%.
Oncologie | 2011
Philippe Colombat; A. Altmeyer; Florence Barruel; Chantal Bauchetet; Pierre Blanchard; L. Copel; G. Ganem; Manuel Jorge Rodrigues; M. Ruszniewski
la perte de sens et de l’accomplissement de soi au tra• vail : c’est le sentiment de ne pas être effi cace, surtout dans sa relation à l’autre. On retrouve une perte du sens des missions du soignant et un sentiment de culpabilité. Elle peut entraîner une démotivation, un absentéisme ou un manque de rigueur (accident d’expo sition au sang, lumbago, fautes professionnelles...). Ces trois dimensions sont indépendantes. Il ne s’agit pas d’une triade diagnostique et l’on peut avoir une atteinte importante d’une dimension sans aucune répercussion sur une des autres. Il s’agit d’un phénomène dynamique (possibilité d’évolution d’une dimension à l’autre) qui peut être « contagieux » au sein d’une équipe.
Bulletin Du Cancer | 2013
Manuel Jorge Rodrigues; Carlos Gomez-Roca
New sequencing technologies are one of the most important technical advances in biology in the last 10 years. These technologies allow sequencing millions of DNA fragments in parallel, covering billions of bases in a short period of time. These techniques allowed discovering millions of variants, which functional and clinical value rest yet to be confirmed. This technology allows us to search new constitutional and somatic mutations in various samples in a short time. The complexity of data interpretation and size of data as well as the important investment needed to implement make these technologies to be present only in big institutions. The objective of this article is to present the different techniques, their associated technologies and to discuss their current applications.
Journal of Clinical Oncology | 2012
Jean-Sebastien Frenel; Manuel Jorge Rodrigues; Julien Péron; Vano Yann-Alexandre; Johanna Wassermann; Marc Debled; Francois Picaud; Laurence Albiges; Anne Vincent-Salomon; Paul Cottu
601 Background: Increasingly patients with IV stage colorectal cancer received systemic chemotherapy combined with targeted therapy among which bevacizumab. In neoadjuvant situation, a delay of at least 6 weeks between discontinuation of bevacizumab and surgery is recommended, not to increase the risk of complications (delayed healing, bleeding) related to bevacizumab. The goal of this study was to analyze the potential impact of bevacizumab on early morbidity after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis of colorectal origin. METHODS From 2004 to 2010, in three hospitals, 183 patients treated with complete cytoreduction followed by HIPEC for colorectal carcinomatosis, received preoperative treatment. It was either systemic chemotherapy alone (Chemo group, n = 100) or by chemotherapy combined with bevacizumab (Beva group, n = 83). RESULTS Both patient groups were comparable in the extent of carcinomatosis, assessed on peritoneal cancer index means (10.4 vs 10, p> 0.05), number of resected organs (4.3 vs 3.8, p> 0.05), operative time (420 vs. 380 minutes, p> 0.05) and volume of blood loss (470 vs 510ml, p> 0.05). The median time from discontinuation of bevacizumab and HIPEC was 7 weeks (6-10), always greater than 6 weeks. Nine patients postoperatively died, 4 (4%) in the chemo group and 5 (6%) in the beva group (ns). Grade 3 to 5 complication rate was higher in the beva group (25 vs 12%, p <0.05). Whatever the hospital, complications that may be related to bevacizumab occurred more frequently in patients in the beva group: with more digestive fistulas (18 vs 8%, p <0.05), deep abscesses (13 vs 3 %, p <0.01) and delayed healing (11 vs 2%, p <0.02). CONCLUSIONS Administration of bevacizumab before surgery with complete cytoreduction followed by HIPEC for carcinomatosis colorectal is associated with increased morbidity, probably due to multiple organ resections performed during the surgery. The oncologic benefit of bevacizumab before HIPEC remains to be evaluated.
Annals of Oncology | 2011
Manuel Jorge Rodrigues; S. Haberer; D. Dionysopoulos; J. Barrière; J. Wassermann; Y. Tazi; S. Rajpar; J. Giroux; François-Clément Bidard; Y. Loriot
During the last decade, Internet has become an essential tool in private and in professional life worldwide. Simultaneously, the number of Web sites dedicated to health issues and more particularly to cancer has been growing rapidly. Several studies have already reported that Internet is one of the sources of information most consulted by patients with cancer in search of health information [1–3]. In parallel, enrolment in clinical trials has become a key issue in clinical oncology and increasing accrual is highly encouraged. Companies are designing new Internet tools and Web sites to accelerate trials [4] but whether Internet can help recruit more patients is not known. A recent publication [5] indirectly suggested that USA patients use the net to gain access to trials. To address the potential role and receptivity of Internet on the enrolment of patients with cancer, we carried out a French prospective multiinstitutional study. From January to April 2009, we prospectively assessed patients treated in the day-hospital in 12 French oncology centers (2 of which dedicated to early trials). The patients were given a 7-page questionnaire containing 28 questions regarding Internet use. Additional data were obtained through a retrospective chart review by a resident from the French Association of Residents in Oncology (AERIO; http:// www.aerio-oncologie.org/). Overall, 570 consecutive patients were included in this study. Sixty-five percent of patients were women; median age was 59 years. The most common cancer types were breast (n = 224, 40%), colorectal (n = 52, 9%) and lung (n = 43, 8%). Thirty-seven percent (n = 206) were enrolled in clinical trials, 39% (n = 81) of which were phase I trials. Seventy-three percent (n = 389) of patients had Internet access at home. Fifty-two percent (n = 289) used Internet to look up information about their cancer. Out of the 570 patients assessed, patients with breast, lung or colorectal cancer (n = 319) did not consult more Internet than other patients (53% versus 51%, P = 0.7). Among patients enrolled in clinical trials, 51% of patients enrolled in phase I clinical trials used Internet for cancer issues versus 59% of patients enrolled in phase II/III trials versus 51% of patients not enrolled in clinical trials. These differences were not significant (Fisher’s exact test, P > 0.05). The major factors predicting the use of the Web were age and education level. Seventy-two percent (n = 64/89) of patients of less than 45 consulted the net for cancer issues versus 49% (n = 225/463) of olders (Fisher’s exact test, P < 0.0001). Sixty percent (182/307) of patients with at least ‘A’ level (college level) versus 42% (99/238) of patients who have stopped studies in secondary school (high school level) used the net (Fisher’s exact test, P = 0.004). The timing of questions was of particular interest. Eighty percent of the patients (n = 265) began their research after the diagnosis of cancer but only 41% (n = 136) began before the treatment decision or inclusion in the trial. Overall, 78% of patients thought that Internet was a reliable source of health information. Nonetheless, the main sources of information for the patients were general practitioners/pharmacists (n = 236, 65%), television (n = 152, 42%) and friends/family (n = 100, 27%). Patients have three wishes for Internet use: to access to their health data (n = 195, 61%), a Web site with information about treatment and trials validated by oncologists (n = 189, 59%) and to contact their healthcare providers (n = 160, 50%). In conclusion, patients enrolled in clinical trials do not consult Internet more frequently than other oncology patients in France. Nonetheless, they consider Web information reliable but insufficient. For 65% (n = 61) of patients who were proposed to be enrolled in clinical trials, Web information was insufficient to help them chose to enter a trial. Seventy-three percent (n = 232) of patients would like to have access to a Web site with information relative to clinical trials. Thirty-three percent (n = 103) would not trust this site if promoted by industry. Web sites designed for the public containing information on clinical trials may be useful to increase clinical trial accrual.
Lancet Oncology | 2018
Michael Friedlander; Val Gebski; Emma Gibbs; Lucy Davies; Ralph Bloomfield; Felix Hilpert; Lari Wenzel; Daniel Eek; Manuel Jorge Rodrigues; Andrew R Clamp; Richard T. Penson; Diane Provencher; Jacob Korach; Tomasz Huzarski; Laura Vidal; Vanda Salutari; Clare L. Scott; Maria Ornella Nicoletto; Kenji Tamura; David Espinoza; Florence Joly; Eric Pujade-Lauraine
BACKGROUND In the phase 3 SOLO2 trial (ENGOT Ov-21), maintenance therapy with olaparib tablets significantly prolonged progression-free survival (primary endpoint) compared with placebo in patients with a germline BRCA1 or BRCA2 (BRCA1/2) mutation and platinum-sensitive, relapsed ovarian cancer who had received two or more lines of previous chemotherapy. The most common subjective adverse effects included fatigue, nausea, and vomiting, which were typically low grade and self-limiting. Our a-priori hypothesis was that maintenance olaparib would not negatively affect health-related quality of life (HRQOL) and additionally that the prolongation of progression-free survival with olaparib would be underpinned by additional patient-centred benefits. METHODS In SOLO2, 196 patients were randomly assigned to olaparib tablets (300 mg twice daily) and 99 to placebo. Randomisation was stratified by response to previous chemotherapy (complete vs partial) and length of platinum-free interval (>6-12 vs >12 months). The prespecified primary HRQOL analysis evaluated the change from baseline in the Trial Outcome Index (TOI) score during the first 12 months of the study. To be assessable, patients had to have an evaluable score at baseline and at least one evaluable follow-up form. Secondary planned quality-of-life (QOL) analyses included the duration of good quality of life (defined as time without significant symptoms of toxicity [TWiST] and quality-adjusted progression-free survival [QAPFS]). Efficacy and QOL outcomes were analysed in all randomly assigned patients (the full analysis set), and safety outcomes were analysed in all randomly assigned patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01874353, and is closed to new participants. FINDINGS The adjusted average mean change from baseline over the first 12 months in TOI was -2·90 (95% CI -4·13 to -1·67) with olaparib and -2·87 (-4·64 to -1·10) with placebo (estimated difference -0·03; 95% CI -2·19 to 2·13; p=0·98). Mean QAPFS (13·96 [SD 10·96] vs 7·28 [5·22] months; difference 6·68, 95% CI 4·98-8·54) and mean duration of TWiST (15·03 [SD 12·79] vs 7·70 [6·42] months; difference 7·33, 95% CI 4·70-8·96) were significantly longer with olaparib than with placebo. INTERPRETATION Olaparib maintenance therapy did not have a significant detrimental effect on HRQOL compared with placebo. There were clinically meaningful patient-centred benefits in both TWiST and QAPFS despite the adverse effects associated with olaparib. These patient-centred endpoints support the improvement in progression-free survival, the primary endpoint in SOLO2, and should be included in future trials of maintenance therapies. FUNDING AstraZeneca.