Georges Francois Leclerc Cancer Center

Plombières-lès-Dijon, France

Georges Francois Leclerc Cancer Center

Plombières-lès-Dijon, France

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Guiu S.,Georges Francois Leclerc Cancer Center | Michiels S.,Jules Bordet Institute | Andre F.,CNRS Gustave Roussy Institute | Cortes J.,Vall dHebron Institute of Oncology | And 9 more authors.
Annals of Oncology | Year: 2012

The 2012 IMPAKT task force investigated the medical usefulness of current methods for the classification of breast cancer into the 'intrinsic' molecular subtypes (luminal A, luminal B, basal-like and HER2). A panel of breast cancer and/or gene expression profiling experts evaluated the analytical validity, clinical validity and clinical utility of two approaches for molecular subtyping of breast cancer: the prediction analysis of microarray (PAM)50 assay and an immuno-histochemical (IHC) surrogate panel including oestrogen receptor (ER), HER2 and Ki67. The panel found the currently available evidence on the analytical validity and clinical utility of Ki67 based on a 14% cut-off and PAM50 to be inadequate. The majority of the working group members found the available evidence on the analytical validity, clinical validity and clinical utility of ER/HER2 to be convincing. The panel concluded that breast cancer classification into molecular subtypes based on the IHC assessment of ER, HER2 and Ki67 with a 14% cut-off and on the PAM50 test does not provide sufficiently robust information to modify systemic treatment decisions, and recommended the use IHC for ER and HER2 for the identification of clinically relevant subtypes of breast cancers. Methods for breast cancer classification into molecular subtypes should, however, be incorporated into clinical trial design. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


PubMed | French National Quality of Life in Oncology Platform, French Institute of Health and Medical Research, University of Franche Comte, Georges Francois Leclerc Cancer Center and University Hospital of Dijon
Type: Journal Article | Journal: Health and quality of life outcomes | Year: 2016

Health-related quality of life (HRQoL) has been positioned as one of the major endpoints in oncology. Thus, there is a need to validate cancer-site specific survey instruments. This study aimed to perform a transcultural adaptation of the 50-item Expanded Prostate cancer Index Composite (EPIC) questionnaire for HRQoL in prostate cancer patients and to validate the psychometric properties of the French-language version.The EPIC questionnaire measures urinary, bowel, sexual and hormonal domains. The first step, corresponding to transcultural adaptation of the original English version of the EPIC was performed according to the back translation technique. The second step, comprising the validation of the psychometric properties of the EPIC questionnaire, was performed in patients under treatment for localized prostate cancer (treatment group) and in patients cured of prostate cancer (cured group). The EORTC QLQ-C30 and QLQ-PR25 prostate cancer module were also completed by patients to assess criterion validity. Two assessments were performed, i.e., before and at the end of treatment for the Treatment group, to assess sensitivity to change; and at 2 weeks interval in the Cured group to assess test-retest reliability. Psychometric properties were explored according to classical test theory.The first step showed overall good acceptability and understanding of the questionnaire. In the second step, 215 patients were included from January 2012 to June 2014: 125 in the Treatment group, and 90 in the Cured group. All domains exhibited good internal consistency, except the bowel domain (Cronbachs =0.61). No floor effect was observed. Test-retest reliability assessed in the cured group was acceptable, expect for bowel function (intraclass coefficient=0.68). Criterion validity was good for each domain and subscale. Construct validity was not demonstrated for the hormonal and bowel domains. Sensitivity to change was exhibited for 5/8 subscales and 2/4 summary scores for patients who experienced toxicities during treatment.The French EPIC questionnaire seems to have adequate psychometric properties, comparable to those exhibited by the original English-language version, except for the construct validity, which was not available in original version.


Lorgis V.,Georges Francois Leclerc Cancer Center | Chauffert B.,University Hospital Amiens | Gentil J.,Georges Francois Leclerc Cancer Center | Ghiringhelli F.,Georges Francois Leclerc Cancer Center | And 2 more authors.
Anticancer Research | Year: 2012

Background: Metastatic pancreatic carcinoma is an incurable disease and gemcitabine remains the standard of care in first-line chemotherapy. Recently, fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) demonstrated their superiority in first-line therapy. The objective of this study was to determine the efficacy of FOLFIRINOX in either first- and second-line treatment and to compare its efficacy in regard to the location of the primary tumor. Patients and Methods: We performed a retrospective analysis of clinical factors associated with patients' survival using a cohort of 42 patients treated by FOLFIRINOX in either first- or second-line (2006-2011) and a control cohort of 42 patients matched on sex and age without FOLFIRINOX treatment was obtained from a previous period of time (2001-2005). Results: The median follow-up was 10 months. The median overall survival was 10 months for the whole cohort and 10 and 12 months for patients treated at first- and second-line, respectively (p<0.05). In this cohort using a multivariate model, among classical prognosis factors, only primary location in the head was associated with poor outcome. The median overall survival was 8 months for patients with primary location in the head and 14 months for patients with primary location in the corpse or tail (p=0.02). In the gemcitabine cohort, the median follow-up was 8 months. Using a multivariate model, only performance status was associated with outcome. The median overall survival was 9 versus 6.5 months for patients with tumor, of the head versus tail or corpse tumor respectively (p<0.05). Conclusion: This retrospective study suggests the same efficacy of FOLFIRINOX used either in first- or second- line therapy for pancreatic cancer. Importantly, FOLFIRINOX compared favorably to gemcitabine only for patients with tumor of the corpse or tail. Further prospective trials are warranted to evaluate the efficacy of FOLFIRINOX in patients with tumor of the head of the pancreas.


Kaidar-Person O.,Rambam Health Care Campus | Roach III M.,University of California at San Francisco | Crehange G.,Georges Francois Leclerc Cancer Center
International Journal of Radiation Oncology Biology Physics | Year: 2013

Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted conventional radiation therapy to the prostate only. In high-risk prostate cancer patients, there is accumulating evidence that either dose escalation to the prostate or hypofractionation may improve outcome. Nevertheless, selected patients who have a high risk of lymph node involvement may benefit from whole-pelvic radiation therapy (WPRT). Although combining WPRT with hypofractionated prostate radiation therapy is feasible, it remains investigational. By combining modern advances in radiation oncology (high-dose-rate prostate brachytherapy, intensity modulated radiation therapy with an improved image guidance for soft-tissue sparing), it is hypothesized that WPRT could take advantage of recent results from hypofractionation trials. Moreover, the results from hypofractionation trials raise questions as to whether hypofractionation to pelvic lymph nodes with a high risk of occult involvement might improve the outcomes in WPRT. Although investigational, this review discusses the challenging idea of WPRT in the context of hypofractionation for patients with high-risk prostate cancer. © 2013 Elsevier Inc.


Lepinoy A.,University of Burgundy | Lepinoy A.,University Hospital Jean Minjoz | Cochet A.,University of Burgundy | Cochet A.,Georges Francois Leclerc Cancer Center | And 9 more authors.
Radiotherapy and Oncology | Year: 2014

Introduction The purpose of this study was to describe the pattern of nodal relapse with 18F-fluoro-choline (FCH) Positron Emission Tomography/Computerized Tomography (PET/CT) in prostate cancer patients after radiotherapy. Materials and methods Eighty-three patients had a FCH PET/CT at time of biochemical failure. Of 65 patients with positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy with or without a prior radical prostatectomy. Each FCH positive node was assigned to a lymph node station with respect to the CTV defined by the RTOG guidelines (CTVRTOG). 3D mapping was performed after each node was manually placed in a reference planning CT scan after automatic co-registration of the two scans based on bone anatomy. Eighteen patients (58%) underwent focal salvage FCH PET-guided stereotactic radiotherapy with no hormones. Results Fourteen patients (45.2%) had a relapse outside the CTVRTOG. Of the 17 patients with a positive node inside the CTV RTOG, 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTVRTOG had ≥2 positive nodes on FCH PET/CT (OR = 8.75, [95% CI: 1.38-54.80], p = 0.020). Relapses that occurred outside the CTVRTOG involved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2-L3. Conclusion 3D mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2-L3 safely to cover 95% of nodal stations at risk of an occult relapse. © 2014 Elsevier Ireland Ltd. All rights reserved.


Ghiringhelli F.,Georges Francois Leclerc Cancer Center | Vincent J.,University Hospital Dijon | Guiu B.,University Hospital Dijon | Chauffert B.,University Hospital Amiens | Ladoire S.,Georges Francois Leclerc Cancer Center
Investigational New Drugs | Year: 2012

Background: The optimal chemotherapeutic regimen suitable for metastatic colorectal cancer (mCRC) patients previously treated with 5-fluorouracil (5FU), oxaliplatin, irinotecan and biotherapies remains an unresolved issue. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI-3 in mCRC after failure of prior chemotherapy including fluoropyrimidine, irinotecan and oxaliplatin. Methods: Patients were treated with bevacizumab in combination with FOLFIRI-3 every 14 days. The association between treatment efficacy and visceral fat area as measured by CT scan or Carcinoembryonic Antigen (CEA) change after 2 months was also studied. Results: Forty-nine consecutive patients were treated. Four hundred and twenty four cycles of chemotherapy were delivered. Median follow-up was 11 months. Eleven patients (22.4%) had an objective partial response and 26 (53.1%) were stabilized. Median progression-free survival (PFS) and overall survival (OS) were 7 and 13 months respectively. Four grade 4 adverse events occurred (1 digestive perforation, 1 rectal ulcer, 1 pulmonary embolism, and 1 febrile aplasia) but no toxic death was observed. Grade 3 adverse events occurred in 18 patients (38%) including asthenia in 15 patients (30%), nausea and vomiting in 4 patients (8%), diarrhea in 11 patients (22%), anemia in 4 patients (8%), neutropenia in 10 patients (20%) and thrombopenia in 4 patients (8%). Visceral Fat area was significantly lower in responder patients. CEA change at 2 months predicted improved overall survival. Conclusion: This study suggests that bevacizumab combined with FOLFIRI3 may be active in mCRC patients after failure of all classical lines of chemotherapy. © Springer Science+Business Media, LLC 2010.


Guiu B.,Georges Francois Leclerc Cancer Cente | Guiu B.,Le Bocage University Hospital | Petit J.M.,Le Bocage University Hospital | Petit J.M.,French Institute of Health and Medical Research | And 13 more authors.
Gut | Year: 2010

Background: Adipose tissue releases angiogenic factors that may promote tumour growth. Objective: To determine whether body mass index (BMI), subcutaneous fat area (SFA) and visceral fat area (VFA) are associated with outcomes in patients given first-line bevacizumab-based treatment for metastatic colorectal cancer (MCC). Patients: CT was used to measure SFA and VFA in 120 patients with MCC who received bevacizumab-based treatment (bevacizumab group, n=80) or chemotherapy alone (chemotherapy group, n=40) as first-line treatment. Associations linking BMI, SFA and VFA to tumour response, time-to-progression (TTP) and overall survival (OS) were evaluated. Results: In the bevacizumab group, median follow-up lasted for 24 months (3-70). BMI, SFA and VFA values above the median (ie, high BMI, high VFA and high SFA) were significantly associated with absence of a response. TTP was shorter in patients with high BMI (9 vs 12 months; p=0.01) or high VFA (9 vs 14 months; p=0.0008). High VFA was associated with shorter OS (p=0.0493). By multivariate analysis, high VFA was independently associated with response, TTP and OS (HR=7.18, p=0.008, HR=5.79, p=0.005 and HR=2.88, p=0.027, respectively). In the chemotherapy group, median follow-up lasted for 30 months (4-84). BMI, SFA and VFA were not associated with response, TTP or OS. In the whole population, interaction between VFA and bevacizumab administration was significant for response (OR=3.31, p=0.005) and TTP (HR=1.64, p=0.022), thereby confirming the results. Conclusion: This study provides the first evidence that high VFA independently predicts a poorer outcome in patients given first-line bevacizumab-based treatment for MCC. However, this predictive biomarker needs to be validated in a different dataset.


Hudry D.,Georges Francois Leclerc Cancer Center | Hudry D.,Paoli Calmettes Institute | Cannone F.,Paoli Calmettes Institute | Houvenaeghel G.,Paoli Calmettes Institute | And 4 more authors.
Surgical Endoscopy and Other Interventional Techniques | Year: 2013

Background Extraperitoneal para-aortic lymphadenectomy (PAL) is used to treat gynecological cancers. This laparoscopic approach was first described using a multiport technique, and more recently, a single-port technique was developed. Our aim was to experimentally compare both approaches-conventional laparoscopy (CL) and singleport laparoscopy (SPL)-via the extraperitoneal laparoscopic approach. Methods From November 2006 to July 2012, extraperitoneal PAL was performed by CL or SPL using the Gel- POINT device (Applied Medical). The surgical outcomes of the 2 groups were statistically analyzed. Results The study involved 69 patients; 36 underwent PAL with CL, and 33 patients underwent PAL with SPL. The mean operative times were 211.2 (range, 132-390) min and 159.6 (range, 120-255) min for the CL and SPL groups, respectively. The mean blood loss was not significantly different between the CL (52.5 mL; range, 0-100 mL) and SPL (40.5 mL; range, 0-100 mL, p = 0.62) groups. The average lymph node count was lower in the CL group (11.1; range, 4-29) compared to the SPL group (15; range, 3-19) (p = 0.03). However, this difference was not confirmed in the multivariate analysis (p = 0.16). The mean hospital stay was lower for the SPL group (2.2 days; range, 1-8 days) than the CL group (3.1 days; range, 1-5 days). In this case, the significant difference found in the univariate analysis (p = 0.02) was confirmed by the multivariate analysis (p = 0.0003). There were no conversions to open technique and no major complications. Conclusions The SPL method appears to be a feasible approach, with surgical outcomes that are not statistically different from the CL method. The cosmetic aspect, the role of SPL in decreasing postoperative pain, and its impact on hospital stay must be confirmed prospectively in larger series. © Springer Science+Business Media New York 2013.


Guiu S.,Georges Francois Leclerc Cancer Center | Wolfer A.,CHUV | Jacot W.,Institute of Cancerology of Montpellier | Fumoleau P.,Georges Francois Leclerc Cancer Center | And 3 more authors.
Critical Reviews in Oncology/Hematology | Year: 2014

The WHO classification of breast tumors distinguishes, besides invasive breast cancer 'of no special type' (former invasive ductal carcinoma, representing 60-70% of all breast cancers), 30 special types, of which invasive lobular carcinoma (ILC) is the most common (5-15%). We review the literature on (i) the specificity and heterogeneity of ILC biology as documented by various analytical techniques, including the results of molecular testing for risk of recurrence; (ii) the impact of lobular histology on prediction of prognosis and effect of systemic therapies in patients. Though it is generally admitted that ILC has a better prognosis than IDC, is endocrine responsive, and responds poorly to chemotherapy, currently available data do not unanimously support these assumptions. This review demonstrates some lack of specific data and a need for improving clinical research design to allow oncologists to make informed systemic therapy decisions in patients with ILC. Importantly, future studies should compare various endpoints in ILC breast cancer patients among the group of hormonosensitive breast cancer. © 2014 Elsevier Ireland Ltd.


PubMed | Center Georges Francois Leclerc and Georges Francois Leclerc Cancer Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

190 Background: To compare the 3-dimensional intra-fraction variations of prostate position within the pelvis with whole-pelvic fixed-field intensity-modulated radiation therapy (IMRT) vs. intensity-modulated arc therapy (IMAT) in high-risk prostate cancer.Fifteen PCa patients underwent whole pelvic radiotherapy using either dynamic IMRT with a sliding window technique (n= 8) or IMAT (n= 7). All the patients had a kV cone-beam computed tomography (CBCT) before and immediately after each fraction of IMRT or IMAT. Intra-fraction motions of the prostate were determined using a 2-step procedure performed on each pre- and post-treatment imaging: 1) planning CT and CBCT were matched on bony structures after automatic semi-rigid fusion alongside the 3 axis (x, y, z), 2) planning CT and CBCT were matched on the prostate with respect to intra-prostatic markers: xTwo hundred and ninety four CBCT were reviewed for this analysis. The average fraction duration was shorter with IMAT than with IMRT (449, vs. 1100, p< 0.001). During fractions of IMRT the prostate showed statistically significant shifts in the longitudinal (p= 0,049) and lateral (p=0,013) axis while it was not statistically significant during fractions of IMAT. Intra-fraction rCSA increased neither during IMAT nor IMRT whereas A-blad increased only during fractions of IMRT but with no correlation with prostate displacements.The prostate moves within the pelvis during an IMRT course which could lead to a greater daily geographic miss when compared to the IMAT technique.

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