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Gravis G.,French Institute of Health and Medical Research | Boher J.-M.,Aix - Marseille University | Fizazi K.,University Paris - Sud | Joly F.,Caen University Hospital Center | And 27 more authors.
European Urology | Year: 2015

Background The Glass model developed in 2003 uses prognostic factors for noncastrate metastatic prostate cancer (NCMPC) to define subgroups with good, intermediate, and poor prognosis. Objective To validate NCMPC risk groups in a more recently diagnosed population and to develop a more sensitive prognostic model. Design, setting, and participants NCMPC patients were randomized to receive continuous androgen deprivation therapy (ADT) with or without docetaxel in the GETUG-15 phase 3 trial. Potential prognostic factors were recorded: age, performance status, Gleason score, hemoglobin (Hb), prostate-specific antigen, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), metastatic localization, body mass index, and pain. Outcome measurements and statistical analysis These factors were used to develop a new prognostic model using a recursive partitioning method. Before analysis, the data were split into learning and validation sets. The outcome was overall survival (OS). Results and limitations For the 385 patients included, those with good (49%), intermediate (29%), and poor (22%) prognosis had median OS of 69.0, 46.5 and 36.6 mo (p = 0.001), and 5-yr survival estimates of 60.7%, 39.4%, and 32.1%, respectively (p = 0.001). The most discriminatory variables in univariate analysis were ALP, pain intensity, Hb, LDH, and bone metastases. ALP was the strongest prognostic factor in discriminating patients with good or poor prognosis. In the learning set, median OS in patients with normal and abnormal ALP was 69.1 and 33.6 mo, and 5-yr survival estimates were 62.1% and 23.2%, respectively. The hazard ratio for ALP was 3.11 and 3.13 in the learning and validation sets, respectively. The discriminatory ability of ALP (concordance [C] index 0.64, 95% confidence interval [CI] 0.58-0.71) was superior to that of the Glass risk model (C-index 0.59, 95% CI 0.52-0.66). The study limitations include the limited number of patients and low values for the C-index. Conclusion A new and simple prognostic model was developed for patients with NCMPC, underlying the role of normal or abnormal ALP. Patient summary We analyzed clinical and biological factors that could affect overall survival in noncastrate metastatic prostate cancer. We showed that normal or abnormal alkaline phosphatase at baseline might be useful in predicting survival. © 2014 European Association of Urology.


Fizazi K.,Institute Gustave Roussy | Faivre L.,Institute Gustave Roussy | Lesaunier F.,Center Francois Baclesse | Delva R.,Institute Of Cancerologie Of Louest | And 27 more authors.
The Lancet Oncology | Year: 2015

Background: Early risk-stratified chemotherapy is a standard treatment for breast, colorectal, and lung cancers, but not for high-risk localised prostate cancer. Combined docetaxel and estramustine improves survival in patients with castration-resistant prostate cancer. We assessed the effects of combined docetaxel and estramustine on relapse in patients with high-risk localised prostate cancer. Methods: We did this randomised phase 3 trial at 26 hospitals in France. We enrolled patients with treatment-naive prostate cancer and at least one risk factor (ie, stage T3-T4 disease, Gleason score of ≥8, prostate-specific antigen concentration >20 ng/mL, or pathological node-positive). All patients underwent a staging pelvic lymph node dissection. Patients were randomly assigned (1:1) to either androgen deprivation therapy (ADT; goserelin 10·8 mg every 3 months for 3 years) plus four cycles of docetaxel on day 2 at a dose of 70 mg/m2 and estramustine 10 mg/kg per day on days 1-5, every 3 weeks, or ADT only. The randomisation was done centrally by computer, stratified by risk factor. Local treatment was administered at 3 months. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was relapse-free survival in the intention-to-treat population. Follow-up for other endpoints is ongoing. This study is registered with ClinicalTrials.gov, number NCT00055731. Findings: We randomly assigned 207 patients to the ADT plus docetaxel and estramustine group and 206 to the ADT only group. Median follow-up was 8·8 years (IQR 8·1-9·7). 88 (43%) of 207 patients in the ADT plus docetaxel and estramustine group had an event (relapse or death) versus 111 (54%) of 206 in the ADT only group. 8-year relapse-free survival was 62% (95% CI 55-69) in the ADT plus docetaxel and estramustine group versus 50% (44-57) in the ADT only group (adjusted hazard ratio [HR] 0·71, 95% CI 0·54-0·94, p=0·017). Of patients who were treated with radiotherapy and had data available, 31 (21%) of 151 in the ADT plus docetaxel and estramustine group versus 26 (18%) of 143 in the ADT only group reported a grade 2 or higher long-term side-effect (p=0·61). We recorded no excess second cancers (26 [13%] of 207 vs 22 [11%] of 206; p=0·57), and there were no treatment-related deaths. Interpretation: Docetaxel-based chemotherapy improves relapse-free survival in patients with high-risk localised prostate cancer. Longer follow-up is needed to assess whether this benefit translates into improved metastasis-free survival and overall survival. Funding: Ligue Contre le Cancer, Sanofi-Aventis, AstraZeneca, Institut National du Cancer. © 2015 Elsevier Ltd.


Gravis G.,Institute Paoli Calmettes | Fizazi K.,University Paris - Sud | Joly F.,University of Caen Lower Normandy | Oudard S.,University of Paris Descartes | And 29 more authors.
The Lancet Oncology | Year: 2013

Background: Early chemotherapy might improve the overall outcomes of patients with metastatic non-castrate (ie, hormone-sensitive) prostate cancer. We investigated the effects of the addition of docetaxel to androgen-deprivation therapy (ADT) for patients with metastatic non-castrate prostate cancer. Methods: In this randomised, open-label, phase 3 study, we enrolled patients in 29 centres in France and one in Belgium. Eligible patients were older than 18 years and had histologically confirmed adenocarcinoma of the prostate and radiologically proven metastatic disease; a Karnofsky score of at least 70%; a life expectancy of at least 3 months; and adequate hepatic, haematological, and renal function. They were randomly assigned to receive to ADT (orchiectomy or luteinising hormone-releasing hormone agonists, alone or combined with non-steroidal antiandrogens) alone or in combination with docetaxel (75 mg/m2 intravenously on the first day of each 21-day cycle; up to nine cycles). Patients were randomised in a 1:1 ratio, with dynamic minimisation to minimise imbalances in previous systemic treatment with ADT, chemotherapy for local disease or isolated rising concentration of serum prostate-specific antigen, and Glass risk groups. Patients, physicians, and data analysts were not masked to treatment allocation. The primary endpoint was overall survival. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00104715. Findings: Between Oct 18, 2004, and Dec 31, 2008, 192 patients were randomly allocated to receive ADT plus docetaxel and 193 to receive ADT alone. Median follow-up was 50 months (IQR 39-63). Median overall survival was 58·9 months (95% CI 50·8-69·1) in the group given ADT plus docetaxel and 54·2 months (42·2-not reached) in that given ADT alone (hazard ratio 1·01, 95% CI 0·75-1·36). 72 serious adverse events were reported in the group given ADT plus docetaxel, of which the most frequent were neutropenia (40 [21%]), febrile neutropenia (six [3%]), abnormal liver function tests (three [2%]), and neutropenia with infection (two [1%]). Four treatment-related deaths occurred in the ADT plus docetaxel group (two of which were neutropenia-related), after which the data monitoring committee recommended treatment with granulocyte colony-stimulating factor. After this recommendation, no further treatment-related deaths occurred. No serious adverse events were reported in the ADT alone group. Interpretation: Docetaxel should not be used as part of first-line treatment for patients with non-castrate metastatic prostate cancer. Funding: French Health Ministry and Institut National du Cancer (PHRC), Sanofi-Aventis, AstraZeneca, and Amgen. © 2013 Elsevier Ltd.


PubMed | Clinique Pasteur, Groupe Hospitalier Saint Joseph, Catholic University of Louvain, Center Georges Francois Leclerc and 25 more.
Type: Clinical Trial, Phase III | Journal: European urology | Year: 2015

The Glass model developed in 2003 uses prognostic factors for noncastrate metastatic prostate cancer (NCMPC) to define subgroups with good, intermediate, and poor prognosis.To validate NCMPC risk groups in a more recently diagnosed population and to develop a more sensitive prognostic model.NCMPC patients were randomized to receive continuous androgen deprivation therapy (ADT) with or without docetaxel in the GETUG-15 phase 3 trial. Potential prognostic factors were recorded: age, performance status, Gleason score, hemoglobin (Hb), prostate-specific antigen, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), metastatic localization, body mass index, and pain.These factors were used to develop a new prognostic model using a recursive partitioning method. Before analysis, the data were split into learning and validation sets. The outcome was overall survival (OS).For the 385 patients included, those with good (49%), intermediate (29%), and poor (22%) prognosis had median OS of 69.0, 46.5 and 36.6 mo (p=0.001), and 5-yr survival estimates of 60.7%, 39.4%, and 32.1%, respectively (p=0.001). The most discriminatory variables in univariate analysis were ALP, pain intensity, Hb, LDH, and bone metastases. ALP was the strongest prognostic factor in discriminating patients with good or poor prognosis. In the learning set, median OS in patients with normal and abnormal ALP was 69.1 and 33.6 mo, and 5-yr survival estimates were 62.1% and 23.2%, respectively. The hazard ratio for ALP was 3.11 and 3.13 in the learning and validation sets, respectively. The discriminatory ability of ALP (concordance [C] index 0.64, 95% confidence interval [CI] 0.58-0.71) was superior to that of the Glass risk model (C-index 0.59, 95% CI 0.52-0.66). The study limitations include the limited number of patients and low values for the C-index.A new and simple prognostic model was developed for patients with NCMPC, underlying the role of normal or abnormal ALP.We analyzed clinical and biological factors that could affect overall survival in noncastrate metastatic prostate cancer. We showed that normal or abnormal alkaline phosphatase at baseline might be useful in predicting survival.


PubMed | Center Hospitalier Of Nimes, Hopital Saint Louis, Center Leon Berard, Center Hospitalier La Timone and 23 more.
Type: Clinical Trial, Phase III | Journal: The Lancet. Oncology | Year: 2015

Early risk-stratified chemotherapy is a standard treatment for breast, colorectal, and lung cancers, but not for high-risk localised prostate cancer. Combined docetaxel and estramustine improves survival in patients with castration-resistant prostate cancer. We assessed the effects of combined docetaxel and estramustine on relapse in patients with high-risk localised prostate cancer.We did this randomised phase 3 trial at 26 hospitals in France. We enrolled patients with treatment-naive prostate cancer and at least one risk factor (ie, stage T3-T4 disease, Gleason score of 8, prostate-specific antigen concentration >20 ng/mL, or pathological node-positive). All patients underwent a staging pelvic lymph node dissection. Patients were randomly assigned (1:1) to either androgen deprivation therapy (ADT; goserelin 108 mg every 3 months for 3 years) plus four cycles of docetaxel on day 2 at a dose of 70 mg/m(2) and estramustine 10 mg/kg per day on days 1-5, every 3 weeks, or ADT only. The randomisation was done centrally by computer, stratified by risk factor. Local treatment was administered at 3 months. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was relapse-free survival in the intention-to-treat population. Follow-up for other endpoints is ongoing. This study is registered with ClinicalTrials.gov, number NCT00055731.We randomly assigned 207 patients to the ADT plus docetaxel and estramustine group and 206 to the ADT only group. Median follow-up was 88 years (IQR 81-97). 88 (43%) of 207 patients in the ADT plus docetaxel and estramustine group had an event (relapse or death) versus 111 (54%) of 206 in the ADT only group. 8-year relapse-free survival was 62% (95% CI 55-69) in the ADT plus docetaxel and estramustine group versus 50% (44-57) in the ADT only group (adjusted hazard ratio [HR] 071, 95% CI 054-094, p=0017). Of patients who were treated with radiotherapy and had data available, 31 (21%) of 151 in the ADT plus docetaxel and estramustine group versus 26 (18%) of 143 in the ADT only group reported a grade 2 or higher long-term side-effect (p=061). We recorded no excess second cancers (26 [13%] of 207 vs 22 [11%] of 206; p=057), and there were no treatment-related deaths.Docetaxel-based chemotherapy improves relapse-free survival in patients with high-risk localised prostate cancer. Longer follow-up is needed to assess whether this benefit translates into improved metastasis-free survival and overall survival.Ligue Contre le Cancer, Sanofi-Aventis, AstraZeneca, Institut National du Cancer.


Morice P.,Institute Gustave Roussy | Morice P.,University Paris - Sud | Morice P.,French Institute of Health and Medical Research | Rouanet P.,Center Val dAurelle | And 12 more authors.
Oncologist | Year: 2012

Background. Concomitant chemoradiation (CRT) (including brachytherapy) is considered the standard management for stage IB2 or II cervical cancer in many countries. Nevertheless, some of them discuss completion surgery (hysterectomy [HT]) after CRT. The aim of this study was to investigate the therapeutic impact of such surgery. Methods. A randomized trial was opened in France in 2003 to evaluate the interest in HT after CRT. Inclusion criteria were: (a) stage IB2 or II cervical cancer without extrapelvic disease on conventional imaging; (b) pelvic external radiation therapy (45 Gy with or without parametrial or nodal boost) with concomitant cisplatin chemotherapy (40 mg/m2 per week) followed by uterovaginal brachytherapy (15 Gy to the intermediate risk clinical target volume); and (c) complete clinical and radiological response 6 - 8 weeks after brachytherapy. Patients were randomized between HT (arm A) and no HT (arm B). Unfortunately this trial was closed because of poor accrual: 61 patients were enrolled (in 2003-2006) and are reported on here. Results. Thirty one and 30 patients were enrolled, respectively, in arm A and arm B. Twelve patients recurred (five of them died): respectively, eight and four in arm A and arm B. The 3-year event-free survival rates were 72% (standard error [SE], 9%) and 89% (SE, 6%) (not significant [NS]) in arm A and arm B, respectively. The 3-year overall survival rates were 86% (SE, 6%) and 97% (SE, 3%) (NS) in arm A and arm B, respectively. Conclusions. Results of the current trial seem to suggest that completion HT had no therapeutic impact in patients with clinical and radiological complete response after CRT (but this conclusion is limited by the lack of power). © AlphaMed Press.


Pascual D.,Center Hospitalier La Timone | Roig R.,boulevard Lord Duveen | Chossegros C.,Center Hospitalier La Timone
Revue de Stomatologie, de Chirurgie Maxillo-faciale et de Chirurgie Orale | Year: 2014

Introduction Pre-implant bone graft in posterior mandibular segments is difficult because of masticatory and lingual mechanical constraints, because of the limited bone vascularization, and because of the difficulty to cover it with the mucosa. The formwork technique is especially well adapted to this topography. Technical note The recipient site is abraded with a drill. Grooves are created to receive and stabilize the grafts. The bone grafts were harvested from the ramus. The thinned cortices are assembled in a formwork and synthesized by mini-plates. The gaps are filled by bone powder collected during bone harvesting. Discussion The bone volume reconstructed with the formwork technique allows anchoring implants more than 8 mm long. The proximity of the inferior alveolar nerve does not contra indicate this technique. The formwork size and its positioning on the alveolar crest can be adapted to prosthetic requirements by using osteosynthesis plates. The lateral implant walls are supported by the formwork cortices; the implant apex is anchored on the native alveolar crest. The primary stability of implants is high, and the torque is important. The ramus harvesting decreases operative risks. © 2014 Elsevier Masson SAS. All rights reserved.


PubMed | Aix - Marseille University and Center hospitalier La Timone
Type: Journal Article | Journal: Revue de stomatologie, de chirurgie maxillo-faciale et de chirurgie orale | Year: 2015

Sialendoscopy, extracorporeal lithotripsy and transoral removal are the usual treatments for parotid lithiasis. These techniques cannot treat all the patients. In fact, removal of lithiasis bigger than the ductal diameter and situated in the middle or posterior third of the duct may fail with such techniques. For this reason the combined approach has been developed. Our technical note describes this procedure.Preoperative check-up needs an ultrasound or a CT scan of the parotid region. The procedure is conducted under general anesthesia. It begins with the localization of the lithiasis with help of the sialendoscope light visible through the skin. A face lift approach is performed giving access to the SMAS that is opened over the lithiasis and the transilluminated area. A window is opened on the duct and the lithiasis is removed. Proximal duct permeability is assessed with the sialendoscope. The different layers are sutured and a suction drainage is left in place.Combined approach is indicated in case of failure of conservative techniques. It provides good results in removal of lithiasis located in the posterior or middle thirds of the duct. Its morbidity is low. It can avoid performing a parotidectomy and lowers the risk of facial palsy. In case of failure, botulinum toxin injection may be indicated.


PubMed | Aix - Marseille University and Center Hospitalier La Timone
Type: Journal Article | Journal: Annals of vascular surgery | Year: 2015

The aim of this study was to determine the predictive factors of reduction in diameter 10mm of the aneurysm sac after endovascular treatment and analyze evolution in these patients.Between December 1997 and December 2008, all patients electively treated at our center for an infrarenal abdominal aortic aneurysm (AAA) were included in a prospective registry. We did a retrospective study between patients whose aneurysm was reduced by at least 10mm in diameter on computed tomography scan during follow-up (Group 1) and the other patients who did not (Group 2). A univariate and multivariate statistical analysis was performed.The files of 197 patients (mean age 74.8years) with a mean follow-up of 54.8months were reviewed. One hundred two patients (51.8%) had a reduction of 10mm of AAA diameter (Group 1); this reduction was achieved after an average follow-up of 23.6months. The delay to obtain at least a 10-mm diameter reduction was not influenced by any preoperative characteristics of patients or characteristics of the AAA. Patients in Group 1 were younger (74 vs. 76 years, P=0.039), with a longer (31 vs. 27.7mm, P=0.038) and narrower upper neck (23.1 vs. 24.0mm, P=0.02) compared with Group 2. After multivariate analysis, these 3 variables were independently predictive of reduction in AAA diameter. In Group 1, secondary procedures were performed in 13 patients after a diameter reduction of 10mm, including 3 type 1 endoleaks treated after 36months (1 case) and after 123months (2 cases) and 1 type 3 endoleak treated after 78months. In Group 2, secondary procedures were performed in 28 patients, including 9 type 1 endoleaks treated after a median time of 26months and no type 3 endoleak. Secondary procedures were significantly more frequent in Group 2 than in Group 1 (29.4% vs. 12.7%, respectively; P=0.005). Freedom from secondary procedure at 5years was 87.9% in Group 1 and 65.4% in Group 2 (P=0.003). Freedom from AAA rupture at 8years was significantly superior in Group 1 than in Group 2 (100% vs. 83.5%, P=0.008).Sac shrinkage after endovascular aortic aneurysm repair is more likely observed in younger patients with long and small proximal neck anatomy and is associated with better long-term outcomes. However, late failures do occur even in those with significant sac shrinkage; therefore, follow-up should continue lifelong.


PubMed | Center hospitalier La Timone
Type: Comparative Study | Journal: Revue de stomatologie, de chirurgie maxillo-faciale et de chirurgie orale | Year: 2013

Two different types of suture are used in our unit after wisdom tooth extraction, Polyglactin 910 [PGS] (Vicryl, Ethicon) and rapid absorption irradiated Polyglactin 910 [PGI]. No objective comparative study was available so we decided to conduct a preliminary prospective study to check if there was any difference between these two types of suture.Forty patients were included in our study, consecutively operated for impacted wisdom teeth by the same surgeons, between April and June 2010. The symmetry of impaction was systematically controlled on panoramic views before including a patient in the study. PGS and PGI were both used for every patient, PGS on one side and PGI on the other. The right or left PGS-PGI distribution was randomized and double-blinded. The patient was his own control. Thirty-two patients were examined at the postoperative consultation, during which an evaluation questionnaire was completed with the surgeon. Pain, difficulty to chew, duration of swelling, dysgeusia, and major complications (inflammation, disunion, infection) were analyzed.The statistical analysis revealed that postoperative pain was greater on the PGS side (VAS=3.7) than on the PGI side (VAS=2.8) without any significant difference. The duration of swelling was significantly higher on the PGS side (5.5days) than on the PGI side (3.1days). Coming back to normal food intake did not seem different; it was not interrupted. PGI also significantly reduced the difficulty to chew and dysgeusia. There was no difference in complications between PGS and PGI.This study proved the superiority of PGI over PGS during the three postoperative weeks after extraction of wisdom teeth, in terms of comfort and edema.

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