Showing papers by "Laurence Collette published in 2010"
TL;DR: In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity.
Abstract: Summary Background We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results. Methods For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1–2 prostatic adenocarcinoma with WHO histological grade 3 or T3–4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0–2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082. Findings Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1–12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3–29·7) in the radiotherapy-alone group and 47·7% (39·0–56·0) in the combined treatment group (hazard ratio [HR] 0·42, 95% CI 0·33–0·55, p vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment. Interpretation In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity. Funding AstraZeneca; Ligue Nationale Contre le Cancer (France), through the EORTC Charitable Trust.
824 citations
TL;DR: Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gem citabine after resection of pancreatic cancer should be evaluated in a phase III trial.
Abstract: Purpose The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer. Patients and Methods Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a 40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS). Results Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58....
231 citations
TL;DR: IM-MS irradiation seems well tolerated and does not significantly impair WHO PS at three years, suggesting that treatment-related toxicity does not impair patient's daily activities.
Abstract: Introduction. The EORTC 22922/10925 trial investigated the potential survival benefit and toxicity of elective irradiation of the internal mammary and medial supraclavicular (IM-MS) nodes Accrual completed in January 2004 and first results are expected in 2012. We present the toxicity reported until year 3 after treatment. Patients and methods. At each visit, toxicity was reported but severity was not graded routinely. Toxicity rates and performance status (PS) changes at three years were compared by χ2 tests and logistic regression models in all the 3 866 of 4 004 patients eligible to the trial who received the allocated treatment. Results. Only lung (fibrosis; dyspnoea; pneumonitis; any lung toxicities) (4.3% vs. 1.3%; p < 0.0001) but not cardiac toxicity (0.3% vs. 0.4%; p = 0.55) significantly increased with IM-MS treatment. No significant worsening of the PS was observed (p = 0.79), suggesting that treatment-related toxicity does not impair patient's daily activities. Conclusions. IM-MS irradi...
106 citations
TL;DR: In patients with advanced and aggressive disease who are at a high risk to die from PCa and who are treated for their primary tumour with curative intent, immediate and sustained ADT improves OS and CSS significantly.
79 citations
TL;DR: expression of TMPRSS2-ERG is frequent in lymph node metastases of patients with untreated PCa; however, expression of this androgen-regulated fusion gene did not correspond with duration of response to endocrine therapy.
37 citations
TL;DR: Early assessment of radiotherapy quality in the ongoing EORTC trial comparing primary temozolomide versus RT in low-grade gliomas indicates that most centres conformed to protocol requirements, and systematic calculation of U and either CI or CN is recommended, both of which measure the amount of irradiated normal brain tissue.
20 citations
TL;DR: Until more sensitive and more specific screening tools are available that can detect the few cases of prostate cancer with aggressive biological potential among the majority of indolent cases, physicians and patients must understand that most diagnosed prostate cancers will never lead to death and that men can only profit from early detection if local and systemic treatment are limited to those patients who truly need it.
Abstract: Objectives The interim analyses of the long-awaited erSPC and PlCo trial data have generated conflicting conclusions regarding the value of screening for prostate cancer based on measurements of PSA. Materials and methods We review the two publications and speculate on reasons underlying the contradicting conclusion of the two studies. Results The apparently negative results of the PlCO trial may be in part because a part of the patients enrolled were “prescreened”, because of failure to biopsy some patients with PSA > 4 ng/ml, because of contamination in the control arm and because of the relatively short follow-up. However, both reports address the serious problem of overdetection and subsequent overtreatment, as the positive predictive value of positive biopsies triggered by positive PSA in the ERPC study was only 24% and many detected cancers were of low-risk. Conclusions Until more sensitive and more specific screening tools are available that can detect the few cases of prostate cancer with aggressive biological potential among the majority of indolent cases, physicians and patients must understand that most diagnosed prostate cancers will never lead to death and that men can only profit from early detection if local and systemic treatment are limited to those patients who truly need it.
16 citations
TL;DR: A simple prognostic index that can be used to estimate risks of LRR in patients with early breast cancer is constructed and enables patients to be stratified into three subgroups with different outcomes with regard to LRR.
Abstract: Aims: After treatment, early breast cancer patients undergo follow-up according to standard regimens. After the first year, the main goal is particularly to detect locoregional recurrences (LRR). Our aim was to develop a simple prognostic index to predict LRR to tailor the follow-up programme. Methods: We used data from four large international clinical randomised trials and constructed the prognostic index using Cox proportional hazards regression. The bootstrap (a resampling method) was used for internal validation. Results: A total of 6516 patients treated according to current guidelines with complete covariable information were used for analysis. Covariables important for LRR in patients treated with breast conserving therapy were age, pathological tumour status, boost and surgical margins. The same variables were important for patients treated with a mastectomy, however, instead of the boost, the pathological nodal status was important. The index is composed to consist of three groups based on LRR risk after 10-years. Conclusions: We constructed a simple prognostic index that can be used to estimate risks of LRR in patients with early breast cancer. The prognostic index enables patients to be stratified into three subgroups with different outcomes with regard to LRR. (C) 2010 Elsevier Ltd. All rights reserved.
16 citations
TL;DR: A phase II trial to test OXP with PI5FU and EBRT for PTS with EA with pCR produced the highest pCRrate reported, and significant but manageable non-hematologic TOX was observed.
Abstract: complete response (pCR) are needed. Based on phase I data, SWOG designed a phase II trial (S0356) to test OXP with PI5FU and EBRT for PTS with EA. Objectives included pCR $ 25%, acceptable toxicity (TOX), PFS, OS and exploration of molecular parameters relevant to pCR. Materials/Methods: Eligibility: clinical stage II/III EA, $ 18 years, Zubrod PS # 2, standard hematologic/non-hematologic values, and tumor # 2 cm into the gastric cardia. OXP 85 mg/m 2 was given day (d) 1, 15, and 29; PI5FU 180 mg/m 2 /d was given d 8-d43. EBRT 180 c Gy/d started d 8 x 25 fractions, 5 d/week to total dose 4500 c Gy. S was planned 2-4 weeks after NACMTx, with a second cycle of OXP/ PI5FU after S. Central pathology review of surgical specimens was mandated. The trial used a 2-stage design; the trial was halted at 45 PTS to review pCR rate; it reopened to full accrual. Results: Ninety-eight PTS enrolled between 9/15/04 and 8/18/08. Six PTS were ineligible; 2 PTS did not receive therapy (TX). Ninety PTS, 84 men (93%), median age 61.7 years, were analyzed. Four deaths (4.5%) were due to protocol TX; 2 due to NACMTX, 2 to S. Forty-three percent and 18% of PTS had grade 3/4 toxicity, respectively: 39% GI, 22% flu-like/fatigue, 17% pulmonary, 16%, hematologic, 14% mucositis and 3% neurologic. Seventy-seven PTS (86%) underwent S. 30 PTS (33%) had pCR at treating institution; 4 of these patients were found to have residual cancer by central pathology review. Twelve PTS (10%) had in situ cancer or T1N0M0. 50% received postoperative CTX. At 2 years, survival is $ 55%. Conclusions:OXP,PI5FU,andEBRTforPTSwithEAhasproducedthehighestpCRratereportedtodateforacooperativegroup trial. Significant but manageable non-hematologic TOX was observed. S mortality is acceptable. Future trials built on this platform shouldplantocompleteallTXbeforeS. TrialsusingpCRasanendpointrequirecentralpathologyreview.Furtherdata onPFSand OS will follow.
14 citations
TL;DR: In the patients with apparent local control of the disease, the incidence of metastasis decreased significantly after a few years, whereas it progressively increased in the group of patients without local control, suggesting that the primary tumor continues to shed PCa cells into the blood circulation.
10 citations
TL;DR: Pooled data of 496 patients who underwent RARC at the hands of 21 surgeons from 14 institutions from 2003 to 2009 are analyzed and interesting results are presented regarding the learning curve for robot-assisted radical cystectomy.