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Eric Lepage

Publications and source records attributed to Eric Lepage.

At least 19 recordsLinked to original sources
PubMed2005

[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome.

Assessment of early therapeutic response using metabolic imaging is potentially useful to determine prognosis in aggressive lymphoma. Between January 2000 and January 2004, 90 patients with newly diagnosed aggressive lymphoma (median age 53 years, 94% diffuse large B-cell) were prospectively explored with [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) prior to induction chemotherapy, after 2 cycles ("early PET"), and after induction completion. Therapeutic response was evaluated using conventional diagnostic methods at 4 cycles. Induction treatment with an anthracycline-containing regimen was administered to all patients, associated with rituximab in 41%. According to the International Prognostic Index (IPI), 37 patients and 53 patients belonged to the lower- and higher-risk groups, respectively. At midinduction, "early PET" was considered negative in 54 patients and positive in 36. After completion of induction, 83% of PET-negative patients achieved complete remission compared with only 58% of PET-positive patients. Outcome differed significantly between PET-negative and PET-positive groups; the 2-year estimates of event-free survival reached 82% and 43%, respectively (P < .001), and the 2-year estimates of overall survival reached 90% and 61%, respectively (P = .006). Predictive value of "early PET" was observed in both the lower-risk and higher-risk groups, indicating prognostic independence from the IPI. Therefore, FDG-PET should be an early guide to first-line strategies in aggressive lymphoma.

Adolescent↗
PubMed2005

ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma.

BACKGROUND: Chemoradiotherapy is standard treatment for localized aggressive lymphoma. To determine the optimal therapy for nonelderly persons with low-risk localized lymphoma, we conducted a randomized trial comparing chemoradiotherapy with chemotherapy alone. METHODS: Previously untreated patients less than 61 years old with localized stage I or II aggressive lymphoma and no adverse prognostic factors according to the International Prognostic Index were randomly assigned to three cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus involved-field radiotherapy (329 patients) or chemotherapy alone with dose-intensified doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) plus sequential consolidation (318 patients). RESULTS: With a median follow-up of 7.7 years, event-free and overall survival rates were significantly higher in the group given chemotherapy alone than in the group given CHOP plus radiotherapy (P<0.001 and P=0.001, respectively). The five-year estimates of event-free survival were 82 percent (95 percent confidence interval, 78 to 87 percent) for patients receiving chemotherapy alone and 74 percent (95 percent confidence interval, 69 to 78 percent) for those receiving chemoradiotherapy. The respective five-year estimates of overall survival were 90 percent (95 percent confidence interval, 87 to 93 percent) and 81 percent (95 percent confidence interval, 77 to 86 percent). In a multivariate analysis, event-free and overall survival rates were affected by treatment group, independently of tumor stage and the presence or absence of bulky disease. CONCLUSIONS: In patients under 61 years of age, chemotherapy with three cycles of ACVBP followed by sequential consolidation is superior to three cycles of CHOP plus radiotherapy for the treatment of low-risk localized lymphoma.

Adolescent↗
PubMed2004

CD10 expression in diffuse large B-cell lymphomas does not influence survival.

CD10 expression is considered as a marker of centrofollicular-derived diffuse large B-cell lymphomas (DLBCL). The aim of our study was to determine retrospectively among 98 patients with DLBCL, enrolled in the LNH93 trial of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) and homogeneously treated with high-dose cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like regimen [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP)], the expression of CD10 using immunohistochemistry and its correlation with morphological features and clinical parameters. Of the 98 patients studied, 33 (34%) expressed CD10. There was no correlation among clinical parameters, International Prognostic Index risk groups and CD10 expression, with the exception of lactic dehydrogenase levels, which were lower in CD10-negative cases (P=0.005). There was no significant correlation between CD10 expression and morphological subtyping of DLBCL. Indeed, centrofollicular-derived DLBCL may present with numerous immunoblasts or as an immunoblastic lymphoma. Overall survival rate and event-free survival were not significantly different according to CD10 expression (P=0.44 and P=0.34 respectively). Therefore, it appears that CD10 expression does not influence survival or event-free survival in DLBCL.

Biomarkers, Tumor↗
PubMed2004

TiA1 in advanced-stage classical Hodgkin's lymphoma: no prognostic impact for positive tumour cells or number of cytotoxic cells.

No reliable marker still exists for predicting those patients with Hodgkin's lymphoma (HL) who may experience a fatal outcome. Among the factors tested in the literature, it has been suggested that the number of activated cytotoxic T cells may represent a prognostic marker in HL. In 244 samples from patients with stage-IIIB/IV HL issued from the GELA H89 trial, we have analysed TiA1 expression on Reed Sternberg (RS) cells as well as the percentage of positive reactive lymphocytes. There were 34 cases (13.7%) that showed TiA1 expression on tumour cells; whereas, in 32 cases (13.1%), TiA1-positive reactive lymphocytes represented more than 30% of the reactive lymphocytes. LMP-1 was found co-expressed with TiA1 in 10 of the 22 positive cases tested. Our study confirms that a subset of classical HL expresses cytotoxic proteins, with occasional co-expression of CD20. In stage-IIIB/IV disease, neither TiA1 expression by RS cells nor a high percentage of TiA1-positive reactive lymphocytes have a prognostic impact on outcome.

Adult↗
PubMed2004

A regression shrinkage method tailored to qualitative regressors and clustered data.

We propose a shrinkage method for estimation in linear regression models with qualitative regressors. Due to the nature of the shrinkage constraint, this method tends to give estimates that are exactly zero for some groups of coefficients belonging to the same regressor. The method hence results in concise models, since some of the regressors are entirely eliminated. In conjunction with this estimation method, a model with a fixed cluster effect turns out to be closely related to frailty models. We apply the method for modelling hospital readmissions.

Adolescent↗
PubMed2004

Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial.

In myelodysplastic syndromes (MDS), anemia responds to recombinant human erythropoietin (rHuEPO) alone and in combination with recombinant human granulocyte-colony-stimulating factor (rHuGCSF) in 10% to 20% and in 35% to 40% of patients, respectively. We randomly divided 60 patients with low-grade anemic MDS and serum EPO levels lower than 500 IU/L (500 mU/mL) into 2 groups: rHuEPO + rHuG-CSF (arm A) and supportive care (arm B). After 12 weeks, those who had erythroid responses were given rHuEPO alone for 40 additional weeks. They were also given rHuG-CSF if they had relapses. A response was considered major if the hemoglobin (Hb) level was 115 g/L (11.5 g/dL) or higher and minor Hb increase was 15 g/L (1.5 g/dL) or more or if it remained stable without transfusion. Ten of 24 patients responded in arm A, and 0 of 26 responded in arm B (P =.01). Eight patients in arm A continued rHuEPO therapy alone, and 6 had relapses. Responses were always restored when rHuG-CSF was reintroduced. Mean direct costs per patient were 26,723 euros (arm A) and 8,746 euros (arm B). Quality of life was assessed with a Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. Similar percentages of patients from both arms showed significant clinical improvement. rHuEPO plus rHuG-CSF led to responses in 41.7% of MDS patients. This treatment was expensive. No effect on quality of life was demonstrated.

Adult↗
PubMed2004

Measuring performance in health care: case-mix adjustment by boosted decision trees.

OBJECTIVE: The purpose of this paper is to investigate the suitability of boosted decision trees for the case-mix adjustment involved in comparing the performance of various health care entities. METHODS: First, we present logistic regression, decision trees, and boosted decision trees in a unified framework. Second, we study in detail their application for two common performance indicators, the mortality rate in intensive care and the rate of potentially avoidable hospital readmissions. RESULTS: For both examples the technique of boosting decision trees outperformed standard prognostic models, in particular linear logistic regression models, with regard to predictive power. On the other hand, boosting decision trees was computationally demanding and the resulting models were rather complex and needed additional tools for interpretation. CONCLUSION: Boosting decision trees represents a powerful tool for case-mix adjustment in health care performance measurement. Depending on the specific priorities set in each context, the gain in predictive power might compensate for the inconvenience in the use of boosted decision trees.

Decision Trees↗
PubMed2004

Bone marrow histological patterns can predict survival of patients with grade 1 or 2 follicular lymphoma: a study from the Groupe d'Etude des Lymphomes Folliculaires.

The influence of bone marrow biopsy (BMB) histology on prognosis and management of follicular lymphomas (FL) remains controversial. A total of 390 patients with grade 1 or 2 FL were prospectively included in the multicentric Groupe d'Etude des Lymphomes Folliculaires trial and their BMB reviewed in order (i) to quantify the ratio of lymphomatous foci (LFo) area to that of BMB size (LFo/BMB), (ii) to determine the BMB patterns for a practical grading of marrow infiltration, (iii) to assess the intra- and inter-observer reproducibility of this grading and (iv) to analyse this grading on event-free (EFS) and overall survival (OS), using univariate and multivariate analyses. A total of 267 patients (68%) had BMB involvement, with inter- and intra-observer reproducibility for classifying the patterns of involvement of 91 and 96%, respectively. Uni- and multivariate analyses demonstrated the adverse influence of (i) a ratio of LFo/BMB > or = 0.1, i.e. three or four nodules/medullary space or > or = 1 nodule + foci of diffuse involvement on EFS (P = 0.03) and (ii) two different histological patterns in the same BMB on EFS (P = 0.004) and OS (P = 0.001). This latter finding was only significant in patients with a high tumour burden and remained significant in multivariate analysis. These results indicate that BMB histology can predict survival of FL patients with a high tumour burden, and may help in defining their treatment.

Adolescent↗
PubMed2003

Normal spinal bone marrow in adults: dynamic gadolinium-enhanced MR imaging.

PURPOSE: To determine the patterns of dynamic enhancement of normal spinal bone marrow in adults at gadolinium-enhanced magnetic resonance (MR) imaging and the changes that occur with aging. MATERIALS AND METHODS: Dynamic contrast material-enhanced MR imaging of the thoracolumbar spine was performed in 71 patients. The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from bone marrow enhancement time curves (ETCs). The bone marrow signal intensity on T1-weighted spin-echo MR images was qualitatively classified into three grade categories. Quantitative ETC values were correlated with patient age and bone marrow fat content grade. Statistical analysis included mean t test comparison, analysis of variance, and regression analysis of the correlations between age and quantitative MR parameters. RESULTS: Emax, slope, and washout varied widely among the patients. Emax values were obtained within 1 minute after contrast material injection and ranged from 0% to 430%. Emax values were significantly higher in patients younger than 40 years than in those aged 40 years or older (P <.001). These values decreased with increasing age in a logarithmic relationship (r = 0.71). Emax values decreased as fat content increased, but some overlap among the fat content grades was noted. Analysis of variance revealed that Emax was significantly related to age (younger than 40 years vs 40 years or older) (P <.001) and fat content grade (P <.001) but not significantly related to sex. CONCLUSION: Dynamic contrast-enhanced MR imaging patterns of normal spinal bone marrow are dependent mainly on patient age and fat content.

Adolescent↗
PubMed2003

Bone marrow with diffuse tumor infiltration in patients with lymphoproliferative diseases: dynamic gadolinium-enhanced MR imaging.

PURPOSE: To evaluate gadolinium enhancement of bone marrow in patients with lymphoproliferative diseases and diffuse bone marrow involvement. MATERIALS AND METHODS: Dynamic contrast material-enhanced magnetic resonance (MR) imaging of the thoracolumbar spine was performed in 42 patients with histologically proved diffuse bone marrow involvement and newly diagnosed myeloma (n = 31), non-Hodgkin lymphoma (n = 8), or Hodgkin disease (n = 3). The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from enhancement time curves (ETCs). A three-grade system for scoring bone marrow involvement was based on the percentage of neoplastic cells in bone marrow samples. Quantitative ETC values for the 42 patients were compared with ETC values for healthy subjects and with grades of bone marrow involvement by using mean t test comparisons. Receiver operating characteristic (ROC) analysis was conducted by comparing Emax values between patients with and those without bone marrow involvement. Baseline and follow-up MR imaging findings were compared in nine patients. RESULTS: Significant differences in Emax (P <.001), slope (P <.001), and washout (P =.005) were found between subjects with normal bone marrow and patients with diffuse bone marrow involvement. ROC analysis results showed Emax values to have a diagnostic accuracy of 99%. Emax, slope, and washout values increased with increasing bone marrow involvement grade. The mean Emax increased from 339% to 737%. Contrast enhancement decreased after treatment in all six patients who responded to treatment but not in two of three patients who did not respond to treatment. CONCLUSION: Dynamic contrast-enhanced MR images can demonstrate increased bone marrow enhancement in patients with lymphoproliferative diseases and marrow involvement.

Adult↗
PubMed2003

Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma.

We conducted a randomized trial to compare the intensive conventional chemotherapy regimen ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) with standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated patients with poor-risk aggressive lymphoma. Patients aged 61 to 69 years who had aggressive non-Hodgkin lymphoma with at least one prognostic factor of the age-adjusted international prognostic index (IPI) were included. ACVBP consisted of an induction phase of intensified chemotherapy and central nervous system (CNS) prophylaxis followed by a sequential consolidation phase. Of the 708 patients registered for the study, 635 were eligible. The rate of complete response was 58% in the ACVBP group and 56% in the CHOP group (P =.5). Treatment-related death occurred in 13% of the ACVBP group and 7% of the CHOP group (P =.014). At 5 years, the event-free survival was 39% in the ACVBP group and 29% in the CHOP group (P =.005). The overall survival was significantly longer for patients treated with ACVBP, at 5 years it was 46% compared with 38% for patients treated with CHOP (P =.036). CNS progressions or relapses were more frequent in the CHOP group (P =.004). Despite higher toxicity, the ACVBP regimen, used as first-line treatment for patients with poor-risk aggressive lymphoma, is superior to standard CHOP with regard to both event-free survival and overall survival.

Aged↗
PubMed2003

An intranet-based automated system for the surveillance of nosocomial infections: prospective validation compared with physicians' self-reports.

OBJECTIVE: To examine the reliability of the data produced by an automated system for the surveillance of nosocomial infections. SETTING: A 906-bed, tertiary-care teaching hospital. DESIGN: Three surveillance techniques were concurrently performed in seven high-risk units during an 11-week period: automated surveillance (AS) based on the prospective processing of computerized medical records; laboratory-based ward surveillance (LBWS) based on the retrospective verification by ward clinicians of weekly reports of positive bacteriologic results; and a reference standard (RS) consisting of the infection control team reviewing case records of patients with positive bacteriology results. Bacteremia, urinary tract infections, and catheter-related infections were recorded for all inpatients. The performances (sensitivity, specificity, and time consumption) of AS and LBWS were compared with those of RS. RESULTS: Of 548 positive bacteriology samples included during the study period, 229 (42%) were classified as nosocomial infections. The overall sensitivity was 91% and 59% for AS and LBWS, respectively. The two methods had the same overall specificity value (91%). Kappa measures of agreement were 0.81 and 0.54 for AS and LBWS, respectively. AS required less time to collect data (54 seconds per week per unit) compared with LBWS (7 minutes and 43 seconds per week per unit) and RS (37 minutes and 15 seconds per week per unit). CONCLUSION: Our results confirm that the retrospective review of charts and laboratory data by physicians lacks sensitivity for the surveillance of nosocomial infections. The intranet-based automated method developed for this purpose was more accurate and less time-consuming than the weekly, retrospective LBWS method.

Automation↗
PubMed2003

Teaching Arden Syntax using a simulated environment.

The Arden Syntax is a simple syntax that allows physicians to encode medical knowledge in small modules, called medical logic modules (MLM). These MLM are well suited to data-driven alerts and reminders. While the Arden syntax is simple to teach, the students are most of the time limited to the writing of modules and the verification of the module's syntax. Our work proposes an environment that simulates various elements required by MLMs, allowing the students to execute the MLMs they have written immediately. This provides the necessary feedback to understand in depth the inner workings of MLMs.

Computer Simulation↗
PubMed2002

Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma.

PURPOSE: Randomized trial LNH93-3 was conducted on patients who had poor-prognosis aggressive lymphoma and were younger than 60 years with two to three factors of the age-adjusted International Prognostic Index to evaluate the benefit of early high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Patients were randomized between doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) chemotherapy followed by sequential consolidation and an experimental shortened treatment consisting of three cycles with escalated doses of cyclophosphamide, epirubicin, vindesine, bleomycin, and prednisone and collection of peripheral-blood stem cells. On day 60, HDT was administered with 1,3-bis(2-chloroethyl)-1-nitrosourea, etoposide, cytarabine, and melphalan followed by ASCT. RESULTS: Eligible patients (n = 370) with aggressive lymphoma were analyzed. For ACVBP (181 patients) and HDT (189 patients), respective complete remission rates were 64% and 63%. With a median follow-up of 60 months, 5-year overall survival and event-free survival for ACVBP and HDT were 60% +/- 8% and 46% +/- 8% (P =.007) and 52 +/- 8% and 39 +/- 8% (P =.01), respectively. Survival was independently affected by age greater than 40 years (P =.0003), T-cell phenotype (P =.009), bone marrow involvement (P =.003), and HDT treatment group (P =.04). CONCLUSION: Early HDT with ASCT in high-risk patients was inferior to the ACVBP chemotherapy regimen. These results indicate that the received dose-intensity before HDT was too low when compared with ACVBP and HDT and was given too early.

Adolescent↗
PubMed2002

Long-term kidney graft survival across a positive historic but negative current sensitized cross-match.

BACKGROUND: The sensitive cross-match (XM) techniques that have been introduced for clinical transplantation can detect anti-donor immune reactivity despite a negative standard National Institute of Health (NIH) cross-match. One of them uses anti-kappa human light chain globulins (AHG). But there is some discussion about the clinical consequences of a positive AHG-XM in the historical sera that became negative in the sera collected just before the transplantation (pretransplant sera). This study was intended to assess the risk of kidney graft failure associated with a positive historic but negative pretransplant AHG-XM in allosensitized patients having a negative historic NIH-XM. METHODS: This retrospective study includes 90 consecutive renal transplants in immunized patients performed at one center between 1985 and 1991. All of the patients had negative historical and pretransplant standard NIH lymphocytotoxic cross-matches and received the same immunosuppressive regimen. The AHG-XMs were done retrospectively using peak historic and sera collected on the day of the transplantation. RESULTS: The AHG cross-match (AHG-XM) was positive in 17 patients, although the standard NIH cross-match was negative. Fourteen of them had a positive historical but negative pretransplant AHG-XM. The actuarial graft survival in this group of 14 patients was 100% at 1 year and 78% at 9 years compared with 90 and 67%, respectively, in patients with negative historical AHG-XM. In addition, the number of rejection episodes per patient as well as renal function at 1, 2, and 5 years were similar in the two groups. IgG anti-donor HLA class I accounted for the XM positivity in 12 of the 14 patients; most rapidly lost all antibody reactivity by NIH technique in an average time of 8 months before the transplantation. In conclusion, this study suggests that transplant patients having a negative historic NIH-XM but a positive historic AHG-XM may not be at high risk of graft failure especially if there is a well-documented sera history showing a marked decrease in PRA level before transplantation and a negative pretransplant AHG-XM.

Adult↗
PubMed2002

CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.

BACKGROUND: The standard treatment for patients with diffuse large-B-cell lymphoma is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Rituximab, a chimeric monoclonal antibody against the CD20 B-cell antigen, has therapeutic activity in diffuse large-B-cell lymphoma. We conducted a randomized trial to compare CHOP chemotherapy plus rituximab with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. METHODS: Previously untreated patients with diffuse large-B-cell lymphoma, 60 to 80 years old, were randomly assigned to receive either eight cycles of CHOP every three weeks (197 patients) or eight cycles of CHOP plus rituximab given on day 1 of each cycle (202 patients). RESULTS: The rate of complete response was significantly higher in the group that received CHOP plus rituximab than in the group that received CHOP alone (76 percent vs. 63 percent, P=0.005). With a median follow-up of two years, event-free and overall survival times were significantly higher in the CHOP-plus-rituximab group (P<0.001 and P=0.007, respectively). The addition of rituximab to standard CHOP chemotherapy significantly reduced the risk of treatment failure and death (risk ratios, 0.58 [95 percent confidence interval, 0.44 to 0.77] and 0.64 [0.45 to 0.89], respectively). Clinically relevant toxicity was not significantly greater with CHOP plus rituximab. CONCLUSIONS: The addition of rituximab to the CHOP regimen increases the complete-response rate and prolongs event-free and overall survival in elderly patients with diffuse large-B-cell lymphoma, without a clinically significant increase in toxicity.

Aged↗
PubMed2002

[Volume and costs of the hospital management of cancer in France in 1999].

The volume of hospitalization care for cancer is hardly measured; this, in particular, because there are various structures assuming those responsibilities and heterogeneous information systems. The objective of this study is to present a model of precise algorithm of selection of hospital stays for cancers from French National databases of hospital discharges, and its results for 1999. Cancer stays are selected firstly, according to the presence of a tumor diagnosis code. Then, a refine in/out sort is done, based on a precise criteria grid issued from an expert group. A financial valorisation of hospital activity is realised from national cost weight scale. On the whole, the 1999 cancer database contains 5,428,518 inpatients and outpatients stays. Cancer weight 15.8 % of the whole hospitalization care activity, and costs around 6.04 billion. Surgery is the first expense with 2,100 millions, then chemotherapy with 1 135 millions and radiotherapy with 670 millions. Digestive tumors represent about 26 % of total cost, tumors of the respiratory system and breast tumor 11 % each. A work of validation of this algorithm is being realized on a sample of care providers.

Algorithms↗