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Biomedical subjects

E Lepage

Publications and source records attributed to E Lepage.

At least 109 records · Page 6Linked to original sources

Metaanalysis: methodology, biostatistic rules, application in onco-hematology.

Metaanalysis are proposed in order to increase statistical power and draw better conclusion about the efficacy of a treatment. After inclusion of trials corresponding to an objective, a statistical procedure is performed permitting to obtain an estimate of the common effect with the confidence interval after model validation. The main problem is posed by the selection of trials in order to avoid positive bias linked to the greater number of positive published studies. Application of metaanalysis in oncohematology should be proposed in case of weakness size of population in the individual trials.

Algorithms↗

[The place of bone marrow autografts in the treatment of Hodgkin's and non-Hodgkin's lymphoma].

The therapeutic approach to relapses in aggressive non-Hodgkin's lymphoma has been changed by high dose chemotherapy and autologous bone marrow graft. In the absence of dramatic improvement following the conditioning regimen, such a procedure should be reserved for patients still sensitive to salvage therapy. Up to 40%-50% of these selected cases can expect prolonged disease-free survival. Autologous bone marrow graft in first remission should only be considered in poor prognosis patients in a carefully randomized study. In Hodgkin's disease, relapses and patients in partial remission after MOPP and ABVD treatment are potential candidates for autologous bone marrow graft. Preliminary results indicate a disease-free survival up to 50%.

Antineoplastic Combined Chemotherapy Protocols↗

[Autografts of blood cells at various stages].

Thirty-nine patients with acute myeloblastic or lymphoblastic leukaemia had peripheral blood mononuclear cells collected by 3 continuous-flow leukapheresis as they entered first remission after induction chemotherapy. CFU-GM were assayed as a measure of the number of haemopoietic stem cells in each collection. Numbers of CFU-GM harvested varied among the patients (for example 0.27 to 155.10(4)/kg for ANLL patients). Nineteen patients underwent peripheral blood stem cells autografts after a conditioning regimen with high dose cyclophosphamide and TBI. The patients were transfused with a median of 2.2.10(4)/kg CFU-GM cells (0.28 to 100.10(4) CFU-GM/kg). Only 1 patient had a graft failure. The rate of haemopoietic recovery was studied for our patients and those reported in the literature. A strong correlation exists between the numbers of CFU-GM transfused and the rate of granulocytes and platelets recovery. Very rapid recovery are regularly obtained when the number of CFU-GM transfused is superior to 5.10(4)/kg.

Adult↗

[Residual masses after chemotherapy of non-Hodgkin's lymphoma].

Among 149 patients treated for high grade non-Hodgkin's lymphoma, 22 post-therapy mediastinal and abdominal residual masses were observed (14.7%). In 12 cases, initial histology was malignant lymphoma, diffuse large cell. The follow-up of these patients was similar to those without residual masses. Magnetic resonance imaging may be helpful in distinguishing viable tissue from fibrotic tissue.

Fibrosis↗

[Low-grade non-Hodgkin's lymphoma in the adult: new therapeutic approaches].

Treatment of disseminated low grade non-Hodgkin's lymphomas (NHL) remains unsolved. Despite an initial high remission rate (50%-70%) with chemotherapy, relapses occur and only 20 to 40% of patients are expected to be free of disease after 10 years. From 1981 to 1984, 113 low grade NHL were studied in order to determine factors influencing survival without progression. In a randomized trial, patients received either PCOP combination or PACOP for 6 months followed by chlorambucil or CVP for 12 months. Histological distribution was: follicular small cleaved cells 70 patients, follicular mixed 31 patients, small cells CLL type 12 patients. Stage distribution was: stage IV 88 patients with 74 bone marrow involvement, stage III 17 patients, stage II with bulky masses 8 patients. Complete response (CR) was observed in 49 patients at the end of treatment. Among the ten variables studied, only stage and the number of sites involved had a significant effect on the probability of achieving CR. Only CR significantly affected the freedom from progression (P less than 0.01). Median survival after progression was 21 months. Recently, alpha recombinant interferon has been proposed as treatment for low grade NHL. Cumulative results from the literature give a response rate of 42% on 139 patients. The response rate was higher in follicular NHL than in the CLL type, and response did not clearly correlate with dose. The CR rate was low (less than 20%) and relapses occurred after stopping therapy. Combined use of interferon and chemotherapy is proposed for future clinical trials.

Adult↗

[Termination rules in therapeutic trials. Application of sequential methods in 2 clinical trials in hematology].

In haematology, randomized clinical trials often use survival or disease-free interval as response criterion (censored data). For ethical reasons, interim analyses are usually performed, but these interim analyses lead to an increasing Type I error. Sequential methods allow for repeated testing. Three sequential methods are well-adapted to censored data: group sequential analysis, the sequential probability ratio test and the triangular test. The triangular test has the best properties: it allows an early termination of the trial whatever the difference between the treatment groups and without the risk of long duration trials. Sequential analyses can be performed at the same frequency as the usual interim analyses. These three sequential procedures have been applied to the analysis of two cooperative trials in haematology. It appears that the use of sequential methods has to be recommended in the design of randomized clinical trials with a censored response criterion.

Antibiotics, Antineoplastic↗

[Therapy of acute leukemia in the adult. Role of anthracyclines].

Anthracyclines chemotherapy has changed the outcome of adult acute leukemia. Daunomycin, Adriamycin and Zorubicine are the three main analog derivatives. In adult ALL, in randomized study, anthracyclines in induction regimen improve significantly the remission rate up to 80%. In AML, combination chemotherapy of Ara-C and anthracyclines is the standard induction regimen. In randomized study, Daunomycin has the same activity than adriamycin at the same dose with less toxicity. Comparison of Daunomycin: 60 mg/m2 X 3 d with Zorubicin: 120 mg/m2 X 3 d shows the same activity in association with Ara-C with less toxicity. In protocol 01 AM 81, Zorubicin has been used at the dose of 200 mg/m2 X 4 d in association with Ara-C: 200 mg/m2 X 5 d. 444 patients has been included in the study. The complete remission rate is 83% with a mortality rate of 7% and only 11% failure. Zorubicin allows intensification of induction regimen with similar or less toxicity than conventionnal regimens.

Adult↗

[Inhibition of DNA repair, major objective of anticancer chemotherapy. Apropos of 680 cases with continuous platin bleomycin combination].

Six hundred and eighty seven cases of cancers of various sites, essentially of squamous structure are presented. Their treatment consisted of a combination of cisplatinum, given 5 days in a row every 3 weeks and of continuously infused bleomycin, also 5 days every 3 weeks. Objective (greater than 50 p. 100) regressions were seen in 70 p. 100 of cases, a significantly greater proportion than obtained by other chemotherapies or by cisplatinum and bleomycin given for one day. This difference is attributed to the fact that bleomycin, a potent inhibitor of type II DNA polymerase, inhibits DNA repair. The authors evaluate the extent of DNA repair to be about 80 p. 100 of all the lesions created by platinum salts and consider DNA repair to be a major limitation of cytostatic therapy, often neglected in the design of chemotherapy protocols.

Adenocarcinoma↗

[Advanced epithelial cancers of the ovary: results of 4 chemotherapy protocols (110 cases)].

Following surgery for epithelial carcinoma of the ovary, FIGO stages IIc, III and IV, 110 patients received chemotherapy in one of four treatment regimens (Melphalan; Cyclophosphamide-Methotrexate-Fluoro uracil; Cyclophosphamide-Cisplatinum; Cyclophosphamide-Cisplatinum-Fluoro-uracil). Melphalan alone was as effective as combination chemotherapy and less toxic. The study confirms that the survival duration is inversely correlated to the stage of the disease and to the amount of residual disease following surgery. It also confirms the role of the "second look" surgery in the evaluation of the response to chemotherapy, and in the overall management of the disease.

Adult↗

Treatment of low-grade non-Hodgkin's lymphomas: assessment of doxorubicin in a controlled trial.

From 1981 to 1984 a randomized clinical trial was conducted to evaluate the role of doxorubicin in low grade malignancy non-Hodgkin's lymphoma (NHL). One hundred and thirteen patients were treated by an induction regimen including cyclophosphamide 400 mg/m2 day 1 and 8, vincristine 1.4 mg/m2 day 1 and 8, procarbazine 80 mg/m2 day 1 to 14, prednisone 60 mg/m2 day 1 to 5 (PCOP regimen) randomly associated to doxorubicin: 20 mg/m2 day 1 and 8 (PACOP regimen). Maintenance therapy consisted of 12 monthly courses of chlorambucil 10 mg/m2 for 5 days or association of cyclophosphamide 300 mg/m2 for 3 days, vincristine 1.4 mg/m2 day 1 and prednisone 60 mg/m2 for 5 days. Complete response (CR) was obtained in 51 patients (45 per cent), in 30 patients after induction regimen and in 21 patients after maintenance therapy, without difference according to regimens. Bone marrow involvement (p = 0.02) and number of involved nodal sites (p = 0.001) were found to influence probability of achieving CR. The median time to progression was estimated to 39 months without difference between regimens. Median overall survival is not reached with a median follow-up of 53 months. Multivariate regression analysis permits observation of negative influence on survival of three parameters: initial bone marrow involvement, age over 50 years and incomplete response to treatment. The initial adjunction of doxorubicin did not seem to influence the appearance of histologic progression.

Antineoplastic Combined Chemotherapy Protocols↗

A UMLS-based knowledge acquisition tool for rule-based clinical decision support system development.

Decision support systems in the medical field have to be easily modified by medical experts themselves. The authors have designed a knowledge acquisition tool to facilitate the creation and maintenance of a knowledge base by the domain expert and its sharing and reuse by other institutions. The Unified Medical Language System (UMLS) contains the domain entities and constitutes the relations repository from which the expert builds, through a specific browser, the explicit domain ontology. The expert is then guided in creating the knowledge base according to the pre-established domain ontology and condition-action rule templates that are well adapted to several clinical decision-making processes. Corresponding medical logic modules are eventually generated. The application of this knowledge acquisition tool to the construction of a decision support system in blood transfusion demonstrates the value of such a pragmatic methodology for the design of rule-based clinical systems that rely on the highly progressive knowledge embedded in hospital information systems.

Artificial Intelligence↗

Model-based methodology for analyzing incomplete quality-of-life data and integrating them into the Q-TWiST framework.

BACKGROUND: The standard Q-TWiST approach defines a series of health states and weights each state's duration according to its quality of life (QOL) to calculate quality-adjusted lifetimes. However, a fixed weight may not adequately reflect time variations in QOL. METHODS: To account for measurements derived from irregular visits and informative missing data, the authors estimated the mean QOL profile using a mixed-effect growth curve model for the response, combined with a logistic regression model for the drop-out process. RESULTS: Using data from a clinical study of lymphoma patients, the authors demonstrated better readaptation to normal life for patients younger than 30. Sensitivity analyses and computer simulations demonstrated that modeling the drop-out probability as a function of the QOL measurements is necessary if conditioning by health state is not possible. CONCLUSION: Our model-based approach is useful to analyze studies with incomplete QOL data, especially when approximate QOL assessment by health state is not possible.

Adult↗