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P Lagarde

Publications and source records attributed to P Lagarde.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Current knowledge on the action of retinoids in carcinoma of the head and neck].

The retinoids are a pharmacologic class based on the vitamin A or retinol. The most known related derivatives are the all-trans (ATRA), 13 and 9 Cis retinoic acids. The antitumor and differenciative activities have been demonstrated in: in vitro, in vivo and clinical studies. In head and neck cancers, the clinical phase III trials in chemoprevention of second primary tumors have shown discordant results related to the type of retinoic acid. Nuclear retinoic acid receptors are members of the steroid-thyroid and vitamin D3 superfamily of nuclear receptors which regulate differenciation proliferation and apoptosis in cooperation with mediated proteins of the apoptosis (especially p53 protein). A thorough knowledge on the earlier mechanisms involved in carcinogenesis of squamous cell carcinomas would lead to futur reversal therapy with the reversal of pathologic to normal tissues by the restauration of mechanisms of the physiologic control. This futur clinical trial research could provide cancer prevention and control by the induction of cellular differentiation rather than proliferation (retinoids) and/or the expression of tumor-suppressor genes (p53 protein transfection). Finally, the retinoids treatment should be performed in control studies because of the toxicity at high doses.

Apoptosis↗
PubMed1995

[In vitro effects of piracetam on the radiosensitivity of hypoxic cells (adaptation of MTT assay to hypoxic conditions)].

This paper describes the adaptation of the MTT assay to hypoxic conditions in order to test the in vitro effect of piracetam on hypoxic cells and particularly on the radiosensitivity of hypoxic cells since this drug has shown clinical effect on acute and chronic hypoxia. The V79 cell line was selected by reference to preliminary hypoxic experiments using clonogenic assay and euoxic experiments using clonogenic and MTT assays. Cell growth and survival in our hypoxic conditions were assessed using MTT assay with an enclosure and special 48-well plates both made of glass. Growth curves on glass versus reference polystyrene plates were comparable and confirm the validity of using special glass plates. Growth curves on glass plates after 1-hour exposure to nitrogen versus air were comparable, so there is no bias effect due to gas composition. Survival curves using MTT versus reference clonogenic assay were comparable after radiation exposure in eu- and hypoxic conditions, and confirm the validity of our original technique for creating hypoxia. The Oxygen Enhancement Ratio was of about 3 for 1-hour hypoxic exposure. Piracetam gave no cytotoxic effect up to 10 mM of piracetam. Growth curves after continuous drug exposure and 1-hour euoxic versus hypoxic exposure gave no cytotoxic effect up to 10 mM of piracetam. Survival curves after continuous drug exposure to 10 mM of piracetam gave no significant effect on the radiosensitivity of hypoxic V79 cells using MTT or clonogenic assay. However, this does not preclude a potential in vivo effect of piracetam on the radiosensitivity owing to its action on microcirculation and its rheologic properties. The adaptation of the MTT assay to hypoxic irradiation conditions yields the easy screening of radiosensitizing drugs: shorter incubation, semi-automatic method and simultaneous analysis with different serial concentrations thanks to the special 48-well glass plates.

Animals↗
PubMed1994

Radiobiological features of acute myeloblastic leukemia: comparison of self-renewal versus terminally differentiated populations.

PURPOSE: To evaluate the radiosensitivity of self-renewing progenitor cells in acute myeloblastic leukemia (AML), we have compared the radiosensitivity of the cells grown either in methylcellulose alone for 7 days, or first in suspension culture for 7 days before being plated in methylcellulose. Methylcellulose selects for terminal-dividing cells and suspension cultures have been developed because they allow self-renewal to occur: The exponential growth of the progenitors of AML cultured in suspension is due to self-renewal. METHODS AND MATERIALS: Cells were harvested from previously untreated leukemic human bone marrows. The myeloblastic lineage of the colonies was assessed by morphological, cytochemical, and immunophenotypic analysis, and by the use of growth factors that did not stimulate the growth of T-lymphocytes. The cell-cycle distribution of the blasts was analyzed by flow cytometry and was comparable for all samples. The irradiation was performed with gamma-photons at a dose-rate of 0.05 Gy/min, similar to the clinical conditions used in our institution for total body irradiation (TBI). RESULTS: The culture methods selected aggressive leukemias. There were large variations of the individual radiosensitivity whatever culture method was used. The progenitor cells capable of self-renewal were more radiosensitive than terminal dividing cells. In two cases, a shoulder was found in the initial part of the cell-survival curves of cells capable of self-renewal. In these two cases, the best fit for the data was the linear quadratic model (survival = e-alpha D-beta D2) with alpha/beta values of 1.49 Gy and 3.12 Gy, respectively. CONCLUSION: The very low values of alpha/beta suggest a reduced antileukemic effect in case of fractionated TBI, and may lead to more reliable screening methods to determine the most appropriate technique for radiation ablation of bone marrow prior to bone marrow transplantation (BMT).

Adolescent↗
PubMed1993

Ethmoidal cancers: a retrospective study of 22 cases.

From April 1978 to June 1990, 22 patients with ethmoidal cancer were treated at Fondation Bergonié by a combination of surgery and radiation therapy. The mean age was 59.6 years (range 34-79 years) and the sex ratio is 2.7 (16 males/6 females). Histologic types were: adenocarcinoma, 13 cases; squamous carcinoma, 4 cases; undifferentiated carcinoma, 3 cases and esthesioneuroblastoma, 2 cases. Exposure to wood dust was encountered in 11 patients, especially in cases of adenocarcinoma: 10/13 (77%). Staging according to the classification of the University of Florida was: Stage I, 10 patients; Stage II, 5 patients and Stage III, 7 patients. Resection was considered as complete in 16 cases and only one orbital exenteration was performed. The postoperative radiation therapy delivered a mean given dose of 55.7 Gy (range 50-70 Gy) expressed to the hot spot using a technique adapted to tumor location and extension. Complete remission was achieved in 20 cases. Median follow-up is 28 months. The 5-year overall and disease-free survival are 44% and 38%, respectively. Analysis of recurrences according to staging gives: 5/10 Stage I, 2/5 Stage II and 5/7 Stage III. Recurrence is pejorative since death occurs in all cases within an average of 6 months following salvage treatment, except for three patients still alive within less than 6 months and in second remission. Prognosis of ethmoidal cancer depends on staging and local control.

Adenocarcinoma↗
PubMed1992

Results of postoperative radiation therapy in medullary carcinoma of the thyroid: a retrospective study by the French Federation of Cancer Institutes--the Radiotherapy Cooperative Group.

Between 1971 and 1989, 59 patients received external radiation therapy with a curative intent. There were 25 females and 34 males, ranging in age from 19 to 87. No patients had distant metastasis at the onset of treatment. The majority of patients had a total thyroidectomy (55/59), generally combined with neck dissection. Residual tumour was left in 11 cases, and 44 patients had positive cervical nodes. Using megavoltage radiotherapy, the whole neck and the upper mediastinum area were most often irradiated through a large anterior Y-shaped field without laryngeal shielding. The mean dose to the tumoral bed was 54 Gy. Dysphagia was observed in 32 patients (11, 17 and 5 scores were grade 1, 2 and 3, respectively). Dyspnea occurred in five cases and in two of these cases, it was considered to be severe. Local recurrences were noted in 18 (30%) patients, most of them occurring within the fields of irradiation. Parameters such as age, sex, total dose, irradiated volumes or cervical node enlargement did not modify the local control rate. The same conclusions can be drawn for distant failures. Thirty five patients are still alive and among them, 24 have no evidence of disease. The average length of survival is 70.5 months and is shortened by the occurrence of distant failures except in patients with bone metastases.

Adult↗
PubMed1992

Prognostic variables for the selection of patients with operable soft tissue sarcomas to be considered in adjuvant chemotherapy trials.

From 1975 to 1988, 144 patients naive of treatment, with non-metastatic soft tissue sarcoma were treated at Fondation Bergonié by surgery, followed by radiotherapy and without chemotherapy. An analysis of prognostic variables was done on this population to determine patients for whom an adjuvant chemotherapy would be relevant. Prognostic variables in overall survival (OS), metastasis-free survival (MFS), disease-free and local free recurrence survivals were analysed by univariate and multivariate analysis. In multivariate analysis using Cox's model, only tumour depth and tumour grade were significant with the MFS end point, while tumour depth, tumour grade and tumour site were significant when considering OS. A predictive stratification for patients is proposed: a favourable prognostic group with grade 1 tumour or superficial, grade 2 tumour (5-year OS: 97.8%; 5-year MFS: 100%); an intermediate prognostic group with deep, grade 2 tumour or superficial, grade 3 tumour (5-year OS: 58.8%; 5-year MFS: 48.1%); and finally a poor prognostic group with deep, grade 3 tumour (5-year OS: 31.7%; 5-year MFS: 34.1%). Patients in the intermediate and poor prognostic groups who present a high metastatic risk are to be considered for adjuvant chemotherapy trials.

Adolescent↗
PubMed1992

Evaluation of medical students' hospital training: interest of students' essays.

To evaluate the impact of teaching during hospital training in an adult cancer ward, 107 consecutive students were asked to freely select the chart of a patient representative of their course and to write comments on it, at the end of their course. Students selected charts of young patients rather than older ones (P less than 0.0001). Most of the patients had a poor prognosis (69%). Students frequently emphasized psychosocial aspects of cancer and patient's information (patient-student relationship: 50%; diagnosis acceptance: 36%; information: 19%), but rarely considered post-treatment sequelae of cured patients (4%), palliative care (9%), and truth (10%). The selection of a large majority of poor prognosis patients led us to invite them to attend consultations to meet patients who are cured or in fair condition. Other topics must be emphasized (palliative care, truth, and post-treatment morbidity). Finally, such an evaluation provides good information on the course of the students and is easily performed and analysed.

Education, Medical↗
PubMed1991

A survey in general practice about undergraduate cancer education: results from Gironde (France).

In Bordeaux University (France), oncology teaching was individualized in 1972, and an optional oncology course devoted to general practice was created in 1980. To evaluate the adequacy of these two oncology classes for general practitioners and so to adapt our current teaching, we sent to each of 1,219 general practitioners (GP's) of Gironde (county of the southwest of France) an anonymous questionnaire about oncology teaching in prevention, screening and cancer detection, cancer management, and curriculum balance. We received 688 (56.4%) responses. GPs said that as undergraduates, they were insufficiently instructed about screening programs (65%), pain control (80%), palliative care (50%) and fundamental or biological data (greater than 55%). This situation, which showed signs of improvement from 1975 on, has improved even more since 1985. General practitioners, as well as undergraduates, are not yet adequately educated about cancer for general practice, so we have to adapt better our current teaching for undergraduates and those in continuing medical education.

Curriculum↗
PubMed1991

[Role of radiotherapy in cancer of the ethmoid. Retrospective study of a series of 24 cases].

From april 1978 to december 1988, 24 patients were treated were by radiotherapy at the Bergonié Foundation cases were for ethmoidal cancer cases. Twenty two for initial treatment and two refermed for local recurrence. The mean age was 51.4 years and the sex ratio was 5.2 (21 men/4 women). Histologically there were 15 adenocarcinomas, 3 squamous carcinomas, 4 undifferentiated carcinomas and 2 esthesioneuroblastomas. According to the classification of the University of Florida, they were retrospectively classified as stage I = 9 pts, stage II = 5 and stage III = 10. Twenty one patients had postoperative radiotherapy and 3 had exclusive radiotherapy. The average dose was 55.3 Gy. Local control was obtained in 12 pts. Seven patients have recurred locally (within an average period of 12 months) and 5 patients showed progression of disease after treatment. The overall actuarial survival and the disease free survival at 5 years were respectively 50% and 53%. The actuarial survival by stage at 2 years and 5 years was: stage I (88% and 61%), stage II (100% and 50%), stage III (0%). The prognosis of ethmoidal cancer is strictly correlated to local control. For this reason, radiotherapy (with or without surgery) remains important in the treatment of this disease.

Adult↗
PubMed1990

[Radiotherapy of carcinoma of the nasopharynx].

Cancer of the cavum is a rare condition in France. These tumors have, however, a poor prognosis and in general occur in young subjects. While radiotherapy would appear to be the best mean of ensuring local control, life expectancy depends solely on distant metastases. Analysis of a series of 58 cases treated at the Fondation Bergonié from 1975 to 1985 demonstrated a 30% five year survival rate. Among the 25 cases of recurrence, 1 was exclusively local and 6 were loco-regional (T and N), while 18 patients presented metastatic progression, either exclusively, or with local or lymph node failure. The prognostic factors found in this series were: age, extension beyond the cavum, the dose of radiotherapy. Results in the literature in terms of survival remain poor, especially in advanced stages and the future perspectives for better control of this disease remain early diagnosis and other forms of therapy such as combined chemotherapy and radiotherapy.

Adolescent↗
PubMed1990

[Pure ovarian dysgerminoma. Evaluation of experiences and definition of a therapeutic strategy].

The authors present a series of 10 pure dysgerminoma of the ovary treated between 1976 and 1984; mean age = 19.5 years, range 15-46 years. All patients had initial surgery: 8 annexectomies for 5 stages Ia and 3 stages IIIc nodal disease, 1 hysterectomy with bilateral adnexectomy for a 46 year old stade Ib patient and 1 case of salvage surgery for a progressive disease after a single adnexectomy. Two patients had no adjuvant therapy after initial adnexectomy (stage Ia tumors less than 10 cm in diameter). Four patients received a prophylactic subdiaphragmatic radiation therapy (3 stages Ia tumors larger than 10 cm, 1 stage Ib disease). Three patients received an irradiation for a subdiaphragmatic bulky disease and a prophylactic supradiaphragmatic irradiation (stage IIIc nodal disease). Two patients received chemotherapy, one for recurrence, the other for progressive disease. The authors discuss the therapeutic indications of pure dysgerminoma of the ovary, especially the conservative management of young patients wishing to preserve an hormonal and obstetric future and the value of radiologic and serologic follow-up. Recent data in the literature underline the efficacy of new combinations of cytotoxic agents and their role as an adjuvant of surgery in early as well as in advanced stages.

Actuarial Analysis↗
PubMed1990

[Postoperative radiotherapy in soft tissue sarcomas of the limbs. Analysis of irradiation volumes and doses in a series of 31 cases].

From October 1985 to October 1988, 31 patients with a soft tissue sarcoma of extremities were treated in our institute by conservative resection and post-operative radiation therapy. The initial target volume encompasses the entire musculoskeletal area occupied by the tumor. The compartmental definition of this initial target volume is based on clinical, radiographic, histopathologic and operative findings. We analyzed the irradiated volume in terms of the anatomical definition and feasibility. We then evaluated the distribution of the dose in the irradiated volume. The variation of the dose is always less than 10%. Accordingly, the range of dose in the irradiated volume varies from 45 to 50 Gy in the compartmental volume after a complete resection, and from 55 to 60 Gy in the tumor bed after a marginal or incomplete resection. For this series, the median follow-up is 27 months. We observed 3 distant metastases and 1 progressive disease in the irradiated volume. No locoregional recurrence appeared in the margins or outside the irradiated volume. These preliminary results validate the compartmental definition of the initial target volume. Furthermore, they point out the lack of opportunity to encompass tendinous insertions in the irradiated volume and to boost the scar. Finally, the definition of optimal dose for the control of microscopic residual tumor is discussed.

Adult↗
PubMed1989

Influence of dose intensity and density on therapeutic and toxic effects in Hodgkin's disease.

From 1972 to 1976, 95 patients with clinical stages I-IIIA Hodgkin's disease were treated by chemotherapy with cyclophosphamide, vinblastine, procarbazine and prednisone (CVPP) before and after extended field radiotherapy. The CVPP schedule gave: (1) a constant drug dosage for each patient independent of body surface or weight; and (2) a total drug dosage dependent on haematological tolerance, since the treatment was given for 21 days or until the leukocyte count dropped to 2 x 10(9) l-1. The drug dosage per unit body surface (or 'dose density') significantly correlates with the drop in leukocyte count (P less than 0.001) and the tumour regression at the end of the induction course (P = 0.020). Disease-free survival is significantly related to dose density (P = 0.050) but not to dose intensity calculated on the duration of treatment (P = 0.240). However, after exclusion of three marginal recurrences due to border-line radiotherapy, the dose intensity significantly correlates with the disease-free survival (P = 0.031) and with the duration of complete remission (r = 0.870).

Adolescent↗
PubMed1989

[Radiotherapy and cerebral stereotaxis. Examples of dosimetry with 3D reconstruction].

External stereotactic radiotherapy allows to irradiate a small and carefully delimited intracranial volume according to the spatial definition of the target. To determine the distribution of the dose in the volume irradiated, we developed a dosimetric programme adapted to our particular treatment conditions (arc therapy in the frontal and oblique planes converging onto the centre of the target volume with circular beams 8 to 20 mm in diameter using 18 MV X photons). The principle of the programme is a 3D reconstruction based on ten transverse CT slices. This reconstruction, related to the stereotactic coordinates defined during stereotactic localization, visualises the outline of each oblique frontal treatment plane and the outline of the three perpendicular reference planes passing through the centre of the target volume (i.e. transverse, sagittal, coronal). The isodose distribution is then calculated in the planes defined by these reconstructions. Under treatment conditions, we use the parameters measured for each beam with their additional collimation. We present an evaluation of this software performed on a phantom consisting of a skull containing a defined target.

Humans↗
PubMed1988

Brief chemotherapy associated with extended field radiotherapy in Hodgkin's disease. Long-term results in a series of 102 patients with clinical stages I-IIIA.

From 1972 to 1976, 102 patients with stages I-IIIA Hodgkin's disease (HD) were treated by chemotherapy with cyclophosphamide, vinblastine, procarbazine and prednisone (CVPP: two courses) associated with extended field radiotherapy. Staging included neither laparotomy nor splenectomy (clinical staging). Treatment included neither splenic irradiation nor maintenance therapy. Complete remission was achieved for 98 patients and 11 of them recurred up to 94 months after treatment. Median follow-up of this controlled study is 13 years. Disease free survival (DFS) is 87% at 6 years and 84% at 10 and 15 years. Overall survival is 77% at 10 and 74% at 15 years. Disease specific survival is better (91% at 10 and 87% at 15 years) since only 38% (10/26) deaths were due to HD. The other deaths (16/26) with no evidence of HD were due to second cancer and intercurrent disease. Prognostic analysis of DFS by log-rank test gives significance to the following factors: contiguous extra-nodal involvement (P = 0.008), more than 3 involved sites (P = 0.01), signs of compression (P = 0.02), clinical stage IIIA (P = 0.03), infradiaphragmatic stages I-II (P = 0.04). The potential risk of secondary cancer is difficult to assess.

Adult↗