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J M Cosset

Publications and source records attributed to J M Cosset.

At least 73 records · Page 4Linked to original sources
PubMed1997

Persistent improved results after adding vincristine and bleomycin to a cyclophosphamide/hydroxorubicin/Vm-26/prednisone combination (CHVmP) in stage III-IV intermediate- and high-grade non-Hodgkin's lymphoma. The EORTC Lymphoma Cooperative Group.

CHOP has been and still is regarded by many as the 'standard' treatment of advanced non-Hodgkin's lymphoma. In 1980 the EORTC Lymphoma Cooperative Group started a study to evaluate the addition of vincristine and bleomycin to its standard four-drug combination chemotherapy, CHVmP (cyclophosphamide, hydroxorubicin, Vm-26, prednisone). Eligible patients were stage III or IV, intermediate- to high-grade non-Hodgkin's lymphoma (Working Formulation E-I). One-hundred-eighty-nine patients were entered, of whom 140 were eligible and evaluable. A previous report showed an improved response rate and failure-free survival (FFS) and overall survival for the combination CHVmP-VB. At ten years, the outcome still favors the addition of vincristine and bleomycin. The FFS was 34% vs. 23% and the overall survival 34% vs 22%. This difference was mainly due to a difference in CR rate (74% vs. 49%), Relapse-free survival for patients reaching a CR was the same in both arms. When the patients were grouped according to the International Prognostic Factor Index, no statistically significant difference could be observed in favor of one treatment within either group. This trial clearly demonstrates the benefit gained by the addition of vincristine and bleomycin to 'standard' chemotherapy for intermediate and high-grade non-Hodgkin's lymphoma.

Adolescent↗
PubMed1996

Childhood Hodgkin's disease in Campinas, Brazil.

PURPOSE: Little clinical information about Hodgkin's disease in children is available from poor countries. The object of this study is to evaluate our data in Campinas, Brazil and hope "to make one dot on the geographic map of this disease more clear." PATIENTS AND METHODS: Between 1978 and 1988, 46 patients under the age of 17 years with biopsy-proven Hodgkin's Disease (HD) were referred for evaluation at Centro Boldrini in Campinas, São Paulo state, in Brazil. Thirty-seven of them were treated and followed-up only at this Center and are the subjects of this analysis. All the original histological slides were obtained, reviewed, and classified according to the Rye system. Staging procedures included exploratory laparotomy in 33 of 37 children, but none had lymphangiography. Treatment was individualized until January 1986 when the German protocol was adopted. RESULTS: Nineteen cases were classified as nodular sclerosis, 14 as mixed cellularity, and three as lymphocyte depleted. Mean age was 7 years; male/female ratio was 2:1. Fifty percent were advanced stages III and IV and 46% (17/37) had at least one of the systemic B symptoms. Mean follow-up was 81 months (range from 41 to 174 months). Five-year actuarial overall survival was 78%. Two children (5%) had acute myeloid leukemia at 25 and 49 months after diagnosis. CONCLUSIONS: Although distribution of histological subtypes of our cases is similar to other reports in developed countries, as well as percentage of advanced stages III/IV, our patients fared worse when compared to those reports. The reason for this continues to remain unclear but it does not seem to be related to histology subtypes.

Adolescent↗
PubMed1996

High incidence of secondary myelodysplastic syndromes following PROMACE-MOPP and involved field radiotherapy for localized gastric non-Hodgkin's lymphomas.

The incidence of secondary myelodysplastic syndromes (MDS) are rarely reported in an homogeneous patient population treated for non-Hodgkin's lymphoma (NHL). Less than 10 per cent of secondary MDS are usually observed in patients treated for Hodgkin's disease and NHL. Data on the incidence of secondary MDS induced by modern chemotherapeutic regimens is needed. Between January 1985 and January 1989, 20 patients with localized gastric non-Hodgkin's lymphomas (stage I to IIE) were prospectively treated at the Institut Gustave-Roussy with PROMACE-MOPP multi-agent chemotherapy and involved-field irradiation. The mean age was 54 years (range 23 to 69 years). Seven patients died while on therapy or relapsed 2 to 28 months after therapy. Thirteen patients were followed up for at least 5 years. Three of the 13 long-term survivors (23 per cent) developed a myelodysplastic syndrome (MDS) 48, 62 and 72 months after the end of therapy. Cytogenetic analysis was performed in two cases and showed-7 and 18q- in one case, t(9;21)(q13;q22), 21q+, i17q in the other case. PROMACE-MOPP plus radiotherapy should not be recommended in patients with localized gastric non-Hodgkin's lymphoma due to the high risk of developing secondary myelodysplastic syndromes.

Adult↗
PubMed1996

Alternating chemotherapy and radiotherapy for limited-stage intermediate and high-grade non-Hodgkin's lymphomas: long-term results for 96 patients with tumors > 5 cm.

BACKGROUND: The role and timing of radiotherapy for optimal treatment of localized aggressive non-Hodgkin's lymphoma (NHL) is controversial. We report the long-term results of a single-institution pilot study of alternating chemotherapy (CT) and radiotherapy (RT) in patients with clinical stages I or II tumors exceeding 5 cm. PATIENTS AND METHODS: From 1981 to 1992, 96 patients with stages I-II aggressive NHL received an alternating regimen of CT and RT consisting of 8 cycles of CT with 3 courses of RT interjected after the 2nd, 3rd and 4th cycles of CT. The CT combined cyclophosphamide, doxorubicin, teniposide and prednisone every 28 days. Each RT course was started 8 to 10 days after CT (15 Gy in 6 fractions to initially involved and contiguous areas). RESULTS: The median age was 54 years. The disease predominantly located in the head and neck area was stage II in 63% of patients. Bulky tumors (10 cm or larger) were found in 24% of patients. Six patients discontinued CT because of acute toxicity (mucositis). The mean relative dose intensity achieved for doxorubicin, cyclophosphamide and teniposide were 72%, 82%, and 78%, respectively. Late toxicity consisted mostly of severe xerostomia lasting more than 2 years in 7 patients irradiated in Waldeyer's ring. The complete response (CR) rate was 91%; 20 of the 86 patients in CR relapsed (3 locally only). The median follow-up was 61 months, and at 5 years, overall survival (OS) was 77%. Classification according to the International Prognostic Factor Index was possible for 54 patients, all but three of whom were in the 'low risk' group (0-1 factor). Bulky disease was the only unfavorable prognostic factor (P < 0.001) for CR, freedom from progression (FFP) and OS rates; the low relative dose intensity of CT achieved in this study did not affect outcome. CONCLUSION: Alternating chemo-radiotherapy for localized aggressive NHL was feasible and yielded long-term results comparable to those obtained with standard treatments, despite a reduction in dose intensity considerably below that of CHOP which suggested synergistic effects of CT and RT in this scheme.

Adolescent↗
PubMed1996

Anemia is associated with lower local-regional control and survival after radiation therapy for head and neck cancer: a prospective study.

PURPOSE: To evaluate the prognostic value of anemia in squamous cell carcinomas in the head and neck treated with curative radiation therapy alone. MATERIALS AND METHODS: In a prospective study, the hemoglobin level was measured prior to radiation therapy in 217 patients (188 [87%] men and 29 [13%] women) with cancer of the oral cavity (n = 61 [28%]), oropharynx (n = 53 [24%]), hypopharynx (n = 21 [10%]), and larynx (n = 82 [38%]). Anemia, defined as hemoglobin level below 13.5 g/dL in men and below 12.0 g/dL in women, was diagnosed in 58 (31%) of the men and five (17%) of the women. Median follow-up was 29 months (range, 2-63 months). RESULTS: The 2-year actuarial probability of local-regional control was 69% (95% confidence interval, 63%, 76%). Multivariate analysis showed the relative risk of failure of local-regional control to increase for stage T3 and T4 tumors (1.8 [95% confidence interval, 1.1, 3.1]), stage N3 nodes (3.6 [95% confidence interval, 1.8, 7.1]), weight loss (2.2 [95% confidence interval, 1.3, 4.0]), and anemia (1.6 [95% confidence interval, 1.0-2.7]). The relative risk of death increased for stage T3 and T4 tumors (2.5 [95% confidence interval, 1.4, 4.3]), N3 nodes (4.0 [95% confidence interval, 1.0, 7.9]), oral cavity tumors (2.0 [95% confidence interval, 1.2, 3.2]), male sex (4.1 [95% confidence interval, 1.3, 13.1]), weight loss (2.2 [95% confidence interval, 1.3, 3.7]), and anemia (1.7 [95% confidence interval, 1.03, 2.7]). CONCLUSION: Moderate anemia appeared to be an independent prognostic factor in squamous cell carcinoma of the head and neck treated with radiation therapy alone.

Actuarial Analysis↗
PubMed1996

[Gene transfer and radiotherapy].

Recent studies have shown that experimental tumors could be treated more efficiently with ionizing radiation if genetic material was transfered into tumor cells. Several approaches have been reported, and among them, the first one consisted of increasing the apoptotic response to radiation by modulating genes involved in the regulation of the apoptotic pathway. Indeed the modulation of p53 and bcl-2 gene expression has recently been used successfully in several experimental models to increase the apoptotic death after radiation. A second approach consisted of taking advantage of the conditional expression of some genes after exposure to ionizing radiation. Indeed, some genes exhibit a radio-inducible promoter which can be combined to a gene, able to enhance or decrease the biological effect of radiation. The irradiation of such a transgene under the control of a radio-inducible promoter can lead to a second biological effect, concomitant to the irradiation, as reported for the TNF alpha under the control of the EGR (early growth response) promoter. A third approach consisted of enhancing the effect of radiation induced tumor cell death by the expression of a suicide gene in these cells, as suggested recently for the HSV-tk (herpes virus thymidine kinase gene). These preliminary results obtained in experimental models appear to be very promising and might improve the efficacy and specificity of radiation therapy in a not too distant future.

Animals↗
PubMed1996

[Therapeutic approaches of hematopoietic syndrome following accidental total whole body irradiation].

Since the first radiation accidents which resulted in severe health effects in the workforce or the population, great progress has been made in the fields of diagnosis, prognosis and treatment of accidentally overexposed victims. Since then, progress has also been made in the medical management of diseases such as aplasia. Because of the relative scarcity of radiation accidents, there is a need for complementary researches, in order to take advantage of new techniques and medical approaches. After whole body overexposure, the key issue is the therapeutic decision, ie, the choice between bone marrow transplantation and other strategies. The indications of bone marrow transplantation cover only a short range of doses, provided the exposure is distributed uniformly within the body. The last accidental overexposures which happened in the world have demonstrated the possible efficiency of haematopoietic growth factors, most of them being still under clinical trials. Actions based on these various approaches are summarized, as well as the lessons which have been learned.

Adult↗
PubMed1996

Hematopoiesis research in aplastic anaemia induced by accidental protracted radiation.

Over the past few years there have been 2 radiation-related accidents involving a large number of individuals: the April 1986 accident in Chernobyl nuclear power station in the Ukraine and the September 1987 accident in Goiania, Brazil. These 2 radiation-related accidents highlight the major question raised by radiation-induced injury to the haematopoietic system, that is: does a given patient suffer from a reversible or an irreversible haematopoietic stem cell damage? Although about 350 radiation accidents involving several thousand people are known from the literature, in-depth haematopoiesis analyses of individuals after a radiation-related accident have rarely been reported. In this paper we present the case of a young man with radiation-induced aplasia and compare some biological data to those of 16 normal individuals and of 17 patients with acquired aplastic anaemia. Our patient was clinically and biologically (as assessed by long-term bone marrow culture) indistinguishable from patients with idiopathic acquired aplastic anaemia. Furthermore, therapeutic attitudes in this patient are discussed. In-depth study of such radiation-induced aplastic anaemia cases can shed some light in the understanding of this disease and may help in therapeutic decisions.

Adolescent↗
PubMed1995

Multicolor flow cytometry analysis of blood cell subsets in patients given total body irradiation before bone marrow transplantation.

PURPOSE: Bone marrow transplantation has often been closely linked with accidental or intentional therapeutical irradiation. In both situations, study of the radiosensitivity of human blood cell subsets is of interest. Using one-color flow cytometry analysis of B lymphocytes, T cell subsets, and natural killer cells, we previously reported that lymphocyte subsets exhibit equal radiosensitivity. Taking advantage of recent developments in the knowledge of leukocyte differentiation antigens and flow cytometry technology we undertook a study of blood cell subsets to search for rare populations exhibiting different radiosensitivity. METHODS AND MATERIALS: Thirty patients, who were delivered a 12 Gy fractionated total body irradiation as part of their conditioning regimen before transplantation for malignant disorders, were studied using multicolor flow cytometry. RESULTS: T and B lymphocytes showed a sharp, radiation-induced decrease, with the B lymphocytes (cluster of differentiation (CD) 19+) being the most sensitive. When analyzed by multicolor flow cytometry, all major lymphocyte subsets appeared equally sensitive to the in vivo irradiation; that is, CD3+4+45RO+, CD3+4+45RA+, CD3+4+8-, CD3+4-8+. Therefore, all major lymphocyte subsets sharing the helper phenotype (naive or memory) and the cytotoxic phenotype appeared equally sensitive to in vivo whole body irradiation. In parallel, the CD34+ cell subset remained basically unchanged after whole body irradiation. Finally, the CD3-, 56+, 16+ natural killer cell subset was relatively radioresistant (91 and 74% of its initial value, after 2 and 4 Gy, respectively) as compared to other lymphocyte subsets. CONCLUSION: Our study provides evidence that T and B cell subsets seem to be highly radiosensitive in vivo. The CD34+ progenitor/stem cells and NK cells seem to be more radioresistant. This latter result might provide clues to the understanding of the pathophysiogeny of radiation-induced aplasia and of the engrafment/rejection process following bone marrow transplantation.

Adolescent↗
PubMed1995

Prognostic value of tumor regression during radiotherapy for head and neck cancer: a prospective study.

OBJECTIVE: Prospective evaluation of tumor regression during external irradiation for head and neck squamous cell carcinomas and its association with long-term local control. METHODS AND MATERIALS: Two hundred twenty-eight patients with histologically confirmed squamous cell carcinoma [oral cavity: 59 (26%), oropharynx: 65 (29%), hypopharynx: 37 (16%), larynx: 67 (29%)] were included between January 1986 and December 1990. Curative intent external irradiation delivered 65-70 Gy over a period of 7 weeks (five 2 Gy fractions per week). Tumor regression was evaluated clinically and endoscopically every week. RESULTS: Tumor regression, assessed at 2 weeks, was as follows: no response: 62 (30%), 25% response: 121 (59%); 50% response: 23 (11%). At 5 weeks, 9 (4%) patients showed 0-25% regression, 75 (33%) showed 50% regression, 115 (50%) showed 75% regression, and 29 (13%) showed complete regression. Median follow-up was 79 months (range: 6-96 months). The local control probability was 68% (62-74%) at 2 years, 65% (59-70%) at 5 years. Univariate analysis showed that, at 2 weeks, local control was significantly different between the nonresponders and the patients with 25% or greater response (p < 0.025) and that, at the fifth week, local control was very different between the major responders (75 and 100%) and the minor responders (0-50%) (p < 0.0001). Multivariate analysis (Cox Proportional Hazards Model) showed that the probability of local relapse was significantly and independently increased for minor regression at 5 weeks [Relative risk (RR) of failure was 2.3 (1.4-3.7)], for nonlaryngeal tumors [RR: 2.4 (1.3-4.5)], and for Stage T3-T4 [RR:2.4 (1.4-4)]. Three prognostic groups can, therefore, be proposed: 1) low risk of recurrence when regression > or = 75% and laryngeal tumor or T1-T2 tumors in other sites: 106 (46.5%) patients, 2-year local control probability: 84% (77-92%); 2) high risk of recurrence: regression < or = 50% and T3-T4 nonlaryngeal tumors: 44 (19%) patients, 2-year local control probability: 27% (13-41%); 3) intermediate risk of recurrence: 78 (34.5%) patients, 2-year local control probability: 69% (58-80%). CONCLUSION: The present study suggests that tumor regression during external radiotherapy is an independent predictive factor of local control in head and neck carcinomas.

Carcinoma, Squamous Cell↗
PubMed1995

[Exposure of patients to radiation risk in common medical practice].

Medical radiation includes radiodiagnosis, nuclear medicine, and radiation therapy. This radiation exposure differs from occupational public exposure, since a direct benefit is conferred upon the patient. The theoretical risks include genetic mutations, carcinogenesis and teratogenesis. In radiodiagnosis and nuclear medicine, the absorbed doses are very low, and no hazardous effect has been observed. In radiation therapy however, where high doses are delivered to a small number of patients, radio-induced carcinogenesis is well documented. It is by no means sure that the nuclear risk must be taken into account, and fully justifies the accomplishments and recommendations of the French radiation protection programs. There is no question that the nuclear risk-benefit equation resulting from medical exposure is tipped heavily in favor of benefit.

Humans↗
PubMed1995

[Care of severe accidental irradiation victims].

Two types of "severe accidental irradiation" can be schematically described: high dose localized irradiations and accidental total body overexposure. Actually, these two pathologies may coexist, and may be associated with external or internal radioactive contamination, and with all the "catastrophe medicine" syndromes. For high dose localized irradiation, physicians must manage as well as possible complex surgical procedures which unfortunately cannot always avoid being mutilating. For total body overexposure, haematological problems are at the forefront. In according with various situations, hematological growth factors or even allogeneic bone marrow transplantation will be discussed in specialized haematology (and transplant) units. The optimal management of severe accidental irradiation victims implies a close--and rapidly organized--cooperation between general practitioners, firemen, intensive care units, radiopathologists, specialist surgeons (hand and burns) and haematologists.

Humans↗
PubMed1995

Fractionated or single-dose total body irradiation in 171 acute myeloblastic leukemias in first complete remission: is there a best choice? SFGM. Société Française de Greffe de Moelle.

PURPOSE: To evaluate the importance of fractionating total body irradiation (TBI) in patients receiving an allogenic bone marrow transplant (BMT) for an acute myeloblastic leukemia (AML) in first complete remission (CR1). METHODS AND MATERIALS: Between 1983 and 1990, 171 consecutive patients received either single dose TBI (STBI) (n = 65) or fractionated TBI (FTBI) (n = 106) after being conditioned with cyclophosphamide and before receiving a non-T-depleted Human Leucocyte Antigen (HLA)-identical marrow. Both groups were comparable except for date of BMT and diagnosis-to-BMT interval (D-BMT). RESULTS: After 63 months median follow-up, transplant-related mortality (TRM), probability of relapse, and 5-year disease-free survival (DFS) were 0.38 and 0.27 (p = 0.04), 0.29 and 0.26 (p = 0.22), 0.43 and 0.56 (p = 0.06), respectively, for STBI and FTBI. The supposed influence of the schedule of TBI disappeared in the multivariate analysis: TRM was enhanced by severe acute graft vs. host disease (p = 0.0002), early years of transplant (before January 1, 1987) (p = 0.0003), and longer D-BMT intervals (p = 0.038). Relapse was linked to early years of transplant (p < 0.00001), and the absence of chronic GVHD (p = 0.007). Longer DFSs were observed for later years of transplant (after January 1, 1987 and later) (p = 0.001), milder acute GVHD (p = 0.005), and shorter D-BMT intervals (p = 0.045). Important improvements of the results were made during the 7-year observation period: TRM, probability of relapse, and DFS were, respectively, 0.36, 0.28, and 0.46 for patients transplanted before January 1, 1987 vs. 0.21, 0.15, and 0.67 after that date. CONCLUSION: Our data strongly suggest that allogenic BMT is the best postremission treatment for AML in CR1, and the results are better when BMT shortly follows the achievement of remission. The schedule of TBI was of little importance compared with the improvements made in the management of patients undergoing BMT during the 1980s, and, therefore, reports concerning data prior to 1985 should be interpreted cautiously.

Adult↗
PubMed1995

New particles in radiotherapy: an introduction.

Since the discovery of x-rays and radioactivity, the radiotherapeutic management of malignancy has seen numerous spectacular improvements. Beside the widely used photons and electrons, one area of particular interest is the development and refinement of what has become known as "new particles". In this paper we give a brief outline of the properties of such particles and catalogue the impact these have made on the clinical outcome.

Bone Neoplasms↗
PubMed1995

Clinical applications of proton therapy. Experiences and ongoing studies.

Proton therapy offers potentially considerable advantages in the management of slow-growing, poorly resectable or non-resectable tumors resistant to x-rays and located close to critical radiosensitive anatomical structures, such as the brain stem of the spinal cord. Among over 13,000 irradiated patients in the USA, Europe, and Japan, two major clinical indications have been documented: 1. The conservative management of choroidal melanomas, in which 98% 5-year local control can be expected at the price of low toxicity and visual preservation in approximately half of them. 2. The curative management of low-grade chondrosarcomas and chordomas of the base of the skull and cervical spine, leading to, in combination with maximal tumor resection, 84%-94% long-term survival. Other ongoing studies concern prostate, head and neck carcinomas as well as various intracranial tumors. Radiosurgical programs are being conducted generally with single fractions and under stereotactic conditions.

Bone Neoplasms↗
PubMed1995

Radiation-induced lung damage after thoracic irradiation for Hodgkin's disease: the role of fractionation.

PURPOSE: to estimate the alpha/beta ratio for damage to human lung after thoracic irradiation for Hodgkin's disease. PATIENTS AND METHODS: The criterion for lung injury was the presence of radiological changes in the vicinity of the mediastinum as assessed on regular follow-up chest X-ray examinations. Patients with supradiaphragmatic stage I-II Hodgkin's disease received mantle field irradiation as part of their treatment between 1964 and 1981 (E.O.R.T.C. protocols H1, H2, and H5). The total mediastinal doses fixed by the protocols were 35-40 Gy. The fractional doses were left to the decision of the physicians in charge: the most frequent regimens were 5 x 1.8, 5 x 2.0, 4 x 2.5 and 3 x 3.3 Gy per week. The data were fit to the linear-quadratic (L.Q.) model using time-to-injury as endpoint. RESULTS: 1048 (97%) of 1082 patients were evaluable. The mean follow-up duration was 8 years. One hundred and ninety-five cases of radiologically-visible lung damage were observed after a median interval of 6 months (range: 0-101). The 3-year actuarial probability of lung damage was 19% (95% confidence limits: 17, 21). Multivariate analysis (Cox model, stratified by protocol) showed an increased risk of damage with dose per fraction (relative risk, R.R. = 2.22 per Gy (1.75, 2.82)), the presence of systemic symptoms (R.R. = 1.53 (1.09, 2.15)), and total mediastinal dose (R.R. = 1.06 per Gy (1.01, 1.12)). Age, sex, histological type, number of involved nodal sites and radiotherapy duration did not significantly modify the risk of lung damage. The L.Q. model parameters were: alpha = 0.031 Gy-1 (0.003, 0.059), beta = 0.010 Gy-2 (0.007, 0.013), alpha/beta = 3.07 Gy (-0.23, 8.46). CONCLUSION: this low alpha/beta ratio is consistent with late effects values from animals and humans, and illustrates the influence of large fraction sizes on the occurrence of late pulmonary complications.

Adolescent↗