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Biomedical subjects

T Girinski

Publications and source records attributed to T Girinski.

At least 19 recordsLinked to original sources
PubMed1997

Predictive assays of radiation response in patients with head and neck squamous cell carcinoma: a review of the Institute Gustave Roussy experience.

PURPOSE: The aim of the study was to present the updated Institut Gustave Roussy experience of the predictive value of three biological parameters in patients with squamous cell carcinoma of the Head and Neck (HNSCC) treated with radiation therapy. METHODS AND MATERIALS: Three parameters have been investigated independently: tumor cell kinetics (TS, Tpot and LI), oxygen tension measurements (PO2) and intrinsic radiosensitivity (SF2Gy). RESULTS: No relationship has been found between local-regional control and Tpot or LI in a series of 74 patients. Our data also support that the surviving fraction at 2 Gy, (SF2) was unlikely to predict the clinical outcome in a series of 92 patients. Differences in PO2 measurements have been observed between tumors, and tumor oxygenation was lower than that of normal tissue for the majority of patients. However PO2 measurements did not predict clinical outcome, but further investigations are needed to draw definitive conclusions, given the limited number of patients entered in our study (35 patients). In addition, we were able to measure the three parameters in 10 patients showing no correlation between PO2, SF2 and Tpot. CONCLUSIONS: The method used to evaluate Tpot and SF2 did not provide clinically relevant predictive parameters for this type of cancer. Further investigations are needed to assess the predictive value of PO2 measurements and of new biological parameters in a multiparametric approach, taking into account other possible clinical and biological confounding factors.

Adult↗
PubMed1997

Hepatic veno-occlusive disease after myeloablative treatment and bone marrow transplantation: value of gray-scale and Doppler US in 100 patients.

PURPOSE: To determine the value of gray-scale ultrasonography (US) and Doppler US in the prediction, diagnosis, and prognostic assessment of hepatic veno-occlusive disease (HVOD). MATERIALS AND METHODS: One hundred patients (median age, 22 years; range, 18 months to 59 years) receiving total body irradiation or busulfan therapy as intensive treatment before hematopoietic stem cell transplantation were studied prospectively. Each patient underwent gray-scale and Doppler US examination before transplantation and weekly thereafter while hospitalized (about four examinations per patient). Seven gray-scale morphologic criteria and seven Doppler criteria were studied, yielding three individual scores: gray-scale score, Doppler score, and total score. RESULTS: Twenty-five patients developed HVOD; nine of these patients died. Positive predictive values of the 14 criteria were 31%-95%, and negative predictive values were 85%-96%. The three scores correlated with the clinical diagnosis of HVOD. Depending on the cutoff value, the positive predictive value of the total score was 44%-89% and the negative predictive value was 91%-98%. The gray-scale and Doppler criteria differed significantly between patients with HVOD and those with graft-versus-host disease of the liver (P = 10(-4)). CONCLUSION: Even if there is overlap in findings between patients with and those without HVOD, gray-scale and Doppler US are valid for positive and differential diagnosis and have predictive and prognostic relevance.

Adult↗
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↗
PubMed1993

Follow-up thallium-201 scintigraphy after mantle field radiotherapy for Hodgkin's disease.

PURPOSE: Assessment of the long-term cardiac effects of mediastinal radiotherapy for Hodgkin's disease, by Thallium scintigraphy. METHODS AND MATERIALS: 32 patients (14 males and 18 females) who underwent mantle field radiotherapy for Hodgkin's disease were included in this study. Twenty patients received 4 fractions of 2.5 Gy per week and 12, five fraction of 2 Gy per week, delivered on alternate days. All the patients, except three, performed exercise testing electrocardiogram and Thallium-201 tomoscintigraphy. The average time interval from completion of treatment to the study was 7 years (range 3-13 years). No patients had clinical symptoms of cardiac disease. Mean age at the time of the study was 35 years (range 23-48 years). RESULTS: Two electrocardiograms revealed left bundle branch block and the patients were excluded from the study. Only one out of 27 exercise electrocardiograms was abnormal in a patient with mitral valve prolapse, who was also excluded from the study. Twenty-six scintigraphies were evaluable. Twenty-two (85%) were clearly abnormal with partial or complete redistribution on delayed images. The anterior region was affected in 19 of these cases (86%). Four explorations were undoubtedly normal. Coronary angiography was not performed for ethical reasons in these asymptomatic patients. CONCLUSION: Despite possible false positive tests, the high rate of abnormality (85%) in this small series is striking. These preliminary data justify larger studies and a close long-term follow-up of these patients.

Adult↗
PubMed1993

Class I and II HLA typing after a 10 Gy-4 hour therapeutic total body irradiation.

Class I and II HLA typing was investigated before and at various intervals after a 10 Gy total body irradiation delivered over 4 h, prior to allogeneic bone marrow graft for various hematological malignancies, in 14 patients. A reliable class I HLA typing appeared to be possible in almost all cases 6-8 hours after the start of irradiation but was only possible in 5 patients after 24 h. Preliminary results with class II antigens might suggest a more marked "fragility" of this antigen class after irradiation. These results encourage the drawing of blood samples for HLA grouping as soon as possible after accidental whole-body irradiation.

Accidents↗
PubMed1992

Post-irradiation hyperamylasemia as a biological dosimeter.

Serum alpha-amylase was measured before and 24 h after either total body (31 patients) or localized irradiation including the salivary glands (40 patients) or the pancreatic area (22 patients). A significant increase in amylasemia was observed for doses to the parotid glands larger than 0.5 Gy. A sigmoid function of dose was fitted to the data and predicted a maximum amylasemia level for doses larger than 4 Gy and smaller than 10 Gy. The raw data from other published series were adequately described by the same model. However, the confidence limits of the parameters remained wide, because of a considerable interindividual variability. Post-irradiation hyperamylasemia appears to provide a good criterion for triage of accidentally irradiated patients: 24 h after a dose larger than 2 Gy to the parotid glands, 91% of the patients had an amylasemia level higher than 2.5-fold the upper normal value (sensitivity). Conversely, 96% had their serum amylasemia lower than 2.5-fold the upper normal value when dose was smaller than 2 Gy (specificity). However, a retrospective estimation of the absorbed dose (dosimetry) is not likely to be very precise because of the large interindividual variability.

Adult↗
PubMed1991

Pericarditis and myocardial infarctions after Hodgkin's disease therapy.

From 1971 to 1984, 499 patients with all stages of Hodgkin's disease received mediastinal irradiation at the Institut Gustave-Roussy by 25 MV photons from a linear accelerator. Thirty-five pericarditis (10-year cumulative incidence rate of 9.5%) and 13 myocardial infarctions (MI) (10-year cumulative incidence rate of 3.9%) were observed. In contrast, no cases were diagnosed in a parallel series of 138 Hodgkin's disease patients treated without mediastinal irradiation during the same period of time (p less than 0.005 for pericarditis, p less than 0.05 for MI). By multivariate analysis, the role of total radiation dose given to the mediastinum and that of fraction size were evaluated, adjusting for age, sex, mediastinal involvement, and type of chemotherapy. The pericarditis risk was significantly increased with total dose greater than or equal to 41 Gy (relative risk (RR) = 3.25, p = 0.006) and with dose per fraction greater than or equal to 3.0 Gy (RR = 2.0, p = 0.06). The myocardial infarction risk was not found to be related to total dose nor to fraction size in this series, possibly because of the small number of events.

France↗
PubMed1990

Similar effects on murine haemopoietic compartment of low dose rate single dose and high dose rate fractionated total body irradiation. Preliminary results after a unique dose of 750 cGy.

This study was designed to compare two different modalities of TBI which are currently used in clinical practice. The same dose of 750 cGy was given to CBA mice either in a single dose at a low dose rate (4 cGy min-1) (STBI) or in a fractionated regimen (six fractions of 125 cGy three times a day) at a higher dose rate (25 cGy min-1) (FTBI). After TBI completion we simultaneously studied the in vivo radiation response of bone marrow cells, two murine bone marrow clonogenic cells (CFU-S and GM-CFC) and peripheral blood lymphocytes and granulocytes for a period of 1 month. The percentage of spleen erythrocytic and granulocytic colonies was also determined. No significant differences were observed between the two groups in the first 48 hours after irradiation except in bone marrow cell numbers, probably due to differences in the overall treatment time between the two TBI schedules. After the first 48 hours the repopulation patterns of the different cells were very similar in both groups. These findings suggest that the different dose rates and fractionation used in this study caused similar radiation damage to the murine haemopoietic system. Moreover, no significant repopulation occurred during the longer overall treatment time of the fractionated regimen. These preliminary results must be corroborated with a larger range of doses before any firm conclusion can be drawn.

Animals↗
PubMed1989

Single dose versus hyperfractionated total body irradiation before allogeneic bone marrow transplantation: a non-randomized comparative study of 54 patients at the Institut Gustave-Roussy.

At the Institut Gustave-Roussy (IGR), from January 1982 to December 1986, 54 patients received total body irradiation (TBI) as a part of the conditioning regimen before allogeneic bone marrow transplantation. The patients were non-randomly assigned to either single dose TBI (STBI) (31 patients receiving 10 Gy at a 4.5 cGy/min dose rate, 8 Gy to the lungs) or to a hyperfractionated scheme (HTBI) (23 patients receiving 13.2 Gy in 11 fractions, 3 fractions per day, 9 Gy to the lungs). Relapse rate and overall survival were not significantly different in the two STBI and HTBI groups, in spite of a larger number of 2nd and 3rd remission patients in the HTBI subset. The incidence of interstitial pneumonitis (IP) was significantly reduced in the HTBI group (13%, versus 45% after STBI, p = 0.02). Lethality by IP was also lower after HTBI (4%, versus 26% after STBI, p = 0.08). There was no case of veno-occlusive disease of the liver in the HTBI group, whereas three cases were observed after STBI. Based on these results, the IGR activated, in January 1987, a randomized trial comparing the single dose 10 Gy TBI (8 Gy to the lung) to a new hyperfractionated schedule (11 fractions of 1.35 Gy, 3 fractions per day, 9 Gy to the lungs).

Adult↗
PubMed1989

Prognostic value of hemoglobin concentrations and blood transfusions in advanced carcinoma of the cervix treated by radiation therapy: results of a retrospective study of 386 patients.

A retrospective study was carried out on 386 patients with advanced cervical carcinomas treated with radiation therapy between 1973 and 1983. The influence of hemoglobin concentrations and blood transfusions before and/or during treatment on the occurrence of distant and/or local regional failures were examined in a univariate and multivariate analyses. In the multivariate analysis hemoglobin concentrations were prognostic only during treatment and patients with at least one value below the threshold of 10 gm% had a significantly higher risk of local regional failure than the patients with all their values above the threshold. Moreover 70% of these high risk patients had less than half of their values below the threshold. It is possible that blood transfusions might be beneficial when given before treatment. However, although it was not significant, blood transfusions given during treatment tended to be an adverse prognostic factor suggesting that blood transfusions might not have completely offset acute anemia prior to transfusion. Our study suggests that anemia during treatment, even of short duration might be detrimental to patients.

Adenocarcinoma↗
PubMed1989

[Focus on research and results of unusual radiotherapy technics (heavy particles, hyperthermia, radiosensitizers)].

Heavy particles have been used in transcutaneous radiotherapy for almost 50 years. If these particles and pi mesons remain the domain of highly specialized centers, neutron therapy and, to a lesser degree, proton therapy can be considered common clinical protocols; their limits, complications, efficacities and costs are sufficiently well known to encourage several centers to acquire the necessary equipment. Their practical advantages involve a limited number of patients however, for the patients implicated, the prognoses are appreciably improved by the application of these therapies. Hyperthermia-associated radiotherapy is limited by the poor technical capabilities of the currently available hyperthermia machines. If biological experimentation was highly promising, clinical results to date have been unfulfilling. Nonetheless, hyperthermia-associated interstitial radiotherapy represents an interesting clinical possibility. Radiosensitizers are being extensively developed. The results of randomized therapeutic trials are still contradictory and the toxicity of these products renders their use difficult. New products are being tested; their lower toxicity and potent radiosensitization capacity are encouraging for the future use of this class of compounds.

Helium↗
PubMed1989

Unusual localization of cutaneous chronic graft-versus-host disease in the radiation fields in four cases.

Chronic graft-versus-host disease (GVHD) is a very heterogeneous entity with variable clinical expression. The pathophysiology involves autoimmune disorders and features of fibrosis. Four patients transplanted for severe aplastic anaemia conditioned with cyclophosphamide and thoraco-abdominal irradiation developed skin scleroderma specifically localized in the irradiation fields. This syndrome was remarkable for its late onset and the absence of factors known to trigger chronic GVHD. It is postulated that irradiation used in this protocol may induce keratinocyte damage and trigger chronic GVHD.

Abdomen↗
PubMed1988

Late toxicity of radiotherapy in Hodgkin's disease. The role of fraction size.

From 1972 to 1976 patients at the Gustave Roussy Institute were irradiated for Hodgkin's disease using a modified fractionation schedule (3 fractions of 3.3 Gy per week) for operational reasons. From 1964 to 1971 and from 1977 to 1981, a more conventional regimen (4 fractions of 2.5 Gy per week) was used. The rates of the late complications in these two subsets of patients treated with different fractionation schedules at the same total dose of 40 Gy during the same overall time were compared. Mediastinitis was observed in 19% of the '4 X 2.5 Gy/week' group versus 56% in the '3 X 3.3 Gy/week' group. Pericarditis in 0% versus 9%, gastroduodenal ulceration and severe gastritis in 10 versus 21% and small bowel obstruction in 5 versus 8%. When using the linear quadratic model with an alpha/beta of 2.5 Gy to evaluate the equivalent dose of 40 Gy given in 12 fractions of 3.3 Gy when delivered by fractions of 2.5 Gy, a value of 46.6 Gy is found. This difference of 6.6 Gy in the equivalent doses (for late toxicity) is likely to account for the significant increase of late radiation injuries, such as mediastinitis and pericarditis, in the present study. The local relapse rate was found to be slightly lower in the 3 X 3.3 Gy group. However, this possible benefit cannot offset the considerable increase of late complications.

Dose-Response Relationship, Radiation↗
PubMed1988

[Comparison between single-dose and hyperfractionated total-body irradiation for the conditioning of allogenic grafts of the bone marrow. A retrospective study of 54 patients with malignant hematologic diseases].

The present study is a retrospective analysis of 54 patients with hematological malignancies who were treated by total body irradiation (TBI) and allogenic bone-marrow transplantation from 1982-1986. Patients were not randomly assigned to receive either single dose total body irradiation (STBI) (10 Gy x 1-4 cGy/min-lung dose 8 Gy) or hyperfractionated total body irradiation (HTBI) (1,20 Gy x 11-3 fractions/day-lung dose 9 Gy). Thirty one patients received STBI and 23 a HTBI regimen. Despite the presence of a large proportion of patients with a high risk of leukemic relapse in the HTBI group, the incidence of relapse did not differ significantly in the two groups: STBI (16%), HTBI (21%). Lung and liver toxicity were predominant in the STBI group. Interstitial pneumonitis occurred in 45% of the STBI patients versus 13% in the HTBI group. This difference remains significant when adjusted to the incidence of graft versus host disease (GVHD) in the two groups. Three cases of veino-occlusive disease were observed (10%), but only in the STBI group. Even when differences in age and the frequency of GVHD are considered in the two groups, these findings suggest that HTBI is at least as effective as STBI and that toxicity is reduced with this schedule.

Actuarial Analysis↗