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J Dutreix

Publications and source records attributed to J Dutreix.

At least 19 recordsLinked to original sources
PubMed1998

The hazy dawn of brachytherapy.

The discovery of radium by Pierre and Marie Curie in December 1898 opened a new era in science and within a few years provided medicine with a new means of tumor treatment. Their personal contribution to the start and early development of clinical applications should not be overlooked. The Curies did not limit their support to providing radium sources to medical pioneers but took a deep interest in the horizons of radium therapy. Pierre was one of the first to search for and demonstrate a biological effect of radium radiation. He investigated the radioactivity of the waters of hydrotherapeutic resorts. Marie took care of the measurement of the medical sources personally, convinced that the result of the treatment depends on the precise knowledge of the amount of radium applied. Her perseverance resulted in the establishment of the Institut du Radium (1909) in which, besides the physico-chemical laboratory, a biological department was set up. The latter became the Fondation Curie (1920), a leading medical center of treatment and training, with an integrated team of physicists, radiobiologists and clinicians led by Regaud. One hundred years after the discovery of radium, patients benefit today from the extensive clinical experience that has been collected over the years and from sophisticated developments in application techniques, dosimetry and quality assurance; the professional risk has been precisely assessed and the improvements in material and procedure have enabled the medical personnel to work in hazard-free conditions. This outcome results from the continuous progress that the pioneers gave impulse to. This paper intends to recall their efforts and achievements, as well as the difficulties and the problems they encountered during the first 2 decades when the sturdy foundations of brachytherapy were built.

Animals↗
PubMed1996

[From X-rays to radioactivity and radium. The discovery and works of Henri Becquerel (1851-1908)].

The discovery of radioactivity was the outcome of a methodical experimental study achieved by Becquerel. He continued his discovery with studies which give evidence of his scientific and experimentative mind. These studies explored the nature and properties of the emitted radiation and brought basic data to the disintegration theory. The twin discoveries of Röntgen and Becquerel opened new scientific areas, and their practical applications were unprecedented. They gave a new dimension to basic and applied research.

France↗
PubMed1990

Characterization of two sulfate-reducing bacteria from the gut of the soil-feeding termite, Cubitermes speciosus.

Two sulfate-reducing bacteria (SRB) were isolated from a mixed culture enriched with benzoate obtained from gut homogenate of the soil-feeding higher termite, Cubitermes speciosus. The organisms were vibrioid rods, staining Gram-negative, which performed incomplete substrate oxidation. They differed in several features. The smaller one, strain STp, was motile with a single polar flagellum. This strain differed from Desulfovibrio desulfuricans only by its inability to oxidize malate and pentanol. The bigger one, strain STg, differed from Desulfovibrio giganteus only by its nonmotility and a lower length. It is the first evidence of the presence of SRB in termite gut.

Animals↗
PubMed1990

Clinical basis for TBI fractionation.

Most available clinical data strongly suggest a sparing effect of TBI fractionation for the lungs, liver, lens, the growth cartilage and, perhaps the prepubertal ovary; the usual fractionated TBI regimens, delivering from 12 to 15 Gy, appear to be constantly less toxic than the "standard" 10 Gy single dose TBI scheme. However, there is also some clinical suggestion, essentially coming from the T-depleted graft experience, that the largely used 12 Gy fractionated scheme (6 X 2 Gy) might be less effective than the standard 10 Gy single dose TBI for leukemia cell killing and for eradication of the recipient bone marrow. Additional clinical data, ideally coming from well designed randomised trial or from careful large-scale retrospective evaluations, should help to optimize the TBI delivery.

Bone Marrow Transplantation↗
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↗
PubMed1990

[Biological equivalency of high single doses used in intraoperative irradiation].

UNLABELLED: Intra-operative radiotherapy is being used more and more frequently; this raises the problem of the equivalence of these large doses delivered in a single fraction, especially when a second line, complementary external irradiation is planned afterwards. The linear quadratic (LQ) model is probably the most convenient way to compare 2 irradiation schedules delivered with different doses per fraction. However, in the case of intra-operative radiotherapy, one should question the use of the LQ equation; this model actually predicts a continuous bending of the survival curve, while most experimental curves show a trend towards exponential at high dose levels. As a result, with the very large doses (20-30 Gy) given here, the LQ model would lead to overestimate the efficacy--and the toxicity--of intra-operative irradiation. We thus propose to calculate the equivalent fractionated doses by combining 2 models; the LQ model, considered to be reliable up to 7 Gy, and the 2 components' target model, which tends towards an exponential at high dose level. Moreover, we must take into account the hypoxic component of the tumour, since the single fraction, intra-operative technique cannot benefit from the reoxygenation occurring during conventional fractionated irradiations. Calculations indicate that for a partially hypoxic tumour, the effect of a large dose (20-30 Gy) is very similar to the one which would be achieved by the same dose given in a conventionally fractionated way, increased by the dose necessary to compensate for the proliferation occurring during treatment. For healthy tissues, assuming that all cells are well oxygenated, the equivalent fractionated dose is, in particular, much higher for late responding tissues. IN CONCLUSION: 1) there is little hope for sterilizing any carcinoma with only one fraction of 20-30 Gy; 2) however, intra-operative irradiation, focussing on a small volume, could contribute to the tumour eradication; 3) the intra-operative irradiation technique should, as much as possible, spare the neighbouring normal tissues, regarding the risks of long term complications.

Humans↗
PubMed1989

Expression of the dose rate effect in clinical curietherapy.

The role of the dose rate on the biological effect can be assessed by a simple formula involving only two parameters related to the repair ability (alpha/beta) and to the repair kinetics (repair time constant t or repair half time Tr). The result of the computation provides a value in which the dose rate is taken into account along with the physical dose. It can be expressed by: the ERD (extrapolated response dose), the equivalent dose at a constant dose rate used as a reference, or by the equivalent dose for a conventionally fractionated dose (5 x 2 Gy/week). The computation permits a description of the treatment by the ERD distribution or the "equivalent dose" distribution which is more significant than the dose distribution. It expresses the relative decline in the effect in the low dose region, and the relative increase in the high dose region which are related to the difference in dose rate: the quantitative comparison of different treatments with identical dose distribution delivered in different times; a rational timing of a partial removal of the sources when a uniform treatment time would result in an overdosage of a part of the treated volume. The computation has been used for an analysis of the conflicting clinical data on the variation of the isoeffect dose as a function of the treatment time. The basic radiobiological mechanisms implied in the method of computation and the values of the parameters which have been used are discussed.

Brachytherapy↗
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

[Blood amylase: a biological marker in irradiation accidents? Preliminary results obtained at the Gustave-Roussy Institut (GRI) and a literature review].

The retrospective evaluation of the dose after an irradiation accident is of paramount importance; it allows an adequate selection of patients and the most appropriate treatment can then be proposed. Classical physical dosimetry often lacks precision for dose assessment in such accidents. Cytogenetics, usually more reliable, is not 100% accurate and cannot be used in some particular instances. At the Institut Gustave-Roussy, we studied amylasemia in 15 patients who received a total body irradiation (TBI) for bone marrow grafting, at various dose levels (10, 2 and 1.35 Gy). Hyperamylasemia was found to be constant and dose-dependent. Ten additional patients given a localized irradiation of 2 Gy in the Waldeyer ring had a similar rise in amylasemia as did TBI patients who had received the same dose. In contrast, 13 patients given a pancreatic irradiation (as part of a localized abdominal irradiation) did not show any increase in amylasemia. This study seems to confirm reported data, which suggested that post-TBI hyperamylasemia is almost only related to salivary gland irradiation. Amylasemia could possibly be used as a "biological dosimeter"; however, the dose-effect relationship should be more precisely defined, as well as individual variations. Moreover, the definition of a "threshold-dose" below which hyperamylasemia can never be detected, would be of interest for radioprotection.

Amylases↗
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

An approach to the interpretation of clinical data on the tumour control probability-dose relationship.

A conventional statistical model allows predicting the sterilisation rate as a function of dose. However, the computation requires data on biological parameters (proportion of clonogenic cells, survival per fraction, multiplication rate) which are inaccessible for human tumours. The curative dose 50% (TCD50) can be used as a synthesis of these parameters and its significance for the response-dose relationship of a population of tumours of uniform radiosensitivity is discussed. The slope of the dose-control curve provides vital information regarding the variation in radiocurability of the various individual tumours. The model allows the analysis of the clinical data and the separation of tumour subsets with different radiation responsiveness. It provides an evaluation of the benefit which could be obtained from the identification of the subsets and a guidance for the clinical, pathological and biological studies which relate to this identification. The change in the response-dose relationships with the tumour size cannot (usually) be explained by the cell number increase alone. Other possible factors of reduced radiocurability are discussed.

Cell Survival↗
PubMed1988

Applicability of animal tumor data to cancer therapy in humans.

The problem of applying experimental tumor studies to clinical cancer therapy is a complex one. The radiotherapy literature contains many examples of premature efforts to apply laboratory observations to the clinic, and many examples of failures to adequately consider animal tumor observations in the design of clinical studies. This review covers three areas: tumor hypoxia, where clinical trials based on animal tumor data have been conducted with radiosensitizers, hyperbaric oxygen, and systemic oxygen carriers; dose fractionation, where current trials of hyperfractionation are based in part on animal tumor studies; and chemo-radiotherapy, where clinical trials are only beginning to exploit concepts developed in animal tumor systems. The use of animal tumor systems extends past the screening of new agents. Animal tumor models can be used in biological, physiological, and pharmacological studies to elucidate the biological factors influencing the efficacy of therapeutic agents. Tumor studies can be combined with studies of normal tissues to predict the toxicities to be anticipated in clinical trials, and to assess the potential for therapeutic gain. Animal studies can also provide data which are useful in designing optimal clinical trials of new agents and maximizing the potential for successful clinical application of new approaches. In general, it is not possible to apply specific laboratory data directly to man. To translate, rather than transpose, information from the laboratory to the clinic, the model studies must be directed at evaluating principles, rather than merely quantifying results. Only through studies of mechanisms, by designing experiments to test or refute a hypothesis, will it be possible to apply model studies to man.

Animals↗
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↗
PubMed1987

Blood cell kinetics and total body irradiation.

The early response of blood cells to irradiation has been studied in leukemia patients who received total body irradiation (TBI) prior to cyclophosphamide and bone marrow transplantation. After a single session treatment (10 Gy in 4 h) the most dramatic variation was observed in the granulocytes. At the end of the irradiation their concentration was 2 to 6 times higher. Because of a subsequent rapid decline, the peak may be overlooked if the blood counts are delayed. Lymphocytes decreased to 50% at the end of the single session TBI and continue to decrease exponentially, with a half time of 30 h. During a fractionated irradiation (11 X 1.2 Gy in 4 days) the lymphocyte number dropped to 60%, 13 h after the first fraction and this decline continued with a half time of 30 h during the treatment. From the data obtained in vivo, a lymphocyte D0 value of 1.2 Gy was computed. The lymphocyte subsets (B.T. OKT4 OKT8) did not exhibit different radiosensitivities either in vivo or in vitro. The disappearance of lethally hit lymphocytes from the blood exhibits a biphasic kinetic: 50% of the cells disappear in a few hours and 50% with a half time at 30 h. Lymphocytes irradiated either in vitro or in vivo when in culture disappear slowly, contrasting with the in vivo findings. It may suggest that lethally hit lymphocytes are quickly removed from the circulating pool in vivo.

Blood Cell Count↗