Biomedical subjects

J M Cosset

Publications and source records attributed to J M Cosset.

At least 37 records · Page 2Linked to original sources

PubMed2001

Conformal radiotherapy (CRT) planning for lung cancer: analysis of intrathoracic organ motion during extreme phases of breathing.

PURPOSE: Conformal radiotherapy beams are defined on the basis of static computed tomography acquisitions by taking into account setup errors and organ/tumor motion during breathing. In the absence of precise data, the size of the margins is estimated arbitrarily. The objective of this study was to evaluate the amplitude of maximum intrathoracic organ motion during breathing. METHODS AND MATERIALS: Twenty patients treated for non-small-cell lung cancer were included in the study: 10 patients at the Institut Curie with a personalized alpha cradle immobilization and 10 patients at Tenon Hospital with just the Posirest device below their arms. Three computed tomography acquisitions were performed in the treatment position: the first during free breathing and the other two during deep breath-hold inspiration and expiration. For each acquisition, the displacements of the various intrathoracic structures were measured in three dimensions. RESULTS: Patients from the two centers were comparable in terms of age, weight, height, tumor site, and stage. In the overall population, the greatest displacements were observed for the diaphragm, and the smallest displacements were observed for the lung apices and carina. The relative amplitude of motion was comparable between the two centers. The use of a personalized immobilization device reduced lateral thoracic movements (p < 0.02) and lung apex movements (p < 0.02). CONCLUSION: Intrathoracic organ movements during extreme phases of breathing are considerable. Quantification of organ motion is necessary for definition of the safety margins. A personalized immobilization device appears to effectively reduce apical and lateral displacement.

Aged↗

PubMed2001

A high and sustained response rate in refractory or relapsing low-grade lymphoma masses after low-dose radiation: analysis of predictive parameters of response to treatment.

PURPOSE: To determine the efficacy of small doses of radiation in patients with recurrent or refractory low-grade lymphoma masses. METHODS AND MATERIALS: Patients with refractory or relapsing low-grade lymphoma masses. The two largest diameters of the tumor mass were measured, whenever possible, before and after treatment. A dose of 4 Gy of radiotherapy was delivered to tumor sites in 2 fractions. Patients were evaluated for response 1-4 months later and at regular follow-up visits. RESULTS: Forty-eight patients with low-grade lymphomas according to the working formulation received low-dose radiotherapy between March 1987 and November 1998. Most patients had advanced disease at the time of radiation treatment, and 80% had received at least two chemotherapy regimens before treatment. The median interval between the initial diagnosis and radiotherapy was 2.7 years (range 0-22 years). Low-dose radiation was delivered to 135 tumor sites. Nodal and extranodal tumor sites represented 80% and 20% of masses, respectively. An objective response was obtained in 81% of the sites, with 57% attaining a complete remission. The 2-year actuarial freedom from local progression (FFLP) rate was 56% (95% CI, 46-66%). Tumor masses </=5 cm in diameter had a significantly higher 2-year FFLP rate than larger masses (51% vs. 27%). It is noteworthy that the 2-year FFLP rate for patients treated with less than 2 chemotherapy regimens before radiotherapy was significantly higher than the 2-year FFLP rate for more heavily treated patients (96% vs. 48%). The 2-year FFLP rates for extranodal tumor sites and nodal sites were not significantly different. The tumor size (< or =5 cm vs. > 5 cm), the number of chemotherapy regimens (0-1 vs. more), and age at time of radiation treatment (< or =65 years or > 65 years) were significant predictive parameters of response to treatment. CONCLUSIONS: In this retrospective study, low-dose radiation proved efficient, with long-lasting effects in the majority of patients with recurrent or refractory low-grade lymphomas. This simple and nontoxic treatment should be investigated prospectively in patients with advanced disease and a low tumor burden not immediately warranting chemotherapy.

Adult↗

PubMed2001

CT and (18)F-deoxyglucose (FDG) image fusion for optimization of conformal radiotherapy of lung cancers.

PURPOSE: To validate a computed tomography (CT) and (18)F-deoxyglucose (FDG) image fusion procedure and to evaluate its usefulness to facilitate target definition and treatment planning in three-dimensional conformal radiation therapy (3D-CRT) for non-small-cell lung cancer. METHODS AND MATERIALS: Twelve patients were assessed by CT and FDG-coincidence mode dual-head gamma camera (CDET) before radiotherapy. The patients were placed in a similar position during CT and FDG-CDET. Matching was achieved by minimizing the cost function by 3D translation and rotation between four landmarks drawn on the patient's skin. Virtual simulation was performed from image fusion and estimated dose-volume histograms (DVH) were calculated. RESULTS: Quantitative analysis indicated that the matching error was < 5 mm. Fusion of anatomic and metabolic data corrected staging of lymph nodes (N) for 4 patients and staging of metastases for 1 patient. In these 5 patients, DVH revealed that the lung volume irradiated at 20 Gy (Vl(20)) was decreased by an average of 22.8%, and tumor volume irradiated at the 95% isodose (V(95)) was increased by 22% and 8% for 2 patients, respectively, and was decreased by an average of 59% for 3 patients after fusion. No difference in terms of Vl(20) and V(95) was observed for the other 7 patients. CONCLUSION: We have validated CT and FDG-CDET lung image fusion to facilitate determination of lung cancer volumes, which improved the accuracy of 3D-CRT.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

[Hodgkin's disease: from gross tumor volume to clinical target volume, firm data and unresolved problems].

The purpose of this article is to specify the target volumes, using ICRU criteria in the treatment of Hodgkin's disease. Because of the complexity of irradiation fields, the literature was carefully reviewed. However, with the variations of the recommendations and in the absence of large-scale studies, usual criteria can still be used. A consensus about the precise specification of the target volumes on CAT scan is still urgently awaited.

Hodgkin Disease↗

PubMed2001

[Estimation of the probability of mediastinal involvement: a statistical definition of the clinical target volume for 3-dimensional conformal radiotherapy in non-small-cell lung cancer?].

PURPOSE: Conformal irradiation of non-small cell lung carcinoma (NSCLC) is largely based on a precise definition of the nodal clinical target volume (CTVn). The reduction of the number of nodal stations to be irradiated would render tumor dose escalation more achievable. The aim of this work was to design an mathematical tool based on documented data, that would predict the risk of metastatic involvement for each nodal station. METHODS AND MATERIAL: From the large surgical series published in the literature we looked at the main pre-treatment parameters that modify the risk of nodal invasion. The probability of involvement for the 17 nodal stations described by the American Thoracic Society (ATS) was computed from all these publications and then weighted according to the French epidemiological data. Starting from the primitive location of the tumour as the main characteristic, we built a probabilistic tree for each nodal station representing the risk distribution as a function of each tumor feature. From the statistical point of view, we used the inversion of probability trees method described by Weinstein and Feinberg. RESULTS: Taking into account all the different parameters of the pre-treatment staging relative to each level of the ATS map brings up to 20,000 different combinations. The first chosen parameters in the tree were, depending on the tumour location, the histological classification, the metastatic stage, the nodal stage weighted in function of the sensitivity and specificity of the diagnostic examination used (PET scan, CAT scan) and the tumoral stage. A software is proposed to compute a predicted probability of involvement of each nodal station for any given clinical presentation. CONCLUSION: To better define the CTVn in NSCLC 3DRT, we propose a software that evaluates the mediastinal nodal involvement risk from easily accessible individual pre-treatment parameters.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

Hodgkins disease.

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Combined Modality Therapy↗

PubMed2000

Thallium-201 scintigraphy is not predictive of late cardiac complications in patients with Hodgkin's disease treated with mediastinal radiation.

PURPOSE: To assess whether abnormalities depicted by Thallium-201 scintigraphy can predict the occurrence of late cardiac complications in patients with Hodgkin's disease treated with mantle field radiation therapy. METHODS AND MATERIALS: Thallium scintigraphy was performed in 49 patients at a median of 75 months after initial treatment (range 28-208 months). Initial treatment consisted in chemotherapy, given to two-thirds of the patients and mantle field radiation, delivered to all patients, using a 25-MV linear accelerator. Myocardial perfusion defects were observed in 78% of patients on thallium scintigraphy. These patients had their cardiac status reassessed at a median follow-up of 13.5 years after treatment. RESULTS: Forty-two patients were assessable, as data on the cardiac status were missing in 7 patients. The majority of patients received at least 40 Gy, and 75% of them were treated with one field per day. The median follow-up of patients is 13.5 years (range 9-24.5). Eleven cardiac complications were observed in 9 patients (coronary artery disease [n = 2], conduction-system abnormalities [n = 3], valvular defects [n = 5], and congestive heart disease [n = 1]). The median 15-year actuarial incidence of cardiac complications was 21% (95% confidence interval of 9-40%). The positive and negative predictive value of thallium scintigraphy was 19% and 77%, respectively. The univariate analysis showed that the extent of left ventricle exposure to irradiation was an adverse prognostic factor, and chemotherapy administered before mantle field irradiation was of borderline significance. CONCLUSION: Thallium scintigraphy is not predictive of late cardiac complications. The extent of left ventricle exposure to radiation and possibly chemotherapy given before radiation treatment are adverse prognostic factors.

Adolescent↗

PubMed2000

Evaluation of microscopic tumor extension in non-small-cell lung cancer for three-dimensional conformal radiotherapy planning.

PURPOSE: One of the most difficult steps of the three-dimensional conformal radiotherapy (3DCRT) is to define the clinical target volume (CTV) according to the degree of local microscopic extension (ME). In this study, we tried to quantify this ME in non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: Seventy NSCLC surgical resection specimens for which the border between tumor and adjacent lung parenchyma were examined on routine sections. This border was identified with the naked eye, outlined with a marker pen, and the value of the local ME outside of this border was measured with an eyepiece micrometer. The pattern of histologic spread was also determined. RESULTS: A total of 354 slides were examined, corresponding to 176 slides for adenocarcinoma (ADC) and 178 slides for squamous cell carcinoma (SCC). The mean value of ME was 2.69 mm for ADC and 1.48 mm for SCC (p = 0.01). The usual 5-mm margin covers 80% of the ME for ADC and 91% for SCC. To take into account 95% of the ME, a margin of 8 mm and 6 mm must be chosen for ADC and SCC, respectively. Aerogenous dissemination was the most frequent pattern observed for all groups, followed by lymphatic invasion for ADC and interstitial extension for SCC. CONCLUSION: The ME was different between ADC and SCC. The usual CTV margin of 5 mm appears inadequate to cover the ME for either group, and it must be increased to 8 mm and 6 mm for ADC and SCC, respectively, to cover 95% of the ME. This approach is obviously integrated into the overall 3DCRT procedure and with other margins.

Adenocarcinoma↗

PubMed2000

The radiation accident in Georgia: clinical appearance and diagnosis of cutaneous radiation syndrome.

BACKGROUND: Eleven male Georgian soldiers were accidentally exposed to radiation by cesium 137 during their training in a military exercise camp in Lilo, Georgia between November 1996 and May 1997. OBJECTIVE: The characteristic sequelae of accidental cutaneous irradiation and available diagnostic methods are described. METHODS: Magnetic resonance imaging (MRI) of radiation ulcers was performed in all patients; thermography was performed in 2. In 7 patients ulcers and white macules were examined with high-frequency 20 MHz sonography; histologic results were obtained from all patients. RESULTS: Predominant lesions were radiation ulcers in 11 patients and white hairless macules in 7. MRI showed ulcers down to the muscles and an increase of signal intensity in the musculature in 9 cases. The corresponding muscle histology demonstrated vasculitis in 7 patients and necrosis in 2. In 2 patients, MRI signal intensity of the musculature was normal. In 3 patients, 20 MHz sonography showed dermal defects; 1 patient had cutaneous fibrosis. Thermography demonstrated hypothermic zones with extended inflammatory zones adjacent to the radiation ulcers in both patients examined. CONCLUSION: High-frequency 20 MHz sonography, MRI, and thermography are useful noninvasive methods for diagnosis of the extent of cutaneous radiation syndrome and for therapy planning.

Adult↗

PubMed2000

Prospective randomized comparison of single-dose versus hyperfractionated total-body irradiation in patients with hematologic malignancies.

PURPOSE: Fractionated total-body irradiation (HTBI) is considered to induce less toxicity to normal tissues and probably has the same efficacy as single-dose total-body irradiation (STBI) in patients with acute myeloid leukemia. We decided to determine whether this concept can be applied to a large number of patients with various hematologic malignancies using two dissimilar fractionation schedules. PATIENTS AND METHODS: Between December 1986 and October 1994, 160 patients with various hematologic malignancies were randomized to receive either a 10-Gy dose of STBI or 14.85-Gy dose of HTBI. RESULTS: One hundred forty-seven patients were assessable. The 8-year overall survival rate and cause-specific survival rate in the STBI group was 38% and 63.5%, respectively. Overall survival rate and cause-specific survival rate in the HTBI group was 45% and 77%, respectively. The incidence of interstitial pneumonitis was similar in both groups. However, the incidence of veno-occlusive disease (VOD) of the liver was significantly higher in the STBI group. In the multivariate analysis with overall survival as the end point, the female sex was an independent favorable prognostic factor. On the other hand, when cause-specific survival was considered as the end point, the multivariate analysis demonstrated that sex and TBI were independent prognostic factors. CONCLUSION: The efficacy of HTBI is probably higher than that of STBI. Both regimens induce similar toxicity with the exception of VOD of the liver, the incidence of which is significantly more pronounced in the STBI group.

Adolescent↗

PubMed2000

[Brachytherapy in the curative treatment of localized prostatic cancer].

The treatment of clinically localized prostate cancer is based on total prostatectomy, radiotherapy or surveillance. The adverse effects of these treatments have led to an increasing interest in alternatives with decreased morbidity. Brachytherapy consists of placing radioactive sources in the prostatic tissue. High doses can therefore be delivered to the cancer while avoiding excessive irradiation of the bladder and rectum. Brachytherapy generally uses permanent implants (Iodine 125 or Palladium 103). The so-called Seattle technique requires planning before implantation, while, in the "ProCeed" technique, the position of the grains is determined at the time of treatment, with the help of a computer programme which determines the dosimetry. Brachytherapy is a reliable and reproducible technique with minimal morbidity, providing 10-year results comparable to those of total prostatectomy.

Brachytherapy↗

PubMed2000

Genetic susceptibility to radiations. Which impact on medical practice?

Recent progress especially in the field of gene identification and expression have raised more attention on genetic susceptibility to cancer possibly enhanced by radiation. Radiation therapists are mostly concerned by this question since hypersensitive patients may suffer from adverse effects in normal tissues following a standard radiation therapy and normally sensitive patients could benefit from higher doses of radiation for better treatment of their malignant tumors. Although only a small percentage of individuals are "hypersensitive" to radiation effects, all medical specialists using ionising radiation should be aware of this new progress in medical knowledge. The present paper reviews the main pathologies (diseases, syndromes...) known or strongly suspected to be associated with a hypersensitivity to ionizing radiation. Then the main tests capable of detecting in advance such pathologies are analyzed and compared. Finally guidelines are provided, especially to the radiation therapists to limit the risk of severe complications (or even deaths) for this specific subset of patients suffering from a genetic disorder with a susceptibility to radiations.

Genetic Predisposition to Disease↗

PubMed1999

Analysis by alkaline comet assay of cancer patients with severe reactions to radiotherapy: defective rejoining of radioinduced DNA strand breaks in lymphocytes of breast cancer patients.

Therapeutic exposure to ionising radiation reveals inter-individual variations in normal tissue responses. To examine whether a defect in DNA repair capacity might be involved in such hypersensitive phenotypes, we analysed, using the alkaline comet assay, the response as a function of time to in vitro irradiation at 5 Gy of lymphocytes from 17 breast cancer and 9 Hodgkin's disease patients who developed severe reactions to radiotherapy in comparison with 22 patients with "average" reactions and 24 healthy donors. A difference between breast cancer over-reactors and both patients with normal reactions and healthy donors was observed 30 and 60 min after exposure. A subgroup of breast cancer over-reactors (7/17) reproducibly demonstrated increased levels of residual damage. When the kinetic analyses were prolonged to 120 min, results were in favour of delayed kinetics of rejoining in these patients. Among Hodgkin's disease over-reactors, only one patient showed defective repair. Interestingly, all patients with the most severe complications (grade 4 RTOG/EORTC), i.e., 5 breast cancer and 1 Hodgkin's disease, showed impaired rejoining. Our results suggest that impairment in DNA strand break processing may be associated, in specific subgroups of breast cancer patients, with an individual risk of major toxicity of radiation therapy. Thus, the alkaline comet assay appears to be useful for documenting the DNA repair phenotype in cancer patients.

Adult↗

PubMed1999

Cancer of the base of the tongue: past and future.

BACKGROUND: Squamous cell carcinomas of the base of the tongue often are diagnosed at advanced stages, in a context of undernutrition with a history of smoking and alcoholism. The local treatment of these tumours is based on external irradiation, either alone or combined with brachytherapy, followed by salvage surgery in the case of failure. Surgery was rarely performed as first-line treatment in our institution until 1992. METHODS: From 1960 to 1992, 216 patients were treated, without prior selection, according to the same protocol comprising external irradiation and salvage surgery in the case of failure. The tumour classification (UICC 88) was as follows: 14% of T1, 26% of T2, 44% of T3; 16% of T4; the median age was 58 years; tumour regression was evaluated during and at the end of irradiation. RESULTS: The locoregional control rates were 45% at 5 years, 37% at 10 years: 82% at 5 and 10 years for stage I, 65% and 54% for stage II, 51% and 45% for stage III, 35% and 32% for stage IV. Overall survival rates were 27% at 5 years and 14% at 10 years; 53% and 27% for stage I, 34% and 17% for stages II and III, 18% and 12% for stage IV. Causes of death were primarily local failures (58%), intercurrent disease (15%), metastases (10%), and second cancers (8%). Multivariate analysis demonstrated three predictive factors of locoregional control and survival: tumour regression at the end of irradiation (p = 0.0001), age (p = 0.04), and tumour stage (p = 0.06). CONCLUSION: The results of this retrospective series confirm the poor prognosis of tumours of the base of the tongue. Irradiation and surgery remain the standard treatments; possibilities of improvement are currently under evaluation, such as acceleration of irradiation, and concomitant radiochemotherapy combinations, which currently appear to be the most promising approaches.

Adult↗

PubMed1999

Increased sensitivity of CLL-derived lymphocytes to apoptotic death activation by the proteasome-specific inhibitor lactacystin.

Ubiquitin-proteasome-dependent protein processing appears to be an essential component in the control of radiation-induced apoptosis in human lymphocytes. This control is altered in chronic lymphocytic leukaemia (CLL), compared to that of normal human lymphocytes which mainly showed high apoptotic values after irradiation, but in some cases no sensitivity was observed. Interestingly, lactacystin activated the apoptotic pathway in both radio-resistant and sensitive CLL cells, at doses which had no effect in normal cells where significantly higher concentrations were required. Therefore the resistance of some CLL cells to apoptosis initiation by radiation does not correlate to observed increased sensitivity to lactacystin. The nuclear level of the transcription factor NF-kappaB or the cytoplasmic level of IkappaBalpha remained unaltered upon irradiation or lactacystin CLL cells treatment, suggesting that the activity of the other factors involved in apoptotic death control were altered through proteasomal inhibition. These results strongly suggest an essential role of the ubiquitin system in apoptotic cell death control in CLL lymphocytes. The inhibition of proteasome-ubiquitin-dependent processing could be a discriminatory apoptotic stimulus between normal versus malignant lymphocytes and therefore might potentially be of use in this specific human pathology.

Acetylcysteine↗

PubMed1999

The 1951-98 experience of the Paris Institut Curie Radiopathology Unit: a preliminary report.

From 1 January 1951 to 30 June 1998, 696 patients presented spontaneously or were referred to the French Institut Curie Radiopathology Unit following a more or less severe accidental irradiation. Of these, 568 patients came from France, while 128 were sent by various foreign countries. The very great majority of irradiation accidents occurred in the workplace, particularly in industry. Interestingly, 'non-nuclear' industry was responsible for three times more events than the nuclear industry. While incidental irradiation of the public by lost radioactive sources was exceedingly rare in France, it seemed to be more frequent in our cohort of foreign patients. Radiation phobia accounted for about 10% of cases in the French cohort, but the number of cases did not seem to increase with time. Overall, the accrual of patients over time appears to be stable, with 10 to 25 new cases consulting each year. Fortunately, a majority of cases corresponded to low-level irradiation (and even no irradiation at all). In the French cohort, only 21.6% of patients, showing deterministic effects, required some form of treatment, with 4.9% considered as 'severe' cases. Not unexpectedly, more patients required treatment in the foreign cohort (35.2%), with 24.2% of severe cases, including four deaths. The main features of this database are consistent with the data previously reported by the IAEA, UNSCEAR and REAC/TS. Although the number of severe cases is small, it should still be considered to be too high, especially as most of these accidents could have been easily avoided if a few basic radioprotection rules had been fully respected.

Accidents, Occupational↗

PubMed1999

A lost pigtail.

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Adult↗

PubMed1999

Histopathological and cellular studies of a case of cutaneous radiation syndrome after accidental chronic exposure to a cesium source.

This study was designed for the histopathological, cellular and biochemical characterization of a skin lesion removed surgically from a young male several months after accidental exposure to cesium-137, with an emphasis on expression of transforming growth factor beta1 (TGFB1) and tumor necrosis factor alpha (TNFA) and the occurrence of apoptosis. Under a hypertrophic epidermis, a highly inhomogeneous inflammatory dermis was observed, together with fibroblastic proliferation in necrotic areas. Immunostaining revealed overexpression of TGFB1 and TNFA inside the keratinocytes of the hypertrophic epidermis as well as in the cytoplasm of the fibroblasts and connective tissue of the mixed fibrotic and necrotic dermis. Inside this dermis, the TUNEL assay revealed areas containing numerous apoptotic fibroblasts next to areas of normal viable cells. Overexpression of TGFB1 was found in the conditioned medium and cellular fractions of both hypertrophic keratinocytes and fibrotic fibroblasts. This overexpression lasted for at least three passages in tissue culture. The present observations were consistent with the central role of TGFB1 in the determination of chronic radiation-induced damage to the skin and a significant involvement of TNFA. In addition, programmed cell death appeared to take place during the remodeling of the mixed fibrotic and necrotic tissue.

Adult↗