PubMed Health⌕ Search

Biomedical subjects

B Dubray

Publications and source records attributed to B Dubray.

At least 19 recordsLinked to original sources
PubMed2006

[Diagnosis and treatment of soft-tissue tumors].

The diagnostic and therapeutic management of patients with soft-tissue tumors would be similar to the approach used for bone tumors if it were not for one crucial factor: the absolute necessity to recognize a sarcoma. The predominant features are the size of the tumor and its superficial or deep localization. If the tumor is small and superficial, biopsy can be associated with immediate resection without risk of dissemination to the deep tissues: this is the biopsy-resection approach. If the tumor is deep or superficial but large sized, search for locoregional spread with MRI is necessary before undertaking any surgical procedure. MRI can help guide the biopsy and plan resection if the tumor is a sarcoma. A first biopsy is necessary to establish the histological diagnosis and elaborate the therapeutic strategy. Samples should be sent immediately to the pathology lab which should examine sterile fresh tissue. Experience has demonstrated that proper rules for diagnosis and treatment are not necessarily applied initially in approximately one-fourth of all subjects with a malignant soft-tissue tumor. Besides the medical problems caused by this situation, the patient loses a chance for cure. When the tumor is a sarcoma, surgery is the basis of treatment. Complementary radiation therapy may be necessary, particularly for high-grade tumors or if the surgical margin was insufficient. Systemic or locoregional chemotherapy can also be used for high-grade or non-resectable tumors.

Biopsy↗
PubMed2004

[Preliminary results of the assessment of intensity modulated radiotherapy (IMRT) for prostatic and head and neck tumors (STIC 2001)].

INTRODUCTION: Between May 2002 and May 2004, eight French comprehensive cancer centres did a prospective nonrandomized study including 200 patients, 100 with cancer of the prostate and 100 with head and neck cancers. Half of each patient group was treated by IMRT and the others by RTC 3D. This clinical study was associated with an economic study and a physics study. We report here the first results. PATIENTS AND METHODS: For the clinical study, the analysis of the data of the first 88 patients irradiated for a prostatic cancer shows that 39 received RTC and 49 IMRT with a mean dose of 78 Gy at the ICRU point at 2 Gy per fraction. For H&N tumours, the preliminary analysis was done on the 87 first patients with a mean follow-up of 11.5 months (2 to 25 months) and a median of 8.4 months for the IMRT groups and 13.2 months for the RTC group. The economic study was done on the first 157 patients included during the first 18 months: 71 treated by RTC (35 for H&N and 36 for prostate) and 86 treated by IMRT (38 for H&N and 48 for prostate). The assessment of the direct costs was realized by a micro-costing technique. The physical study compared dose distributions for both techniques and has created quality control recommendations. RESULTS: Clinical studies of the acute reactions do not show any difference between groups, but we want to point out the short follow-up and the relatively high dose delivered to cancers of the prostate. The physics study demonstrates that IMRT is technically feasible in good clinical conditions with high quality assurance, a good reproducibility and precision. Dosimetric data show that IMRT could certainly spare organs at risk more than RTC for H&N tumours. The direct costs of "routine" treatments for H&N tumours were 4922 euros for IMRT versus 1899 euros for RTC and for the prostatic cancers 4911 euros for IMRT versus 2357 for RTC.

Adolescent↗
PubMed2003

[Quality control during radiation therapy].

The aim of quality control procedures during radiation therapy is to check the consistency between actual and prescribed treatments. Given the technical complexity of modern radiotherapy, stricter policies are necessary to meet increasing requirements for quality and safety. Among the various tools available, electronic imaging systems play an increasing role in patient-beam position checking and in vivo dose measurements. Written procedures will have to be established in order to describe the control modalities and frequency, as well as the rules for error corrections according to the treatment intent. Non medical staff will be devoted to new tasks, under the radiation oncologist's responsibility. A special attention should be directed at electronic archives, since the present technology is unlikely to meet the legal requirement to keep medical records accessible for at least 30 years.

Diagnostic Imaging↗
PubMed2003

[Respiration-gated radiotherapy: current techniques and potential benefits].

Respiration-gated radiotherapy offers a significant potential for improvement in the irradiation of tumor sites affected by respiratory motion such as lung, breast and liver tumors. An increased conformality of irradiation fields leading to decreased complications rates of organs at risk (lung, heart...) is expected. Respiratory gating is in line with the need for improved precision required by radiotherapy techniques such as 3D conformal radiotherapy or intensity modulated radiotherapy. Reduction of respiratory motion can be achieved by using either breath hold techniques or respiration synchronized gating techniques. Breathhold techniques can be achieved with active, in which airflow of the patient is temporarily blocked by a valve, or passive techniques, in which the patient voluntarily breath-hold. Synchronized gating techniques use external devices to predict the phase of the respiration cycle while the patient breaths freely. These techniques presently investigated in several medical centers worldwide. Although promising, the first results obtained in lung and liver cancer patients require confirmation. Physical, technical and physiological questions still remain to be answered. This paper describes the most frequently used gated techniques and the main published clinical reports on the use of respiration-gated radiotherapy in order to evaluate the impact of these techniques.

Breast Neoplasms↗
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

[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↗
PubMed2000

Analysing the effects of anaemia on local recurrence of head and neck cancer when covariate values are missing.

We present a case study in the analysis of the prognostic effects of anaemia and other covariates on the local recurrence of head and neck cancer in patients who have been treated with radiation therapy. Because it is believed that a large fraction of the patients are cured by the therapy, we use a failure time mixture model for the outcomes, which simultaneously models both the relationship of the covariates to cure and the relationship of the covariates to local recurrence times for subjects who are not cured. A problematic feature of the data is that two covariates of interest having missing values, so that only 75 per cent of the subjects have complete data. We handle the missing-data problem by jointly modelling the covariates and the outcomes, and then fitting the model to all of the data, including the incomplete cases. We compare our approach to two traditional methods for handling missingness, that is, complete-case analysis and the use of an indicator variable for missingness. The comparison with complete-case analysis demonstrates gains in efficiency for joint modelling as well as sensitivity of some results to the method used to handle missing data. The use of an indicator variable yields results that are very similar to those from joint modelling for our data. We also compare the results obtained for the mixture model with results obtained for a standard (non-mixture) survival model. It is seen that the mixture model separates out effects in a way that is not possible with a standard survival model. In particular, conditional on other covariates, we find strong evidence of an association between anaemia and cure, whereas the evidence of an association between anaemia and time to local recurrence for patients who are not cured is weaker.

Anemia↗
PubMed1999

Reproducibility of measurements of potential doubling time of tumour cells in the multicentre National Cancer Institute protocol T92-0045.

We compared the flow cytometric measurement and analysis of the potential doubling time (Tpot) between three centres involved in the National Cancer Institute (NCI) protocol T92-0045. The primary purpose was to understand and minimize the variation within the measurement. A total of 102 specimens were selected at random from patients entered into the trial. Samples were prepared, stained, run and analysed in each centre and a single set of data analysed by all three centres. Analysis of the disc data set revealed that the measurement of labelling index (LI) was robust and reproducible. The estimation of duration of S-phase (T(S)) was subject to errors of profile interpretation, particularly DNA ploidy status, and analysis. The LI dominated the variation in Tpot such that the level of final agreement, after removal of outliers and ploidy agreement, reached correlation coefficients of 0.9. The sample data showed poor agreement within each of the components of the measurement. There was some improvement when ploidy was in agreement, but correlation coefficients failed to exceed values of 0.5 for Tpot. The data suggest that observer-associated analysis of T(S) and tissue processing and tumour heterogeneity were the major causes of variability in the Tpot measurement. The first two aspects can be standardized and minimized, but heterogeneity will remain a problem with biopsy techniques.

Aneuploidy↗
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

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↗
PubMed1998

Comparative analysis of apoptosis measured by Hoechst and flow cytometry in non-Hodgkin's lymphomas.

Fine-needle samples of 75 non-Hodgkin's lymphomas were investigated for apoptosis immediately and after 24 h of culture after in vitro irradiation (2 Gy, 10 Gy, and nonirradiated controls). Apoptotic cells were simultaneously quantified by fluorescence microscopic enumeration of apoptotic cells using Hoechst 33342 staining, and by flow cytometric detection of sub-G1 peak cells. The nonirradiated controls showed a similar mean percent apoptotic cells using both methods, analyzed immediately (9% by morphology vs. 10% by flow) or after 24 h of culture (40% by morphology vs. 41% by flow). In the irradiated samples, the mean percent apoptotic cells quantified by morphology was higher than by flow cytometry (64% by morphology vs. 55% by flow after 2 Gy irradiation, and 71% vs. 58% after 10 Gy). The results of the two methods were correlated, although large differences were seen between the techniques in individual tumors. In our system, flow cytometric sub-G1 peak analysis appears to underestimate apoptosis. Of these two methods, we find the Hoechst morphology method to be more reliable for quantitation of apoptosis utilizing fresh fine-needle sample material, in that discrimination of apoptotic cells from debris is easier and that both early and late apoptotic cells are detectable.

Apoptosis↗
PubMed1998

In vitro radiation-induced apoptosis and early response to low-dose radiotherapy in non-Hodgkin's lymphomas.

PURPOSE: Prospective investigation of spontaneous and in vitro radiation-induced apoptosis to predict early response to palliative radiotherapy in patients with non-Hodgkin's lymphomas. PATIENTS AND METHODS: Fine-needle sampling was performed in 28 tumor sites (26 patients) and yielded adequate cell numbers in 27 cases. Apoptotic cells were counted by fluorescence microscopy immediately after sampling and after 24-h culture (spontaneous apoptosis) and 24 h after 2- and 10-Gy in vitro irradiation (radiation-induced apoptosis). Early response to low-dose in vivo radiotherapy (mostly 4 Gy in two fractions over 3 days) was evaluated 15 days after treatment. RESULTS: The tumor response rates at 15 days were 11 (39%) complete responses, nine (32%) responses of greater than 50% reduction in volume, six (21%) responses of less than 50% reduction in volume and two (7%) cases of no response. Tumors achieving complete or major response after in vivo irradiation had higher percentages of apoptotic cells after in vitro irradiation, while no significant differences in terms of spontaneous apoptosis were observed between responders and non-responders. CONCLUSION: Spontaneous and in vitro radiation-induced apoptosis can be easily and quickly assessed on cells obtained by fine-needle sampling of non-Hodgkin's lymphoma lesions. The present results suggest that in vitro radiation-induced apoptosis could be used as a predictive assay of early response to low-dose in vivo irradiation in patients with non-Hodgkin's lymphomas.

Adult↗
PubMed1997

Soluble interleukin-2 receptor serum level as a predictor of locoregional control and survival for patients with head and neck carcinoma: results of a multivariate prospective study.

BACKGROUND: The diagnosis and follow-up of head and neck carcinoma patients are based exclusively on clinical staging, which cannot always predict clinical outcome accurately. Because oral squamous cell carcinomas produce interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha and express IL-2 receptors, the authors assessed the prognostic value of the serum levels of these markers. METHODS: Serum levels of IL-6, TNF-alpha, soluble IL-2 receptors (s-IL-2-R), and acute phase proteins were measured at the time of diagnosis in a prospective study of 85 patients with primary squamous cell carcinoma of the head and neck. The influence of each clinical and laboratory parameter on locoregional control and survival was analyzed. RESULTS: At presentation, a relationship was observed between advanced tumor (T) classification and high serum levels of CRP (P = 0.0015) and s-IL-2-R (P < 0.05). A high lymph node (N) classification was significantly associated with elevated serum IL-6 (P = 0.01) and CRP levels (P = 0.0002). In the univariate analysis, T classification, N classification, performance status, Prognostic Inflammatory and Nutritional Index, and serum s-IL-2-R level were significantly correlated with both locoregional control and survival. Multivariate analysis showed that the only significant prognostic factors related independently to locoregional control were N classification (P = 0.02) and serum s-IL-2-R level (P = 0.02). In a Cox multivariate analysis, serum s-IL-2-R level was found to be the most predictive factor of survival (P = 0.0001). CONCLUSIONS: This study shows that serum s-IL-2-R level at the time of diagnosis represents a new independent prognostic variable for predicting the risk of locoregional recurrence and survival for patients with head and neck squamous cell carcinoma.

Adult↗
PubMed1997

[Biological mechanisms of late effects of ionizing radiations].

The daily practice of radiation oncology is increasingly influenced by the late tolerance of normal tissues. The treatment decision must be based on detailed arguments and the physician's duty to extensively inform his patients is emphasised every day. The incidence and severity of radiation-induced sequelae and late complications can be reduced by decreasing the total dose to the normal tissues, and by decreasing the dose protraction, provided that the interval between fractions remains longer than 6 to 8 hours. This approach yields a selective protection of late responding normal tissues, since tumours are less sensitive to the effects of fractionation. Despite its own limitations, the linear- quadratic model is nowadays the standard method to compare the biological effects of different radiation treatments.

Animals↗
PubMed1997

[Late effects of mammary radiotherapy on skin and subcutaneous tissues].

Late damages to the skin and subcutaneous tissues are almost inescapable because of the high skin doses required in the irradiation of breast tumours. While the clinical and histological descriptions date back to the first decades of the therapeutic use of ionising radiation, the recent advances in cellular and molecular biology have significantly contributed to the increased understanding of late skin injury mechanisms. In particular, sub-cutaneous fibrosis appears to be the partly reversible results of a continuous and self-maintained local process, possibly sensitive to therapeutic intervention. A second very active research avenue is the development of biologic assays potentially able to predict the probability of increased normal tissue injury after irradiation in individual patients. Such a test would allow the adaptation of the treatment modalities to the radiobiological behaviour of normal tissues. To date, these expectations have not been met. The quality of the irradiation and its modalities (total dose, fractionation, inter fraction interval) remain the main ways to achieve an optimal functional and cosmetic outcome.

Breast Neoplasms↗
PubMed1997

[A combined radiochemotherapy trial for non-small cell lung cancers: initial results].

PURPOSE: Analysis of the preliminary results of a phase I study investigating the feasibility of concomitant chemotherapy with daily doses of carboplatin (20 to 25 mg/m2/d over 45 or 10 min) and accelerated chest irradiation (60 to 64 Gy over 4 weeks, 2 Gy per fraction, using the concomitant boost technique). MATERIALS AND METHODS: This combination was given alone or following three cycles of induction chemotherapy (cisplatin, 25 mg/m2 per day from d1 to d5; 5-fluorouracil, 600 mg/m2 per day from d1 to d5 and vinorelbine, 25 mg/m2 per day at d1 and d5 with a 4-week interval) in 15 patients with locally advanced unresectable non-small cell lung cancer. All patients received the planned sequence. RESULTS: The dose-limiting toxicity was esophagitis (5 out of 15 grade 4). No toxic deaths were observed. The tumor response rate was high: six out of 15 complete responses and 14 out of 15 tumor regressions greater than 50%. The median survival was not reached after a mean follow-up of 14 months (range, 6-28 months). CONCLUSION: We are now planning a multicenter phase II study using the following combination: 20 mg/m2 of daily carboplatin over 10 min and a 60-Gy irradiation dose over 4 weeks.

Adult↗
PubMed1997

[Predictive tests of response to radiotherapy. Assessment and perspectives in 1997].

The potential tailoring of radiotherapy modalities to the biological characteristics of individual tumours and normal tissues appears to be an exciting way to improve the therapeutic, ratio in radiation therapy patients. Numerous assays have been proposed to provide the clinician with the biological information necessary to predict the outcome after irradiation and to guide the treatment prescription, but none of them has made its way to daily practice. Major difficulties are due to the technical burden of the procedures, the poor characterization of the assayed cells, and, moreover, the high complexity of tumour and normal tissues biology. The present paper reviews the present status of the assessment of tumour cells radiosensitivity, proliferation and oxygenation. Research remains extremely active in the field of biological predictors of response to irradiation. Future steps forwards are expected from progress in the available technologies, (re-)discovery of apoptosis and investigation of normal tissue tolerance.

Apoptosis↗