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Biomedical subjects

E Lartigau

Publications and source records attributed to E Lartigau.

At least 37 records · Page 2Linked to original sources

[Quality control of intensity modulated treatments in radiotherapy].

Since January 2001, radiotherapy treatments with modulated intensity beams (IMRT) have started at the Centre Oscar-Lambret. This paper presents the tests and measurements made before the clinical implementation as well the quality control performed before each routine treatment. We use the treatment planning system Helax-TMS (MDS-Nordion) and the Primus accelerator (Siemens) linked to the Lantis network with Primeview and Simtec modules (Siemens) allowing to deliver intensity modulated beams with Step-and-Shoot technique. A prostate case and a head and neck case have been studied and have permitted to evaluate the benefit of IMRT compared to a "classical" conformal radiotherapy. In a second time, we have tested the accelerator's capabilities to deliver these intensity modulated beams, id-est, the accuracy of the leaf positions and the linearity of the monitor chamber. The third step has been the verification of the dose distributions calculated by Helax-TMS, id-est, the dose for different segment sizes, the dose profiles for an intensity modulated beam and the dose distribution for all the traitment beams. The used phantom has been especially developed at the Centre Oscar-Lambret for IMRT. The results have allowed to start clinical treatments and to establish a quality control set for this technique. The next step is the real time dosimetry with a portal imager.

Humans↗

[Probabilities of controlling tumors and complications (TCP/NTCP) after radiotherapy: methodologic, physical, and biological aspects].

Radiotherapy is aimed at getting the best possible therapeutic ratio (tumor local control versus morbidity). Physicists and radiation oncologists have to evaluate explicitly or implicitly the probability of induced complications to normal surrounding tissues. This is based on published data and clinician's experience. Quantitative methods have been introduced with different models in order to predict the impact of partial or global irradiation on a normal organ. These models correspond to the Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP). These biological models may be useful to evaluate the quality of a treatment planning or for the optimization process. The methodologies used and the clinical data are developed and discussed.

Dose-Response Relationship, Radiation↗

[Ionizing radiation and hyperplasia of the intimal matrix: current data and perspectives].

Vascular reconstruction (bypasses or endoluminal procedures) is still associated with a significant rate of restenosis. For restenosis, smooth muscular cells are the principal actor by their property to migrate, proliferate and secrete extra-cellular substance after their change of phenotype. A variety of pharmacological and mechanical strategies have been directed with limited success. Using ionizing radiation have been recently developed, aiming to reduce the cell proliferation and consecutive restenosis following vessel injury (anastomoses or angioplasty). We reviewed the use of radiations on animals, cellular action and recent clinical trials. Recent clinical trials confirm an effective action of using radiations for restenosis prevention. We reviewed methods of delivering radiations also drawback and consequences using these hopefully methods.

Animals↗

[Epidemiology of soft tissue sarcomas in adults].

INCIDENCE: Soft tissue sarcoma accounts for a approximately 1% of all cancers. Excluding Kaposi sarcoma, the incidence of soft tissue sarcoma has remained stable in Europe (3-4/100,000). ENDOGENOUS FACTORS: Endogenous factors are related to rare genetic syndromes (Li-Fraumeni syndrome, neurofibromatosis, Werner syndrome, bilateral retinoblastom). EXOGENOUS FACTORS: Exogenous factors associated with soft tissue sarcoma are essentially iatrogenic: radiation therapy (prevalence of radiation-induced sarcoma: 0.17-0.21%) and chronically edematous arms after radical mastectomy for breast cancer (Stewart-Treves syndrome). Many studies suggest that environmental or occupational exposure to chlorophenol, phenoxy-herbicides or dioxin increase the risk of soft tissue sarcoma. FURTHER RESEARCH: Little is known about the epidemiology of soft tissue sarcoma. Case-control studies are needed.

Adult↗

[Definitions of target volumes in soft tissue sarcomas of the extremities].

Soft tissue sarcomas of the extremities are currently treated with more conservative and functional approaches, combining surgery, radiotherapy and chemotherapy. The role of external beam radiotherapy and brachytherapy has been defined through randomised studies performed in the 80's and 90's. However, the ubiquity of tumour location for these tumours makes difficult a systematic definition of local treatments. Tumour volume definition is based on pre and post surgical imaging (MRI) and on described pathological report. The clinical target volume will take into account quality of the resection and anatomical barriers and will be based on an anatomy and not only on safety margins around the tumour bed. General rules for this irradiation (doses, volumes) and principal results will be presented.

Brachytherapy↗

Indium-111 octreotide scintigraphy of Merkel cell carcinomas and their metastases.

BACKGROUND: Somatostatin receptor scintigraphy (SRS) may be of interest for staging Merkel Cell Carcinoma (MCC). This study was undertaken to evaluate the sensitivity and specificity of SRS and to determine its role compared to conventional investigations. PATIENTS AND METHODS: From 1993 to December 2000, 20 patients (10 females and 10 males, aged from 38 to 88, mean 66 years) were included prospectively. At the time of SRS: 12 patients had been diagnosed as having stage I disease, 6 stage II and 4 stage III. Two patients had two SRS studies during the course of their disease. SRS was performed with Indium-111 pentetreotide (Octreoscan), a radiolabelled somatostatin analogue. Patients were treated according to the clinical stage. A regular follow-up was scheduled every three months. RESULTS: SRS depicted stage I and II MCC tumour sites with an overall sensitivity of 78% (95% confidence interval (CI): 40%-97%) and a specificity of 96% (81%-100%). The histopathological diagnosis was used as the gold standard. Sites visualised by SRS were compared to those detected with conventional modalities and to follow-up data for all stages: SRS visualised four out of five primary tumour sites, six out of eight lymph node sites, no skin metastases (14 sites in 2 patients), two out of three thoracic metastases and zero out of two hepatic metastases. SRS did not influence treatment decision-making in any of the cases. CONCLUSIONS: Although SRS seems highly specific in MCC and could be of help in difficult cases, it cannot be recommended for routine evaluation.

Adult↗

High-dose-rate brachytherapy as sole modality for early-stage endobronchial carcinoma.

PURPOSE: To evaluate exclusive high-dose-rate brachytherapy for localized early-stage non-small-cell bronchial carcinoma; to develop new insights in treatment-catheter positioning and tumor-volume assessment by computed tomography (CT) scan. METHODS AND MATERIALS: Between 1992 and 1996, 34 patients with non-small-cell bronchial carcinoma were treated by brachytherapy alone. All patients were medically inoperable and had contraindications for external beam irradiation. The treatment protocol was six sessions of 5 Gy over 6 weeks. The treatment catheter was placed under fiberoscopy and was positioned with the help of spacer catheters or with a surrounding plastic tube; CT scan was performed in 50% of the cases to measure the spacing between the applicator and the bronchial wall. Dose prescription was individually based on clinical and radiologic evaluation of tumor volume. RESULTS: Local disease failure occurred in 5 patients (15%). With a median follow-up of 2 years, the local control rate was 85% and the survival rate 78%. No acute toxicity was found, except one pneumothorax. CONCLUSION: Brachytherapy alone can give an optimal therapeutic ratio in small endobronchial carcinomas without radiation-induced morbidity. Such results are achieved after careful tumor volume evaluation and individualized treatment catheter positioning.

Adult↗

Biological dosimetry after total body irradiation (TBI) for hematologic malignancy patients.

PURPOSE: Biological dosimetry based on scoring chromosomal aberrations in peripheral lymphocytes was compared to physical dosimetry done for total body irradiation (TBI) before bone marrow transplantation (BMT) in patients with hematologic malignancies. PATIENTS AND METHODS: Fifteen patients undergoing TBI were included in the study. A total dose of 12 Gy in 2.5 days was fractionated into 2 or 3 daily doses of 1.8 Gy delivered by a 18 MV linear accelerator (dose rate: 15.8 cGy x min(-1)). Blood samples were obtained from patients before irradiation and after the first fraction of 1.8 Gy. A standard dose-effect curve was established by in vitro irradiation of healthy volunteer lymphocytes. Chromosomal aberrations were scored by the conventional cytogenetics (CCG) method for unstable anomalies and by fluorescent in situ hybridization (FISH) for stable anomalies. RESULTS: Healthy donor lymphocytes before irradiation yielded 0.1% dicentrics and 0.3% translocations of chromosome 4 (Chr. 4), that is 2.5% for the whole genome. Patients before irradiation had 2% of dicentrics and 1.1% of chromosome 4 translocations. The biologically estimated dose of the 15 patients after exposure to 1.8 Gy was 1.93 Gy (95% CI: 1.85-2.05) according to CCG, and 2.06 Gy (95% CI: 1.75-2.15) by FISH. CONCLUSION: The dose estimated by biological dosimetry, in this case of homogeneously distributed radiation of TBI agrees well with the absorbed radiation dose calculated by physical dosimetry.

Adult↗

[Cerebral magnetic resonance imaging (MRI) in the diagnosis of leptomeningeal carcinomatosis in melanoma patients].

OBJECTIVE: Meningeal involvement is frequent in metastatic melanoma, approximately 30% in autopsy series. Functional signs may be misleading and the neurological examination may be normal. Certain diagnosis requires identification of tumor cells in the cerebrospinal fluid. CSF cytology is however sometimes negative and magnetic resonance imaging (MRI) with gadolinium injection may provide the diagnosis. The aim of this retrospective study was to assess the role of imaging in the diagnosis of leptomeningeal carcinomatosis. PATIENTS AND METHODS: The diagnosis of leptomeningeal carcinomatosis was made in 8 patients between 1992 and 1998. All had signs of neurological function impairment, but the neurology examination was abnormal in only 2. RESULTS: Cytology examination of the cerebrospinal fluid provided the diagnosis of leptomeningeal carcinomatosis in 5 patients. One out of 5 brain CT scans were positive, showing meningeal enhancement confirmed by brain MRI. The spinal tap was not contributive in 2 cases and was not done in 1. In these three cases, the brain CT did not provide any diagnostic element while the brain MRI with gadolinium injection confirmed the diagnosis of leptomeningeal carcinomatosis. DISCUSSION: Forty-one percent of patients with autopsy proven leptomeningeal carcinomatosis have a normal ante mortem spinal tap. Brain MRI with gadolinium injection has better sensitivity than brain CT scan. All patients with nonspecific neurological signs and a normal spinal tap should be explored with a brain MRI.

Adolescent↗

[Biomodulation and radiotherapy].

Recent improvement in the understanding of the mechanisms involved in the response to ionizing radiation have made it possible to identify new therapeutic targets to increase the anti-tumor efficacy or, alternatively, to decrease the effect on normal tissues. These approaches included targeting genes involved in the regulation of radio-induced DNA-repair and cell death as well as genes involved in the regulation of radio-induced apoptosis. Many other molecular targets have been recently identified to potentially interfere with the response to ionizing radiation, such as some cell membrane growth factor receptors (EGFr, TGFb) or molecules involved in intra-cellular signal transduction pathways, cell cycle regulation, etc. In addition, other promising ways to modulate radiation-induced response concern extracellular or tissue factors such as hypoxia and angiogenesis.

Antineoplastic Agents↗

Postoperative radiotherapy in the management of adult soft tissue sarcoma of the extremities: results with two different total dose, fractionation, and overall treatment time schedules.

PURPOSE: This retrospective study was performed to evaluate two postoperative radiotherapy schedules in terms of dose, fractionation, and overall treatment time in soft tissue sarcoma (STS) of the extremities. METHODS AND MATERIALS: Between January 1984 and December 1993, 62 patients with newly diagnosed localized STS of the extremities were treated with maximal conservative surgery and postoperative radiotherapy (RT). Forty-five patients received 50 Gy with conventional fractionation plus a boost dose (5 to 20 Gy). Seventeen patients had hyperfractionated accelerated radiotherapy (HFART) up to a dose of 45 Gy in 3 weeks. RESULTS: With a median follow-up of 72 months, the 5-year local failure rate was 25%, the 5-year disease-free and overall survival rates were respectively 42% and 62%. The 3-year local relapse, disease-free, and overall survival rates were respectively 16%, 44%, and 70% in the conventional radiotherapy group, and 36%, 47%, and 82% in the HFART group (NS). No factor significantly influenced local control with a trend, however, in favor of conventional RT (p = 0.10). CONCLUSION: HFART at the dose of 45 Gy does not seem to be superior to the standard RT schedule, neither in terms of local control, survival, nor in terms of long-term side effects. However this dose could be considered too low as well as the power of comparison between the two groups to draw definitive conclusions.

Adolescent↗

How can laparoscopic management assist radiation treatment in cervix carcinoma?

PURPOSE: To determine the role of laparoscopic lymphadenectomy (pelvis +/- para-aortic nodes) and laparoscopic hysterectomy in cervical cancer compared to 'classic radical surgery' in patients undergoing surgery in comparison with modern imaging in patients treated with radiotherapy alone. MATERIALS AND METHODS: The limitations of modern imaging are presented as well as how complication rates can be increased when classic laparotomy is followed by radiation therapy. Laparoscopic procedures are described with particular emphasis on how to provide information on lymph node metastases with the risk of overlooking microscopic involvement. A number of clinical experiences are cited to illustrate this problem and show how treatment approaches can be adapted. RESULTS: The role of laparoscopy is evaluated according to different clinical situations and treatment protocols emphasizing the possibilities offered by this method to the radiotherapist. CONCLUSION: When developing laparoscopic techniques for the management of cervical carcinoma, caution must be exercised to ensure that these techniques are not detrimental to the prognosis.

Female↗

Phases IB and II multidose trial of gadolinium texaphyrin, a radiation sensitizer detectable at MR imaging: preliminary results in brain metastases.

PURPOSE: To evaluate magnetic resonance (MR) imaging results after administration of gadolinium texaphyrin, a tumor-selective radiation sensitizer that is detectable at MR imaging, and to determine an appropriate intravenous dose of gadolinium texaphyrin for repeated injections during radiation therapy, the dose-limiting toxicity of reiterated doses of gadolinium texaphyrin, the maximal tolerated dose, the biolocalization of gadolinium texaphyrin (as assessed at MR examinations), and the response to treatment. MATERIALS AND METHODS: Ten daily intravenous injections of gadolinium texaphyrin, each followed by whole-brain radiation therapy (total of 10 fractions, 30 Gy), were administered to patients with brain metastases in a multicenter study. At the study institution, 11 patients underwent MR imaging before and after the first injection, after the 10th injection, and 8 weeks after entry into the study. RESULTS: MR imaging revealed selective drug uptake in metastases, without enhancement of normal brain tissue. In 10 patients, tumor uptake was higher after the 10th injection than after the first injection, which indicated accumulation of gadolinium texaphyrin in metastases. One lesion was visible only after the 10th injection and not at the pretherapeutic MR examination with injection of conventional gadolinium-based contrast material. Response to treatment was defined as a reduction in the size of the metastases between the preinjection MR study and the last MR study; seven patients achieved partial remission with tumor regression exceeding 50% of the initial size, and four achieved a minor response with less than 50% tumor regression. CONCLUSION: These preliminary results indicate that gadolinium texaphyrin is tumor selective and that brain metastases can be depicted at MR imaging long after the administration of gadolinium texaphyrin.

Adult↗

Variations in tumour oxygen tension (pO2) during accelerated radiotherapy of head and neck carcinoma.

The study was performed to assess the effect of accelerated radiotherapy on oxygenation of primary tumours and metastatic nodes in patients with advanced head and neck tumours. In 14 patients with head and neck tumour, oxygen tension (pO2) was evaluated in normal tissues and tumours (primary tumour or metastatic neck node) before (0 Gy) and after 2 weeks (32 Gy) of accelerated radiotherapy (70 Gy in 3.5 weeks, with three daily fractions). Radiotherapy was combined with carbogen breathing in 5 patients. pO2 was measured using a polarographic technique. For pooled normal tissues, median pO2 was 38 mmHg before treatment and 46 mmHg after 2 weeks. For tumours, very low values (< 2 mmHg) represented 20% of the recorded values before treatment and 10% after 2 weeks. The relative increase in tumour oxygenation was more pronounced for primary tumours (median pO2 12 mmHg before treatment versus 26 mmHg after 2 weeks, P < 0.05) than for metastatic nodes (respectively, 20 and 27 mmHg P = 0.1). For the 5 patients who breathed carbogen during accelerated radiotherapy, the median pO2 was 44 mmHg at 2 weeks, compared with 13.5 mmHg before treatment (P = 0.05). Very low pO2 values, corresponding to tumour hypoxia, were found in the tumours (primary and metastatic neck nodes) prior to accelerated treatment. During the first 2 weeks of accelerated treatment, an increase in median pO2 was found in nine of the 14 tumours, together with a decrease in the frequency of very low values.

Aged↗

[Radiation sensitizing agents for hypoxic cells: past, present and future].

Hypoxic cells are present in rodent and xenografted human tumours and it has been known for a long time that the absence of oxygen in tumours is a factor of resistance against ionising radiation. The dose modifying role of oxygen (oxygen enhancement ratio) has been largely studied in experimental models. For pO2 values of 2 mmHg, the relative radiosensitivity of tumour cells is intermediate between the maximum sensitivity observed in air and the minimal one observed in hypoxia. The measurement of tumour pO2 in patients (polarographic technique) has demonstrated the presence of low values (< 10 mmHg) in many different tumour sites (ENT, uterine cervix, breast, melanoma, etc). In order to sensitise hypoxic tumours, imidazole have been used in patients, but most of the results were negative. New methods have been developed in the combination of bioreductive drugs of cytotoxic cells to radiotherapy. In this article, we will describe the clinical results obtained in patients with radiosensitising chemical agents.

Animals↗

[Microcystic sclerosing adnexal carcinoma: 2 case reports. Diagnostic and therapeutic difficulties].

Microcystic adnexal carcinoma is a recently described malignant neoplasm of adnexal structure. It remains frequently misdiagnosed. These tumors are characterized by their slow progression and by local aggressivity with local recurrences. The best treatment appears to be surgical excision with microscopically controlled margin. We report two cases of microcystic adnexal carcinoma recently observed at Institute Gustave Roussy.

Carcinoma, Skin Appendage↗

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↗