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J L Lagrange

Publications and source records attributed to J L Lagrange.

At least 19 recordsLinked to original sources

[Role of the combination of external radiotherapy--partial cystectomy--interstitial brachytherapy in pT1 G3, pT2 and pT3 bladder tumors].

Although it is still the reference method for curative treatment of invasive bladder cancer, radical cystectomy is a major surgical procedure justifying the evaluation of surgical tumoral excision in combination with curietherapy. At Nice University Hospital, between 1986 and 1998, 29 men with invasive bladder cancer were treated by partial cystectomy and interstitial brachytherapy. All the patients received external preoperative radiation of the pelvis of 10.5 Gy (Three 3.5 Gy flashes) three days before partial cystectomy associated with implantation of curietherapy guides carried out on average Five days after surgery with the dose of 50 Gy. After between 5 to 17 years of follow-up, eight deaths out of 14 occurred due to the disease and/or treatment, three patients had a superficial recurrence and one patient underwent salvage prostatocystectomy. Curietherapy gave rise to no direct complications, three patients suffered an eventration and 1 evisceration. Two out of 15 surviving patients suffer from invalidating pollakiuria and one from chronic retention. This study shows that overall survival corrected for intercurrent deaths is lower than data in the literature, though the low sample size makes it impossible to compare the carcinological results and survival per pT category. In addition, this strategy results in fewer complications after radiation therapy. Hence, although a certain number of questions remain unanswered, it seems possible for suitably selected patients to expect the same cure rates as radical surgery with reduced morbidity.

Adult↗

[Study of theoretical cases of intensity-modulated beams with step-and-shoot technique].

To initiate Intensity-Modulated Radiation Therapy (IMRT) in our department, theoretical cases were used as a training, to define methods of measurements and to verify the software by comparing results of calculation and measurement on a PMMA phantom. Irradiation was performed with 6 and 25 MV X-rays from a linear accelerator. For measurements, films and ionization chambers have been chosen. The comparison between calculations and measurements shows some discrepancies at the level of junctions and also in areas of low doses especially when many segments were used. These theoretical cases provide a first step on the way towards treatments with intensity modulation.

Bias↗

Validation of intensity modulation on a commercial treatment planning system.

For two years now, a study on intensity modulated radiotherapy (IMRT) has been in progress at the Antoine Lacassagne Hospital Center for Cancer Therapy (in Nice) in collaboration with the University of Nice-Sophia Antipolis. The kind of intensity modulation that was used is the "step and shoot" technique in which the modulated beam is created both by adding andjoining elementary fields. Before carrying out clinical tests, several problems regarding the production of modulated beams has to be mastered. The current developments of our study enable us to dosimetrically produce (in water phantom and in the PMMA phantom) complexmodulated whose segmentation was calculated by one commercial treatment planning system (TPS). Nevertheless, we showed and studied some critical discrepancies between standard clinical calculations and the calculations using field segmentation. We showed that with nonoptimal conditions of segmentation the discrepancies, which are due to the type of algorithm used, could bring about significant errors inside the field of up to 10% of maximum dose. Another point of our study is the quantification and resolution of differences between measurements and calculations due to the internal segmentation of calculated modulated fields and their realization on Linac. Once again, in none optimal conditions of segmentation and inside the field we obtained discrepancies up to 20% of maximum dose between calculations using field segmentation and measurements. That was mainly due to the tongue and groove effect and penumbra phenomena. This study allows us to show that the discrepancies between segmentation calculations and standard clinical calculations should be solved by the use of penumbra models during segmentation calculations. We will introduce both the study and its near-future perspectives.

Algorithms↗

[Standards, options, and recommendation for external radiotherapy of prostatic cancer: evaluation of the effect of dosage].

CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical speciality societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery. OBJECTIVES: Produce clinical practice guidelines for the radiotherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC and the French Urology Association (AFU) designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers. RESULTS: The main recommendations are: 1/ a minimal dose of 70 Gy must be used, whatever the prognostic factors; 2/ it appeared that patients with favourable prognostic indicators (stage T1-2, PSA < or = 10 micrograms/L and Gleason score < or = 6) do not benefit from a dose escalation effect for doses over 70-74 Gy; 3/ patients with intermediate prognosis are the ones who benefit most from the dose escalation effect over 74 Gy, provided they receive exclusive radiation therapy; 4/ whenever possible, patients should be included in controlled trials designed to assess the effects of dose escalation and hormonotherapy.

Humans↗

[Radiation recall dermatitis after docetaxel and external beam radiotherapy. Report of two cases and review of the literature].

Radiation recall refers to a tissue reaction produced by a chemotherapeutic agent in a previously irradiated field that would not occur in a nonirradiated field. Docetaxel is a member of the taxane group of antineoplastic agents that cause disruption of cell division by enhancing microtubule assembly and inhibiting tubulin depolymerisation. As well as in breast cancer and lung cancer treatment, its association in a chemoradiation planned treatment becomes frequent and effective. Most of radiation recall dermatitis (RDD) reported in literature concerned paclitaxel or other drugs. We report two particularly striking cases of RDD with docetaxel and radiotherapy. Even if etiology remains undetermined, a number of hypotheses can be formulated. Familiarity with this phenomenon and potential complications of chemotherapy following tumor irradiation may expedite early diagnosis and appropriate lifesaving treatment.

Antineoplastic Agents, Phytogenic↗

[Target-volume and critical-organ delineation for conformal radiotherapy of prostate cancer: experience of French dose-escalation trials].

The delineation of target volume and organs at risk depends on the organs definition, and on the modalities for the CT-scan acquisition. Inter-observer variability in the delineation may be large, especially when patient's anatomy is unusual. During the two french multicentric studies of conformal radiotherapy for localized prostate cancer, it was made an effort to harmonize the delineation of the target volumes and organs at risk. Two cases were proposed for delineation during two workshops. In the first case, the mean prostate volume was 46.5 mL (extreme: 31.7-61.3), the mean prostate and seminal vesicles volume was 74.7 mL (extreme: 59.6-80.3), the rectal and bladder walls varied respectively in proportion from 1 to 1.45 and from 1 to 1.16; in the second case, the mean prostate volume was 53.1 mL (extreme: 40.8-73.1), the volume of prostate plus seminal vesicles was 65.1 mL (extreme: 53.2-89), the rectal wall varied proportionally from 1 to 1, 24 and the vesical wall varied from 1 to 1.67. For participating centers to the french studies of dose escalation, a quality control of contours was performed to decrease the inter-observer variability. The ways to reduce the discrepancies of volumes delineation, between different observers, are discussed. A better quality of the CT images, use of urethral opacification, and consensual definition of clinical target volumes and organs at risk may contribute to that improvement.

Adenocarcinoma↗

Establishment of two new human bladder carcinoma cell lines, CAL 29 and CAL 185. Comparative study of cell scattering and epithelial to mesenchyme transition induced by growth factors.

We describe here two new human urothelial carcinoma cell lines, CAL 29 and CAL 185, established from two patients with high-grade tumours and which display very different properties in vitro. We have shown that CAL 29 cells were tumorigenic in mice and expressed characteristic features of both cell scattering and transition from epithelial to mesenchymal phenotype (EMT) after triggering by the EGF receptor ligands, TGFalpha and EGF. At the opposite, the CAL 185 cells were not tumorigenic in mice and neither scattered nor expressed vimentin intermediary filaments in the presence of growth factors. We further demonstrated that CAL 29 cell scattering was reversible after growth factor removal and that both scattering and EMT were markedly impaired after treatment with MEK, Src and PI3-kinase inhibitors suggesting that these kinases might be important components of the cellular responses to EGF and TGF-alpha leading to scattering and EMT. These agents could help to understand the intracellular pathways involved in invasiveness and to find new targets for limiting metastasis. In conclusion, these two new cell lines could be good models to dissect the molecular mechanisms involved in invasion and metastasis development in human bladder cancer.

Aged↗

[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↗

[Concomitant bifractionated radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in locally progressive, non-resectable epidermoid carcinomas of the pharynx: ten years experience at the Antoine Lacassagne center].

PURPOSE: Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors. PATIENTS AND METHODS: From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21-day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (750 mg/m2/day at 1st course; 430 mg/m2/day at 2nd and 3rd courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy. RESULTS: Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 2 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall survival were the Karnofsky index (71% survival at 3 years for patients with a Karnofsky index of 90-100% versus 30% for patients with a Karnofsky index of 80% versus 0% for patients with a Karnofsky index of 60-70%, p = 0.0001) and tumor location (55% at 3 years for oropharynx versus 37% for panpharynx versus 28% for hypopharynx, p = 0.009). CONCLUSION: These results confirm the efficacy of concomitant bid radiotherapy and chemotherapy in advanced unresectable tumor of the pharynx. The improvement in results will essentially depend on our capacity to restore in a good nutritional status the patients before beginning this heavy treatment.

Adult↗

[Standards, Options, and Recommendations for brachytherapy in patients with prostate cancer: efficacy and toxicity].

CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical specialty societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by a critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery. OBJECTIVES: Produce clinical practice guidelines for the brachytherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC and the French Urology Association (AFU) first designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers. RESULTS: The main recommendations are: 1/Brachytherapy with permanent seeds alone is a possible curative treatment for prostate cancer patients with the following prognosis factors: tumour stage T1 or T2a (TNM 1992), Gleason score < or = 6 and PSA < 10 micrograms/L. 2/Combined treatment with brachytherapy and hormonal therapy could be more efficient than brachytherapy alone for prostate cancer patients with Gleason score > 7 and/or PSA > 10.3/Combination of brachytherapy and external beam radiation therapy can be proposed to prostate cancer patients with intermediate prognosis. 4/Before and after seed implantation, risks of infection must be prevented by appropriate antibiotic therapy (recommendation). 5/Brachytherapy must not be performed within 2 months of transurethral prostate resection. 6/The height of the urethra receiving more than 200% of the prescribed dose must be reported. The portion of the rectum receiving 100 and 120% of the prescribed dose must be limited to 10 and 5 mm length, respectively.

Antineoplastic Agents, Hormonal↗

Non-Hodgkin's lymphoma of the testis: a retrospective study of 84 patients treated in the French anticancer centres.

Primary non-Hodgkin's lymphoma of the testicle is rare. We analysed cases treated in French anticancer centres from 1969 to 1995. All cases were reviewed and classified according to the R.E.A.L. Classification. Eighty-four cases were included in this study. The median age was 67 years (17-85). Disease was classified as stages I in 42 cases, stages II in 19 and stages III-IV in 23. Diffuse large B-cell lymphoma was diagnosed in 75% of cases. Treatment included orchidectomy and radiotherapy and/or chemotherapy. A complete response was obtained in 72.6% of the patient population and in 100%, 68% and 33% of stage I, II and III-IV disease respectively. Recurrence occurred in 32 cases and the most frequent site was the central nervous system: six of these patients presented stage I disease. Median overall survival was 32 months for the entire population, 52 months for stage I, 32 months for stage II, and 12 months for stage III-IV cases (P < 0.0001). Among patients presenting stage I disease, no difference was found between those treated with combined surgery and chemotherapy or surgery followed or not followed by radiotherapy. This study confirms that non-Hodgkin's lymphoma of the testicle carries a poor prognosis. Systemic adjuvant chemotherapy should be discussed because of the high recurrence rate. Inclusion of these cases in large co-operative prospective studies is recommended.

Adolescent↗

Radiotherapy for a solitary brain metastasis during pregnancy: a method for reducing fetal dose.

A patient presented during the second half of pregnancy with a solitary brain metastasis from lung cancer. This case shows that, using a new patient position, it is possible to shield the fetus efficiently. This new method consisted of whole brain irradiation with parallel pair treatment by lateral fields with the patient in a supine position with maximal neck extension. The dose to the fetus has been considerably reduced (0.3 cGy total dose) compared with previous techniques. The prescribed tumour dose was 30 Gy.

Adult↗

[Standards, options and recommendations for the management of locally advanced non small cell lung carcinoma].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of locally advanced non small cell lung carcinoma. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations are: 1) The management of the locally advanced non small cell lung carcinoma has two main goals: firstly to obtain local control of the disease (or to at least delay local progression in order to improve the survival or relapse free survival), and secondly to prevent the development of metastases. 2) There is a consensus that locally advanced non small cell lung carcinoma should be irradiated. External beam radiotherapy should be of optimal quality and delivered at a minimal dose of 60 Gy by standard fractionation. For patients with a poor life expectancy, this can be delivered as a split-course or hypofractionated scheme. 3) Treatment for patients with a performance status of 0-1 should consist of short duration induction chemotherapy (with a least two drugs one of which must be cisplatin), combined sequentially with conventional radiotherapy. 4) Surgery is contraindicated in extensive N3 disease. Combined radio-chemotherapy (adjuvant or neoadjuvant) is not indicated outside clinical trials. Surgery is justified in stage N2 disease as good local control can be achieved. T4-N0 disease should be treated surgically with curative intent.

Adult↗

[Multicenter study on dose escalation with conformal and conventional radiotherapy for the treatment of localized prostatic cancer. Preliminary results of tolerance and quality of life].

OBJECTIVE: To study the safety of conformal radiotherapy dose escalation up to 80 Gy for curative treatment of prostate cancer. MATERIAL AND METHODS: A multicentre trial sponsored by the PHRC include 164 patients under the age of 75 years with stage T1b-T3 N0 M0 prostatic adenocarcinoma, between 1995 and 1998. The prostate was treated at 5 dose levels: 18 patients at 66 Gy, 28 at 70 Gy, 49 at 74 Gy, 48 at 78 Gy, 21 at 80 Gy. The acute and delayed toxicity was graded according to a multidisciplinary glossary. Quality of life was evaluated before and one year after treatment using the EORTC QLQ-C30 questionnaire and additional questions. RESULTS: 89% and 55% of mild or moderate gastrointestinal and urinary adverse effects were observed during treatment, respectively. At long-term follow-up, of the 162 evaluable patients, 12.3% presented grade 2 adverse effects and 2.5% presented grade 3 adverse effects (1 case of haematuria, 2 urethral strictures, 1 bladder neck lesion) with no significant difference between the various dose levels. Two successive quality of life questionnaires were available for 119 patients: tiredness, pain and dyspnoea increased in parallel, but non-significantly in the groups receiving conventional doses or high doses. The proportion of patients reporting sexual activity without endocrine therapy decreased from 48% before treatment to 35% one year later. The proportion of patients with no clinical or laboratory signs of progression was higher in the high-dose group. CONCLUSION: No significant difference was observed between conventional dose levels and high dose levels in terms of toxicity or quality of life. As the adverse effects were acceptable, a randomized trial comparing 70 Gy and 80 Gy has been initiated.

Adenocarcinoma↗

[Standards, Options and Recommendations for the management of stage I or II primary bronchial cancers treated exclusively with radiotherapy].

CONTEXT: The 'Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French cancer centres and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French cancer centres. RESULTS: The main recommendations for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone are: 1) The curative external irradiation with a continual course is an alternative to surgery only in the case of medically inoperable tumors or because the patient refuses surgery; 2) The external irradiation of the primary tumor only without the mediastinum could be proposed in peripheral stage IA. In proximal stage IA and IB, external irradiation should be carried out only as part of prospective randomised controlled trials comparing a localised irradiation of the primary tumor with a large irradiation of the mediastinum and the primary tumor. The treated volume must include the macroscopic tumoral volume with or without the microscopic tumoral volume and with a security margin from 1.5 to 2 cm; 3) There is a benefit to delivering a total dose in the primary tumor higher than 60 Gy in so far as the proposed irradiation, taking into account the respiratory function, does not increase the likelihood of severe adverse events due to radiation; and 4) The change in fractionation, the radiochemotherapy combination, the endobronchial brachytherapy with high dose rate alone or with external irradiation could be proposed only as part of prospective controlled trials for tumors classified as stage IB or II.

Aged↗