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J L Habrand

Publications and source records attributed to J L Habrand.

At least 19 recordsLinked to original sources
PubMed1999

Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma.

Occlusive vasculopathy is a potential complication of radiotherapy in children with optic pathway glioma. With a median follow-up of 7 years, 13 of 69 children in this study developed clinical and radiological signs of occlusive vasculopathy after radiotherapy within a median interval of 36 months. The major risk factor was neurofibromatosis type 1. Radiotherapy should no longer be the first treatment in these settings. When radiotherapy is unavoidable, regular screening for cerebral vasculopathy is mandatory, as preventive treatment is available.

Cerebrovascular Disorders↗
PubMed1999

Proton beam therapy (PT) in the management of CNS tumors in childhood.

At the Centre de Protontherapie d'Orsay, nine children with intra-cranial malignancies were treated between July 1994 and January 1998. Immediate and late tolerances were excellent in all cases (follow-up 2 to 50 months). Two patients recurred locally (marginal failures), seven are alive and doing well. At Loma Linda, 28 children were treated between 1991 and 1994, 16 for a benign tumor of the brain and twelve for a malignant one. With a follow-up of seven to 49 months, three patients died (grade 2 to 4 gliomas), one is living with a persistent disease. Four children had treatment-related toxicity (one cataract, two hormonal failures and two seizures). The other children are doing well. At MGH Boston, 18 children with skull base-cervical spine chordomas have been reported. At five years, actuarial survival and disease-free survival have been 68 and 63%, respectively. Children with cervical sites had a worse prognosis (p = 0.008). Four children had radiation-related morbidity: two pituitary failures, one temporal lobe necrosis, one temporal muscle fibrosis. In this experience, such rare tumors seemed to behave in children like in adults.

Adolescent↗
PubMed1999

The role of preoperative chemotherapy in the treatment of nephroblastoma: the SIOP experience. Societe Internationale d'Oncologie Pediatrique.

Treatment of Wilms' tumor is an example of success of modern oncology. A combination of surgery, radiotherapy, and chemotherapy is widely accepted as the efficacious treatment of nephroblastoma. However, timing of each part of the treatment differs, in various protocols: the Societe Internationale d'Oncologie Pediatrique (SIOP) recommends the diagnosis based on imaging and metabolic exclusion of neuroblastoma to reduce the biopsy-related risk of spillage. In patients more than 6 months old, the treatment starts with the preoperative chemotherapy to improve the stage distribution at surgery and decrease the complications rate. Patients with advanced nephroblastoma, as those with vena cava thrombus and lung metastases, can benefit the most from the pretreatment. Results from the SIOP studies 6 and 9 confirm these statements: the stage distribution after the pretreatment reveals more than 50% of cases staged I, the 4-year disease-free survival in pulmonary stages IV was 83%, and of 42 patients with vena cava thrombus still present at surgery, 38 are alive from 27 to 109 months.

Child↗
PubMed1998

A preliminary comparative treatment planning study for radiotherapy of age-related maculopathy.

PURPOSE: We present a comparative planning of different approaches for external radiotherapy in age-related maculopathies. MATERIALS AND METHODS: Calculated dose distributions and dose-volume histograms for (a) bilateral irradiation with 6 MV photons, (b) a single lateral-oblique beam using either photons, electrons or protons and (c) an anterior circular proton beam. RESULTS: For lateral photon or electron beams the dose to the lens is usually lower than 10% of the dose to the macula. The entrance doses for bilateral photon beams are about 50% which increase up to 100% at the orbital bone. About 5 mm of optic nerves are irradiated at the maximal dose while the optic chiasma is spared. A single photon beam gives 50% of the dose to the fellow eye. The electron beam spares the fellow eye but gives a rather inhomogeneous dose to the target volume. For a lateral proton beam, 4 mm of optic nerve receives 90% of the dose, the skin dose is at least 70% of the dose to the macula and the lens and the fellow eye are spared. An anterior proton beam gives 90% of the dose to 1 mm of optic nerve and the 50% isodose approaches the periphery of the lens. CONCLUSION: Doses to the critical structures can be dramatically diminished for all the techniques by reducing the beam size, but only if very precise set-up techniques are used. Proton beams are an attractive solution, but the impact of such a choice on the use of proton facilities and on the national health system should be carefully evaluated, as well as the risk of radio-induced secondary neoplasias.

Humans↗
PubMed1998

Treatment of non-metastatic rhabdomyosarcomas in childhood and adolescence. Results of the second study of the International Society of Paediatric Oncology: MMT84.

The second International Society of Paediatric Oncology (SIOP) study for rhabdomyosarcoma (MMT84) had several goals. The two principal aims were: (1) to improve the survival of children with rhabdomyosarcoma; and (2) to reduce the late effects from therapy by restricting the indications for surgery and/or radiotherapy after good response to initial chemotherapy. A further aim was to investigate the role of high-dose chemotherapy in young patients with parameningeal primary tumours. 186 previously untreated eligible patients entered the study. Patients with completely resected primary tumour received three courses of IVA (ifosfamide, vincristine and actinomycin D). Patients with incompletely resected tumour received six to 10 courses of IVA according to stage. Patients achieving complete remission with chemotherapy alone did not usually receive radiotherapy or undergo extensive surgery, but patients remaining in partial remission received local therapy with surgery and/or radiotherapy. Only patients over 5 years of age with parameningeal disease and patients over 12 years with tumours at any site were given systematic irradiation. Complete remission was achieved in 91% (170/186) of all patients. With a median follow-up of 8 years, the 5-year overall survival was 68% (+/- 3% standard error of the mean (SEM) and the 5-year event-free survival 53% (+/- 4% SEM). These results show an improvement over previous SIOP study (RMS75) in which survival was 52% and event-free survival was 47%. Among the 54 patients who exhibited isolated local relapse, 35% (19/54) survived in further remission longer than 2 years after retreatment, including local therapy (surgery +/- radiotherapy). Analysis of the overall burden of therapy received by all surviving children (including primary treatment and treatment for relapse if required) showed that 24% (28/116) were treated by limited surgery followed by three courses of IVA, 29% (34/116) were treated by chemotherapy alone (after initial biopsy) and 13% (15/116) received chemotherapy plus conservative local treatment (limited surgery or radiotherapy for residual disease). Only 34% (39/116) received intensive local therapy defined as radical wide field radiotherapy or radical surgery or both. Compared with the results obtained in the previous SIOP study, treatment in MMT84 was based on response to initial chemotherapy and, despite an overall reduction of the use of local therapy, significantly improved survival for patients with non-metastatic disease. This trial, also for the first time, provides evidence that retreatment after local relapse can achieve long-term second remissions.

Adolescent↗
PubMed1998

[Combined chemoradiotherapy of tumors in the child].

The high chemosensitivity of pediatric tumors along with their natural propensity for an early distant dissemination have stimulated the interest for chemo-radiation combinations in children since the mid 50s. Following the early experiments in nephroblastomas on the interaction of Actinomycin-D and radiotherapy, multiple national and international studies have been conducted since the mid 70s with considerable success: nowadays most pediatric tumors enjoy a long term survival in excess of 70%. Like their adult counterparts, these associations aim to induce an early control of the primary tumor and distant spreading (spatial cooperation) but also, more specifically in children, to limit the toxicity on normal tissues when treatment intensity can be further reduced. The association of an initial chemotherapy followed by local radiation at a dose and in a volume adapted to the response to chemotherapy along with associated prognostic factors has become widely tested in national and international studies conducted in Hodgkin's disease, Ewing's sarcoma, medulloblastomas, and brain tumors in the very young. Conversely, concomitant associations have remained limited to high-risk subgroups (parameningeal rhabdomyosarcomas for example) due to their potential hazards.

Adult↗
PubMed1998

Long-term follow up of 69 patients treated for optic pathway tumours before the chemotherapy era.

AIM: To analyse the long-term results of conservative management with radiotherapy in patients with optic pathway tumours. DESIGN: All 69 patients were symptomatic at diagnosis and most neoplasms involved the optic chiasm and hypothalamus. RESULTS: At 10 years, overall survival and progression free survival were 83% and 65.5%, respectively. After radiotherapy, vision improved in 18 patients and remained stable in 29 other patients. Cerebrovascular complications occurred in nine of 53 patients treated with radiotherapy after a median interval of two and a half years. These complications were five times more frequent in patients with neurofibromatosis type 1 (NF1). Severe intellectual disabilities were present in 18 children, most of whom underwent irradiation at a very young age (median age, 4 years). IMPLICATIONS: Radiotherapy is a valuable treatment in terms of tumour response, visual outcome, and progression free survival. However, in young children and in patients with NF1, major sequelae are encountered and new treatment strategies should be proposed for these patients.

Adolescent↗
PubMed1998

Primitive cerebral neuroectodermal tumors excluding medulloblastomas: a retrospective study of 30 cases.

We present a retrospective study of 30 cases of primitive cerebral neuroectodermal tumors (PNET), excluding medulloblastomas, referred to us postoperatively for additional therapy to evaluate prognostic factors and treatment efficiency. The histologic types were: pinealoblastomas (n = 7); ependymoblastomas (n = 2); medulloepitheliomas (n = 4), and other PNET (n = 17). The tumor was located in the supratentorial area in 24 patients and in the posterior fossa in 6 patients. Among the supratentorial tumors, 8 were metastatic. Maximal surgical resection was performed. Sixteen of 30 patients had no measurable disease after surgery and were considered as standard-risk (SR) cases, and 14 with a local residue or metastasis as high-risk (HR) cases. The objective of postsurgical treatment was to avoid radiotherapy in children below 4 years of age. It consisted of radiotherapy alone in 6 patients, chemotherapy alone in 17, and radiotherapy with chemotherapy in 7. Furthermore, high-dose chemotherapy (busulfan, thiotepa) and autologous bone marrow transplantation, performed in 6 patients, yielded a response rate of 3/6. Event-free survival (EFS) of SR patients was 37% at 3 years (95% confidence interval (CI) 14-60%) and overall survival 44% (95% CI 26-62%). Only 1 of the HR patients achieved a complete remission and all of them died early. The critical prognostic factors appear to be the completeness of initial surgical resection and absence of metastasis. These tumors have a poor prognosis. Novel strategies (high-dose chemotherapy) are needed to improve their outcome because the children concerned are very young and the effects of radiotherapy are particularly deleterious when tumors are situated in the supratentorial area.

Adolescent↗
PubMed1998

Effectiveness of protons and argon ions in initiating lipid peroxidation in low-density lipoproteins.

In this study, human low-density lipoprotein (LDL) vesicles were irradiated with 73 MeV protons (LET of 1 keV/microm) and 11.4 MeV/nucleon argon ions (LET of 1.52 MeV/pm) and the effectiveness of charged particles in initiating peroxidation of LDLs was investigated. The LDL suspension (6 g/l) was exposed to protons and to argon ions in a dose range of 24 Gy to 2.4 kGy. Irradiations were carried out at the synchrocyclotron at the CPO and at the UNILAC of the GSI. After irradiation three chemical assays were used to study the progression of peroxidation of LDLs: the formation of conjugated dienes, the formation of thiobarbituric acid-reactive substances (TBARS) and the increase in the relative electrophoretic mobility of the LDLs. The results were compared with those obtained after gamma irradiation. For protons the yields of the peroxidation products were 10 times lower than after gamma irradiation. However, for doses below 200 Gy, protons appeared to be more effective than gamma rays in damaging the protein moiety, as deduced from the observed increase in the relative electrophoretic mobility of the LDLs. The irradiation with argon ions led to a negligible formation of peroxidation products, but an increase in the relative electrophoretic mobility of the LDLs was observed. The results are indicative of a lower yield of lipid peroxidation after irradiation with high-LET particles. In contrast, protons and argon ions appear to be more effective in inducing bulk protein and phospholipid damage than gamma rays.

Argon↗
PubMed1997

Nonmetastatic intracranial germinoma: the experience of the French Society of Pediatric Oncology.

BACKGROUND: Standard treatment of localized intracranial germinoma is focal irradiation of the primary tumor (45-50 grays [Gy]) combined with craniospinal radiotherapy (RT). To decrease late effects related to extensive fields of RT, the French Society of Pediatric Oncology decided in 1990 to replace prophylactic RT with chemotherapy (CT) and to deliver focal RT at 40 Gy. METHODS: Twenty-nine patients with localized, biopsy proven germinoma were included in this study between January 1990 and December 1994. CT consisted of 2 cycles of carboplatin 600 mg/m2 on Day 1, etoposide 150 mg/m2 on Days 1-3, ifosfamide 1.8 g/m2 on Days 22-26, and etoposide 150 mg2 on Days 22-24, followed by RT delivered to the initial tumor volume (40 Gy). RESULTS: The median age of the 19 boys and 10 girls was 12.8 years; 25 patients had a unifocal tumor in the pineal (13), suprasellar (10), or thalamic (2) area, and 4 patients had a bifocal tumor. Three patients initially had complete surgery. Of the 26 patients evaluable for CT response, 11 had a small amount of tumor residue and 15 no residue; no patient underwent surgery after CT or RT. One patient recurred 3 years after diagnosis and is in his second complete remission. Twenty-eight patients are in their first complete remission after a median follow-up of 32 months (range, 7-68 months); 9 of the 28 have a small amount of tumor residue that is considered nonevolving. Overall survival at 4 years is 100% and event free survival is 93.3% (+/- 6%) after a median follow-up of 32 months. CONCLUSIONS: This treatment strategy avoids craniospinal RT and reduces focal RT, with results equivalent to those achieved with extensive RT. Thus, the authors consider it a valid treatment of nonmetastatic germinoma.

Adolescent↗
PubMed1997

Proton dosimetry comparison involving ionometry and calorimetry.

A comparison of the absorbed dose to tissue determined by various ionization chambers, Faraday cups, and an A-150 plastic calorimeter was performed in the 200 MeV proton beam of Orsay, France. Four European proton-therapy centers (Clatterbridge, UK, Louvain la Neuve, Belgium, and Nice and Orsay, France) participated in the comparison. An agreement of better than 1% was observed in the absorbed dose to A-150 measured with the different chambers of the participating groups. The mean ratio of the absorbed dose to A-150 determined with the calorimeter to that determined by the different ionization chambers in the different irradiation conditions was found to be 0.952 +/- 0.007 [1 standard deviation (SD)] according to the code of practice used by all the participating centers, based on Janni's tables of stopping powers and a value of 35.2 J/Coulomb for (W(air)/e)p. A better agreement in the mean ratio calorimeter/chamber, 0.985 +/- 0.007 (1 SD) is observed when using the proton stopping power ratio values recently published by the International Commission on Radiation Units and Measurements in Report no. 49. The mean ratio of these doses determined in accordance with the American Association of Physicists in Medicine protocol and using the new recommended stopping power tables becomes 1.002 +/- 0.007 (1 SD). Two Faraday cups agree in measured charge to within 0.8%; however, the calculation of dose is underestimated by up to 17%; compared with ion chamber measurements and seems to be very sensitive to measurement conditions, particularly to the distance to the collimator.

Calibration↗
PubMed1997

Efficacy of proton therapy in circumscribed choroidal hemangiomas associated with serious retinal detachment.

OBJECTIVE: The purpose of the study is to evaluate the efficacy and safety of proton therapy in complicated circumscribed choroidal hemangiomas. DESIGN: The study design was a retrospective review. PARTICIPANTS: Studied were 13 patients (13 eyes) who had circumscribed choroidal hemangioma associated with serous retinal detachment. Of these, four eyes previously underwent laser unsuccessfully. INTERVENTION: Proton therapy including a total dose of 30 Cobalt-Gray-Equivalent was administered to each eye. MAIN OUTCOME MEASURES: Patients were controlled for initial and final best-corrected visual acuity, slit-lamp examination, intraocular pressure, fundus examination, fluorescein angiography, and tumor thickness on B-scan ultrasonography. RESULTS: The mean follow-up period was 26 months (range, 9-48 months). Retinal reattachment was obtained in all cases after a mean period of 52 days. The tumor height decreased in all cases. Visual acuity improved to two lines or more in eight eyes (62%) and reached 20/200 or more in nine eyes (69%). No radiation complication was detected during follow-up. CONCLUSIONS: Proton radiation seems to be effective and safe in the management of choroidal hemangioma associated with serous retinal detachment. It may be useful when photocoagulation can not be performed.

Adult↗
PubMed1997

[Late effects of radiotherapy in children].

Although most pediatric tumors can be cured with lower doses of radiation than their adult counterparts, long-term radiation-induced complications and sequelae remain a major concern both in terms of frequency and intensity. Most of them have been extensively documented in the pre-chemotherapeutic era like those affecting bone, cartilage and soft tissue growth or CNS and endocrine glands. More recently the emphasis has been put on the apparent increasing incidence of reported second malignancies. This could have been favored by the chemo-radiation combinations used in most children but also has been made possible mainly by the extensive follow-up of the increasing cohort of cured children.

Adolescent↗
PubMed1997

[Initial results of proton therapy in choroidal melanoma at the d'Orsey Center for Proton Therapy; the first 464 cases].

PURPOSE: Retrospective analysis of the treatment of choroidal melanoma with protontherapy at the Centre de protonthérapie d'Orsay, France. PATIENTS AND METHODS: Between September 1991 and September 1995, 612 patients presenting with choroidal melanoma were treated by protontherapy in Orsay. Following initial management of the first 464 patients, results were analyzed, as were results after a 1-year follow-up for 305 patients, a 2-year follow-up for 169 patients, and a 3-year follow-up for 59 patients. RESULTS: Univariate analysis showed that the actuarial local recurrence rate was 5%, the 3-year survival rate 88%, and the overall metastasic rate 5%. The initial tumor volume was the most significant predictive factor for visual results and metastases. Multivariate analysis revealed that visual results were significantly related to the initial tumor volume, initial retinal detachment, and total dose delivered to the optic nerve and macula. CONCLUSION: Protontherapy of choroidal melanoma allows in most cases conservation of the eye without modification of survival. Visual results mainly depend on the site and size of the tumor.

Choroid Neoplasms↗
PubMed1996

[Quality assurance in protontherapy: a systematic approach in progress at Orsay].

The degree of accuracy and reliability required in proton therapy can only be guaranteed if a comprehensive quality assurance (QA) programme is established. Such a programme obviously has common features with general QA in radiotherapy, but some aspects are specific to the use of protons and particularly to the characteristics of each facility. A study is in progress at Orsay to convert a series of quality controls into a systematic quality assurance programme. It includes some basic steps on organisation, setting up a QA committee and QA task groups, organising meetings, policies, procedures, records, qualifications, and determining some examples of tolerance in controls. Among some critical and specific points identified in this process are the combined treatment with photons at different institutions, the specificity of a non-hospital-based and complex facility, the high degree of precision required for the patient setup, and the need to develop in-house basic tools such as the treatment planning system. The inclusion of all the patients in prospective well-defined clinical trials, the comparison with alternative techniques and the radiobiological studies are considered as fundamentals for the QA programme. Present dosimetric and radiobiological intercomparisons between protontherapy centres are considered as partial audits. A study is in progress to establish common dosimetric and clinical protocols, radiobiological models and dose and volume specifications. In spite of the differences between the existing facilities, it should also be possible to obtain international consensus on general guidelines for a QA programme in proton therapy.

Clinical Competence↗
PubMed1996

Clinical applications of proton therapy.

Proton therapy offers considerable potential advantages in the management of poorly resectable, radio-resistent tumors close to critical anatomical structures. So far over 15,000 patients have been treated worldwide with two major indications: conservative management of ocular melanomas in which local control exceeds 95% at 5 years and curative irradiation of sarcomas at the base of the skull and cervical canal, with a survival rate between 84 and 94% at 5 years. The different protocols tested currently worldwide are discussed.

Adolescent↗