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Biomedical subjects

E Benhamou

Publications and source records attributed to E Benhamou.

At least 19 recordsLinked to original sources
PubMed1996

Will high dose chemotherapy followed by autologous bone marrow transplantation supplant cranio-spinal irradiation in young children treated for medulloblastoma?

UNLABELLED: Cranio-spinal irradiation is the gold standard treatment used in non metastatic medulloblastoma as prophylaxis against central nervous system (CNS) metastases. However, given the severe late effects caused by this procedure in children under 3 years of age, most pediatric oncologists are currently treating these patients with conventional chemotherapy in order to postpone or even avoid irradiation. In the French Society of Pediatric Oncology (SFOP) this attitude has been adopted since 1987. Among the patients treated without radiotherapy, 20 relapsed while on conventional chemotherapy and were entered in a study of high-dose chemotherapy (HDC) followed by ABMT. Their median age at diagnosis was 23 months (R5-71) and the relapse occurred at a median time of 6.3 months after the initiation of chemotherapy. Complete surgical removal of the local relapse was the first treatment in 4/20 patients who were not evaluable for response. Sixteen of the twenty patients had measurable disease at the primary site (9 patients), or at metastatic sites (3 patients) or both (4 patients). The conditioning regimen consisted of combination Busulfan 600 mg/m2 over 4 days and Thiotepa 900 mg/m2 over three days. After recovery from aplasia, patients with a local relapse received local radiotherapy limited to posterior fossa. RESULTS: among the 16 patients with measurable disease, 6 CR, 6 PR, 3 NR, were observed following HDC (response rate 75%). One patient was not evaluable. For the 20 patients, the EFS is 50%. Among the surviving patients, the median follow up is 31 months post BMT (R12-82). Ten patients who developed a local relapse or local progression are alive with NED without craniospinal irradiation. Among the 7 patients who developed metastases or progression of metastases, only one is alive. Toxicity was high but manageable: the median duration of granulocytopenia < 0.5 x 109/l and thrombocytopenia < 50 x 10(9)/l was 13 and 41 days respectively. Bacteremia was documented in 4 cases. Grade > 2 mucositis and diarrhea were observed in 60% of patients. One complication-related death occurred 1 month post BMT. CONCLUSION: With a 75% response rate, this HDC proved to be very efficient in relapsed medulloblastoma. A longer follow up is necessary to demonstrate whether, after a local relapse, HDC could replace craniospinal irradiation as prophylaxis against CNS metastases.

Antineoplastic Agents↗
PubMed1996

Phase I study of high-dose continuous intravenous infusion of VP-16 in combination with high-dose melphalan followed by autologous bone marrow transplantation in children with stage IV neuroblastoma.

The purpose of the study was to determine the maximum tolerated dose of continuous infusion of high-dose VP-16 in combination with high-dose melphalan (HDM) for conditioning before autologous bone marrow transplantation (ABMT). Thirteen children (median age 27 months) with stage IV neuroblastoma were treated with high-dose VP-16 and HDM followed by ABMT as consolidation treatment. All had previously received conventional chemotherapy with a mean number of six drugs. Surgery of the primary tumor had been performed in 12/13. We performed a dose-escalating study of VP-16 from 1800 mg/m2/72 h with 300 mg/m2/72 h dose increments according to toxicity. VP-16 was administered as a 72-h i.v. infusion. Melphalan (140 mg/m2/day) was administered once as an i.v. push. VP-16 pharmacokinetics were analyzed in 12 patients. Five children received 1800 mg/m2/72 h of VP-16, five received 2100 mg/m2/72 h and three, 2400 mg/m2/72 h. The mean duration of granulocytopenia (< 0.5 x 10(9)/1) was 24 days and thrombocytopenia (< 50 x 10(9)/1) was 36 days. No major infectious complications occurred. Gastrointestinal (GI) toxicity was the dose-limiting toxicity. Five severe manifestations of GI toxicity in three patients led us to consider 2400 mg/m2/72 h as the MTD. The mean VP-16 clearance rate was 17.3 ml/min/m2 with continuous infusion. A mean steady-state plasma concentration of 24.2 micrograms/ml (s.d. = 2) and 28.3 micrograms/ml (s.d. = 1.9) was achieved at the 1800 mg/ml and 2100 mg/m2 dose levels, respectively, GI toxicity is dose limiting when VP-16 at 2400 mg/m2/72 h, is associated with HDM. When given as a continuous i.v. infusion, at 2100 mg/m2/72 h, VP-16 associated with HDM is well tolerated before ABMT in young heavily pre-treated children.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Previous conventional chemotherapy is the principal risk factor for immunoglobulin deficiency during the early post-ABMT period in children.

Humoral immunodeficiency after ABMT may worsen the course of infectious complications as already described in this clinical setting; children with low Ig values of the three isotypes during the first week after ABMT experienced more severe infections during the procedure than those with normal values. The aim of the study was to establish the prevalence, the duration and the risk factors of Ig deficiency after ABMT. Serum Ig levels of 160 children treated with high-dose chemotherapy (HDCT) followed by ABMT for solid tumors were studied prospectively before HDCT and weekly from the day after transplantation until the patients were discharged from the unit, as were the associations of the following covariates: patient characteristics, previous conventional chemotherapy (CCT), conditioning regimens, marrow graft and complications following ABMT. Serum Ig deficiency for at least one isotype was already present before HDCT in half of the children and mean serum Ig values decreased after HDCT. Serum Ig deficiency was early (day 7), inconstant, heterogeneous (IgM deficiency was more frequent and lasted longer) and brief (< 1 month). Children with low Ig values before HDCT were at high risk of profound and prolonged humoral immune deficiency. Previous CCT with more than six different drugs was the main risk factor for low serum IgM values before HDCT, on day 7 and on day 21 post-HDCT. This study shows that Ig replacement therapy could be useful after ABMT provided it is given to the patients defined on the basis of these specific risk factors and serum Ig levels before HDCT.

Adolescent↗
PubMed1995

Local relapse and contralateral tumor rates in patients with breast cancer treated with conservative surgery and radiotherapy (Institut Gustave Roussy 1970-1982). IGR Breast Cancer Group.

BACKGROUND: Breast conservation is now established treatment for patients with small breast cancers. The authors reviewed a large series of patients with long term follow-up who underwent conservative treatment. Clinical and pathologic factors were analyzed to identify patients at an increased risk of relapse in the breast (local relapse) or development of a contralateral tumor. METHODS: Seven hundred fifty-seven patients with unilateral invasive breast cancer (T0-2, N0-1, M0) were treated conservatively (wide local excision and radiotherapy) at the Institut Gustave-Roussy between 1970 and 1982. The median follow-up was 9 years. The risk of local relapse or development of a contralateral tumor (as first event) was studied by univariate analysis for the main clinical, pathologic, and treatment factors. Those found to be significant were entered into a Cox proportional regression analysis. RESULTS: Fifty-one patients relapsed in the treated breast (actuarial local relapse rates at 5 and 10 years were 5% and 8%, respectively) and 34 in the contralateral breast (actuarial contralateral tumor rates at 5 and 10 years were 3% and 6%, respectively). Multivariate analysis of the risk factors for local relapse showed that only age younger than 40 years (P < 0.02) or inadequate surgical excisioin (P < 0.02) were significant. No particular risk factors for contralateral tumor development were identified. CONCLUSIONS: Overall, for most patients, the risk of local relapse or of developing a contralateral tumor was low. A small number of young patients with inadequately excised tumors are at higher risk of local relapse, need more meticulous surgery, and may merit higher dose radiotherapy.

Actuarial Analysis↗
PubMed1995

[High dose chemotherapy followed by autologous bone marrow graft in solid tumors in children: arguments for].

Arguments for the use of high-dose chemotherapy followed by autologous bone marrow transplantation in pediatric solid tumors are discussed. The dose effect relationship in pediatric oncology conventional chemotherapy is emphasized. Results of high-dose chemotherapy followed by autologous bone marrow transplantation are encouraging in metastatic neuroblastoma and Ewing's sarcoma. The probability of event free survival is increased of about 30% as compared to that of conventional treatments. This therapeutic approach could be of value in other pediatric solid tumors, particularly in some poor prognosis forms of Wilm's tumors. However, until now, the results remain preliminary. On the other hand, the role of this strategy in chemoresistant tumors, such as malignant gliomas, remains under investigation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Prevention of oral mucositis in patients treated with high-dose chemotherapy and bone marrow transplantation: a randomised controlled trial comparing two protocols of dental care.

Between February 1986 and November 1989, 166 patients who were candidates for a bone marrow transplantation entered a randomised controlled clinical trial to compare limited oral hygiene care (LIM) and intensive oral hygiene care (INT) in the prevention of mucositis. Randomisation was stratified on the initial oral status (good vs. bad IOS). Intensive oral hygiene care included an initial treatment of dental lesions and tooth and gum brushing during aplasia. Limited oral hygiene care excluded preventive dental treatment and gingival and tooth brushing. Mucositis was classified as absent, mild, moderate or severe, according to the clinical aspects of the different sites in the mouth and to two scales of pain evaluation. Of the 150 evaluable patients (75 in each group), 134 developed moderate/severe mucositis (64 in the INT group and 70 in the LIM group) (log-rank test P < 0.02). The superiority of intensive oral care was observed both in patients with and without total body irradiation (TBI) and in patients with a good or bad IOS; the observed risk of mucositis was reduced by 70% in each of these four subgroups. Duration of moderate/severe mucositis was, although not significantly, lower in the INT group (17 days, S.D. = 12) than in the LIM group (19 days, S.D. = 13). The median time of mucositis occurrence was 11 days in the INT group and 9 days in the LIM group. Contrary to a widespread belief, the percentage of documented septicaemia was not higher in patients who underwent intensive oral care. We conclude that, although statistically significant, the superiority of intensive oral hygiene care is not clinically impressive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Differential effects of tar content, type of tobacco and use of a filter on lung cancer risk in male cigarette smokers.

BACKGROUND: To date, the effect of tar exposure, the use of a filter and the type of tobacco (light or dark) on the risk of lung cancer have not been studied together. METHODS: Data from a case-control study on lung cancer were used to evaluate the specific effects of these three parameters. Cases of lung cancer and controls were interviewed in hospitals in France from 1976 to 1980. The past tar content of cigarettes distributed by the French Tobacco Monopoly was obtained. The results presented concern an exclusively male population of lifelong smokers of French cigarettes and lifelong smokers of light imported cigarettes. The population comprised 1114 cases of histologically confirmed lung cancer and 1466 hospitalized controls. RESULTS: An increase in risk was found among smokers of both dark and light cigarettes (relative risk [RR] = 2.6, 95% confidence interval [CI]:1.1-6.5) and among lifelong smokers of dark cigarettes (RR = 1.7, 95% Cl: 0.9-3.2) compared to lifelong smokers of light cigarettes. Similarly, the risk of lung cancer was higher among smokers of both non-filter and filter cigarettes (RR = 1.6, 95% Cl: 0.9-2.7) and among lifelong smokers of non-filter cigarettes (RR = 1.6, 95% Cl: 0.9-2.8) than among lifelong smokers of filter cigarettes. A borderline significant increase in risk was observed for smokers of French cigarettes compared to smokers of light imported cigarettes (RR = 2.6, 95% Cl: 0.9-7.7). No significant difference in the risk of lung cancer was observed among smokers of French cigarettes according to the proportion of years of smoking high tar cigarettes. CONCLUSION: This study tends to demonstrate a separate effect of type of tobacco, use of a filter and tar content in addition to the usual characteristics of cigarette smoking on lung cancer risk.

Case-Control Studies↗
PubMed1994

[How to measure the risk of breast cancer in a population?].

One can read that one woman in 11 in France and one in nine in the USA will get breast cancer. This high risk is the result of the irrealistic assumption that all women remain exposed to the risk of breast cancer until age 90, and ignores the risk of death before that age. It is possible to allow for the occurrence of death before age 90. We describe the method, and find a risk of getting breast cancer before age 90 of one in 14 in France. The estimation of the risk of breast cancer over limited periods of life may also be useful. We describe how these estimates can be obtained, and present some results. For instance the risk of breast cancer between age 50 and 69 is one in 29, and the risk between 50 and 79 is one in 19.

Adolescent↗
PubMed1993

Long-term effects on the thyroid of irradiation for skin angiomas in childhood.

Thyroid morphological and functional tests were carried out on 396 patients who were recalled because their thyroid gland had been exposed during hemangioma irradiation in childhood 11-43 years before (median, 22 years). The irradiations have been classified into two categories based on their duration: short duration, from a few seconds to a few minutes (90S and X rays), and long duration, from 30 min to several hours (336Ra, 192Ir, and 32P). The risk of a thyroid nodule increased significantly with the total dose received by the thyroid; it was linked to the dose delivered in the short duration (excess relative risk per Gy = 10), but not to that delivered in the long duration. The risk of a simple diffuse goiter, which also increased with the dose received by the thyroid, did not depend on the duration of the irradiation. In conclusion, this study emphasizes the role of the dose rate in the risk of thyroid nodule, the detection of which does not appear to be improved by plasma thyroid marker determination.

Child↗
PubMed1993

Chronic gastritis: prevalence in the French population. CIRIG.

Chronic gastritis (CG) which can be associated with severe complications, is a frequent phenomenon in gastroenterological practice. No data concerning the prevalence of GC are available in France. The aim of this study was to evaluate the prevalence of CG on biopsy specimens in the French population. All outpatients coming from different towns of seven French areas and undergoing an upper endoscopy on one or two randomly selected consecutive days were included in the study. A case report form was filled out and 5 biopsy specimens were taken from the fundus and antrum. Pathologists graded the specimens on the basis of Whitehead's classification. Seven hundred and forty-two patients were enrolled by 102 private gastroenterologists. Mean age was 53 years; 52% were males. Endoscopically, the gastric mucosa was abnormal in 53%. Superficial and atrophic CG was diagnosed in 53% of cases. Superficial gastritis was observed in 101 patients (14%), antral chronic atrophic gastritis (CAG) in 189 (26%) and fundic CAG in 17 (2%). Patients with CAG were significantly older than the other patients. There were more smokers and heavy alcohol drinkers in the group of CAG patients. Endoscopy and histology were in accordance in only 55.2% of the patients: most cases of CAG were not detected by endoscopy. These results are similar to other studies in European populations. The principal pattern among the various types of gastritis was CAG. The other forms were rare. Autoimmune gastritis was uncommon in this French population (4% of the CAG patients).

Adolescent↗
PubMed1992

Risk factors for hepatic veno-occlusive disease after high-dose busulfan-containing regimens followed by autologous bone marrow transplantation: a study in 136 children.

Risk factors for hepatic veno-occlusive disease (HVOD) were analysed in a population of 136 autografted children who received high-dose busulfan (BU) as part of a conditioning regimen. HVOD was diagnosed according to McDonald's clinical criteria. The incidence of HVOD was particularly high in this series (22%) compared with series with other conditioning regimens but the outcome was favorable in 26 patients (87%). Four deaths occurred (13%), one of which was HVOD related. The clinical presentation of HVOD was similar to that described in previous reports. Although statistical analysis failed to demonstrate any factors predictive of outcome, it did identify risk factors for the occurrence of HVOD: these were (1) a total dose of BU exceeding the standard 16 mg/kg dose; (2) the use of three as opposed to two alkylating agents; (3) the sequence of BU administration when given in the conditioning regimen containing three alkylating agents; and (4) concomitant ketoconazole therapy.

Adolescent↗
PubMed1991

Computed tomographic density of metastatic lymph nodes as a treatment-related prognostic factor in advanced head and neck cancer.

Pretherapeutic identification of patients likely to benefit from neoadjuvant chemotherapy for head and neck epidermoid cancer is of interest. We retrospectively analyzed the pretherapeutic computed tomographic (CT) scans of lymph nodes of 70 patients with head and neck cancer. All 70 patients were clinically classified as having stage IV disease. The purpose of our analysis was to compare the prognostic value of CT node density with that of the following factors: age, T and N categories, Eastern Cooperative Oncology Group performance status, tumor site, histopathologic type of disease [squamous cell carcinoma (SCC) or undifferentiated carcinoma of nasopharyngeal type (UNCT)], and type of local-regional treatment. A simple two-grade nodal density grading system was devised. The density of normal adjacent muscle was chosen as the density standard. A node was classified grade 1 if less than 33% of the node consisted of hypodense zones. A node was classified grade 2 if more than 33% of the node consisted of hypodense zones. Patients with grade 1 nodes had a complete response rate of 68% (21/31) compared with 8% (3/39) for those with grade 2 nodes (P less than .0001). The only other factor associated with complete node response was UCNT (P less than .03). However, node density remained the significant prognostic factor after adjustment for histopathologic type. Follow-up ranged from 16 to 44 months, with a median of 29 months. Patients with grade 1 nodes had a median survival time of 32 months versus 13 months for those with grade 2 nodes (P less than .01). A prospective study should validate the prognostic value of CT node density and its possible use in determining optimal multimodal therapy for advanced head and neck cancers.

Adolescent↗
PubMed1991

Long-term effects in skin and thyroid after radiotherapy for skin angiomas: a French retrospective cohort study.

To evaluate the long-term effects of skin angioma irradiation, a recall programme was established which included the systematic recalculation of the radiation dose to the skin and the thyroid. 22% of the 6229 patients contacted had a dermatological examination which revealed cutaneous dystrophy in 81% of the 1137 exposed angiomas and in 39% of the 208 unexposed angiomas. The risk of dystrophy (telangiectasia, hypopigmentation, superficial and subcutaneous atrophy) was 12.1 higher (P less than 0.0001) among patients who had received a surface skin dose above 30 Gy than among those who had received a dose of 10 Gy or less. The relative risk for each dystrophy component increased significantly (P less than 0.001) with surface skin dose. Furthermore, 14 basal cell carcinomas (BCC) were observed in 12 patients from the exposed group for all quantities of radiation, with a mean latency period of 22 years. No BCC was observed for a surface skin dose below 10 Gy. Thyroid testing was done on a subgroup of 431 patients whose thyroid gland had been particularly exposed during angioma irradiation. After recalculation, the dose delivered to the gland was below 1 Gy in 98% of patients. Only 13 thyroid nodules were discovered (1 hot and 12 cold). 1 patient with a cold nodule had a malignant thyroid tumour 21 years after irradiation. He belonged to the group of 7 patients who had received a thyroid dose above 1 Gy. Although no morphological abnormality was found in 98% of the tested patients, most (92%) had a thyroid iodine content below 15 mg (the standard French value), while a raised serum thyroglobulin level (greater than 30 ng/ml) was observed in 17%. This might confer a higher risk of subsequently developing thyroid nodules.

Adolescent↗
PubMed1991

Trends in cancer mortality, France 1950-1985.

Trends in mortality for main cancer sites in France between 1950 and 1985 are presented by sex. In the population aged 35-65, where long term trends can most reliably be assessed, an overall 1.1% mean annual increase is observed for males and a 0.6% mean annual decrease is observed for females. For males, this increase in total cancer mortality is mostly due to the sites associated with tobacco and alcohol. The important increase for lung cancer, and lesser increases for bladder, pancreas and kidney cancers are related to the increase in tobacco consumption from 4.7 g per adult per day in 1950 to 6.3 g in 1976. For cancer sites associated with alcohol and tobacco, namely oesophagus, pharynx, larynx, tongue and mouth, mortality is increasing similarly for males and for females, although these cancers are much less frequent among females. For females, the overall moderate decrease is mostly due to the decrease in cervix and stomach cancer mortality, uncompensated by the observed increase in breast cancer; there is no marked increase in lung cancer mortality for women, contrary to what is observed in other Western countries.

Adult↗