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Biomedical subjects

C Kalifa

Publications and source records attributed to C Kalifa.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cross-cultural adaptation of a health status classification system in children with cancer. First results of the French adaptation of the Health Utilities Index Marks 2 and 3.

Our objective was to adapt and validate the Health Utilities Index Mark 2 (HUI 2) and HUI 3 health status classification systems self-report questionnaire in a population of children with cancer, a group of 42 children already included in a multi-centre database designed by the Group on Brain Tumors in Children of the French Society for Pediatric Oncology. Children were recruited during a routine consultation. Most of them had completed treatment. The version of the questionnaire for French adults was adapted linguistically for children. Open-ended queries by children about the comprehensiveness of the questions and very low non-response rates showed a good acceptability of the questionnaire. The main psychometric properties of the HUI 2 and HUI 3 classification systems were assessed in 3 groups of raters (child, parent, physician): construct validity was tested against the rating of the child's health state on a Likert scale and through comparison with clinical data, and internal consistency was determined through multi-trait analysis. Weighted and unweighted kappa values were used to measure the inter-rater agreement between the child's, parent's and physician's assessment of the child's health state. The convergent validity was satisfactory, with better results when the physician's assessment was used. The most affected attributes were the expected ones (i.e., cognition, pain and emotion). Disagreement was observed between the 3 raters, more often in the same direction: taking the child's assessment as the reference, the parents tended to under-estimate the health status while physicians tended to over-estimate it.

Adolescent↗
PubMed1998

Prognostic factors in pediatric spinal cord astrocytoma.

BACKGROUND: Factors that could optimize the management of pediatric spinal cord astrocytoma remain unclear and controversial. METHODS: To determine the factors that influence the prognosis of pediatric patients with spinal cord astrocytomas, a series of 73 consecutive patients at 13 French treatment centers with histologically proven spinal cord astrocytomas was retrospectively reviewed. Hospital records, operative records, and results of radiologic investigations were available in all cases. Follow-up was achieved in 94% of cases. RESULTS: Seventy percent of the patients had low grade (1 or 2) tumors. Total or subtotal surgical resection was achieved in 43%. Thirty-six patients were irradiated following surgery. Fifty-one patients were alive at a median follow-up of 54 months. Twenty-three patients relapsed. Univariate analysis showed that good outcome was correlated with male gender, age younger than 7 years, duration of presenting symptoms longer than 2 months, the presence of spinal deformities, and low grade histology, whereas sensory loss was associated with decreased survival. Multivariate analysis using the Cox proportional hazards model confirmed that histology (relative risk [RR] = 7.69) and the interval between first symptoms and diagnosis (RR = 4.93) were significant independent prognostic factors. The extent of surgery or radiotherapy had no clear influence on survival. CONCLUSIONS: This review sheds light on the prognoses of pediatric patients with spinal cord astrocytomas and may help to determine therapeutic strategies based on patients' clinical, radiologic, and pathologic features.

Adolescent↗
PubMed1998

[Neuropsychological sequelae of children treated for brain tumors: evaluation and risk factors].

The analysis of neuropsychological sequelae in children with brain tumors is a major concern in the debate for the definition of the therapeutic strategies. The authors review the recent literature in this field in the light of their own experience at the Gustave-Roussy Institute. Three main risk factors emerge from the analysis: radiation, age and surgical complications. The need for a longitudinal evaluation in these patients is emphasized in order to plan the subsequent appropriate readaptation.

Antineoplastic Agents↗
PubMed1998

An attempt to treat pediatric intracranial alphaFP and betaHCG secreting germ cell tumors with chemotherapy alone. SFOP experience with 18 cases. Société Française d'Oncologie Pédiatrique.

PURPOSE: Intracranial alphaFP and betaHCG secreting germ cell tumors have a very poor prognosis with local treatment alone. Because of efficacy of chemotherapy in extracranial forms, we tried in the SFOP (Société Française d'Oncologie Pédiatrique) to treat them with chemotherapeutic treatment exclusively. PATIENTS AND METHODS: Eighteen patients (10 alphaFP, 2 betaHCG, 6 alphaFP and betaHCG secretion) were enrolled from January 1988 to December 1992. After biological diagnosis patients were to receive 6 cycles of chemotherapy (vinblastine bleomycin - carboplatin or etoposide - carboplatin/ifosfamide - etoposide). After completion of chemotherapy, surgery was to be performed in case of residual tumor. Focal radiation was only to be delivered in case of viable residual tumor. RESULTS: All patients had biological remission and tumor reduction. Fifteen patients were treated according to the protocol by chemotherapy alone (13) or chemotherapy and radiation of residue (2). Twelve of the 13 non irradiated patients relapsed, 8 in local and/or regional area, 3 in cerebrospinal area and 1 in undeterminated area with mild elevation of markers except in one case. Six patients are alive in second complete remission after chemotherapy and/or surgery and then a consolidation treatment with radiation and/or high dose chemotherapy (5) or craniospinal radiation (1). Three patients received radiation after 2 or 3 cycles of chemotherapy as protocol violations and didn't relapse. Thus, 12 patients out of the 18 patients are alive with a median follow up of 68 months. All but 1 had focal radiation as part of treatment. No toxic death was observed. CONCLUSION: Although survival rate is noteworthy (66%), these tumors were not curable with this conventional chemotherapy alone and focal radiotherapy should be part of the treatment.

Adolescent↗
PubMed1998

Phase II study of high-dose thiotepa and hematopoietic stem cell transplantation in children with solid tumors.

From 1987 to 1995, 22 children with refractory solid tumors entered a phase II study of high-dose thiotepa (HDT) (900 mg/m2) followed by stem cell transplantation (SCT) in the Pediatrics Department of the Institut Gustave Roussy. Tumor types were rhabdomyosarcoma (eight), osteosarcoma (seven), neuroblastoma (three), Ewing's sarcoma (three) and Burkitt's lymphoma (one). Before HDT, all had been extensively treated with conventional chemotherapy, surgical resection of the primary tumor (13/22) and of metastases (6/22), and radiotherapy of the primary tumor in three patients. All had measurable disease, at the site of the primary tumor (3 patients), of the metastases (9 patients) or both (10 patients). Toxicity from the HDT was severe but acceptable. No toxicity-related death occurred. The median duration of neutropenia and thrombocytopenia was 18 days (5-37) and 30 days (7-377), respectively. Septicemia was documented in four patients. Severe diarrhea was observed in seven patients. Mild hepatic toxicity occurred 18 times. No CR and 11/22 PR were documented: osteosarcoma 4/7, rhabdomyosarcoma 4/8, Ewing's sarcoma 2/3; 1/1 Burkitt's lymphoma progressed. We conclude that at a dose of 900 mg/m2 followed by SCT support in these heavily pretreated children, the main toxicity induced by thiotepa was digestive. The response rate observed, especially in sarcoma, is particularly encouraging. Thiotepa should be further evaluated in HDC regimens either in combination with other alkylating agents or in rapidly cycled courses of HDC with SCT.

Adolescent↗
PubMed1998

Choroid plexus carcinomas in childhood: clinical features and prognostic factors.

OBJECTIVE: Choroid plexus carcinomas are rare tumors with dismal prognosis. The role of surgery has been well established, but the benefit of either chemotherapy or radiotherapy remains controversial. To determine prognostic factors and effects of different therapeutic modalities on the outcome, we have reviewed the French experience of choroid plexus carcinoma. METHODS: Twenty-two children were registered in the Société Française d'Oncologie Pédiatrique between 1984 and 1995. All these children underwent surgical resection of the primary tumor. The intent of postoperative treatment was to delay or to avoid radiation therapy. Nineteen children received postoperative treatment, with chemotherapy in 17 and radiation therapy in 2. Two responding patients underwent high-dose chemotherapy with stem cell rescue. RESULTS: The 5-year survival rate was 26%. The sole relevant prognostic factor was the extent of surgery. Patients with total or gross total resection had a 86% survival rate. Survival did not correlate with age, sex, delay between first appearance of symptoms and diagnosis, location of the primary tumor, tumor volume, or response to postoperative treatment. All but one patient with incomplete surgery had tumor recurrence within 2 to 23 months. CONCLUSION: Choroid plexus carcinoma has a very poor prognosis when surgery is incomplete. Aggressive surgical resection of the tumor is necessary for survival. Although chemotherapy gives promising responses, local control remains the main challenge, and "second look" surgery has to be considered for patients with incomplete resection.

Antineoplastic Combined Chemotherapy Protocols↗
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

Papillomas and carcinomas of the choroid plexus in children.

OBJECT: Choroid plexus tumors are rare intraventricular tumors (1% of all intracranial tumors) that occur mainly in children. The pathophysiological characteristics of associated hydrocephalus, surgical management, and oncological issues related to these tumors remain a matter of debate. To understand more about these tumors, the authors have reviewed their experience with the management of 38 children with choroid plexus tumors. METHODS: There were 25 cases of papilloma and 13 of carcinoma. The mean age of the patients at presentation was 22.5 months, and one-half of the patients were younger than 2 years of age. Hydrocephalus was present in 33 patients and poorly correlated with the size, site, and pathological characteristics of the tumor. In nine children, a ventriculoperitoneal shunt was required after tumor excision, calling into question the notion that cerebrospinal fluid oversecretion is the only cause of hydrocephalus. Complete excision was achieved in 96% of the cases of papilloma and 61.5% of the cases of carcinoma. These surgical procedures were complicated by the risks of intraoperative hemorrhage, which proved to be fatal in two cases, and postoperative brain collapse, which led to subdural fluid collections requiring subdural shunt placement in six patients. Preoperative embolization was partially successful in four cases and significantly assisted surgery. Preoperative controlled drainage of excessively dilated ventricles and intraoperative gluing of the cortical incision have been used to address the problem of postoperative brain collapse. Patients with carcinomas were treated postoperatively by chemotherapy alone (seven cases), radiotherapy (one case), or chemotherapy plus radiotherapy (one case). The overall 5-year survival rate was 100% for patients with papillomas and 40% for those with carcinomas. CONCLUSIONS: Total surgical excision is curative in cases of papillomas. For carcinomas, the most effective treatment remains total surgical excision; however, adjuvant treatment in the form of chemotherapy in patients younger than age 3 years, supplemented by radiation therapy in older children, can moderately reduce the risk of recurrence.

Adolescent↗
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

Potent therapeutic activity of irinotecan (CPT-11) and its schedule dependency in medulloblastoma xenografts in nude mice.

The anti-tumor activity of irinotecan (CPT-11), a DNA-topoisomerase 1 inhibitor, was evaluated in 5 advanced stage subcutaneous medulloblastoma xenografts in nude mice, using different schedules of administration. With a 5-day schedule, the highest i.v. dose tested (40 mg kg-1 day-1) induced complete regressions in all xenografts but 1, and delays in tumor growth always exceeded 30 days. Two xenografts, IGRM11 and IGRM33, were highly sensitive, and animals survived tumor-free beyond 120 days after treatment. CPT-11 clearly retained its anti-tumor activity at a lower dosage (27 mg kg-1 day-1). CPT-11 was significantly more active than cyclophosphamide, thiotepa and etoposide against the 3 xenografts evaluated. To study the schedule dependency of its anti-tumor activity, CPT-11 was given i.v. at the same total doses over the same period (33 days) using either a protracted or a sequential schedule in IGRM34-bearing mice. With a dose of 10 mg kg-1 day-1 given on days 0-4, days 7-11, days 21-25 and days 28-32 (total dose, 200 mg kg-1), 3 of 6 animals were tumor free on day 378. The same total dose given with a sequential schedule, i.e., 20 mg kg-1 day-1 on days 0-4 and days 28-32, failed to induce complete regression. The plasma pharmacokinetics of CPT-11 and SN-38 were studied in IGRM34-bearing animals after a single i.v. dose of 10 and 40 mg kg-1. The plasma clearance rate of CPT-11 was dose dependent. The ratio between the SN-38 and CPT-11 area under the curve in plasma was 0.4-0.65, i.e., significantly higher than that observed in humans at the maximum tolerated dose (0.01-0.05). Conversely, this ratio was 10-fold lower in tumor than in plasma. Clinical development of irinotecan is warranted in pediatric malignancies.

Animals↗
PubMed1997

Dural sinus thrombosis in children with cancer.

Dural sinus thrombosis (DST) has been reported in association with cancer in both adults and children. We describe the seven patients seen with this complication in our centre between 1981 and 1995. Diagnosis was confirmed by either cerebral CT scanning, MRI or angiography. Median age was 13 years (range 8-15). Six patients were boys. Six children were being treated for non-Hodgkin lymphoma and one for neuroblastoma. Presenting symptoms were seizures and transient neurologic deficit, often preceded by headaches. The probable cause of DST was found in two cases. Tumour localisation in the central nervous system (CNS) probably caused DST in one patient who was treated for ki 1 lymphoma. Dehydration in combination with a poor general condition seemed to be the cause of DST in the patient with neuroblastoma. In five children with stage III or IV non-Hodgkin lymphoma (three lymphoblastic lymphoma; two Burkitt's lymphoma), etiology remained unknown. In these children, DST occurred early in the course of therapy. The median interval between start of chemotherapy and onset of symptoms was 19 days (range 8-40). No child had received L-asparaginase. Prognosis was favourable, with symptoms completely disappearing without therapy within 1 to 5 days. The incidence of DST in patients with advanced stage non-Hodgkin lymphoma during induction and consolidation was calculated to be below 3%. We conclude that DST is rarely diagnosed in children with cancer. Occurrence during the initial phase of therapy for non-Hodgkin lymphoma is associated with a benign prognosis.

Adolescent↗
PubMed1997

Ifosfamide and etoposide in childhood osteosarcoma. A phase II study of the French Society of Paediatric Oncology.

The aim of this phase II study was to determine the efficacy of high-dose ifosfamide with moderate dose etoposide in childhood osteosarcoma. From January 1992 to January 1995, 27 children (15 male, 12 female) with relapsed or refractory evaluable osteosarcoma were included in a phase II study of two courses of ifosfamide 3g/m2/day and etoposide 75 mg/m2/day for 4 days. Median age was 14 years (7-19 years). All but one had received high-dose methotrexate and doxorubicin as first-line treatment. 22 patients had previously received ifosfamide. This regimen was given as first-line in 1 patient, second-line in 23 and third-line in 3. Evaluable disease was lung metastases in 21 patients, local relapse in 5 and adenopathy in 1. There were six complete responses, seven partial responses, three minor responses, six stable disease and five progressive disease (including one mixed response). Response rate was 48% (95% confidence interval, 29-67%). Duration of response was not available (10 responding patients had other treatments). Response rate was equivalent in the subgroup of 22 patients who had previously received ifosfamide (4 CR, 6 PR). Among 3 patients who received the phase II regimen as third-line chemotherapy, there was 1 PR. All but 4 patients had a well tolerated grade 4 neutropenia. Transient mild confusion or seizures were each observed once. 5 patients are alive 15-31 months after the beginning of chemotherapy. This combination of drugs at this dosage has tolerable toxicity, is efficient and deserves evaluation in phase III studies.

Adolescent↗
PubMed1997

Adult height in 24 patients treated for growth hormone deficiency and early puberty.

This study evaluates the capacity of treatment with the combination of growth hormone (GH) and gonadotropin releasing hormone (GnRH) analog to preserve the height potential of 24 patients (15 girls, 9 boys) with GH deficiency and early puberty (onset at 7.8 +/- 0.5 SE yr in girls and 9.0 +/- 0.7 yr in boys). All but 4 were given cranial irradiation. They (group 1) were compared with 17 patients of normal pubertal age treated with GH for cranial irradiation-induced GH deficiency (group 2) and with 19 girls treated with GnRH analog for idiopathic central precocious puberty (group 3). The adult heights in groups 1, 2 and 3 were -0.5 +/- 0.2, -1.3 +/- 0.2, and -0.2 +/- 0.2 SD, significantly lower (P < 0.01) in group 2. They were lower than the target heights in groups 1 and 2 (P < 0.001), and similar in group 3. They were similar to the predicted heights at the onset of therapy (combined, GH, or GnRH analog therapy), except in group 3 (adult height > predicted height, P < 0.0001) In group 1, as in group 3, the differences between adult and predicted heights (1.1 +/- 1.3 and 6.5 +/- 1.4 cm respectively) correlated positively with the difference between bone and chronological ages (P < 0.05), negatively with the predicted height (P < 0.002), and positively with the difference between the target and predicted heights (P < 0.001) at the onset of therapy. In conclusion, treatment with the combination of GH and GnRH analog in patients with GH deficiency and early puberty leads to a normal adult height. This height is similar to the predicted height at the onset of therapy but lower than the target height.

Adult↗
PubMed1997

[High-dose chemotherapy in relapse of medulloblastoma in young children].

Craniospinal 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 1990. 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 autologous bone marrow transplantation (ABMT). Their median age at diagnosis was 23 months (range: 5-71 months) 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 20 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 3 days. After recovery from aplasia, patients with a local relapse received local radiotherapy limited to posterior fossa. Among the 16 patients with measurable disease, 6 complete responses, 6 partial responses, 3 non response, were observed following HDC (response rate 75%). One patient was not evaluable. For the 20 patients, the event free survival (EFS) is 50%. Among the surviving patients, the median follow-up is 39.5 months post BMT (range: 21-92 months). Ten patients who developed a local relapse or local progression are alive with non evidence of disease (NED) without craniospinal irradiation. Among the 7 patients who developed a metastases or progression of metastases, only 1 is alive. Toxicity was high but manageable. One complication-related death occurred 1 month post BMT. 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 Combined Chemotherapy Protocols↗
PubMed1996

Tumorigenicity of cerebellar primitive neuro-ectodermal tumors in athymic mice correlates with poor prognosis in children.

The histogenesis of medulloblastoma, also described as a cerebellar primitive neuro-ectodermal tumor (PNET), remains controversial and unresolved. In addition, genetic markers which characterize cerebellar PNETs with poor prognosis in children have not been identified. Since xenografts can be valuable tools for better understanding the genetic events involved in cerebellar PNETs, small fragments of tumor samples from 17 children with newly diagnosed cerebellar PNETs were transplanted s.c. into female athymic Swiss mice. Eleven were non-metastatic and 6 were metastatic PNETs. Eight tumors (47%) were tumorigenic. Histological analysis showed 6 typical medulloblastomas, 1 PNET with melanin pigment and 1 PNET with a rhabdoid phenotype. Wide heterogeneity was observed in tumor growth, with a doubling time ranging from 8 to 81 days after the first passage. Tumorigenicity was correlated with the metastatic phenotype of the tumor (p < 0.001). All the patients but one with a tumorigenic tumor relapsed and died. The survival of patients with a non-tumorigenic PNET (67%) was significantly higher than that of patients with a tumorigenic PNET (13%) (p < 0.02). None of the xenografts or tumors from patients exhibited N-myc-gene alteration. Only one xenograft showed c-myc amplification, with an abnormal 15-kilobase fragment. None of the 17 tumors from patients showed amplification or c-myc-gene rearrangement. In conclusion, tumorigenicity of cerebellar PNETs strongly correlates both with the metastatic phenotype of the tumors and with the disease-free survival of the patients. In addition, genetic events other than c-myc-gene amplification might be involved in cerebellar PNETs with poor prognosis.

Animals↗