Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome--the French pediatric experience

BACKGROUND: The objective of this report was to estimate long-term outcome and prognostic factors in children and adolescents who presented with metastatic osteosarcoma at diagnosis. Patients were treated in six French pediatric oncology centers with surgery and multiagent chemotherapy, mainly with high-dose methotrexate. Their medical records were reviewed retrospectively. METHODS: The medical records of patients who were treated for metastatic osteosarcoma from 1987 to 2000 were reviewed. Patients were treated with the chemotherapy regimens recommended for nonmetastatic disease in children (the French Society of Pediatric Oncology OS 87 and OS 94 protocols) or, in a few patients, with other chemotherapy regimens. Surgical excision of the primary tumor and, when possible, of all metastatic sites was performed based on a personalized assessment of each patient's situation. RESULTS: Seventy-eight patients age < 20 years were treated. Forty-six patients (59%) had only 1 metastatic site (35 to the lungs and 11 to bone). Twenty-eight patients (36%) achieved a complete remission after combination chemotherapy and surgery. The event-free survival and overall survival rates at 5 years were 14% and 19%, respectively. To date, 14 patients (18%) have remained alive with a median follow-up of 112 months. Pretreatment features associated with a shorter event-free survival in the multivariate analysis were metastasis to at least two organs and high alkaline phosphatase level. Patients with at least 1 of these poor prognostic factors had a 2.6% event-free survival rate at 5 years despite treatment. CONCLUSIONS: The survival of patients with metastatic osteosarcoma were treated with conventional chemotherapy and surgery remained very poor. Patients should be classified into different prognostic groups and treated accordingly. New therapeutic approaches are warranted to improve the prognosis for patients with the most severe disease.     

Therapeutic schedules influence the pattern of intellectual decline after irradiation of posterior fossa tumors

BACKGROUND: To evaluate intellectual decline in children with posterior fossa (PF) tumors treated with different therapeutic protocols. PROCEDURE: Forty children had a complete neuropsychological evaluation prospectively twice, at least 6 months year (y) after the end of their treatment. Patients were classified into four groups according to treatment schedules: Group 1 (n = 7) PF radiotherapy (PFRT) alone at 50 Gy; Group 2 (n = 13) reduced-dose cranio-spinal irradiation (CSI) at 25 Gy with a PF boost; Group 3 (n = 9) standard CSI at 35 Gy and a PF boost; and Group 4 (n = 11) high-dose chemotherapy with stem cell support followed by PFRT at 50 Gy. RESULTS: At the first evaluation (mean interval since diagnosis 3.7 y), the mean Full-Scale Intellectual Quotient (FSIQ) was 80 (SD = 19). Only patients in Group 1 had a normal mean IQ score of 92 (SD = 14). At the second evaluation (mean interval since diagnosis 6.3 y), the mean FSIQ scores were significantly lower with a mean difference of 2.4 points, i.e., a yearly decline of one point. The magnitude of the FSIQ decline was positively correlated with the first IQ score (P = 0.0001) and inversely correlated with age at diagnosis (P = 0.0005). A FSIQ decline was observed in all treatment groups except Group 1 (P = 0.005). The differences in FSIQ observed initially between the four treatment groups persisted at the second evaluation. CONCLUSIONS: This study shows that FSIQ continues to decline more than 4 years after the diagnosis but this yearly decline seems to decrease with time from diagnosis. Therapeutic schedules influence the magnitude of this decline. Long-term follow-up into adulthood is necessary to effectively adapt patient rehabilitation.     

Sedation in children undergoing CT scan or MRI: effect of time-course and tolerance of rectal chloral hydrate

The aim of this paper was to describe the time-course of the sedative effect of rectal chloral hydrate (75 mg/kg) in children undergoing CT scan or MRI. Twenty children (2.13 +/- 1.43 years old) were administered 75 mg/kg chloral hydrate rectally (chloralhydrat-rectiole rectal formulation, Dr Mann-Pharma Lab, Berlin, Germany), before a CT scan or an NMR imaging. Sedation was measured at specific times using a sedation score of 1-6. Patients were continuously monitored for respiratory and heart rate, systolic and diastolic blood pressures, and oxygen saturation. About 82.35 and 94.11% of the patients had a score of sedation > or = 3 within 15 and 30 min, respectively. The mean time to effective sedation (score > or = 3) was of 0.30 +/- 0.14 h (median time, 0.25 h). The mean duration of effective sedation (score > or = 3) was 1.29 +/- 1.05 h (median duration, 0.75 h). A total of 93.1% of the X-ray sections were obtained without artifact and sedation was considered by radiologists to be efficient for 83.3% of the procedures. This sedation procedure appeared efficient and safe during ambulatory CT scan and NMR imaging. The long-term effect of chloral hydrate, however, remains to be evaluated.     

Proton beam therapy in the management of central nervous system tumors in childhood: the preliminary experience of the Centre de Protonthérapie d'Orsay

BACKGROUND: The purpose of the study was to evaluate clinical results and complications of a combination of proton and photon irradiation administered to 17 children with selected central nervous system (CNS) tumors. PROCEDURE: Between July 1994 and September 2000, 17 children, aged from 5 to 17 years (median: 12 years) with intracranial benign (6 cases) or malignant (11 cases) tumors, were treated with photons (median dose: 40 Gy; 24-54) and protons (median dose: 20 CGE; 9-31) at the Centre de Protonthérapie d'Orsay (CPO). RESULTS: Mean follow-up was 27 months (3-81). Two patients recurred locally (one marginal and one in situ). Fifteen patients are alive and doing well. Overall, 12, 24, and 36-month local control rate was 92 +/- 8% and, 12, 24, and 36-month overall survival rates were 93 +/- 6%, 83 +/- 11%, and 83 +/- 11%, respectively. Clinical initial symptoms remained stable or subsided in all patients. Early toxicities were in the expected range. CONCLUSIONS: With a mean 27 months follow-up, protontherapy was well tolerated for doses upto 69 CGE and with an excellent local control rate.     

Supratentorial embryonal tumors in children under 5 years of age: an SFOP study of treatment with postoperative chemotherapy alone

BACKGROUND: To determine the effectiveness of multiagent chemotherapy as sole post-operative treatment of supratentorial central nervous system (CNS) embryonal tumors in young children. PROCEDURE: The data of 25 children under 5 years of age diagnosed with supratentorial embryonal tumors (17 primitive neuroectodermal tumors, four pinealoblastomas, and four medulloepitheliomas) treated exclusively by postoperative chemotherapy (CT) between 1990 and 1997 were reviewed. RESULTS: Fifteen tumors were hemispheric and 10 were deeply seated. Four children presented with disseminated leptomeningeal disease. Total resection was performed in nine patients, subtotal in 9, partial in 3, and a diagnostic biopsy only in 2. Two children did not undergo surgery. Twenty-four children relapsed with a median time of 5.5 months. The median overall survival was 12 months, and the 2-, and 5- year survivals were 30 and 14%, respectively. The 2- year disease-free survival was 4%. There was a significantly worse prognosis in patients undergoing incomplete resection and in the group with deeply situated tumors. Four relapses were treated by second surgery followed by high-dose chemotherapy and radiotherapy. Two of them remain in CR2, and all these children are free of late sequelae. CONCLUSIONS: CT alone failed to maintain disease-free survival in most of the children, although, disease progression was delayed to some extent. Children under 5 years with supratentorial embryonal tumors should undergo total surgical resection if possible.     

Radiological aspects of the small bowel after extensive resection in children

The authors present radiological aspects of small bowel after extensive resection. They describe the main phenomena related to compensatory hypertrophy: dilatation of the loops, muscosal fold thickening and motor disturbances. The main complications demonstrated by the radiological examination are presented; gallstones, non-functionning anastomosis, bacterial overgrowth.     

Endocrine aspects and tumoral markers in intracranial germinoma: an attempt to delineate the diagnostic procedure in 14 patients

This work outlines the endocrine abnormalities associated with intracranial germinomas (14 patients before treatment). Diabetes insipidus of various intensity was present in all cases. Adipsia is often present as well. In six patients, the first neuroradiologic examination after the onset of DI was normal. Growth hormone secretion was deficient in 11 of 13 patients. Abnormalities of TSH response to TRH were present in nine of ten (four insufficient and five exaggerated responses to TRH). Anterior pituitary dysfunction could not be predicted by the tumor site as determined by radiologic criteria. Tumoral markers have also been studied. Elevated plasma tumoral markers were found in four patients of 11 studied. Tumoral germinoma cells were present in CSF in five patients of ten, in one of them before radiologic confirmation. Pertinent endocrine evaluation and search for tumoral markers was of great value in systematic follow-up of patients with central diabetes insipidus, and could lead to early diagnosis and treatment of the tumor.     

La protonthérapie en radiothérapie pédiatrique

Pediatric tumors still represent a formidable challenge despite the considerable therapeutical advances that have been reported for the past 30 years. This is largely related with the untowards side-effects of local therapy that are still acknowledged as the “price for cure”. In this setting, Proton therapy a sophisticated radiotherapeutical modality seems to represent a real breakthrough due to its unique ability to spare close and distant normal organs compared with modern photons techniques. We summarize in this paper current clinical and dosimetrical evidences including an update of the Orsay series on 108 children.     

Brain tumours under the age of three. The price of survival

Summary Between 1975 and 1989, 98 children with brain tumours under the age of three at time of diagnosis were entered into a retrospective study. Twenty of them are alive and free of tumour more than five years after treatment and were evaluated in this study. Thirteen tumour localizations were infratentorial and 7 were supratentorial. A histological examination was performed in 15 patients: 5 ependymomas, 6 medulloblastomas and 4 astrocytomas were identified. Fifteen patients underwent surgical removal of tumour, all but one received radiotherapy and 8 were given chemotherapy.Only two children have not late effects. Analysis of long-term sequelae in survivors showed central endocrinopathies in 14 (70%), a neurological handicap in 13 (65%) and impaired cognitive functions in 17 (85%). Irradiation was clearly responsible for mental sequelae in 7 patients and endocrinopathies in 6 patients. The other possible causes are tumour injury, hydrocephalus or surgery. The risks incurred with radiotherapy and advances in infant brain tumour therapy are discussed.