RESUMO
This chapter presents guidelines for the follow-up of children with brain tumors, whether benign or malignant, in their transition to adulthood. The consequences of their disease and its treatment overlap greatly. The complications and long-term follow-up are detailed based on the specialists involved.
Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Procedimentos Neurocirúrgicos , Adolescente , Adulto , Neoplasias Encefálicas/psicologia , Sistema Cardiovascular/crescimento & desenvolvimento , Sistema Cardiovascular/fisiopatologia , Criança , Glândulas Endócrinas/patologia , Glândulas Endócrinas/fisiopatologia , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Desenvolvimento Maxilofacial/fisiologia , Neoplasias Induzidas por Radiação/patologia , Neoplasias Induzidas por Radiação/cirurgia , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/fisiopatologia , Qualidade de Vida , Radiocirurgia/efeitos adversos , Sistema Respiratório/crescimento & desenvolvimento , Sistema Respiratório/fisiopatologia , Adulto JovemRESUMO
UNLABELLED: School achievement of children with brain tumors is hampered by progressive neurologic and cognitive sequelae. To help the children and their family, we have created in 1997 a multidisciplinary consultation together with Necker's hospital. MATERIAL AND METHODS: The study describes the organization of the consultation and analyses the files of 69 children seen between September 2001 and June 2002. RESULTS AND CONCLUSION: The authors conclude that this consultation is an irreplaceable mean to coordinate the complex rehabilitation process of a child treated for a brain tumor.
Assuntos
Neoplasias Encefálicas/epidemiologia , Equipe de Assistência ao Paciente , Encaminhamento e Consulta , Adolescente , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Feminino , França/epidemiologia , Humanos , Lactente , Masculino , Testes NeuropsicológicosRESUMO
OBJECTIVE: The primary objective of this study was to decrease the late effects of prophylactic radiation without reducing survival in standard-risk childhood medulloblastoma. PATIENTS AND METHODS: Inclusion criteria were as follows: children between the ages of 3 and 18 years with total or subtotal tumor resection, no metastasis, and negative postoperative lumbar puncture CSF cytology. Two courses of eight drugs in 1 day followed by two courses of etoposide plus carboplatin (500 and 800 mg/m(2) per course, respectively) were administered after surgery. Radiation therapy had to begin 90 days after surgery. Delivered doses were 55 Gy to the posterior fossa and 25 Gy to the brain and spinal canal. RESULTS: Between November 1991 and June 1998, 136 patients (median age, 8 years; median follow-up, 6.5 years) were included. The overall survival rate and 5-year recurrence-free survival rate were 73.8% +/- 7.6% and 64.8% +/- 8.1%, respectively. Radiologic review showed that 4% of patients were wrongly included. Review of radiotherapy technical files demonstrated a correlation between the presence of a major protocol deviation and treatment failure. The 5-year recurrence-free survival rate of patients included in this study with all optimal quality controls of histology, radiology, and radiotherapy was 71.8% +/- 10.5%. In terms of sequelae, 31% of patients required growth hormone replacement therapy and 25% required special schooling. CONCLUSION: Reduced-dose craniospinal radiation therapy can be proposed in standard-risk medulloblastoma provided staging and radiation therapy are performed under optimal conditions.
Assuntos
Neoplasias Cerebelares/radioterapia , Meduloblastoma/radioterapia , Adolescente , Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Encéfalo/efeitos da radiação , Carboplatina/administração & dosagem , Neoplasias Cerebelares/mortalidade , Quimioterapia Adjuvante , Criança , Pré-Escolar , Terapia Combinada , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Meduloblastoma/mortalidade , Dosagem Radioterapêutica , Canal Medular/efeitos da radiação , Taxa de SobrevidaRESUMO
The aim of this study was to evaluate a chemotherapy strategy that avoids radiotherapy in first-line treatment of young children with high-grade glioma. A total of 21 children under 5 years of age received the BBSFOP protocol, comprising seven cycles of three drug pairs (carboplatin/procarbazine, cisplatin/etoposide and vincristine/cyclophosphamide) administered over a 16 month period. Radiotherapy was performed in case of recurrence/progression. Median age at diagnosis was 23 months. Histology was classified as World Health Organisation (WHO) grade III in 13 and grade IV in 8. Of the 13 children with a residual tumour, chemotherapy induced 2 partial responses (PR), 1 minor response (MR) and 1 stable disease (SD) with no recurrent disease. Five-year progression-free survival was 35% and 5-year overall survival was 59%, with a median follow-up of 5.2 years. At the last update, 12 children were alive (10 without radiotherapy). In conclusion, this study shows that an adjuvant chemotherapy first approach is safe and allows radiotherapy to be avoided in selected children.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Pré-Escolar , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Lactente , Masculino , Neoplasia Residual , Procarbazina/administração & dosagem , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
AIM: Improvement of EFS of children older than 3 years with high risk medulloblastoma. METHODS: Between 1993 and 1999, 115 patients (3-18 years, mean 8 years) with high risk medulloblastoma were included. After surgery treatment consisted of chemotherapy ('8in1' and etoposide/carboplatin) before and after craniospinal radiotherapy. RESULTS: Patients were staged using Chang-criteria (PF residue only, M1 and M2/M3) by local investigator as well as by central review panel (82.4% concordance). Chemotherapy was well tolerated without major delays in radiotherapy. With a mean follow up of 81 months (9-119), 5-year EFS was 49.8% and OS 60.1%. In detail according to subgroups EFS was 68.8% for PF residue only, 58.8% for M1 disease and 43.1% for M2/M3. CONCLUSION: M1 patients are legitimate high risk patients. Survival rates are still very low for high risk medulloblastoma patients and future trials should therefore focus on more intensive (chemotherapy/radiotherapy) treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cerebelares , Meduloblastoma , Adolescente , Carboplatina/administração & dosagem , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/radioterapia , Neoplasias Cerebelares/cirurgia , Criança , Pré-Escolar , Terapia Combinada/métodos , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Humanos , Meduloblastoma/tratamento farmacológico , Meduloblastoma/radioterapia , Meduloblastoma/cirurgia , Cuidados Pós-Operatórios , Estudos Prospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Twenty-four poor-risk patients with acute lymphoblastic leukemia received a modified regimen of carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) followed by autologous bone marrow transplantation (ABMT). Nineteen patients were in second or subsequent complete remission (CR) when treated with this regimen; 3 died early, 2 died of pneumonia in CR, 11 relapsed within 3 months (median), and 3 remain in CR with no maintenance therapy 14-24 months after ABMT. Of the 5 patients with measurable disease who were treated, 3 had CR and 1 remains in CR without maintenance therapy more than 28 months after ABMT. The toxicity of this regimen was acceptable, but late pulmonary toxic effects remain a major concern. These results are poor in terms of efficacy, and new effective methods of eradicating acute lymphoblastic leukemia in patients with poor prognosis should be investigated.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Leucemia Linfoide/terapia , Adolescente , Adulto , Carmustina/efeitos adversos , Carmustina/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Feminino , Humanos , Masculino , Recidiva , Risco , Tioguanina/efeitos adversos , Tioguanina/uso terapêutico , Transplante AutólogoRESUMO
Undifferentiated carcinoma of nasopharyngeal type (UCNT) is a geographically endemic, Epstein-Barr virus-related carcinoma of epidermoid origin with reported 5-year survival rates of 15%-40% when treated with radiotherapy alone. Although UCNT can be well controlled locally by radiation therapy, in advanced nodal stage N3 [International Union Against Cancer-American Joint Committee on Cancer (UICC-AJCC, 1987)] the survival rate is below 20%, primarily because of metastatic spread in 80% of the fatalities. We report a pilot study of 41 patients with nonmetastatic, locoregionally advanced disease (85% of the patients had a nodal status greater than or equal to N2C-N3; 43% had T4 primaries), during which we used a combination of 100 mg of cisplatin/m2 on day 1, 15 mg of bleomycin by intravenous push and 12 mg/m2 by continuous infusion on days 1-5, and 70 mg of epirubicin/m2 on day 1 every 21 days for three cycles before definitive radiation therapy with 70 Gy for 7 weeks. Twenty-seven of 41 patients (66%; 95% confidence interval = 52.5%-80.5%) achieved a clinical complete response, and 40 of 41 (98%) had a major objective response after chemotherapy. Two deaths were treatment related, but side effects were moderate, and the overall treatment sequence was feasible. At the end of radiation therapy, all 39 assessable patients were in complete response, with a median follow-up of 21+ months (greater than 10-greater than 31); 33 (80%) patients had no evidence of disease. We believe that such a complete response rate in a high-volume disease with the use of combined modality treatment indicates a therapeutic gain in UCNT. Researchers performing a multicenter international controlled trial will test this hypothesis and compare local control, disease-free, and overall survival of the therapeutic sequence presented here with radiotherapy alone.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Carcinoma de Células Escamosas/radioterapia , Criança , Cisplatino/administração & dosagem , Esquema de Medicação , Epirubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/radioterapia , Projetos Piloto , Análise de SobrevidaRESUMO
Busulfan is known to be neurotoxic in animals and humans, but its acute neurotoxicity remains poorly characterized in children. We report here a retrospective study of 123 children (median age, 6.5 years) receiving high-dose busulfan in combined chemotherapy before bone marrow transplantation for malignant solid tumors, brain tumors excluded. Busulfan was given p.o., every 6 hours for 16 doses over 4 days. Two total doses were consecutively used: 16 mg/kg, then 600 mg/m2. The dose calculation on the basis of body surface area results in higher doses in young children than in older patients (16 to 28 mg/kg). Ninety-six patients were not given anticonvulsive prophylaxis; 7 (7.5%) developed seizures during the 4 days of the busulfan course or within 24 h after the last dosing. When the total busulfan dose was taken into account, there was a significant difference in terms of neurotoxicity incidence among patients under 16 mg/kg (1 of 57, 1.7%) and patients under 600 mg/m2 (6 of 39, 15.4%) (P less than 0.02). Twenty-seven patients were given a 600-mg/m2 busulfan total dose with continuous i.v. infusion of clonazepam; none had any neurological symptoms. Busulfan levels were measured by a gas chromatographic-mass spectrometry assay in the plasma and cerebrospinal fluid of 9 children without central nervous system disease under 600 mg/m2 busulfan with clonazepam:busulfan cerebrospinal fluid:plasma ratio was 1.39. This was significantly different (P less than 0.02) from the cerebrospinal fluid:plasma ratio previously defined in children receiving a 16-mg/kg total dose of busulfan. This study shows that busulfan neurotoxicity is dose-dependent in children and efficiently prevented by clonazepam. A busulfan dose calculated on the basis of body surface area, resulting in higher doses in young children, was followed by increased neurotoxicity, close to neurotoxicity incidence observed in adults. Since plasma pharmacokinetic studies showed a faster busulfan clearance in children than in adults, this new dose may approximate more closely the adult systemic exposure obtained after the usual 16-mg/kg total dose, with potential inferences in terms of anticancer or myeloablative effects. The busulfan dose in children and infants undergoing bone marrow transplantation should be reconsidered on the basis of pharmacokinetic studies.
Assuntos
Bussulfano/toxicidade , Convulsões/induzido quimicamente , Adolescente , Bussulfano/administração & dosagem , Bussulfano/sangue , Bussulfano/líquido cefalorraquidiano , Bussulfano/uso terapêutico , Criança , Pré-Escolar , Avaliação de Medicamentos , Humanos , Lactente , Neoplasias/tratamento farmacológico , Convulsões/sangue , Convulsões/líquido cefalorraquidianoRESUMO
Twenty children with advanced, nonleukemic malignancies entered a phase II study of high-dose busulfan-cyclophosphamide followed by bone marrow transplantation (BMT). All had disease refractory to conventional and/or high-dose chemotherapy (HDC). There were ten neuroblastoma patients, six non-Hodgkin's lymphoma, three Ewing's sarcoma, and one rhabdomyosarcoma. Eight had primarily resistant disease, ten were in second progressive relapse, and two in third progressive relapse. One patient was not evaluable for response. Among the 19 evaluable patients the responses observed were complete response (CR), seven; partial response (PR), three; objective effect, five; and failure, four. However, survival was poor: 15 patients died, two are alive with disease, and three are alive with no evidence of disease (NED) at 8+, 11+, 14+ months post-BMT. Toxicity was high but considered as acceptable, taking into account the terminal state of these patients. Seven treatment-related deaths were observed. This combination therapy proved to be highly effective, with a response rate of 50%, and its value for eradication of residual disease in less advanced patients should be investigated.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Neoplasias/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/administração & dosagem , Avaliação de Medicamentos , Doenças Hematológicas/induzido quimicamente , Humanos , Lactente , Pneumopatias/induzido quimicamente , Neoplasias/mortalidade , Neoplasias/patologia , Convulsões/induzido quimicamente , Sepse/induzido quimicamente , Dermatopatias/induzido quimicamenteRESUMO
PURPOSE AND METHODS: Between January 1981 and June 1993, 137 children and adolescents were each treated at the Institut Gustave Roussy for an initially nonmetastatic osteosarcoma of the extremities. We report the retrospective analysis of 42 cases of recurrence that occurred in this population. RESULTS: The median interval between the diagnosis of the primary osteosarcoma and the first recurrence was 21 months (range, 5 to 60). The site of the first recurrence was limited to the lung in 20 patients, the bone in seven patients, was local in six patients, and was confined to soft tissue in one patient. In eight patients, the first recurrence affected multiple sites. Subsequent recurrences often involved unusual or multiple sites. Management of recurrences included surgery and/or various regimens of second-line chemotherapy, and in one case involved high-dose chemotherapy followed by autologous bone marrow transplantation. Overall survival and event-free survival were, respectively, 36% and 27% at 36 months. At present, 13 patients are alive without evidence of disease. Response of the primary tumor to preoperative chemotherapy, the time between the diagnosis and the first recurrence, and the number of metastatic lesions did not correlate with survival. The survival rate is better in patients with a local or a pulmonary first recurrence. CONCLUSION: The most important prognostic indicator at first recurrence seems to be the possible complete resection of disease. Patients not amenable to surgery and patients with a second or a third recurrence have a poor prognosis. The potential benefit of more aggressive treatments such as high-dose chemotherapy and autologous bone marrow transplantation should be investigated for these patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Osteossarcoma/tratamento farmacológico , Adolescente , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Extremidades , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Leucovorina/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Recidiva Local de Neoplasia/terapia , Osteossarcoma/mortalidade , Osteossarcoma/secundário , Osteossarcoma/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vindesina/administração & dosagemRESUMO
Sixteen children with non-Hodgkin's lymphoma (NHL) who had relapsed were treated with high-dose chemotherapy with BCNU, cyclophosphamide, cytarabine, 6-thioguanine (high-dose chemotherapy [HDC]) and autologous bone marrow transplantation (ABMT). Eleven complete responses were obtained and five patients remain in prolonged complete unmaintained remission 77+ to 152+ weeks after treatment. The best results were obtained in patients with CNS involvement and when this regimen was used after complete remission or partial response was obtained by other means. The results appear to be better in B-cell than in T-cell lymphomas, but the numbers are too small for statistical assessment. The use of ABMT rendered the pancytopenic period short and safe, despite the use of drug doses higher than those previously described for this HDC. The frequency of interstitial pneumonitis, possibly related to pulmonary toxicity of chemotherapy, remains a major concern. These results show that this regimen can help to cure some patients but its toxicity prohibits its use in primary therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Carmustina/administração & dosagem , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Feminino , Humanos , Masculino , Neoplasias do Sistema Nervoso/tratamento farmacológico , Recidiva , Tioguanina/administração & dosagemRESUMO
Undifferentiated nasopharyngeal carcinoma (UCNT) is known to be radiosensitive and chemosensitive, but the latter has never been studied prospectively with phase II methodology. After an intensive work-up, 49 patients with recurrent (REC) and/or metastatic (MTS) UCNT were treated with three monthly cycles of cisplatin (CDDP) 100 mg/m2 day 1; bleomycin 15 mg intravenously (IV) day 1, and 16 mg/m2/d continuous infusion (CI) days 1 to 5; and fluorouracil (5FU) 650 mg/m2/d CI days 1 to 5 (PBF). Of the 49 patients, 33 were North African. The sex ratio was three males:one female, and the median World Health Organization (WHO) performance status was 1.6. In the 48 patients assessable for response, we observed nine (19%) complete responses (CRs) and 29 (60%) partial responses (PRs) (60%), for a 79% overall response rate (95% confidence interval, 68% to 90%) in the assessable group and a 78% global rate. There were eight CRs (24%) observed in the group without previous chemotherapy (33 patients) compared with one CR in the chemotherapy pretreated group (16 patients). Four patients are still alive without evidence of disease after 52+, 54+, 58+, and 58+ months, respectively. All of them had less than three bone MTS sites, and received radiation therapy in these sites. The results confirm the chemosensitivity of UCNT, and the observation of unmaintained long-term responders makes curability a possible consideration.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/secundário , Neoplasias Nasofaríngeas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Terapia Combinada , Avaliação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/radioterapiaRESUMO
Two hundred ninety-one courses of high-dose chemotherapy (HDC) with bone marrow transplantation (BMT) in children with malignancies were reviewed in order to assess the incidence, clinical course, outcome, and predisposing factors of hemorrhagic cystitis. Hemorrhagic cystitis occurred in 19 HDC courses (6.5%). Three patients had grade I hematuria linked to thrombopenia, nine had grade II hematuria despite platelet levels greater than 50 x 10(9)/L, and seven had grade III hematuria with clots and bladder obstruction. Severe complications occurred in grade III patients, but no deaths were directly linked to the cystitis. Fourteen patients recovered within two to 120 days of onset. The other patients died before the cystitis resolved, either of a relapse of the malignancy or of infection. Predisposing factors were age (increased incidence in older children), conditioning regimen containing cyclophosphamide, previous vesical irradiation, association with prolonged aplasia, and hepatic complications. The role of busulfan was also probable. No viral agent was found.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Medula Óssea , Cistite/etiologia , Hematúria/etiologia , Neoplasias/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Cistite/epidemiologia , Feminino , Hematúria/epidemiologia , Humanos , Lactente , Masculino , PrognósticoRESUMO
Among 62 children over 1 year of age at diagnosis, who were treated for stage IV neuroblastoma, 33 entered complete remission (CR) or good partial remission (GPR) after conventional therapy and received high-dose chemotherapy (HDC) with in vitro purged autologous bone marrow transplantation (ABMT) as consolidation therapy. The HDC was a combination of carmustine (BCNU), teniposide (VM-26), and melphalan. Thirty-three patients received one course of this regimen, and 18 received two courses. At present, 16 of the 33 grafted patients are alive in continuous CR, with a median follow-up of 28 months. Toxicity of this regimen was tolerable, principally marked by bone marrow depression and gastrointestinal (GI) tract complications. Four complication-related deaths were observed. Relapse post-ABMT occurred most often in the bone marrow. Under this treatment, actuarial disease-free survival is improved compared with that observed under conventional therapy.
Assuntos
Neoplasias Abdominais/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Neuroblastoma/secundário , Neoplasias Torácicas/secundário , Neoplasias Abdominais/tratamento farmacológico , Neoplasias Abdominais/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças da Medula Óssea/induzido quimicamente , Carmustina/administração & dosagem , Carmustina/efeitos adversos , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Gastroenteropatias/induzido quimicamente , Humanos , Lactente , Infecções/induzido quimicamente , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/terapia , Teniposídeo/administração & dosagem , Teniposídeo/efeitos adversos , Neoplasias Torácicas/tratamento farmacológico , Neoplasias Torácicas/terapia , Transplante Autólogo , Vincristina/administração & dosagemRESUMO
PURPOSE: We analyzed the clinical features and outcome of patients with radiation-associated osteosarcoma treated during the era of contemporary chemotherapy. PATIENTS AND METHODS: The characteristics and outcome of 23 patients (17 males and six females) treated during childhood or adolescence for a solid tumor who later developed osteosarcomas within the radiation field between 1981 and 1996 were reviewed. RESULTS: The median dose of radiation delivered to the first cancer was 47 Gy. Nineteen patients also received chemotherapy. The median time between radiotherapy and the diagnosis of secondary osteosarcoma was 8 years. Histologic slide review showed conventional central osteosarcoma with various differentiation patterns in 21 cases, together with one case of high-grade surface osteosarcoma and one of periosteal osteosarcoma. The sites of involvement were the craniofacial bones in six cases, the first cervical vertebra in one, the girdle bones in seven, and the extremities of long bones in nine. Three patients had metastatic disease at the diagnosis of osteosarcoma. Palliative therapy was administered to seven patients. The aim of treatment was curative for 16 patients, two of whom underwent amputation without further therapy. Intensive chemotherapy regimens were administered to 14 patients before and/or after surgery. Fifteen patients achieved complete surgical remission. Twelve patients were alive and disease-free at a median follow-up duration of 7.5 years. Overall and event-free survivals at 8 years were 50% and 41%, respectively. CONCLUSION: Patients with radiation-related osteosarcoma and resectable lesions can be cured with surgery and intensive preoperative and postoperative chemotherapy.
Assuntos
Neoplasias Ósseas/terapia , Neoplasias Induzidas por Radiação/terapia , Segunda Neoplasia Primária/terapia , Osteossarcoma/terapia , Adolescente , Adulto , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Ósseas/mortalidade , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Masculino , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Neoplasias Induzidas por Radiação/mortalidade , Segunda Neoplasia Primária/mortalidade , Osteossarcoma/mortalidade , Dosagem Radioterapêutica , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/radioterapia , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/radioterapiaRESUMO
PURPOSE: To evaluate a strategy that avoids radiotherapy in first-line treatment in children under 5 years of age with brain or posterior fossa ependymoma, by exclusively administering 16 months of adjuvant multiagent chemotherapy after surgery. PATIENTS AND METHODS: Between June 1990 and October 1998, 73 children with ependymoma (82% with high-grade tumors) were enrolled onto this multicenter trial. Children received adjuvant conventional chemotherapy after surgery consisting of seven cycles of three courses alternating two drugs at each course (procarbazine and carboplatin, etoposide and cisplatin, vincristine and cyclophosphamide) over a year and a half. Systematic irradiation was not envisaged at the end of chemotherapy. In the event of relapse or progression, salvage treatment consisted of a second surgical procedure followed by local irradiation with or without second-line chemotherapy. RESULTS: Conventional chemotherapy was well tolerated and could be administered in outpatient clinics. No radiologically documented response to chemotherapy more than 50% was observed. With a median follow-up of 4.7 years (range, 5 months to 8 years), the 4-year progression-free survival rate in this series was 22% (95% confidence interval [CI], 13% to 43%) and the overall survival rate was 59% (95% CI, 47% to 71%). Overall, 40% (95% CI, 29% to 51%) of the patients were alive having never received radiotherapy 2 years after the initiation of chemotherapy and 23% (95% CI, 14% to 35%) were still alive at 4 years without recourse to this modality. In the multivariate analysis, the two factors associated with a favorable outcome were a supratentorial tumor location (P =.0004) and complete surgery (P =.0009). Overall survival at 4 years was 74% (95% CI, 59% to 86%) for the patients in whom resection was radiologically complete and 35% (95% CI, 18% to 56%) for the patients with incomplete resection. CONCLUSION: A significant proportion of children with ependymoma can avoid radiotherapy with prolonged adjuvant chemotherapy. Deferring irradiation at the time of relapse did not compromise overall survival of the entire patient population.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Ependimoma/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Carboplatina/administração & dosagem , Quimioterapia Adjuvante , Pré-Escolar , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Ependimoma/cirurgia , Etoposídeo/administração & dosagem , Feminino , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia , Procarbazina/administração & dosagem , Prognóstico , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
PURPOSE: The usual therapy of osteosarcoma is neoadjuvant chemotherapy, followed by surgery, then by postoperative chemotherapy. There is no prognostic factor to predict, at diagnosis, the histologic response and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS: Forty-seven patients with primary osteosarcoma, treated in four French institutions, were studied. LOH was studied by polymerase chain reaction (PCR) of an informative RB DNA polymorphism. RESULTS: Assessment of LOH at the RB gene could be completed on 34 heterozygous patients only. LOH was found in 24 cases (70%). The event-free survival (EFS) rate at 60 months is 100% for patients without LOH, 43% for all patients with RB LOH, and 65% for nonmetastatic patients with RB LOH. The difference in EFS is highly significant at P = .008 and P = .024, respectively. Histologic response after preoperative chemotherapy did not show significant correlation with LOH status. CONCLUSION: RB gene LOH appears to be an early predictive feature for osteosarcomas that indicates a potential unfavorable outcome. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.
Assuntos
Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Genes do Retinoblastoma , Osteossarcoma/genética , Osteossarcoma/mortalidade , Adolescente , Adulto , Sequência de Bases , Criança , Heterozigoto , Humanos , Dados de Sequência Molecular , PrognósticoRESUMO
We previously demonstrated that Busulfan-Thiotepa (Bu-Thio) and ASCT effectively treated patients with locally relapsed medulloblastoma after surgery and conventional chemotherapy. We thus evaluated the administration of Bu-Thio in patients relapsing after conventional CNS irradiation. Patients were scheduled to receive Busulfan (600 mg/m(2)) and Thiotepa (900 mg/m(2)) and ASCT. Resection of residual tumour and additional irradiation were performed if necessary and feasible after Bu-Thio. Toxicity was compared to that observed in 35 patients treated without previous CNS irradiation. From 5/88 to 3/02, 15 patients were treated according to this strategy. Toxicity was significantly higher than that observed in unirradiated patients: thrombocytopenia <50,000/mm(3) lasting 56 days (13-732) (P=0.02) and 30 days (4-124), respectively, HVOD (10/15 and 12/35 patients, respectively) (P=0.06), neurological toxicity (8/15 vs 3/35 patients) (P=0.01). Tumour response was assessable in seven patients and consisted in two CR, three PR and two NR. Currently, two of 15 patients are alive with no evidence of disease. In conclusion, the toxicity of Bu-Thio was significantly more severe in previously irradiated patients. In spite of a high response rate, this strategy failed to improve the prognosis of previously irradiated patients with a relapse from a medulloblastoma.
Assuntos
Bussulfano/administração & dosagem , Irradiação Craniana , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Meduloblastoma/terapia , Tiotepa/administração & dosagem , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Bussulfano/toxicidade , Criança , Pré-Escolar , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Masculino , Meduloblastoma/complicações , Meduloblastoma/mortalidade , Síndromes Neurotóxicas/etiologia , Indução de Remissão/métodos , Taxa de Sobrevida , Tiotepa/toxicidade , Trombocitopenia/etiologia , Transplante Autólogo , Resultado do TratamentoRESUMO
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.
Assuntos
Estatura , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Puberdade Precoce/tratamento farmacológico , Adulto , Criança , Feminino , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , MasculinoRESUMO
Contrary to major advances in cure rates observed for almost all childhood cancers, progress in reducing brain tumour survival rates remains very limited. Although new drug development in oncology is founded on principles outlined in the organised methodology of phase I, II, and III trials, based on rigorous study design using standardised criteria, this approach has been applied very slowly in the field of neuro-oncology. There are multiple explanations for the paucity of well-conducted prospective clinical trials, such as the rarity and the heterogeneity of these tumours, and the reluctance of some investigators to enroll their patients in constraining trials. Data from the past two decades shows that several methodological problems preclude the drawing of any definite conclusions for the majority of drugs assessed. Among them, the necessity of a central neuropathological and neuroradiological review has been highlighted in, at least, two multicentric studies. Changes in histological diagnosis and grade have been reported in a proportion as high as 20%, and changes in response rate in 14% of the cases. This review of phase II trials for brain tumours reveals a wide array of sometimes arbitrary response definitions, that is if response is defined at all, and most series have enrolled small numbers of patients. We report on the different problems encountered in childhood brain tumours in these phase II trials, and their impact on phase III trials.