RESUMO
BACKGROUND AND PURPOSE: Selumetinib is a promising MAP (mitogen-activated protein) kinase (MEK) 1/2 inhibitor treatment for pediatric low-grade gliomas. We hypothesized that MR imaging-derived ADC histogram metrics would be associated with survival and response to treatment with selumetinib. MATERIALS AND METHODS: Children with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with KIAA1549-BRAF fusion or the BRAF V600E mutation (stratum 1), neurofibromatosis type 1-associated pediatric low-grade gliomas (stratum 3), or sporadic non-neurofibromatosis type 1 optic pathway and hypothalamic glioma (OPHG) (stratum 4) were treated with selumetinib for up to 2 years. Quantitative ADC histogram metrics were analyzed for total and enhancing tumor volumes at baseline and during treatment. RESULTS: Each stratum comprised 25 patients. Stratum 1 responders showed lower values of SD of baseline ADC_total as well as a larger decrease with time on treatment in ADC_total mean, mode, and median compared with nonresponders. Stratum 3 responders showed a greater longitudinal decrease in ADC_total. In stratum 4, higher baseline ADC_total skewness and kurtosis were associated with shorter progression-free survival. When all 3 strata were combined, responders showed a greater decrease with time in ADC_total mode and median. Compared with sporadic OPHG, neurofibromatosis type 1-associated OPHG had lower values of ADC_total mean, mode, and median as well as ADC_enhancement mean and median and higher values of ADC_total skewness and kurtosis at baseline. The longitudinal decrease in ADC_total median during treatment was significantly greater in sporadic OPHG compared with neurofibromatosis type 1-associated OPHG. CONCLUSIONS: ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.
Assuntos
Neoplasias Encefálicas , Glioma , Neurofibromatose 1 , Benzimidazóis , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Criança , Imagem de Difusão por Ressonância Magnética , Glioma/diagnóstico por imagem , Glioma/tratamento farmacológico , Glioma/genética , Humanos , Neurofibromatose 1/diagnóstico por imagem , Neurofibromatose 1/tratamento farmacológico , Proteínas Proto-Oncogênicas B-rafRESUMO
BACKGROUND AND PURPOSE: 2D measurements of diffuse intrinsic pontine gliomas are limited by variability, and volumetric response criteria are poorly defined. Semiautomated 2D measurements may improve consistency; however, the impact on tumor response assessments is unknown. The purpose of this study was to compare manual 2D, semiautomated 2D, and volumetric measurement strategies for diffuse intrinsic pontine gliomas. MATERIALS AND METHODS: This study evaluated patients with diffuse intrinsic pontine gliomas through a Phase I/II trial (NCT02607124). Clinical 2D cross-product values were derived from manual linear measurements (cross-product = long axis × short axis). By means of dedicated software (mint Lesion), tumor margins were traced and maximum cross-product and tumor volume were automatically derived. Correlation and bias between methods were assessed, and response assessment per measurement strategy was reported. RESULTS: Ten patients (median age, 7.6 years) underwent 58 MR imaging examinations. Correlation and mean bias (95% limits) of percentage change in tumor size from prior examinations were the following: clinical and semiautomated cross-product, r = 0.36, -1.5% (-59.9%, 56.8%); clinical cross-product and volume, r = 0.61, -2.1% (-52.0%, 47.8%); and semiautomated cross-product and volume, r = 0.79, 0.6% (-39.3%, 38.1%). Stable disease, progressive disease, and partial response rates per measurement strategy were the following: clinical cross-product, 82%, 18%, 0%; semiautomated cross-product, 54%, 42%, 4%; and volume, 50%, 46%, 4%, respectively. CONCLUSIONS: Manual 2D cross-product measurements may underestimate tumor size and disease progression compared with semiautomated 2D and volumetric measurements.
Assuntos
Neoplasias do Tronco Encefálico/diagnóstico por imagem , Glioma Pontino Intrínseco Difuso/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Neuroimagem/métodos , Adolescente , Aminopiridinas/uso terapêutico , Neoplasias do Tronco Encefálico/tratamento farmacológico , Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Criança , Glioma Pontino Intrínseco Difuso/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Purinas/uso terapêutico , Software , Carga Tumoral/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Supratentorial primitive neuroectodermal tumors and pineoblastomas have traditionally been grouped together for treatment purposes. Molecular profiling of these tumors has revealed a number of distinct entities and has led to the term "CNS-primitive neuroectodermal tumors" being removed from the 2016 World Health Organization classification. The purpose of this study was to describe the MR imaging findings of histologically diagnosed primitive neuroectodermal tumors and pineoblastomas and correlate them with molecular diagnoses and outcomes. MATERIALS AND METHODS: Histologically diagnosed primitive neuroectodermal tumors and pineoblastomas were enrolled in this Children's Oncology Group Phase III trial, and molecular classification was retrospectively completed using DNA methylation profiling. MR imaging features were systematically studied and correlated with molecular diagnoses and survival. RESULTS: Of the 85 patients enrolled, 56 met the inclusion criteria, in whom 28 tumors were in pineal and 28 in nonpineal locations. Methylation profiling revealed a variety of diagnoses, including pineoblastomas (n = 27), high-grade gliomas (n = 17), embryonal tumors (n = 7), atypical teratoid/rhabdoid tumors (n = 3), and ependymomas (n = 2). Thus, 39% overall and 71% of nonpineal tumor diagnoses were discrepant with histopathology. Tumor location, size, margins, and edema were predictors of embryonal-versus-nonembryonal tumors. Larger size and ill-defined margins correlated with poor event-free survival, while metastatic disease by MR imaging did not. CONCLUSIONS: In nonpineal locations, only a minority of histologically diagnosed primitive neuroectodermal tumors are embryonal tumors; therefore, high-grade glioma or ependymoma should be high on the radiographic differential. An understanding of molecularly defined tumor entities and their relative frequencies and locations will help the radiologist make more accurate predictions of the tumor types.
Assuntos
Tumores Neuroectodérmicos Primitivos/diagnóstico por imagem , Tumores Neuroectodérmicos Primitivos/genética , Pinealoma/diagnóstico por imagem , Pinealoma/genética , Neoplasias Supratentoriais/diagnóstico por imagem , Neoplasias Supratentoriais/genética , Adolescente , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Feminino , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/patologia , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/patologia , Tumores Neuroectodérmicos Primitivos/classificação , Tumores Neuroectodérmicos Primitivos/patologia , Glândula Pineal/diagnóstico por imagem , Glândula Pineal/patologia , Pinealoma/patologia , Estudos Retrospectivos , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/genética , Tumor Rabdoide/patologia , Neoplasias Supratentoriais/patologia , Teratoma/diagnóstico por imagem , Teratoma/genética , Teratoma/patologia , Adulto JovemRESUMO
BACKGROUND: Cerebral lacunes, which generally appear on magnetic resonance imaging as foci of white matter loss, usually occur in adults after ischemic infarcts. We report the development of lacunes in children after therapy for brain tumors. PATIENTS AND METHODS: We reviewed the clinical characteristics and radiologic studies of 524 consecutive children with brain tumors treated over a 10-year period. We documented the neuropsychologic findings associated with lacunes and the factors predictive of lacunar development. RESULTS: Lacunes developed in none of the 103 patients observed or treated with surgery alone. Twenty-five of the 421 patients treated with chemotherapy or radiation therapy or both had lacunes. Patients were a median of 4.5 years old at the time of both diagnosis (range, 0.3 to 19.8 years) and radiotherapy (range, 1.5 to 20 years). Fourteen patients were treated with craniospinal irradiation, and 11 were treated with local radiotherapy. The median time from radiotherapy to the appearance of lacunes was 2.01 years (range, 0.26 to 5.7 years). For all patients, lacunes were an incidental finding with no corresponding clinical deficits. The factor most predictive of lacunar development was age less than 5 years at the time of radiotherapy (P =.010). There was no significant difference in estimated decline in intelligence quotient scores between patients with lacunes and age and diagnosis-matched controls. CONCLUSION: Lacunes may be caused by therapy-induced vasculopathy in children with brain tumors, with the most significant predictor being age less than 5 years at the time of radiotherapy.
Assuntos
Encefalopatias/diagnóstico , Neoplasias Encefálicas/radioterapia , Imageamento por Ressonância Magnética , Lesões por Radiação/diagnóstico , Adolescente , Adulto , Fatores Etários , Encefalopatias/etiologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Estudos de Casos e Controles , Quimioterapia Adjuvante , Criança , Pré-Escolar , Irradiação Craniana , Feminino , Seguimentos , Previsões , Humanos , Lactente , Inteligência , Masculino , Neuropsicologia , Lesões por Radiação/etiologia , Radioterapia Adjuvante , Estudos Retrospectivos , Coluna Vertebral/efeitos da radiação , Estatística como Assunto , Fatores de TempoRESUMO
PURPOSE: Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with medulloblastoma or primitive neuroectodermal tumor (PNET). Examination of CSF for malignant cells, detection of LMD on spinal magnetic resonance imaging (MRI), or both are the methods routinely used to diagnose LMD. A recent study suggested 100% correlation between CSF and MRI findings in children with medulloblastoma. To determine the validity of this hypothesis, we compared the rate of detection of LMD between concurrent lumbar CSF cytology and spinal MRI performed at diagnosis in patients with medulloblastoma or PNET. PATIENTS AND METHODS: As a part of diagnostic staging, 106 consecutive patients newly diagnosed with medulloblastoma or PNET were evaluated with concurrent lumbar CSF cytology and spinal MRI. CSF cytology was examined for the presence of malignant cells and spinal MRI was reviewed independently for the presence of LMD. RESULTS: Thirty-four patients (32%) were diagnosed with LMD based on CSF cytology, spinal MRI, or both. There were 21 discordant results. Nine patients (8.5%) with positive MRI had negative CSF cytology. Twelve patients (11.3%) with positive CSF cytology had negative MRIs. The exact 95% upper bounds on the proportion of patients with LMD whose disease would have gone undetected using either CSF cytology or MRI as the only diagnostic modality were calculated at 14.4% and 17.7%, respectively. CONCLUSION: With the use of either CSF cytology or spinal MRI alone, LMD would be missed in up to 14% to 18% of patients with medulloblastoma or PNET. Thus, both CSF cytology and spinal MRI should routinely be used to diagnose LMD in patients with medulloblastoma or PNET.
Assuntos
Neoplasias Cerebelares/diagnóstico , Líquido Cefalorraquidiano/citologia , Meduloblastoma/diagnóstico , Neoplasias Meníngeas/secundário , Tumores Neuroectodérmicos Primitivos/diagnóstico , Adolescente , Adulto , Neoplasias Cerebelares/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Meduloblastoma/patologia , Neoplasias Meníngeas/diagnóstico , Meninges/patologia , Tumores Neuroectodérmicos Primitivos/patologia , Prognóstico , Sensibilidade e EspecificidadeRESUMO
PURPOSE: Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with primary CNS tumors. Cytologic examination of lumbar CSF is routinely used to detect LMD. To determine whether examination of CSF obtained from ventricular shunt taps is a more sensitive method of detecting LMD in these patients, we designed a prospective study to compare the findings of cytologic examinations of CSF obtained from concurrent lumbar and ventriculoperitoneal (VP) shunt taps. PATIENTS AND METHODS: As a part of diagnostic staging, follow-up testing, or both, 52 consecutive patients underwent concurrent lumbar and shunt taps on 90 separate occasions, ranging from the time of diagnosis to treatment follow-up. CSF from both sites was examined cytologically for malignant cells. RESULTS: The median age of the 28 males and 24 females was 7.5 years (range, 0.6 to 21.4 years). The primary CNS tumors included medulloblastoma (n = 29), astrocytoma (n = 10), ependymoma (n = 5), germinoma (n = 3), atypical teratoid rhabdoid tumor (n = 2), choroid plexus carcinoma (n = 2), and pineoblastoma (n = 1). Each site yielded a median CSF volume of 1.0 mL. Fourteen of 90 paired CSF test results were discordant: in 12, the cytologic findings from shunt CSF were negative for malignant cells, but those from lumbar CSF were positive; in two, the reverse was true. Malignant cells were detected at a higher rate in lumbar CSF than in shunt CSF (P =.0018). When repeat analyses were excluded, examination of lumbar CSF remained significantly more sensitive in detecting malignant cells (P =.011). Analysis of the subset of patients with embryonal tumors showed similar results (P =.0008). CONCLUSION: Cytologic examination of lumbar CSF is clearly superior to cytologic examination of VP shunt CSF for detecting leptomeningeal metastases in pediatric patients with primary CNS tumors.
Assuntos
Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/patologia , Líquido Cefalorraquidiano/citologia , Neoplasias Meníngeas/líquido cefalorraquidiano , Neoplasias Meníngeas/diagnóstico , Adolescente , Adulto , Neoplasias Encefálicas/diagnóstico , Criança , Pré-Escolar , Estudos de Avaliação como Assunto , Feminino , Humanos , Lactente , Região Lombossacral , Masculino , Neoplasias Meníngeas/secundário , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Derivação VentriculoperitonealRESUMO
To describe the clinical features, histologic characteristics, and management of patients with pleomorphic xanthoastrocytoma (PXA), we reviewed data on 13 children who had histologically confirmed PXA and were referred to the neuro-oncology service between 1985 and 1999. Neuro-imaging with CT and/or MRI documented the anatomic location, tumor extent, and degree of resection. There were 3 males and 10 females; median age was 12.9 years (range, 8.2-17.2 years). The most frequent presentations included seizures (n = 8) and headache (n = 5). Tumor sites included temporal (n = 5), parietal (n = 3), frontal (n = 1), frontoparietal (n = 1), parietooccipital (n = 1), and temporoparietal (n = 1) lobes and the spinal cord (n = 1). CT/MRI revealed a cystic component in 6 patients, with cyst wall enhancement in 3 patients. The solid component was uniformly enhancing in 11 patients. Vasogenic edema was present in 9 patients, and calcification was noted in 4 patients. Histopathologic findings included meningeal invasion in 12 patients, calcifications in 4, and necrosis in 2. Mitotic figures (1-12 per high-power field) were seen in 8 patients. Gross total resection was achieved in 8 patients, near total resection in 1, and subtotal resection in 4. Ten patients were alive with a median follow-up of 41 months at this writing. Two patients died of progressive disease, and 1 died of an unrelated cause. In conclusion, pleomorphic xanthoastrocytoma is a rare neoplasm in childhood, commonly presenting with seizures. Gross total resection without adjuvant therapy provides prolonged disease control, as seen in 6 of 7 patients (85%) in our series.
Assuntos
Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Adolescente , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Criança , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Multi-agent immunosuppressive therapy has produced improved survival for severe acquired aplastic anemia in children. Recently, some investigators have suggested that immunosuppressive therapy may replace bone marrow transplantation as first-line therapy for this disorder. To assess its validity, we compared the outcomes of bone marrow transplantation vs immunosuppressive therapy in one institution from 1987 to 1997. We studied 46 consecutive patients less than 18 years of age who presented between January 1987 and April 1997. Inherited marrow failure syndromes and myelodysplastic syndromes were excluded. Patients received immunosuppressive therapy vs bone marrow transplantation based on availability of HLA-matched donors. The main outcome measures were survival, complete marrow and hematological remission, or partial remission but achieving independence from transfusional support. Twenty patients received multi-agent immunosuppressive therapy (cyclosporine, antithymocyte globulin and methylprednisolone); 11 attained complete remission and three partial remission for a transfusion-independent survival of 70%. Six patients died of infectious and hemorrhagic complications. Twenty-six patients were transplanted and 24 (93%) achieved complete remission; one achieved a PR, 25 remain transfusion independent with a median follow-up of 5.9 years or 70 months. One patient developed AML 34 months after successful transplant and one patient died due to graft failure and complications of transplant. There has been a striking improvement in survival for pediatric patients treated with multi-agent immunosuppression in the last decade. However, transplantation results have also improved and this remains the definitive first-line therapy for severe acquired aplastic anemia in this age group.
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea , Imunossupressores/uso terapêutico , Adolescente , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Taxa de Sobrevida , Resultado do TratamentoRESUMO
This report and the accompanying review of the literature address the challenges, when using surveillance magnetic resonance (MR) imaging, of establishing the origin of newly detected central nervous system lesions. Routine surveillance MR imaging in a 16-year-old boy, whose medulloblastoma had been successfully treated, demonstrated asymptomatic nodular leptomeningeal enhancement of the brain and spinal cord, which was consistent with recurrent disease. Examination of the cerebrospinal fluid, however, led to the diagnosis of bacterial meningitis. Two weeks after completion of antibiotic therapy, the original MR imaging findings were seen to have resolved. This case illustrates the importance of considering clinical and laboratory data, including results from a complete examination of the cerebrospinal fluid, when interpreting the origin of new lesions revealed by MR imaging.
Assuntos
Neoplasias Cerebelares/diagnóstico , Imageamento por Ressonância Magnética , Meduloblastoma/diagnóstico , Meningites Bacterianas/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Infecções Estafilocócicas/diagnóstico , Staphylococcus epidermidis , Adolescente , Antibacterianos/uso terapêutico , Neoplasias Encefálicas/diagnóstico , Humanos , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/tratamento farmacológico , Neoplasias da Medula Espinal/diagnóstico , Infecções Estafilocócicas/líquido cefalorraquidiano , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/uso terapêuticoRESUMO
Temozolomide (TMZ) is currently being evaluated for the treatment of high-grade gliomas in children. Myelosuppression (the suppression of bone marrow activity) is the dose-limiting toxicity for TMZ in adults and children. Empirical methods (i.e. relations between the percent change in absolute neutrophil count (ANC) and the area under the plasma concentration curve (AUC) of TMZ or its active metabolite MTIC) showed poor results when attempting to describe myelosuppression from serial data derived during TMZ therapy in a Phase II study of children with high-grade glioma. Therefore, to improve our understanding of the myelosuppressive effects of TMZ and MTIC in children we developed a mechanistic mathematical model. The model describes the progression of neutrophils from their production in the bone marrow to their release in the plasma. Included in the model are the feedback effects of granulocyte colony stimulating factor (G-CSF), which stimulates neutrophil production when there is a decrease in circulating neutrophils. The model is fit to serial ANC measurements obtained after TMZ dosing and it is able to explain, among other things, the lag in ANC reduction following a dose of TMZ, the ANC nadir, and the 'rebound effect' observed where the ANC recovers to levels greater than that observed pre-TMZ dose. This model will be useful for the prospective design of clinical trials of TMZ in children with cancer.
Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Células da Medula Óssea/efeitos dos fármacos , Dacarbazina/análogos & derivados , Dacarbazina/efeitos adversos , Glioma/sangue , Hematopoese/efeitos dos fármacos , Modelos Biológicos , Adolescente , Adulto , Glioma/tratamento farmacológico , Humanos , Neutrófilos/efeitos dos fármacos , TemozolomidaRESUMO
In a prospective study of 34 patients with high post-operative astigmatism (mean 6.90 D, range 2.75-15.00 D) following extracapsular cataract surgery (13 limbal sections and 21 corneal sections), we used keratometry to assess the changes in corneal curvature seen within 30 minutes of suture removal and compared these with the astigmatism found 2 weeks later. The greatest change occurred within the first 5 minutes of suture removal (mean 3.63 D; 95% confidence interval (95% CI) 2.85-4.41). The rate of decay then declined so that between 15 and 30 minutes the mean change was 0.56 D (95% CI 0.43-0.69). At 2 weeks a further mean decay of 1.29 D (95% CI 0.99-1.61) occurred. Of the 6 patients exhibiting a residual astigmatism greater than 3.00 D at 30 minutes, 4 continued to do so 2 weeks later. Our study suggests that keratometry 30 minutes following suture removal is only moderately different from that seen 2 weeks later. Although not stable enough to suggest that patients could be routinely refracted within 30 minutes of suture removal, in cases where early visual recovery is essential, such as in monocular patients, it may be reasonable to offer a temporary spectacle correction immediately following suture removal. Furthermore keratometry at 30 minutes after suture removal accurately predicts the necessity for further removal of sutures and indicates which patients can be discharged to the care of their own optometrist, making a further hospital visit unnecessary.
Assuntos
Astigmatismo/etiologia , Extração de Catarata/efeitos adversos , Suturas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Optometria , Cuidados Pós-Operatórios , Período Pós-Operatório , Estudos ProspectivosRESUMO
BACKGROUND: Amifostine protects normal tissues against chemotherapy and radiation-induced toxicity without loss of antitumor effects. Evidence suggests that multiple daily doses of amifostine may improve its cytoprotective effects. The purpose of this study was to assess the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of twice-daily doses of amifostine with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy for children with refractory malignancies and to determine the pharmacokinetic properties of amifostine, WR-1065, and the disulfide metabolites of amifostine. METHODS: Patients with refractory malignancies were treated with amifostine 15 minutes before and 2 hours after chemotherapy with ifosfamide (3 g/m(2) per dose on Days 1 and 2) and carboplatin (635 mg/m(2) on Day 3). Etoposide was administered on Days 1 and 2 (150 mg/m(2)). The starting dose of amifostine was 740 mg/m(2). Pharmacokinetic studies were performed after the first dose of amifostine. RESULTS: Twelve patients received 23 courses of ICE and amifostine. Dose-limiting toxicities for amifostine at 740 mg/m(2) were somnolence and anxiety. The other Grade 3 and 4 toxicities included asymptomatic, reversible hypocalcemia, vomiting, and reversible hypotension. At a dose of 600 mg/m(2), amifostine was well tolerated. Hypocalcemia, due to rapid, transient suppression of parathyroid hormone production, required close monitoring and aggressive intravenous calcium supplementation. Pharmacokinetic studies revealed high interpatient variability with rapid plasma clearance of amifostine and WR-1065. The median elimination half-life of amifostine (9.3 minutes) and WR-1065 (15 minutes) was much shorter than the disulfide metabolites (74.4 minutes). CONCLUSIONS: The recommended pediatric dose of amifostine for a twice-daily regimen is 600 mg/m(2) per dose (1200 mg/m(2)/day) with DLTs of anxiety and somnolence, lower than the previously recommended single dose of 1650 mg/m(2).
Assuntos
Amifostina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Adolescente , Amifostina/metabolismo , Amifostina/farmacocinética , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Masculino , Mercaptoetilaminas/farmacocinética , Falha de TratamentoRESUMO
Despite the improved outcome for patients with ependymoma treated by surgery and radiotherapy, their prognosis remains relatively poor. To assess the impact of adjuvant chemotherapy, we reviewed the overall survival of consecutive patients with anaplastic ependymoma treated over a 10-year period with surgery and ICE (ifosfamide+ VP 16+carboplatin) chemotherapy with or without radiation at our institution. There were 11 patients (6 male, 5 female), with a median age of 3.4 years (range 1.2-1 1.1): 4 under 2 years and 7 were over 2 years old. Overall, 5 had gross total resections: 4 are alive, 2 in continuous complete remission and 2 in second complete remission. One patient who was less than 2 years old died. Among the 6 with subtotal resection, 2 achieved a complete remission after chemotherapy. However, 5 of the 6 patients have since died of progressive disease, with a median overall survival of 75 months. Overall survival was 24% and progression-free survival was 39%. In 2 of 6 patients with residual postoperative disease a temporary objective response was noted with adjuvant ICE chemotherapy. This regimen did not confer an overall survival advantage.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cerebelares/tratamento farmacológico , Ependimoma/tratamento farmacológico , Envelhecimento/fisiologia , Carboplatina/uso terapêutico , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/radioterapia , Neoplasias Cerebelares/cirurgia , Criança , Pré-Escolar , Terapia Combinada , Ependimoma/mortalidade , Ependimoma/radioterapia , Ependimoma/cirurgia , Etoposídeo/uso terapêutico , Feminino , Humanos , Ifosfamida/uso terapêutico , Lactente , Masculino , Análise de SobrevidaRESUMO
Concern about long-term sequelae of irradiation has led to the use of adjuvant chemotherapy with lower dose irradiation in the treatment of intracranial germinomas. To assess the feasibility of this approach versus radiation only, the survival of 16 evaluable patients (13 boys, 3 girls) with biopsy-proven intracranial germinomas treated at the Hospital for Sick Children was assessed. Between 1977 and 1988, 8 patients were treated with radiation only: 7 received tumour doses between 4000 and 5100 cGy and spinal prophylaxis; 1 received 3060 cGy to the tumour with no prophylaxis. After a median follow-up of 84 months, 7 are in continuous first CR and 1 is in second CR. Between 1988 and 1996, 8 patients received adjuvant platinum- and etoposide-based chemotherapy for two or three cycles followed by local irradiation to the tumour (2500-3500 cGy). After a median follow-up of 40 months, 6 are in continuous first CR and 1 in second CR; 1 has died of progression. Survival outcomes in the two groups are similar. Prospective trials to assess event-free survivals, neurocognitive and neuroendocrine outcomes are needed before definitive treatment recommendations can be made.