Beverly Hockenberger

Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study.

PURPOSE The Pediatric Oncology Group (POG) conducted a randomized phase II study to evaluate the activity of carboplatin and iproplatin in children with progressive or recurrent brain tumors. PATIENTS AND METHODS The study was designed to evaluate the activity of these agents and to compare the toxicities associated with their use. Treatment consisted of carboplatin 560 mg/m2 at 4-week intervals or iproplatin 270 mg/m2 at 3-week intervals. RESULTS The major toxicity observed was myelosuppression, particularly thrombocytopenia, for both agents. Ototoxicity (grade 1 or 2) was seen in 2.5% of patients treated with carboplatin and 1.3% of patients treated with iproplatin. The majority of patients with low-grade astrocytic neoplasms treated with carboplatin (nine of 12 patients) or iproplatin (eight of 12 patients) demonstrated tumor response or prolonged stable disease that persisted off-therapy. The duration of stable disease produced by carboplatin was particularly striking, ranging from 2 months to 68 + months (median, 40 + months). Neither drug demonstrated appreciable activity in the treatment of medulloblastoma (two of 26 responses to carboplatin, one of 14 responses to iproplatin), ependymoma (two of 17 responses to carboplatin, none of seven responses to iproplatin), high-grade glioma (two of 19 responses to carboplatin, one of 14 responses to iproplatin), or brain-stem tumors (one of 23 responses to carboplatin, none of 14 responses to iproplatin). CONCLUSION Carboplatin is active against low-grade gliomas. Further evaluation of the role of carboplatin in the preirradiation treatment of children with low-grade gliomas of the optic pathway is currently underway in a clinical trial.

FDG-PET in pediatric posterior fossa brain tumors

Seventeen pediatric patients with posterior fossa brain tumors were studied with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET). The FDG uptake was ranked by two observers, and the results were correlated with tumor histology. Increased FDG uptake was associated with more malignant and aggressive tumor types. Heterogeneity of FDG uptake was associated with previous therapy, including radiation therapy and chemotherapy. 2-[18F]Fluoro-2-deoxy-D-glucose PET will likely be an important adjunct in the management of pediatric posterior fossa tumors, much as in adult patients with brain tumors.

Leptomeningeal Dissemination of Optic Pathway Gliomas in Three Children

We treated three children with optic pathway gliomas who had progressive disease associated with metastatic spread to the leptomeninges. One patient had radiographic resolution of leptomeningeal disease after treatment with intravenous carmustine and oral mercaptopurine but died of progressive pulmonary fibrosis. The second patient was treated with intravenous thiotepa, and the leptomeningeal disease remained stable. The third patient was treated with intravenous vincristine sulfate, cyclophosphamide, cisplatin, and etoposide and had a significant size reduction of the leptomeningeal lesion. Although leptomeningeal dissemination is a seemingly rare event, it is important that all children with optic pathway gliomas be considered for this possibility, particularly after the onset of new, atypical neurologic symptoms.

Reversal of radiation‐induced neutropenia by granulocyte colony‐stimulating factor

Myelosuppression is a common sequelae of radiotherapy, occasionally delaying the completion of treatment. In this report, we describe successful reversal of radiation-induced neutropenia in a child receiving craniospinal irradiation by granulocyte colony-stimulating factor (G-CSF). We suggest that G-CSF be considered as supportive care in patients in whom neutropenia develops during radiotherapy.

Postradiation cerebellar necrosis mimicking tumor : MR appearance

Cerebellar necrosis associated with therapy of primary gliomas is unusual. We present the MR findings in a patient with postradiation multifocal cerebellar necrosis mimicking tumor dissemination.

Surgery, hyperfractionated craniospinal irradiation, and adjuvant chemotherapy in the management of supratentorial embryonal neuroepithelial neoplasms in children

Supratentorial embryonal neuroepithelial tumors are undifferentiated neoplasms. We have used this term in preference to the controversial classification primitive neuroectodermal tumors (PNET). These lesions in children are malignant neoplasms which are usually fatal within 2 years of diagnosis in spite of therapy with surgery, radiotherapy, and chemotherapy. We have adopted an aggressive approach to the treatment of these tumors with surgical resection, hyperfractionated craniospinal irradiation of 30.6-43.9 Gy followed by a tumor boost to a total dose of 50-63.7 Gy, and adjuvant chemotherapy with cyclophosphamide, vincristine, and cis-platinum. We have treated five children, aged 4-18 years, with this approach. In contrast to the results reported in the literature, four children are alive without evidence of tumor from 4.3 to 8.0 years following diagnosis. One has suffered a tumor relapse at 2.3 years following diagnosis but remains alive. The basis of our therapeutic strategy for childhood supratentorial embryonal neuroepithelial tumors and the implications of our clinical results are discussed.

Phase III clinical evaluation of gadoteridol injection: Experience in pediatric neuro-oncologic MR imaging

Twenty-two pediatric patients with known CNS neoplasms underwent magnetic resonance (MR) imaging before and after intravenous injection of 0.1 mmol/kg gadoteridol injection as part of a Phase IIIB open label multicenter clinical trial. Intravenous administration of this neutral, nonionic contrast agent was found to be safe in children. No clinically relevant changes in vital signs or laboratory values (including complete blood count, blood chemistry, serum electrolytes, thyroid and metabolic panel and clotting function) were attributed to the administration of gadoteridol injection. There were no systemic complaints. The imaging characteristics of gadoteridol in pediatric CNS disease appeared similar to those of gadopentetate dimeglumine. Contrast enhancement was present in 17 of 22 patients (77%). The administration of gadoteridol injection provided additional clinically relevant information including improved visualization and delineation of the primary lesion, detection of additional lesions, determination of tumor recurrence and narrowing the list of differential considerations in all 17 enhancing studies as well as in 2 of 5 studies without signal intensity enhancement. The very low toxicity, inherent to this nonionic low osmolal paramagnetic contrast formulation may allow administration of increased doses at increased infusion rates for an increased number of indications with improved sensitivity.

Reversal of radiation-induced neutropenia by granulocyte colony-stimulating factor

Myelosuppression is a common sequelae of radiotherapy, occasionally delaying the completion of treatment. In this report, we describe successful reversal of radiation-induced neutropenia in a child receiving craniospinal irradiation by granulocyte colony-stimulating factor (G-CSF). We suggest that G-CSF be considered as supportive care in patients in whom neutropenia develops during radiotherapy.