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Biomedical subjects

E H Kovnar

Publications and source records attributed to E H Kovnar.

28 records · Page 2Linked to original sources

Ependymomas in children.

Ependymomas originate throughout the central nervous system (CNS), representing 10-12% of CNS tumors in children. The majority occur in children less than 5 years of age. Tumors occur most often in the 4th ventricular region. Current controversies regarding ependymomas include histologic categorization or 'differentiation'. It is estimated that approximately 25% of childhood tumors are appropriately categorized as anaplastic or 'high-grade' lesions. Surgical resection is curative for tumors originating in the cauda equina; recent data suggest that surgery alone has achieved disease control in 75% of intramedullary tumors. For intracranial ependymomas, postoperative irradiation has been shown to improve survival in series dating from the 1960-1980 era. Debate regarding the necessary volume for radiation therapy (i.e. local treatment or craniospinal irradiation) centers on the reported rate of neuraxis seeding. An overall incidence of 12% has been documented in the literature, with clinico-histologic correlation suggesting that anaplastic or high-grade infratentorial ependymomas are associated with the highest frequency of subarachnoid spread. Recent reports of chemotherapy show response to several single agents, with no clear documentation that adjuvant chemotherapy has improved survival to date. Current studies utilizing preirradiation chemotherapy address tumor response and ultimate control in a sequence of surgery, chemotherapy, and irradiation primarily in very young children or those with anaplastic or high-grade tumors.

Child↗

Psychologic and neurologic function following treatment for childhood temporal lobe astrocytoma.

Seven school-aged children treated for temporal lobe astrocytomas with surgical resection and irradiation were prospectively tested to evaluate their intellectual, academic, personality, and neurologic status after therapy. At their most recent follow-up examination, neuropsychologic functioning was adequate in only two patients. The other five children manifested either intellectual deterioration, learning disability, mental retardation, or psychopathology. These deficits were associated with poor postoperative performance status, inadequate seizure control, tumor recurrence, and younger age at diagnosis. No pattern of intellectual, academic, or personality dysfunction emerged in association with left- versus right-hemisphere tumors.

Achievement↗

Feasibility and efficacy of preirradiation chemotherapy for pediatric brain tumors.

Preirradiation chemotherapy is a potentially important component of combined treatment for brain tumors; however, concerns over its side effects and antitumor activity have impeded its evaluation in clinical trials. To determine the feasibility of administering such therapy to children, we assessed the responses of 38 brain tumor patients (median age, 2 years) to 12 weeks of combination chemotherapy given after surgical resection but before irradiation. Transient myelosuppression was noted in all patients, but was not associated with infections or complications of surgical wounds. The ability of the patients to perform activities of daily life, as rated with the Karnofsky performance scale, was either improved (n = 14) or unchanged (n = 18) at the end of the evaluation period. In the remainder of the group, functional deterioration was clearly related to causes other than drug treatment. Prior chemotherapy did not compromise the delivery of radiation except for a brief interruption of spinal irradiation in 3 patients. Objective responses to chemotherapy, defined as a greater than 50% decrease in tumor masses, occurred in 16 of the 31 patients who had subtotal resections; only 6 patients in the entire group showed disease progression during the 12 weeks of drug administration. We conclude that chemotherapy of the type used in this study is well tolerated and produces beneficial effects in children with brain tumors.

Adolescent↗

Potentiation of ifosfamide neurotoxicity, hematotoxicity, and tubular nephrotoxicity by prior cis-diamminedichloroplatinum(II) therapy.

We investigated the relationship between prior therapy and three distinct forms of toxicity that developed during ifosfamide administration (1.6 g/m2/day for 5 days) in 36 children with malignant solid tumors. Of ten therapies that were studied by multiple regression techniques, only the number of doses of cisplatin that patients had received was significantly related to neurotoxicity, hematotoxicity, and tubular nephrotoxicity, with the more severe cases occurring after three or more doses (P less than 0.05). Increased urinary concentrations of the renal tubular enzyme N-acetyl-beta-D-glucosaminidase, measured before each course of ifosfamide, were predictive of neurotoxicity (P = 0.02) and hematotoxicity (P = 0.01). We suggest that cisplatin-induced renal tubular damage, leading to the impaired clearance of ifosfamide metabolites, may account for this added toxicity.

Acetylglucosaminidase↗

Serial neuropsychological studies of a child with acute lymphoblastic leukemia and subsequent glioblastoma multiforme.

A 10-year-old boy had a right posterior parietal glioblastoma 5 years after completing treatment for acute lymphoblastic leukemia. Interim findings included seizures, leukoencephalopathy, diffuse mineralizing microangiopathy, and abnormal changes in neuropsychological test performance, which, in retrospect, provided information about the location of the tumor. This case highlights unusual sequelae of childhood leukemia and its treatment, as well as the value of neuropsychological procedures in assessing functional status and integrity of the brain.

Brain Neoplasms↗

Normal neurologic development and marked reconstitution of cerebral mantle after postnatal treatment of intrauterine hydrocephalus.

We treated an infant who had severe congenital hydrocephalus and a massively enlarged head at birth. Despite extreme attenuation of the cerebral mantle, placement of a ventriculoperitoneal shunt at 4 weeks of age was followed by essentially normal neurologic development after several months. In addition, there was a striking reconstitution of the cerebral mantle.

Brain↗

Response of pediatric low grade gliomas to chemotherapy.

Thirteen patients with low grade astrocytomas were treated with alkylating agent or platinum-based chemotherapy regimens. Eleven of these patients received chemotherapy as their initial postoperative treatment modality, and 2 others as treatment for progressive disease postradiation therapy. Responses were objectively determined using CT or MRI. One patient had a complete response (CR), 6 had partial responses (PR), and 3 others had stable disease (SD) as their best response. Clinical responses paralleled those determined objectively. Chemotherapy was well tolerated with the exception of ototoxicity in 4 patients treated with cisplatin. Despite good initial responses, 5 of 6 patients who received no further treatment postchemotherapy (4 PR, 1 SD) developed progressive disease 5-13 months after completing chemotherapy. The remaining 4 patients with objective responses or stable disease (1 CR, 2 PR, 1 SD), all received further postchemotherapy treatment with radiation therapy or surgery, and have not demonstrated disease progression. Our experience suggests that alkylator or platinum-based chemotherapy can successfully delay the growth of these locally infiltrative neoplasms, and should be considered in their primary management. Despite the experience of others, further therapy appears necessary in patients with residual CT or MRI abnormalities postchemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗