Growth impairment and growth hormone therapy in children treated for malignant brain tumours.

UNLABELLED: Eighty-two children with malignant brain tumours were treated according to the "8 in 1" chemotherapy protocol in Finland during 1986 to 1993. Thirty-seven with brain tumours not involving the hypothalamic-pituitary region are still alive and tumour-free. The growth and response to growth hormone (GH) therapy in these children was analysed. Children who received craniospinal irradiation had the most severe loss of height SDS, being -1.07 within 3 years of the diagnosis. Even children with no irradiation to the hypothalamic-pituitary axis had a mean change in height SDS of -0.5 after 3 years. Fifteen of 23 children who received craniospinal irradiation and two out of eight children who received cranial irradiation have received GH therapy. A catch-up growth response to the daily GH therapy with the mean dose of 0.7 IU/kg per week was complete in 3 years (+1.87 SDS), irrespective of craniospinal irradiation, in children who were treated at prepubertal age but was seen in none of the children who had reached pubertal age. CONCLUSION: Growth impairment and GH deficiency are common in children treated for malignant brain tumours. The response to GH therapy is good in prepubertal children in terms of increased growth velocity, although the final height is not yet known.

Improving outcome of malignant brain tumours in very young children: a population-based study in Finland during 1975-93.

Sixty-four children with malignant brain tumours diagnosed at less than 3 years of age were reported to the Finnish Cancer Registry from 1975 to 1993. The survival rate has improved significantly: the 5-year survival rate was 26% for all children, 13% for children diagnosed during 1975-85 (n = 30) and 40% for those diagnosed during 1986-93 (n = 34). Of the surviving children in 1986-93, 43% were categorized in Bloom's group I or II and could lead active lives without major disabilities. The remaining children had severe neurologic late complications, such as hemiplegia, intractable seizures, and mental retardation.

Ototoxicity in children with malignant brain tumors treated with the "8 in 1" chemotherapy protocol.

BACKGROUND: Adjuvant chemotherapy has improved the outcome of childhood malignant brain tumors in large randomized trials. With increasing survival rates, treatment toxicity has become a matter of concern. Radiation therapy and cisplatinum are known to be ototoxic. METHODS: We evaluated the incidence and factors predisposing to ototoxicity in children treated with the "8 in 1" chemotherapy protocol in Finland during 1986--1993. Thirty-five of the 82 children survived for at least 1 year after diagnosis. Thirty of these children were old enough to have an audiogram. RESULTS: Seventeen of the 30 children had normal hearing, seven had hearing loss at high frequencies, and six (20%) had severe hearing loss in the speech range. The risk factors for severe hearing loss were young age, a high cumulative dose of cisplatinum, and deteriorating renal function. In the presence of these factors, the risk of severe hearing loss was over 50%. Hearing loss at high frequencies could occur after low cumulative doses of cisplatinum, but severe hearing loss correlated with high cumulative doses. CONCLUSIONS: Cisplatinum-induced hearing loss at high frequencies is common, but hearing loss in the speech range also occurs, particularly in children with predisposing factors, and may progress insidiously and rapidly. Therefore a hearing test before each "8 in 1" course is important.

Neuropsychologic late effects in children with malignant brain tumors treated with surgery, radiotherapy and "8 in 1" chemotherapy.

Sixty-eight children with malignant brain tumors were treated with the "8 in 1" chemotherapy protocol from 1986 to 1993 in Finland. The overall 5-year survival rate was 43%. Thirty-one children are still alive and tumor-free, and have been evaluated in the present study. Of these 31 children, 26% had hemi- or tetraplegia, 13% intractable seizures, and 30% attend special schools. The mean full scale (FS) IQ was 85 (range 45-138), 24% had an FSIQ value less than 70, and 36% more than 90. One-half of the survivors were placed in Bloom's group I or II, are able to lead an active life, and have only mild neurologic disabilities. In the other, neurologic late complications accumulated and these children were relegated to Bloom's group III or IV, with major disabilities such as hemiplegia, intractable epilepsy, or mental retardation. The most important prognostic factors were severe perioperative complications, young age at diagnosis, and cranial irradiation.

Chemotherapy with the "8 in 1" protocol for malignant brain tumors in children: a population-based study in Finland.

We evaluated the outcome of 68 children with malignant brain tumors treated with the "8 in 1" chemotherapy protocol in Finland from 1986 to 1993, comparing 5-year survival rates with those for a historical control group (from 1975 to 1985). For all malignant brain tumors, overall survival was 43% (vs 28% in the control group; P <0.05), and progression-free survival (PFS) was 43% (vs 23%; P <0.05). For medulloblastoma and primitive neuroectodermal tumor, survival was 63% (vs 35%; P <0.05), and the corresponding PFS was 59% (vs 35%; P = 0.15). For high-grade glioma, both the survival rate and the PFS were 27% (vs 17%; P = NS). Thus the outcome was significantly better for our "8 in 1" -treated patients than for the historical controls, especially among the children with primitive neuroectodermal tumor and medulloblastoma. In contrast, those with high-grade gliomas and brain stem tumors seem to have received little benefit; different, more effective treatments are needed for these patients.

Congenital intraocular teratoma.

PURPOSE: The clinical and histopathologic findings of an intraocularly located congenital teratoma are reported. METHODS: In addition to routine histologic stainings, the tissue types present and the fate of the neuroectodermal elements of the disorganized eye were analyzed by immunohistochemistry. RESULTS: An otherwise healthy baby girl was born with a large greenish mass replacing the left eye without invading the orbit. The enucleated eye showed a firm polycystic intraocular tumor filling the intraocular space. Normal sclera and a massively distended cornea enclosed the globe. Fairly normal choroid and a disorganized ciliary muscle were present, but the ciliary body and iris had not formed. The tumor was surrounded by maldeveloped remnants of the optic vesicle and consisted of derivatives of all three germinal layers such as adnexal glands, brain, choroid plexi, intestinal and respiratory epithelium, cartilage, adipose tissue, as well as smooth and skeletal muscle. DISCUSSION: The clinical history with presentation at birth, female sex of the patient, and both macroscopic and microscopic findings are typical of a benign orbital teratoma, but the intraocular location is unique. Lack of truly medulloepitheliomatous elements in this case and the absence of derivatives from three germinal layers in all previously reported teratoid medulloepitheliomas of the ciliary body exclude the latter diagnosis. The teratoma may have arisen in the orbit with subsequent entrapment within the developing eye when the embryonic fissure closed.