L. Besenzon

CNS-85 trial: a cooperative pediatric CNS tumor study--results of treatment of medulloblastoma patients.

Between 1985 and 1989, 38 children with newly diagnosed medulloblastoma entered our therapeutic protocol. After surgery and postoperative staging assessments, patients were assigned to risk groups. Eleven with “standard-risk” (SR) tumors were treated with radiation therapy alone, while 27 with “high-risk” (HR) tumors received radiation therapy plus adjuvant chemotherapy with vincristine, methotrexate, VM-26, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). After a minimum follow-up of 5 years (range 5–9 years) 21/38 children had developed a recurrence or progression of their disease and 19/38 patients had died. Five-year event-free survival rates and 5-year total survival rates for all 38 patients were 47.4% and 50% respectively. The event-free survival rates at 5 years for SR and HR patients separately were 27.3% and 55.6%, respectively. The corresponding 5-year total survival rates were 27.3% and 59.3%. The differences were not statistically significant. Univariate analysis showed age at diagnosis to be the most important prognostic factor. Infants aged 5 years or less had a significantly shorter event-free survival time than older patients (P=0.00897). Similar effects were found when total survival time was considered. There were significant differences in outcome in patients receiving different doses of radiation, suggesting a dose-response relationship. A Cox stepwise multivariate analysis showed age at diagnosis as the only independent prognostic factor. Variables relating to treatment entered the model, suggesting that chemotherapy could play an important role in determining outcome.

Thyroid diseases in patients treated during pre-puberty for medulloblastoma with different radiotherapic protocols

We evaluated thyroid disease in 32 patients treated, during pre-puberty, for medulloblastoma, followed for at least 4 years and without relapse during observation. After surgery the patients underwent chemotherapy (CT) and radiotherapy (RT). The protocols were as follows: 20 patients (group A) SNC 76 and SNC 85 protocols which included conventional fractionated RT (36–40 Gy to the craniospinal axis and a 14–18 Gy boost to the posterior fossa, administered as 1.5–1.8 Gy per fraction per day) and a junction between the cranial and the spinal fields at C2–C3 level; 12 patients (group B) SNC 91 protocol which included hyperfractionated RT (36 Gy to the craniospinal axis and a 30 Gy boost to the posterior fossa; this was administred as 1 Gy per fraction twice per day) and a junction at levels C5–C6 or C6–C7 level. The mean age at diagnosis was 7.4±3.2 years for group A and 8.4±2.6 years for group B. Thyroid function was evaluated yearly and ultrasonographic characteristics every 2 years. The patients were followed for a mean of 10.8±3.8 for group A and 6±1.4 years for group B. Primary hypothyroidism was diagnosed in 16 group A patients and 4 group B patients, and central hypothyroidism was diagnosed in 2 group A patients (difference in risk of developing hypothyroidism evaluated with a Wilcoxon-test: p=0.048). Ultrasonography showed reduced thyroid volume in 7 group A cases, and structural changes in 21 patients (17 group A, 4 group B); 9 L-thyroxine-treated patients were confirmed hypothyroid after having stopped therapy. A thyroid nodule was detected in two cases (one from each group). In conclusion, our data indicate that thyroid injury may be diminished by the use of hyperfractionation and low-junction radiotherapy in the treatment of medulloblastoma.

Etoposide-containing regimens with autologous bone marrow transplantation in children with malignant brain tumors

Despite improvements in neurosurgical and neuroradiotherapeutic techniques, children with malignant brain tumors have a dismal prognosis. In an attempt to improve the efficacy of cytotoxic therapy, dose intensification of effective chemotherapeutic agents followed by autologous bone marrow transplantation (BMT) has been tried. Between May 1991 and August 1996, high-dose chemotherapy and autologous BMT were administered to 11 children with malignant brain tumors: 10 had recurrent (n=8) or progressive (n=2) disease, and 1 was treated before progression. The histological diagnoses were medulloblastoma (3), glioblastoma multiforme (2), supratentorial PNET (2), ependymoma (2), anaplastic astrocytoma (1), and anaplastic oligodendroglioma (1). In 6 of the 11 patients measurable disease was present at the time of BMT. The preparative regimen included BCNU 600 mg/m2and VP16 1500 mg/m2in 5 cases, and thiotepa 900 mg/m2and VP16 1500 mg/m2in 6 cases. The median times to achieve a neutrophil count over 0.5×109/l and a platelet count over 50×109/l were 14 and 28 days, respectively. The overall incidence of severe toxicity (grade III–IV) was 18% and consisted of oropharyngeal mucositis and diarrhea. Among the 6 patients with measurable disease at the time of BMT there were 2 with stable disease, whereas 4 patients had tumor progression: all these patients died of tumor recurrence 2–10 months after BMT. Five patients in whom there was no evidence of disease at the time of BMT are alive and free of progression with a median follow-up of 20 months (range 3–67). These preliminary results show that high-dose chemotherapy and BMT may be effective in children with malignant brain tumors. Etoposide-containing regimens seem to have significant activity in this setting, and the toxicity was manageable. The most important variable prognostic for progression-free survival is the disease status at the time of transplantation.

Acute Lymphoblastic Leukemia in a Girl Treated for Osteosarcoma

Acute lymphoblastic leukemia (ALL) was diagnosed in a 13-year-old girl who had been treated previously for osteosarcoma of the left distal femur (23 months after her first cancer onset and 12 months after the end of treatment). The patient started chemotherapy for ALL and achieved complete remission; she is in continuous complete remission 5 years after the diagnosis of secondary ALL and 7 years after the onset of osteosarcoma.

GROWTH HORMONE TREATMENT IN IRRADIATED CHILDREN WITH BRAIN TUMORS

We assessed the efficacy of GH treatment in 25 GH deficient patients irradiated for brain tumors (eight with glioma cranio-irradiated, eleven with medulloblastoma and six with ependymoma craniospinal-irradiated). We administered GH at doses of 0.6-0.9 IU/kg/week for one to three years at least two years after diagnosis of the tumor. We assessed the efficacy of the treatment each year by comparing the values of height velocity over bone age and change in the ratios progression of chronological age/progression of bone age and progression of statural age/progression of bone age. The treatment promoted satisfactory growth; better results were obtained in patients with glioma, who received cranial irradiation only, than in those with medulloblastoma or ependymoma, who received spinal irradiation as well. Moreover, the growth prognosis improved, especially in the cranio-irradiated patients. In our series of patients four presented tumor recurrence; these results did not differ significantly from those in irradiated patients with cerebral tumors who were not treated with GH.

Results of a Multicenter Retrospective Study on Pediatric Brain Tumors in Italy

This retrospective study was undertaken to evaluate the clinical characteristics, course and treatment of children (0–14 years of age) diagnosed with a primary CNS tumor during the period 1976–1982 in Italy. Four hundred and sixty-two patients (263 males and 199 females) were followed by 18 various neurosurgical and pediatric oncology centers. The histologic types most frequently reported were: medulloblastoma (23 %), astrocytoma (16 %), ependymoma (11 %) and spongioblastoma (11 %). Of the 388 patients who underwent surgery, radical excision was reported in 42 %, partial excision in 32 %, biopsy only in 6 %, and unqualified surgery in 4 %; 19 % had no surgery. Radiotherapy and chemotherapy combined were administered in 61 % of the 143 patients followed at pediatric oncology centers; 19 % received radiotherapy alone, 3 % chemotherapy alone, and 17 % neither treatment. Forty-six percent of the patients were reported alive, 40 % dead, and 14 % lost to follow-up. Performance status was identified for 62 patients. The investigation revealed marked differences in the therapeutic treatment administered, thus precluding valid data analysis. This emphasizes the need to coordinate efforts among the institutions and the disciplines involved in the treatment of this form of childhood cancer.