Alessandro Sandri

Treatment with oral etoposide for childhood recurrent ependymomas

In this study the authors retrospectively evaluated the feasibility and effectiveness of prolonged oral etoposide therapy in children with recurrent ependymoma. Twelve ependymoma patients with documented recurrent or persistent disease were treated between May 1998 and October 2003. All patients were treated monthly with oral VP-16 administered at a dose of 50 mg/m2/d for 21 days, with a 7-day interval between cycles, for a planned minimum number of six cycles. Response (complete plus partial) after two cycles occurred in 5 of the 12 patients (41.6%). Response plus stable disease occurred in 10 of the 12 (83.3%), with a median duration of response or stable disease of 7 months (range 4-30). The median survival was 7 months; the 2-year progression-free survival was 16.7%. These results emphasize that oral etoposide is an attractive option for childhood recurrent ependymomas in terms of administration, tolerability, and neuroradiologic response.

Survival after relapse in children with solid tumors: A follow-up study from the Italian off-therapy registry†

Despite the increased survival of children with solid tumors, a significantproportion of cases still relapse following treatment discontinuation, and knowledge about the long‐term outcome of this selected group of patients remains incomplete.

Schinzel-Giedion syndrome with sacrococcygeal teratoma

A case of Schinzel-Giedion syndrome, a rare malformation syndrome, is described. In addition to the classic features of the syndrome, the patient had a malignant sacrococcygeal teratoma and agenesis of the corpus callosum. So far, this patient is the fifth case with a sacrococcygeal tumor and the eighth with anomalies of the corpus callosum. According to this occurrence of uncommon tumors, risk of malignancy could be a component of Schinzel-Giedion syndrome.

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.

A child with hyperferritinemia: Case report

Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare condition caused by mutations in the gene coding for the light chain of ferritin; it does not lead to iron overload, but it is associated with the risk of developing a bilateral nuclear cataract also in childhood. On the contrary, a raise of serum ferritin levels is a common finding in pediatrics. We describe here a case of HHCS that offers some interesting clues for the daily practice. Our patient is a 6 year old Italian boy who came to our attention after some time of diagnostic uncertainties because of persistently high levels of ferritin with no apparent cause. We were guided to the suspect of this syndrome by the family history (5 members with various degrees of cataract developed in first infancy). High levels of serum ferritin and specific genetic testing (mutation A37C) confirmed the diagnosis. This case underlines the need of considering rare genetic syndromes, including hereditary hyperferritinemia cataract syndrome, in the differential diagnosis of raised serum ferritin in children and the importance of paying attention to family history in considering a patient with isolated raised levels of serum ferritin.

A complex karyotype including a t(2;11) in a paediatric ependymoma: case report and review of the literature

Ependymomas are glial tumours representing approximately 5–10% of all intracranial tumours and are the third most common primary brain tumour in childhood. Only a few karyotypic studies on paediatric ependymomas have been published and no specific chromosomal aberration has been specifically related to this type of cancer. We performed cytogenetic analysis of an ependymoma in an 11-year-old boy. Our patient showed a complex karyotype, characterized by a near-tetraploidy and a sole structural unbalanced aberration: der(2)t(2;11)(q11.2;q13.1), which has not been described before. We here discuss such cytogenetic findings, comparing our data with those reported in the literature.