Bone metastases in medulloblastoma--single institution experience.

BACKGROUND: Medulloblastoma has one of the highest rates of metastasis outside the central nervous system (CNS). Bone metastases are the most common lesions, although lymph node and visceral spread have also been reported. OBJECTIVE: To present patients with bone metastasis in medulloblastoma and discuss their radiologic appearances and treatment approach. PATIENTS AND METHODS: From 1993 to 2008, 82 patients diagnosed with medulloblastoma were treated at the Institute for Oncology and Radiology of Serbia. Three (3.6%) developed extraneural metastasis (ENM). In primary treatment, patients were treated with surgery, craniospinal radiotherapy with local boost to tumor bed, and adjuvant chemotherapy [lomustine (CCNU) and vincristine]. Of the three patients with ENM, all developed bone metastases at the time of relapse. Relapse occurred within 17 to 42 months of initial diagnosis. Patients received secondary chemotherapy and palliative radiotherapy to the affected bone in two cases. RESULTS: Among these three patients, case 1 had initially a solitary lytic lesion. Case 2 had diffuse blastic lesions and also bone marrow involvement. Case 3 had multiple mixed lytic-sclerotic lesions but later developed lymph node metastasis and metastases to both breasts, as well. All patients were without concurrent CNS involvement at the time of ENM. Unfortunately, after initial partial response, the three patients died at 24, 13, and 18 months after detection of metastases, respectively. CONCLUSION: With prolonged survival times in children with medulloblastoma, more emphasis should be placed on the possibility of systemic involvement. A greater understanding of the pathogenesis of the systemic metastases may be valuable in designing future, more aggressive multimodal therapy.

Incidence of primary central nervous system tumors among children in Belgrade (Serbia), 1991-2004.

The aim of this survey was to estimate the incidence of primary CNS tumors among children aged 0-14 in Belgrade during the period 1991-2004. Incidence rates were age-adjusted according to the world standard population. The average age-adjusted incidence rates were 3.4/100,000 for boys, 2.4/100,000 for girls, and 2.9/100,000 for both genders. There was a nonsignificant tendency toward increased CNS tumor incidence (y = 2.547 + 0.052 x, p = .549). The age-specific incidence rates were 3.0/100,000 (0-4 years), 2.2/100,000 (5-9 years), and 3.8/100,000 (10-14 years). Among the population aged between 0 and 14, the cumulative probability of acquiring primary CNS tumors was 1 per 1961 for boys and 1 per 2778 for girls. Astrocytoma was the most common pathohistological type of primary CNS tumors accounting for 41.5% of cases.

The role of magnetic resonance imaging in the diagnosis of postoperative spondylodiscitis.

BACKGROUND: Spondylodiscitis, discitis associated with vertebral osteomyelitis may follow disc-removal surgery. A targeted successful treatment of spinal infections requires clinical and laboratory data that are completed by the contribution of imaging procedures. Neuroimaging provides precise information on correct topography, localization, propagation, and differential diagnosis of spinal infectious lesions. The aim of this study was to present magnetic resonance imaging (MRI) findings in patients with postoperative spondylodiscitis. METHODS: MRI was performed in 6 patients aged 29-50, with clinically suspected postoperative spondylodiscitis. Initial examination was performed 3-8 weeks after surgery and 3, 6, or 12 months after the treatment by antibiotics. Patients underwent MRI on a IT imaging unit (Siemens, Magnetom-Impact), including sagittal T1W and T2W images and axial T1W images before and after the administration of gadolinium contrast medium. RESULTS: MRI findings included: significantly decreased signal intensity with the loss of distinction between vertebral body and intervertebral disc space on T1W, increased signal intensity in the adjacent vertebral body and end-plates on T2W, contrast enhancement of vertebral body and disc space and paravertebral soft tissue changes. Follow-up examinations performed 3, 6, or 12 months after the treatment showed less abnormal signal intensities on both T1- and T2-weighted images. CONCLUSION: Postoperative spondylodiscitis is a rare but severe complication of lumbar disc surgery. Since conventional imaging techniques are not reliable for detecting spondylodiscitis in its early stages, MRI is of great significance in the diagnosis of postoperative spondylodiscitis.

[Craniospinal radiotherapy in combined therapy of medulloblastoma in children and adolescents]. / Kraniospinalna radioterapija u kombinovanom lecenju meduloblastoma dece i omladine.

PURPOSE: The aim of this study was: 1. to evaluate treatment results of combined therapy (surgery, postoperative craniospinal radiotherapy with or without chemotherapy) and 2. to assess factors affecting prognosis (extend of tumor removal, involvement of the brain stem, extent of disease, postoperative meningitis, shunt placement, age, sex and time interval from surgery to start of postoperative radiotherapy). PATIENTS AND METHODS: During the period 1986-1996, 78 patients with medulloblastoma, aged 1-22 years (median 8.6 years), were treated with combined modality therapy and 72 of them were evaluable for the study endpoints. Entry criteria were histologically proven diagnosis, age under 22 years, and no history of previous malignant disease. The main characteristics of the group are shown in Table 1. Twenty-nine patients (37.2%) have total, 8 (10.3%) near total and 41 (52.5%) partial removal. Seventy-two of 78 patients were treated with curative intent and received postoperative craniospinal irradiation. Radiotherapy started 13-285 days after surgery (median 36 days). Only 13 patients started radiotherapy after 60 days following surgery. Adjuvant chemotherapy was applied in 63 (80.7%) patients. The majority of them (46; 73%) received chemotherapy with CCNU and Vincristine. The survival rates were calculated with the Kaplan-Meier method and the differences in survival were analyzed using the Wilcoxon test and log-rank test. RESULTS: The follow-up period ranged from 1-12 years (median 3 years). Five-year overall survival (OS) was 51% and disease-free survival (DFS) 47% (Graph 1). During follow-up 32 relapses occurred. Patients having no brain stem infiltration had significantly better survival (p = 0.0023) (Graph 2). Patients with positive myelographic findings had significantly poorer survival compared to dose with negative myelographic findings (p = 0.0116). Significantly poorer survival was found in patients with meningitis developing in the postoperative period, with no patient living longer than two years (p = 0.0134) (Graph 3). By analysis of OS and DFS in relation to presence of the malignant cells in liquor, statistically significant difference, i.e. positive CSF cytology was not obtained, which was of statistical importance for survival (p = 0.8207). Neither shunt placement nor shunt type showed any impact on survival (p = 0.5307 and 0.7119, respectively). Children younger than three years had significantly poorer survival compared to those older than 16 years (p = 0.0473). Although there was a better survival rate in females than in males this was not statistically significant (p = 0.2386). The analysis results of treatment showed that significantly better survival occurred in patients in whom total or subtotal tumor removal was possible (p = 0.0022) (Graph 4). Patients who started radiotherapy within two months after surgery have better survival, but again this was not statistically significant, probably due to the small number of patients receiving delayed radiotherapy (p = 0.2231) (Graph 5). CONCLUSION: Based on this factors standard and high risk group could be defined. Combined chemotherapy should to be investigated particularly for high risk subgroup. Future research should be done to define new therapeutic modalities (gene therapy, compounds active in tumor antiangiogenesis etc).

The impact of cranial irradiation on GH responsiveness to GHRH plus GH-releasing peptide-6.

Patients treated with cranial radiation are at risk of GH deficiency (GHD). We evaluated somatotroph responsiveness to maximal provocative tests exploring the GH releasable pool in relation to the impact of radiation damage to the hypothalamic-pituitary unit. The GH-releasing effect of GHRH plus GH secretagogue [GH-releasing peptide (GHRP)-6] (GHRH+GHRP-6) was studied in 22 adult patients (age, 23.2 +/- 1.4 yr; 8 female and 14 male; mean body mass index, 22.6 +/- 0.7 kg/m(2)) who received cranial radiation for primary brain tumor distant from hypothalamic-pituitary region 7.6 +/- 0.7 yr before GH testing. Two stimulatory tests for GH secretion were employed: insulin tolerance test (ITT, 0.15 IU/kg regular insulin i.v. bolus); and GHRH+GHRP-6 test: GHRH (Geref Serono, Madrid, Spain; l microg/kg) plus GHRP-6 (CLINALFA, Laufelingen, Switzerland; 1 microg/kg) as i.v. bolus. Serum GH was measured (Delphia; Perkin Elmer, Wallac, Turku, Finland) at -30, -15, 0, 15, 30, 45, 60, 90, and 120 min. Anterior pituitary function was normal in all except in 1 female with hyperprolactinemia. Twelve out of 22 irradiated patients were GH-deficient (GHD) with both tests. Eleven out of 22 (50%) irradiated patients were severely GHD, according to the ITT (GH < 3 microg/liter; mean GH peak, 1.5 +/- 0.5 microg/liter). In 9 irradiated patients, in whom ITT was performed as well, mean peak GH after the GHRH+GHRP-6 test was 6.2 +/- 0.8 microg/liter, which is considered as severe GHD, according to our own cut-off for the test (peak GH < 10 microg/liter). GH responses to both tests were highly concordant, but the differential in the GH peak concentrations between GHD and non-GHD irradiated patients was significantly larger for the GHRH+GHRP-6 test than that for the ITT. The 2 discordant responses, i.e. poor response to the ITT and good response to the GHRH+GHRP-6 test, were found in 1 hyperprolactinemic female patient and in 1 other female. One irradiated patient was diagnosed as GHD only with the combined test, because ITT was contraindicated because of epilepsy. PRL and cortisol responses to ITT were normal in all irradiated patients and did not depend on the GH status. IGF-I levels were not informative or discriminative between the GHD and non-GHD irradiated adult patients. In conclusion, the use of GH secretagogues plus GHRH is an easy, reliable and accurate way of assessing GH secretion in cranially irradiated patients. Impairment of the GH releasable pool in the irradiated patients, with a maximal provocative test, reflects alterations in the hypothalamic-pituitary unit caused by radiotherapy.