Search

Objective: The aim of the CWS 96 Study was to achieve an optimal treatment in children and adolescents with soft tissue sarcoma (STS) implementing a further refinement of risk-adapted allocation to chemotherapy, surgery and radiotherapy., Methods: Treatment stratification was based on tumour histology, TNM status, postsurgical stage, localisation and age. Local tumour control was ensured by surgery and risk-adapted radiotherapy., Results: From 1995 to 2002, 89 patients were registered in Austria. The 3-year event-free survival (EFS) and overall survival rates (OS) were 63% +/- 6% and 71% +/- 6%, respectively. 59/89 patients had localised RMS-like (rhabdomayosarcoma) STS (EFS 73% +/- 7%), 14 had localised NON-RMS STS (EFS 54% +/- 16%) and 15 patients had metastatic disease at diagnosis (EFS 33% +/- 12%), 1 patient had fibromatosis. The EFS rates at 3 years in patients with localised RMS-like tumours according to risk group were 92% +/- 8% for low and standard risk (12 patients) and 67% +/- 8% for high risk (47 patients). Favourable primary tumour sites of nonmetastatic RMS-like STS i.e. orbit, head/neck nonparameningeal or genitourinary non-bladder/prostate were diagnosed in 15 patients (1/15 patients died). In 44 patients with unfavourable localisation such as parameningeal, genitourinary bladder/prostate, extremity and others, 7 deceased. The 3 year EFS according to histology in patients with RMS-like STS was 61% +/- 11% for RME (embryonal RMS ) (28 patients) and 71% +/- 15% for RMA (alveolar RMS) (10 patients). The most common treatment failure was local relapse occurring in 21% of patients in the high-risk group., Conclusion: Risk-adapted individualisation of treatment led to a reduction of chemotherapy in the low and standard risk group without compromising survival. The outcome of RME and RMA was similar in this cohort of patients. These preliminary results after a median observation time of 2.5 years confirm the CWS 96 strategy.

Background: Identification of biological factors may provide tools to discriminate poor risk neuroblastoma patients of diagnosis, to ultimately offer risk adapted treatment intensity., Procedures: Tumour cell DNA content, MYCN amplification (NMA), deletion of the short arm of chromosome 1 (del 1p) as well as three serological markers were assessed in 179 children with neuroblastoma., Results: Localised regional disease (stage 1 to 3) was diagnosed in 98 patients, and disseminated disease in 81 patients (65 with stage 4, 16 with stage 4s). Median age at diagnosis was 12 months and the median observation time 4 years. Sixty-seven of 179 patients had near di-tetraploid tumours (37%), with a significantly worse prognosis of 44% overall survival at 4 years in comparison with 88% in near triploid tumours (P < .001). The near di-tetraploid group showed a significant correlation with additional adverse biological factors (NMA, del 1p: P < 0.001), age over 1 year (P< 0.001), clinical stage 4 (P< 0.001), elevated ferritin (P = 0.023), and elevated LDH (P< 0.001). Multivariate analysis based on the overall (OS) and event free survival (EFS) estimations revealed that near di-tetraploidy was the most powerful biological factor, with a P-value of <0.001 for EFS and OS, followed by NMA (P = 0.015) for OS and del 1p (P= 0.047) for EFS., Conclusions: This analysis underlines the important influence of near di-tetraploidy on prognosis, and suggests that more efforts should be undertaken to implement this factor in future studies.

Background: Encouraged by Japanese reports of the benefits of screening 6 month-old infants for neuroblastoma, a neuroblastoma screening program was introduced in Austria in 1991. However, because of concerns related to "overdiagnosis" by screening at this age, the screening test was performed at a later age., Methods: From March 1991 to February 1995 neuroblastoma screening was performed on filter paper urine specimens in 100,043 Austrian infants (median age 8.5 months). Primary analysis of urine catecholamines (vanillylmandelic acid and homovanillic acid was performed by use of an E1A method. Questionable or positive results were confirmed by high performance liquid chromatography (HPLC). A double retest was requested following a positive HPLC result., Results: Twenty-one infants were admitted to a hospital following repeatedly elevated values of vanillymandelic acid (VMA) and/or homovanillic acid (HVA). Eleven infants were found to have neuroblastoma (three stage 1, four stage 2B, four stage 3). Treatment consisted of surgery alone with total or subtotal resection in eight cases, surgery and chemotherapy in two cases, and chemotherapy alone in one case. Biologic features were assessed in all tumors excluding ploidy in one case. The majority of the tumors analyzed were near-triploid (9/10), however, two tumors revealed N-myc amplification., Conclusions: Our results demonstrate that stage distribution and biologic features of neuroblastomas diagnosed by screening at 8.5 months are different from the results of screening at 6 months. Furthermore, the detection of one neuroblastoma among 9,100 screened infants is significantly lower than the incidence of the Japanese screening program. Our results suggest that screening at an age of 7 to 10 months reduces overdiagnosis and may be of more benefit than earlier screening.

The aim of this study was to investigate the feasibility of a neuroblastoma screening programme for children in late infancy, based on collaboration of general paediatricians and practitioners in Austria, using the technique of enzyme-linked immunoassay (EIA) for biochemical analyses. Analysis of catecholamine metabolites in spot urine samples by EIA with high performance liquid chromatography as a backup was undertaken. Austrian infants (median age 8.7 months) were screened. Overall compliance was 30%. The EIA method had a high rate (6.7%) of false-positive results. 28 infants were admitted to hospital. In 15 cases, neuroblastoma was found (four stage 1, five stage 2B, six stage 3). The EIA method can be used for neuroblastoma screening, but requires a backup analytical technique in order to avoid unnecessary hospital admissions. The stage distribution and biological features of neuroblastomas diagnosed by screening at a later age are different from those detected by earlier screening. Screening in late infancy might be of more benefit than early screening.

Aims: A multivariate analysis was performed to evaluate the impact of various prospectively evaluated risk factors., Patients and Methods: From January 1987 to December 1993, 120 patients were registered in the study. 108/120 patients were eligible. There were 49 girls and 59 boys with a median age at diagnosis of 14 months (range, 0 to 224 months). Patients were classified according to the Evans classification system. LDH, NSE, Ferritin, N-myc amplification, 1p-deletion and ploidy were evaluated at diagnosis. Treatment intensity was based on the results of primary surgery: surgery only for 22 (20%) stage I and IIA patients (macroscopic residue without lymph node involvement), the 9 IIB patients (8,5%) (macroscopic residue with lymph node involvement) had mild chemotherapy in addition (6 x VCR/CYC) and elective radiation (Rx). Stage III patients were divided into 2 groups: IIIA patients (n = 17/16%) had to have ferritin levels under 300 micrograms/ml, NSE lower than 100 ng/ml and age below 2 years at diagnosis and received 6 alternating cycles of DAMO/ MVDOC. If one of these three criteria was not fulfilled, patients were assigned to the more intensive treatment arm stage IIIB (n = 12/11%), i.e. 9 alternating cycles of DAMO/MVDOC/IPE. Stage IV pts (n = 35/32.5%) received 8 MVDOC/IPE cycles and 20 patients received megatherapy followed by stem cell reinfusion in addition. 13 stage IVs patients (12%) were registered and had elective VCR/CYC and/or liver radiation in case of poor clinical condition. The median observation time is 4.2 years (range, 1 to 7.5)., Results: The survival rate at 3 years was excellent for localized disease and stage IVs with survival rates of 100% for stage I/IIA and 92% for stage IVs. Stage IIIA patients had an EFS rate of 81% whereas stage IIB patients achieved only 69%. Stage IV patients reached 51%, however outcome was especially poor for stage IIIB patients (20%) due to treatment related toxicities. The toxic death rate in the study was 13% (2 surgical deaths, 8 infections, 4 multiple organ failures). Univariate analysis demonstrated the following significant unfavorable risk factors: age over 1 year at diagnosis (58/108 pts, p = 0.006), NSE > 100 ng/ml (26/95 pts, p < 0.0001), Ferritin > 300 ng/ml (19/98 pts, p = 0.007), LDH > 300 (400) U/L, 51/87 pts, p = 0.004), presence of N-myc amplification (17/59 pts, p = 0.001), deletion of the short arm of chromosome 1 (19/74 pts, p < 0.0001) and di/tetraploidy (32/72 pts, p = 0.008). The power of these factors was even stronger in patients with localized disease whereas no significant prediction was observed for stage IV patients. Furthermore a significant correlation of the serological (NSE, ferritin, LDH) and biological factors (N-myc, deletion 1p, di/tetraploidy) was detected in this study. Only NSE was identified as an independent prognostic factor (p = 0.018) whereas no independent factor could be identified within the 3 biological parameters due to their high correlations (Kendall's tau for N-myc and deletion 1p:0.7). However, N-myc (p = 0.005) as well as deletion 1p (p = 0.01) were found significantly more important than di/tetraploidy., Conclusions: Biological classification of neuroblastomas should be mandatory and be the prerequisite for any risk adapted treatment. One serological and 2 biological factors could be a good standard evaluation to identify neuroblastoma patients at risk.