Purpose: Precise and comprehensive analysis of neuroblastoma genetics is essential for accurate risk evaluation and only pangenomic/multilocus approaches fulfill the present-day requirements. We present the establishment and validation of the PCR-based multiplex ligation-dependent probe amplification (MLPA) technique for neuroblastoma.Experimental Design: A neuroblastoma-specific MLPA kit was designed by the SIOP Europe Neuroblastoma Biology Committee in cooperation with MRC-Holland. The contained target sequences cover 19 chromosomal arms and reference loci. Validation was performed by single locus and pangenomic techniques (n ¼ 174). Dilution experiments for determination of minimal tumor cell percentage were performed and testing of reproducibility was checked by interlaboratory testing (n ¼ 15). Further 156 neuroblastomas were used for establishing the amplification cutoff level.Results: The MLPA technique was tested in 310 neuroblastomas and 8 neuroblastoma cell lines (including validation and amplification cutoff level testing). Intertechnique validation showed a high concordance rate (99.5%). Interlaboratory MLPA testing (k ¼ 0.95, P < 0.01) revealed 7 discrepant of 1,490 results (0.5%). Validation by pangenomic techniques showed a single discordance of 190 consensus results (0.5%). The test results led to formulation of interpretation standards and to a kit revision. The minimal tumor cell percentage was fixed at 60%.Conclusions: The recently designed neuroblastoma-specific MLPA kit covers all chromosomal regions demanded by the International Neuroblastoma Risk Group for therapy stratification and includes all hitherto described genetic loci of prognostic interest for future studies and can be modified or extended at any time. Moreover, the technique is cost effective, reliable, and robust with a high interlaboratory and intertechnique concordance.

ZusammenfassungFragestellung: Nicht kostendeckende Durchführung von onkologischen Chemotherapien kann für jede Klinik der finanzielle Ruin sein. Im Folgenden wird über ein erfolgreiches Konzept zum aktiven Kostenmanagement von gynäkologisch-onkologischen Therapien einer Universitätsfrauenklinik berichtet. Material und Methodik: Das Modell beinhaltet vier Stufen: 1. finanzielle Ist-Analyse, 2. Vorkalkulation der standardisierten Medikamentenkosten, 3. ein ¹Case-by-Case-Managementª mit kostenoptimierender Einzelfallentscheidung und 4. Nachkalkulation der tatsächlichen individuellen Medikamentenkosten und Korrektur von möglichen Abrechnungsfehlern. Ergebnisse: In Abhängigkeit verschiedener Faktoren konnte jeder einzelnen Patientin eine kostendeckende Abrechnung unter Aufrechterhaltung des Therapieniveaus zugeordnet werden. Innerhalb eines Jahres wurden so die onkologischen Medikamentenkosten um 523 208 EUR (± 58,7%) gesenkt, die Anzahl der Chemozyklen aber nur um 9,1% reduziert. Weitere Ursachen für finanzielle Verluste wurden erkannt und abgestellt. Schlussfolgerung: Ein aktives Kostenmanagement kann dazu beitragen, dass onkologische Therapien unter Beibehaltung des Therapiestandards kostendeckend an einer Universitätsklinik durchgeführt werden können. AbstractPurpose: Non cost-covering oncological chemotherapies can be the financial ruin of any clinic. We report here on a successful concept for active cost management of gynecological-oncological therapies in a university OB/GYN clinic. Material and Method: The model consists of four steps: 1. financial as-is analysis, 2. pre calculation of standardised pharmaceutical costs, 3. a case-by-case management with cost-optimizing individual decisions, and 4. post calculation of actual individual pharmaceutical costs and correction of potential reimbursement mistakes. Results: Depending on several factors for each individual patient a cost-covering pathway was defined while maintaining the standard of care. Within one year the cost of oncological pharmaceuticals could be reduced by 523 208 EUR (± 58.7 %), although the number of chemo cycles only decreased by 9.1%. Additional sources of financial deficits were identified and eliminated. Conclusion: An active cost management can contribute to making oncologic therapies cost covering without reducing the standard of care in a university clinic.