All reovirus subtypes show oncolytic potential in primary cells of human high-grade glioma.

Reoviridae are non-human pathogenic viruses. The family of reoviridae consists of 4 different subtypes. Many studies have proven that the Dearing subtype 3 has oncolytic potential. This potential is related to the RAS protein expression in tumour cells. The aim of this study, was to investigate whether all reovirus subtypes have oncolytic potential and whether there are differences in their efficacy, in particular for high-grade glioma. To evaluate the oncolytic potential, we performed an in vitro head-to-head study for all reovirus subtypes in 5 primary cell cultures of high-grade gliomas. The oncolytic activity was determined using end-point titration with observation of the cytopathogenic effect. For measurement of RAS activity, we performed an immunofluorescent detection stain on all cell cultures. For quantification of the virus, an RT-PCR measurement for all subtypes was performed. All reovirus subtypes showed oncolytic activity in the observed glioma biopsies. These observations correlated with RAS overexpression in the observed cells. All glioma biopsies overexpressed the RAS protein. The quantitative oncolytic potential differed in relation to the single observed cell culture and in relation to the chosen reovirus subtype. To our knowledge, this is the first study showing oncolytic activity for all reovirus subtypes. We show the relationship and correlation between RAS protein overexpression and vulnerability of cells to reovirus. Efficacy of the different subtypes is interindividually different and cannot be forecast.

Update on relapses in unilateral nephroblastoma registered in 3 consecutive SIOP/GPOH studies - a report from the GPOH-nephroblastoma study group.

INTRODUCTION: Treatment and stratification of progressive/relapsed unilateral nephroblastoma (PD) has significantly evolved over the last 20 years. Early PD (≤ 6 months), initial high risk histology, local stage III, multiple site PD and stage IV have been implemented as high risk classification factors and novel drugs have been introduced. PATIENTS AND METHODS: We analysed all 251 patients having had a unilateral nephroblastoma (Stage I-IV) and progressive disease who had been treated according to SIOP9/GPO (n = 77), SIOP93-1/GPOH (n = 93) and SIOP2001/GPOH (n = 81) initially. RESULTS: 3y-overall survival (OS) increased from 43% to 61% and 59% respectively (both p<0.01). 3y-OS for localized stage I-III rose from 43% to 65% and 68% respectively while only little improvement can be seen for initial stage IV patients with 43%, 53% and 44% respectively. Multivariate analysis confirmed high risk histology, local stage III, shorter time to PD, combined relapse as independent risk factors. 26 patients had received high-dose chemotherapy showing 64% 3y-OS compared to 54% for all non-transplanted (p=0.11). CONCLUSION: Structuring the treatment of progressive nephroblastoma as well as introducing new drugs have improved the outcome significantly. However improvement is depending on the specific risk profile. Very high risk tumours are often resistant to conventional treatment, hence an international uniform treatment concept is needed to achieve conclusive results in this small group.

Consultation within the nephroblastoma trial SIOP 2001/GPOH as part of the workload in the trial office.

BACKGROUND: More than 90% of children with cancer are treated in prospective clinical trials and studies in Germany. Consultations are part of the daily work in every study centre. Nevertheless little is known about the kind of requests, the time needed to handle these, and the effect on outcome due to an optimized treatment. PATIENTS: 763 consultations were carried out in 257 patients between the 1st of January 2003 and the 31st of December 2005. 237 of these patients were enrolled in the nephroblastoma trials SIOP 93-01/GPOH (33) and SIOP 2001/GPOH. 20 patients were not registered in any trial at the time of consultation. RESULTS: 61% of all newly diagnosed patients had a consultation by the trial centre during the three year period. The number of consultations per patient was higher in non-university hospitals compared to university hospitals. The mean duration for a consultation was 27 min with a standard deviation of 53.5 min. Most of the requests were related to chemotherapy, 36% to the general management of patients and 15% of all consultations concerned relapsed patients. A highly significant improved 5 year overall survival rate was found for relapsed patients with consultation (65 vs. 10%). This difference may be partly explained by other risk factors for relapse. CONCLUSIONS: Trial centres are competence centres for a specific disease. Consultations are an important task and help to increase the quality of care for patients enrolled in clinical trials and studies. For consultation purposes about 25% of a person month was needed for every 100 new patients enrolled in the SIOP 2001/GPOH trial and study. We estimate this effort to be comparable to other studies.