[Register for the evaluation of side effects after radiation in childhood and adolescence--first results]. / Register zur Erfassung von Spätfolgen nach Strahlentherapie im Kindes- und Jugendalter--erste Ergebnisse.

BACKGROUND: Late effects after radiotherapy in childhood and adolescence have mainly been characterized retrospectively with small patient numbers. Therefore the German Group of Pediatric Radiation Oncology (APRO) established the "RegIster for the evaluation of late Side effects after radiation in childhood and adolescence" (RiSK). After a pilot phase starting in 2001 documentation has been performed all over Germany since 2004. This analysis shows the first results of "RiSK". PATIENTS AND METHODS: Radiation parameters including detailed organ doses as well as toxicity evaluations were collected prospectively from centers all over Germany in the study center. Standardized documentation forms were used. Documentation is planned for all children who receive radiotherapy in one of the German pediatric therapy trials. RESULTS: Until December 31st 2006, 696 documentations of radiotherapy and 526 acute as well as 836 late follow-up documentation forms have been collected. Altogether, 41 patients with late grade 3 and 16 patients with late grade 4-side effects were identified. Side effects mainly concerned joints with functional impairment (after combined radiotherapy and surgery), the bowel, skin and subcutis as well as blood parameters under continued chemotherapy. Patients with late side effects of a higher grade were mainly treated for Ewing's or soft tissue sarcomas (n=235 patients), representing 33.8% of all patients in this study. CONCLUSION: Fortunately, up to now only a few late grade 3 or 4 side effects of radiotherapy are shown for almost 700 documented patients. For further results, especially for the characterization of dose-effect-relationships, this study has to be continued with a higher patient number and a longer follow-up.

Sensitivity of neutral filter elution but not PFGE can be modified by non-dsb chromatin damage.

Hamster V79 fibroblast cells and human squamous carcinoma cells (Caski) were exposed to 60Co radiation and DNA double-strand break (dsb) induction was analysed by DNA elution at neutral pH from polycarbonate filter or out of an agarose matrix in pulsed-field electrophoresis (PFGE). While dsb yields were equal for the two cell lines (using 125-iodine calibration) a reduced responsiveness of filter elution was found for V79 versus Caski cells. This difference could be abolished when additional single-strand breaks (ssb) were introduced by an incubation at 10(-4) M H2O2 for up to 40 min that itself did not give a response in neutral elution. No such lack of specificity for the detection of dsb was seen in electrophoretic elution where also the influence of peroxide incubation was absent. The presumed potential of ssb to modify dsb detection was paralleled by the kinetics of dsb rejoining: a pronounced transient increase of DNA elution from filters was observed for V79 cells (less prominent with Caski cells) at 15-40 which is thought to reflect the occurrence of secondary ssb from incisions during base damage repair. Rejoining measured by PFGE did not show this behaviour. The results suggest that ssb may aid decondensation of the chromatin during lysis of cells required for an efficient release of dsb fragments when supported on filters, but which depends on cell type and is less critical in electrophoretic elution out of an agarose matrix. This involvement of ssb in the neutral filter elution assay appears to be contrary to published data obtained with different experimental systems. The finding of an increase of DNA elution from filters due to hyperthermia at 45 degrees C is also taken to indicate an involvement of non-dsb chromatin damage in the response of filter elution at neutral pH with V79 but not with Caski cells.