Background: Ewing’s tumors (ET) are rare in patients over the age of 40 years. Published data on presentation, treatment, and clinical outcome are limited. Patients and Methods: We present a retrospective analysis of data from 47 patients in this age group diagnosed with ET and enrolled in the 2 consecutive trials, EICESS 92 and EURO-E.W.I.N.G. 99. The median age at diagnosis was 47.7 years (range, 40–68.6 years). Results: The median follow-up was 2.23 years from diagnosis (range, 0.35–12.92 years). 72.3% of patients were found to have localized disease, and 27.7% had primary metastases. Good clinical response to induction therapy was observed in 55%, and 73% of patients showed good histological response. The event-free survival was 0.77 at 1 year and 0.50 at 3 years (n = 44). Conclusion: ET are rare in patients over the age of 40 years. With adequate multimodal therapy, the results in terms of survival are comparable to those in adolescence. Specific age-adapted treatment regimens are not established. Patients should be enrolled in international trials, and if necessary treatment should be adjusted for lower tolerance and co-morbidity.

Resistance to systemic drug therapy is a major reason for the failure of anticancer therapies. Here, we tested doxorubicin-loaded human serum albumin (HSA) nanoparticles in the neuroblastoma cell line UKF-NB-3 and its ABCB1-expressing sublines adapted to vincristine (UKF-NB-3rVCR1) and doxorubicin (UKF-NB-3rDOX20). Doxorubicin-loaded nanoparticles displayed increased anticancer activity in UKF-NB-3rVCR1 and UKF-NB-3rDOX20 cells relative to doxorubicin solution, but not in UKF-NB-3 cells. UKF-NB-3rVCR1 cells were re-sensitised by nanoparticle-encapsulated doxorubicin to the level of UKF-NB-3 cells. UKF-NB-3rDOX20 cells displayed a more pronounced resistance phenotype than UKF-NB-3rVCR1 cells and were not re-sensitised by doxorubicin-loaded nanoparticles to the level of parental cells. ABCB1 inhibition using zosuquidar resulted in similar effects like nanoparticle incorporation, indicating that doxorubicin-loaded nanoparticles successfully circumvent ABCB1-mediated drug efflux. The limited re-sensitisation of UKF-NB-3rDOX20 cells to doxorubicin by circumvention of ABCB1-mediated efflux is probably due to the presence of multiple doxorubicin resistance mechanisms. So far, ABCB1 inhibitors have failed in clinical trials probably because systemic ABCB1 inhibition results in a modified body distribution of its many substrates including drugs, xenobiotics, and other molecules. HSA nanoparticles may provide an alternative, more specific way to overcome transporter-mediated resistance.

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