This manuscript describes the experience from registration until randomisation for a cohort of 2260 patients with osteosarcoma who joined the EURAMOS-1 trial. This includes pre-operative chemotherapy and surgery. It sets out the practical issues in collaboration and in achieving randomisation.

To our knowledge, this is the first report of survival estimates derived from large cohorts of unselected patients with second and subsequent osteosarcoma recurrences. It confirms the overwhelming importance of surgical clearance. Prognostic indicators after rerecurrences resemble those known from first recurrence. The exact role of re-treatment with chemotherapy, particularly in the adjuvant situation, remains to be defined.