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.

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Osteosarcoma, the most common type of primary malignant tumour that develops in bone, can be classified into several different sub-types. While the majority of osteosarcomas are highly malignant, there are some lowgrade variants. Since the introduction of chemotherapy into the multi-modal treatment regimen of high-grade osteosarcoma, its prognosis has impressively improved, with longterm survival being achieved in two-thirds of all patients. This review summarises current chemotherapeutic treatment strategies in classical osteosarcoma and also addresses the indication for chemotherapy in more unusual types and variants. It emphasises the need for treatment in specialised centres and within prospective, multi-institutional trials, amongst which EURAMOS1 and EURO-B.O.S.S are currently active in many European countries.Résumé L'ostéosarcome est la tumeur osseuse la plus fréquente, cependant la plupart des ostéosarcomes ont une haute malignité, peu sont de malignité de bas de grade. Depuis l'utilisation de la chimio thérapie dans le traitement des ostéosarcomes de haute malignité, le pronostic a été très nettement amélioré, permettant une survie à long terme chez les deux tiers des patients. Cet article fait la revue des différentes stratégies thérapeutiques de chimiothérapie dans le traitement de l'ostéosarcome et de ses différents types. Il met en évidence que les traitements doivent être réalisés dans des centres spécialisés avec des études prospectives, multi sites, comme celles réalisées avec EURAMOS 1 et EURO-BOSS dans les pays européens.

Background: Local recurrence (LR) in osteosarcoma is associated with very poor prognosis. We sought to evaluate which factors correlate with LR in patients who achieved complete surgical remission with adequate margins. Patients and methods:We analyzed 1355 patients with previously untreated high-grade central osteosarcoma of the extremities, the shoulder and the pelvis registered in neoadjuvant Cooperative Osteosarcoma Study Group trials between 1986 and 2005. Seventy-six patients developed LR.Results: Median follow-up was 5.56 years. No participation in a study, pelvic tumor site, limb-sparing surgery, soft tissue infiltration beyond the periosteum, poor response to neoadjuvant chemotherapy, failure to complete the planned chemotherapy protocol and biopsy at a center other than the one performing the tumor resection were significantly associated with a higher LR rate. No differences were found for varying surgical margin widths. Surgical treatment at centers with small patient volume and additional surgery in the primary tumor area, other than biopsy and tumor resection, were significantly associated with a higher rate of ablative surgery.Conclusions: Patient enrollment in clinical trials and performing the biopsy at experienced institutions capable of undertaking the tumor resection without compromising the oncological and functional outcome should be pursued in the future.

Bone tumors, particularly osteosarcomas and members of the Ewing Sarcoma Family of Tumors (ESFT), are typical malignancies of adolescents and young adults. Current diagnostic and therapeutic guidelines for patients of all ages were developed in this specific age group. The aim of bone sarcoma therapy should be to cure the patient from both the primary tumor and all (micro-)metastatic deposits while maintaining as much (extremity) function and causing as few treatment-specific late effects as possible. Bone sarcoma therapy requires close multidisciplinary cooperation. Usually, it consists of induction chemotherapy, followed by local therapy of the primary tumor (and, if present, primary metastases) and further, adjuvant chemotherapy. Local treatment for osteosarcoma should be surgery whenever feasible. Surgery is also gaining importance in ESFT, which was long considered a domain of radiotherapy. Modern reconstructive techniques continue to expand the indications for limb salvage, particularly for patients who have not yet reached skeletal maturity. Treatment within the framework of prospective, multi-institutional trials should be considered standard of care not only for children, but also for affected adolescents and (young) adults. Such trials are essential in guaranteeing that all patients have access to appropriate care and that progress from biological studies can be translated into prognostic improvements without undue delay. The rarity of bone sarcomas increasingly requires trials to be multinational.

The management of pulmonary metastases poses a challenge to the multidisciplinary team involved in the treatment of osteosarcoma. A postal survey on the management of pulmonary metastases in osteosarcoma involving 17 representatives from international study groups and selected institutions was performed in which a response rate of 94% was achieved. The results showed uniform approaches in areas like the imaging methods used for initial staging and the use of manual exploration with thoracotomy. However, it demonstrated diverse practices regarding exploration of the unaffected site in unilateral pulmonary disease, and the approach to lesions disappearing under chemotherapy. Furthermore, agreement on the size of a lesion considered to distinguish between benign and of metastatic origin, varied. Based on the survey and a review of the current literature, detection methods and principles of multimodal therapy will be discussed. Prognostic factors in synchronous and metachronous pulmonary metastases and their implications for a multimodal therapy is also presented.

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