Primary Multi-Systemic Metastases in Osteosarcoma: Presentation, Treatment, and Survival of 83 Patients of the Cooperative Osteosarcoma Study Group

Vanessa L Mettmann; Claudia Blattmann; Godehard Friedel; Semi Harrabi; Thekla von Kalle; Leo Kager; Matthias Kevric; Thomas Kühne; Michaela Nathrath; Benjamin Sorg; Mathias Werner; Stefan S Bielack; Stefanie Hecker-Nolting

doi:10.3390/cancers16020275

Primary Multi-Systemic Metastases in Osteosarcoma: Presentation, Treatment, and Survival of 83 Patients of the Cooperative Osteosarcoma Study Group

Cancers (Basel). 2024 Jan 8;16(2):275. doi: 10.3390/cancers16020275.

Authors

Affiliations

¹ Cooperative Osteosarcoma Study Group, Paediatrics 5 (Oncology, Haematology, Immunology), Centre for Paediatric, Adolescent and Women's Medicine, and Stuttgart Cancer Centre, Klinikum Stuttgart-Olgahospital, 70174 Stuttgart, Germany.
² Department of Thoracic Surgery, Faculty of Science, University of Tubingen, 72076 Tubingen, Germany.
³ Heidelberg Ion Beam Therapy Centre (HIT), Department of Radiation Oncology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
⁴ Radiologic Institute, Centre for Paediatric, Adolescent and Women's Medicine, Stuttgart Cancer Centre, Klinikum Stuttgart-Olgahospital, 70174 Stuttgart, Germany.
⁵ St. Anna Children's Hospital, University Hospital for Paediatric and Adolescent Medicine of the Medical University and St. Anna Children's Cancer Research Institute (CCRI), 1090 Vienna, Austria.
⁶ University Children's Hospital Basel, 4031 Basel, Switzerland.
⁷ Department of Paediatrics and Children's Cancer Research Centre, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.
⁸ Paediatric Haematology and Oncology, Klinikum Kassel, 34125 Kassel, Germany.
⁹ Osteopathology Reference Centre, Institute of Pathology, Vivantes Klinikum im Friedrichshein, 10249 Berlin, Germany.
¹⁰ Department for Paediatric Haematology and Oncology, University's Children's Hospital Muenster, 48149 Muenster, Germany.

Abstract

Background: To evaluate patient and tumour characteristics, treatment, and their impact on survival in patients with multi-systemic metastases at initial diagnosis of high-grade osteosarcoma. Precedure: Eighty-three consecutive patients who presented with multi-systemic metastases at initial diagnosis of high-grade osteosarcoma were retrospectively reviewed. In cases of curative intent, the Cooperative Osteosarcoma Study Group recommended surgical removal of all detectable metastases in addition to complete resection of the primary tumour and chemotherapy.

Results: Eighty-three eligible patients (1.8%) were identified among a total of 4605 individuals with high-grade osteosarcoma. Nine (10.8%) of these achieved complete surgical remission, of whom seven later had recurrences. The median follow-up time was 12 (range, 1-165) months for all patients. Actuarial event-free survival after 1, 2, and 5 years was 9.6 ± 3.2%, 1.4 ± 1.4%, and 1.4 ± 1.4%, and overall survival was 54.0 ± 5.6%, 23.2 ± 4.9%, and 8.7 ± 3.3%. In univariate analyses, elevated alkaline phosphatase before chemotherapy, pleural effusion, distant bones as metastatic sites, and more than one bone metastasis were negative prognostic factors. Among treatment-related factors, the microscopically complete resection of the primary tumour, a good response to first-line chemotherapy, the macroscopically complete resection of all affected tumour sites, and local treatment (surgery ± radiotherapy) of all bone metastases were associated with better outcomes. Tumour progression under first-line treatment significantly correlated with shorter survival times.

Conclusion: The outlook for patients with multi-systemic primary metastases from osteosarcoma remains very poor. The utmost importance of surgical resection of all tumour sites was confirmed. For unresectable bone metastases, radiotherapy might be considered. In the patient group studied, standard chemotherapy was often insufficiently effective. In the case of such advanced disease, alternative treatment options are urgently required.

Keywords: combined metastases; multi-systemic metastases; osteosarcoma; primary metastases; survival.

Grants and funding

The studies from which these patients originate were supported by Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Fördergemeinschaft Kinderkrebs Zentrum Hamburg, and Förderkreis krebskranke Kinder Stuttgart. Michaela Nathrath was supportet by the Helga und Heinrich Holzhauer Stiftung.