The aim of the project is to improve treatment outcomes in patients with primary malignant bone tumours, refractory to standard therapy, by increasing the availability of advanced therapy, as well as to develop treatment options using advanced molecular diagnostics for patients who have not responded to the standard therapeutic regimen, and to introduce modern diagnostics for risk stratification and for the use in molecularly targeted therapies.
The Project will be conducted at the Institute of Mother and Child (IMC) and the National Research Institute of Oncology (as a Collaborator). The scope of the project is to cover the entire population of children, adolescents and young adults aged 9 to 21, who progressed to first-line therapy or who presented with a recurrence of Ewing’s sarcoma or osteosarcoma. The Project also provides for collaboration with a patient organisation – SARCOMA Association for Helping Patients with Sarcomas and Melanomas (as a Collaborator). Within the scientific part of the Project, it is also planned to engage subcontractors, in particular, a research unit having the potential for cell and tissue culture work and molecular biology, and with the unit specializing in bioequivalence and bioavailability studies of medicinal products.
Primary bone tumours are ultra-rare diseases. Approximately 1,100 - 1,200 new instances of malignant tumours in children are diagnosed annually in Poland, with bone tumours accounting for approximately 6-7% of cases. The incidence increases with age and they are most commonly found in adolescents and young adults, however incidences in early childhood have also been observed. Bone sarcomas are usually characterised by an aggressive clinical course and a high probability of metastases which account for 20-40% of cases at the onset of the disease. Many years of clinical research have resulted in the development of treatment methods that allow patients with localized disease to achieve OS (overall survival) rates of 60-65% for osteosarcoma and 70-80% for Ewing’s sarcoma. In the latter stages of the disease, the OS decreases significantly to about 30%, and in the case of bone sarcoma recurrence, the OS drops even further to ca. 15%. Unfortunately, despite intensification of therapy in patients with dissemination as well as refractory to first-line (1L) therapy, the outcomes have not been improved for over 30 years. Second-line and subsequent therapies for bone cancers are often non-standardized and are dependent on the centre's expertise, knowledge and therapeutic capabilities.
The identification of new mutations in bone tumours has led to a better insight into the molecular basis of these tumours, which has enhanced the role of genetic research in everyday practice. Although standard histopathological examinations are currently the foundation for the diagnosis of bone tumours, new molecular biology techniques allow for the refinement of the diagnosis in many cases and, in the near future, will become the basis for the categorization of these neoplasms. Furthermore, these methods are intended to enable patients to be qualified for advanced molecular targeted therapies.
Based on the above data, the objectives of the REGBONE project are as follows: (1) to estimate the nature and frequency of mutations in the tumour tissue, (2) to compare molecular test results with clinical data (which will allow for the initial assessment of the impact of the mutation status on the clinical condition, course of treatment and prognosis), (3) to include new targeted treatment – broad spectrum tyrosine kinase inhibitor – Regorafenib in standard therapy.
