Treatment of intermediate (i.e. atypical cartilaginous tumour, ACT) and malignant cartilaginous tumours (i.e. chondrosarcoma) involves surgical resection, while effects of systemic therapies are limited. Thus, it is of importance to diagnose these tumours timely, estimate their prognosis, and detect recurrences at early stages. Apart from diagnosis and disease monitoring with cost-intensive, as well as ionizing radiation-exposing imaging modalities, liquid biopsy constitutes a potent, non-invasive diagnostic, prognostic and predictive tool in oncology. Intermediate/malignant cartilaginous neoplasms are known to frequently harbour specific mutations, as Isocitrate dehydrogenase 1/2 (IDH1/2). These may well be detectable with liquid biopsy, a non-invasive diagnostic measure. Further, other genetic alterations found in primary tumour tissue as well as cytokines/chemokines may be of additive diagnostic and prognostic value.
This prospective cohort study aims at answering 4 questions: 1) Possibility to differentiate between ACT and higher-grade chondrosarcoma by measuring mutant IDH1/2 circulating free DNA (cfDNA) in blood stream; 2) Feasibility to detect recurrences during follow-up by monitoring mutant IDH1/2 cfDNA; 3) Prognostic potential of high mutant IDH1/2 cfDNA levels; 4) Additive diagnostic/prognostic value of other genetic alterations found in primary tumour tissue as well as cytokine profiling.
Over 2 years, an estimated 60 patients with intermediate/malignant cartilaginous tumours will meet the inclusion criteria. At 11 time points (preoperatively, postoperatively, after 6 weeks, as well as 3, 6, 9, 12, 15, 18, 21 and 24 months), blood samples will be ascertained. The following methodological steps will be carried out: 1) next generation sequencing of primary tumour tissue towards IDH1/2 mutations (and further genetic alterations); 2) selection of digital droplet polymerase chain reaction (ddPCR) assays with patient-specific probes; 3) blood sample collection; 4) cfDNA extraction from blood samples; 5) Quantification of mutant IDH1/2 cfDNA with ddPCR; 6) cytokine and chemokine profiling in blood samples. Patients will be followed-up for 2 years, resulting in an overall study period of 4 years.
This study may help to elucidate the role of liquid biopsy in diagnosis and follow-up of patients with chondrosarcoma.