A research project funded by the Bone Cancer Research Trust has found a promising clinical biomarker that offers pathologists an accurate and reproducible test to diagnose and stage chondrosarcoma, informing clinical management and deciding the type of surgery a patient would need. This could also provide a non-invasive way to monitor patients and detect the early stages of recurrence, before the disease spreads, allowing further surgical intervention.​

Prognosis and clinical management of chondrosarcoma are determined by the grade of the primary tumour and its anatomical location. Grading is achieved by a combination of imaging and pathology assessment. When grading tumours, sometimes discrepancies arise between pathologists and radiologists. These are often due to tumour heterogeneity and the biopsy not containing the high-grade component of the disease during biopsy.

There is a clear need for finding a robust and objective diagnostic biomarker to predict chondrosarcoma relapse risk and survival, which could also be used for assessing the response to treatment in clinical trials.

Small pieces of DNA find their way from cells into the blood stream. DNA fragments that are released by tumour cells into the circulation are known as Circulating tumour DNA (ctDNA). Circulating tumour-derived DNA (ctDNA) can be measured and characterised using sensitive techniques from a simple blood sample and are therefore ideal biomarker candidates. Most central conventional and dedifferentiated chondrosarcoma tumours present mutations in the IDH1 or IDH2 genes.

This research aimed to determine whether the level of circulating tumour DNA (ctDNA) containing IDH1- and IDH2-mutations in the blood of chondrosarcoma patients could be used as a diagnostic tool.

The project, led by Professor Adrienne Flanagan at University College London was a multi-institutional study. Thanks to Infrastructure Grant funding from the Bone Cancer Research Trust, samples donated by chondrosarcoma patients were collected by the bone cancer specialist centres at Newcastle, Birmingham, Stanmore, and Oswestry. The study opened in October 2017 and closed at the end of December 2020, which included a six-month extension due to the COVID pandemic. The study recruited 145 patients.

These are often due to tumour heterogeneity and the biopsy not containing the high-grade component of the disease during biopsy

Key results

IDH1/2 mutations were detected in 80% of tumours. Detection of ctDNA containing IDH1/2 mutations was more accurate than pathology for identification of high-grade tumours and was associated with a poor prognosis. ctDNA containing IDH1/2 mutations was never associated with chondrosarcoma grade 1/atypical cartilaginous tumours (ACT) in the long bones, in tumours of the small bones of the hands and feet or in tumours measuring less than 80mm.

Dr Iben Lyskjær, Post-Doctoral Researcher at University College London, explains what this discovery means for chondrosarcoma patients:

This is the first step towards implementing a blood-based test for patients with chondrosarcoma. The test should provide a more accurate prognosis (how the disease will behave) and allow doctors to provide a more personalised treatment plan for individual patients. In time, it should also allow a new way of monitoring patients for relapse.

These very promising results offer pathologists an accurate and reproducible tool to diagnose and stage chondrosarcoma, informing clinical management and deciding the type of surgery a patient needs. They also provide a non-invasive way to monitor patients and detect the early stages of recurrence, before the disease spreads, allowing further surgical intervention. However, they are still based on a relatively small number of patients. The introduction of this minimally invasive blood test into clinical practice would allow the research to be assessed more stringently and hopefully developed for a more personalised approach for the treatment of patients with chondrosarcoma.

This research is published in Molecular Oncology.