Dr Amy Gerrish and her team have been working to develop a form of liquid biopsy, using cell-free DNA (cfDNA) found in eye fluid, to discover if a patient has the heritable or non-heritable form of retinoblastoma (Rb). This information is vital in identifying individuals at risk of developing further Rb tumours, as well as those individuals and relatives at very low risk, who can then avoid unnecessary examinations under anaesthetic (EUAs). This project was joint-funded by CHECT and Fight for Sight.
As treatment options for retinoblastoma improve, and enucleation rates decline, access to tumour tissue is decreasing and with it, the opportunity to identify the genetic changes in the tumour that have caused the retinoblastoma. This project has expanded an initial pilot study by Dr Gerrish’s group which shows that the analysis of cell-free DNA within eye fluid can be used as an alternative to direct tumour tissue analysis for the diagnosis of retinoblastoma. This project has also determined the best time point for collecting eye fluid to maximise the chance of getting a diagnostic result. This will be essential to making this test part of the clinical service, which is planned within the next 24 months.
The distinction between heritable and non-heritable retinoblastoma is vital, as heritable cases need close monitoring: in childhood for the presence of new tumours in both eyes; and later in life for possible second cancers. If it can be confirmed that a retinoblastoma is non-heritable, additional screening examinations, which occur over a number of years and often need general anaesthetic, can be reduced or discontinued, as can surveillance for cancers outside of the eye in later life. There are also important implications for both siblings and offspring, who may otherwise require screening if a heritable cause of the retinoblastoma cannot be ruled out. In addition to the benefits to patients and their families, this would provide significant cost savings to the healthcare system.
As well as using cell-free DNA within eye fluid to diagnose retinoblastoma, scientists also think that this type of cell-free DNA may contain prognostic information to identify those tumours which are more resistant to treatment, and which make it less likely that the eye can be saved. Bringing this test into clinical practice could identify those cases which would be best managed with immediate enucleation. Within this project, Dr Gerrish and her team have shown that both diagnostic and prognostic information of a retinoblastoma tumour can be determined from the same test. This will hopefully help bring this additional prognostic test into clinical practice, as there is a limited amount of eye fluid/cfDNA available for testing.
Dr Gerrish commented “The funding we have received from CHECT and Fight for Sight has been crucial in allowing us to continue our work to develop new genetic tests for both the diagnosis and prognosis of retinoblastoma. These tests examine samples of eye fluid, which contain DNA from the retinoblastoma tumour. Analysis of this DNA could help determine the best care plan for retinoblastoma patients and their families. Specifically through this funding, we have determined that the timing of sample collection is critically important for the tests to work. This information will be essential in order to implement these tests into clinical practice.”
To read the full final report for this research go to https://chect.org.uk/research/previous-chect-research/, and you can hear Dr Gerrish talking about the research at https://chect.org.uk/transforming-the-treatment-of-childrens-eye-cancer/
Glossary:
Heritable: can be passed from parent to child
Liquid biopsy: a laboratory test done on a sample of body fluid to look for cancer cells or DNA that has been released from cancer cells
Cell-free DNA: fragments of DNA circulating in body fluids
Diagnosis: identification of an illness by examination of the symptoms as well as results from laboratory tests.
Prognosis: the likely course of a medical condition