Purpose: Retinoblastoma (RB) is the most common intraocular malignancy in children. The diagnosis of RB is mainly based on clinical features and imaging characteristics. Prognosis is based on stage of disease and response to treatment. In salvaged globes, direct tumor biopsy for genetic analysis and prognostication is an absolute contraindication at this point of time for the fear of extraocular tumor spread. Currently, there is a search for surrogate markers to allow accurate diagnosis and for prognostication, to predict the chances of globe salvage in RB. Therefore, biofluids such as plasma or aqueous humor have been studied to detect circulating tumor DNA (ctDNA) or cell-free DNA (cfDNA), respectively, to allow for treatment decision making, monitoring treatment response, and prognostic counselling.
Methods: A search of electronic databases (PubMed, Google Scholar and MEDLINE) of all articles on liquid biopsy in retinoblastoma published in English was performed. The keywords used for the search included "retinoblastoma", "liquid biopsy", "aqueous humor" "circulating tumor cells", "cell-free DNA", "cfDNA", "circulating tumor DNA", "ctDNA", "tumor fraction", "RB1 mutation" and "SNCA". Additionally, historic articles on the advent of liquid biopsy in medicine were also reviewed. Pertinent cross-references from the studies were reviewed. Retrospective interventional and observational case series, observational case series, prospective cohort studies, reviews, case reports, surgical techniques, invited commentary and letters were included.
Results: A total of 40 relevant articles were selected. Biomarkers in aqueous humor, serum and cerebrospinal fluid and their clinical applications are discussed.
Conclusion: Harvesting aqueous humor from eyes with retinoblastoma has been found safe and superior to blood for the detection of chromosomal changes. cfDNA from aqueous can be a surrogate marker to detect somatic copy number alterations and other genetic alterations in RB. ctDNA in plasma also has potential to help in diagnosis and prognosis of RB. Liquid biopsy in RB is an emerging topic, which could pave way for a better understanding of mechanisms for treatment response, resistance and recurrence in RB as well as possibly provide specific therapeutic targets to improve globe salvage.
Keywords: Aqueous humor; Cell-free DNA; Circulating tumor DNA; Circulating tumor cells; Liquid biopsy; RB1 mutation; Retinoblastoma; SNCA; Tumor fraction; cfDNA; ctDNA.