International Retinoblastoma Liquid Biopsy Consortium (IRB-LBC): A Multi-Center, Multi-National Collaborative Study on Aqueous Humor as a Liquid Biopsy Tool for Retinoblastoma

Abstract

Purpose : Retinoblastoma (RB) is a rare pediatric ocular cancer that cannot be biopsied without risk of extraocular tumor spread. Our novel research has shown that aqueous humor (AH) biopsy is a safe, valid method for acquiring molecular and genomic tumor information in the absence of tissue. We created an international consortium to examine the diagnostic and prognostic value of AH for RB.

Methods : Children’s Hospital Los Angeles (CHLA) is the lead institution, recruiting investigators with active RB programs. Researchers obtain local IRB approval for the collection of AH, blood, tumor and clinical data, and recruit their own patients. Samples are maintained on site per protocol, with AH stored at -80C. After a Materials Transfer Agreement, 23 sites ship RB biospecimens to CHLA for DNA extraction and sequencing, while 7 sites process their own samples and share genomic data.

Results : There are 30 centers involved. Started by CHLA in May of 2019, this project recruited 7 US sites and 1 Canadian hospital. Eight additional US centers, 6 international centers (IND, São Paulo + Goiânia, BRA, MX, ISR, NZL/AUS) and the broad European RB Group recently joined. The CHLA biorepository has 691 samples from 125 patients, including 35 from multisite studies. Our first multisite publication detailed nucleic acid concentrations in RB AH samples (Oph. Science, 2023) and was recognized as the ‘Best Paper Presentation’ for ocular oncology at the AAO 2023 conference. We also reported on MYCN amplification in RB AH Genomic data from 263 samples sequenced at CHLA was released to the NIH Database of Genotypes and Phenotypes (https://www.ncbi.nlm.nih.gov/gap/) in 2023 and is now publicly available.

Conclusions : Our multisite, international research collaboration provides a mechanism to capture data on more RB patients under varied treatment protocols. Future research will examine the impact of treatment stratification on AH biomarkers, assess the clinical utility of AH as a companion diagnostic, and AH biomarkers to stratify prospective clinical trials. This project has been essential for advancing innovative and translational research for RB.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.