June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Establishing Clinical Utility of ctDNA Analysis for Diagnosis, Prognosis, and Treatment Monitoring of Retinoblastoma: the Aqueous Humor Liquid Biopsy
Author Affiliations & Notes
  • Liya Xu
    Children's Hospital of Los Angeles, Los Angeles, California, United States
    Biological Sciences, University of Southern California, Los Angeles, California, United States
  • Mary E Kim
    Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Ashley Polski
    Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Rishvanth K. Prabakar
    Biological Sciences, University of Southern California, Los Angeles, California, United States
  • Lishuang Shen
    Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Chen-Ching Peng
    Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Mark Reid
    Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Patricia Chevez-Barrios
    Houston Methodist Hospital, Houston, Texas, United States
  • Jonathan Kim
    Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Peter Kuhn
    Biological Sciences, University of Southern California, Los Angeles, California, United States
  • David Cobrinik
    Children's Hospital of Los Angeles, Los Angeles, California, United States
  • James Hicks
    Biological Sciences, University of Southern California, Los Angeles, California, United States
  • Jesse L Berry
    Children's Hospital of Los Angeles, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Liya Xu, Children's Hospital of Los Angeles (P); Mary Kim, None; Ashley Polski, None; Rishvanth K. Prabakar, None; Lishuang Shen, None; Chen-Ching Peng, None; Mark Reid, None; Patricia Chevez-Barrios, None; Jonathan Kim, None; Peter Kuhn, None; David Cobrinik, None; James Hicks, University of Southern California (P); Jesse Berry, Children's Hospital of Los Angeles (P)
  • Footnotes
    Support  Wright Foundation, KTEF, NCI K08CA232344, NIH P30EY029220, NCI P30CA014089, Hyundai Hope on Wheels RGA012351
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2839. doi:
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      Liya Xu, Mary E Kim, Ashley Polski, Rishvanth K. Prabakar, Lishuang Shen, Chen-Ching Peng, Mark Reid, Patricia Chevez-Barrios, Jonathan Kim, Peter Kuhn, David Cobrinik, James Hicks, Jesse L Berry; Establishing Clinical Utility of ctDNA Analysis for Diagnosis, Prognosis, and Treatment Monitoring of Retinoblastoma: the Aqueous Humor Liquid Biopsy. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2839.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : There are currently no eye-specific molecular biomarkers in clinical practice for retinoblastoma (RB), a rare, pediatric intraocular cancer, because direct tumor biopsy is prohibited. We overcome this problem by using the aqueous humor (AH) as a liquid biopsy source of cell-free tumor DNA (ctDNA).This study is aim to detail the first prospective data using the AH liquid biopsy to identify diagnostic and prognostic molecular biomarkers present at diagnosis and discuss the validity and clinical utility of the platform.

Methods : Subjects included 7 eyes of 6 RB patients with at least 12 months of follow-up. The AH liquid biopsy was used at diagnosis and prospectively throughout therapy until the eye was cured or required enucleation due to persistent disease. Cell-free DNA (cfDNA) was isolated and sequenced to assess genome-wide somatic copy number alterations (SCNAs) and mutation in RB1 gene. Results were compared to peripheral blood RB1 testing. Tumor fraction (TFx) was calculated using ichorCNA. Primary clinical endpoint was ocular salvage versus enucleation.

Results : Tumoral genomic information was detected in 100% of diagnostic AH samples. Of the 7 diagnostic AH samples, 5/7 were positive for RB SCNAs. Mutational analysis identified RB1 variants in 5/7 AH samples, including the 2 samples in which no SCNAs were detected. Two eyes failed therapy and required secondary enucleation; both had poor prognostic biomarkers (chromosome 6p gain and MYCN amplification) present in the AH at the time of diagnosis. No patients had any complications from AH sampling or demonstrated extraocular spread of disease.

Conclusions : This initial prognostic study demonstrates feasibility, safety, and utility of an AH liquid biopsy at diagnosis. Molecular profiling of AH provides impactful tumor-derived diagnostic and prognostic information from a single 100 µL AH sample. In the context of previously established pre-analytical, analytical, and clinical validity, this provides evidence for larger, prospective studies to further establish the clinical utility of the AH liquid biopsy and its applications to precision oncology for RB.

This is a 2021 ARVO Annual Meeting abstract.

 

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