July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Chromosomal Analysis in the Aqueous Humor of Retinoblastoma eyes is predictive of globe salvage: the Surrogate Tumor Biopsy
Author Affiliations & Notes
  • Jesse L Berry
    Children's Hospital Los Angeles, Los Angeles, California, United States
    USC Roski Eye Institute, Los Angeles, California, United States
  • Irsan Kooi
    ISA Pharmaceuticals, Leiden, Netherlands
  • Liya Xu
    Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, Los Angeles, California, United States
  • A Linn Murphree
    Children's Hospital Los Angeles, Los Angeles, California, United States
    USC Roski Eye Institute, Los Angeles, California, United States
  • Bao Han Allison Le
    Children's Hospital Los Angeles, Los Angeles, California, United States
    USC Roski Eye Institute, Los Angeles, California, United States
  • Subramanian Krishnan
    Children's Hospital Los Angeles, Los Angeles, California, United States
  • Kevin Stachelek
    Children's Hospital Los Angeles, Los Angeles, California, United States
  • Thomas C Lee
    Children's Hospital Los Angeles, Los Angeles, California, United States
    USC Roski Eye Institute, Los Angeles, California, United States
  • Jonathan W Kim
    Children's Hospital Los Angeles, Los Angeles, California, United States
    USC Roski Eye Institute, Los Angeles, California, United States
  • Peter Kuhn
    Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, Los Angeles, California, United States
    Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, los Angeles, California, United States
  • David Cobrinik
    Children's Hospital Los Angeles, Los Angeles, California, United States
    USC Roski Eye Institute, Los Angeles, California, United States
  • James Hicks
    Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, Los Angeles, California, United States
    Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Jesse Berry, None; Irsan Kooi, None; Liya Xu, None; A Murphree, None; Bao Han Le, None; Subramanian Krishnan, None; Kevin Stachelek, None; Thomas Lee, None; Jonathan Kim, None; Peter Kuhn, None; David Cobrinik, None; James Hicks, None
  • Footnotes
    Support  Knights Templar Eye Foundation
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1637. doi:
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      Jesse L Berry, Irsan Kooi, Liya Xu, A Linn Murphree, Bao Han Allison Le, Subramanian Krishnan, Kevin Stachelek, Thomas C Lee, Jonathan W Kim, Peter Kuhn, David Cobrinik, James Hicks; Chromosomal Analysis in the Aqueous Humor of Retinoblastoma eyes is predictive of globe salvage: the Surrogate Tumor Biopsy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1637.

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

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Abstract

Purpose : The aim of this study was to identify somatic chromosomal copy number alterations (SCNA) in tumor-derived cell-free DNA (cfDNA) in the aqueous humor (AH) of retinoblastoma (Rb) eyes and to correlate with clinical outcomes particularly globe salvage.

Methods : AH was extracted via paracentesis from Rb eyes at the time of intravitreal injection of chemotherapy or enucleation; cfDNA was extracted. Shallow whole genome sequencing was performed on an Illumina platform to assess the presence of cell-free tumor DNA fractions and known, highly recurrent SCNAs in Rb which include gain of 1q, 2p, 6p and loss of 13q and 16q. Patient demographics including age at diagnosis, Group Classification, treatment regimen and globe salvage were recorded.

Results : Twenty-six patients with Rb were included. Three patients underwent primary enucleation, 3 intra-arterial chemotherapy and 20 systemic chemotherapy; 3 patients had both eyes included for 29 total eyes. Group B classification was diagnosed in 1, Group C in 2, Group D in 18 and Group E in 8 eyes. From the 29 eyes, 63 samples of AH were analyzed; 5 post-enucleation and 58 from 24 eyes during intravitreal chemotherapy injection. Ultimately 13 eyes required enucleation and 16 eyes were salvaged with treatment. Follow-up ranged from 8-43 months (median 17 months).

6p gain was the most common SCNA found in 10/13 (77%) enucleated eyes compared to 4/16 (25%) of salvaged eyes. 6p gain is significantly more common in enucleated than salvaged eyes (p=0.009). The average amplitude of 6p gain was 1.8 in the enucleated group versus 1.4 in the salvaged group. The presence of a detectable SCNA in enucleated eyes was 11/13 (85%); the rate of in salvaged eyes was 6/16 (38%) (p=0.022). The average of the CNA profiles in each of the two groups are compared in Figure 1. The probability of globe salvage was improved in eyes without detectable SCNAs (p=0.028) (Figure 2).

Conclusions : This is the first study to correlate clinical outcomes with highly-recurrent SCNAs in the AH from Rb eyes. This study suggests that not only can the AH serve as a surrogate to tumor biopsy but could contribute to prognostication of tumor response to therapy.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Figure 1: CNA profile from the AH from salvaged eyes (A) and enucleated eyes (B). The amplitude of 6p gain is greater in enucleated eyes.

Figure 1: CNA profile from the AH from salvaged eyes (A) and enucleated eyes (B). The amplitude of 6p gain is greater in enucleated eyes.

 

Figure 2: Kaplan-Meier Curves Demonstrating Globe Salvage by the presence of SCNAs

Figure 2: Kaplan-Meier Curves Demonstrating Globe Salvage by the presence of SCNAs

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