Diffuse Infiltrating Retinoblastoma with Anterior Chamber Involvement: Conservative Management and Identification of RB1 Alterations in Aqueous Humor

Nathalie Cassoux; Denis Malaise; Livia Lumbroso-Le-Rouic; Jessica Le Gall; Lisa Golmard; Liesbeth Cardoen; Paul Freneaux; Yassine Bouchoucha; Isabelle Aerts; François Doz; Alexandre Matet

doi:10.1159/000531233

Diffuse Infiltrating Retinoblastoma with Anterior Chamber Involvement: Conservative Management and Identification of RB1 Alterations in Aqueous Humor

Ocul Oncol Pathol. 2023 Sep;9(3-4):96-100. doi: 10.1159/000531233. Epub 2023 Jun 16.

Authors

Nathalie Cassoux^{1

2}, Denis Malaise¹, Livia Lumbroso-Le-Rouic¹, Jessica Le Gall³, Lisa Golmard³, Liesbeth Cardoen⁴, Paul Freneaux⁵, Yassine Bouchoucha^{2

6}, Isabelle Aerts⁶, François Doz^{2

6}, Alexandre Matet^{1

2}

Affiliations

¹ Department of Ocular Oncology, Institut Curie, Paris, France.
² Faculté de Médecine, Université Paris Cité, Paris, France.
³ Department of Genetics, Institut Curie, Paris, France.
⁴ Department of Radiology, Institut Curie, Paris, France.
⁵ Department of Pathology, Institut Curie, Paris, France.
⁶ SIREDO Oncology Center of Care, Innovation and Research for Children, Adolescent and Young Adults with Cancer, Institut Curie, Paris, France.

Abstract

Introduction: The aim of the study was to describe the successful conservative management of diffuse infiltrating retinoblastoma (DIR). Identification of RB1 pathogenic variant was done after cell-free DNA (cfDNA) analysis in aqueous humor.

Case presentation: Herein, we report 2 patients with unilateral, non-familial DIR with anterior and posterior involvement. Both patients underwent liquid biopsy for tumor cfDNA analysis in aqueous humor. Treatment consisted of a combination of systemic and intra-arterial chemotherapy, with consecutive intracameral and intravitreal injections of melphalan. One patient also required iodine-125 brachytherapy. In both cases, tumor cfDNA analysis revealed biallelic somatic alterations of the RB1 gene. These alterations were not found in germline DNA. Both patients retained their eyes and had a useful vision after a follow-up of 2 years.

Conclusion: In selected cases, conservative management of DIR is safe and effective. Tumor cfDNA analysis in aqueous humor is an effective technique to disclose RB1 somatic alterations that guide the germline molecular explorations and improve genetic counseling after conservative treatment.

Keywords: Cell-free DNA; Conservative treatment; Diffuse infiltrating retinoblastoma; Intracamerular chemotherapy; Intravitreal chemotherapy; Liquid biopsy; RB1 mutation; Retinoblastoma; Retinoblastoma genetics.

Grants and funding

The authors declare that no funding was received for this study.