A Multicenter Analysis of Nucleic Acid Quantification Using Aqueous Humor Liquid Biopsy in Retinoblastoma

Im, Deborah H.; Pike, Sarah; Reid, Mark W.; Peng, Chen‐Ching; Sirivolu, Shreya; Grossniklaus, Hans E.; Hubbard, G. Baker; Skalet, Alison H.; Bellsmith, Kellyn N.; Shields, Carol L.; Lally, Sara E.; Stacey, Andrew W.; Reiser, Bibiana J.; Nagiel, Aaron; Shah, Rachana; Xu, Liya; Berry, Jesse L.

doi:10.1016/j.xops.2023.100289

Cited by 10 publications

(11 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One 100 µL AH sample currently suffices for detection of SCNA via sequencing, identification of RB1 variant profiles, and measurement of TFx. 31 Fortunately, recent advancements have provided evidence that 1 µL of AH allows measurements of various circulating analytes such as microRNA, double- and single-stranded DNA, and protein in samples collected at diagnosis, during, and post treatments 59 ; this evidence eases the concern on material limitation, although small tumors (Group A eyes in the International Intraocular RB Classification 60 ) in this study proved unreliable for yielding usable analytes. Another limitation is the need for more than one AH cfDNA analysis to assess SCNA and SNVs individually, which are time consuming and could cause diagnostic delay.…”

Section: Potential Promise Challenges and Future Directionsmentioning

confidence: 76%

The Potential of Aqueous Humor Sampling in Diagnosis, Prognosis, and Treatment of Retinoblastoma

Muniyandi,

Jensen,

Devanathan

et al. 2024

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Retinoblastoma (RB) is a rare malignant tumor that arises in the developing retina in one or both eyes of children. Pathogenic variants of the RB1 tumor suppressor gene drive the majority of germline and sporadic RB tumors. Considering the risk of tumor spread, the biopsy of RB tumor tissue is contraindicated. Advancement of chemotherapy has led to preservation of more eye globes. However, this has reduced access to tumor material from enucleation specimens. Recently, liquid biopsy of aqueous humor (AH) has advanced the RB tumor- or eye-specific genetic analysis. In particular, nucleic acid analysis of AH demonstrates the genomic copy number profiles and RB1 pathogenic variants akin to that of enucleated RB eye tissue. This advance reduces the previous limitation that genetic assessment of the primary tumor could be done only after enucleation of the eye. Additionally, nucleic acid evaluation of AH allows the exploration of the genomic landscape of RB tumors at diagnosis and during and after treatment. This review explores how AH sampling and AH nucleic acid analysis in RB patients assist in diagnosis, prognosis, and comprehending the pathophysiology of RB, which will ultimately benefit individualized treatment decisions to carefully manage this ocular cancer in children.

show abstract

Section: Potential Promise Challenges and Future Directionsmentioning

confidence: 76%

The Potential of Aqueous Humor Sampling in Diagnosis, Prognosis, and Treatment of Retinoblastoma

Muniyandi,

Jensen,

Devanathan

et al. 2024

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…For example, logistic regression-based analysis of nucleic acid content from aqueous humor samples has been used to better quantify disease burden at diagnosis and during treatment. 76 …”

Section: Studies In Rbmentioning

confidence: 99%

Clinical Applications of Machine Learning in the Management of Intraocular Cancers: A Narrative Review

Chandrabhatla

Horgan

Cotton

et al. 2023

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose There is great promise in use of machine learning (ML) for the diagnosis, prognosis, and treatment of various medical conditions in ophthalmology and beyond. Applications of ML for ocular neoplasms are in early development and this review synthesizes the current state of ML in ocular oncology. Methods We queried PubMed and Web of Science and evaluated 804 publications, excluding nonhuman studies. Metrics on ML algorithm performance were collected and the Prediction model study Risk Of Bias ASsessment Tool was used to evaluate bias. We report the results of 63 unique studies. Results Research regarding ML applications to intraocular cancers has leveraged multiple algorithms and data sources. Convolutional neural networks (CNNs) were one of the most commonly used ML algorithms and most work has focused on uveal melanoma and retinoblastoma. The majority of ML models discussed here were developed for diagnosis and prognosis. Algorithms for diagnosis primarily leveraged imaging (e.g., optical coherence tomography) as inputs, whereas those for prognosis leveraged combinations of gene expression, tumor characteristics, and patient demographics. Conclusions ML has the potential to improve the management of intraocular cancers. Published ML models perform well, but were occasionally limited by small sample sizes owing to the low prevalence of intraocular cancers. This could be overcome with synthetic data enhancement and low-shot ML techniques. CNNs can be integrated into existing diagnostic workflows, while non-neural networks perform well in determining prognosis.

show abstract

“…Aqueous humor paracentesis is a straightforward and safe procedure commonly conducted under general anesthesia in conjunction with eye examinations in RB infants, which can also be combined with intravitreal administration of chemotherapy [24]. In recent decades, the identification of specific biomarkersalso detectable in in liquid biopsies -revolutionized cancer research and clinical practice [25][26][27]. Biomarkers, as measurable indicators of biological processes or disease states, play a crucial role in early detection, diagnosis, prognosis, and the development of targeted therapies for various malignancies [28,29] including RB.…”

Section: Introductionmentioning

confidence: 99%

TFF1—A New Biomarker in Liquid Biopsies of Retinoblastoma under Therapy

Busch,

Haase,

Alefeld

et al. 2023

Preprint

View full text Add to dashboard Cite

Effective management of retinoblastoma (RB), the most prevalent childhood eye cancer, depends on reliable monitoring and diagnosis. A promising candidate in this context is the secreted trefoil family factor peptide 1 (TFF1), recently discovered as a promising new biomarker in patients with a more advanced subtype of retinoblastoma. The present study investigated TFF1 expression within aqueous humor (AH) of enucleated eyes and compared TFF1 levels in AH and corresponding blood serum samples from RB patients undergoing intravitreal chemotherapy (IVC). TFF1 was consistently detectable in AH, confirming its potential as a biomarker. Crucially, our data confirmed that TFF1 secreting cells within the tumor mass originate from RB tumor cells, not from surrounding stromal cells. IVC therapy responsive patients exhibited remarkably reduced TFF1 levels post-therapy. By contrast, RB patients` blood serum displayed low to undetectable levels of TFF1 even after sample concentration and no therapy-dependent changes were observed. Our findings suggest that compared to blood serum AH represents the more reliable source for TFF1 if used for liquid biopsy RB marker analysis in RB patients. Thus, analysis of TFF1 in AH of RB patients potentially provides a minimal invasive tool for monitoring RB therapy efficacy, suggesting its importance for effective treatment regimens.

show abstract

A Multicenter Analysis of Nucleic Acid Quantification Using Aqueous Humor Liquid Biopsy in Retinoblastoma

Cited by 10 publications

References 28 publications

The Potential of Aqueous Humor Sampling in Diagnosis, Prognosis, and Treatment of Retinoblastoma

The Potential of Aqueous Humor Sampling in Diagnosis, Prognosis, and Treatment of Retinoblastoma

Clinical Applications of Machine Learning in the Management of Intraocular Cancers: A Narrative Review

TFF1—A New Biomarker in Liquid Biopsies of Retinoblastoma under Therapy

Contact Info

Product

Resources

About