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Retinoblastoma Surveillance Guidelines Include Genetic Testing, Counseling in Risk Stratification

NEW YORK (GenomeWeb) – New guidance from American Association of Ophthalmic Oncologists and Pathologists (AAOOP) calls for genetic counseling and testing for children at potential risk of retinoblastoma.

"The goal of these screening guidelines is to educate primary care providers and ophthalmologists and to optimize care by creating a more uniform approach to care for children with a family history of retinoblastoma, ensuring that children receive timely and appropriate genetic counseling, testing, and screening for familial retinoblastoma," wrote corresponding author Patricia Chévez-Barrios, a pathology and genomic medicine researcher affiliated with Houston Methodist Hospital, the Retinoblastoma Center of Houston, and other centers, and her colleagues.

The new consensus report, published online yesterday in the journal Ophthalmology, stems from an effort by the AAOOP, with input from the American Academy of Pediatrics and the American Association for Pediatric Ophthalmology and Strabismus, to carve out ophthalmic screening guidelines for the childhood eye cancer.

Among their recommendations, the report's authors — a group of ophthalmologists, pathologists, geneticists, and oncologists representing several retinoblastoma treatment centers in the US and Canada — highlighted the need for genetic counseling and testing to identify retinoblastoma-related mutations in the RB1 gene in children suspected of being at enhanced risk of the disease.

The team focused on coming up with appropriate surveillance strategies for children who might be prone to retinoblastoma, namely those with an affected first or second degree relative such as a parent, sibling, or grandparent. Classifying children into low-, medium-, and high-risk groups with the help of RB1 status provides an opportunity to come up with appropriate examination schedules, they noted, adding that anesthesia may be beneficial for some high-risk children undergoing frequent exams.

The presence of a pathogenic or likely pathogenic variant in the retinoblastoma risk gene RB1 would place a child in a high-risk group, for example, particularly if he or she has a retinoblastoma-affected family member with mutations in the gene. On the other hand, the authors noted that "the majority of at-risk relatives who do not carry the RB1 mutation do not require specific retinoblastoma screening."

Past research has demonstrated that certain RB1 germline mutations not only increase retinoblastoma risk, but also correspond to more frequent recurrence of the disease or secondary tumor development.

Several firms and centers in the US and Canada offer testing for germline changes to RB1 alone or as part of a broader sequencing panel, including Ambry Genetics, Invitae, Prevention Genetics, EGL Genetics, ARUP Laboratories, Blueprint Genetics, Fulgent Genetics, and Parabase Genomics.

Hospital for Sick Children ophthalmologist Brenda Gallie, a co-author on the consensus report, is a founder and unsalaried medical advisor for the Canadian testing firm Impact Genetics, which has been acquired by LabCorp in the US and Dynacare in Canada.

In addition, the Children's Hospital of Los Angeles launched its RB1 NextGen test, a sequencing-based strategy for picking up germline mutations in the gene in 2014. The University of Pennsylvania's genetic diagnostic lab offers its own RB1 sequencing test, along with tests for other alterations that affect the gene such as promoter methylation changes or duplications or deletions.

The new AAOOP consensus guidelines were primarily targeted for a US setting, and investigators penning the report acknowledged that it may not be possible to follow the retinoblastoma recommendations in countries with limited access to the genetic tests or screening tools suggested.

Even so, the recommendations are intended to "create a structured approach to care in which expected risk based on familial relationship to the affected family member initially determines screening frequency for children, and genetic testing clarifies this risk," Chévez-Barrios and co-authors concluded. "This approach allows clinicians to provide an immediate individualized care plan based on the expected risk for RB1 mutation for each child."