Serial RB1 ctDNA tracks extraocular progression and treatment response in retinoblastoma

A multi-institutional observational study in Clinical Cancer Research examined whether serial RB1 circulating tumor DNA (ctDNA) variant allele frequency in plasma and cerebrospinal fluid (CSF) was associated with retinoblastoma outcomes. Investigators reviewed patients treated at MSKCC and SCEH who underwent serial testing, assessing extraocular progression, treatment response and recurrence.

Among 33 patients with intraocular retinoblastoma, four developed extraocular disease, all with increased plasma RB1 ctDNA. The remaining 29 had persistently undetectable plasma ctDNA. Among 16 patients with extraocular disease, plasma ctDNA was detectable in 15 at diagnosis and became undetectable in 13 of 14 assessed after treatment; the patient with rising ctDNA died of disease. Two stage 4a patients with residual bone lesions after chemotherapy but negative ctDNA remained in remission.

CSF ctDNA was detectable in all seven patients with CNS disease at diagnosis and became undetectable after treatment in three of four assessed patients; the patient with rising levels died of disease. Two CNS recurrences after treatment were associated with positive or rising CSF ctDNA. Two stage 4a patients with CSF ctDNA positivity at initial diagnosis subsequently developed CNS recurrence.

These findings suggest a potential role for longitudinal ctDNA in monitoring and risk stratification. However, the small observational cohorts do not establish clinical utility or whether ctDNA-guided management improves outcomes. Only the abstract was available, limiting assessment of assay methods, follow-up and patient selection.