Retinoblastoma is the most common pediatric intraocular malignancy, with an estimated annual incidence of 1 in 16,000 to 18,000 live births globally.1 This disease is highly curable with timely diagnosis, and reported long-term survival rates exceed 80% in this patient population.2 However, there are opportunities for improvement in the evaluation and comparison of therapies in clinical trials for retinoblastoma.

Although the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines have been widely accepted and used in assessing tumor response to new cancer therapeutics since their publication in 2000, they do not generalize well to retinoblastoma trials.3,4 For example, although the RECIST guidelines advise against the use of ultrasound in measuring tumor response, ultrasound represents the primary imaging modality in diagnosing and monitoring therapeutic response in intraocular malignancies.5

Accordingly, ocular oncology trials have typically relied on progression-free patient or ocular survival, rather than measures of objective tumor response, to evaluate therapeutic efficacy. The expanding range of novel therapies in this area underscores the need for well-defined, tumor-specific response criteria to enable more accurate assessment of treatment response in ocular oncology trials.5

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To address this gap, a multicenter, international team of experts modified the RECIST criteria to create proposed retinoblastoma-specific response guidelines (RB-RECIST) to be used as objective endpoints in clinical trials investigating retinoblastoma therapies.  The recommendations were published online in February 2021 in Pediatric Blood and Cancer.5

Because active cancer cells from a primary retinal tumor can extend into the vitreous and subretinal spaces, with each space potentially showing a different therapeutic response, the proposed criteria summarized below cover all 3 anatomical areas. “A combination of these responses will inform the overall disease response for the eye in patients with intraocular, nonmetastatic disease,” wrote the authors.5

Response Criteria for Retinoblastoma Tumors

Complete response (CR). Type 0, I, or IV regression or Type II or III regression showing clinical stability on ultrasound and fundus photography for 6 months or more following cessation of first-line therapy and/or second-line therapies and local consolidation therapy. There is no visible active disease, and calcified or chorioretinal scarring is stable. Additional treatment is not indicated in these cases.

Partial response (PR). A 30% or greater reduction in apical tumor height from baseline and/or Type II or III regression with demonstrated clinical stability on fundus photography for less than 6 months. Local consolidation therapy may be ongoing and there is no worsening of disease.

Stable disease (SD). A less than 30% reduction in apical tumor height from baseline with minimal or no regression observed on fundus photography, or a less than 30% increase in apical tumor height from baseline. Consolidation therapy may be limited or ongoing. There may be persistent disease and continued therapy, with no worsening of disease.

Progressive disease (PD). A 30% or greater increase in tumor measurements from baseline (from tumor nadir in at least 1 dimension), and/or the appearance of new lesions. PD includes cases of tumor recurrence, which the guidelines define as “a new secondary growth at any location occurring after more than 2 event-free months following completion of first- or second-line therapies.”5