What are some notable points in the RB-RECIST guidelines, and can you share a bit about the reasoning behind these?

This is a multicenter collaborative set of consensus guidelines for how we evaluate the way retinoblastoma responds to therapy. Even in today’s age, retinoblastoma remains a very subjective cancer — meaning, the [response] to therapy is judged subjectively by the treating surgeon because you can look into the eye and see the tumor or tumors directly. Aside from being subjective, gauging response to therapy is complicated by the fact that children can have multiple separate tumors in one or both eyes and disease in different compartments of the eye.

One of the main contributions of this paper, aside from setting consensus guidelines on how to gauge whether an eye is responding to chemo, is acknowledging the separate compartments of the eye that can be affected with this cancer. This includes not only the retinal tumors, but also tumor seeding in either the vitreous or the subretinal space. The disease in these separate compartments can be active at different times; a retinal tumor may be responding to therapy while the vitreous seeds are not.


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This has made it difficult to classify intraocular cancer in the same way that we classify cancer in other organs. Do you call it complete response because the retinal tumor has responded even though the other compartment has not? To address this, we established definitions of CR/PR/SD/PD specific to these separate compartments in the eye.

What are some ways in which the RB-RECIST guidelines differ from the general RECIST guidelines?

RECIST guidelines are considered standard guidelines for both clinicians and researchers to gauge therapeutic response. These have been applied as the gold standard across multiple tumors in multiple studies. Adapting these guidelines for retinoblastoma is important because it ensures that oncologists, ocular oncologists, and researchers are speaking the same language regarding these definitions.

An important part of RECIST-RB is the use of ultrasound for the eye, to measure the tumors. Ocular ultrasound is safe, noninvasive, and already used clinically for retinoblastoma. Children with this cancer require examinations under anesthesia, and this imaging modality is performed at that time. It does not require separate clinical visits with general anesthesia to measure the tumor like an MRI would. There are other eye-specific imaging modalities [including fundus photography and spectral domain optical coherence tomography (SD-OCT)] that can be used to evaluate vitreous seeding.5

How do you anticipate that the proposed criteria would improve the landscape of therapies in ocular oncology?

We hope that like RECIST for other tumors, these guidelines will be applicable regardless of therapy — and this is not meant to guide specific therapy choices.

What should be next steps in terms of moving toward adoption of these guidelines?

The next step is prospective validation of these guidelines across multiple centers. The Pediatric Cancer Data Commons, an initiative sponsored by [the National Cancer Institute] and the Children’s Cancer Research Fund, is working towards consolidating clinical information for rare pediatric tumors like retinoblastoma in order to address these and other needs.

We also hope that [the Children’s Oncology Group] will use these guidelines in future retinoblastoma clinical trials. The overarching goal is to ensure that regardless of where a child with retinoblastoma is treated, or what specific therapy is chosen, the way the efficacy of that therapy is judged is similar.

Disclosure:Dr Berry “has filed a provisional patent application entitled, Aqueous Humor Cell Free DNA for Diagnostic and Prognostic Evaluation of Ophthalmic Disease.”

References

  1. Fabian ID, Sagoo MS. Understanding retinoblastoma: epidemiology and genetics. Community Eye Health. 2018;31(101):7.
  2. World Health Organization (WHO) Union for International Cancer Control. 2014 review of cancer medicines on the WHO list of essential medicines – Retinoblastoma. Accessed online April 19, 2021.
  3. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92(3):205-216. doi:10.1093/jnci/92.3.205
  4. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. doi:10.1016/j.ejca.2008.10.026
  5. Berry JL, Munier FL, Gallie BL, et al. Response criteria for intraocular retinoblastoma: RB-RECIST. Pediatr Blood Cancer. Published online February 23, 2021. doi:10.1002/pbc.28964