Adjuvant therapy of histopathological risk factors of retinoblastoma in Europe: A survey by the European Retinoblastoma Group (EURbG)

Abstract

Introduction Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. Method Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma Group (EURbG) network. Extended information was gathered via personal email communication. Results Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo‐ and radiotherapy. Conclusion Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.

Current Indications of Secondary Enucleation in Retinoblastoma Management: A Position Paper on Behalf of the European Retinoblastoma Group (EURbG)

“…The establishment of clear guidelines regarding the optimal timing of SE and the need for post-enucleation adjuvant chemotherapy is hindered by the present lack of studies having focused on that subject with only little information available from the studies reporting their treatment outcomes (especially regarding retention times or management of cases with loss of fundus view, and clinicopathologic correlations) and the overall low rates of metastatic disease. On the other hand, the absence of a consensus for the definition of high-risk pathologic factors, with some considering anterior chamber invasion or isolated massive choroidal invasion as a high-risk features for metastasis [ 95 ], while others not [ 64 , 96 , 97 ], as well as considerable variations in the use and type of post-enucleation adjuvant therapies precludes any conclusions regarding the metastasis risk and comparison of survival rates [ 95 ]. The use of the recently-proposed classification of retinoblastoma at relapse (RSU classification), which aims to standardize the treatment for relapse based on the recurrence localization [ 57 ], and the classification of regressed retinoblastoma (RB-Recist) [ 98 ] should allow a better comparison of treatment outcomes and help define SE criteria in the coming years.…”

Twenty-Year Retrospective Study of Post-Enucleation Chemotherapy in High-Risk Patients with Unilateral Retinoblastoma

“…Regimens for adjuvant chemotherapy in retinoblastoma have varied over the years, and protocols differ worldwide. The agents most often used are a combination of carboplatin, etoposide, and/or vincristine, or a combination of vincristine, idarubicin, and cyclophosphamide [ 11 , 13 , 14 , 15 ]. Regarding cycles, six to eight cycles seem to be the norm for high-risk groups, and some propose four or even two cycles for intermediate groups.…”

“…Regarding cycles, six to eight cycles seem to be the norm for high-risk groups, and some propose four or even two cycles for intermediate groups. Intrathecal chemotherapy and ocular radiotherapy are usually reserved only for tumors that extend beyond the sclera or surgical margin [ 11 , 23 , 24 ]. Radiotherapy is losing popularity due to the high incidence of late endocrinological side effects, as well as the reduced number of advanced diseases with earlier detection.…”

“…The histological presence of high-risk factors (HRFs) is important for predicting local recurrence, distant metastasis, and overall survival, dictating further treatment [ 8 , 9 ]. Although large institutions adopt similar protocols, there is no universal international consensus on the appropriate subject, intensity, or duration of adjuvant chemotherapy following enucleated advanced unilateral retinoblastoma [ 10 , 11 ]. A regimen including cyclophosphamide, vincristine, doxorubicin, and intrathecal methotrexate (CVDM) has been in place for post-enucleation chemotherapy in Seoul National University Children’s Hospital since the 1990s [ 12 ].…”

Targeted chemotherapy in retinoblastoma: A step forward from patient survival to globe survival

“…Another indication for combined chemotherapy and radiotherapy was transscleral extension of the tumor. 13…”