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Use of Adjuvant Chemotherapy for Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features


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In a Children’s Oncology Group study (COG ARET0332) reported in the Journal of Clinical Oncology, Chévez-Barrios et al found discrepancies between central and institutional identification of high-risk features of enucleated unilateral retinoblastoma, and that use of adjuvant chemotherapy based on strict high-risk feature criteria resulted in good outcomes.

Study Details

The study involved 321 eligible prospectively enrolled children with newly diagnosed enucleated unilateral retinoblastoma. After central histopathology review, patients with specific high-risk features received chemotherapy, whereas those without such high-risk features underwent observation. The indications for adjuvant chemotherapy were: massive choroid replacement defined as posterior uveal invasion grades IIC (largest dimension ≥ 3 mm, massive) and IID (posterior uveal tumor noted grossly); any posterior uveal involvement < 3 mm with concomitant optic nerve involvement (optic nerve head, prelamina, and lamina cribrosa only); and optic nerve involvement posterior to the lamina cribrosa.

The primary endpoint was event-free survival. The study opened in December 2005 and closed in May 2010; the current analysis used data through June 2018.

“Adequate handling and interpretation of histopathology of eyes with retinoblastoma is necessary to assign metastatic risk ... Strict criteria for adjuvant therapy may improve outcomes of children who undergo enucleation at diagnosis and may avoid unnecessary adjuvant chemotherapy for those who are not at risk for recurrence.”
— Chévez-Barrios et al

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Key Findings

Overall, central review reclassified institutional assignment of high-risk features in 59 patients (18%). Of 88 patients classified as having high-risk features by institutional report, 19 (22%) were reclassified to no high-risk features (1 reclassified as unknown). Of the 233 patients classified as not having high-risk features by institutional report, 29 (12%) were reclassified to high-risk features (10 reclassified as unknown).

On central review, postlaminar optic nerve involvement was identified in 53 patients; 42 had massive posterior uveal invasion (≥ 3 mm); 15 had concomitant peripapillary ≥ 3 mm choroid and postlaminar optic nerve involvement; and 15 had focal (< 3 mm) choroidal involvement concomitant with lamina or prelamina optic nerve involvement.

Among all 321 patients with central review, 2-year event-free survival and overall survival rates were 98% and 99%; since no events occurred after 2 years, 5-year rates were identical to 2-year rates.

Among the 216 eligible patients without high-risk features requiring chemotherapy, the 2-year (and 5-year) event-free survival and overall survival rates were 99% and 100%. Among the 94 eligible patients with high-risk features requiring chemotherapy, the 2-year (and 5-year) event-free and overall survival rates were 96% and 97%.

The investigators concluded, “Adequate handling and interpretation of histopathology of eyes with retinoblastoma is necessary to assign metastatic risk. Concomitant less than 3 mm choroidal and any prelaminar/laminar optic nerve invasion show no recurrence and may warrant no adjuvant chemotherapy. In contrast, concomitant greater than 3 mm peripapillary choroidal invasion and 1.5 mm or greater of postlaminar optic nerve invasion have the poorest outcomes, supporting the need for a more intensive adjuvant chemotherapy regimen for this subgroup. Strict criteria for adjuvant therapy may improve outcomes of children who undergo enucleation at diagnosis and may avoid unnecessary adjuvant chemotherapy for those who are not at risk for recurrence.”

Patricia Chévez-Barrios, MD, of Houston Methodist Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Clinical Trials Network Operations Center and National Clinical Trials Network Statistics and Data Center and by St. Baldrick’s Foundation. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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