Patricia Chévez-Barrios1,2, Ralph C Eagle3,4, Mark Krailo5, Jin Piao5, Daniel M Albert6, Yun Gao5, Geeta Vemuganti7,8, Mohammad Javed Ali8, Vikas Khetan9, Santosh G Honavar10, Joan O'Brien11,12, Ann-Marie Leahey12, Katherine Matthay13, Anna Meadows12, Murali Chintagumpala14,15,2. 1. Houston Methodist Hospital, Houston, TX. 2. Retinoblastoma Center of Houston, Houston, TX. 3. Will's Eye Hospital, Philadelphia, PA. 4. Children's Hospital of Philadelphia, Philadelphia, PA. 5. Children's Oncology Group, Monrovia, CA. 6. Oregon Health and Science University, Portland, OR. 7. University of Hyderabad, Hyderabad, India. 8. L.V. Prasad Eye Institute, Hyderabad, India. 9. Vision Research Foundation, Chennai, India. 10. National Retinoblastoma Foundation Centre for Sight, Hyderabad, India. 11. Scheie Eye Institute, Philadelphia, PA. 12. University of Pennsylvania, Philadelphia, PA. 13. University of California at San Francisco, San Francisco, CA. 14. Baylor College of Medicine, Houston, TX. 15. Texas Children's Cancer Center, Houston, TX.
Abstract
PURPOSE: To prospectively determine the prevalence of high-risk histopathologic features (HRFs) in patients with unilateral retinoblastoma who undergo enucleation and to evaluate the role of chemotherapy in preventing recurrences. PATIENTS AND METHODS: Children newly diagnosed with enucleated unilateral retinoblastoma were enrolled prospectively. After central histopathology review, patients with specific HRFs received chemotherapy; others were observed. Primary end points were event-free survivals (EFS). RESULTS: Of the 331 patients enrolled during 2005 to 2010, 321 eligible patients had central histopathologic review. Discordance between central review and contributing institutions occurred in 23% of patients with HRFs and in 17% of patients without HRFs. Postlaminar optic nerve involvement was present in 53 patients; 42 had massive posterior uveal invasion (≥ 3 mm); 15 had concomitant peripapillary 3 mm or greater choroid and postlaminar optic nerve involvement; and 15 had focal (< 3 mm) choroidal concomitant with lamina or prelamina optic nerve involvement. Two-year EFS for patients with HRFs requiring adjuvant chemotherapy was 0.96 (95% CI, 0.89 to 0.98), and 2-year EFS for patients without HRFs for which observation was indicated was 0.99 (95% CI, 0.96 to 1.0). The 2-year EFS for all patients was 0.98 (95% CI, 0.96 to 0.99). CONCLUSION: 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.
PURPOSE: To prospectively determine the prevalence of high-risk histopathologic features (HRFs) in patients with unilateral retinoblastoma who undergo enucleation and to evaluate the role of chemotherapy in preventing recurrences. PATIENTS AND METHODS: Children newly diagnosed with enucleated unilateral retinoblastoma were enrolled prospectively. After central histopathology review, patients with specific HRFs received chemotherapy; others were observed. Primary end points were event-free survivals (EFS). RESULTS: Of the 331 patients enrolled during 2005 to 2010, 321 eligible patients had central histopathologic review. Discordance between central review and contributing institutions occurred in 23% of patients with HRFs and in 17% of patients without HRFs. Postlaminar optic nerve involvement was present in 53 patients; 42 had massive posterior uveal invasion (≥ 3 mm); 15 had concomitant peripapillary 3 mm or greater choroid and postlaminar optic nerve involvement; and 15 had focal (< 3 mm) choroidal concomitant with lamina or prelamina optic nerve involvement. Two-year EFS for patients with HRFs requiring adjuvant chemotherapy was 0.96 (95% CI, 0.89 to 0.98), and 2-year EFS for patients without HRFs for which observation was indicated was 0.99 (95% CI, 0.96 to 1.0). The 2-year EFS for all patients was 0.98 (95% CI, 0.96 to 0.99). CONCLUSION: 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.
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