Junyang Zhao1, Zhao Xun Feng2, Meirong Wei3, Guohua Liu4, Carlos E Solarte5, Bin Li6, Yizhuo Wang6, Chengyue Zhang1, Brenda L Gallie7. 1. Pediatric Oncology Center, Beijing Children's Hospital, Beijing, China. 2. Faculty of Medicine, University of Ottawa, Ottawa, Canada. 3. Department of Ophthalmology, Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, China. 4. Department of Ophthalmology, Qilu Children's Hospital of Shandong University, Jinan, China. 5. Department of Ophthalmology, University of Alberta, Edmonton, Canada. 6. Department of Ophthalmology, Beijing Tongren Hospital, Beijing, China. 7. Department of Ophthalmology, Hospital for Sick Children, Toronto, Canada; Krembil Research Institute, Toronto, Canada; Techna Institute, Toronto, Canada. Electronic address: brenda@gallie.ca.
Abstract
PURPOSE: Primary enucleation is a well-established method to achieve cure for advanced intraocular retinoblastoma. Recent treatment advances have induced a trend toward trial eye salvage using chemotherapy or other modalities. We investigated how pre-enucleation/postenucleation systemic chemotherapy and the resulting delayed enucleation affect patient survival after failed trial eye salvage. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Children with Group D and E retinoblastoma primarily or secondarily enucleated at 29 Chinese treatment centers. METHODS: Data reviewed included clinical staging, time from diagnosis to enucleation, numbers of cycles of carboplatin, etoposide/teniposide and vincristine chemotherapy, disease-specific survival (DSS), histopathology, and follow-up. MAIN OUTCOME MEASURES: Primary outcome was DSS. Secondary outcome was histopathology of enucleated eyes. RESULTS: Primarily enucleated eyes had significantly shorter delay from diagnosis to enucleation than eyes treated with pre-enucleation chemotherapy (P < 0.001). Delay between diagnosis and enucleation >3.5 months (Group D) and >2 months (Group E) decreased survival (Group D: P = 0.018; Group E: P = 0.017). Compared with primarily enucleated children, children with 1 to 3 cycles of pre-enucleation chemotherapy for Group E eyes had no significant difference in survival (P = 0.74), but those who received ≥4 cycles had worse survival (P = 0.025). After pre-enucleation chemotherapy, more children with Group E (but not Group D) eyes had high-risk histopathology (pT3/pT4) (Group D: P = 0.076; Group E: P < 0.001) and worse survival than those primarily enucleated (P < 0.001). Postenucleation chemotherapy improved survival of children with high-risk histopathology (pT3/pT4) (P = 0.001) but did not change survival of children with low-risk histopathology (pT1/pT2) (P = 0.52). CONCLUSIONS: We observed that pre-enucleation chemotherapy offered no survival benefit and timely enucleation minimized risk of metastatic death. Postenucleation chemotherapy improved survival of children with high-risk histopathology but was not useful for those with low-risk histopathology. These findings facilitate informed discussion on the risks and benefits of delayed enucleation, the use of systemic chemotherapy for trial salvage of eyes with advanced intraocular retinoblastoma, and the specific children who benefit from postenucleation chemotherapy.
PURPOSE: Primary enucleation is a well-established method to achieve cure for advanced intraocularretinoblastoma. Recent treatment advances have induced a trend toward trial eye salvage using chemotherapy or other modalities. We investigated how pre-enucleation/postenucleation systemic chemotherapy and the resulting delayed enucleation affect patient survival after failed trial eye salvage. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Children with Group D and E retinoblastoma primarily or secondarily enucleated at 29 Chinese treatment centers. METHODS: Data reviewed included clinical staging, time from diagnosis to enucleation, numbers of cycles of carboplatin, etoposide/teniposide and vincristine chemotherapy, disease-specific survival (DSS), histopathology, and follow-up. MAIN OUTCOME MEASURES: Primary outcome was DSS. Secondary outcome was histopathology of enucleated eyes. RESULTS: Primarily enucleated eyes had significantly shorter delay from diagnosis to enucleation than eyes treated with pre-enucleation chemotherapy (P < 0.001). Delay between diagnosis and enucleation >3.5 months (Group D) and >2 months (Group E) decreased survival (Group D: P = 0.018; Group E: P = 0.017). Compared with primarily enucleated children, children with 1 to 3 cycles of pre-enucleation chemotherapy for Group E eyes had no significant difference in survival (P = 0.74), but those who received ≥4 cycles had worse survival (P = 0.025). After pre-enucleation chemotherapy, more children with Group E (but not Group D) eyes had high-risk histopathology (pT3/pT4) (Group D: P = 0.076; Group E: P < 0.001) and worse survival than those primarily enucleated (P < 0.001). Postenucleation chemotherapy improved survival of children with high-risk histopathology (pT3/pT4) (P = 0.001) but did not change survival of children with low-risk histopathology (pT1/pT2) (P = 0.52). CONCLUSIONS: We observed that pre-enucleation chemotherapy offered no survival benefit and timely enucleation minimized risk of metastatic death. Postenucleation chemotherapy improved survival of children with high-risk histopathology but was not useful for those with low-risk histopathology. These findings facilitate informed discussion on the risks and benefits of delayed enucleation, the use of systemic chemotherapy for trial salvage of eyes with advanced intraocularretinoblastoma, and the specific children who benefit from postenucleation chemotherapy.
Authors: Ankit Singh Tomar; Paul T Finger; Brenda Gallie; Tero T Kivelä; Ashwin Mallipatna; Chengyue Zhang; Junyang Zhao; Matthew W Wilson; Rachel C Brennan; Michala Burges; Jonathan Kim; Jesse L Berry; Rima Jubran; Vikas Khetan; Suganeswari Ganesan; Andrey Yarovoy; Vera Yarovaya; Elena Kotova; Denis Volodin; Yacoub A Yousef; Kalle Nummi; Tatiana L Ushakova; Olga V Yugay; Vladimir G Polyakov; Marco A Ramirez-Ortiz; Elizabeth Esparza-Aguiar; Guillermo Chantada; Paula Schaiquevich; Adriana Fandino; Jason C Yam; Winnie W Lau; Carol P Lam; Phillipa Sharwood; Sonia Moorthy; Quah Boon Long; Vera Adobea Essuman; Lorna A Renner; Ekaterina Semenova; Jaume Català-Mora; Genoveva Correa-Llano; Elisa Carreras Journal: Ophthalmology Date: 2022-04-15 Impact factor: 14.277