Swathi Kaliki1, Carol L Shields2, Nathalie Cassoux3, Francis L Munier4, Guillermo Chantada5, Hans E Grossniklaus6, Hiroshi Yoshikawa7, Ido Didi Fabian8, Jesse L Berry9, John D McKenzie10, Kahaki Kimani11, M Ashwin Reddy12, Manoj Parulekar13, Mika Tanabe7, Minoru Furuta14, Natalia Grigorovski15, Patricia Chevez-Barrios16, Patricia Scanlan17, Ralph C Eagle18, Riffat Rashid19, Rosdali Díaz Coronado20, Sadia Sultana19, Sandra Staffieri10,21,22, Shahar Frenkel23, Shigenobu Suzuki24, Tatiana L Ushakova25,26, Xunda Ji27. 1. Operation Eyesight Universal Institute for Eye Cancer, LV Prasad Eye Institute India, Hyderabad, India. 2. Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. 3. Department of Surgical Oncology, Insitut Curie Université de Paris, Paris, France. 4. Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, Lausanne, Switzerland. 5. Oncology Department, Hospital Sant Joan de Déu, Barcelona, Spain. 6. Department of Pathology, Emory University School of Medicine, Atlanta, Georgia. 7. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 8. Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Tel-Aviv University, Tel-Aviv, Israel. 9. USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles. 10. Department of Ophthalmology, Royal Children's Hospital, Melbourne, Victoria, Australia. 11. Department of Ophthalmology, University of Nairobi, Nairobi, Kenya. 12. Retinoblastoma Service, Royal London Hospital, Barts Health National Health Service Trust, London, United Kingdom. 13. Retinoblastoma Service, Birmingham Women's and Children's National Health Service Foundation Trust, Birmingham, United Kingdom. 14. Department of Ophthalmology, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan. 15. Department of Pediatric Oncology, Clinical Division, National Institute of Cancer, Rio de Janeiro, Brazil. 16. Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas. 17. Department of Pediatrics, Muhimbili National Hospital, Dar es Salaam, Tanzania. 18. Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania. 19. Department of Oculoplasty and Ocular Oncology, Ispahani Islamia Eye Institute and Hospital, Dhaka, Bangladesh. 20. Retinoblastoma Service, Instituto Nacional de Enfermedades Neoplasicas, Lima, Perú. 21. Retinoblastoma Service, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia. 22. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. 23. Division of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 24. Department of Ophthalmic Oncology, National Cancer Center Hospital, Tokyo, Japan. 25. Department of Pediatric Oncology and Hematology, N. N. Blokhin National Medical Research Center Oncology of Russian Federation, Moscow, Russia. 26. Retinoblastoma Service, Medical Academy of Postgraduate Education, Moscow, Russia. 27. Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract
IMPORTANCE: High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving. OBJECTIVE: To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world. DESIGN, SETTING, AND PARTICIPANTS: An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers. INTERVENTION: Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma. MAIN OUTCOMES AND MEASURES: High-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis. RESULTS: Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration (27 [100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (≥3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (<3 mm) choroidal invasion (5 [19%]), and prelaminar optic nerve infiltration (2 [7%]). The other histopathologic features considered high risk included Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]). Four respondents (15%) said that the presence of more than 1 high-risk feature, especially a combination of massive peripapillary choroidal invasion and postlaminar optic nerve infiltration, should be considered very high risk for metastasis. CONCLUSIONS AND RELEVANCE: Responses to this nonvalidated survey conducted in 2020-2021 showed little uniformity in the definition of high-risk retinoblastoma. Postlaminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly considered as high risk for metastasis across all oncology practices. These findings suggest that the relevance about their value in the current scenario with advanced disease being treated conservatively needs further evaluation; there is also a need to arrive at consensus definitions and conduct prospective multicenter studies to understand their relevance.
IMPORTANCE: High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving. OBJECTIVE: To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world. DESIGN, SETTING, AND PARTICIPANTS: An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers. INTERVENTION: Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma. MAIN OUTCOMES AND MEASURES: High-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis. RESULTS: Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration (27 [100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (≥3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (<3 mm) choroidal invasion (5 [19%]), and prelaminar optic nerve infiltration (2 [7%]). The other histopathologic features considered high risk included Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]). Four respondents (15%) said that the presence of more than 1 high-risk feature, especially a combination of massive peripapillary choroidal invasion and postlaminar optic nerve infiltration, should be considered very high risk for metastasis. CONCLUSIONS AND RELEVANCE: Responses to this nonvalidated survey conducted in 2020-2021 showed little uniformity in the definition of high-risk retinoblastoma. Postlaminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly considered as high risk for metastasis across all oncology practices. These findings suggest that the relevance about their value in the current scenario with advanced disease being treated conservatively needs further evaluation; there is also a need to arrive at consensus definitions and conduct prospective multicenter studies to understand their relevance.
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