Retinoblastoma seeds: Impact on American Joint Committee on Cancer clinical staging

Aim To investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding. Methods Multicentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method. Results Clinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; p<0.001). There was insufficient evidence to prove or disprove an association between vitreous seed type and local treatment failure risk(p=0.06). Conclusion This international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.Fil: Tomar, Ankit Singh. New York Eye Cancer Center; Estados UnidosFil: Finger, Paul T.. New York Eye Cancer Center; Estados UnidosFil: Gallie, Brenda. University Of Toronto. Hospital For Sick Children; CanadáFil: Kivelä, Tero. University of Helsinki; Finlandia. Helsinki University Hospital; FinlandiaFil: Mallipatna, Ashwin. University Of Toronto. Hospital For Sick Children; Canadá. Narayana Nethralaya; IndiaFil: Zhang, Chengyue. Beijing Children's Hospital; ChinaFil: Zhao, Junyang. Beijing Children's Hospital; ChinaFil: Wilson, Matthew. University of Tennessee; Estados UnidosFil: Brennan, Rachel. St Jude Children's Research Hospital; Estados UnidosFil: Burges, Michala. University of Tennessee; Estados UnidosFil: Kim, Jonathan. Keck Medical School of the University of Southern California; Estados UnidosFil: Berry, Jesse L.. Children's Hospital Los Angeles; Estados UnidosFil: Jubran, Rima. Childrens Hospital Society of Los Angeles; Estados UnidosFil: Khetan, Vikas. Vitreo Retinal Services; IndiaFil: Ganeshan, Suganeswari. Vitreo Retinal Services; IndiaFil: Yarovoy, Andrey. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Yarovaya, Vera. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Kotova, Elena. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Volodin, Denis. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Yousef, Yacoub. King Hussein Cancer Center; JordaniaFil: Nummi, Kalle. University of Helsinki; Finlandia. Helsinki University Hospital; FinlandiaFil: Ushakova, Tatiana L.. N.N. Blokhin Russian Cancer Research Center; Rusia. Russian Academy of Postgraduate Medical Education; RusiaFil: Yugay, Olga V.. N.N. Blokhin Russian Cancer Research Center; RusiaFil: Polyakov, Vladimir G. N.N. Blokhin Russian Cancer Research Center; Rusia. Russian Academy of Sciences; RusiaFil: Ramirez Ortiz, Marco Antonio. Hospital Infantil de Mexico Federico Gomez; MéxicoFil: Esparza Aguiar, Elizabeth. Hospital Infantil de Mexico Federico Gomez; MéxicoFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Yam, Jason C.. The Chinese University of Hong Kong Faculty of Medicine; Hong Kon

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

A Multicenter, International Collaborative Study for AJCC-Staging of Retinoblastoma: Metastasis-Associated Mortality

Purpose: To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB). Design: International, multicenter, registry-based retrospective case series. Participants: A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. Methods: Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied. Main Outcome Measures: Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the KaplaneMeier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait. Results: Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n ¼ 92) from diagnosis to metastasis was 9.50 months. The 5-year KaplaneMeier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97e99) for cT1b and cT2a, 96% (95% CI, 95e97) for cT2b, 89% (95% CI, 88e90) for cT3 tumors, and 45% (95% CI, 31e59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55e25.70; P < 0.001) and cT4 (HR, 48.55; 95% CI, 12.86e183.27; P < 0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease. Conclusions: Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.Fil: Tomar, Ankit Singh. The New York Eye Cancer Center; Estados UnidosFil: Finger, Paul T.. The New York Eye Cancer Center; Estados UnidosFil: Gallie, Brenda. The Eye Cancer Clinic, Princess Margaret Cancer Centre; CanadáFil: Mallipatna, Ashwin. Hospital for Sick Children; CanadáFil: Kivelä, Tero T.. Helsinki University Hospital; FinlandiaFil: Zhang, Chengyue. Beijing Children's Hospital; ChinaFil: Zhao, Junyang. Beijing Children's Hospital; ChinaFil: Wilson, Matthew W.. University of Tennessee; Estados UnidosFil: Kim, Jonathan. University of Southern California; Estados UnidosFil: Khetan, Vikas. Sankara Nethralaya; IndiaFil: Ganesan, Suganeswari. Sankara Nethralaya; IndiaFil: Yarovoy, Andrey. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Yarovaya, Vera. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Kotova, Elena. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Yousef, Yacoub A.. King Hussein Cancer Center; JordaniaFil: Nummi, Kalle. University of Helsinki; FinlandiaFil: Ushakova, Tatiana L.. Blokhin National Medical Research Center Oncology of Russian Federation; RusiaFil: Yugay, Olga V.. Blokhin National Medical Research Center Oncology of Russian Federation; RusiaFil: Polyakov, Vladimir G.. Blokhin National Medical Research Center Oncology of Russian Federation; RusiaFil: Ramirez Ortiz, Marco A.. Hospital Infantil de México Federico Gómez; MéxicoFil: Esparza Aguiar, Elizabeth. Hospital Infantil de México Federico Gómez; MéxicoFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fandino, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Yam, Jason C.. The Chinese University of Hong Kong; Hong KongFil: Lau, Winnie W.. The Chinese University of Hong Kong; Hong KongFil: Lam, Carol P.. The Chinese University of Hong Kong; Hong KongFil: Sharwood, Phillipa. University of Sydney; AustraliaFil: Moorthy, Sonia. KK Women's and Children's Hospital; SingapurFil: Long, Quah Boon. KK Women's and Children's Hospital; Singapu

Global Retinoblastoma Treatment Outcomes: Association with National Income Level

Purpose: To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels.Design: International, multicenter, registry-based retrospective case series.Participants: Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents.Methods: Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes.Main outcome measures: Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy).Results: Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P < 0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P < 0.001).Conclusions: This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.Fil: Tomar, Ankit Singh. New York Eye Cancer Center; Estados UnidosFil: Finger, Paul T.. New York Eye Cancer Center; Estados UnidosFil: Gallie, Brenda. University of Toronto; CanadáFil: Kivelä, Tero T.. Helsinki University Hospital; Finlandia. University of Helsinki; FinlandiaFil: Mallipatna, Ashwin. University Of Toronto. Hospital For Sick Children; CanadáFil: Zhang, Chengyue. Beijing Children’s Hospital; ChinaFil: Zhao, Junyang. Beijing Children’s Hospital; ChinaFil: Wilson, Matthew W.. University of Tennessee; Estados UnidosFil: Brenna, Rachel C.. University of Tennessee; Estados UnidosFil: Burges, Michala. University of Tennessee; Estados UnidosFil: Kim, Jonathan. Keck Medical School of the University of Southern California; Estados UnidosFil: Khetan, Vikas. Sankara Nethralaya; IndiaFil: Ganesan, Suganeswari. Sankara Nethralaya; IndiaFil: Yarovoy, Andrey. The S. N. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Yarovaya, Vera. The S. N. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Kotova, Elena. The S. N. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Yousef, Yacoub A.. King Hussein Cancer Center; JordaniaFil: Nummi, Kalle. Helsinki University Hospital; Finlandia. University of Helsinki; FinlandiaFil: Ushakova, Tatiana L.. N. N. Blokhin National Medical Research Center Oncology of Russian Federation; Alemania. Medical Academy of Postgraduate Education; AlemaniaFil: Yugay, Olga V.. N. N. Blokhin National Medical Research Center Oncology of Russian Federation; AlemaniaFil: Polyakov, Vladimir G.. N. N. Blokhin National Medical Research Center Oncology of Russian Federation; AlemaniaFil: Ramirez Ortiz, Marco A.. Hospital Infantil de Mexico Federico Gomez; MéxicoFil: Esparza Aguiar, Elizabeth. Hospital Infantil de Mexico Federico Gomez; MéxicoFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Fandino, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Yam, Jason C.. Chinese University Of Hong Kong; Hong KongFil: Lau, Winnie W.. Chinese University Of Hong Kong; Hong KongFil: Lam, Carol P.. Chinese University Of Hong Kong; Hong KongFil: Sharwood, Phillipa. University of Sydney; Australi

An International Survey of Classification and Treatment Choices For Group D Retinoblastoma

AIM: To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region. METHODS: An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012. Participants were asked to record which version of the IIRC was used for classification, how many group D eyes were diagnosed, and how many eyes were treated with enucleation versus globe salvaging therapies. Averages of eyes per treatment modality were calculated and stratified by both IIRC version and geographic region. Statistical significance was determined by Chi-square, ANOVA and Kruskal-Wallis tests using Prism. RESULTS: The survey was completed by 29% of physicians invited to participate. Totally 1807 D eyes were diagnosed. Regarding IIRC system, 27% of centers used the Children's Hospital of Los Angeles (CHLA) version, 33% used the Children's Oncology Group (COG) version, 23% used the Philadelphia version, and 17% were unsure. The rate for primary enucleation varied between 0 and 100% and the mean was 29%. By IIRC version, primary enucleation rates were: Philadelphia, 8%; COG, 34%; and CHLA, 37%. By geographic region, primary enucleation rates were: Latin America, 57%; Asia, 40%; Europe, 36%; Africa, 10%, US, 8%; and Middle East, 8%. However, systemic chemoreduction was used more often than enucleation in all regions except Latin America with a mean of 57% per center (P<0.0001). CONCLUSION: Worldwide there is no consensus on which IIRC version is used, systemic chemoreduction was the most frequently used initial treatment during the study period followed by enucleation and primary treatment modality, especially enucleation, varied greatly with regards to IIRC version used and geographic region.WoSScopu

Retinoblastoma seeds: impact on American Joint Committee on Cancer clinical staging

AimTo investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding.MethodsMulticentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method.ResultsClinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; pConclusionThis international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma. Part II: Treatment Success and Globe Salvage

Purpose: To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma(RB).Design: International, multicenter, registry-based retrospective case series PARTICIPANTS: 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents.Methods: Patient-specific data fields for RB were designed by participating eye cancer specialists. All RB patients with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied.Main outcome measures: Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan-Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait.Results: Of the 2190 patients, the records of 2085 patients(95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. 1260 (65.4%) had unilateral RB. Amongst the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b 168 (8.1%), cT2a 197 (9.4%), cT2b 812 (38.9%), cT3 835 (40.0%) and cT4 in 18 (0.9%) patients. Of these, 1397 eyes in 1353 patients(48.1%) were treated with enucleation. One hundred and nine patients (5.2%) developed metastases and died. The median time(n=92) from diagnosis to metastasis was 9.50 months. The 5- year Kaplan-Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval[CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89%(95% CI, 88-90) for cT3 tumors, and 45%(95% CI, 31-59) for cT4 tumors, respectively. Risk of metastasis increased with increasing cT (and pT) category(p < .001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55-25.70; p<0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; p< 0.001) compared to category cT1. Age, tumor laterality and presence of heritable trait did not influence the incidence of metastatic disease.Conclusion: Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real life, heterogenous RB patient population.Fil: Singh Tomar, Ankit. The New York Eye Cancer Center; Estados UnidosFil: Finger, Paul T.. The New York Eye Cancer Center; Estados UnidosFil: Gallie, Brenda. Princess Margaret Cancer Centre; CanadáFil: Mallipatna, Ashwin. University Of Toronto. Hospital For Sick Children; CanadáFil: Kivelä, Tero T.. University of Helsinki; FinlandiaFil: Zhang, Chengyue. Beijing Children's Hospital; ChinaFil: Zhao, Junyang. Beijing Children's Hospital; ChinaFil: Wilson, Matthew W.. University of Tennessee; Estados UnidosFil: Brenna, Rachel C.. University of Tennessee; Estados UnidosFil: Burges, Michala. University of Tennessee; Estados UnidosFil: Kim, Jonathan. The Vision Center at Children's Hospital Los Angeles; Estados UnidosFil: Khetan, Vikas. Sankara Nethralaya; IndiaFil: Ganesan, Suganeswari. Sankara Nethralaya; IndiaFil: Yarovoy, Andrey. The S.N. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Yarovaya, Vera. The S.N. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Kotova, Elena. The S.N. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Yousef, Yacoub A.. King Hussein Cancer Center; JordaniaFil: Nummi, Kalle. University of Helsinki; FinlandiaFil: Ushakova, Tatiana L.. N.N. Blokhin National Medical Research Center Oncology of Russian Federation; RusiaFil: Yugay, Olga V.. N.N. Blokhin National Medical Research Center Oncology of Russian Federation; RusiaFil: Polyakov, Vladimir G.. N.N. Blokhin National Medical Research Center Oncology of Russian Federation; RusiaFil: Ramirez Ortiz, Marco A.. Hospital Infantil de México Federico Gómez; MéxicoFil: Esparza Aguiar, Elizabeth. Hospital Infantil de México Federico Gómez; MéxicoFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fandino, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Yam, Jason C.. The Chinese University of Hong Kong; Hong KongFil: Lau, Winnie W.. The Chinese University of Hong Kong; Hong KongFil: Lam, Carol P.. The Chinese University of Hong Kong; Hong KongFil: Sharwood, Phillipa. University of Sydney; AustraliaFil: Moorthy, Sonia. KK Women’s and Children’s Hospital; SingapurFil: Long, Quah Boon. KK Women’s and Children’s Hospital; SingapurFil: Essuman, Vera Adobea. University of Ghana; GhanaFil: Renner, Lorna A.. University of Ghana; GhanaFil: Semenova, Ekaterina. The New York Eye Cancer Center; Estados UnidosFil: Català, Jaume. Hospital Sant Joan de Déu; EspañaFil: Correa Llano, Genoveva. Hospital Sant Joan de Déu; EspañaFil: Carreras, Elisa. Hospital Sant Joan de Déu; Españ