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This inexpensive approach is an effective first step toward improving survival of childhood retinoblastoma. Abandonment and refusal of therapy are continuing obstacles.

Global Retinoblastoma Study Group 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 PARTICIPANTSA 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 MEASURESAge at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. RESULTSThe 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,, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI,). CONCLUSIONS AND RELEVANCEThis 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.

Bridging the survival gap for children with cancer, between those (the great majority) in low and middle income countries (LMIC) and their economically advantaged counterparts, is a challenge that has been addressed by twinning institutions in high income countries with centers in LMIC. The long-established partnership between a Central American consortium--Asociación de Hemato-Oncología Pediátrica de Centro América (AHOPCA)--and institutions in Europe and North America provides a striking example of such a twinning program. The demonstrable success of this endeavor offers a model for improving the health outcomes of children with cancer worldwide. As this remarkable enterprise celebrates its 15th anniversary, it is appropriate to reflect on its origin, subsequent growth and development, and the lessons it provides for others embarking on or already engaged in similar journeys. Many challenges have been encountered and not all yet overcome. Commitment to the endeavor, collaboration in its achievements and determination to overcome obstacles collectively are the hallmarks that stamp AHOPCA as a particularly successful partnership in advancing pediatric oncology in the developing world.

Pediatric cancer programs in low-income countries (LIC) can improve outcomes. However, treatment must be tailored to the patient's living conditions and the availability of supportive care. In some cases, a more intense regimen will decrease survival since the increase in death from toxicity may exceed any decrease in relapse. Attempts to practice evidence-based pediatric oncology are thwarted by the lack of evidence derived from local experience in LIC to determine optimal therapy. This report summarizes treatment regimens used by pediatric oncologists from 15 countries of the Caribbean, Central and South America who participate in the Monza International School of Pediatric Hematology/Oncology (MISPHO). Patients with hepatoblastoma, Wilms tumor, and histiocytosis treated on unmodified published protocols had outcomes comparable to those in high-income countries (HIC). Those with rhabdomyosarcoma, osteosarcoma, Hodgkin lymphoma, and acute myeloid leukemia treated with unmodified regimens had event-free survival estimates 10%-20% lower than those reported in HIC due to higher rates of toxic death, abandonment of therapy, and relapse. Treatment of retinoblastoma is complicated by advanced stages and extraocular disease at diagnosis; improved outcomes depend on education of pediatricians and the public to recognize early signs of this disease. Use of unmodified protocols for Burkitt lymphoma and acute lymphoblastic leukemia have been associated with unacceptable toxicity in LIC, so MISPHO centers have modified published regimens by giving lower doses of methotrexate and reducing use of anthracyclines. Despite the use of all-trans-retinoic acid during induction for acute promyelocytic leukemia, the incidence of fatal hemorrhage remains unacceptably high.