{
  "abstract": "Background To determine the unique clinical characteristics and treatment outcomes of diffuse infiltrating retinoblastoma (DIR).Methods This international, multicentre, registry-based retrospective case series analysed pooled data from January 2001 to December 2013, including 132 eyes from 132 patients with DIR.Results Among 2854 eyes with retinoblastoma, 132 (4.6%; 95% CI, 3.9 to 5.5) had DIR. The median age at diagnosis for DIR patients was 24 months (IQR, 15–33), with no bilateral cases of DIR. The American Joint Committee on Cancer staging showed 4.5% cT2 and 95.5% cT3 categories, with no cT1 or cT4 cases. Clinical features associated with DIR included secondary glaucoma (67%), retinal detachment (38%), diffuse vitreous seeds (37%), anterior segment involvement (24%), vitreous haemorrhage (50%) and hyphema (6%). Primary enucleation was the predominant treatment (81%), while 19% initially received systemic chemotherapy, with 6% requiring subsequent enucleation. The 5-year Kaplan-Meier survival rate for cT3 DIR was 82% (95% CI, 78 to 86), significantly lower than the 94% (95% CI, 93 to 95) for cT3 non-DIR cases (p<0.001). Cox proportional hazards regression returned a higher risk of metastatic death for DIR cT3 compared with non-DIR cT3 (HR, 3.3; 95% CI, 1.8 to 5.9; p<0.001). High-risk pathological features were more frequent in DIR (41% vs 28%, p=0.004). There was no association between DIR and local treatment failure.Conclusions Approximately 1 in 20 patients with retinoblastoma had DIR, which often presented with glaucoma, anterior segment involvement or intraocular bleeding. DIR was more lethal than non-DIR cT3, with enucleation revealing high-risk pathology.",
  "authors": [
    {
      "affiliations": [
        "Ocular Tumor, Orbital Disease, and Ophthamic Radiation Therapy, The New York Eye Cancer Center, New York, New York, USA"
      ],
      "name": "Ankit Singh Tomar"
    },
    {
      "affiliations": [
        "Ocular Tumor, Orbital Disease, and Ophthamic Radiation Therapy, The New York Eye Cancer Center, New York, New York, USA"
      ],
      "name": "Paul T Finger"
    },
    {
      "affiliations": [
        "Department of Ophthalmology and Vision Sciences, Retinoblastoma Program, Hospital for Sick Children, Toronto, Ontario, Canada"
      ],
      "name": "Brenda Gallie"
    },
    {
      "affiliations": [
        "Ocular Oncology Service, Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Uusimaa, Finland"
      ],
      "name": "Tero T Kivelä"
    },
    {
      "affiliations": [
        "Department of Ophthalmology and Vision Sciences, Retinoblastoma Program, Hospital for Sick Children, Toronto, Ontario, Canada",
        "Department of Ocular Oncology, Narayana Nethralaya Eye Hospital, Bangalore, India"
      ],
      "name": "Ashwin Mallipatna"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Pediatric Oncology Center, Beijing Children’s Hospital, Beijing, China"
      ],
      "name": "Chengyue Zhang"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Pediatric Oncology Center, Beijing Children’s Hospital, Beijing, China"
      ],
      "name": "Junyang Zhao"
    },
    {
      "affiliations": [
        "Department of Ophthalmic Oncology, The Hamilton Eye Institute, Memphis, Tennessee, USA"
      ],
      "name": "Matthew W Wilson"
    },
    {
      "affiliations": [
        "Ophthalmology Division, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA"
      ],
      "name": "Rachel C Brennan"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, College of Medicine, Memphis, Tennessee, USA"
      ],
      "name": "Michala Burges"
    },
    {
      "affiliations": [
        "Ocular Oncology and Retinoblastoma, Doheny Eye Institute, Children's Hospital Los Angeles, Los Angeles, California, USA"
      ],
      "name": "Jesse L Berry"
    },
    {
      "affiliations": [
        "Cancer and Blood Diseases, Children’s Hospital Los Angeles, los Angeles, California, USA"
      ],
      "name": "Rima Jubran"
    },
    {
      "affiliations": [
        "Ocular Oncology and VitreoRetina, Sankara Nethralaya, Chennai, Tamil Nadu, India"
      ],
      "name": "Vikas Khetan"
    },
    {
      "affiliations": [
        "Ocular Oncology and VitreoRetina, Sankara Nethralaya, Chennai, Tamil Nadu, India"
      ],
      "name": "Suganeswari Ganesan"
    },
    {
      "affiliations": [
        "Ocular Oncology Department, The SN Fyodorov Eye Microsurgery Federal State Institution, Moscow, Russian Federation"
      ],
      "name": "Andrey Yarovoy"
    },
    {
      "affiliations": [
        "Ocular Oncology Department, The SN Fyodorov Eye Microsurgery Federal State Institution, Moscow, Russian Federation"
      ],
      "name": "Vera Yarovaya"
    },
    {
      "affiliations": [
        "Ocular Oncology Department, The SN Fyodorov Eye Microsurgery Federal State Institution, Moscow, Russian Federation"
      ],
      "name": "Elena Kotova"
    },
    {
      "affiliations": [
        "Ocular Oncology Department, The SN Fyodorov Eye Microsurgery Federal State Institution, Moscow, Russian Federation"
      ],
      "name": "Denis Volodin"
    },
    {
      "affiliations": [
        "Surgery (Ophthalmology), King Hussein Cancer Center, Amman, Jordan"
      ],
      "name": "Yacoub A Yousef"
    },
    {
      "affiliations": [
        "Ocular Oncology Service, Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Uusimaa, Finland"
      ],
      "name": "Kalle Nummi"
    },
    {
      "affiliations": [
        "Pediatric Oncology, Medical Academy of Postgraduate Education, Moscow, Russian Federation",
        "SRI of Pediatric Oncology and Hematology of NN Blokhin National Medical Research Center Oncology of Russian Federation, Moscow, Russian Federation"
      ],
      "name": "Tatiana L Ushakova"
    },
    {
      "affiliations": [
        "SRI of Pediatric Oncology and Hematology of NN Blokhin National Medical Research Center Oncology of Russian Federation, Moscow, Russian Federation"
      ],
      "name": "Olga V Yugay"
    },
    {
      "affiliations": [
        "Pediatric Oncology, Medical Academy of Postgraduate Education, Moscow, Russian Federation",
        "SRI of Pediatric Oncology and Hematology of NN Blokhin National Medical Research Center Oncology of Russian Federation, Moscow, Russian Federation"
      ],
      "name": "Vladimir G Polyakov"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico"
      ],
      "name": "Marco A Ramirez-Ortiz"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico"
      ],
      "name": "Elizabeth Esparza-Aguiar"
    },
    {
      "affiliations": [
        "Hematooncology, Hospital JP Garrahan, Buenos Aires, Argentina, Buenos Aires, Argentina",
        "Oncology, Sant Joan de Deu Hospital, Barcelona, Barcelona, Spain"
      ],
      "name": "Guillermo Chantada"
    },
    {
      "affiliations": [
        "Hospital de Pediatria JP Garrahan, Buenos Aires, Buenos Aires, Argentina"
      ],
      "name": "Paula Schaiquevich"
    },
    {
      "affiliations": [
        "Hospital de Pediatria JP Garrahan, Buenos Aires, Buenos Aires, Argentina"
      ],
      "name": "Adriana Fandiño"
    },
    {
      "affiliations": [
        "Department of Ophthalmology and Visual Sciences, Hong Kong Eye Hospital, Hong Kong, Hong Kong"
      ],
      "name": "Jason C Yam"
    },
    {
      "affiliations": [
        "Department of Ophthalmology and Visual Sciences, Hong Kong Eye Hospital, Hong Kong, Hong Kong"
      ],
      "name": "Winnie W Lau"
    },
    {
      "affiliations": [
        "Department of Ophthalmology and Visual Sciences, Hong Kong Eye Hospital, Hong Kong, Hong Kong"
      ],
      "name": "Carol P Lam"
    },
    {
      "affiliations": [
        "University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "Phillipa Sharwood"
    },
    {
      "affiliations": [
        "KK Women's and Children’s Hospital, Singapore"
      ],
      "name": "Sonia Moorthy"
    },
    {
      "affiliations": [
        "KK Women's and Children’s Hospital, Singapore"
      ],
      "name": "Quah Boon Long"
    },
    {
      "affiliations": [
        "University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana"
      ],
      "name": "Vera Adobea Essuman"
    },
    {
      "affiliations": [
        "Department of Child Health, College of Health Sciences University of Ghana, Accra, Ghana"
      ],
      "name": "Lorna A Renner"
    },
    {
      "affiliations": [
        "Ocular Tumor, Orbital Disease, and Ophthamic Radiation Therapy, The New York Eye Cancer Center, New York, New York, USA"
      ],
      "name": "Ekaterina Semenova"
    },
    {
      "affiliations": [
        "Ophthalmology, Hospital Universitari Sant Joan de Déu, Barcelona, Spain"
      ],
      "name": "Jaume Catala-Mora"
    },
    {
      "affiliations": [
        "Oncology, Sant Joan de Deu Hospital, Barcelona, Barcelona, Spain"
      ],
      "name": "Genoveva Correa-Llano"
    },
    {
      "affiliations": [
        "Ophthalmology, Hospital Universitari Sant Joan de Déu, Barcelona, Spain"
      ],
      "name": "Elisa Carreras"
    },
    {
      "affiliations": [],
      "name": "on behalf of AJCC OOTF"
    }
  ],
  "title": "Diffuse infiltrating retinoblastoma: a multicentre, international, data-sharing study",
  "uid": "b48fe3cc-4fc6-5ab3-b4ab-8f8e8586cdf4"
}