Dr.Sima Das, D10596, Dr.Vikas Menon, Dr.Bhaduri Anirban, Dr.Deepanjali Arya
Introduction
Retinoblastoma is the most common intraocular malignant tumor in children.Worldwide, increased awareness about the disease and advances in the management techniques have allowed for early diagnosis and improved survival of these children. Survival rates reported from the Western countries range from 88% in United Kingdom to 93% in United States1, 2. In India, Nepal, Africa and South Americancountries, the prognosis remains poor with increased proportion of these children presenting at an advanced stage of disease. Orbital retinoblastoma has been reported to be 18% in Mexico, 36% in Taiwan and 40% in studies from Nepal. In India, the proportion of orbital retinoblastoma has a geographical variation with incidence of 37% reported in study from North India and 9% in a study from South India. Despite the availability of a standard treatment protocol, extraocular retinoblastoma carries a poor prognosis. This study aims to highlight the clinical profile, treatment outcome of extraocular retinoblastoma patients and to identify factors responsible for delay in diagnosis or treatment leading to extraocular extension of disease.
Method
Medical records of all extraocular retinoblastoma patients who were treated at the Ocular Oncology clinic of three tertiary care eye hospital of North and East India from Jan 2010 to December 2017 were reviewed. Retrospective data from medical records were collected and in patients who were lost to follow up, the current status was telephonically reviewed by the investigators. Data were collected about the demographic profile of the patient, socioeconomic status of the patient as the modified Kuppuswamy scale, presenting signs and symptoms, treatment lag time, reasons for the delayed presentation and treatment, clinical staging of the disease as par International retinoblastoma staging system. Data was also collected about the treatment given and the outcome of treatment.Data was analysed to find the factors responsible for delay in the diagnosis and treatment.
Result
Seventy four patients of extraocular retinoblastoma were identifiedduring the study period. The mean age at presentation was 35.02(7-84mths) months. 56% were male and 44% were females.Disease was bilateral in 19% and unilateral in 81% patients. Most patients belonged to Hindu religion(70.2%). The average number of siblings were 2.54.(1-5)thirteen patients(17%)gave a family history of retinoblastoma. Majority of the patients (77.19%) belonged to upper –lower category in the kuppuswamyeconomic scale The first symptom noticed by parents was leukocoria(38.59%). Proptosis with a fungating orbital mass is the most common presenting sign seen in 65% of patients.The average presentation lag time was 4.61 months(1 to 24) months, average physician lag time was 2.04(1 to 12). Total treatment lag time was 8.17 months.54% of patients travelled more than 250Km distance for treatment at the Ocular Oncology Centre. In patients with a prolonged treatment lag time, 30% cited the lack of availability of treatment facilities in the vicinity and the need to travel long distance as the reason for delay in reaching the treatment centre. In 14% patients lack of financial resources was the reason cited for delay in treatment. 12% patients refused enucleation and abandoned treatment leading to extraocular extension of disease.
Orbital involvement was noted at presentation in 28(38%) patients. 10(13.5%) patients presented with extraocular tumor after discontinuing treatment and was lost to follow up. Orbital involvementwas primary in 47% patients, secondary in 23% patients, accidental in 4%patients, overt in 9% patients and microscopic in 12% patients. 5% patients had bone marrow metastasis without any apparent orbital extension of the disease. .
21 patient(28%) had distant metastasis at presentation, 4% had lymph node involvement, 7%had CNS involvement , 8% had only bone marrow involvement and 10.5% had bone marrow, CSF and lymph node involvement at presentation.17 patients (23%)developed metastasis during the course of the treatment.
17 patients(23%) received palliative treatment. 37 % patients completed the treatment regimen and 9% of these patients developed distant metastasis after completion of treatment. 17 patients(23%) patients developed metastasis during the course of treatment. At last follow up, mortality due to disease was 53%, 2% died due to other cause, survival rate was 27% and 18 % patients were lost to follow up.
Discussion
Retinoblastoma is the most common intraocular malignant tumor in children. Timely detection at an early stage of tumor can slavage life and eye in these patients. In India, a major proportion of patients still presents at an advanced stage of disease worsening prognosis. In the current study, retinoblastoma was extraocular in 38%of patients and metastatic in 28% of patients at presentation. indicating a delay in the diagnosis or treatment initiation.Other Indian studies from North India has reported a 37% incidence of extraocular retinoblastoma. This is in contrast to Western countries where extraocular Rb has been reported to range from 6.3 to 7.6%.Also, results from the different parts of India show a variable incidence of extraocular retinoblastoma.Kalki et al in a large cohort of patient from Southern India has reported a 9% incidence of extraocular retinoblastoma at presentation. This difference could be because of the cultural and ethnic difference causing better acceptance of prescribed treatment. Also, Lack of available treatment facility in the vicinity and inability to travel long distance was the most common reason cited for the delay in treatment initiation in our study. Southern part of India has several dedicated Ocular Oncology units specifically aimed for retinoblastoma treatment. Setting up similar dedicated treatment centres in the areas of need should help in making the treatment more available and acceptance thus allowing for early treatment and improving prognosis.
Extraocular retinoblastoma carries a poor prognosis despite the use of a high dose chemotherapy treatment as exemplified by the 53% mortality in our study. Hence, early detection is the key to improving survival and prognosis in these patients. In 27% of patients in this study, the orbital retinoblastoma was secondary or overt, resulting from accidental intraocular surgery in patients with retinoblastoma or residual orbital disease in the transected optic nerve following primary enucleation for which no further treatment was given. Hence, there is need to train the treating ophthalmologist about the standard protocol for treatment of retinoblastoma as well as the techniques of retinoblastoma enucleation.
Lack of financial resources was also a major reason for delay in treatment initiation. Retinoblastoma is most commonly seen in patients belonging to poor socioeconomic strata, hence making the treatment affordable as well providing other support facilities like travel and lodging facilities to treating centres will help in improving the treatment acceptance.
Extraocular retinoblastoma carries a poor prognosis. High dose vincristine, etoposide and carboplatin based chemotherapy protocol along with local resection by enucleation or exenteration followed by external beam radiotherapy is the currently used management protocol for extraocular retinoblastoma. Despite the use of this treatment protocol, 32% patients developed distant metastasis during the course or after completion of treatment.
In conclusion, extraocular retinoblastoma carries a poor prognosis despite treatment. Making treatment facilities available and affordable will help in early treatment of retinoblastoma patients thus reducing mortality due to the disease.
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