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Retinoblastoma: A review of clinical profile at a regional cancer center in Northwest India


1 Department of Ophthalmology, Sardar Patel Medical College, Bikaner, Rajasthan, India
2 Department of Radiation Oncology, Sardar Patel Medical College, Bikaner, Rajasthan, India
3 Department of Medical Oncology, Sardar Patel Medical College, Bikaner, Rajasthan, India
4 Department of Internal Medicine, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India

Date of Submission30-Aug-2020
Date of Decision19-Sep-2020
Date of Acceptance26-Nov-2020
Date of Web Publication20-Aug-2021

Correspondence Address:
Surender Beniwal,
Department of Medical Oncology, Sardar Patel Medical College, Bikaner, Rajasthan
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_1263_20

 > Abstract 


Background: Retinoblastoma is the most common primary intraocular malignancy of childhood. The present study was undertaken to overcome the scarcity of data regarding the epidemiology, demographic and clinical profile, and nature of the first health-care professional consulted.
Materials and Methods: A retrospective analysis of medical records was performed for all cases of retinoblastoma who presented to the department of ophthalmology and oncology between 2010 and 2017. A total of 54 cases were reviewed.
Results: Unilateral disease was seen in 85.2% while 14.8% presented with bilateral disease with a median age of 3 years and 2 years, respectively, at diagnosis. The male: female ratio was 2:1. The most common presenting symptom was leukocoria which was noticed in 42 patients (77.7%), followed by red eye (33.3%) and proptosis (20.3%). The most common stage of presentation was Stage I (44.4%), followed by Stage IV (20.4%), Stage III (9.3%), and Stage II (5.6%). The median time to diagnosis was 8.7 months (range, 0.5–98.7 months), and the median time to treatment was 37.4 days (range, 0–645 days). Majority of the patients were referred by local ophthalmologists (48%), followed by general practitioners (20%), nurses (19%), and quacks (13%). Enucleation was the most preferred treatment modality (48.1%), followed by chemotherapy (33.3%), radiotherapy (13%), photocoagulation (3.7%), and exenteration (1.9%). The overall remission rate was 79.6%, while 12.3% had relapse and 7.4% died.
Conclusion: The study showed a dire need for timely detection and treatment of retinoblastoma which is possible with improved awareness and better accessibility to health-care facilities. It also revealed a decrease in histopathological risk factors with chemoreduction.

Keywords: Enucleation, leukocoria, ocular malignancy, retinoblastoma



How to cite this URL:
Beniwal V, Maheshwari G, Beniwal S, Dhanawat A, Tantia P, Adlakha P. Retinoblastoma: A review of clinical profile at a regional cancer center in Northwest India. J Can Res Ther [Epub ahead of print] [cited 2021 Dec 5]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=324162




 > Introduction Top


Retinoblastoma is the most common primary intraocular malignancy of children, arising from the embryonic neural retina. In most developed nations, where the disease is diagnosed in intraocular stage, it has a good survival rate (>90%) when treated timely.[1] However, the scenario in developing countries is different wherein the burden of the disease is high and the survival rates are poor owing to advanced disease at presentation which limits globe salvage.[2],[3] Latin America, Africa, and Asia including India have shown a high disease burden.[4],[5],[6] It has a global incidence of 1 in every 20,000 live births.[7] India witnesses around 1500 new cases every year, accounting for 33% of the worldwide burden, with a mortality as high as 24%. Most of the patients (98%) are diagnosed by the age of 5 years.

Delayed diagnosis and referral to an equipped center leads to poor ocular results and decreased patient survival among developing nations.[8],[9] Lack of education and income adds to the current problem of incomplete treatment.[9] The incidence of retinoblastoma is on a rise as reported by the Indian Council of Medical Research in numerous hospital-based cancer registries.[10]

Although the overall survival of children with retinoblastoma has improved over the past couple of decades, it is at the expense of greater morbidity manifesting as various late effects of treatment such as contracted socket, impaired orbital growth, visual and hearing impairments, and psychosocial and intellectual deficits to name a few. These complications justify the need for long-term follow-up of retinoblastoma survivors for evaluation of primary disease, relapse, eye care as well as their blending in the society.

Data detailing the demographic and clinical parameters of retinoblastoma are scarce in the Indian setting, and hence, the present study was undertaken to discuss the epidemiology, demographic profile, pattern of presentation to the first health-care professional, and clinical features in patients with retinoblastoma presenting/being referred to a tertiary care cancer center in Northwest India.


 > Materials And Methods Top


A retrospective analysis of medical records was performed for all cases of retinoblastoma that presented at the retinoblastoma clinic in the department of ophthalmology and at a regional cancer center in Northwest India from January 2010 to December 2017. For extracting the data, the hospital-based registry and hard copies of case files were reviewed. A total of 54 patients were analyzed for demographic parameters such as age at presentation, gender, locality, and date of diagnosis. The stage of disease and treatment given were also recorded.

All patients were subjected to an external ocular examination. The status of the lids/adnexa, extraocular movement, and presence or absence of vitreous seeding were noted. Visual acuity was also recorded. Anterior segment evaluation was performed via slit-lamp biomicroscopy (Haag-Streit Burn 900 or a Shin Nippon Hand-Held Slit Lamp). Fundus was evaluated following full pupil dilation with both direct and indirect ophthalmoscopy (Heine with Volk + 20D). When tumor masses were identified, their size, quadrant, number, and location were noted. Intraocular pressure was measured using Schiotz tonometry.

Following the diagnosis of retinoblastoma, the available treatments included enucleation, exenteration, radiotherapy, and chemotherapy. Due to unavailability of cryotherapy and photocoagulation, patients requiring the same were referred to other higher centers. A complete histopathological examination was performed on all enucleated/exenterated specimens and was classified based on differentiation, optic nerve infiltration, and orbital involvement. Chemotherapy was administered in the form of OPEC protocol over 55 h, beginning with vincristine (1.5 mg/m2) and cyclophosphamide (600 mg/m2) followed by cisplatin (80 mg/m2) and etoposide (200 mg/m2).

Statistical analysis

Descriptive statistics were used to describe demographic and clinical characteristics.


 > Results Top


Incidence of retinoblastoma

Out of a total of 529 childhood (age < 15 years) cancer cases registered over a period of 8 years (January 2010–December 2017), 54 children were diagnosed as retinoblastoma. Most of the patients were from the state Rajasthan (74.1%), followed by Punjab (11.1%) and Haryana (7.4%). Unilateral disease was seen in 46 patients (85.2%), while 8 patients (14.8%) presented with bilateral disease. The median age at diagnosis was 3 years for patients with unilateral disease and 2 years for those with bilateral disease. The male: female ratio was 2:1 (36 boys and 18 girls). Three patients (5.55%) had a family history of retinoblastoma [Table 1].
Table 1: Demographicprofileofpatients(n=54)

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Clinical symptoms and stage-wise distribution of patients

All the patients were symptomatic at presentation and none were discovered by screening. The earliest and most common presenting symptom was leukocoria [Figure 1] which was noticed in 42 patients (77.7%), followed by red eye in 18 patients (33.3%) and proptosis in 11 patients (20.3%). Strabismus and fungating mass were noted in 6 (11.1%) and 2 (03.7%) patients, respectively. Other clinical presentations included vitreous hemorrhage, hyphema, glaucoma, anisocoria, and orbital cellulitis [Table 2]. Stage I was observed in 44.4% of the patients, while 5.6% presented as Stage II, 9.3% as Stage III, and 20.4% as Stage IV, according to the International Retinoblastoma Staging System [Table 3]. Out of the 24 patients in Stage I, 3.7% presented in Group A, 11.1% in Group B and C each, and 9.3% in Group D and E each, according to the International Intraocular Retinoblastoma Classification [Table 4]. Few patients also presented with features of metastatic disease such as weight loss, vomiting, headache, neurologic impairment, orbital mass, fever, or soft-tissue mass.
Table 2: Frequencyofpresentingsymptomsandtheirduration

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Table 3: Stage-wisedistributionofpatientsaccordingtotheInternationalRetinoblastomaStagingSystem

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Table 4: Group-wisedistributionofpatientsofStageIInternationalRetinoblastomaStagingSystem(n=24)accordingtoInternationalIntraocularRetinoblastomaClassification

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Figure 1: Leukocoria (white eye), the most common presenting symptom of retinoblastoma

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Diagnosis

The median time to diagnosis was 8.7 months (range, 0.5–98.7 months), and the median time to treatment was 37.4 days (range, 0–645 days) [Table 5]. The histopathological characteristics with the duration of symptoms and age of presentation of 27 patients who had undergone enucleation/exenteration were tabulated [Table 6] and [Figure 2]. In most cases, the signs of retinoblastoma were recognized by the family members (88%), followed by ophthalmologist (5%), general practitioner (4%), and nurse (1%), though all patients presenting to our hospital were referred by local ophthalmologists (48%), general practitioners (20%), nurses (19%), and quacks (13%). The study found that the time to diagnosis was shortest when the initial health-care professional consulted was an ophthalmologist (6 ± 1 months) as compared to others. Surprisingly, nurses had a shorter time to diagnosis (9 ± 1 months) when compared with general practitioners (10 ± 2 months) or quacks (19 ± 3 months).
Table 5: Timetodiagnosisandtreatmentofretinoblastoma

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Table 6: Histopathologicalfindingsofenucleated/exenteratedspecimenswithdurationofsymptomsandageatpresentation

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Figure 2: Histopathological findings (H and E, ×40) of retinoblastoma showing a small round blue cell tumor in sheets with marked areas of calcification, Flexner–Wintersteiner rosettes, and Homer Wright rosettes

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Treatment and outcomes

Twenty-six (48.1%) patients underwent enucleation while one (1.9%) had to undergo exenteration [Figure 3]. Radiotherapy was received by 13% while 33.3% received chemotherapy as neoadjuvant/primary/adjuvant treatment and 3.7% of the patients were sent for photocoagulation at higher centers [Table 7]. Out of the enucleated patients, 81% had a complete remission while 11.5% developed relapse and 7.7% died. With radiotherapy, 71% of the patients showed remission while those with a relapse or mortality were 14% each. Patients who received chemotherapy either as monotherapy or in combination with radiotherapy in the neoadjuvant/primary/adjuvant setting had an 83% remission rate and 11% relapse rate while having a 5.6% mortality [Table 8].
Table 7: Treatment-wisedistributionofpatientsaccordingtolateralityofdisease

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Table 8: Treatmentoutcomeswithvariousmodalities

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Figure 3: Postenucleation of unilateral retinoblastoma

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 > Discussion Top


The majority of primary intraocular malignancy in children is attributed to retinoblastoma which represents nearly 4% of all pediatric cancers with considerably higher rates in developing countries.[11],[12] In most developed nations, it is responsible for 2.5%–4% of all childhood cancers, while in India, the incidence of tumors of the eye (majority of which are retinoblastoma in children <15 years of age) is 2–3-fold higher.[11],[12],[13],[14] Around one-third of the retinoblastoma cases in the Asia-Pacific region are accounted for by India.[6] The present study analyzed retinoblastoma patients for demographics, symptomatology, stage at diagnosis, and treatment from a regional cancer center in Northwest India over a period of 8 years from 2010 to 2017.

Most of the patients presented with unilateral disease (85%). The median age at diagnosis was 36 months and 24 months for unilateral and bilateral diseases, respectively, which is comparable to the range of 29–33 months in previous reports from India.[6],[13],[15] It is also similar to studies from other countries such as Egypt[16] (36 months) and Mali[17] (50 months). The age difference between the unilateral and bilateral groups could be due to lower age of presentation of heritable retinoblastoma which is usually bilateral, and this difference is similar to reports from other countries.[18],[19] This study shows a predilection for males (66.7%), which is similar to the literature from Mexico[11] (52.4%), Mali[17] (54.5%), Egypt[20] (60.25), and Jordan[21] (70.0%). Three patients (5.5%) had a family history of retinoblastoma which was comparable to 6.67% in Singapore[22] and 4.8% in Iran.[23]

The most common presenting feature of patients in our study was leukocoria (77.7%), followed by red eye, proptosis, strabismus, and fungating mass. Advanced disease at presentation was seen in 55.6% of our patients which was similar to various studies from India[6],[24] and other developing countries with respect to late diagnosis, advanced stage at presentation and poor outcomes/loss of follow-up.[25],[26] The median time to diagnosis in our study was 8.7 months, and the median time to treatment was 37.4 days. In most cases, the signs of retinoblastoma were recognized by the family members (88%), followed by ophthalmologists, general practitioners, nurses, and quacks. The study found that the time to diagnosis was shortest when the initial health-care professional consulted was an ophthalmologist (6 months) as compared to others. Cases of delayed metastasis have also been reported in the literature which warrants a long-term follow-up in retinoblastoma.[27]

In our setup, primary enucleation was difficult owing to the advanced presentation and risk of dissemination of the disease in most patients. Hence, chemoreduction was achieved with the help of 2–3 cycles of chemotherapy after which the tumor was surgically resected and rest of the chemotherapy cycles were completed in the adjuvant setting. Among those enucleated, 81% had a complete remission while 11.5% developed relapse and 7.7% died. Patients who were treated with radiotherapy also showed a good remission rate of 71%, while relapse and mortality were observed in 14% each. Those who received chemotherapy either as monotherapy or in combination with radiotherapy in the neoadjuvant/primary/adjuvant setting had an 83% remission rate and 11% relapse rate while having a 5.6% mortality. These data are similar to other studies conducted across India.[28]


 > Conclusion Top


A lot of patients present to local quacks due to poor accessibility to health care resulting in delay in diagnosis. It is imperative to educate the masses about treatment options and remove the taboo related to enucleation and alternative medicine. National level programs, screening camps, and national retinoblastoma registry will help us in achieving better outcomes.

Acknowledgments

The authors would like to thank the doctors and support staff of the Department of Ophthalmology, Medical Oncology, and Radiation Oncology, Sardar Patel Medical College, Bikaner, Rajasthan, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

 
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