PROPOSAL

A 5 years retrospective case series on the clinical profile and management of retinoblastoma at Maputo Central Hospital,

Mozambique.

Supervisors:PROF.  DUNERA R.  ILAKODR  E.M. NYENZEDR  Y. ZAMBUJO

Principal investigator LACEA  S. A. DIMANDE 

INTRODUCTION

• Retinoblastoma accounts for about 3% of all childhood cancers.

• Commonest solid tumour in children after brain/nervous system tumours and lymphomas in UK and USA,1 and second commonest after Burkitt’s  lymphoma in Africa:

- Nigeria: Burkitt’s lymphoma 36%/ Retinoblastoma 21% 2

- Ghana: Burkitt’s lymphoma 67%/ Retinoblastoma 8.6% 3

- Kenya: Non-Hodgkin's lymphoma 34%/ Retinoblastoma 5% 4

1. Foucher ES, Stiller CA. International classification of Childhood Cancer, third edition. Cancer 2005 apr 1; 103(7):1457-1467

2. Agboola AO, Adekanmbi FA, Musa AA et al. Pattern of childhood malignant tumours in a teaching hospital in south-western Nigeria ,Med J Aust. 2009 Jan 5; 190(1):12-4.

3.  Welbeck JE, Hesse AA. Pattern of childhood malignancy in Korle Bu Teaching Hospital, Ghana. West Afr. Med. J. 1998; 17(2) 81-4.

4. Mostert S,  Njuguna F, Kemps L, et al. Epidemiology of diagnosed childhood cancer in western Kenya Arch Dis Child 2012 ; 97:508-512 . 

    

INTRODUCTION• Commonest intraocular malignancy in childhood affecting children less than 5 years with over

90% being diagnosed before 3 years: 5

• 7000 to 9000 cases are diagnosed each year worldwide. 6

5. Ophthalmologists, American Academy of. Ophthalmic Pathology and Intraocular Tumours: Section 4 - BCSC. Singapore : AAO, 2012- 2013.

6. Kivela T. The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death. Br J Ophthalmol2009; 93: 1129–31

7. Nyawira G, Kahaki K, Kariuki M.  Survival among Retinoblastoma patients at KNH, Kenya. Journal of Ophthalmology of Eastern Central and Southern Africa August 2013; 17(1):

15-19

Mean age at diagnosis  Bilateral cases  Unilateral cases

Developed countries 5 12months (30%-40% cases)

24 months(60%-70% cases)

 Mean age at presentation Bilateral cases  Unilateral cases

Kenya: 37.5 month(3.1 yr) 7 24.4month (2.2years) 39.9 month (3years)

LITERATURE REVIEW

• Frequency of retinoblastoma has increased over the past 60 years, varying according with the country:

5.       Ophthalmologists, American Academy of. Ophthalmic Pathology and Intraocular Tumours: Section 4 - BCSC. Singapore : AAO, 2012- 2013

8. Broaddus E, Topham A, Singh AD. Incidence of retinoblastoma in the USA: 1975-2004. Br J Ophthalmol 2009; 93:21-23

9. Seregard S, Lundell G, SvedbergH, Kivelä  T: Incidence of retinoblastoma from 1958 to 1998 in Northern Europe: Advantages of birth cohort analysis. Ophthalmology

2004;111:1228

10. Owoeye JFA, Afolayan EAO, Ademola-Popoola DS.  Retinoblastoma – a clinicopathologic study in Ilorin Nigeria. Afr J Health Sci 2005; 12(3-4): 94-100

11. Nyamori JM, Kimani K, Njuguna MW,  Dimaras H. The incidence and distribution of retinoblastoma in Kenya. no. 1; pp. 141–3, s.l.: The British Journal of Ophthalmology,

Jan 2012, Vols. vol. 96

  Incidence

Worldwide 1:14,000-1:20,000 live births 5

Developed countries: USA and Northern Europe 1: 15,000 -1:20,000 live births 8,9

Developing countries of Africa and in Asia 1: 18,000 live births 10

Kenya 1: 17,030 live births 11

Mozambique No published data was found

LITERATURE REVIEW

• In developed countries retinoblastoma patients present early with white reflex (60%) and squint(20%) 5:

-Leukocoria was the most common presenting complaint (56.2%), followed by squint (23.6%) 12

• While in developing countries patients present very late with orbital disease:

-Proptosis was the commonest presenting complaint(42.3%) followed by leukocoria (26,9%) 13

-White reflex (71% cases) was commonest presenting complaints followed by eye swelling (37%). Advanced disease (48% of cases with proptosis /recurrence socket mass) 7

5. Ophthalmologists, American Academy of. Ophthalmic Pathology and Intraocular Tumours: Section 4 - BCSC. Singapore : AAO, 2012- 2013

7.        Nyawira G, Kahaki K, Kariuki M.  Survival among Retinoblastoma patients at KNH, Kenya. Journal of Ophthalmology of Eastern Central and Southern Africa August 2013; 17(1): 15-19

12. Abramson DH, Frank CM, Susman M. Presenting signs of retinoblastoma J Pediatr. 1998 Mar; 132(3 Pt 1):505-8.

13. Kimani K, Ilako D, Kollmann M, A review of retinoblastoma, presentation, diagnosis and management at Kenyatta National Hospital. University of Nairobi, 2000

LITERATURE REVIEW

• The survival rate in developed countries has been shown to be very good(over 95%) 14 while in developing countries it is poor (Africa less than 50%): 7,15

• Study of Survival among Retinoblastoma patients at KNH showed: 7

- Cumulative 3-year survival rate was 26.6% - Mean survival time for the survivors was 68 months (5.6yr)

7. Nyawira G, Kahaki  K, Kariuki M. Survival among Retinoblastoma patients at KNH, Kenya. Journal of Ophthalmology of Eastern Central and Southern Africa

Agust 2013; 17(1): 15-19

14. A. MacCarthy, J. M. Birch, G. J. Draper et al. “Retinoblastoma: treatment and survival in Great Britain 1963 to 2002,” British Journal of Ophthalmology, vol. 93,

no. 1, pp. 38–39, 2009.

15. Bowman RJC, Mafwiri M, Luthert P,  et al.  Outcome of Retinoblastoma in East Africa Pediatr Blood Cancer 2008;50:160–162.

STUDY JUSTIFICATION

1. In Mozambique no study has been done to document the demographic characteristic, clinical presentation, management and follow up of children with retinoblastoma and there is a need for updated data .

2. The results from the study will be useful in informing policy makers the status of retinoblastoma in the country and thus lead to the formation of Management Guidelines of retinoblastoma.

OBJECTIVES

 Broad objective

To determine the pattern of presentation, management and follow up of retinoblastoma patients at "Maputo Central Hospital" during a period of 5 years. (1st January 2007 to 31st December 2011)

Specific objectives

1. To identify the demographic characteristic and clinical presentation of retinoblastoma patients seen at "Maputo Central Hospital" in Mozambique during a period of 5 years.

2. To describe the method of diagnosis of retinoblastoma.

3. To describe the methods of management of retinoblastoma patients.

METHODOLOGYStudy Area

Maputo Central Hospital located at Maputo city

Mozambique (Southeast Africa) bordered by: -Indian Ocean (East)-Tanzania (North), -Malawi and Zambia (Northwest)-Zimbabwe (West)-Swaziland and South Africa (Southwest)

Capital:  Maputo

Population: 21,397,000

Area: 801,590 km2

Language: Portuguese

    METHODOLOGY

Study  Area:

Administratively Mozambique is divided in 3 regions and each region has a referral Central hospital:

• Southern (Maputo Central Hospital)

• Central (Beira Central Hospital )

• Northern (Nampula Central Hospital )

METHODOLOGYStudy Setting

-Health Care System in Mozambique is free in government health facilities and comprise

offering

- MCH is the biggest government and teaching hospital.

- There are 8 mozambican and 2 foreigners ophthalmologists.

District Health Centres District Health Centres Primary Health

CarePrimary Health

Care

Provincial Hospitals

Provincial Hospitals

Secondary Health Care

Secondary Health Care

Central Hospitals Central Hospitals Tertiary Health

Care

Tertiary Health Care

METHODOLOGY

Study design A descriptive retrospective case series of retinoblastoma patients, who presented at MCH,

Mozambique, during a 5 years period (1st January 2009 to 31st December 2013)

Study  periodThe study will be carried out for a period of approximately 1 year (January 2014- May 2015)

Source population All ophthalmologic medical records of retinoblastoma patients from Eye clinic, Oncology

ward and Theatre (Admission, discharge/death records) during the study period

METHODOLOGY

Inclusion Criteria

• All recorded presumptive clinical diagnosis of retinoblastoma with or without confirmed histological diagnosis of retinoblastoma seen at MCH during the study period.

• Patients with incomplete records on the file will be analyzed up to the level reached. The rest of information needed will be recorded as missing information.

Exclusion Criteria

• Patients whose files are missing or cannot be traced at all will be excluded from the study.

METHODOLOGYSampling method and sampling size

• Formula used to determine sample size for an unknown population is:

SS ₌ Z ² × (P) × (1- P) C ² SS= Sample Size Z = Z Score or standard score (the study will use 1.96

for a 95% Confidence Level)

P = Percentage picking a given choice expressed as a decimal (the study will use 0.5)

C = Confidence interval expressed as decimal (the study will use 0.05 for a 5 margin of error)

• Equation for an unknown population gives a 384 (sample size)

• The average number of retinoblastoma patients attending both units is around 34 individuals/year.

• The  estimated population of the 5 year period to be 170 individuals. 

METHODOLOGY

1. Identification of the IP number of relevant records of retinoblastoma patients from: Attendance, admission, discharge/death and surgery registers books

Ophthalmology Services

Paediatric Oncology ward Theatres

2. IP number will be used to retrieve relevant files from the records department with the help of a records clerk.

3. After all the files during the study period are retrieved, will be accessed in chronological order (from the oldest) and information will be extracted.

Data Collection

METHODOLOGY

Generating an “Information List ”of patients with Retinoblastoma

Data Collection: Information

METHODOLOGY

Data Collection

• If the histopathology reports of retinoblastoma patients are not available in the files, help will be sought from the Histopathology department at MCH to reconcile histology records with the identified patients.

METHODOLOGY

Data Management

• Data collected via the “Questionnaire” will be transferred into a computer based SQL database (MySQL version 5.5) through manual data entry and validation of each questionnaire.

  Data Storage

• Data will be stored on the database on a laptop computer with a compressed and encrypted backup stored separately on a removable flash disc.

METHODOLOGY

Data Analysis

• Data collected will be analysed using the Statistical Package for Social Scientists (SPSS) version 21.0

• The record tables of the SQL database will be exported directly into SPSS. • Descriptive statistics such as frequencies, mode, median and mean will be used to

summarize the data.

• Graphs, charts and tables will be use to present the results.

METHODOLOGY

Required Tools

• Questionnaire

• Hard Copy patient records (including admission notes, surgical/theatre notes, discharge and death registers)

• Laptop Computer • Flash Disc.

ETHICAL CONSIDERATIONS

• Ethical approval will be sought from the Kenyatta National Hospital/University of Nairobi Ethics and Research Committee

• Ethical approval will also be sought from the Ministry of Health of Mozambique and the Hospital Director of MCH before the commencement of the study

• Patients IP number will be use for purposes of tracing:

– They may have been admitted in different wards at different times or duplicated findings– To match their histopathology results obtained from the Pathology department

ETHICAL CONSIDERATIONS

• Data collected in the structured questionnaire will be stored safely and confidentially in the database on a laptop computer and only will be available to the principal researcher and the statistician.

• Confidentiality of the medical records will be maintained throughout the study.

• Steps will be taken to secure all electronic data collected through the use of strong passwords and firewalls to prevent unauthorised access.

• The results of the study will be shared with the district health management teams in the referring District/Provincial Hospitals, also the Central Hospitals and the directorate of clinical services at the ministry of health.