**3. Magnitude and distribution of Rb**

#### **3.1 Global incidence and prevalence**

The reported incidence of Rb is constant worldwide at one case per 16,000– 18,000 live births [8, 9]. In 2009 the estimated global annual incidence of Rb ranged from 7200 to 8100 children. The global birth rate has dropped since then, from 20.3 to 18.6 births per 1000 population, but the world's population has grown from 6593 to 7550 million [10], resulting in an estimated 7800–8800 newly diagnosed Rb cases globally in 2017. The highest disease prevalence is recorded in areas with high birth rates, which is the case of many low- and middle-income countries (LMICs).

#### **3.2 Global distribution and survival**

Over 80% of the newly diagnosed cases are in LMICs in Asia and Africa (**Table 1** and **Figure 1**) [3]. These regions also show the lowest survival rate, reporting up to 70% mortality from Rb. Only about 15% of children with Rb reside in high-income

**19**

**4.1 Age**

**Figure 1.**

*Epidemiological and Genetic Considerations in Retinoblastoma*

*Estimated number of newly diagnosed retinoblastoma patients in 2017.*

**High incidence (1:16,000)**

North America 273 242 258 (3.1) Latin America and the Caribbean 669 595 632 (7.7) Africa 2567 2282 2425 (29.5) Asia 4656 4139 4398 (53.5) Europe 504 448 476 (5.8) Oceania 37 32 35 (0.4)

Low 1413 1256 1335 (16.2) Lower-middle 4221 3752 3987 (48.5) Upper-middle 2272 2020 2146 (26.1) High 800 711 756 (9.2)

**Low incidence (1:18,000)**

*n n n* **(%)**

**Average incidence**

countries, and their prognosis is considered to be very good, with an estimated

*Estimated average number of newly diagnosed Rb patients in 2017 by national income level. Income level data* 

According to the World Health Organization's compendium of data from cancer registries, the average Rb incidence rate in children aged 0–4 years is >10

disease-free survival rate of nearly 100% [11].

*source: United Nations, Department of Economic and Social Affairs PD [10].*

**4. Rb determinants**

*DOI: http://dx.doi.org/10.5772/intechopen.86811*

**Continent**

**National income level**

**Table 1.**


#### *Epidemiological and Genetic Considerations in Retinoblastoma DOI: http://dx.doi.org/10.5772/intechopen.86811*

**Table 1.**

*Retinoblastoma - Past, Present and Future*

In hereditary Rb cases, a single *RB1* allele is mutated in most or every cell of a child's body. An additional "hit" in the second allele in the retina will result in clinical Rb. These cases usually present with bilateral and multifocal disease at a median age of 15 months, but can present also in unilateral disease, albeit less frequently. Between 30 and 37% of Rb cases are bilateral [2], and all bilateral cases are hereditary. However, it is estimated that up to 18% of unilateral cases are also hereditary [3]. This emphasizes the importance of genetic testing in addition to clinical examination, as it has direct impact on the recommended screening frequency of

Non-hereditary cases (i.e., somatic) usually present at a later age (median: 24 months) with unilateral unifocal disease. In order for the disease to develop in this scenario, two consecutive "hits" occur in a retinal cell, resulting in both *RB1*

All familial cases are hereditary, but not necessarily vice versa. A mutation can occur at or after conception in an individual with no family history of Rb, and depending on the stage at which it occurs, some of the fetus' cells will have a mutated *RB1* allele, resulting in mosaicism. Children with mosaicism are at increased risk of developing Rb. The disease in this scenario is not inherited, hence siblings of the proband are not at risk, but offspring potentially are, and therefore

Hereditary Rb has been associated with an increased risk of developing secondary non-Rb malignancies [4, 5], including sarcomas, carcinomas, malignant melanoma, and neuroectodermal cancers. Secondary tumors were reported to occur in up to 20% of cases in 10 years and the incidence was reported to directly correlate with the time lag from initial diagnosis. It is also well established that treatment by radiotherapy increases the risk of developing secondary tumors, both in and outside the field of radiation [6]. Draper et al. showed in a series of nearly 400 hereditary cases that close to 10% developed secondary malignancies, mainly osteosarcomas,

Trilateral Rb is a syndrome consisting of unilateral or bilateral hereditary Rb associated with an intracranial neuroblastic tumor that develops most often in the pineal gland (i.e., Pinealblastoma). On a meta-analysis by Kivelä [7], 2% of trilateral Rb cases had a brain tumor but no intraocular Rb, 12% had unilateral Rb and

The reported incidence of Rb is constant worldwide at one case per 16,000– 18,000 live births [8, 9]. In 2009 the estimated global annual incidence of Rb ranged from 7200 to 8100 children. The global birth rate has dropped since then, from 20.3 to 18.6 births per 1000 population, but the world's population has grown from 6593 to 7550 million [10], resulting in an estimated 7800–8800 newly diagnosed Rb cases globally in 2017. The highest disease prevalence is recorded in areas with high birth rates, which is the case of many low- and middle-income countries (LMICs).

Over 80% of the newly diagnosed cases are in LMICs in Asia and Africa (**Table 1** and **Figure 1**) [3]. These regions also show the lowest survival rate, reporting up to 70% mortality from Rb. Only about 15% of children with Rb reside in high-income

the fellow eye and occasionally on management decisions.

alleles mutated and the development of clinical Rb.

most of which were in the field of radiation [6].

should be screened soon after birth.

the remaining had bilateral disease.

**3. Magnitude and distribution of Rb**

**3.1 Global incidence and prevalence**

**3.2 Global distribution and survival**

**18**

*Estimated number of newly diagnosed retinoblastoma patients in 2017.*

**Figure 1.**

*Estimated average number of newly diagnosed Rb patients in 2017 by national income level. Income level data source: United Nations, Department of Economic and Social Affairs PD [10].*

countries, and their prognosis is considered to be very good, with an estimated disease-free survival rate of nearly 100% [11].
