Acta Pædiatrica ISSN 0803-5253
REGULAR ARTICLE
Treating retinoblastoma in the first year of life in a national tertiary paediatric hospital in Mexico Laura Asencio-Lopez, Alan A. Torres-Ojeda, Gabriela Isaac-Otero, Carlos A. Leal-Leal ([email protected]) Departament of Oncology, Instituto Nacional de Pediatrıa SS, Mexico City, Mexico
Keywords Infants, Ocular rescue, Retinoblastoma, Second malignancy, Survival Correspondence Carlos A. Leal-Leal, Departament of Oncology, Instituto Nacional de Pediatrıa SS, Insurgentes Sur 3700 C, Insurgentes Cuicuilco Del. Coyoacan, Mexico City, Mexico. Tel: +52-55540955 | Email: [email protected] Received 30 September 2014; revised 7 November 2014; accepted 22 April 2015. DOI:10.1111/apa.13033
ABSTRACT Aim: Retinoblastoma is the most common primary ocular malignancy in childhood, but little has been documented on the clinical and biological differences in children diagnosed before one year of age. We observed patients in this age group and followed them for up to 19 years. Methods: This retrospective, descriptive, observational study reviewed the medical records of Mexican patients, who were diagnosed with retinoblastoma before one year of age at a national paediatric hospital from 1995 to 2014. The variables analysed were age at diagnosis, weight, presenting signs, the time from first symptoms to diagnosis, family history, laterality, ocular rescue and survival rate. Results: The 108 patients had a mean age of 7.65 months and 15.7% had a family history of retinoblastoma. The majority (55.5%) had bilateral retinoblastoma, the most common presenting sign was leukocoria (86.1%), and the most common stage of diagnosis was Group V (84.1%). More than half were underweight for their age. The overall survival rate was 92% and the disease-free survival rate was 84%. Conclusion: Retinoblastoma is a malignancy that can be present at birth, especially if it is a bilateral hereditary form of the disease. Leukocoria was the main presenting sign. Early diagnosis dramatically improved the prognosis for ocular rescue.
BACKGROUND Retinoblastoma is the most common primary ocular malignancy in childhood (1), with an estimated worldwide incidence of one case in every 18 000 to 30 000 live births (2). In Mexico, retinoblastoma is the second most frequent solid malignancy in paediatrics, with only central nervous system tumours (1) occurring more frequently. The age at diagnosis varies from country to country, and in Mexico, the mean age is 27.68 months, ranging from one day to 182 months (1). Most patients present with the disease when they are less than four years of age, but patients exhibit clinical and biological differences if the diagnosis occurs before the child is one year of age. However, little has been documented about this since 2002 when Abamsom et al. studied 46 patients diagnosed before they were one month old (3). This study presents the results of our observations in patients diagnosed during the first year of life, with a maximum follow-up period of 19 years.
MATERIAL AND METHODS In this retrospective, descriptive, observational study, we reviewed the medical records of patients diagnosed with retinoblastoma between birth and twelve months of age at the Instituto Nacional de Pediatria, Mexico, from July 1995
e384
to February 2014. The variables analysed were age at diagnosis, weight, presenting signs, the number of weeks between the time that the primary carer had detected the first clinical manifestations and the date of diagnosis, any family history of retinoblastoma, laterality, ocular rescue, the overall survival rate and the disease-free survival rate. Statistical analyses were performed using the SPSS system (IBM Corp. Released 2010. IBM SPSS Statistics for Windows, version 19.0., Armonk, NY, USA). Descriptive statistics were obtained for each variable.
Key notes
Retinoblastoma is the most common primary ocular malignancy in childhood, and we studied the clinical and biological differences in 108 children diagnosed before one year of age. The majority of the children (55.5%) had bilateral retinoblastoma, 15.7% had a family history of the disease, the overall survival rate was 92%, and the disease-free survival rate was 84%. Bilateral, hereditary retinoblastoma was more common at birth and early diagnosis dramatically improved ocular rescue.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e384–e387
pez et al. Asencio-Lo
The Kaplan–Meier log-rank test was used to assess overall and disease-free survival rates from the date of diagnosis to the last recorded visit to the clinic.
RESULTS Between 1995 and 2014, 1150 patients were diagnosed with retinoblastoma at the Instituto Nacional de Pediatrıa. Of these, 108 (10.6%) were under one year of age, a mean of 5.6 new cases per year. There were 50 females and 58 males, with a mean age of 7.95 months and an age range of 1.6– 11.9 months. We analysed overall survival based on the age at diagnosis, by splitting the infants into two groups: birth to six months of age and six to 12 months. This showed that 30 infants (27.5%) were diagnosed before to the age of six months and 78 were diagnosed when they were between six and 12 months. This analysis showed that there were no differences in the survival rates between the two groups (Fig. 1). Weight was evaluated using the percentile curves of weight for age in children published in MchGrowth (4), which were last updated in September 2013. We found that 60.2% of patients were below the 50th percentile and 21.3% exceeded it. Only 18.5% of the infants in our group were at the right weight for age at diagnosis. The most frequent symptom that was reported was leukocoria, which occurred in 93 (86.1%) of the cases, followed by strabismus in 26 cases (24.1%). In addition, nine patients (8.3%) had epiphora, five (4.6%) had palpebral oedema, five (4.6%) had nystagmus, and five (4.6%) had an inability to track objects. Only three (2.8%) patients
Figure 1 Overall survival among age groups.
Retinoblastoma in the first year of life
had conjunctivitis and two (1.9%) presented with a red eye. The time delay from the primary carer noticing the first symptom to diagnosis was one to 44 weeks, with a mean of 12.8, a standard deviation (SD) of 9.76 and a variance of 95.44. We used the Reese–Ellsworth grouping system for staging patients at diagnosis. The majority (84.2%, n = 91) were in Group V, 9.2% (n = 10) were in Group IV, 3.7% (n = 4) were in Group III, 1.8% (n = 2) were in Group II, and only 0.92% (n = 1) were in Group I. Most of our patients (96%, n = 104) were in the ocular stage of the St. Jude staging scheme (5). Two of the remaining four were in the orbital stage and two were disease beyond to the orbit. These four patients died as a result of activity linked to the tumour. Of the 108 patients diagnosed during the first year of life, only 17 (15.7%) had a positive family history for retinoblastoma and three of these had more than one family member with the disease. The family members who were affected were of first and second degree. We found that 48 (44.4%) of our patients were unilaterally affected and 60 were bilaterally affected (55.5%), which represented a total of 168 eyes and a ratio of 1.25:1.00, respectively. We were able to rescue 11 (22.9%) eyes in the unilateral affected group and 53 (44.1%) of the 120 eyes in the bilateral affected group, including two treated with intra-arterial chemotherapy (Fig. 2). We assessed the overall survival and the disease-free survival rate in the entire sample using the Kaplan–Meier log-rank test and then evaluated both variables in each group. The total overall survival rate was 92% and the disease-free survival rate was 84% during the 200 months of follow-up (mean 65.5, SD 61.03). None of the patients with unilateral disease died, with a disease-free survival rate of 84%, while the overall survival rate in the patients who were bilaterally affected was 84%, with a disease-free survival rate of 75% (Fig. 3).
Figure 2 Laterality and ocular rescue. IA, Intra-arterial chemotherapy; DFS, Disease-free survival; OS, Overall survival.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e384–e387
e385
pez et al. Asencio-Lo
Retinoblastoma in the first year of life
Figure 3 Disease-free survival by laterality.
We defined an event as an intraocular or extraocular relapse. Any intraocular relapses in unilateral patients happened at an advanced stage, and enucleation was performed to save their lives, which was successful in all cases.
DISCUSSION Retinoblastoma is a malignant tumour, which can present before birth, especially in bilateral disease cases (6), and represents the most common intraocular tumour in childhood (7). In Mexico, retinoblastoma is the second most frequent solid malignancy in paediatric patients with a mean of 83.3 new cases per year (1). Most patients are diagnosed before the age of four, and a considerable proportion of them are detected during the first year of life. This study assessed clinical and epidemiological characteristics of diagnosed retinoblastomas in the first year of life. We found that the largest proportion of patients was diagnosed between the ages of six and 12 months (71.6%). The duration of symptoms was prolonged and highly variable in our patients. However, retinoblastoma was diagnosed earlier only in patients with a family background (15.7%). The rest of our patients experienced a long gap between their primary carer first noticing symptoms and being diagnosed. No patient in the series was examined before that the clinic signs appeared, despite having a family history of
e386
retinoblastoma. It could be that our patients with bilateral disease did not show up until they presented clinical manifestations because the parents were in denial about them being ill despite having been advised of this by the specialist who treated their infant from birth. There were no differences in the reasons for consultations during the first year of life compared to those reported in older Mexican children (8). Regarding nutritional status, more than half of our patients were underweight for their age and 22.2% of them were below the 5th percentile at diagnosis. No causal association has been described between nutritional status and the risk of develop retinoblastoma. However, it has been reported that in developing countries, the incidence of retinoblastoma may be higher and these countries also have a higher prevalence of nutritional deficiency (9). We did not include a control group of children with another condition to show that malnutrition and being underweight were associated with the development of retinoblastoma. The major presenting sign was leukocoria, which occurred in 86.1% of patients, followed by strabismus in 24.1%. In half of the cases, the only clinical manifestation of the disease was leukocoria. When the clinical stage is limited to the eye, the most common sign will undoubtedly be leukocoria. However, primary care physicians must consider strabismus as an important sign that a patient may have retinoblastoma at this stage of life and just regard it as a sign of neurological immaturity. The red eye reflex examination should be a mandatory exploration test in all infants. The time from the primary carer’s first noticing signs of the disease and diagnoses ranged from one to 44 weeks, with a mean of 12.8, an SD of 9.76 and a variance of 95.44. Although the mean was acceptable, there was wide variability in the time from first symptoms to diagnosis. Abramson et al. (10) reported that 77% of bilateral cases and 84% of unilateral cases, with an overall mean of 80.5%, were in Group V of the Reese–Ellsworth staging system at the time of diagnosis. In our series, 84.2% of the overall cases were in Group V, with a tendency to decrease in frequency as the Reese–Ellsworth stage decreased, down to just 0.92% in Group I. Only 15.7% of the patients had a relative affected by retinoblastoma and they all had bilateral disease. Abramson et al. (10) noted that, regardless of whether or not there was a family history, those who were diagnosed in the first year of life were hiding an unidentified germ line mutation. Overall survival was consistent with what is known in other age groups, with 92% of patients surviving and the disease-free survival rate being 84%. All patients with unilateral disease survived during the follow-up and only 16% had relapsed, but this exceeds the figures presented by Abramson in his work in children under the age of one (10). The overall survival rate in the bilateral cases was 84%, with a 25% relapse, while Abramson found a 6% incidence
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e384–e387
pez et al. Asencio-Lo
of metastatic disease in the same age group. This might be explained by late diagnosis in our patients. In Abramson’s study, most of the patients were diagnosed in the first three months of life, whereas in ours almost every patient was almost one year old at diagnosis (10). This means that the time from first symptoms to diagnosis in our patients with congenital disease was directly proportional to advanced stages. However, patients with bilateral disease could suffer from second malignancies, especially 10 years after diagnosis, and this could reduce their survival. Abramson et al. (11) have reported that up to 50% of cases with bilateral disease may die due to a second tumour in irradiated and nonirradiated sites, with other studies identifying neoplasms such as osteosarcoma (9), soft tissue sarcomas (12), leukaemias (13) and epithelial cancer (14). With regard to ocular rescue in our study, 11 eyes were saved in the unilateral group and 53 eyes in the bilateral group, including two which were treated with intra-arterial chemotherapy. Thermo-chemotherapy and photocoagulation were used for the remaining cases.
CONCLUSION Retinoblastoma is a malignancy that can be present at birth, especially if it is a bilateral hereditary form of the disease. The main presenting signs for possible retinoblastoma are leukocoria and, or, strabismus. Early diagnosis drastically improves the prognosis for saving one or both eyes. A long-term follow-up will allow us to check on patients who develop secondary tumours, due to the molecular genetic alterations that allow them to develop.
ACKNOWLEDGEMENTS None.
CONFLICT OF INTEREST None.
Retinoblastoma in the first year of life
References n a, Cerecedo-Dıaz 1. Leal-Leal C, Flores-Rojo M, Medina-Sanso nchez-Felix S, Gonza lez-Ramella O, et al. A multicentre F, Sa report from the Mexican Retinoblastoma Group. Br J Ophthalmol [Internet] 2004; 88: 1074–7. 2. Abramson DH, Schefler A. Update on retinoblastoma. Retina 2004; 24: 828–48. 3. Abramson DH, Du TT, Beaverson KL. (Neonatal) retinoblastoma in the first month of life. Arch Ophthalmol 2002; 6: 738–42. 4. MchGrowth. 2013. Available from URL http://www.education. vic.gov.au/childhood/parents/health/Pages/default.aspx. 5. Pratt C, Fontanesi J, Lu X, Parham D, Elfervig J, Meyer D. Proposal for a new staging scheme for intraocular and extraocular retinoblastoma based on an analysis of 103 globes. Oncologist [Internet] 1997; 2: 1–5. 6. Canadian Retinoblastoma Society. National Retinoblastoma Strategy Canadian Guidelines for Care Strategie therapeutique du retinoblastome guide clinique Canadien. Can J Ophthalmol 2009; 44: 1–45. 7. Dimaras H, Kimani K, Dimba EAO, Gronsdahl P, White A, Chan HSL, et al. Retinoblastoma. Lancet [Internet] 2012; 379: 1436–46. stico y Manejo de Retinoblastoma. 8. Secretarıa-de-Salud. Diagno mite Mexico: Secretaria De Salud, 2013. En Tra 9. Berman SD, Calo E, Landman AS, Danielian PS, Miller ES, West JC, et al. Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. Proc Natl Acad Sci U S A [Internet] 2008; 105: 11851–6. 10. Abramson DH, Camille S. Retinoblastoma in the first year of life. Ophthalmic Paediatr Genet 1992; 13: 191–203. 11. Abramson DH, Frank CM. Second nonocular tumors in survivors of bilateral retinoblastoma: a possible age effect on radiation-related risk. Ophthalmology [Internet] 1998; 105: 573–9; discussion 579–80. 12. Castelino-Prabhu S, Stoll LM, Li QK. Metastatic retinoblastoma presenting as a left shoulder soft tissue mass: FNA findings and review of the literature. Diagn Cytopathol [Internet] 2010; 38: 440–6. 13. Gombos DS, Hungerford J, Abramson DH, Kingston J, Chantada G, Dunkel IJ, et al. Secondary acute myelogenous leukemia in patients with retinoblastoma: is chemotherapy a factor? Ophthalmology [Internet] 2007; 114: 1378–83. 14. Marees T, Moll AC, Imhof SM, de Boer MR, Ringens PJ, van Leeuwen FE. Risk of second malignancies in survivors of retinoblastoma: more than 40 years of follow-up. J Natl Cancer Inst [Internet] 2008; 100: 1771–9.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e384–e387
e387
REGULAR ARTICLE
Treating retinoblastoma in the first year of life in a national tertiary paediatric hospital in Mexico Laura Asencio-Lopez, Alan A. Torres-Ojeda, Gabriela Isaac-Otero, Carlos A. Leal-Leal ([email protected]) Departament of Oncology, Instituto Nacional de Pediatrıa SS, Mexico City, Mexico
Keywords Infants, Ocular rescue, Retinoblastoma, Second malignancy, Survival Correspondence Carlos A. Leal-Leal, Departament of Oncology, Instituto Nacional de Pediatrıa SS, Insurgentes Sur 3700 C, Insurgentes Cuicuilco Del. Coyoacan, Mexico City, Mexico. Tel: +52-55540955 | Email: [email protected] Received 30 September 2014; revised 7 November 2014; accepted 22 April 2015. DOI:10.1111/apa.13033
ABSTRACT Aim: Retinoblastoma is the most common primary ocular malignancy in childhood, but little has been documented on the clinical and biological differences in children diagnosed before one year of age. We observed patients in this age group and followed them for up to 19 years. Methods: This retrospective, descriptive, observational study reviewed the medical records of Mexican patients, who were diagnosed with retinoblastoma before one year of age at a national paediatric hospital from 1995 to 2014. The variables analysed were age at diagnosis, weight, presenting signs, the time from first symptoms to diagnosis, family history, laterality, ocular rescue and survival rate. Results: The 108 patients had a mean age of 7.65 months and 15.7% had a family history of retinoblastoma. The majority (55.5%) had bilateral retinoblastoma, the most common presenting sign was leukocoria (86.1%), and the most common stage of diagnosis was Group V (84.1%). More than half were underweight for their age. The overall survival rate was 92% and the disease-free survival rate was 84%. Conclusion: Retinoblastoma is a malignancy that can be present at birth, especially if it is a bilateral hereditary form of the disease. Leukocoria was the main presenting sign. Early diagnosis dramatically improved the prognosis for ocular rescue.
BACKGROUND Retinoblastoma is the most common primary ocular malignancy in childhood (1), with an estimated worldwide incidence of one case in every 18 000 to 30 000 live births (2). In Mexico, retinoblastoma is the second most frequent solid malignancy in paediatrics, with only central nervous system tumours (1) occurring more frequently. The age at diagnosis varies from country to country, and in Mexico, the mean age is 27.68 months, ranging from one day to 182 months (1). Most patients present with the disease when they are less than four years of age, but patients exhibit clinical and biological differences if the diagnosis occurs before the child is one year of age. However, little has been documented about this since 2002 when Abamsom et al. studied 46 patients diagnosed before they were one month old (3). This study presents the results of our observations in patients diagnosed during the first year of life, with a maximum follow-up period of 19 years.
MATERIAL AND METHODS In this retrospective, descriptive, observational study, we reviewed the medical records of patients diagnosed with retinoblastoma between birth and twelve months of age at the Instituto Nacional de Pediatria, Mexico, from July 1995
e384
to February 2014. The variables analysed were age at diagnosis, weight, presenting signs, the number of weeks between the time that the primary carer had detected the first clinical manifestations and the date of diagnosis, any family history of retinoblastoma, laterality, ocular rescue, the overall survival rate and the disease-free survival rate. Statistical analyses were performed using the SPSS system (IBM Corp. Released 2010. IBM SPSS Statistics for Windows, version 19.0., Armonk, NY, USA). Descriptive statistics were obtained for each variable.
Key notes
Retinoblastoma is the most common primary ocular malignancy in childhood, and we studied the clinical and biological differences in 108 children diagnosed before one year of age. The majority of the children (55.5%) had bilateral retinoblastoma, 15.7% had a family history of the disease, the overall survival rate was 92%, and the disease-free survival rate was 84%. Bilateral, hereditary retinoblastoma was more common at birth and early diagnosis dramatically improved ocular rescue.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e384–e387
pez et al. Asencio-Lo
The Kaplan–Meier log-rank test was used to assess overall and disease-free survival rates from the date of diagnosis to the last recorded visit to the clinic.
RESULTS Between 1995 and 2014, 1150 patients were diagnosed with retinoblastoma at the Instituto Nacional de Pediatrıa. Of these, 108 (10.6%) were under one year of age, a mean of 5.6 new cases per year. There were 50 females and 58 males, with a mean age of 7.95 months and an age range of 1.6– 11.9 months. We analysed overall survival based on the age at diagnosis, by splitting the infants into two groups: birth to six months of age and six to 12 months. This showed that 30 infants (27.5%) were diagnosed before to the age of six months and 78 were diagnosed when they were between six and 12 months. This analysis showed that there were no differences in the survival rates between the two groups (Fig. 1). Weight was evaluated using the percentile curves of weight for age in children published in MchGrowth (4), which were last updated in September 2013. We found that 60.2% of patients were below the 50th percentile and 21.3% exceeded it. Only 18.5% of the infants in our group were at the right weight for age at diagnosis. The most frequent symptom that was reported was leukocoria, which occurred in 93 (86.1%) of the cases, followed by strabismus in 26 cases (24.1%). In addition, nine patients (8.3%) had epiphora, five (4.6%) had palpebral oedema, five (4.6%) had nystagmus, and five (4.6%) had an inability to track objects. Only three (2.8%) patients
Figure 1 Overall survival among age groups.
Retinoblastoma in the first year of life
had conjunctivitis and two (1.9%) presented with a red eye. The time delay from the primary carer noticing the first symptom to diagnosis was one to 44 weeks, with a mean of 12.8, a standard deviation (SD) of 9.76 and a variance of 95.44. We used the Reese–Ellsworth grouping system for staging patients at diagnosis. The majority (84.2%, n = 91) were in Group V, 9.2% (n = 10) were in Group IV, 3.7% (n = 4) were in Group III, 1.8% (n = 2) were in Group II, and only 0.92% (n = 1) were in Group I. Most of our patients (96%, n = 104) were in the ocular stage of the St. Jude staging scheme (5). Two of the remaining four were in the orbital stage and two were disease beyond to the orbit. These four patients died as a result of activity linked to the tumour. Of the 108 patients diagnosed during the first year of life, only 17 (15.7%) had a positive family history for retinoblastoma and three of these had more than one family member with the disease. The family members who were affected were of first and second degree. We found that 48 (44.4%) of our patients were unilaterally affected and 60 were bilaterally affected (55.5%), which represented a total of 168 eyes and a ratio of 1.25:1.00, respectively. We were able to rescue 11 (22.9%) eyes in the unilateral affected group and 53 (44.1%) of the 120 eyes in the bilateral affected group, including two treated with intra-arterial chemotherapy (Fig. 2). We assessed the overall survival and the disease-free survival rate in the entire sample using the Kaplan–Meier log-rank test and then evaluated both variables in each group. The total overall survival rate was 92% and the disease-free survival rate was 84% during the 200 months of follow-up (mean 65.5, SD 61.03). None of the patients with unilateral disease died, with a disease-free survival rate of 84%, while the overall survival rate in the patients who were bilaterally affected was 84%, with a disease-free survival rate of 75% (Fig. 3).
Figure 2 Laterality and ocular rescue. IA, Intra-arterial chemotherapy; DFS, Disease-free survival; OS, Overall survival.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e384–e387
e385
pez et al. Asencio-Lo
Retinoblastoma in the first year of life
Figure 3 Disease-free survival by laterality.
We defined an event as an intraocular or extraocular relapse. Any intraocular relapses in unilateral patients happened at an advanced stage, and enucleation was performed to save their lives, which was successful in all cases.
DISCUSSION Retinoblastoma is a malignant tumour, which can present before birth, especially in bilateral disease cases (6), and represents the most common intraocular tumour in childhood (7). In Mexico, retinoblastoma is the second most frequent solid malignancy in paediatric patients with a mean of 83.3 new cases per year (1). Most patients are diagnosed before the age of four, and a considerable proportion of them are detected during the first year of life. This study assessed clinical and epidemiological characteristics of diagnosed retinoblastomas in the first year of life. We found that the largest proportion of patients was diagnosed between the ages of six and 12 months (71.6%). The duration of symptoms was prolonged and highly variable in our patients. However, retinoblastoma was diagnosed earlier only in patients with a family background (15.7%). The rest of our patients experienced a long gap between their primary carer first noticing symptoms and being diagnosed. No patient in the series was examined before that the clinic signs appeared, despite having a family history of
e386
retinoblastoma. It could be that our patients with bilateral disease did not show up until they presented clinical manifestations because the parents were in denial about them being ill despite having been advised of this by the specialist who treated their infant from birth. There were no differences in the reasons for consultations during the first year of life compared to those reported in older Mexican children (8). Regarding nutritional status, more than half of our patients were underweight for their age and 22.2% of them were below the 5th percentile at diagnosis. No causal association has been described between nutritional status and the risk of develop retinoblastoma. However, it has been reported that in developing countries, the incidence of retinoblastoma may be higher and these countries also have a higher prevalence of nutritional deficiency (9). We did not include a control group of children with another condition to show that malnutrition and being underweight were associated with the development of retinoblastoma. The major presenting sign was leukocoria, which occurred in 86.1% of patients, followed by strabismus in 24.1%. In half of the cases, the only clinical manifestation of the disease was leukocoria. When the clinical stage is limited to the eye, the most common sign will undoubtedly be leukocoria. However, primary care physicians must consider strabismus as an important sign that a patient may have retinoblastoma at this stage of life and just regard it as a sign of neurological immaturity. The red eye reflex examination should be a mandatory exploration test in all infants. The time from the primary carer’s first noticing signs of the disease and diagnoses ranged from one to 44 weeks, with a mean of 12.8, an SD of 9.76 and a variance of 95.44. Although the mean was acceptable, there was wide variability in the time from first symptoms to diagnosis. Abramson et al. (10) reported that 77% of bilateral cases and 84% of unilateral cases, with an overall mean of 80.5%, were in Group V of the Reese–Ellsworth staging system at the time of diagnosis. In our series, 84.2% of the overall cases were in Group V, with a tendency to decrease in frequency as the Reese–Ellsworth stage decreased, down to just 0.92% in Group I. Only 15.7% of the patients had a relative affected by retinoblastoma and they all had bilateral disease. Abramson et al. (10) noted that, regardless of whether or not there was a family history, those who were diagnosed in the first year of life were hiding an unidentified germ line mutation. Overall survival was consistent with what is known in other age groups, with 92% of patients surviving and the disease-free survival rate being 84%. All patients with unilateral disease survived during the follow-up and only 16% had relapsed, but this exceeds the figures presented by Abramson in his work in children under the age of one (10). The overall survival rate in the bilateral cases was 84%, with a 25% relapse, while Abramson found a 6% incidence
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e384–e387
pez et al. Asencio-Lo
of metastatic disease in the same age group. This might be explained by late diagnosis in our patients. In Abramson’s study, most of the patients were diagnosed in the first three months of life, whereas in ours almost every patient was almost one year old at diagnosis (10). This means that the time from first symptoms to diagnosis in our patients with congenital disease was directly proportional to advanced stages. However, patients with bilateral disease could suffer from second malignancies, especially 10 years after diagnosis, and this could reduce their survival. Abramson et al. (11) have reported that up to 50% of cases with bilateral disease may die due to a second tumour in irradiated and nonirradiated sites, with other studies identifying neoplasms such as osteosarcoma (9), soft tissue sarcomas (12), leukaemias (13) and epithelial cancer (14). With regard to ocular rescue in our study, 11 eyes were saved in the unilateral group and 53 eyes in the bilateral group, including two which were treated with intra-arterial chemotherapy. Thermo-chemotherapy and photocoagulation were used for the remaining cases.
CONCLUSION Retinoblastoma is a malignancy that can be present at birth, especially if it is a bilateral hereditary form of the disease. The main presenting signs for possible retinoblastoma are leukocoria and, or, strabismus. Early diagnosis drastically improves the prognosis for saving one or both eyes. A long-term follow-up will allow us to check on patients who develop secondary tumours, due to the molecular genetic alterations that allow them to develop.
ACKNOWLEDGEMENTS None.
CONFLICT OF INTEREST None.
Retinoblastoma in the first year of life
References n a, Cerecedo-Dıaz 1. Leal-Leal C, Flores-Rojo M, Medina-Sanso nchez-Felix S, Gonza lez-Ramella O, et al. A multicentre F, Sa report from the Mexican Retinoblastoma Group. Br J Ophthalmol [Internet] 2004; 88: 1074–7. 2. Abramson DH, Schefler A. Update on retinoblastoma. Retina 2004; 24: 828–48. 3. Abramson DH, Du TT, Beaverson KL. (Neonatal) retinoblastoma in the first month of life. Arch Ophthalmol 2002; 6: 738–42. 4. MchGrowth. 2013. Available from URL http://www.education. vic.gov.au/childhood/parents/health/Pages/default.aspx. 5. Pratt C, Fontanesi J, Lu X, Parham D, Elfervig J, Meyer D. Proposal for a new staging scheme for intraocular and extraocular retinoblastoma based on an analysis of 103 globes. Oncologist [Internet] 1997; 2: 1–5. 6. Canadian Retinoblastoma Society. National Retinoblastoma Strategy Canadian Guidelines for Care Strategie therapeutique du retinoblastome guide clinique Canadien. Can J Ophthalmol 2009; 44: 1–45. 7. Dimaras H, Kimani K, Dimba EAO, Gronsdahl P, White A, Chan HSL, et al. Retinoblastoma. Lancet [Internet] 2012; 379: 1436–46. stico y Manejo de Retinoblastoma. 8. Secretarıa-de-Salud. Diagno mite Mexico: Secretaria De Salud, 2013. En Tra 9. Berman SD, Calo E, Landman AS, Danielian PS, Miller ES, West JC, et al. Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. Proc Natl Acad Sci U S A [Internet] 2008; 105: 11851–6. 10. Abramson DH, Camille S. Retinoblastoma in the first year of life. Ophthalmic Paediatr Genet 1992; 13: 191–203. 11. Abramson DH, Frank CM. Second nonocular tumors in survivors of bilateral retinoblastoma: a possible age effect on radiation-related risk. Ophthalmology [Internet] 1998; 105: 573–9; discussion 579–80. 12. Castelino-Prabhu S, Stoll LM, Li QK. Metastatic retinoblastoma presenting as a left shoulder soft tissue mass: FNA findings and review of the literature. Diagn Cytopathol [Internet] 2010; 38: 440–6. 13. Gombos DS, Hungerford J, Abramson DH, Kingston J, Chantada G, Dunkel IJ, et al. Secondary acute myelogenous leukemia in patients with retinoblastoma: is chemotherapy a factor? Ophthalmology [Internet] 2007; 114: 1378–83. 14. Marees T, Moll AC, Imhof SM, de Boer MR, Ringens PJ, van Leeuwen FE. Risk of second malignancies in survivors of retinoblastoma: more than 40 years of follow-up. J Natl Cancer Inst [Internet] 2008; 100: 1771–9.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e384–e387
e387
