lnr. J. Radiatmn Onrolo~v Biol. Phys Vol. 4. Pp. Q-S24 0 Pergamon Prev Inc.. 197X Printed in the U.S.A.
0
Editorial
RETINOBLASTOMA: GEORGE Professor
of Clinical Ophthalmology,
Retinobiastoma,
Heredity, Metastases,
R.
SOME CONSIDERATIONS MERRIAM,
JR.,
M.D.
Edward S. Harkness Eye Institute, NY 10032, U.S.A.
635 W. 165 St., New York,
Treatment.
This is shown
In this issue, the report by Gaitan-Yanguas (pages 359-365) on a large series of advanced cases of retinoblastoma is of particular interest in that it may have first occurred in the Maya Indians in Mexico about 2000 B.C. Retinoblastoma is the most common ocular tumor in children. However, it is rare (about 1 in 20,000 births), and the average ophthalmologist will see only one or two cases in his lifetime. It is a highly malignant tumor capable of widespread dissemination; hence early diagnosis and treatment is essential. As with any form of, carcinoma, the longer the survival, the better the prognosis. While it is true that most recurrences appear within 2 years, they can develop later, although the possibility is remote after 3 years. Furthermore, these children have a much higher incidence of second, non-ocular tumors (unrelated to retinoblastoma) which may appear between 1 and 40 years after successful treatment of the original lesion. Most of these occurred in patients with bilateral disease and were 95% fatal. Therefore, it is essential that the survivors be followed regularly throughout their -lifetime. This is particularly important when a survivor reaches maturity and considers marriage, for the hereditary aspects are most important. The fact that few patients with a family history were found in this series is undoubtedly a reflection of the high mortality. Extensive studies on the hereditary aspects of retinoblastoma have been detailed in Reese’s book* in the excellent chapter by Kitchin. In sibships with an affected parent, the children are almost always affected bilaterally, but in sibships with phenotypically normal parents, the proportion drops substantially. Dominant inheritance occurs in families where the parent is affected bilaterally. Unilaterally affected parents have fewer affected children, even though the children usually have bilateral disease.
below:
Retinoblastoma type and laterality (%) Bilateral Unilateral Total Hereditary Non-hereditary
25-30 0
15-20 50-60
40-50 50-60
Total
25-30
70-75
100
If the survivor’s parents or one or more siblings were affected, each of his children will have a 50% chance (1 in 2) of receiving the mutant gene. An unaffected subject in a hereditary situation has a chance of carrying the gene for retinoblastoma but not manifesting its effects. The chance of being a carrier has been found to be 1 in 8 with a 5% (1 in 20) chance of the children of a carrier developing retinoblastoma. The offspring of a person with unilateral sporadic retinoblastoma will have, on average, about a 20% chance of inheriting the disease. This is due to germinal mutations that by chance affect only one eye. The remaining 80% are not hereditary (somatic mutations) and cannot transmit the tumor, except when there are multiple tumors in one eye. These special cases represent a germinal mutation. For the persons with a solitary tumor, the chance of having an affected child is about 1 in 12 (8%). Production of an affected child reveals the hereditary basis, and all subsequent children will fall into the high-risk group, 1 in 2. A bilaterally affected person has received a germinal mutation, and his children will be in the high-risk group, 1 in 2. The reported sites of metastases are incomplete when compared to other series.’ Direct extension locally or intracranially does occur, but in the study 523
324
Radiation Oncology 0 Biology 0 Physics
by Merriam’ as many died from generalized metastases as from intracranial extension. Retinoblastoma has a predilection for bone, but almost any tissue can be invaded. As mentioned previously, early diagnosis is essential. The offspring of survivors should be examined before leaving the hospital and regularly thereafter for at least 2 years. Examinations must be done with the pupils widely dilated and under general anesthesia. Pediatricians should examine the eyes at each visit with retinoblastoma in mind. Every white pupil and all cases of strabismus, glaucoma or poor vision should have a thorough fundus examination. Therapy has undergone various modifications over the years. Radiation is the primary modality used, but small lesions can be adequately treated with light coagulation or cryotherapy. Furthermore, with the newer chemicals available, chemotherapy is assuming greater importance. The decision as to when to treat small lesions with only light coagulation or cryosurgery must be based on wide experience. Lacking this, radiation is the better and safer choice. At times, when indicated, both modalities can be utilized. Our current program is basically the following in which an effort is being made to avoid radiation wherever possible to lessen the possibility of late radiation induced carcinomas: Unilateral retinoblastoma Grades I, II, III Solitary lesion. External
coagulation Multiple
beam radiation and/or light
or cryotherapy. lesions.
light coagulation
External beam radiation or cryotherapy.
and/or
Grade IV Solitary.
External beam radiation or radioactive cobalt plaque. Multiple. External beam radiation or enucleation. Grade V
Enucleation
May-June
1978, Vol. 4, No. 5 and No. 6
Bilateral retinoblastoma Grades I, II, III Small lesions. External
beam radiation and/or light coagulation or cryotherapy. Occasionally a cobalt 60 plaque may be used. Larger lesions. External beam radiation.
Grades IV, V (a) Enucleate
more advanced eye: radiate less involved eye. (b) Symmetrical involvement: bilateral radiation and chemotherapy. For the extensive intraocular tumors and patients with local and metastatic disease, various combinations of chemotherapeutic agents are being used according to a detailed protocol. Whatever form of treatment is used, it is imperative that the patients be followed at regular intervals. For the first 2 years, they are examined every 3-4 months. For the next 3 years, if the tumors have regressed satisfactorily, they are seen at 6month intervals and yearly thereafter. If there is any question of inadequate regression or reactivation, they must be examined more frequently. Until the patients are old enough to permit an adequate fundus examination, with scleral depression, the examinations must be done under general anesthesia with the pupils widely dilated. As with any form of carcinoma, the earlier the diagnosis is made and the smaller the tumors, the better the results of treatment. About 95% of patients with small lesions who had an early diagnosis have survived 5 years or longer with useful vision. The survival rate decreases as the extent of involvement increases. Thus, only about 30% of the patients with advanced disease are alive and well with useful vision after 5 years. The overall mortality is 12-13%, with no essential difference between unilateral or bilateral disease.
and chemotherapy. REFERENCES
1. Merriam, seventeen
G.R., Jr.: Retinoblastoma: An analysis of autopsies. Arch. Ophthal. 44: 71-108, 1950.
2. Reese, Harper
A.B.: Tumors of the Eye, 3rd Edn. & Row, 1976.
New
York,
0
Editorial
RETINOBLASTOMA: GEORGE Professor
of Clinical Ophthalmology,
Retinobiastoma,
Heredity, Metastases,
R.
SOME CONSIDERATIONS MERRIAM,
JR.,
M.D.
Edward S. Harkness Eye Institute, NY 10032, U.S.A.
635 W. 165 St., New York,
Treatment.
This is shown
In this issue, the report by Gaitan-Yanguas (pages 359-365) on a large series of advanced cases of retinoblastoma is of particular interest in that it may have first occurred in the Maya Indians in Mexico about 2000 B.C. Retinoblastoma is the most common ocular tumor in children. However, it is rare (about 1 in 20,000 births), and the average ophthalmologist will see only one or two cases in his lifetime. It is a highly malignant tumor capable of widespread dissemination; hence early diagnosis and treatment is essential. As with any form of, carcinoma, the longer the survival, the better the prognosis. While it is true that most recurrences appear within 2 years, they can develop later, although the possibility is remote after 3 years. Furthermore, these children have a much higher incidence of second, non-ocular tumors (unrelated to retinoblastoma) which may appear between 1 and 40 years after successful treatment of the original lesion. Most of these occurred in patients with bilateral disease and were 95% fatal. Therefore, it is essential that the survivors be followed regularly throughout their -lifetime. This is particularly important when a survivor reaches maturity and considers marriage, for the hereditary aspects are most important. The fact that few patients with a family history were found in this series is undoubtedly a reflection of the high mortality. Extensive studies on the hereditary aspects of retinoblastoma have been detailed in Reese’s book* in the excellent chapter by Kitchin. In sibships with an affected parent, the children are almost always affected bilaterally, but in sibships with phenotypically normal parents, the proportion drops substantially. Dominant inheritance occurs in families where the parent is affected bilaterally. Unilaterally affected parents have fewer affected children, even though the children usually have bilateral disease.
below:
Retinoblastoma type and laterality (%) Bilateral Unilateral Total Hereditary Non-hereditary
25-30 0
15-20 50-60
40-50 50-60
Total
25-30
70-75
100
If the survivor’s parents or one or more siblings were affected, each of his children will have a 50% chance (1 in 2) of receiving the mutant gene. An unaffected subject in a hereditary situation has a chance of carrying the gene for retinoblastoma but not manifesting its effects. The chance of being a carrier has been found to be 1 in 8 with a 5% (1 in 20) chance of the children of a carrier developing retinoblastoma. The offspring of a person with unilateral sporadic retinoblastoma will have, on average, about a 20% chance of inheriting the disease. This is due to germinal mutations that by chance affect only one eye. The remaining 80% are not hereditary (somatic mutations) and cannot transmit the tumor, except when there are multiple tumors in one eye. These special cases represent a germinal mutation. For the persons with a solitary tumor, the chance of having an affected child is about 1 in 12 (8%). Production of an affected child reveals the hereditary basis, and all subsequent children will fall into the high-risk group, 1 in 2. A bilaterally affected person has received a germinal mutation, and his children will be in the high-risk group, 1 in 2. The reported sites of metastases are incomplete when compared to other series.’ Direct extension locally or intracranially does occur, but in the study 523
324
Radiation Oncology 0 Biology 0 Physics
by Merriam’ as many died from generalized metastases as from intracranial extension. Retinoblastoma has a predilection for bone, but almost any tissue can be invaded. As mentioned previously, early diagnosis is essential. The offspring of survivors should be examined before leaving the hospital and regularly thereafter for at least 2 years. Examinations must be done with the pupils widely dilated and under general anesthesia. Pediatricians should examine the eyes at each visit with retinoblastoma in mind. Every white pupil and all cases of strabismus, glaucoma or poor vision should have a thorough fundus examination. Therapy has undergone various modifications over the years. Radiation is the primary modality used, but small lesions can be adequately treated with light coagulation or cryotherapy. Furthermore, with the newer chemicals available, chemotherapy is assuming greater importance. The decision as to when to treat small lesions with only light coagulation or cryosurgery must be based on wide experience. Lacking this, radiation is the better and safer choice. At times, when indicated, both modalities can be utilized. Our current program is basically the following in which an effort is being made to avoid radiation wherever possible to lessen the possibility of late radiation induced carcinomas: Unilateral retinoblastoma Grades I, II, III Solitary lesion. External
coagulation Multiple
beam radiation and/or light
or cryotherapy. lesions.
light coagulation
External beam radiation or cryotherapy.
and/or
Grade IV Solitary.
External beam radiation or radioactive cobalt plaque. Multiple. External beam radiation or enucleation. Grade V
Enucleation
May-June
1978, Vol. 4, No. 5 and No. 6
Bilateral retinoblastoma Grades I, II, III Small lesions. External
beam radiation and/or light coagulation or cryotherapy. Occasionally a cobalt 60 plaque may be used. Larger lesions. External beam radiation.
Grades IV, V (a) Enucleate
more advanced eye: radiate less involved eye. (b) Symmetrical involvement: bilateral radiation and chemotherapy. For the extensive intraocular tumors and patients with local and metastatic disease, various combinations of chemotherapeutic agents are being used according to a detailed protocol. Whatever form of treatment is used, it is imperative that the patients be followed at regular intervals. For the first 2 years, they are examined every 3-4 months. For the next 3 years, if the tumors have regressed satisfactorily, they are seen at 6month intervals and yearly thereafter. If there is any question of inadequate regression or reactivation, they must be examined more frequently. Until the patients are old enough to permit an adequate fundus examination, with scleral depression, the examinations must be done under general anesthesia with the pupils widely dilated. As with any form of carcinoma, the earlier the diagnosis is made and the smaller the tumors, the better the results of treatment. About 95% of patients with small lesions who had an early diagnosis have survived 5 years or longer with useful vision. The survival rate decreases as the extent of involvement increases. Thus, only about 30% of the patients with advanced disease are alive and well with useful vision after 5 years. The overall mortality is 12-13%, with no essential difference between unilateral or bilateral disease.
and chemotherapy. REFERENCES
1. Merriam, seventeen
G.R., Jr.: Retinoblastoma: An analysis of autopsies. Arch. Ophthal. 44: 71-108, 1950.
2. Reese, Harper
A.B.: Tumors of the Eye, 3rd Edn. & Row, 1976.
New
York,
