In the 1930s and 1940s the thought of patients with Rb tumours retaining an eye with useful vision was inconceivable. Today the majority of patients retain useful vision in one or both eyes. The method of treatment chosen depends on several factors: the size and location of the tumour, the number of tumours in each eye, the patient's age, whether the disease is unilateral or bilateral, and whether there is vitreous involvement. In many cases clinical management involves a combination of therapies. Other than enucleation, among the method of treatments available these days are cryotherapy, lens sparing laser treatment, radiation treatment (external beam and radioactive 'plaques') and chemotherapy for metastasis.
The traditional method of treatment for Rb has been removal of the eye - enucleation. It was first suggested in 1809 by James Wardrop (Sang and Albert 1977, Albert 1987, McCartney et at 1988) but only became the accepted form of treatment after the introduction of chloroform as a general anaesthetic and with the availability of the ophthalmoscope for earlier diagnosis (in 1851). For many decades after that, enucleation remained the only form of treatment for Rb. These days enucleation is the only treatment in unilateral cases when the tumour fills most of the globe and there is little
hope of retaining useful vision and a strong possibility the tumour will escape the orbit. In bilateral cases, the surgeon will try to save at least one eye and so the one with the more advanced tumour is usually enucleated; the less involved eye is usually treated. Sanders et al (1988) compared the treatment for Rb, in the UK, between periods 1962-1968 and 1969-1980 and found a trend which was towards more conservative treatment (table 1.1). 5% of children with unilateral tumours in the later period (1969-1980) did not have enucleation as compared with 1% in the earlier period. For the bilateral cases at least one eye was retained for 83 % of children in the later period, as compared with 73 % in the earlier.
Table 1.1 Comparison of treatment in the UK for Rb between periods 1962-1968 and 1969-1980 (Sanders et at 1988).
Years Total cases Unilateral
Enucleation No (%) Conservative treat. No (%) 1962-1968 157 155 (99) 2 (1) 1969-1980 282 269 (95) 13(5) Bilateral Enucleation Conservative
One eye Both eyes treatment
No (%) No (%) No (%)
1962-1968 1 1 1 6 6 (59) 30 (27) 15 (14)
1969-1980 149 101 (6 8) 25 (17) 23 (15)
The move away from enucleation has been brought about mainly by the introduction of radiation as a form of therapy. The first attempt to treat Rb with X-rays occurred in 1903 (Hilgartner 1903, cited by Dunphy 1964, Sang and Albert 1977) although it was not until 1921 that the first well-documented cure of bilaterally affected patients was reported (Verhoeff 1921). Since then several techniques of external beam irradiation have been used successfully.
There are, however, complications with the use of external beam irradiation, including damage to the lachrymal gland (dry eyes), muscle wasting in the irradiation field and bone growth deformities. Nowadays radiation treatment is usually limited to bilateral tumours and unilateral tumours having good central vision potential. Consequently, efforts to optimise treatment have become important. In 1930 Moore and co-workers treated Rb by placing radon seeds through a puncture in the sclera (Moore et al 1931). Stallard (1958) refined this work by designing special "plaques" that followed the curvature of the sclera. The radiation was directed towards the tumour and was blocked from irradiating surrounding tissue. The radioactive plaque technique was found to be very advantageous when treating localised tumours as a high dose of radiation is delivered to the areas of interest while minimising radiation effects to the extraocular structures. Rb is probably the most radiation sensitive tumour known, usually a single treatment is sufficient to kill the tumour. A small scar is left on the retina following successful treatment. However, when tumours are very small, photocoagulation, laser therapy and cryotherapy are the treatments of choice for primary and supplementary treatment, although some small tumours might not be suitable for these treatments due to their location. Photocoagulation destroys small retinal tumours by obliterating the blood vessels supplying the tumour with the use of a powerful light beam (Shields and Augsburger 1981). Cryotherapy for Rb was first reported in 1968 (Lincoff 1968) and involves freezing of tumours using a cryoprobe pushed up against the tumour. As a result the tumours cells are killed by ice crystal formation, dehydration and obliteration of the capillary circulation. Cryotherapy is occasionally used as primary treatment but more frequently employed to supplement other treatment modalities.
Chemotherapy is used in advanced (usually metastasing) cases of Rb where the prognosis is poor. It was first described by Kupfer in the treatment of Rb in 1953. In the 1950s and 60s nitrogen mustard and its analogue triethylene
melamine were used. Today other chemotherapeutic agents inducing
cyclophosphamide, vincristine doxorubicin, 5-fluoracil are used singly or in combination in cases involving metastasis. Métastasés of Rb are uncommon in countries where the tumour is diagnosed and treated early. Dissemination of the tumour may be haematogenous or lymphatic. The central nervous system (CNS) can become involved via continuous spread along the optic nerve (JE Kingston, personal communication). The majority of the patients
with métastasés show involvement of the CNS (MacKay et al 1984). The main sites of métastasés outside the CNS are the orbital and periorbital tissues including the cranial bones. Occasionally, distant areas of involvement include bones and bone marrow, lymph nodes, liver, and kidneys. Most of métastasés are seen within three years after diagnosis of Rb (MacKay et al
1984). The prognosis of children with metastatic disease remains poor and they rarely survive more than a year although longer survivals have been reported (Judisch et al 1980).
In many cases, a combination of above mentioned treatment modalities are used in the management of Rb and a trend towards more conservative treatment has been reported (Sanders et al 1988). As a result of many years of painstaking research on the treatment of Rb the survival rate is the highest of all children's cancers. This fact is primarily responsible for the increased frequency of hereditary cases and their documentation.