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Epidemic Kaposi's sarcoma of the conjunctiva: Considerations for radiotherapy
Clinical Oncology (1990) 2:358-361 © 1990 The Royal College of Radiologists
Clinical Oncology
Case Report Epidemic Kaposi's Sarcoma of the Conjunctiva: Considerations for Radiotherapy R . G l y n n e - J o n e s 1, J. L. H u n g e r f o r d 2, M. A . J o h n s o n 3 a n d P. N. P l o w m a n 1 Departments of 1Radiotherapy and 2Ophthalmology, St Bartholomew's Hospital, London and 3Department of Respiratory Medicine, Royal Free Hospital, London, UK
Abstract. A case of epidemic Kaposi's sarcoma involving the conjunctiva is reported. The lesion responded completely to local irradiation without the loss of normal tissue tolerance which has been described at other sides. A review of the literature and guidelines for therapy are presented. Keywords: Kaposi's sarcoma; AIDS; Conjunctiva; Radiotherapy; Normal tissue tolerance
INTRODUCTION Until the last decade, Kaposi's sarcoma (KS) was considered an unusual tumour outside the confines of Africa, with a characteristically indolent natural history. The commonest site of involvement was the skin of the lower limb in elderly males. Ocular lesions were exceptionally rare. However, the epidemic form of AIDS-related KS is often a systemic disease which is characterized by rapidly growing multiple cutaneous lesions and involvement of lymph nodes, lung, mucosa of the gastrointestinal tract, and latterly conjunctiva. To our knowledge, less than 50 cases of conjunctival KS have been reported in the world literature. A larger number of reports derive post 1981 when the first evidence of a disorder of the immune system and associated KS was published (Nicolitz, 1981; Kalinske and Leone, 1982; Macher et al., 1983; Palestine et al., 1984; Jaimovich et al., 1986; Visser and Bos, 1986; Cooper and Fried, 1988; Shuler et al., 1989), but only one emanates from the United Kingdom (Brunt and Phillips, 1990). However, with the increasing prevalence of epidemic KS, this site of disease is likely to become a more common clinical problem. In a recent prospective examination of a Correspondence and offprint requests to: Dr P. N. Plowman, Department of Radiotherapy, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK.
sample of 100 male homosexuals with known AIDS-related KS, 16 had lesions of the eyelid and in seven the conjunctiva was involved (Shuler et al., 1989). The therapeutic options will vary according to the disease characteristics and symptoms, but include surgery, local radiotherapy, chemotherapy (both intralesional and systemic) and interferons. Considerable experience has been gained in the use of radiotherapy in classical KS. The epidemic form of AIDs-related KS can also be effectively treated by local radiotherapy (Cooper and Fried, 1987b). However, there is clear evidence that some sites, in particular the oropharynx (Cooper and Fried, 1987a; Watkins et al., 1987; Stafford et al., 1989) and foot (Chak et al., 1988), often exhibit unexpectedly severe acute radiation morbidity, such that these acute effects can be dose-limiting. For this reason many clinicians do not recommend radiation as the optimal treatment modality for KS in these sites. We report a case of epidemic KS affecting the conjunctiva, which was treated with small fractions of radiation to a modest overall dose. Complete response has been achieved (albeit with remaining pigmentation) without any attendant enhanced acute morbidity. The literature regarding conjunctival KS is reviewed and the aetiology of this enhanced radiation reaction and its relevance to irradiation of conjunctival lesions, is discussed.
HISTORY A 35-year-old human immunodeficiency virus (HIV)-positive homosexual male had noted a conjunctival haemorrhage in the right eye in June 1988. This lesion slowly progressed over the medial aspect of the bulbar conjunctiva, to become a red raised and injected tumour. He was noted to have other skin lesions, particu-
Epidemic Kaposi's Sarcoma of the Conjunctiva: Considerations for Radiotherapy
Fig. 1. Photograph of conjunctival lesion prior to radiotherapy.
359
Fig. 2. Photograph showing conjunctival injection at height of radiation reaction.
larly on the arms, which had the classical appearances of epidemic KS, and a biopsy of the conjunctival lesion in January 1989 confirmed this histology. He had also suffered from recurrent oral thrush. Examination revealed an extensive area with the appearances of a conjunctival haemorrhage (Fig. 1) and diffuse red tumour covering both bulbar and palpebral conjunctiva, especially on the medial aspect. Eye movements were full. The fundi appeared normal, with no evidence of cotton-wool spots. Vision was 6/6 in the right eye and 6/5 in the left.
TREATMENT
Fig. 3. Photograph showing conjunctiva one week after completion of radiotherapy.
Radiotherapy was delivered using 5 MeV electrons with a 5 cm diameter circular applicator. The radiation field was centred on the pupil, and the patient instructed to close his eyes. An applied dose of 30 Gy was administered in 20 daily treatments of 1.5 Gy per fraction over 28 days. Treatment was well tolerated and almost complete regression had been achieved by the completion of treatment. Only a minor and transient acute radiation reaction was observed locally, manifested by conjunctival injection. Photographs of the eye prior to (Fig. 1), during (Fig. 2) and subsequent to irradiation are shown (Fig. 3). The patient remains in remission at the treated site 5 months after the completion of radiotherapy.
(Kalinske and Leone, 1982), but the incidence has risen rapidly. Table 1 summarizes the published reports of the 26 patients with conjunctival KS in the English language from 1981 to date. However, up to 7% of patients who now present with AIDS and KS may be affected at this site (Shuler et al., 1989). All may not require therapy, because the disease often progresses slowly. Lesions are usually seen on the eyelids, caruncles, lacrimal sac, palpebral and bulbar conjunctiva (Reich et al., 1985), and most commonly the inferior fornix. (Shuler et al., 1989). Lesions often appear as circumscribed nodular masses which may spare the tarsal conjunctiva. Other forms, because of the diffuse haemorrhagic infiltrative process, can be mistaken for inflammatory conditions, chronic subconjunctival haemorrhage or a cavernous haemangioma. Eyelid or conjunctival KS which is symptomatic can be treated by cryotherapy or surgical excision if small and involving the tarsal conjunctiva. A recent report describes the use of a strontium-90 ophthalmic applicator (Brunt and Phillips, 1990). Larger lesions involving the bulbar conjunctiva may be treated effectively by local external beam radiotherapy (Visser and Bos, 1986). Intralesional injection
DISCUSSION
Classical (non-epidemic) KS rarely involves the conjunctiva. Prior to 1982 few cases of KS at this site had been reported in the world literature
R. Glynne-Jones et al.
360 Table 1.
Conjunctival Kaposi's sarcoma: characteristics and manifestations
Authors
Patient numbers
Uni/multi focal KS
Age
Sex
Site
Treatment
Outcome
Weiter et al. (1980)
1
M
77
M
Excision
CR
36/12
Bedrick et al. (1981)
1
M
69
M
Medial canthus Bulbar
PR
Jinhou et al. (1981) Nieolitz (1981)
1 1
M M
10 82
M M
? CR
2/12 Recurs ? 24/12
Kalinske and Leone (1982) Holland et al. (1983)
1 3
U M
88 36
M M
Excision ?
?CR ?
?
M
31
M
?
?
?
M
26
M
?
?
?
M M M
38 ? 66
M M M
Inferior cul-de-sac Tarsal Inferior fornix Inferior fornix Inferior fornix Palpebra Bulbar Sac
Excision XRT ? Excision
CR ?
? ?
M
37
M
-
CR CR
27/12 24/12
74 68 77 ? 31
M M M ? M
Plica Palpebra Bulbar Bulbar Palpehra
Excision ? 90 Sr 40 Gy/4F 100Kv 18 Gy/3F Biopsy XRT ? XRT XRT 23.4 Gy/14F 94Kv 30 Gy/10F XRT (4)
CR CR ? CR PR
? ? ? ? 7/12 died 4/12
Macher et al. (1983) Palestine et al. (1984) EI-Akkad et al. (1986)
1 1" 2
Jaimovich et al. (1986)
3
Visser and Bos (1986) Hommel et al. (1987)
1 1
M M M ? M
Cooper and Fried (1988)
1
M
52
M
Upper
Shuler et al. (1989)
7
M (6) U (1)
?
M
Inferior fornix (all)
CR ? CR ? PR
Excision
(1) Zidovudine
CR
3/12
? 12/12 ? 1/12 recurs 1/12 recurs 36/12
(1) (None)
N/A
(1) Brunt and Phillips (1990)
1
M
29
M
Bulbar
Glynne-Jones et al. (1990)
1
M
35
M
Bulbar
Total
27
Sr-90 12 Gy/3F/4 days XRT 30 Gy/20F/28 days
PR
6/52
CR
5/12
* in addition to case described by Macher et al. (1983).
of vincristine or vinblastine which has a useful role in the palliation of multiple cutaneous and oropharyngeal KS (Epstein and Scully, 1989) is possible for eyelid lesions, but where the bulbar conjunctiva is involved there is a risk of severe local toxicity. There are no reports of enhanced radiation reactions in the eye. In contrast enhanced mucosal reactions to irradiation in epidemic KS have been reported by many centres (Real et al., 1985; Watkins et al., 1987) and observed by the present authors. A large fraction size may exacerbate the phenomenon (Watkins et al., 1987) but even with conventionally fractionated doses of 1.8-2.0 Gy per day a fierce confluent mucositis with erythema, ulceration and bleeding may be encountered at
a total dose of 12-14 Gy, i.e. 6-10 days after the start of radiotherapy. This exaggerated reaction contrasts with that observed in patients with squamous carcinomas in the oropharynx, in whom the mucositis is usually observed at 14-18 days and is rarely dose limiting. The reduction in normal tissue tolerance of oropharyngeal mucosa in KS possibly represents a defect of repair mechanisms to radiation-induced damage, but the aetiology remains uncertain. Speculations as to the cause of the decreased tolerance include various hypotheses; immunological defects innate in AIDS which impair the cellular repair mechanisms in this site; widespread subclinical oral candidiasis or other infection in the mouth
Epidemic Kaposi's Sarcoma of the Conjunctiva: Considerations for Radiotherapy
which is common in the immunocompromised; concurrent interferon therapy (Real et al., 1985); increased free radical activity in patients infected with HIV (Sonnerborg et al., 1988); and the oxidant effect of nitrite abuse and ejaculated sperm (Papadopulos-Eleopulos et al., 1989). A convincing explanation remains to be propounded. However, it is interesting to note that in conditions where DNA repair mechanisms may be compromised, such as Fanconi's anaemia, the oropharynx is the site of increased radiation toxicity which may be life threatening (Gluckman et al., 1983).
CONCLUSION
The fractionation of the radiotherapy delivered to the above patient was perhaps over cautious. However, this patient demonstrates that radiation is an effective and safe treatment of conjunctival lesions. Normal tissue tolerance was not exceeded by this dose prescription. This view is supported by the lack of evidence for enhanced radiation reactions at this site in any other series. In conclusion, conjunctival KS which is causing local problems can be treated by surgical excision if small and involving the tarsal conjunctiva. Larger lesions involving the bulbar conjunctiva may be treated effectively by local radiotherapy without the risk of enhanced radiation reactions. Intralesional injection of vincristine or vinblastine which has a useful role in the palliation of multiple cutaneous and orpharyngeal KS (Epstein and Scully, 1989) may run the risk of severe local toxicity.
References Bedrick JJ, Savino PJ, Schatz NJ (1981). Conjunctival Kaposi's sarcoma in a patient with myasthenia gravis. Archives of Ophthalmology, 99, 1607-1609. Brunt AM, Phillips RH (1990). Strontium-90 for conjunctival AIDS-related Kaposi's sarcoma: the first case report. Clinical Oncology, 2, 118-119. Chak LY, Gill PS, Levine AM, Meyer PR, Anselmo JA, Petrovich Z (1988). Radiation therapy for acquired immunodeficiency syndrome-related Kaposi's sarcoma. Journal of Clinical Oncology, 6, 863-867. Cooper JS, Fried PR (1987a). Toxicity of oral radiotherapy in patients with acquired immunodeficiency syndrome. Archives of Otolaryngology, 113, 327-328. Cooper JS, Fried PR (1987). Defining the role of radiation therapy in the management of epidemic Kaposi's sarcoma.
361
International Journal of Radiation Oncology, Biology, Physics, 13, 35-39. Cooper JS, Fried PR (1988). Treatment of aggressive epidemic Kaposi's sarcoma of the conjunctiva by radiotherapy. Archives of Ophthalmology, 106, 20-21. E1-Akkad S, Bull CA, E1-Senoussi MA, Griffin JT, Amer M (1986). Kaposi's sarcoma and its management by radiotherapy. Archives of Dermatology, 122, 1396-1399. Epstein JB, Scully C (1989). Intralesional vinblastine for oral Kaposi sarcoma in HIV infection. Lancet, ii, 1100-1101. Gluckman E, Devergie A, Dutreix J (1983). Radiosensitivityin Fanconi's anaemia: application to the conditioning regimen for bone marrow transplantation. British Journal of Haematology, 54, 431-440. Holland GN, Pepose JS, Pettit TH, Gottlieb MS, Yee RD, Foos RY et al. (1983). Acquired immune deficiency syndrome: ocular manifestations. Ophthalmology, 90, 859-873. Hommel D J, Brown ML, Kinzie JJ (1987). Response to radiotherapy of head and neck tumours in AIDS patients. American Journal of Surgery, 154, 443-446. Jaimovich L, Calh I, Kaminsky A (1986). Kaposi's sarcoma of the conjunctiva. Journal of the American Academy of Dermatology, 14, 589-592. Jinhou L, Yuezhen H, Chengsheng N, Kangning X (1981). Kaposi's sarcoma. Chinese Medical Journal, 94, 535--542. Kalinske M, Leone CR (1982). Kaposi's sarcoma involving eyelid and conjunctiva. Annals of Ophthalmology, 14, 874878. Macher AM, Palestine A, Masur H, Bryant G, Chan C-C, Nussenblatt RB et al. (1983). Multicentric Kaposi's sarcoma of the conjunctiva in a male homosexual with the acquired immunodeficiency syndrome. Ophthalmology, 90, 879-884. Nicolitz E (1981). Kaposi's sarcoma of the conjunctiva. Annals of Ophthalmology, 13, 205-207. Palestine AG, Rodrigues MM, Macher AM, Chan C-C, Lane HC, Fauci AS et al. (1984). Ophthalmic involvement in acquired immunodeficiency syndrome. Ophthalmology, 91, 1092-1099. Papadopoulos-Eleopulos E, Hedland Thomas B, Causer DA, Dufty AP (1989). An alternative explanation for the radiosensitization of AIDS patients. International Journal of Radiation Oncology, Biology, Physics, 17, 695--696. Real FX, Krown SE, Nisce LZ, Oettgen HF (1985). Unexpected toxicity from radiation therapy in two patients with Kaposi's sarcoma receiving interferon. Journal of Biological Response Modifiers, 4, 141-146. Reich H, Hollwich F, Uthoff D (1985). Kaposi-Sarkom and AIDS. Klinische MonatsblatterfurAugenheilkunde, 187, 1-8. Shuler JD, Holland GN, Miles SA, Miller BJ, Grossman I (1989). Kaposi sarcoma of the conjunctiva and eyelid associated with the acquired immunodeficiency syndrome. Archives of Ophthalmology, 107, 858--862. Sonnerborg A, Carlin G, Akerlund B, Jarstrand C (1988). Increased production of malondialdehyde in patients with HIV infection. Scandinavian Journal of Infectious Diseases, 20, 287-290. Stafford ND, Herdman RC, Forster S, Munro AJ (1989). Kaposi's sarcoma of the head and neck in patients with AIDS. Journal of Laryngology and Otology, 103, 379-382. Visser OHE, Bos PJM (1986). Kaposi's sarcoma of the conjunctiva and CMV-retinitis in AIDS. Documenta Ophthalmologica, 64, 77-85. Watkins EB, Findlay P, Gelmann E, Lane HC, Zabell A (1987). Enhanced mucosai reactions in AIDS patients receiving oropharyngeal irradiation. International Journal of Radiation Oncology, Biology, Physics, 13, 1403--1408. Weiter J J, Jakobiec FA, Iwamoto T (1980). The clinical and morphologic characteristics of Kaposi's sarcoma of the conjunctiva. American Journal of Ophthalmology, 89, 546-552. Received for publication March 1990 Accepted March 1990
Clinical Oncology
Case Report Epidemic Kaposi's Sarcoma of the Conjunctiva: Considerations for Radiotherapy R . G l y n n e - J o n e s 1, J. L. H u n g e r f o r d 2, M. A . J o h n s o n 3 a n d P. N. P l o w m a n 1 Departments of 1Radiotherapy and 2Ophthalmology, St Bartholomew's Hospital, London and 3Department of Respiratory Medicine, Royal Free Hospital, London, UK
Abstract. A case of epidemic Kaposi's sarcoma involving the conjunctiva is reported. The lesion responded completely to local irradiation without the loss of normal tissue tolerance which has been described at other sides. A review of the literature and guidelines for therapy are presented. Keywords: Kaposi's sarcoma; AIDS; Conjunctiva; Radiotherapy; Normal tissue tolerance
INTRODUCTION Until the last decade, Kaposi's sarcoma (KS) was considered an unusual tumour outside the confines of Africa, with a characteristically indolent natural history. The commonest site of involvement was the skin of the lower limb in elderly males. Ocular lesions were exceptionally rare. However, the epidemic form of AIDS-related KS is often a systemic disease which is characterized by rapidly growing multiple cutaneous lesions and involvement of lymph nodes, lung, mucosa of the gastrointestinal tract, and latterly conjunctiva. To our knowledge, less than 50 cases of conjunctival KS have been reported in the world literature. A larger number of reports derive post 1981 when the first evidence of a disorder of the immune system and associated KS was published (Nicolitz, 1981; Kalinske and Leone, 1982; Macher et al., 1983; Palestine et al., 1984; Jaimovich et al., 1986; Visser and Bos, 1986; Cooper and Fried, 1988; Shuler et al., 1989), but only one emanates from the United Kingdom (Brunt and Phillips, 1990). However, with the increasing prevalence of epidemic KS, this site of disease is likely to become a more common clinical problem. In a recent prospective examination of a Correspondence and offprint requests to: Dr P. N. Plowman, Department of Radiotherapy, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK.
sample of 100 male homosexuals with known AIDS-related KS, 16 had lesions of the eyelid and in seven the conjunctiva was involved (Shuler et al., 1989). The therapeutic options will vary according to the disease characteristics and symptoms, but include surgery, local radiotherapy, chemotherapy (both intralesional and systemic) and interferons. Considerable experience has been gained in the use of radiotherapy in classical KS. The epidemic form of AIDs-related KS can also be effectively treated by local radiotherapy (Cooper and Fried, 1987b). However, there is clear evidence that some sites, in particular the oropharynx (Cooper and Fried, 1987a; Watkins et al., 1987; Stafford et al., 1989) and foot (Chak et al., 1988), often exhibit unexpectedly severe acute radiation morbidity, such that these acute effects can be dose-limiting. For this reason many clinicians do not recommend radiation as the optimal treatment modality for KS in these sites. We report a case of epidemic KS affecting the conjunctiva, which was treated with small fractions of radiation to a modest overall dose. Complete response has been achieved (albeit with remaining pigmentation) without any attendant enhanced acute morbidity. The literature regarding conjunctival KS is reviewed and the aetiology of this enhanced radiation reaction and its relevance to irradiation of conjunctival lesions, is discussed.
HISTORY A 35-year-old human immunodeficiency virus (HIV)-positive homosexual male had noted a conjunctival haemorrhage in the right eye in June 1988. This lesion slowly progressed over the medial aspect of the bulbar conjunctiva, to become a red raised and injected tumour. He was noted to have other skin lesions, particu-
Epidemic Kaposi's Sarcoma of the Conjunctiva: Considerations for Radiotherapy
Fig. 1. Photograph of conjunctival lesion prior to radiotherapy.
359
Fig. 2. Photograph showing conjunctival injection at height of radiation reaction.
larly on the arms, which had the classical appearances of epidemic KS, and a biopsy of the conjunctival lesion in January 1989 confirmed this histology. He had also suffered from recurrent oral thrush. Examination revealed an extensive area with the appearances of a conjunctival haemorrhage (Fig. 1) and diffuse red tumour covering both bulbar and palpebral conjunctiva, especially on the medial aspect. Eye movements were full. The fundi appeared normal, with no evidence of cotton-wool spots. Vision was 6/6 in the right eye and 6/5 in the left.
TREATMENT
Fig. 3. Photograph showing conjunctiva one week after completion of radiotherapy.
Radiotherapy was delivered using 5 MeV electrons with a 5 cm diameter circular applicator. The radiation field was centred on the pupil, and the patient instructed to close his eyes. An applied dose of 30 Gy was administered in 20 daily treatments of 1.5 Gy per fraction over 28 days. Treatment was well tolerated and almost complete regression had been achieved by the completion of treatment. Only a minor and transient acute radiation reaction was observed locally, manifested by conjunctival injection. Photographs of the eye prior to (Fig. 1), during (Fig. 2) and subsequent to irradiation are shown (Fig. 3). The patient remains in remission at the treated site 5 months after the completion of radiotherapy.
(Kalinske and Leone, 1982), but the incidence has risen rapidly. Table 1 summarizes the published reports of the 26 patients with conjunctival KS in the English language from 1981 to date. However, up to 7% of patients who now present with AIDS and KS may be affected at this site (Shuler et al., 1989). All may not require therapy, because the disease often progresses slowly. Lesions are usually seen on the eyelids, caruncles, lacrimal sac, palpebral and bulbar conjunctiva (Reich et al., 1985), and most commonly the inferior fornix. (Shuler et al., 1989). Lesions often appear as circumscribed nodular masses which may spare the tarsal conjunctiva. Other forms, because of the diffuse haemorrhagic infiltrative process, can be mistaken for inflammatory conditions, chronic subconjunctival haemorrhage or a cavernous haemangioma. Eyelid or conjunctival KS which is symptomatic can be treated by cryotherapy or surgical excision if small and involving the tarsal conjunctiva. A recent report describes the use of a strontium-90 ophthalmic applicator (Brunt and Phillips, 1990). Larger lesions involving the bulbar conjunctiva may be treated effectively by local external beam radiotherapy (Visser and Bos, 1986). Intralesional injection
DISCUSSION
Classical (non-epidemic) KS rarely involves the conjunctiva. Prior to 1982 few cases of KS at this site had been reported in the world literature
R. Glynne-Jones et al.
360 Table 1.
Conjunctival Kaposi's sarcoma: characteristics and manifestations
Authors
Patient numbers
Uni/multi focal KS
Age
Sex
Site
Treatment
Outcome
Weiter et al. (1980)
1
M
77
M
Excision
CR
36/12
Bedrick et al. (1981)
1
M
69
M
Medial canthus Bulbar
PR
Jinhou et al. (1981) Nieolitz (1981)
1 1
M M
10 82
M M
? CR
2/12 Recurs ? 24/12
Kalinske and Leone (1982) Holland et al. (1983)
1 3
U M
88 36
M M
Excision ?
?CR ?
?
M
31
M
?
?
?
M
26
M
?
?
?
M M M
38 ? 66
M M M
Inferior cul-de-sac Tarsal Inferior fornix Inferior fornix Inferior fornix Palpebra Bulbar Sac
Excision XRT ? Excision
CR ?
? ?
M
37
M
-
CR CR
27/12 24/12
74 68 77 ? 31
M M M ? M
Plica Palpebra Bulbar Bulbar Palpehra
Excision ? 90 Sr 40 Gy/4F 100Kv 18 Gy/3F Biopsy XRT ? XRT XRT 23.4 Gy/14F 94Kv 30 Gy/10F XRT (4)
CR CR ? CR PR
? ? ? ? 7/12 died 4/12
Macher et al. (1983) Palestine et al. (1984) EI-Akkad et al. (1986)
1 1" 2
Jaimovich et al. (1986)
3
Visser and Bos (1986) Hommel et al. (1987)
1 1
M M M ? M
Cooper and Fried (1988)
1
M
52
M
Upper
Shuler et al. (1989)
7
M (6) U (1)
?
M
Inferior fornix (all)
CR ? CR ? PR
Excision
(1) Zidovudine
CR
3/12
? 12/12 ? 1/12 recurs 1/12 recurs 36/12
(1) (None)
N/A
(1) Brunt and Phillips (1990)
1
M
29
M
Bulbar
Glynne-Jones et al. (1990)
1
M
35
M
Bulbar
Total
27
Sr-90 12 Gy/3F/4 days XRT 30 Gy/20F/28 days
PR
6/52
CR
5/12
* in addition to case described by Macher et al. (1983).
of vincristine or vinblastine which has a useful role in the palliation of multiple cutaneous and oropharyngeal KS (Epstein and Scully, 1989) is possible for eyelid lesions, but where the bulbar conjunctiva is involved there is a risk of severe local toxicity. There are no reports of enhanced radiation reactions in the eye. In contrast enhanced mucosal reactions to irradiation in epidemic KS have been reported by many centres (Real et al., 1985; Watkins et al., 1987) and observed by the present authors. A large fraction size may exacerbate the phenomenon (Watkins et al., 1987) but even with conventionally fractionated doses of 1.8-2.0 Gy per day a fierce confluent mucositis with erythema, ulceration and bleeding may be encountered at
a total dose of 12-14 Gy, i.e. 6-10 days after the start of radiotherapy. This exaggerated reaction contrasts with that observed in patients with squamous carcinomas in the oropharynx, in whom the mucositis is usually observed at 14-18 days and is rarely dose limiting. The reduction in normal tissue tolerance of oropharyngeal mucosa in KS possibly represents a defect of repair mechanisms to radiation-induced damage, but the aetiology remains uncertain. Speculations as to the cause of the decreased tolerance include various hypotheses; immunological defects innate in AIDS which impair the cellular repair mechanisms in this site; widespread subclinical oral candidiasis or other infection in the mouth
Epidemic Kaposi's Sarcoma of the Conjunctiva: Considerations for Radiotherapy
which is common in the immunocompromised; concurrent interferon therapy (Real et al., 1985); increased free radical activity in patients infected with HIV (Sonnerborg et al., 1988); and the oxidant effect of nitrite abuse and ejaculated sperm (Papadopulos-Eleopulos et al., 1989). A convincing explanation remains to be propounded. However, it is interesting to note that in conditions where DNA repair mechanisms may be compromised, such as Fanconi's anaemia, the oropharynx is the site of increased radiation toxicity which may be life threatening (Gluckman et al., 1983).
CONCLUSION
The fractionation of the radiotherapy delivered to the above patient was perhaps over cautious. However, this patient demonstrates that radiation is an effective and safe treatment of conjunctival lesions. Normal tissue tolerance was not exceeded by this dose prescription. This view is supported by the lack of evidence for enhanced radiation reactions at this site in any other series. In conclusion, conjunctival KS which is causing local problems can be treated by surgical excision if small and involving the tarsal conjunctiva. Larger lesions involving the bulbar conjunctiva may be treated effectively by local radiotherapy without the risk of enhanced radiation reactions. Intralesional injection of vincristine or vinblastine which has a useful role in the palliation of multiple cutaneous and orpharyngeal KS (Epstein and Scully, 1989) may run the risk of severe local toxicity.
References Bedrick JJ, Savino PJ, Schatz NJ (1981). Conjunctival Kaposi's sarcoma in a patient with myasthenia gravis. Archives of Ophthalmology, 99, 1607-1609. Brunt AM, Phillips RH (1990). Strontium-90 for conjunctival AIDS-related Kaposi's sarcoma: the first case report. Clinical Oncology, 2, 118-119. Chak LY, Gill PS, Levine AM, Meyer PR, Anselmo JA, Petrovich Z (1988). Radiation therapy for acquired immunodeficiency syndrome-related Kaposi's sarcoma. Journal of Clinical Oncology, 6, 863-867. Cooper JS, Fried PR (1987a). Toxicity of oral radiotherapy in patients with acquired immunodeficiency syndrome. Archives of Otolaryngology, 113, 327-328. Cooper JS, Fried PR (1987). Defining the role of radiation therapy in the management of epidemic Kaposi's sarcoma.
361
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