Clare Stannard

Malignant melanoma of the eyelid and palpebral conjunctiva treated with iodine-125 brachytherapy

OBJECTIVE To evaluate the results on malignant melanomas of the eyelid and palpebral conjunctiva treated with iodine-125 (125I) brachytherapy with shielding of the eye. DESIGN Noncomparative case series. PARTICIPANTS Fourteen patients treated with 125I brachytherapy at an ocular oncology referral center from 1974 through 1996, all of whom had had previous debulking, incomplete resection, or recurrence after surgery. INTERVENTION A stainless steel pericorneal ring eyeshield was attached to the extraocular muscles, over which a lid was fitted to protect the cornea without touching it. Iodine-125 seeds in polythene tubes were inserted into the eyelid and attached to the lid margin for a single plane implant. In five cases additional seeds were glued on to the shield as well for a volume implant. A median dose of 37 Gy (range, 17.3-67.6 Gy) was given over the course of 113 hours (range, 47-190 hours) to the outer surface of target volume. MAIN OUTCOME MEASURES Local control is regarded as freedom from recurrence in those without measurable disease and complete clinical regression in those with measurable disease. Morbidity is assessed in terms of function and cosmesis. Survival is given from the time of the implant. RESULTS There was local control in 13 patients maintained from 11 to 227 months (median, 39 months). There were two recurrences at 8 and 13 months in the first patient who received 17.3 Gy. Late complications consisted of mild eyelid telangiectasia, mild eyelid atrophy, and loss of eyelashes in most patients. Five patients, four of whom had upper eyelid tumors, experienced a dry eye, which was managed with tear supplements, and one of these patients developed a cataract. A corneal ulcer developed in one eye, which later perforated after treatment of a subsequent bulbar melanoma and was exenterated. Another eye was enucleated after treatment for a subsequent melanoma in the fornix. Cosmesis was acceptable to patient and doctor in the other 12 patients. Vision was maintained in seven patients, reduced in two, and not recorded in the remaining three patients. Three patients died of hematogenous metastases at 44, 62, and 79 months after implant, one of bronchial carcinoma at 46 months and one of an astrocytoma at 39 months. All patients were clear of local disease. The remainder survived for a median of 45 months (range, 18-227 months). CONCLUSIONS Iodine-125 brachytherapy can be used as an alternative to wide excision or exenteration of these tumors. There was good local control, reasonable maintenance of vision, and good cosmesis.

Postenucleation orbits in retinoblastoma: treatment with 125I brachytherapy

PURPOSE Children with retinoblastoma that extends into or through the choroid, sclera, or optic nerve are at risk of developing orbital disease, as well as metastases. Previously, these enucleated orbits were treated with external beam radiotherapy in addition to chemotherapy. 125I brachytherapy for tumors in and around the eye was pioneered by Sealy in Cape Town, South Africa, in 1974. In 1983, he developed a technique to irradiate the contents of the orbit while limiting the dose to the bony orbit and eyelids. METHODS AND MATERIALS Six nylon tubes containing 125I seeds were implanted through the eyelids around the periphery of the orbit. Each contained a metal gutter that screens the outer part of the seeds from the bony orbit. A seventh unscreened tube was placed in the center, and a metal disc with 125I seeds on its posterior surface was secured beneath the eyelids. Between 1983 and 2000, 57 orbits were treated in 56 children with retinoblastoma. Thirty-six were treated prophylactically and 21, with tumor at the resection line of the nerve, extrascleral tumor, or metastases, were treated therapeutically. They received a median dose of 34 Gy in 70 h; 30 also received chemotherapy. Children with tumor at the resection line of the nerve also received treatment to the craniospinal axis. RESULTS The median follow-up of the 35 patients treated prophylactically was 35 months (range 0-187). Seven patients died, 6 of metastases, at a median of 10 months (range 4-29) after the implant. Eight of the 13 patients with microscopic extraocular tumor survived a median of 29 months (range 5-156). None of the 8 patients presenting with orbital tumor or metastases survived. No orbital recurrences developed in any of the patients. Cosmesis was considerably improved compared with previous forms of irradiation. CONCLUSION Orbital brachytherapy is an effective method of irradiating the orbit to prevent recurrent tumor, the treatment time is short, and the cosmesis is much more acceptable than with other forms of irradiation. No facial atrophy or second nonocular tumors have occurred.

Malignant salivary gland tumours: Can fast neutron therapy results point the way to carbon ion therapy?

BACKGROUND AND PURPOSE To evaluate the outcome of malignant salivary gland tumours treated with neutron therapy to assess the potential for other high linear energy transfer (LET) beams. MATERIALS AND METHODS Neutrons at iThemba LABS are produced by the reaction of 66MeV protons on a beryllium target. A median dose 20.4Gy, in 12 fractions in 4weeks or 15 fractions in 5weeks, was given to 335 patients with 176 irresectable, 104 macroscopically residual and 55 unresected tumours. RESULTS Locoregional control was 60.6% at 5years and 39.1% at 10years and DSS was 66.8% and 53.7% at 5 and 10years respectively. In the univariate analysis T4, >4cm, high grade, squamous carcinoma, unresected and irresectable tumours, and positive nodes were significantly worse for LRC. In the multivariate analysis tumours >6cm, squamous carcinoma, irresectable tumours and nodes were significantly worse for LRC. Tumours >6cm, high grade, squamous carcinoma and nodes were significantly worse for DSS. Neither LRC nor DSS was influenced by age, sex, site, dose, fractionation or for initial or recurrent disease. CONCLUSIONS Neutron therapy appears to be the treatment of choice for macroscopically incompletely excised and irresectable salivary gland tumours with improved survival rates. Further improvement may be achieved with other high LET modalities with a superior dose profile, such as carbon ions.

The use of iodine-125 plaques in the treatment of retinoblastoma

125I has an energy of 27-35 keV which permits highly effective screening and makes it eminently suitable for treating ophthalmic tumours. It was first used for this in 1974 (Sealy et al., 1976), and since then a flexible system has been developed to treat a variety of such tumours including localized retinoblastoma. A gold foil backed plaque is custom built to cover the tumour(s). The turned edges reduce the dose and thus protect vital adjacent structures such as the optic nerve and lens. The iodine seeds are sealed in the plaque in a predetermined position to give the required dose. A range of doses and times have been used but the authors now aim to give a TDF of 100 to the apex of the tumour in two to three days. Ten tumours in the remaining eye of seven patients with bilateral retinoblastoma were treated. The size ranged from 3 X 3 X 2 to 10 X 10 X 6 mm. There were nine complete responses from 17-90 months and a partial response in one patient who died of metastases at ten months. Vision was maintained in all. Eight recurrent tumours in seven patients were also treated together with a subsequent new tumour in one of the patients. There were three complete responses at 28-39 months and six tumours persisted. Vision was maintained in three of seven patients. The only complication was a vitreous haemorrhage which was mild in two patients, moderate in one patient and severe in three previously treated patients. These latter three patients subsequently had the eye enucleated and were found to have recurrent tumour.

Iodine-125 orbital brachytherapy with a prosthetic implant in situ.

AbstractPurpose: Brachytherapy is one method of irradiating the orbit after enucleation of an eye with a malignant tumor that has a potential to recur. It consists of 6 trains of I-125 seeds placed around the periphery of the orbit, a shorter central train, and a metal disc, loaded with seeds, placed beneath the eyelids. The presence of a prosthetic orbital implant requires omission of the central train and adjustment of the activity of the seeds in the anterior orbit around the prosthesis.Patients and Methods:This is a retrospective review of the technical modifications and outcome of 12 patients treated in this manner: 6 with retinoblastoma, 5 with malignant melanoma, and 1 with an intraocular rhabdomyosarcoma. The median dose was 35.5 Gy in 73 hours for retinoblastoma and 56 Gy in 141 hours for malignant melanoma. Patients with retinoblastoma and rhabdomyosarcoma also received chemotherapy.Results:The tubes can be placed satisfactorily around the prosthesis. The increased activity in the anterior half of the tubes produced comparable dose distributions. There have been no orbital recurrences, no extrusion of the prosthesis, and cosmesis is good.Conclusion:Insertion of a prosthetic implant at the time of enucleation greatly enhances the subsequent cosmetic appear-ance. This should be encouraged unless there is frank tumor in the orbit. Orbital brachytherapy without the central train continues to give excellent local control. The short treatment time and good cosmesis are added advantages. The patient is spared the expense and inconvenience of removing and replacing the prosthetic implant.ZusammenfassungHintergrund:Bei hohem intraorbitalen Rezidivrisiko nach Enukleation eines tumortragenden Auges kann die Orbita mit einer I-125 Brachytherapietechnik schonend bestrahlt werden. Dabei werden 6 I-125 Seed-trains zirkulär in der Orbita platziert, zusammen mit einem kürzeren zentralen Seed-train und einem münzförmigen Applikator hinter den Lidern, mit der strahlenden Seite in Richtung Orbita. Inzwischen wird nach Enukleation häufig ein kugelförmiges intraorbitales Implant zur Verbesserung der Kosmetik eingebracht, so dass eine Adaptation dieser Technik notwendig wird. Der zentrale Seed-train entfällt, die Aktivität der peripheren Applikatoren muss angepasst werden.Patienten und Methodik:Die technischen Modifikationen und die damit erzielten Ergebnisse bei 12 Patienten (6 Retinoblastome, 5 Aderhautmelanome, 1 Rhabdomyosarkom) werden dargestellt. Der Median der applizierten Dosis betrug in der Gruppe der Retinoblastome 35,5 Gy in 73 Stunden, bei den malignen Melanomen 56 Gy in 141 Stunden. Bei Retinoblastomen bzw. dem Rhabdomyosarkom wurde zusätzlich eine Chemotherapie gegeben.Ergebnisse:Die schlauchförmigen Applikatoren konnten problemlos um das zentrale Orbita-Implant eingesetzt werden. Durch Erhöhung der Aktivität im vorderen Abschnitt der Applikatoren ließ sich eine gute Dosisverteilung auch ohne zentralen Applikator erreichen. Es traten keine Rezidive und keine Wunddehiszenz mit Verlust des Orbita-Implants auf. Das kosmetische Ergebnis war in allen Fällen gut.Schlussfolgerung:Ein Orbita-Implant ergibt nach Enukleation ein ausgezeichnetes kosmetisches Resultat und sollte außer bei ausgedehntem Tumorbefall anderen Techniken vorgezogen werden. Die hier neu vorgestellte Technik erbringt auch ohne zentralen Applikator eine hervorragende lokale Kontrollrate und erspart dem Patienten die aufwendige und nicht immer erfolgreiche Entfernung und Wiedereinlage des Orbita-Implantats. Kurze Behandlungszeit und exzellente kosmetische Ergebnisse stellen einen weiteren Vorteil der Methode dar.

Improved cosmesis in retinoblastoma patients treated with iodine-125 orbital irradiation

Patients who are at risk for developing an orbital recurrence after enucleation of the eye for retinoblastoma are those with full thickness choroidal invasion or further extension into the sclera or extension into the optic nerve beyond the lamina cribrosa. The authors have treated these patients routinely with external irradiation to the orbit but this usually resulted in a dry contracted socket that often would not accept a prosthesis. An orbital implant was designed with 125I seeds in an attempt to improve the cosmetic result. It consisted of seven rows of 125I seeds, six of which were partially screened and implanted around the periphery of the orbit so that the contents were irradiated whilst reducing the dose to the bony orbit. The seventh central row was unscreened. A metal disc, with 125I seeds sealed to the posterior surface, was sutured beneath the eyelids thus protecting them and the accessory lacrimal glands. A TDF of 90-100 over two to three days was given. Thirteen patients have been treated, nine prophylactically and four therapeutically. Three of the latter patients have died of metastases but no local recurrences have been seen. All 13 patients were left with a moist socket that accepted a prosthesis.

Localized whole eye radiotherapy for retinoblastoma using a 125I applicator, “claws”

PURPOSE To treat children with retinoblastoma, who require whole eye radiotherapy, with a specially designed (125)I applicator that irradiates the eye while sparing the surrounding tissues. METHODS AND MATERIALS Under general anesthesia, a pericorneal ring is attached to the 4 extraocular muscles, and 4 appendages, each loaded with (125)I seeds, are inserted beneath the conjunctiva in-between each pair of muscles and attached anteriorly to the ring. Twenty-nine eyes were treated. Eighteen received a median dose of 28 Gy during 91 hours and 11 received 40 Gy during 122 hours, when the relative biologic effectiveness was taken as 1 instead of 1.5. Six had received prior chemotherapy. RESULTS Twenty-four eyes were followed up for 2-157 months (median 29). Although 22 eyes responded, local control was achieved in 13 patients, 3 of whom required additional treatment for new tumors; a further 3 required additional treatment for tumor recurrence as well as new tumors. One of these eyes was enucleated for neovascular glaucoma. All 6 Group I-III eyes and 6 of 18 Group V eyes were retained for 2-157 months (median 39), with good vision in 10 eyes. Three developed cataracts 7, 8, and 12 years later, 1 of which has been removed. CONCLUSIONS This is a new way of irradiating the whole eye with a minimal dose to the surrounding tissues. The treatment time is only 5 days. It is effective in Groups I-III, but only 33% of Group V eyes retained vision. No late cosmetic defects occurred.

Neutron versus photon radiotherapy for local control in inoperable breast cancer

Background and Purpose:By virtue of their high linear energy transfer (LET) characteristics the biologic effectiveness of neutrons is less dependent on tissue oxygenation tension and cell cycle phase as compared to that with photons. Hence, an improved clinical benefit is to be expected predominantly in large, hypoxic and slowly growing tumors. Since a short course of radiotherapy is required for clinical reasons, it prompted the authors to initiate a randomly controlled trial on locally advanced breast cancer.Patients and Methods:Between 1996 and 1999, 27 patients with locally advanced breast cancer were irradiated with photons (60 Gy, 30 fractions; 8 MV, 60Co) or neutrons (18 Gy, twelve fractions; 66 MeVp→Be). The mean tumor diameters were 699 ± 399 ml for the photon group and 1,097 ± 831 ml in the neutron group.Results:After a mean follow-up period of 21.5 months tumor involution was evaluated in 22 patients. Partial and complete remissions were registered in 6/10 patients of the photon group and 5/12 patients of the neutron group. Late grade 3–4 morbidity according to RTOG definition was scored in 5/10 patients in the photon group and in 6/12 patients in the neutron group. With regard to tumor control and late radiation morbidity no differences between the two treatment arms were observed.Conclusion:The underlying data indicate that no benefit is to be expected from neutron therapy in breast cancer.Hintergrund und Ziel:Die biologische Wirkung von Neutronen beruht im Wesentlichen auf der geringeren Abhängigkeit von der Sauerstoffkonzentration und der Zellzyklusphase im Vergleich zu dünn ionisierender Strahlung. Klinische Vorteile sind deswegen insbesondere bei großvolumigen, hypoxischen und langsam wachsenden Tumoren zu erwarten. Dies veranlasste die Autoren, eine kontrollierte, randomisierte Studie bei lokal fortgeschrittenen Mammakarzinomen durchzuführen.Patienten und Methodik:Zwischen 1996 und 1999 wurden 27 Patientinnen mit lokal fortgeschrittenen Mammakarzinomen mit Photonen (60 Gy, 30 Fraktionen; 8 MV, 60Co) oder Neutronen (18 Gy, zwölf Fraktionen; 66 MeVp→Be) bestrahlt. Die mittleren Tumorvolumina betrugen 699 ± 399 ml in der Photonengruppe und 1 097 ± 831 ml in der Neutronengruppe.Ergebnisse:Nach einer mittleren Nachbeobachtungszeit von 21,5 Monaten waren die Ergebnisse von 22 Patientinnen auswertbar. Partielle und komplette Remissionen fanden sich bei 6/10 Patientinnen aus der Photonengruppe und 5/12 Patientinnen aus der Neutronengruppe. Normalgewebsreaktionen Grad 3–4 entsprechend der RTOG-Definition wurden bei 5/10 Patientinnen aus der Photonengruppe und 6/12 Patientinnen aus der Neutronengruppe festgestellt. Somit ergab sich kein Unterschied in den Remissions- und Spätmorbiditätsraten zwischen beiden Behandlungsarmen.Schlussfolgerung:Aufgrund der vorliegenden Ergebnisse ist kein Vorteil einer Neutronentherapie bei Mammakarzinom zu erwarten.

The treatment of carcinoma in situ and squamous cell carcinoma of the conjunctiva with fractionated strontium-90 radiation in a population with a high prevalence of HIV

Background This study explores the safety and efficacy of strontium 90 (Sr-90) brachytherapy as the sole adjuvant therapy for carcinoma in situ (CIS) and squamous cell carcinoma (SCC) of the conjunctiva in a high HIV prevalent area. Methods This is a retrospective case review of patients treated with 60 Gray Sr-90 brachytherapy in four divided doses after resection with a 2 mm margin and histological confirmation. Cryotherapy or alcohol debridement was not performed at the time of excision due to limited resources. Two plaque sizes, 8.5 mm and 18 mm, were used. Results Sixty-nine patients were treated and had a median follow-up of 27 months (range 6–127). Thirty-three (47.8%) were HIV-positive. CIS was present in 40.6% and SCC in 59.4%. The surgical margins were positive in 39 (56.5%). Twenty patients (29.0%) were treated with the 18 mm plaque and 49 (71.0%) with the 8.5 mm plaque. Eight (11.6%) patients developed a recurrence at a median of 5 months (range 2–40). Recurrences only occurred in patients treated with the 8.5 mm plaque (p=0.094). There was no significant effect of HIV status, positive margins or staging on the number of recurrences. Treatment side effects were a dry eye in five patients which was successfully managed with topical lubricants, and induced astigmatism of 1 dioptre of cylinder in one patient. Conclusions Sr-90 brachytherapy is safe and effective in preventing recurrences in ocular surface squamous neoplasia in a high HIV prevalent setting. The 18 mm plaque size is superior to the 8.5 mm plaque size.

Brachytherapy and endoresection for choroidal melanoma: a cohort study

Aim To report and compare the outcomes of brachytherapy and endoresection in the conservative treatment of medium sized choroidal melanoma. Methods A retrospective cohort study. Medium tumours were defined as 2.5–10 mm in height and less than 16 mm in the widest diameter. Consecutive patients undergoing brachytherapy at Groote Schuur Hospital were compared with a cohort undergoing endoresection from a national database. Results 148 brachytherapy and 22 endoresection patients were followed for a median of 55.4 and 62.4 months, respectively. Tumours undergoing endoresection were thicker (7.3 vs 4.9 mm, p<0.001, Wilcoxon rank-sum test) and further from the fovea (5.2 vs 3.7 mm, p=0.05, Wilcoxon rank-sum test) than those treated with brachytherapy. Visual acuity of 6/18 or better was maintained in 41% of the endoresection group and 35% of the brachytherapy group. The likelihood of achieving a final visual acuity of better than 2/60 was 22% higher in the endoresection group (risk ratio 1.22, 95% CI 1.02 to 1.28, p=0.034). Rates of local recurrence (18.2% vs 14.9%, p=0.75) and metastases or death (18.2% vs 14.2%, p=0.75) were higher in the endoresection group, and the enucleation rate was lower in this group (4.6% vs 10.8%, p=0.70) but these were not statistically significant. Conclusions The outcomes observed in this small cohort of endoresection patients suggest that endoresection of selected tumours may achieve better visual outcomes than brachytherapy. Rates of local recurrence, enucleation and metastases following endoresection require further research. Local recurrence is likely to be influenced by consolidation treatment methods.