Sebaceous carcinoma of the eyelid associated with retinoblastoma.

OBJECTIVE: To analyze the association between retinoblastoma (Rb) and sebaceous carcinoma (SC) of the eyelid to improve surveillance of survivors of RB: DESIGN: Case report and systematic literature review. METHODS: Ten patients who had SC develop after Rb were identified by systematic literature review, and a child who died with lymph node, lung, and liver metastases 7 years after irradiation for Rb is described. The data were analyzed by univariate statistics, including cumulative frequency distribution plots and Kaplan-Meier analysis. RESULTS: Of 11 children with SC of the eyelid who all had hereditary RB, 9 (82%; 95% confidence interval, 48-98) received a median of 46 Gy (range, 21-89) of radiotherapy at a median age of 16 months (range, 0.5-15 years) and had SC develop within the field of radiation. Their median age at diagnosis of SC was 14 years (range, 8-30 years), median diagnostic delay 12 months (range, 6 months-3 years), and median interval from irradiation 11 years (range, 5-26 years); 7 of them (78%; 95% confidence interval, 40-97) were diagnosed between 5 and 15 years after radiotherapy. SC also developed at the age of 32 and 54 years in two nonirradiated Rb patients. Five patients had regional lymph node metastases after a median time of 12 months (range, 1 month-24 years). The 5-year cumulative probability of survival was 87%. CONCLUSIONS: SC of the eyelid may occur in patients with hereditary Rb regardless of primary treatment, especially within the field 5 to 15 years after radiotherapy.

Visual function after strontium-90 plaque irradiation in patients with age-related subfoveal choroidal neovascularization.

PURPOSE: To report 2-year visual and angiographic results in eyes treated with strontium plaque irradiation for subfoveal choroidal neovascular membranes (CNVM) in age-related macular degeneration. METHODS: Twenty eyes with recent subfoveal CNVM were treated with local irradiation. The impact of the treatment on visual function was evaluated by visual acuity, contrast sensitivity and reading speed testing. RESULTS: At 12 months visual acuity had improved or remained the same in 9/ 20 eyes (45%). At 24 months visual acuity was stable in 5/18 eyes (28%). Eyes with signs of CNVM regression (13/18, 72%) lost a mean of 3.3 lines, but eyes with recurrent CNVM lost a mean of 5.1 lines of vision. The mean contrast sensitivity was better in the irradiated eyes than in the fellow eyes with late age-related macular degeneration at 24 months. Six of 17 irradiated eyes (35%) could read at least some words at 24 months. CONCLUSIONS: Visual function decreases in patients treated with strontium irradiation, but less in eyes showing regression of the CNVM than in eyes with further growth of the CNVM.

Strontium plaque irradiation of subfoveal neovascular membranes in age-related macular degeneration.

PURPOSE: To determine the effect of focal strontium-90 plaque radiotherapy on subfoveal choroidal neovascularization in patients with age-related macular degeneration. METHODS: Twenty patients with age-related macular degeneration, presenting with a recent subfoveal neovascular membrane, were treated with local episcleral radiotherapy using a strontium-90 applicator. The applicator was applied to the sclera under the macular region and held there tightly for 54 min to obtain a dose of 15 Gy at a depth of 1.75 mm. The main parameters evaluated at follow-up after 3, 6 and 12 months were visual acuity and changes in fluorescein angiography. Twelve untreated patients with the same criteria were followed as controls. RESULTS: Early effects of radiation could be seen at 3 months, but became more obvious after follow-up for 6 and 12 months. At 6 months, regression of the choroidal neovascularization was detected in 14/19 patients (74%) as a decrease in the size of the lesion or as diminished leakage in late-phase fluorescein angiography. Likewise, in 14/19 patients (74%) at 12 months the neovascular membrane was partially or totally occluded. In all patients showing regression of the choroidal neovascular membrane, the neurosensory detachment had also dried. Visual acuity was unchanged (within 1 line) or improved in 11/20 (55%) and 9/20 (45%) treated patients after 6 and 12 months, respectively. In the controls, the choroidal neovascularization had increased in size in 9/12 patients (75%) at the last follow-up (mean 12.0 months). Visual acuity was unchanged in 3/12 patients (25%). CONCLUSION: Local low-energy beta irradiation with a strontium-90 applicator can induce regression of choroidal neovascularization. The effect of irradiation is seen as a decrease in the size of the choroidal neovascular membrane and disappearance of the neurosensory detachment and exudates.

Radiation related complications after ruthenium plaque radiotherapy of uveal melanoma.

AIMS/BACKGROUND: To analyse radiation related complications and secondary enucleation after irradiation of malignant uveal melanoma with ruthenium-106 plaques. METHODS: A series of 100 consecutive eyes irradiated in 1981-91 was analysed using the life table method and the Cox proportional hazards model. The median apical and scleral tumour dose was 100 Gy (range 15-200 Gy) and 1000 Gy (range 200-1200 Gy), respectively. The median follow up time was 2.8 and 2.0 years (range 1 month to 10 years) for anterior and posterior segment complications, respectively. RESULTS: The 3 and 5 year probabilities of being without radiation cataract were 73% and 63%, without neovascular glaucoma 91% and 81%, without vitreous haemorrhage 83% and 74%, without radiation maculopathy 85% and 70%, and without radiation optic neuropathy 90% and 88%, respectively. The risk of radiation cataract was highest with large tumour size (T1 + T2 v T3, p = 0.0027; height < or = 5 v > 5 mm, p = 0.029; largest basal diameter (LBD) < or = 15 v > 15 mm, p < 0.0001) and location of anterior tumour margin anterior v posterior to the equator (p = 0.0003); the risk of neovascular glaucoma with large size (T1 + T2 v T3, p = 0.039; LBD < or = 15 mm v 15 mm, p = 0.021); and the risk of maculopathy and optic neuropathy with proximity of the posterior tumour margin to the fovea and the optic disc (< or = 1.5 v > 1.5 mm; p = 0.030 and p = 0.0004, respectively). In Cox's multivariate analysis the strongest risk indicator for radiation cataract (RR 1.5, 95% CI 1.4-1.6) and vitreous haemorrhage (RR 1.6, 95% CI 1.4-1.8) was the height of the tumour; for neovascular glaucoma the TNM class (RR 6.2, 95% CI 2.7-13.8); for radiation maculopathy location of posterior tumour margin within 2 mm from the fovea (RR 3.4, 95% CI 2.0-6.0); and for radiation optic neuropathy location of tumour margin within 1 DD of the optic disc (RR 6.1, 95% CI 3.0-12.4). The 3 and 5 year probabilities of avoiding enucleation were 92% and 85%, respectively. Ten eyes were enucleated--six because of recurrent tumour growth, three because of treatment complications, and one because of mistakenly suspected extraocular growth. CONCLUSION: The results suggest that the frequency of radiation related complications after ruthenium brachytherapy of uveal melanoma is acceptable, in particular as regard irradiation of small and medium sized tumours for which ruthenium therapy generally is recommended.

Interstitial radiotherapy of 25 parasellar/clival meningiomas and 19 meningiomas in the elderly. Analysis of short-term tolerance and responses.

I-125 seeds were permanently implanted into 25 parasellar-clival meningiomas (median age of patients, 56 y) and 19 globoid meningiomas in the elderly (median age of patients, 77 y) using stereotactic technique and 3-D dose planning. Total dose at the tumour margin was increased during the series from 100 Gy to 150 Gy. The procedure caused no mortality and no serious bleeding, but injury to the III cranial nerve due to puncture occurred in one (4%) of the 25 parasellar-clival meningiomas. In two (4.5%) of the 44 cases the postoperative CT scan showed a misplaced seed, located at the tumour surface. Nonenhancing hypodense rings developed around the seeds ('hot spots') with a median diameter of 10.5 mm at 12 months corresponding to a median initial activity of 8.7 mCi. In general, meningiomas responded by slow reduction in volume. The parasellar-clival meningiomas were followed-up for a median of 19 months (6-32), and so far 4 tumours have shrunk moderately, 13 slightly, and 5 not at all. Pre-operative III, V or VI cranial nerve signs were present in 17 patients and subsided in 8 of them. On the other hand, facial numbness developed or increased in 9 of the 25 patients, indicating that the V nerve is rather sensitive to this type of irradiation. In the 19 meningiomas of the elderly, the median follow-up time was 14 months (5-26). The median relative tumour volume was 46% at 12 months. Accounting for tumour-related deaths only, the actuarial survival rate was 78% at 12 months and 62% at 24 months. In general, brain oedema persisted despite reduction in tumour volume. Stereotactic implantation of I-125 seeds into intracranial meningiomas is relatively safe. Interstitial radiotherapy represents a potential tool in the control of medium-sized intracranial meningiomas with minimal brain oedema, but its long-term impact and untoward effects remain to be followed-up.

Visual outcome of eyes with malignant melanoma of the uvea after ruthenium plaque radiotherapy.

BACKGROUND AND OBJECTIVE: To analyze the overall visual outcome in 100 consecutive eyes with malignant uveal melanoma irradiated with ruthenium-106 plaques between 1981 and 1991. PATIENTS AND METHODS: The follow-up ranged from 4 months to 10.1 years (median 3.0 years). Scattergrams of equal follow-up periods, life-table survival analysis, and Cox's proportional hazards analysis were used to analyze visual outcome. RESULTS: VA increased for some time in 14 eyes. By 3 years, VA of at least 20/70, 20/200, counting fingers, and light perception were retained in 27%, 41%, 67% and 82% of eyes, respectively. Macular pathology cause loss of reading vision; neovascular glaucoma or enucleation caused loss of light perception. In univariate analysis, large tumor size (height > 5 mm or TNM class T3) predicted visual loss of all VA levels. For the loss of light perception, the tumor's largest basal diameter > 15 mm reached significance. In Cox's multivariate analysis tumor height > 5 mm was the only significant independent risk indicator for loss of VA levels 20/70 and 20/200. For the level CF, largest basal tumor diameter also reached significance, but location of the tumor within 1 disc diameter of the optic disc, either alone or in addition to the fovea, had the greatest risk ratio (6.3, 95% CI 4.1-9.8). For losing light perception, large TNM size (T3) was the strongest risk indicator (risk ratio 10.0; 95% CI 4.5-22.5), followed by proximity of the tumor to the optic disc (risk ratio 4.3, 95% CI 2.4-7.8). CONCLUSION: Ruthenium brachytherapy may retain vision in an eye with a malignant melanoma of the uvea for a considerable period of time. The data presented are useful in patient counseling and allow comparison to subsequent series.

Survival of patients and metastatic and local recurrent tumor growth in malignant melanoma of the uvea after ruthenium plaque radiotherapy.

A series of 100 consecutive patients treated by ruthenium plaque radiotherapy for uveal malignant melanoma from 1981 to 1991 was studied to evaluate local recurrences, metastases, and melanoma-specific mortality. Follow up ranged from 1.0 to 10.1 years (mean, 3.3; median, 3.0 years). Local relapse was observed in 19 patients from 0.1 to 2.7 years (median, 0.7 years) after therapy. Six of these eyes were enucleated. The 5-year probability of local tumor control was 59%. Seven patients with local relapse developed metastasis 0 to 4.3 years (median, 1.4 years) later. Altogether, 18 patients developed metastases 0.9 to 4.6 years (median, 2.0 years) after the irradiation, and 15 of them died of melanoma 5 days to 3.3 years (median, 0.5 years) after detection of metastases. The 5-year probability of metastasis not developing was 61%. The overall 5-year survival was 78%, excluding causes other than malignant melanoma. Large tumor size and anterior tumor location, with or without ciliary body involvement, predicted poor prognosis both in terms of local growth, metastases, and melanoma-specific mortality. Local recurrent tumor growth was associated with a significant increase in metastasis but a nonsignificant increase in melanoma-specific mortality.

Image subtraction analysis with technetium-99M labeled monoclonal antibody and colloid for evaluation of liver lesions. Phantom measurements and patient studies.

The ideal radiolabeled monoclonal antibodies (MoAbs) against cancer antigens are taken up by liver metastases; the background activity of normal liver, however, causes problems for delineation and detectability. In order to study these phenomena, a liver phantom containing hot and cold lesions of different sizes (diameters 5-32 mm) was constructed. It was placed into an elliptic cylindrical container representing a cross section of the abdomen. The specific activities in hot lesions varied from 1.85 to 14.8 MBq/ml, whereas liver phantom and cylinder activities were kept constant during different measurements. Lesions of size 1.3 cm3 could be detected without any subtractions, if the signal to background ratio was larger than 1.2. Lesions larger than 5 mm in diameter could also be detected using subtraction, which gave additional information by a factor 2-9, when the lesion sizes varied from 0.3 to 5.3 cm3 and when the specific activity in the lesions was at least twice as high as in adjacent liver. This subtraction technique was applied in 32 breast and lung cancer patients after injecting about 1,000 MBq 99mTc-labeled anti-CEA MoAb; 24 h after the antibody injection 75 MBq 99mTc-phytate was injected. The phytate + residual MoAb image was subtracted from the original antibody image. Thirteen patients had liver metastases verified by (CT, US), but only four patients had clearly observable abnormal liver uptakes in planar MoAb images. In 9 cases, additional information concerning liver metastases was obtained by subtraction technique. To judge by our phantom measurements the enhanced detectability was not an artefact.

Radioimmunoimaging of non-small cell lung cancer with 111In- and 99mTc-labeled monoclonal anti-CEA-antibodies.

Radiolabeled monoclonal anti-CEA antibodies were used for radioimmunolocalization (RIL) of non-small cell lung cancer; in 30 patients with 111In labeled anti CEA F(ab')2 fragment (BW 431/31) and in 16 with 99mTc-labeled intact MoAb (BW 431/26). RIL results were compared with those of other imaging modalities. Paraffin sections from some patients were also studied immunohistochemically using anti-CEA antibody. Patients with 111In labeled MoAB were imaged twice 1-4 days after injection and for image enhancement pulmonary and liver/spleen subtraction were performed. Twenty-seven of 28 primary tumors were positive and metastases were detected in all patients. The total number of lesions was 78 of which 61 (78%) could be detected by RIL. For verification CT was applied to the study of 46 lesions detected by RIL. We found 6 unknown lesions subsequently verified histologically. Using subtraction techniques we detected 9 lesions in 4 patients, later verified as pulmonary metastases, not detected in unprocessed images. Pleural, mediastinal and pericardial lesions were also better delineated in subtracted images than in unprocessed images. Imaging of non-small cell lung cancer with 99mTc-labeled MoAB was performed twice 4-24 h after injection. RIL results were compared with other imaging methods; CT US, conventional radiography, and immunohistochemistry. Twelve out of 16 patients with suspected or known lung cancer had positive immunoscintigrams; 19 of 25 lesions could be detected by RIL. There were 5 false positive and 2 true negative findings. Immunoperoxidase (IP) stainings of paraffin sections of the tumours from 7 patients were performed using two different anti-CEA antibodies; BW 431/26 and ZCEA1. None of the seven tumors examined by immunohistochemistry were negative when stained by BW 431/26, which was the antibody used for immunoscintigraphy.

Radiotherapy of malignant melanoma of the uvea with I-125 seeds.

Nineteen patients with malignant uveal melanomas were treated with I-125 applicators. There were 10 males and 9 females with a median age of 61 years (range 42-76). The tumour was located in the choroid in 12 eyes and in the choroid and ciliary body in 7 eyes. The size of the tumours was 7-18 mm in maximal basal diameter (median 12), 5-16 mm in minimal basal diameter (median 10), and 5.5-15 mm in thickness (median 8.5). The volume of the tumours was 123-1890 mm3 (median 540). All tumours were classified as large (T3). For the irradiation, a computer program, which calculates three-dimensional dose distribution of I-125 seeds in gold plaques, was developed. By modifying the seed positions, activity and the orientation, patients can be treated individually. Iodine-125 emits low energy photons, ideal for intraocular tumour therapy and tissue. Extra-ocular tissue located behind the applicator can be completely shielded by a 0.5 mm gold layer. The dose at the apex of the tumour ranged from 30 to 120 Gy (median 93). The treatment time ranged from 44 to 600 h (median 235). Preliminary results are good. After a median follow-up of 6 months, the tumour growth has been arrested in all eyes and in 10 eyes the tumour has decreased in size.

Imaging of soft-tissue sarcomas with indium-111-labeled monoclonal antimyosin Fab fragments.

Some soft-tissue sarcomas contain intracellular myosin. We therefore studied the possibility of localizing various soft-tissue sarcomas with 111In-labeled monoclonal antibody Fab fragments binding specifically to myosin, assuming that damage to the cell membrane could expose intracellular myosin. Nineteen patients with different types of soft-tissue sarcomas were studied. Eighteen patients were found to have abnormal antibody uptakes. Antibody uptake was not observed in an additional patient operated for a benign tumor (gastric leiomyoma). The immunoscintigraphy results were generally in good agreement with those of other radiologic findings (computed tomography, ultrasound, magnetic resonance imaging). Surprisingly, the immunohistochemistry results showed that tumors not stainable for myosin can also be imaged with antimyosin. Thus, the mechanism of antibody uptake does not seem to be related entirely to specific antigen recognition. Irrespective of the exact mechanism for the uptake of labeled antibody this method appears to be useful for localizing soft-tissue sarcomas.

Regional blood flow in human tumours measured with argon, krypton and xenon.

Blood perfusion in 19 superficial tumour metastases was measured by injecting three tracers, 41Ar, 85Krm and 135Xe or 133Xe, simultaneously into the tissue. The blood flow rate was calculated from the constants of the biexponential functions fitted to the measured counts. The mean blood flow in the 19 tumours studied was 18 ml/(100 g min) (SD +/- 10). Alternatively, the relative partition coefficients of argon, krypton and xenon were calculated from the equations obtained using compartmental analysis. The mean values for the ratios of the partition coefficients of these nuclides were found to be between 0.82 and 1.07.

Partition coefficient ratios and tumour perfusion studied with 85mKr and 133Xe.

The relative partition coefficients of krypton and xenon, and the regional blood flow in 27 superficial malignant tumour nodules in 22 patients with diagnosed tumours were measured using the 85mKr- and 133Xe-clearance method. In order to minimize the effect of biological variables on the measurements the radionuclides were injected simultaneously into the tumour. The distribution of the radiotracers was assumed to be in equilibrium at the beginning of the experiment. The blood perfusion was calculated by fitting a two-exponential function to the measuring points. The mean value of the perfusion rate calculated from the xenon results was 13 +/- 10 ml/(100 g.min) [range 3 to 38 ml/(100 g.min)] and from the krypton results 19 +/- 11 ml/(100 g.min) [range 5 to 45 ml/(100 g.min)]. These values were obtained, if the partition coefficients are equal to one. The equations obtained by using compartmental analysis were used for the calculation of the relative partition coefficient of krypton and xenon. The partition coefficient of krypton was found to be slightly smaller than that of xenon, which may be due to its smaller molecular weight.

A computer program for I-125 seed implant.

A computer program, written in FORTRAN, for I-125 permanent interstitial implants has been developed. After implantation, isocentric radiographs are taken using radiotherapy simulator (Siemens) in order to obtain two X-ray images of seeds on the same film. Honeywell DPS8 computer and Hewlett-Packard 7221A plotter are used for the dose calculation. The program calculates the dose distribution at the plane desired using 100 X 100 matrix.

Theoretical analysis of regional blood flow studies.

Regional blood flow measurements were analyzed using a two-compartment model. The distribution of injected tracer between blood and tissue was assumed to be in equilibrium only at the beginning of the experiment. Equations for the determination of the partition coefficient of injected radionuclides from in vivo measurements were derived. These equations can also be used for estimation of the relative blood content of a tumor or an organ. The results were applied to experiments, where three diffusible radionuclides were injected simultaneously into patients with diagnosed tumors.