Cell proliferation activity in posterior uveal melanoma after Ru-106 brachytherapy: an EORTC ocular oncology group study.
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AIM: To evaluate the cell proliferation activity in posterior uveal melanomas after Ru-106 brachytherapy. METHODS: Eyes containing choroidal or ciliary body melanoma from seven ocular oncology centres, which were enucleated after first being treated by Ru-106 brachytherapy and which had enough melanoma tissue to enable histological assessment, were included. The 57 eligible specimens were divided into a group of 44 eyes that were enucleated because of tumour regrowth, and a non-recurrent group of 13 eyes that were enucleated because of complications such as neovascular glaucoma. 46 non-irradiated eyes harbouring uveal melanoma served as a control group. All specimens underwent routine processing. They were cut into 5 microm sections, and were stained with two main cell proliferation markers: PC-10 for PCNA and MIB-1 for Ki-67. The stained sections were assessed, and the cells that were positive in the immunostaining were counted in each section. The results were evaluated by various statistical methods. RESULTS: The PC-10 score showed a statistically significant difference across the three groups (p = 0.002). The control group showed the highest PC-10 score (median 31.0 PCC/HPF) followed by the tumour regrowth group (median 4.9 PCC/HPF). The lowest PC-10 scores were found in the non-recurrent tumours (median 0.05 PCC/HPF). The MIB-1 score in the control group (median 5.77 PCC/HPF) was similar to the regrowth group (median 5.4 PCC/HPF). In contrast, the MIB-1 score in the non-recurrent tumours was statistically significantly lower (median 0.42 PCC/HPF). The PC-10 and MIB-1 scores were similar in tumours composed of either spindle cells or epithelioid cells in all groups. CONCLUSIONS: The non-recurrent melanomas demonstrate significantly lower cellular proliferation activity than melanomas that showed regrowth or that were not irradiated at all. In our hands, PCNA gave more meaningful information than Ki-67. Our findings strongly support the need for treating regrowing posterior uveal melanoma either by enucleation or re-treatment by brachytherapy. On the other hand, also in the non-recurrent uveal melanomas there are viable cells with potential for proliferation, although fewer in number, with unknown capacity for metastatic spread. Therefore, the irradiated tumours should be followed for many years, probably for life. (+info)
Quantitative color Doppler imaging in untreated and irradiated choroidal melanoma.
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Histological data indicate the importance of tumor vascularization as a determinant of the biological behavior and the response to radiotherapy in choroidal melanoma. Duplex ultrasound and color Doppler imaging, the combination of B-mode ultrasound and pulse-waved Doppler analysis, were used to measure quantitatively neovascular blood flow in 31 patients with choroidal melanoma. Follow-up studies (20 patients) were performed to investigate the change of tumor blood flow in choroidal melanomas after radiotherapy. Blood flow was detected in 30 out of 31 melanomas (size 3.1-17.8 mm) within the tumor and at the tumor base with a mean peak systolic frequency of 1.0 kHz (range 0.3-2.7 kHz), a mean end diastolic frequency of 0.3 kHz (range 0.1-1.0 kHz), and a mean frequency of 0.7 kHz (range 0.2-1.3 kHz). Two and six months after 106Ru/106Rh beta-ray application, 19 patients showed a significant decrease in peak systolic frequency. This occurred with and in advance of the decrease in the tumor size. In one patient, a rising maximum systolic frequency after radiotherapy marked a recurrent tumor growth. Results indicate that the quantitative measurement of tumor blood flow by duplex ultrasound and color Doppler imaging may be a new diagnostic modality for monitoring the effectiveness of radiotherapy in choroidal melanoma. (+info)
Combined plaque radiotherapy and transpupillary thermotherapy in choroidal melanoma: 5 years' experience.
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AIM: To evaluate the results of combined plaque radiotherapy and transpupillary thermotherapy (TTT) in 50 consecutive patients 5 years after treatment. METHODS: 50 adult patients with choroidal melanoma were treated with ruthenium-106 ((106)Ru) plaque radiotherapy combined with TTT. A flat scar was the preferred end point of treatment. The mean tumour thickness was 3.9 mm (range 1.5-8.0 mm), the mean tumour diameter was 11.3 mm (range 5.8-15.0 mm). TTT was performed with an infrared diode laser at 810 nm, a beam diameter of 2-3 mm, and 1 minute exposures. Tumours >5 mm thick received an episcleral contact dose of 800 Gy (106)Ru; tumours 3 mm thick (log rank test p = 0.01). Eight melanomas were amelanotic, seven of which required multiple TTT sessions. In one patient the tumour recurred at the central margin of the treated area; this eye was enucleated. In one patient the tumour failed to regress 6 months after treatment and enucleation was performed at the patient's request. Three eyes developed severe proliferative retinopathy. Radiation maculopathy caused a loss of the best corrected visual acuity: before treatment 31 patients had a best corrected visual acuity of 20/60 or better but in only 12 patients did it remain in this range 5 years after treatment. Three patients developed distant metastasis to the liver. CONCLUSION: The 5 year results for combined plaque radiotherapy and TTT as treatment for choroidal melanoma are favourable in terms of complete tumour regression and low rate of recurrences; however, there was considerable loss of visual acuity as a result of radiation maculopathy. (+info)
Ruthenium-106 plaque brachytherapy for symptomatic vasoproliferative tumours of the retina.
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AIM: To investigate the safety and efficacy of beta ray brachytherapy in treatment of vasoproliferative tumours of the retina (VTR). METHODS: 35 consecutive patients with symptomatic VTR were treated with a ruthenium-106 ((106)Ru) plaque. Three tumours had been treated previously (two with cryotherapy; one with transpupillary thermotherapy). 32 VTR (91.4%) were located in the lower half of the retina and all of them were found between the mid-periphery and the ora serrata. The mean tumour thickness was 2.8 mm. An exudative retinal detachment was present in 25 eyes (71.4%) and in 15 cases (42.9%) hard exudates were found in the macula. The major symptom was loss of vision (77.1%). RESULTS: Brachytherapy was well tolerated by every patient. The mean applied dose was 416 Gy at the sclera and 108 Gy at the tumour apex. In all but four eyes (88.6%), it was possible to control the VTR activity. The median follow up time was 24 months. Three of the above mentioned four eyes with treatment failure had had secondary glaucoma before therapy. There was no case of radiation induced neuropathy or retinopathy. Cataract surgery was necessary for five patients. The development of epiretinal gliosis was the most common event during follow up (n = 10, 28.6%). The mean visual acuity decreased slightly (0.33 before and 0.29 after brachytherapy). Multivariate analysis showed that the presence of macular pathology before treatment was associated with a 6.1-fold risk of vision of 0.25 or better (p = 0.03). CONCLUSIONS: beta ray brachytherapy with (1106)Ru plaques was able to control the activity of VTR and retain vision. Cases with secondary glaucoma before treatment had a very poor prognosis. (+info)
Ru106 brachytherapy for management of choroidal melanoma: do we need to adjust total dose according to the new NIST calibration measurement?
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PURPOSE: To detect the need of adjusting the apical total dose according to the new NIST calibration measurement introduced by BEBIG Isotopen und Medizintechnik GmbH for the treatment of choroidal melanoma. As the total radiation dose should not be individualized depending on errors pf previous calibration but can be applicable if based on a radiosensitivity test that was able to predict the final response of tumor to radiation for each particular patient. PATIENTS AND METHODS: Twenty patients with choroidal melanomas were treated between November 2002 and July 2004 at "Suzanne Mubarak Eye Tumor Centre", National Eye centre Rod-EL Farag, Cairo, Egypt. The prescribed dose was calculated according to the new NISTcalibrated dosimetry introduced by BEBIG, but without dose modification by using a conversion factor F(type,z) from the ASMW calibrated measurement to the NIST calibrated measurement that have been calculated depending on the plaque type and the distance z from the inner concave plaque surface along the central axis. For the treatment of choroidal melanoma in this study the apical dose ranged from 9000-10400cGy with a mean of 9855 +/- 385. RESULTS: After a follow up period from 12-28 months (median of 19 months) there was a local control rate of 100 % and the three years actuarial disease specific survival was 95% as only one patient died of liver metastases. Fourteen patients had a best corrected pre-treatment visual acuity of better than 6/60 in the affected eye. At the last follow up available, useful visual acuity of>0.5 was preserved in 7 of the patients. CONCLUSION: Recalculation of the apical total dose (mostly increasing of the total dose) according to the conversion factor F(type,z), suggested by BEBIG after the new NIST calibration measurement, does not seem to have an effect on both local control and survival, in this study. (+info)
Plaque radiotherapy treatment with ruthenium-106 for iris malignant melanoma.
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Ruthenium-106 eye plaque brachytherapy in the conservative treatment of uveal melanoma: a mono-institutional experience.
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BACKGROUND: Traditional treatment for uveal melanoma is the enucleation of the eye with outcomes cosmetically unacceptable and loss of useful vision. Plaque brachytherapy, compared to enucleation, had the advantage to preserve the eye with outcomes cosmetically acceptable and preservation of vision. PATIENTS AND METHODS: From July 1990 to December 2009 one hundred forty-two (142) patients (51 males and 91 females) with small to medium uveal melanoma were treated with 106Ru plaque brachytherapy. The patients underwent a complete staging before brachytherapy with indirect ophthalmoscopy and ultrasounds. Mean tumour thickness was 3.26 mm (1.6-6 mm). The dose scheduled was 80-100 Gy to the apex with a maximum dose of 800 Gy to the sclera. RESULTS: One hundred forty-two have been treated, nine patients had lost the follow-up and drop out; 133 patients were assessed. Mean follow-up was 7.7 years (6 months-18 years). The overall survival at 5, 10 and 15 years was 92%, 85% and 78% respectively. Cancer fee survival was 95%, 90% and 83%, respectively at 5, 10 and 15 year. Radiation-induced toxicity was represented in 47 patients with a 5 year actuarial survival rate free from complications of 54%. CONCLUSIONS: 106Ru plaque brachytherapy is a valid approach for treatment of uveal melanoma. This technique is efficacy and safe, with a low toxicity profile. (+info)
Post-brachytherapy tumor endoresection for treatment of toxic maculopathy in choroidal melanoma.
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