FP1614 : Local tumor control by adjuvant plaque brachytherapy in conjunctival melanomaDR. ROLIKA BANSAL
Dr. KAUSTUBH MULAY, Dr. SANTOSH G. HONAVAR
Abstract
Purpose:Considering high malignant potential, local tumor recurrence of conjunctival melanoma, enucleation was often performed. We assessed role of adjuvant plaque brachytherapy in a retrospective case series of 15 consecutive patients.Results:Median age 33(range 8-65)y. Mean diameter 9.9+3.2(range 4-17)mm, mean height 2.9+1.2(range 1.5-6)mm. Corneal and scleral invasion was assessed clinically (UBM, OCT or MRI), intraoperatively and by histopathology (HPE). Ru-106 plaque brachytherapy was done at primary excision in 8(54%) or following HPE confirmation of base invasion in 7(46%) to 2-3mm depth, 10000 cGy apex dose, mean duration37.4+18.9(range 11.5-74)h. Two patients had regional lymph node metastasis. At mean follow-up of 8.1 y, vision salvage and local tumor control was achieved in all, with no mortality.Conclusion: Adjuvant Ru106 plaque brachytherapy patients with corneal and/or scleral invasion aids in preservation of the eye and vision and minimizes local tumor recurrence.
Full Text
Purpose:
Considering high malignant potential, local tumor recurrence of conjunctival melanoma, enucleation was often performed. We assessed role of adjuvant plaque brachytherapy in a retrospective case series of 15 consecutive patients.
Results:
Median age 33(range 8-65)y. Mean diameter 9.9+3.2(range 4-17)mm, mean height 2.9+1.2(range 1.5-6)mm. Corneal and scleral invasion was assessed clinically (UBM, OCT or MRI), intraoperatively and by histopathology (HPE). Ru-106 plaque brachytherapy was done at primary excision in 8(54%) or following HPE confirmation of base invasion in 7(46%) to 2-3mm depth, 10000 cGy apex dose, mean duration37.4+18.9(range 11.5-74)h. Two patients had regional lymph node metastasis. At mean follow-up of 8.1 y, vision salvage and local tumor control was achieved in all, with no mortality.
Conclusion:
Adjuvant Ru106 plaque brachytherapy patients with corneal and/or scleral invasion aids in preservation of the eye and vision and minimizes local tumor recurrence.
Introduction
Conjunctival melanoma (CM) is a rare, aggressive pigmented ocular surface tumor accounting to 0.25% of all melanomas overall, 2% of all eye tumors and 5% of melanomas in ocular region with an incidence of 0.24 to 0.80 per million. [1–3]
Tumor staging is done based on the American Joint Committee on Cancer (AJCC) staging system. In CM there are high chances of metastasis occurring via lymphatic drainage, hematogemously and locally via the sub-epithelial space and the risk factors have been considered to be non-bulbar tumor location, multi-focality, higher AJCC stage, high baseline tumor thickness, BRAF-mutated tumor and associated ulceration.[4,5] Several treatment modalities have been practised over the years including wide excision with cryptherapy, topical chemotherapy with or without adjuvant radiotherapy (primary or secondary). Despite all efforts, CM has a local recurrence rate of 26-60% at 5 years and 38-69% by 10 years. This spikes the morbidity and mortality rates making the 5-year mortality and 10-year mortality to be 83-93% and 82-90% respectively[1] and considering these facts it is essential to know about the corneal and scleral invasion in these patients.
Enucleation used to be a necessary intervention in the patients with corneal and scleral invasion. However, the advent of plaque brachytherapy has revolutionised the treatment approaches and a multi-modal management approach can certainly help in reducing the morbidity and mortality. Therefore, this study aims at exploring the role of multi-modal treatment by surgical excision and adjuvant plaque brachytherapy in patients with conjunctival melanoma with corneal and scleral invasion.
Methods
A retrospective interventional case series was carried out which included patients with CM managed with wide excisional biopsy of tumor and conjunctival cryotherapy who were found to have clinical and histopathologically proven scleral or corneal invasion. Ruthenium-106 plaque brachytherapy was done for all the patients either as primary or as secondary adjuvant treatment at an ocular oncology centre in southern india between 2013-2021. Institutional review board approval was obtained and written informed consent was taken from all patients.
Patient data were extracted from medical records and included patient age at diagnosis (years), gender (male or female), presenting symptoms, carcinomas elsewhere in the body, prior ocular treatment, and lymph node involvement (submandibular, anterior cervical, or preauricular). The ocular features included best-corrected visual acuity (VA), intraocular pressure (mm Hg), tumor laterality (unilateral or bilateral), configuration (nodular, flat, papillomatous, or sessile), tumor extent, tumor multiplicity (unifocal or multifocal), tumor basal dimensions and thickness (millimeters), corneal involvement, presence of feeder and/or intrinsic blood vessels, and associated ocular findings. The tumor basal diameter and thickness were measured clinically and with slitlamp biomicroscopy and confirmed with ultrasound biomicroscopy (UBM). All findings were documented with anterior segment drawings, slitlamp photography, anterior-segment optical coherence tomography, and UBM. Histopathologic diagnosis of CM was confirmed in all cases.
The advantages, disadvantages and the potential risks of plaque radiotherapy were discussed with the patient, and written informed consent was obtained. Each tumor was treated with a ruthenium-125 (Ru) plaque either as primary of adjuvant secondary treatment after complete surgical excision. Initial follow-up examination was performed at 6 weeks after plaque removal. Features recorded at each follow-up visit included best-corrected VA, tumor response (including basal diameter and thickness, measured by both slitlamp biomicroscopy and UBM), status of tumor, recurrence, complications from treatment, and globe salvage. Patient outcome (alive, alive with metastasis, death due to metastasis, or death due to other causes) was noted.
Results
The median patient age was 33 years (range, 8-65 years) with 7 (46.7%) males and 8 (53.3%) females. The lesions originated from primary acquired melanosis (PAM) in 7 (46.7%) and a nevus in 6 (40%) and denovo in 2 (13.3%). The most common presentation included a pigmented, elevated or flat lesion with a prominent feeder vessel and intrinsic vascularity with or without scleral fixity and corneal invasion with assessment of the involved clock hours. At baseline the mean tumor thickness was 9.9+3.2 mm (range 4-17mm) and the mean height was 2.9+1.2 mm (range 1.5-6 mm). Corneal and scleral invasion was assessed clinically (UBM, OCT or MRI), intraoperatively and by histopathology (HPE).
Ru-106 plaque brachytherapy was done at primary excision in 8(54%) or following HPE confirmation of base invasion in 7(46%). The dosimetry was obtainted by the radiation oncologist and for all the cases radiation exposure was given to 2-3mm depth with 10000 cGy apex dose for a mean duration of 37.4+18.9(range 11.5-74)hours. Two patients had regional lymph node metastasis.
Following the procedure complications included symblepharon (n=2), scleral thinning (n=2) and psuedopterygium formation (n =2). These were unrelated to plaque dosage. At mean follow-up of 8.1 years (median, 7.5 years; range, 5-14 years), local tumor control was achieved in all 15 cases (100%). However, further tumor recurrence at a distant conjunctival site remote from the radiotherapy and within the globe was detected in 1 case which was managed with excision and cryotherapy. Vision salvage and local tumor control was achieved in all, with no mortality
Discussion
As per the assessment of time trend by Triay et al, the tumors became smaller and thinner over the years with a tendency to arise from the parts exposed to ultraviolet radiation [11] with a higher incidence in men and women > or = 65 years (1.48 and 1.39 cases/million, respectively) than in younger men and women (0.3 and 0.2 cases/million, respectively).[11] We did not observe any such trend in our cases over the years and saw an equal gender distribution i.e. 7 (46.7%) males and 8 (53.3%) females.
Lommatzcsh et al in 1990 stated that less recurrence occurred in the radiated patients with a 10-year survival rate of 76.3%.[6] Similarly Krause et al in 2008 studied 15 patients of CM and observed that in 8 cases there was recurrence in the non-radiated area whereas 3 developed recurrence even in the radiated area.[7] In 2009, Walsh-Conway et al concluded at a mean follow up of 23.4 months that 2 patients out of 5 developed recurrence at a site distant from the treatment site along with corneal ulcerations as complications.[8] Corneal ulcerations were also seen in 6 out of 19 cases in a study in 2010 by Karim et al.[9] A multi-center study in 2020 by Jain et al showed a cumulative recurrence of 36.9% at a 10-years follow-up.[10] Isager et al stated that the 5-year and 10-year mortality rate was 83-93% and 82-90% respectively as per a 55-year analysis in Denmark which included 115 patients of CM. [1]
Previously done studies have shown variable usage of plaque type including strontium, yttrium, iodine and ruthenium plaque with or without histopathology assessment. Variable local recurrence was observed in the previously done studies with survival rate as 76.3% or recurrence rate of 36.9%. Ours was the first study worldwide performed by a single surgeon with 15 consecutive cases undergoing plaque brachytherapy with zero local recurrence. Multimodal treatment includes image guided assessment followed by surgical excision with 4mm clinically clear margins, lamellar sclerectomy, alcohol keratoepithelectomy, double freeze thaw cryotherapy to edge and base thus ensuring margin and base control, adjuvant plaque brachytherapy and histopathological confirmation and in our study all the patients were alive and well by the end of a mean follow-up of 8.1 years thus achieving life and globe salvage.
Conclusion
Multi-modal management with adjuvant Ru106 plaque brachytherapy in patients with corneal and/or scleral invasion aids in preservation of the eye and vision and minimizes local tumor recurrence.
References
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