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  5. FP1398 : Ruthenium106 Plaque Brachy in Management of Ocular Surface Squamous Neoplasia with Scleral Invasion

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Dr. Sumeet Lahane, L19136, Dr. Surbhi D Joshi, Dr. Sonal Chaugule, Dr. Santosh G Honavar

 

Abstract:

PURPOSE: Outcome of OSSN with scleral invasion managed by Ruthenium106(106Ru) plaque . 

METHODS: Retrospective case series included 49 eyes with scleral invasion managed by 106Ru plaque.Plaque was used as an adjuvant treatment for residual(base-positive on histopatholgy) tumors or as primary treatment for tumors with scleral invasion.Outcome measures were tumor regression, eye and vision salvage,metastasis.

 RESULTS: Mean age was49±13years. Mean tumor diameter was9.5±4.8(range 4.0-18.0)mm and treated height was2.2±0.4(range 1.5-3.0)mm.Mean prescribed radiation dose was5284±570cGy.Mean duration of follow-up was10(12-48)months.44(90%) eyes s had complete tumor regression with eye and vision salvage.Vision improved (>2lines)in10(20%)and was stable in 34(70%)eyes.5(10%) with local tumor recurrence were managed by extended enucleation (n=4) or orbital exenteration (n=1).None had metastasis

CONCLUSION: 106Ru plaque brachytherapy is safe and effective in the management of OSSN with scleral invasion

Keywords – OSSN, Plaque brachytherapy , Ruthenium 106

INTRODUCTION –

Incidence of Ocular surface squamous cell neoplasia (OSSN)  between 0.13 to 1.9/100000 as per multiple studies. 1-3 The average age of occurrence is 60 years           ( Range  20 to 88 years )  . The Invasive OSSN is known to occur 5-9 years later than  carcinoma in situ lesions with an exception of Patients of xeroderma pigmentosa and human immunodeficiency virus (HIV) who  develop OSSN at  early age.

OSSN can present as Mild dysplasia to  extensive invasive orbital squamous cell carcinoma 1-3 Histopathological evaluation about  thickness of the epithelium  involved is used to identify disease severity . In mild dysplasia, less than one third of the epithelial thickness is involved by atypical cells. In moderate dysplasia, atypical cells occupy one third to two thirds of the epithelial thickness. Full thickness epithelial  involvement is severe dysplasia . Carcinoma in situ (CIS) presents  as full-thickness atypia. Extension of atypical cells through basement membrane into the substantia propria is defined as  squamous cell carcinoma .3-5

Ultraviolet A and B exposure, ionizing radiation exposure, infection with human papillo- mavirus (types 6, 11, 16, and 18), and immune suppression from infection (human immunodeficiency virus [HIV]), medication (post-organ transplant immunosuppressive agents), or neoplasia (lymphoma, leukemia) are few important risk factors 6 

 There is tremendous shift in management of OSSN over a period.  is managed by  surgical excision which was most common treatment modality is been largely replace by  by topical chemotherapy specially for small lesions ,recurrence and diffuse lesions with corneal involvement.7,8  

Though surgical excision still remains treatment of choice for small to medium lesions with unreliable patient follow up in developing countries ; recurrence due to incomplete excision with  positive  margin and base  on histopathology is a significant risk factor. Residual tumor with corneoscleral involvement still poses as difficult to treat disease. Intraocular and anterior orbital extension of OSSN need extended enucleation or  orbital exenteration . As an alternative to such extensive surgeries we used Ruthenium-106 plaque brachytherapy in invasive OSSN.9,10

METHODS –

This retrospective interventional case series included patients with OSSN  managed with excisional biopsy  with 4 mm clinically clear margins by no touch technique , alcohol assisted epithelial  keratectomy, and conjunctival edge double thaw cryotherapy who were found on clinical and histopathology examination to have scleral invasion.   Ru-106 , plaque radiotherapy was applied at the Ocular Oncology Service, Centre For Sight Hospital,Hyderabad,India in conjunction with the Department of Radiation Oncology,Apollo Hospital,Hyderabad  between October 2013 and September 2017. All procedures were carried out by the same surgeon (SH).

Institutional review board approval was obtained at Centre For Sight Hospital and written informed consent was obtained from patients.

Patient data were extracted from medical records and included patient age at diagnosis (years), sex (male or female), presenting symptoms, immunosuppression, prior  treatment and lymph node involvement (preauricular, submandibular, anterior cervical). The ocular features included best corrected visual acuity (BCVA), intraocular pressure (mm Hg),  laterality (unilateral or bilateral), basal dimensions and thickness (millimeters), corneal involvement, number of quadrants involved by tumor, presence of intrinsic blood vessels, intraocular involvement and associated ocular findings (pinguecula, pterygium, actinic keratosis). The tumor basal diameter and thickness were measured with slitlamp biomicroscopy and confirmed with ultrasound biomicroscopy  (UBM),anterior ocular coherence tomography ( OCT )  was done in cases of clinically suspected invasive tumor.  (UBM). Histopathologic diagnosis of invasive OSSN with edge and base positivity was confirmed in all cases.

Patients were explained  advantages and disadvantages of  plaque radiotherapy  and written  informed consent was obtained. Each tumor was treated with Ru-106 plaque to cover the residual invasive tumor with a surrounding 2-mm margin for duration calculated by radiation oncologist for  clinically estimated height and dose . Post operatively patients were reviewed every 1 to 3 monthly . Clinical data in the form of  BCVA,tumor measurements , status of tumor, recurrence, complications and eye salvage, lymph node spread was noted .

RESULTS –

The mean patient age was 49±13years. Pre operative mean tumor diameter was  was9.5±4.8(range 4.0-18.0)mm and treated height was2.2±0.4(range 1.5-3.0)mm.

19 referred  patients were managed with a variety of treatments from excision , incision biopsy to topical chemotherapy prior to referral and  all of them  patients with  were treated with  excisional biopsy 4 mm clinically clear margins by no touch technique , alcohol assisted epithelial  keratectomy, and conjunctival edge double thaw cryotherapy.

Following excision, histopathology  proved base positivity in all cases. 42 patients were treated with plaque brachytherapy 3-4 weeks post excision biopsy while 7 patients were treated with plaque RU-106 as primary procedure along with excision biopsy.

Plaque radio- therapy was applied for a mean  radiation dose  of 5284±570cGy  and duration of  20 ± 9 hours (median 19.5  hours; range, 7- 41  hours) .

Complications included cataract (n = 2 ), corneal epithelial defect (n = 10). There were no patients with scleral thinning .

The BCVA improved in 10 ( 20%) patients and   remained stable in 34 ( 70 %) eyes . At mean follow-up of 18  months ( 3- 48  months), local tumor control was achieved in 44 cases (90 %).  Tumor recurrence   was detected in 7  cases at a mean follow-up of 8  months post plaque. Treatment for remote recurrence included repeat plaque brachytherapy (n =2 ) ,  extended  enucleation (n=4) and  orbital exenteration (n = 1) . 

DISCUSSION

Excision biopsy by no touch technique with cryotherapy is most commonly followed treatment protocol for OSSN. 11-15 Margin and base positive with tumor cells is an important risk factors for recurrence of lesion.

High recurrence rate which ranges from 15% to 52% is been noted following primary excision with incidence upto 69 % with positive margins.  OSSN extending through sclera or cornea requires enucleation or exenteration. 13,15

Newer drugs of topical chemotherapy  MMC and 5-fluorouracil and immunotherapy Interferon alpha-2b is effective in treatment of OSSN,  small size recurrence and diffuse corneal –conjunctival mass . Scleral penetration of these drugs being poor they are ineffective for invasive OSSN. Plaque brachytherapy  to treat invasive lesion is known modality in literature.   16-20

Walsh-Conway and Conway  reported 6 patients with scleral-invasive OSSN  with I 125 radiotherapy 18.They had 1 episode of distant conjunctival recurrence in follow of  23 months. Arepalli et al treated  15 cases of invasive OSSN with plaque brachytherapy with I 125 and recurrence was seen in  4 patients (26.66%) ; management with enucleation (n=2) , exenteration(n=2) was done. Single eye had to be enucleated due to irritation post radiotherapy.15

Zehetmayer et al , Buc et al each reported single case of invasive tumor treated with plaque brachytherapy with complete regression of tumor .16,20

In present study we analysed 49 eyes of 49 patients with OSSN histopathological proven scleral invasion . Most of cases were referred with prior therapy done elsewhere and recurrence. In all this cases we differed morbid surgery of exenteration and excision followed by  Ru-106 plaque brachytherapy  was done. 7 patients showed local recurrence following radiotherapy. 2 of these patients were managed with repeat plaque and  achieved complete regression. Rest 5 patients had rapid intraocular and orbital spread led to the enucleation (n=4) ,Exenteration (n=1). Primarily aggressive tumor following multiple excision could be the cause for progression.   21

Radiation complications in the form of cataract (n=2)  and transient corneal epithelial defect (n=10) were seen. Lens being the radiosensitive structure can be affected even with radiation of 1 Gy . 22  None of the patients developed scleral thinning , Neovascularization of iris or neovascular glaucoma.

CONCLUSION

Brachytherapy is safe modality to provide targeted therapy to lesion and minimum dose to surrounding normal structures. Precise radiotherapeutic dose  and plaque placement can result in  complete regression of  invasive OSSN and can salvage vision , eye and life.

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