33. Pterygium - The GEC-ESTRO Handbook of Brachytherapy

SECOND EDITION

The GEC ESTRO Handbook of Brachytherapy

PART II: CLINICAL PRACTICE 33 Pterygium Bruno Fionda, Monica Maria Pagliara, Ramin Jaberi

Editors Bradley Pieters Erik Van Limbergen Richard Pötter

Peter Hoskin Dimos Baltas

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THE GEC ESTROHANDBOOKOF BRACHYTHERAPY | Part II Clinical Practice Version 1 - 01/03/2023

33 Pterygium

Bruno Fionda, Monica Maria Pagliara, Ramin Jaberi

1. Summary 2. Introduction 3. Anatomy 4. Pathology

3 3 3 4 4 4 4 4

9. Treatment planning

4 6 6 6 6 6 8

10. Dose, dose rate and fractionation

11. Monitoring

12. Results

5. Work up

13. Adverse Events 14. Key messages 15. References

6. Indications, contra-indications 7. Clinical Target Volume

8. Technique

1. SUMMARY

Pterygium is an ocular surface disease characterized by a wing-shaped growth of limbal and conjunctival tissue, within the palpebral fissure, with progressive involvement of the cornea. After primary pterygium surgery there is a high risk of recurrence, therefore, adjuvant treatment after surgical excision should be considered. Adjuvant irradiation, delivered immediately after surgery, can effectively prevent pterygium recurrence. The standard and classical technique is using a beta emitter (such as strontium-90) applicator which is an epibulbar shape and adapted to the target volume as closely as possible.

2. INTRODUCTION

the cornea in the direction of the growing pterygium (especially for lesions>2mm) [5]. In advanced cases, pterygium can affect vision as it invades the cornea with the potential to obscure the optical centre of the cornea. After primary pterygium surgery there is a high risk of recurrence in the range of 24% to 89%, therefore adjuvant treatment after surgical excision should be considered [6].

Using beta radiation sources has a long history of successful treatments that have been published in radiotherapy and ophthalmology. It is a convenient and practical method of applying radiation and has the advantage of minimal tissue penetration. Today, this well-established local radiotherapy method has undergone a revival [1]. Several authors have emphasised that adjuvant radiotherapy is practical, effective and owing to its long history, we are more aware of its long-term effects than is the case with other modalities [2]. Pterygium is an ocular surface disease characterized by a wing- shaped growth of limbal and conjunctival tissue, within the palpebral fissure, with progressive involvement of the cornea. Risk factors for developing pterygium include demographic, environmental, and lifestyle factors [3]. Since the main risk factor for the development and the progression of pterygium is ultraviolet exposure, the prevalence varies with geographical location and ranges from 1% to more than 30% [4]. Though frequently asymptomatic, if it becomes inflamed, irritation and dry eye, by interrupting the tear film can occur. In later stages, the growing tissue may cause astigmatism by flattening

3. ANATOMY

Pterygiummay be located from the cornea to the internal cantus, in the interpalpebral opening [7]. Critical organs for radiotherapy are all the structures of the eye in particular the lens. When radiation is used the dose received by the lens and other critical sites in the anterior eye segment must be strictly evaluated. A schematic representation is presented in figure 1.

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7. CLINICAL TARGET VOLUME

The treatment decision should represent the consensus of a multidisciplinary specialist board. Regarding the Clinical Target Volume (CTV) it is recommended that the radiation oncologist evaluates the pterygiumbefore surgery to adequately choose the applicator size.

The CTV should include the entire surface of the resected lesion.

8. TECHNIQUE

Figure 1: Schematic drawing of the right eye.

The standard technique is using an epibulbar shaped strontium (strontium-90) applicator which is adapted with the treated volume as closely as possible. The applicator has a central radioactive disc and a non-radioactive rimof 2mm (figure 3). Standard treatment is under a local anaesthetic using eye drops containing procaine.The time of application is very important, treatment should be given as soon as possible after surgery (see section 10; Dose, dose rate and fractionation). The eyelids must be opened by a lid retractor. For better accessibility to the lesion, this spreader should be inserted carefully around the exterior region of the pterygium. The surface of the strontium-90 is brought into contact with the pterygium conjunctiva for a precise time which is calculated to deliver the prescribed dose (figure 4). Because of the limited variety in strontium-90 applicator sizes, amanual “radiation field-overlapping” technique was frequently practiced – resulting in higher toxicity rates because of the overdosed overlapping area. The radiation delivery time can be calculated based on thickness of the CTV, half-life of the source and date which we are using the applicator. Surface dose rate is normally about 1 Gy/s at the time of applicator manufacture. The surface dose rate in the central area of 4 mm diameter is reported in the calibration report [16]. Recently two other kinds of plaques have been proposed for pterygium, ruthenium-106 eye plaques, which are used for ocular melanoma and also other ophthalmic malignancies and phosphorus-32 in the same applicator shape as strontium-90. An advantage of phosphorus-32 applicators is that they can be used intraoperatively. However, long term results with this method are not yet published [17,18].

4. PATHOLOGY

The main histologic findings in a pterygium in layers from the surface include invading pterygium epithelial cells with proliferative features, squamous metaplasia, hyperplasia of goblet cells, underlying disrupted Bowman’s layer, stromal fibroblast and vessels, altered extracellular matrix (ECM) with accumulation of collagen and elastin fibers, and inflammatory infiltration [8].

5. WORK UP

A complete eye exam should be performed on all patients with pterygium focusing on assessment of visual acuity and changes in manifest refraction; corneal topography can help to determine the preoperative astigmatism and visual impact of pterygium. A series of typical clinical presentation is provided in figure 2.

6. INDICATIONS, CONTRA-INDICATIONS

Simple excision may result in a high recurrence rate, therefore following surgery adjuvant therapy should be considered [9]. Conjunctival-limbal autografting, as well as topical drugs, have proven to be effective choices with a reported recurrence rate of 5-10%. Adjuvant irradiation, delivered immediately after surgery, can effectively prevent pterygium recurrence and is an alternative to other adjuvant strategies such as cyclosporine, mitomycin C, 5-fluorouracil or bevacizumab [10,11,12,13]. Some authors advise radiotherapy alone for small pterygia and such a strategy has been successful in pterygia < 2mm horizontal length [14].

9. TREATMENT PLANNING

The dose prescription is always to the applicator surface which is assumed to be identical to the sclera/cornea surface. Dose per fraction and total dose at the applicator surface is decided, written and dated on the patient chart by the radiation oncologist on the case, then treatment time is generally calculated manually using a calculator based on the calibrated surface dose rate on the day of application (incorporating decay) by a physicist. Double checking data by another member of the physics team is strongly recommended. The target area should encompass the surgical

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Figure 2: A series of typical clinical presentation

Figure 3: (a) Example of Strontium-90 eye applicator type SIA-1 with a stainless-steel filter of 0.1 mm (screenage) - (b) Example of Strontium-90 eye applicator type SIA-6. (Reproduced from Cohen et al. [15]).

Figure 4: Placement of strontium ophthalmic applicator in the nasal bulbar conjunctiva as adjuvant treatment for pterygium (Courtesy of B. Pieters).

Figure 5: Rapid dose fall-off near the strontium-90 applicators, from 100% to 0.5 percent in 5 mm

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11. MONITORING

bed with an additional safety margin of 1mm of the cornea and 3-4 mm of the eye limbus. As shown in figure 3 it is important to consider that the applicator consists of a central radioactive area and an inactive rim zone. In some cases where the surgical resection area is too large, then two applications should be used usually overlapping each other to a limited extent. If faced with a large circular applicator and healthy cornea overlying, an individual protector can be made of thin lead foil to conserve the healthy part of cornea. Care is needed considering the thickness of foils allowing for possible X-ray contamination. A thicker layer may produce soft X-rays.The delivered dose to the lens with strontium-90 applicators is less than 5%, consistent with the very rapid dose fall-off near the strontium-90 applicator (figure 5). Several attempts to use radiotherapy to treat pterygiumhave been performed during the last century [19] and several authors have tried to identify the optimal regimen in terms of timing, total dose and fractionation [20]. The first fraction should be delivered a few hours (less than 24 hours) after the excision. Currently, there is a huge variety of postoperative dose and fractionation schemes, ranging from 20 Gy as single dose to 60 Gy in 6 fractions [6]. The largest and latest series available in the literature mainly used 30-35 Gy in 3, 5 or 7 fractions. A randomized postoperative dose finding study showed no significant differences between 30 Gy in three fractions over 15 days compared to 40 Gy in 4 fractions over 22 days prescribed to the surface of the eye for primary lesions in terms of local control rates. No differences in terms of acute and late complications were noted. A comprehensive report of doses and fractionations used in literature is reported in table 1. 10. DOSE, DOSE RATE, FRACTIONATION

During the application tolerance is quite acceptable because of the local anaesthesia. It is important to carefully keep the correct position of the applicator during the radiation time. In applications lasting for several minutes it is advised to stop halfway, to relax a while and to check correct positioning. During the days following irradiation a local reaction with redness, tear formation and sometimes minor conjunctivitis is noted and may last for 4 - 6 weeks following the treatment. A topical ointment application is prescribed with 3-4 days local antibiotics and corticosteroids until inflammation has disappeared (usually within one week).

12. RESULTS

A comprehensive literature review collected data regarding over 6000 lesions treated by radiotherapy. The results of combined resection and postoperative beta irradiation are reported in table 1. It is important to underline that prospective randomized trials are scarce andmost of the clinical evidence available from retrospective studies. It was reported that eighty percent of recurrences developed within 3 years after treatment [21].

13. ADVERSE EVENTS

Among the most common adverse effects are visual disturbances (4.2%) and congestion (2.5%); less frequently encountered adverse events include scleromalacia (1,2%), adhesion of eye lids (1%), scleral ulcer (1%), cataract (0.8%), scleral thinning (0.8%) and ulceration (0.5%). Generally, ocular morbidities, in particular scleral necrosis, are more frequent and more severe if radiotherapy is performed in the presence of a conjunctival defect [36].

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TABLE 1 LIST OF STUDIES ABOUT ADJUVANT RADIOTHERAPY IN PTERYGIUM.

Interval Surgery/ start BT

Primary (P)/ Recurrent (R) Study type

Year of publication

Number of lesions

Dose/ Fractions*

Author

Follow-up Local control

93.8% (35 Gy scheme) and 92.3% (20 Gy scheme)

P: 100% R: 0

Viani et al. [22]

2012

216

Prospective 35 Gy/7 or 20 Gy/10 <3 days

3 years

Range from 20 Gy to 30 Gy/3

P: 87% R: 13% Prospective

Qin et al. [23]

2012

120

<6 days

10 years

100%

100% (40 Gy scheme) and 77.9% (20 Gy scheme)

P: 100% R: 0

Yamada et al. [24]

2011

95

Retrospective 40 Gy/2 or 20 Gy/1 <7 days

10 years

P: 87% R: 13% Retrospective P: 88% R: 12% Retrospective

35 Gy/7 or 35 Gy/5 <5 days 30 Gy/3 or 35 Gy/3 <2 days

Median 60 months Median 45 months Mean 18 months

Viani et al. [25]

2008

737

90%

Isohashi et al. [26]

2006

1253

90%

P: 100% R: 0

Jürgenliemk-Schulz et al. [27] 2004

86

Prospective 25 Gy/1

<1 day

93.2%

87% (30 Gy scheme) and 70% (4 0 Gy scheme) Ranging from 76.9% to 94% according to the fractionation

P: 100% R: 0

Median 2 years

Nakamatsu et al. [37]

2004

73

Prospective 30 Gy/3 or 40 Gy/4 <3 days

Range from 20 Gy to 60 Gy/1-6 Range from 7.4 Gy to 49.9 Gy/1–5

P: 37% R: 63% Retrospective

Median 49 months

Monteiro-Grillo et al. [28]

2000

100

<1 day

P: 92% R: 8%

Nishimura et al. [29]

2000

490

Retrospective

<86 days Median 61 months

88%

P: 89% R: 11% Retrospective P: 72% R: 28% Prospective

30 Gy/3 or 35 Gy/3 <2 days 27 Gy/3 or 30 Gy/3 <1 day

Median 17 months

Fukushima et al. [30]

1999

393

93.7%

6 month –7 years Median >8 years

De Keizer [31]

1998

57

100%

P: n.a. R: n.a. P: n.a. R: n.a.

Paryani et al. [32]

1994

825

Retrospective 60 Gy/6

<1 day

98.3%

Wesberry et al. [33]

1993

171

Retrospective 20 Gy/1

<1 day

Up to 17 years 92%

Range from 10 Gy to 24 Gy/1-3 Range from 30 Gy to 45 Gy/1-3

P: 84% R: 16% Retrospective

Median 2 years

Wilder et al. [34]

1992

338

<1 day

88%

P: n.a. R: n.a.

Median 13 months

Beyer [35]

1991

146

Retrospective

<1 day

87%

* The prescription dose is to the surface of the eye

14. KEYMESSAGES

• Pterygium is an ocular surface disease characterized by a wing-shaped growth of limbal and conjunctival tissue, with progressive involvement of the cornea • Risk factors for developing pterygium include demographic, environmental, and lifestyle factors. • After primary pterygium surgery there is a high risk of recurrence, therefore, adjuvant treatment after surgical excision should be considered. • The clinical outcomes of brachytherapy treatment with a beta emitter epibulbar applicator include high local control rates and low toxicity rates.

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15. REFERENCES

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ACKNOWLEDGMENTS The authors of this chapter are much indebted to Alain Gerbaulet and Erik Van Limbergen, authors of the original version of the chapter on Pterygium in the first edition of the GEC-ESTRO Handbook of Brachytherapy 2002.

AUTHORS

Bruno Fionda U.O.C. Radioterapia Oncologica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome, Italy Monica Maria Pagliara U.O.C. Oncologia Oculare Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome, Italy Ramin Jaberi Radiation Oncology Research Centre (RORC) Cancer Institute, Tehran University of Medical Sciences Tehran, Iran