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Fractionated Stereotactic Radiotherapy for Cavernous Venous Malformations of the Orbital Apex

Ratnayake, Gishan S. M.B.B.S.*; McNab, Alan A. D.Med.Sc., F.R.A.N.Z.C.O.; Dally, Michael J. M.B.Ch.B., F.R.A.N.Z.C.R.; Zajarski, Catherine B.App.Sc., M.H.A.*; Senthi, Sashendra M.B.Ch.B., F.R.A.N.Z.C.R., Ph.D., M.P.H.*,§; Ruben, Jeremy D. M.B.B.Ch., F.C.RadOnc, F.R.A.N.Z.C.R., M.med., M.D.*,§

Ophthalmic Plastic & Reconstructive Surgery: July/August 2019 - Volume 35 - Issue 4 - p 322–325
doi: 10.1097/IOP.0000000000001239
Original Investigations
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Purpose: The objective of this study was to investigate the efficacy and safety of fractionated stereotactic radiotherapy in the treatment of cavernous venous malformation of the orbital apex.

Methods: The authors reviewed a prospective database from a single center of patients with cavernous venous malformation of the orbital apex who had treatment with fractionated stereotactic radiotherapy. The authors compared the symptoms, visual function and the size of the tumor pre- and posttreatment as well as reviewed the treatment details and the incidence of complications.

Results: Six patients received treatment with fractionated stereotactic radiotherapy for cavernous venous malformation involving the orbital apex. The median age was 48 (range, 32–63), and 50% were female. Patients received a dose of 45 to 50.4 Gy in 1.8 to 2 Gy fractions. Median follow up was 33 months (range, 18–66 months). The average tumor volume reduction at posttreatment imaging after 12 months was 63%. All lesions reduced in size postradiotherapy and remained controlled for the duration of follow up. All patients who had proptosis or a visual field defect had an improvement in the symptoms posttreatment. There were no complications of the treatment.

Conclusion: Fractionated stereotactic radiotherapy appears to be a safe and effective management option for cavernous venous malformation of the orbital apex and leads to a sustained reduction of the volume of the lesion with associated improvement in symptoms and visual function.

Fractionated stereotactic radiotherapy for cavernous venous malformation of the orbital apex is a safe and effective alternative to surgery and can provide long-term control with improvements in symptoms and visual function.

*Alfred Health Radiation Oncology, The Alfred Hospital

Orbital Plastic and Lacrimal Clinic, Royal Victorian Eye and Ear Hospital

Radiation Oncology, Epworth Healthcare

§Monash University, Melbourne, Australia.

Accepted for publication August 14, 2018.

The authors have no financial or conflicts of interest to disclose.

Address correspondence and reprint requests to Gishan Ratnayake, M.B.B.S., Alfred Health Radiation Oncology, Alfred Hospital, 55 Commercial Road, Melbourne, 3004, VIC, Australia. E-mail: g.ratnayake@alfred.org.au

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Cavernous venous malformation (CVM) is the most common vascular lesion of the orbit in adults.1 Previously referred to as an orbital cavernous hemangioma, it has been more appropriately defined as a venous malformation rather than as a neoplasm.2–4 It generally remains asymptomatic until adulthood when it most commonly presents with symptoms in the fourth and fifth decade.5 It is usually solitary and unilateral and most commonly occurs in the middle third of the orbit within the intraconal space lateral to the optic nerve.6,7 This location leads to the common presentation of progressive axial proptosis, which can be complicated by visual deterioration.8

The management of CVM of the orbital apex can be complex due to the lesion sharing a tight space with critical nervous and vascular structures that are often poorly delineated on imaging.9,10 In some cases, observation over time with serial imaging and visual field testing is an option.11 However, treatment should be considered if there is deterioration in visual fields or new symptoms. Surgical approaches with anterior and lateral orbitotomy carry a significant risk of diplopia, ptosis, loss of accommodation, corneal anesthesia, pupillary abnormalities, and rarely can result in profound vision loss.6,12–14 Diagnosis is also less dependent on surgical histology as advances in MRI particularly with dynamic contrast enhancement sequences can provide a confident radiologic diagnosis.15–17 As a result, the noninvasive approach of stereotactic radiotherapy has been considered an option in the treatment of CVM.

Stereotactic radiotherapy delivers high dose radiation to the tumor with precision in a highly conformal manner such that there is minimal dose to adjacent normal tissue. Most experience in the literature is with high dose single fraction treatment known as stereotactic radiosurgery.18–21 However, an attractive alternative is using fractionated stereotactic radiotherapy (FSRT), which delivers the radiation dose to a similar accuracy over an extended period. Due to the inherent radiobiology of fractionating the radiation dose, there is less risk of toxicity to normal structures with FSRT.22 This is especially important as lesions are often in close proximity to the optic nerve where fractionation keeps the nerve dose within safe limits.

A Canadian case series described 5 patients treated with FSRT for CVM of the orbital apex who had a durable clinical and radiological response to treatment.23 In this study, the authors looked to provide further evidence to confirm the efficacy of FSRT in treating CVM and the associated toxicity and risk of complications.

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METHODS

Study Group.

The institutional database was reviewed and patients who received FSRT for CVM in the Alfred Health Radiation Oncology centre between January 2010 and December 2016 who had 18 months or more follow up were analyzed. Patients included for analysis had a diagnosis of CVM based on MRI findings (with T1 contrast enhanced and T2-weighted sequences). The authors collected data including age, sex, visual acuity, visual fields, and MRI imaging. Alfred Health Human Research Ethics provided approval for the study.

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Treatment Protocol.

All patients underwent coregistration of a gadolinium-enhanced MRI with the planning CT scan images for delineation of the gross tumor volume. A 1-mm planning target volume expansion was placed on the gross tumor volume. No clinical target volume expansion was used. The radiation dose was prescribed to the 85%, 90%, or 95% isodose line. All patients were planned using iPlan software and treated using a Novalis 6MV linac with ExacTrac image guidance and 6D positional correction (BrainLAB-AG, Heimstetten, Germany).

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Follow Up.

Patients were followed up after completion of FSRT at least 12 monthly by a radiation oncologist and an ophthalmologist who completed visual function testing. MRI with gadolinium contrast was completed on all patients at pretreatment and within 6 to 24 months posttreatment, followed by subsequent 12 to 24 monthly imaging. Tumor volume was calculated using the ABC/2 method based on dimension reported by the radiologist.24

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Statistical Analysis.

Summary statistics calculated for patient baseline characteristics and treatment outcomes. All statistical analysis was performed on Stata (StataCorp. 2017. Stata Statistical Software: Release 15. College Station, TX: StataCorp LLC).

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RESULTS

Six patients were treated with FSRT for a CVM involving the orbital apex during the study period (Table 1). The mean age of the group was 48 years (range, 32–63), and 3 patients were female. The tumors were all unilateral with 3 on the left and 3 on the right. The mean baseline volume of the tumor was 3.0 cm3 (range, 0.067 cm3 to 6.1 cm3).

TABLE 1

TABLE 1

All patients had treatment with FSRT (Table 1). One patient (case 1) had prior surgical debulking of the tumor, and this case was treated to 45 Gy in 1.8 Gy per fraction. The authors used the postdebulking volume for analysis. The remainder of the patients were treated definitively with FSRT with 50 Gy in 2 Gy per fraction or 50.4 Gy in 1.8 Gy per fraction. The maximum dose to the optic nerve ranged from 48.2 Gy to 52.5 Gy. The median follow up was 74 months.

All patients had a volume reduction over time postradiotherapy (Figs. 1 and 2). The mean volume reduction at the first surveillance scan post the 12-month time point was 64% (range, 14–77%). The rate of reduction after the initial 12-month period appeared to slow down and began to stabilize. One patient harbored a small 0.068 cm3 tumor, and the lesion was not detectable at 27 months. However, even the largest lesion at 6.12 cm3 regressed by 55% at 21 months. No lesions progressed. All patients with proptosis or a deficit in visual acuity, fields, pupil function, or eye movement as a result of the tumor had an improvement in their clinical signs postradiotherapy (Table 2). Two patients with pain symptoms at presentation exhibited complete resolution of pain posttreatment. There were no reported complications of the treatment.

TABLE 2

TABLE 2

FIG. 1

FIG. 1

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DISCUSSION

In this small series, CVM of the orbital apex treated with FSRT exhibited a 100% response rate to radiotherapy and ongoing local control. In addition, it was associated with a favorable clinical response in terms of vision, proptosis, and pain.

Surgical resection of tumors extending into the orbital apex is challenging and carries a high risk of operative injury to the optic nerve and its vascular supply, or to the nerve supply of the extra- and intraocular muscles, and sensory nerves. The surgical risks are highlighted in a series of 214 CVM of the orbit managed with anterior and lateral orbitotomy, where 22.9% had a motility deficit, 13.6% had ptosis, 12.1% had a deterioration in their vision, and 4.2% had total loss of vision after the operation.25 In another surgical series of 14 patients, there was deterioration of vision in 14% of patients at 6 months post procedure.13

Stereotactic radiotherapy is an important alternative to consider in this scenario. The largest series of radiation therapy for CVM of the orbit is 23 patients receiving 12 to 20 Gy in a single fraction with stereotactic radiosurgery.21 All had a decrease in tumor size, while 11 of 14 patients with visual symptoms showed subsequent improvement and the majority that were affected by proptosis also improved. Two other series containing 1 and 3 patients with CVM, respectively, receiving single fraction stereotactic radiosurgery confirm similar tumor regression.18,19 However, the risk of toxicity increases markedly beyond doses of 12 Gy in a single fraction.26–28 Optic neuropathy is a late toxicity that may occur years following treatment and may not have been captured in the larger series, which had a median follow up of only 12 months.21,29

FSRT uses the same principles and equipment as single fraction stereotactic radiosurgery with the same benefits in terms of accuracy and conformity, but reduces the risk of optic neuropathy through the radiobiological advantage of fractionated delivery, which uses smaller daily doses over an extended treatment duration.30 This allows the normal tissue to repair between fractions leading to a significantly lower risk of toxicity.22 All patients treated had radiation doses to the optic nerve below 55 Gy, which is generally accepted to be associated with a risk of optic neuropathy of less than 3%.28 The radiation dose to the lens was low with a mean 1.44 Gy (0.53–2.22 Gy) but was within the threshold dose for cataractogenesis (> 1–2 Gy).31

Our findings using FSRT were similar to the Canadian case series of 5 patients involving the orbital apex that described an average tumor shrinkage of 60%, and rapid resolution of the visual deficit at 3 months.23 The study described very similar delivery techniques with doses ranging from 40 Gy in 20 fractions to 55.1 Gy in 29 fractions. The mean follow up was 23.4 months (range, 5–50 months) in this series with no evidence of progression or complications from treatment in any of the cases. A case report of orbital CVM treated with FSRT reported a reduction in lesion size and improvement in visual function.20 Together with these studies, our series provides further evidence of FSRT as a valid treatment option for this condition.

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CONCLUSION

The authors found that FSRT is a safe and effective treatment for CVM of the orbital apex with an average 64% volume reduction at 12 months and improvement in visual function, proptosis, and pain, maintained over a median follow up of 33 months. There were no complications from the treatment in our cohort. FSRT is a safe and effective treatment modality to consider in CVM of the orbital apex.

FIG. 2

FIG. 2

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