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Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 5  |  Page : 1438-1441

Adjuvant Gamma Knife Radiosurgery for Advanced Juvenile Nasopharyngeal Angiofibroma

1 Department of Neurosurgery, All India Institute of Medical Sciences, Ansari Nagar, India
2 Department of Neurosurgery, Mayo Clinic Health System, Mankato, Minnesota, USA
3 Department of Otorhinolaryngology, All India Institute of Medical Sciences, Ansari Nagar, India

Date of Submission26-Sep-2017
Date of Decision01-Apr-2018
Date of Acceptance08-Nov-2019
Date of Web Publication30-Oct-2021

Correspondence Address:
Shashank S Kale
Department of Neurosurgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.329611

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How to cite this article:
Raheja A, Sharma MS, Singh M, Agrawal D, Kale SS, Sharma SC. Adjuvant Gamma Knife Radiosurgery for Advanced Juvenile Nasopharyngeal Angiofibroma. Neurol India 2021;69:1438-41

How to cite this URL:
Raheja A, Sharma MS, Singh M, Agrawal D, Kale SS, Sharma SC. Adjuvant Gamma Knife Radiosurgery for Advanced Juvenile Nasopharyngeal Angiofibroma. Neurol India [serial online] 2021 [cited 2021 Dec 7];69:1438-41. Available from:


Juvenile nasopharyngeal angiofibroma (JNA) is a rare, benign tumor found typically in adolescent males. Although histologically benign, this tumor is locally invasive and becomes symptomatic via local tissue destruction causing nasal obstruction, epistaxis, chronic sinusitis, vision loss, headache, and cranial neuropathies.[1],[2] It classically originates in the nasopharynx at the postero-superior margin of the sphenopalatine foramen.[3] Surgery may be curative for smaller lesions and is the mainstay of treatment. Locally advanced tumors (Fisch stages III, IV) have higher rates of subtotal resection and therefore recurrence. Adjuvant modalities of treatment include preoperative embolization, external beam radiotherapy (conventional and stereotactic), and more recently, gamma knife radiosurgery (GKRS).[2],[4],[5],[6],[7] The role of GKRS remains poorly defined. Only five studies (17 cases) are detailed in the literature.[4],[5],[6],[7],[8] We report 2 cases of residual/recurrent advanced stage JNA who received secondary GKRS after being operated twice [Figure 1],[Figure 2],[Figure 3],[Figure 4] and [Table 1], [Table 2]. Both patients showed good functional and radiological outcome in long-term follow-up. Traditionally, surgery is considered to be the primary modality of treatment, especially for stage I, II, and IIIa tumors.[7],[8],[9],[10],[11],[12],[13],[14],[15],[16] Despite aggressive surgical resection, recurrence rates as high as 39.5% have been described in advanced-stage disease.[17] Historically, an operative mortality of 6.6% has been described.[18] Hence, the optimal management of advanced JNA (IIIb and IV), often involving cavernous sinus, remains controversial. Surgery for lesions within the cavernous sinus is certainly not without risk. Although a non-meningiomatous aetiology has been associated with a better outcome, mortality still ranges from 2.4% to 9.5% in series performed by leading international experts in the field.[19],[20],[21],[22],[23] Morbidity remains even higher because of the anatomical proximity of the vital neurovascular structures. Unfortunately, the chances of leaving a residual tumor behind remain high (20–86%).[21],[22],[23],[24],[25],[26],[27] Thus, the need for some form of adjuvant therapy often arises.
Figure 1: Patient 1: Treatment planning–Axial, contrast-enhanced stereotactic axial MR image, reveals a 4 cc residual juvenile nasopharyngeal angiofibroma in the region of the left pterygopalatine fossa extending into the cavernous sinus. The 50% isodose line (marked in yellow) corresponded to a 20 Gy marginal dose and covered 97% of the tumor (marked in red). The brainstem was segmented in magenta

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Figure 2: Patient 1: Complete 3D treatment plan demonstrating the principles of isodose line (marked in yellow), marginal dose, and tumor coverage. Planning is done in accordance to avoid radiation dose of >10 Gy to adjacent radiosensitive structures such as brainstem (marked in magenta) and optic apparatus (marked in blue). Conformity between radiation dose pattern and tumor morphology is well maintained by adjusting the number and size of isocenters. Shielding technique is further utilized do further tailor the treatment plan

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Figure 3: Pre (a) and post (b) Gamma Knife MR images for patient 2-(a) Treatment planning. Stereotactic, axial, contrast-enhanced, MR image, acquired at the level of the VIIth–VIIIth complex, reveals a large (24 cc) residual juvenile nasopharyngeal angiofibroma in the region of the right cavernous sinus producing ipsilateral proptosis. The 14 Gy (50%) isodose line (marked in yellow) covered 99% of the tumor, which was segmented in red. The 10 Gy isodose line (green) does not intersect the brainstem, which was segmented in magenta. (b) Corresponding, 78th month follow-up, axial contrast-enhanced MR image reveals a significant reduction in tumor volume and resolution of proptosis

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Figure 4: Patient 2: Complete 3D treatment plan demonstrating the principles of isodose lines (50% marked in yellow and 10 Gy marked in green), marginal dose, and tumor coverage (marked in red). Planning is done in accordance to avoid radiation dose of >10 Gy to adjacent radiosensitive structures such as brainstem (marked in magenta) and optic apparatus (marked in green). Conformity between radiation dose pattern and tumor morphology is well maintained by adjusting the number the size of isocenters. Shielding technique is further utilized do further tailor the treatment plan

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Table 1: Treatment planning

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Table 2: Review of literature

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GKRS involves the use of multiple confocal beams of Gamma rays with a steep dose fall-off and the surrounding, critical, neurovascular structures are consequently spared. It has a proven role in the management of cavernous sinus pathology and the use of high prescription doses can overcome the supposed radio-resistance of benign tumors. One of the largest series reports a nil mortality, tumor growth control rates of 98% at 47 months,[28] actuarial 10-year tumor control rates of 91.6–93%,[29],[30],[31] complication rates from 6–12%, and a serious morbidity rate of 0.8%.[28] In the series by Hasegawa et al., GKRS as the initial treatment was associated with a significant improvement of symptoms (P = 0.006).[31] The relative safety of GKRS in benign pediatric brain tumors has not been extensively documented because of their relative rarity and, possibly, the fear of secondary malignancies.[32],[33] On the other hand, GKRS has been used far more frequently in children with intracranial arteriovenous malformations (AVMs).[34],[35],[36],[37],[38],[39] Although the risk of developing a cranial malignancy after GKRS has not been reported, two patients did develop asymptomatic meningiomas 10 and 12 years post-procedure.[39] The role of GKRS for JNA remains poorly defined though intuitively logical. Till date, only 5 studies (17 cases) have shown a beneficial role of secondary GKRS for residual lesions [Table 2]. To these, we add two more cases, with a favorable long-term outcome and no permanent complications. This represents an advance over conventional radiotherapy, which is limited by potential long-term side effects such as the emergence of new malignancies, malignant transformation, cataracts, hypopituitarism, glaucoma, optic atrophy, xerostomia, temporal lobe necrosis, osteonecrosis, osteomyelitis, and caries.[4],[5],[6],[7],[40] The convenience of the same-day treatment, rare association with secondary neoplasms,[33] low complication rates, and an overall favorable outcome with good tumor control rates makes this a suitable modality for the treatment of advanced JNA after primary surgery has been done [Table 1] and [Table 2]. However, SRS is primarily reserved as an adjunct treatment option. Traditionally size limitation for instituting GKRS therapy is 3 cm, beyond which only hypofractionated GKRS using 5 or fewer fractions have been tried. Besides, there is a risk for “marginal miss” with GKRS because of necessarily tight dose distribution leading to potentially higher recurrence rates as compared to conventional radiotherapy along the tumor margins.

To sum up the cumulative data of all 19 patients, a median prescription dose of 20 Gy (range 14–30 Gy) delivered at a median isodose of 50% (range 45–55%) resulted in tumor control rates of 100% at a mean follow-up of 77.5 months (range 8–180 months). One-third of these tumors demonstrated a volume reduction after GKRS and received a prescription dose of less than 24 Gy. Three tumors disappeared (15.8%) after GKRS.[5],[6],[8] There were no neurological complications attributable to GKRS. We were unable to determine a dose-volume-outcome relationship because of insufficient data. These excellent results seem to mirror a pattern that we observed when using GKRS for glomus jugulare and pediatric intracranial AVMs.[34],[40] JNA too is a vascular tumor. It is possible that conformal, high dose, single fraction GKRS may induce obliterative endarteritis within the abnormal blood vessels of the tumor and yet spare adjacent normal structures because of the steep dose fall-off.[5],[41] Interestingly, Hayashi et al. reported the greatest shrinkage in tumor volume in patients with cavernous sinus hemangiomas after GKRS.[28] We believe that it is important to highlight the sensitivity of even large JNAs to GKRS as is evident in this report (Patient 2, tumor volume 24 cc, marginal dose 14 Gy; [Table 1] and [Figure 3], [Figure 4]. We were able to treat such a large tumor by reducing the marginal dose to 14 Gy and limiting the maximum exposure of the visual pathways to less than 10 Gy. This decision was taken after a multidisciplinary team of experts deemed further surgery as high risk. Surprisingly, despite the lower marginal dose, the tumor volume reduced significantly within a few months of the procedure and his proptosis recovered significantly, and there was no tumor recurrence noted during long-term 78-month follow-up for this patient. This report again raises a controversial question—is there a role for a planned sub-total resection with elective GKRS for strategically located residual tumors in patients with advanced JNA?[7],[41] On the one hand, this could potentially save a young patient from undergoing multiple, potentially mutilating procedures only to have him/her eventually undergo adjuvant GKRS for a large residual tumor, as seen in this series. On the other hand, it is possible that GKRS may induce a late recurrence/malignant transformation, which could jeopardize further definitive surgery. Certainly, recommendations cannot be made on the basis of available data at this point in time till a longer follow-up of a greater number of patients is available. To conclude, GKRS is a safe and effective adjuvant modality of treatment for residual tumors in and around the cavernous sinus following surgery for advanced JNA. Long-term tumor control/regression was seen in this series despite treating large volumes with a 14 Gy (50% isodose) marginal dose.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]


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