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Year : 2015  |  Volume : 11  |  Issue : 1  |  Page : 73-77

Conformal radiotherapy for locally advanced juvenile nasopharyngeal angio-fibroma

Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication16-Apr-2015

Correspondence Address:
Supriya Mallick
Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.150349

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 > Abstract 

Purpose: To assess the efficacy of radiation in the treatment of juvenile nasopharyngeal angiofibroma (JNA).
Materials and Methods: Data were retrieved for JNA treated with radiotherapy from 1987-2012. The demographics, treatment and outcome data were recorded in predesigned proforma.
Results: Data of 32 patients were retrieved. Median age was 17 years (range: 12-33 years). All patients received radiation because of refractory, residual or unresectable locally advanced disease. All patients were planned with a three-dimensional conformal technique (3DCRT). The median radiation dose was 30 Gray (range: 30-45 Gray). Median follow-up was 129 months (range: 1-276 months). At the last follow-up, 13 patients were found to have a radiological complete response. Two patients progressed 38 and 43 months after completion of treatment and opted for alternative treatment. One patient developed squamous cell carcinoma of the nasal ale 15 years after radiation.
Conclusion: Conformal radiotherapy shows promise as an alternative treatment approach for locally advanced JNA and confers long-term disease control with minimal toxicity.

Keywords: Angiofibroma, conformal, juvenile, nasopharyngeal, radiotherapy

How to cite this article:
Mallick S, Benson R, Bhasker S, Mohanti BK. Conformal radiotherapy for locally advanced juvenile nasopharyngeal angio-fibroma. J Can Res Ther 2015;11:73-7

How to cite this URL:
Mallick S, Benson R, Bhasker S, Mohanti BK. Conformal radiotherapy for locally advanced juvenile nasopharyngeal angio-fibroma. J Can Res Ther [serial online] 2015 [cited 2022 Jul 5];11:73-7. Available from: https://www.cancerjournal.net/text.asp?2015/11/1/73/150349

 > Introduction Top

Juvenile nasopharyngeal angiofibroma (JNA) is a benign, highly vascular, locally aggressive tumor found commonly in adolescent boys representing 0.05% to 0.5% of all head and neck tumors. [1],[2] It has been hypothesized to originate from the sphenopalatine foramen and has high propensity for intracranial extension. [3] Intracranial involvement has been reported to occur in 10% to 37% of all cases, with the pituitary, anterior, and middle cranial fosse being the most common sites of intracranial invasion. [4],[5] There is little consensus about the staging of JNA. Staging is largely based on anatomic tumor extension, and the Andrews (modified Fisch), Chandler, and Radkowski systems are used most frequently. Over the years, surgical excision has remained the standard treatment. [6] Transnasal endoscopic resection has been established as the standard treatment approach in early stage JNA with limited morbidity. In advanced cases craniofacial approaches appear to be the current standard of treatment. [7] However, there is hardly any consensus about the treatment approach in advanced stage. [6] The high rate of recurrence in cases with intracranial extension necessitates aggressive therapy paving for adjuvant or salvage radiotherapy. The long-term morbidity associated with radiotherapy has remained a concern. [8] In recent years, the introduction of conformal radiotherapy has made it possible to deliver radiation with precision and minimal morbidity. [9],[10]

 > Materials and methods Top


We performed a retrospective analysis of JNA patients undergoing radiotherapy in our institute. Charts were reviewed from 1987 to 2012. Demographic and disease characteristics and treatment details in this patient cohort were recorded in a predesigned proforma.



The patients referred for radiotherapy were evaluated by a board of radiation oncologist and ENT surgeon. The presence of recurrent and residual tumor after surgery or intracranial extension of tumor was taken as criteria for radiation therapy. A customized thermoplastic cast was used for immobilization. A contrast-enhanced CT simulation was done using Philips TM large bore CT scanner with 3 mm slice thickness with intravenous contrast injection one ml per kg body weight. Whole cranium and the para-nasal sinus were scanned. The Gross tumor volume (GTV) was delineated as evident on the planning CT scan. An isotropic expansion of 5 mm was added to form the , Planning target volume (PTV). The planning was done using Eclipse treatment planning system version 6.5 (Varian Medical Systems, Palo Alto, CA) or Pinnacle treatment planning system version 9.0 for three-dimensional conformal technique (3DCRT). During the radiotherapy planning, first priority was given to achieve a conformal dose distribution to the PTV followed by maximal sparing of the optic structures. The radiation dose of 30-45 Gray (median 30 Gray) was prescribed at 1.8-2 Gray per fraction. Radiation plans were normalized at 93-95% isodose [Figure 1].
Figure 1: CECT scan showing extension of disease

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Response assessment and follow-up

The patients were followed one month after the completion of radiation and subsequently every three months with clinical examination and endoscopy. A contrast-enhanced CT of the head and face was ordered once in a year. The nature of slow regression has been reported by different authors. [8],[11] Sometimes, it takes as long as three years for complete radiological remission. Therefore, we defined no evidence of disease (NED) as clinical and radiological absence of disease. A slow regression or no evidence of radiological progression was taken as partial response. [12]

 > Results Top

Data were retrieved for 32 patients of JNA treated with radiotherapy from 1987-2012. The patients' characteristics are presented in [Table 1]. Median age was 17 years (range: 12-33 years). Epistaxis was the commonest presenting symptom found in 22 patients followed by nasal blockade (n = 12), proptosis (n = 11), loss of vision (n = 5) and ear discharge (n = 4). Detailed visual evaluation revealed no perception of light (PL) in five cases, PL only in one case, and vision limited to finger counting in seven patients. All patients were thoroughly evaluated with contrast-enhanced CT scan or MRI. Five patients were found in Radkowski stage IIIa and remaining in stage IIIb. All patients had variable extension and intracranial extension was noted in 18 cases, whereas disease was in middle cranial fossa (MCF) in 17 cases, infratemporal fossa (ITF) in 10 and cavernous sinus in 12 cases [Figure 2]. Surgery was attempted in 19 cases. Trans-maxillectomy approach and lateral rhinotomy approach was the commonest surgical approach, whereas craniotomy was done in three cases. Radical radiotherapy was delivered in 14 cases, whereas six patients received radiotherapy after surgery for residual disease and 12 patients received radiotherapy for salvage. Radiotherapy was planned by 3DCRT technique for all cases. A three-field technique with one anterior and two lateral oblique field designs was the commonest field arrangement. The median radiation dose was 30 Gray (range: 30-45 Gray) at 1.8-2 Gray per fraction. In addition, two patients received radiation for hemostasis after definitive radiation. The hemostatic dose used was 8 Gray and 10 Gray, respectively. Target volume coverage and sparing of normal organ was evaluated in all conformal plans. The dosimetric parameters are tabulated in [Table 2]. Median follow-up was 129 months (range: 1-276 months). At the last follow-up, 13 patients were found to have a radiological complete response. Two patients progressed 38 and 43 months after completion of treatment and opted for alternative treatment. It may be noted that one patient in both RT alone and surgery followed by radiotherapy progressed. The remaining patients showed features of slow regression documented in MRI/contrast-enhanced CT scan done every three months. All patients tolerated the prescribed dose without grade III or grade IV acute toxicity. Grade II mucosal reaction was noted to be the commonest acute toxicity followed by grade I skin reaction and grade II conjunctival reaction. Late toxicity was extremely uncommon and no patient had any grade of xerostomia. However, one patient developed diminished vision but detailed ophthalmological evaluation did not reveal cataract. Another patient developed squamous cell carcinoma of the nasal ale 15 years after radiation. The patient underwent a surgical salvage and was disease-free seven years after the salvage treatment.
Figure 2: Dose color washes of 3D CRT plan of JNA and dose volume histogram

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Table 1: Patient characteristics

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Table 2: Dosimetry of 3D - conformal plan

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 > Discussion Top

JNA is a highly vascular, locally aggressive tumor occurring in adolescent boys. Friedberg in 1940 first termed this tumor as angiofibroma. JNA is one of the commonest differentials for adolescent boys with persistent history of epistaxis. The symptoms largely depend on the extension of the disease. Epistaxis has been reported to be the commonest symptom followed by nasal blockade with subsequent difficulty in respiration the commonest presenting symptom. A detailed radiological examination with contrast-enhanced CT or MRI is necessary to assess the extension of the tumor and design the management plan. The classic radiographic finding is widening of the pterygopalatine fossa and anterior bowing of the posterior wall of the maxillary antrum. Though benign, JNA is known for its local aggressiveness and propensity for spread to adjacent structure. Intracranial extension is seen in 2-37% of patients and has been reported to be a challenge to manage. In a retrospective series reported by Mistry et al., about 90% patients had advanced disease in stage III/IV. [13] The diagnostic dilemma, poor referral system and lack of rural health care facility in the developing countries are attributable to the cause of such high rate of advanced disease. A gross total excision is always attempted whenever possible for a long-term disease control. But, the presence of intracranial extension makes most patients not amenable for surgical resection. [14] A staged excision is often attempted for locally advanced JNA. In advanced JNA with intracranial extension, even after surgical resection recurrence is high due to incomplete excision. Tyagi et al., in a review of 10 patients reported residual disease in 80% patients after surgical excision with 30% subsequent recurrence. [15] Fagan et al. reported 37.5% recurrence after surgical excision for JNA with intracranial extension. [16] Leong et al. systematically analyzed the outcome in 72 patients with intracranial extension. Sixty-five patients underwent different forms of craniofacial exposure and 25% patients had sub-total tumor resection. [6] Total 18% recurrence was reported after a median follow-up of 47 months. The authors also reported 46% complication, including facial paresthesia, CSF leak and ophthalmoplegia. It is important to note that there was no difference in the rate of recurrence between gross total resection (GTR) and subtotal resection (STR) group. The observation demands alternative treatment approach in particular for this subgroup of patients and a multimodality approach with STR followed by adjuvant radiation seems to be optimum. [17],[18],[19] However, the use of adjuvant radiation has remained controversial owing to its anticipated long-term morbidity and second primary neoplasm. In the last two decades, the introduction of sophisticated radiation delivery technique has allowed the investigators to use radiation and limiting the morbidity to minimum.

In a review, Reddy et al., reported the efficacy of radiation in 10 patients with intracranial extension. [10] A total of 30 Gray was delivered with customized field design with megavoltage X-rays. After a median follow-up of 2.5 years, the authors reported 85% local control. The authors reported incidence of basal cell carcinoma in one patient 14 years after radiation. The authors concluded a moderate dose of radiation to confer long-term disease control for such cases.

Lee et al., in a retrospective review analyzed treatment outcome of 27 patients treated with radiotherapy and reported 85% local control. [8] In this study, the radiation dose ranged from 30-55 Gray. However, the radiation dose was restricted to 36-40 Gray for patients treated after 1999. The authors reported 15% long-term complication, including cataract, hypopituitarism, and temporal lobe necrosis (TLN) and growth retardation in one case each. However, the patient with TLN received a cumulative dose of 75 Gray within a time span of three years. Lee et al., also reviewed the reports of radiation necrosis and radiation myelitis. However, the dose of radiation and the direct association was not clearly established. [8]

The long-term disease control reached a new horizon but the long-term morbidity remained an area of concern. The introduction of conformal radiotherapy has evolved as a promising treatment approach for locally advanced cohort of JNA. Beriwal et al., in a report of two cases showed promising results in JNA treated with Intensity modulated radiotherapy (IMRT). [9] Subsequently, two large series published by Chakraborty et al. and Kuppersmith et al. looked into the effectiveness of radiation when delivered with conformal technique. [11],[19] Chakraborty et al., in a larger series of eight patients treated by conformal radiotherapy (7-IMRT, one 3DCRT) reported progressive resolution in seven cases at a median follow-up of 17 months. [11] The authors reported 87.5% actual control at two years with excellent sparing of organ at risk. In other reported series, the long-term disease control was in excess of 70%−100%. Kuppersmith et al. in a series of three patients treated with highly conformal IMRT aimed at limiting radiation doses to the optic nerves, optic chiasm, brainstem, brain, spinal cord, lens, retina, mandible, and parotid. [19] The dose delivered ranged from 34-45 Gray. There was no endoscopic evidence of disease in two cases at 15 months and 40 months. The author highlighted excellent sparing of critical normal organ as well as excellent disease control.

But, both the series have not reported any long-term toxicity. In the last two decades, the technological advance has made the radiation practice state of the art and extremely localized delineated target with sparing of the normal organs. The late toxicity has been reported very rarely. Cummings et al., from PMH, reported two cases with basal cell carcinoma and thyroid carcinoma in two cases after 3-26 years of follow-up. [18] Reddy et al., reported incidence of basal cell carcinoma in one patient 14 years after radiation. [10] Jereb et al., reported incidence of osteo radio-necrosis in one case after a follow up of 1-16 years. [17] Similarly, Lee et al., reported temporal lobe necrosis in one patient. [8] But, it should be noted that a total of 60-75 Gray was delivered with Cobalt-60 machine in these cases. It is worth noting that there is no report of late complication in the studies using conformal technique, including IMRT. In our study, we found one patient with SCC of the nasal ale. However, this patient was treated with Co-60 and was disease-free after a successful salvage surgery. Therefore, despite the incidence of an isolated event of long-term complication, radiation can be used with success for a group of JNA patients with poor prognostic features. The advanced technologies can further reduce the morbidity and improve quality of life as well as disease control. Chemotherapy has been reported to have limited role for JNA and can be offered for patients with extensive disease not amenable for surgery or radiation therapy. [20] Estrogen and Flutamide has also been tried for select group of patients with limited benefit. [21],[22]

 > Conclusion Top

Conformal radiotherapy has evolved as an alternative treatment approach for locally advanced JNA. Moderate dose of radiation at 30-35 Gray, delivered by conformal technique can achieve durable disease control with limited morbidity.

 > References Top

Gullane PJ, Davidson J, O′Dwyer T, Forte V. Juvenile angiofibroma: A review of the literature and a case series report. Laryngoscope 1992;102:928-33.  Back to cited text no. 1
Wiatrak BJ, Koopman CF, Turrisi AT. Radiation therapy as an alternative to surgery in the management of intracranial juvenile nasopharyngeal angiofibroma. Int J Pediatr Otorhinolaryngol 1993;28:51-61.  Back to cited text no. 2
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Harwood AR, Cummings BJ, Fitzpatrick PJ. Radiotherapy for unusual tumors of the head and neck. J Otolaryngol 1984;13:391-4.  Back to cited text no. 4
Jafek BW, Krekorian EA, Kirsch WM, Wood RP. Juvenile nasopharyngeal angiofibroma: Management of intracranial extension. Head Neck Surg 1979;2:119-28.  Back to cited text no. 5
Leong SC. A systematic review of surgical outcomes for advanced juvenile nasopharyngeal angiofibroma with intracranial involvement. Laryngoscope 2013;123:1125-31.  Back to cited text no. 6
Marshall AH, Bradley PJ. Management dilemmas in the treatment and follow-up of advanced juvenile nasopharyngeal angiofibroma. ORL J Otorhinolaryngol Relat Spec 2006;68:273-8.  Back to cited text no. 7
Lee JT, Chen P, Safa A, Juillard G, Calcaterra TC. The role of radiation in the treatment of advanced juvenile angiofibroma. Laryngoscope 2002;112:1213-20.  Back to cited text no. 8
Beriwal S, Eidelman A, Micaily B. Three-dimensional conformal radiotherapy for treatment of extensive juvenile angiofibroma: Report on two cases. ORL J Otorhinolaryngol Relat Spec 2003;65:238-41.  Back to cited text no. 9
Reddy KA, Mendenhall WM, Amdur RJ, Stringer SP, Cassisi NJ. Long-term results of radiation therapy for juvenile nasopharyngeal angiofibroma. Am J Otolaryngol 2001;22:172-5.  Back to cited text no. 10
Chakraborty S, Ghoshal S, Patil VM, Oinam AS, Sharma SC. Conformal radiotherapy in the treatment of advanced juvenile nasopharyngeal angiofibroma with intracranial extension: An institutional experience. Int J Radiat Oncol Biol Phys 2011;80:1398-404.  Back to cited text no. 11
Liu L, Wang R, Huang D, Han D, Ferguson EJ, Shi H, et al. Analysis of intra-operative bleeding and recurrence of juvenile nasopharyngeal angiofibromas. Clin Otolaryngol Allied Sci 2002;27:536-40.  Back to cited text no. 12
Mistry RC, Qureshi SS, Gupta S, Gupta S. Juvenile nasopharyngeal angiofibroma: A single institution study. Indian J Cancer 2005;42:35-9.  Back to cited text no. 13
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Patil RN, Agarwal AK, Prakash B, Ghosh P. Extra-nasopharyngeal extensions of angiofibroma. J Laryngol Otol 1982;96:1053-64.  Back to cited text no. 14
Tyagi I, Syal R, Goyal A. Staging and surgical approaches in large juvenile angiofibroma-study of 95 cases. Int J Pediatr Otorhinolaryngol 2006;70:1619-27.  Back to cited text no. 15
Fagan JJ, Snyderman CH, Carrau RL, Janecka IP. Nasopharyngeal angiofibromas: Selecting a surgical approach. Head Neck 1997;19:391-9.  Back to cited text no. 16
Jereb B, Anggård A, Båryd I. Juvenile nasopharyngeal angiofibroma. A clinical study of 69 cases. Acta Radiol Ther Phys Biol 1970;9:302-10.  Back to cited text no. 17
Cummings BJ, Blend R, Keane T, Fitzpatrick P, Beale F, Clark R, et al. Primary radiation therapy for juvenile nasopharyngeal angiofibroma. Laryngoscope 1984;94:1599-605.  Back to cited text no. 18
Kuppersmith RB, Teh BS, Donovan DT, Mai WY, Chiu JK, Woo SY, et al. The use of intensity modulated radiotherapy for the treatment of extensive and recurrent juvenile angiofibroma. Int J Pediatr Otorhinolaryngol 2000;52:261-8.  Back to cited text no. 19
Goepfert H, Cangir A, Lee YY. Chemotherapy for aggressive juvenile nasopharyngeal angiofibroma. Arch Otolaryngol 1985;111:285-9.  Back to cited text no. 20
Labra A, Chavolla-Magaña R, Lopez-Ugalde A, Alanis-Calderon J, Huerta-Delgado A. Flutamide as a preoperative treatment in juvenile angiofibroma (JA) with intracranial invasion: Report of 7 cases. Otolaryngol Head Neck Surg 2004;130:466-9.  Back to cited text no. 21
Gatalica Z. Immunohistochemical analysis of steroid hormone receptors in nasopharyngeal angiofibromas. Cancer Lett 1998;127:89-93.  Back to cited text no. 22


  [Figure 1], [Figure 2]

  [Table 1], [Table 2]

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