Treatment of Periocular Basal Cell Carcinoma Using ...

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Abstract. Basal cell carcinoma (BCC) is the most common malignant periocular tumor. When there is periorbital invasion, orbital exenteration is necessary.
No: 16964-P Please mark the appropriate section for this paper ■ Experimental ■ Clinical ■ Epidemiological

ANTICANCER RESEARCH 34: xxx-xxx (2014)

Treatment of Periocular Basal Cell Carcinoma Using Advanced Stereotactic Device ANTONIO PONTORIERO, GIUSEPPE IATÌ, ALFREDO CONTI, FABIO MINUTOLI, ANTONIO BOTTARI, STEFANO PERGOLIZZI and COSTANTINO DE RENZIS

School of Medicine, Department of Biomedical Sciences and Morphological and Functional Image Section of Medical Imaging and Radiotherapy. University of Messina, Italy

Abstract. Basal cell carcinoma (BCC) is the most common malignant periocular tumor. When there is periorbital invasion, orbital exenteration is necessary. A 73-year-old man with recurrent BCC of the inner canthus of the left eye with diffusion to the extrinsic muscles of the orbit and periorbital fat was treated with CyberKnife in stereotactic body radiation therapy (SBRT) modality. The treatment resulted in rapid tumor regression, with a complete remission after six months without toxicities. To the best of our knowledge, this is the first report in English literature describing a locally advanced BCC treated with SBRT alone.

gland, conjunctiva and cornea). Brachytherapy is a therapeutic approach which permits an optimal dose distribution even to a curved surface, but it is invasive when deeper targets have to be treated. Modern external beam radiation therapy, such as those using stereotactic techniques, is able to deliver high doses to complexly shaped targets. Cyberknife is a robotic device used to treat both intracranial and extracranial targets. Here we describe a patient with a locally advanced BCC of the medial canthus and lower eyelid treated with Cyberknife system emulated brachytherapy dose distribution to the target.

Basal cell carcinoma (BCC) is the most common malignant periocular tumor, accounting for 90% of malignant eyelid lesions (1). The most frequent periocular site for BCC is the lower eyelid, followed by the medial canthus, upper eyelid, and lateral canthus (2-3). The goal of treatment is complete tumor removal in order to prevent recurrence (4). The incidence of orbital invasion is approximately 2-4%, and risk factors include multiple recurrences, large lesion size, aggressive histological subtype, medial canthus location, and advanced patient age (4). In advanced cases (about 5.5%), the radical surgical approach for periocular BCC (i.e. rectal muscle diffusion) is orbital exenteration (4-6). Radiation therapy is an organsparing treatment. Using radiation, particular attention has to be devoted to sparing organs at risk (lens, retina, lacrimal

Case Report

Correspondence to: Professor Stefano Pergolizzi, School of Medicine, Department of Biomedical Sciences and Morphological and Functional Image - Section of Medical Imaging and Radiotherapy, University of Messina, A.O.U. G. Martino, Via Consolare Valeria 98100 Messina, Italy. Tel: +39 902217173, Fax: +39 902213192, e-mail:[email protected] Key Words: Basal cell carcinoma, Cyberknife, stereotactic body radiation therapy, periocular tumor.

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A 73-year-old Caucasian male had a diagnosis of BCC of the the inner canthus of the left eye in May 2009. Initial therapy was surgical resection. Pathological analysis confirmed a nodular type BCC, focally ulcerated, with disease in one of the lateral margins. In January 2012, a local recurrence was observed and a physical examination revealed a loss of substance with destruction of the eye’s inner canthus, lacrimal apparatus and medial half of the left lower eyelid. A computed tomographic (CT) scan revealed pathological tissue along the edge of the left lower orbital, which invaded the periorbital fat; it had an intimate contact with the anterior lower boundary and the extrinsic muscles of the eye (right medial, inferior and oblique inferior). No bone infiltration was evident (Figure 1). In April 2012, the patient refused both surgical extentoration and brachytherapy, and for this reason in May 2012 was admitted to our Department for stereotactic technique using Cyberknife (Accuray, Inc.), a robotic Linear Accelerator based stereotactic device. The patient was placed supine on the treatment couch and immobilized with a custom-fitted thermoplastic mask; in such position, a multislice CT scan (Siemens SOMATOM Sensation 16) was performed. A total dose of 1.5 ml/kg of contrast medium was infused using a pump in the cubital vein. The CT protocol was carried out according to 3

ANTICANCER RESEARCH 34: xxx-xxx (2014) CyberKnife-specific requirements: acquisition 16×0.75 mm, 120 kV, 320 mAs , rotation time 1 s, pitch 1.15; and reconstruction slice 1.5 mm, reconstruction increment 1.5 mm, filter reconstruction H31 (smooth), 512×512 matrix. The axial source images were transferred to the CyberKnife workstation for treatment planning. After the contouring of the tumor and critical volumes on the CT images, an inverse planning algorithm using a non-isocentric technique determined the optimal treatment planning. We utilized three collimators with different diameter: 7.5 mm, 12.5 mm and 15 mm. The volume of the tumor was 6 cc. The dose to the target was 40 Gy delivered in a 10 sessions, prescribed to the 70% isodose line. The maximal dose (Dmax) was 5714.29 cGy. The coverage of the target was 99.5%, the number of beams was 175, the conformality index 1.55, the homogeneity index 1.43 and the new conformality index 1.55. The number of total monitor units was 54705. The Dmax to critical organs was: 655 cGy to right optic nerve, 103 cGy to the right eye, 1463 cGy to the right lens, 2987 cGy to the left optic nerve, 432 cGy to the optic chiasma and 1034 cGy to the right lacrimal gland. Figure 2 shows the isodose distribution and Figure 3 shows complete clinical remission in December 2012.

Discussion Here we report on a case which had some peculiar characteristics: an elderly patient, with recurrent BCC involving both orbital extrinsic muscles and periorbital fat. All these features lead to a poor prognosis with respect to conservative approaches. Using SBRT, we obtained clinical long-term complete remission, preserving visual function. Few reports describe SBRT in primary or recurrent head and neck cancer (7-12) , and as far as we are aware, none describes locally advanced BCC which invades deeper structures or the orbit. Using tomotherapy, Kramkimal et al. reported eight patients with BCC, and among these, one had locally advanced disease of the right eye (13); in this case, a total dose of 66 Gy was delivered and a complete clinical remission was observed after eight months; as a late adverse event, a teary eye was reported. We believe that our therapeutic approach is feasible and could be proposed for elderly patients who refuse brachytherapy, or for frail patients not suitable for a surgical approach. We underline that this is the first case report on this issue using SBRT. Considering the actual worldwide availability of stereotactic devices, it is important to report such a case so that more patients might be offered a conservative approach with both esthetic and functional preservation.

References 1 Margo CE and Waltz K: Basal cell carcinoma of the eyelid and periocular skin. Surv Ophthalmol 38(2): 169-192, 1993.

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Figure 1. Recurrent basal cell carcinoma of the inner canthus of the left eye. Panel A shows a pre-treatment CT. Panel B shows a loss of substance and destruction of the inner canthus of the left eye, lacrimal apparatus and medial half of the lower left eyelid.

2 Cook BE Jr. and Bartley GB: Treatment options and future prospects for the management of eyelid malignancies: An evidence-based update. Ophthalmology 108(11): 2088-2098, 2001. 3 Cook BE Jr. and Bartley GB: Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmsted County, Minnesota. Ophthalmology 106(4): 746-750, 1999. 4 Iuliano A, Uccello G., Diplomatico A, Tebaldi S and Bomnavolontà G: Risk factors for orbital exenteration in periocular basal cell carcinoma. Am J Ophthalmol 153(2): 238241, 2012. 5 Howard GR, Nerad JA, Carter KD and Whitaker DC: Clinical characteristics associated with orbital invasion of cutaneous basal cell and squamous cell tumors of the eyelid. Am J Ophthalmol 113(2): 123-133, 1992. 6 Nemet AY, Deckel Y, Martin PA, Kourt G, Chilov M, Sharma V and Benger R: Management of periocular basal and squamous cell carcinoma: A series of 485 cases. Am J Ophthalmol 142(2): 293-297, 2006. 7 Siddiqui F, Patel M, Khan M, McLean S, Dragovic J, Jin JY, Movsas B and Ryu S: Stereotactic body radiation therapy for primary, recurrent, and metastatic tumors in the head-and-neck region. Int J Radiat Oncol Biol Phys 15 74(4): 1047-1053, 2009. 8 Kawaguchi K, Sato K, Horie A, Iketani S, Yamada H, Nakatani Y, Sato J and Hamada Y: Stereotactic radiosurgery may contribute to overall survival for patients with recurrent head and neck carcinoma. Radiant Oncol 5: 51, 2010. 9 Kodani N, Yamazaki H, Tsubokura T, Shiomi H, Kobayashi K, Nishimura T, Aibe N, Ikeno H and Nishimura T: Stereotactic body radiation therapy for head and neck tumor: Disease control and morbidity outcomes. J Radiat Res 52: 24-31, 2011. 10 Lim CM, Clump DA, Heron DE and Ferris RL: Stereotactic body radiotherapy (SBRT) for primary and recurrent head and neck tumors. Oral Oncology 49: 401-406, 2013. 11 Thariat J, Badoual C, Faure C, de Mones E, Butori C, Santini J, Poissonnet G, Maingon P, Faivre S, Klijanienko J, Saint-Guily JL, Righini CA; Groupe Refcor (Réseau d’Expertise Français sur les Cancers ORL Rares): Basaloid squamous cell carcinomas of the head and neck. Bull Cancer 96(10): 989-1004, 2009.

Pontoriero et al: Cyberknife for Basall Cell Carcinoma

Figure 2. Non-isocentric treament planning with Multipan-CyberKnife emulating brachytherapy; dose distribution and dose−volume histogram are shown.

12 Vargo JA, Wegner RE, Heron DE, Ferris RL, Rwigema JC, Quinn A, Gigliotti P, Ohr J, Kubicek GJ and Burton S: Stereotactic body radiation therapy for locally recurrent, previously irradiated nonsquamous cell cancers of the head and neck. Head Neck 34(8): 1153-61, 2012. 13 Kramkimel N, Dendale R, Bolle S, Zefkili S, Fourquet A and Kirova YM: Management of advanced non-melanoma skin cancers using helical tomotherapy. J Eur Acad Dermatol Venereol Apr 6. [Epub ahead of print], 2013. Figure 3. Complete clinical remission six months after the CyberKnife treatment. Panel A shows a post-treatment CT. Panel B shows the good post-treatment esthetic result.

Received December 9, 2013 Revised January 4, 2014 Accepted January 7, 2014

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