Combined Proton and Photon Radiotherapy for Orbital Granular Cell Tumor: A Case Report and Review of the Literature

Combined Proton and Photon Radiotherapy for Orbital Granular Cell Tumor: A Case Report and Review of the Literature | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Combined Proton and Photon Radiotherapy for Orbital Granular Cell Tumor: A Case Report and Review of the Literature Colin Burns, Lisa Stephenson, Sydney Seracino, Fred Wu, Grace Lee, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8903206/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Granular cell tumors (GCTs) are rare Schwann cell–derived neoplasms, with malignant variants comprising approximately 1–2% of cases. Orbital involvement is exceedingly uncommon, and optimal management remains undefined due to limited published experience. While maximal safe surgical resection is the primary treatment, complete excision may be precluded by proximity to critical structures such as the optic nerve and extraocular muscles. The role of adjuvant radiotherapy in malignant orbital GCT is not well established. Case Presentation: A 47-year-old man presented with progressive left orbital swelling, redness, and intermittent diplopia. Magnetic resonance imaging demonstrated a 3.1 × 2.4 × 2.0 cm heterogeneously enhancing left orbital mass. Orbitotomy with biopsy confirmed malignant GCT. Despite initial stability on imaging, interval progression with extraocular muscle invasion prompted subtotal surgical debulking with preservation of the optic nerve and globe. Given residual disease in close proximity to critical visual structures, the patient underwent a second combined endonasal and transorbital resection followed by adjuvant radiotherapy. He received proton beam therapy to 45 Gy in 25 fractions, followed by a sequential CyberKnife boost of 9 Gy in 5 fractions. Treatment was well tolerated. Serial imaging demonstrated sustained tumor regression, decreasing to 1.8 × 1.2 × 2.2 cm at seven months post-radiotherapy. At 22 months following initial orbitotomy and nearly one year after completion of radiotherapy, the lesion remained radiographically stable with continued response. Visual function was preserved, and no significant long-term radiation-related toxicity was observed. Conclusions Malignant orbital GCT is rare and poses significant surgical challenges when complete excision risks vision loss. This case demonstrates durable local control with subtotal resection followed by adjuvant proton therapy and stereotactic radiosurgical boost, with preservation of visual function. Multimodal therapy incorporating advanced radiation techniques may represent a viable strategy in select patients with anatomically constrained malignant orbital GCT. Further investigation is needed to better define the role and optimal dosing of radiotherapy in this setting. Figures Figure 1 Figure 2 Introduction Granular cell tumors (GCTs) are rare, Schwann cell-derived oft tissue tumors with malignant forms comprising 1–2% of cases 1 . The incidence of GCTs in surgical specimens over a 32-year period at a single institution was found to be 0.03%. 2 The prevalence of GCTs in males versus females varies. Most reports have shown GCTs to occur most frequently in women, specifically middle-aged African-American women, although an epidemiological study of 263 patients found a majority (68%) of GCTs arising in men. 3,4 GCTs often present as a solitary (90%) painless mass with varying size, firmness, and color (greyish-white to pale yellow) depending on the primary tumor location. 2 Several origins of GCTs have been proposed, but presently, GCTs are believed to be derived from Schwann cells. 5 Histopathologically, GCTs are characterized by sheets or cords of large, polygonal cells with small, round, central nuclei and an eosinophilic, coarse, granular cytoplasm. GCT can be identified from other granular lesions due to its proximity to nerves and identification of S-100, CD68, and membranous vimentin. 6–8 While GCTs can appear anywhere in the body, they have been reported most commonly in the skin, oral cavity, gastrointestinal tract, and subcutaneous tissue. GCTs have also been associated with multiple ophthalmologic presentations, including the orbit. 9 The incidence of orbital GCTs is very low, and our knowledge is limited to case reports and small retrospective studies. According to these reports, orbital GCTs commonly present with exophthalmos, diplopia, and/or decreased visual acuity depending on optic nerve involvement. 10 Primary surgical excision remains the main treatment option for orbital GCTs, but local control rates have been mixed among the reported cases. 11–31 Additionally, the tumor's proximity to extraocular muscles and/or optic nerve greatly increases the associated risks and morbidity of the surgery, such as the possibility of vision loss and permanent muscle dysfunction. In such cases, there are reports outlining the potential role for radiation. 31 In the setting of non-orbital malignant GCT, recommended treatment following surgical resection includes adjuvant radiotherapy and/or chemotherapy. However, presently, no specific chemotherapy or radiotherapy regimen has been established for malignant orbital GCT. 13 Chemotherapy, for the most part is ineffective at treating GCT, except for a case that achieved clinical benefits from pazopanib monotherapy in the treatment of malignant orbital GCT. 30 Furthermore, adjuvant radiotherapy has been documented in five cases of orbital GCTs, but results were mixed. 21,28–31 In the present study, we report on a case of malignant GCT of the left orbit treated with subtotal surgical resection and adjuvant radiotherapy (protons + Cyberknife boost), resulting in excellent response with continued interval decrease of the left orbital mass. Case Presentation A 47-year-old male initially presented in July 2021 with complaints of left eye redness and swelling, initially managed with topical eye drops. His symptoms persisted, and over the next several months, he developed progressive ocular redness, swelling of the left orbit, and intermittent diplopia. He was referred to ophthalmology for further evaluation. Orbital MRI revealed a heterogeneously enhancing left orbital mass measuring 3.1 × 2.4 × 2.0 cm. A left orbitotomy with biopsy was subsequently performed, and pathology confirmed a malignant GCT Approximately five months later, follow-up CT imaging of the orbits and sella demonstrated that the intraorbital mass remained stable in size (3.1 x 2.4 x. 2.1 cm). A concurrent CT head showed no evidence of intracranial abnormality. Two months later and seven months following the left orbitotomy, a repeat orbital MRI revealed a 3.0 × 2.6 × 2.3 cm enhancing mass with mass effect and invasion of the extraocular musculature. Given the progression, the patient underwent surgical debulking of the left orbital mass with preservation of the optic nerve and extraocular muscles. Histopathology again confirmed malignant GCT. Two months following the initial debulking, a multidisciplinary team, including neurosurgery and radiation oncology, reviewed the case. Due to the tumor’s location near the globe and optic nerves, the team recommended further debulking with orbit preservation, followed by adjuvant radiotherapy. Preoperative CT of the paranasal sinuses showed a stable, uniform soft tissue mass in the left anteromedial orbit, measuring 2.0 × 2.8 × 2.4 cm. Approximately one month later, the patient underwent a combined endonasal and transorbital resection at a tertiary academic medical center. The day following surgery, the patient was evaluated by ophthalmology for acute onset left eye pain. Examination was consistent with expected postoperative swelling and a new inferior corneal epithelial defect measuring 1 mm × 3 mm. Visual acuity in the left eye was 20/200, with mild restriction of extraocular movements in all directions. Roughly three and a half months after the second surgery, the patient-initiated adjuvant radiotherapy, receiving a total dose of 45 Gy in 25 fractions to the left orbit with proton therapy (Fig. 1 ), followed by a sequential CyberKnife boost of 9 Gy in 5 fractions (Fig. 2 ). Serial post-treatment imaging demonstrated a continued and sustained decrease in tumor size. At three months post-radiotherapy, MRI revealed interval regression to 2.4 × 1.9 cm x 2.3 cm. Further reductions were observed on subsequent follow-up scans at three- and seven-months post-treatment, with dimensions decreasing to 2.0 × 1.3 cm x 2.2 cm and later to 1.8 × 1.2 × 2.2 cm, respectively. Nearly one year after the final resection and 22 months following the initial orbitotomy, the lesion remained stable with a maximum dimension of 2.1 cm, reflecting a sustained treatment response. Discussion Primary management for orbital GCT is maximal safe surgical resection. However, definitive complete surgical resection is not an option for patients who decline surgery and those with a tumor in close proximity to extraocular muscles as well as the optic nerve, requiring an orbital exenteration. 31 In such cases, adjuvant radiotherapy has been utilized with mixed results. We provide a review of 28 reported cases of orbital GCT (Tables 1 and 2 ). 23 cases underwent surgical resection without the use of adjuvant radiotherapy in the setting of malignant or benign orbital GCT (Table 1 ), and 5 cases underwent surgery with adjuvant radiotherapy (Table 2 ). Table 1 Case Reports of Orbital GCT treated with surgery alone Reference Year Age Sex Side Location Compression of Optic Nerve (y/n) Surgery Follow-up period Last known status of pt/tumor McNab & Daniel 1991 18 F OS Superior Yes Subtotal 24 mo. Symptoms Persisted McNab & Daniel 1991 27 F OD SR NR NR 24 mo. No Clinical Progression McNab & Daniel 1991 54 M OS IO NR Complete 4 mo. Symptoms Persisted Simsir et al. 1996 30 M OS Infero-temporal NR Subtotal 12 mo. Recurrence Golio et al. 2006 49 F OD Superior, SR NR Complete 6 mo. Improved Sterker et al. 2007 26 M OS Superior Yes Subtotal 6 mo. Improved Guerriero et al. 2011 65 F OD Lateral NR Subtotal NR NR Fernandes et al. 2012 53 F OS Infero- temporal No Complete NR NR Ribeiro et al. 2012 74 M OS IO No Complete 4 mo. Symptoms Persisted Emesz et al. 2014 42 M OD Infero- temporal NR Complete 12 mo. Improved De la Vega et al. 2015 37 M OS SR Yes Complete No NR Germano et al. 2015 49 M OD Infero- temporal NR Complete 72 mo. Improved Li et al. 2016 53 M OS MR Yes Subtotal 91 mo. Recurrence, NLP Li et al. 2016 56 F OS IR, IO No Complete Lost NR Li et al. 2016 29 F OS SR No Subtotal 73 mo. Improved Li et al. 2016 35 F OS NR Yes Subtotal 47 mo. NR Li et al. 2016 54 F OD IR No Subtotal 9 mo. NR Yuan et al. 2016 37 F OD IR, LR, MR Yes Subtotal 9 mo. Symptoms persisted Yang et al. 2017 39 F OS MR Yes Complete 7 mo. Symptoms Persisted, NLP Yang et al. 2017 54 M OS MR Yes Complete 12 mo. NR Che et al. 2018 45 M OD IR No Complete NR Symptoms persisted Yokoyama et al. 2022 80 F OD MR No Subtotal 30 mo No Clinical Progression Wang et al. 2024 36 F OS SR Yes Subtotal NR NR IO = inferior oblique muscle, LR = lateral rectus muscle, MR = medial rectus muscle, NLP = no light perception, NR = not reported, ON = Optic Nerve, SR = superior rectus muscle, PBRT = proton beam radiotherapy, N/A = not applicable Table 2 Case reports of Orbital GCT treated with surgery and adjuvant radiotherapy Reference Year Age Sex Side Location Compression of Optic Nerve (y/n) Surgery Radiation Radiation Dose and Fractionation Proton/ photon Follow-up period Last known status of pt/tumor Callejo et al. 2000 72 M OS Superior, LR Yes Subtotal Yes 30 Gy / NR NR < 12 mo. Deceased Salour et al. 2013 50 F OD IR Yes Subtotal Yes 40 Gy / 20 Fractions NR 6 mo. NLP, Recurred Morita et al. 2015 38 F OD NR NR Complete Yes 50 Gy / 25 Fractions Proton 16 mo. Recurred Li et al. 2016 31 F OD IR Yes Complete Yes NR Photon (𝜸-knife) 55 mo. Recurred Barrantes et al. 2022 32 M OS Superior Yes Subtotal Yes 54 Gy / 6 Fractions Proton (PBRT) 20 mo. Improved IO = inferior oblique muscle, LR = lateral rectus muscle, MR = medial rectus muscle, NLP = no light perception, NR = not reported, ON = Optic Nerve, SR = superior rectus muscle, PBRT = proton beam radiotherapy, N/A = not applicable Our experience adds to the current literature relating to radiotherapy in orbital GCT. In Table 2 , we summarize cases of orbital GCT treated with adjuvant radiotherapy. Interpretation of these studies is limited by the varying clinical situations and heterogeneous radiotherapies used. In a retrospective study by Callejo et al., adjuvant radiotherapy (30 Gy) was used following a subtotal left lateral orbitotomy for a GCT in the left orbit between the optic nerve and the lateral orbital wall. The mass was not distinctly separate from the lateral rectus muscle and demonstrated apparent encasement of the optic nerve at the orbital apex. One month following surgery, a bone scan revealed metastatic recurrence, and the patient died as a result of metastatic disease less than one year following surgery and radiotherapy. 28 Salour et al. used radiotherapy (40 Gy/20 Fractions) following subtotal resection of the patient’s GCT located in the right orbit involving the right inferior rectus. Complete excision of the mass was not possible due to the tumor's infiltration within the rectus muscle. Within six months of surgery and radiotherapy, the patient’s best corrected visual acuity in the right eye decreased, and the tumor growth was unable to be controlled, ultimately resulting in further visual deterioration to no light perception. 29 Morita et al. used multiple courses of radiotherapy in a patient presenting following local recurrence of malignant GCT in the right orbit, which was initially surgically resected two years prior, followed by two other resections for local recurrence. Additionally, the patient exhibited multiple metastases to the pulmonary and cervical lymph nodes. Radiotherapy (50 Gy/25 fractions) to the orbital tumor was initiated before adding on a phosphatidylinositol 3-kinase inhibitor in the setting of a clinical trial, and the tumor remained stable for 9 months. Following subsequent tumor growth, the patient was started on pazopanib monotherapy (800 mg QD) and additional radiotherapy to the recurrent tumor (34 Gy/17 fractions) and the cervical lymph nodes (40 Gy/20 fractions) were given. The patient’s lung metastases remained stable for the next 7 months. 30 Li et al. used 𝜸-knife following exenteration and tumor excision for a right orbital GCT associated with the inferior rectus muscle. Local recurrence occurred at 18 months postoperatively with cavernous sinus and maxillary sinus metastases occurring at 32 and 37 months following surgery, respectively. 21 Barrantes et al. used radiotherapy (54 Gy/6 fractions) in a patient presenting with recurrence after two prior subtotal surgeries of a histologically diagnosed benign GCT located in the deep, apical portion of the left orbit that abutted the optic nerve. Six months following radiotherapy, the patient had resolution of his left retrobulbar pain and a noticeable radiographic decrease in tumor size. The patient also experienced 3 months of non-proliferative radiation retinopathy that resolved without treatment. 31 The scarcity and heterogeneity of cases using radiotherapy in orbital GCT make the exact role of radiotherapy in treating orbital GCT difficult to interpret. To our knowledge, this is one of the only reported cases of malignant orbital GCT demonstrating continued radiographic improvement 22 months after subtotal resection and adjuvant radiotherapy using both proton therapy and CyberKnife boost. While complete surgical excision is generally the preferred treatment, this case highlights the feasibility of a conservative surgical approach supplemented with targeted radiation to achieve long-term tumor control, particularly when anatomical constraints or risk to vision preclude complete resection. Proton therapy was selected to minimize radiation exposure to surrounding critical structures, and CyberKnife was employed to deliver a conformal boost to the residual tumor. The dosing schedule for both the proton beam (45 Gy in 25 fractions) and Cyberknife (9 Gy in 5 fractions) was determined based upon recommendations for benign disease whereby sparing of surrounding tissue such as the lens, optic nerve, and macula is critical over a longer timeframe. 32,33 The patient experienced excellent local control, with serial imaging showing continued tumor regression up to 22 months post-treatment. While the patient did experience transient postoperative complications such as corneal epithelial defect and mild extraocular motility limitations, these resolved with standard supportive care, and vision remained stable. Some potential downsides regarding the utilization of both proton beam and cyberknife are that sequential boosting is less conformation compared to a simultaneous integrated boost plan. Additionally, access to both protons and stereotactic radiosurgery machines such as the Cyberknife is not commonplace at many radiation oncology centers. Our experience suggests that adjuvant radiotherapy, including advanced techniques like proton therapy and stereotactic radiosurgery, can be an effective and well-tolerated option for managing malignant orbital GCTs when maximal resection is not feasible. Further studies are needed to define optimal radiation regimens, but this case supports consideration of multimodal treatment in select patients with orbital GCT. Abbreviations GCT Granular Cell Tumor IO Inferior oblique muscle LR Lateral rectus muscle MR Medial rectus muscle NLP No light perception NR Not reported ON Optic Nerve SR Superior rectus muscle PBRT Proton beam radiotherapy N/A Not applicable Declarations Ethics approval and consent to participate Not applicable. Consent for publication Written informed consent for publication of this case report and any accompanying images was obtained from the patient. The consent form is held by the authors and is available for review by the Editor of BMC Ophthalmology upon reasonable request. A copy of the consent form has not been submitted with this manuscript in accordance with the journal’s editorial policies but can be provided at any stage, including after publication, if required. Availability of data and materials All data generated or analyzed during this study are included in this published article. Competing interests The authors declare that they have no competing interests. Funding The authors received no specific funding for this work. Authors’ contributions Colin Burns collected the clinical data, performed the literature review, and drafted the manuscript. Daniel Kim MD, MBA contributed to patient management and critically revised the manuscript. Dr. Kim additionally supervised the project and revised the manuscript for important intellectual content. All authors read and approved the final manuscript. Acknowledgements Not applicable. References Aoyama K, Kamio T, Hirano A, Seshimo A, Kameoka S. Granular cell tumors: a report of six cases. World J Surg Oncol . 2012;10(1):204. doi:10.1186/1477-7819-10-204 Lack EE, Worsham RGF, Callihan MD, et al. Granular cell tumor: A clinicopathologic study of 110 patients. J Surg Oncol . 1980;13(4):301-316. doi:10.1002/jso.2930130405 Nasser H, Ahmed Y, Szpunar SM, Kowalski PJ. Malignant granular cell tumor: A look into the diagnostic criteria. 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Radiother Oncol J Eur Soc Ther Radiol Oncol . 2019;131:112-119. doi:10.1016/j.radonc.2018.12.007 Indelicato DJ, Rotondo RL, Mailhot Vega RB, et al. 45 GyRBE for group III orbital embryonal rhabdomyosarcoma. Acta Oncol . 2019;58(10):1404-1409. doi:10.1080/0284186X.2019.1627412 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 25 Feb, 2026 Editor assigned by journal 25 Feb, 2026 Editor invited by journal 25 Feb, 2026 Submission checks completed at journal 24 Feb, 2026 First submitted to journal 24 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8903206","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":598214244,"identity":"957aa24e-3459-40ca-bb57-f50aee6aade9","order_by":0,"name":"Colin Burns","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIiWNgGAWjYFAC5oYDjA1gxgEQCWHjB4wwLWwJDAeI1QJVxmNAnBb+9sbGw4U7Dueb85/5Jv2BwUZ2wwECWiTOHGw4PPPMYcudM3K3SRxgSDMmqMVAIrHhMG/bYQODG7ybDQ4wHE4kQcv5M4+BWv6TouVADuODAwwHCGsB+4X3TDrQYWmGD84YJBvPJKSFv7358GfeHdZAhx1+cKCiwk62j5AWdHeSpnwUjIJRMApGAQ4AAPLXTKsRBHhXAAAAAElFTkSuQmCC","orcid":"","institution":"Virginia Tech","correspondingAuthor":true,"prefix":"","firstName":"Colin","middleName":"","lastName":"Burns","suffix":""},{"id":598214245,"identity":"db6d1182-2782-4718-8f52-028cb9bc53fd","order_by":1,"name":"Lisa Stephenson","email":"","orcid":"","institution":"Inova Health System","correspondingAuthor":false,"prefix":"","firstName":"Lisa","middleName":"","lastName":"Stephenson","suffix":""},{"id":598214247,"identity":"9b29aac1-6a35-43e8-b890-4e5ac5b5bb9b","order_by":2,"name":"Sydney Seracino","email":"","orcid":"","institution":"Inova Health System","correspondingAuthor":false,"prefix":"","firstName":"Sydney","middleName":"","lastName":"Seracino","suffix":""},{"id":598214248,"identity":"08186494-90a2-4884-a051-9eb18313d0ff","order_by":3,"name":"Fred Wu","email":"","orcid":"","institution":"Inova Health System","correspondingAuthor":false,"prefix":"","firstName":"Fred","middleName":"","lastName":"Wu","suffix":""},{"id":598214249,"identity":"423bd79d-962a-4224-9d2c-f938c219a78d","order_by":4,"name":"Grace Lee","email":"","orcid":"","institution":"Inova Health System","correspondingAuthor":false,"prefix":"","firstName":"Grace","middleName":"","lastName":"Lee","suffix":""},{"id":598214250,"identity":"7c41bf93-1038-4176-99a1-0f3eb0b86753","order_by":5,"name":"Daniel Kim","email":"","orcid":"","institution":"Inova Health System","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2026-02-17 17:10:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8903206/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8903206/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104167748,"identity":"b6d509d9-a54d-4aa8-a7e8-e0e760692803","added_by":"auto","created_at":"2026-03-08 14:25:18","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":81908,"visible":true,"origin":"","legend":"\u003cp\u003eProton treatment plan for orbital GCT\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8903206/v1/ea3654296d3577f4bed69410.jpg"},{"id":104167752,"identity":"39f95cda-1d5a-49e0-920a-281b03609bd5","added_by":"auto","created_at":"2026-03-08 14:25:19","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":109734,"visible":true,"origin":"","legend":"\u003cp\u003eCyberknife treatment plan for orbital GCT\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8903206/v1/f022c10fcbc7a5a7ee079d80.jpg"},{"id":104167767,"identity":"a2e55da7-6f75-41f9-9a67-8d82321fb9a5","added_by":"auto","created_at":"2026-03-08 14:25:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":911164,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8903206/v1/ce6564b1-dcbe-4cbf-9ab9-2c9e11214714.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Combined Proton and Photon Radiotherapy for Orbital Granular Cell Tumor: A Case Report and Review of the Literature","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGranular cell tumors (GCTs) are rare, Schwann cell-derived oft tissue tumors with malignant forms comprising 1\u0026ndash;2% of cases\u003csup\u003e1\u003c/sup\u003e. The incidence of GCTs in surgical specimens over a 32-year period at a single institution was found to be 0.03%.\u003csup\u003e2\u003c/sup\u003e The prevalence of GCTs in males versus females varies. Most reports have shown GCTs to occur most frequently in women, specifically middle-aged African-American women, although an epidemiological study of 263 patients found a majority (68%) of GCTs arising in men.\u003csup\u003e3,4\u003c/sup\u003e GCTs often present as a solitary (90%) painless mass with varying size, firmness, and color (greyish-white to pale yellow) depending on the primary tumor location.\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSeveral origins of GCTs have been proposed, but presently, GCTs are believed to be derived from Schwann cells.\u003csup\u003e5\u003c/sup\u003e Histopathologically, GCTs are characterized by sheets or cords of large, polygonal cells with small, round, central nuclei and an eosinophilic, coarse, granular cytoplasm. GCT can be identified from other granular lesions due to its proximity to nerves and identification of S-100, CD68, and membranous vimentin.\u003csup\u003e6\u0026ndash;8\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWhile GCTs can appear anywhere in the body, they have been reported most commonly in the skin, oral cavity, gastrointestinal tract, and subcutaneous tissue. GCTs have also been associated with multiple ophthalmologic presentations, including the orbit.\u003csup\u003e9\u003c/sup\u003e The incidence of orbital GCTs is very low, and our knowledge is limited to case reports and small retrospective studies. According to these reports, orbital GCTs commonly present with exophthalmos, diplopia, and/or decreased visual acuity depending on optic nerve involvement.\u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePrimary surgical excision remains the main treatment option for orbital GCTs, but local control rates have been mixed among the reported cases.\u003csup\u003e11\u0026ndash;31\u003c/sup\u003e Additionally, the tumor's proximity to extraocular muscles and/or optic nerve greatly increases the associated risks and morbidity of the surgery, such as the possibility of vision loss and permanent muscle dysfunction. In such cases, there are reports outlining the potential role for radiation.\u003csup\u003e31\u003c/sup\u003e In the setting of non-orbital malignant GCT, recommended treatment following surgical resection includes adjuvant radiotherapy and/or chemotherapy. However, presently, no specific chemotherapy or radiotherapy regimen has been established for malignant orbital GCT.\u003csup\u003e13\u003c/sup\u003e Chemotherapy, for the most part is ineffective at treating GCT, except for a case that achieved clinical benefits from pazopanib monotherapy in the treatment of malignant orbital GCT.\u003csup\u003e30\u003c/sup\u003e Furthermore, adjuvant radiotherapy has been documented in five cases of orbital GCTs, but results were mixed.\u003csup\u003e21,28\u0026ndash;31\u003c/sup\u003e In the present study, we report on a case of malignant GCT of the left orbit treated with subtotal surgical resection and adjuvant radiotherapy (protons\u0026thinsp;+\u0026thinsp;Cyberknife boost), resulting in excellent response with continued interval decrease of the left orbital mass.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 47-year-old male initially presented in July 2021 with complaints of left eye redness and swelling, initially managed with topical eye drops. His symptoms persisted, and over the next several months, he developed progressive ocular redness, swelling of the left orbit, and intermittent diplopia. He was referred to ophthalmology for further evaluation. Orbital MRI revealed a heterogeneously enhancing left orbital mass measuring 3.1 \u0026times; 2.4 \u0026times; 2.0 cm. A left orbitotomy with biopsy was subsequently performed, and pathology confirmed a malignant GCT\u003c/p\u003e \u003cp\u003eApproximately five months later, follow-up CT imaging of the orbits and sella demonstrated that the intraorbital mass remained stable in size (3.1 x 2.4 x. 2.1 cm). A concurrent CT head showed no evidence of intracranial abnormality. Two months later and seven months following the left orbitotomy, a repeat orbital MRI revealed a 3.0 \u0026times; 2.6 \u0026times; 2.3 cm enhancing mass with mass effect and invasion of the extraocular musculature. Given the progression, the patient underwent surgical debulking of the left orbital mass with preservation of the optic nerve and extraocular muscles. Histopathology again confirmed malignant GCT.\u003c/p\u003e \u003cp\u003eTwo months following the initial debulking, a multidisciplinary team, including neurosurgery and radiation oncology, reviewed the case. Due to the tumor\u0026rsquo;s location near the globe and optic nerves, the team recommended further debulking with orbit preservation, followed by adjuvant radiotherapy. Preoperative CT of the paranasal sinuses showed a stable, uniform soft tissue mass in the left anteromedial orbit, measuring 2.0 \u0026times; 2.8 \u0026times; 2.4 cm. Approximately one month later, the patient underwent a combined endonasal and transorbital resection at a tertiary academic medical center.\u003c/p\u003e \u003cp\u003eThe day following surgery, the patient was evaluated by ophthalmology for acute onset left eye pain. Examination was consistent with expected postoperative swelling and a new inferior corneal epithelial defect measuring 1 mm \u0026times; 3 mm. Visual acuity in the left eye was 20/200, with mild restriction of extraocular movements in all directions.\u003c/p\u003e \u003cp\u003eRoughly three and a half months after the second surgery, the patient-initiated adjuvant radiotherapy, receiving a total dose of 45 Gy in 25 fractions to the left orbit with proton therapy (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), followed by a sequential CyberKnife boost of 9 Gy in 5 fractions (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSerial post-treatment imaging demonstrated a continued and sustained decrease in tumor size. At three months post-radiotherapy, MRI revealed interval regression to 2.4 \u0026times; 1.9 cm x 2.3 cm. Further reductions were observed on subsequent follow-up scans at three- and seven-months post-treatment, with dimensions decreasing to 2.0 \u0026times; 1.3 cm x 2.2 cm and later to 1.8 \u0026times; 1.2 \u0026times; 2.2 cm, respectively. Nearly one year after the final resection and 22 months following the initial orbitotomy, the lesion remained stable with a maximum dimension of 2.1 cm, reflecting a sustained treatment response.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrimary management for orbital GCT is maximal safe surgical resection. However, definitive complete surgical resection is not an option for patients who decline surgery and those with a tumor in close proximity to extraocular muscles as well as the optic nerve, requiring an orbital exenteration.\u003csup\u003e31\u003c/sup\u003e In such cases, adjuvant radiotherapy has been utilized with mixed results.\u003c/p\u003e \u003cp\u003eWe provide a review of 28 reported cases of orbital GCT (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). 23 cases underwent surgical resection without the use of adjuvant radiotherapy in the setting of malignant or benign orbital GCT (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and 5 cases underwent surgery with adjuvant radiotherapy (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCase Reports of Orbital GCT treated with surgery alone\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eYear\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSide\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLocation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCompression of Optic Nerve (y/n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFollow-up period\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLast known status of pt/tumor\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e\u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMcNab \u0026amp; Daniel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1991\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSuperior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e24 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSymptoms Persisted\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMcNab \u0026amp; Daniel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1991\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e24 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo Clinical Progression\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMcNab \u0026amp; Daniel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1991\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSymptoms Persisted\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimsir et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInfero-temporal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e12 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eRecurrence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGolio et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSuperior, SR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSterker et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSuperior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGuerriero et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFernandes et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInfero- temporal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRibeiro et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSymptoms Persisted\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmesz et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInfero- temporal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e12 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDe la Vega et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGermano et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInfero- temporal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e72 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLi et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e91 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eRecurrence, NLP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLi et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIR, IO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLi et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e73 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLi et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e47 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLi et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYuan et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIR, LR, MR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSymptoms persisted\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYang et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSymptoms Persisted, NLP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYang et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e12 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChe et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSymptoms persisted\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYokoyama et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e30 mo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo Clinical Progression\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWang et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIO\u0026thinsp;=\u0026thinsp;inferior oblique muscle, LR\u0026thinsp;=\u0026thinsp;lateral rectus muscle, MR\u0026thinsp;=\u0026thinsp;medial rectus muscle, NLP\u0026thinsp;=\u0026thinsp;no light perception, NR\u0026thinsp;=\u0026thinsp;not reported, ON\u0026thinsp;=\u0026thinsp;Optic Nerve, SR\u0026thinsp;=\u0026thinsp;superior rectus muscle, PBRT\u0026thinsp;=\u0026thinsp;proton beam radiotherapy, N/A\u0026thinsp;=\u0026thinsp;not applicable\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCase reports of Orbital GCT treated with surgery and adjuvant radiotherapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eYear\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSide\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLocation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCompression of Optic Nerve (y/n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRadiation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRadiation Dose and Fractionation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eProton/ photon\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFollow-up period\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLast known status of pt/tumor\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e\u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCallejo et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSuperior, LR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e30 Gy / NR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;12 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eDeceased\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSalour et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e40 Gy / 20 Fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e6 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNLP, Recurred\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMorita et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e50 Gy / 25 Fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eProton\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e16 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eRecurred\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLi et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003ePhoton (\u0026#120632;-knife)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e55 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eRecurred\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBarrantes et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSuperior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSubtotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e54 Gy / 6 Fractions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eProton (PBRT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e20 mo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"13\"\u003eIO\u0026thinsp;=\u0026thinsp;inferior oblique muscle, LR\u0026thinsp;=\u0026thinsp;lateral rectus muscle, MR\u0026thinsp;=\u0026thinsp;medial rectus muscle, NLP\u0026thinsp;=\u0026thinsp;no light perception, NR\u0026thinsp;=\u0026thinsp;not reported, ON\u0026thinsp;=\u0026thinsp;Optic Nerve, SR\u0026thinsp;=\u0026thinsp;superior rectus muscle, PBRT\u0026thinsp;=\u0026thinsp;proton beam radiotherapy, N/A\u0026thinsp;=\u0026thinsp;not applicable\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOur experience adds to the current literature relating to radiotherapy in orbital GCT. In Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, we summarize cases of orbital GCT treated with adjuvant radiotherapy. Interpretation of these studies is limited by the varying clinical situations and heterogeneous radiotherapies used. In a retrospective study by Callejo et al., adjuvant radiotherapy (30 Gy) was used following a subtotal left lateral orbitotomy for a GCT in the left orbit between the optic nerve and the lateral orbital wall. The mass was not distinctly separate from the lateral rectus muscle and demonstrated apparent encasement of the optic nerve at the orbital apex. One month following surgery, a bone scan revealed metastatic recurrence, and the patient died as a result of metastatic disease less than one year following surgery and radiotherapy.\u003csup\u003e28\u003c/sup\u003e Salour et al. used radiotherapy (40 Gy/20 Fractions) following subtotal resection of the patient\u0026rsquo;s GCT located in the right orbit involving the right inferior rectus. Complete excision of the mass was not possible due to the tumor's infiltration within the rectus muscle. Within six months of surgery and radiotherapy, the patient\u0026rsquo;s best corrected visual acuity in the right eye decreased, and the tumor growth was unable to be controlled, ultimately resulting in further visual deterioration to no light perception.\u003csup\u003e29\u003c/sup\u003e Morita et al. used multiple courses of radiotherapy in a patient presenting following local recurrence of malignant GCT in the right orbit, which was initially surgically resected two years prior, followed by two other resections for local recurrence. Additionally, the patient exhibited multiple metastases to the pulmonary and cervical lymph nodes. Radiotherapy (50 Gy/25 fractions) to the orbital tumor was initiated before adding on a phosphatidylinositol 3-kinase inhibitor in the setting of a clinical trial, and the tumor remained stable for 9 months. Following subsequent tumor growth, the patient was started on pazopanib monotherapy (800 mg QD) and additional radiotherapy to the recurrent tumor (34 Gy/17 fractions) and the cervical lymph nodes (40 Gy/20 fractions) were given. The patient\u0026rsquo;s lung metastases remained stable for the next 7 months.\u003csup\u003e30\u003c/sup\u003e Li et al. used \u0026#120632;-knife following exenteration and tumor excision for a right orbital GCT associated with the inferior rectus muscle. Local recurrence occurred at 18 months postoperatively with cavernous sinus and maxillary sinus metastases occurring at 32 and 37 months following surgery, respectively.\u003csup\u003e21\u003c/sup\u003e Barrantes et al. used radiotherapy (54 Gy/6 fractions) in a patient presenting with recurrence after two prior subtotal surgeries of a histologically diagnosed benign GCT located in the deep, apical portion of the left orbit that abutted the optic nerve. Six months following radiotherapy, the patient had resolution of his left retrobulbar pain and a noticeable radiographic decrease in tumor size. The patient also experienced 3 months of non-proliferative radiation retinopathy that resolved without treatment.\u003csup\u003e31\u003c/sup\u003e The scarcity and heterogeneity of cases using radiotherapy in orbital GCT make the exact role of radiotherapy in treating orbital GCT difficult to interpret.\u003c/p\u003e \u003cp\u003eTo our knowledge, this is one of the only reported cases of malignant orbital GCT demonstrating continued radiographic improvement 22 months after subtotal resection and adjuvant radiotherapy using both proton therapy and CyberKnife boost. While complete surgical excision is generally the preferred treatment, this case highlights the feasibility of a conservative surgical approach supplemented with targeted radiation to achieve long-term tumor control, particularly when anatomical constraints or risk to vision preclude complete resection. Proton therapy was selected to minimize radiation exposure to surrounding critical structures, and CyberKnife was employed to deliver a conformal boost to the residual tumor. The dosing schedule for both the proton beam (45 Gy in 25 fractions) and Cyberknife (9 Gy in 5 fractions) was determined based upon recommendations for benign disease whereby sparing of surrounding tissue such as the lens, optic nerve, and macula is critical over a longer timeframe.\u003csup\u003e32,33\u003c/sup\u003e The patient experienced excellent local control, with serial imaging showing continued tumor regression up to 22 months post-treatment. While the patient did experience transient postoperative complications such as corneal epithelial defect and mild extraocular motility limitations, these resolved with standard supportive care, and vision remained stable. Some potential downsides regarding the utilization of both proton beam and cyberknife are that sequential boosting is less conformation compared to a simultaneous integrated boost plan. Additionally, access to both protons and stereotactic radiosurgery machines such as the Cyberknife is not commonplace at many radiation oncology centers. Our experience suggests that adjuvant radiotherapy, including advanced techniques like proton therapy and stereotactic radiosurgery, can be an effective and well-tolerated option for managing malignant orbital GCTs when maximal resection is not feasible. Further studies are needed to define optimal radiation regimens, but this case supports consideration of multimodal treatment in select patients with orbital GCT.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eGCT\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eGranular Cell Tumor\u003c/p\u003e\n\u003cp\u003eIO\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Inferior oblique muscle\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Lateral rectus muscle\u003c/p\u003e\n\u003cp\u003eMR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Medial rectus muscle\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNLP\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;No light perception\u003c/p\u003e\n\u003cp\u003eNR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Not reported\u003c/p\u003e\n\u003cp\u003eON\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Optic Nerve\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Superior rectus muscle\u003c/p\u003e\n\u003cp\u003ePBRT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Proton beam radiotherapy\u003c/p\u003e\n\u003cp\u003eN/A \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Not applicable\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Written informed consent for publication of this case report and any accompanying images was obtained from the patient. The consent form is held by the authors and is available for review by the Editor of\u0026nbsp;\u003cem\u003eBMC Ophthalmology\u003c/em\u003e upon reasonable request. A copy of the consent form has not been submitted with this manuscript in accordance with the journal\u0026rsquo;s editorial policies but can be provided at any stage, including after publication, if required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;All data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors received no specific funding for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Colin Burns collected the clinical data, performed the literature review, and drafted the manuscript. Daniel Kim MD, MBA contributed to patient management and critically revised the manuscript. Dr. Kim additionally supervised the project and revised the manuscript for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAoyama K, Kamio T, Hirano A, Seshimo A, Kameoka S. Granular cell tumors: a report of six cases. \u003cem\u003eWorld J Surg Oncol\u003c/em\u003e. 2012;10(1):204. doi:10.1186/1477-7819-10-204\u003c/li\u003e\n\u003cli\u003eLack EE, Worsham RGF, Callihan MD, et al. Granular cell tumor: A clinicopathologic study of 110 patients. \u003cem\u003eJ Surg Oncol\u003c/em\u003e. 1980;13(4):301-316. doi:10.1002/jso.2930130405\u003c/li\u003e\n\u003cli\u003eNasser H, Ahmed Y, Szpunar SM, Kowalski PJ. 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Case report: an intriguing sign in a patient with an inferior rectus muscle granular cell tumor. \u003cem\u003eMedicine (Baltimore)\u003c/em\u003e. 2018;97(50):e13624. doi:10.1097/MD.0000000000013624\u003c/li\u003e\n\u003cli\u003eYokoyama T, Vaidya A, Kakizaki H, Takahashi Y. Granular Cell Tumor in the Medial Rectus Muscle: A Case Report. \u003cem\u003eCase Rep Ophthalmol\u003c/em\u003e. 2022;13(1):33-36. doi:10.1159/000521685\u003c/li\u003e\n\u003cli\u003eWang P, Han Z, Peng L, Li X, Yuan H. Orbital granular cell tumor involving the superior rectus muscle: a case report. \u003cem\u003eFront Oncol\u003c/em\u003e. 2024;14:1456960. doi:10.3389/fonc.2024.1456960\u003c/li\u003e\n\u003cli\u003eCallejo SA, Kronish JW, Decker SJ, Cohen GR, Rosa RH. Malignant granular cell tumor metastatic to the orbit. \u003cem\u003eOphthalmology\u003c/em\u003e. 2000;107(3):550-554. doi:10.1016/S0161-6420(99)00135-9\u003c/li\u003e\n\u003cli\u003eSalour H, Tavakoli M, Karimi S, Rezaei Kanavi M, Faghihi M. Granular cell tumor of the orbit. \u003cem\u003eJ Ophthalmic Vis Res\u003c/em\u003e. 2013;8(4):376-379.\u003c/li\u003e\n\u003cli\u003eMorita S, Hiramatsu M, Sugishita M, et al. Pazopanib monotherapy in a patient with a malignant granular cell tumor originating from the right orbit: A case report. \u003cem\u003eOncol Lett\u003c/em\u003e. 2015;10(2):972-974. doi:10.3892/ol.2015.3263\u003c/li\u003e\n\u003cli\u003eBarrantes PC, Zhou P, MacDonald SM, Ioakeim-Ioannidou M, Lee NG. Granular Cell Tumor of the Orbit: Review of the Literature and a Proposed Treatment Modality. \u003cem\u003eOphthal Plast Reconstr Surg\u003c/em\u003e. 2022;38(2):122-131. doi:10.1097/IOP.0000000000002038\u003c/li\u003e\n\u003cli\u003eLi PC, Liebsch NJ, Niemierko A, et al. Radiation tolerance of the optic pathway in patients treated with proton and photon radiotherapy. \u003cem\u003eRadiother Oncol J Eur Soc Ther Radiol Oncol\u003c/em\u003e. 2019;131:112-119. doi:10.1016/j.radonc.2018.12.007\u003c/li\u003e\n\u003cli\u003eIndelicato DJ, Rotondo RL, Mailhot Vega RB, et al. 45 GyRBE for group III orbital embryonal rhabdomyosarcoma. \u003cem\u003eActa Oncol\u003c/em\u003e. 2019;58(10):1404-1409. doi:10.1080/0284186X.2019.1627412\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8903206/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8903206/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eGranular cell tumors (GCTs) are rare Schwann cell\u0026ndash;derived neoplasms, with malignant variants comprising approximately 1\u0026ndash;2% of cases. Orbital involvement is exceedingly uncommon, and optimal management remains undefined due to limited published experience. While maximal safe surgical resection is the primary treatment, complete excision may be precluded by proximity to critical structures such as the optic nerve and extraocular muscles. The role of adjuvant radiotherapy in malignant orbital GCT is not well established.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eA 47-year-old man presented with progressive left orbital swelling, redness, and intermittent diplopia. Magnetic resonance imaging demonstrated a 3.1 \u0026times; 2.4 \u0026times; 2.0 cm heterogeneously enhancing left orbital mass. Orbitotomy with biopsy confirmed malignant GCT. Despite initial stability on imaging, interval progression with extraocular muscle invasion prompted subtotal surgical debulking with preservation of the optic nerve and globe. Given residual disease in close proximity to critical visual structures, the patient underwent a second combined endonasal and transorbital resection followed by adjuvant radiotherapy. He received proton beam therapy to 45 Gy in 25 fractions, followed by a sequential CyberKnife boost of 9 Gy in 5 fractions. Treatment was well tolerated. Serial imaging demonstrated sustained tumor regression, decreasing to 1.8 \u0026times; 1.2 \u0026times; 2.2 cm at seven months post-radiotherapy. At 22 months following initial orbitotomy and nearly one year after completion of radiotherapy, the lesion remained radiographically stable with continued response. Visual function was preserved, and no significant long-term radiation-related toxicity was observed.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eMalignant orbital GCT is rare and poses significant surgical challenges when complete excision risks vision loss. This case demonstrates durable local control with subtotal resection followed by adjuvant proton therapy and stereotactic radiosurgical boost, with preservation of visual function. Multimodal therapy incorporating advanced radiation techniques may represent a viable strategy in select patients with anatomically constrained malignant orbital GCT. Further investigation is needed to better define the role and optimal dosing of radiotherapy in this setting.\u003c/p\u003e","manuscriptTitle":"Combined Proton and Photon Radiotherapy for Orbital Granular Cell Tumor: A Case Report and Review of the Literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 14:24:34","doi":"10.21203/rs.3.rs-8903206/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-02-25T13:41:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-25T13:39:37+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-25T12:59:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-25T00:18:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2026-02-25T00:14:11+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"20d98902-66e9-4456-b54b-311c27633b61","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-08T14:24:35+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 14:24:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8903206","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8903206","identity":"rs-8903206","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}