Radiotherapy for Refractory, Corticosteroid-Resistant Orbital Inflammatory Diseases: Plan Design, Clinical Efficacy, and Prognosis/Outcomes

Radiotherapy for Refractory, Corticosteroid-Resistant Orbital Inflammatory Diseases: Plan Design, Clinical Efficacy, and Prognosis/Outcomes | 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 Research Article Radiotherapy for Refractory, Corticosteroid-Resistant Orbital Inflammatory Diseases: Plan Design, Clinical Efficacy, and Prognosis/Outcomes Yan Ma, Haiyang Chen, Fujing Huang, Xiaolin Pang, Jian Zheng, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4614680/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Orbital inflammatory diseases (OID), including Graves’ ophthalmopathy (GO), orbital pseudotumor (OP), and IgG4-related ophthalmic disease (IgG4-ROD), often require prolonged corticosteroid therapy, which may lead to severe hormonal side effects. These diseases are notably refractory and resistant to corticosteroids. While opposing lateral-field radiotherapy has shown positive results, the potential of volumetric-modulated arc therapy (VMAT) to enhance efficacy and reduce side effects remains uncertain. This study evaluates the radiation dose, clinical efficacy, side effects, and outcomes of orbital VMAT in patients with refractory, corticosteroid-resistant OID. Methods and materials: A retrospective analysis was conducted on 58 patients with refractory, corticosteroid-resistant OID treated with orbital VMAT from November 2019 to July 2022. The primary endpoint was the reduction or cessation of corticosteroid use following radiotherapy, with secondary endpoints including improvements in ocular clinical symptoms (diplopia, proptosis, visual acuity, and extraocular movement) and long-term side effects. Results The median target dose was 20 Gy, with an average lens irradiation dose of 5.4 Gy. Initially, all 58 patients received corticosteroids. After a median follow-up of 27.5 months, 89.7% (52/58) of patients responded positively to radiotherapy: specifically, 55.2% (32/58) completely tapered off corticosteroids, while 34.5% (20/58) reduced their dosage. Symptomatic improvements were observed in diplopia (66.0%), proptosis (63.5%), visual acuity (55.2%), and extraocular movements (66.7%). Regarding the long-term side effects of radiotherapy, incidences of dry eye syndrome and lens opacities were reported at 3.4% and 1.7%, respectively. Conclusions Orbital VMAT is an effective treatment for refractory, corticosteroid-resistant OID, reducing corticosteroid use and improving ocular symptoms with minimal side effects. Further prospective clinical trials are warranted to validate more appropriate VMAT doses and planning models, enhancing treatment outcomes without increasing radiotherapy side effects. Orbital volumetric-modulated arc therapy Orbital inflammatory diseases Radiotherapy plan design Clinical efficacy Prognosis Figures Figure 1 Introduction Orbital inflammatory diseases (OID), including conditions such as Graves’ ophthalmopathy (GO), orbital pseudotumor (OP) (also known as idiopathic orbital inflammation), and immunoglobulin G4-related ophthalmic disease (IgG4-ROD), are immune-associated disorders characterized by symptoms including proptosis, pain, tearing, impaired extraocular mobility, diplopia, periorbital edema, visual impairment, and rarely blindness ( 1 – 4 ). The treatment of OID is typically based on the patient's clinical presentation, disease severity, and response to initial therapies. Presently, clinical treatment options include observation, corticosteroids, immunosuppressive medications, orbital radiotherapy, and surgery ( 2 , 5 ). However, every treatment approach has its limitations and uncertainties. Due to the heterogeneous nature of these conditions and the lack of large-scale randomized controlled trials, there is currently no universally established standard treatment protocol. Corticosteroids usually serve as the first line of therapy for OID, yet their long-term or high-dose use may result in significant hormonal side effects and other complications such as hyperglycemia, hypertension, immune suppression, osteoporosis, weight gain, and mood alterations ( 6 , 7 ). Despite their efficacy, with approximately 80% of patients experiencing improvement, corticosteroids carry a high risk of relapse with up to 50% of patients encountering symptom recurrence ( 8 ), and they may be unsuitable for some individuals due to adverse reactions or contraindications. Orbital radiotherapy, as a non-invasive treatment modality, has shown efficacy in alleviating orbital inflammation and visual symptoms in some studies. Response rates vary between 50% and 97% based on different evaluation criteria, with a median recurrence rate of 10% ( 7 , 9 – 12 ). It proves particularly beneficial for patients who are unresponsive to or intolerant of corticosteroid therapy. A meta-analysis indicates that combining radiotherapy with corticosteroids yields superior outcomes compared to either therapy alone ( 13 ). Nevertheless, conflicting opinions persist, trials compared orbital radiotherapy with control radiotherapy (sham radiotherapy) suggesting no benefit from radiotherapy ( 14 , 15 ), which employed a 20 ~ 29 Gy dose of three-dimensional conformal radiation therapy (3D-CRT). Overall, while radiotherapy demonstrates favorable response rates, variations in inclusion criteria, radiation doses, techniques, and outcome parameters across studies make comparisons challenging ( 10 ). Now, volumetric-modulated arc therapy (VMAT) has become the mainstream in radiotherapy. It’s an advanced radiation therapy technique designed to deliver precise radiation doses to the target area while minimizing exposure to surrounding healthy tissues. VAMT dynamically modulates the beam shape, intensity, and dose rate during arc delivery, which may be suitable for OID patients ( 16 ). To address this issue, we employed the VMAT technique with modified target delineation and dose limitation, retrospectively analyzing therapeutic efficacy and side effects for refractory, corticosteroid-resistant OID patients. Methods and materials Patients selection The refractory, corticosteroid-resistant OID patients receiving VMAT between November 2019 and July 2022 in our department were retrospectively recruited. The inclusion criteria were as follows: (a) 18–75 years of age, (b) moderate to severe cases, (c) no prior orbital radiotherapy, and (d) patients who were unable to tolerate or respond to hormonal drugs. Of the initial 60 patients identified, 2 patients with GO were excluded due to an inability to complete the planned course of radiotherapy. The study was approved by the local ethics committee of the Sixth Affiliated Hospital. Target delineation and plan design Patients were positioned supine and immobilized using a thermoplastic mask system, utilizing the Philips Brilliance Big Bore CT scanner (Philips Medical Systems) following established protocols, with a 3-mm slice thickness spanning from the calvaria to the C2 level. Additionally, axial 3.0-mm-thick magnetic resonance images (MRI) were acquired within the region of interest to facilitate precise delineation of the target volume. Clinical target volume (CTV) was defined to encompass the inflamed orbital tissues, meticulously excluding structures such as the lenses, eyes, and anterior chambers, based on symptoms and imaging modalities such as CT or MRI. Experienced radiation oncologists meticulously contoured organs at risk (OARs), including lenses, eyeballs, optic nerves, chiasm, and bilateral hippocampi, on the CT dataset. Subsequently, a 5 ~ 10 mm expansion was applied to the left and right lenses to generate the lenses avoidance (LA) region. Planning target volume (PTV) was then outlined with a 3 mm margin from CTV, excluding the LA region. The total prescription dose for the PTV was 20 ~ 30 Gy at 2 Gy per once-daily fraction, tailored to individual patient characteristics, extent of inflammation, and severity of symptoms. The planning objective was to ensure that 95% of the PTV received the prescription dose while sparing OARs as low as possible. For treatment delivery, the Elekta Synergy accelerator equipped with 80 multileaf collimators (MLC) and the Monaco treatment planning system (Version 5.11.03) were utilized. All patients underwent treatment with VMAT utilizing 6 MV photon fields. The treatment optimization process employed constraints based on biological cost functions (i.e. Serial or parallel complication model for OARs and Poisson cell kill function for the PTV). Plan evaluation A quantitative evaluation of the VMAT plans was conducted using a standard dose-volume histogram (DVH). For PTV, the following parameters were assessed: volume receiving the prescribed dose (V P ) was reported as the target coverage, D 98% and D 2% (the dose received by 98% and 2% of the PTV volume) were defined as the minimum dose and maximum dose of the PTV ( 17 ). For OARs, the evaluation included: the maximum dose (denoted as D max ), which was defined as the dose to the hottest 0.03-cc volume of the OARs, and D 100% (the dose received by 100% of the OAR volume). Follow-up and Outcomes The study implemented a structured follow-up protocol to assess the outcomes of patients undergoing radiotherapy for OID. Here are the key aspects of the follow-up process and the outcomes measured: Follow-up duration: The follow-up duration was defined as the period from the first day of radiotherapy to the date of the last examination. Patients were routinely assessed at 3-month intervals during the first year post-radiotherapy, followed by 6-month intervals thereafter. Primary endpoint - Response to Radiotherapy: The primary endpoint was the response to radiotherapy. This was defined as the ability of patients to discontinue or reduce their corticosteroid usage at 6 months post-radiotherapy completion without experiencing any further flares beyond 6 months. A “flare” was defined as the need for additional intervention, such as increased corticosteroid dosage or surgery, due to increased symptoms occurring after 6 months from radiotherapy completion ( 18 ). Descriptive statistics: This was used to report various aspects of the study outcomes, including corticosteroid requirements, the incidence of flares, and changes in eye symptoms such as diplopia, proptosis, visual acuity, and extraocular movements. Long-term side effects of radiotherapy: The study focused on dry eye syndrome and lens opacities. The evaluation focused on measuring the occurrence and progression of these effects starting from 6 months post-radiotherapy completion and onwards. Statistical Methods Statistical analysis and tabulations were conducted using JMP software (SAS Institute, Cary, NC, USA). The Kaplan-Meier product limit method was employed to provide an estimate of local control. Results Patients Characteristics The study population comprised a total of 58 enrolled patients, categorized into different subgroups based on their underlying condition: 33 patients with GO, 21 patients with OP, and 3 patients with IgG4-ROD. Table 1 provides a summary of the main patient and tumor characteristics. In the GO subgroup, of the 36 patients, 17 were female (47.2%) and 19 were male (52.8%). The median age was 45 years, ranging from 27 to 68 years. The median CTV was recorded at 69.26 cm³, with a range spanning from 25.22 to 76.92 cm³. Bilateral manifestation of the condition was predominant, observed in 34 patients, while unilateral affliction was comparatively rare, noted in 2 cases affecting the right eye. In the OP subgroup, there was a nearly balanced gender distribution, with 11 females (52.4%) and 10 males (47.6%). The median age was slightly lower compared to the GO subgroup, at 43 years, ranging from 20 to 58 years. The median CTV was 32.61 cm³, varying between 22.91 and 64.87 cm³. Unilateral conditions were more prevalent in the OP subgroup, with 11 patients experiencing right-eye involvement and 5 patients experiencing left-eye involvement. Bilateral affliction was confirmed in 5 cases. In the IgG4-ROD subgroup, only 3 patients were comprised, with 1 female (33.3%) and 2 males (66.7%). The median age in this subgroup was 49 years, within a narrower range of 34 to 51 years. The median CTV was noted as 62.58 cm³, spanning from 32.12 to 66.65 cm³. Bilateral disease was present in 2 patients, with 1 patient having left-eye involvement and none with right-eye involvement. Target delineation, plan design, and radiation dose analysis Figure 1A and Figure 1B illustrate the delineation of the CTV for one patient, which encompasses the extraocular muscles delineated in red. This volume represents the area requiring treatment to address inflammation and associated symptoms. Additionally, Figure 1C and Figure 1D depict the typical dose distribution of a VMAT plan for this patient. A low-dose zone around the lenses, referred to as the LA region, is also shown in Figure 1. This area is spared from high doses of radiation to prevent complications such as dry eye syndrome and lens opacities. The plan optimization protocol, detailed in Table 2 (e.g., 30 Gy over 15 fractions), incorporates stringent dose limitations for OARs, with a special emphasis on the lenses. Contrary to conventional cancer treatment planning, where the high dose limit for the PTV is typically restricted to 110% of the prescribed dose, covering less than 5% of the PTV, our modified threshold permits up to 125% of the prescribed dose, restricted to less than 2% of the PTV. This adjustment reflects a strategic shift in dose distribution, aligning with the nuanced requirements of our specific treatment objectives: achieving a steep dose fall-off gradient between the PTV and lenses, ensuring comprehensive coverage of the prescribed dose for the PTV while restricting the dose to the lenses to a maximum of 6 Gy. Additionally, in consideration of hippocampal memory protection, dose constraints were set as follows: D max ≤ 16 Gy, D 100% ≤ 9 Gy (19). Table 3 provides detailed dosimetry statistics on target coverage and OARs. The average coverage of the PTV reached 95.8% with a D2 value of 1.26%. Additionally, Dmax of the lenses was recorded at 5.4 Gy. For the left and right bilateral hippocampi, the Dmax values were 9.6 Gy and 10.9 Gy, respectively, while the D100% values were 2.3 Gy and 3.4 Gy, respectively. Those results indicate strict compliance with the established protocol outlined in Table 2. Such dosimetry data are crucial for assessing the balance between effective tumor control and minimizing the risk of radiation-induced damage to OARs. Radiation treatment response and toxicities The median follow-up duration in the study was 27.5 months, ranging from 2 to 47 months, with 83.3% of the patients having follow-ups ≥ 12 months. Further details regarding corticosteroid tapering can be found in Table 4. Corticosteroids were administered as the initial treatment modality to the entire cohort of 58 patients. Of those, 52 patients (52/58, 89.7%) responded positively to radiotherapy, while 6 patients (6/58, 10.3%) failed to respond due to uncontrolled symptoms and required further intervention. Specifically, 32 patients (32/58, 55.2%) were able to completely taper off corticosteroids due to symptom control, while 20 patients (20/58, 34.5%) experienced a reduction in corticosteroid dosage among the remaining 26 patients who were unable to fully decrease their corticosteroid dosage. The symptom changes and long-term side effects before and after radiotherapy are presented in Table 5. Notably, symptomatic improvements were observed in diplopia (33/50, 66.0%), proptosis (33/52, 63.5%), visual acuity (32/58, 55.2%), and extraocular movements (30/45, 66.7%) among the patients. As for the long-term side effects of radiotherapy, the incidences of dry eye syndrome and lens opacities were reported at 3.4% (2/58) and 1.7% (1/58), respectively. Discussion Benign orbital diseases, while not inherently life-threatening, can significantly compromise visual function by affecting critical structures such as the optic nerve, extraocular muscles, or cornea (3, 4). The best clinical management of patients diagnosed with OID remains uncertain, despite various treatment modalities that have demonstrated efficacy (4). As an alternative option to OID, orbital radiotherapy has shown potential in alleviating orbital inflammation and improving visual symptoms in numerous studies, however, its efficacy remains a subject of debate (14, 15). To address this ambiguity, our study aimed to assess the effectiveness of radiotherapy for for refractory, corticosteroid-resistant OID patients based on several key outcome measures. Our primary focus was on the patient's ability to taper corticosteroids without experiencing further exacerbations of orbitopathy symptoms, serving as a crucial indicator of treatment efficacy. Additionally, we evaluated changes in specific symptoms such as diplopia, proptosis, visual acuity, and extraocular movements before and after radiotherapy. Furthermore, we examined long-term side effects, with a particular emphasis on dry eye syndrome and lens opacities. By comprehensively analyzing these parameters, we aimed to provide valuable insights into the overall effectiveness and safety profile of radiotherapy as a treatment option for OID, ultimately guiding clinical decision-making and improving patient outcomes. In our study, 89.7% of patients on corticosteroids had a significant reduction in corticosteroid requirements after orbital VMAT. Among these patients, 55.2% were able to discontinue corticosteroid use entirely, and 34.5% experienced reductions in corticosteroid dosage. This aligns with previous studies that have used corticosteroid requirements as a primary measure of radiotherapy effectiveness at specific time points (18, 20). Furthermore, our study reports relatively low incidences of dry eye syndrome (3.4%) and lens opacities (1.7%) among the patient population. These findings highlight the role of radiotherapy help stabilize the disease process and minimize the duration of corticosteroid therapy and its acceptable side effects. Previous reports have also established the efficacy of the 20 Gy in 10 fractions as the most efficacious and minimally toxic treatment dose (9, 18). However, other reports have suggested doses less than 20 Gy are sufficient for patients with predominantly soft tissue signs without ocular dysmotility (16). Our study, with a prescription of 20~30 Gy depending on the severity of symptoms, showed a highly favorable outcome. Orbital radiotherapy offers an advantage over surgery by preserving eye structure, potentially leading to a better appearance after treatment. Historically, conventional radiotherapy or 3D-CRT was commonly employed for OID treatment but lacked dose-modulating techniques. In one approach, protecting the lenses involved forced avoidance, which resulted in inadequate dose coverage of the target area, while in the other approach, aimed at ensuring adequate target coverage, which runed the risk of overexposure the lenses. In a study by Matthiesen (21), a dose of 20 Gy in 10 fractions was delivered using two opposing lateral 6-MV fields. Notably, they reported a 12% incidence of dry eye syndrome. In our investigation, we applied a 5~10 mm expansion to generate the LA region around the lenses, and we delineated the PTV with a 3 mm margin excluding the LA region, which effectively reducing forced avoidance in opposing lateral fields. With the advanced orbital VMAT, we achieved a steeper dose gradient between the tumor target and OARs in our study, in which we set strict dose constraints with D max of lenses ≤ 6Gy and PTV coverage ≥ 95%. Our orbital VMAT plans yielded a D max of 5.4 Gy to the lenses and 95.8% average PTV coverage, contributing to low incidences of dry eye syndrome (3.4%) and lens opacities (1.7%), which was consistent with the findings by Li (22). Thus, our meticulous delineation of PTV, prescription of dose, and dose constraints on OARs proved effective in minimizing radiation-induced side effects while maintaining treatment efficacy. These results underscore the importance of adopting advanced radiotherapy techniques like VMAT in the management of OID, highlighting the potential for improved patient outcomes and quality of life. Further studies are warranted to explore the long-term efficacy and safety of this approach, as well as its impact on patient-reported outcomes. However, there are several limitations to our retrospective analysis: (1) The number of cases is limited to just over 50, suggesting the need for larger sample sizes in future follow-up studies. (2) Retrospective studies are inherently prone to selection bias, and unidentified confounding factors may influence the results. (3) The therapeutic dose ranges from 20 to 30 Gy, lacking uniformity, and the optimal radiotherapy dose remains uncertain, warranting further investigation through prospective trials. Therefore, prospective studies with well-defined cohort characteristics and outcome definitions are essential. Conclusion Orbital radiotherapy has shown promising results in improving visual symptoms and reducing the dependence on corticosteroids in patients with OID. It provides an alternative treatment option for patients who cannot tolerate or have contraindications to prolonged corticosteroid therapy. The use of radiotherapy has demonstrated acceptable side effects, although long-term effects still need to be monitored and evaluated through further follow-up. Larger and well-designed prospective trials are warranted to establish standardized protocols and guidelines for the radiotherapy management of OID. List Of Abbreviations OID: Orbital inflammatory diseases; GO: Graves’ ophthalmopathy; OP: Orbital pseudotumor; IgG4-ROD: IgG4-related ophthalmic disease; VMAT: Volumetric-modulated arc therapy; 3D-CRT: Three-dimensional conformal radiation therapy; MRIs: Magnetic resonance images; CTV: Clinical target volume; OARs: Organs at risk; LA: Lenses avoidance; PTV: Planning target volume; MLC: Multileaf collimators; DVH: Dose-volume histogram; Vp: Volume receiving the prescribed dose; Dmax: the maximum dose; D 98% and D 2% : the dose received by 98% of the PTV volume; D 2% : the dose received by 2% of the PTV volume. Declarations Ethics approval and consent to participate The study was approved by the local ethics committee of the Sixth Affiliated Hospital (2023ZSLYEC-084). We confirm that all methods were carried out under relevant guidelines and regulations. Consent for publication The patients gave their informed consent for the use of the data for research purposes. Availability of data and materials The datasets used during the current study are available from the corresponding author on reasonable request . Competing interests The authors declare that they have no competing interests. Funding This work was supported by the program of Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004). Authors’ contributions YM: Methodology, Writing; HYC: Conceptualization, Data Curation; FJH: Preparation of figures and tables; XLP: Methodology. JZ and FH: Methodology, Writing. All authors read and approved the final manuscript. Acknowledgements Not applicable. 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Tables Table 1 Patient and disease characteristics Characteristic Value GO Females/males, n 17 (47.2) /19 (52.8) Age(y), median (range) 45 (27–68) CTV volume, cm 3 , median (range) 69.26 (25.22–76.92) Location Left eye: 0 Right eye: 2 Both eyes: 34 OP Females/males, n 11 (52.4) /10 (47.6) Age(y), median (range) 43 (20–58) CTV volume, cm 3 , median (range) 32.61 (22.91–64.87) Location Left eye:5 Right eye:11 Both eyes:5 IgG4-ROD Females/males, n 1 (33.3) /2 (66.7) Age(y), median (range) 49 (34–51) CTV volume, cm 3 , median (range) 62.58 (32.12–66.65) Location Left eye: 1 Right eye: 0 Both eyes: 2 Abbreviations: GO, graves’ ophthalmopathy; OP, orbital pseudotumor; IgG4-ROD, IgG4-related ophthalmic disease; CTV, clinical target volume. Table 2 Radiotherapy planning optimization protocol (30 Gy/15f, for example) Name of Structure Dosimetric Parameter Per Protocol Notes PTV_30 D 2% ≤ 37.5 Gy a Dose to hottest 2% of PTV_30 D 98% ≥ 25 Gy Dose to 98% of PTV_30 V 30Gy ≥ 95% Volume receiving prescription dose of 30 Gy Lens (Left side) b D max ≤ 6 Gy Dose to hottest 0.03-cc volume of left lens Lens (Right side) b D max ≤ 6 Gy Dose to hottest 0.03-cc volume of right lens Eyeball (Left side) D max ≤ 37.5 Gy a Dose to hottest 0.03-cc volume of left eyeball D mean ≤ 25 Gy Mean dose to left eyeball Eyeball (Right side) D max ≤ 37.5 Gy a Dose to hottest 0.03-cc volume of right eyeball D mean ≤ 25 Gy Mean dose to right eyeball Optic nerve (Left side) D max ≤ 37.5 Gy a Dose to hottest 0.03-cc volume of left optic nerve Optic nerve (Right side) D max ≤ 37.5 Gy a Dose to hottest 0.03-cc volume of right optic nerve Hippocampi (Left side) D max ≤ 16 Gy Dose to hottest 0.03-cc volume of left hippocampi D 100% ≤ 9 Gy Dose to 100% of left hippocampi Hippocampi (Right side) D max ≤ 16 Gy Dose to hottest 0.03-cc volume of right hippocampi D 100% ≤ 9 Gy Dose to 100% of right hippocampi Abbreviations: PTV, planning target volume; D, dose; cc, cubic centimeters. a 37.5 Gy is 125% of the prescription dose. b There are no specified dose parameters for the lens avoidance region because this region represents a transition region for dosing. Table 3 Target coverage and OARs sparing statistical results Structures Dosimetric Parameter Value PTV_ P V P 95.80% V 125% 1.26% Lens (Left side) D max (Gy) 5.4 Lens (Right side) D max (Gy) 5.4 Eyeball (Left side) D max (Gy) 22.3 D mean (Gy) 16.2 Eyeball (Right side) D max (Gy) 24.4 D mean (Gy) 17.6 Optic chiasm D max (Gy) 17.9 Optic nerve (left side) D max (Gy) 22.7 Optic nerve (Right side) D max (Gy) 24.4 Bilateral hippocampi (Left side) D max (Gy) 9.6 D 100% (Gy) 2.3 Bilateral hippocampi (Right side) D max (Gy) 10.9 D 100% (Gy) 3.4 Abbreviations: PTV, planning target volume; D, dose; cc, cubic centimeters. Table 4 Corticosteroid therapy post orbital radiotherapy Characteristic GO (n = 34) OP (n = 21) IgG4-ROD (n = 3) Overall(n = 58) Able to discontinue Corticosteroids 20(58.9%) 11(52.4%) 1(33.3%) 32 (55.2%) Unable to discontinue Corticosteroids 14(41.1%) 10(47.6%) 2(66.7%) 26 (44.8%) Patients decrease in steroid dose in those who were unable to fully reduce their corticosteroid dose 9(26.5%) 9(42.9%) 2(66.7%) 20 (34.5%) Responded to radiotherapy 29 (85.3%) 20 (95.2%) 3 (100.0%) 52 (89.7%) Failed radiotherapy 5(14.7%) 1(4.8%) 0(0.0%) 6 (10.3%) Abbreviations: GO, graves’ ophthalmopathy; OP, orbital pseudotumor; IgG4-ROD, IgG4-related ophthalmic disease. Table 5 Symptom outcomes and long-term side effects post orbital radiotherapy Outcome GO (n = 34) OP (n = 21) IgG4-ROD (n = 3) Overall (n = 58) Symptom outcomes Diplopia 30 18 2 50 Improved 18 (60.0%) 14 (77.8%) 1 (50.0%) 33 (66.0%) Unchanged 8 (26.7%) 3 (16.7%) 1 (50.0%) 12 (24.0%) Worsened 4 (13.3%) 1 (5.6%) 0 (0.0%) 5 (10.0%) Proptosis 34 16 2 52 Improved 20 (58.8%) 12 (75.0%) 1 (50.0%) 33 (63.5%) Unchanged 13 (38.2%) 4 (25.0%) 1 (50.0%) 18 (34.6%) Worsened 1 (2.9%) 0 (0.0%) 0 (0.0%) 1 (1.9%) Decreased visual acuity 34 21 3 58 Improved 18 (52.9%) 12 (57.1%) 2 (66.7%) 32 (55.2%) Unchanged 15 (44.1%) 8 (38.1%) 1 (33.3%) 24 (41.4%) Worsened 1 (2.9%) 1(4.8%) 0 (0.0%) 2 (3.4%) Restricted extraocular movements 26 17 2 45 Improved 17 (65.4%) 12 (70.6%) 1 (50.0%) 30 (66.7%) Unchanged 8 (30.8%) 4 (23.5%) 1 (50.0%) 13 (28.9%) Worsened 1 (3.8%) 1 (5.9%) 0 (0.0%) 2 (4.4%) Long-term side effects 1 2 0 3 Dry eye syndrome 1(2.9%) 1(4.8%) 0(0.0%) 2(3.4%) Lens opacities 0(0.0%) 1(4.8%) 0(0.0%) 1 (1.7%) Abbreviations: GO, graves’ ophthalmopathy; OP, orbital pseudotumor; IgG4-ROD, IgG4-related ophthalmic disease. 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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-4614680","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":324692979,"identity":"bfaa9fa0-1bba-4273-aee9-994e87c616cf","order_by":0,"name":"Yan Ma","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIiWNgGAWjYNCCChsGBmbmBhjXgAgtZ9KAWhhJ0cLYdhhEEqlFt/2M4eeCM+ej+dsZGxh/ttUlNrA3b5NgqLmDU4vZmRxj6RkVt3NnHGZsYOZtO5zYwHOsTILh2DPcWg7kGEjznLmd2wDSwth2ILFBIsdMgrHhMG4t598Y/+ZtO5c7/zDMYfJvCGi5kWMmzdt2IHcDUAsDbxsz0BYeQlqelVnznEnO3QjUcpjn3GHjNp60YouEY/gclrz5Nk+FXe6884cPPvxRVifbz354440PNbi1MDBwIGLhACMbAwMbiJWARwMDA/sDJM4fvEpHwSgYBaNghAIAKZRZtrNC1NIAAAAASUVORK5CYII=","orcid":"","institution":"Sixth Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":true,"prefix":"","firstName":"Yan","middleName":"","lastName":"Ma","suffix":""},{"id":324692980,"identity":"de7682b9-5013-420b-b9ad-624c0a87a314","order_by":1,"name":"Haiyang Chen","email":"","orcid":"","institution":"Sixth Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Haiyang","middleName":"","lastName":"Chen","suffix":""},{"id":324692986,"identity":"483db8e9-c1f7-40a3-87ab-9523090fa25d","order_by":2,"name":"Fujing Huang","email":"","orcid":"","institution":"Shandong Second Provincial General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fujing","middleName":"","lastName":"Huang","suffix":""},{"id":324692989,"identity":"3b1e0ffe-5cfc-4ff2-a155-677e17ad1abd","order_by":3,"name":"Xiaolin Pang","email":"","orcid":"","institution":"Sixth Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Xiaolin","middleName":"","lastName":"Pang","suffix":""},{"id":324692992,"identity":"31c70acf-319e-4253-9e43-71b5eb5cb981","order_by":4,"name":"Jian Zheng","email":"","orcid":"","institution":"Sixth Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Zheng","suffix":""},{"id":324692993,"identity":"a29f00d8-1ab5-44a5-9744-e4255cca028d","order_by":5,"name":"Fang He","email":"","orcid":"","institution":"Sixth Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"He","suffix":""}],"badges":[],"createdAt":"2024-06-21 03:45:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4614680/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4614680/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60619523,"identity":"7f4830b5-bb8c-4d4d-b2fd-0794468036a4","added_by":"auto","created_at":"2024-07-18 20:45:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":663181,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRepresentative images of a VMAT plan for Graves’ ophthalmopathy.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Axial CT image with CTV delineated in red, PTV delineated in blue, and OARs. (B) Sagittal CT image with CTV, PTV, and OARs. (C) Axial CT image with prescription dose distribution. (D) Sagittal CT image with prescription dose distribution.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: \u003c/em\u003eVMAT, volumetric modulated arc therapy; CT, computed tomography; CTV, clinical target volume; PTV, planning target volume; OARs, organs at risk.\u003c/p\u003e","description":"","filename":"Figure.png","url":"https://assets-eu.researchsquare.com/files/rs-4614680/v1/e9cac59b878834650780c6d0.png"},{"id":65355264,"identity":"0bbf46f1-7fc2-43ea-8560-8803ac02d0a9","added_by":"auto","created_at":"2024-09-26 12:02:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1697357,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4614680/v1/7df73c3a-a511-41ae-8dc9-0b8bb872e9dc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Radiotherapy for Refractory, Corticosteroid-Resistant Orbital Inflammatory Diseases: Plan Design, Clinical Efficacy, and Prognosis/Outcomes","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOrbital inflammatory diseases (OID), including conditions such as Graves\u0026rsquo; ophthalmopathy (GO), orbital pseudotumor (OP) (also known as idiopathic orbital inflammation), and immunoglobulin G4-related ophthalmic disease (IgG4-ROD), are immune-associated disorders characterized by symptoms including proptosis, pain, tearing, impaired extraocular mobility, diplopia, periorbital edema, visual impairment, and rarely blindness (\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The treatment of OID is typically based on the patient's clinical presentation, disease severity, and response to initial therapies. Presently, clinical treatment options include observation, corticosteroids, immunosuppressive medications, orbital radiotherapy, and surgery (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). However, every treatment approach has its limitations and uncertainties. Due to the heterogeneous nature of these conditions and the lack of large-scale randomized controlled trials, there is currently no universally established standard treatment protocol.\u003c/p\u003e \u003cp\u003eCorticosteroids usually serve as the first line of therapy for OID, yet their long-term or high-dose use may result in significant hormonal side effects and other complications such as hyperglycemia, hypertension, immune suppression, osteoporosis, weight gain, and mood alterations (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Despite their efficacy, with approximately 80% of patients experiencing improvement, corticosteroids carry a high risk of relapse with up to 50% of patients encountering symptom recurrence (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), and they may be unsuitable for some individuals due to adverse reactions or contraindications.\u003c/p\u003e \u003cp\u003eOrbital radiotherapy, as a non-invasive treatment modality, has shown efficacy in alleviating orbital inflammation and visual symptoms in some studies. Response rates vary between 50% and 97% based on different evaluation criteria, with a median recurrence rate of 10% (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). It proves particularly beneficial for patients who are unresponsive to or intolerant of corticosteroid therapy. A meta-analysis indicates that combining radiotherapy with corticosteroids yields superior outcomes compared to either therapy alone (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Nevertheless, conflicting opinions persist, trials compared orbital radiotherapy with control radiotherapy (sham radiotherapy) suggesting no benefit from radiotherapy (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), which employed a 20\u0026thinsp;~\u0026thinsp;29 Gy dose of three-dimensional conformal radiation therapy (3D-CRT). Overall, while radiotherapy demonstrates favorable response rates, variations in inclusion criteria, radiation doses, techniques, and outcome parameters across studies make comparisons challenging (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Now, volumetric-modulated arc therapy (VMAT) has become the mainstream in radiotherapy. It\u0026rsquo;s an advanced radiation therapy technique designed to deliver precise radiation doses to the target area while minimizing exposure to surrounding healthy tissues. VAMT dynamically modulates the beam shape, intensity, and dose rate during arc delivery, which may be suitable for OID patients (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTo address this issue, we employed the VMAT technique with modified target delineation and dose limitation, retrospectively analyzing therapeutic efficacy and side effects for refractory, corticosteroid-resistant OID patients.\u003c/p\u003e"},{"header":"Methods and materials","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients selection\u003c/h2\u003e \u003cp\u003eThe refractory, corticosteroid-resistant OID patients receiving VMAT between November 2019 and July 2022 in our department were retrospectively recruited. The inclusion criteria were as follows: (a) 18\u0026ndash;75 years of age, (b) moderate to severe cases, (c) no prior orbital radiotherapy, and (d) patients who were unable to tolerate or respond to hormonal drugs. Of the initial 60 patients identified, 2 patients with GO were excluded due to an inability to complete the planned course of radiotherapy. The study was approved by the local ethics committee of the Sixth Affiliated Hospital.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTarget delineation and plan design\u003c/h2\u003e \u003cp\u003ePatients were positioned supine and immobilized using a thermoplastic mask system, utilizing the Philips Brilliance Big Bore CT scanner (Philips Medical Systems) following established protocols, with a 3-mm slice thickness spanning from the calvaria to the C2 level. Additionally, axial 3.0-mm-thick magnetic resonance images (MRI) were acquired within the region of interest to facilitate precise delineation of the target volume.\u003c/p\u003e \u003cp\u003eClinical target volume (CTV) was defined to encompass the inflamed orbital tissues, meticulously excluding structures such as the lenses, eyes, and anterior chambers, based on symptoms and imaging modalities such as CT or MRI. Experienced radiation oncologists meticulously contoured organs at risk (OARs), including lenses, eyeballs, optic nerves, chiasm, and bilateral hippocampi, on the CT dataset. Subsequently, a 5\u0026thinsp;~\u0026thinsp;10 mm expansion was applied to the left and right lenses to generate the lenses avoidance (LA) region. Planning target volume (PTV) was then outlined with a 3 mm margin from CTV, excluding the LA region.\u003c/p\u003e \u003cp\u003eThe total prescription dose for the PTV was 20\u0026thinsp;~\u0026thinsp;30 Gy at 2 Gy per once-daily fraction, tailored to individual patient characteristics, extent of inflammation, and severity of symptoms. The planning objective was to ensure that 95% of the PTV received the prescription dose while sparing OARs as low as possible.\u003c/p\u003e \u003cp\u003eFor treatment delivery, the Elekta Synergy accelerator equipped with 80 multileaf collimators (MLC) and the Monaco treatment planning system (Version 5.11.03) were utilized. All patients underwent treatment with VMAT utilizing 6 MV photon fields. The treatment optimization process employed constraints based on biological cost functions (i.e. Serial or parallel complication model for OARs and Poisson cell kill function for the PTV).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePlan evaluation\u003c/h2\u003e \u003cp\u003eA quantitative evaluation of the VMAT plans was conducted using a standard dose-volume histogram (DVH). For PTV, the following parameters were assessed: volume receiving the prescribed dose (V\u003csub\u003eP\u003c/sub\u003e) was reported as the target coverage, D\u003csub\u003e98%\u003c/sub\u003e and D\u003csub\u003e2%\u003c/sub\u003e (the dose received by 98% and 2% of the PTV volume) were defined as the minimum dose and maximum dose of the PTV (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). For OARs, the evaluation included: the maximum dose (denoted as D\u003csub\u003emax\u003c/sub\u003e), which was defined as the dose to the hottest 0.03-cc volume of the OARs, and D\u003csub\u003e100%\u003c/sub\u003e (the dose received by 100% of the OAR volume).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up and Outcomes\u003c/h2\u003e \u003cp\u003eThe study implemented a structured follow-up protocol to assess the outcomes of patients undergoing radiotherapy for OID. Here are the key aspects of the follow-up process and the outcomes measured:\u003c/p\u003e \u003cp\u003eFollow-up duration: The follow-up duration was defined as the period from the first day of radiotherapy to the date of the last examination. Patients were routinely assessed at 3-month intervals during the first year post-radiotherapy, followed by 6-month intervals thereafter.\u003c/p\u003e \u003cp\u003ePrimary endpoint - Response to Radiotherapy: The primary endpoint was the response to radiotherapy. This was defined as the ability of patients to discontinue or reduce their corticosteroid usage at 6 months post-radiotherapy completion without experiencing any further flares beyond 6 months. A \u0026ldquo;flare\u0026rdquo; was defined as the need for additional intervention, such as increased corticosteroid dosage or surgery, due to increased symptoms occurring after 6 months from radiotherapy completion (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDescriptive statistics: This was used to report various aspects of the study outcomes, including corticosteroid requirements, the incidence of flares, and changes in eye symptoms such as diplopia, proptosis, visual acuity, and extraocular movements.\u003c/p\u003e \u003cp\u003eLong-term side effects of radiotherapy: The study focused on dry eye syndrome and lens opacities. The evaluation focused on measuring the occurrence and progression of these effects starting from 6 months post-radiotherapy completion and onwards.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Methods\u003c/h2\u003e \u003cp\u003eStatistical analysis and tabulations were conducted using JMP software (SAS Institute, Cary, NC, USA). The Kaplan-Meier product limit method was employed to provide an estimate of local control.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatients Characteristics\u003c/h2\u003e \u003cp\u003eThe study population comprised a total of 58 enrolled patients, categorized into different subgroups based on their underlying condition: 33 patients with GO, 21 patients with OP, and 3 patients with IgG4-ROD. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e provides a summary of the main patient and tumor characteristics.\u003c/p\u003e \n\u003cp\u003eIn the GO subgroup, of the 36 patients, 17 were female (47.2%) and 19 were male (52.8%). The median age was 45 years, ranging from 27 to 68 years. The median CTV was recorded at 69.26 cm\u0026sup3;, with a range spanning from 25.22 to 76.92 cm\u0026sup3;. Bilateral manifestation of the condition was predominant, observed in 34 patients, while unilateral affliction was comparatively rare, noted in 2 cases affecting the right eye.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the OP subgroup, there was a nearly balanced gender distribution, with 11 females (52.4%) and 10 males (47.6%). The median age was slightly lower compared to the GO subgroup, at 43 years, ranging from 20 to 58 years. The median CTV was 32.61 cm\u0026sup3;, varying between 22.91 and 64.87 cm\u0026sup3;. Unilateral conditions were more prevalent in the OP subgroup, with 11 patients experiencing right-eye involvement and 5 patients experiencing left-eye involvement. Bilateral affliction was confirmed in 5 cases.\u003c/p\u003e\n\u003cp\u003eIn the IgG4-ROD subgroup, only 3 patients were comprised, with 1 female (33.3%) and 2 males (66.7%). The median age in this subgroup was 49 years, within a narrower range of 34 to 51 years. The median CTV was noted as 62.58 cm\u0026sup3;, spanning from 32.12 to 66.65 cm\u0026sup3;. Bilateral disease was present in 2 patients, with 1 patient having left-eye involvement and none with right-eye involvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTarget delineation, plan design, and radiation dose analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFigure 1A and Figure 1B illustrate the delineation of the CTV for one patient, which encompasses the extraocular muscles delineated in red. This volume represents the area requiring treatment to address inflammation and associated symptoms. Additionally, Figure 1C and Figure 1D depict the typical dose distribution of a VMAT plan for this patient. A low-dose zone around the lenses, referred to as the LA region, is also shown in Figure 1. This area is spared from high doses of radiation to prevent complications such as dry eye syndrome and lens opacities.\u003c/p\u003e\n\u003cp\u003eThe plan optimization protocol, detailed in Table 2 (e.g., 30 Gy over 15 fractions), incorporates stringent dose limitations for OARs, with a special emphasis on the lenses. Contrary to conventional cancer treatment planning, where the high dose limit for the PTV is typically restricted to 110% of the prescribed dose, covering less than 5% of the PTV, our modified threshold permits up to 125% of the prescribed dose, restricted to less than 2% of the PTV. This adjustment reflects a strategic shift in dose distribution, aligning with the nuanced requirements of our specific treatment objectives: achieving a steep dose fall-off gradient between the PTV and lenses, ensuring comprehensive coverage of the prescribed dose for the PTV while restricting the dose to the lenses to a maximum of 6 Gy. Additionally, in consideration of hippocampal memory protection, dose constraints were set as follows:\u0026nbsp;D\u003csub\u003emax\u003c/sub\u003e \u0026le; 16 Gy, D\u003csub\u003e100%\u003c/sub\u003e \u0026le; 9 Gy (19).\u003c/p\u003e\n\u003cp\u003eTable 3 provides detailed dosimetry statistics on target coverage and OARs. The average coverage of the PTV reached 95.8% with a D2 value of 1.26%. Additionally, Dmax of the lenses was recorded at 5.4 Gy. For the left and right bilateral hippocampi, the Dmax values were 9.6 Gy and 10.9 Gy, respectively, while the D100% values were 2.3 Gy and 3.4 Gy, respectively. Those results indicate strict compliance with the established protocol outlined in Table 2. Such dosimetry data are crucial for assessing the balance between effective tumor control and minimizing the risk of radiation-induced damage to OARs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRadiation treatment response and toxicities\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median follow-up duration in the study was 27.5 months, ranging from 2 to 47 months, with 83.3% of the patients having follow-ups \u0026ge; 12 months.\u003c/p\u003e\n\u003cp\u003eFurther details regarding corticosteroid tapering can be found in Table 4. Corticosteroids were administered as the initial treatment modality to the entire cohort of 58 patients. Of those, 52 patients (52/58, 89.7%) responded positively to radiotherapy, while 6 patients (6/58, 10.3%) failed to respond due to uncontrolled symptoms and required further intervention. Specifically, 32 patients (32/58, 55.2%) were able to completely taper off corticosteroids due to symptom control, while 20 patients (20/58, 34.5%) experienced a reduction in corticosteroid dosage among the remaining 26 patients who were unable to fully decrease their corticosteroid dosage.\u003c/p\u003e\n\u003cp\u003eThe symptom changes and long-term side effects before and after radiotherapy are presented in Table 5. Notably, symptomatic improvements were observed in diplopia (33/50, 66.0%), proptosis (33/52, 63.5%), visual acuity (32/58, 55.2%), and extraocular movements (30/45, 66.7%) among the patients. As for the long-term side effects of radiotherapy, the incidences of dry eye syndrome and lens opacities were reported at 3.4% (2/58) and 1.7% (1/58), respectively.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBenign orbital diseases, while not inherently life-threatening, can significantly compromise visual function by affecting critical structures such as the optic nerve, extraocular muscles, or cornea (3, 4). The best clinical management of patients diagnosed with OID remains uncertain, despite various treatment modalities that have demonstrated efficacy (4). As an alternative option to OID, orbital radiotherapy has shown potential in alleviating orbital inflammation and improving visual symptoms in numerous studies, however, its efficacy remains a subject of debate (14, 15). To address this ambiguity, our study aimed to assess the effectiveness of radiotherapy for for refractory, corticosteroid-resistant OID patients based on several key outcome measures. Our primary focus was on the patient\u0026apos;s ability to taper corticosteroids without experiencing further exacerbations of orbitopathy symptoms, serving as a crucial indicator of treatment efficacy. Additionally, we evaluated changes in specific symptoms such as diplopia, proptosis, visual acuity, and extraocular movements before and after radiotherapy. Furthermore, we examined long-term side effects, with a particular emphasis on dry eye syndrome and lens opacities. By comprehensively analyzing these parameters, we aimed to provide valuable insights into the overall effectiveness and safety profile of radiotherapy as a treatment option for OID, ultimately guiding clinical decision-making and improving patient outcomes.\u003c/p\u003e\n\u003cp\u003eIn our study, 89.7% of patients on corticosteroids had a significant reduction in corticosteroid requirements after orbital VMAT. Among these patients, 55.2% were able to discontinue corticosteroid use entirely, and 34.5% experienced reductions in corticosteroid dosage. This aligns with previous studies that have used corticosteroid requirements as a primary measure of radiotherapy effectiveness at specific time points (18, 20). Furthermore, our study reports relatively low incidences of dry eye syndrome (3.4%) and lens opacities (1.7%) among the patient population. These findings highlight the role of radiotherapy help stabilize the disease process and minimize the duration of corticosteroid therapy and its acceptable side effects. Previous reports have also established the efficacy of the 20 Gy in 10 fractions as the most efficacious and minimally toxic treatment dose (9, 18). However, other reports have suggested doses less than 20 Gy are sufficient for patients with predominantly soft tissue signs without ocular dysmotility (16). Our study, with a prescription of 20~30 Gy depending on the severity of symptoms, showed a highly favorable outcome. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOrbital radiotherapy\u0026nbsp;offers an advantage over surgery by preserving eye structure, potentially leading to a better appearance after treatment. Historically, conventional radiotherapy or 3D-CRT was commonly employed for OID treatment but lacked dose-modulating techniques. In one approach, protecting the lenses involved forced avoidance, which resulted in inadequate dose coverage of the target area, while in the other approach, aimed at ensuring adequate target coverage, which runed the risk of overexposure the lenses.\u0026nbsp;In a study by Matthiesen (21), a dose of 20 Gy in 10 fractions was delivered using two opposing lateral 6-MV fields. Notably, they reported a 12% incidence of dry eye syndrome. In our investigation, we applied a 5~10 mm expansion to generate the LA region around the lenses, and we delineated the PTV with a 3 mm margin excluding the LA region, which effectively reducing forced avoidance in\u0026nbsp;opposing lateral fields.\u0026nbsp;With the advanced orbital VMAT, we achieved a steeper dose gradient between the tumor target and OARs in our study, in which we set strict dose constraints with D\u003csub\u003emax\u0026nbsp;\u003c/sub\u003eof lenses\u0026nbsp;\u0026le;\u0026nbsp;6Gy and\u0026nbsp;PTV coverage \u0026ge; 95%. Our orbital VMAT plans yielded a D\u003csub\u003emax\u003c/sub\u003e of 5.4 Gy to the lenses and 95.8% average PTV coverage, contributing to low incidences of dry eye syndrome (3.4%) and lens opacities (1.7%), which was consistent with the findings by Li (22).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThus, our meticulous delineation of PTV, prescription of dose, and dose constraints on OARs proved effective in minimizing radiation-induced side effects while maintaining treatment efficacy. These results underscore the importance of adopting advanced radiotherapy techniques like VMAT in the management of OID, highlighting the potential for improved patient outcomes and quality of life. Further studies are warranted to explore the long-term efficacy and safety of this approach, as well as its impact on patient-reported outcomes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHowever, there are several limitations to our retrospective analysis: (1) The number of cases is limited to just over 50, suggesting the need for larger sample sizes in future follow-up studies. (2) Retrospective studies are inherently prone to selection bias, and unidentified confounding factors may influence the results. (3) The therapeutic dose ranges from 20 to 30 Gy, lacking uniformity, and the optimal radiotherapy dose remains uncertain, warranting further investigation through prospective trials. Therefore, prospective studies with well-defined cohort characteristics and outcome definitions are essential.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOrbital radiotherapy has shown promising results in improving visual symptoms and reducing the dependence on corticosteroids in patients with OID. It provides an alternative treatment option for patients who cannot tolerate or have contraindications to prolonged corticosteroid therapy. The use of radiotherapy has demonstrated acceptable side effects, although long-term effects still need to be monitored and evaluated through further follow-up. Larger and well-designed prospective trials are warranted to establish standardized protocols and guidelines for the radiotherapy management of OID.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eOID: Orbital inflammatory diseases; GO: Graves\u0026rsquo; ophthalmopathy; OP: Orbital pseudotumor; IgG4-ROD: IgG4-related ophthalmic disease; VMAT: Volumetric-modulated arc therapy; 3D-CRT:\u0026nbsp;Three-dimensional conformal radiation\u0026nbsp;therapy; MRIs:\u0026nbsp;Magnetic resonance images; CTV: Clinical target volume; OARs: Organs at risk; LA: Lenses avoidance; PTV: Planning target volume; MLC: Multileaf collimators; DVH: Dose-volume histogram; Vp: Volume receiving the prescribed dose; Dmax: the maximum dose; D\u003csub\u003e98%\u003c/sub\u003e and D\u003csub\u003e2%\u003c/sub\u003e: the dose received by 98% of the PTV volume; D\u003csub\u003e2%\u003c/sub\u003e: the dose received by 2% of the PTV volume.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the local ethics committee of the Sixth Affiliated Hospital (2023ZSLYEC-084). We confirm that all methods were carried out under relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patients gave their informed consent for the use of the data for research purposes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used during the current study are available from the corresponding author on reasonable request\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the program of Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYM: Methodology, Writing; HYC: Conceptualization, Data Curation; FJH: Preparation of figures and tables; XLP: Methodology. JZ and FH: Methodology, Writing. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMauriello JA Jr, Flanagan JC. Management of orbital inflammatory disease. A protocol. Surv Ophthalmol. 1984;29(2):104\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLutt JR, Lim LL, Phal PM, et al. Orbital inflammatory disease. Semin Arthritis Rheum. 2008;37(4):207\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePakdaman MN, Sepahdari AR, Elkhamary SM. Orbital inflammatory disease: Pictorial review and differential diagnosis. World J Radiol. 2014;6(4):106\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYuen SJ, Rubin PA. Idiopathic orbital inflammation: distribution, clinical features, and treatment outcome. Arch Ophthalmol. 2003;121(4):491\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMod H, Jha AK. Review of radiation therapy in benign ocular diseases. J Nepal Health Res Counc. 2014;12(27):130\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFardet L, Flahault A, Kettaneh A, et al. Corticosteroid-induced clinical adverse events: frequency, risk factors and patient's opinion. Br J Dermatol. 2007;157(1):142\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoulanouar L, Grunenwald S, Imbert P, et al. Effect of orbital radiotherapy on the outcome of surgical orbital decompression for thyroid-associated orbitopathy (TAO): a retrospective study in 136 patients. Endocrine. 2020;67(3):605\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMendenhall WM, Lessner AM. Orbital pseudotumor. Am J Clin Oncol. 2010;33(3):304\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmitt MC, Donaldson SS. Radiation therapy for benign disease of the orbit. Semin Radiat Oncol. 1999;9(2):179\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFionda B, Pagliara MM, Lancellotta V, et al. The Role of Radiotherapy in Orbital Pseudotumor: A Systematic Review of Literature. Ocul Immunol Inflamm. 2022;30(5):1162\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrummel MF, Terwee CB, Gerding MN, et al. A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves' ophthalmopathy. J Clin Endocrinol Metab. 2004;89(1):15\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMourits MP, Kempen-Harteveld ML, Garc\u0026iacute;a MB, et al. Radiotherapy for Graves' orbitopathy: randomised placebo-controlled study. Lancet. 2000;355(9214):1505\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStiebel-Kalish H, Robenshtok E, Hasanreisoglu M, et al. Treatment modalities for Graves' ophthalmopathy: systematic review and metaanalysis. J Clin Endocrinol Metab. 2009;94(8):2708\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGorman CA. Radiotherapy for Graves\u0026rsquo; ophthalmopathy: results at one year. Thyroid. 2002;12(3):251\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeldon SE. Radiation therapy for Graves' ophthalmopathy: trick or treat? Ophthalmology. 2001;108(9):1521\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatuszak MM, Yan D, Grills I, et al. Clinical applications of volumetric modulated arc therapy. Int J Radiat Oncol Biol Phys. 2010;77(2):608\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHodapp N, The ICRU. Report 83: prescribing, recording and reporting photon-beam intensity-modulated radiation therapy (IMRT). Strahlenther Onkol;188(1):97\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHahn E, Laperriere N, Millar BA, et al. Orbital radiation therapy for Graves' ophthalmopathy: measuring clinical efficacy and impact. Pract Radiat Oncol. 2014;4(4):233\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown PD, Gondi V, Pugh S, et al. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol. 2020;38(10):1019\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrabhu RS, Liebman L, Wojno T, et al. Clinical outcomes of radiotherapy as initial local therapy for Graves\u0026rsquo; ophthalmopathy and predictors of the need for post-radiotherapy decompressive surgery. Radiat Oncol. 2012;19:7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatthiesen C, Thompson JS, Thompson D, et al. The efficacy of radiation therapy in the treatment of Graves' orbitopathy. Int J Radiat Oncol Biol Phys. 2012;82(1):117\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi YJ, Luo Y, Xie XQ, et al. The efficacy of intensity modulated radiation therapy in treating thyroid-associated ophthalmopathy and predictive factors for treatment response. Sci Rep. 2017;7(1):17533.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\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\u003ePatient and disease characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemales/males, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (47.2) /19 (52.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge(y), median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (27\u0026ndash;68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCTV volume, cm\u003csup\u003e3\u003c/sup\u003e, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69.26 (25.22\u0026ndash;76.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLocation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft eye: 0\u003c/p\u003e \u003cp\u003eRight eye: 2\u003c/p\u003e \u003cp\u003eBoth eyes: 34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemales/males, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (52.4) /10 (47.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge(y), median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (20\u0026ndash;58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCTV volume, cm\u003csup\u003e3\u003c/sup\u003e, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.61 (22.91\u0026ndash;64.87)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLocation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft eye:5\u003c/p\u003e \u003cp\u003eRight eye:11\u003c/p\u003e \u003cp\u003eBoth eyes:5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgG4-ROD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemales/males, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (33.3) /2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge(y), median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (34\u0026ndash;51)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCTV volume, cm\u003csup\u003e3\u003c/sup\u003e, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.58 (32.12\u0026ndash;66.65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLocation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLeft eye: 1\u003c/p\u003e \u003cp\u003eRight eye: 0\u003c/p\u003e \u003cp\u003eBoth eyes: 2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e GO, graves\u0026rsquo; ophthalmopathy; OP, orbital pseudotumor; IgG4-ROD, IgG4-related ophthalmic disease; CTV, clinical target volume.\u003c/p\u003e\n \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\u003eRadiotherapy planning optimization protocol (30 Gy/15f, for example)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eName of Structure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDosimetric Parameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePer Protocol\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNotes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTV_30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003e2%\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;37.5 Gy \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to hottest 2% of PTV_30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003e98%\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;25 Gy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to 98% of PTV_30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eV\u003csub\u003e30Gy\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;95%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVolume receiving prescription dose of 30 Gy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLens (Left side) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;6 Gy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to hottest 0.03-cc volume of left lens\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLens (Right side) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;6 Gy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to hottest 0.03-cc volume of right lens\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEyeball (Left side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;37.5 Gy \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to hottest 0.03-cc volume of left eyeball\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emean\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;25 Gy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean dose to left eyeball\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEyeball (Right side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;37.5 Gy \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to hottest 0.03-cc volume of right eyeball\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emean\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;25 Gy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean dose to right eyeball\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptic nerve (Left side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;37.5 Gy \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to hottest 0.03-cc volume of left optic nerve\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptic nerve (Right side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;37.5 Gy \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to hottest 0.03-cc volume of right optic nerve\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHippocampi (Left side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;16 Gy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to hottest 0.03-cc volume of left hippocampi\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003e100%\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;9 Gy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to 100% of left hippocampi\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHippocampi (Right side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;16 Gy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to hottest 0.03-cc volume of right hippocampi\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003e100%\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;9 Gy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDose to 100% of right hippocampi\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e PTV, planning target volume; D, dose; cc, cubic centimeters.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 37.5 Gy is 125% of the prescription dose.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u0026nbsp;\u003c/sup\u003eThere are no specified dose parameters for the lens avoidance region because this region represents a transition region for dosing.\u003c/p\u003e\n \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTarget coverage and OARs sparing statistical results\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStructures\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDosimetric Parameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTV_\u003csub\u003eP\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eV\u003csub\u003eP\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e95.80%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eV\u003csub\u003e125%\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.26%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLens (Left side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLens (Right side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEyeball (Left side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emean\u003c/sub\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEyeball (Right side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emean\u003c/sub\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptic chiasm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptic nerve (left side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptic nerve (Right side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral hippocampi (Left side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003e100%\u003c/sub\u003e(Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral hippocampi (Right side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003emax\u003c/sub\u003e (Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD\u003csub\u003e100%\u003c/sub\u003e(Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \n\u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e PTV, planning target volume; D, dose; cc, cubic centimeters.\u003c/p\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorticosteroid therapy post orbital radiotherapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGO (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOP (n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIgG4-ROD (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOverall(n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAble to discontinue Corticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20(58.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11(52.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1(33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e32 (55.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnable to discontinue Corticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14(41.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10(47.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2(66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26 (44.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients decrease in steroid dose in those who were unable to fully reduce their corticosteroid dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9(26.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9(42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2(66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e20 (34.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponded to radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29 (85.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20 (95.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e52 (89.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFailed radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5(14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1(4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \n\u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e GO, graves\u0026rsquo; ophthalmopathy; OP, orbital pseudotumor; IgG4-ROD, IgG4-related ophthalmic disease.\u003c/p\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSymptom outcomes and long-term side effects post orbital radiotherapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGO (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOP (n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIgG4-ROD (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOverall (n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSymptom outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiplopia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (77.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33 (66.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnchanged\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 (24.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWorsened\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProptosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (58.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (75.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33 (63.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnchanged\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (38.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18 (34.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWorsened\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDecreased visual acuity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (52.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32 (55.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnchanged\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (44.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (38.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24 (41.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWorsened\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRestricted extraocular movements\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (65.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (70.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnchanged\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (30.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (23.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (28.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWorsened\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLong-term side effects\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDry eye syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2(3.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLens opacities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations:\u003c/em\u003e GO, graves\u0026rsquo; ophthalmopathy; OP, orbital pseudotumor; IgG4-ROD, IgG4-related ophthalmic disease.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Orbital volumetric-modulated arc therapy, Orbital inflammatory diseases, Radiotherapy plan design, Clinical efficacy, Prognosis","lastPublishedDoi":"10.21203/rs.3.rs-4614680/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4614680/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eOrbital inflammatory diseases (OID), including Graves\u0026rsquo; ophthalmopathy (GO), orbital pseudotumor (OP), and IgG4-related ophthalmic disease (IgG4-ROD), often require prolonged corticosteroid therapy, which may lead to severe hormonal side effects. These diseases are notably refractory and resistant to corticosteroids. While opposing lateral-field radiotherapy has shown positive results, the potential of volumetric-modulated arc therapy (VMAT) to enhance efficacy and reduce side effects remains uncertain. This study evaluates the radiation dose, clinical efficacy, side effects, and outcomes of orbital VMAT in patients with refractory, corticosteroid-resistant OID.\u003c/p\u003e\u003ch2\u003eMethods and materials:\u003c/h2\u003e \u003cp\u003eA retrospective analysis was conducted on 58 patients with refractory, corticosteroid-resistant OID treated with orbital VMAT from November 2019 to July 2022. The primary endpoint was the reduction or cessation of corticosteroid use following radiotherapy, with secondary endpoints including improvements in ocular clinical symptoms (diplopia, proptosis, visual acuity, and extraocular movement) and long-term side effects.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe median target dose was 20 Gy, with an average lens irradiation dose of 5.4 Gy. Initially, all 58 patients received corticosteroids. After a median follow-up of 27.5 months, 89.7% (52/58) of patients responded positively to radiotherapy: specifically, 55.2% (32/58) completely tapered off corticosteroids, while 34.5% (20/58) reduced their dosage. Symptomatic improvements were observed in diplopia (66.0%), proptosis (63.5%), visual acuity (55.2%), and extraocular movements (66.7%). Regarding the long-term side effects of radiotherapy, incidences of dry eye syndrome and lens opacities were reported at 3.4% and 1.7%, respectively.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOrbital VMAT is an effective treatment for refractory, corticosteroid-resistant OID, reducing corticosteroid use and improving ocular symptoms with minimal side effects. Further prospective clinical trials are warranted to validate more appropriate VMAT doses and planning models, enhancing treatment outcomes without increasing radiotherapy side effects.\u003c/p\u003e","manuscriptTitle":"Radiotherapy for Refractory, Corticosteroid-Resistant Orbital Inflammatory Diseases: Plan Design, Clinical Efficacy, and Prognosis/Outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-18 20:45:24","doi":"10.21203/rs.3.rs-4614680/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bce7cbbc-f8f7-4993-8bb3-33ced229390c","owner":[],"postedDate":"July 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-26T11:54:01+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-18 20:45:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4614680","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4614680","identity":"rs-4614680","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}