Prospective assessment of peripapillary microvasculature using optical coherence tomography angiography in para-optic intracranial and sinonasal tumors treated with proton therapy.

PURPOSE: Radiation-induced optic neuropathy (RION) is rare but may lead to blindness. The mechanisms by which this occurs include endothelial and neuronal damage, but RION has been assessed very little in the case of extraocular tumors treated with high-energy proton therapy, the use of which is expanding worldwide. We assessed peripapillary microvascular changes by optical coherence tomography angiography (OCT-A) in patients undergoing high-energy proton therapy for para-optic intracranial or head and neck tumors. MATERIALS AND METHODS: In this prospective institutional review board approved study, patients receiving>40Gy_RBE maximal PBT dose to their optic nerve between 2018 and 2020 underwent quantitative OCT-A analyses. ImageJ software was used to assess changes in the peripapillary superficial vascular complex (SVC) using vascular area density (VAD), vessel length density (VLD) and fractal dimension (FDsk). Uni- and multivariate analyses were performed. RESULTS: Of 47 patients (78 eyes) with 29±6 months of follow-up (range 18-42), 29 patients (61.7%) had previously undergone surgery and 18 (32.1%) had microvascular abnormalities prior to proton therapy. Total radiotherapy dose was the most relevant factor in decreased peripapillary microvasculature. Duration of follow-up was associated with lower VAD (P=0.005) and mean retinal nerve fiber layer (RNFLm) thickness also decreased. There was no significant correlation between OCT-A changes and mean visual defect. CONCLUSION: Peripapillary microvasculature changes may occur from tumor compression or surgery and proton therapy for extraocular tumors. OCT-A may provide quantitative and mechanistic insights into RION before the occurrence of clinical symptoms.

Radiation Optic Neuropathy: Management Options.

Background: Radiation optic neuropathy may be one side effect of ionizing radiation exposure to the eye found in a minority of patients. It is generally devastating for visual function and has been the subject of a small but growing literature with respect to its pathophysiology, treatment, and expected outcomes. Summary: Clinical features include optic disc edema, peripapillary hemorrhages, cotton wool spots, and hard exudates. Visual acuity is generally significantly reduced. Treatment has been attempted with outcomes that have not been assessed by randomized trials. Observation may be indicated in addition to treatment. Key Messages: Radiation optic neuropathy is known to generally be devastating to vision though an uncommon side effect of radiation. Treatment has been attempted with mixed results.

Promising Outcomes in Acromegaly Patients Receiving CyberKnife Stereotactic Hypofractionated Radiotherapy.

BACKGROUND: The primary treatment for patients with acromegaly has traditionally been transsphenoidal surgery, with decreasing reliance on radiotherapy (RT) due to advancements in pharmacotherapy (PT). Despite these advancements, a substantial portion of patients still face persistent acromegaly, necessitating novel treatment approaches. This study investigates the role of CyberKnife Stereotactic Hypofractionated Radiotherapy (CK-HFRT) in persistent acromegaly. OBJECTIVE: The primary objective was to assess the impact of CK-HFRT on endocrine remission (ER) rates while maintaining acceptable toxicity levels. METHODS: The study retrospectively analyzed 31 consecutive patients with acromegaly who received CK-HFRT following multiple unsuccessful surgeries and prolonged PT without ER. Various CK-HFRT dose fractionation regimes were administered, and dose volume histograms were evaluated. Tumor control, cured disease (CD), endocrine remission (ER) rates, and overall survival were estimated at a median follow-up of 62 months. Acute and late toxicity, including pituitary insufficiency and radiation-induced optic neuropathy (RION), were also assessed. RESULTS: At 62 months of follow-up, the study group demonstrated excellent tumor control with 100% nonprogressive adenomas. Endocrine remission was achieved in 86.7% of patients, with a 22.4% CD rate at five years. Pituitary insufficiency occurred in 32.3% of patients, and no cases of RION were reported. The study observed three deaths related to cardiovascular diseases, all in patients receiving PT. Overall survival at five years was 79.2%. CONCLUSION: CyberKnife stereotactic hypofractionated radiotherapy, as an adjunct to PT, provides a viable treatment option for patients with persistent acromegaly following unsuccessful surgeries. The therapy results in substantial ER rates and tumor control while minimizing the risk of permanent radiation-induced optic neuropathy. However, the decision to administer CK-HFRT should be individualized, considering the patient's overall condition and treatment history.

Intensity-Modulated Radiation Therapy for Bilateral Choroidal Metastases Involving Macula and Optic Disc.

This case report discusses the case of a 76-year-old woman with choroidal metastasis from breast cancer who was treated with intensity-modulated radiation therapy (IMRT). Choroidal metastasis is a common ocular tumor, and the occurrence of this condition has increased due to improved diagnostic tools and longer survival of metastatic patients. IMRT is an innovative radiation therapy technique that reduces complications and improves the curative effect by concentrating radiation on the tumor while minimizing exposure to surrounding tissues. In this case, the patient had a history of breast cancer and was undergoing chemotherapy when she presented with vision loss and blurred vision. Imaging tests confirmed choroidal metastasis, and IMRT was performed under the guidance of a radiation oncologist. After treatment, the choroidal lesion dramatically reduced in size, and the patient's vision improved. The text concludes that radiation therapy, including IMRT, is becoming more common as a treatment for ocular metastasis to improve vision and preserve the eye. When choosing radiation therapy, it is essential to consider the size of the tumor and the impact on surrounding tissues. IMRT is an effective treatment that enables precise and concentrated irradiation of the tumor tissue while minimizing exposure to normal tissues.

Single fraction and hypofractionated radiosurgery for perioptic meningiomas-tumor control and visual outcomes: a systematic review and meta-analysis.

Perioptic meningiomas, defined as those that are less than 3 mm from the optic apparatus, are challenging to treat with stereotactic radiosurgery (SRS). Tumor control must be weighed against the risk of radiation-induced optic neuropathy (RION), as both tumor progression and RION can lead to visual decline. We performed a systematic review and meta-analysis of single fraction SRS and hypofractionated radiosurgery (hfRS) for perioptic meningiomas, evaluating tumor control and visual preservation rates. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we reviewed articles published between 1968 and December 8, 2022. We retained 5 studies reporting 865 patients, 438 cases treated in single fraction, while 427 with hfRS. For single fraction SRS, the overall rate of tumor control was 95.1%, with actuarial rates at 5 and 10 years of 96% and 89%, respectively; tumor progression was 7.7%. The rate of visual stability was 90.4%, including visual improvement in 29.3%. The rate of visual decline was 9.6%, including blindness in 1.2%. For hfRS, the overall rate of tumor control was 95.6% (range 92.1-99.1, p < 0.001); tumor progression was 4.4% (range 0.9-7.9, p = 0.01). Overall rate of visual stability was 94.9% (range 90.9-98.9, p < 0.001), including visual improvement in 22.7% (range 5.0-40.3, p = 0.01); visual decline was 5.1% (range 1.1-9.1, p = 0.013). SRS is an effective and safe treatment option for perioptic meningiomas. Both hypofractionated regimens and single fraction SRS can be considered.

Clinical characteristics of radiation-induced optic neuropathy: A single-center retrospective study.

Purpose: To observe the clinical and imaging characteristics of radiation-induced optic neuropathy (RION). Methods: We retrospectively reviewed the clinical data of 43 patients (69 eyes) who were diagnosed with RION at the Chinese PLA General Hospital from 2010 to 2021. Results: The latency from radiotherapy to onset of visual loss ranged from 1 to 132 (36.33 â€‹± â€‹30.48) months. Optic disc pallor and optic disc edema were found in 27.0% (10/37) and 8.1% (3/37) of the eyes, respectively, within 2 months. After treatment, the best corrected visual acuity (BCVA) was restored in 24.6% (17/69) of the eyes and the final BCVA improved in 13.0% (9/69) of the eyes. An 82.5% (33/40) of the eyes with magnetic resonance imaging (MRI) showed enhancement of the affected optic nerve, mostly (69.7%) in the intracranial segment, and 36.4% (12/33) of the eyes with expansion and T2-high signals also showed enhancement of the affected optic nerve. The superior retinal nerve fiber layer (RNFL) and the outer circle superior quadrant (OS) of the inner limiting membrane to retinal pigment epithelium (ILM-RPE) layer thinned significantly during the first month. The center of the ILM-RPE layer thickened significantly during the first two months and the inner circle temporal quadrant (IT) of the ILM-RPE layer thickened significantly from the third to sixth month. The RNFL thinned significantly after 6 months except for the temporal quadrant, and the average inner circle superior quadrant (IS) and outer circle of the ILM-RPE layer thinned significantly after 6 months. There was no significant difference between hyperbaric oxygen therapy (HBOT) and high-dose intravenous methylprednisolone (IVMP) therapy in improving BCVA recovery or final BCVA (P â€‹> â€‹0.05). Conclusions: The structural damage of the RNFL and ILM-RPE layer occurred during the first month, the RNFL showed progressive thinning during the follow-up period, while the ILM-RPE layer showed thinning during the first month, thickening from the third to sixth month, and thinning after 6 months. There was a discrete region of enhancement of the optic nerve, often with expansion and high-T2 signals on MRI. HBOT and high-dose IVMP therapy were hardly effective for treating RION in the non-acute stage.

Effects and Assessment of the Optic Pathway After Management with Stereotactic Radiosurgery for Intracranial Tumors: A Comprehensive Literature Review.

Intracranial tumors are treated through a minimally invasive procedure called stereotactic radiosurgery (SRS), which uses precisely targeted radiation beams. When SRS is used to treat tumors in or near the optic pathway, which is responsible for transmitting visual information from the eyes to the brain, it is essential to assess the effects of treatment on visual function. The optic pathway is considered relatively radiation-sensitive, and high doses of radiation can lead to visual impairment or loss. Various methods can be used to assess the effects of SRS on the optic pathway, including visual acuity testing, visual field testing, and imaging studies. These assessments can be performed before and after treatment to track changes in visual function and detect potential complications or side effects. Assessing the optic pathway after management with SRS for intracranial tumors is essential to the treatment process to ensure that patients receive the best possible outcomes while minimizing the risk of complications. Close collaboration between the multidisciplinary team is often necessary to optimize treatment planning and monitoring of treatment response. In this review, we conducted an extensive analysis of the effects of radiation in patients with intracranial tumors after receiving radiotherapy.

Outcomes of systemic bevacizumab in radiation-induced optic neuropathy, case series.

PURPOSE: Optic neuropathy is a rare, delayed complication after radiation with no universally accepted treatment modality. We report the outcomes of 6 patients with radiation-induced optic neuropathy (RION) who were treated with systemic bevacizumab. METHODS: This is a retrospective series of 6 cases of RION, treated with intravenous (IV) bevacizumab. "Improved" or "worse" visual outcomes were defined as a change in best corrected visual acuity of ≥ 3 Snellen lines. Otherwise, the visual outcome was noted as "stable". RESULTS: In our series, RION was diagnosed 8 to 36 months after radiotherapy. IV bevacizumab was initiated as treatment within 6 weeks of the onset of visual symptoms in 3 cases and after 3 months in the other cases. Although no improvement in visual function was observed, stabilization of vision was noted in 4 of the 6 cases. In the other 2 cases, the level of vision declined from counting fingers to no light perception. In 2 cases, bevacizumab treatment was discontinued prior to completion of the planned course due to renal stone formation or worsening of renal disease. One patient developed ischemic stroke 4 months after bevacizumab completion. CONCLUSION: Systemic bevacizumab may stabilize vision in some patients with RION, though the limitations of our study do not allow us to draw this conclusion definitively. Therefore, the risks and potential benefits of using IV bevacizumab should be considered in each individual case.

Evaluation of Retinal and Optic Disc Vascular Changes and Retinal Nerve Fiber Layer Thickness in Patients with Nasopharyngeal Carcinoma Following Image Guided Intensity-Modulated Radiation Therapy Using Optical Coherence Tomography Angiography.

BACKGROUND: Radiation-induced optic neuropathy (RION) is one of the most important late complications during head and neck radiotherapy and is recognized usually between 2-9 years after RT. Our study aims to prospectively without baseline measurement evaluate retinal and optic disc vascular changes and retinal nerve fiber layer thickness (RNFL) using optical coherence tomography angiography (OCTA) in nasopharyngeal cancer (NPC) patients previously treated with intensity-modulated radiation therapy (IMRT) and with optic nerve doses are above 45 Gy. METHODS: Fourteen NPC patients and sixteen age-matched healthy control subjects were included in our study. A complete ophthalmological examination including the best-corrected visual acuity (BCVA), intraocular pressure, slit-lamp biomicroscopic, fundoscopic examination and OCTA were performed for all patients and healthy volunteers. OCTA findings of RT and control groups were compared and correlation analysis was performed to find the association between the radiation-related factors and OCTA findings. RESULTS: Inferior hemi disc, parafovea and perifovea superficial/deep vessel densities were were statistically significantly lower in RT patients. Negative correlations were found between Dmax of optic tract and both RNFL and vessel densities. Furthermore, there were negative correlations found between the Dmean of glob and vessel densities. CONCLUSION: Although none of the patients in our study had marked vision loss and retinal abnormalities with the examination, OCTA findings showed that perifoveal and parafoveal vascularity were statistically significantly affected due to the RT.

The Impact of Optic Nerve Movement on Intracranial Radiation Treatment.

Purpose: In radiotherapy, high radiation exposure to optic nerve (ON) can cause optic neuropathy or vision loss. In this study, we evaluated the pattern and extent of the ON movement using MRI, and investigated the potential dosimetric effect of this movement on radiotherapy. Methods: MRI was performed in multiple planes in 5 human subjects without optic pathway abnormalities to determine optic nerve motion in different scenarios. The subjects were requested to gaze toward five directions during MRI acquisitions, including neutral (straight forward), left/right (horizontal movement), and up/down (vertical movement). Subsequently, the measured displacement was applied to patients with peri-optic tumors to evaluate the potential dosimetric effect of this motion. Results: The motion of ON followed a nearly conical shape. By average, the anterior end of ONs moved with 10.8 ± 2.2 mm horizontally and 9.3 ± 0.8 mm vertically, while posterior end has negligible displacement. For patients who underwent stereotactic radiotherapy to a peri-optic tumors, the movement of ON in this measured range introduced non-negligible dosimetric effect. Conclusion: The range of motion of the anterior portions of the optic nerves is on the order of centimeters, which may need to be considered with extra attention during radiation therapy in treating peri-optic lesions.

A long-term survival case with proton beam therapy for advanced sphenoid sinus cancer with hypopituitarism.

Sphenoid sinus malignancies are rare diseases. Secondary hypopituitarism associated with sphenoid sinus malignancy is not well known. A 41-year-old male complained of right ptosis. Neurological findings revealed right oculomotor, trochlear and glossopharyngeal nerve palsy. Imaging diagnosis suggested a tumor that had spread bilaterally from the sphenoid sinus to the ethmoid sinus, nasopharynx and posterior pharyngeal space. Biopsy revealed squamous cell carcinoma (SCC). Based on these findings, a clinical diagnosis of SCC of the sphenoid sinus was made. Removal of the tumor without damaging nearby organs would have been difficult because the tumor extended to the bilateral optic nerves, optic chiasma and internal carotid artery, and surgeons, therefore, recommended proton beam therapy (PBT). Before PBT, the hypopituitarism occurred in the patient and we administered hydrocortisone and levothyroxine. During treating for hypopituitarism, we performed PBT with nedaplatin and 5-fluorouracil. The daily PBT fractions were 2.2 relative biological effectiveness (RBE) for the tumor received total dose of 81.4 Gy RBE. The acute side effect of grade 2 dermatitis according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Occurred after PBT. The patient needs to take hydrocortisone and levothyroxine, but he remains in complete remission 8 years after treatment without surgery or chemotherapy. Visual function is gradually declining, but there is no evidence of severe radiation-induced optic neuropathy.

Necrosis of the optic nerve and chiasm with safe radiation doses: Report of two rare cases.

INTRODUCTION: Radiation-induced optic neuropathy (RION) is still a devastating complication of brain and skull base radiation that has no effective treatment up until today, thus uttermost caution must be taken in treating patients that brain radiotherapy is needed. We present two cases of RION that happened in seemingly safe radiation doses. CASE DESCRIPTION: A 48-year-old female with a history of pleomorphic pituitary adenoma developed bilateral and painless loss of vision 10 months after radiation to the brain; the total radiation dose was 45 Gy in 25 fractions and no other risk factors of RION were found. Magnetic resonance imaging of the brain depicted bilateral prechiasmatic optic nerve enhancement with involvement of the optic chiasm. Treatment with high doses of corticosteroids was unsuccessful. A 62-year-old female with a history of lung adenocarcinoma and brain metastases presented with a 1-month history of decreased vision in both eyes. He had undergone whole-brain radiotherapy with a total dose of 30 Gy over 10 fractions and concurrent chemotherapy with cisplatin and pemetrexed. Brain magnetic resonance imaging (MRI) with contrast showed bilateral intracranial optic nerve enhancement. CONCLUSIONS: This is the second case report of RION in a patient with a history of brain radiotherapy and concurrent chemotherapy with pemetrexed. History of chiasmal compression, concurrent use of chemotherapeutic agents, and high fraction size (despite the safety of total radiation dose) were possible contributing risk factors to develop RION in our cases. Hence, adjusting the radiation dose according to the presence of these risk factors is recommended.

Analysis of clinical and imaging characteristics of radiation-induced optic neuritis / 中华眼底病杂志

Objective:To observe the clinical and imaging characteristics of radiation optic neuropathy (RION).Methods:A retrospective clinical study. A total of 43 patients (69 eyes) who were diagnosed with RION at the Chinese PLA General Hospital from 2010 to 2021 were included in this study. There were 23 males (36 eyes) and 20 females (33 eyes). The age of patients at the time of radiation therapy was 49.54±13.14 years. The main dose of radiotherapy for lesions was 59.83±14.12 Gy. Sixteen patients were treated with combined chemotherapeutic agents. The clinical details of best corrected visual acuity (BCVA) and color photography of the fundus were collected. Forty-six eyes underwent optical coherence tomography (OCT), visual field were examined in 30 eyes, magnetic resonance imaging (MRI) were performed in 40 eyes. The BCVA examination was performed using Snellen visual acuity chart, which was converted to minimum resolution angle logarithm (logMAR) visual acuity during recording. Hyperbaric oxygen therapy (HBOT) was performed in 10 patients (13 eyes), 9 patients (12 eyes) were treated with intravenous methylprednisolone (IVMP), 12 patients (23 eyes) were treated with HBOT combined with IVMP and control group of 12 patients (21 eyes) were only treated with basal treatment. And grouped accordingly. To observe the changes in onset, recovery, and final BCVA of the affected eye as well as thickness changes of the retinal nerve fiber layer (RNFL) of the optic disc and inner limiting membrane-retinal pigment epithelium (ILM-RPE) layer of the macular area, and final outcome of BCVA with different treatment modalities in affected eyes. The RNFL and ILM-RPE layer thicknesses were compared between patients with different disease duration as well as between treatment regimens using independent samples t-test. Results:Of the 43 cases, vision loss was monocular in 17 patients (39.53%, 17/43) and binocular in 26 patients (60.47%, 26/43). The latency from radiotherapy to onset of visual loss was 36.33±30.48 months. The duration of RION ranged from 1 week to 10 years, in which the disease duration of 37 eyes ≤2 months. Subacute visual acuity loss was present in 41 eyes. logMAR BCVA<1.0, 1.0-0.3, >0.3 were 45, 15, and 9 eyes, respectively. Optic disc pallor and optic disc edema were found in 10 (27.03%, 10/37), 3 (8.11%, 3/37) eyes, respectively, within 2 months. The superior RNFL [95% confidence interval ( CI) 2.08-66.56, P=0.038] and the outer circle of the inner limiting membrane to retinal pigment epithelium (ILM-RPE) (95% CI 4.37-45.39, P=0.021) layer thinned significantly during the first month. The center of the ILM-RPE layer thickened (95% CI-32.95--4.20, P=0.015) significantly during the first two months. The inner circle temporal quadrant of the ILM-RPE layer thickened (95% CI -42.22--3.83, P=0.022) significantly from the third to sixth month, and the RNFL except for the temporal quadrants and the average RNFL, inner circle superior quadrant and outer circle of the ILM-RPE layer thinned significantly after 6 months ( P<0.05). Among the 40 eyes that underwent MRI examination, 33 eyes (82.50%, 33/40) were affected by T1 enhancement of optic nerve, including 23 eyes (69.70%, 23/33) in intracranial segment; 12 eyes with thickening and long T2 signal (36.36%, 12/33). After treatment, BCVA was restored in 17 eyes (24.6%, 17/69) and final BCVA improved in 9 eyes (13.0%, 9/69). There was no significant difference between HBOT, IVMP and HBOT combined with IVMP therapy in improving BCVA recovery or final BCVA compared with the control group, respectively ( t=-1.04, 0.61, 1.31,-1.47, -0.42, 0.46; P>0.05). Conclusions:The structural damage of the RNFL and ILM-RPE layer occurred during the first month, the RNFL showed progressive thinning during the follow-up period, while the ILM-RPE layer showed thinning-thickening-thinning. MRI shows T1 enhancement of the optic chiasma and segments of the optic nerve, and the enhanced segments are usually accompanied by thickening and long T2. HBOT and IVMP have no obvious effect on RION.

Mimics of Optic Neuritis in Neuromyelitis Optica Spectrum Disorder: A Case Report.

The optic nerve can be involved in a myriad of pathologies underscoring the importance of ruling out both surgical as well as medical causes. Often, it is the temporal profile, clinical presentation and imaging that helps to establish the final diagnosis. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder involving the optic nerves and the spinal cord, which if promptly and adequately managed, may yield gratifying outcomes. We report an unusual presentation of NMOSD, mimicking a compressive optic neuropathy. A comprehensive review of the history, extensive investigations including brain and spinal cord imaging, and positive anti-aquaporin 4 antibodies helped in the definitive management.

Prospective Assessment of Early Proton Therapy-Induced Optic Neuropathy in Patients With Intracranial, Orbital or Sinonasal Tumors: Impact of A Standardized Ophthalmological Follow Up.

PURPOSE: Proton therapy (PT) can be a good option to achieve tumor control while reducing the probability of radiation induced toxicities compared to X-ray-based radiotherapy. However, there are still uncertainties about the effects of PT on the organs in direct contact with the irradiated volume. The aim of this prospective series was to report 6-month follow-up of clinical and functional optic neuropathy rates of patients treated by proton therapy using a standardized comprehensive optic examination. METHODS AND MATERIALS: Standardized ophthalmological examinations were performed to analyze subclinical anomalies in a systematic way before treatment and 6 months after the end of proton therapy with: Automatic visual field, Visual evoked potential (VEP) and optic coherence of tomography (OCT). RESULTS: From October 2018 to July 2020 we analyzed 81 eyes. No significant differences were found in the analysis of the clinical examination of visual functions by the radiation oncologist. However, considering VEP, the impairment was statistically significant for both fibers explored at 30'angle (p:0.007) and 60'angle (p <0.001). In patients with toxicity, the distance of the target volume from the optical pathways was more important with a p-value for 30'VEP at 0.035 and for 60'VEP at 0.039. CONCLUSIONS: These results confirm uncertainties concerning relative biological effectiveness of proton therapy, linear energy transfer appears to be more inhomogeneous especially in areas close to the target volumes. The follow-up of patients after proton therapy is not an easy process to set up but it is necessary to improve our knowledges about the biological effects of proton therapy in real life. Our study which will continue during the coming years, suggests that follow-up with in-depth examinations such as VEP as a biomarker could improve the detection of early abnormalities.

Loosening Neuro-Optic Structures Dosimetric Constraints Provides High 5-Year Local Recurrence-Free Survival With Acceptable Toxicity in T4 Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiotherapy.

OBJECTIVE: Whether the original dosimetric constraints of neuro-optic structures (NOS) are appropriate for patients with nasopharyngeal carcinoma (NPC) undergoing intensity-modulated radiotherapy (IMRT) remains controversial. The present study compared the survival rates and radiation-induced optic neuropathy (RION) occurrence between T4 NPC patients whose NOS were irradiated with a near maximum dose received by 2% of the volume (D2%) >55 Gy and ≤55 Gy. Moreover, the NOS dosimetric parameters and their correlation with RION occurrence were also evaluated. METHODS: In this retrospective study, 256 T4 NPC patients treated with IMRT between May 2009 and December 2013 were included. Patient characteristics, survival rates, dosimetric parameters, and RION incidence were compared between the D2% ≤55 Gy and D2% >55 Gy groups. RESULTS: The median follow-up durations were 87 and 83 months for patients in the D2% >55 Gy and D2% ≤55 Gy groups, respectively. The 5-year local recurrence-free survival rates were 92.0 and 84.0% in the D2% >55 Gy and D2% ≤55 Gy groups (P = 0.043), respectively. There was no significant difference in the 5-year overall survival (OS) between both groups (D2% >55 Gy, 81.6%; D2% ≤55 Gy, 79.4%; P = 0.586). No patients developed severe RION (Grades 3-5), and there was no significant difference (P = 0.958) in the incidence of RION between the two groups. The maximum dose of NOS significantly affected the RION incidence, with a cutoff point of 70.77 Gy. CONCLUSION: Appropriately loosening NOS dosimetric constraints in order to ensure a more sufficient dose to the target volume can provide a better 5-year local recurrence-free survival and acceptable neuro-optic toxicity in T4 NPC patients undergoing IMRT.

Radiation-induced impairment of optic nerve axonal transport in tree shrews and rats monitored by longitudinal manganese-enhanced MRI.

PURPOSE: Radiation-induced optic neuropathy (RION) is a serious complication that occurs after radiation therapy of tumors in the vicinity of the optic nerve, yet its mechanism and imaging features are poorly understood. In this study, we employed manganese-enhanced MRI (MEMRI) to assess optic nerve axonal transport in tree shrews and rats after irradiation. MATERIALS AND METHODS: A comparison of normal visual projections in tree shrews and rats was conducted by intravitreal MnCl2 injection followed by MRI. Adult male tree shrews and rats received a total dose of 20 Gy delivered in two fractions (10 Gy per fraction) within 5 days. Longitudinal MEMRI was conducted 5, 10, 20 and 30 weeks after radiation. At the end of observation, motor proteins involved in axonal transport were detected by western blotting, and the axon cytoskeleton was assessed by immunofluorescence. RESULTS: The eyeballs, lens sizes, vitreous volumes, optic nerves and superior colliculi of tree shrews were significantly larger than those of rats on MEMRI (P < 0.05). The Mn2+-enhancement of the optic nerve showed no significant changes at 5 and 10 weeks (P > 0.05) but decreased gradually from 20 to 30 weeks postirradiation (P < 0.05). The enhancement of the superior colliculus gradually decreased from 5 weeks to 30 weeks, and the decrease was most significant at 30 weeks (P < 0.05). The levels of the motor proteins cytoplasmic dynein-1, kinesin-1 and kinesin-2 in the experimental group were significantly decreased (P < 0.05). The immunofluorescence results showed that the α-tubulin, ß-tubulin and SMI 31 levels in the experimental groups and control groups were not significantly different (P > 0.05). CONCLUSION: Tree shrews show great advantages in visual neuroscience research involving MEMRI. The main cause of the decline in axonal transport in RION is an insufficient level of motor protein rather than damage to the axonal cytoskeletal structure. Longitudinal MEMRI can be used to detect changes in axonal transport function and to observe the relatively intact axon structure from the early to late stages after radiation administration.

Radiation-induced optic neuropathy after stereotactic and image guided intensity-modulated radiation therapy (IMRT).

BACKGROUND/PURPOSE: To quantify the risk of radiation-induced optic neuropathy (RION) after stereotactic/image-guided positioning and intensity-modulated radiotherapy (IMRT) with ≥50 Gy to the anterior visual pathway (AVP). METHODS: Patients irradiated with ≥50 Gy to the AVP using stereotactic/image-guided positioning between 2002 and 2011 in Mannheim were identified. Detailed dosimetric data were collected and patients or family members were retrospectively asked to rate visual acuity and visual disorders. RESULTS: 125 patients fulfilled the eligibility criteria. Average maximum equivalent point dose (Dmax-EQD-2[α/ß=1.6]) to the AVP was 53.1 ±â€¯3.9 Gy. 99 patients received ≥50 Gy bilaterally (chiasm or both optic nerves), resulting in 224 (99x2 bilateral plus 26 unilateral) visual-fields-at-risk (VFAR) for RION. Eighty-two patients provided pre/post-IMRT visual status information (n = 151 VFARs). Permanent visual deterioration occurred in 18 (22%) patients. In seven, visual deterioration was possibly related to radiotherapy (two-sided deterioration in one patient) for a crude incidence of 8.5% (7/82 patients) and 5.3% (8/151 VFARs). Two cases were caused by chronic keratitis/conjunctivitis; in five patients RION could not be excluded (one two-sided). In one of 13 patients with Dmax-EQD-2 > 58 Gy, RION could not be excluded. In all affected patients, visual acuity post-IMRT had decreased only mildly (1-2 points on the 5-point-scale). One patient with relevant baseline visual impairment (3/5) developed unilateral blindness (crude incidence of blindness on patient-/VFAR-level: 1.2% and 0.66%; competing risk-adjusted/actuarial 24-month incidence: patient/VFAR-level: 1.8% and 0.95%). CONCLUSION: Risk of RION was low in this cohort with accurate positioning and precise dosimetric information. Less conservative tolerance doses may be considered in patients with high risk of recurrence.

Predictors of the therapeutic effect of corticosteroids on radiation-induced optic neuropathy following nasopharyngeal carcinoma.

Radiation-induced optic neuropathy (RION) is a severe visual complication resulting from radiotherapy of the head and neck, which mostly occurs in patients with nasopharyngeal carcinoma (NPC) in the southern part of China. The mechanism of RION is unclear. Therefore, identifying risk factors for RION is an important step towards enhancing our understanding. In the current study, we retrospectively reviewed patients with NPC who were admitted to Sun Yat-Sen Memorial Hospital for visual loss between 2006 and 2017. The study included 38 participants (68 eyes) in the corticosteroid-effective group and 35 participants (64 eyes) in the corticosteroids-ineffective group. We analyzed potential risk factors for RION and developed a prediction model for the therapeutic effect of corticosteroid effect based on a random forests method. The prediction model showed a high accuracy with an area under the receiver operating characteristic curve of 0.932 (95% confidence interval = 0.889-0.975). Our results revealed that blood urea nitrogen (BUN) was significantly associated with RION and that RION patients with higher BUN levels responded better to corticosteroid treatment. Altogether, these results suggest that a prediction model, based on clinical factors, could be applied to estimate the therapeutic effect of corticosteroids on RION. Further investigation, however, is needed to confirm the study conclusion.

Radiation tolerance of the optic pathway in patients treated with proton and photon radiotherapy.

INTRODUCTION: Radiation-induced optic neuropathy (RION) is a complication of radiation therapy (RT) that causes blindness. We aimed to define the tolerance of the anterior optic pathway to fractionated RT and identify risk factors for RION. MATERIALS/METHODS: Patients with chordoma or chondrosarcoma of the skull base treated with proton and photon therapy between 1983 and 2013, who received a minimum of 30 Gy (relative biologic effectiveness [RBE]) to the anterior optic pathway were assessed. Optic neuropathy with radiographic correlation occurring ≥6 months after completion of RT in the absence of tumor recurrence or other probable cause was diagnosed as RION. RESULTS: Of 514 patients, 17 developed RION. With median follow-up of 4.8 years, cumulative incidence of RION was 1% among patients receiving <59 Gy (RBE) and 5.8% among patients receiving ≥60 Gy (RBE) to the optic pathway. Higher maximum point dose to the optic pathway (subhazard ratio [SHR] = 1.2, 95% CI 1.05-1.2, p = 0.001), older age (SHR = 1.1, 95% CI 1.02-1.08, p < 0.0005), and female sex (SHR = 16.3, 95% CI 2.2-122.4, p = 0.007) were statistically significant risk factors for RION in multivariate analysis. CONCLUSION: In our study cohort, rates of RION were very low with conventionally fractionated RT up to 59 Gy. At doses ≥60 Gy, there is an increased risk of RION, with greater risk for women and older patients.