Radiation-induced Optic Neuropathy Research Articles

Survival outcomes and toxicity profiles among patients with nonmetastatic nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) versus IMRT + carbon-ion radiotherapy: A propensity score-matched analysis.

To compare survival outcomes and toxic effects among patients with newly diagnosed nonmetastatic nasopharyngeal carcinoma (NPC) when treated with intensity-modulated radiotherapy (IMRT) versus IMRT + carbon-ion radiotherapy (CIRT). We performed a retrospective propensity score matching analysis (1:1) of patients treated with IMRT and IMRT + CIRT. Descriptive statistics were used to examine the baseline characteristics of the patients. Survival was estimated using the Kaplan-Meier method. Univariate and multivariable logistic regression analysis were used to identify the independent predictors of survival. We examined the association between risk factors and adverse events (AEs) using chi-square tests. Cox model and logistic regression were used to analyze AEs. Hundred and nine patients who received IMRT + CIRT were included and the median follow-up time was 20.6 months (range: 4.6-82 months). There were no statistically significant differences in locoregional failure-free survival, distant metastasis-free survival, disease-free survival, or overall survival between the two groups, but potentially better in IMRT + CIRT group (p > 0.05, respectively). Nodal boost was the only significant factor associated with LRFS and DFS on multivariable analysis. Thirty-seven patients (34.0%) developed grade 3 acute OMs and no grade 4 acute OMs were observed in IMRT + CIRT group. All patients in IMRT + CIRT group developed grade 1 dermatitis; while in the match group, 76 patients developed grade 1 dermatitis, 27 patients developed grade 2 dermatitis, 5 patients developed grade 3 dermatitis, 1 patient developed grade 4 dermatitis. IMRT + CIRT treatment was associated with a significant trend of lower grades of OM and dermatitis (p < 0.05, respectively). Any severe (i.e., grade 3) chronic AEs, such as xerostomia, skin fibrosis, temporal lobe necrosis, osteoradionecrosis, or radiation-induced optic neuropathy, was not observed. In this study, IMRT + CIRT was associated with significantly reduced acute toxicity burden compared with full course of IMRT, with excellent survival outcomes. Patients with persistent disease after treatment and treated with nodal boost had a worse outcome. More accurate assessments of IMRT + CIRT to primary nonmetastatic NPC patients will be imperative.

Treatment-Related Complications and Functional Results after Ruthenium-106 Brachytherapy in Small to Medium Size Uveal Melanomas (Part 2).

To analyze the treatment-related complications after ruthenium-106 brachytherapy in patients with uveal melanoma in terms of radiation-induced optic neuropathy, maculopathy and retinopathy, radiation-related vitreous hemorrhage, and retinal detachment, as well as secondary glaucoma and radiogenic cataract. In addition, the course of visual acuity was analyzed. This retrospective study included 608 patients treated with ruthenium-106 brachytherapy between January 2008 and December 2010 at the Department of Ophthalmology, University Hospital Essen. The follow-up time was 11 years. The occurrence of the radiation-induced complications was analyzed using the Kaplan-Meier method. Cox regression was used for univariate and multivariate risk factor analyses. Hazard ratios were calculated for each variable. Regarding the complications, 34% (N = 207) of the patients had no reported side effects or complications during follow-up. Radiation optic neuropathy was observed in 18.8% (N = 114) of the patients, with a median time to onset of 16 months (range: 3 - 78 months). Radiation maculopathy occurred in 8.2% (N = 50) after a median time of 17 months (range: 3 - 67 months). Radiation retinopathy was observed in 20.1% (N = 122), with a median time to onset of 21 months (range: 6 - 67 months). Secondary glaucoma developed in 9.7% of the patients (N = 53) and radiogenic cataract in 46.8% (N = 227). Vitreous hemorrhage (11.8%, N = 72) and scleral necrosis (2.1%, N = 13) occurred relatively rarely. The observed radiogenic complication rate is comparable with that reported in previous studies.

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 3mm 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 10years 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

PurposeTo observe the clinical and imaging characteristics of radiation-induced optic neuropathy (RION). MethodsWe 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. ResultsThe latency from radiotherapy to onset of visual loss ranged from 1 to 132 (36.33 ​± ​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 ​> ​0.05). ConclusionsThe 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.

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

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. 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". 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. 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.

Effects of two different radiotherapies for craniopharyngiomas using stereotactic radiosurgery/ stereotactic radiotherapy or fractionated stereotactic radiotherapy.

Numerous studies have reported about good tumor control with both stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) for residual and recurrent craniopharyngiomas, but no studies have reported on the appropriate use of different types of radiation modalities. This study aimed to report the outcomes of SRS/stereotactic radiotherapy (SRT) or FSRT and compare tumor control in a single center. From 2014 when TrueBeamTM STx with Novalis was introduced in our hospital to 2021, 21 patients underwent SRS/SRT or FSRT with gamma knife surgery (GKS) and Novalis. We have selected the radiation modalities considering mainly the distance of the optic nerve and chiasm. Imaging and clinical follow-up data were sent and reviewed. The mean age was 52 years and there were 11 men. Of the 21 total patients, three experienced SRS (GKS, 50% isodose 12-15 Gy), five underwent SRT (GKS or Novalis, 19.5-24 Gy 3 fractions), and 13 patients underwent FSRT (Novalis, 54 Gy 30 fractions). The median follow-up was 32.6 (range 17-44) months after SRS/SRT and 34.0 (range 4-61) months after FSRT. In the SRS/SRT group, the mean tumor volume decreased from 1.103 to 0.131 cm3 (P < 0.01), and in the FSRT group, from 3.015 to 1.012 cm3 (P < 0.01). No radiation-induced optic neuropathy and other acute toxicity occurred. Craniopharyngioma can be expected to have very good tumor control by selecting SRS/SRT or FSRT depending on the distance between the optic nerve and the tumor.

Surgery for clinoidal meningiomas with cavernous sinus extension: Near-total excision and chiasmopexy

BackgroundThe main factors limiting the extent of resection for clinoidal meningiomas are cavernous sinus extension and vessel adventitia involvement. The proximity to the optic apparatus and the risk of radiation-induced optic neuropathy often prevents many surgeons from proposing adjuvant radiosurgery.MethodWe describe a simple technical solution that is to place a fat graft between the optic apparatus and the residual tumor to maintain the distance gained at surgery and facilitates the identification of anatomic structures.ConclusionThis technique allows to deliver optimal therapeutic doses to the residue reduces the dose received by the optic nerve below 8 Gy.

Clinical and radiologic outcomes after stereotactic radiosurgery for meningiomas in direct contact with the optic apparatus: an international multicenter study.

Resection of meningiomas in direct contact with the anterior optic apparatus carries risk of injury to the visual pathway. Stereotactic radiosurgery (SRS) offers a minimally invasive alternative. However, its use is limited owing to the risk of radiation-induced optic neuropathy. Few SRS studies have specifically assessed the risks and benefits of treating meningiomas in direct contact with the optic nerve, chiasm, or optic tract. The authors hypothesized that SRS is safe for select patients with meningiomas in direct contact with the anterior optic apparatus. The authors performed an international multicenter retrospective analysis of 328 patients across 11 institutions. All patients had meningiomas in direct contract with the optic apparatus. Patients were followed for a median duration of 56 months after SRS. Neurological examinations, including visual function evaluations, were performed at follow-up visits. Clinical and treatment variables were collected at each site according to protocol. Tumor volumes were assessed with serial MR imaging. Variables predictive of visual deficit were identified using univariable and multivariable logistic regression. SRS was the initial treatment modality for 64.6% of patients, and 93% of patients received SRS as a single fraction. Visual information was available for 302 patients. Of these patients, visual decline occurred in 29 patients (9.6%), of whom 12 (41.4%) had evidence of tumor progression. Visual decline in the remaining 17 patients (5.6%) was not associated with tumor progression. Pre-SRS Karnofsky Performance Status predicted visual decline in adjusted analysis (adjusted OR 0.9, 95% CI 0.9-1.0, p < 0.01). Follow-up imaging data were available for 322 patients. Of these patients, 294 patients (91.3%) had radiographic evidence of stability or tumor regression at last follow up. Symptom duration was associated with tumor progression in adjusted analysis (adjusted OR 1.01, adjusted 95% CI 1.0-1.02, adjusted p = 0.02). In this international multicenter study, the vast majority of patients exhibited tumor control and preservation of visual function when SRS was used to treat meningioma in direct contact with the anterior optic pathways. SRS is a relatively safe treatment modality for select patients with perioptic meningiomas in direct contact with the optic apparatus.

Long-Term Evaluation and Normal Tissue Complication Probability (NTCP) Models for Predicting Radiation-Induced Optic Neuropathy after Intensity-Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma: A Large Retrospective Study in China.

Purpose To quantify the long-term evaluation of optic chiasma (OC) and/or optic nerve(s) (ONs) and to develop predictive models for radiation-induced optic neuropathy (RION) in nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT). Methods and Materials A total of 3,662 patients' OC/ONs with full visual acuity and dosimetry data between 2010 and 2015 were identified. Critical dosimetry predictors of RION were chosen by machine learning and penalized regression for survival. A nomogram containing dosimetry and clinical variables was generated for predicting RION-free survival. Results The median follow-up was 71.79 (2.63–120.9) months. Sixty-six eyes in 51 patients (1.39%) developed RION. Two patients were visual field deficient, and 49 patients had visual acuity of less than 0.1 (20/200). The median latency time was 36 (3–90) months. The 3-, 5-, and 8-year cumulative incidence of RION was 0.78%, 1.19%, and 1.97%, respectively. Dmax was the most critical dosimetry variable for RION (AUC: 0.9434, the optimal cutoff: 64.48 Gy). Patients with a Dmax ≥64.48 Gy had a significantly higher risk of RION (HR = 102.25; 95%CI, 24.86–420.59; P < 0.001). Age (>44 years) (HR = 2.234, 95% CI = 1.233–4.051, p = 0.008), advanced T stage (T3 vs. T1-2: HR = 7.516, 95% CI = 1.725–32.767, p=0.007; T4 vs. T1-2: HR = 37.189, 95% CI = 8.796–157.266, P < 0.001), and tumor infiltration/compression of the OC/ONs (HR = 4.572, 95% CI = 1.316–15.874, p=0.017) were significant clinical risk factors of RION. A nomogram comprising age, T stage, tumor infiltration/compression of the OC/ON, and Dmax significantly outperformed the model, with only Dmax predicting RION (C-index: 0.916 vs. 0.880, P < 0.001 in the training set; 0.899 vs. 0.874, P=0.038 in the test set). The nomogram-defined high-risk group had a worse 8-year RION-free survival. Conclusions In the IMRT era, Dmax <60 Gy is safe and represents an acceptable dose constraint for most NPC patients receiving IMRT. A reasonable trade-off for selected patients with unsatisfactory tumor coverage due to proximity to the optic apparatus would be Dmax <65 Gy. Caution should be exercised when treating elderly and advanced T-stage patients or those with tumor infiltration/compression of the OC/ON. Our nomogram shows strong efficacy in predicting RION.

Long‐term experience of one‐day stereotactic irradiation in patients with uveal melanoma

AbstractPurposeUveal melanoma (iris, ciliary body, choroid) is the most frequent intraocular malignant tumor in adults. One day session stereotactic radiosurgery (SRS) with 35.0 Gy is one of current treatment options. Radiation complications can lead to visual acuity reduction or secondary enucleation of the eye globe. Radiation‐induced optic neuropathy (RION) is a severe ocular complication developing in high‐risk patients with uveal melanoma after SRS.MethodsLong‐term analysis of 210 patients with intraocular uveal melanoma treated by SRS at linear accelerator LINAC in Slovakia by ‘One‐day session’ method: we analyzed association between the secondary enucleation and the presence of secondary glaucoma as well as the radiation‐induced optic neuropathy after SRS.ResultsThe median tumor volume at baseline was 0.3cm3 with range from 0.1 to 2.7 cm3. The therapeutic dose was 35.0Gy by 99% of DVH (dose volume histogram). Average overall survival after stereotactic irradiation was 1st year after SRS 95%, 2nd year 81%, in 5 years 80%.Secondary enucleation was necessary 17% patients due to secondary glaucoma. The presence of RION was significantly associated with a higher dose on the optic nerve (p = 0.0122 in invariable and 0.0039 in multivariable analysis, respectively). Importantly, the overall survival of patients who underwent secondary enucleation was not different from the survival of patients without enucleation (p = 0.691).ConclusionsSurvival rates at 5‐year interval and percentage of secondary enucleation due to complications after one‐day session linear accelerator irradiation are comparable to those achieved with other irradiation techniques (brachytherapy, proton beam irradiation).

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.

Assessment of Radiation-Induced Optic Neuropathy in a Multi-Institutional Cohort of Chordoma and Chondrosarcoma Patients Treated with Proton Therapy.

Simple SummaryProton therapy is an effective therapeutic option for the treatment of skull-base tumors that require high radiation doses to be controlled. On rare occasions, patients suffer from radiation-induced optic neuropathy (RION) to the detriment of their post-treatment quality-of-life. We have collected multi-institutional data of 289 skull-base patients having received high doses to the optic apparatus from proton therapy or proton–photon mixed treatments and have observed a RION incidence rate (all grades) of 4.2% (12). We have furthermore confirmed older age and hypertension as risk factors for the onset of this side effect, with tumor involvement or its proximity to the optic apparatus and repeated surgical procedures showing moderate association. Our findings were consolidated into a NTCP model that can support pre-treatment patient segmentation into risk groups and the planning of necessary treatment countermeasures. However, further data and validation are necessary to confirm validity of the model. Radiation-induced optic neuropathy (RION) is a rare side effect following radiation therapy involving the optic structures whose onset is, due to the low amount of available data, challenging to predict. We have analyzed a multi-institutional cohort including 289 skull-base cancer patients treated with proton therapy who all received >45 GyRBE to the optic apparatus. An overall incidence rate of 4.2% (12) was observed, with chordoma patients being at higher risk (5.8%) than chondrosarcoma patients (3.2%). Older age and arterial hypertension, tumor involvement, and repeated surgeries (>3) were found to be associated with RION. Based on bootstrapping and cross-validation, a NTCP model based on age and hypertension was determined to be the most robust, showing good classification ability (AUC-ROC 0.77) and calibration on our dataset. We suggest the application of this model with a threshold of 6% to segment patients into low and high-risk groups before treatment planning. However, further data and external validation are warranted before clinical application.

Clinical Characteristics and Post-Operative Complications as Predictors of Radiation Toxicity After Treatment With I125 Eye Plaque Brachytherapy for Uveal Melanomas

I125 Eye Plaque brachytherapy is the standard treatment for medium size uveal melanomas. As a result, most patients have late radiation toxicities (RTT) such as radiation-induced maculopathy (RM), radiation-induced neovascular glaucoma/iris neovascularization (RNGI) and radiation-induced optic neuropathy (RON) that result in vision loss. While tumor size, location and radiation dose have been identified as predictors of radiation toxicity, we hypothesize demographics, pre-treatment tumor characteristics and post-operative complications may also impact radiation toxicities.An IRB-approved retrospective chart review was performed from 2011-2019 to evaluate patients with posterior uveal melanomas who were treated with brachytherapy at a single institution in the Southeast with a large Hispanic population, with a minimum of 3 months follow-up. We collected patient demographics, pre-treatment tumor characteristics, tumor margin to fovea/optic disk and post-operative complications as potential predictors of RTT. RTT was defined as an event of RM, RNGI, or RON following plaque removal. Univariable analysis (UVA) and multivariable analysis (MVA) were performed using logistic regression model to examine the associations between study variables and the development of RTT. Odds ratios (ORs) and corresponding P-values were reported. All tests were two-sided and statistical significance was considered when P < 0.05. SAS version 9.4 and R version 4.0.8 3 were used for statistical analysis.A total of 262 patients were evaluated over 8 years. Median follow up was 33.5 months (range 3.02 - 97.31). 178 pts (67.9%) had RTT. 131 pts (50.0%) developed RM. 19 pts (7.3%) developed RNGI. 56 pts (21.4%) developed RO. 41 pts (15.8%) identified as Hispanic. UVA found shorter distance to fovea (OR = 0.97, P = 0.025), post-operative subretinal fluid/exudative retinal detachment (RD) (OR = 2.89, P = 0.002) and vitreous hemorrhage (OR = 3.73, P = 0.002) are associated with RTT and Hispanic ethnicity is not significantly associated with RTT when compared to non-Hispanics (OR = 1.54, P = 0.219). MVA found shorter distance to fovea (OR = 0.95, P = 0.004), post-operative subretinal fluid/exudative RD (OR = 3.14, P = 0.006) and vitreous hemorrhage (OR = 4.50, P = 0.003) are associated with increased RTT.These data suggest that shorter distance to fovea and post-operative complications such as subretinal fluid/exudative RD and vitreous hemorrhage are associated with increased risk of RTT. This study can serve as prognostic tools to better counsel patients on the risks and benefits of brachytherapy and allow for early intervention in the management of RTT. These data need to be validated in a prospective trial investigating post-operative complications and subsequent RTT after the treatment of posterior uveal melanomas.V.A. Peters: None. A. Gurayah: None. D. Kwon: None. W. Zhao: None. W. Jin: Stock; Vit Inc. Partnership; Vit Inc. N.V. Patel: None. A.M. Markoe: None. Z. Correa: None. M.T. Studenski: None. J. Harbour: None. S. Samuels: None.

No Light Perception Vision in Neuro-Ophthalmology Practice.

To determine differential diagnosis and visual outcomes of patients with no light perception (NLP) vision related to neuro-ophthalmic conditions. Retrospective case series of patients seen at tertiary neuro-ophthalmology practices. Patients were included if they had NLP vision any time during their clinical course. Outcome measures were final diagnosis, treatment, and visual outcome. Seventy-two eyes of 65 patients were included. The average age was 57.6 (range 18-93) years, and 58% were women. The Most common diagnosis (21 patients) was compressive optic neuropathy (CON) with meningioma being the most common culprit (12). Other diagnoses included optic neuritis (ON) (11 patients), infiltrative optic neuropathies (8), posterior ischemic optic neuropathy (7), nonarteritic anterior ischemic optic neuropathy (4), arteritic anterior ischemic optic neuropathy (3), ophthalmic artery occlusion (3), nonorganic vision loss (3), radiation-induced optic neuropathy (2), cortical vision loss (1), retinitis pigmentosa with optic disc drusen (1), and infectious optic neuropathy (1). Ten patients recovered vision: 7 ON, 2 infiltrative optic neuropathy, and 1 CON. Corticosteroids accelerated vision recovery in 7 of the 11 patients with ON to mean 20/60 (0.48 logMAR) over 9.0 ± 8.6 follow-up months. Eleven patients deteriorated to NLP after presenting with at least LP; their diagnoses included CON (3), ophthalmic artery occlusion (2), infiltration (2), ON (1), posterior ischemic optic neuropathy (1), arteritic anterior ischemic optic neuropathy (1), and radiation-induced optic neuropathy (1). NLP vision may occur because of various diagnoses. Vision recovery was mainly seen in patients with ON. Serious systemic conditions may present or relapse with NLP vision, which clinicians should consider as an alarming sign in patients with known malignancies.

The long-term outcome of CyberKnife-based stereotactic radiotherapy for central skull base meningiomas: a single-center experience.

Few reports exist demonstrating the effects of stereotactic radiotherapy (SRT) on the central skull base meningiomas (CSMs). A retrospective analysis of 113 patients was performed. The median age was 62 (IQR 50-72) years old, and 78 patients (69%) were female. Upfront SRT was performed in 41 (36%), where 17 (15%) patients were asymptomatic. The other SRT was for postoperative adjuvant therapy in 32 (28%), and for the recurrent or relapsed tumors in 40 (35%) patients. Previous operation was done in 74 patients (66%). Among the available pathology in 46 patients, 37 (80%) were WHO grade I, 8 (17%) were grade II, and 1 (2%) was grade III. The median prescribed dose covered 95% of the planning target volume was 25 (IQR 21-25) Gy, and the median target volume was 9.5 (IQR 3.9-16.9) cm3. The median progression-free survival (PFS) was 48 (IQR 23-73) months and 84% and 78% were free of tumor progression at 5 and 10years respectively. The median follow-up was 49 (IQR 28-83) months. PFS was better in grade I than grade II (p = 0.02). No other baseline factors including the history of previous operation were associated with PD or PFS. Adverse events of radiation therapy were radiation-induced optic neuropathy (0.9%), and cerebral edema (4.4%). Asymptomatic cavernous carotid stenosis was found in three (2.7%), five (4.4%) underwent ventriculoperitoneal shunt placement for normal pressure hydrocephalus, and five (4.4%) died. SRT is useful for the management of CSMs with a low rate of adverse events.

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

ObjectiveWhether 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.MethodsIn 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.ResultsThe 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.ConclusionAppropriately 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.

Combining Clinical and Dosimetric Features in a PBS Proton Therapy Cohort to Develop a NTCP Model for Radiation-Induced Optic Neuropathy

Radiation-induced optic neuropathy (RION) is a rare, yet severe complication following radiation therapy for brain, head and neck, or skull-base tumors. Although several risk factors, such as age, metabolic syndrome, and delivered dose, have been identified, we aimed at expanding the understanding of the mechanisms of interplay regarding dosimetry and patient variables leading to the onset of RION with a focus on proton therapy. In this retrospective study, we have investigated proton-specific risk factors by comparing common phenomenological normal tissue complication probability models with a multivariate analysis that includes clinical features on a cohort of patients with skull-base and head and neck cancer treated with pencil beam scanning. Although predictive power of the Lyman-Kutcher-Burman and Poisson models was limited for this data set, the addition of clinical variables such as age, tumor involvement, hypertension, or sex remarkably increased model performance. Based on our assessment, the maximum dose in the optical apparatus is confirmed the most intuitive risk factor. However, above a certain dose threshold, clinical patient characteristics are the deciding factors for the onset of RION. We observed a tendency toward a volume effect that, if confirmed, would imply a benefit for high precision radiation therapy techniques such as proton therapy for the treatment of patients with high clinical risk for RION.

Chorioretinal Side Effects of Therapeutic Ocular Irradiation: A Multimodal Imaging Approach.

Radiation chorioretinopathy, radiation maculopathy, and radiation optic neuropathy are the major complications of ophthalmic radiotherapy. Optical coherence tomography (OCT) and OCT angiography (OCTA) are revolutionary imaging methods, allowing the visualization of the retinal cellular architecture and the retinal vascular system, respectively. In recent years this multimodal imaging approach has been applied to several retinal disease, but its role in the clinical characterization of retinal complications secondary to ophthalmic radiotherapy has not yet been defined. The purpose of this review is to critically evaluate the role of OCT and OCTA in the clinical assessment of radiation-induced chorioretinopathy, maculopathy, and optic neuropathy.

Clinical outcomes of fractionated stereotactic radiosurgery in treating perioptic meningiomas and schwannomas: A single-institutional experience

Application of radiosurgery to the newly diagnosed or post-operative residual perioptic lesions has been proved to improve tumor control. However, risk of vision injury induced by radiosurgery may increase substantially if the radiation dose is too high or tumor is close to the optic apparatus. The purpose of this study was to evaluate the safety and the effectiveness of fractionated stereotactic radiosurgery (FSRS) for perioptic tumors. We retrospectively analyzed 60 consecutive patients with 53 meningiomas and 7 schwannomas treated with FSRS between October 2007 and February 2020. We administered a marginal dose of 6–7 Gy (mean 6.8 Gy) per fraction and delivered 3 fractions in 3 consecutive days. The median tumor volume was 6.31 cm3 (range 0.3–58.23 cm3). The mean minimum lesion-optic distance (MLOD) is 0.85 mm (range 0–3 mm). After mean follow-up period of 69.6 months (range 6.82–156.32 months; median 58.9 months), the tumor control rates at 1, 3, 5, 8 and 13 years were 98.3%, 93.4%, 90.60%, 88.4% and 88.4%, respectively. Four out of the 60 tumors (6.7%) experienced a transient volume increase after FSRS. None of the patients developed visual impairment related to radiation induced optic neuropathy (RION) after FSRS. In conclusion, FSRS offers an alternative treatment option in treating perioptic meningiomas and schwannomas with acceptable tumor control rates and good visual preservation in the present study.

Cdk5-mediated Drp1 phosphorylation drives mitochondrial defects and neuronal apoptosis in radiation-induced optic neuropathy

Radiation-induced optic neuropathy (RION) is a devastating complication following external beam radiation therapy (EBRT) that leads to acute vision loss. To date, no efficient, available treatment for this complication, due partly to the lack of understanding regarding the developmental processes behind RION. Here, we report radiation caused changes in mitochondrial dynamics by regulating the mitochondrial fission proteins dynamin-related protein 1 (Drp1) and fission-1 (Fis1). Concurrent with an excessive production of reactive oxygen species (ROS), both neuronal injury and visual dysfunction resulted. Further, our findings delineate an important mechanism by which cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of Drp1 (Ser616) regulates defects in mitochondrial dynamics associated with neuronal injury in the development of RION. Both the pharmacological inhibition of Cdk5 by roscovitine and the inhibition of Drp1 by mdivi-1 inhibited mitochondrial fission and the production of ROS associated with radiation-induced neuronal loss. Taken together, these findings may have clinical significance in preventing the development of RION.