Clinical, Pathologic, and Dosimetric Predictors of Head and Neck Lymphedema Following Definitive or Adjuvant Radiation Therapy for Head and Neck Cancer.

Purpose: Head and neck lymphedema (HNL) following radiation therapy for head and neck cancer (HNC) causes patient morbidity. Predicting individual patients' risk of HNL after treatment is challenging. We aimed to identify the demographic, disease-related, and treatment-related factors associated with external and internal HNL following treatment of HNC with definitive or adjuvant radiation therapy. Methods and Materials: Relevant clinical, pathologic, and dosimetric data for 76 consecutive patients who received definitive or adjuvant radiation ± chemotherapy were retrospectively collected from a single institution. Multivariable models predictive of external and internal lymphedema using clinicopathologic variables alone and in combination with dosimetric variables were constructed and optimized using competing risk regression. Results: After median follow-up of 550 days, the incidence of external and internal HNL at 360 days was 70% and 34%, respectively. When evaluating clinical and treatment-related factors alone, number of lymph nodes removed and advanced adenopathy status were predictive of external lymphedema. With incorporation of dosimetric variables, the optimized model included the percentage volume of the contralateral lymph node level VII receiving 30Gy V30 ≥50%, number of lymph nodes removed, and advanced adenopathy status. For internal lymphedema, our clinicopathologic model identified both adjuvant radiation, as opposed to definitive radiation, and advanced adenopathy status. With inclusion of a dosimetric variable, the optimized model included larynx V45 ≥50% and advanced adenopathy. Conclusions: HNL following HNC treatment is common. For both external and internal lymphedema, nodal disease burden at diagnosis predicts increased risk. For external lymphedema, increasing extent of lymph node dissection prior to adjuvant therapy increases risk. The contralateral level VII lymph node region is also predictive of external lymphedema when radiation dose to V30 is ≥50%, meriting investigation. For internal lymphedema, we confirm that increasing radiation dose to the larynx is the most significant dosimetric predictor of mucosal edema when larynx V45 is ≥50%.

Brolucizumab-associated intraocular inflammation in Indian patients by VRSI study group.

CONTEXT: Concerns about brolucizumab's (Pagenax®) association with intraocular inflammation (IOI) limit its use despite its cost-effectiveness and efficacy. This multicentric study analyzes IOI incidence across 21 tertiary eyecare centers in India since its introduction in October 2020. PURPOSE: To determine the real-world incidence rate of IOI in Indian patients secondary to intravitreal brolucizumab across 21 tertiary eye care centers in India. SETTINGS AND DESIGN: Retrospective multicentric, survey-based study. METHODS: Data including number of patients treated, clinical indications, side effects encountered, and IOI case details was collected via Google Forms in 21 Indian tertiary eye care centers since October 2020. Mean, median, frequency, and standard deviation were calculated for statistical analysis. RESULTS: All centers used pro re nata protocol for brolucizumab injections with a minimum injection interval of 8 weeks. The incidence of IOI was 0.79% (21 events out of 2655 eyes). Treatment indications included idiopathic polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, diabetic macular edema, and off-label uses. IOI was experienced after the first injection (57%) in majority of cases with a median onset of 14 days (range: 1-65 days). IOI was mild in 28.5%, moderate in 33%, and severe in 38% of cases. Eighteen out of 21 IOI eyes recovered preinjection best corrected visual acuity or better. CONCLUSIONS: Our study found a lower IOI incidence (0.79%) with brolucizumab (Pagenax) in Indian patients compared to previously reported literature. IOI events were mostly mild to moderate, and post-treatment, most patients improved or maintained BCVA. Larger prospective multicentric studies with PRN dosing protocol are needed to confirm these findings.

Progression of diabetic retinopathy following uncomplicated phacoemulsification: A prospective study from South India.

AIM: The aim of this study was to study the progression of diabetic retinopathy (DR) and macular edema in uncomplicated phacoemulsification in patients with diabetes mellitus with a follow-up of 6 months. METHODS: A prospective, nonrandomized study was conducted on patients with established or no DR in a known case of diabetes mellitus undergoing cataract surgery by phacoemulsification, with no intraoperative complications. Detailed ophthalmic evaluation including fundus examination was done in all cases, and DR staging was done. Optical coherence tomography and fundus fluorescein angiography were done in indicated cases. Fundus evaluation was done during the follow-up visits in 3 weeks, 3 months, and 6 months postsurgery and the tests were repeated if necessary. RESULTS: In the current study, there was a statistically significant improvement in best-corrected visual acuity after cataract surgery compared to the preoperative value. From the 330 eyes we analyzed, there was a progression of DR in only 18 eyes (5.45%) following phacoemulsification. There was a statistically significant increase in central macular thickness (CMT) at 3 weeks postoperative (433.82 ± 137.572) compared to that of the preoperative CMT (295.98 ± 97.959). From the 22 eyes which showed a progression of diabetic maculopathy, 11 eyes had developed new-onset macular edema following the cataract surgery, 11 eyes had progression of preexisting edema, and 4 of them had to undergo intravitreal anti-vascular endothelial growth factor injections as the treatment. CONCLUSION: The chance of progression of DR staging is low after uncomplicated phacoemulsification, on a short term. However, the chances of worsening of macular edema as well as worsening of proliferative stages should be kept in mind while advising a patient for cataract surgery.

Determining risk and predictors of head and neck cancer treatment-related lymphedema: A clinicopathologic and dosimetric data mining approach using interpretable machine learning and ensemble feature selection.

Background and purpose: The ability to determine the risk and predictors of lymphedema is vital in improving the quality of life for head and neck (HN) cancer patients. However, selecting robust features is challenging due to the multicollinearity and high dimensionality of radiotherapy (RT) data. This study aims to overcome these challenges using an ensemble feature selection technique with machine learning (ML). Materials and methods: Thirty organs-at-risk, including bilateral cervical lymph node levels, were contoured, and dose-volume data were extracted from 76 HN treatment plans. Clinicopathologic data was collected. Ensemble feature selection was used to reduce the number of features. Using the reduced features as input to ML and competing risk models, internal and external lymphedema prediction capability was evaluated with the ML models, and time to lymphedema event and risk stratification were estimated using the risk models. Results: Two ML models, XGBoost and random forest, exhibited robust prediction performance. They achieved average F1-scores and AUCs of 84 ± 3.3 % and 79 ± 11.9 % (external lymphedema), and 64 ± 12 % and 78 ± 7.9 % (internal lymphedema). Predictive ML and risk models identified common predictors, including bulky node involvement, high dose to various lymph node levels, and lymph nodes removed during surgery. At 180 days, removing 0-25, 26-50, and > 50 lymph nodes increased external lymphedema risk to 72.1 %, 95.6 %, and 57.7 % respectively (p = 0.01). Conclusion: Our approach, involving the reduction of HN RT data dimensionality, resulted in effective ML models for HN lymphedema prediction. Predictive dosimetric features emerged from both predictive and competing risk models. Consistency with clinicopathologic features from other studies supports our methodology.

Determination of thePrpand radial dose correction factor in reference dosimetry.

Objectives.In an addendum to AAPM TG-51 protocol, McEwenet al, (DOI:10.1118/1.4866223) introduced a new factorPrpto account for the radial dose distribution of the photon beam over the detector volume mainly in flattening filter free (FFF) beams.Prpand its extension to non-FFF beam reference dosimetry is investigated to see its impact in a clinical situation.Approches.ThePrpwas measured using simplified version of Sudhyadhomet al(DOI:10.1118/1.4941691) for Elekta and Varian FFF beams with two commonly used calibration detectors; PTW-30013 and Exradin-A12 ion chambers after acquiring high resolution profiles in detectors cardinal coordinates. For radial dose correction factor, the ion chambers were placed in a small water phantom and the central axis position was set to center of the sensitive volume on the treatment table and was studied by rotating the table by 15-degree interval from -90 to +90 degrees with respect to the initial (zero) position.Main results.The magnitude ofPrpvaries very little with machine, detector and beam energies to a value of 1.003 ± 0.0005 and 1.005 ± 0.0005 for 6FFF and 10FFF, respectively. The radial anisotropy for the Elekta machine with Exradin-A12 and PTW-30013 detector the magnitudes are in the range of (0.9995±0.0011 to 1.0015±0.0010) and (0.9998±0.0007 to 1.0015±0.0010), respectively. Similarly, for the Varian machine with Exradin-A12 and PTW-30013 ion chambers, the magnitudes are in the range of (1.0004±0.0010 to 1.0018±0.0018) and (1.0006±0.0009 to 1.0027±0.0007), respectively.Significance.ThePrpis ≤ 0.3% and 0.5% for 6FFF and 10FFF, respectively. The radial dose correction factor in regular beams also does not impact the dosimetry where the maximum magnitude is ±0.2% which is within experimental uncertainty.

Relevance of multicolor imaging, its component channels, and fundus autofluorescence in describing macular telangiectasia type-2 (MacTel) lesion characteristics.

PURPOSE: The aim of the study was to describe imaging characteristics and detection rates of phenotypic features in macular telangiectasia type-2 (MacTel) on multicolor (MC), blue reflectance (BR), green reflectance (GR), infrared reflectance (IR), and fundus autofluorescence (FAF) and to evaluate sensitivity, specificity, and predictive values across modalities. METHODS: In this monocentric observational study, 282 eyes of 148 patients with MacTel underwent color fundus photograph, MC, BR, GR, IR, FAF, spectral-domain optical coherence tomography (SD-OCT), OCT-angiography (OCT-A), and fundus fluorescein angiography (FFA). Grading was done by two graders qualitatively and quantitatively for the presence of the following prespecified MacTel findings [crystals, right-angle vessels (RAVs), plaques, subretinal neovascularization (SRNV), and MacTel area]. Across each imaging modality, the detection rate of RAVs and SRNV was compared with reference standard OCT-A (RAVs and SRNV) and FFA (SRNV), whereas that of plaques was compared with reference standard SD-OCT. RESULTS: MC identified overall MacTel characteristics in 92.7% of eyes. Regarding the presence, number, and quadrants of RAVs and the presence and number of crystals, MC and GR had superior detection rates as well as the highest sensitivity and negative predictive value. Retinal plaques were better detected using FAF (97%), followed by MC (88%). In proliferative MacTel, SRNV was identified in 86% and 79% of eyes on MC and IR, respectively. While BR clearly delineated MacTel area in 100% eyes, FAF was able to ascertain a larger area of involvement in proliferative MacTel. CONCLUSION: The findings demonstrate the ability of MC, its component channels, and FAF to describe MacTel characteristics qualitatively and quantitatively.

Role of cystatin C in the detection of sight-threatening diabetic retinopathy in Asian Indians with type 2 diabetes.

AIM: To study the association between cystatin C and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2DM). METHODS: In a cross-sectional study carried out at two tertiary centres in India in 2022, individuals with T2DM underwent clinical and ophthalmic assessments and estimation of serum cystatin C. Grading of DR was done by retina specialists. STDR was defined by the presence of severe non-proliferative DR (NPDR), proliferative DR (PDR) and/or diabetic macular edema. Receiver operating characteristic (ROC) curves were used to identify cystatin C cut-off value for detecting STDR. RESULTS: Among 420 individuals with T2DM (mean age 56 ± 9 years; mean duration of diabetes 14.5 ± 7.9 years), 121 (24.1 %) had No-DR, 119 (28.3 %) had No-STDR and 200 (49.6 %) had STDR. Mean cystatin C level was significantly higher in individuals with STDR compared to those with no-STDR and No-DR (1.34 vs 1.06 vs 0.93 mg/L, p < 0.001). Cystatin C cut-off value ≥1.11 mg/L had a C statistic of 0.944 (95 % CI: 0.909-0.968, p < 0.001), 96.8 % sensitivity and 78.2 % specificity for detection of STDR. CONCLUSION: Elevated serum cystatin C was strongly associated with STDR and could possibly be used as a biomarker for screening for sight-threatening diabetic retinopathy.

Toward Systematic Assessment and Improvement of Radiation Therapy Plan Quality of Cooperative Group Trial Submissions: A Report From the Children's Oncology Group.

PURPOSE: This study evaluates the quality of plans used for the treatment of patients in the Children's Oncology Group study ACNS1123. Plan quality is quantified based on a scoring system specific to the protocol. In this way, the distribution of plan quality scores is determined that can be used to identify plan quality issues for this study and for future plan quality improvement. METHODS AND MATERIALS: ACNS1123 stratum 1 patients (70) were evaluated. This included 50 photon and 20 proton plans. Digital Imaging and Communications in Medicine (DICOM) structure and dose data were obtained from the Children's Oncology Group. A commercially available plan quality scoring algorithm was used to create a scoring system we designed using the protocol dosimetric requirements. The whole ventricle and boost planning target volumes (PTVs) could earn a maximum of 70 points, whereas the organs at risk could earn 30 points (total maximum score of 100 points). The scoring algorithm adjusted scores based on the difficulty in achieving the structure dose requirements, which depended on the proximity of the PTVs and the dose gradients achieved relative to the organs at risk. The distribution of plan scores was used to determine the mean, median, and range of scores. RESULTS: The median adjusted plan quality scores for the 20 proton and 50 photon plans were 83.3 and 86.9, respectively. The range of adjusted scores (maximum to minimum) was 50 points. The average score adjustment was 7.4 points. Photon and proton plans performed almost equally. Average plan quality by individual structure revealed that the brain stem, PTV boost, and cochlea lost the most points. CONCLUSIONS: This report is the first to systematically analyze overall radiation therapy plan quality scores for an entire cohort of patients treated in a cooperative group clinical trial. The methodology demonstrated a large variation in plan quality in this trial. Future clinical trials could potentially use this method to reduce plan quality variability, which may improve outcomes.

Relation of interdigitation zone changes and right-angle vessels in Macular Telangiectasia Type-2 (MacTel).

BACKGROUND: To study the relation between interdigitation zone (IDZ) and right-angle vessel (RAV) in Macular Telangiectasia Type-2 (MacTel). METHODS: A total of 43 eyes of 38 patients with presence of definite RAV on colour fundus photograph (Gass and Blodi-only stage-3) were confirmed on multimodal imaging. The relation of IDZ changes and associated ellipsoid zone (EZ) alterations on spectral-domain optical coherence tomography (OCT) with RAV were studied at baseline and these OCT changes were followed up in 15 eyes over a mean of 3.86 years. RESULTS: A total of 58 RAVs were found in the 43 eyes and 53/58 (91.3%) RAVs were associated with IDZ alterations in 39 eyes. On follow-up, IDZ attenuation progressed to IDZ loss and subsequent EZ attenuation and loss. A pre-existing IDZ loss was associated with subsequent EZ defect (P = 0.002). In 36 eyes that had OCT angiography, eyes with RAV showed deep capillary plexus telangiectasia in all 36 (100%) eyes and 32/36 (89%) eyes showed IDZ changes with or without EZ loss. CONCLUSIONS: IDZ attenuation and/or loss are associated with RAV and may serve as predictor of EZ loss in MacTel.

OUTER FOVEAL DEFECTS IN TYPE-2 MACULAR TELANGIECTASIA.

PURPOSE: To report characteristics of outer foveal defects (OFDs) in type-2 macular telangiectasia (MacTel) on spectral domain optical coherence tomography. METHODS: This was a single-center observational study. From a registry of 745 patients with MacTel, patients with OFDs were characterized. All patients underwent multimodal imaging including color fundus photography, confocal blue reflectance, fundus autofluorescence, and spectral domain optical coherence tomography. Staging of eyes was done using the Gass and Blodi classification. Spectral domain optical coherence tomography characteristics in the central 1 mm of the macula in eyes with OFD are reported. RESULTS: Outer foveal defect was observed in 21 eyes of 15/745 (2%) patients with MacTel. These defects were bilateral in 6/15 (40%) patients and seen in stage 2 MacTel eyes. In order of prevalence, foveal parameters seen in OFD included hyper-reflective dots in outer retina in 19/21 (90%), ellipsoid zone loss in 18/21 (86%) eyes, interdigitation zone loss in 17/21 (81%) eyes, outer retinal hyporeflective cavitation in 14 (67%) eyes, hyporeflective cavitation at foveal pit in 8 (38%) eyes, and loss of external limiting membrane in 1 (5%) eye. The mean baseline length of the foveal ellipsoid zone loss was 240.17 ± 117.249 µm. The mean baseline central subfield thickness was 155.43 ± 17.215 µm. A total of 8/11 eyes (73%) showed an increase in size of OFD on follow-up. CONCLUSION: Outer foveal defect in MacTel eyes is characterized predominantly by foveal loss of ellipsoid zone and interdigitation zone with relative preservation of external limiting membrane.

Retrospective diagnosis of COVID-19 following the detection of central retinal artery occlusion.

Thromboembolic complications are being increasingly reported in patients with COVID-19 due to the associated hypercoagulability and are an important cause for morbidity and mortality. Retinal vascular occlusions especially arterial occlusions are one of the gravest ocular complications reported. This complication may occur in severe cases with cytokine storm or even in mild or asymptomatic patients and presentation can be anytime from few days to weeks after the onset of symptoms. Ophthalmologists should be aware of this new etiology when dealing with patients having features of retinal vascular occlusions and should investigate for the same in this pandemic situation. Although reverse transcriptase polymerase chain reaction is the diagnostic test for COVID-19, serological assays have a role in patients with delayed presentation. We describe the clinical features and multimodal imaging findings in a patient who presented with features of central retinal artery occlusion with cilioretinal artery sparing wherein his ophthalmic condition led to the diagnosis of previously undetected COVID-19 through serology. To the best of our knowledge, this is the first documentation of a case of isolated central retinal artery occlusion leading to a retrospective diagnosis of COVID-19.

Deterministic small-scale undulations of image-based risk predictions from the deep learning of lung tumors in motion.

INTRODUCTION: Deep learning (DL) models that use medical images to predict clinical outcomes are poised for clinical translation. For tumors that reside in organs that move, however, the impact of motion (i.e., degenerated object appearance or blur) on DL model accuracy remains unclear. We examine the impact of tumor motion on an image-based DL framework that predicts local failure risk after lung stereotactic body radiotherapy (SBRT). METHODS: We input pre-therapy free breathing (FB) computed tomography (CT) images from 849 patients treated with lung SBRT into a multitask deep neural network to generate an image fingerprint signature (or DL score) that predicts time-to-event local failure outcomes. The network includes a convolutional neural network encoder for extracting imaging features and building a task-specific fingerprint, a decoder for estimating handcrafted radiomic features, and a task-specific network for generating image signature for radiotherapy outcome prediction. The impact of tumor motion on the DL scores was then examined for a holdout set of 468 images from 39 patients comprising: (1) FB CT, (2) four-dimensional (4D) CT, and (3) maximum-intensity projection (MIP) images. Tumor motion was estimated using a 3D vector of the maximum distance traveled, and its association with DL score variance was assessed by linear regression. FINDINGS: The variance and amplitude in 4D CT image-derived DL scores were associated with tumor motion (R2  = 0.48 and 0.46, respectively). Specifically, DL score variance was deterministic and represented by sinusoidal undulations in phase with the respiratory cycle. DL scores, but not tumor volumes, peaked near end-exhalation. The mean of the scores derived from 4D CT images and the score obtained from FB CT images were highly associated (Pearson r = 0.99). MIP-derived DL scores were significantly higher than 4D- or FB-derived risk scores (p < 0.0001). INTERPRETATION: An image-based DL risk score derived from a series of 4D CT images varies in a deterministic, sinusoidal trajectory in a phase with the respiratory cycle. These results indicate that DL models of tumors in motion can be robust to fluctuations in object appearance due to movement and can guide standardization processes in the clinical translation of DL models for patients with lung cancer.

Mean Brain Dose Remains Uninfluenced by the Lesion Number for Gamma Knife Stereotactic Radiosurgery for 10+ Metastases.

OBJECTIVE: Gamma Knife (GK) stereotactic radiosurgery (SRS) is increasingly used as an initial treatment for patients with 10 or more brain metastases. However, the clinical and dosimetric consequences of this practice are not well established. METHODS: We performed a single-institution, retrospective analysis of 30 patients who received Gamma Knife SRS for 10 or more brain metastases in 1 session. We utilized MIM Software to contour the whole brain and accumulated the doses from all treated lesions to determine the mean dose delivered to the whole brain. Patient outcomes were determined from chart review. RESULTS: Our cohort had a median number of 13 treated lesions (range 10-26 lesions) for a total of 427 treated lesions. The mean dose to the whole brain was determined to be 1.8 ± 0.91 Gy (range 0.70-3.8 Gy). The mean dose to the whole brain did not correlate with the number of treated lesions (Pearson r = 0.23, P = 0.21), but was closely associated with tumor volume (Pearson r = 0.95, P < 0.0001). There were no significant correlations between overall survival and number of lesions or aggregate tumor volume. Fourteen patients (47%) underwent additional SRS sessions and 6 patients (20%) underwent whole-brain radiotherapy with a median of 6.6 months (range 3.0-50 months) after SRS. Two patients (6.6%) developed grade 2 radionecrosis following SRS beyond earlier whole-brain radiotherapy. CONCLUSION: The mean dose to the whole brain in patients treated with Gamma Knife SRS for 10 or more brain metastases remained low with an acceptable rate of radionecrosis. This strategy allowed the majority of patients to avoid subsequent whole-brain radiotherapy.

Validity of equivalent square field concept in small field dosimetry.

PURPOSE: The equivalent square (ES) concept has been used for traditional radiation fields defined by the machine collimating system. For small fields, the concept Sclin was introduced based on measuring dosimetric field width (full-width half maximum, FWHM) of the cardinal axis of the beam profiles. The pros and cons of this concept are evaluated in small fields and compared with the traditional ES using area and perimeter (4A/P) method based on geometric field size settings, for example, light field settings. METHODS: One hundred thirty-seven square and rectangular fields from 5-50 mm with every possible permutation (keeping one jaw fixed and varying other jaw from 5 to 50 mm) were utilized to measure FWHM for the validation of Sclin . Using a microSilicon detector and a scanning water tank, measurements were performed on an Elekta (Versa) machine with Agility head and a Varian TrueBeam with different MLC/Jaw design to evaluate the Sclin concept and to understand the effect of exchange factor in small fields. Field output factors were also measured for all 137 fields. RESULTS: The data fitting for fields ranging from 5-50 mm between the traditional 4A/P method and Sclin shows differences and indicates a linear relationship with distinct separation of slope for Elekta and Varian machines. For Elekta Agility machine ES based on 4A/P < Sclin and for the VarianTrueBeam  4A/P > Sclin for square fields. Our measured data show that both methods are equally valid but does vary by the machine design. The field output factor is dependent on the elongation factor as well as machine design. For fields with sides ≥10 mm, the exchange factor is nearly identical in both machines with magnitude up to 4%, which is close to measurement uncertainty (±3%), but for small fields (< 10 mm), the Elekta machine has higher exchange factors compared to the Varian machine. CONCLUSION: The results demonstrate that the two concepts for defining equivalent field (Sclin and 4A/P) are equivalent and can be directly related through an empirical equation. This study confirms that 4A/P is still valid for small fields except for very small fields (≤10 mm) where source occlusion is a dominating factor. The Sclin method is potentially sensitive to measurement uncertainty due to measurement of FWHM which is machine-, detector- and user-dependent, while the 4A/P method relies mainly on geometry of the machine and has less dependency on type of machine, detector, and user. The exchange factors are comparable for both types of machines. The conclusion is based on data from an Elekta with Agility head and a Varian TrueBeam machine that may have potential for bias due to light field/collimator set up and alignment. Care should be taken in extrapolating these data to any other machine.

Microvascular changes precede visible neurodegeneration in fellow eyes of patients with asymmetric type 2 macular telangiectasia.

IMPORTANCE: Macular telangiectasia type 2 (MacTel) is bilateral disease with characteristic alterations of the macular capillary network along with decreased macular pigment in the parafoveal area. The purpose of this study was to highlight that some eyes show microvascular changes which precede any visible neuronal changes on spectral-domain optical coherence tomography (SD-OCT). METHODS: This observational study was conducted at a tertiary eye institute. From a registry of 630 patients with MacTel, we identified 4 patients with typical MacTel characteristics in only one eye with no visible changes on colour photographs or SD-OCT in the fellow eye. These 4 patients had findings of MacTel documented by colour fundus photograph, multicolour imaging (MCI), fundus autofluorescence (FAF), confocal blue reflectance (CBR), SD-OCT, and OCT-Angiography (OCT-A) in one eye. OCT-A was performed in MacTel patients using the High-resolution Spectralis (Heidelberg Engineering) module with a full-spectrum probabilistic approach and we employed a 30° x 15° (~8.8 mm × 4.4 mm) scan pattern covering the macula. MCI was done at the end so as to avoid fading the confocal blue reflectance hyperreflectivity seen in MacTel. RESULTS: On OCT-A, all 4 fellow eyes showed telangiectasia and foveal avascular zone changes in the superficial and deep capillary plexuses with no changes on SD-OCT. None of the eyes showed typically increased reflectance on CBR around the foveal area. CONCLUSION: These findings show that microvascular changes on OCT-A may occur before visible neurodegenerative changes on OCT, providing new insights into the course of the disease.

The effects of palbociclib in combination with radiation in preclinical models of aggressive meningioma.

BACKGROUND: Meningiomas are the most common tumor arising within the cranium of adults. Despite surgical resection and radiotherapy, many meningiomas invade the brain, and many recur, often repeatedly. To date, no chemotherapy has proven effective against such tumors. Thus, there is an urgent need for chemotherapeutic options for treating meningiomas, especially those that enhance radiotherapy. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 that has been shown to enhance radiotherapy in preclinical models of other cancers, is well-tolerated in patients, and is used to treat malignancies elsewhere in the body. We, therefore, sought to determine its therapeutic potential in preclinical models of meningioma. METHODS: Patient-derived meningioma cells were tested in vitro and in vivo with combinations of palbociclib and radiation. Outputs included cell viability, apoptosis, clonogenicity, engrafted mouse survival, and analysis of engrafted tumor tissues after therapy. RESULTS: We found that palbociclib was highly potent against p16-deficient, Rb-intact CH157 and IOMM-Lee meningioma cells in vitro, but was ineffective against p16-intact, Rb-deficient SF8295 meningioma cells. Palbociclib also enhanced the in vitro efficacy of radiotherapy when used against p16-deficient meningioma, as indicated by cell viability and clonogenic assays. In vivo, the combination of palbociclib and radiation extended the survival of mice bearing orthotopic p16 deficient meningioma xenografts, relative to each as a monotherapy. CONCLUSIONS: These data suggest that palbociclib could be repurposed to treat patients with p16-deficient, Rb-intact meningiomas, and that a clinical trial in combination with radiation therapy merits consideration.

Practice Patterns of Pediatric Total Body Irradiation Techniques: A Children's Oncology Group Survey.

PURPOSE: The aim of this study was to examine current practice patterns in pediatric total body irradiation (TBI) techniques among COG member institutions. METHODS AND MATERIALS: Between November 2019 and February 2020, a questionnaire containing 52 questions related to the technical aspects of TBI was sent to medical physicists at 152 COG institutions. The questions were designed to obtain technical information on commonly used TBI treatment techniques. Another set of 9 questions related to the clinical management of patients undergoing TBI was sent to 152 COG member radiation oncologists at the same institutions. RESULTS: Twelve institutions were excluded because TBI was not performed in their institutions. A total of 88 physicists from 88 institutions (63% response rate) and 96 radiation oncologists from 96 institutions (69% response rate) responded. The anterior-posterior/posterior-anterior (AP/PA) technique was the most common technique reported (49 institutions [56%]); 44 institutions (50%) used the lateral technique, and 14 (16%) used volumetric modulated arc therapy or tomotherapy. Midplane dose rates of 6 to 15 cGy/min were most commonly used. The most common specification for lung dose was the midlung dose for both AP/PA techniques (71%) and lateral techniques (63%). Almost all physician responders agreed with the need to refine current TBI techniques, and 79% supported the investigation of new TBI techniques to further lower the lung dose. CONCLUSIONS: There was no consistency in the practice patterns, methods for dose measurement, and reporting of TBI doses among COG institutions. The lack of standardization precludes meaningful correlation between TBI doses and clinical outcomes including disease control and normal tissue toxicity. The COG radiation oncology discipline is currently undertaking several steps to standardize the practice and dose reporting of pediatric TBI using detailed questionnaires and phantom-based credentialing for all COG centers.

Treatment Landscape of Macular Disorders in Indian Patients with the Advent of Razumab™ (World's First Biosimilar Ranibizumab): A Comprehensive Review.

Ranibizumab is approved for the treatment of several macular disorders, including wet age-related macular degeneration (wet AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and myopic choroidal neovascularization (mCNV), among others. The unaffordability of the innovator ranibizumab among patients from developing countries such as India led to the development of the world's first biosimilar ranibizumab, which is a cost-effective alternative that does not compromise efficacy and safety. Razumab™, developed and produced by Intas Pharmaceuticals Ltd., India, is the world's first biosimilar of ranibizumab, and is approved in India for the treatment of various macular disorders, including wet AMD, DME, RVO and mCNV. The efficacy and safety of Razumab for the treatment of these macular disorders have been evaluated in both prospective and real-world retrospective studies. Razumab has shown an efficacy similar to that of the innovator ranibizumab, achieving improved visual acuity, as measured by the best corrected visual acuity, and reduction in the central macular thickness, leading to improved patient outcomes. The safety profile of Razumab is comparable to that of the innovator ranibizumab and is well tolerated without any new safety concerns. Here, we review the clinical and real-world data of Razumab in the treatment of macular disorders.

Subretinal hyperreflective material morphology in neovascular age-related macular degeneration: A case control study.

Purpose: The aim of this study was to evaluate the association of morphological features of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA) and scar formation in eyes with neovascular age-related macular degeneration (neovascular AMD) and to compare with controls of neovascular AMD without SHRM. Methods: Retrospective analysis of 157 wet AMD eyes with SHRM and 50 eyes without SHRM treated with Anti-VEGF. Baseline spectral domain-OCT characteristics (SHRM location, height, width, area, reflectivity, border definition) were collected and were correlated with VA at baseline, 3, 6, 12 months and looked for development of scar and geographical atrophy (GA) and were compared to the control group. Results: When compared to the control, baseline parameters with a significant predictive value of 12-VA were presence of SHRM, foveal involvement of SHRM, high reflective SHRM, well-defined SHRM borders and thick SHRM. VA was decreased with greater SHRM height, width and area (P < 0.001). Decreasing reflectivity of SHRM lesions and disappearance of SHRM correlated with better VA at 12 months (P < 0.05). At 12 months, scar and GA was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved and those without SHRM in the control group. Conclusion: SHRM can be considered as a surrogate OCT biomarker in predicting final visual outcome in neovascular age-related macular degeneration. Baseline parameters predicting poorer vision at 12-follow-up were presence of SHRM involving the fovea, well-defined SHRM borders, greater SHRM height, width and area and persistence of SHRM with Anti-VEGF therapy.

Adaptability and Resilience of Academic Radiation Oncology Personnel and Procedures during COVID-19 Pandemic.

BACKGROUND: A comprehensive response to the unprecedented SARS-CoV-2 (COVID-19) challenges for public health and its impact on radiation oncology patients and personnel for resilience and adaptability is presented. METHODS: The general recommendations included working remotely when feasible, implementation of screening/safety and personal protective equipment (PPE) guidelines, social distancing, regular cleaning of treatment environment, and testing for high-risk patients/procedures. All teaching conferences, tumor boards, and weekly chart rounds were conducted using a virtual platform. Additionally, specific recommendations were given to each section to ensure proper patient treatments. The impact of these measures, especially adaptability and resilience, were evaluated through specific questionnaire surveys. RESULTS: These comprehensive COVID-19-related measures resulted in most staff expressing a consistent level of satisfaction in regard to personal safety, maintaining a safe work environment, continuing quality patient care, and continuing educational activities during the pandemic. There was a significant reduction in patient treatments and on-site patient visits with an appreciable increase in the number of telemedicine e-visits. CONCLUSIONS: Survey results demonstrated substantial adaptability and resilience, including in the rapid recovery of departmental activities during the reactivation phase. In the event of a future public health emergency, the measures implemented may be adopted with good outcomes by radiation oncology departments across the globe.