Tumor Basal Diameter Research Articles

Neoadjuvant chemotherapy for advanced eyelid and periocular sebaceous gland carcinoma: a study of 25 cases.

To report the outcomes of platinum-based neoadjuvant chemotherapy (NACT) for eyelid and periocular sebaceous gland carcinoma (eSGC). Retrospective study of 25 patients. The mean age at presentation of eSGC was 59years. The mean tumor basal diameter was 46mm. By the 8th edition of AJCC classification, tumors belonged T2 (n = 2, 8%), T3 (n = 6, 24%), and T4 (n = 17, 68%); N1 (n = 12,48%); and M1 (n = 1, 4%). NACT with 5-fluorouracil (5-FU) and cisplatin/carboplatin was administered in 21 (84%)/4 (16%) patients, respectively. The mean number of cycles of neoadjuvant systemic chemotherapy per patient was 2 (median, 3). The mean percentage reduction of tumor basal volume after neoadjuvant chemotherapy was 65% (median, 60%). After NACT, 12 (48%) patients underwent surgical treatment, 6 (12%) patients underwent EBRT, and 4 (8%) underwent adjuvant chemotherapy. A total of 11 (44%) patients were lost to follow-up during the course of treatment, of whom 3 died from metastatic disease. In 16 patients followed up for ≥ 3months, complete tumor control was achieved in 11 (69%) patients, local tumor control in 14 (88%), and globe salvage in 7 (44%) at a mean follow-up of 25months (median, 7months; range, 3 to 110months). No tumor recurrence was seen in any case. One (4%) serious adverse event of cardiotoxicity was noted. Platinum-based NACT is a suitable option for eSGC with advanced tumors and locoregional metastasis. Adverse events are rare and in patients compliant with treatment, NACT-based combination therapy offers globe salvage and systemic tumor control.

Predicting Choroidal Nevus Transformation to Melanoma Using Machine Learning

PurposeTo develop and validate machine learning (ML) models to predict choroidal nevus transformation to melanoma based on multimodal imaging at initial presentation. DesignRetrospective multicenter study. ParticipantsPatients diagnosed with choroidal nevus on the Ocular Oncology Service at Wills Eye Hospital (2007-2017) or Mayo Clinic Rochester (2015-2023). MethodsMultimodal imaging was obtained, including fundus photography, fundus autofluorescence, spectral domain OCT, and B-scan ultrasonography. ML models were created (XGBoost, LGBM, Random Forest, Extra Tree) and optimized for area under receiver operating curve (AUROC). The Wills Eye Hospital cohort was utilized for training and testing (80% training-20% testing) with 5-fold cross validation. The Mayo Clinic cohort provided external validation. Model performance was characterized by AUROC and area under the precision recall curve (AUPRC). Models were interrogated using SHapley Additive exPlanations (SHAP) to identify the features most predictive of conversion from nevus to melanoma. Differences in AUROC and AUPRC between models were tested using 10,000 bootstrap samples with replacement and results. Main Outcome MeasuresAUROC and AUPRC for each ML model. ResultsThere were 2,870 nevi included in the study, with conversion to melanoma confirmed in 128 cases. Simple AI Nevus Transformation System (SAINTS; XGBoost) was the top performing model in the test cohort [pooled AUROC 0.864 (95% confidence interval (CI): 0.864-0.865), pooled AUPRC 0.244 (0.243-0.246)] and in the external validation cohort [pooled AUROC 0.931 (95% CI: 0.930-0.931), pooled AUPRC 0.533 (0.531-0.535)]. Other models also had good discriminative performance: LGBM (test set pooled AUROC 0.831, validation set pooled AUROC 0.815), Random Forest (test set pooled AUROC 0.812, validation set pooled AUROC 0.866), and Extra Tree (test set pooled AUROC 0.826, validation set pooled AUROC 0.915). A model including only nevi with at least 5 years of follow up demonstrated the best performance in AUPRC (test: pooled 0.592 (95% CI: 0.590-0.594); validation: pooled 0.656 (95% CI: 0.655-0.657)). The top five features in SAINTS by SHAP values were: tumor thickness, largest tumor basal diameter, tumor shape, distance to optic nerve, and subretinal fluid extent. ConclusionsWe demonstrate accuracy and generalizability of a ML model for predicting choroidal nevus transformation to melanoma based on multimodal imaging.

Comparison of the therapeutic effects of photodynamic therapy, transpupillary thermotherapy, and their combination on circumscribed choroidal haemangioma

ObjectiveTo characterize the clinical and imaging features of circumscribed choroidal hemangioma (CCH), and to evaluate individualized treatment efficiency of photodynamic therapy (PDT), transpupillary thermotherapy (TTT), or their combination, followed by retrobulbar injection of betamethasone on CCH resolvement. MethodsForty-nine patients with CCHs who underwent PDT, TTT or PDT+TTT treatments were retrospectively analyzed. Their treatment efficacy was compared by analyzing the change of best corrected visual acuity (BCVA), subretinal fluid (SRF) and CCH lesion characteristics. ResultsPDT, TTT and PDT+TTT were respectively administrated in 17, 11 and 21 patients. No significant difference in age, gender, affected eyes and tumor location across the three groups. Baseline BCVA were 0.41 ± 0.28, 0.62 ± 0.30 and 0.24 ± 0.24 for PDT, TTT and PDT+TTT groups, respectively (F = 6.572, P = 0.003). CCH treated by three strategies showed significant difference in maximum tumor basal diameter, SRF areas and macula involvement prior to the treatment (P < 0.05). Patients receiving PDT+TTT exhibited larger tumor basal diameter, more SRF, higher ratio of macular involvement than other groups. A total of 38 (77.6 %) cases had good visual acidity with final BCVA ≥0.5 after treatments. PDT and PDT+TTT treatment groups acquired more vision improvement (0.27 ± 0.23 and 0.31 ± 0.26) in BCVA than TTT group (0.09 ± 0.13). All SRF were resolved within two weeks of treatment and no recurrent SRF were found. ConclusionThe three treatments showed good performance in improving visual function and controlling SRF, and individualized treatment should be selected primarily by the tumor location, and then the tumor size and presence of SRF.

Ruthenium-106 Plaque Brachytherapy for Circumscribed Choroidal Hemangioma: A Case Series and Review of Literature

Introduction: We aim to report the anatomical and functional outcomes of ruthenium-106 brachytherapy in the management of circumscribed choroidal hemangiomas (CCH). Methods: This is a single-center, retrospective case series including patients with unilateral symptomatic CCH treated with ruthenium-106 brachytherapy at the Cairo University Ocular Oncology Service. Patient records were analyzed for patients’ demographics, best corrected visual acuity (BCVA), tumor dimensions (thickness and largest base diameter), foveal subretinal fluid, radiation-related complications, and recurrence. Results: Seven patients were included in the study (including 6 males) with a mean age of 39.3 ± 15.4 years; ruthenium-106 plaque was used to deliver 50 Gray to the tumor apex. After a mean follow-up duration of 12.5 months, all patients had significant improvement in BCVA after treatment, mean tumor height decreased significantly from 4.76 ± 1.76 mm to 1.70 ± 1.2 mm (p value 0.01). The largest tumor base diameter also decreased significantly from 9.13 ± 2.68 mm to 4.65 ± 3.75 mm (p value 0.05). Subretinal fluid and exudative retinal detachment resolved in all patients, and no significant radiation-related complications were observed in any patient. None of the patients needed any further treatment or experienced recurrence within the follow-up period. Conclusion: Ruthenium-106 brachytherapy is an effective tool in the management of symptomatic CCH with a good visual prognosis and safety profile.

Local resection via partial lamellar sclerouvectomy for ciliary body tumors — a case series

BackgroundCiliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China.MethodsFour patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months.ResultsFour patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00–10.00) and the mean tumor thickness was 3.50 mm (range: 2.00–5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up.ConclusionsLocal tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

Sensitivity of Magnetic Resonance Imaging in Detection of Choroidal Metastases

Introduction: The objective of this study was to determine the sensitivity of brain magnetic resonance imaging (MRI) in the detection of choroidal metastasis (CM) from systemic primary cancers. Methods: A retrospective chart review identified patients with clinically confirmed CM seen on the Oncology Service (Byers Eye Institute) between January 2018 and March 2022. Patients had an MRI brain and/or orbits performed within 3 months of CM diagnosis. Evaluation of CM detection by MRI was then divided into two parts: an initial “standard read,” where determination of CM detection was based solely on the original radiology report, to reflect real-world performance, and a subsequent “dedicated read,” for which a board-certified neuroradiologist, blinded to the laterality and location of the CM, reevaluated the studies to provide an objective “gold standard” interpretation regarding the radiographic detection of CM. Results: The study included 42 eyes of 40 patients with confirmed CM. On standard read, MRI detection of CM occurred in 21 of 42 eyes (50%), with no significant difference between MRI brain and orbit protocols (p = 0.249). Features associated with improved detection were increased tumor basal diameter (p < 0.001) and ultrasonographic tumor thickness (p = 0.003). On dedicated read, MRI detection of CM improved to 26 of 33 eyes (76%; limited to eyes with full complement of pre- and post-gadolinium sequences). Post-gadolinium 3D fluid-attenuated inversion recovery (FLAIR) sequence with fat suppression was the most sensitive (88%) for CM detection. 42% and 58% of lesions were visualized using conventional pre-gadolinium T1- and T2-weighted imaging, respectively. Conclusions: MRI sensitivity to detect CM improved from 50% to 76% with focused reinterpretation. Increased utilization of the post-gadolinium 3D FLAIR sequence and increased ocular scrutiny in cancer patients undergoing brain imaging may facilitate earlier diagnosis of CM.

Correlation of fitzpatrick skin type and iris color with tumor size in 823 patients with uveal melanoma

PurposeTo determine the correlation of Fitzpatrick Skin Type (FST) and iris color with tumor size (tumor thickness and basal diameter) in patients with uveal melanoma. DesignRetrospective Cohort MethodsRetrospective cohort from a single ocular oncology center of 823 patients with uveal melanoma and documented FST, iris color, and tumor size. Patients were classified by FST (type I, II, and III–V) and iris color (blue, green, and brown) on the basis of external facial photography. There were no FST type VI patients. Tumor thickness was classified into small [< 3 millimeter (mm)], medium (3.1–8.0 mm), or large (> 8.0 mm), and basal diameter into small (< 10 mm), medium (10.1–15 mm) or large (> 15 mm). The correlation of FST and iris color with tumor thickness and basal diameter was evaluated using the Kruskal-Wallis H test. ResultsThe FST classification was type I (n = 92, 11%), type II (n = 643, 78%), or III–V (n = 88, 11%), and iris color was blue (n = 472, 57%), green (n = 102, 12%), or brown (n = 249, 30%). A comparison of FST revealed differences in mean tumor thickness (P = 0.04) and basal diameter (P = 0.006). Iris color showed no difference for mean tumor thickness (P = 0.41) or basal diameter (P = 0.48). There was a statistically significant difference with brown iris color relative to FST III–V for mean tumor thickness (P = 0.003) and basal diameter (P = 0.001) but no difference with blue or green iris color (P > 0.05). ConclusionsIris color alone showed no difference in tumor size, but those with brown iris color and FST type III–V demonstrated larger tumor thickness and basal diameter.

Factors affecting recurrence and metastasis in conjunctival melanoma.

To evaluate clinical and demographic characteristics and factors affecting recurrence, metastasis, and survival in conjunctival melanoma (CM). The clinical records of 45 patients who were treated for CM between October 1998 and June 2022 were retrospectively evaluated. Age, gender, presence of underlying conjunctival nevus-primary acquired melanosis (PAM), tumor stage according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, tumor basal diameter, tumor thickness, lymph node (LN) involvement, metastasis, presence of tumor at the surgical margin, treatment method, need for adjuvant therapy, local tumor control, recurrence, and survival were recorded. Twenty-one (46.7%) patients were female and 24 (53.3%) patients were male. The mean age at diagnosis was 53.2 ± 16.1years. Median follow up time was 12 (1-300) months. Fifteen (33.3%) patients had conjunctival PAM; 2 (4.4%) patients had conjunctival nevus. The tumor stage was T1 in 24 (55.8%), T2 in 13 (30.2%), and T3 in 6 (14.0%) of the cases. The T stage in 2cases could not be determined.For stage T1 and T2 CM, in addition to excisional biopsy (EB) and cryotherapy, alcohol epitheliectomy (AE) was performed in 17 cases (37.8%), superficial sclerectomy (SS) was performed in 7 (15.6%), and amnion membrane transplantation (AMT) due to a large conjunctival defect in 9 (20.0%). Six (14.0%) T3 cases underwent primary exenteration. Positive surgical margins were observed in 23 (51.1%) of the excised tumors at histopathologic examination. Adjuvant topical mitomycin-C (MMC) was used in 7 (30.4%) and strontium-90 episcleral brachytherapy in 4 (17.4%) of the 23 cases with tumor-positive borders. During the follow-up, recurrence was seen in 14 (31.1%) cases. According to Kaplan Meier analysis, the mean time to recurrence development was 90.5 ± 16.1months and the 5-year recurrence free rate was 52.0%. Fourteen of the recurrent cases underwent EB + cryotherapy, 3 underwent AE + SS, and 3 underwent secondary exenteration. Metastasis and LN involvement occurred in 11 (24.4%) and 8 (17.8%) of the cases, respectively. Four (8.9%) cases expired during follow-up. According to Kaplan-Meier analysis, the mean time to metastasis was 106.2 ± 17.3months and the 5-year metastasis free rate was 52.0%. While recurrence was more frequent in CM developing from PAM/nevus, metastasis was more frequent in men and those with LN involvement. Conjunctival melanoma was a malignant tumor with high recurrence and metastasis rates. Precursor nevus/PAM is a risk factor for recurrence, while male gender and regional LN involvement were risk factors for metastasisin this study.

Факторы эффективности лазерной термотерапии ретинобластомы

Purpose. To determine major predictors of thermotherapy (TT) success in retinoblastoma (Rb) treatment using multivariate analysis. Material and methods. A retrospective study of 232 patients (295 eyes, 1623 tumors) that were treated by thermotherapy was performed. The median patients' age was 15±14,1 mo. (from 1 to 78 mo.). Tumor thickness varied from 0,3 to 4,5 mm (Me – 0,7±0,4 mm), tumor basal diameter – from 0,5 to 13,4 mm (Mе – 1,5±1,05 mm). Thermotherapy was conducted both by transpupillary and transscleral routes with the following parameters: wavelength – 810 nm, spot size – 1000–1200 microns, power – from 180 to 850 mW (Ме – 400±156 mW), power density – from 15 to 71 W/сm² (Ме – 33±12,5 W/сm²) in application and scanning modes. Results. Multivariate analysis using Kaplan-Meier estimates and Cox regression analysis showed that tumor thickness ≤0,8 mm (p&lt;0,0001), tumor basal diameter ≤1,5 mm (p&lt;0,0001), preequatorial and postequatorial localization (p&lt;0,0001), dark and medium fundus pigmentation (p=0,0001) and number of treatment sessions ≤2 (p&lt;0,0001) are associated with higher thermotherapy efficacy. ROC-analysis demonstrated that the highest rate of tumor control is associated with three and more predictors of thermotherapy success. Conclusion. Laser thermotherapy proved to be a highly effective method of Rb treatment with 92% rate of tumor control, meanwhile thermotherapy is most effective for tumors that have three or more predictors of thermotherapy success. This should be considered in application of thermotherapy and local modality choice. Key words: laser thermotherapy, retinoblastoma, predictors of efficacy, multivariate analysis, local treatment

Edge Creep: Increased Pigmentation at the Border of Choroidal Melanomas Treated with Plaque Brachytherapy

Introduction: There is an increase in pigmentation that occurs in many tumors following plaque brachytherapy for choroidal melanoma. Correctly distinguishing between increased pigment at the tumor border versus true growth is imperative. We performed a retrospective review of patients treated with I-125 brachytherapy for choroidal melanoma at our institution to study this phenomenon. Methods: Records were reviewed for all patients undergoing plaque brachytherapy for uveal melanoma for a 5-year period (N = 195). Patients with iris and anterior tumors were excluded. Tumors treated more than 31 days after presentation were excluded. Fundus images for patients with increased pigmentation at any of the borders of the tumor at 6-month follow-up that extended beyond the initial pigmented margin were included (N = 20; 8 F, 12 M). Imaging at the last follow-up was reviewed, and it was confirmed that all tumors involuted appropriately with no evidence of local recurrence. The date of initial exam, time to treatment, and follow-up interval were recorded for each included patient. Results: Twenty patients (10%) exhibited increased pigment deposition at any of the borders of the tumor at 6-month follow-up that extended beyond the initial pigmented margin. Average tumor thickness was 3.2 mm (1.3–5.1); average largest tumor basal diameter was 11.6 mm (7–15.5). Average time from diagnosis to treatment was 25 days (17–31). Average length of follow-up was 35 months (16–68). No patient developed recurrence during the duration of follow-up, and 1 patient had developed metastasis. Conclusion: We describe the phenomenon of increased pigment deposition, “edge creep,” at the borders of choroidal melanomas treated with plaque brachytherapy that gave the appearance of initial tumor growth but then subsequently remained stable over time. It is important that treating ocular oncologists be aware of this phenomenon to avoid unnecessary diagnosis of local recurrence.

Retinoblastoma associated with total exudative retinal detachment: Treatment and outcomes.

To study the clinical presentation, treatment, and outcomes of eyes presenting with retinoblastoma (RB) and total retinal detachment (RD). Retrospective study of 50 eyes in 43 patients. Mean age at presentation was 15 months (median, 9 months). RB associated total RD was unilateral (n=36; 84%) or bilateral (n=7; 16%). The mean tumor basal diameter was 17 mm (median, 18 mm) and the mean tumor thickness was 13 mm (median, 12 mm). Associated features included subretinal seeds (n=26; 52%), vitreous seeds (n=13; 26%), and subretinal exudation in (n=4; 8%). Based on 8th edition of American Joint Committee on Cancer classification, the tumors were classified as cT2a (n=19; 38%), cT2b (n=28; 56%), or cT3c (n=3; 6%). Primary treatment included intravenous (n=48; 96%) or intra-arterial chemotherapy (n=2; 4%). Over a mean follow-up period of 30 months (median, 29 months; range, 7 to 62 months), RD resolved in 41 (82%) eyes, tumor recurrence was noted in 39 (78%) eyes, globe salvage was achieved in 35 (70%) eyes and one (2%) patient died due to metastasis. Relatively high tumor recurrence rate is noted in RB presenting with total RD. With appropriate treatment, 70% of the globes can be salvaged.

Is Tumour Thickness Measurement Required for MOLES Scoring of Melanocytic Choroidal Tumours?

Introduction: It can be challenging to distinguish between choroidal naevi and melanomas in the community setting, particularly without access to ultrasonography (US), required to measure the thickness of melanocytic choroidal tumours. We aimed to determine whether thickness measurement is required for MOLES scoring of melanocytic choroidal tumours. Methods: The dataset of a recent MOLES evaluation was reviewed. Patients were selected for the present study if their MOLES tumour size category was determined by tumour thickness measured with US. The largest basal tumour diameter and tumour thickness were then measured from ultra-widefield fundus images and optical coherence tomography (OCT) images, respectively. Results: The tumour size category was determined by tumour diameter in 203/222 (91.4%) with no influence of tumour thickness. The tumour thickness influenced the MOLES score in 19/222 (8.6%) patients. In 11/19 patients with OCT measurements of tumour thickness, the US measurement exceeded the OCT by more than 25% in 5 patients, more than 50% in 2 patients, and more than 75% in 1 patient. As a result, the revised tumour thickness based on OCT determined the size category in 4/216 (1.8%) patients. The ultra-widefield fundus images measurements increased the diameter score by 1 in 5 patients. As a result, the revised tumour thickness determined the size category in 4/216 (1.8%) patients. If both the revised diameter and thickness scores were considered, the MOLES score reduced in 4 patients. If both the diameter and thickness scores were considered, the MOLES score reduced in 5 and increased in 1. Only 0.94% (2/211) of melanocytic choroidal tumours assessed with MOLES when using Optos ultra-widefield fundus images diameter and OCT to measure tumour diameter and thickness, respectively, required a change in management from a reduction in MOLES score from 1 to 0. Discussion/Conclusion: This study suggests that the MOLES category for size is influenced more by the tumour diameter, if it can be measured accurately, than by the thickness. This study suggests ignoring tumour thickness if this cannot be measured accurately with OCT, unless the tumour has a mushroom shape.

Factors affecting eye conservation and metastasis in posterior uveal melanomas.

To determine the effect of patient and tumor features and different treatments on eye removal (enucleation or exenteration) and metastasis in posterior uveal melanoma (PUM). Retrospective analysis. Patient age (≤60 vs >60 years), sex (female vs male), visual acuity (VA, ≤20/40 vs >20/40), largest tumor basal diameter (LTBD), tumor thickness, tumor stage according to American Joint Committee on Cancer (AJCC) 8th edition, ciliary body involvement, distance to optic disc (OD)/fovea (≤3 mm vs >3 mm), OD involvement, and histopathology were evaluated. Primary treatment options were transpupillary thermotherapy, plaque radiotherapy, Cyberknife radiosurgery, exoresection, and eye removal. Risk factors for primary eye removal were determined using logistic regression test and those for secondary eye removal and metastasis with Cox regression analysis. Of 387 cases, 153 (39.5%) underwent primary eye removal. Multivariable risk factors for primary eye removal included AJCC tumor stage (p = 0.001, OR:4.586; p < 0.001, OR:34.545; p < 0.001, OR:103.468 for stages T2, T3, and T4 vs stage T1, respectively), and VA≤20/40 (p = 0.014, OR:2.597). Multivariable risk factors for secondary eye removal were VA≤20/40 (p = 0.019, RR:2.817) and AJCC stage T3 vs T1 (p = 0.021, RR:2.666). Eye preservation rates in patients undergoing eye-conserving treatments were 80.3%, 69.6%, and 51.5% at 5, 10, and 15 years, respectively. Metastasis-free survival rates were 81.0%, 73.0%, and 56.7% at 5, 10, and 15 years, respectively. Multivariable risk factors for metastasis included eye removal as primary treatment (p = 0.005, RR:2.828) and mixed type histopathology (p < 0.001, RR:4.804). Early diagnosis is crucial for both eye preservation and survival in PUM. Increasing AJCC tumor stage and lower VA were risk factors for eye removal in this study. Mixed type histopathology and primary eye removal were risk factors for metastasis.

Robotic CyberKnife Radiosurgery for the Treatment of Choroidal and Ciliary Body Melanoma

To present the results of robotic assisted radiosurgery in choroidal and ciliary body melanomas treated at the Department of Ophthalmology of Ludwig-Maximilians-University and the European CyberKnife Center in Munich, Germany. Interventional case series METHODS AND MATERIALS: This retrospective study included 594 consecutive patients referred to our clinic for the treatment of choroidal and ciliary body melanomas with robotic radiosurgery (CyberKnife) from 2005 to 2019. Eye retention, local control and disease-specific survival rates were calculated as Kaplan-Meier and actuarial estimates. The impact of prescription dose, tumor size and ciliary body involvement was assessed by likelihood ratio tests and Cox regression. Among all patients that were staged according to the TNM classification system (8th edition), 22.7% were I, 57.9% II, 18.9% III and 0.5% of patients were classified as IV. Median apical tumor height and base diameter were 5.8 and 11.4 mm. The mean follow-up was 41.7 months. Local control after three and five years was 92.0% (95% CI 88.2 - 94.7%)and 84.3% (95% CI 77.9 - 89.0%) respectively for 21-22 Gy and 86.9% (95% CI 79.7 - 91.7%) and 77.7% (95% CI 68.5 - 84.6%) respectively when treated with 20 Gy or less. Eye retention was achieved in 89.9% and 81.0% after three and five years with 21-22 Gy and 85.9% and 80.0% for 20 Gy or less. Disease-specific survival rates were 93.1% (95% CI 90.2 - 95.2%) after three years, 89.8% (95% CI 86.0 - 92.6%) after five years and 87.8% (95% CI 82.8 - 91.4%) after seven years. This is the largest series of patients treated for choroidal and ciliary body melanomas with CyberKnife. Our results reflect an improvement in the outcome of CyberKnife therapy for patients suffering from choroidal and ciliary body melanoma treated with single session radiosurgery in the last decade.

Conjunctival Melanoma in 430 Cases: Comparative Analysis of the Impact of Orbital Invasion on Tumor Recurrence, Metastasis, and Death.

To compare the clinical features at presentation and treatment outcomes of conjunctival melanoma by absence/presence of orbital invasion. A retrospective review of patients with conjunctival melanoma managed at a single tertiary referral center from April 18, 1974, to September 9, 2019. Of 430 patients with conjunctival melanoma, 21 (5%) had orbital invasion at presentation. A comparison between the 2 groups (orbital invasion absent vs. present) revealed that the orbital invasion group had a higher frequency of prior eyelid incisional biopsy (5% vs. 24%, P = 0.006), greater tumor basal diameter (12.2 vs. 17.3, P = 0.009), greater tumor thickness (2.4 vs. 7.0, P < 0.001), more quadrants involved (1.8 vs. 2.5, P = 0.002), and more clock hours involved (4.4 vs. 5.8, P = 0.037). In addition, those with orbital invasion were more likely to undergo exenteration as primary treatment (1% vs. 24%, P < 0.001). Multivariate relative risk regression analysis revealed that variables predictive of orbital invasion included greater tumor thickness (P < 0.001) and greater involvement of the fornix (P = 0.031) and tarsus (P = 0.033). Outcomes revealed orbital invasion group with greater 5-year/10-year distant metastatic rate (16%/21% vs. 63%/63%, P = 0.005), and greater melanoma-related death rate (7%/13% vs. 38%/53%, P = 0.001). Conjunctival melanoma with orbital invasion at presentation demonstrate larger, more extensive tumors involving the fornix or tarsus, and with greater rate of melanoma-related metastasis and death.

Yttrium-90 (90Y) Brachytherapy for Small Iridociliary Melanomas

<h3>Purpose/Objective(s)</h3> Beta irradiation has been useful in treating numerous ocular tumors and benign growths. However, strontium-90 applicators are no longer supported and ruthenium-106 is not available for high dose rate (HDR) brachytherapy. Herein we present the first clinical use of a new HDR ⁹⁰Y brachytherapy source that is FDA 510(k) cleared for the treatment of ocular tumors and benign growths. <h3>Materials/Methods</h3> The iWand A® is a new single-use ophthalmic hand-held brachytherapy applicator, with a surface contact diameter of 10 mm. In addition, the applicator's translucent polymer backing both attenuates radiation exposure towards the surgeon and ancillary staff and allows visualization of the disc-shaped ⁹⁰Y source during treatment. A well-shaped recess on the anterior surface of the applicator accommodates a 6-mm disc-shaped source, where it is flush-mounted and affixed by biocompatible adhesive. The titanium shell of the source provides rigid encapsulation of the radioactive ⁹⁰Y source. Though the LV Y-90 Disc is FDA cleared to be utilized at up to 20 millicuries (mCi); the activity used for these 2 treatments was mean 12.4 mCi. For example, a 20 mCi LV ⁹⁰Y Disc which decays by β-emission with an end point energy of 2.28 MeV (0.98 MeV average), yields 30.0, 21.6, 16.2, and 4.8 Gy/minute at depths of 0.0, 0.6, 1.0, and 2.6 mm, respectively. While planning tool simulations were used to demonstrate the treatment volume and penumbra characteristics of the ⁹⁰Y disc, NIST-traceable preoperative calibrations were performed by an independent authorized medical physicist. <h3>Results</h3> Two patients (mean age=74 years) were diagnosed with AJCC 8^th edition T1-sized, biopsy-proven iridociliary melanoma. High-frequency ultrasound was used to measure tumor size, basal dimensions and distance from the overlying sclera. Measurements revealed a mean maximum tumor thickness of 0.7 mm (0.6-0.8) and a mean maximum largest tumor basal diameter of 3.0 mm (2.9-3.1). Surgery required a minor conjunctival recession to expose the episcleral target zone. The 10 mm application site was marked with tissue dye on the cornea and sclera. Then the ⁹⁰Y source, affixed within the iWand A® applicator, was applied to deliver HDR episcleral brachytherapy to doses of 25 - 30 Gy to a 2.5-mm depth. Treatment durations ranged from 5 to 13 minutes. During treatment, the acrylic of the iWand A® applicator was found capable of shielding the patient, surgeon and operating-room personnel. No acute or post-operative ⁹⁰Y-radiation-related complications were noted. The ⁹⁰Y source's 64-hour half-life allowed for single-use, decay in storage, and return for disposal. <h3>Conclusion</h3> A novel, FDA-cleared, HDR ⁹⁰Y beta source was used to treat 2 patients with uveal melanoma. It was affixed within a hand-held, single-use applicator that aids guidance, targeting and facilitates radiation safety (as measured during both surgeries). Future research is needed to explore additional applications for this novel ⁹⁰Y HDR brachytherapy source.

Automatic Three-Dimensional Magnetic Resonance-based measurements of tumour prominence and basal diameter for treatment planning of uveal melanoma.

Three-dimensional (3D) Magnetic Resonance Imaging (MRI) is increasingly used to complement conventional two-dimensional ultrasound in the assessment of tumour dimension measurement of uveal melanoma. However, the lack of definitions of the 3D measurements of these tumour dimensions hinders further adaptation of MRI in ocular radiotherapy planning. In this study, we composed 3D MR-based definitions of tumour prominence and basal diameter and compared them to conventional ultrasound. Tumours were delineated on 3DT2 and contrast-enhanced 3DT1 (T1gd) MRI for 25 patients. 3D definitions of tumour prominence and diameter were composed and evaluated automatically on the T1gd and T2 contours. Automatic T1gd measurements were compared to manual MRI measurements, to automatic T2 measurements and to manual ultrasound measurements. Prominence measurements were similar for all modalities (median absolute difference 0.3mm). Automatic T1gd diameter measurements were generally larger than manual MRI, automatic T2 and manual ultrasound measurements (median absolute differences of 0.5, 1.6 and 1.1mm respectively), mainly due to difficulty defining the axis of the largest diameter. Largest differences between ultrasound and MRI for both prominence and diameter were found in anteriorly located tumours (up to 1.6 and 4.5mm respectively), for which the tumour extent could not entirely be visualized with ultrasound. The proposed 3D definitions for tumour prominence and diameter agreed well with ultrasound measurements for tumours for which the extent was visible on ultrasound. 3D MRI measurements generally provided larger diameter measurements than ultrasound. In anteriorly located tumours, the MRI measurements were considered more accurate than conventional ultrasound.

Paradoxical GH increase during oral glucose load may predict overall remission in acromegalic patients

BackgroundThe nadir growth hormone (nGH) during the oral glucose tolerance test (OGTT) is the gold standard method for diagnosing acromegaly. A paradoxical growth hormone (GH) response to oral glucose (OG) in acromegaly can be observed. The role of the paradoxical GH response on how the patients with acromegaly respond to the treatment has been addressed in few studies. The aim of this study was to investigate the association between glucose-dependent growth hormone results and and the responses of acromegalic patients to surgical and/or medical therapy following surgery. Material and methodsThis retrospective cohort study included patients with acromegaly who underwent surgery (n = 189) or received primary medical treatment (n = 9). The mean age was 50.44 ± 12.81 years (M/F: 84/114). The patients were grouped into paradoxical (GH-P) and non-paradoxical (GH-nP) according to GH response to OG and were compared in terms of clinical and pathological features, pituitary tumor size, invasiveness, biochemical profiles, and how they responded to the treatment. ResultsThe mean age, gender distribution, and basal tumor diameter were all similar in both groups (p > 0.05). The GH-P group had a higher remission rate in response to medical therapy followed by surgery (83% vs. 55%; p = 0.026). Although a higher surgical remission rate in favor of GH-P was observed, it did not reach statistical significance (63% vs. 48%; p = 0.059). Overall treatment response rates were also higher in the GH-P group compared to the GH-nP group (89% vs. 71%; p = 0.005). ConclusionA paradoxical GH response to OG load may help to predict the response to medical treatment in patients with acromegaly.

Machine learning models demonstrate that clinicopathologic variables are comparable to gene expression prognostic signature in predicting survival in uveal melanoma

PurposeSince molecular assays are not accessible to all uveal melanoma patients, we aim to identify cost-effective prognostic tool in risk stratification using machine learning models based on routine histologic and clinical variables. Experimental designWe identified important prognostic parameters in a discovery cohort of 164 enucleated primary uveal melanomas from 164 patients without prior therapies. We then validated the prognostic prediction of top important parameters identified in the discovery cohort using 80 uveal melanomas from the Tumor Cancer Genome Atlas database with available gene expression prognostic signature (GEPS). The performance of three different survival analysis models (Cox proportional hazards (CPH), random survival forest (RSF), and survival gradient boosting (SGB)) was compared against GEPS using receiver operating curves (ROC). ResultsIn all three selection methods, BAP1 status, nucleoli size, age, mitotic rate per 1 mm2, and ciliary body infiltration were identified as significant overall survival (OS) predictors; and BAP1 status, nucleoli size, largest basal tumor diameter, tumor-infiltrating lymphocyte density, and tumor-associated macrophage density were identified as significant progression-free survival (PFS) predictors. ROC plots for the median survival time point showed that significant parameters in SGB studied model can predict OS better than GEPS. For PFS, SGB model performed similarly to GEPS. The time-dependent area under the curve (AUC) showed SGB model performing better than GEPS in predicting OS and metastatic risk. ConclusionsOur study shows that routine histologic and clinical variables are adequate for patient risk stratification in comparison with not readily accessible GEPS.

Primary Macular Retinoblastoma: Clinical Presentation and Treatment Outcomes.

Purpose: To describe the clinical features and treatment outcomes in eyes with primary macular retinoblastoma (RB). Methods: Patients with primary macular RB were analyzed. Results: Of 41 patients (47 eyes), 20 (49%) were boys and 21 (51%) were girls. The mean age at diagnosis was 16 months (range, 1-60 months). The RB was bilateral in 6 patients (15%). At presentation, the macula was completely covered with the tumor in 22 eyes (47%) and partially covered with the fovea spared in 13 eyes (28%) and the fovea involved 12 eyes (25%). Based on the International Classification of Intraocular Retinoblastoma, 25 (53%), 15 (32%), and 7 (15%) of tumors were in Group B, Group C, and Group D, respectively. The tumor had exophytic features in 36 eyes (77%). The mean tumor basal diameter was 10.0 mm and the mean thickness, 5.6 mm. Associated features included subretinal seeds (10 eyes; 21%) and surrounding subretinal fluid (16 eyes; 34%). Forty-three eyes (92%) were treated with intravenous chemotherapy, 2 (4%) with intra-arterial chemotherapy, and 2 (4%) with transpupillary thermotherapy. Local tumor control was achieved in 45 eyes (96%), with 33 eyes (70%) showing a type III regression pattern. Over a mean follow-up of 23 months (range, 3-48 months), the macular tumor recurred in 5 eyes (11%), the globe was salvaged in all eyes with associated foveal atrophy (36 eyes; 77%), and 1 patient (2%) died. Conclusions: Macular RB has a good prognosis for globe salvage while vision salvage might be compromised as a result of associated foveal atrophy.