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Melanoma: HELP
Articles by Jerry A. Shields
Based on 100 articles published since 2008
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Between 2008 and 2019, J. A. Shields wrote the following 100 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Editorial Bilateral uveal melanoma: hunting for the source. 2018

Shields, Carol L / Masoomian, Babak / Shields, Jerry A. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. ·Clin Exp Ophthalmol · Pubmed #30003677.

ABSTRACT: -- No abstract --

2 Editorial Surgical removal of intraocular tumors: dismissing old wives' tales. 2013

Shields, Carol L / Shields, Jerry A. · ·Am J Ophthalmol · Pubmed #23791370.

ABSTRACT: -- No abstract --

3 Editorial Uveal melanoma trapped in the temple of doom. 2012

Shields, Carol L / Ganguly, Arupa / O'Brien, Joan / Sato, Takami / Shields, Jerry A. · ·Am J Ophthalmol · Pubmed #22813447.

ABSTRACT: -- No abstract --

4 Review Small choroidal melanoma: detection with multimodal imaging and management with plaque radiotherapy or AU-011 nanoparticle therapy. 2019

Shields, Carol L / Lim, Li-Anne S / Dalvin, Lauren A / Shields, Jerry A. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. ·Curr Opin Ophthalmol · Pubmed #30844944.

ABSTRACT: PURPOSE OF REVIEW: To explore risk factors for choroidal nevus transformation into melanoma using multimodal imaging and review current treatment options. RECENT FINDINGS: A recently published longitudinal study of 3806 choroidal nevi, imaged with optical coherence tomography (OCT), ultrasonography, and standard wavelength autofluorescence, revealed transformation into melanoma in 5.8% at 5 years and 13.9% at 10 years, using Kaplan-Meier analysis. Multivariate factors predictive of transformation included thickness more than 2 mm (by ultrasonography), fluid subretinal (by OCT), symptoms vision loss (by Snellen acuity), orange pigment (by autofluorescence), melanoma hollow (by ultrasonography), and DIaMeter more than 5 mm (by photography). These important factors can be recalled by the mnemonic 'To Find Small Ocular Melanoma Doing IMaging' (TFSOM-DIM). The mean 5-year estimate of nevus growth into melanoma was 1.1% for those with 0 risk factor, 11% with one factor, 22% with two factors, 34% with three factors, 51% with four factors, and 55% with five risk factors. Management of small choroidal melanoma typically involves plaque radiotherapy with 5 and 10-year rates of tumor recurrence at 7 and 11%, visual acuity loss (≥3 Snellen lines) at 39 and 49%, and melanoma-related metastasis at 4 and 9%. A novel infrared dye-conjugated virus-like nanoparticle (AU-011) is currently under investigation for treatment of small choroidal melanoma, with a goal to induce tumor regression and minimize vision loss. SUMMARY: The mnemonic, TFSOM-DIM, can assist the clinician in detection of small choroidal melanoma. Treatment of small melanoma with plaque radiotherapy offers tumor control but with potential vision loss. A novel nanoparticle therapy using AU-011 is currently under trial.

5 Review Prognosis of uveal melanoma based on race in 8100 patients: The 2015 Doyne Lecture. 2015

Shields, C L / Kaliki, S / Cohen, M N / Shields, P W / Furuta, M / Shields, J A. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA. · 1] Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA [2] Dr Kaliki currently practices at the Ocular Oncology Service, L.V. Prasad Eye Institute, Hyderabad, India. ·Eye (Lond) · Pubmed #26248525.

ABSTRACT: A retrospective, nonrandomized, interventional case series of 8100 patients with uveal melanoma were evaluated for melanoma-related metastasis based on patient race. The patient race was Caucasian (n=7918, 98%), Hispanic (n=105, 1%), Asian (n=44, <1%), or African American (n=33, <1%). On the basis of race (Caucasian, Hispanic, Asian, and African American), significant differences were noted in mean age at presentation (58, 48, 44, and 52 years; P<0.001), distance of posterior tumor margin to foveola (5, 5, 6, and 4 mm; P<0.001), distance of posterior tumor margin to optic disc (5, 5, 6, and 4 mm) (P<0.001), tumor base (11, 12, 12, and 13 mm; P<0.001), tumor thickness (5.4, 7.1, 6.5, and 7.5 mm; P<0.001), intraocular hemorrhage (10, 14, 11, and 24%; P=0.02), and rupture of Bruch's membrane (20, 27, 39, and 36%; P=0.001). On the basis of multivariate analysis, the rate of metastasis increased with increasing age (P<0.001), ciliary body location (P<0.001), increasing tumor base (P<0.001), increasing tumor thickness (P<0.001), pigmented tumor (P=0.001), subretinal fluid (P=0.001), intraocular hemorrhage (P=0.045), and extraocular extension (P=0.036). Kaplan-Meier estimates of metastasis at 3, 5, and 10 were 8, 15, and 25% in Caucasians; 13, 13, and 13% in Hispanics; 4, 4, and 36% in Asians; and 8, 8, and 8% in African Americans. Compared with Caucasians, despite relative risk for metastasis of 0.31 for African Americans, 0.73 for Hispanics, and 1.42 for Asians, there was no statistical difference in metastasis, or death from uveal melanoma based on race. In summary, uveal melanoma showed similar prognosis for all races.

6 Review Uveal melanoma: estimating prognosis. 2015

Kaliki, Swathi / Shields, Carol L / Shields, Jerry A. ·Institute for Eye Cancer, L V Prasad Eye Institute, Banjara Hills, Support provided by Operation Eyesight Institute for Eye Cancer (SK) and Hyderabad Eye Research Foundation (SK), Hyderabad, India. ·Indian J Ophthalmol · Pubmed #25827538.

ABSTRACT: Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

7 Review Melanoma of the eye: revealing hidden secrets, one at a time. 2015

Shields, Carol L / Kels, Jane Grant / Shields, Jerry A. ·The Ocular Oncology Service, Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA. Electronic address: carol.shields@shieldsoncology.com. · Department of Dermatology, University of Connecticut Health Center, Farmington, CT. · The Ocular Oncology Service, Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA. ·Clin Dermatol · Pubmed #25704938.

ABSTRACT: Melanoma of the eye can involve the uveal tract with iris, ciliary body, or choroid involvement or it can involve the conjunctiva, eyelid, or orbit. Uveal involvement with choroidal melanoma is the most common, found in light complexion Caucasians with an age-adjusted incidence of 4.3 per million persons. Early detection of uveal melanoma is critical. The ABCDEF guide helps to differentiate iris nevus from iris melanoma. The letters represent: A, age young (≤40 years); B, blood in anterior chamber; C, clock hour of mass inferiorly; D, diffuse configuration; E, ectropion; and F, feathery margins. The mnemonic of TFSOM-UHHD (To Find Small Ocular Melanoma-Using Helpful Hints Daily) helps to differentiate choroidal nevus from small melanoma and represents: T, thickness over 2 mm; F, fluid; S, symptoms; O, orange pigment; M, margin within 3 mm of the optic disc; UH, ultrasound hollow; H, halo absent; and D, drusen absent. Patients with 3 or more of these factors are likely to have melanoma. These key clinical features help to identify small melanoma at a time when therapy could be life-saving. Conjunctival melanoma usually arises from primary acquired melanosis, a flat pigmentation that can lead to melanoma. Wide excision using no touch strategy is important to tumor control. Ocular examination is advised annually for all persons for detection of refractive error, cataract, glaucoma, and other conditions, but also for the detection of asymptomatic malignancies like melanoma. One at a time, we have uncovered the secrets of ocular melanoma and we forge ahead with the goal to solve the riddle of this challenging disease.

8 Review Choroidal melanoma: clinical features, classification, and top 10 pseudomelanomas. 2014

Shields, Carol L / Manalac, Janet / Das, Chandana / Ferguson, Kyle / Shields, Jerry A. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. ·Curr Opin Ophthalmol · Pubmed #24614143.

ABSTRACT: PURPOSE OF REVIEW: To review the current features and classification of choroidal melanoma, and to identify the lesions that clinically simulate choroidal melanoma (pseudomelanoma). RECENT FINDINGS: Uveal melanoma is a serious life-threatening intraocular malignancy, most often found in Caucasians (98%) and primarily involving the choroid (90%), ciliary body (7%), or iris (2%). This review will concentrate on choroidal melanoma. At diagnosis, choroidal melanoma usually appears as a pigmented (85%) tumor underlying the retina with a median basal dimension of 11 mm and a mean thickness of 4.5 mm. The American Joint Committee on Cancer classification allows for categorization and staging of melanoma. Following ocular therapy, adjuvant systemic therapy is provided for patients with high-risk melanoma who demonstrate alterations in chromosomes 3, 6, and 8 or those with class 2 on gene-expression profiling, detected by needle biopsy or solid tumor biopsy. The prognosis of choroidal melanoma depends most importantly on the genetic alterations and tumor size. Every millimeter increase in thickness leads to a 5% increased risk for metastasis. The leading conditions that simulate choroidal melanoma include choroidal nevus, peripheral exudative hemorrhagic chorioretinopathy, congenital hypertrophy of the retinal pigment epithelium (RPE), hemorrhagic RPE detachment, choroidal hemangioma, age-related macular degeneration, RPE hyperplasia, and others. These pseudomelanomas can be differentiated from choroidal melanoma by their unique clinical features. SUMMARY: Choroidal melanoma is a serious malignancy with characteristic features. Early detection and therapy is important. Pseudomelanomas can lead to diagnostic confusion; however, clinical features aid in differentiation.

9 Review Ocular melanoma: relatively rare but requiring respect. 2009

Shields, Carol L / Shields, Jerry A. ·Ocular Oncology Service, Wills Eye Institute, Philadelphia, PA 19107, USA. carol.shields@shieldsoncology.com ·Clin Dermatol · Pubmed #19095158.

ABSTRACT: Primary ocular melanoma can involve the uveal tract, conjunctiva, eyelid, or orbit. Uveal melanoma is the most common ocular melanoma and carries a serious prognosis, especially if the tumor is medium or large in size. Conjunctival melanoma manifests on the surface of the eye and has been increasing in incidence. Eyelid and primary orbital melanoma are the least common variants. Early diagnosis from annual ocular examination by an experienced ophthalmologist and treatment strategies are reviewed.

10 Article Iris Melanoma in a Child Simulating Juvenile Xanthogranuloma. 2018

Shields, Jerry A / Shields, Carol L / Lally, Sara E / Milman, Tatyana / Eagle, Ralph C. ·Department of Ocular Oncology, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA. · Department of Pathology, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA. ·Middle East Afr J Ophthalmol · Pubmed #30122859.

ABSTRACT: An 8-year-old girl was referred for an amelanotic iris tumor believed to have enlarged slightly over 3 months, suspicious for juvenile xanthogranuloma (JXG). The affected right eye had a lightly pigmented, vascular iris mass measuring 6 mm in basal dimension and 2 mm in thickness. There were no feeder vessels, seeding, inflammatory cells, or cutaneous abnormalities. Diagnostic fine needle aspiration biopsy (FNAB) was performed, revealing spindle B melanoma cells that were immunoreactive for melanocytic markers HMB45 and Melan-A. Complete tumor resection by basal sector iridectomy was performed. Histopathology confirmed spindle B melanoma. At 14-years follow up, there has been no recurrence or metastasis and visual acuity remains 20/25. Iris melanoma can develop in children and clinically resemble nodular JXG.

11 Article LARGE UVEAL MELANOMA (≥10 MM THICKNESS): Clinical Features and Millimeter-by-Millimeter Risk of Metastasis in 1311 Cases. The 2018 Albert E. Finley Lecture. 2018

Shields, Carol L / Sioufi, Kareem / Robbins, Justin S / Barna, Laura E / Harley, Maxwell R / Lally, Sara E / Say, Emil Anthony T / Mashayekhi, Arman / Shields, Jerry A. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. ·Retina · Pubmed #29528980.

ABSTRACT: PURPOSE: To analyze the clinical features and rate of metastatic disease in eyes with large (≥10 mm thickness) uveal melanoma. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: There were 1,311 consecutive patients. METHODS: Retrospective medical chart review. MAIN OUTCOME MEASURES: Clinical features and rate of metastatic melanoma. RESULTS: Of 1,311 patients with large melanoma, the mean age was 59 years (median 60, range 6-98 years) and 95% were white. Mean tumor basal dimension was 17 mm (median 17, range 7-25 mm), and mean tumor thickness was 12 mm (median 12, range 10-24 mm). Mean distance to the foveola was 6 mm (median 6, range 0-19 mm) and to optic nerve was 6 mm (median 5, range 0-19 mm). Of all eyes, using Kaplan-Meier analysis, metastasis occurred in 11, 30, 45, and 52% at 1, 3, 5, and 7 years, respectively. According to tumor thickness (10.0-11.0, 11.1-12.0, 12.1-13.0, 13.1-14.0, 14.1-15.0, 15.1-16.0, and >16.0 mm), metastasis at 1 year was found in 7, 12, 13, 15, 18, 22, and 20%; metastasis at 3 years was 24, 27, 37, 35, 51, 69, and 57%; metastasis at 5 years was 38%, 42%, 56%, 48%, 61%, not available, and 66%; and metastasis at 7 years was 47%, 47%, 61%, 57%, 61%, not available, and 66%. Clinical features associated with fewer metastatic events included Bruch membrane rupture (7-year metastasis at 48%, P = 0.018) and macular location (7-year metastasis at 32%, P = 0.014), whereas those with worse outcome included extraocular extension (7-year metastasis at 79%, P < 0.001). There was no significant difference in rate of melanoma-related metastasis for patients treated with plaque radiotherapy versus enucleation. CONCLUSION: Large uveal melanoma demonstrates 7-year rate of metastasis at 52%, with generalized increasing risk per 1-mm or 2-mm thickness increments. Extraocular extension was associated with greater metastatic rate, whereas Bruch membrane rupture and macular location demonstrated lower rate.

12 Article Adjuvant Sunitinib in High-Risk Patients with Uveal Melanoma: Comparison with Institutional Controls. 2018

Valsecchi, Matias E / Orloff, Marlana / Sato, Rino / Chervoneva, Inna / Shields, Carol L / Shields, Jerry A / Mastrangelo, Michael J / Sato, Takami. ·Department of Medical Oncology, Sidney Kimmel Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania; Huntington Internal Medicine Group, Huntington, West Virginia. · Department of Medical Oncology, Sidney Kimmel Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania. · Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania. · Ocular Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania. · Department of Medical Oncology, Sidney Kimmel Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: Takami.sato@jefferson.edu. ·Ophthalmology · Pubmed #28935400.

ABSTRACT: PURPOSE: To compare overall survival in high-risk patients with primary uveal melanoma who received adjuvant sunitinib with institutional controls. DESIGN: Retrospective cohort. PARTICIPANTS: Selection criteria were (1) monosomy 3 and 8q amplification by cytogenetic or DecisionDx-UM Class 2 and (2) monosomy 3 and large tumor size (T3-4 by American Joint Committee on Cancer classification). Exclusion criteria were date of diagnosis before 2007 or after 2013 and age <18 years. METHODS: A cohort of patients who intended to receive adjuvant sunitinib for 6 months was compared with institutional historical controls with the same risk factors. Kaplan-Meier and Cox proportional hazards models were used to analyze the outcome. Propensity score was used to adjust for nonrandom assignment to sunitinib. MAIN OUTCOME MEASURES: Overall survival. RESULTS: From the Wills Eye Hospital Oncology Service Uveal Melanoma Cytogenetic Database (N = 1172), 128 patients fulfilled the selection and exclusion criteria. Median follow-up was 52.7 months (range, 0.26-108 months). A total of 54 patients received sunitinib. Their median age was 56 years (range, 29-81 years), and 48% were men. A total of 74 historical controls in the same risk category were identified. Their median age was 62 years (21-80 years), and 48% were men. Patients in the sunitinib group had worse cytogenetic or molecular features (monosomy 3 and 8q amplification or class 2 87% vs. 57%; P < 0.001), had smaller tumor sizes (T3-4 56% vs. 83%; P = 0.001), and were younger. There were 51 deaths, 14 (26%) in the sunitinib group and 37 (50%) in the control group. In the univariate analysis, the sunitinib group had longer overall survival (hazard ratio, 0.53; 95% confidence interval, 0.29-0.99; P = 0.041). In multivariate Cox regression analysis, interaction between use of sunitinib and age as a dichotomous variable was highly significant (P = 0.003). The following variables were statistically associated with prediction of overall survival: cytogenetic/molecular status (P = 0.015), T-size category (P = 0.022), gender (P = 0.040), and adjuvant sunitinib in patients aged <60 years (P = 0.004). Results were confirmed by propensity score analysis. CONCLUSIONS: In this retrospective study, the use of sunitinib in the adjuvant setting was associated with better overall survival.

13 Article COUGHING-INDUCED SUPRACHOROIDAL HEMORRHAGE SIMULATING MELANOMA IN TWO CASES. 2018

Marous, Charlotte L / Sioufi, Kareem / Shields, Carol L / Mashayekhi, Arman / Shields, Jerry A. ·Division of Ophthalmology, Saint George's University School of Medicine, Great River, New York. · Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. ·Retin Cases Brief Rep · Pubmed #27893592.

ABSTRACT: PURPOSE: To describe two cases of coughing-induced suprachoroidal hemorrhage referred as choroidal melanoma. METHODS: Observational case reports. RESULTS: Two female patients (ages 54 and 60 years) were referred with possible choroidal melanoma. Both gave a history of 1 day of heavy coughing with Valsalva maneuver within 2 weeks before discovery of the tumor. In one case, the patient used anticoagulants for aortic valve replacement and the other patient used antiasthma medications. One patient noted sharp ocular pain one week before presentation to this service. In both cases, the choroidal lesion was at the globe equator, near a vortex ampulla, and appeared homogeneously dark brown and with acoustic hollowness on ultrasonography, concerning for choroidal melanoma. However, neither lesion demonstrated intrinsic vascularity on fluorescein angiography or indocyanine angiography. Both lesions showed isoautofluorescence and optical coherence tomography evidence of shallow choroidal folds with inner choroidal elevation over a dome-shaped, optically-lucent deep choroidal mass, consistent with suprachoroidal hemorrhage. Fine needle aspiration biopsy in 1 case confirmed blood without melanoma. Both cases were observed with complete spontaneous resolution of the hemorrhage and normal-appearing choroid within 2 months. CONCLUSION: Coughing-induced suprachoroidal hemorrhage can simulate melanoma. Clinical and imaging features can assist in diagnosis. The hemorrhage generally resolves within few months.

14 Article Personalized Prognosis of Uveal Melanoma Based on Cytogenetic Profile in 1059 Patients over an 8-Year Period: The 2017 Harry S. Gradle Lecture. 2017

Shields, Carol L / Say, Emil Anthony T / Hasanreisoglu, Murat / Saktanasate, Jarin / Lawson, Brendan M / Landy, Jeffrey E / Badami, Anjali U / Sivalingam, Meera D / Hauschild, Alexander J / House, Robert J / Daitch, Zachary E / Mashayekhi, Arman / Shields, Jerry A / Ganguly, Arupa. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: carolshields@gmail.com. · Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. · Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. ·Ophthalmology · Pubmed #28495150.

ABSTRACT: PURPOSE: To determine the personalized rate of uveal melanoma-related metastasis on the basis of individual tumor cytogenetic profile. DESIGN: Retrospective case series. PARTICIPANTS: A total of 1059 patients with uveal melanoma. METHODS: Fine-needle aspiration biopsy (FNAB) for DNA amplification and whole genome array-based assay were performed for analysis of chromosomes 3, 6, and 8. MAIN OUTCOME MEASURES: Melanoma-related metastasis. RESULTS: The mean patient age was 57 years, and most were white (1026/1059, 97%). The melanoma involved the choroid (938/1059, 89%), ciliary body (85/1059, 8%), or iris (36/1059, 3%), with 19% being macular in location. The mean largest basal diameter was 11 mm (median, 12 mm; range, 3-24 mm), and mean thickness was 5 mm (median, 4 mm; range, 1-20 mm). On the basis of individual chromosomal mutations, risk for metastasis was increased for chromosome 3 partial monosomy (hazard ratio [HR], 2.84; P = 0.001), 3 complete monosomy (HR, 6.7, P < 0.001), 6q loss (HR, 3.1, P = 0.003), 8p loss (HR, 21.5, P < 0.001), and 8q gain (HR, 9.8, P < 0.001). Kaplan-Meier estimate for melanoma-related metastasis in 1, 3, 5, and 7 years for 3 partial monosomy was 1%, 5%, 14%, and 17%; for 3 complete monosomy was 3%, 19%, 28%, and 37%; for 6q loss was 8%, 23%, 49%, and 49%; for 8p loss was 8%, 29%, not estimable (NE), and NE; and for 8q gain was 6%, 21%, 35%, 48%, respectively. On the basis of personalized cytogenetic profiles, Kaplan-Meier estimates (1, 3, and 5 years) for melanoma-related metastasis for 3, 6, and 8 disomy (1%, 1%, 4% [HR, 1]) were low compared with the higher-risk combinations of 3 complete monosomy, 6p gain, and 8q gain (0%, 29%, 29% [HR, 10.6, P = 0.02]); 3 complete monosomy, 6 disomy, 8q gain, and 8p gain (14%, 14%, NE [HR, 18.3, P = 0.02]); 3 complete monosomy, 6 disomy, and 8q gain (8%, 27%, 39% [HR, 19.5, P < 0.001]); and 3 complete monosomy, 6 disomy, 8q gain, and 8p loss (3%, 28%, NE [HR, 31.6, P < 0.001]), respectively. CONCLUSIONS: Risk for melanoma-related metastasis strongly correlates with personalized cytogenetic profiles, with 5-year Kaplan-Meier estimates ranging from 4% with chromosomes 3, 6, and 8 disomy up to 39% for 3 complete monosomy, 6 disomy, and 8q gain.

15 Article Cytogenetic Abnormalities in Uveal Melanoma Based on Tumor Features and Size in 1059 Patients: The 2016 W. Richard Green Lecture. 2017

Shields, Carol L / Say, Emil Anthony T / Hasanreisoglu, Murat / Saktanasate, Jarin / Lawson, Brendan M / Landy, Jeffrey E / Badami, Anjali U / Sivalingam, Meera D / Mashayekhi, Arman / Shields, Jerry A / Ganguly, Arupa. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: carolshields@gmail.com. · Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. · Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. ·Ophthalmology · Pubmed #28159380.

ABSTRACT: PURPOSE: To determine the risks for altered cytogenetic profile based on melanoma features and size. DESIGN: Retrospective case series. PARTICIPANTS: A total of 1059 patients with uveal melanoma. METHODS: Fine-needle aspiration biopsy (FNAB) of tumor for DNA amplification and whole genome array-based assay. MAIN OUTCOME MEASURES: Risk for cytogenetic abnormalities based on features and size: small (≤3 mm thickness), medium (>3-<8 mm), and large (≥8 mm). RESULTS: Of 1059 patients with uveal melanoma sampled for status of chromosomes 3, 6, and 8, comparison (normal [disomy] chromosomes 3, 6, and 8 vs. any 3, 6, or 8 abnormality) revealed differences in mean age (55 vs. 58 years, P = 0.018), ocular melanocytosis (1% vs. 5%, P = 0.027), mean visual acuity (VA) (20/30 vs. 20/50, P = 0.011), poor VA (≤20/200) (9% vs. 15%, P = 0.041), ciliary body location (5% vs. 11%, P < 0.001), extramacular location (73% vs. 87%, P < 0.001), increased mean distance to optic disc (3.3 vs. 5.0 mm, P < 0.001) and foveola (3.1 vs. 4.7 mm, P < 0.001), and increased mean basal diameter (9.8 vs. 12.6 mm, P < 0.001) and thickness (3.8 vs. 5.9 mm, P < 0.001). Tumors classified as small, medium, and large showed abnormalities with loss of disomy of chromosomes 3 (35%/52%/65%), 6 (15%/34%/51%), and 8 (19%/41%/69%), respectively. By comparison (medium/large vs. small melanoma), the odds ratio (OR) included complete monosomy 3 (3.09, P < 0.001), partial monosomy 3 (1.44, P = 0.053), 6p gain (3.78, P < 0.001), 6q gain (1.37, P = 0.537), 6p loss (2.52, P = 0.410), 6q loss (12.61, P < 0.001), 8p gain (6.16, P < 0.001), 8p loss (6.04, P < 0.001), and 8q gain (4.87, P < 0.001). For chromosome 3 monosomy, the OR was highest for ciliary body location (8.17, P < 0.001), tumor thickness ≥8 mm (2.70, P < 0.001), tumor base ≥10 mm (2.59, P < 0.001), and age ≥60 years (1.83, P < 0.001). For chromosome 8p loss, the OR was highest for ciliary body location (53.91, P = 0.008), ocular melanocytosis (3.95, P = 0.038), and thickness ≥8 mm (5.14, P < 0.001), whereas for 8q gain, the OR was highest for ciliary body location (102.87, P = 0.001), thickness >8 mm (4.44, P < 0.001), and ocular melanocytosis (2.75, P = 0.049). CONCLUSIONS: Increasing melanoma size demonstrates greater cytogenetic alterations. Alterations in chromosome 8 show unique correlation with melanocytosis. This suggests that prompt management of small melanoma might reduce chromosomal instability and could improve overall patient survival.

16 Article OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE MACULA AFTER PLAQUE RADIOTHERAPY OF CHOROIDAL MELANOMA: Comparison of Irradiated Versus Nonirradiated Eyes in 65 Patients. 2016

Shields, Carol L / Say, Emil Anthony T / Samara, Wasim A / Khoo, Chloe T L / Mashayekhi, Arman / Shields, Jerry A. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. ·Retina · Pubmed #26960015.

ABSTRACT: PURPOSE: To study radiation retinopathy after plaque radiotherapy of choroidal melanoma using optical coherence tomography angiography. METHODS: Retrospective comparative analysis of 65 consecutive patients with choroidal melanoma, treated with standard dose I-125 plaque radiotherapy and imaged with optical coherence tomography angiography. A comparison of irradiated versus contralateral, nonirradiated (control) eyes was performed. RESULTS: The mean patient age was 55 years. Underlying medical diseases included diabetes mellitus (4/65, 4%) or hypertension (25/65, 38%), but no patient demonstrated disease-related retinopathy. The mean pretreatment melanoma diameter was 11 mm and mean thickness was 5 mm. The mean radiation dose to the foveola was 5663 centiGray. At mean follow-up of 46 months after plaque radiotherapy, the most frequent qualitative finding on optical coherence tomography angiography (irradiated eye) was nonperfusion in the superficial capillary plexus (19/65, 29%) and deep capillary plexus (20/65, 31%), followed by loss of choriocapillaris within tumor margins (11/65, 17%). The quantitative findings revealed foveal avascular zone with significantly larger mean area (irradiated vs. nonirradiated eye) in the superficial plexus (0.961 vs. 0.280 mm, P < 0.0001) and deep plexus (1.396 vs. 0.458 mm, P < 0.0001), even in eyes without clinical evidence of radiation maculopathy (superficial 0.278 mm, P = 0.03; deep 0.454 mm, P = 0.02). Parafoveal capillary density (superficial and deep) was decreased in all irradiated eyes (P < 0.001). This difference was maintained after subgroup analysis of eyes with (P < 0.001) or without (P < 0.001) clinical evidence of radiation maculopathy. Mean logMAR visual acuity was significantly reduced in irradiated eyes (0.7 vs. 0.1 [Snellen equivalent 20/100 vs. 20/25], P < 0.001) and the reduced vision was significant even in eyes without clinical evidence of radiation maculopathy (0.4 vs. 0.1 [Snellen equivalent 20/50 vs. 20/25], P < 0.001). CONCLUSION: Optical coherence tomography angiography demonstrated significant enlargement of the foveal avascular zone and decreased parafoveal capillary density of both superficial and deep capillary plexuses in eyes after plaque radiotherapy of choroidal melanoma, even in eyes with no clinical evidence of radiation maculopathy.

17 Article Malignant Melanoma Presenting as Pedunculated Lesion of the Caruncle. 2016

Shields, Jerry A / Pointdujour-Lim, Renelle / Lally, Sara E / Eagle, Ralph C / Shields, Carol L. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. ·JAMA Ophthalmol · Pubmed #26868483.

ABSTRACT: -- No abstract --

18 Article EXTRAOCULAR EXTENSION OF CILIOCHOROIDAL MELANOMA AFTER TRANSSCLERAL FINE-NEEDLE ASPIRATION BIOPSY. 2016

Mashayekhi, Arman / Lim, Renelle P / Shields, Carol L / Eagle, Ralph C / Shields, Jerry A. ·*Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania; and †Department of Pathology, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. ·Retin Cases Brief Rep · Pubmed #26655386.

ABSTRACT: PURPOSE: To describe development of extraocular extension of ciliochoroidal melanoma after transscleral fine-needle aspiration biopsy (FNAB) for cytogenetic studies. METHODS: Transscleral FNAB was performed for cytogenetic analysis of melanoma using a long 27-gauge needle attached to a 10-mL syringe by connector tubing entering obliquely through the sclera overlying the tumor base. An iodine 125 radioactive plaque was immediately applied to the sclera over the tumor and biopsy site after FNAB. PATIENTS: One patient with large ciliochoroidal melanoma of the right eye. RESULTS: Cytogenetic analysis of the melanoma revealed monosomy of chromosome 3. On examination, 18 months after plaque radiotherapy, there was regression of the tumor; however, a few small subepithelial pigmented lesions were noted in the conjunctiva close to the FNAB site. Excisional biopsy of the conjunctival pigmented lesions with 3 mm margins and with supplemental cryotherapy to the surrounding conjunctival margins and to the underlying sclera was performed. Histopathologic evaluation showed an oval nodule composed of a mixture of spindle and epithelioid cells deep within the substantia propria consistent with extraocular extension of uveal melanoma. Magnetic resonance imaging of the orbits showed no evidence of orbital involvement. This is the only case of extraocular extension developing among 408 consecutive transscleral biopsies (0.2%) performed at our center for cytogenetic or cytopathologic analysis. CONCLUSION: Although rare, transscleral FNAB of ciliochoroidal melanoma can lead to extraocular extension of the tumor through the biopsy site. Possible techniques to reduce the risk of this problem are discussed.

19 Article Periocular Melanoma In Situ Treated With Imiquimod. 2016

Elia, Maxwell D / Lally, Sara E / Hanlon, Allison M / Choi, Jennifer N / Servat, Juan J / Shields, Jerry A / Shields, Carol L / Levin, Flora. ·*Department of Ophthalmology and Visual Sciences, Yale School of Medicine, New Haven, Connecticut; †Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania; ‡Department of Dermatology, Yale School of Medicine, New Haven, Connecticut; and §Oculofacial Plastic Surgeons of Georgia, Atlanta, Georgia, U.S.A. ·Ophthalmic Plast Reconstr Surg · Pubmed #26325381.

ABSTRACT: PURPOSE: To evaluate the efficacy of topical 5% imiquimod cream in the treatment of periocular melanoma in situ (lentigo maligna). DESIGN: Retrospective case series. SUBJECTS: There were 12 patients in this series, and the mean patient age was 77 years. The anatomical locations were the lower eyelid (n=5), upper and lower eyelid (n=4), lower eyelid including the eyelid margin (n=1), brow (n=1), and the medial canthus (n=1). Topical 5% imiquimod cream was used as a primary treatment (n=6) or as an adjunctive therapy following local excision (n=2), cryotherapy (n=2), or excisional biopsy with cryotherapy (n=2). METHODS: Twelve patients with periocular melanoma in situ were treated with topical 5% imiquimod cream daily for a mean treatment period of 3.9 months. The clinical features of the patients and the responses to treatment were evaluated in a retrospective case series. MAIN OUTCOME MEASURES: Histologic clearance of atypical melanocytes. RESULTS: Eleven patients achieved complete histologic clearance of atypical melanocytes on post-treatment biopsy. One patient could not tolerate local irritation from imiquimod and stopped in the first month of therapy with residual disease. The median follow-up time was 1.5 years. Side effects included redness (n=12), discomfort (n=6), swelling (n=4), ectropion (n=1), and conjunctival chemosis (n=1). The patients experienced no systemic side effects from the treatment. CONCLUSIONS: Topical 5% imiquimod cream is an effective option as primary or adjunct therapy in the treatment of periocular melanoma in situ.

20 Article SUBMILLIMETER CHOROIDAL MELANOMA DETECTION BY ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY IN A PATIENT WITH OCULODERMAL MELANOCYTOSIS. 2016

Daitch, Zachary / Shields, Carol L / Say, Emil A T / Mashayekhi, Arman / Shields, Jerry A. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA. ·Retin Cases Brief Rep · Pubmed #26110523.

ABSTRACT: PURPOSE: To describe a tiny subclinical choroidal melanoma visualized only with enhanced depth imaging optical coherence tomography in a newly symptomatic patient with known oculodermal melanocytosis. METHODS: Case report. RESULTS: A 52-year-old white man with heterochromia and known oculodermal melanocytosis of the right eye, followed for 2 years without change, developed blurred vision and was referred for possible central serous chorioretinopathy. On examination, visual acuity was 20/20 in each eye. There was oculodermal melanocytosis in the right eye involving the periocular skin, episclera, iris, and choroid. On ophthalmoscopy and ocular ultrasonography, there was no appreciable mass, but subtle subfoveal fluid and perifoveal orange pigment were detected, as well as equatorial drusen. Enhanced depth imaging optical coherence tomography demonstrated a subtle optically dense focal choroidal mass measuring 4.5 mm in basal dimension and 0.7 mm in enhanced depth imaging optical coherence tomography thickness. There was choroidal vascular compression, obliteration of choroidal details, and related overlying subretinal fluid with shaggy photoreceptors, consistent with early choroidal melanoma in an eye with oculodermal melanocytosis. The patient elected early treatment considering the risk factors for growth and the risk for metastasis associated with melanoma in the setting of oculodermal melanocytosis. Plaque radiotherapy was performed with complete tumor regression clinically and by enhanced depth imaging optical coherence tomography. At 2-year follow-up, visual acuity remains 20/20, with regressed tumor and no systemic metastasis. CONCLUSION: Enhanced depth imaging optical coherence tomography is a useful tool in the evaluation of eyes with oculodermal melanocytosis, permitting high-resolution visualization of the choroid and detection of submillimeter early melanoma that might not be apparent with indirect ophthalmoscopy or ultrasonography.

21 Article American Joint Committee on Cancer Classification of Uveal Melanoma (Anatomic Stage) Predicts Prognosis in 7,731 Patients: The 2013 Zimmerman Lecture. 2015

Shields, Carol L / Kaliki, Swathi / Furuta, Minoru / Fulco, Enzo / Alarcon, Carolina / Shields, Jerry A. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: carol.shields@shieldsoncology.com. · Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. ·Ophthalmology · Pubmed #25813452.

ABSTRACT: PURPOSE: To analyze the clinical features and prognosis of posterior uveal melanoma based on the American Joint Committee on Cancer (AJCC) (7th edition) tumor staging. DESIGN: Retrospective interventional case series. PARTICIPANTS: A total of 7731 patients. METHODS: Uveal melanoma management. MAIN OUTCOME MEASURES: Melanoma-related metastasis and death. RESULTS: Of 7731 patients with posterior uveal (ciliary body and choroidal) melanoma, the AJCC tumor staging was stage I in 2767 (36%), stage II in 3735 (48%), stage III in 1220 (16%), and stage IV in 9 (<1%). Based on tumor staging (I, II, III, and IV), features that showed significant increase with tumor staging included age at presentation (57, 58, 60, 60 years) (P < 0.001), tumor base (8, 12, 17, 17 mm) (P < 0.001), tumor thickness (2.9, 6.0, 10.1, 10.2 mm) (P < 0.001), distance to optic disc (3, 5, 5, 5 mm) (P < 0.001), distance to foveola (3, 5, 5, 5 mm) (P < 0.001), mushroom configuration (6%, 24%, 34%, 33%) (P < 0.001), plateau configuration (3%, 4%, 7%, 11%) (P < 0.001), tumor pigmentation (48%, 53%, 69%, 78%) (P < 0.001), and extraocular extension (0%, 1%, 11%, 22%) (P < 0.001). After therapy, Kaplan-Meier estimates of metastasis at 1, 5, 10, and 20 years were <1%, 5%, 12%, and 20% for stage I, 2%; 17%, 29%, and 44% for stage II; 6%, 44%, 61%, and 73% for stage III, and 100% by 1 year for stage IV. Kaplan-Meier estimates of death at 1, 5, 10, and 20 years were <1%, 3%, 6%, and 8% for stage I; <1%, 9%, 15%, and 24% for stage II; 3%, 27%, 39%, and 53% for stage III, and 100% by 1 year for stage IV. Compared with stage I, the hazard ratio for metastasis/death was 3.1/3.1 for stage II and 9.3/10.1 for stage III. CONCLUSIONS: Compared with uveal melanoma classified as AJCC stage I, the rate of metastasis/death was 3 times greater for stage II, 9 to 10 times greater for stage III, and further greater for stage IV. Early detection of posterior uveal melanoma, at a point when the tumor is small, can be lifesaving.

22 Article Early subclinical macular edema in eyes with uveal melanoma: association with future cystoid macular edema. 2015

Mashayekhi, Arman / Schönbach, Etienne / Shields, Carol L / Shields, Jerry A. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: arman_mash@yahoo.com. · Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. ·Ophthalmology · Pubmed #25687025.

ABSTRACT: PURPOSE: To determine the frequency of early subclinical macular edema in eyes with uveal melanoma and its association with future cystoid macular edema (CME). DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 306 patients with uveal melanoma; 260 patients had follow-up of 1 or more years after plaque radiotherapy (follow-up cohort). METHODS: Review of medical records and spectral-domain optical coherence tomography (OCT) images. MAIN OUTCOME MEASURES: Frequency of early subclinical macular edema (increased central macular thickness of >10 μm without cystoid changes before or at 4 months after plaque radiotherapy); rate of future CME. RESULTS: At baseline, 164 patients (54%) had subclinical macular edema in the involved eye. On multivariate analysis, factors associated with subclinical macular edema at baseline were increasing tumor diameter (P = 0.001), increasing tumor thickness (P = 0.010), and subretinal fluid (P = 0.001). Of 260 patients in the follow-up cohort, 105 (40%) developed CME during a median follow-up of 31 months (mean, 34; range, 12-70 months). Eyes with subclinical macular edema at baseline (and at 4 months after plaque radiotherapy) had a significantly higher rate of future CME (n = 66; 50%) compared with eyes without subclinical macular edema at baseline (n = 39; 30%) (P = 0.005; hazard ratio, 1.77; 95% confidence interval, 1.19-2.64). On multivariate analysis, the factors associated with future development of CME included female gender (P = 0.004), increasing tumor thickness (P < 0.001), decreasing tumor distance to foveola (P = 0.002), hemorrhage over tumor (P = 0.017), and increased CMT of >10% at baseline in the involved eyes compared with the opposite eyes (P = 0.012). CONCLUSIONS: Subclinical macular edema is common in eyes with uveal melanoma before and at 4 months after plaque radiotherapy and is associated with initial larger tumor size. Eyes with early subclinical macular edema are at significantly higher risk for future CME. These findings suggest that tumor-related factors, most likely mediated through proinflammatory cytokines, may play an important role in development of post-radiation CME.

23 Article Double-blinded, randomized phase II study using embolization with or without granulocyte-macrophage colony-stimulating factor in uveal melanoma with hepatic metastases. 2015

Valsecchi, Matias E / Terai, Mizue / Eschelman, David J / Gonsalves, Carin F / Chervoneva, Inna / Shields, Jerry A / Shields, Carol L / Yamamoto, Akira / Sullivan, Kevin L / Laudadio, MaryAnn / Berd, David / Mastrangelo, Michael J / Sato, Takami. ·Department of Medical Oncology, Jefferson Medical College of Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107. · Department of Radiology, Division of Interventional Radiology, Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107. · Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107. · Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107. · Department of Radiology, Graduate School of Medicine, Osaka City University, Osaka. Japan. · Fresenius Vascular Care, Decatur, Georgia. · Department of Medical Oncology, Jefferson Medical College of Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107. Electronic address: takami.sato@jefferson.edu. ·J Vasc Interv Radiol · Pubmed #25678394.

ABSTRACT: PURPOSE: To investigate the effects of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with uveal melanoma (UM) with liver-only metastasis. MATERIALS AND METHODS: In this double-blind phase II clinical trial, patients were randomized to undergo immunoembolization or bland embolization (BE). Lobar treatment was performed with GM-CSF or normal saline solution mixed with ethiodized oil followed by embolization with gelatin sponge emulsified with iodinated contrast medium. Fifty-two patients (immunoembolization, n = 25; BE, n = 27) were enrolled. Response was assessed after every two treatments. The primary endpoint was overall response rate (ORR) of liver metastases. Progression-free survival (PFS), overall survival (OS), and immunologic responses were secondary endpoints. RESULTS: There were five partial responses in the immunoembolization group (ORR, 21.2%; 90% confidence interval [CI], 10.3%-30.5%) and three in the BE group (ORR, 16.7%; 90% CI, 6.3%-26.9%). Stable disease was seen in 12 patients in the immunoembolization group and 19 in the BE group. OS times were 21.5 months (95% CI, 18.5-24.8 mo) with immunoembolization and 17.2 months (95% CI, 11.9-22.4 mo) with BE. The degree of proinflammatory cytokine production was more robust after immunoembolization and correlated with time to "systemic" extrahepatic progression. In the immunoembolization group, interleukin (IL)-6 levels at 1 hour (P = .001) and IL-8 levels at 18 hours after the procedure (P < .001) were significant predictors of longer systemic PFS. Moreover, a dose-response pattern was evident between posttreatment serum cytokine concentrations and systemic PFS. CONCLUSIONS: Immunoembolization induced more robust inflammatory responses, which correlated with the delayed progression of extrahepatic systemic metastases.

24 Article Management of posterior uveal melanoma: past, present, and future: the 2014 Charles L. Schepens lecture. 2015

Shields, Jerry A / Shields, Carol L. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: jerryashields@gmail.com. · Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. ·Ophthalmology · Pubmed #25439609.

ABSTRACT: PURPOSE: To review the management of ciliary body and choroidal melanoma (posterior uveal melanoma [PUM]) over the last century with an emphasis on changing concepts. DESIGN: Retrospective review. PARTICIPANTS: Review of personal experience over 40 years and pertinent literature on management of PUM. METHODS: Diagnosis and therapy for PUM. MAIN OUTCOME MEASURES: Patient survival. RESULTS: In the early 1900s, most patients presented with a large symptomatic melanoma that necessitated enucleation, and the systemic prognosis was poor. In the 1970s, controversy erupted regarding the role of enucleation for PUM. Some authorities advocated prompt enucleation, and others proposed that enucleation promoted metastasis, known as the "Zimmerman hypothesis." Others recommended observation, withholding treatment until tumor growth was documented. During the 1970s, there was a trend toward eye-saving procedures, including laser photocoagulation, surgical removal of tumor, and techniques of radiotherapy. Despite local treatment success, systemic prognosis remained guarded with approximately 40% mortality overall. However, there was convincing evidence that smaller tumors offered a significantly better prognosis. Currently, there is a movement toward earlier identification and treatment of small melanomas using clinical factors predictive of malignant potential, in keeping with similar philosophy regarding other cancers. Further understanding of melanoma cytogenetics and molecular pathways have helped to recognize patients at risk for metastasis. At-risk patients are offered systemic therapeutic trials to prevent metastasis. We anticipate that the future management of PUM will focus on detection of clinical and imaging clues for earliest diagnosis, prompt local tumor treatment, and systemic targeted therapies for microscopic metastasis or prevention of metastasis. Personalized evaluation of patient-specific melanoma molecular pathway signature could allow for therapeutic intervention at a site specific to the pathway abnormality that leads to the development of melanoma. CONCLUSIONS: Management of PUM has made major strides over the past century from the days of enucleation for massive, fatal tumor to early detection of smallest tumors with a more favorable prognosis. Current and future targeted specific tumor pathway interruption using systemic agents could improve survival.

25 Article Primary transpupillary thermotherapy for choroidal melanoma in 391 cases: importance of risk factors in tumor control. 2015

Mashayekhi, Arman / Shields, Carol L / Rishi, Pukhraj / Atalay, Hatice T / Pellegrini, Marco / McLaughlin, John P / Patrick, Kaitlin A / Morton, Spenser J / Remmer, Meredith H / Parendo, Anthony / Schlitt, Meghan A / Shields, Jerry A. ·Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: arman_mash@yahoo.com. · Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. ·Ophthalmology · Pubmed #25439431.

ABSTRACT: PURPOSE: To report the long-term outcome of primary transpupillary thermotherapy (TTT) for choroidal melanoma. DESIGN: Retrospective review of medical records. PARTICIPANTS: We included 391 patients with choroidal melanoma treated between 1995 and 2012 at the Oncology Service, Wills Eye Hospital, Philadelphia. METHODS: We delivered TTT with an infrared diode laser. MAIN OUTCOME MEASURES: Local tumor recurrence, Snellen visual acuity after TTT, and distant metastasis. RESULTS: Of 391 patients, 311 (80%) were treated from 1995 to 2000 and 80 (20%) from 2001 to 2012. Tumors in the 2001 to 2012 group were ultrasonographically thinner (2.2 vs. 2.7 mm), more distant from the optic disc (3.2 vs. 2.5 mm) and foveola (4.0 vs. 2.0 mm), were less often located in the macular area (14% vs. 40%), and had lower rates of acoustic hollowness on B-scan ultrasonography (63% vs. 84%), subretinal fluid (58% vs. 90%), and orange pigment (50% vs. 70%). Kaplan-Meier estimates for tumor recurrence in the 1995 to 2000 group were 29% at 5 years and 42% at 10 years, whereas estimates for tumor recurrence in the 2001-2012 group were 11% at 5 years and 15% at 10 years. Of 108 recurrent tumors 20 were controlled with additional TTT and 62 required plaque radiation (n=60) or proton beam radiation (n=2), with enucleation necessary in 26 patients. Tumor recurrence correlated with the number of high-risk tumor features: 10-year recurrence was 18% in those with 1 or 2 risk factors, 35% in those with 3 to 5 factors, and 55% in those with 6 or 7 factors. On multivariate analysis, features predictive of tumor recurrence were presence of symptoms (P<0.001), shorter distance between the tumor and the optic disc (P=0.026), subretinal fluid (P=0.035), thickness of residual tumor scar (P<0.001), and elevation of residual tumor scar (P<0.001). The only factor predictive of extraocular tumor extension was intraocular tumor recurrence after TTT treated with additional TTT (P=0.007). Presence of orange pigment before TTT (P=0.019), tumor recurrence (P=0.002), and extraocular tumor extension (P=0.017) were predictive of distant metastasis. CONCLUSION: This study shows a direct correlation between a larger number of high-risk tumor features and higher rates of tumor recurrence after primary TTT of (small) choroidal melanoma. We advise that, when possible, small choroidal melanomas with multiple risk factors be treated with methods other than TTT.

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