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Radiation therapy for exudative choroidal hemangioma [Comment]

Finger, Paul T
PMID: 31007211
ISSN: 1998-3689
CID: 4096452

Intraocular Leiomyoma: Current Concepts

Tomar, Ankit Singh; Finger, Paul T; Iacob, Codrin
Intraocular leiomyoma is a benign smooth muscle tumor. First described prior to the era of immunohistochemistry, uveal leiomyomas have been described in case reports and small case series. We add 3 new cases, for a total of 80. Of these, there were 29 men and 51 women. The mean and median ages were 35.8 and 30.5 years, respectively, with a range of 8 to 80 years. Curiously, ciliary body tumors were more common in females, while iris and posterior choroidal leiomyomas were more prevalent in males. Infrequently associated with systemic fibroids, nuclear expression of sex steroid receptors was inconsistent. Iris and posterior choroidal leiomyoma were predominantly amelanotic, while 40% of ciliary body leiomyomas were brown. Two-thirds of the leiomyomas blocked transillumination partially or completely, a feature shared by uveal melanoma. In general, low-frequency ultrasound imaging reveals low to moderate internal reflectivity; however, high frequency anterior uveal ultrasound was used to localize a leiomyoma as resident in the suprachoroidal space with an overlying layer of intact choroid. In the few cases examined by physiologic imaging, increased metabolic activity (typically associated with malignancy and inflammation) has been noted. This review found that pigmented uveal leiomyomas can be clinically identical to melanoma. Therefore, histopathology with immunohistochemical staining for smooth muscle actin was the most reliable diagnostic method to differentiate pigmented uveal leiomyoma from melanoma. Treatment has been governed by the clinical diagnosis, tumor size and location, as well as prognosis for vision and globe preservation.
PMID: 31923479
ISSN: 1879-3304
CID: 4258772

The COMS Randomized Trial of Iodine 125 Brachytherapy for Choroidal Melanoma: IV. Local Treatment Failure and Enucleation in the First 5 Years after Brachytherapy. COMS Report No. 19

Jampol, Lee M; Moy, Claudia S; Murray, Timothy G; Reynolds, Sandra M; Albert, Daniel M; Schachat, Andrew P; Diddie, Kenneth R; Engstrom, Robert E; Finger, Paul T; Hovland, Kenneth R; Joffe, Leonard; Olsen, Karl R; Wells, Craig G
OBJECTIVE:) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial. DESIGN/METHODS:Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial. PARTICIPANTS/METHODS:Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension. METHODS:brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis. MAIN OUTCOME MEASURES/METHODS:Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation. RESULTS:As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [CI], 10.0%-15.6%); the risk of treatment failure was 10.3% (95% CI, 8.0%-13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P = 0.08). CONCLUSIONS:brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe.
PMID: 32200815
ISSN: 1549-4713
CID: 4357432

Early anti-VEGF treatment for radiation maculopathy and optic neuropathy: lessons learned

Powell, Brittany E; Chin, Kimberly J; Finger, Paul T
Radiation therapy has saved both sight and life for eye cancer patients. The most common methods include ophthalmic plaque brachytherapy and external beam techniques. However, subsequent dose-dependent radiation vasculopathy invariably occurs within and around the targeted zone. In 2006, Finger discovered that periodic intravitreal anti-vascular endothelial growth factor (anti-VEGF) bevacizumab could reverse and suppress intraocular radiation vasculopathy. At first, it was administered at the onset of radiation-related vision loss. Though bevacizumab induced regression of macular oedema, retinal haemorrhages and cotton-wool infarcts, most patients were left with residual retinal damage, manifest as metamorphopsia and loss of vision. These results led to earlier and earlier anti-VEGF interventions: first after signs of progressive radiation retinopathy, and then for signs of radiation maculopathy, and finally for high-risk eyes with no clinical signs of retinopathy. Earlier initiation of intravitreal anti-VEGF therapy typically resulted in greater restoration and preservation of macular anatomy, reductions of retinal haemorrhages, resolution of cotton-wool spots and vision preservation. Recent research on optical coherence tomography angiography (OCT-A) has revealed that radiation vasculopathy occurs prior to clinical ophthalmic signs or symptoms. Therefore, it seemed reasonable to consider treating high-risk patients (considered certain to eventually develop radiation maculopathy) to prevent or delay vision loss. Herein, we describe the evolution of treatment for radiation maculopathy as well as recent research supporting anti-VEGF treatment of high-risk patients immediately following radiation to maximize vision outcomes.
PMID: 35974178
ISSN: 1476-5454
CID: 5453162

Patients presenting with metastases: stage IV uveal melanoma, an international study

Garg, Gaurav; Finger, Paul T; Kivelä, Tero T; Simpson, E Rand; Gallie, Brenda L; Saakyan, Svetlana; Amiryan, Anush G; Valskiy, Vladimir; Chin, Kimberly J; Semenova, Ekaterina; Seregard, Stefan; Filì, Maria; Wilson, Matthew; Haik, Barrett; Caminal, Josep Maria; Catala-Mora, Jaume; Gutiérrez, Cristina; Pelayes, David E; Folgar, Anibal Martin; Jager, Martine Johanna; DoÄŸrusöz, Mehmet; Luyten, Gregorius P M; Singh, Arun D; Suzuki, Shigenobu
OBJECTIVE:To analyse ocular and systemic findings of patients presenting with systemic metastasis. METHODS AND ANALYSIS/UNASSIGNED:It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases. RESULTS:Of 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1-T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category. CONCLUSIONS:Though higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.
PMID: 33452185
ISSN: 1468-2079
CID: 4760072

Primary choroidal melanoma followed by two metachronous ipsilateral ocular metastases

Finger, Paul T.; Yin, Claire T.; Pavlick, Anna C.; Farhat, Nada
Purpose. To describe two ipsilateral, metachronous, ocular choroidal melanoma metastases. Material and methods. A 64-year-old choroidal melanoma patient was initially treated with palladium-103 ophthalmic plaque brachytherapy which induced local control of the primary cancer. Seven years later, ophthalmic findings of a second, ipsilateral, discrete choroidal melanoma prompted restaging which revealed new hepatic and nodal metastases. Systemic immunotherapy (ipilimumab 3 mg/kg with nivolumab 1 mg/kg IV every 3 weeks 4 doses) resulted in intraocular tumor regression and was followed by maintenance nivolumab 480 mg IV every 4 weeks with follow-up ophthalmic examinations. Results. Three years after initiation of systemic immunotherapy, the patient was found to have a second ipsilateral local recurrence of choroidal melanoma. It presented with retinal detachment, uveitis, and optic neuritis. Then, due to its anterior uveal location, extrascleral tumor extension was amenable to a diagnostic biopsy. Overall, 3 years after onset of metastatic uveal melanoma and 2 months after her second ocular metastasis, the patient died. This was 10 years after the initial diagnosis of choroidal melanoma. Conclusions. Metastatic choroidal melanoma can present twice in the same eye as the primary tumor. Ophthalmic and systemic examinations allowed for immunotherapy to affect initial systemic regression, vision sparing, and globe salvage.
ISSN: 2072-0076
CID: 5314962

Interstitial Brachytherapy for Orbital Sebaceous Carcinoma

Li, Feng; Stewart, Robert D; Finger, Paul T
Sebaceous carcinoma is characterized by its aggressive local tumor behavior and ability to metastasize. Small periocular sebaceous carcinoma are typically treated by excision with cryotherapy. Larger tumors often require adjuvant external beam radiotherapy (EBRT) and/or exenteration surgery. When used alone, EBRT techniques typically exceed the tolerance of critical normal ocular structures. The interstitial orbital brachytherapy-boost technique permits dose escalation to the tumor bed, while minimizing radiation dose to critical normal ocular structures. Here, we present a case of orbital sebaceous carcinoma treated with excision, cryotherapy, and super-thick amniotic membrane fornix reconstruction. Then, after 3 weeks of healing, adjuvant-combined electron interstitial high-dose rate brachytherapy-boost was added to electron-beam radiotherapy to optimize the orbital radiation dose distribution, increase dose to inferonasal orbit, and allow relative sparing of orbital tissues. At 1-year follow-up, there was no evidence of orbital tumor, no significant eye lash loss, normal ocular motility, no radiation retinopathy, optic neuropathy and a visual acuity of 20/20.
PMID: 34314398
ISSN: 1537-2677
CID: 4949272

Conjunctival melanoma treatment outcomes in 288 patients: a multicentre international data-sharing study

Jain, Puneet; Finger, Paul T; Fili, Maria; Damato, Bertil; Coupland, Sarah E; Heimann, Heinrich; Kenawy, Nihal; J Brouwer, Niels; Marinkovic, Marina; Van Duinen, Sjoerd G; Caujolle, Jean Pierre; Maschi, Celia; Seregard, Stefan; Pelayes, David; Folgar, Martin; Yousef, Yacoub A; Krema, Hatem; Gallie, Brenda; Calle-Vasquez, Alberto
BACKGROUND:To relate conjunctival melanoma characteristics to local control. METHODS:Retrospective, registry-based interventional study with data gathered from 10 ophthalmic oncology centres from 9 countries on 4 continents. Conjunctival melanoma patients diagnosed between January 2001 and December 2013 were enrolled in the study. Primary treatments included local excision, excision with cryotherapy and exenteration. Adjuvant treatments included topical chemotherapy, brachytherapy, proton and external beam radiotherapy (EBRT). Cumulative 5-year and 10-year Kaplan-Meier local recurrence rates were related to clinical and pathological T-categories of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system. RESULTS:288 patients had a mean initial age of 59.7±16.8 years. Clinical T-categories (cT) were cT1 (n=218,75.7%), cT2 (n=34, 11.8%), cT3 (n=15, 5.2%), cTx (n=21,7.3%) with no cT4. Primary treatment included local excision (n=161/288, 55.9%) followed by excision biopsy with cryotherapy (n=108/288, 37.5%) and exenteration (n=5/288, 1.7%). Adjuvant therapies included topical mitomycin (n=107/288, 37.1%), plaque-brachytherapy (n=55/288, 19.1%), proton-beam (n=36/288, 13.5%), topical interferon (n=20/288, 6.9%) and EBRT (n=15/288, 5.2%). Secondary exenteration was performed (n=11/283, 3.9%). Local recurrence was noted in 19.1% (median=3.6 years). Cumulative local recurrence was 5.4% (3.2-8.9%), 19.3% (14.4-25.5%) and 36.9% (26.5-49.9%) at 1, 5 and 10 years, respectively. cT3 and cT2 tumors were twice as likely to recur than cT1 tumours, but only cT3 had statistically significantly greater risk of local recurrence than T1 (p=0.013). Factors such as tumour ulceration, plica or caruncle involvement and tumour thickness were not significantly associated with an increased risk of local recurrence. CONCLUSION/CONCLUSIONS:This multicentre international study showed that eighth edition of AJCC tumour staging was related to the risk of local recurrence of conjunctival melanoma after treatment. The 10-year cumulative local recurrence remains high despite current management.
PMID: 32892167
ISSN: 1468-2079
CID: 4588702

Doppelgänger dilemma: Leiomyoma versus uveal melanoma [Case Report]

Tomar, Ankit Singh; Fam, Anthony; Finger, Paul T; Iacob, Codrin E
Background/UNASSIGNED:Ciliary body tumors can remain undetected and achieve large dimensions. Pigmented ciliary body tumors include: melanoma, leiomyoma and melanocytoma, however correct diagnosis may require tissue diagnosis with immunohistochemical stains. Case presentation/UNASSIGNED:Two men presented with identical ciliochoroidal tumors. Both had darkly pigmented dome-shaped anterior uveal masses, exudative retinal detachments and transillumination shadowing. Ocular PET-CT imaging revealed that both were metabolically active consistent with a diagnosis of cancer. However, immunohistochemical examination revealed one a leiomyoma and the other melanoma. Conclusion/UNASSIGNED:Uveal leiomyoma can be an indistinguishable doppelgänger to ciliochoroidal melanoma, where the diagnosis can only be established by immunohistopathology.
PMID: 33748534
ISSN: 2451-9936
CID: 4822242

Global Retinoblastoma Treatment Outcomes: Association with National Income Level

Tomar, Ankit Singh; Finger, Paul T; Gallie, Brenda; Kivelä, Tero T; Mallipatna, Ashwin; Zhang, Chengyue; Zhao, Junyang; Wilson, Matthew W; Brenna, Rachel C; Burges, Michala; Kim, Jonathan; Khetan, Vikas; Ganesan, Suganeswari; Yarovoy, Andrey; Yarovaya, Vera; Kotova, Elena; Yousef, Yacoub A; Nummi, Kalle; Ushakova, Tatiana L; Yugay, Olga V; Polyakov, Vladimir G; Ramirez-Ortiz, Marco A; Esparza-Aguiar, Elizabeth; Chantada, Guillermo; Schaiquevich, Paula; Fandino, Adriana; Yam, Jason C; Lau, Winnie W; Lam, Carol P; Sharwood, Phillipa; Moorthy, Sonia; Long, Quah Boon; Essuman, Vera Adobea; Renner, Lorna A; Semenova, Ekaterina; Català, Jaume; Correa-Llano, Genoveva; Carreras, Elisa
PURPOSE/OBJECTIVE:To compare metastasis-related mortality, local treatment failure and globe salvage after retinoblastoma (RB) in countries with different national income levels. DESIGN/METHODS:International, multicenter, registry-based retrospective case series PARTICIPANTS: Two thousand one hundred and ninety patients, 18 ophthalmic oncology centers, 13 countries within 6 continents. METHODS:edition AJCC staging and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects and included high-income countries (HIC), upper middle-income countries (UMIC) and lower middle-income countries (LMIC). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes. MAIN OUTCOME MEASURES/METHODS:Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy). RESULTS:The majority (60%) of study patients resided in UMIC and LMIC. The global median age at diagnosis was 17.0 months [higher in UMIC (20.0 months) and LMIC (20.0 months) than HIC (14.0 months; p<0.001)]. Patients in UMIC and LMIC reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HIC, metastasis-related mortality was 10.3-fold higher for UMIC and 9.3-fold higher for LMIC, and the risk for local treatment failure was 2.2-fold and 1.57-fold higher, respectively (all p<0.001). CONCLUSION/CONCLUSIONS:This international, multicenter, registry-based analysis of RB management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure and lower globe salvage.
PMID: 33007338
ISSN: 1549-4713
CID: 4617372