Mustafa Mehyar

Team management, twinning, and telemedicine in retinoblastoma: A 3-tier approach implemented in the first eye salvage program in Jordan†

This study evaluated the outcome of retinoblastoma patients, when employing a telemedicine‐based twinning program in Jordan.

Retinoblastoma in Jordan: An epidemiological study (2006-2010)

BACKGROUND AND OBJECTIVE The epidemiological characteristics of retinoblastoma have been extensively studied in developed countries, however epidemiological data is scarce in the Middle East. We present a de- tailed epidemiological analysis of retinoblastoma in Jordan in an attempt to aid national and regional strategies for improved cancer surveillance and control. DESIGN AND SETTING Retrospective review of retinoblastoma cases presenting to the sole and exclusive ocular oncology referral center in Jordan. PATIENTS AND METHODS Forty children (59 eyes) presenting with clinically and/or histologically confirmed retinoblastomas were treated at King Hussein Cancer Center (Amman, Jordan) between January 2006 and December 2010. This case series included 28 boys and 12 girls. Data relating to age at diagnosis, laterality, gender, treatment modality and survival were recorded. RESULTS The mean age-adjusted incidence of retinoblastoma in Jordan was 9.32 cases per million children per year for children aged 0-5 years. The male: female ratio was 2.3:1. Bilateral cases were encountered in 19 pa- tients (47.5%) while 21 patients (52.5%) harbored unilateral retinoblastoma. At the time of follow-up, 38 patients (95%) were alive. Overall, 40 eyes (67.8%) were successfully preserved without the need for enucleation. CONCLUSIONS The national epidemiological data gathered in this study indicates that the incidence of retinoblastoma in Jordan is similar to that reported in various countries of the world. Jordanian boys, however, are at significantly higher risk for developing retinoblastoma than age-matched girls. Furthermore, Jordanian patients are more likely to harbor bilateral retinoblastoma.

PREDICTIVE VALUE OF TNM CLASSIFICATION, INTERNATIONAL CLASSIFICATION, AND REESE-ELLSWORTH STAGING OF RETINOBLASTOMA FOR THE LIKELIHOOD OF HIGH-RISK PATHOLOGIC FEATURES.

Purpose: To evaluate the predictive value of the seventh edition American Joint Committee on Cancer (AJCC/UICC) TNM classification, the International Classification of Retinoblastoma (ICRB), and Reese–Ellsworth staging for retinoblastoma for the likelihood of high-risk pathologic features. Methods: A retrospective study of 50 primarily enucleated eyes from 49 retinoblastoma patients. Main outcome measures included demographics, TNM stage, ICRB group, Reese–Ellsworth stage, choroid, optic nerve, and anterior chamber invasion. Results: The median age at enucleation was 30 months. High-risk pathologic features mandating adjuvant chemotherapy were seen in 5 of T2 eyes (22%), in 15 of T3 eyes (56%) (P = 0.021), in 1 of ICRB Group C eyes (13%), 8 of Group D eyes (33%), and 11 of Group E eyes (61%) (P = 0.035). High-risk pathologic features were 4.61 and 3.68 times more likely to be diagnosed at a more advanced T stage and ICRB group consecutively, whereas 0.133 time less likely to be diagnosed at a more advanced Reese–Ellsworth stage. At median follow-up of 40 months, no single case had metastasis or was dead. Conclusion: The higher tumor clinical TNM stage and the more advanced ICRB group at presentation are associated with higher frequency of high-risk pathologic features and may predict which patients should receive adjuvant chemotherapy.

Management and outcome of uveal melanoma in a single tertiary cancer center in Jordan

Abstract Objective: The aim of this study was evaluate the features and outcome of management of uveal melanoma in King Hussein Cancer Center as an example of a referral tertiary cancer center in the Middle East. Material and Method: This was aetrospective, observational case series of 46 eyes of 46 patients with uveal melanoma. Data collection required access to medical records, radiology and pathology reports, and laboratory results. The main outcome measures included age at diagnosis, tumor location and dimensions, TNM stage, treatment modality, visual outcome, metastasis, and mortality. Results: There was slight female preference, and the median age at diagnosis was 45 years. Eighteen (39%) eyes were treated by primary enucleation, and 28 (61%) eyes were treated by I-125 radioactive plaque. The melanoma was in the choroid in 40 (87%) eyes and in the ciliary body in 6 (13%) eyes, with no single tumor in the iris. According to the 7th edition of the American Joint Committee on Cancer staging system (UICC/AJCC); 8 (17%) were T1, 17 (36%) were T2, 16 (35%) were T3, and 5 (11%) were T4. One (2%) patient showed lymph node metastasis (N1), and 6 (13%) patients showed distant metastasis (M1). Pathologically, 2 (10%) of the enucleated eyes were spindle cell type, 4 (20%) were epithelioid cell type, and 14 (70%) were mixed type. Extrascleral extension was seen in three (15%) eyes, and optic nerve invasion in two (10%) eyes. After brachytherapy, 26 (93%) eyes were salvaged, and 2 eyes were consecutively enucleated; one for tumor recurrence, and one for uncontrolled painful neovascular glaucoma. The eye salvage rate post plaque was 93% (26/28), and the visual acuity for the salvaged eyes was equal or better than 0.5 in 11 (42%) eyes, 0.1-0.4 in 5 (19%) eyes, and less than 0.1 in 10 (38%) eyes. Conclusion: The incidence of uveal melanomas in our region is low compared to that in the West with a younger age at presentation. Candidate tumors for radioactive plaque therapy were successfully controlled in 93% of cases.

External Beam Radiation Therapy for RetinoblastomaResistant to Chemotherapy and Focal Treatment: Outcome and Predictive Factors

External Beam Radiation Therapy for Retinoblastoma Resistant to Chemotherapy and Focal Treatment: Outcome and Predictive Factors Abstract: Purpose: To evaluate the outcome of external beam radiation therapy (EBRT) for treatment of retinoblastoma resistant to chemotherapy and focal therapy. Methods and Materials: A retrospective case series of 24 eyes for 20 retinoblastoma patients treated by EBRT after failure of tumor control by chemotherapy and focal therapy. The main outcome measures included: international intraocular retinoblastoma stage (IIRC) and Reese Ellsworth (RE) stage, tumor seeding, treatment modalities, eye salvage, and survival. Results: The median age at diagnosis was 12 months. There were 12 (60%) males and 16 (80%) bilateral cases. All eyes were treated initially by systemic chemotherapy (range: 6-8 cycles). The dose of 45Gy was used in all eyes. The mean follow-up was 55months. Eye salvage rate after EBRT was 45% (11eyes); 67% ( 2/3) for IIRC group B, 63% (5/8) for group C, and 31% (4/13) for group D eyes. Vitreous seeds and tumor stage migration during management by chemotherapy were the most important significant predictive factors for tumor control (p=0.0327 and 0.0333 consecutively). Post EBRT complication rate was 80% (19/24) including; retinal detachment (3), vitreous hemorrhage (4), neovascular glaucoma (1), cataract (16), and radiation retinopathy (2). Conclusion: Eyes with retinoblastoma that failed chemotherapy were controlled with EBRT. However the presence of vitreous seeds, stage migration during chemotherapy, as well as good vision in the other eye may not justify the known risks of EBRT.

A histopathologic analysis of 50 eyes primarily enucleated for retinoblastoma in a tertiary cancer center in Jordan.

Abstract Objective: To analyze the histopathologic features of the eyes with intraocular retinoblastoma primarily treated by enucleation in a tertiary cancer center in Jordan. Material and Method: A retrospective case series of 50 eyes for 49 patients who had pathologically confirmed retinoblastoma after enucleation as primary therapy. The main outcome measures included demographics, laterality, international classification of intraocular retinoblastoma, choroid invasion, optic nerve invasion, anterior chamber invasion, and tumor differentiation. Results: The median age at enucleation was 30 months. Twenty-seven (55%) patients were males, and 19 (39%) patients had bilateral retinoblastoma. High risk pathological features were seen as massive choroid invasion in 9 (18%) eyes, post-laminar optic nerve invasion in 7 (14%) eyes, and anterior chamber, iris or ciliary body invasion in 7 (14%) eyes. Thirty-seven (74%) tumors were well/moderately differentiated, and 13 (26%) were poorly differentiated. Poorly differentiated tumors presented later (median 31 months) than well/ moderately differentiated tumors (26 months) and were associated with a higher incidence of high-risk pathological features. No single ICRB group C eye had high-risk pathological features, while 17% and 4% of group D eyes and 28% and 33% of group E eyes had massive choroid invasion and post-laminar optic nerve invasion, respectively. Eighteen (36%) patients received adjuvant chemotherapy for high risk pathological features, and at median follow up of 40 months, no single case had metastasis or was dead. Conclusion: Our pathologic findings were similar to the developed world. They were supportive of the predictive power of the international classification of retinoblastoma staging system for the likelihood of high risk pathological features. Poorly differentiated tumors were associated with a higher incidence of high risk pathological features than well/moderately differentiated tumors. Öz Amaç: Ürdün’ de üçüncü basamak kanser merkezinde primer olarak enükleasyon ile tedavi edilen intraoküler retinoblastomalı gözlerin histopatolojik özelliklerinin araştırılması. Gereç ve Yöntem: Primer tedavi olarak enükleasyon uygulandıktan sonra patolojiyle retinoblastoma tanısı alan 49 hastaya ait 50 gözden oluşan retrospektif olgu serisi. Demografik bulgular, lateralite, Uluslararası Retinoblastoma Sınıflaması, koroid invazyon, optik sinir invazyonu, ön kamera invazyonu ve tümör farklılaşması ana sonuç verileri olarak dahil edildi. Bulgular: Enükleasyon sırasında ortalama yaş 30 aydı. Yirmi yedi (%55) hasta erkekti ve 19 (%39) hastanın bilateral retinoblastoması vardı. Yüksek riskli patolojik özellikler; 9 (%18) gözde massif koroid invazyonu, 7’sinde (%14) post-laminar optik sinir invazyonu ve 7’sinde (%14) ön kamera, iris veya silier cisimcik invazyonu şeklindeydi. Otuz yedi (%74) tümör iyi/orta derecede diferansiye ve 13 (%26) az diferansiye idi. Az diferansiye tümörler (ortalama 31 ay), iyi/orta derecedeki tümörlere göre daha geç (ortalama 26 ay) ortaya çıkmakta ve yüksek riskli patolojik özellikler ile daha sıkı ilişki göstermektedir. Uluslararası Retinoblastoma Sınıflandırmasına göre grup D olanların %17 ve %4’ünde, grup E olanların %28 ve %33’ünde sırasıyla massif koroid invazyonu ve post-laminar optik sinir invazyonu varken, grup C olanlarda ise yüksek riskli patolojik özellik yoktu. On sekiz (%36) hasta yüksek riskli patolojik özellikler için adjuvan kemoterapi aldı ve 40 aylık ortalama takip süresince hiçbir olgunun metastazı yoktu ve hiçbiri ölmemişti. Sonuç: Sonuçlarımız, gelişmiş ülkelere benzerdir. Yüksek risk faktörleri için Uluslararası Retinoblastoma Sınıflandırma evreleme sisteminin öngörü değerini destekleyicidir. İyi/orta derecede diferansiye tümörlere göre az diferansiye tümörler, yüksek risk faktörleri ile daha sıkı ilişkilidir.

Characteristics, management, and outcome of patients with uveal melanoma treated by Iodine-125 radioactive plaque therapy in a single tertiary cancer center in Jordan

Objective To evaluate King Hussein Cancer Center experience in using Iodine-125 COMS radioactive plaque for treatment of Uveal Melanoma in Jordan. Methods Retrospective case series of eyes with uveal melanoma treated by Iodine-125 COMS radioactive plaque therapy. Data collection required access to medical, radiology, Labs and pathology reports. Main outcomes studied includes: Demographics, tumor features, eye salvage, visual outcome, metastasis, and mortality. Results Between September 2008 and March 2015, 28 eyes for 28 patients had intraocular uveal melanoma and treated by Iodine-125 radioactive plaque therapy. The mean age at diagnosis was 48 years and 16(57%) were males. The mean tumor thickness was 8 mm (range: 4–13 mm), and 27(96%) patients had medium or large size tumor. The radioactive plaques used had a median size of 16 mm (range: 12–20 mm). The mean apical dose was 83.5 Gy (range 81–87 Gy), and the median radiation rate was 7.25 (range: 4.5–13). At median follow up of 2 years (range 0.5–7 years), eye salvage rate was 93%. Four (15%) patients had distance metastasis, and 3(11%) were dead. Fifty percent of patient had visual acuity better than 20/200 at the last date of follow up. Conclusion Our preliminary results are encouraging and are comparable to another countries worldwide. The use of Iodine-125 COMs plaque therapy at the inspection of implementation of plaque therapy in the developing countries can lead to eye salvage in more than 90% of cases, and reserves functional vision in more than 50% of cases.

Chemoreduction of Progressive Intraocular Retinoblastoma by Systemic Topotecan

Abstract Purpose: To evaluate our experience with systemic Toptecan (TPT) chemotherapy as a second-line systemic chemotherapeutic regimen for treatment of refractory or recurrent intraocular retinoblastoma (RB). Methods and Materials: A retrospective case series of 14 eyes from patients with intraocular RB who received systemic TPT as second-line chemotherapy from April 2008 until June 2010. The following data were collected: patient demographics, laterality, international intraocular retinoblastoma stage (ICRB) at diagnosis, treatment received before and after TPT, side effects related to TPT, eye salvage, and survival. Results: The median age at diagnosis was 5 months (range, 1–16 months), and the median age at starting TPT was 10 months (range, 8–24 months). There were 6 (60%) females and 9 (90%) patients; all with bilateral retinoblastoma. The median number of TPT cycles was three per patient (range, 1–6), and the total number of administered cycles was 29. After TPT therapy; 4 (29%) eyes showed favorable response, 3 (21%) eyes showed minimal regression, 5 (36%) eyes had stable disease, and 2 (14%) eyes showed tumor progression. At a median follow-up of 48 months; 9 (64%) eyes were salvaged, 3 (21%) eyes received radiation therapy, and 3 (21%) eyes were enucleated (one was post radiation). Grade 3/4 neutropenia were noticed in a total of 59% of given cycles and admission for febrile neutropenia was required after seven cycles. Conclusions: Our report suggests that systemic TPT chemotherapy could be used as a salvage second-line regimen with low toxicity for patients with progressive intraocular retinoblastoma if systemic therapy is needed.

A Histopathologic Analysis of 50 Eyes Primarily Enucleated for Retinoblastoma in a Tertiary Cancer Center in Jordan Ürdün'de Üçüncü Basamak Kanser Merkezinde Retinoblastoma Nedeniyle Primer Enükleasyon Uygulanan 50 Gözün Histopatolojik İncelemesi

Abstract Objective: To analyze the histopathologic features of the eyes with intraocular retinoblastoma primarily treated by enucleation in a tertiary cancer center in Jordan. Material and Method: A retrospective case series of 50 eyes for 49 patients who had pathologically confirmed retinoblastoma after enucleation as primary therapy. The main outcome measures included demographics, laterality, international classification of intraocular retinoblastoma, choroid invasion, optic nerve invasion, anterior chamber invasion, and tumor differentiation. Results: The median age at enucleation was 30 months. Twenty-seven (55%) patients were males, and 19 (39%) patients had bilateral retinoblastoma. High risk pathological features were seen as massive choroid invasion in 9 (18%) eyes, post-laminar optic nerve invasion in 7 (14%) eyes, and anterior chamber, iris or ciliary body invasion in 7 (14%) eyes. Thirty-seven (74%) tumors were well/moderately differentiated, and 13 (26%) were poorly differentiated. Poorly differentiated tumors presented later (median 31 months) than well/ moderately differentiated tumors (26 months) and were associated with a higher incidence of high-risk pathological features. No single ICRB group C eye had high-risk pathological features, while 17% and 4% of group D eyes and 28% and 33% of group E eyes had massive choroid invasion and post-laminar optic nerve invasion, respectively. Eighteen (36%) patients received adjuvant chemotherapy for high risk pathological features, and at median follow up of 40 months, no single case had metastasis or was dead. Conclusion: Our pathologic findings were similar to the developed world. They were supportive of the predictive power of the international classification of retinoblastoma staging system for the likelihood of high risk pathological features. Poorly differentiated tumors were associated with a higher incidence of high risk pathological features than well/moderately differentiated tumors. Öz Amaç: Ürdün’ de üçüncü basamak kanser merkezinde primer olarak enükleasyon ile tedavi edilen intraoküler retinoblastomalı gözlerin histopatolojik özelliklerinin araştırılması. Gereç ve Yöntem: Primer tedavi olarak enükleasyon uygulandıktan sonra patolojiyle retinoblastoma tanısı alan 49 hastaya ait 50 gözden oluşan retrospektif olgu serisi. Demografik bulgular, lateralite, Uluslararası Retinoblastoma Sınıflaması, koroid invazyon, optik sinir invazyonu, ön kamera invazyonu ve tümör farklılaşması ana sonuç verileri olarak dahil edildi. Bulgular: Enükleasyon sırasında ortalama yaş 30 aydı. Yirmi yedi (%55) hasta erkekti ve 19 (%39) hastanın bilateral retinoblastoması vardı. Yüksek riskli patolojik özellikler; 9 (%18) gözde massif koroid invazyonu, 7’sinde (%14) post-laminar optik sinir invazyonu ve 7’sinde (%14) ön kamera, iris veya silier cisimcik invazyonu şeklindeydi. Otuz yedi (%74) tümör iyi/orta derecede diferansiye ve 13 (%26) az diferansiye idi. Az diferansiye tümörler (ortalama 31 ay), iyi/orta derecedeki tümörlere göre daha geç (ortalama 26 ay) ortaya çıkmakta ve yüksek riskli patolojik özellikler ile daha sıkı ilişki göstermektedir. Uluslararası Retinoblastoma Sınıflandırmasına göre grup D olanların %17 ve %4’ünde, grup E olanların %28 ve %33’ünde sırasıyla massif koroid invazyonu ve post-laminar optik sinir invazyonu varken, grup C olanlarda ise yüksek riskli patolojik özellik yoktu. On sekiz (%36) hasta yüksek riskli patolojik özellikler için adjuvan kemoterapi aldı ve 40 aylık ortalama takip süresince hiçbir olgunun metastazı yoktu ve hiçbiri ölmemişti. Sonuç: Sonuçlarımız, gelişmiş ülkelere benzerdir. Yüksek risk faktörleri için Uluslararası Retinoblastoma Sınıflandırma evreleme sisteminin öngörü değerini destekleyicidir. İyi/orta derecede diferansiye tümörlere göre az diferansiye tümörler, yüksek risk faktörleri ile daha sıkı ilişkilidir.

Ürdün'de üçüncü basamak kanser merkezinde retinoblastoma nedeniyle primer enükleasyon uygulanan 50 gözün histopatolojik İncelemesi

Abstract Objective: To analyze the histopathologic features of the eyes with intraocular retinoblastoma primarily treated by enucleation in a tertiary cancer center in Jordan. Material and Method: A retrospective case series of 50 eyes for 49 patients who had pathologically confirmed retinoblastoma after enucleation as primary therapy. The main outcome measures included demographics, laterality, international classification of intraocular retinoblastoma, choroid invasion, optic nerve invasion, anterior chamber invasion, and tumor differentiation. Results: The median age at enucleation was 30 months. Twenty-seven (55%) patients were males, and 19 (39%) patients had bilateral retinoblastoma. High risk pathological features were seen as massive choroid invasion in 9 (18%) eyes, post-laminar optic nerve invasion in 7 (14%) eyes, and anterior chamber, iris or ciliary body invasion in 7 (14%) eyes. Thirty-seven (74%) tumors were well/moderately differentiated, and 13 (26%) were poorly differentiated. Poorly differentiated tumors presented later (median 31 months) than well/ moderately differentiated tumors (26 months) and were associated with a higher incidence of high-risk pathological features. No single ICRB group C eye had high-risk pathological features, while 17% and 4% of group D eyes and 28% and 33% of group E eyes had massive choroid invasion and post-laminar optic nerve invasion, respectively. Eighteen (36%) patients received adjuvant chemotherapy for high risk pathological features, and at median follow up of 40 months, no single case had metastasis or was dead. Conclusion: Our pathologic findings were similar to the developed world. They were supportive of the predictive power of the international classification of retinoblastoma staging system for the likelihood of high risk pathological features. Poorly differentiated tumors were associated with a higher incidence of high risk pathological features than well/moderately differentiated tumors. Öz Amaç: Ürdün’ de üçüncü basamak kanser merkezinde primer olarak enükleasyon ile tedavi edilen intraoküler retinoblastomalı gözlerin histopatolojik özelliklerinin araştırılması. Gereç ve Yöntem: Primer tedavi olarak enükleasyon uygulandıktan sonra patolojiyle retinoblastoma tanısı alan 49 hastaya ait 50 gözden oluşan retrospektif olgu serisi. Demografik bulgular, lateralite, Uluslararası Retinoblastoma Sınıflaması, koroid invazyon, optik sinir invazyonu, ön kamera invazyonu ve tümör farklılaşması ana sonuç verileri olarak dahil edildi. Bulgular: Enükleasyon sırasında ortalama yaş 30 aydı. Yirmi yedi (%55) hasta erkekti ve 19 (%39) hastanın bilateral retinoblastoması vardı. Yüksek riskli patolojik özellikler; 9 (%18) gözde massif koroid invazyonu, 7’sinde (%14) post-laminar optik sinir invazyonu ve 7’sinde (%14) ön kamera, iris veya silier cisimcik invazyonu şeklindeydi. Otuz yedi (%74) tümör iyi/orta derecede diferansiye ve 13 (%26) az diferansiye idi. Az diferansiye tümörler (ortalama 31 ay), iyi/orta derecedeki tümörlere göre daha geç (ortalama 26 ay) ortaya çıkmakta ve yüksek riskli patolojik özellikler ile daha sıkı ilişki göstermektedir. Uluslararası Retinoblastoma Sınıflandırmasına göre grup D olanların %17 ve %4’ünde, grup E olanların %28 ve %33’ünde sırasıyla massif koroid invazyonu ve post-laminar optik sinir invazyonu varken, grup C olanlarda ise yüksek riskli patolojik özellik yoktu. On sekiz (%36) hasta yüksek riskli patolojik özellikler için adjuvan kemoterapi aldı ve 40 aylık ortalama takip süresince hiçbir olgunun metastazı yoktu ve hiçbiri ölmemişti. Sonuç: Sonuçlarımız, gelişmiş ülkelere benzerdir. Yüksek risk faktörleri için Uluslararası Retinoblastoma Sınıflandırma evreleme sisteminin öngörü değerini destekleyicidir. İyi/orta derecede diferansiye tümörlere göre az diferansiye tümörler, yüksek risk faktörleri ile daha sıkı ilişkilidir.