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Background: Although survival rates for retinoblastoma (RB) are over 95% in high-income countries, its high mortality rate in low and middle-income countries remains a great concern. Few studies investigated treatment outcome and factors contributing to RB survival in these latter settings. Aims of this study are to determine treatment outcome of Indonesian children diagnosed with RB and to explore factors predictive of treatment outcome. Methods: This study was a retrospective medical records review combined with an illustrative case report. Children newly diagnosed with RB between January 2011 and December 2016 at a tertiary care referral hospital in Indonesia were included. A home visit was conducted to perform an in-depth interview with a mother of two children affected by RB. Results: Of all 61 children with RB, 39% abandoned treatment, 21% died, 20% had progressive or relapsed disease and 20% event-free survival. Progressive or relapsed disease was more common in older (≥ 2 years at diagnosis, 29%) than young (<2 years at diagnosis, 0%) children (P=0.012). Event-free survival estimate at 5 years was higher in young (42%) than older (6%) children (P=0.045). Odds-ratio for event-free survival was 6.9 (95% CI: 1.747 – 27.328, P=0.006) for young versus older children. Other clinical and socio-demographic characteristics had no significant correlation with treatment outcome or event-free survival. The case report elucidated conditions and obstacles that Indonesian families face when their children are diagnosed with RB. Conclusion: Survival of children with RB in Indonesia is much lower compared to high-income and many other low and middle-income countries. Abandonment of treatment is the most common cause of treatment failure. Older age at diagnosis is associated with more progressive or relapsed disease and worse survival. Interventions to improve general public and health-care providers’ awareness, early detection and treatment adherence are required.

Purpose: Treatment abandonment because of enucleation refusal is a limitation of improving outcomes for children with retinoblastoma in countries with limited resources. Furthermore, many children present with buphthalmos and a high risk of globe rupture during enucleation. To address these unique circumstances, the AHOPCA II protocol introduced neoadjuvant chemotherapy with delayed enucleation., Patients and Methods: Patients with advanced unilateral intraocular disease (International Retinoblastoma Staging System [IRSS] stage I) were considered for upfront enucleation. Those with diffuse invasion of the choroid, postlaminar optic nerve, and/or anterior chamber invasion received six cycles of adjuvant chemotherapy (vincristine, carboplatin, and etoposide). Patients with buphthalmos and those with a perceived risk for enucleation refusal and/or abandonment were given two to three cycles of chemotherapy before scheduled enucleation followed by adjuvant chemotherapy to complete six cycles, regardless of pathology., Results: A total of 161 patients had unilateral IRSS stage I disease; 102 underwent upfront enucleation, and 59 had delayed enucleation. The estimated 5-year abandonment-sensitive event-free and overall survival rates for the group were 0.81 ± 0.03 and 0.86 ± 0.03, respectively. The 5-year estimated abandonment-sensitive event-free survival rates for patients undergoing upfront and delayed enucleation were 0.89 ± 0.03 and 0.68 ± 0.06, respectively ( P = .001). Compared with AHOPCA I, abandonment for patients with IRSS stage I retinoblastoma decreased from 16% to 4%., Conclusion: AHOPCA describes the results of advanced intraocular retinoblastoma treated with neoadjuvant chemotherapy. In eyes with buphthalmos and patients with risk of abandonment, neoadjuvant chemotherapy can be effective when followed by enucleation and adjuvant chemotherapy. Our study suggests that this approach can save patients with buphthalmos from ocular rupture and might reduce refusal of enucleation and abandonment.

Purpose: To prospectively determine the prevalence of high-risk histopathologic features (HRFs) in patients with unilateral retinoblastoma who undergo enucleation and to evaluate the role of chemotherapy in preventing recurrences., Patients and Methods: Children newly diagnosed with enucleated unilateral retinoblastoma were enrolled prospectively. After central histopathology review, patients with specific HRFs received chemotherapy; others were observed. Primary end points were event-free survivals (EFS)., Results: Of the 331 patients enrolled during 2005 to 2010, 321 eligible patients had central histopathologic review. Discordance between central review and contributing institutions occurred in 23% of patients with HRFs and in 17% of patients without HRFs. Postlaminar optic nerve involvement was present in 53 patients; 42 had massive posterior uveal invasion (≥ 3 mm); 15 had concomitant peripapillary 3 mm or greater choroid and postlaminar optic nerve involvement; and 15 had focal (< 3 mm) choroidal concomitant with lamina or prelamina optic nerve involvement. Two-year EFS for patients with HRFs requiring adjuvant chemotherapy was 0.96 (95% CI, 0.89 to 0.98), and 2-year EFS for patients without HRFs for which observation was indicated was 0.99 (95% CI, 0.96 to 1.0). The 2-year EFS for all patients was 0.98 (95% CI, 0.96 to 0.99)., Conclusion: Adequate handling and interpretation of histopathology of eyes with retinoblastoma is necessary to assign metastatic risk. Concomitant less than 3 mm choroidal and any prelaminar/laminar optic nerve invasion show no recurrence and may warrant no adjuvant chemotherapy. In contrast, concomitant greater than 3 mm peripapillary choroidal invasion and 1.5 mm or greater of postlaminar optic nerve invasion have the poorest outcomes, supporting the need for a more intensive adjuvant chemotherapy regimen for this subgroup. Strict criteria for adjuvant therapy may improve outcomes of children who undergo enucleation at diagnosis and may avoid unnecessary adjuvant chemotherapy for those who are not at risk for recurrence.

Purpose: To summarize the clinicopathological characteristics and prognosis of uveal melanoma (UM) after enucleation in Chinese patients., Methods: Between 2003 and 2012, a series of 171 patients with UM received enucleation at the Eye & ENT Hospital of Fudan University in Shanghai. Patient clinical information was collected. Pathological examination and BAP1 staining of the enucleated eyes were conducted. Univariate and multivariate Cox proportional hazard regressions were conducted to determine the risk factors, and the survival rates were calculated and compared., Results: The study included 83 (49%) men and 88 (51%) women, with a mean age of 48.6 years. The mean largest basal tumor diameter and mean largest tumor thickness were 11.8 and 8.6 mm, respectively. Ciliary body involvement was observed in 19 tumors (11%). Spindle and nonspindle patterns were observed in 100 (58%) and 71 eyes (42%), respectively. Extrascleral extension was observed in three eyes (2%). BAP1 staining was negative in 34% (53/156) of all tumors and 53% (19/36) of the cases with melanoma-related metastasis. The mean follow-up period was 63.4 months for all patients with the exception of 11 patients, who were excluded because they were lost during follow-up. A large basal tumor diameter, ciliary body involvement, nonspindle cell type, extrascleral extension, and negative BAP1 staining were associated with a worse prognosis. The survival curves significantly differed between the BAP1-negative and BAP1-positive groups (P = 0.004). According to Kaplan-Meier analysis, the 5- and 10-year metastasis-free survival rates were 80% and 70%, respectively., Conclusions: A large basal tumor diameter, ciliary body involvement, nonspindle cell type, extrascleral extension, and negative BAP1 staining may be risk factors for the prediction of the UM prognosis. A younger age at diagnosis and a similar prognosis between genders may be unique features in Asian patients compared to the Caucasian population.

Purpose: Intraocular retinoblastoma is curable, but survivors with a heritable predisposition are at high risk for second malignancies. Because second malignancies are associated with high mortality, prognostic factors for second malignancy influence long-term overall survival. This study investigates the impact of all types of eye-preserving therapies on long-term survival in the complete German cohort of patients with heritable retinoblastoma., Patients and Methods: Overall survival, disease staging using international scales, time period of diagnosis, and treatment type were analyzed in the 633 German children treated at the national reference center for heritable retinoblastoma., Results: The 5-year overall survival of children diagnosed in Germany with heritable retinoblastoma between 1940 and 2008 was 93.2% (95% CI, 91.2% to 95.1%), but long-term mortality was increased compared with patients with nonheritable disease. Overall survival correlated with tumor staging, and 92% of patients were diagnosed with a favorable tumor stage (International Retinoblastoma Staging System stage 0 or I). Despite a 5-year overall survival of 97.4% (95% CI, 96.0% to 98.8%) in patients with stage 0 or I, only 79.5% (95% CI, 74.2% to 84.8%) of these patients survived 40 years after diagnosis. Long-term overall survival was reduced in children treated with eye-preserving radiotherapy compared with enucleation alone, and adding chemotherapy aggravated this effect., Conclusion: The benefits of preserving vision must be balanced with the impact of eye-preserving treatments on long-term survival in heritable retinoblastoma, and the genetic background of the patient influences choice of eye-preserving treatment. Germline RB1 genetic analysis is important to identify heritable retinoblastoma among unilateral retinoblastoma cases. Eye-preserving radiotherapy should be carefully considered in patients with germline RB1 mutations. Life-long oncologic follow-up is crucial for all retinoblastoma survivors, and less detrimental eye-preserving therapies must be developed., (© 2016 by American Society of Clinical Oncology.)

Background: We present our experience in treating ocular melanoma at the National Centre for Stereotactic Radiosurgery in Sheffield, UK over the last 20 years., Method: We analysed 170 patients treated with Gamma Knife radiosurgery, recorded the evolution of visual acuity and complication rates, and compared their survival with 620 patients treated with eye enucleation. Different peripheral doses (using the 50% therapeutic isodose) were employed: 50-70 Gy for 24 patients, 45 Gy for 71 patients, 35 Gy for 62 patients., Findings: There was no significant difference in survival between the 35-Gy, 45-Gy and 50- to 70-Gy groups when compared between themselves (p = 0.168) and with the enucleation group (p = 0.454). The 5-year survival rates were: 64% for 35 Gy, 62.71% for 45 Gy, 63.6% for 50-70 Gy and 65.2% for enucleated patients. Clinical variables influencing survival for radiosurgery patients were tumour volume (p = 0.014) and location (median 66.4 vs 37.36 months for juxtapapillary vs peripheral tumours, respectively; p = 0.001), while age and gender did not prove significant. Regarding complications, using 35 Gy led to more than a 50% decrease, when compared with the 45-Gy dose, in the incidence of cataract, glaucoma and retinal detachment. Retinopathy, optic neuropathy and vitreous haemorrhage were not significantly influenced. Blindness decreased dramatically from 83.7% for 45 Gy to 31.4% for 35 Gy (p = 0.006), as well as post-radiosurgery enucleation: 23.9% for 45 Gy vs 6.45% for 35 Gy (p = 0.018). Visual acuity, recorded up to 5 years post-radiosurgery, was significantly better preserved for 35 Gy than for 45 Gy (p = 0.0003)., Conclusions: Using 35 Gy led to a dramatic decrease in complications, vision loss and salvage enucleation, while not compromising patient survival.

Purpose: To retrospectively compare survival in recurrent uveal melanoma, between patients treated by enucleation or by a second course of fractionated proton beam therapy (PBT)., Methods and Materials: Tumor recurrence was documented in 73 patients treated with PBT for uveal melanoma. Of the patients, 31 received a second course of PBT and 42 underwent enucleation. The mean patient age was 56 and 61 years for those undergoing enucleation and those undergoing reirradiation, respectively. Both primary and recurrent tumors were larger in patients undergoing enucleation. Tumor location and the presence or absence of ciliary body involvement did not differ significantly between the groups. The median follow-up after enucleation and after re-treatment was 79 and 59 months, respectively. Cumulative rates of outcomes and differences in rates between the reirradiated and enucleation groups were calculated by the Cox proportional hazards model and the log-rank test, respectively., Results: The median survival duration in the enucleated and reirradiated groups was 42 and 90 months, respectively. The median time free of metastases was 38 months in enucleated patients and 97 months in reirradiated patients. At 5 years after enucleation and after reirradiation, the probability of overall survival was 36% and 63%, respectively (p=0.040, log-rank test); the probability of freedom from metastases was 31% and 66%, respectively (p=0.028, log-rank test). These differences persisted after adjustment for recurrent tumor largest diameter and volume at the time of reirradiation or enucleation., Conclusions: This retrospective analysis suggests that survival in reirradiated patients is not compromised by administration of a second course of PBT for recurrent uveal melanoma., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Metastatic spread in retinoblastoma is a rare occurrence in developed countries but still associated with a poor prognosis., Patients and Methods: Medical records of all metastatic retinoblastoma diagnosed during a 20-year period were retrospectively reviewed., Results: Six patients out of 104 presented a metastatic disease with an incidence at diagnosis of 2%. Three had a metastatic disease at diagnosis, one patient a trilateral retinoblastoma and two a metastatic spread after enucleation. All but one were sporadic retinoblastoma. Central nervous system (CNS) involvement was reported in five patients, while one patient had an intraorbital lesion, and bone and bone marrow spread. Different treatment strategies were administered based on local treatment plus chemotherapy and radiotherapy with or without high-dose chemotherapy. An ifosfamide/carboplatin/etoposide regimen was administered in three patients resulting in a partial response. Out of six patients, four died, and two patients are alive at 60 and 63 months from diagnosis. Both children with a long follow-up were treated with high-dose chemotherapy. All but one of the patients with CNS involvement died; the survivor was a patient with pineal involvement., Conclusion: This retrospective review confirms a curable strategy based on local treatment and conventional plus high-dose chemotherapy. Patients with CNS involvement remain incurable.

Aims: Ruthenium-106 brachytherapy is an effective method for treating small to medium uveal melanomas. The purpose of this study was to examine its effectiveness and safety in the management of thick posterior uveal melanoma (apical height >/=8.0 mm) and to compare it with enucleation., Methods: 126 consecutive patients with thick uveal melanoma were included. 63 patients treated with Ruthenium-106 brachytherapy were compared with 63 patients treated with enucleation. The main outcome measures were visual acuity, eye retention, local recurrence, metastases, all-cause mortality and melanoma-related mortality., Results: Patients treated with brachytherapy were significantly younger and had significantly smaller tumours, compared with patients treated with enucleation. Tumour thickness in the brachytherapy group was 9.3 (SD 0.9) mm compared with 12.2 (1.9) mm in the enucleation group. The 5- and 10-year melanoma-related mortality was 20.5% and 46.2% for brachytherapy patients and 28.1% and 44.0% for enucleation patients (p = 0.6 and p = 0.9). When comparing 15 brachytherapy with 15 matched enucleation patients, the 5-year melanoma-related mortalities were similar, 28.6% and 33.3% respectively (p = 0.7). Complications associated with brachytherapy included tumour regrowth (n = 15), scleral melt (n = 3), neovascular glaucoma (n = 5) and vitreous haemorrhage (n = 3). In the brachytherapy group, no significant difference in survival was noted between patients who did and did not develop local recurrence (p = 0.9). Of the eyes that were initially treated with brachytherapy, 71.4% were saved from enucleation. Of these, 70.8% had a final visual acuity of 20/200 or better., Conclusions: Ruthenium-106 brachytherapy is an alternative to enucleation in some thick posterior uveal melanomas.

Aim: This paper describes the treatment and survival of 1576 children with retinoblastoma in Great Britain diagnosed 1963-2002., Methods: Survival rates were analysed according to period of diagnosis and tumour laterality., Results: Survival was calculated by calendar period of diagnosis, 1963-1982 and 1983-2002. For both unilateral and bilateral retinoblastoma, survival improved between the two periods. The survival curves for the two periods were significantly different: for unilateral retinoblastoma p<0.00001, for bilateral p<0.01. For unilateral cases, the estimated 5-year survival rates rose from 85% for those diagnosed in 1963-1967 to 97% for those diagnosed in 1998-2002. The equivalent rates for bilateral cases were 88% and 100%., Conclusion: Survival rates were already high at the start of the study period. They increased with changes in treatment regimens.

Background: Most uveal melanomas are currently treated by eye-preserving radiotherapies. However, for melanomas of the largest size or with initial complications, enucleation remains the reference treatment. Enucleation is called primary when it is proposed as the only local treatment option for a melanoma. There is very little literature on the use of primary enucleation after the introduction of conservative treatments. Our main goal was to evaluate the survival of melanoma patients treated by primary enucleation since the introduction of proton-beam therapy in France in 1991., Methods: All melanoma patients undergoing primary enucleation in our department between 1991 and 2002 were included in this retrospective study. The 5-year melanoma-specific survival rate was calculated using the Kaplan-Meier method. The multivariate prognostic analysis was performed using the Cox proportional hazards model., Results: Forty patients, representing 8% of all patients with choroidal uveal melanoma diagnosed and followed up in our department during an 11-year period, were included in the study. No patient was lost to follow-up. The 5-year melanoma-specific survival rate was 31.45% (SE: 7.8) after primary enucleation. Significant prognosis factors in the multivariate analysis were: tumor thickness > 12 mm (p = 0.03), anterior margin of the tumor involving the iris (p = 0.018), and presence of epithelioid cells (p = 0.02)., Conclusions: The very low survival rate reported reflects the evolution of primary enucleation, which is currently indicated only for melanomas with the worst prognosis. The knowledge of current post-enucleation survival rates represents an essential achievement for both correct assessment of conservative therapies and patient counseling.

Background: Radiotherapy of an eye before enucleation, so called preenucleation radiotherapy (PER), of patients with uveal melanoma was initiated to reduce enucleation-induced systemic metastasis. Earlier studies with a short follow-up period have not demonstrated a significant effect on survival., Objective: To study the effect of PER on melanoma-related mortality after more than 9 years of follow-up., Design: In a prospective study, 167 patients with uveal melanoma were treated between 1978 and 1992 by irradiation with 800 rad (8 Gy) given in 2 fractions 2 days before enucleation. A group of 108 patients with uveal melanoma treated between 1971 and 1992 by enucleation only in the same hospital served as a historical control group. Patients were followed up until December 2002 or death., Results: Melanoma-related death occurred in 32.3% of the PER-treated group and in 40.7% of the enucleation only group. Mean follow-up was 9.25 years. After 48 months of follow-up, a significant difference in survival became evident in favor of the PER group. The estimated 15-year survival rates for patients with melanoma in the PER group and enucleation only group were 63.7% and 51.0%, respectively. For patients dying of all causes, these percentages were 47.5% and 25.2%, respectively. In both groups, women had a better prognostic outcome than men., Conclusion: This study suggests that PER improves long-term survival in patients with uveal melanoma.

Purpose: To evaluate prognostic factors for the survival of patients treated by enucleation for choroidal and ciliary body melanomas., Methods: The study included 293 consecutive patients (147 men and 146 women) treated by enucleation for a choroidal or ciliary body melanoma during the period 1955-2000. The median age at treatment was 61 years (range 26-88 years). Clinical and histopathological findings, vital status at October 1st, 2002, and cause of death were registered. Prognostic factors for survival were evaluated by univariate and multivariate Cox proportional hazards analysis and by Kaplan-Meier survival analysis., Results: Follow-up was complete. The median follow-up time was 6.2 years (range 21 days to 43.4 years) and the median potential follow-up time was 25.7 years (range 1.9-47.7 years). In multivariate Cox proportional hazards analysis an increased risk of melanoma-related death was found for largest basal diameter (n = 264, p < 0.001, mortality rate ratio (RR) = 1.09 for continuous parameter in mm), anterior tumour margin at the iris/ciliary body versus choroid (p < 0.001, RR = 2.22), and non-spindle cell type versus spindle cell (p = 0.047, RR = 1.45). An increased risk of death from all causes was found for men versus women (n = 266, p = 0.02, RR = 1.41), high age (p < 0.001, RR = 1.41 for continuous parameter in 10-year age groups), largest basal diameter (p < 0.001, RR = 1.07), anterior tumour margin at the iris/ciliary body (p = 0.02, RR = 1.52), and non-spindle cell type (p = 0.04, RR = 1.34)., Conclusion: The risk of melanoma-related death after enucleation for a choroidal or ciliary body melanoma was high for tumours with large basal diameter, of non-spindle cell type and anterior location. Additional risk factors for death from all causes were male sex and high age.

The records of 265 consecutive patients with juxtapapillary choroidal melanoma were reviewed and a statistical non-randomised retrospective study was performed to evaluate the risk for metastasis and compare the survival rate of patients treated with plaque radiotherapy or enucleation. To obtain sufficient overlap between the enucleation and plaque radiotherapy, the statistical analysis was limited to an adjusted subgroup of 127 patients who met eligibility criteria for plaque radiotherapy and who had a minimum of 3 years of follow up after treatment. In the adjusted subgroup of 127 patients, 92 patients (72%) were initially treated with enucleation and 35 (28%) with plaque radiotherapy. In both univariate and multivariate logistic analysis models, the age of the patient (> 50 years), tumour thickness (> 3 mm), and treatment by age interaction were found to be significant factors for development of distant metastasis. In patients younger than 50 years, the method of treatment (enucleation versus plaque radiotherapy) did not significantly affect the risk of metastasis. For those older than 50 years, there was a non-significant trend for patients in the enucleation group to be at a higher risk for metastasis than those in the plaque group. In the enucleation group, patients older than 50 years had a significantly higher incidence of distant metastasis than those younger than 50 years. In the plaque radiotherapy group, there was no significant higher incidence of metastasis in patients younger than 50 years than in those older than 50 years. When a Cox proportional hazards model was used to evaluate the survival rate, there was the same statistically significant effect of treatment by age interaction as was found in the multivariate logistic model on survival time. Moreover, there was a significant effect of treatment by tumour thickness interaction on survival time. Patients in the enucleation group had a better survival rate when the thickness of the tumour was less than 3 mm compared with a tumour of more than 3 mm. There were no apparent effects of tumour thickness on survival for patients treated with plaque radiotherapy. From these results, the authors currently recommend plaque radiotherapy as a viable option to enucleation in patients with juxtapapillary choroidal melanoma.

Follow up information was retrieved on 111 patients who underwent enucleation for uveal melanoma between 1964 and 1987, allowing a minimum postoperative period of 5 years. Univariate survival analysis was carried out using Kaplan-Meier curves and the differences between the curves were analysed with the Mantel-Cox test. Multivariate analysis used the Cox proportional hazards model. Univariate analysis isolated each of the following as significant prognosticators: largest tumour diameter (LTD) (p < 0.002), presence of epithelioid cells (p < 0.03), and glaucoma (p < 0.001). A combination of cell type, glaucoma, and LTD (p < 0.0001) had strong and independent prognostic significance in multivariate analysis. The results of this series are compared with previous studies and the value of cell type information and new quantitative parameters is discussed.

With the use of data published during the period from 1966 through 1988, a pooled analysis (meta-analysis) of 5-year mortality rates among patients who had an eye enucleated for choroidal melanoma was performed to provide a more robust estimate of this rate than could be obtained from any single study. The literature concerning mortality following a diagnosis of choroidal melanoma has been reviewed systematically and described in a separate article. Of 76 reports published from 1966 through 1988, 29 were excluded from the meta-analysis because there were no cases treated by enucleation alone, mortality was not reported by time from enucleation, fewer than 10 cases were reported, or 5-year mortality rates were not reported or derivable from the data presented. Ten additional reports were excluded because they were based on data for the same set of patients as another article in the series. Of the remaining 37 reports, 29 contained data for patients with tumors of varying sizes that could not be separated into subgroups based on the size of the tumor at the time of treatment. The remaining eight articles reported 5-year mortality rates by tumor size, specifically for small, medium, or large tumors. The combined weighted estimates of 5-year mortality rates following enucleation were 16% for small tumors (95% confidence interval [CI]: [14%, 18%]), 32% for medium tumors (95% CI: [29%, 34%]), and 53% for large tumors (95% CI: [50%, 56%]). Different methods of pooling the data yielded consistent estimates for all three tumor size categories.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors performed retrospective investigations and evaluated the influence of the period of time between the onset of the first symptoms of the disease and the enucleation on the life expectations; the groups of patients treated by enucleation and non-treated were compared. Various opinions on the influence of enucleation on the prognosis in patients with uveal melanoma were discussed.