Largest Basal Tumor Diameter Research Articles

THE RELATIONSHIP BETWEEN COMBINED POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY AND CLINICAL AND LIGHT MICROSCOPIC FINDINGS IN CHOROIDAL MELANOMA

To investigate the correlation between the clinical and light microscopic features of choroidal melanoma with combined PET/CT findings. This is a retrospective interventional case series of 14 patients with choroidal melanoma referred to the vitreoretinal service at the Mayo Clinic, Rochester, MN. All underwent preoperative combined PET/CT scanning and enucleation. Standardized uptake values (SUV) were correlated with the clinical and light microscopic features of the choroidal melanomas. All 14 eyes showed uptake. The mean patient age was 62 years (SD 12.5 years). The mean tumor thickness was 9.3 mm (range 3-23 mm). Histopathology showed choroidal melanoma in all with the following cell types: 6 mixed cell type, 7 spindle cell type, and 1 epithelioid cell type. The average of the SUV means was 3.7 (range 1.7-12.8). The individual SUV means were correlated with lesion thickness (r = 0.85; P < 0.01) and largest tumor basal diameter (r = 0.65; P = 0.01). Melanomas with focal necrosis (P = 0.03) and of the mixed cell type (P < 0.01) appeared to have higher SUV means. The majority of the choroidal melanomas had low to medium mean SUVs. Lesion size accounted for a significant portion of the variation, though nonspecific necrosis and cell type were also associated with higher SUV means.

Artificial Neural Networks Estimating Survival Probability after Treatment of Choroidal Melanoma

To describe neural networks predicting survival from choroidal melanoma (i.e., any uveal melanoma involving choroid) and to demonstrate the value of entering age, sex, clinical stage, cytogenetic type, and histologic grade into the predictive model. Nonrandomized case series. Patients resident in mainland Britain treated by the first author for choroidal melanoma between 1984 and 2006. A conditional hazard estimating neural network (CHENN) was trained according to the Bayesian formalism with a training set of 1780 patients and evaluated with a test set of another 874 patients. Conditional hazard estimating neural network-generated survival curves were compared with those obtained with Kaplan-Meier analyses. A second model was created with information on chromosome 3 loss, using training and test sets of 211 and 140 patients, respectively. Comparison of CHENN survival curves with Kaplan-Meier analyses. Representative results showing all-cause survival and inferred melanoma-specific mortality, according to age, sex, clinical stage, cytogenetic type, and histologic grade. The predictive model plotted a survival curve with 95% credibility intervals for patients with melanoma according to relevant risk factors: age, sex, largest basal tumor diameter, ciliary body involvement, extraocular extension, tumor cell type, closed loops, mitotic rate, and chromosome 3 loss (i.e., monosomy 3). A survival curve for the age-matched general population of the same sex allowed estimation of the melanoma-related mortality. All-cause survival curves generated by the CHENN matched those produced with Kaplan-Meier analysis (Kolmogorov-Smirnov, P<0.05). In older patients, however, the estimated melanoma-related mortality was lower with the CHENN, which accounted for competing risks, unlike Kaplan-Meier analysis. Largest basal tumor diameter was most predictive of mortality in tumors showing histologic and cytogenetic features of high-grade malignancy. Ciliary body involvement and extraocular extension lost significance when cytogenetic and histologic data were included in the model. Patients with a monosomy 3 melanoma of a particular size were predicted to have shorter survival if their tumor showed epithelioid cells and closed loops. Estimation of survival prognosis in patients with choroidal melanoma requires multivariate assessment of age, sex, clinical tumor stage, cytogenetic melanoma type, and histologic grade of malignancy.

Monosomy of Chromosome 3 and an Inflammatory Phenotype Occur Together in Uveal Melanoma

In uveal melanoma, different predictors of poor prognosis have been identified, including monosomy of chromosome 3, HLA expression, and the presence of infiltrating leukocytes and macrophages. Each of these parameters can be used to differentiate prognostically the favorable tumors from the unfavorable ones, and thus the hypothesis for the present study was that they are related, and that monosomy of chromosome 3 occurs in the same tumors as the unfavorable inflammatory phenotype. Tumor tissue was obtained from 50 cases of uveal melanoma treated between 1999 and 2004. After enucleation, nuclei were isolated from paraffin-embedded tissue for fluorescence in situ hybridization, to determine the chromosome 3 copy number. Each tumor-containing globe was further processed for conventional histopathologic examination and for immunohistochemical analysis with HLA class I and II-specific antibodies and with macrophage marker CD68. Of 50 uveal melanomas, 62% (31/50) were categorized as having monosomy of chromosome 3. Monosomy 3 was associated with the presence of epithelioid cells, an increased density of tumor-infiltrating macrophages, and a higher HLA class I and II expression. Survival analyses showed a correlation between monosomy 3 and decreased survival and identified monosomy 3, ciliary body involvement, and largest basal tumor diameter as the best prognostic markers. Monosomy 3 in uveal melanoma is associated with the presence of an inflammatory phenotype, consisting of a high HLA class I and II expression as well as an increased number of tumor-infiltrating macrophages. In a multivariate Cox regression analysis, the presence of monosomy 3 was one of the best prognostic markers of metastatic disease and survival, although the follow-up time was short.

Ocular conservation in patients with uveal melanoma by a multimodality approach to treatment

Abstract Purpose: To analyse eye survival in patients with uveal melanoma with a multimodality approach to treatment Methods: 273 patients with uveal melanoma diagnosed at Ocular Oncology Unit of the University Hospital of Valladolid from 1997 September to 2007 April. Pearson’s Chi‐square test was used to identify between variables and primary enucleation. Logistic regression was used to identify independent variables predicting primary enucleation. Cox’s univariate proportional hazards model was used to identify associations between variables and time to secondary enucleation.Kaplan‐Meier estimates were used to draw survival curves for time to secondary enucleation Results: 273 patients were included in the study. Primary enucleation was performed in 80 patients. Secondary enucleation in 12. Gender (p=0,032), basal tumour diameter &gt;15mm (p&lt;0,001), tumour weight &gt;10mm (p&lt;0,001), anterior tumour margin (p&lt;0,001) and extraocular spread (p&lt;0,001) were associated with primary enucleation. Predictive factors for primary enucleation were largest basal tumor diameter (odds ratio [OR], 3,8; 95% confidence interval [IC], 1,5‐9,1) and tumour weight (OR, 2,7; IC, 1‐7,5). Ocular conservation probability 5 years after conservative treatment was 88%. Largest basal tumor diameter, anterior tumour margin and extraocular spread had influence in ocular survival after conservative treatment. Only largest basal tumor diameter was a predictive factor of secondary enucleation Conclusions: In the present series 69,9% of patiens had a conservative treatment and 88% of them conserved treated eye 5 years

Predicting the prognosis of ciliochoroidal uveal melanoma by its clinical characteristics: a European ophthalmic oncology group collaborative study

Abstract Purpose: To assess clinical characteristics independently associated with mortality from uveal melanoma using a large contemporary European dataset in order to improve future classifications. Methods: Data of 8340 patients who had a choroidal and ciliary body melanoma managed by one of five participating ocular oncology centers directed by members of the European Ophthalmic Oncology Group (OOG) were collated. Variables requested included date of treatment and last follow‐up, survival status, largest basal tumour diameter (LBD), tumour thickness, ciliary body involvement and extraocular extension. Data were analysed with the product‐limit method and Cox regression. Results: Valid LBD and thickness was available for for 7922 and 8111 melanomas, and ciliary and extraocular extension for 7418 and 6087 tumours, respectively. Complete data for all 4 variables were available for 5469 tumours (66%). Mean follow‐up time was 4.0 years (interquartile range, 1.5‐7.3). In Cox regression, all variables were significantly (P&lt;0.0001) and independently associated with melanoma‐related mortality. Covariate‐adjusted hazard ratio (HR) was 1.15 for LBD and 1.06 for thickness (each 1 mm increase), and 1.72 for ciliary body involvement and 2.29 for presence of extraocular extension (yes or no). Conclusions: Choroidal and ciliary body melanomas may effectively be categorised by LBD and thickness, and subcategorized by presence of ciliary body and extraocular extension. All four variables are recommended to be included in future clinical classifications of uveal melanoma. How ciliary body and extraocular extension could be collaboratively coded in more detail remains to be discussed.

Estimating Choroidal Melanoma Volume: Comparison of Methods

To evaluate published methods of estimating choroidal melanoma volume. Prospective consecutive case series. Ten consecutive patients with primary choroidal melanoma. After determination of tumor dimensions (largest tumor basal diameter, basal perpendicular diameter, and height), tumor volume was calculated for each tumor by using the 5 published methods. Percent differences in tumor volume were determined for each tumor as calculated by different methods. Choroidal melanoma volume. The mean variation in estimated tumor volume expressed as a ratio was 2.33 (range, 1.64-3.84). Choroidal melanoma volume calculation methods are inconsistent and caution is needed when volume measures are used for prognostic classification.

Vascular Endothelial Growth Factor A in Eyes With Uveal Melanoma

To determine the presence of vascular endothelial growth factor A (VEGF-A) in the aqueous humor of eyes with uveal melanoma and to identify its source. The VEGF-A concentrations were determined in aqueous humor samples obtained after enucleation from 74 eyes with untreated uveal melanoma and from 8 eyes with treated uveal melanoma. Patient survival and clinical and histopathological tumor variables were compared. In situ hybridization, Western blot analysis, and enzyme-linked immunosorbent assay were used to determine expression of VEGF-A in tumor tissue and in overlying retina. Aqueous VEGF-A concentrations ranged from 18 to 826 pg/mL in 74 untreated eyes, while concentrations in 30 control eyes were significantly lower (median, 50.1 pg/mL) (P<.001). Concentrations in 8 treated eyes were much higher (median, 364 pg/mL). In situ hybridization on tissue sections and Western blot analysis and enzyme-linked immunosorbent assay on tissue extracts revealed VEGF-A in uveal melanoma tissue and in retinal tissue. Uveal melanoma is associated with increased concentrations of VEGF-A in aqueous humor. Aqueous VEGF-A concentration correlates with largest basal tumor diameter and with the tumor height. In eyes with uveal melanoma, tumor and retinal tissues are sources of VEGF-A.

Survival after proton-beam irradiation of uveal melanomas

PurposeTo evaluate the independent prognostic factors for survival, metastasis, local recurrence, and enucleation in patients who had undergone proton-beam therapy for posterior uveal melanomas. DesignInterventional case series. MethodsIn this retrospective study, 224 consecutive incident cases were treated at the Biomedical Cyclotron Centre (Nice, France) from June 1991 to December 1997. Overall, metastasis-free, local recurrence-free, and enucleation-free survival rates were calculated according to the Kaplan-Meier method using the log-rank test. The multivariate prognostic analysis was performed using the Cox proportional hazards model. ResultsThe 5-year overall survival rate was 78.1% (SE: 3.7%). A largest basal tumor diameter (LTD) below 10 mm and female sex were independently associated with a better prognosis. The 5-year metastasis-free survival rate was 75.6% (SE: 3.6%). Only an LTD above 10 mm and ciliary body involvement were independently associated with metastasis. Ten patients (4.5%) had a local recurrence, which was correlated with the risk of metastasis (P = .045). The 5-year enucleation-free survival rate was 69.6% (SE: 4.0%). Once again, an LTD below 10 mm and female sex were predictive of a better prognosis. ConclusionOur results with proton-beam therapy correspond to those reported in the literature. This treatment strategy is safe and yields predictably good results. In addition to the two independent prognostic factors for survival and metastasis, namely LTD and ciliary body involvement, sex also had a significant impact in our case series, but the clinical relevance of this finding is unknown.

Modelling survival after treatment of intraocular melanoma using artificial neural networks and Bayes theorem

This paper describes the development of an artificial intelligence (AI) system for survival prediction from intraocular melanoma. The system used artificial neural networks (ANNs) with five input parameters: coronal and sagittal tumour location, anterior tumour margin, largest basal tumour diameter and the cell type. After excluding records with missing data, 2331 patients were included in the study. These were split randomly into training and test sets. Date censorship was applied to the records to deal with patients who were lost to follow-up and patients who died from general causes. Bayes theorem was then applied to the ANN output to construct survival probability curves. A validation set with 34 patients unseen to both training and test sets was used to compare the AI system with Cox's regression (CR) and Kaplan–Meier (KM) analyses. Results showed large differences in the mean 5 year survival probability figures when the number of records with matching characteristics was small. However, as the number of matches increased to >100 the system tended to agree with CR and KM. The validation set was also used to compare the system with a clinical expert in predicting time to metastatic death. The rms error was 3.7 years for the system and 4.3 years for the clinical expert for 15 years survival. For <10 years survival, these figures were 2.7 and 4.2, respectively. We concluded that the AI system can match if not better the clinical expert's prediction. There were significant differences with CR and KM analyses when the number of records was small, but it was not known which model is more accurate.

Iodine brachytherapy as an alternative to enucleation for large uveal melanomas

Purpose To evaluate the safety and efficacy of iodine 125 plaque brachytherapy (IBT) for large uveal melanomas. Design Retrospective, nonrandomized comparative trial (historical control). Participants One hundred twenty-one consecutive patients with a large uveal melanoma according to the Collaborative Ocular Melanoma Study (COMS) criteria who attended a national ocular oncology service. Methods Ninety-seven patients (80%) underwent primary IBT (mean dose to tumor apex, 87 Gy) with noncollimated 20- to 25-mm plaques. Assessment of metastatic disease at death and visual outcome followed COMS guidelines. Time to low vision (20/70 or worse) and blindness (loss of 20/400 vision) in the study eye were modeled by Cox proportional hazards regression, based on both single- and repeated-failure data sets. Person-years of retained vision were calculated. Main outcome measures All-cause and melanoma-specific survival, local and distant recurrence, and preservation of vision and cosmesis. Results Median tumor height was 10.7 mm (range, 4.5–16.8 mm), and largest basal tumor diameter was 16.1 mm (range, 7.3–25.0 mm). The Kaplan-Meier estimate for all-cause and melanoma-specific survival was 62% (95% confidence interval [CI], 49%–72%) and 65% (95% CI, 52%–75%) at 5 years. The corresponding estimate for local tumor recurrence was 6% (95% CI, 2%–14%) and for major cosmetic abnormality was 38% (95% CI, 26%–52%). The median visual acuity in the study eye was 20/100 at baseline and 20/1600 at 2 years after treatment. The Kaplan-Meier estimate for avoiding low vision and blindness was 11% (95% CI, 4%–24%) and 26% (95% CI, 16%–37%) at 2 years, respectively. Tumor height and location entirely posterior to the ora serrata were the most robust predictors of visual loss. In this series, 49 person-years without low vision (median, 0.6 years; range, 0.04–8.2 years) and 111 person-years without blindness (median, 1.0 years; range, 0.03–8.6 years) in the treated eye were conserved. Conclusions Iodine 125 plaque brachytherapy seems to be a safe and effective alternative to enucleation with regard to survival and local tumor control. It provides a fair chance of preserving the eye with acceptable cosmesis and a reasonable chance of conserving useful vision for 1 to 2 years.

Transscleral resection versus iodine brachytherapy for choroidal malignant melanomas 6 millimeters or more in thickness: A matched case–control study

Objective To assess differences in treatment outcome after transscleral resection (TSR) and iodine brachytherapy (IBT) of choroidal melanomas too thick for ruthenium brachytherapy. Design Matched case–control study. Setting Two national ocular oncology services. Participants Forty-nine pairs of patients with choroidal melanoma 6 mm thick or more (range = 6–14), treated within 3 years of each other by either TSR or IBT, and retrospectively matched by age, visual acuity at diagnosis, largest basal tumor diameter, and posterior extension of the tumor. Intervention Iodine brachytherapy in Finland or TSR in United Kingdom. Prospectively collected time-to-event data were compared with parametric Weibull regression, adjusting for matching. Main outcome measures Tumor control, complications, and visual acuity. Results Risk of local recurrence after IBT was smaller than that after TSR (hazard ratio [HR] = 0.02, 95% confidence interval [CI] = 0.01–0.11, P<0.001, Weibull regression adjusted for matching), but the 8-year all-cause and melanoma-specific (HR = 0.81, 95% CI = 0.30–2.22, P = 0.69) survivals did not differ. The risks of cataract (HR = 2.05, 95% CI = 1.08–3.89, P = 0.029), maculopathy (HR = 2.28, 95% CI = 0.96–5.43, P = 0.062), and vitreous hemorrhage (HR = 2.30, 95% CI = 0.95–5.57, P = 0.064) were higher after IBT. Rubeosis, neovascular glaucoma, and optic neuropathy developed only after IBT. Risk of retinal detachment, exudative after IBT and rhegmatogenous after TSR (HR = 0.84, 95% CI = 0.40–1.75, P = 0.63), and risk of losing 20/60 vision (HR = 1.37, 95% CI 0.76–2.45, P = 0.29) were comparable between the groups, but risk of losing 20/200 vision was higher after IBT (HR = 2.38, 95% CI = 1.48–3.83, P<0.001). No overall difference in quality of life was found. Conclusions This study suggests that TSR preserves 20/200 vision better than IBT and avoids some of its major complications, but increases the risk of local recurrence. About 350 patients would need to be randomized to prove that TRS preserves 20/60 vision better than IBT.

Visual Outcome of Eyes With Malignant Melanoma of the Uvea After Ruthenium Plaque Radiotherapy

To analyze the overall visual outcome in 100 consecutive eyes with malignant uveal melanoma irradiated with ruthenium-106 plaques between 1981 and 1991. The follow-up ranged from 4 months to 10.1 years (median 3.0 years). Scattergrams of equal follow-up periods, life-table survival analysis, and Cox's proportional hazards analysis were used to analyze visual outcome. VA increased for some time in 14 eyes. By 3 years, VA of at least 20/70, 20/200, counting fingers, and light perception were retained in 27%, 41%, 67% and 82% of eyes, respectively. Macular pathology cause loss of reading vision; neovascular glaucoma or enucleation caused loss of light perception. In univariate analysis, large tumor size (height > 5 mm or TNM class T3) predicted visual loss of all VA levels. For the loss of light perception, the tumor's largest basal diameter > 15 mm reached significance. In Cox's multivariate analysis tumor height > 5 mm was the only significant independent risk indicator for loss of VA levels 20/70 and 20/200. For the level CF, largest basal tumor diameter also reached significance, but location of the tumor within 1 disc diameter of the optic disc, either alone or in addition to the fovea, had the greatest risk ratio (6.3, 95% CI 4.1-9.8). For losing light perception, large TNM size (T3) was the strongest risk indicator (risk ratio 10.0; 95% CI 4.5-22.5), followed by proximity of the tumor to the optic disc (risk ratio 4.3, 95% CI 2.4-7.8). Ruthenium brachytherapy may retain vision in an eye with a malignant melanoma of the uvea for a considerable period of time. The data presented are useful in patient counseling and allow comparison to subsequent series.

Impact of delayed treatment in growing posterior uveal melanomas.

To investigate the impact of pretreatment tumor growth on survival in patients with primary posterior uveal melanoma. Retrospective case-by-case matched comparative survival study. Thirty patients with documented tumor growth of at least 3 mm in basal diameter, 1.5 mm in thickness, or both during a pretreatment interval of 6 months or more and a matched control group of 30 promptly treated patients. Matching criteria included patient age (+/- 10 years), largest basal tumor diameter (+/- 2 mm), tumor thickness (+/- 1.5 mm), location of anterior tumor margin (same defined zone), and visual symptoms (present or absent). The Oncology Unit of the Retina Service at Wills Eye Hospital, Philadelphia, Pa. All patients were treated in a nonrandomized fashion by conventional therapeutic methods appropriate to the tumor's size, location, and other factors. Actuarial melanoma-specific mortality and all-cause mortality. The mean +/- SE cumulative 5-year probability of melanoma-specific mortality relative to the date of initial examination was 17.1% +/- 7% in the delayed treatment group and 18.4% +/- 8% in the prompt treatment group. This difference is not statistically significant (P > .5, log rank test). These results lend support to the belief that delayed treatment of selected small and dormant-appearing choroidal and ciliary body melanomas does not substantially increase the probability of melanoma-specific mortality; however, they do not prove that observation is the correct management option for all patients with a posterior uveal melanoma.