Anterior Tumor Margin Research Articles

Anterior segment swept-source optical coherence tomography and ultrasound biomicroscopy in iris and ciliary body lesions

ABSTRACT Objectives Differentiation of iris and ciliary body lesions as benign or malignant and cystic or solid is important. The aim of this study was to compare anterior segment swept-source optical coherence tomography (AS SS-OCT) and ultrasound biomicroscopy (UBM) findings in iris and ciliary body tumors. Research design and methods Forty-two eyes of 38 cases with iris and ciliary body tumors imaged with UBM and AS SS-OCT between September 2018 and September 2023 were evaluated retrospectively. Results Of 42 eyes, 14 had melanoma, 14 iris pigment epithelial (IPE) cysts, 7 nevi, 3 Lisch nodules, 2 iris stromal cysts, 1 pars plana cysts, and 1 iris mammillations. An equivalent (100%) visualization of the anterior tumor margin was obtained with both techniques. Compared to AS SS-OCT, UBM was superior for posterior margin visualization in melanocytic tumors and IPE cysts. Bland-Altman plots demonstrated good agreement between UBM and AS SS-OCT for melanocytic tumors < 2.5 mm in base diameter and < 2 mm in thickness. Conclusions Although, UBM is the gold standard for ciliary body and iridociliary tumors. AS SS-OCT should be considered as an excellent alternative to UBM, especially in minimally elevated iris lesions.

Individualized dosimetry in Ru-106 ophthalmic brachytherapy based on MRI-derived ocular anatomical parameters

PurposeTo estimate ocular geometry-related inaccuracies of the dosimetric plan in Ru-106 ophthalmic brachytherapy. Methods and MaterialsThirty patients with intraocular lesions were treated with brachytherapy using a Ru-106 plaque-shell of inner radius of 12 mm. Magnetic resonance imaging was employed to determine the external scleral radius at tumor site and the tumor margins. A mathematical model was developed to determine the distance between the external sclera and the internal surface of the plaque associated with the tangential application of the plaque on the treated eye. Differences in delivered dose to the tumor apex, sclera and tumor margins as derived by considering the default eye-globe of standard size (external sclera radius = 12 mm) against the individual-specific eye globe were determined. ResultsThe radius of external sclera at the tumor site was found to range between 10.90 and 13.05 mm for the patient cohort studied. When the patient specific eye-globe/tumor geometry is not taken into account, the delivered dose was found to be overestimated by 8.1% ± 4.1% (max = 15.3%) at tumor apex, by 1.5% ± 2.8% (max = 5.7%) at anterior tumor margin, by 16.6% ± 7.5% (max = 36.4%) at posterior tumor margin and 8.1% ± 3.8% (max = 13.2%) at central sclera of eyes with lower than the default radius. The corresponding dose overestimations for eyes with higher than the default radius was 13.5% ± 4.3% (max = 22.3%), 1.5% ± 2.8% (max = 5.7%), 12.6% ± 4.5% (max = 20.0%), and 15.1% ± 5.0% (max = 24.4%). ConclusionsThe proposed patient-specific approach for Ru-106 brachytherapy treatment planning may improve dosimetric accuracy. Individualized treatment planning dosimetry may prevent undertreatment of intraocular tumors especially for highly myopic or hyperopic eyes.

Possible role of standardized echography complementing ultrasound biomicroscopy in tumors of the anterior eye segment: a study in a series of 13 patients

To evaluate the efficacy of standardized A-scan echography (ASE) complementing ultrasound biomicroscopy (UBM) to propose the most efficient method as grounds for the diagnosis, treatment, and follow-up of anterior eye-segment tumors. The inclusion criteria were tumors of the ciliary body and peripheral choroidal tumors, whose anterior border could not be visualized with a 10MHz ultrasound probe. The largest basal dimension and the highest prominence of the tumor were measured with a UBM Lin 50 probe. A standardized A-scan examination determined the tumor's thickness and internal reflectivity. Thus, tissue differentiation led to a standardized echography-based diagnosis (SED). The study included 13 patients. SED was achieved in all examined tumors. The smallest thickness of the tumor of the ciliary body enabling SED was only 1.78mm. The highest prominence of the tumor (3.66 ± 1.39mm) was generally larger than its thickness (3.30 ± 1.71mm). When approaching ciliary body tumors, both ASE and UBM should be performed, the former to accurately differentiate the tumor and measure its height, and the latter to delineate anterior tumor margins and iris involvement. Standardized echography-based diagnosis was grounds for further evaluation and/or treatment in this case series. The highest prominence of the ciliary body tumor perpendicular to the sclera as evidenced by UBM was generally higher than the thickness obtained with standardized echography. Hence, we propose ASE thickness to be the grounds for staging the severity of ciliary body tumors in the algorithm for their management.

Endoscopic endonasal surgery for olfactory groove meningiomas: outcomes and limitations in 50 patients.

Recently, endoscopic endonasal surgery (EES) has been introduced in the management of skull base tumors, with constantly improving outcomes and increasing indications. The authors retrospectively reviewed the effectiveness of EES in the management of olfactory groove meningiomas. Between February 2003 and December 2012, 50 patients (64% female) with olfactory groove meningiomas underwent EES at the University of Pittsburgh Medical Center. The authors present the results of EES and analyze the resection rates, clinical outcome, complications, and limitations of this approach. Forty-four patients presented with primary tumors, whereas six were previously treated elsewhere. The patients' mean age was 57.1 years (range 27-88 years). Clinical presentation included altered mental status (36%), visual loss (30%), headache (24%), and seizures (20%). The mean maximum tumor diameter was 41.6 mm (range 18-80 mm). All patients underwent EES, which was performed in stages in 18 giant tumors. Complete tumor resection (Simpson Grade I) was achieved in 66.7% of the 45 patients in whom it was the goal, and 13 (28.9%) had neartotal resection (> 95% of the tumor). Tumor size, calcification, and absence of cortical cuff from vasculature were significant factors that influenced the degree of resection (p = 0.002, p = 0.024, and p = 0.028, respectively). Tumor residual was usually at the most lateral and anterior tumor margins. Following EES, mental status was improved or normalized in 77.8% of the cases, vision was improved or restored in 86.7%, and headaches resolved in 83.3%. There was no postoperative deterioration of presenting symptoms. Complications were increased in tumors > 40 mm and included CSF leakage (30%), which was significantly associated with lobular tumor configuration (p = 0.048); pulmonary embolism/deep vein thrombosis, more commonly in elderly patients (20%); sinus infections (10%); and delayed abscess months or years after EES (6%). One patient had an intraoperative vascular injury resulting in transient hemiparesis (2%). There were no perioperative deaths. During a mean follow-up period of 32 months (median 22 months, range 1-115 months), 1 patient underwent repeat EES for tumor regrowth. Endoscopic endonasal surgery has shown good clinical outcomes regardless of patient age, previous treatment, or tumor characteristics. Tumor size > 40 mm, calcification, and absence of cortical vascular cuff limit GTR with EES; in addition, large tumors are associated with increased postoperative complications. Significant lateral and anterior dural involvement may represent indications for using traditional craniotomies for the management of these tumors. Postoperative CSF leakage remains a problem that necessitates innovations in EES reconstruction techniques.

Metastasis from Uveal Melanoma Associated with Congenital Ocular Melanocytosis: A Matched Study

To determine the rate of metastasis resulting from uveal melanoma associated with congenital ocular melanocytosis (COM) and to compare it with the rate of metastasis resulting from uveal melanoma not associated with COM. Matched retrospective study. Fifty-seven patients with uveal melanoma associated with ocular melanocytosis (melanocytosis group). Each patient in the melanocytosis group was matched with 2 patients with uveal melanoma not associated with ocular melanocytosis (no melanocytosis group) for age, gender, location of anterior tumor margin, location of tumor epicenter, tumor basal diameter, and tumor thickness. Review of medical records. Metastasis resulting from uveal melanoma. The mean basal diameter and thickness of tumors in the melanocytosis group were 10 and 4.9 mm, respectively, and most were located between the macula and equator (70%). The melanocytosis and no melanocytosis groups were similar with regard to all patient, ocular, and tumor features studied. Nineteen (33%) of 57 patients in the melanocytosis group and 18 (16%) of 114 patients in the no melanocytosis group demonstrated systemic metastasis during mean follow-up periods of 77 months (range, 1-402) and 64 months (range, 1-252), respectively (P = 0.013). The Kaplan-Meier estimates for systemic metastasis in the melanocytosis group at 5 and 15 years were 27% and 59%, respectively, compared with 15% and 33%, respectively, in the no melanocytosis group (hazard ratio, 1.99; 95% confidence interval, 1.16-3.41). In this matched study, patients with uveal melanoma associated with COM were twice as likely to have systemic metastasis compared with patients with uveal melanoma not associated with COM. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Scleral Necrosis after Plaque Radiotherapy of Uveal Melanoma: A Case-Control Study

To identify risk factors and outcome of scleral necrosis after plaque radiotherapy of uveal melanoma. Case-control study. A total of 73 cases with scleral necrosis and 73 controls without necrosis after plaque radiotherapy. Controls were matched for anteroposterior tumor epicenter and follow-up duration. Plaque radiotherapy with iodine-125, cobalt-60, iridium-192, or ruthenium-106. Scleral necrosis. Of 5057 patients treated with plaque radiotherapy for uveal melanoma, 73 (1%) developed radiotherapy-induced scleral necrosis. Scleral necrosis occurred in <1% of patients (3/1140) when plaque radiotherapy was used for tumors <3 mm in thickness, 1% of patients (33/3155) with 3- to 8-mm tumor thickness, and 5% of patients (37/762) with >8-mm-thick tumors. On the basis of tumor location, scleral necrosis was detected after plaque radiotherapy of iris melanoma in 0% of patients (0/91), ciliary body melanoma in 29% of patients (67/235), and choroid melanoma in <1% of patients (6/4731). The mean time interval between plaque radiotherapy and scleral necrosis was 32 months (median, 23 months; range, 4-126 months). The mean basal dimension of scleral necrosis was 4 mm (median, 3 mm; range, 1-15 mm), equivalent to 29% of mean tumor base (median, 24%; range, 6%-100%) and 22% of mean plaque size (median, 19%; range, 5%-75%). Multivariate analysis of factors that predicted clinically evident scleral necrosis included ciliary body (P = 0.0001) and pars plana to ora serrata (P < 0.0001) locations of anterior tumor margin, tumor thickness ≥ 6 mm (P = 0.0001), and radiation dose ≥ 400 Gy to the outer sclera (P = 0.0455). Scleral necrosis remained stable in 48% of patients (35/73), increased in size/severity in 48% of patients (35/73), or progressed to scleral perforation in 4% of patients (3/73) over a mean follow-up of 79 months (median, 54 months; range, 5-351 months). Treatment of scleral necrosis included observation in 81% of patients (59/73), scleral patch graft in 14% of patients (10/73), and enucleation in 5% of patients (4/73). Scleral necrosis after plaque radiotherapy of uveal melanoma was detected in 1% of cases. Factors predictive of scleral necrosis included increasing tumor thickness, ciliary body and peripheral choroidal location, and higher radiation dose to sclera. Most patients (81%) did not require treatment, and 4% evolved to full-thickness perforation. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Routes of Extraocular Extension of Uveal Melanoma: Risk Factors and Influence on Survival Probability

To correlate extraocular spread with other survival predictors and with metastatic death and determine whether there was any relationship between the size of the extraocular tumor and survival. Nonrandomized retrospective case series. Eight hundred forty-seven patients with uveal melanoma treated by primary enucleation between January 1993 and December 2006. Baseline variables were age, gender, largest basal tumor dimension, tumor height, anterior tumor margin, route of extraocular spread (i.e., aqueous channels, vortex veins, ciliary arteries, or ciliary nerves), tumor cell type, mitotic rate, closed connective tissue loops, and monosomy 3. Determination of death was based on the National Health Service Cancer Registry. Prevalence and route of extraocular extension and correlation with intraocular tumor characteristics and metastatic death. The 847 patients had a mean age of 64 years. Extraocular tumor extension was recorded in 124 patients and occurred via aqueous channels (37, 29.8%); ciliary arteries (34, 27.4%); vortex veins (28, 18.5%); ciliary nerves (11, 8.9%); optic nerve (1, 0.8%), and a variety of rare combinations of these routes (13, 10.4%). Extraocular spread via aqueous channels occurred in 15.2% of tumors involving ciliary body or angle, but through other channels in <6% tumors at risk. Extraocular spread correlated with anterior tumor extension, large basal tumor diameter, epithelioid cellularity, closed loops, high mitotic rate, and monosomy 3. Extraocular spread along aqueous drainage channels correlated inversely with intraocular tumor dimensions. Venous spread correlated with large basal tumor diameter. Arterial spread correlated with location near optic disc. Neural spread correlated weakly with mitotic rate. Log rank analysis showed metastatic death to correlate with extraocular extension, irrespective of the route. Multivariate Cox analysis showed the correlation between metastatic death and extraocular spread to be weaker than with largest basal tumor diameter, closed loops, epithelioid cells, and mitotic rate. Size of extraocular tumor was not significant (P = 0.3). Extraocular spread correlated with increased mortality because it was associated with increased tumor malignancy and, in the case of posterior tumors, more advanced disease. Type of scleral route and size of extraocular tumor were unimportant regarding risk of systemic dissemination and tumor-related death.

Characterization of Pancreatic Tumor Motion Using 4D MRI: Surrogates for Tumor Position Should be Used With Caution

Delivering adequate doses of radiotherapy (RT) for pancreatic cancer is challenging due to nearby organs at risk. Uncertainty about tumor location leads to large PTV expansions, which can increase toxicity. In this study, we used 4D MRI to assess motion of pancreatic tumor margins and their relationships with abdominal wall and diaphragmatic positions, with the goal of individualizing PTV margins and assessing the accuracy of abdominal wall or diaphragmatic surrogates for pancreatic tumor position. 17 patients with unresectable pancreatic cancer were enrolled in a prospective IRB-approved study and imaged free-breathing using non-contrast dynamic MRI on a 3T scanner. MR images were taken for one minute, at a rate of 3 images/sec, in single sagittal and coronal planes, using a 2D balanced fast field echo (BFFE) sequence. Images were acquired prior to and during treatment with chemoRT. Tumors were contoured with input from an abdominal MRI radiologist. Superior (sup), inferior (inf), anterior (ant), posterior (post), and lateral tumor margin motion were quantified using an in-house functional imaging analysis tools (FIAT) program. Average amplitudes and standard deviations of tumor margin motion were calculated. Pearson coefficients were used to assess correlation between motion of different tumor margins as well as diaphragmatic motion and abdominal excursion. Finally, a time-weighted distribution of tumor position relative to end-exhale was constructed. Pancreatic tumors moved inferiorly and anteriorly with inspiration as expected. In coronal slices, mean motion (std dev, range) of the sup and inf margins were 13 (4, 8–22) and 14 (6, 6–25) mm, respectively. In sagittal slices, mean motion (std dev, range) of the sup, inf, ant, and post margins were 14 (4, 6–25), 13 (4, 6–23), 6 (3, 2–13), and 4 (3, 0–9) mm. Lateral motion was negligible. Mean differences in motion between sequential scans for a single patient ranged from 2–6 mm. Movement of each tumor margin was poorly correlated with the others with the exception of the sup and inf margins on a single slice orientation (r = 0.62 and 0.72, p < 0.0001 for both), consistent with observed deformation of the pancreas during breathing. Despite similarity between the magnitude of diaphragmatic and sup or inf margin motion, diaphragmatic motion was poorly correlated with that of all tumor margins, with r values between −0.05 and 0.26 (p < 0.01). Abdominal wall excursion was also poorly correlated (r = −0.091 to −0.27, p < 0.0001). Distribution analysis revealed that the inf margin was >10 mm from end-exhale position 10–12% of the time, but it was >15 mm only 2–3% of the time. The sup margin spent 9–11% of the time >10 mm from end-exhale, but only 2% of the time further than 15 mm. Motion of the margins of pancreatic tumors is highly variable between patients and is generally larger than typically accounted for. The data suggest that there is substantial deformation with breathing, and motion of margins does not correlate well with abdominal wall or diaphragmatic motion. Treatment plans which rely on motion of a single fiducial or surrogates for tumor tracking should be used with caution. Instead, since tumors spend only a small proportion of time >10 mm from end exhale, treatment strategies employing time-weighted tumor position in dose calculation should be explored.

Plaque radiation therapy for malignant melanoma of the iris and ciliary body

PURPOSE: To report on plaque radiation therapy for malignant melanomas involving the iris and ciliary body. METHODS: Twenty-two eyes (22 patients) with anterior uveal melanomas were treated with 103Pd ophthalmic plaque radiation therapy. Transillumination and ultrasonography were used to evaluate ciliary body involvement and posterior iris extension. Plaques were placed onto the cornea to treat the anterior tumor margins. The targeted-zone included the tumor and a 2 to 3 mm tumor-free margin. After plaque removal, patients were examined at 1 day, 7 days, 4 weeks, and then every 3 to 6 months thereafter. Systemic evaluations for possible metastatic disease were performed every 6 months. RESULTS: After plaque radiation therapy, the melanomas decreased in thickness (mean 47%) in all 22 eyes, and no secondary enucleation was performed. One patient died of metastatic melanoma 5 years after radiation therapy. Despite anterior plaque placement that covered portions of the cornea, no epiphora, eyelash loss, or visually significant corneal opacities were noted. Whereas 15 of 21 phakic eyes (71%) developed secondary cataract, no eyes developed ischemic or neovascular radiation maculopathy. Four eyes were noted to have glaucoma before treatment, and two developed it after irradiation. Twenty of 22 eyes (91%) were within 2 lines of their pretreatment visual acuity. After radiation, the mean ± SD follow-up was 56 ± 34.4 months (range, 9 to 117 months). CONCLUSIONS: Plaque radiotherapy of melanomas involving the iris and ciliary body resulted in excellent local control with preservation of vision. Although there was high incidence of secondary cataracts, 103Pd plaque radiation therapy resulted in no visually significant corneal opacity or radiation retinopathy.

Plaque radiotherapy for uveal melanoma: long-term visual outcome in 1106 consecutive patients.

To identify clinical predictive factors for visual outcome in a large series of patients who underwent plaque radiotherapy for uveal melanoma. Clinical factors, including patient data, tumor features, and radiation variables, were analyzed for their impact on visual acuity using Cox proportional hazards regression models. Patients with uveal melanoma and initial visual acuity of 20/100 or better in the affected eye who were treated with plaque radiotherapy between July 1976 and June 1992. Two end points were used to evaluate posttreatment visual acuity: (1) final visual acuity (good [20/20-20/100] vs poor [20/200 to no light perception]) and (2) loss of visual acuity (minimal [<5 lines Snellen visual acuity] vs moderate [> or = 5 lines Snellen visual acuity]). Of 1300 consecutive patients with uveal melanoma treated by plaque radiotherapy, 1106 had a visual acuity of 20/100 or better at the time of treatment. In this group, poor visual acuity was found in 34% at 5 years and 68% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted poor visual acuity were increasing tumor thickness, proximity to foveola of less than 5 mm, notched plaque shape, tumor recurrence, patient age 60 years or older, subretinal fluid, cobalt isotope, anterior tumor margin posterior to equator, and worse initial visual acuity. Moderate loss of visual acuity of 5 Snellen lines or more was found in 33% at 5 years and 69% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted moderate visual acuity loss included increasing tumor thickness, worse initial visual acuity, notched plaque shape, tumor recurrence, proximity to foveola of less than 5 mm, patient age of 60 years or older, subretinal fluid, and diabetes mellitus or hypertension. When analyzing visual outcome with regard to tumor thickness, ultimate poor visual acuity of 20/200 or worse at 5 years was found in 24% with a small melanoma (< or = 3.0 mm), 30% with a medium melanoma (3.1-8.0 mm), and 64% with a large melanoma (>8.0 mm). When analyzing visual outcome with regard to tumor proximity to visually important structures, tumors less than 5 mm from the optic disc or foveola demonstrated poor visual acuity in 35% at 5 years, whereas those 5 mm or more from the optic disc and foveola showed poor visual acuity in 25% at 5 years. Ultimate visual acuity after plaque radiotherapy for uveal melanoma depends on many factors, including patient age and general health, initial visual acuity, tumor location and size, subretinal fluid, radioactive isotope, and final tumor control. At 10 years' follow-up, 68% of patients demonstrate poor visual acuity. Visual acuity is most effectively preserved in eyes with small tumors outside a radius of 5 mm from the optic disc and foveola. Arch Ophthalmol. 2000;118:1219-1228

Ultrasound Biomicroscopic Imaging of the Anterior Aspect of Peripheral Choroidal Melanomas

To correlate ultrasound biomicroscopic features of the anterior aspect of peripheral choroidal melanoma with respect to histopathology. We examined 17 eyes of 17 patients who had clinically diagnosed peripheral choroidal melanomas that approached the ora serrata or extended into the ciliary body and who had been assessed with ultrasound biomicroscopy before enucleation. Comparisons were made between anterior tumor margins imaged by ultrasound biomicroscopy and histopathologic specimens. Anatomic features noted on ultrasound biomicroscopy before enucleation were correlated with enucleation specimens, including supraciliary effusion, rotation of the ciliary body, angle involvement, and internal reflectivity patterns. Anterior tumor margin position was determined with reference to the scleral spur. Mean distances from the anterior tumor margin to the scleral spur were 1.47 mm on ultrasound biomicroscopy and 1.65 mm on pathologic examination. This difference was not statistically significant (P = .325). Tumor features evident on ultrasound biomicroscopy were also seen on pathologic examination: supraciliary choroidal effusions in seven of seven, ciliary body rotation in seven of eight, and angle involvement in seven of eight. All tumors were mixed-cell melanomas, and 12 of 17 (70%) demonstrated homogeneous ultrasound biomicroscopic internal reflectivity. Irregular internal reflectivity was seen in five of 17 tumors (29%) and was related to prominent internal vascularity on pathology in three of five. Ultrasound biomicroscopy is an accurate imaging technique for the in vivo assessment of anterior tumor margins of peripheral choroidal melanomas and can provide detailed imaging of the tumor's interface with the ciliary body.

Choroidal—Ciliary Body Melanoma: A Multivariate Survival Analysis of Tumor Location

Posterior uveal melanomas with ciliary body involvement have greater mortality when compared with choroidal melanomas. This study was conducted to determine if this association is due to an independent effect or to correlations with other parameters. From the 4335 cases of uveal melanoma with follow-up data in the Registry of Ophthalmic Pathology, 664 were selected; therefore, approximately two thirds of the patients died of metastatic melanoma. Ciliary body involvement was determined by the location of the anterior tumor margin. Kaplan-Meier survival, Cox regression, and Gamel-Boag log-normal regression analyses were performed. Covariables included ciliary body involvement, largest tumor dimension, mean diameter of the largest ten nucleoli, and modified Callender classification. Kaplan-Meier and univariate Cox analyses indicated a significant association between ciliary body involvement and tumor-related death but when included in a multivariate Cox model, ciliary body involvement was not statistically significant. Similarly, when ciliary body involvement was included in a multivariate Gamel-Boag model, ciliary body involvement was not statistically significant. Melanomas that involve the ciliary body were more likely to be larger (Student's t = 10.5; P = 10(-6)), contain larger nucleoli (Student's t = 2.43; P = 0.015), and be of mixed cell type (chi-square = 17.2; P = 3 x 10(-5)). Ciliary body involvement is associated with tumor-related mortality but this association is primarily due to ciliary body tumors being larger with more malignant cytology.

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.

Impact of Local Tumor Relapse on Patient Survival after Cobalt 60 Plaque Radiotherapy

AbstractThe authors investigated the impact of local intraocular tumor relapse on survival in a matched-group comparison study of patients with primary choroidal or ciliary body melanoma managed with cobalt 60 plaque radiotherapy. Sixty-two patients with local relapse were matched with an equal number of relapse-free patients in terms of known clinical prognostic factors for both melanoma-specific mortality (largest linear tumor dimension, location of anterior tumor margin, age) and local tumor relapse (location of posterior tumor margin). The follow-up of every relapse-free patient equaled or exceeded the interval to relapse for each matched patient with local relapse. The estimated 5-year survival (Kaplan-Meier) in the relapse-free patients was 87% (standard error = 4%), while that in the local relapse group was 58% (standard error = 6%). This difference is statistically significant (P < 0.0001, log rank test). These results support the hypothesis that local tumor relapse after cobalt 60 plaque radiotherapy is an important post-treatment clinical indicator of the tumor's greater malignant potential and the patient's increased risk of melanoma-specific mortality.

Matched Group Study of Preenucleation Radiotherapy Versus Enucleation Alone for Primary Malignant Melanoma of the Choroid and Ciliary Body

We report the results of a nonrandomized, matched group survival study comparing 29 patients with a choroidal or ciliary body melanoma managed by enucleation alone to 29 patients managed by enucleation following external beam ocular irradiation (20 Gy in five fractions over 5-7 days just prior to enucleation). Variables on which the patients in the two groups were matched included age at time of enucleation, largest linear tumor dimension, location of the anterior tumor margin relative to the equator and ora serrata, melanoma cell type, and extrascleral tumor extension. The cumulative 5-year survival in the enucleation alone group was 57.9% (SE = 9.9%), whereas that in the preenucleation radiation therapy group was 63.9% (SE = 12.2%). This difference is not statistically significant (p greater than 0.5, Mantel-Haenszel test). The authors discuss the strengths and limitations of their study and the implications of their results.

Matched Group Study of Surgical Resection Versus Cobalt-60 Plaque Radiotherapy for Primary Choroidal or Ciliary Body Melanoma

We report the results of a nonrandomized, matched-group, survival and visual preservation study of patients with a choroidal or ciliary body melanoma managed by microsurgical resection of the tumor versus cobalt-60 episcleral plaque radiotherapy. Each treatment group consisted of 30 patients. All patients were matched on a case-by-case basis in terms of tumor size (largest linear tumor dimension), location of the anterior tumor margin relative to the ora serrata, location of the posterior tumor margin relative to the equator, and age at the time of treatment. Although the estimated actuarial 5-year survival probability was slightly greater in the resection group (85.2%) than in the cobalt plaque group (81.8%), this difference was neither clinically impressive nor statistically significant. In contrast, there was a substantially higher rate of early posttreatment severe visual loss in the resection group (P = .0008, Mantel-Haenszel test).

The Risk of Enucieatlon after Proton Beam Irradiation of Uveal Melanoma

Enucleation after proton beam irradiation of uveal melanomas occurred in 64 (6.4%) of 994 eyes with a median follow-up time of 2.7 years. The median time between irradiation and enucleation in the 64 enucleated eyes was 13 months. The probability of retaining the eye was 95 and 90%, 2 and 5 years postirradiation, respectively. Three percent of eyes were enucleated during posttreatment year 1, and the yearly rate was 1 % by the fourth year. No patient had enucleation later than 5 1/2 years posttreatment. The complication most likely to result in enucleation was neovascular glaucoma although this was frequently managed without enucleation. Other common reasons for enucleation were documented or suspected tumor growth and complete retinal detachment with associated loss of vision. The leading risk factors for enucleation were anterior tumor margin involving the ciliary body, tumor height greater than 8 mm, and proximity of the tumor to the fovea. Based on the presence or absence of these factors, 5-year eye retention rates were 99, 92, and 76% for low-, moderate-, and high-risk groups, respectively. Thus, the probability of eye retention after proton beam irradiation is high even among those at greatest risk of enucleation.

Death from uveal melanoma. Number of epithelioid cells and inverse SD of nucleolar area as prognostic factors.

Criteria for the Callender classification of uveal melanoma are subjective and lead to variations among observers of the same tumor. Two other measures for cell type-the number of epithelioid cells per high-power field (Epi/HPF) and the inverse SD of nucleolar area (ISDNA)-were evaluated as prognostic factors for survival following enucleation for uveal melanoma in 232 patients. Variables significantly related to the number of Epi/HPF were related to ISDNA. Larger, more anteriorly located tumors had a high number of Epi/HPF and a low ISDNA. The two measures were also correlated. Using Kaplan-Meier survival analysis, both measures were related to tumor deaths. Worse prognosis was associated with a higher number of Epi/HPF and a lower ISDNA. Considered together in Cox' proportional hazards analysis, both measures independently predicted outcome. Separately, each measure predicted uveal melanoma-related deaths, in combination with largest tumor dimension, invasion of tumor to the line of transection, and location of the anterior tumor margin. Although ISDNA is the more objective measure of cell type, its practicality compared with other measures of cell type must also be considered.