To refine the anatomic classification and staging of ciliary body and choroidal melanomas in the TNM classification.
Tumor largest basal diameter and thickness of 7,369 patients were analyzed based ...on registry data from five ocular oncology centers. T categories were derived empirically by dividing data into blocks representing 3- × 3-mm fractions. Blocks with similar survival were grouped together so that no T category comprised a large majority of tumors, and each was uniform in survival, using randomly drawn 60% building and 40% validation data sets. Presence of ciliary body involvement (CBI) and extraocular extension (EXE) was analyzed among 5,403 patients to define T subcategories. Stages were generated by iteratively combining subcategories with similar survival.
Of the 7,369 tumors analyzed, 24% were classified as T1, 33% as T2, 31% as T3, and 12% as T4. Ten-year Kaplan-Meier survival estimates for the T categories were 89%, 77%, 58%, and 39%, respectively (P < .001). Survival of patients in four subcategories based on presence or absence of CBI and EXE differed significantly within each T category (P = .018 for T1; P < .001 for T2 to T4). EXE exceeding 5 mm in largest diameter carried a worse prognosis than smaller extensions (P < .001) and was assigned a separate subcategory. Ten-year Kaplan-Meier survival estimates for stages I, IIA to IIB, and IIIA to IIIC were 88%, 80%, 67%, 45%, 27%, 10%, respectively (P < .001).
This evidence-based anatomic classification provides a basis for staging ciliary body and choroidal melanomas in the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer.
To determine the size at which choroidal melanomas can metastasize and to report the characteristics of small fatal choroidal melanomas (SFCM).
Retrospective case series.
Ten ocular oncology services ...submitted 45 patients with a choroidal melanoma 3 mm or less in thickness and 9 mm or less in largest basal diameter (LBD), when treated, who developed metastases.
Median tumor thickness was 2.4 mm (range, 1.0–3.0 mm) and LBD 7.3 mm (range, 3.0–9.0 mm). Of 14 (31%) tumors that were first observed, 12 grew a median of 0.5 mm (range, 0.1–1.2 mm) in thickness and 1.0 mm (range, 0–3.0 mm) in LBD within a median of 7 months; 3 were initially smaller than 3 mm in LBD. Number of risk factors for growth and metastasis was 0 for 4% of the tumors; 60% were over 2 mm in thickness, 63% had subretinal fluid, 84% caused symptoms, 57% had orange pigment, and 92% were within 3 mm of the disc. Local recurrence occurred in 8 of 31 eyes (26%) treated conservatively. Median metastasis-free survival was 4.5 years (range, 0.8–15.7 years). Kaplan-Meier estimate of metastasis developing was 15% (95% confidence interval CI, 7–26), 51% (95% CI, 36–64) and 85% (95% CI, 71–92) by 2, 5, and 10 years, respectively. By the time of analysis, 37 patients had died of metastasis after a median of 7 months.
Choroidal melanomas less than 3.0 mm in LBD are highly unlikely to metastasize. Risk factors of an SFCM are similar to those for all choroidal melanomas of similar size.
•Choroidal melanomas more than 3.0 mm in diameter are able to metastasize.•Observation beyond this size limit may alter survival.•Small fatal melanomas appear clinically similar to reported small nonfatal ones.
In parapapillary melanoma patients, radiation-induced optic complications are frequent and visual acuity is often compromised. We investigated dose-effect relationships for the optic nerve with ...respect to visual acuity after proton therapy.
Of 5205 patients treated between 1991 and 2014, those treated using computed tomography (CT)-based planning to 52 Gy (prescribed dose, not accounting for relative biologic effectiveness correction of 1.1) in 4 fractions, with minimal 6-month follow-up and documented initial and last visual acuity, were included. Deterioration of ≥0.3 logMAR between initial and last visual acuity results was reported.
A total of 865 consecutive patients were included. Median follow-up was 69 months, mean age was 61.7 years, tumor abutted the papilla in 35.1% of patients, and tumor-to-fovea distance was ≤3 mm in 74.2% of patients. Five-year relapse-free survival rate was 92.7%. Visual acuity was ≥20/200 in 72.6% of patients initially and 47.2% at last follow-up. A wedge filter was used in 47.8% of the patients, with a positive impact on vision and no impact on relapse. Glaucoma, radiation-induced optic neuropathy, maculopathy were reported in 17.9%, 47.5%, and 33.6% of patients, respectively. On multivariate analysis, age, diabetes, thickness, initial visual acuity and percentage of macula receiving 26 Gy were predictive of visual acuity. Furthermore, patients irradiated to ≥80% of their papilla had better visual acuity when limiting the 50% (30-Gy) and 20% (12-Gy) isodoses to ≤2 mm and 6 mm of optic nerve length, respectively.
A personalized proton therapy plan with optic nerve and macular sparing can be used efficiently with good oncological and functional results in parapapillary melanoma patients.
Abstract Purpose To validate a staging system for metastatic uveal melanoma that will facilitate planning, reporting and interpreting the results of clinical trials. Design Reliability and validity ...study. Methods The performance index, the largest diameter of the largest metastasis and alkaline phosphatase level at the time of diagnosis of metastases, and overall survival of 249 patients from 7 ocular oncology centers who died of dissemination were analyzed. Predicted median survival time calculated according to the Helsinki University Hospital Working Formulation was used to assign patients to stages IVa, IVb, and IVc that correspond to predicted survival times of ≥12, <12-6, and <6 months, respectively. The predictions were compared against observed survival. Results The three variables used to assign stage were independent predictors of survival in the validation dataset. Of the 249 patients, 44%, 44%, and 12% classified to Working Formulation stages IVa, IVb, and IVc, respectively. Corresponding median observed survival times were 18.6, 10.7 and 4.6 months and worsened by increasing stage ( P <. 001). Of 201 patients managed without surgical resection of metastases, 41%, 44%, and 15% classified to stages IVa to IVc, and their median observed survival times were 17.2, 10.0 and 4.6 months ( P < .001). Survival of 47 patients who underwent resection did not differ by working formulation stage ( P = .69). Conclusions This multicenter study confirms that the Working Formulation is a reliable and valid, repeatable system for dividing metastatic uveal melanoma into distinct prognostic subgroups, especially for stage-specific reporting of survival in prospective clinical trials.
To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ...ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI.
Retrospective, multicenter observational study.
Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults.
Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression.
Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality.
Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate HR, 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival.
This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.
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Purpose: To evaluate the efficacy and the safety of uveal melanoma transretinal biopsy using 25‐gauge vitrectomy system.
Methods: At the patient’s request of a tissue diagnosis, nine posterior ...uveal melanomas treated by proton‐beam therapy were biopsied during the insertion of tantalium markers.
Results: The diagnosis was uveal melanoma, confirmed in all cases using cytological (7 of 9) and histological analysis (2 of 9). Immunocytochemistry was performed on all samples (9 of 9). In eight of nine patients, minor postoperative vitreous haemorrhages were seen, which resolved in 1 day. No other ocular complications were noticed.
Conclusion: Uveal melanoma biopsy using 25‐gauge vitrectomy system is a valuable procedure to confirm the diagnosis, with adequate sample and low ocular morbidity.
Summary Germline DICER1 gene mutation has been described in ocular medulloepithelioma associated with pleuropulmonary blastoma family tumor and dysplasia syndrome. We present a case of sporadic ...ocular medulloepithelioma in an 18-year-old woman with D1709N somatic mutation in DICER1 gene, which has not been previously described. This case highlights the potential use of DICER1 gene sequencing to resolve the diagnostic challenge in recurrent and metastatic malignant medulloepithelioma, when morphology and immunohistochemistry are inconclusive. Further studies in larger series of this type of tumor are needed to confirm the relevance of this molecular abnormality in the tumorigenesis of this embryonic-type ocular tumor.
Purpose
Small choroidal melanomas have a better prognosis than large tumours. However, these small tumours can spread, often late in their course. The aim of the study was to analyse survival and ...tumour characteristics of six cases of late metastatic diseases after conservative treatment.
Methods
A retrospective study was conducted at the Croix‐Rousse University Hospital of Lyon among 523 patients treated between 1991 and 2010 by proton beam therapy (508) or brachytherapy with 106 Ru/Rh (15) for uveal melanomas. We have selected patients with small choroidal melanoma (thickness ≤3 mm and diameter ≤9 mm) (59 patients), who have developed hepatic metastases (six of 59).
Results
At the time of diagnosis, median age was 57 years (range, 37–82 years). The mean tumour thickness was 2.9 mm (range 2.5–3 mm), and the mean diameter was 7 mm (5–8 mm). Orange pigment was observed in four cases, subretinal fluid was observed in two cases, and one tumour touched the optic disc. Five patients had proton beam therapy. One patient had beta brachytherapy (106 Ru/106 Rh). Average follow‐up was 8.3 years (range 4.2–11.8 years). None of the six patients developed local tumour recurrence. The mean survival time after diagnosis of melanoma was 9.8 years (range, 4.9–14.6 years). The average time from treatment of primary tumour to detection of liver metastasis was 7 years (range 3.9–12 years). The mean survival time from the diagnosis of metastasis was 35.2 months (range 9–101 months). Small melanoma‐related death was 0% at 3 years, 1.7% at 5 years, 5.1% at 10 years and 10.2% at 15 years in our series.
Conclusions
Despite a small tumoral size and an early and effective local treatment, six of 59 small choroidal melanomas have developed metastasis after local treatment. Small tumours represent a significant risk of metastasis.
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