Chen Liang, Lanya Peng, Ming Zou, Xuemei Chen, Yingying Chen, Hou Chen, Lirong Xiao, Naihong Yan, Junjun Zhang, Qing Zhao, Xi Huang
Purpose To determine whether the GNAQ/11 mutation correlated with the outcome of patients with uveal melanoma (UM) when genetic heterogeneity was considered.
Methods We performed a retrospective study of sixty-seven patients with UM. The heterogeneity of GNAQ/11 was examined by using droplet digital PCR. The correlation between metastasis and heterogeneity of the GNAQ/11 mutation was analysed. Disease free survival curves were constructed using the Kaplan-Meier method, and the Wilcoxon log-rank test was used to compare the curves.
Results The GNAQ/11 mutation ratio was varied between each case. Among these patients, 28.35% of them harboured homogeneous mutation of GNAQ/11, 62.69% present heterogeneous mutation and 8.96% didn’t present either GNAQ or GNA11 mutation. The tumour with heterogeneous mutation of GNAQ/11 has a higher metastatic rate than that with homogeneous mutation (13/29 vs 1/18, p=0.027). In Kaplan-Meier analysis, metastasis-free survival was not significantly associated with either homogeneous or heterogeneous mutation of GNAQ/11.
Conclusion The mutation ratio of GNAQ/11 in UM was quite variable. The tumour with heterogeneous mutation of GNAQ/11 is more likely to develop a poor prognosis than that with homogeneous mutation of GNAQ/11.
Roman Dunavoelgyi, Tatyana Milman & Jose S. Pulido
Uveal melanoma is the most common primary intraocular tumor in adults, with an incidence of 5.1 per million in the United States of America . Although we are able to provide the majority of patients satisfactory local tumor control and eye retention rates using various radiotherapeutic and surgical techniques, up to almost 40% of patients will develop metastatic disease .
In the absence of clinically evident metastatic disease, current treatment options for uveal melanoma are limited at this time by inadequate diagnostic abilities.
Regarding primary ocular treatments, successful tumor control with local radiation reaches >90% . In terms of systemic metastasis, imaging often can detect remote tumor once it reaches a certain size but our treatments have been ineffective [4, 5].
Recently, the concept of minimal residual disease (MRD) has been introduced to ocular oncology for vitreoretinal lymphoma by Stacey and Pulido . Generally speaking, in the field of systemic oncology, MRD describes the concept of a small number of malignant cells that are impossible to image and remain viable in the patient following primary treatment of malignancy . In time, these residual cells can proliferate and cause recurrent disease either at the original site or remotely leading to metastasis. In leukemia, MRD is common terminology and is further subclassified into undetectable MRD and detectable MRD. Detectable MRD is the lowest number of leukemic cells that can be found using present methods . The reason that the MRD terminology is important is threefold. First, there is often misperception by patients that they are free of disease, especially after they reach 5-year follow-up. By stating that they have undetectable MRD, the patients realize that they still need to be followed. Second, MRD pushes the physician to develop methods to evaluate the for subclinical metastasis with even more sensitivity than the existing methods. Third, detection of MRD allows for earlier therapy aimed to control and, hopefully, eradicate the detectable MRD prior to overt disease recurrence……. FULL TEXT
Talisa E. de Carlo & William F. Mieler
To determine if commercial OCTA measurements can provide quantitative biomarkers for detection of radiation retinopathy (RR) s/p I-125 plaque brachytherapy in patients with uveal melanoma.
Retrospective review of 6 × 6 mm OCTA images of nonirradiated fellow eyes (group 1, 28 eyes), eyes without RR (group 2, 22 eyes), eyes with RR (group 3, 13 eyes). We used automated AngioVue AngioAnalytics OCTA software determinations of FAZ size, perimeter size, and 27 capillary density measurements (nine regions of each segmentation: full-thickness retina, superficial plexus, deep plexus).
Average time since irradiation was 1.9 years in group 2, and 3.7 years in group 3. FAZ size was 1.2 mm in group 3 compared with 0.2 mm in group 1 and 0.3 mm in group 2 (both p < 0.001). Capillary density was statistically significantly reduced in group 3 compared with group 1 in all 27 regions. Group 2 had significantly decreased superficial plexus capillary density compared with group 1 in three regions. Group 3 had significantly reduced capillary density compared with group 2 in 6/27 (22%) regions. Linear regression showed a change in whole-scan density of −1.5 per year after irradiation in the full-thickness retina segmentation (p = 0.008).
Quantitative OCTA may aid in early detection of RR.
Lindsay K. Klofas,Carley M. Bogan,Alice C. Coogan,Stephen J. Schultenover,Vivian L. Weiss,Anthony B. Daniels
To systematically evaluate and compare the effects of using small-gauge needles and vitrectors on the ability to obtain adequate diagnostic and prognostic uveal melanoma biopsy specimens.
Comparative evaluation of biopsy instruments.
Survival of uveal melanoma cells was evaluated in vitro following needle aspiration. Five therapeutically enucleated eyes were sampled in triplicate for ex vivo diagnostic biopsy experiments with 25 gauge (25 G) needle, 27 gauge (27 G) needle, and 27 G vitrector. During surgery in 8 patients, paired diagnostic transscleral fine needle aspiration biopsies were performed using both 25 G and 27 G needles. A review of cytologic specimens was performed by a panel of 3 expert cytopathologists. A retrospective chart review was performed to evaluate 100 consecutive tumors undergoing prognostic biopsy for gene expression profiling to assess the relationship between needle gauge and prognostic adequacy.
No significant cell shearing of uveal melanoma cells occurred in vitro with 25 G, 27 G, or 30 G needles. For ex vivo biopsy samples, diagnostic yield was 100% using 25 G needle (5/5) or 27 G vitrector (5/5) but 60% using a 27 G needle (3/5). For in vivo samples, no difference in diagnostic yield was found between 25 G (75%, 6/8) or 27 G (75%, 6/8) needle sizes. Of 100 molecular prognostic biopsy samples evaluated, 65 were obtained using 27 G needles; for these biopsies, the prognostic yield was 65/65 (100%).
For diagnostic biopsy of uveal melanoma, a larger-gauge needle or a 27 G vitrector may have better overall cellularity and diagnostic yield when compared to a 27 G needle. However, for much more common molecular prognostic testing, a 27 G needle provided adequate sample in 100% (65/65) of cases, and a larger needle provided no additional benefit.
Fausto de Souza D. · Tsering T. · Burnier M.N. · Bravo-Filho V. · Dias A.B.T. · Abdouh M. · Goyeneche A. · Burnier J.V.
Introduction: Acetylsalicylic acid (ASA) has been investigated for a potential anticancer role in several cancers, such as colorectal, ovarian, and endometrial cancer. Moreover, ASA has been shown to abrogate various processes that contribute to tumor growth and progression. Objective: The aim of this study was to evaluate the effects of ASA on cutaneous melanoma (CM) and uveal melanoma (UM). Methods: Human CM and UM cells were treated with 5 mM ASA and assessed for changes in cellular functions. Antiangiogenic effects of ASA were determined using an ELISA-based assay for 10 proangiogenic cytokines, and then validated by Western blot. Finally, proteomic analysis of ASA-treated cells was performed to elucidate the changes that may be responsible for ASA-mediated effects in melanoma cells. Results: Treatment with ASA significantly inhibited the proliferation, invasion, and migration capabilities, and caused a significant decrease in angiogenin and PIGF secretion in both CM and UM. Mass spectrometry revealed 179 protein changes associated with ASA in the CM and UM cell lines. Conclusions: These results suggest that ASA may be effective as an adjuvant therapy in metastatic CM and UM. Future studies are needed to determine the regulating targets that are responsible for the antitumor effects of ASA.
Van Ly D. · Wang D. · Conway R.M. · Giblin M. · Liang S. · Lukeis R. · Lim L.-A. · Hesson L. · Cherepanoff S.
Uveal melanoma (UM) is the commonest primary intraocular malignancy in adults. There is limited published data on lipid production in UM. Here, we describe the clinical, histological, immunohistochemical, and molecular findings in a ciliochoroidal melanoma with lipid production and expression of the enzyme HMG-CoA reductase. This case highlights an unusual UM tumour phenotype with a high-risk molecular metastatic profile and discusses tumour lipogenesis and activation of the mevalonate pathway as a potential therapeutic target in managing lipidised ciliochoroidal UM.
Sussman T.A. · Funchain P. · Singh A.
Background: Uveal melanoma is a rare subtype of melanoma. Prognosis and survival rates for patients with metastatic uveal melanoma remain poor. No current FDA-approved standard of care therapy is available for patients with metastatic uveal melanoma. Thus, clinical trials are essential for the development of new therapies and to provide patients hope for improved survival and outcomes. Summary: In this article, we review clinical trials identified on the database https://clinicaltrials.gov that are open and enrolling patients with metastatic uveal melanoma as of November 26, 2019. This search produced 17 active trials involving liver-directed therapy, CNS-directed therapy, and systemic therapy with immunotherapy, targeted therapy, or oncolytic virus therapy. Here, we discuss liver and CNS-directed therapy as well as systemic targeted therapy and oncolytic virus therapy. Immunotherapy clinical trials are discussed in a companion review article by Dr. Marlana Orloff. Key Messages: Various novel therapeutic targets and immunomodulatory approaches are on the horizon for patients with metastatic uveal melanoma and may yield incremental therapeutic benefit. Selecting a clinical trial must be individualized and made jointly with the patient and his/her oncologist.
Kheir W.J. · Kim J.S. · Materin M.A.
Introduction: Multiple uveal melanoma is a rare occurrence and includes bilateral melanoma, unilateral multiple/multifocal melanoma, or melanoma with metastasis to the ipsilateral or contralateral eye. Methods: A chart review of patients diagnosed with uveal melanoma between January 2013 and January 2019 at the Duke University Eye Center Ophthalmic Oncology Service was performed. Results: Three patients with multiple, sequential melanoma were identified; patient 1 had bilateral choroidal melanoma and patients 2 and 3 had 2 choroidal melanomas occurring in the same eye. In all 3 patients, both the first and sequential choroidal melanomas were treated with I-125 radioactive plaque brachytherapy (PBT). Two patients were found to have developed secondary metastatic uveal melanoma as a presenting sign of systemic metastases. Patient 4, initially treated with PBT, was diagnosed with ipsilateral metastatic choroidal melanoma, also treated with PBT. Patient 5 had right eye enucleation for choroidal melanoma and developed vision-threatening metastasis in the left eye, which was treated with PBRT. None of the patients had history of cancer prior to their first diagnosis. Patients 1 and 5 were tested with a systemic melanoma panel; both were negative for BAP1, but patient 1 had a variant of unknown significance in BRCA2. Patient 3 had oculodermal melanocytosis, an established risk factor of uveal melanoma. Conclusion: Although rare, the possibility of multiple uveal melanoma does exist. Examination of the treated and contralateral eye on a regular basis is crucial, not only to identify local failure but also new metastases from the primary tumor and additional primary tumors.
Anasua Ganguly Kapoor, Swathi Kaliki, Vijitha S. Vempuluru, Sai Divya Jajapuram, Mohammad Hasnat Ali & Ashik Mohamed
To evaluate the presenting features, treatment, and outcomes of posterior uveal melanoma (PUM) in Asian Indians based on the 8th edition of American Joint Committee on Cancer (AJCC) classification.
Retrospective interventional case series of 321 Asian Indian patients with PUM.
Based on AJCC, PUM was classified into categories T1 (n = 36; 11%), T2 (n = 74; 23%), T3 (n = 126; 39%), and T4 (n = 85; 27%). Regarding tumor features, T4 was more likely to have pre-equatorial epicenter (vs T1 and T2; p ≤ 0.011), iris abnormalities (vs T2 and T3; p ≤ 0.002), and extraocular tumor extension (vs T3; p = 0.001), whereas T1 was more likely to have macular epicenter (vs T2, T3, T4; p ≤ 0.013), lipofuscin deposits (vs T3 and T4; p ≤ 0.008), and amelanotic tumors (vs. T4; p = 0.003). On multivariate analysis, factors predictive of systemic metastasis were increasing tumor thickness (p = 0.002) and extraocular tumor extension (p = 0.009). The 5-, 10-, and 15-year melanoma-related metastases rates were 0%, 0%, and 0% in T1, 0%, 60%, and 60% in T2, 7%, 40%, and 70% in T3 and 13%, 36%, and 76% in T4, respectively. Risk for metastasis was 1.23 times more for every 1-mm increase in tumor thickness and 9 times more with extraocular tumor extension.
The AJCC 8th edition provides prognostic classification for PUM in Asian Indian patients. The significant risk factors for metastasis were increasing tumor thickness and extraocular tumor extension.
Sonia Anchouche,Jiaru Liu,Fatma Zaguia,Georges Nassrallah,Jean Deschênes
The aim of this study is to examine the quality of life (QOL) outcomes of patients undergoing different uveal melanoma (UM) treatments and to appraise the literature on the topic.
Design and Participants
A systematic review was conducted to address the study objective. Patients undergoing UM treatment with or without metastasis were eligible for inclusion in this review.
A literature search was performed using National Library of Medicine (PubMed), Embase, Ovid online, and Cochrane Central Register of Controlled Trials databases. We included all English, original retrospective or prospective studies published between January 1998 to September 2019 in which the primary outcome was the QOL of patients with treated UM.
Our search strategy yielded 101 articles. Of these, 18 articles met all our inclusion criteria. The majority of included articles (61%) are cross-sectional studies. On average, each study employed 2 different QOL assessment tools. Overall, physical functioning and mental well-being are impaired in patients with UM after treatment compared with the general population. The severity of the impairment decreases as early as 3 months post-treatment; 8 of 12 studies comparing treatment options reported no statistical difference in physical functioning between treatments; 4 of 12 studies reported better visual function with radiation therapy compared with enucleation, 2 of which described no difference between the 2 options at long-term. Anxiety is more prevalent than depression, and both decrease to less than 10% at 1-year follow-up.
Overall, there is no significant difference in long-term QOL in patients with UM from different treatment groups past 1-year follow-up. This work underscores the need for and importance of developing a standardized, complete assessment tool tailored to the challenges inherent to the diagnosis of UM.