The Liverpool uveal melanoma liver metastases pathway: Outcome following liver resection

Gomez, Dhanny; Wetherill, C.; Cheong, Jae Ho; Jones, Louise; Marshall, Ernest; Damato, Bertil; Coupland, Sarah E.; Ghaneh, Paula; Poston, Graeme J.; Malik, Hassan; Fenwick, Stephen

doi:10.1002/jso.23535

Cited by 67 publications

(68 citation statements)

References 35 publications

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“…Retrospective data also suggest that, compared with no surgery, resection of liver metastases is associated with a median survival that is increased by a factor of 3.7 93 . Similar data have been reported elsewhere [94][95][96] . However, the results in those noncomparative cohorts could be influenced by leadtime bias or favourable tumour biology in patients who are candidates for resection.…”

Section: Surgical Resection In the Setting Of Metastatic Diseasesupporting

confidence: 91%

Management of Uveal Melanoma: A Consensus-Based Provincial Clinical Practice Guideline

et al. 2016

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Section: Surgical Resection In the Setting Of Metastatic Diseasesupporting

confidence: 91%

Management of Uveal Melanoma: A Consensus-Based Provincial Clinical Practice Guideline

et al. 2016

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“…Surgical treatment is regarded as the first choice, but most patients are (90-95 %) present with diffuse liver metastasis and therefore are not candidates for surgery [2,5,12,13]. In the largest series to date, Mariani et al reported on 255 patients in 2009.…”

Section: Discussionmentioning

confidence: 99%

“…There is no consensus on a standard management of metastatic uveal melanoma. Unfortunately, the median survival is 2-7 months without treatment and depends heavily on the progression of liver disease [5][6][7]. Therefore, there is merit in considering liverdirected therapies to prolong survival.…”

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confidence: 99%

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Laparoscopic management of liver metastases from uveal melanoma

et al. 2015

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“…Compared with cutaneous melanoma, uveal melanoma is characterized by its distinct genetic profile and clinical presentation, where most metastases are detected in the liver [5][6][7][8][9][10]. Once uveal melanoma metastasizes, prognosis is poor because metastatic uveal melanoma (MUM) tends to be widespread within the liver and only surgically resectable in some cases [11,12]. Therefore, there is an unmet need for investigating effective systemic therapies.…”

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confidence: 99%

PD-L1 Expression in Tumor Metastasis is Different Between Uveal Melanoma and Cutaneous Melanoma

et al. 2017

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Aim:To compare PD-L1 expression between metastatic uveal melanoma (MUM) and metastatic cutaneous melanoma (MCM). Materials & methods: A total of 295 MCM and 78 MUM specimens were analyzed for tumor cell PD-L1 expression. Additionally, 91 MCM and 45 MUM specimens were analyzed for PD-1 expression on tumor-infiltrating lymphocytes. Results: A total of 77/295 (26.1%) MCM specimens expressed PD-L1 as compared to 4/78 (5.1%) MUM specimens (p < 0.0001). PD-1 expression on tumor-infiltrating lymphocytes was greater in MCM (73.6%; 67/91) than in MUM (51.1%; 23/45), respectively (p = 0.009). Conclusion: Significant differences exist in PD-L1 expression between MCM and MUM. The lower PD-L1 expression in MUM may provide a rationale for failure of PD-1 inhibitor therapy and suggests that immune evasion in this disease may occur via alternative mechanisms. Uveal melanoma originates from melanocytes in the choroid, ciliary body and iris of the eye [1]. It is the most common primary intraocular malignancy in adults and occurs almost exclusively in Caucasians, with an incidence of approximately 5-7/million/year in certain European populations [2]. In the USA, it represents about 5% of all melanoma diagnoses [1,3]. Uveal melanoma tends to recur in approximately 50% of the cases despite successful therapy of the primary tumor, in particular those whose tumors have certain risk factors for metastasis, such as large tumor size, ciliary body location, epithelioid cell morphology, high mitotic count and chromosomal abnormalities (e.g., chromosome 3 loss, 8q gain) [4]. Compared with cutaneous melanoma, uveal melanoma is characterized by its distinct genetic profile and clinical presentation, where most metastases are detected in the liver [5][6][7][8][9][10]. Once uveal melanoma metastasizes, prognosis is poor because metastatic uveal melanoma (MUM) tends to be widespread within the liver and only surgically resectable in some cases [11,12]. Therefore, there is an unmet need for investigating effective systemic therapies.Systemic immunotherapy with checkpoint inhibitors has vastly improved the treatment of metastatic cutaneous melanoma (MCM), leading to long-term durable responses [13,14]. MUM patients are often treated with immune checkpoint inhibitors identical to those used in the treatment of MCM (anti-programmed death-1 [PD-1] and anti-CTLA4 [Cytotoxic T-lymphocyte-associated protein 4] antibodies), either as monotherapy or in combination. Contrary to MCM, MUM demonstrates a poor response to these immune checkpoint blockades [15] (Table 1) [16][17][18][19][20][21][22][23] One of the mechanisms by which tumors evade the immune system is through upregulation and expression of PD-L1 protein on their surface. PD-L1 on tumor cells interacts with PD-1 receptor expressed on activated T cells, leading to T-cell exhaustion, anergy and ultimately, immune response abandonment [24,25]. Inhibition of the PD-1/PD-L1 interaction is the mechanism by which anti-PD-1 antibodies induce T-cell activation and antitumor effect.We evaluated the express...

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The Liverpool uveal melanoma liver metastases pathway: Outcome following liver resection

Abstract: Patients who can undergo surgical resection for metastatic uveal melanoma have a more favorable survival compared to those who do not.

Cited by 67 publications

References 35 publications

Management of Uveal Melanoma: A Consensus-Based Provincial Clinical Practice Guideline

Management of Uveal Melanoma: A Consensus-Based Provincial Clinical Practice Guideline

Laparoscopic management of liver metastases from uveal melanoma

PD-L1 Expression in Tumor Metastasis is Different Between Uveal Melanoma and Cutaneous Melanoma

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