Genetic characterization of advanced conjunctival melanoma and response to systemic treatment

Lodde, Georg; Jansen, Philipp; Möller, Inga; Sucker, Antje; Hassel, Jessica C.; Forschner, Andrea; Eckardt, Julia; Meier, Friedegund; Reinhardt, Lydia; Kähler, Katharina C.; Ziemer, Mirjana; Schlaak, Max; Rahimi, Farnaz; Schatton, Kerstin; Meiß, Frank; Gutzmer, Ralf; Pföhler, Claudia; Terheyden, Patrick; Schilling, Bastian; Sachse, Michael Max; Heppt, Markus V.; Sindrilaru, Anca; Leiter, Ulrike; Zaremba, Anne; Thielmann, Carl Maximilian; Ugurel, Selma; Zimmer, Lisa; Hadaschik, Eva; Bechrakis, Nikolaos E.; Schadendorf, Dirk; Westekemper, Henrike; Livingstone, Elisabeth; Griewank, Klaus G.

doi:10.1016/j.ejca.2022.01.008

Cited by 12 publications

(16 citation statements)

References 37 publications

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“…Lung, lymph nodes, and bone were the most common sites of metastases in patients with CM in our series. Lodde et al also found the most involved sites of distant metastases at start of first systemic treatment of CM were lung and lymph nodes 13 . Studies had showed that most patients that develop metastatic disease are diagnosed with metastasis within 5 years after initial diagnosis.…”

Section: Discussionmentioning

confidence: 94%

“…The similarity between CM and cutaneous melanoma in terms of genetics makes us learn experience from the treatment of cutaneous melanoma. Patients with BRAF ‐mutated metastatic CM have been reported to respond to BRAF inhibition 13,36 . However, Lodde et al claimed patients with BRAF‐mutated CM achieved a DCR of 37.5% and a median PFS of 12.6 months following BRAF inhibitor with or without MEK inhibitor, which demonstrating that patients with CM can derive long‐term benefit from targeted therapy 13 .…”

Section: Discussionmentioning

confidence: 99%

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Clinical features and prognosis of patients with metastatic ocular and orbital melanoma: A bi‐institutional study

et al. 2023

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PurposeMetastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established.Materials and MethodsWe retrospectively analyzed patients with metastatic ocular and orbital melanoma from Fudan University Shanghai Cancer Center and Eye & ENT Hospital of Fudan University between January 2012 and May 2022.ResultsOverall, 51 patients with metastatic ocular and orbital melanoma were included. The most common primary sites were uvea (73%), followed by conjunctiva (22%), lacrimal sac (4%), and orbit (2%). Patients with uveal melanoma (UM) had a significantly younger age (48 vs. 68 years, p < 0.001), higher incidence of liver metastases (89% vs. 9%, p<0.001), a lower incidence of lymph nodes metastases (16% vs. 46%, p = 0.043) and a lower incidence of BRAF mutation (0% vs. 55%, p<0.001) compared with patients with conjunctival melanoma (CM). The overall response rate of the first‐line treatment was 18%. Three of the four patients with BRAF‐mutated CM responded to dabrafenib and trametinib treatment. The median progression‐free survival (PFS) and overall survival (OS) of first‐line treatment were 5.1 and 11.9 months, respectively. Among patients with liver metastases, liver‐directed treatment was correlated with better patient PFS (p < 0.001) and OS (p < 0.001) after adjusting for number of metastatic sites and primary sites.ConclusionCM and UM have different characteristics. Patient with CM had a high incidence of BRAF mutation, and the treatment of BRAF and MEK inhibitors conferred clinical benefit. Liver directed therapies had a potential benefit in disease control in patients with liver metastases.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Clinical features and prognosis of patients with metastatic ocular and orbital melanoma: A bi‐institutional study

et al. 2023

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“…Molecular biological research is an important field for the treatment of CM at present ( 24 - 27 ). There have been studies to detect the genetic characteristics of CM patients, and frequent mutations in BRAF (46.7%, 7/15), NRAS (26.7%, 4/15), NF1 (20%, 3/15) and TERT promoter (46.7%, 7/15) have been found in CM patients ( 28 , 29 ), It is also found that targeted therapy (TT) (BRAF ± MEK inhibitor) ( 30 , 31 ) or immune checkpoint inhibitor (ICI) [anti-programmed cell death protein 1 (PD-1) ± anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4)] can improve the survival of patients with advanced CM ( 28 , 32 ). However, we have not obtained such data from the SEER database.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a nomogram to predict overall survival of conjunctival melanoma: a population-based study

Peng,

Yuan,

Zou

et al. 2024

Transl Cancer Res

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Background Conjunctival melanoma (CM) is a rare, invasive tumor in the eye that readily metastasizes and spreads. Based on some significant clinicopathological information, we aimed to develop a prognostic model to predict the overall survival (OS) of CM patients. Methods Data of patients diagnosed with CM from 2000 to 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were extracted and integrated based on competing risk regression to build a nomogram. Harrell’s concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration plots were used to evaluate the performance of the nomogram. Results The study included 272 patients with CM, with a median age of 63 years. A nomogram was developed using age and tumor-node-metastasis (TNM) stage as variables. The model’s C-index was 0.755, and the area under the curve (AUC) was 0.774, 0.812, and 0.815 at 5, 8, and 10 years, respectively. The calibration plot used to predict CM demonstrated good consistency between the predicted OS probability and the actual OS probability. Conclusions We have developed a nomogram model to predict the OS of patients with CM, which can predict the survival of these patients. The model’s prognostic value is higher than that of the American Joint Committee on Cancer (AJCC) staging system alone. This tool can help evaluate the tumor-specific prognosis, identify patients at high risk of cancer-specific death, and guide clinical decision-making.

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“…30–33 SD was observed in 2 patients and partial response (PR) was observed in 8 patients; however, information regarding the individual follow-up periods and side effects of the patients has not been provided in every article. 27–29,34 In 2 case reports in which the results were reported, Pinto Torres et al 30 and Glass et al 31 reported that CR was observed without any signs of recurrence after 3 years and 23 months after the combined BRAF and MEK inhibitor therapy, respectively. In another study in which 6 patients were treated with combined BRAF and MEK inhibitors and 2 patients with BRAF inhibition alone, Lodde et al 34 reported SD was observed in 37% of patients with a median progression-free survival of 12.6 months and overall survival of 29.1 months…”

Section: Conjunctival Melanomamentioning

confidence: 99%

“…Other patient developed CR initially; however, cutaneous metastasis was observed after 3 years. Lodde et al 34 reported 26 metastatic CM patients with treated ICI (anti-PD-1 in 10 patients, cytotoxic T-lymphocyte-associated protein-4 in 4 patients, combined cytotoxic T-lymphocyte-associated protein-4 + anti-PD-1 in 11 patients, and triple therapy-dual MAPKinh + anti-PD-1 in 1 patient). PR was observed in 3 patients, SD was observed in 7 patients, and PD was observed in 16 patients after a mean follow-up of 10.7 months.…”

Section: Conjunctival Melanomamentioning

confidence: 99%

Targeted Therapy and Immunotherapy for Advanced Malignant Conjunctival Tumors: Systematic Review

Serbest Ceylanoglu,

Guneri Beser,

Singalavanija

et al. 2024

Ophthalmic Plastic &Amp; Reconstructive Surgery

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Purpose: To review the outcomes of targeted therapy and immunotherapy in advanced conjunctival tumors, including conjunctival squamous cell carcinoma, conjunctival melanoma, and conjunctival lymphoma. Methods: A Pubmed database systematic search was performed between January 1999 and December 2022. The literature search was limited to studies published in English. Results: This review included 142 patients with advanced malignant conjunctival tumors from 42 articles. In the conjunctival squamous cell carcinoma group, 2 cases of advanced conjunctival squamous cell carcinoma treated with epidermal growth factor receptor inhibitors showed significant tumor size improvement after 7.5 months of follow-up. Among 7 cases treated with systemic immunotherapy, 5 cases (72%) had complete response (CR), 1 case (14%) showed partial response (PR), and 1 case (14%) had stable disease (SD) after 16 months. In the conjunctival melanoma group, among 18 cases treated with combined v-raf murine sarcoma viral oncogene homolog B1/mitogen-activated extracellular signal-regulated kinase inhibitors, 6 (33%) had CR, 5 (28%) had PR, 2 (11%) had SD, and 5 (28%) had progressive disease after 24.8 months of follow-up. Of 44 conjunctival melanoma cases treated with immunotherapy, 12 (28%) had CR, 9 (20%) had PR, 7(16%) had SD, and 16 (36%) had progressive disease after 14.2 months. Systemic Rituximab treatment for conjunctival lymphoma cases resulted in CR in 21 patients (63%), PR in 11 patients (33%), and SD in 1 patient (3%) after 20.5 months of follow-up. Intralesional Rituximab injections in 38 conjunctival lymphoma cases showed CR in 28 patients (75%), PR in 7 patients (19%), SD in 1 patient (2%), and progressive disease in 2 patients (4%) after 20.4 months of follow-up. Conclusions: Despite limited clinical case reports and short-term follow-ups, targeted therapy and immunotherapy have shown promising results for advanced malignant conjunctival tumors.

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Genetic characterization of advanced conjunctival melanoma and response to systemic treatment

Cited by 12 publications

References 37 publications

Clinical features and prognosis of patients with metastatic ocular and orbital melanoma: A bi‐institutional study

Clinical features and prognosis of patients with metastatic ocular and orbital melanoma: A bi‐institutional study

Development and validation of a nomogram to predict overall survival of conjunctival melanoma: a population-based study

Targeted Therapy and Immunotherapy for Advanced Malignant Conjunctival Tumors: Systematic Review

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