Current Immunotherapy Practices in Melanoma

Rothermel, Luke D.; Sarnaik, Amod A.; Sondak, Vernon K.

doi:10.1016/j.soc.2019.02.001

Cited by 20 publications

(13 citation statements)

References 75 publications

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“…Cutaneous melanoma has become the most rapidly increasing cancer in Caucasian populations [1], causing 90% of skin cancer mortality [2]. The recent introduction of immune checkpoint inhibitors (ICI) has revolutionized the treatment of advanced melanoma [3], leading to a significantly higher life expectancy in treated melanoma patients [4]. However, an accurate patient selection for immunotherapy remains challenging given not only the heterogeneous mutation profile of cutaneous melanoma [5], but also the risk of exposing treatment-resistant patients to higher immune-related toxicity [6,7].…”

Section: Introductionmentioning

confidence: 99%

Prediction of Early Response to Immune Checkpoint Inhibition Using FDG-PET/CT in Melanoma Patients

Kudura

Dimitriou

Basler

et al. 2021

Cancers

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We aimed to investigate, whether 18F-2-fluoro-2-desoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans performed at baseline (time point 0; TP 0) and three months after initiation of immunotherapy (time point 1; TP 1) can be used on a metastasis- and patient-level to predict the response to immune-checkpoint inhibition using FDG-PET/CT six months after treatment start (time point 2; TP 2) in metastatic melanoma patients. This single-center retrospective study considered metastatic melanoma patients treated with immune checkpoint inhibition from TP 0 to TP 2. An analysis on a metastasis- and patient-level was carried out. Tumor volume, standardized uptake values SUV (mean, maximum, and peak), metabolic tumor volume MTV and total lesion glycolysis TLG of each included metastasis were recorded at each time point, respectively TP 0, TP 1 and TP 2. Total tumor volume, total metabolic tumor volume and total lesion glycolysis per patient were also calculated at TP 0, TP 1 and TP 2. Treatment response was assessed at metastasis- and patient-level based on FDG-PET/CT scans at TP 2. 612 melanoma metastases in 111 patients were included. The analysis on a metastasis-level showed that metastatic SUVpeak at TP 1 and volume variation between TP 0 and TP 1 were the strongest negative predictive biomarkers for response. However, at TP 0, metastatic SUVmean and SUVpeak indicated a low negative prediction power, whereas initial metastatic volume was not a predictive biomarker. Also, melanoma metastases located in bone structures had a negative influence on the outcome at TP 2, particularly in women. The analysis on a patient-level showed, that total tumor volume, total metastatic tumor volume and total lesion glycolysis of all metastases three months after treatment initiation were strong negative predictive biomarkers for response to immunotherapy six months after initiation. Age and female sex were also found to be negative predictive biomarkers with lower predictive power. Interestingly, total tumor volume at TP 0 and number of metastases at TP 0 as well as the occurrence of early immune-related adverse events between TP 0 and TP 2 did not have any predictive value for early treatment response. FDG-PET/CT performed for treatment response assessment three months after initiation of immune checkpoint inhibition in metastatic melanoma patients can also be used to predict early response to treatment. On a metastasis-level SUV peak and volume variation of metastases are strong outcome predictive biomarkers. On a patient-level total tumor volume and semiquantitative parameters such as total metabolic tumor volume MTV and total lesion glycolysis TLG of all metastases are promising outcome predictive biomarkers. Also, early complete response on a metastasis- and patient-level seems to be predictive for lasting complete response.

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Section: Introductionmentioning

confidence: 99%

Prediction of Early Response to Immune Checkpoint Inhibition Using FDG-PET/CT in Melanoma Patients

Kudura

Dimitriou

Basler

et al. 2021

Cancers

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“…Immunotherapy mainly acts by restoring the body's normal anti-tumor immune response by restarting and maintaining the tumor-immune cycle, thus controlling and eliminating tumors [18,19]. Up to date, immunotherapy has been shown to have a strong anti-tumor effect against a number of solid tumors such as melanoma, non-small cell lung cancer, kidney cancer and prostate cancer [20][21][22][23][24]. However, immunotherapy of glioma is still a challenge due to lack of immune organs in the central nervous system and the protective effect of the blood-cerebrospinal uid barrier on tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of SLC1A5 as a Novel Candidate Oncogene for Glioma and Its Involvement in the LGG Immune Microenvironment

Chen

Guo

Huang

et al. 2021

Preprint

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Background: Solute Carrier Family 1 Member 5 (SLC1A5), a member of the amino acid carrier system, is considered an oncogene in various tumors. Several targeted drugs targeting SLC1A5 are being developed. However, the molecular mechanisms of SLC1A5 in gliomas are not fully known. Methods: In this study, multiple datasets from Chinese Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) database were analyzed. Gene Set Enrichment Analysis (GSEA) was performed to identify biological functions and signaling pathways of SLC1A5. The correlation between SLC1A5 expression and immune infiltrates or gene signatures of immune cells was then determined using CIBERSORT and online analysis tools (TIMER, TSIDB). Finally, a reliable prognostic signature based on SLC1A5-related immunomodulators prognostic signature (SLC1A5-IPS) was established using the lasso-cox method. The model divided patients into low- and high-risk groups. The prognostic value of the risk scores was evaluated with univariate, multivariate, nomogram and receiver operating characteristic (ROC) curves.Results: It was found that high expression of SLC1A5 was associated with poor prognosis of glioma. Enrichment analysis indicated that SLC1A5 was regulated tumor immune response. Moreover, SLC1A5 was closely associated with immune cells infiltration and gene signatures of CD8 cells were positively correlated with SLC1A5 expression. Moreover, the developed SLC1A5-IPS risk model showed that the high-risk scores of SLC1A5-IPS accurately predicted poor prognosis of LGG. The constructed nomogram exhibited good prediction of the overall survival (OS) of LGG patients in all datasets. Finally, in vitro assays verified that SLC1A5 knockdown led to a loss of migration and proliferation ability of U87 and U251 cells. Conclusions: SLC1A5 regulates immune cells infiltration in glioma and promotes the proliferation and migration ability of glioma cells, thereby affecting the prognosis of patients. It therefore holds huge potential as a treatment target in glioma and provide a new direction for drug development.

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“…Recently, immunotherapy has revolutionized both cutaneous and non‐cutaneous melanoma treatment impacting the role of surgical approach 59 . Postoperative immunotherapy is reported to have a significant effect on survival, increasing the disease‐free period 60 .…”

Section: Discussionmentioning

confidence: 99%

Primary gastric melanoma in adult population: a systematic review of the literature

Schizas

Tomara

Katsaros

et al. 2020

ANZ Journal of Surgery

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Background Primary gastric melanoma (PGM) is a rare malignant tumour of the stomach with poor prognosis. The aim of this systematic review was to assess the available literature on this entity and to highlight its biological behaviour and preferred treatment approach. Methods PubMed and Cochrane bibliographical databases were independently searched (last search: 2 February 2020) by two investigators for articles reporting on PGM in the adult population. Results Twenty‐five studies met the inclusion criteria and concerned collectively 25 patients (18 males and seven females) with an age of 63.4 ± 8.97 years (mean ± standard deviation). Main symptoms included abdominal pain (64%), weight loss (48%) and hematemesis or melena (32%). The most frequent tumour location was the body of the stomach (54.2%). All tumours were surgically resected and the majority of the patients had a partial gastrectomy (52%). Median recurrence time was 5 months and 12% of patients reached 5‐year survival landmark. Conclusion PGM is a rare disease characterized by an aggressive malignant behaviour. Its differential diagnosis from a metastatic lesion is crucial. A prompt diagnosis and therapeutic approach are needed. Further studies are required to elucidate the optimal management of this clinical entity.

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Current Immunotherapy Practices in Melanoma

Cited by 20 publications

References 75 publications

Prediction of Early Response to Immune Checkpoint Inhibition Using FDG-PET/CT in Melanoma Patients

Prediction of Early Response to Immune Checkpoint Inhibition Using FDG-PET/CT in Melanoma Patients

Identification of SLC1A5 as a Novel Candidate Oncogene for Glioma and Its Involvement in the LGG Immune Microenvironment

Primary gastric melanoma in adult population: a systematic review of the literature

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