Dataset Information

Exploration of Feasible Immune Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma Treatment in Real World Clinical Practice.

ABSTRACT: Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The combination of targeted therapy and conventional chemotherapy has significantly improved clinical outcomes. In recent years, the development of immunotherapies, such as immune checkpoint inhibitors (ICIs), has further increased treatment responses and prolonged survival. However, the limited response rate, risk of immunotherapy-related adverse effects and high cost of immunotherapy make the identification of predictive markers to optimize treatment efficacy a critical issue. Biomarkers are biological molecules that have been widely utilized to predict treatment response to certain treatments and clinical outcomes or to detect disease. An ideal biomarker should exhibit good predictive ability, which can guide healthcare professionals to achieve optimal treatment goals and bring clinical benefit to patients. In this review, we summarized the results of recent and important studies focused on HNSCC ICI immunotherapy and discussed potential biomarkers including their strengths and limitations, aiming to gain more insight into HNSCC immunotherapy in real world clinical practice.

SUBMITTER: Wang HC

PROVIDER: S-EPMC7589088 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Exploration of Feasible Immune Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma Treatment in Real World Clinical Practice.

Wang Hui-Ching HC Yeh Tsung-Jang TJ Chan Leong-Perng LP Hsu Chin-Mu CM Cho Shih-Feng SF

International journal of molecular sciences 20201015 20

Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The combination of targeted therapy and conventional chemotherapy has significantly improved clinical outcomes. In recent years, the development of immunotherapies, such as immune checkpoint inhibitors (ICIs), has further increased treatment responses and prolonged survival. Howeve ...[more]

PMID: 33076306

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Project description:PurposeImmunotherapy is changing head and neck squamous cell carcinoma (HNSCC) treatment pattern. According to the Chinese Society of Clinical Oncology (CSCO) guidelines, immunotherapy has been deemed as first-line recommendation for recurrent/metastatic HNSCC, marking that advanced HNSCC has officially entered the era of immunotherapy. Long non-coding RNAs (lncRNAs) impact every step of cancer immunity. Therefore, reliable immune-lncRNAs able to accurately predict the immune landscape and survival of HNSCC are crucial to clinical management.MethodsIn the current study, we downloaded the transcriptomic and clinical data of HNSCC from The Cancer Genome Atlas and identified differentially expressed immune-related lncRNAs (DEir-lncRNAs). Further then, Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to identify proper DEir-lncRNAs to construct optimal risk model. Low-risk and high-risk groups were classified based on the optimal cut-off value generated by the areas under curve for receiver operating characteristic curves (AUC), and Kaplan-Meier survival curves were utilized to validate the prediction model. We then evaluated the model based on the clinical factors, immune cell infiltration, and chemotherapeutic and immunotherapeutic efficacy between two groups.ResultsIn our study, we identified 256 Deir-lncRNAs in HNSCC. A total of 18 Deir-lncRNA pairs (consisting of 35 Deir-lncRNAs) were used to construct a risk model significantly associated with survival of HNSCC. Cox proportional hazard regression analysis confirmed that our risk model could be served as an independent prognostic indicator. Besides, HNSCC patients with low-risk score significantly enriched of CD8+ T cell, and corelated with high chemosensitivity and immunotherapeutic sensitivity.ConclusionOur risk model could be served as a promising clinical prediction indicator, effective discoursing of the immune cell infiltration of HNSCC patients, and distinguishing patients who could benefit from chemotherapy and immunotherapy.

Project description:BackgroundThe outcomes of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal. A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors (ICIs). The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field.AimTo evaluate the evidence on the effectiveness of ICIs in HNSCC, based on published phase-3 clinical trials.MethodsWe searched PubMed, Cochrane Library, Embase, and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC (R/M HNSCC) and locally advanced head and neck squamous cell carcinoma (LAHNSCC). We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma, recurrent, metastatic, locally advanced, immunotherapy, immune checkpoint inhibitors, monoclonal antibodies, programmed cell death protein-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T- lymphocyte associated protein-4 (CTLA-4), and phase-3 clinical trial. A sensitive search filter was used to limit our results to randomized controlled trials.ResultsFive phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far: Four in R/M HNSCC and one in LAHNSCC. In patients with R/M HNSCC, anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care (standard single-agent systemic therapy). While the net gain in overall survival (OS) with nivolumab was 2.4 mo [hazard ratio (HR) = 0.69, P = 0.01], that with pembrolizumab was 1.5 mo (HR = 0.80 nominal P = 0.0161). The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T- lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes. In the first-line setting, in R/M HNSCC, pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo (HR = 0.77, P = 0.0034) in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive (combined positive score > 20) population compared to standard of care (EXTREME regime). In patients with PD-L1 positive R/M HNSCC, monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME. In LAHNSCC, immunotherapy using avelumab (an anti-PD-L1 agent) along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy.ConclusionAnti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings, with acceptable toxicity profiles compared to standard therapy. There is no proven efficacy in the curative setting to date.

Dataset Information

Exploration of Feasible Immune Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma Treatment in Real World Clinical Practice.

Publications

Exploration of Feasible Immune Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma Treatment in Real World Clinical Practice.

Similar Datasets

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