Personalised medicine: Development and external validation of a prognostic model for metastatic melanoma patients treated with ipilimumab

Valpione, Sara; Martinoli, Chiara; Fava, Paolo; Mocellin, Simone; Campana, Luca Giovanni; Quaglino, Pietro; Ferrucci, Pier Francesco; Pigozzo, Jacopo; Astrua, Chiara; Testori, Alessandro; Chiarion-Sileni, Vanna

doi:10.1016/j.ejca.2015.06.130

Cited by 47 publications

(39 citation statements)

References 32 publications

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“…Stress-induced processes can directly modulate these tumor hallmarks and a large body of preclinical and clinical evidence supports the role of inflammation as an essential factor for tumor growth and progression 1 . Pro-inflammatory cytokines are produced by tumor and stromal cells, as well as by tumor-associated macrophages and infiltrating T-cells, and play an important role in tumor angiogenesis, metastatic spread, and possibly resistance to therapy 22,33 . In addition, stress-related effects on angiogenesis may be regulated by neural control mechanisms.…”

Section: The Role Of Stress and Inflammationmentioning

confidence: 99%

Depression in cancer: The many biobehavioral pathways driving tumor progression

Bortolato

Hyphantis

Valpione

et al. 2017

Cancer Treatment Reviews

262

179

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Major Depressive Disorder (MDD) is common among cancer patients, with prevalence rates up to four-times higher than the general population. Depression confers worse outcomes, including non-adherence to treatment and increased mortality in the oncology setting. Advances in the understanding of neurobiological underpinnings of depression have revealed shared biobehavioral mechanisms may contribute to cancer progression. Moreover, psychosocial stressors in cancer promote:(1) inflammation and oxidative/nitrosative stress; (2) a decreased immunosurveillance; and (3) a dysfunctional activation of the autonomic nervous system and of the hypothalamic-pituitary-adrenal axis. Consequently, the prompt recognition of depression among patients with cancer who may benefit of treatment strategies targeting depressive symptoms, cognitive dysfunction, fatigue and sleep disturbances, is a public health priority. Moreover, behavioral strategies aiming at reducing psychological distress and depressive symptoms, including addressing unhealthy diet and life-style choices, as well as physical inactivity and sleep dysfunction, may represent important strategies not only to treat depression, but also to improve wider cancer-related outcomes. Herein, we provide a comprehensive review of the intertwined biobehavioural pathways linking depression to cancer progression. In addition, the clinical implications of these findings are critically reviewed.

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Section: The Role Of Stress and Inflammationmentioning

confidence: 99%

Depression in cancer: The many biobehavioral pathways driving tumor progression

Bortolato

Hyphantis

Valpione

et al. 2017

Cancer Treatment Reviews

262

179

View full text Add to dashboard Cite

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“…Low serum concentrations of soluble CD25 (14) or C-reactive protein (CRP) (23), and the presence of specific tumor mutations have been recorded in patients with favorable outcomes on ipilimumab treatment (19). The absolute lymphocyte count (ALC) (11–13, 23, 24), the neutrophil count (25), or the neutrophil to lymphocyte ratio (26) was reported by different groups as other possible biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Baseline Peripheral Blood Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab

Martens

Wistuba‐Hamprecht

Foppen

et al. 2016

Clinical Cancer Research

470

366

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Purpose To identify baseline peripheral blood biomarkers associated with clinical outcome following ipilimumab treatment in advanced melanoma patients. Experimental design Frequencies of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), serum lactate dehydrogenase (LDH), routine blood counts, and clinical characteristics were assessed in 209 patients. Endpoints were overall survival (OS) and best overall response. Statistical calculations were done by Kaplan-Meier- and Cox-regression-analysis including calibration and discrimination by C-statistics. Results Low baseline LDH, absolute monocyte counts (AMC), Lin−CD14+HLA-DR−/low-MDSC frequencies, and high absolute eosinophil counts (AEC), relative lymphocyte counts (RLC), and CD4+CD25+FoxP3+-Treg frequencies were significantly associated with better survival, and were considered in a combination model. 43.5% of patients presenting with the best biomarker signature had a 30% response rate and median survival of 16 months. In contrast, patients with the worst biomarkers (27.5%) had only a 3% response rate and median survival of 4 months. The occurrence of adverse events correlated with neither baseline biomarker signatures nor the clinical benefit of ipilimumab. In another model, limited to the routine parameters LDH, AMC, AEC, and RLC, the number of favorable factors (4 vs. 3 vs. 2-0) was also associated with OS (p<0.001 for all pairwise comparisons) in the main study and additionally in an independent validation cohort. Conclusions A baseline signature of low LDH, AMC and MDSCs as well as high AEC, Tregs and RLC is associated with favorable outcome following ipilimumab. Prospective investigation of the predictive impact of these markers following ipilimumab and other treatments, e.g. PD-1 antibodies, is warranted.

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“…Elevated lactate dehydrogenase (LDH) has been demonstrated to predict poor prognosis in various malignancies . Recent studies have shown that elevated LDH levels at baseline and post‐treatment were associated with poor response and OS in melanoma patients treated with ipilimumab, pembrolizumab, and nivolumab . In a multivariable analysis conducted in melanoma patients treated with ipilimumab, low baseline LDH, low absolute monocyte counts (AMCs), high absolute eosinophil counts, relative lymphocyte counts, and frequencies of certain subsets of myeloid‐derived suppressor cells, as well as regulatory T cells, were associated with improved survival .…”

Section: Introductionmentioning

confidence: 99%

“…14 Recent studies have shown that elevated LDH levels at baseline and post-treatment were associated with poor response and OS in melanoma patients treated with ipilimumab, pembrolizumab, and nivolumab. [15][16][17][18][19][20][21][22][23][24][25][26] In a multivariable analysis conducted in melanoma patients treated with ipilimumab, low baseline LDH, low absolute monocyte counts (AMCs), high absolute eosinophil counts, relative lymphocyte counts, and frequencies of certain subsets of myeloid-derived suppressor cells, as well as regulatory T cells, were associated with improved survival. 22 Nevertheless, the predictive and prognostic roles of LDH in ESCC patients treated with ICIs have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Lactate dehydrogenase and baseline markers associated with clinical outcomes of advanced esophageal squamous cell carcinoma patients treated with camrelizumab (SHR‐1210), a novel anti‐PD‐1 antibody

Zhang

Chen

et al. 2019

Thoracic Cancer

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Background A small proportion of patients with advanced esophageal squamous cell carcinoma (ESCC) could benefit from immune checkpoint inhibitors; however, reliable peripheral blood biomarkers for outcomes of anti‐PD‐1 immunotherapy in ESCC have not been identified. Methods The data of 43 patients in the ESCC cohort of a phase I trial at our center were retrospectively reviewed. All patients were administered intravenous camrelizumab (SHR‐1210), a novel anti‐PD‐1 antibody, at doses of 60 mg, 200 mg, or 400 mg (4‐week interval after first dose followed by a 2‐week schedule) until disease progression or intolerable toxicity. Associations between lactate dehydrogenase (LDH) and other peripheral blood biomarkers at baseline and the efficacy of camrelizumab were also investigated. Results After median follow‐up of 19.6 months, the overall response rate was 25.6% (11/43), including one complete response. Median progression‐free and overall survival rates were 2.0 and 8.0 months, respectively. Patients with an elevated baseline LDH had lower tumor response rates ( P = 0.02) and shorter progression‐free ( P = 0.002) and overall ( P < 0.0001) survival than patients with normal LDH levels. An increase in LDH levels during treatment was significantly associated with disease progression. Multivariate Cox analysis identified LDH (hazard ratio [HR] 0.18), CRP (HR 0.27), the number of organs involved (HR 0.31), absolute monocyte count (HR 0.33), and Eastern Cooperative Oncology Group performance status (HR 0.36) as independent prognostic factors. Conclusions Serum LDH, which is readily available in routine clinical practice, is a potential marker for response and a powerful independent factor for survival in advanced ESCC patients treated with anti‐PD‐1 therapy.

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Personalised medicine: Development and external validation of a prognostic model for metastatic melanoma patients treated with ipilimumab

Cited by 47 publications

References 32 publications

Depression in cancer: The many biobehavioral pathways driving tumor progression

Depression in cancer: The many biobehavioral pathways driving tumor progression

Baseline Peripheral Blood Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab

Lactate dehydrogenase and baseline markers associated with clinical outcomes of advanced esophageal squamous cell carcinoma patients treated with camrelizumab (SHR‐1210), a novel anti‐PD‐1 antibody

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