ABSTRACT
BACKGROUND: Brain metastases (BM) from non-small-cell lung cancer (NSCLC) is the most common brain malignancy. Systemic inflammation biomarkers have recently been evaluated as prognosis indicators in several tumors. The combination of these markers has not been evaluated in NSCLC with BM yet. Here, we explored the predictive value of pretreatment inflammatory biomarkers and established a novel, clinically applicable prognostic index for NSCLC patients with BM. METHODS: A retrospective investigation of 951 NSCLC patients newly diagnosed with BM at Sun Yat-sen University Cancer Center was conducted. We randomly divided patients into a training cohort (n = 674) or validation cohort (n = 277). Receiver operating characteristic (ROC) curve analysis was carried out to obtain the optimal cut-off values of pretreatment systemic inflammatory indexes. The associations between serum biomarkers and overall survival (OS) were analyzed by Kaplan-Meier curves and Cox proportional models. The resulting prediction model has been externally verified through the validation cohort. RESULTS: The optimal cut-off value of the neutrophil-lymphocyte ratio (NLR) in predicting OS was 4.71, while the clinical standard of 40 mg/L was chosen as the optimal cut-off value of albumin. Univariate and multivariate analyses revealed that patients receiving local treatment, chemotherapy, a NLR < 4.71 and albumin ≥ 40 mg/l independently predicted improved survival. We combined the two inflammatory indexes (NLR and albumin level) to establish the modified systemic inflammation score (mSIS) which divides patients into low risk, medium risk or high-risk groups. The 1-year OS rates of three groups were 59.7%, 40.5% and 29.4%, respectively in the training cohort. The same result was verified in the validation cohort with the 1-year OS rates 69.7%, 47.0% and 7.7%, respectively. The mSIS exhibited better discrimination power than the American Joint Committee on Cancer's (AJCC) 7th T + N staging system in the training cohort (Harrell's concordance index (C-index): 0.744 vs 0.502, P < 0.05), and the discrimination was also superior to that of AJCC's 7th T + N staging system in the validation cohort (C-index: 0.724 vs 0.527, P < 0.05). The 1-year and 2-year OS rates of the AUC also exhibited superior survival predictive ability to that of the AJCC's 7th T + N staging system in NSCLC patients with BM. CONCLUSION: The pretreatment mSIS may be an independent prognostic factor for OS in NSCLC patients with BM and warrants further research.
ABSTRACT
Introduction: Immune status was evaluated by means of lymphocyte subset counts and immune factors in cancer. This study analyzed the peripheral blood immune index and survival outcomes in intracranial germ cell tumor (iGCT) patients. Methods: Peripheral blood lymphocyte subset counts and levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), and interferon-γ (IFN) from 133 iGCT patients were collected and retrospectively analyzed. Their clinical information was extracted from the hospital database, and prognosis was confirmed by telephone visit. Patients (n=11) underwent prospective review and their samples of peripheral blood lymphocytes were verified. Results: A total of 113 (84.2%) patients received comprehensive treatments, including 96 standard therapy (combination of full course chemotherapy and radiology with or without surgery) and 17 comprehensive but non-standard therapy (either without full course chemotherapy or with non-standard radiotherapy) and 98 (73.7%) reached complete or partial response. T lymphocytes (CD3+), cytotoxic T cells (CD3+CD8+ or Tc), and B lymphocytes (CD19+) decreased (p=0.047, p=0.004, and p<0.001, respectively), while activated cytotoxic T lymphocytes (CD8+CD25+) and IFN increased (p<0.001 and p=0.002, respectively) after treatment. Median survival was 45.33 months, and patients with increased Tc cells and activated Tc cells as well as IFN presented encouraging outcomes (p=0.039, p=0.041, and p=0.017 respectively). Regression analysis showed that non-increased Tc cells and non-increased activated Tc cells were independent factors of poor prognosis (p=0.016, HR=3.96, 95%CI=1.288-12.20; p=0.002, HR=4.37 95%CI= 1.738-10.97). Standard chemo-radiotherapy was independently related to reduced risk of death(p=0.022, HR=0.19, 95%CI=0.044-0.79). Consistence was seen in a nomogram established through retro and prospective studies. An immune risk model indicated the activated group (with both increased activated T cells and IFN levels) had the best prognosis, the mildly activated type with elevated IFN levels had intermediate outcome, and patients with the silent immune status had the worst outcomes (Log rank test, p=0.011). Conclusion: Implementation of standard comprehensive treatments led to positive responses. Dynamic monitoring of peripheral blood lymphocyte subsets can be used as an auxiliary indicator for prognosis judgment.
