scholarly journals A Novel Score Combining Magnetic Resonance Spectroscopy Parameters and Systemic Immune-inflammation Index Improves Prognosis Prediction in Non-small-cell Lung Cancer With Brain Metastases

Author(s):  
Dong Guo ◽  
Jiafeng Liu ◽  
Yanping Li ◽  
Qingqing Chen ◽  
Yunzheng Zhao ◽  
...  

Abstract Background: The aim of this study was to evaluate the significance of combination of the magnetic resonance spectroscopy (MRS) parameters and systemic immune-inflammation (SII) in patients with brain metastases (BM) from non-small-cell lung cancer (NSCLC) treated with stereotactic radiotherapy. Methods: 118 NSCLC patients with BM who treated with stereotactic radiotherapy were retrospectively enrolled into this study. All patients underwent MRS and blood samples test for SII analysis before the initiation of stereotactic radiotherapy. The correlation between the parameters of MRS and SII level were assessed using the spearman correlation coefficient. The cut-off values for the parameters of MRS, SII and clinical laboratory variables were defined by the receiver operating characteristic (ROC) curve analysis to quantify these predictive value. The prognostic factors of overall survival (OS) and progression-free survival (PFS) curves were assessed using Kaplan-Meier and Cox proportional hazards models.Results: The median follow-up time was 25 months (range, 12-49months). The optimal cutoff point for the cho/cr and SII were 1.50 and 480, respectively. The cho/cr was negatively correlated with SII (rs = 0.164, P = 0.075), but there was a trend. C-SII score was established by combining cho/cr and SII. Patients with both an elevated cho/cr (> 1.50) and an elevated SII (> 480) were given a C-SII score of 2, and patients with one or neither were given a C-SII score of 1 or 0, respectively. Kaplan–Meier analysis showed that the C-SII score of 2 was significantly linked with poor OS and PFS (P < 0.001, P < 0.001). In the Cox proportional hazards model, the C-SII score independently predicted OS [hazard ratio (HR), 1.749; 95% CI, 1.176-2.601; P = 0.006] and PFS (HR, 2.472; 95% CI, 1.624-3.763; P < 0.001). Conclusion: C-SII score was more accurate for predicting the clinical outcomes of NSCLC patients with BM who undergo stereotactic radiotherapy. The C-SII score, which was superior to either score alone, which could be used to identify for BM from NSCLC patients with poor outcomes.

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yanan Zhang ◽  
Zeyang Chen ◽  
Feng Jin ◽  
Dong Guo ◽  
Qingqing Chen ◽  
...  

Background. As a parameter integrating platelet (P), neutrophil (N), and lymphocyte (L) levels, the systemic immune-inflammation index (SII) has been used as a prognostic marker for patient survival in various types of solid malignant tumors. However, there is no in-depth study in non-small-cell lung cancer (NSCLC) patients with brain metastases after stereotactic radiotherapy. Therefore, we performed a retrospective analysis to determine the clinical and prognostic value of the SII in NSCLC patients with brain metastases who underwent stereotactic radiotherapy. Materials and Methods. We enrolled 124 NSCLC patients with brain metastases treated with stereotactic radiotherapy in our hospital between May 2015 and June 2018. We obtained all baseline blood samples within one week prior to stereotactic radiotherapy. The SII was calculated by the following formula: neutrophil   counts × platelet   counts / lymphocyte   counts . The optimal cutoff value of the SII for predicting prognosis was assessed by receiver operating characteristic (ROC) curves with the maximum log-rank values. The discriminative ability of predicting prognosis was calculated and compared using the Kaplan–Meier method and log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were combined to evaluate the prognostic impact of the blood index on overall survival (OS) and progression-free survival (PFS). Only those parameters that proved to be associated with statistically significant differences in clinical outcomes were compared in multivariate analysis using a multiple Cox proportional hazard regression model to identify independent prognostic factors. Results. Of the total enrolled patients, 53.2% and 46.8% have high SII and low SII, respectively. In this study, Kaplan–Meier curve analysis revealed that the median PFS was 9 months (range: 2–22 months) and the median OS was 18 months (range: 4–37 months). Applying an optimal cutoff of 480 (SII), the median PFS was better in the low SII group patients (11.5 vs. 9 months), and the median OS was significantly longer in the low SII group patients (20 vs. 18 months). A SII > 480 was significantly associated with worse OS (HR: 2.196; 95% CI 1.259–3.832; P = 0.006 ) and PFS (HR: 2.471; 95% CI 1.488–4.104; P < 0.001 ) according to univariate analysis. In multivariate analysis, only age (HR: 2.159; 95% CI 1.205–3.869; P = 0.010 ), KPS (HR: 1.887; 95% CI 1.114–3.198; P = 0.018 ), and SII (HR: 1.938; 95% CI 1.046–3.589; P = 0.035 ) were independently correlated with OS, and SII (HR: 2.224; 95% CI 1.298–3.810; P = 0.004 ) was an independent prognostic predictor of PFS, whereas we found that other inflammation-based indices lost their independent value. Conclusions. The SII, which is an integrated blood parameter based on platelet, neutrophil, and lymphocyte counts, may be an independent prognostic indicator and may be useful for the identification of NSCLC patients with brain metastases after stereotactic radiotherapy at high risk for recurrence.


2020 ◽  
Author(s):  
Linlin Wang ◽  
Lihui Ge ◽  
Guofeng Zhang ◽  
Yi Ren ◽  
Yongyu Liu

Abstract Background: Whether lung segmentectomy is a safe and effective surgical treatment in patients with early non-small cell lung cancer (NSCLC) remains controversial. We have therefore reviewed the clinicopathologic characteristics and survival outcomes of patients receiving a lobectomy vs. segmentectomy to treat early T (>2 cm and ≤3 cm) N0M0 NSCLC.Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database for patients who underwent lobectomy or segmentectomy between 2004 and 2015. To reduce bias and imbalance between the treatment groups, propensity score matching (PSM) analysis was performed. We used Kaplan-Meier curves to estimate overall survival (OS) and lung cancer-specific survival (LCSS), performed univariate and multivariate Cox proportional hazards regression analyses to identify independent prognostic factors for OS and CSS, and applied the Cox proportional hazards model to create forest plots. Results: A total of 5783 patients from the SEER database were included. Of these, 5531 patients underwent lobectomy, and 252 patients underwent segmentectomy. Before matching, both univariate and multivariate Cox regression analyses showed that patients who underwent lobectomy had better OS (hazard ratio [HR]: 1.561; 95% confidence interval [CI] 1.292-1.885; P <0.001) and LCSS (HR: 1.551; 95% CI 1.198-2.009; P=0.001) than patients who underwent segmentectomy. However, survival differences between the groups were not significant; OS (P=0.160) and LCSS (P=0.097) after matching. Regression analyses revealed that age, sex, lymph node dissection, and grade were independent predictors of OS and LCSS (P <0.05).Conclusions: For patients with stage T (>2 cm and ≤3 cm) N0M0 non-small cell lung cancer, segmentectomy can achieve the same OS and LCSS compared with lobectomy. A large number of patients require further long-term follow-up analyses.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3068-3068
Author(s):  
Lingbin Meng ◽  
Rui Ji ◽  
Damian A. Laber ◽  
Xuebo Yan ◽  
Xiaochun Xu

3068 Background: Raf1 kinase inhibitor protein (RKIP) is able to bind Raf1 to inhibit Ras-Raf-MEK-ERK signaling, a major oncogenic pathway. It has been reported that reduced RKIP expression associates with poor prognosis in many cancers, including gastric adenocarcinoma, gliomas and bladder cancer. However, there are only several studies on its role in non-small cell lung cancer (NSCLC) and the conclusion is still controversial. Hence, we performed this study to assess the prognostic significance of RKIP in our NSCLC population. Methods: Between June 2017 and June 2020, 156 NSCLC patients treated at our hospital were included for the present study. None of the patients had received chemotherapy, radiotherapy or surgery before. Their tumor tissues and surrounding normal lung tissues were collected for immunostain and western blot analysis of RKIP expression and ERK signaling. We collected information about gender, age, histological differentiation, tumor size, TNM stage, and lymph node status. Survival curves were analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic value of various variables in a univariate and multivariate setting. Results: Immunostain and western blot results showed a lower RKIP expression and a higher p-ERK level in cancer tissues compared with the surrounding normal tissues. A reduced RKIP expression with high level of p-ERK was also observed in TNM stages III and IV as compared with I and II. Pearson's chi-squared test confirmed low RKIP expression associated with poorer TNM stage ( p< 0.001) and N-stage ( p< 0.05). No significant correlation was observed between RKIP expression level and gender, age, histological type or tumor size. Kaplan-Meier survival analysis revealed that patients with low RKIP expression had significantly worse overall survival than patients with high RKIP expression ( p= 0.019, log-rank). This conclusion was consistent in the stage I&II patients ( p= 0.011, log-rank) but not in the stage III&IV patients ( p= 0.711, log-rank). Univariate Cox proportional hazards regression analysis indicated Tumor size, TNM stage and RKIP expression significantly affected overall survival of the NSCLC patients. Multivariate Cox proportional hazards regression analysis confirmed RKIP expression remained a significant predictor of survival after correcting for the effects of Tumor size and TNM stage (hazard ratio = 1.730, 95% confidence interval = 1.017 – 2.942, p = 0.043). Conclusions: In this study, low RKIP expression was a poor prognostic indicator in NSCLC as it significantly correlated with poorer TNM stage, N-status, and overall survival. Our findings suggest that by inhibiting Ras-Raf-MEK-ERK pathway RKIP may play an anti-tumor role in NSCLC.


2021 ◽  
pp. 1-11
Author(s):  
Dennis London ◽  
Dev N. Patel ◽  
Bernadine Donahue ◽  
Ralph E. Navarro ◽  
Jason Gurewitz ◽  
...  

OBJECTIVE Patients with non–small cell lung cancer (NSCLC) metastatic to the brain are living longer. The risk of new brain metastases when these patients stop systemic therapy is unknown. The authors hypothesized that the risk of new brain metastases remains constant for as long as patients are off systemic therapy. METHODS A prospectively collected registry of patients undergoing radiosurgery for brain metastases was analyzed. Of 606 patients with NSCLC, 63 met the inclusion criteria of discontinuing systemic therapy for at least 90 days and undergoing active surveillance. The risk factors for the development of new tumors were determined using Cox proportional hazards and recurrent events models. RESULTS The median duration to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase (RTK) pathways (e.g., KRAS, EGFR) were more likely to develop new tumors (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33–3.81, p = 2.5 × 10−3; HR 2.51, 95% CI 1.45–4.34, p = 9.8 × 10−4, respectively). CONCLUSIONS The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or RTK pathway mutations have a higher rate of new metastases and should be followed more closely.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jingyao Li ◽  
Yi Liao ◽  
Yaling Ran ◽  
Guiyu Wang ◽  
Wei Wu ◽  
...  

Abstract Background The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrol™ technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC). Methods CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrol™ detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up. Results The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P <  0.001). The mesenchymal CTCs of NSCLC patients was slightly higher than that of benign lung diseases (P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥0.5 had significantly lower DFS than those with CTCs < 0.5 (P = 0.022). Conclusions CTC positive can well predict the recurrence of NSCLC patients. CanPatrol™ technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation.


2019 ◽  
Author(s):  
Takehiro Tozuka ◽  
Satoru Kitazono ◽  
Hiroaki Sakamoto ◽  
Hiroshi Yoshida ◽  
Yoshiaki Amino ◽  
...  

Abstract Background Dissociated responses (DR) are phenomena in which some tumors shrink, whereas others progress during treatment of patients with cancer. The purpose of the present study was to evaluate the frequency and prognosis of DR in non-small cell lung cancer (NSCLC) patients treated with anti-program cell death-1/ligand 1 (anti-PD-1/L1) inhibitors. Methods This retrospective study included NSCLC patients who received anti-PD-1/L1 inhibitor as second- or later-line treatment. We excluded patients without radiological evaluation, including brain imaging within 28 days prior to the treatment, and those without measurable lesions. We evaluated all measurable lesions in each organ. We defined DR as a disease with some shrinking lesions as well as growing or emerging new lesions in patients who showed progressive disease (PD), according to the RECIST 1.1 at the initial CT evaluation. Cases not classified as DR were defined as ‘true PD’. Overall survival was compared between patients with DR and those with true PD using Cox proportional hazards models. Results The present study included 62 NSCLC patients aged 27–82 years (median: 65 years). DR and true PD were observed in 11 and 51 patients, respectively. Nivolumab, pembrolizumab, and atezolizumab were administered to 45, 7, and 10 patients, respectively. Median overall survival was significantly longer in patients with DR versus true PD (14.0 vs. 6.6 months; hazard ratio for death: 0.40; 95% confidence interval: 0.17–0.94). Conclusions The frequency of DR in NSCLC patients who showed PD to anti-PD-1/L1 was 17.7%. Patients with DR exhibited a relatively favorable prognosis.


2020 ◽  
Author(s):  
Duoying Wang ◽  
Dong Guo ◽  
Aijie Li ◽  
Peiliang Wang ◽  
Feifei Teng ◽  
...  

Aim: To investigate the predictive potential of post-treatment neutrophil-to-lymphocyte ratio (NLR) and changes in this ratio (ΔNLR) for stage III non-small-cell lung cancer (NSCLC) patients who received conventionally fractionated radiotherapy (CFRT). Patients & methods: The data of 168 NSCLC patients treated at the Shandong Cancer Hospital were analyzed retrospectively. The relationship between progression-free survival (PFS), overall survival (OS) and post-treatment NLR and ΔNLR were analyzed using both Kaplan–Meier and Cox regression methods. Results: Kaplan–Meier survival analyses showed that post-treatment NLR and ΔNLR were associated with PFS (p < 0.001) and OS (p < 0.001) after CFRT. Multivariate analyses revealed that ΔNLR was an independent predictor of PFS (p = 0.001) and OS (p = 0.018). Post-treatment NLR can only be used as an independent predictor of PFS (p = 0.040). Conclusion: Our results demonstrated the prognostic value of the ΔNLR in predicting PFS and OS in stage III NSCLC patients undergoing CFRT. However, post-treatment NLR has predictive value only for PFS.


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