Pretreatment lymphocyte-to-monocyte ratio as a prognostic factor and influence on dose-effect in fractionated stereotactic radiotherapy for oligometastatic brain metastases in non-small cell lung cancer patients.

Background: Studies on the prognostic factors for patients with brain oligo-metastasis treated with fractionated stereotactic radiotherapy (FSRT) usually focus on the size of metastatic tumor and radiation dose. Some inflammatory indicators have predictive value in non-small cell lung cancer (NSCLC) with brain metastasis receiving stereotactic radiotherapy. However, the prognostic value of inflammatory indicators in NSCLC patients with brain oligo-metastasis treated with FSRT, and their effect on radiotherapy dose is unknown. Methods: A total of 95 advanced NSCLC patients with brain oligo-metastasis who had undergone FSRT treatment at Ningbo Medical Center Lihuili Hospital between January 2015 and April 2022 were enrolled into the study. Neutrophil to lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), tumor diameter and biologically effective dose (BED10) were analyzed using Chi-square test. Univariate and multivariate Cox regressions were used to identify predictors of survival. Results: Tumor diameter (< 2 cm), BED10 (≥ 48Gy) and LMR (≥ 4) were found to be independently associated with good intracranial local control survival (i-LCS) through multivariate analysis. The median i-LCS was longer in patients with 2 independent risk factors (tumor diameter ≥ 2 and LMR < 4) administered with BED10 > 53.6Gy compared with patients administered with BED10 ≤ 53.6Gy (20.7 months vs 12.0 months, P = 0.042). LMR ≥ 4 (P = 0.019) and positivity for driver gene mutations (P = 0.011) were independently associated with better overall survival (OS). Conclusions: LMR is an independent prognostic factor of i-LCS and OS in NSCLC patients with brain oligo-metastasis treated with FSRT. Patients with tumor diameter ≥ 2 and LMR < 4 should be treated with BED10 greater than 53.6Gy.

Inflammation-based prognostic scoring system for predicting the prognosis of advanced small cell lung cancer patients receiving anlotinib monotherapy.

BACKGROUND: According to the randomized multicenter phase II trial (ALTER1202), anlotinib has been approved as a third-line therapy for advanced small-cell lung cancer (SCLC). Some studies showed the predictive function of inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in the different cancers treated with anti-vascular targeting drugs. However, none of the studies showed the roles of NLR, PLR, and LMR in SCLC patients receiving anlotinib. Thus, our objective was to establish a scoring system based on inflammation to individuate patient stratification and selection based on NLR, PLR, and LMR. METHODS: NLR, PLR, and LMR and their variations were calculated in 53 advanced SCLC patients receiving anlotinib as a third- or further-line treatment at Ningbo Medical Center Lihuili Hospital between January 2019 and December 2021. Kaplan-Meier curves were plotted. Both univariate and multivariate Cox regressions were used to identify predictors of survival. RESULTS: Disease control rate was related to pre-NLR, pre-PLR, pre-LMR, post-NLR elevation, post-PLR elevation, and post-LMR elevation. The multivariate analysis determined post-NLR elevation, pre-PLR > 240.56, and pre-LMR ≤1.61 to be independently associated with progression-free survival, not overall survival. The inflammation-based prognostic scoring system demonstrated favorable predictive ability from the receiver operating characteristic curve (AUC: 0.791, 95% CI: 0.645-0.938). CONCLUSIONS: Post-NLR variation, pre-PLR, and pre-LMR were independent prognostic factors for PFS in advanced SCLC receiving anlotinib monotherapy. The inflammation-based prognostic scoring system can accurately predict effectiveness and survival.

Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Their Variations as a Basis for a Prediction Model in Advanced NSCLC Patients Receiving Anlotinib.

Background: A phase III randomized multicenter trial (ALTER0303) reported anlotinib to be significantly beneficial to patient survival. An array of inflammatory biomarkers, such as neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), are associated with the response to treatment in numerous types of cancer. However, we found few studies investigating the predictive value of NLR or PLR in advanced NSCLC treatment with anlotinib. Thus, our objective was to examine the relationship between NLR and PLR and treatment effect, as well as to individuate patient stratification and selection. Methods: NLR and PLR as well as their variations were calculated in 152 advanced NSCLC patients receiving anlotinib as a third or further-line treatment at Ningbo Medical Center Lihuili Hospital between July 2018 and December 2020. The best cut-off values of NLR and PLR for predicting the treatment response were selected. Survival curves were plotted using the Kaplan-Meier method, while univariable and multivariable Cox regression were used to identify and determine dependent and independent predictors of survival. Results: , Low disease control rate (DCR) was related with a high pre-NLR (P = 0.007), high pre-PLR (P = 0.004), and elevated post-NLR (P = 0.010). Multivariate analysis determined high pre-PLR (>205.63) and elevated post-NLR to be independently associated with poor PFS or OS. Patients whose risk score was 2 resulting from the prediction model based on pre-PLR and post-NLR had a 4.52 times higher risk of death compared to patients whose risk score was 0 (HR: 4.516, 95% CI: 2.502-8.152, P ≤ 0.001). Conclusions: Pre-PLR and post-NLR were independent prognostic indicators in patients with advanced NSCLC receiving anlotinib as a third or further-line treatment. Patients whose risk value score was 0 had a higher therapy effectiveness and better survival.

Prognostic value of prognostic nutritional index and its variations in advanced non-small-cell lung cancer patients treated with anlotinib monotherapy.

BACKGROUND: Anlotinib is a third-line or further therapy for advanced non-small-cell lung cancer (NSCLC). However, the lack of simple biomarkers to predict the curative effect of anlotinib creates significant unmet needs in exploring the markers. This study aimed to explore the relationship between the prognostic nutritional index (PNI) and its variations and efficacy of anlotinib. METHODS: Data for patients with advanced NSCLC who received anlotinib were collected at Ningbo Medical Center Lihuili Hospital. The data included the values of pretreatment PNI (pre-PNI), posttreatment PNI (post-PNI), and ΔPNI (post-PNI minus the pre-PNI). The Kaplan-Meier method was used to generate survival curves, whereas univariate and multivariate Cox regression analyses were used to analyze survival predictors. RESULTS: A high disease control rate was associated with a high pre-PNI (p = 0.007), high post-PNI (p = 0.000), and high ΔPNI (p = 0.006). Univariable analysis revealed that pre-PNI ≤41.80, post-PNI ≤42.48, and ΔPNI ≤0.20 were significant risk factors for poor survival. According to the multivariate analysis, progression-free survival (PFS) in patients with post-PNI ≤42.48 was significantly shorter than in patients with higher values (median PFS: 1.5 months vs. 4.0 months, p = 0.010). CONCLUSIONS: Pre-PNI, ΔPNI, and post-PNI were found to be predictive factors for response in advanced NSCLC patients treated with anlotinib as a third-line or further treatment. Only post-PNI was a reliable predictor of PFS. Therefore, PNI and its variations, particularly post-PNI, are affordable and accessible predictors of NSCLC patients treated with anlotinib in clinical work.

Levels of pretreatment blood lipids are prognostic factors in advanced NSCLC patients treated with anlotinib.

BACKGROUND: Anlotinib, a small molecule for multi-target tyrosine kinase inhibition, is the third or further line of defense for treatment of non-small cell lung cancer (NSCLC). Findings from an ALTER0303 phase III trial revealed that this drug confers significant survival benefits in patients. Although numerous inflammatory biomarkers have been shown to play vital roles in treatment, the clinical significance of blood lipid levels before treatment has not been evaluated. Here, this research aims to explore the relationship between blood lipids and efficacy of anlotinib, with a view of generating insights to guide future development of convenient and individualized treatment therapies. METHODS: This study analyzed basal blood lipids levels, including triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), and high density lipoprotein (HDL), among other variables before treatment, in 137 patients with advanced NSCLC who received anlotinib as third or further-line treatment at the Ningbo Medical Center Lihuili Hospital, between July 2018 and December 2020. We determined the best cut off value for predicting treatment responses, generated survival curves using the Kaplan-Meier method, then applied univariate and multivariate Cox regression analyses to assess predictors of survival. RESULTS: The entire study population recorded median progression-free survival (PFS) and overall survival (OS) of 4 (95% CI 3.142-4.858) and 8.3 (95% CI 6.843-9.757) months, respectively. Researchers observed statistically significant differences across subgroups, between blood lipid indexes with different efficacies, except in the HDL subgroup. The low disease control rate (DCR) was associated with significantly elevated TG, TC and LDL levels (P = 0.000). Multivariate analysis demonstrated that elevated TC and LDL levels were independently associated with poor PFS or OS (P ≤ 0.003). Then, we established a prediction model, and set high TC or high LDL as the risk factor, respectively. There were significant differences in PFS (p = 0.000) and OS (p = 0.012) between 0 and ≥ 1 scores. CONCLUSIONS: Prior to anlotinib therapy, TC and LDL levels, are independent prognostic indicators for patients with advanced NSCLC treated with this drug as a third or further-line treatment option. In addition, a risk score of 0 was attributed to a combination of low TC and low LDL, and these patients were exhibited excellent efficacies and survival rates.

Pretreatment Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Factors and Reference Markers of Treatment Options for Locally Advanced Squamous Cell Carcinoma Located in the Middle and Upper Esophagus.

BACKGROUND: Various inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been well authenticated to predict clinical outcomes in numerous types of cancer. The optimal treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC) located in the middle or upper region is still inconclusive. The aim of the study was to examine pretreatment NLR and PLR to select from radical surgery or definitive chemoradiotherapy (dCRT) for these patients. The linkage between pretreatment NLR/PLR and prognosis was also analyzed. METHODS: NLR and PLR were calculated in 113 locally advanced ESCC located in the middle or upper esophagus of patients who underwent radical surgery or dCRT between January 2014 and December 2019. A receiver operating characteristic curve was plotted to select the best cut-off value of NLR and PLR for predicting survival. A survival curve was plotted using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were applied to assess predictors for survival. RESULTS: NLR and PLR were associated with the extent of lymph node metastasis (NLR: P = 0.045; PLR: P = 0.002). Additionally, high PLR and recurrence with distant organ metastasis were closely related (P = 0.014), and NLR was related to the tumor stage (P = 0.043). The results of the multivariate analysis revealed that NLR (>2.07) and PLR (>183.06) were independently associated with poor prognosis. It is noteworthy that surgery was associated with a superior OS compared with dCRT in the low NLR population (P = 0.045). CONCLUSION: Low pretreatment NLR patients are fit to undergo radical surgery with a substantial therapeutic benefit. Pretreatment NLR and PLR are independent predictors for patients with locally advanced ESCC located in the middle and upper esophagus who underwent radical surgery or dCRT.

[Effects of Renshenjian Decoction on blood and urine metabonomics in type 2 diabetes rats based on ~1H-NMR].

Proton nuclear magnetic resonance(~1H-NMR) is used to investigate the effect of Renshenjian Decoction on serum and urine metabolism of type 2 diabetic rats with insulin resistance induced by high-sugar and high-fat diet combined with low-dose streptozotocin(STZ). After the successful establishment of the insulin resistance model of type 2 diabetes, administration for 35 days, the serum and urine of rats were taken. Once the ~1H-NMR data have been collected and processed, PCA and OPLS-DA were used to analyze them. The results show that: compared with the blank group, the contents of methionine, taurine, α-glucose and ß-glucose in the serum of the model group increased significantly(P<0.001), while the contents of 3-hydroxybutyric acid, lactic acid and unsaturated fatty acids decreased significantly(P<0.01). In the model group, the contents of trimethylamine oxide, glycine, α-glucose, ß-glucose, taurine and phosphocholine in urine increased significantly(P<0.05), while the contents of creatine, lactic acid, acetic acid and citric acid decreased significantly(P<0.05). Compared with the model group, the contents of 3-hydroxybutyric acid and unsaturated fatty acids in serum of rats in the treatment group increased significantly(P<0.05), while the contents of taurine, α-glucose and ß-glucose decreased significantly(P<0.01). In the treatment group, the contents of lactic acid, taurine and creatine in urine increased significantly(P<0.05), while the contents of trimethylamine oxide, glycine, α-glucose, ß-glucose and phosphocholine decreased significantly(P<0.01). The results show that Renshenjian Decoction can regulate metabolic disorder and promote the metabolic phenotype to return to the normal range. It displayed therapeutic effect on type 2 diabetic rats with insulin resistance and provided a certain scientific basis for the biological basic research of Renshenjian Decoction by improving insulin resistance in diabetes mellitus.