Reliable prognostic prediction score system is crucial in risk stratification for patients and adjusting appropriate treatment strategy for NSCLC with BM. In the present study, we investigated the utility of cho/cr and SII and C-SII score on prognosis in NSCLC patients. The results showed that C-SII score is independent predictors of OS and PFS among NSCLC patients with BM.
In recent years, stereotactic radiotherapy is used to treat limited numbers of BM, since this therapy is less invasive than drug and surgical resection with better local control.23,24 Therefore, the use of stereotactic radiotherapy is recommended to further control BM risk.25 At present, various blood indicators have been evaluated the prognosis role of NSCLC patients with BM, such as Neuron-specific enolase (NSE),26 Carcinoembryonic antigen (CEA)27 and Lung-molGPA.28 However, there are no more reliable predictors that can reflect different tumor biological behavior. Hence, searching for accurate prognostic factors is of great clinical application value.
The occurrence of tumor is often accompanied by changes in metabolism biochemical composition. MRS is a noninvasive and sensitive imaging method that allows researchers to measure and visualize metabolism biochemical information from brain tumor tissues.29Increasing evidence have indicated that MRS can identify tumor active region and enhance more individualized response-based treatment in High-grade Glioma.15 An ongoing effort at Tehran University of Medical Sciences has shown that MRS parameters can improve the accuracy of predictive nomograms to assess the risk of biochemical recurrence after radical prostatectomy in prostate cancer.30 More comprehensive understanding the biochemical composition changes in metabolites for tumors is more urgent. The typical MRS metabolic abnormalities of BM often include increased cho, decreased NAA and cr. Minicozzi et al observed in thirty-six head and neck cancer cases that cho/cr is significantly elevated in the group with poor response.14 Fink et al found that multi-voxel MRS cho/cr peak-area shows great advantage for distinguishing glioma recurrence.31 Negendank and colleagues conducted a co-operative study with 15 clinical research centers and confirmed that the cho was higher in glial tumors than in non-involved brain tissues.32 Dowling and coworkers revealed that cho concentrations and NAA in tumor tissue were higher than normal values cancer.33 In this study, our result reported that the cho/cr was independent relevant factors for death and progression (P = 0.006; P < 0.001). Whether the cho、cr were not correlated with prognosis on NSCLC with BM.
Accumulating studies have substantiated that peripheral venous blood markers can reflect the condition of the host immune inflammation status. Counts of the peripheral immune inflammatory cells, such as platelet, lymphocytes, and neutrophils have been confirmed the reliable association link between inflammatory cells and prognosis in malignant tumors.34–37 SII is an integrated parameter, including platelets, neutrophils and lymphocytes and has been proved to be an independent predictor of malignant tumors.22,38−43 The value of SII in predicting clinical outcomes for cancer patients may be associated with the function of platelets, neutrophils, and lymphocytes. Platelets release growth factors and pro-angiogenic protein and protect tumor cells from immune response.44 Neutrophils can take part in various stages of growth and metastasis of tumors and generate immunosuppressive effects by producing and secreting cytokines, chemokines, and proteases.45 In contrast to neutrophils, lymphocytes exert important antitumor immune response and have been proved to be related to systematic immune surveillance.46 In this study, the association between SII and clinical outcomes of patients in NSCLC with BM was evaluated. Our results indicated that SII was significantly associated with OS and PFS (P = 0.001; P = 0.002).
The clinician can evaluate clinical indicators such as tumor size, degree of tumor differentiation or tumor location, but these evaluation criteria are based on individual subjective evaluation and judgment. The heterogeneity of individual tumors is largely reflected in the biological characteristics of tumors and host immune inflammatory state. Consider a problem from multiple angles and you may find new breakthroughs. Recently, many scholars have realized that combining two peripheral blood indexes can be considered useful independent prognostic markers in tumors. In the retrospective study initiated by Chen et al, their results revealed that the combination of circulating tumor cells with carcinoembryonic antigen has a better disease prediction than they were alone in NSCLC patients.47 Huang et al showed that preoperative combining neutrophil-to-lymphocyte ratio and fibrinogen concentration can be used an independent prognostic indicator for OS (HR, 1.512; 95% CI, 1.283–1.783; P < 0.001).48Although Guo et al49 and Schernberg et al50 conducted related studies on PET/CT combined with blood inflammation indicators predicting prognosis and obtained positive results, the clinical data focusing on the predictive value of combination of the MRS and SII for BM in NSCLC patients treated with stereotactic radiotherapy has not been reported. We previously used MRS alone to evaluate the prognosis of patients with BM in NSCLC patients and revealed that positive cho/cr was an independent risk factor for OS (P = 0.009) and PFS (P = 0.006).16 The cho/cr or SII alone may are not sufficient to accurately reflect the tumor characteristics. Using C-SII scores system, may be a more accurate choice. As we have studied, our results revealed that C-SII score of 2 (cho/cr > 1.50 and SII > 480) has a poorer clinical outcomes than patients with C-SII score 1 (cho/cr > 1.50 or SII > 480) or C-SII score 0 (cho/cr ≤ 1.50 and SII ≤ 480). In the multivariate Cox regression analyses, study results demonstrated that the C-SII score independently predicted OS (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).
We established a C-SII score system by combining cho/cr and SII in this study, and preliminary results showed that it was an accurate and reliable system for evaluating prognosis in NSCLC patients with BM. However, only 118 NSCLC with BM patients were conducted in this study because of the available limited number of enrolled cases. In addition, incomplete clinical data and loss to follow-up were inevitable because of the long duration of this retrospective study. There is selection bias when clinicians and radiologists use MRS to determine the ROI. These limitations require further evaluation and improvements in the future study.