ABSTRACT
Relapse or metastatic esophageal squamous cell carcinoma (ESCC) has poor prognosis and limited treatment options. Chemotherapy based on platinum agents combined with fluorouracil or taxanes is the standard first-line treatment for it. Molecular-targeting agents, mainly epidermal growth factor receptor inhibitors including cetuximab, panitumumab, nimotuzumab and gefitinib, have failed to improve the survival of patients with advanced ESCC. Anlotinib, one of the small molecule multi-target tyrosine kinase inhibitors, can prolong the median progression free survival in patients treated with above the second line. Compared with chemotherapy, immune checkpoint inhibitors (including nivolumab, pembrolizumab and camrelizumab) significant improve overall survival times in patients with ESCC who fail to the first line chemotherapy, and can be selected as the standard second line treatment. Immunotherapy combined with chemotherapy or anti-angiogenic therapy for first-line treatment of advanced ESCC is also being studied.
ABSTRACT
Objective:To investigate the effects of different treatment modes on the survival of patients with non-small cell lung cancer (NSCLC) brain metastases, and to evaluate the clinical values of diagnosis-specific graded prognostic assessment (DS-GPA) model and graded prognostic assessment model for lung cancer using molecular markers (Lung-molGPA).Methods:The clinical data of 195 NSCLC patients with brain metastases treated in the Cancer Hospital of Shantou University Medical College from January 2011 to December 2015 were retrospectively analyzed, including 112 patients without brain metastasis (metachronous brain metastases) at the first diagnosis, and 83 patients with brain metastases at the first diagnosis (simultaneous brain metastases). The treatment modalities of brain metastases included single local cranial radiation, chemotherapy, target therapy and combined cranial radiation with chemotherapy or target therapy, chemotherapy plus target therapy, et al. Kaplan-Meier method was used for survival analysis, Cox regression method was used for univariate and multivariate survival analyses, and DS-GPA and Lung-molGPA models were used for survival analysis.Results:The median time to brain metastases in all patients was 14.1 months (95% CI 12.2-16.0 months). The median progression-free survival (PFS BM) time of all patients was 4.3 months (95% CI 3.4-5.2 months), and the median overall survival (OS BM) time of brain metastases was 6.7 months (95% CI 4.6-8.8 months). There was no difference in PFS BM and OS BM between patients with synchronous and metachronous brain metastases ( P = 0.446, P = 0.080). Receiving anti-tumor therapy, especially combining targeted therapy could improve median OS BM. Low Karnofsky score ( RR = 1.698, 95% CI 1.238-2.329, P = 0.001) and bone metastasis ( RR = 1.505, 95%CI 1.089-2.081, P = 0.013) were independent risk factors for the OS BM of NSCLC patients with brain metastases, and chemotherapy ( RR = 0.460, 95% CI 0.289-0.731, P = 0.001) and brain radiotherapy ( RR = 0.541, 95% CI 0.391-0.749, P < 0.01) were independent protective factors for the OS BM of NSCLC patients with brain metastases. The OS BM difference between patients grouped by DS-GPA and Lung-molGPA models was statistically significant (median OS BM time of patients with DS-GPA model 0.0-1.0, 1.5-2.0 and 2.5-3.0 points were 4.2, 9.4 and 10.9 months, respectively, P = 0.015; median OS BM time of patients with Lung-molGPA model 0.0-1.0, 1.5-2.0 and 2.5-3.0 points were 4.1, 8.7 and 13.0 months, respectively, P < 0.01). Conclusions:The prognosis of NSCLC patients with brain metastases is poor, and anti-tumor therapy can prolong their survival. High Karnofsky score, without bone metastasis, receiving chemotherapy or brain radiotherapy are independent good prognostic factors for NSCLC patients with brain metastases. Both DS-GPA and Lung-molGPA models can predict the survival of NSCLC patients with brain metastases.