关键词: 癌, 非小细胞肺, 免疫疗法, 预后, 列线图

Abstract:

Objective To explore influencing factors affecting the prognosis of patients with advanced non-small cell lung cancer （NSCLC） receiving immunotherapy based on hematologic indexes， thus to construct and evaluate a nomogram prediction model. Methods The clinical data of 80 patients with advanced NSCLC treated with programmed death-1 inhibitor monotherapy or combination regimen from January 2018 to June 2020 at the Affiliated Hospital of North China University of Science and Technology and Tangshan People's Hospital were retrospectively analyzed. Hematologic indexes at the baseline， the optimal remission and the progressive disease （PD） were collected separately， and independent influencing factors for patient prognosis were analyzed using Cox proportional hazards regression model. A nomogram prediction model was constructed based on the results of the multifactorial analysis， and the predictive performance of the model was evaluated by receiver operating characteristic （ROC） curve， concordance index （C-index） and calibration curves. Results As of the follow-up cut-off date， of the 80 patients， 63 had PD， with a median overall survival （OS） of 16.9 months. Univariate analysis showed that， age （HR=2.09， 95%CI： 1.17-3.74， P=0.013）， number of treatment lines （HR=2.23， 95%CI： 1.21-4.12， P=0.010）， lymphocyte to monocyte ratio （LMR） at the baseline （HR=0.75， 95%CI： 0.57-0.97， P=0.028）， D-dimer （HR=1.00， 95%CI： 1.00-1.00， P=0.002） and lactate dehydrogenase （LDH） （HR=1.01， 95%CI： 1.00-1.01， P=0.006） at the optimal remission， haemoglobin （HR=0.97， 95%CI： 0.96-0.99， P<0.001）， D-dimer （HR=1.00， 95%CI： 1.00-1.00， P=0.002）， C-reactive protein （HR=1.01， 95%CI： 1.00-1.01， P=0.011）， albumin （ALB） （HR=0.91， 95%CI： 0.87-0.96， P=0.001）， neutrophil to lymphocyte ratio （NLR） （HR=1.16， 95%CI： 1.05-1.27， P=0.002） and LMR （HR=0.62， 95%CI： 0.42-0.90， P=0.012） at the PD were all influencing factors for the prognosis of advanced NSCLC patients receiving immunotherapy. Least absolute shrinkage and selection operator regression were used to screen the variables for P<0.10 in the univariate analysis， and nine possible influencing factors were obtained， which were age， fibrinogen and LDH at the optimal remission， haemoglobin， D-dimer， C-reactive protein， LDH， ALB and LMR at the PD. Multivariate analysis of the above variables showed that， age （HR=0.91， 95%CI： 0.86-0.97， P=0.004）， LDH （HR=1.01， 95%CI： 1.00-1.01， P=0.013） and ALB （HR=0.82， 95%CI： 0.67-0.99， P=0.041） at the PD were independent influencing factors for the prognosis of patients with advanced NSCLC who received immunotherapy. The area under curve of the nomogram predicting model based on the above indexes， 1- and 2-year OS rates of patients were 0.77 （95%CI： 0.65-0.89） and 0.75 （95%CI： 0.66-0.88）， respectively， and C-index was 0.71 （95%CI： 0.64-0.78）， the calibration curves showed good consistency between predicted and actual probability of occurrence. Patients in the low-risk group （n=40） had a median OS of 29.9 months （95%CI： 22.5 months-NA）， which was significantly better than that of the high-risk group （n=40） [13.4 months （95%CI： 11.4-23.5 months）， χ²=11.30， P<0.001]. Conclusion Age， LDH and ALB at the PD are independent influencing factors affecting the prognosis of patients with advanced NSCLC receiving immunotherapy， and the nomogram model constructed based on the above indexes has good differentiation and calibration for predicting 1- and 2-year OS rates in advanced NSCLC patients receiving immunotherapy.

Key words: Carcinoma, non-small-cell lung, Immunotherapy, Prognosis, Nomogram