Background:In the era of precision medicine,chemotherapy is still considered the cerstone of treatment for lung cancer patients without gene mutations.How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring.This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy (HCT) for advanced patients with non-small cell lung cancer (NSCLC),especially those with malignant pleural effusion.Methods:We retrospectively evaluated medical records of 93 patients with advanced NSCLC (stage ⅢB-Ⅳ) from March 2011 to January 2014.The patients were divided into HCT and chemotherapy (CT) groups.The HCT group was treated with gemcitabine and cisplatin (GP) regimen combined with regional radiofrequency deep hyperthermia,while the CT group was treated with GP regimen only.Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not.Clinical treatment results and adverse reactions were compared and analyzed after treatment.SPSS 19.0 software (SPSS Inc.,USA) was used for statistical data processing.P values less than 0.05 were accepted to be statistically significant.Results:Among the 93 patients,HCT group included 48 patients (16 patients with malignant pleural effusion),CT group included 45 patients (10 patients with malignant pleural effusion).There was no significant difference between the two groups in patient characteristics.The overall response rate (ORR) of pleural effusions was much better in HCT group than that in CT group (81.2％ vs.40.0％,P=0.046).The patients in HCT2group had lower incidence rate of weakness (12.5％ vs.46.7％,x2=13.16,P ＜ 0.001) and gastrointestinal (25.0％ vs.77.8％,x =25.88,P＜0.001) adverse reactions than that in CT group.The objective tumor response and survival showed no significant differences.Conclusions:Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSCLC with malignant pleural effusion patients.Also,it could greatly reduce the chemotherapy toxic effects in the incidence of weakness and gastrointestinal adverse reactions in advanced NSCLC patients.