| Background and Objectives:Lung cancer is the leading cause of cancer death in China and throughout the world. Operation, chemotherapy, radiotherapy, immune therapy and target therapy has been made great progress in the past 50 years, however, the 5-year-survival for the patients with lung cancer is still poor. The new treatment model and the different sequence of different treatment, such as neoadjuvant chemotherapy(NC), concurrent chemoradiotherapy(CRT) and sequential chemoradiotherapy (SRT) combined with operation, has contributed a lot to improve the survival of lung carcinoma. However, the model of multi-modality in lung carcinoma still remains in debate. Meta-analysis based on the data from pooled patients provided us a novel avenue to evaluate the efficiency and side effects of treatment model, thereby benefiting to the patients. Therefore, we evaluated the difference of efficiency and safety between NC and immediate operation, between CRT and SRT, between non-conventional fractionation radiotherapy (NCRT) and conventional radiotherapy (CR)in the present study.Methods:Randomized studies published in English and Chinese until 2007 were included in the present study. Eligible randomized controlled trails were combined and used in the present Meta-analysis. RR(Relative Risk) or OR(Odds Radio) were calculated from the reports of the studies available and then combined together to get estimate of efficiency.Results:1. NC improved 5-year-survival with a RR of 0.91(95% confidence interval, 0.86-0.96; P=0.0007) compared to the immediate operation group. Furthermore, the 5-year-survival also significantly increased in NC group even in stageⅢ.2. The overall meta-analysis showed that CRT not only significantly increased 3-year-survival (RR, 0.88; 95%CI ,0.83–0.94; P<0.0001), but also increased 5-year-survival (RR, 0.92; 95%CI, 0.86–0.98; P=0.02) in comparison with SRT. Moreover, 3-year-survival was increased in CRT group even in the patients at stageⅢ(RR, 0.89; 95%CI, 0.84–0.95; P=0.0004). However, high-grade (gradeⅢand gradeⅣ) esophagitis was more severe in CRT group compared to SRT group (OR, 4.99; 95%CI, 2.71–9.17; P<0.00001). Interestingly, there was no significant difference regarding to gradeⅢand gradeⅣpneumonitis (OR, 1.16; 95%CI, 0.62–2.16; P=0.64).3. The response ratio to NCRT was significantly higher than that to CR(RR, 1.21; 95%CI, 1.12–1.30; P<0.00001). One-year-survival (OR, 0.70; 95%CI 0.59–0.83; P<0.00001), two-year-survival (RR, 0.88; 95%CI, 0.81–0.94; P=0.0004) and three-year-survival of (RR, 0.92; 95%CI, 0.89–0.96; P<0.0001) were all significantly increased in NCRT compared to CR. However, there was no significantly difference in both 4-year-survival (RR, 0.98; 95%CI, 0.92–1.04; P=0.47) and 5-year-survival (RR, 0.98; 95%CI, 0.94–1.02; P=0.28) between two groups. In regard to side effects, high-grade esophagitis was more severe in NCRT than CR (OR, 2.60; 95%CI 1.91–3.54; P<0.00001), but there was no difference for pneumonitis between two groups (OR,1.04; 95%CI, 0.80–1.34; P=0.77). Interestingly, most of the results including efficiency and side effects from sub-gourp of stageⅢwere similar to that in the overall patients except that there was no difference for 2-year-survival (RR, 0.91; 95%CI, 0.82–1.00; P=0.05). Furthermore, we took chemotherapy combined either with NCRT or CR as sub-group for analysis, but we could not find any difference both in efficiency and side effects. Then, we divided NCRT into hyperfractionated radiotherapy (HRT),accelerated hyperfractionated radiotherapy (HART) and late course accelerated hyperfractionated radiotherapy (LCAF) sub-groups. We found that the response rate(RR,1.33;95%CI ,1.15–1.52;P<0.0001) and 1-year-survial (RR,0.46;95%CI,0.31–0.69;P=0.0002),2-year-survial(RR,0.72;95%CI,0.58 - 0.89; P=0.0003) and 3-year-survial (RR,0.81;95%CI ,0.73–0.91;P=0.0003)were significantly increased in LCAF sub-group compared to CR while the ratio of high-grade esophagitis was increased as well(RR,1.47 ;95%CI ,1.22–1.77; P<0.0001). However, HRT (RR,1.18; 95%CI ,1.07-1.30;P=0.0008)and HART (RR,1.34;95%CI,1.05–1.70;P=0.02) only could increase the response ratio but could not increase 1-year-survial, 2-year-survial and 3-year-survial compared to CR, while the risk of esophagitis was also increased. In all the above subgroups, there was no difference with regard to pneumonitis compared to CR. Conlusions:1. The present meta-analysis showed a benefit of NC to the patients with resectable NSCLC.2. Concurrent radiochemotherapy could increase the 3-year-survival of the patients with unresectable NSCLC, but increases the esophagitis as well. More trials for 5-year-survival is further needed.3. Non-conventional fractionationed radiotherapy increases the response rate and one to three-year-survival, but increases the severe esophagitis of the patients with unresectable NSCLC as well. LCAF seems to be better than the other two non-conventional fractionationed radiotherapy in the survival time for the patients. |
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