Meta分析：局部晚期非小细胞肺癌同期化放疗 VS 序贯化放疗

2010年，NSCLC协助组的一项Meta分析共纳入了6个对比序贯与同步放化疗在Ⅲ期NSCLC疗效的临床研究，结果显示，与序贯放化疗比较，同步放化疗显著改善患者的OS，3年生存率从18.1%提高至23.8%，
5生存率从10.6%提高至15.1%。同步放化疗也显著改善了患者的PFS，并显著降低局部进展风险。
3级以上食管炎增加了14%（4%-18%），但晚期食管炎无差别。
因此与序贯放化疗相比，同步放化疗可提高局部晚期NSCLC患者的生存率，但代价是可控制的急性食管毒性增加。

包含了6项“比较同步放化疗与序贯放化疗治疗LA-NSCLC”的随机研究，共1205例患者，中位随访时间6年时，同步放化疗与序贯放化疗的OS有显著差异（见图5） (HR, 0.84; 95%CI,0.74~0.95; P =0 .004)，5年绝对生存获益提高了4.5%（10.6%~15.1％），3级以上食管炎增加了14%（4%~18%），但晚期食管炎无差别。因此与序贯放化疗相比，同步放化疗可提高局部晚期NSCLC患者的生存率，但代价是可控制的急性食管毒性增加。




To build upon the results of trials such as CALGB 8433 that demonstrated an improvement in overall survival associated with adding chemo- therapy to radiation therapy in locoregionally advanced non-small cell lung cancer, multiple prospective randomized trials evaluated sequen- tial versus concomitant radiochemotherapy for such patients. The Non-small Cell Lung Cancer Collaborative Group performed a meta-analysis of these trials to study the effects on survival and treatment-related morbidity. Their analysis is based on 6 trials that included 1205 patients.

Key Point Overall survival was significantly improved with concurrent versus sequential radiochemotherapy (HR, 0.84; 95% CI, 0.74 to 0.95; P = 0.004). The absolute survival improve- ment was 5.7% at 3 years and 4.5% at 5 years
(Table 3.3).

Key Point  There  was  a  significant  decrease  in locoregional progression rates with concurrent versus sequential radiochemotherapy (HR, 0.77; 95% CI, 0.62 to 0.95; P = 0.01). The 3-year rates of locoregional progression were 28.1% and 34.1%, and 5-year rates were 28.9% and 35% with concurrent and sequential treatment, respectively.

Table 3.3 Overall survival with concurrent and sequential radiochemotherapy at 3 and 5 years

Overall  survival (%)	Concurrent  radiochemotherapy	Sequential  radiochemotherapy
3 years	23.8%	18.1%
5 years	15.1%	10.6%

There was no difference in distant failure rates between the regimens.
An increased rate of acute grade 3 and 4 esophageal toxicity was observed in the concur- rent versus sequential chemoradiation regimens (18 versus 4%).

In summary, this meta-analysis demonstrated an improved overall survival with concurrent ver- sus sequential radiochemotherapy in patients with locoregionally advanced (nonmetastatic) non-small cell lung cancer. This benefit in overall survival was likely due to improved locoregional control since there was no different in distant fail- ure rates between the arms of the trial. Moreover, the gain in overall survival was obtained with an acceptable toxicity profile. Improvements in imaging and radiation therapy techniques, as well as careful attention to esophageal dose-volume histogram guidelines, may allow reductions in esophageal toxicity. Auperin et al. concluded that, “concomitant radiochemotherapy should be considered as the reference treatment for future trials testing new combined treatment approaches integrating the recent developments in three- dimensional conformal radiotherapy.”

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Aupérin A, Le Péchoux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, Yamanaka T, Bozonnat MC, Uitterhoeve A, Wang X, Stewart L, Arriagada R, Burdett S, Pignon JP. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010 May 1;28(13):2181-90. doi: 10.1200/JCO.2009.26.2543. Epub 2010 Mar 29. PMID: 20351327.

• Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer - PubMed (nih.gov)