诱导化疗无效的局限期小细胞肺癌可能不宜原方案同期放化疗

Concurrent Chemoradiotherapy with Original Chemotherapy Regimens may not be Suitable for Patients Who Failed to Respond to Induction Chemotherapy in Limited-stage Small Cell Lung Cancer

背景与目的小细胞肺癌(small cell lung cancer,SCLC)具有高度化疗敏感性,耐药患者不足15%,本研究拟通过回顾性分析诱导化疗无效的局限期SCLC患者放化疗次序和放疗时机与无进展生存期(progression-free survival,PFS)及总体生存(overall survival,OS)的相关性,以探索同期放化疗是否优于序贯放化疗。方法收集2009年1月-2014年12月初治的67例诱导化疗无效的局限期SCLC,分为同期放化疗组32例与序贯放化疗组35例。94%患者临床分期为Ⅲ期,6%患者为Ⅰb期-Ⅱb期。25例行脑预防性照射(prophylactic cranial irradiation,PCI)。Kaplan-Meier法计算生存率并Log-rank法检验,组间分类数据行卡方检验。结果全组2年OS、PFS及局部控制(local control rate,LCR)分别为53.7%、20.9%和58.2%。同期放化疗组与序贯放化疗组2年OS分别为37.5%和54.3%(P=0.048)、2年PFS分别为12.5%与28.6%(P=0.149)。同期放化疗组中,13例患者(40.6%)同步化疗方案改为二线化疗方案,19例患者仍为EP或EC方案,二者2年OS分别为53.8%与26.3%(P=0.741)。同期放化疗组血液学毒性反应多于序贯放化疗组(P=0.031)、3级放射性食管炎、放射性肺炎及胃肠道反应有增多的趋势(9.4%vs 0,P=0.176;12.5%vs 2.9%,P=0.318;12.5%vs 2.9%,P=0.109)。PCI与否2年OS分别为56.0%和38.1%(P=0.029)、PFS分别为24%和19%(P=0.012)。结论诱导化疗无效的局限期SCLC可能不宜继续原方案同期放化疗,可以换用二线方案或者进行单纯放疗,由于是回顾性小样本研究,此结论还需进一步的大样本前瞻性研究证实。

Background and objective The group of small cell lung cancer （SCLC） are usually highly sensitive to chemotherapy, and less than 15% of them are resistant to drugs. We respectively evaluate the correlation of the sequence and timing of radiotherapy with progression-free survival （PFS） and overall survival （OS） in patients with limited-stage SCLC （LS-SCLC）, and to figure out whether concurrent chemoradiotherapy is superior to sequent chemoradiotherapy. Methods Sixty-seven patients diagnosed with LS-SCLC from January 2009 to June 2014 failed to respond to induction chemotherapy. According to the sequence of therapy, they were divided into concurrent chemoradiotherapy group （n=32） and sequent chemoradiotherapy group （n=35）. Ninety-four percent of the patients were diagnosed with stage Ⅲ, and six percent were stage Ib-IIb. Twenty-five patients were treated with prophylactic cranial irradiation （PCI）. The Kaplan-Meier method was used to calculate survival time and Log-rank test was used for between-group comparisons. Between-group comparison of categorical data was made byx2 test. Results In all patients, the 2-year OS, PFS and LC rates were 53.7%, 20.9% and 58.2%. The 2-year OS and PFS rates of concurrent chemoradiotherapy group and sequent chemoradiotherapy were 37.5% vs 54.3% （P=0.048） and 12.5% vs 28.6% （P=0.149）. Hematologic toxicities were more common in concurrent group than sequent one （P=0.031）, and no statistical difference was observed between the two groups in terms of grade 3 radiation esophagitis, pneumonitis and gas- trointestinal reactions （9.4% vs O, P=0.176; 12.5% vs 2.9%, P=0.318; 12.5% vs 2.9%, P=O.109）. Patients treated with PCI have superior OS and PFS comparing with those not （56.0% vs 38.1%j P=0.029; 24% vs 19%, P=O.O12）. Conclusion Concurrent chemoradiotherapy with original chemotherapy regimens may not be suitable for patients who failed to respond to induction chemotherapy in LS-SCLC, and second-line regimens or radiotherapy alone can be used for them, but prospective trils with large sample are still needed to confirm that.