局部进展期中低位直肠癌患者术前同期加量调强放疗联合化疗的疗效观察

Preoperative simultaneous integrated boost intensity-modulated radiotherapy combined with chemotherapy in treatment of locally advanced mid/low rectal cancer

目的观察中低位局部进展期直肠癌患者术前同期加量调强放疗联合希罗达化疗的临床可行性、安全性及疗效。方法解放军总医院第一医学中心放疗科于2012年2月-2013年5月入组19例临床诊断为cT2-3N+M0直肠腺癌患者,行新辅助同期加量调强放疗(simultaneous integrated boost intensity-modulated radiation therapy,SIB-IMRT)联合希罗达同步化疗。放疗剂量分割模式:直肠原发肿瘤及盆腔转移淋巴结(pGTV)照射56.25 Gy/25次(2.25 Gy/次),高危复发区域和区域淋巴引流区(PTV)照射50 Gy/25次(2.0 Gy/次)。希罗达用量为825 mg/m2,2次/d,5 d/周,共5周。放化疗结束后6~10周行全直肠系膜切除术(total mesorectal excision,TME)。研究主要结局指标为病理完全缓解率、保肛率,及3年、5年、7年的总生存(overall survival,OS)、局部复发率(local recurrence rate,LRR)、远处转移率(distant metastasis rate,DMR)、无病生存(disease-free survival,DFS)。次要结局指标为急性期及晚期不良反应、TN降期率、围术期并发症。结果19例患者中位年龄为57(34~70)岁,其中女性3例,男性16例。19例均完成同步放化疗及TME手术,早、晚期不良反应均为1~2级,未见3~4级严重不良反应。病理完全缓解率21.1%(4/19),保肛率73.7%(14/19),R0切除率100%,TN降期率66.7%(20/30)。围术期并发症发生率15.8%(3/19),分别为粘连性肠梗阻、结扎线脱落、直肠阴道瘘各1例。3年OS、LRR、DMR、DFS分别为94.4%(17/18)、5.1%(1/18)、0、94.4%(17/18);5年OS、LRR、DMR、DFS分别为88.2%(15/17)、10.5%(2/17)、5.3%(1/17)、88.2%(15/17);7年OS、LRR、DMR、DFS分别为82.3%(14/17)、15.8%(3/17)、10.5%(2/17)、82.3%(14/17)。结论局部进展期中低位可手术切除直肠癌行术前SIB-IMRT联合化疗,获得较满意的病理完全缓解率、保肛率及3年、5年、7年OS、LRR、DMR、DFS,未见3~4级不良反应,耐受性好,未增加围术期并发症发生率,安全可行。

Objective To evaluate the feasibility,safety and efficacy of preoperative intensity-modulated radiotherapy (IMRT) with oral xeloda in patients with locally advanced mid/low rectal cancer using a simultaneous boost technique.Methods From August 2012 to May 2013,a total of 19 consenting operable patients with stageⅡorⅢadenocarcinoma of the rectum admitted to the First Medical Center of Chinese PLA General Hospital were enrolled in this study.All patients received xeloda (825 mg/m^2 po bid,5 days/week for 5 weeks),and IMRT 50 Gy (2.0 Gy/fraction) was performed in 25 fractions to the pelvic lymph node stations with a simultaneous integrated boost (SIB) of 56.25 Gy (2.25 Gy/fraction) to the rectal tumor and pelvic lymph node metastasis in 25 fractions.All patients were planned to receive a total mesorectal excision after the completion of CRT 6-10 weeks later.Pathological complete response rate (pCR),sphincter preservation rate,overall survival (OS),local recurrence rate (LRR),distant metastasis rate (DMR) and disease-free survival (DFS) were the primary endpoint.The secondary endpoints included acute and late toxicity,tumor down-staging rate and postoperative complication.Results The age of 19 patients ranged from 34 to 70 years old,with a median age of 57 years,and there were 3 females and 16 males.All patients completed a full-dose chemoradiotherapy as planning and then went on to surgical resection.The majority short-term and long-term adverse reactions were grade 1 or 2,and no grade 3-4 adverse event was observed.pCR rate was 21.2% (4/19),the sphincter-preserving rate was 73.3% (14/19),the tumor downstaging rate was 66.7% (20/30) and the R0 resection rate was 100%.Postoperative complications incidence rate was 15.8% (3/19),including 1 case of adhesive intestinal,1 case of obstruction delayed wound healing and 1 case of rectovaginal fistula.The 3-year OS,LRR,DMR,DFS were 94.4% (17/18),5.1% (1/18),0,94.4% (17/18),respectively,and they were 88.2% (15/17),10.5% (2/17),5.3% (1/17),88.2% (15/17) for 5-year,and 82.3% (14/17),15.8% (3/17),10.5% (2/17),82.3% (14/17) for 7-year.Conclusion Preoperative chemoradiation with capecitabine and SIB-IMRT is well tolerated and results in an encouraging pCR rate,anal sphincter operation rate,post-operative complications rate and OS,LRR,DMR,DFS for patients with locally advanced rectal cancer.