中低位局部进展期直肠癌新辅助治疗与全程新辅助治疗的近期疗效和安全性比较

Comparison of short-term efficacy and perioperative safety between neoadjuvant therapy and total neoadjuvant therapy in patients with locally advanced rectal cancer

目的比较中低位局部进展期直肠癌术前采用新辅助放化疗(nCRT)和全程新辅助治疗(TNT)两种模式的近期疗效与安全性。方法采用回顾性队列研究方法。病例入组标准:(1)病理证实为距离肛缘12 cm以内的直肠腺癌;(2)经磁共振(MRI)或直肠腔内超声诊断为cT3~4N0或cT1~4N1~2者;(3)经肠镜证实为直肠单发肿瘤;(4)能够耐受放化疗;(5)既往无其他肿瘤史。排除标准:既往接受过直肠癌根治手术,此次为局部复发者;(2)不能完整完成nCRT疗程者;(3)远处转移者;(4)临床病理资料不完善者。按照上述标准,2016年1月至2019年1月期间,首都医科大学附属北京朝阳医院普通外科收治的134例直肠癌患者纳入本研究。其中男性82例,女性52例,男女比例为1.58∶1.00,年龄26~81(59.6±11.2)岁。根据患者接受的辅助治疗方案(2017年12月前为nCRT治疗,2018年1月后为接受TNT治疗),将患者分为nCRT组(55例)和TNT组(79例)。两组患者年龄、性别、肿瘤距肛缘距离、美国东部肿瘤协作组(ECOG)体力状态评分、肿瘤TNM分期等基线资料的比较,差异均无统计学意义(均P>0.05)。两组患者均采用三维适形调强放疗(IMRT),放疗剂量为50.4 Gy/28 f。nCRT组放疗期间口服卡培他滨化疗,放疗结束休息6~8周后行手术治疗。TNT组于放疗前给予CapeOX方案(奥沙利铂+卡培他滨)诱导化疗1个周期后开始同步放化疗;巩固化疗结束后2周行手术治疗。比较两组新辅助治疗疗效、放化疗不良反应发生情况以及围手术期安全性。结果两组患者均完成nCRT疗程。nCRT组和TNT组患者不良反应发生率比较,中性粒细胞减少[7.3%(4/55)比10.1%(8/79)]、贫血[3.6%(2/55)比3.8%(3/79)]、血小板减少[5.5%(3/55)比7.6%(6/79)]、胃肠功能紊乱[3.6%(2/55)比6.3%(5/79)]和放射性肠炎[9.1%(5/55)比8.9%(7/79)]发生率差异均无统计学意义(均P>0.05)。130例患者完成TME手术,nCRT组54例,TNT组76例。相比nCRT组,TNT组采用经腹会阴联合切除术(APR)的比例较高,差异具有统计学意义[31.6%(25/76)比13.0%(7/54),χ2=9.382,P=0.009],但两组术后并发症发生率以及手术时间、术中出血量、术后住院时间方面的差异也均无统计学意义(均P>0.05)。所有患者的手术远切缘和环周切缘均阴性。nCRT组pCR为7.4%(4/54),TNT组为22.4%(17/76),差异有统计学意义(χ2=5.217,P=0.022)。两组术后病理分期、神经侵犯和脉管癌栓的差异均无统计学意义(均P>0.05)。结论在中低位进展期直肠癌的治疗中,TNT在不增加放化疗不良反应和手术并发症发生率的前提下,pCR率高于nCRT。

Objective To compare the short-term efficacy and perioperative safety of neoadjuvant chemoradiotherapy(nCRT)with total neoadjuvant treatment(TNT)in patients with locally advanced rectal cancer(LARC).Methods A retrospective cohort analysis was carried out.Inclusion criteria:(1)rectal adenocarcinoma confirmed by pathology with a distance from tumor inferior border to anal verge within 12 cm;(2)clinical stage cT3-4N0 or cT1-4N1-2 diagnosed by magnetic resonance imaging(MRI)or endorectal ultrasonography;(3)a single rectal tumor confirmed by colonoscopy;(4)patients suitable for chemoradiotherapy;(5)no previous history of other tumors.Exclusion criteria:(1)patients with previous rectal cancer surgery and local recurrence;(2)those who did not complete nCRT course;(3)those with distant metastases;(4)those with defective clinicopathological data.According to the above criteria,a total of 134 LARC patients at the Department of General Surgery of Beijing Chaoyang Hospital from January 2016 to January 2019 were enrolled,including 82 males and 52 females,with a male-female ratio of 1.58∶1.00 and mean age of(59.6±11.2)(26-81)years.Based on neoadjuvant regimen,patients were divided into nCRT group(n=55)and TNT group(n=79).There were no statistically significant differences in baseline data,such as age,sex,distance from tumor to anal verge,Eastern Cooperative Oncology Group(ECOG)performance status and clinical TNM stage,between the two groups(all P>0.05).All the patients received pelvic intensity-modulated radiotherapy(IMRT)with a total dose of 50.4 Gy in 28 fractions.Patients in nCRT group received oral capecitabine chemotherapy during radiotherapy and underwent surgery 6-8 weeks after chemoradiation.Patients in TNT group received one cycle of induction CapeOX(oxaliplatin and capecitabine)and concurrent chemoradiotherapy,then underwent a radical surgery two weeks after completion of consolidation chemotherapy.The efficacy of neoadjuvant therapy,adverse events of chemoradiotherapy and perioperative safety were compared between the two groups.Results Patients of two groups completed the course of neoadjuvant therapy.There were no statistically significant differences between nCRT group and TNT group in the incidence of adverse events in neutropenia[7.3%(4/55)vs.10.1%(8/79)],anemia[3.6%(2/55)vs.3.8%(3/79)],thrombocytopenia[5.5%(3/55)vs.7.6%(6/79)],gastrointestinal dysfunction[3.6%(2/55)vs.6.3%(5/79)]and radiation enteritis[9.1%(5/55)vs.8.9%(7/79)](all P>0.05).One hundred and thirty patients completed TME surgery,including 54 patients in nCRT group and 76 patients in the TNT group.Compared with the nCRT group,the proportion of abdominoperineal resection(APR)was higher in the TNT group[31.6%(25/76)vs.13.0%(7/54),χ2=9.382,P=0.009].No statistically significant differences in morbidity of postoperative complication,operation time,intraoperative blood loss and postoperative hospital stay between the two groups were found(all P>0.05).The distal and circumferential margins were negative in all the patients.Seventeen patients in the TNT group 22.4%(17/76)got pathologic complete response(pCR),which was significantly higher than 7.4%(4/54)in nCRT group(χ2=5.217,P=0.022).There were no statistically significant differences in ypTNM classification,perineural invasion and venous invasion between the two groups(all P>0.05).Conclusion The pCR of TNT is higher than that of nCRT without increasing the incidence of toxicity and complications of radiotherapy and chemotherapy for patients with locally advanced rectal cancer.