联合贝伐珠单抗的新辅助治疗对局部晚期直肠癌的疗效与安全性分析

Analysis of efficacy and safety of neoadjuvant therapy combined with bevacizumab for locally advanced rectal cancer

背景与目的:目前,手术仍是结直肠癌的主要治疗方式,而新辅助治疗能够将最初不可切除的病变转化为可切除的病变,改善患者预后。贝伐珠单抗联合化疗对于晚期转移性结直肠癌有较好的疗效,但是否将贝伐珠单抗常规用于潜在可切除的转移性结直肠癌患者新辅助治疗仍有争议。因此,本研究探讨局部晚期直肠癌(LARC)患者接受联合贝伐珠单抗的新辅助治疗的效果与安全性。方法:回顾性分析2021—2022年吉林省肿瘤医院结直肠胃腹部肿瘤外一科行联合应用贝伐珠单抗的新辅助治疗的LARC患者临床资料。结果:共纳入45例患者,其中26例行XELOX(奥沙利铂联合卡培宾)+贝伐珠单抗的新辅助治疗方案(化疗+贝伐珠单抗组),19例行放疗同步XELOX联合贝伐珠单抗序贯治疗的新辅助方案(放化疗+贝伐珠单抗组)。术前影像学评估显示,两组患者肿瘤缓解率分别为84.61%和94.74%,疾病控制率均为100.0%;两组患者CEA、CA19-9的指标均较治疗前明显下降(均P<0.05)。手术及术后病理评估中,化疗+贝伐珠单抗组所有患者均进行了Dixion切除+D2淋巴结清扫,其中的10例患者进行了预防性回肠造口;术后病理显示,平均淋巴结清扫18.3枚,转移淋巴结2.1枚;肿瘤退缩分级(TRG)0级2例(7.69%)、1级8例(30.77%)、2级10例(38.46%)、3级6例(23.08%)。放化疗+贝伐珠单抗组中15例患者实施了Dixion切除+D2淋巴结清扫,2例患者实施了Miles手术,1例患者因困难骨盆且盆腔粘连严重无法实施手术治疗,1例患者因盆底粘连严重术中探查无法切除,15例进行Dixion手术的患者均实施了预防性回肠造口手术;术后病理显示,平均淋巴结清扫18.5枚,转移淋巴结1.6枚;TRG 0级2例(10.53%)、1级7例(36.84%)、2级6例(31.58%)、3级2例(10.53%)。两组患者的手术标本显示,肿瘤上下切缘及环周切缘均为阴性,无肿瘤残留。全组共55例次经历了新辅助治疗相关的不良事件,所有的不良反应评估均为1~2级,不影响后续治疗。结论:对于LARC患者,联合贝伐珠单抗的新辅助治疗安全有效,治疗中可以选择贝伐珠单抗联合化疗,同时根据肿瘤位置选择进行放疗或不进行放疗,提高根治性手术切除概率,增加了保肛机会。

Background and Aims:Currently,surgery remains the primary treatment for colorectal cancer,while neoadjuvant therapy can transform initially unresectable lesions into resectable ones,improving patient prognosis.Bevacizumab combined with chemotherapy has shown promising efficacy for advanced metastatic colorectal cancer;however,the routine use of bevacizumab in neoadjuvant therapy for potentially resectable metastatic colorectal cancer patients remains controversial.Therefore,this study was performed to investigate the efficacy and safety of bevacizumab combined neoadjuvant therapy in patients with locally advanced rectal cancer(LARC).Methods:The clinical data of LARC patients who received bevacizumab-combined neoadjuvant therapy in the Department of Colorectal and Gastrointestinal Oncology,Jilin Cancer Hospital,from 2021 to 2022,were retrospectively analyzed.Results:A total of 45 patients were included,of whom 26 received the XELOX(oxaliplatin combined with capecitabine)+bevacizumab neoadjuvant regimen(chemotherapy plus bevacizumab group),and 19 received radiotherapy concurrent with XELOX and sequential bevacizumab neoadjuvant treatment(chemoradiotherapy plus bevacizumab group).Preoperative imaging evaluations showed tumor response rates of 84.61%and 94.74%,respectively,with a disease control rate of 100.0%in both groups.The CEA and CA19-9 levels significantly decreased compared to their pre-treatment levels in both groups(both P<0.05).In the chemotherapy plus bevacizumab group,all patients underwent Dixion resection with D2 lymphadenectomy,with 10 patients receiving preventive ileostomy.Postoperative pathology showed an average of 18.3 lymph nodes removed,with 2.1 metastatic nodes;tumor regression grade(TRG)was 0 in 2 cases(7.69%),1 in 8 cases(30.77%),2 in 10 cases(38.46%),and 3 in 6 cases(23.08%).In the chemoradiotherapy plus bevacizumab group,15 patients underwent Dixion resection with D2 lymphadenectomy,2 patients underwent Miles surgery,1 patient was unable to undergo surgery due to severe pelvic adhesions,and another was unable to have resection due to pelvic floor adhesions found during surgery.Preventive ileostomy was performed in all 15 patients who had Dixion surgery.Postoperative pathology showed an average of 18.5 lymph nodes removed,with 1.6 metastatic nodes;TRG was 0 in 2 cases(10.53%),1 in 7 cases(36.84%),2 in 6 cases(31.58%),and 3 in 2 cases(10.53%).Surgical specimens in both groups showed negative proximal and distal margins,with no tumor residuals.A total of 55 neoadjuvant therapy-related adverse events occurred,all graded 1-2,without affecting subsequent treatment.Conclusion:For LARC patients,bevacizumab-combined neoadjuvant therapy is safe and effective.Bevacizumab combined with chemotherapy can be selected,with radiotherapy as an option based on tumor location,to increase the probability of radical resection and sphincter-preserving opportunities.