回首2018——聚焦结直肠癌
[Looking back 2018--focused on colorectal cancer].
作者信息
Cai Jian, Wang Lei
机构信息
Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.Email:
出版信息
Zhonghua Wei Chang Wai Ke Za Zhi. 2019 Jan 25;22(1):9-16.
Colorectal cancer is one of the most common malignant tumors, and its incidence and mortality are increasing year by year in China. In 2018, for the first time, the FIT-DNA test was written into the expert consensus as the recommended screening technology in China. As the core technology of colorectal cancer screening, colonoscopy for right colon cancer is further supported. With the application of artificial intelligence technology in colonoscopy, the efficiency and accuracy of screening will be greatly improved. New screening technologies represented by circulating tumor cell (CTC) and individualized screening programs based on molecular genetics are future directions. As the core of colorectal cancer treatment, surgery has become quite mature. Traditional laparoscopic surgery has become an optimal choice for colorectal cancer surgery. Open surgery, robotic surgery and single-incision laparoscopic surgery have not been found superior to multiport laparoscopic surgery. The focus of surgical research is to precisely select surgical methods, and to protect normal physiological function of patients. For example, in order to reduce complications and improve quality of life in patients undergoing rectal cancer surgery after neoadjuvant radiotherapy, the "Tianhe surgery" was invented by the authors' team. Chemotherapy as the basis of colorectal cancer treatment has shown good results in many aspects: The PRODIGE-7 trial has confirmed that systemic chemotherapy is more important for colorectal peritoneal metastasis after high quality cytoreductive surgery (CRS). While the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin does not result in the better overall survival (OS), but increases the risk of postoperative complications. The FOWARC study has found that the FOLFOX regimen (oxaliplatin and fluorouracil) achieved a 3-year disease-free survival (DFS) rate similar to that of neoadjuvant chemoradiotherapy, challenging the clinical value of radiotherapy. Although several studies have confirmed that total neoadjuvant therapy (TNT) can improve pathological complete response (pCR) rate and DFS of patients with colorectal cancer, we do not recommend unretricted expansion of chemotherapy. How to combine the clinical characteristics and molecular biological markers to select high-risk groups for chemotherapy, and how to use personalized medicine according to the genetic characteristics of patients, are also hot spots of current research. Immunotherapy is a game-changer in all aspects of colorectal cancer. In order to adapt to the immune therapy, the efficacy evaluation standard of solid tumors (iRECIST) has been revised. Immune score could redefine tumor clinical staging system. Both the Checkmate-142 study for advanced tumors and the NCT03026140 study on neoadjuvant treatment for early tumors showed promising results. Although no significant progress has been seen in the EGFR-targeted therapy and VEGFR-targeted therapy, new targeted drugs such as Eltanexor (ETLA, kpt -8602) and cobimetinib (MEK inhibitor) have been found to be effective in clinical studies. According to the detection results of tumor-related signaling pathways in patients, cross-guidance selection of targeted drug therapy is also the direction of research. Although the IWWD research results give a big blow to the "watch and wait" strategy, with the exploration of TNT plan, more accurate imaging efficacy evaluation and the application of immunotherapy, the "watch and wait" strategy will also receive new attention. In recent years, we have seen the rapid development of artificial intelligence technology. Although it is still in the exploratory stage in the field of medicine, it will certainly reshape all aspects of colorectal cancer diagnosis and treatment in the future, leading the research direction.
结直肠癌是最常见的恶性肿瘤之一,在中国其发病率和死亡率逐年上升。2018年,粪便免疫化学检测联合DNA检测首次被写入专家共识,成为中国推荐的筛查技术。作为结直肠癌筛查的核心技术,右半结肠癌的结肠镜检查得到了进一步支持。随着人工智能技术在结肠镜检查中的应用,筛查的效率和准确性将大大提高。以循环肿瘤细胞(CTC)为代表的新型筛查技术和基于分子遗传学的个体化筛查方案是未来的发展方向。作为结直肠癌治疗的核心,手术已经相当成熟。传统腹腔镜手术已成为结直肠癌手术的最佳选择。尚未发现开放手术、机器人手术和单孔腹腔镜手术优于多孔腹腔镜手术。手术研究的重点是精确选择手术方式,并保护患者的正常生理功能。例如,为了减少新辅助放疗后直肠癌手术患者的并发症并提高生活质量,作者团队发明了“天河手术”。化疗作为结直肠癌治疗的基础,在许多方面都取得了良好的效果:PRODIGE-7试验证实,对于高质量细胞减灭术(CRS)后的结直肠腹膜转移,全身化疗更为重要。虽然添加奥沙利铂的热灌注腹腔化疗(HIPEC)并未带来更好的总生存期(OS),但增加了术后并发症的风险。FOWARC研究发现,FOLFOX方案(奥沙利铂和氟尿嘧啶)的3年无病生存期(DFS)率与新辅助放化疗相似,对放疗的临床价值提出了挑战。尽管多项研究证实,全新辅助治疗(TNT)可提高结直肠癌患者的病理完全缓解(pCR)率和DFS,但我们不建议无限制地扩大化疗。如何结合临床特征和分子生物学标志物来选择化疗的高危人群,以及如何根据患者的基因特征使用个性化药物,也是当前研究的热点。免疫治疗在结直肠癌的各个方面都是一个变革者。为了适应免疫治疗,实体瘤疗效评价标准(iRECIST)已被修订。免疫评分可以重新定义肿瘤临床分期系统。针对晚期肿瘤的Checkmate-142研究和针对早期肿瘤新辅助治疗的NCT03026140研究都显示出了有前景的结果。尽管表皮生长因子受体(EGFR)靶向治疗和血管内皮生长因子受体(VEGFR)靶向治疗没有取得显著进展,但新型靶向药物如Eltanexor(ETLA,kpt-8602)和考比替尼(MEK抑制剂)在临床研究中已被发现有效。根据患者肿瘤相关信号通路的检测结果,交叉指导选择靶向药物治疗也是研究方向。尽管IWWD研究结果对“观察等待”策略造成了重大打击,但随着TNT方案的探索、更精确的影像学疗效评估和免疫治疗的应用,“观察等待”策略也将受到新的关注。近年来,我们看到了人工智能技术的快速发展。尽管它在医学领域仍处于探索阶段,但未来肯定会重塑结直肠癌诊断和治疗的各个方面,引领研究方向。