直肠癌治疗新模式——全程新辅助治疗

全程新辅助治疗（total neoadjuvant therapy, TNT）即将直肠癌术后辅助化疗提至术前。术前进行新辅助化疗和同步放化疗,旨在提高患者化疗依从性及远期生存。国内有关该治疗模式的报道较少,本文就该模式治疗直肠癌的相关研究作一综述,以提高对直肠癌围手术期辅助治疗的认识,促进对直肠癌综合治疗模式的探索。     

直肠癌的新辅助治疗

 直肠癌的新辅助治疗包括新辅助放疗、化疗、化放疗以及分子靶向治疗。新辅助治疗可以使直肠癌退缩变小,达到降期、降级的目的,从而提高R0切除率和保肛率,降低术后局部复发率。目前的新辅助治疗未能改善患者的远期生存。新的化疗药物及方案替代传统药物5-氟尿嘧啶、术前联合应用分子靶向药物等是近年直肠癌新辅助治疗的重要进展,其临床研究的结果值得期待。     

结直肠癌肝转移的新辅助治疗进展

目前,新辅助治疗已逐步应用到结直肠癌肝转移的治疗模式中.临床研究表明,新辅助化疗、新辅助放疗和新辅助放化疗可提高结直肠癌肝转移的手术切除率和根治性,对中下段直肠癌可术前降期、提高手术切除率、保肛率和降低复发率.新辅助治疗在结直肠癌肝转移综合治疗中具有较大的临床应用价值.     

辅助化疗对ypⅠ期直肠癌患者术后生存的影响

[目的]比较Ⅰ期直肠癌与新辅助治疗后降期为ypT1-2N0M0的cT3-4或N+的直肠癌患者5年总生存率的差异.[方法]回顾分析105例直肠癌根治术后病理分期为T1～2N0M0的直肠癌患者的临床病理资料及随访资料.按患者是否行新辅助治疗和辅助化疗分为3组.单纯手术组(A组):未经术前新辅助治疗,pT1～2N0M0的早期直肠癌患者(29例).新辅助降期化疗组(B1组):初始诊断为cT3-4或N+,术前行新辅助治疗后降期为ypT1-2N0M0,且术后行辅助化疗的直肠癌患者(54例).新辅助降期非化疗组(B2组):初始诊断为cT3～4或N+,术前行新辅助治疗后降期为ypT1～2N0M0,且术后未行辅助化疗的直肠癌患者(22例).对3组生存情况进行分析.[结果]新辅助治疗后降期为T1～2N0M0的直肠癌患者(B1+B2组)术后5年生存率为94.0％.单纯手术组(A组)患者术后5年生存率为91.0％,新辅助降期化疗组(B1组)为88.9％,新辅助降期非化疗组(B2组)为90.9％.单因素分析提示3组预后差异无统计学意义(P＞0.05).[结论]新辅助治疗后降期为T1-2N0M0的直肠癌患者无论是否行术后化疗都可获得与Ⅰ期直肠癌患者相同的预后.新辅助治疗后降期为T1～2N0M0直肠癌患者术后化疗并未能提高患者5年总生存率.     

RECIST标准在进展期结直肠癌新辅助化疗CT评价上的应用价值

[目的]探讨RECIST标准在进展期结直肠癌新辅助化疗CT评价上的应用价值。[方法]选自术前行FOLFOX-6新辅助化疗2个周期、再经手术治疗的进展期结直肠癌患者65例。所有病例新辅助化疗前后均行16层螺旋CT检查。分别应用RECIST标准与WHO标准判定新辅助化疗疗效，并结合术后病理，对两者结果进行对照。[结果]不论是应用WHO标准，还是RECIST标准对进展期结直肠癌新辅助化疗疗效进行判定，均具有临床意义（P〈0．01）；应用WHO标准和RECIST标准在判定进展期结直肠癌新辅助化疗疗效上没有显著性差异（P〉0．05）；依据管壁厚度判定进展期结直肠癌新辅助化疗疗效，与依据管腔狭窄长度判断疗效，两者具有同一性（P〈0．01）。[结论]采用MSCT作为检查手段．应用RECIST标准对进展期结直肠癌新辅助化疗疗效进行评价具有明显的临床应用价值。     

MSCT曲面重建技术在评价进展期结直肠癌新辅助化疗疗效上的价值

目的:探讨MSCT曲面重建技术在评价进展期结直肠癌新辅助化疗疗效上的应用价值.方法:选自经手术治疗的进展期结直肠癌患者94例.其中,进展期直肠癌61例,进展期结肠癌33例;男59例,女35例,年龄41-77岁,中位年龄58岁.全部病例术前均行FOLFOX-6新辅助化疗2周期.所有病例新辅助化疗前后均行16或64层螺旋CT检查并均行沿病变长径的曲面重建.统计依据化疗前后病变横断面影像和病变曲面重建影像判定进展期结直肠癌新辅助化疗疗效及依据曲面重建影像上病变管壁厚度改变与长径改变判定进展期结直肠癌新辅助化疗疗效的统计学差异.结果:依据病变横断面影像、曲面重建影像判定进展期结直肠癌新辅助化疗疗效,没有明显统计学差异(P>0.05);依据曲面重建病变管壁厚度判定进展期结直肠癌新辅助化疗疗效,与依据曲面重建病变长径判断疗效具有一致性( P <0.01).结论:采用MSCT曲面重建对进展期结直肠癌新辅助化疗疗效进行评价具有明显的临床应用价值.     

新辅助化疗对直肠癌患者肿瘤标志物与疾病复发转移指标的影响

目的观察新辅助化疗对直肠癌患者肿瘤标志物与疾病复发转移指标的影响。方法选取54例直肠癌患者为研究对象,将其随机分为对照组(常规手术治疗组)27例和观察组(术前新辅助化疗组)27例,然后检测两组患者治疗前和术后不同时间的肿瘤标志物与疾病复发转移相关指标并进行比较。结果治疗前两组患者的肿瘤标志物与疾病复发转移相关指标比较,P均>0.05,而术后不同时间观察组的肿瘤标志物与疾病复发转移相关指标表达均低于对照组,P均<0.05,均有显著性差异。结论新辅助化疗可明显降低直肠癌患者的肿瘤标志物与疾病复发转移指标的表达,因此认为新辅助化疗在直肠癌患者中的应用价值较高。     

新辅助化疗、术中动脉灌注化疗对结直肠癌患者VEGF的影响

目的 探讨新辅助化疗、术中动脉灌注化疗对结直肠癌患者VEGF的影响及临床意义.方法 收集井冈山大学附属医院、南昌大学第二附属医院结直肠癌病例117例,随机分为新辅助化疗组61例、术中动脉灌注化疗组56例,健康人群36例作为空白对照组.比较各组治疗前、手术1周后VEGF水平差异.结果 健康人群组VEGF浓度明显低于结直肠癌组(P＜0.05).新辅助化疗前后VEGF无明显差别(P＞0.05),术中动脉灌注化疗后VEGF水平明显低于术前(P＜0.05).结论 新辅助化疗不能显著降低VEGF水平,术中动脉灌注化疗能显著降低VEGF水平.术中动脉灌注化疗有望降低结直肠癌术后转移、复发率,是安全有效,简单易行的.     

XELOX新辅助化疗治疗局部进展期低位直肠癌初步研究

目的 直肠癌是我国常见的消化道恶性肿瘤,25％的直肠癌患者就诊时已属中晚期,有研究表明,新辅助化疗可降低肿瘤分期,提高患者的术后生存率.本研究评估低位直肠癌患者术前行XELOX方案(奥沙利铂+卡培他滨)治疗的有效性、安全性和患者的预后.方法 收集2010-02-01-2011-10-31梁山县人民医院普外科(18例)和山东大学附属山东省肿瘤医院胃肠外科(31例)临床分期Ⅱ/Ⅲ期的低位直肠癌患者作为研究对象,随机分为新辅助化疗组(26例)和对照组(23例),新辅助化疗组术前接受3个周期的XELOX化疗后行手术治疗,对照组直接予以手术治疗.分析手术治疗的根治性切除率、化疗疗效、不良反应、术后并发症发生率和患者生存率.结果 新辅助化疗组患者化疗有效率为80.8％(21/26),临床3～4级不良事件发生率为23.1％ (6/26),手术R0切除率为92.3％,对照组手术R0切除率为69.6％,差异均有统计学意义,P＜0.05.两组患者均未发生术后吻合口瘘和肠梗阻等严重并发症.新辅助化疗组术后3、5年总生存率分别为92.3％和80.8％,对照组分别为65.2％和52.1％,差异均有统计学意义,P＜0.05.结论 XE-LOX新辅助化疗治疗低位直肠癌是可行和安全的,能够提高患者的临床受益、改善患者的生存率.     

局部进展期直肠癌新辅助化疗后病理完全缓解及肿瘤降期的预测因素分析

目的:探索局部进展期直肠癌(LARC)经新辅助化疗后病理完全缓解（pCR）和肿瘤降期（ypT0-1）的预测因素。方法:回顾性分析71例经新辅助化疗后进行全直肠系膜切除术的局部进展期直肠癌患者的临床资料,分析其临床特征,筛选经新辅助化疗后达到pCR及肿瘤降期（ypT0-1）的预测因子。结果:单因素分析结果显示肿瘤占肠腔＜1/2周（P＜0.001）、基线CEA≤5 ng/mL（P=0.001）、基线临床N分期为N0期（P=0.019）以及新辅助治疗2周期后影像评估为缓解（P=0.002）与直肠癌新辅助化疗后的高pCR率有关;肿瘤占肠腔＜1/2周（P＜0.001）、基线CEA≤5 ng/mL（P=0.029）以及新辅助治疗2周期后影像评估为缓解（P=0.007）与直肠癌新辅助化疗后的高肿瘤降期率（ypT0-1）有关。多因素Logistic回归分析结果显示,肿瘤占肠腔环周大小（P=0.013）、基线CEA水平（P=0.042）以及基线临床N分期（P=0.038）是影响直肠癌新辅助化疗后pCR的独立预测因子;肿瘤占肠腔环周大小（P=0.001）是影响直肠癌新辅助化疗后肿瘤降期（ypT0-1）的独立预测因子。结论:初始诊断时肿瘤占肠腔环周大小、基线CEA水平及淋巴结是否阳性对局部进展期直肠癌新辅助化疗后pCR有预测作用,肿瘤占肠腔环周大小对局部进展期直肠癌新辅助化疗后肿瘤降期（ypT0-1）有预测作用。     

全程新辅助治疗模式用于局部进展期直肠癌治疗的研究进展

大肠癌在全球范围内是一种发病率较高的实体性肿瘤,直肠癌手术难度大、并发症发生率高、局部复发率比较高，尤其是局部进展期直肠癌(locally rectal cancer，LAＲC)治疗效果较差，随着多学科综合治疗理念在直癌中的应用,特别是新辅助放化疗应用于局部进展期直肠癌的治疗,患者的治疗效果得到改善,局部进展期直肠癌领域是目前研究的重点和热点之一,本文对目前最新的2018年美国NCCN直肠癌肿瘤学临床实践指南中局部进展期直肠癌新辅助同步放化疗、新辅助短程放疗、全程新辅助治疗(total neoadjuvant therapy,TNT)的模式进行综述。     

Advances in multidisciplinary treatment of rectal cancer

To summarize the advances in the multidisciplinary treatment of rectal cancer and to analyze the existing problems and development prospects. The full text database retrieval system of MEDLINE and the periodicals of CHKD were searched. The words ＂rectal cancer, diagnosis, surgery, chemotherapy, radiotherapy, targeted therapy, analysis＂ were used as key words for retrieval of literature concerning the values and clinical significance of rectal cancer multidisciplinary treatment from January, 2000 to December, 2007. Thirty papers were selected, of which 26 were used in analysis at last. Accurate preoperative staging of rectal cancer is a key factor in the multidisciplinary and comprehensive treatment of patients. A new therapy which is combined with radical operation can reduce the rate of local recurrence, prolong survival time, and particularly, promote the rate of sphincter preservation. Radical surgery combined with adjuvant therapy is still recognized as standard treatment modality for the patients with rectal cancer in stage Ⅱ-Ⅲ. Total removal of resectable metastases followed by prompt standard adjuvant therapy may extend survival time. The introduction of new chemical drugs, drugs of targeting therapy, and a regimen of combination therapy may improve outcomes in treatment for rectal cancer patients. A treatment standard for rectal cancer patients needs to be actively pursued. Compared with colon cancer patients, there has not been sufficient evidence to confirm that the total survival rate of rectal cancer patients after multidisciplinary and comprehensive treatments has been improved; therefore, it needs to be further studied.     

The present situation regarding postoperative adjuvant chemotherapy

The purpose of postoperative adjuvant chemotherapy is to achieve a higher or rate of surgical radical cure and to eliminate recurrence of cancer. There are many differences between colon cancer and rectal cancer. Recurrence of colon cancer almost always metastasizes to liver and lung Adjuvant chemotherapy is indicated for stage III and high risk stage II. Standard adjuvant chemotherapy is a combination of Leucovorin and 5-FU, or a combination of oxaliplatin, 5-FU and Leucovorin. Combination treatment with VEGF antibody and EGFR antibody has shown no evidence of effectiveness in adjuvant chemotherapy. In rectal cancer, radiation is the standard form of neoadjuvant therapy. In the future, treatment of colorectal cancer may make remarkable improvement with the introduction of new drugs.     

An overview of approaches to adjuvant therapy for colorectal cancer in the United States

Adjuvant chemotherapy for colon cancer and combined chemotherapy and radiation therapy (RT) for rectal cancer increases the proportion of patients cured of their disease. Adjuvant chemotherapy is indicated for stage III colon cancer, and although controversial for stage II disease, there is evidence to suggest that these patients may benefit as well. Adjuvant chemotherapy and RT is recommended for patients with stage II/III rectal cancer. Studies incorporating oral fluoropyrimidines as well as combination chemotherapy have been completed, with results demonstrating the value of these approaches. A new generation of studies will evaluate the biologic agents bevacizumab and cetuximab in the adjuvant therapy of colorectal cancer. For rectal cancer, optimal outcomes are dependent not only on the systemic therapy, but also on the expertise of the surgeon and the timing of RT, with improved local control and toxicity seen with preoperative therapy.     

Progress in adjuvant therapy for colorectal cancer

The progress and role of adjuvant therapy for resectable colorectal cancers are reviewed herein. 5-FU/leucovorin is considered the standard treatment in the postoperative adjuvant chemotherapy for Dukes'C colon cancer. The oral 5-FU prodrugs, such as UFT and capecitabine, will replace 5-FU infusion in the adjuvant chemotherapy in the near future. In Dukes'B colon cancer, the results of postoperative adjuvant chemotherapy are controversial. Many randomized trials in the USA and Europe have demonstrated that pre- or postoperative radiation therapy for rectal cancer decreases local recurrences but has no additional benefit on survival compared with 5-FU-based adjuvant chemotherapy. Adjuvant radiation therapy for rectal cancer is not widely used in Japan, while chemotherapy is considered the adjuvant treatment of choice. The local recurrences of rectal cancer is a surgeon-related phenomenon: the surgical technique used and the skill of the surgeon are major factors influencing outcome.     

The use of capecitabine in the combined-modality therapy for rectal cancer

Locally advanced rectal adenocarcinoma is treated by combined-modality therapy, which consists of surgery, chemotherapy, and radiation therapy. A series of randomized trials established a preferred treatment sequence of preoperative radiation therapy and 5-fluorouracil(5-FU)-based chemotherapy, total mesorectal excision, and adjuvant 5-FU-based chemotherapy for patients with stage II/III disease. Capecitabine is an oral prodrug of 5-FU that has potential advantages compared with intravenous 5-FU, including ease of administration and potentially increased therapeutic effect. Capecitabine is converted by a 3-step enzymatic process; the last step involves the enzyme thymidine phosphorylase, which is overexpressed in tumor tissues and is stimulated by concurrent radiation therapy. Over the past 5 years, several phase I/II trials of capecitabine-based therapy were reported. This review discusses the evolution of combined-modality therapy for rectal cancer with specific attention given to the use of capecitabine in conjunction with radiation therapy.     

An organized multi-institutional interdisciplinary evaluation of role of radiation therapy alone or combined with chemotherapy in treatment of adenocarcinoma of the gastrointestinal tract

Adenocarcinomas of the gastrointestinal tract have generally been considered to be radioresistant. In 1974-1975, following an early lead from the Mayo Clinic (Rochester, MN), the Gastrointestinal Tumor Study Group initiated a series of clinical trials of radiation therapy and chemotherapy as surgical adjuvant programs for patients with pancreatic and rectal cancer and for the treatment of locally unresectable gastric and pancreatic adenocarcinomas. The first protocols for pancreatic cancer included a controlled trial of radiation therapy and chemotherapy following pancreatoduodenectomy or total pancreatectomy and also a randomized trial of high-dose radiation therapy, with or without chemotherapy, compared to a lower dose of radiation therapy combined with chemotherapy for patients with locally unresectable tumors. In the treatment of locally incurable gastric cancer, radiation therapy plus chemotherapy was compared to chemotherapy alone, while the rectal trial was a randomized comparison of radiation therapy; chemotherapy; the combination of radiation therapy and chemotherapy; and no further treatment following surgical extirpation. In all cases, the agent used during the course of radiation was 5-fluorouracil. Subsequent trials in pancreatic cancer compared radiation combined with either 5-fluorouracil or doxorubicin and included a pilot study of hyperfractionated radiation therapy combined with 5-fluorouracil. Confirmatory trials were undertaken and are still under analysis in gastric cancer and in rectal cancer. A follow-up trial in pancreatic cancer was developed to establish the importance of the radiation therapy component of combined modality therapy in the treatment of patients with locally unresectable disease. A final study examined the potential for radiation therapy of the liver and systemic chemotherapy in the prevention of metastatic adenocarcinoma of the colon.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adjuvant Chemotherapy for Rectal Cancer After Neoadjuvant Treatment: FOLFOX, 5-FU,or Observation

A multimodality approach incorporating concurrent chemotherapy with radiotherapy prior to surgery has become the standardized approach in the management of localized rectal cancer. However, it is unknown whether any further therapy after surgery may be beneficial in improving patient outcomes. Previous completed randomized clinical trials have not added any clarity in this regard, whether adjuvant chemotherapy or intensified chemotherapy regimens improve patient outcomes in those who have previously received neoadjuvant therapy. Despite the lack of evidence, based off the survival data in stage III colon cancer, adjuvant chemotherapy has become a standardized practice in the management of resected rectal cancer. Furthermore, recommendations include the consideration of added oxaliplatin to adjuvant therapy in this disease. While it is unclear whether all patients should receive adjuvant chemotherapy, a subset of patients, including those who achieve a pathologic response may benefit from further treatment. Ongoing studies utilizing an individualized, stepwise multimodality approach may define the role of adjuvant therapy and the appropriate regimen in patients with resected rectal cancer.     

Surgical management of rectal cancer

Rectal cancer affects more than 40,000 people in the United States annually. Despite recent advances in radiation and chemotherapy, surgical resection remains an integral part of curative therapy for this disease. Although rectal cancer is thought to be biologically similar to colon cancer, the anatomic complexity of the pelvis makes therapy for this disease considerably more complicated. Local recurrence is also a greater concern in rectal cancer than in colon cancer. The choice of surgical therapy depends on the location of the tumor, depth of rectal wall invasion, and clinical stage. Surgical options include local excision (transanal excision and transanal endoscopic microsurgery) and radical resection (low anterior resection, extended low anterior resection with coloanal anastomosis, abdominoperineal resection [APR], and pelvic exenteration). Technical advances such as transanal endoscopic microsurgery and laparoscopy also are changing the surgical approach to rectal tumors. Finally, chemotherapy and radiation are now frequently recommended in conjunction with surgical therapy. This article reviews the current surgical approach to treating patients with rectal cancer.