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.     

全程新辅助治疗在直肠癌治疗中的意义

跟随时代变迁的脚步,结直肠癌（CRC）的发病率呈现出多差异性和新龄化。在CRC总发病率中直肠癌占比约1/2,且绝大数患者初诊时多为局部晚期直肠癌（LARC）。术前放化疗（NCRT）联合全直肠系膜切除术（TME）+辅助化疗（ACT）是LARC标准治疗方案,这种诊疗模式使局部复发率有了可观的控制。然而,远处转移仍是这部分患者死亡的重要原因。NCRT和术后辅助化疗在临床上虽被普遍推荐,但由于依从性差和生存率不一,ACT这一全身治疗的价值仍是个谜团。因此,目前大量全球试验的研究主题偏向于直肠癌术前化疗的潜力,其中全程新辅助治疗（TNT）就应时而生。该模式体现了新辅助化疗具有更优的病理缓解率（pCR）、降期率、安全性等优势。     

直肠癌的新辅助治疗

近年来,直肠癌发病率逐年上升,随着新辅助治疗的提出与应用,直肠癌的疗效得到提升,引起国内外学者的关注。新辅助治疗包括术前放疗、术前化疗和术前同步放化疗。其中术前放疗方式可分为短程放疗和常规放疗,通过比较T降期率、保肛率、完全缓解率等指标,对两种方式的临床效果进行了评价。尽管单纯术前化疗的经验还不够丰富,但其仍在降低肿瘤分期等方面具有优势。目前,临床应用最多的为术前同步放化疗,且国内外学者均认为该方式在治疗直肠癌时具有明显优势,同时,三维放疗技术可使靶区分布更为均匀,对病灶治疗更为精准。但直肠癌的新辅助治疗在国内却尚未广泛应用于临床,对其临床效果的确定仍需进一步的理论支持,本文就直肠癌的新辅助治疗做一综述。     

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。     

结直肠癌的新辅助治疗

新辅助治疗在提高可切除性结直肠癌患者的手术率和生存率方面取得一些可喜结果。以奥沙利铂、依立替康为基础联合化疗,在提高转移性结直肠癌患者手术率与生存率疗效已较为肯定。肝动脉介入治疗(如HAI、TACE等)在新辅助治疗中的应用疗效有待进一步研究。术前PVE和两步肝切除术可提高手术安全性和切除率。     

局部进展期直肠癌新辅助治疗研究进展

直肠癌是常见的消化道恶性肿瘤，手术难度大，术后并发症较为常见，局部复发率较高，尤其以局部进展期直肠癌(LARC)的治疗效果差。随着多学科综合治疗理念在恶性肿瘤诊疗过程中受到重视，局部进展期直肠癌患者的预后也在术前新辅助治疗的应用下得以改善。因新辅助放化疗能有效降低术后局部复发率，新辅助放化疗联合全直肠系膜切除术(TME)已成为局部进展期直肠癌国际公认的治疗模式，临床医生也逐渐重视该疾病的术前治疗。为探求更佳的直肠癌患者的综合治疗方案，通过阅读国内外相关文献，就直肠癌新辅助治疗的现状与研究进展进行综述。     

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.     

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.     

直肠癌新辅助放化疗

根治性手术结合术后放、化疗一度被作为国际公认的Ⅱ及Ⅲ期直肠癌的标准疗法。近年,新辅助放化疗逐渐得到广泛的关注。大量研究表明,与术后放化疗相比,新辅助放化疗结合根治性手术的多模式联合治疗在降低直肠癌的局部复发率、延长生存时间等方面均显示出更好的效果,特别是在提高保肛率方面具有突出的优势。目前认为,新辅助放化疗适用于局部进展期(T3~4)或有系膜内淋巴结转移的低位直肠癌患者(Ⅱ~Ⅲ期)。随着先进的诊断技术、更优化的放疗模式,以及更多有效的药物及新配伍方案的引入,对直肠癌患者采取个体化的术前新辅助治疗,将使直肠癌的治疗效果得到进一步提高。     

结直肠癌辅助治疗现状

在过去的20年结直肠癌辅助治疗有很大改进。辅助性放化疗已成为结直肠癌综合治疗的重要组成部分。本文综述了结直肠癌术后辅助化疗、术前、术后辅助放疗、免疫治疗、局部门静脉灌注化疗的现状。     

直肠癌同步放化疗与辅助化疗

辅助及新辅助治疗是直肠癌最重要的综合治疗手段,新辅助同步放化疗和术后辅助化疗在直肠癌治疗中起着至关重要的作用。一些新的化疗和靶向药物的出现可以进一步改善直肠癌的治疗效果。     

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.     

功能成像技术对局部晚期直肠癌新辅助治疗预测与评估价值

对于局部晚期直肠癌,新辅助放化疗后行手术切除,再行术后辅助化疗,已发展为标准治疗模式。新辅助治疗可使肿瘤病灶发生不同程度的退缩,部分患者术后病理证实达到完全缓解,有助于增加直肠癌患者根治性手术概率,并降低复发率,改善患者的远期预后。近年来,新辅助治疗疗效的预测和评估,成为临床医生关注的焦点。在影像学方面,常规的形态成像技术,不能够准确反映新辅助放化疗后肿瘤治疗效果,而DWI-MRI、DCE-MRI、PET-CT等功能成像技术不仅能够反映肿瘤退缩程度,还可以反映治疗前后肿瘤功能代谢方面的变化,因而更为准确。现对直肠癌新辅助放化疗影像学疗效评价方法的应用现状进行综述。     

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.     

Pathological Complete Response After Neoadjuvant Therapy for Rectal Cancer and the Role of Adjuvant Therapy

Both the addition of neoadjuvant chemoradiation therapy and improvements in surgical techniques have improved local control and overall survival for locally advanced rectal cancer patients over the past few decades. The addition of adjuvant chemotherapy has likely improved outcomes as well, though the contribution has been more difficult to quantify. At present, the majority of resected locally advanced rectal cancer patients receive adjuvant chemotherapy, though there is great variability in this practice based on both patient and institution characteristics. Recently, questions have been raised regarding which sub-groups of patients benefit most from adjuvant chemotherapy. As pathologic complete response (pCR) is increasingly found to be a reasonable surrogate for long-term favorable outcomes, some have questioned the need for adjuvant therapy in this select group of patients. Multiple retrospective analyses have shown minimal to no benefit for adjuvant chemotherapy in this group. Indeed, the patients most consistently shown to benefit from adjuvant therapy both in terms of disease free survival (DFS) and overall survival (OS) are those who achieve an intermediate pathologic response to neoadjuvant treatment. Tumors that have high expression of thymidylate synthetase have also shown to benefit from adjuvant therapy. More study is needed into clinical and molecular features that predict patient benefit from adjuvant therapy.     

直肠癌的新辅助治疗

为了保留肛门、减少复发、延长生存,新辅助化放疗已成为直肠癌治疗的重要组成部分.本文详细论述了直肠癌新辅助治疗的发展和现状.探讨了新辅助放疗、新辅助放化疗与单纯手术及辅助化放疗相比的优劣.     

Cancer du rectum et chimiothérapie adjuvante : quelles conclusions ?

Adenocarcinoma of the rectum represents about a third of cases of colorectal cancer, with an annual incidence of 12,000 cases in France. On the contrary of colon cancer, the benefice of adjuvant chemotherapy in rectal cancer has not been definitively proved, more because this question was assessed in few recent studies than because negative results. Preoperative radiochemotherapy is now the reference treatment for mid and lower rectal cancers, and allow to increase the local control without improvement of progression free survival and overall survival. The data of the “historical studies” of adjuvant treatment in rectal cancer published before 1990, of the meta-analysis of adjuvant trials in rectal cancer and of the QUASAR study suggest that adjuvant chemotherapy with fluoropyrimidines (intravenous or oral), in absence of pre-operative treatment, decrease the risk of metastatic relapse after curative surgery for a rectal cancer of stage II or III. This benefice seems similar to the one observed in colon cancer. In the EORTC radiotherapy group trial 22921, an adjuvant chemotherapy with 5-fluorouracil and low dose of leucovorin was not associated with a significantly improvement of overall survival but, despite the fact that only 42.9% of patients received all planed cycles, the progression free survival was increased (not significantly) in groups receiving adjuvant chemotherapy. The French recommendations are to discuss the indication of adjuvant chemotherapy by fluoropyrimidines in cases of stage III rectal cancer on histopathologic reports and no chemotherapy in case of stade II. Despite the fact that none study have assessed a combination of fluoropyrimidines and oxaliplatin in adjuvant setting in rectal cancer, like in colon cancer, the Folfox4, modified Folfox6 or Xelox regimens are valid options in stage III (experts opinion). In cases of pathologic complete remission or in absence of involved nodes, the benefice of adjuvant chemotherapy is not assessed. In all cases, the decision of adjuvant chemotherapy has to be taken during a multidisciplinary meeting. The interest of a combination of fluoropyrimidine and oxaliplatin is assessed in currently adjuvant trials (PETTAC-6 and CAO/ARO/AIO-04), and future trials will assess the interest of neoadjuvant chemotherapy.     

Current State of Neoadjuvant Radiotherapy for Rectal Cancer

Colorectal cancer is the third most commonly diagnosed cancer, with rectal cancer accounting for 30% of cases. The current standard of care curative treatment for locally advanced rectal cancer is (chemo)radiotherapy followed by surgery and adjuvant chemotherapy. Although neoadjuvant radiotherapy has reduced the risk of local recurrence to less than 10%, the risk of distant metastasis remained high at 30% affecting patient survival. In addition, there is a recognition that there is heterogeneity in tumor biology and treatment response with good responders potentially suitable for treatment de-escalation. Therefore, new treatment sequencing and regimens were investigated. Here, we reviewed the evidence for current neoadjuvant treatment options in patients with locally advanced rectal adenocarcinoma, and highlight the new challenges in this new treatment landscape.     

直肠癌的辅助放化疗的临床研究

直肠癌是常见的消化道恶性肿瘤，手术是直肠癌的主要治疗手段，放化疗对可手术直肠癌是重要的辅助治疗手段。无论术前或术后放疗均可提高局部控制，术前放疗可增加保肛的机率，放疗的方式以常规分割较佳。术后放疗在中度复发危险的患者中对生存的影响与化疗相似，但需要两者对局控的资料。本文综述的是术前放疗、术后放疔以及术前与术后放疗的比较。