直肠癌围手术期的辅助治疗

直肠癌发病率和死亡率仍不断上升，而外科治疗效果近30年提高并不显著，加上患者多要求保肛，单靠手术难以进一步提高生存率和生活质量，只能谋求多学科综合治疗。现结合国内外有关文献，介绍直肠癌围手术期的辅助治疗，即术前放疗、术中放疗、术后放疗和术后放化疗；术后化疗和术中化疗。     

术前放疗对可切除直肠癌患者远期生存影响的荟萃分析

目的 评估术前放疗对可切除直肠癌患者远期生存率的影响,探讨术前放疗在可切除直肠癌患者中的临床应用价值.方法 通过在Pubmed及CNKI数据库中检索＂术前放疗＂和＂直肠癌＂的相关研究,抽取及计算直肠癌术前放疗与单纯手术生存率的比值比（OR）和95% CI,运用荟萃分析估算汇总的OR值及95% CI,并对纳入的研究进行分层分析及发表偏倚的检验.结果 发表于1990年至2013年间的17篇文献纳入到本研究中,包括4 489例术前放疗患者和4 521名单纯手术患者,术前放疗的总剂量在15~50 Gy之间.和单纯手术组比较,术前放疗可显著延长直肠癌术后患者的生存时间,汇总后OR值为1.18（95% CI为1.08~1.29）.分层分析显示在亚洲人群和使用常规分割放疗方式,术前放疗在延长直肠癌术后患者的生存时间方面,未显示出明显的统计学意义.结论 直肠癌根治术前辅助放疗可提高可切除直肠癌患者的远期生存率,具有较高的临床应用价值.     

直肠癌术前放疗的疗效观察

目的 观察直肠癌术前放疗的临床效果。方法 对28例直肠癌病人进行术前放疗，观察肿块变化情况，不良反应，进行术后随访等。结果 放疗后肿块缩小，保肛率提高、局部复发率降低。结论 术前放疗可以减少复发率，提高切除率，增加保肛率，为直肠癌综合治疗的较佳方式。     

直肠癌术前和术中放疗的探讨

直肠癌术前和术中放疗的探讨柴志康１章青１徐钧１彭莉华１刘泰福２关键词直肠癌术前放疗术中放疗作者单位：１．上海市第六人民医院（上海２００２３３）２．上海医科大学附属肿瘤医院直肠癌是我国发病率高，术后局部复发率与区域淋巴结转移率高的常见恶性肿瘤之一。采用...     

Smac表达水平对预测直肠癌术前放疗敏感性的临床意义

背景与目的:直肠癌患者术前放疗效果个体差异大,寻找与放疗敏感性相关的生物学标志物,对于直肠癌的个体化治疗有着重要的临床意义。本研究旨在探讨Smac蛋白表达与直肠癌术前放疗病理反应程度的关系,评价Smac蛋白表达水平预测直肠癌术前放疗敏感性的价值。方法:收集我院2002年1月至2006年12月期间接受术前放疗的42例直肠癌病例资料,评价其放疗后病理反应程度,免疫组织化学方法检测手术治疗前活检标本和手术后切除标本中Smac蛋白的表达水平,分析活检组织中Smac蛋白表达水平与病理反应程度的关系,以及放疗前后蛋白表达水平的变化。结果:直肠癌术前放疗后病理反应良好,有效率达73.8%,联合放化疗者优于单纯放疗者(P<0.05);而直肠癌组织中Smac蛋白的表达水平与单纯术前放疗效果密切相关,Smac蛋白高表达者术前放疗有效率(83.3%)明显优于低表达者(25.0%),并且肿瘤组织放疗后Smac蛋白表达水平有明显下降。结论:直肠癌组织中Smac蛋白表达水平可作为术前放疗敏感性的预测因子。     

滑膜肉瘤综合治疗分析

我院自1963年10月至1991年1月，收治滑膜肉瘤67例。其中外院手术后转来做术后放疗25例，本院术后放疗25例、术前术后放疗17例。外院术后转来放疗者3、5年生存率为24％和16％，与本院术后放疗者3、5年生存率为48％和40％相比（P＜0．05）。术前术后放疗者5年生存率52％。笔者认为首次手术作广泛切除至关重要；术后放疗可杀灭残存的微小肿瘤灶，降低复发率；术前放疗能缩小瘤体、提高切除率及降低局部复发率。术前放疗、术后放疗、手术的综合治疗可能是中晚期滑膜肉瘤的一种较好的治疗方法。     

直肠癌围手术期的辅助治疗

直肠癌发病率和死亡率仍不断上升,而外科治疗效果近30年提高并不显著,加上患者多要求保肛,单靠手术难以进一步提高生存率和生活质量,只能谋求多学科综合治疗.现结合国内外有关文献,介绍直肠癌围手术期的辅助治疗,即术前放疗、术中放疗、术后放疗和术后放化疗;术后化疗和术中化疗.     

直肠癌新辅助放疗研究进展

在过去的近40年里，直肠癌的治疗方案逐渐标准化。大多数早期直肠癌患者仅通过手术即可得到充分的治疗。然而，相当比例的直肠癌患者处于局部进展期，此类患者需要行新辅助治疗。直肠癌的新辅助放射治疗已被证明能有效地降低患者术前肿瘤分期、改善患者生存以及降低直肠癌局部复发率等，随之而来的是患者放疗后出现的不同程度的放疗不良反应，但随着放射治疗规范化、放射治疗技术及设备的改进，放疗不良反应严重程度在逐渐降低。本文就新辅助放疗中的放疗方案的选择、放射治疗技术、放疗不良反应、放疗后的手术时间以及放疗后的观察与等待等问题的最新研究进展进行了系统性的综述，从而为临床直肠癌新辅助治疗提供有力依据。     

膀胱容积变化对盆腔肿瘤放疗的影响

宫颈癌是全球妇科肿瘤中发病最高的3种肿瘤之一,2008年的流行病学数据显示,每年新发病例约40万[1].宫颈癌在我国是第2大常见妇科肿瘤,仅次于乳腺癌.手术、放疗、化疗是宫颈癌的常用治疗手段,但多数患者错过早期的手术机会,放疗成为首选的治疗方案.对于局部晚期宫颈癌患者,联合放、化疗可以明显提高盆腔局部控制率和改善总生存[2-3].直肠癌的发病率呈上升趋势,目前位居全球恶性肿瘤的第3位[4],直肠癌治疗失败的重要原因是直肠癌术后局部复发,预防和治疗直肠癌术后局部复发的主要手段是放疗.     

外照射联合后装腔内放疗治疗直肠癌术后复发1例

直肠癌术后复发是直肠癌治疗失败的最主要因素,对于直肠癌术后局部区域复发患者,以放疗为主的综合治疗显得尤为重要,无论是手术还是术后放化疗,其目的均为降低复发率,提高患者的生活质量.对于直肠癌术后复发因年龄等因素不能手术的患者来说,外照射联合后装腔内放疗是行之有效的治疗方法.本文报道1例直肠癌术后复发患者通过后装腔内放疗联合外照射治疗取得满意疗效的治疗经过.     

Adjuvant and neoadjuvant chemoradiation therapy for primary colorectal cancer

The management of rectal cancer presents substantial challenges. Patients with T3 and/or node-positive rectal cancers are at high risk for local failure and distant metastases (DM). Adjuvant radiation has been shown to decrease local recurrence (LR) rates; however, this local therapy has not been demonstrated to improve survival when compared to surgery alone. In several prospective randomized trials adjuvant chemoradiation with 5-fluorouracil-(5-FU)-based chemotherapy improved LR rates, DM rates, and overall survival (OS). The optimal chemotherapeutic regimen has not been determined; however, studies comparing standard IV bolus 5-FU administration with continuous infusion (CI) 5-FU demonstrated that CI administration was superior. Preoperative therapy has potential advantages over adjuvant therapy such as less acute bowel toxicity and improved sphincter preservation. Preoperative chemoradiation has been shown in several studies to improve LR rates and OS when compared to surgery alone. Our current approach to patients with resectable T3 or N1 cancer in the distal two-thirds of the rectum on preoperative staging is preoperative chemoradiation with planned postoperative chemotherapy. This regimen offers the best chance for local control and disease-free survival while potentially downstaging the tumor and improving sphincter preservation.     

Preoperative and adjuvant treatment of localized rectal cancer

Although postoperative chemoradiation has a proven role in the treatment of stage II to III localized rectal cancer, recent trials have demonstrated the role of preoperative chemoradiation. A recent randomized trial has shown that preoperative chemoradiation yields higher rates of local control and sphincter preservation and lower rates of toxicity, compared with postoperative chemoradiation. Randomized trials have also shown that preoperative chemoradiation yields higher rates of pathologic complete response and local control, compared with radiotherapy alone. In this article, we review recent trials on preoperative and adjuvant therapy of localized rectal cancer. The roles of newer agents, such as capecitabine, oxaliplatin, and bevacizumab, are also discussed, and other key issues in the treatment of localized rectal cancer are reviewed.     

Progress in the treatment of locally advanced clinically resectable rectal cancer

There have been significant developments in the adjuvant treatment of locally advanced clinically resectable (T3 and/or N+) rectal cancer. Postoperative systemic chemotherapy plus concurrent pelvic irradiation (chemoradiation) significantly improves local control and survival compared with surgery alone. The German Rectal Cancer Trial confirmed that when chemoradiation is delivered preoperatively there is a significant decrease in acute and late toxicity and a corresponding increase in local control and sphincter preservation. Despite these advances, controversies remain. Among these controversies are the role of short-course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery after chemoradiation can be modified based on tumor response. Are there more accurate imaging techniques and/or molecular markers to help identify patients with positive pelvic nodes with the goal of reducing the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve outcome and modify the need for pelvic irradiation? This review examines the advances in chemoradiation as well as addresses these and other opportunities for improvement.     

Role of Combined-Modality Therapy in the Management of Locally Advanced Rectal Cancer

The majority of patients with nonmetastatic rectal cancer are candidates for an aggressive multimodality approach with curative intent. Preoperative staging is critical in determining which patients should be offered neoadjuvant therapy. Available staging tools include digital rectal examination, transrectal ultrasound, computed tomography, positron-emission tomography, and magnetic resonance imaging scans. Magnetic resonance imaging has emerged as the most accurate staging modality in experienced centers. Multidisciplinary preoperative patient evaluation, better staging techniques, neoadjuvant chemoradiation, acceptance of shorter distal rectal margins, and transanal excision of T1 N0 rectal tumors in close proximity to the anal sphincter have resulted in decreased rates of abdominoperineal resections. Total mesorectal excision has been adopted as the standard surgical approach because of a reduction in rates of pelvic relapse. Preoperative and postoperative radiation therapy was shown to decrease the local recurrence rate, but not overall survival, in patients with resectable rectal cancer. The addition of chemotherapy to radiation was consistently shown to improve local control, and in some trials, improved overall survival. Neoadjuvant combined chemotherapy and radiation therapy are superior to adjuvant combined-modality therapy because of higher rates of sphincter preservation, less toxicity, and lower local recurrence rates. For patients with stage II or III disease, neoadjuvant continuous-infusion 5-fluorouracil (5-FU), concurrently with pelvic radiation, followed by postoperative 5-FU–based chemotherapy, remains the standard multimodality approach. Ongoing trials are testing the integration of newer cytotoxic agents such as capecitabine, oxaliplatin, irinotecan, and biologic agents such as cetuximab and bevacizumab to chemoradiation.     

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.     

局部晚期食管癌的新辅助治疗

新辅助治疗是指在成功的术后辅助治疗经验基础上提出的术前辅助治疗,其目的 在于增加手术切除肿瘤的可能性并提高患者的生存率,包括新辅助化疗、新辅助放疗和新辅助放化疗.新辅助放化疗在促进切除率和提高生存率上可能成为局部晚期食管癌新辅助治疗的首选方案.     

Alternative clinical end points in rectal cancer—are we getting closer?

BACKGROUND: In rectal cancer a high risk of local recurrence has been reported for patients treated by surgery alone. It is also recognised that 20%-40% of rectal cancer patients continue to develop distant metastases and die, even when a very low risk of local recurrence has been achieved with the use of preoperative radiotherapy and total mesorectal excision (TME). Hence, the current design of randomised trials in rectal cancer continues to use the standard end points of local control and survival. This strategy is time-consuming. The recently published EORTC 22921 trial, which compared radiotherapy with chemoradiotherapy and tested the role of postoperative adjuvant chemotherapy, has taken 14 years from planning to results. The aim of this review was to use the evidence from both phase II and phase III trials to provide a comprehensive survey of alternative clinical trial end points in rectal cancer, where preoperative chemoradiation has now become the standard treatment. We describe their strengths and weaknesses. Some are clearly defined, easy to assess and can be obtained early, because surgical resection usually takes place within 6-8 weeks of the completion of treatment. Some pathological response end points reflect biological activity, although their effect on survival has yet to be validated in randomised controlled trials. We will propose measurement and analytical techniques for minimising bias and intra- and inter-observer variability of the non-validated end points in the hope of basing these judgements on as firm a ground as possible. METHODS: A literature search identified both randomised and non-randomised trials of preoperative radiation therapy (RT) and chemoradiation therapy (CRT) in rectal cancer from 1993 to 2005. The aim was to find those studies that documented potential alternative end points. RESULTS: Pathological parameters have been used as early end points to compare studies of preoperative radiotherapy or chemoradiation. In the light of the German CAO/ARO/AIO-94 study, which demonstrated an improved therapeutic ratio for preoperative treatment, enthusiasm for preoperative chemoradiation in the management of rectal cancer is increasing. Current evidence cannot indicate whether the degree of response to chemoradiation (e.g. complete pathological response; downsizing the primary tumour; sterilizing the regional nodes; tumour regression grades or residual cell density) or the achievement of a curative resection (CRM/R0 resection) is the best early clinical end point. Problems with these end points include lack of structured measurement and analysis techniques to control for intra- and inter-observer variation and lack of validation as surrogates for long-term clinical end points such as local control and survival. However, retrospective studies in rectal cancer have confirmed a strong association between the presence of microscopic tumour cells within 1 mm of the CRM and increased risks of both local recurrence and distant metastases. Further end points of current clinical relevance for which adequate methodologies for assessment are lacking include sphincter sparing end points, and assessment of long-term toxicities, ano-rectal function and their specific impact on quality of life. Recommendations are made as to the most appropriate information, which should be documented in future trials. CONCLUSIONS: Pathological complete response following preoperative chemoradiation does not reliably predict late outcome. There are other events not mediated through this end point and there are also unintended effects (often an excess of non-cancer related deaths). Disease-free survival currently remains the best (because it is relatively quick) primary end point in designing randomised phase III studies of preoperative chemoradiation in rectal cancer, although it is necessary to control for postoperative adjuvant chemotherapy. However, the CRM status can substantially account for effects on disease-free and overall survival after chemoradiation, radiation or surgery alone. Hopefully, randomised controlled trials, which utilise these alternative clinical end points, will in future determine the precise percentages of the effect of different chemoradiation schedules on disease-free and overall survival.     

Rectal cancer: Preoperative versus postoperative irradiation as a component of adjuvant treatment

The search for improved disease control and survival for resectable but high-risk rectal cancers has led to studies that combine all 3 modalities. For surgically resected, high-risk rectal cancers, postoperative chemoradiation has been shown to improve both disease control (local and distant) and survival (disease free and overall) and was recommended as standard adjuvant treatment at the 1990 National Institute of Health Colorectal Cancer Consensus Conference. Three randomized studies showed improved overall survival (OS) and local control for patients treated with postoperative irradiation and chemotherapy when compared with surgery alone or surgery plus irradiation control arms. These include 2 US trials, Gastrointestinal Tumor Study Group and Mayo/North Central Cancer Treatment Group (NCCTG) and a Norway trial. Although most preoperative external beam radiation trials show reductions in local relapse with the addition of preoperative EBRT to resection, only the large Swedish trial of 1,100 patients showed a survival improvement when compared with a surgery alone control arm for resectable primary rectal cancers. In a recent pooled analysis of 3 postoperative adjuvant rectal cancer trials (NCCTG 794751, NCCTG 864751, and GI Intergroup 0114) survival and disease relapse were dependent on both TN and NT stage of disease (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more positive nodes), T substage influenced 5-year OS (T1-2, 69%; T3, 48%; and T4, 38%; P < .001). Ongoing randomized trials are being conducted for patients with high-risk, resectable primary rectal cancers. The intent is to help define optimal combinations of postoperative chemoradiation (US GI Intergroup), to test sequencing issues of preoperative versus postoperative chemoradiation (Germany trial), and to determine if concurrent and maintenance 5-FU and leucovorin add to the benefits found with preoperative irradiation (European Organization for Research and Treatment of Cancer). For subsequent trials, it may be preferable to perform separate studies, or a planned statistical analysis, for different risk groups of patients (low, intermediate, moderately high, and high), as defined in the rectal cancer pooled analysis.     

Intraoperative radiation therapy in resected pancreatic carcinoma: long-term analysis

PURPOSE: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT+IORT). METHODS AND MATERIALS: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative "flash" RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. RESULTS: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p=0.019). CONCLUSIONS: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT (approximately 50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT+external RT).     

Adjuvant External Beam and Intraoperative Radiation Therapy in Rectal Cancer

The use of radical surgery has maximized local control, sphincter preservation, and overall survival in patients with rectal cancer. Despite the advances in surgical techniques, local recurrence still remains a problem. Following potentially curative surgery, the incidence of local recurrence inpatients with stages B2,C disease varies from 15% to 65%. There are four major approaches in which radiation therapy (RT) has been used in the adjuvant treatment of rectal cancer. These include postoperative RT ± chemotherapy, preoperative RT ± chemotherapy, both pre-and postoperative RT (sandwich technique), and intraoperative RT in conjunction with preoperative external beam RT. In patients with resectable rectal cancer, adjuvant RT has been shown to decrease the incidence of local recurrence and, in some series, may influence survival rates. In patients with locally advanced, unresectable, or recurrent rectal cancer, the use of preoperative radiation therapy, attempted surgical resection, and intraoperative RT further enhances local control.