新辅助化疗方案在可切除结肠癌中的应用进展

新辅助化疗（NACT）是指针对潜在可根治切除的肿瘤患者,以消除微转移、降低肿瘤分期和手术难度、改善术后局部复发和远处转移等为目的,在肿瘤手术切除或放疗之前,先予以全身化疗,待手术或放疗之后继续完成全程化疗的综合方案。结肠癌是最常见的癌症之一,肿瘤根治性切除联合术后辅助化疗是临床潜在可根治切除结肠癌的主要治疗方式。虽然这种治疗模式较前显著改善了患者的预后,但术后局部复发和远处转移仍是患者最主要的致死因素。近年来NACT方案开始被引入局部进展期结肠癌和原发灶可切除的肝转移患者等潜在可根治切除结肠癌患者的治疗。然而,结肠癌患者是否适合NACT及其方案的选择还存在较大的争议。笔者就局部进展期结肠癌、可切除结肠癌肝转移等在NACT中的进展与争议,以及影像学检查对NACT的作用作一综述。     

中晚期胃癌术前新辅助化疗92例分析

目的评价中晚期胃癌术前新辅助化疗的作用。方法总结2003年至2008年间92例入院后经CT、B超、胃镜等检查后诊断为中晚期胃癌并通过新辅助化疗后再行手术治疗的病例,并与2000年至2002年间收治的未经新辅助化疗的中晚期胃癌49例对照分析。结果化疗组肿瘤缩小或明显缩小者66例（71.7%）,行根治性手术切除者69例（75%）,行局部切除者17例（18.5%）,姑息性手术者6例（6.5%）。对照组行根治性手术切除者24例（48.9%）,行局部切除者15例（30.6%）,姑息性手术者10例（20.4%）。所有病例均术后经病理证实,化疗组Ⅲa期46例,Ⅲb期33例,Ⅳ期13例,对照组Ⅲa期25例,Ⅲb期16例,Ⅳ期8例。结论对于以往手术切除较为困难或根治率低的中晚期胃癌,术前配合新辅助化疗,可提高手术切除率及根治率。     

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食管胃结合部腺癌(AEG)的首要治疗方式是手术切除,但根治性切除病例中5年内复发率或病死率均超过50%,提示AEG围手术期放化疗的多学科综合治疗的必要性。近年来AEG的新辅助治疗受到较多关注,当前认为术前新辅助放疗能够提高术后5年总体存活率。而且欧洲癌症研究与治疗组织亦制定了AEG术前新辅助放疗的共识性指南,其对临床实践有很好的指导意义。术前新辅助化疗对提高R0切除率有重要意义,但需与术后辅助化疗序贯应用以提高总体存活率。术后辅助化疗和胃癌相同,NCCN推荐的多药方案为经典的ECF或改良ECF方案,而单药S1的试验结果也有不错的远期存活率。目前术中和术后放疗的证据令人遗憾,并不能提高远期存活率。因此,目前来说术前同步新辅助放化疗联合术后序贯辅助化疗应该是较为理想的方式。     

局部复发直肠癌放射治疗

局部复发是直肠癌,尤其是Ⅱ/Ⅲ期直肠癌手术治疗失败的主要原因,且术后复发病例预后差。20世纪70年代开始局部进展期直肠癌手术前后辅助放化疗的相关研究。大量临床试验结果显示,术后或术前辅助性放化疗较单纯手术可降低局部复发率、提高保肛率和存活率,已经成为I类循证医学证据,作为局部进展期直肠癌的标准治疗方案。而术后局部复发的直肠癌放化疗,目前尚未取得较高级别的循证医学证据。美国国家癌症综合网络（NCCN）指南建议对复发直肠癌病人应该采用多学科合作的综合治疗方案。孤立的盆腔或吻合口复发,如果之前未接受过全量放疗,最适合的处理就是行术前放疗,同期化疗。有条件的医疗机构,可考虑行术前新辅助放化疗+手术切除+术中放疗。     

进展期胃癌围手术期治疗的探索与思考

进展期胃癌患者的围手术期治疗是提高胃癌整体疗效、改善预后的重要环节。可切除胃癌围手术期治疗的主要模式为D 1/D 2手术+围手术期化疗、D 0/D 1手术+辅助放化疗和D 2手术+辅助化疗。多年来,业内围绕如何进一步优化胃癌围手术期治疗模式开展了大量临床研究,包括术后放...     

围手术期胃癌放疗的相关问题

放疗作为胃癌综合治疗的组成部分,在近年来得到较多的关注和重视。可切除胃癌的术后辅助放化疔已在INT0116研究中得到证实．而且在实际治疗人群证实了术后辅助放化疗的获益。近期的ARTIST研究．在D,术后辅助放化疗的优势仅显示在淋巴结阳性患者中．而且另外两项ACT—GC和CLASSIC研究．报道的极低局部复发率．与实际临床的差异．使得这些研究结果在实际临床治疗的应用需要慎重。早期单纯放疗的新辅助治疗．在贲门癌中显示了疗效．随后的Ⅱ期新辅助放化疗研究均显示了较高的病理完全缓解率．但同期联合的化疗毒性较高．值得在降低不良反应同时,探索新辅助放化疗的作用。放疗新技术的应用对胃癌放疗提高肿瘤控制和减轻不良反应有重要价值。确立合适治疗人群、放疗敏感性筛选、联合化疗药物和靶向药物在胃癌放疗中的应用．是胃癌放疗的发展方向。     

区域动脉灌注化疗在进展期胃癌短程新辅助化疗中的应用

目的 探讨短程新辅助化疗应用于进展期胃癌的可行性,并比较不同化疗方式短程新辅助化疗的临床疗效.方法 回顾性分析2008年1月至201 1年12月间在南京中医药大学附属医院接受短程（1个周期）EOF方案（表柔比星、奥沙利铂、氟尿嘧啶加亚叶酸钙）新辅助化疗的310例进展期胃癌患者的临床资料.比较全身静脉化疗方案与区域动脉灌注化疗方案的临床疗效.结果 310例患者均完成了1个周期的短程EOF方案新辅助化疗,无一例因化疗毒副反应而终止.术后病理缓解率为33.9％（105/310）,其中5例（1.6％）获病理完全缓解.接受区域动脉灌注化疗者的病理缓解率为42.4％（72/170）,明显高于全身静脉化疗者的23.6％ （33/140） （P=0.001）.Logistic多因素回归分析证实,化疗方式是影响进展期胃癌短程新辅助化疗后病理缓解率的独立危险因素（HR=1.827; 95％ CI：1.006～3.316; P=0.048）.结论 进展期胃癌短程新辅助化疗病理缓解率总体较低;区域动脉灌注化疗能提高进展期胃癌短程新辅助化疗的术后病理缓解率。     

从日本《胃癌治疗指南》（第5版）修订谈日本胃癌外科发展趋势

日本《胃癌治疗指南》自2001年3月制定以来进行了5次修订,其建立在日本大量经验性数据基础上,采用教科书形式介绍,但第5版《胃癌治疗指南》体现出从经验外科向循证医学外科的转变,包括非治愈性胃癌的减瘤手术、网膜囊外切除、近端和胃体部癌合并脾切除、胃癌侵犯食管的手术入路问题等,采纳了国际多中心临床试验（MRCT）研究结果。推荐cStageⅠ胃癌为腹腔镜手术适应证,而对于进展期胃癌正在进行MRCT（JLSSG0901）研究,有待结果发表。改变单一手术模式,注重术前新辅助化疗,对于临界可切除的高度淋巴结转移病例,进行新辅助化疗（SP方案）2~3疗程后,再行D2+No.16淋巴结清扫。对于胃癌腹膜转移的腹腔镜诊断标准以及食管胃结合部癌和残胃癌区域淋巴结定义和清扫范围,指南提出了日本标准,有待循证医学检验。     

潜在可切除性胃癌的新辅助化疗

目的 总结潜在可切除胃癌的新辅助化疗(neoadjuvant chemotherapy,NAC)的现状.方法 通过PubMed,以胃肿瘤、胃癌/癌、新辅助治疗/化疗及术前治疗/化疗为关键词,检索近5年的相关文献.并检索2007及2008年ASCO年会的相关进展.总结NAC在胃癌中的研究现状,评价其必要性和可行性,分析病例选择依据、缓解预测因子及存在的问题和发展方向. 结果共检索随机对照试验7个,其中3个为Ⅲ期试验.已进行的多数研究显示,NAC在胃癌的治疗中是安全、有效和可行的.但生存取得显著改善的NAC随机研究尚少,缺乏严格NAC与单独手术或围手术期化疗与辅助化疗对比的NAC随机研究.如何选择适当的病例、有效的NAC方案和治疗缓解的预测,尚需要解决.结论 NAC在胃癌的治疗中是安全、有效和可行的,但仍需进一步严格的前瞻性随机Ⅲ期试验证实.新的细胞毒性药物和分子靶向治疗可能是将来进展的实质基础.     

紫杉醇联合FOLFOX4方案新辅助化疗在进展期胃癌中的临床应用

目的 评价紫杉醇联合FOLFOX4方案（氟尿嘧啶、甲酰四氢叶酸和奥沙利铂）新辅助化疗治疗进展期胃癌的临床疗效及不良反应.方法 应用前瞻性随机对照的方法将cTNM分期为Ⅲ或Ⅳ期（M0） 的胃癌患者78例,按入组顺序根据随机数字表法随机分配到试验组（39例）和对照组（39例）.试验组给予紫杉醇联合FOLFOX4方案的新辅助化疗,每2周为1周期,3周期后采用RECIST标准评价临床疗效,2～4周后手术,术后给予原方案化疗3周期.若术前评效为疾病进展（PD）者,术后改为ECF方案（表阿霉素、顺铂和氟尿嘧啶）化疗.对照组确诊后2周内手术.术后给予6周期紫杉醇联合FOLFOX4方案的辅助化疗.结果 试验组紫杉醇联合FOLFOX4方案新辅助化疗的临床有效率为66.7%,R0切除率（82.1%）明显高于对照组（59.0%）（P＝0.025）,淋巴结转移数目[（3.23±2.80）枚]明显少于对照组[（5.79±2.69）枚]（P＝0.001）,术后并发症发生率（5.1%和2.6%）及淋巴结清扫数目[（19.69±2.95）枚和（20.59±3.22）枚]两组差异均无统计学意义（P＞0.05）.试验组和对照组术后中位生存期分别为（27.10±2.32）个月和（18.20±1.30）个月（P＝0.006）.Cox回归多因素分析显示,肿瘤分化程度、R0切除、淋巴结转移均是影响预后的独立因素.化疗不良反应主要为血液学及末梢神经毒性,患者均可耐受,两组化疗不良反应差异无统计学意义（P＞0.05）.结论 紫杉醇联合FOLFOX4方案新辅助化疗有效率高,患者耐受性和依从性好,可提高进展期胃癌患者的R0切除率、降低淋巴结转移率,提高生存率.     

Adjuvant therapy for locally advanced gastric cancer

D2 gastrectomy is now the globally accepted surgical standard for locally advanced gastric cancer. However, since 2000, different evidence has emerged regarding the efficacy of adjuvant chemoradiation, perioperative adjuvant chemotherapy, and postoperative chemotherapy for locally advanced gastric cancer. This review summarizes the background, current status, and future perspectives of adjuvant therapy for locally advanced gastric cancer. The Intergroup 0116 study was the first to show the significant overall survival benefits of adjuvant (chemoradiation) therapy for gastric cancer. The second study was the MAGIC trial, which showed the efficacy of perioperative adjuvant chemotherapy. Although the findings from the Intergroup 0116 study and the MAGIC trial were positive, recent studies, such as the ARTIST and EORTC 40954 studies, found no survival benefit for patients who had undergone D2 gastrectomy for gastric cancer. Regarding the adjuvant chemotherapy strategy, two pivotal phase III trials: the ACTS-GC and the CLASSIC, demonstrated the efficacy of postoperative adjuvant chemotherapy following D2 gastrectomy. However, more intensive chemotherapy is necessary to improve the survival rate. Several studies have analyzed the effectiveness of molecular-targeted therapy against metastatic gastric or gastroesophageal junction carcinoma. Further studies should focus on the survival benefit of more-intensive adjuvant therapy with D2 resection, or with concurrent molecular-targeted therapy.     

Adjuvant therapy for advanced gastric cancer

The importance of surgery (gastrectomy plus lymph node dissection) for the treatment of advanced gastric cancer is unquestionable, although there has been a disparity in methods used to achieve local control in Asia and the West. The superiority of D2 dissection has not been confirmed in a large multiinstitutional trial, and the long-term follow-up results of a Dutch trial revealed that the recurrence rate was lower in the D2 group. Thus, the European Society for Medical Oncology and the US National Comprehensive Cancer Network guidelines recommend D2 dissection, leading to a worldwide consensus. Meanwhile, the focus of oncology should be on multimodality treatment for cure, and numerous large, randomized clinical trials have established effective adjuvant treatment. In gastric cancer, different evidence emerged first in the USA, followed by Europe, and Japan/the Republic of Korea to become the standard for each: adjuvant chemoradiation, perioperative adjuvant chemotherapy, and postoperative chemotherapy, respectively. The Japanese standard has become adjuvant S-1 chemotherapy for 1 year after surgery, and the optimal regimen for stage III should be further investigated in consideration of other robust results. Other issues include the role of surgery in local control with regard to adjuvant treatment such as radiation and molecular-targeted treatment to establish a worldwide standard.     

Stomach carcinoma. Optimizing therapy by neoadjuvant or adjuvant therapy?]

Despite the decreasing frequency of gastric cancer in most Western countries prognosis could not be improved by surgery alone in the past. Advanced tumor stage due to late diagnosis is one of the reasons for this observation. Contrary to breast and colorectal cancer, postoperative chemotherapy failed to improve prognosis in gastric cancer. Small number of patients in Western studies, insufficient surgical procedures and the high frequency of locoregional relapse may be attributed for this observation. Intraperitoneal, adjuvant chemotherapy showed a positive impact on survival in Asian studies only, but was also used successfully as a part of a multimodality approach in Western phase II trials. Since neoadjuvant therapy proved to create downstaging of tumor size in some patients with advanced gastric cancer some working groups tried to influence prognosis of potentially resectable tumors by preoperative chemotherapy, surgical resection and postoperative, adjuvant therapy in the recent past. However, the efficacy of this therapeutic approach has to be reconfirmed in a controlled, phase III fashion.     

Current Status of Neoadjuvant Therapy for Adenocarcinoma of the Distal Esophagus

Prospective studies dealing with preoperative therapy in adenocarcinoma of the esophagus alone are rare. The interpretation of the preferential phase II trials and a few phase III trials is complicated, as most studies include adenocarcinoma of the esophagus (i.e., Barretts carcinoma), adenocarcinoma of the esophagogastric junction (including cardia carcinoma and subcardia carcinoma), or squamous cell carcinoma. Preoperative chemotherapy, generally well tolerated, cannot decrease the incidence of local failure beyond the level achieved with surgery alone, but it might delay systemic relapse. Preoperative radiotherapy can enhance local control, but it fails to improve overall survival. Neoadjuvant chemoradiation was demonstrated in only one randomized trail to have a survival benefit, but survival in the surgery-alone group was unusually low. Generally, survival was ameliorated in patients responding to neoadjuvant treatment. However, preoperative chemoradiation was often accompanied by a remarkable increase in postoperative morbidity and mortality. Nonresponding patients have, in this respect, a worse prognosis than responders after resection. The prediction of responding patients to neoadjuvant therapy as well as the early identification of patients who will not respond is of utmost clinical importance. Today, there is no absolute evidence that neoadjuvant treatment for patients with potentially resectable Barretts cancer prolongs survival. In patients with locally advanced, presumably not completely resectable adenocarcinoma of the esophagus, preoperative treatment appears to increase the chance for a curative resection and enhance survival in responding patients. Neoadjuvant treatment of adenocarcinoma of the esophagus, as a consequence, is currently not the standard treatment and should be performed only within controlled clinical trials.     

Postoperative complications after resection of borderline resectable and locally advanced pancreatic cancer: The impact of neoadjuvant chemotherapy with conventional radiation or stereotactic body radiation therapy

Background

The impact of neoadjuvant stereotactic body radiation therapy on postoperative complications for patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma remains unclear. Limited studies have compared neoadjuvant stereotactic body radiation therapy versus conventional chemoradiation therapy. A retrospective study was performed to determine if perioperative complications were different among patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma receiving neoadjuvant stereotactic body radiation therapy or chemoradiation therapy.

胃癌的综合治疗研究的进展

胃癌是我国常见的恶性肿瘤之一,传统的手术和术后化疗的临床疗效并不理想。多学科合作的综合治疗是胃癌最佳治疗的模式,准确的胃癌术前评估是胃癌综合治疗方案实施的需要,个体化原则基础上进行的术前新辅助放化疗、术中规范化手术、术中腹腔内温热化疗和术后辅助放化疗等多学科合作的综合治疗,可明显改善了胃癌的疗效。本文对此复习相关文献,对国内外胃癌综合治疗进行综述。     

肝外胆管癌术后辅助放化疗治疗进展

肝外胆管癌（ECC）是一种恶性程度较高的肿瘤,即使在病变早期进行根治性切除手术,患者术后仍有较高的复发率,总体生存率低。近几年来,ECC术后辅助治疗的研究逐渐开展,以吉西他滨、氟尿嘧啶等为基础的辅助化疗或联合放、化疗可使ECC患者术后获益,延长患者的总生存期。然而现有的辅助治疗方案各异,缺少ECC术后辅助治疗的标准方案。本文结合最新发表的研究结果,讨论ECC术后辅助治疗的现状和主要措施。     

Adjuvant/Perioperative Therapy in Pancreatic and Periampullary Cancer

The delivery of postoperative combined modality adjuvant therapy for completely resected pancreatic adenocarcinoma was initially shown to be beneficial based on a prospective, randomized trial published 30 years ago. Since then, oncologists have debated whether chemotherapy alone, chemoradiation, or both are optimal adjuvant therapies following pancreatectomy for pancreatic ductal adenocarcinomas (PDAC). No global consensus has emerged, and there is no one superior modality despite randomized trials in part, to poor trial design, poor patient selection, and poor therapy options itself. We need to have a disciplined approach to the selection of patients for pancreatectomy, pathologic assessment of surgical resection margins, and postoperative (pre-treatment) imaging. In the era of the multidetector CT optimized for pancreatic imaging, tumors of “borderline resectability” have emerged as a distinct subset of PDAC. The attempt to standardize the definition of borderline resectable is a work in progress and modified with time. This distinction (between resectable and borderline resectable) is essential to minimize potentially confounding results of clinical trials. Additionally, preoperative therapy is not only preferred but mandatory in a large population of borderline resectable patients. Ultimately, as we develop more effective systemic therapies for PDAC, proceeding with surgery after a period of induction therapy will be even more compelling especially if there is a clear positive impact on overall survival.     

Diagnosis and treatment of non-metastatic esophagogastric junction adenocarcinoma: What are the current options?

While the prevalence of distal gastric cancer is decreasing in the western world, there has been an alarming rise in the incidence of esophagogastric junction adenocarcinoma (EGJA) during recent decades. Current reports show that the prognosis of EGJA remains poor. Therapy strategies are complex due to the anatomical location of the junction between the esophagus and stomach. Surgery, based on Siewert's classification and associated with regional lymphadenectomy, is the mainstay of treatment. Transthoracic esophagectomy is recommended for type I EGJA, while total gastrectomy is recommended for type III EGJA; both approaches can be considered for type II EGJA. Surgery alone can be indicated only for stage I and IIa tumors. Perioperative chemotherapy should be considered for stage IIb, III and non-metastatic stage IV tumors. Adjuvant chemoradiation can be proposed for tumors with high-risk of recurrence in the absence of neoadjuvant therapy. Neoadjuvant chemoradiation can be proposed for predominantly esophageal EGJA, and might well become a standard treatment for all EGJA tumors in the near future. A multidisciplinary approach is essential for optimal diagnosis and management.