食管癌新辅助治疗研究现状与进展

中国是食管癌高发的国家。近年来随着研究的深入,相较于单纯手术以及辅助治疗,新辅助治疗在局部晚期可切除食管癌中的价值得到临床医师的广泛认可。但不同新辅助治疗方案的选择得到的生存结果可能大相径庭,这其中有诸多问题尚无统一结论。本文结合相关文献综述了新辅助放化疗的放疗靶区、放疗剂量、化疗方案及其与手术时间间隔,以及靶向治疗和...     

食管癌新辅助免疫治疗研究进展

新辅助治疗尤其是新辅助放化疗已成为局部晚期可切除食管癌的术前标准治疗, 但患者术后仍有较高的复发率和远处转移率。近年来, 程序性死亡蛋白-1(PD-1)/程序性死亡蛋白配体-1(PD-L1)免疫检查点抑制剂在免疫治疗方面被广泛应用于肿瘤治疗, 在新辅助化疗/新辅助放化疗基础上联合PD-1/PD-L1免疫检查点抑制剂能否进一步提高疗效、增加手术完全切除率以及安全性等方面是目前研究的热点。本文就食管癌新辅助免疫联合化疗/放化疗做一综述。     

局部进展期GEJA综合治疗的现状与思考

胃食管交界部腺癌（gastroesophageal junction adenocarcinoma,GEJA）具有独特的生物学特性和预后,且发病率显著增加,但其诊断和治疗仍存在争议。新辅助治疗和辅助治疗联合手术治疗较单纯手术均可改善局部进展期GEJA患者生存。而新辅助治疗中的新辅助放化疗较新辅助化疗可提高患者手术切除率和局部控制率,改善患者生活质量,联合分子靶向药物可进一步增加疗效。局部进展期GEJA患者的综合治疗数据多来源于食管癌或胃癌的随机临床研究,应开展更多大样本前瞻性随机对照研究,优化新辅助和辅助综合治疗,改善局部进展期GEJA患者的生存。本文对局部进展期GEJA综合治疗的研究进展进行综述。      

新辅助放化疗联合手术与单纯手术治疗局部晚期食管癌的疗效比较

目的探讨新辅助放化疗联合手术治疗局部晚期食管癌较单纯手术治疗能否改善总生存率。方法Ⅱa～Ⅲ期食管癌患者60例,随机分成新辅助放化疗联合手术组及单纯手术治疗组,每组30例。化疗使用PF方案,DDP 75 mg/（m2.d）,d1,5-FU 500 mg/（m2.d）,d1-5持续滴注,第1次化疗与第1次放疗同时实施,每3周1个疗程,放疗期间共2个疗程。放化疗结束后2-4周行食管癌根治术。放疗剂量PTV靶区给予每次2.0 Gy,5次/周,总剂量50 Gy。结果给予新辅助放化疗联合手术组患者必要的对症支持治疗,患者均能够完成同期放化疗。新辅助放化疗联合手术组并发症多于单纯手术组,但两组比较差异无统计学意义。1、2、3年生存率新辅助放化疗联合手术组分别为83.3%、65.3%、42.8%,单纯手术组分别为80.0%、41.6%、25.0%（χ2=3.992,P=0.046）。结论新辅助放化疗联合手术治疗可以改善局部晚期食管癌的总生存率,且不明显增加术后并发症,值得临床推广应用。     

多西他赛联合顺铂行食管癌新辅助化疗的疗效观察

背景与目的：单一采用手术治疗进展期食管癌的效果较差,通过新辅助治疗能否改善进展期食管癌患者的预后是近年来食管癌治疗研究的热点,但仍存在争议。本研究旨在探讨多西他赛联合顺铂在食管癌新辅助化疗中的价值。方法：以多西他赛联合顺铂行食管癌新辅助化疗患者49例为研究组,观察化疗的有效率;以同期行单纯手术患者50例为对照组,比较2组手术切除率及术后1年生存率。结果：研究组49例患者均完成2个疗程的化疗,有48例行手术治疗,客观缓解率ORR（CR＋PR）为59.2%（29例）,术前分期明显降低。对照组50例均顺利完成手术。研究组和对照组行根治性手术切除率差异存在统计学意义（P〈0.05）。新辅助化疗后获得客观缓解患者的术后1年生存率与对照组比较差异有统计学意义（P〈0.05）。结论：多西他赛联合顺铂行食管癌新辅助化疗有助于降低术前分期,提高根治性手术切除率和新辅助化疗后获得客观缓解患者的1年生存率。     

食管癌围术期治疗的争议与共识

食管癌是全球排名第七的恶性肿瘤,在癌症相关的死亡原因中排名第六。手术治疗是可切除食管癌的主要治疗方式,但对于局部晚期食管癌患者,单纯手术治疗后,局部复发和远处转移缩短了患者的生存期,因此除极早期肿瘤外,所有患者推荐术前行新辅助放化疗或新辅助化疗。但是仍然有一部分患者未能在术前行新辅助治疗,这就需要术后辅助治疗来改善患者预后。本文系统回顾了食管癌围术期治疗的研究进展,包括新辅助治疗和辅助治疗,并结合指南对食管癌围术期的治疗方案进行了总结。     

食管癌的新辅助化疗和辅助化疗现状

食管癌是我国最常见的恶性肿瘤之一,严重威胁着人们的健康和生命。早期食管癌的治疗首选手术。为了提高局部晚期食管癌的疗效,人们进行了多种治疗模式的探索,如术前放疗、术前化疗、术前放化疗以及术后化疗等。本文就目前新辅助化疗和辅助化疗在食管癌治疗中的价值作一综述。     

紫杉醇联合顺铂对中晚期食管癌新辅助化疗的疗效观察

食管癌是全球性、常见的、难治的恶性肿瘤之一,手术治疗是早中期患者获得根治的有效方法,但局部晚期患者不能完全切除局部病灶,且70％～80％切除标本在区域淋巴结出现转移,通常术后2～5年出现肿瘤复发,所以单纯依靠手术治疗难以达到理想效果。新辅助化疗能够增加患者手术的可能性和彻底性,提高术后生存时间,是近年来新提出来的化疗概念。我们术前应用紫衫醇＋顺铂（TP方案）新辅助化疗食管癌,并与术后辅助化疗进行比较,探讨TP方案新辅助化疗在Ⅲ期食管癌患者的临床应用价值。     

局部进展期食管鳞癌新辅助治疗模式研究进展

食管癌是全球常见的恶性肿瘤之一，其中包括中国、日本、韩国在内的东亚地区中，食管鳞状细胞癌(esophageal squamous cell cancer, ESCC)占食管癌的90%以上。目前局部进展期食管鳞癌的主要治疗手段为新辅助治疗联合外科手术切除。然而即使按照标准治疗指南进行治疗，局部进展期食管鳞癌患者的总体生存率仍不令人满意。未来寄希望于通过新辅助放化疗、化疗或新兴的免疫治疗相关研究的持续探索，进一步改善食管鳞癌患者总生存期。在此，我们回顾和总结了局部进展期食管鳞癌不同术前新辅助治疗模式的疗效的当前证据。     

食管癌术前新辅助治疗原则及循证医学依据

在中国,手术虽是治疗食管癌的主要手段,但单纯手术治疗局部晚期食管癌的疗效不尽人意.近30年综合治疗的研究结果提示,术前新辅助治疗有望改善局部晚期食管癌患者的预后.本文就术前化疗和术前放化疗的国内外研究进展以及世界各国的应用经验作一综述,并就2011年中国抗癌协会食管癌专业委员会制定的<中国食管癌规范化诊治指南>作推荐指引.     

局部晚期食管癌新辅助治疗的研究进展

近年来,食管癌的治疗越来越倾向于多学科的综合治疗。多项研究已证明在手术的基础上加入放疗、化疗或免疫治疗可提高食管癌的生存获益。对于局部晚期食管癌患者,新辅助联合手术治疗效果明显,新辅助放化疗以及新辅助化疗均能够提高生存获益,但目前这两种治疗模式孰优孰劣尚存在争议。随着诱导化疗和新辅助免疫的加入,新辅助治疗模式更加多样化,进一步提高了病理完全缓解率,为局晚期食管癌患者的治疗提供了新思路。因此,本文旨在对近年来局晚期食管癌的新辅助治疗模式进行探讨,为进一步优化综合治疗策略提供参考。     

A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction

BackgroundNeoadjuvant therapy improves long-term survival after oesophagectomy, treating oesophageal cancer, but the evidence to date is insufficient to determine which of the two main neoadjuvant therapy types, chemotherapy (nCT) or chemoradiotherapy (nCRT), is more beneficial. We aimed to compare the effects of nCT with those of nCRT.Patients and methodsThis multicentre trial, which was conducted in Sweden and Norway, recruited 181 patients with carcinoma of the oesophagus or the gastro-oesophageal junction who were candidates for curative-intended treatment. The primary end point was histological complete response after neoadjuvant treatment, which has been shown to be correlated with increased long-term survival. Study participants were randomized to nCT or nCRT, followed by surgery with two-field lymphadenectomy. Three cycles of platin/5-fluorouracil were administered in both arms, whereas 40 Gy of concomitant radiotherapy was added in the nCRT arm.ResultsThe trial met the primary end point, histological complete response being achieved in 28% after nCRT versus 9% after nCT (P = 0.002). Lymph-node metastases were observed in 62% in the nCT group versus 35% in the nCRT group (P = 0.001). The R0 resection rate was 87% after nCRT and 74% after nCT (P = 0.04). There was no difference in overall survival between the treatment arms.ConclusionThe addition of radiotherapy to neoadjuvant chemotherapy results in higher histological complete response rate, higher R0 resection rate, and a lower frequency of lymph-node metastases, without significantly affecting survival.clinicaltrials.govNCT01362127 (https://clinicaltrials.gov; The full study protocol was registered in the Clinical Trials Database).     

基于多参数CT成像的食管癌新辅助放化疗病理反应预测

目的 建立基于放射组学的生物标记物模型,预测局部进展期食管癌术前新辅助放化疗(nCRT)后病理反应。方法 回顾性选取2008—2018年间 112例局部进展期食管癌患者,均采用术前nCRT联合手术治疗。收集治疗前增强CT图像,手动描绘病变体积。使用Python软件中pyadiomics插件包提取共670个放射组学特征(包括肿瘤强度、形状和大小、纹理和小波特征),运用逐步回归结合最佳子集方法筛选特征,最后采用Logistic回归模型建立预测模型。通过受试者工作特征曲线下面积(AUC)评估性能。结果 全组患者的病理完全缓解率为58.0%(65/112)。最终模型包含10个放射组学特征,与结局相关性最大的为灰度特征(即图像的纹理信息),其次为形状特征和体素强度相关特征。训练集、测试集AUC分别为0.750、0.870,敏感性分别为0.711、0.757,特异性分别为0.778、0.900。结论 基于CT放射组学的多参数模型在不额外增加患者经济负担和侵入性操作前提下,能较好地、有效地预测食管癌nCRT病理反应和较好地指导个体化治疗。     

局部进展期食管鳞癌全新辅助治疗可行方案的探索

新辅助放化疗联合手术为局部进展期食管癌患者的标准治疗方案, 这一治疗方案已得到广泛应用, 其疗效也已得到临床医师的认可。然而, 即使是完成了新辅助放疗和随后的手术治疗, 仍有部分患者在短期内出现局部区域复发和/或远处转移, 其中远处转移成为新辅助放化疗后接受手术患者的主要失败模式, 这从另一方面说明该模式还有进一步改善的必要。借助于直肠癌患者从全新辅助治疗模式中获益的经验, 本文探讨了局部进展期食管癌患者进行全新辅助治疗的可能性及其实施方案。     

Multimodality therapy for the curative treatment of cancer of the esophagus and gastroesophageal junction

This review examines the role of combined-modality therapy in the treatment of locally advanced esophageal cancer. While surgery remains a cornerstone of treatment, recent studies have demonstrated that pre- or perioperative chemotherapy is associated with improved survival. Primary chemoradiotherapy is the accepted standard of care for medically inoperable patients. Neoadjuvant chemoradiotherapy continues to be investigated and is associated with several advantages over neoadjuvant chemotherapy alone, including an improvement in the pathologic complete response rate and resectability; patients who achieve a pathologic complete response also appear to have improved survival. Adjuvant chemoradiotherapy may be considered for patients who undergo primary resection of lower esophageal/gastroesophageal junction adenocarcinoma. Future directions include the investigation of novel chemotherapy regimens, the addition of targeted therapies and the use of PET to provide an early assessment of response.     

Neoadjuvant treatments for locally advanced,resectable esophageal cancer: A network meta‐analysis

The relative survival benefits and postoperative mortality among the different types of neoadjuvant treatments (such as chemotherapy only, radiotherapy only or chemoradiotherapy) for esophageal cancer patients are not well established. To evaluate the relative efficacy and safety of neoadjuvant therapies in resectable esophageal cancer, a Bayesian network meta‐analysis was performed. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for publications up to May 2016. ASCO and ASTRO annual meeting abstracts were also searched up to the 2015 conferences. Randomized controlled trials that compared at least two of the following treatments for resectable esophageal cancer were included: surgery alone, surgery preceded by neoadjuvant chemotherapy, neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy. The primary outcome assessed from the trials was overall survival. Thirty‐one randomized controlled trials involving 5496 patients were included in the quantitative analysis. The network meta‐analysis showed that neoadjuvant chemoradiotherapy improved overall survival when compared to all other treatments including surgery alone (HR 0.75, 95% CR 0.67–0.85), neoadjuvant chemotherapy (HR 0.83. 95% CR 0.70–0.96) and neoadjuvant radiotherapy (HR 0.82, 95% CR 0.67–0.99). However, the risk of postoperative mortality increased when comparing neoadjuvant chemoradiotherapy to either surgery alone (RR 1.46, 95% CR 1.00–2.14) or to neoadjuvant chemotherapy (RR 1.58, 95% CR 1.00–2.49). In conclusion, neoadjuvant chemoradiotherapy improves overall survival but may also increase the risk of postoperative mortality in patients locally advanced resectable esophageal carcinoma.     

Predicting response to neoadjuvant therapy in esophageal cancer

Despite improvements in preoperative staging, surgical techniques and postoperative care, the 5-year survival rate of patients with locally advanced esophageal cancer remains only approximately 15-40%. Therefore, multimodality treatment options have been widely promoted in the therapy of this malignant disease. However, recent meta-analyses evaluating randomized trials of neoadjuvant therapy protocols prior to surgery for patients with advanced esophageal cancer showed only modest improvement of survival for the whole treatment group. Among these patients, those with excellent histopathologic response seem to benefit greatly from neoadjuvant regimens. Therefore, predictive markers to allow individualization of multimodality therapy in locally advanced esophageal cancer are needed to identify those who will benefit the most. Unfortunately, there is still a great lack of markers for response assessment in patients with esophageal cancer undergoing multimodality therapy. Endoscopy, endoscopic biopsies, computed tomography and endoscopic ultrasound do not seem to provide reliable information for assessing the response to neoadjuvant therapy. Whether (18)F-fluorodeoxyglucose-PET can effectively characterize responders in neoadjuvant therapy protocols remains controversial. Finally, although results of mostly retrospective studies on molecular factors for response assessment in esophageal cancer patients are promising, these markers do not yet provide a reliable and cost-effective molecular tool for utilization in clinical practice.     

进展期食管鳞癌新辅助放化疗与新辅助化疗的Meta分析

目的 系统评价新辅助放化疗(NCRT)联合手术与新辅助化疗(NCT)联合手术治疗进展期食管鳞癌的疗效和安全性。方法 利用计算机检索PubMed、The Cochrane Library、EMbase、CBM、CNKI、WanFang、VIP数据库,搜集NCRT与NCT联合手术治疗食管鳞癌的临床对照研究,检索时限均从建库至2019年1月。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果 共纳入8项临床对照研究,包括食管鳞癌患者995例。Meta分析结果显示NCRT对比NCT组,经手术治疗后无肿瘤细胞残存(R0)切除率更高(OR=2.14,95%CI为1.03~4.45,P=0.040)、病理完全缓解率(pCR)更高(OR=4.19,95%CI为1.71~10.28,P=0.002);两组术后并发症发生率(OR=1.37,95%CI为0.76~2.48,P=0.300)和围术期死亡风险(OR=1.28,95%CI为0.58~2.83,P=0.540)相近;NCRT组的食管鳞癌患者的远期生存情况更好(HR=0.77,95%CI为0.64~0.92,P=0.005)。结论 NCRT联合手术对比NCT联合手术治疗进展期食管鳞癌能够有更高的R0切除率、pCR率,并不会明显增加围术期并发症发生和围术期死亡风险,且能够更加明显的改善食管鳞癌患者的远期生存。