直肠癌新辅助放化疗后病理完全缓解的相关研究进展

局部晚期直肠癌标准的治疗方案为术前新辅助放化疗加手术的综合治疗。研究显示,直肠癌患者术前放化疗后达病理完全缓解者预后较好。尽管对这些患者的后续治疗方案有较大分歧,但已倾向于保守治疗而非根治性手术治疗。本文就局部晚期直肠癌术前新辅助放化疗后病理完全缓解的预后及预测等相关研究进展作一简要综述。     

胸腹腔镜联合切除局部晚期食管癌手术视频要点

正1技术背景介绍胸腹腔镜联合微创手术治疗食管癌正在成为主流。相较传统的开放手术,微创手术并发症更少且具有不逊于开放三切口手术的肿瘤切除效果~([1])。新辅助化疗或放化疗对改善进展期和局部晚期食管癌预后的作用已毋庸置疑~([2])。但实际工作中,新辅助化疗无效后需进行挽救性手术的局部晚期食管癌患者仍然是术者经常要面对的难题。     

免疫检查点抑制剂在食管癌新辅助治疗中的研究进展

新辅助放化疗/化疗联合手术已成为局部进展期食管癌的标准治疗方案,尽管使患者生存获益,但仍有多数患者术后出现复发及远处转移。免疫检查点抑制剂通过激活T细胞发挥抗肿瘤作用,随着免疫治疗模式的不断演进,免疫治疗已成为晚期食管癌一线、二线治疗的重要策略之一。大量关于食管癌新辅助免疫治疗的研究正在进行中,有望为食管癌新辅助治疗注入新的活力。本文就目前关于食管癌新辅助免疫治疗的临床研究进展进行综述。     

新辅助放化疗可改善食管癌患者预后

此前,新辅助放化疗在食管癌或食管胃交界部腺癌治疗中作用尚不确定。本研究通过比较单纯手术组与新辅助放化疗联合手术（简称为新辅助放化疗）组预后指标以证实新辅助放化疗的临床意义。     

从NEOCRTEC5010研究看新辅助治疗在局部进展期食管鳞状细胞癌多学科综合治疗中的地位

单一手术治疗局部进展期食管癌效果欠佳,需要多学科的积极参与。新辅助治疗尤其是新辅助同步放化疗可以明显降低肿瘤分期,提高肿瘤根治性切除率并改善患者预后。由我国多家中心共同完成的NEOCRTEC5010研究为局部进展期食管鳞状细胞癌的新辅助同步放化疗提供了充分证据,回答了新辅助同步放化疗后的围手术期并发症、系统性淋巴结清扫...     

食管癌术前的新辅助治疗

我国属于食管癌高发国家．提高我国食管癌的治疗水平．探索出有中国特色的治疗模式当务之急。虽然手术切除仍是实现食管癌局部控制的最佳治疗手段．但中晚期食管癌单纯手术的不良预后促使医生们探索加入辅助放疗或化疗的治疗方案。目前的研究结果显示．术后化疗或放疗均未能改善食管癌患者的预后．术前放疗亦无足够的证据证明其有效。近年的研究焦点集中于新辅助治疗．包括术前放化疗（chemoradiotherapy,CRT）和术前化疗。     

直肠癌新辅助放化疗的适宜人群及疗效评价

新辅助放化疗联合根治性手术是局部进展期直肠癌[T3～T4和（或）N1～N2]的标准治疗模式,20％左右的患者能获得病理完全缓解及更好的预后。选择出真正适合放化疗的患者有利于指导其个体化治疗,避免治疗过度。对放化疗后的疗效进行评价有助于下一步治疗方案的确立,影像学及病理学评价仍是目前最为主要的评价方式。     

食管癌术前放化疗与术前化疗:孰优孰劣?

中国是食管癌高发国家,外科手术是我国食管癌的主要治疗手段,但单纯手术对于中晚期食管癌的治疗效果不尽如人意。为了提高食管癌的疗效,国内外学者进行了多种综合治疗模式的探索,包括术前放疗、术前化疗、术后放疗等,其中术前新辅助治疗的模式特别引人关注。术前新辅助治疗,包括术前放化疗和术前化疗,尤其是前者有望提高食管癌患者的预后。该文拟对以手术为主的食管癌新辅助治疗的循证医学证据进行综述。     

新辅助治疗在局部晚期食管鳞癌中的应用

单纯手术对于局部晚期食管鳞癌的疗效不尽如人意。为提高其疗效, 世界各地学者探究多种综合治疗模式, 特别是新辅助治疗模式, 包括新辅助化疗、新辅助放化疗、新辅助化疗联合免疫治疗以及新辅助放化疗联合免疫治疗等。随着免疫时代的到来, 新辅助化学治疗联合免疫治疗和新辅助放化疗联合免疫治疗的方法备受研究者关注。为此, 本文拟对以手术为主的食管鳞癌新辅助治疗模式这一热点问题进行讨论。     

局部进展期中低位直肠癌新辅助放化疗疗效预测分子标志物的研究进展

新辅助放化疗作为局部进展期直肠癌推荐的术前标准治疗方案,在降低局部复发率、增加保肛率等方面具有明显优势。但因个体差异,不同病人对新辅助放化疗反应不同,部分病人不能从新辅助放化疗中获益甚至出现病情进展。目前用于预测局部进展期直肠癌新辅助放化疗疗效的分子标志物较多,但尚无分子标志物获得临床共识。随着生物组学技术发展,分子标志物的研究已从单个基因或蛋白向全基因组或蛋白组转变,为指导个体化新辅助放化疗提供更多依据。此文将探讨局部进展期中低位直肠癌新辅助分层治疗现状,综述新辅助疗效标志物。     

Perioperative therapy for esophageal cancer

Traditionally, surgery is considered the best treatment for esophageal cancer in terms of locoregional control and long-term survival, but survival after surgery alone for locally advanced esophageal cancer is not satisfactory. A multidisciplinary approach that includes surgery, radiotherapy, and chemotherapy, alone or in combination, has been developed to improve the prognosis. Multiple clinical trials have addressed the preferred treatment strategy, such as neoadjuvant or adjuvant and chemotherapy, radiotherapy, or chemoradiotherapy, in managing locally advanced esophageal cancer. In this review, we provide an update on treatment strategies for locally advanced esophageal cancers. Recent studies indicate that neoadjuvant chemoradiotherapy or chemotherapy has a survival benefit over surgery alone in this patient group. Neoadjuvant chemoradiotherapy is an accepted standard of care in the United States while neoadjuvant chemotherapy is regarded as standard treatment in Japan and the United Kingdom. The standard treatment differs among countries because two large randomized controlled trials that evaluated the effectiveness of neoadjuvant chemotherapy reported conflicting results and no trial has made a comparison between neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy directly. Future trials in locally advanced esophageal cancer should focus on identifying the optimum strategy and its regimen and aim to minimize treatment toxicities and effects on quality of life.     

Treatments for esophageal cancer: a review

Esophageal cancer is the eighth most common form of cancer worldwide. The treatments for esophageal cancer depend on its etiology. For mucosal cancer, endoscopic mucosal resection and endoscopic submucosal dissection are standard, while for locally advanced cancer, esophagectomy remains the mainstay. The three most common techniques for thoracic esophagectomy are the transhiatal approach, the Ivor Lewis esophagectomy (right thoracotomy and laparotomy), and the McKeown technique (right thoracotomy followed by laparotomy and neck incision with cervical anastomosis). Surgery for carcinoma of the cervical esophagus requires an extensive procedure with laryngectomy in many cases. When the tumor is more advanced, neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy is added. The theoretical advantages of adding chemotherapy to the treatment of esophageal cancer are potential tumor down-staging prior to surgery, as well as targeting micrometastases and, thus, decreasing the risk of distant metastasis. Cisplatin- and 5-fluorouracil-based regimes are used worldwide. Chemoradiotherapy is the standard for unresectable esophageal cancer and could also be considered as an option for resectable tumors. For patients who are medically or technically inoperable, concurrent chemoradiotherapy should be the standard of care. Although neoadjuvant chemoradiotherapy followed by surgery or salvage surgery after definitive chemoradiotherapy is a practical treatment; judicious patient selection is crucial. It is important to have a thorough understanding of these therapeutic modalities to assist in this endeavor.     

Oesophageal cancer: current status of multimodality therapy

Multimodality treatment options have been widely promoted in the therapy for locally advanced oesophageal cancer (cT3/4Nx). Generally neoadjuvant chemotherapy and combined radiochemotherapy are frequently used in this setting. The recent meta-analyses evaluating randomised trials of different neoadjuvant therapy protocols prior to surgery for patients with locally advanced oesophageal cancer showed only a modest improvement in survivial of 5-10% survival at 5 years. In contrast, the meta-analyses reveal that patients with excellent histopathological responses seem to highly benefit from neoadjuvant regimens. Patients with poor histopathological responses have no benefit but rather disadvantegeous prognoses. Therefore, predictive markers to allow individualisation of multimodality treatment in locally advanced esophageal cancer are urgently needed.     

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??Radiotherapy of locally recurrent rectal cancer GAO Xian-shu, LI Hong-zhen. Department of Radiation Oncology, Peking University First Hospital, Beijing 100034, China
Corresponding author: LI Hong-zhen, E-mail??doclee0134@163.com
Abstract Local recurrence is the most common clinical failure pattern of rectal cancer, especially in stage II/III rectal cancer cases. The prognosis of postoperative recurrence is poor. To prevent recurrence, related studies on adjuvant/neoadjuvant chemoradiotherapy of locally advanced rectal cancer after surgery started in the 1970s. A large number of clinical trial results showed that preoperative and postoperative adjuvant/neoadjuvant chemoradiotherapy of locally advanced rectal cancer may reduce local recurrence, improve sphincter rate and survival. The pattern of multiple discipline treatment has become an evidence-based medicine I class as a standard treatment options of locally advanced rectal cancer. Chemoradiotherapy of locally recurrent rectal cancer has not yet achieved a high level of evidence-based medicine. NCCN guidelines recommend against recurrent rectal cancer patients should be performed multidisciplinary and comprehensive treatment. For isolated recurrent pelvic or anastomosis, if patients have not received the full amount of radiation, the most appropriate treatment is preoperative radiotherapy, concurrent chemotherapy. In conditional medical institutions, preoperative neoadjuvant chemoradiotherapy plus surgery and intraoperative radiotherapy may be considered.     

REG I Expression Predicts Long-term Survival among Locally Advanced Thoracic Squamous Cell Esophageal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy Followed by Esophagectomy

Background The prognosis for patients with locally advanced thoracic esophageal cancer is extremely unfavorable. We have been administering neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy to these patients and studying whether REG I expression in untreated endoscopic biopsy specimens is predictive of patient responsiveness to CRT and/or survival after treatment.Methods Between 1992 and 2003, 47 patients with T4 (direct invasion of adjacent organs) thoracic esophageal cancers were administered neoadjuvant CRT followed by esophagectomy. REG I expression was assessed in untreated endoscopic biopsy specimens and correlated with clinical and histological responses and survival in 37 patients who had also undergone curative surgery.Results Among the 37 cases that received CRT followed by surgery, the therapeutic response rate for neoadjuvant CRT was 68%, and a complete histological response in resected specimens from the primary lesion was achieved in 8 (22%) patients. These clinical and histological responses to neoadjuvant CRT did not significantly correlate with survival, however. By contrast, 9 patients were judged REG-positive based on analysis of their untreated endoscopic biopsy specimens, and their cumulative survival rate was significantly higher than that of the 28 REG-negative patients (P = 0.0073). Univariate analysis showed REG I expression to be a prognostic factor (P = 0.0386) that increased the risk of death 8.4-fold.Conclusions Evaluation of REG I expression in untreated endoscopic biopsy specimens may provide a basis for new treatments of locally advanced thoracic squamous cell esophageal cancers.     

pMMR局部进展期中低位直肠癌行新辅助放化疗联合替雷利珠单克隆抗体的探索研究

目的 探索长程放化疗联合替雷利珠单克隆抗体作为错配修复基因蛋白无缺失型（pMMR）局部进展期中低位直肠癌病人新辅助治疗方案的安全性和有效性。方法 前瞻性分析2021年4月至2021年12月首都医科大学附属北京友谊医院11例临床分期为cT3-4N0M0或cT1-4N+M0接受全直肠系膜切除手术且术前行新辅助放化疗联合替雷利珠单克隆抗体治疗的pMMR中低位直肠癌病人临床资料。研究主要终点为病理完全缓解,同时分析药物不良反应发生率,手术安全性,术后并发症发生率以及病理组织学改变。结果 11例病人均完成放化疗,10例病人接受3次替雷利珠单克隆抗体治疗,1例接受2次替雷利珠单克隆抗体治疗。1例（9.1%）病人出现3级免疫性肠炎的不良反应。保肛手术率为100.0%。1例病人术后出现Clavien-DindoⅡ级吻合口漏。所有病人肿瘤均为pMMR,共有6例（54.5%）病人达到病理完全缓解,3例（27.3%）达到主要病理缓解,客观缓解率达100.0%。6例病理完全缓解的病人中,有2例（18.2%）达到临床完全缓解。结论 pMMR局部进展期中低位直肠癌病人行长程放化疗联合靶向程序性细胞死亡受体-1（P...     

进展期直肠癌新辅助放疗与化放疗联合TME随机对照试验的Meta分析

目的评价新辅助放疗组与新辅助化放疗组联合全直肠系膜切除术(TME)治疗局部进展期直肠癌的安全性与疗效。 方法检索2002年至2017年PubMed、OVID、Cochrane图书馆、中国生物医学文献数据库(CBM)、中国知网全文数据库(CNKI)、万方数据库关于新辅助治疗联合TME手术治疗局部进展期直肠癌的文献,对符合纳入标准的文献进行质量评价,采用Revman5.0软件检验异质性,进行meta分析。 结果共4个随机对照试验共2 272例直肠癌患者纳入研究,新辅助放疗组1 133例患者,新辅助化放疗组1 139例患者。与新辅助化放疗组相比,单纯新辅助放疗组的完全病理缓解率更低(OR＝0.32, 95%CI: 0.22～0.44, P<0.05),5年局部复发率更高(OR＝2.13, 95%CI: 1.62～2.79, P<0.05),严重不良反应更少(OR＝0.38, 95%CI: 0.17～0.82, P＝0.01),差异有统计学意义。但保肛率、术后并发症发病率、5年无病生存率和总生存率差异无统计学意义。 结论新辅助化放疗总体上优于单纯新辅助放疗治疗进展期直肠癌,但临床应用中仍需要根据患者的耐受情况选择合适的新辅助治疗方案。     

Non-invasive monitoring of tissue oxygenation during laparoscopic donor nephrectomy

Background

A surgical resection is currently the preferred treatment for esophageal cancer if the tumor is considered to be resectable without evidence of distant metastases (cT1-3 N0-1 M0). A high percentage of irradical resections is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone and in trials in which patients are treated with surgery alone. Improvement of locoregional control by using neoadjuvant chemoradiotherapy might therefore improve the prognosis in these patients. We previously reported that after neoadjuvant chemoradiotherapy with weekly administrations of Carboplatin and Paclitaxel combined with concurrent radiotherapy nearly always a complete R0-resection could be performed. The concept that this neoadjuvant chemoradiotherapy regimen improves overall survival has, however, to be proven in a randomized phase III trial.

Methods/design

The CROSS trial is a multicenter, randomized phase III, clinical trial. The study compares neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with potentially curable esophageal cancer, with inclusion of 175 patients per arm. The objectives of the CROSS trial are to compare median survival rates and quality of life (before, during and after treatment), pathological responses, progression free survival, the number of R0 resections, treatment toxicity and costs between patients treated with neoadjuvant chemoradiotherapy followed by surgery with surgery alone for surgically resectable esophageal adenocarcinoma or squamous cell carcinoma. Over a 5 week period concurrent chemoradiotherapy will be applied on an outpatient basis. Paclitaxel (50 mg/m2) and Carboplatin (Area-Under-Curve = 2) are administered by i.v. infusion on days 1, 8, 15, 22, and 29. External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week. After completion of the protocol, patients will be followed up every 3 months for the first year, every 6 months for the second year, and then at the end of each year until 5 years after treatment. Quality of life questionnaires will be filled out during the first year of follow-up.

Discussion

This study will contribute to the evidence on any benefits of neoadjuvant treatment in esophageal cancer patients using a promising chemoradiotherapy regimen.

Trial registration

ISRCTN80832026     

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??Management of complete response after neoadjuvant chemoradiotherapy in rectal cancer SU Xiang-qian, YANG Hong. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education)??Department of Minimally Invasive Gastrointestinal Surgery??Peking University Cancer Hospital & Institute??Beijing 100142??China
Corresponding author: SU Xiang-qian??E-mail: suxiangqian@bjmu.edu.cn
Abstract Neoadjuvant chemoradiotherapy (CRT) followed by radical surgery including total mesorectal excision (TME) is standard treatment in patients with locally advanced rectal cancer. The benefits of neoadjuvant CRT have been well documented and include tumor regression and downstaging associated with increased tumor respectability, reduced local recurrence and a higher rate of sphincter preservation. Radical surgery for rectal cancer carries a high risk of morbidity and mortality and can also greatly detract from a patient’s quality of life. In light of the significant response rates that can be achieved with preoperative CRT, some scholars have suggested limiting further surgical therapy to local excision alone or to observation for patients with clinical complete response (cCR). This article summarizes the latest development of management strategies for complete responders after neoadjuvant CRT for rectal cancer.