靶向治疗联合新辅助放化疗在局部进展期直肠癌中的应用

目前新辅助放化疗联合全直肠系膜切除术（TME）是局部进展期直肠癌（LARC）的标准治疗模式.靶向药物在LARC新辅助治疗中耐受性及安全性良好,但与常规新辅助放化疗相比较,病理完全缓解（pCR）率并无提高,仍需大样本随机对照研究证实其在LARC新辅助治疗中的作用.     

局部进展期直肠癌新辅助治疗后器官保留策略进展

新辅助放化疗联合全直肠系膜切除术为分期T3-T4期或N+的局部进展期直肠癌(LARC)的标准治疗,但往往会带来一系列术后并发症,尤其是接受腹会阴联合直肠癌根治术(Mile′s术)不能保留肛门者,严重影响生活质量。对于新辅助治疗后肿瘤(近)临床完全缓解者,器官保留策略在与根治性手术达到相似治疗疗效的同时,可保留肛门及其功能、保证患者的生活质量。本文对LARC新辅助治疗后器官保留策略、联合局部治疗疗效、再生/复发模式及挽救治疗等方面作总结。     

新辅助放化疗联合动脉栓塞灌注治疗局部晚期直肠癌1例

新辅助放化疗对局部晚期直肠癌(LARC)的肿瘤退缩、R0切除、局部控制率、器官保存率等方面均明显优于传统治疗模式,现已成为LARC的新标准治疗方案,但目前仍存在一些具有争议及未解决的问题。现报道1例LARC患者接受新辅助放化疗联合动脉栓塞灌注治疗后再行手术治疗并取得良好效果,这种新辅助治疗模式可供临床参考。     

NPS与局部晚期直肠癌新辅助放化疗疗效及预后相关性初步分析

目的 分析Naples预后评分(NPS)与局部晚期直肠癌(LARC)新辅助治疗疗效相关性及其预测预后价值。方法 回顾性分析2015-2020年136例LARC患者资料,搜集并计算新辅助治疗前血清白蛋白、总胆固醇、中性粒细胞与淋巴细胞比值和淋巴细胞与单核细胞比值,根据NPS法则对入组患者进行评分分级。采用Kaplan-Meier法计算生存率,Cox模型多因素预后分析。结果 NPS与LARC新辅助治疗后肿瘤退缩程度及术后pCR无相关性(P=0.192、0.163)。Cox多因素分析显示NPS是LARC的总生存(OS)及无瘤生存(DFS)的独立危险因素(P=0.017、0.003),且分层分析提示评分越低者预后较好;此外,肿瘤大小也是OS的独立危险因素,肿瘤大小与N分期也是DFS的独立危险因素。结论 NPS与LARC新辅助放化疗后肿瘤退缩及pCR无相关性,但能作为LARC治疗长期预后的有效预测指标。     

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。     

291例局部进展期直肠癌术前新辅助放化疗的临床意义分析

目的 评价局部进展期直肠癌(LARC)术前新辅助放化疗的疗效及安全性。方法 2003—2012年间291例LARC接受了术前新辅助放化疗+手术±术后辅助化疗。放疗为2DRT、3DRT,45~50 Gy分23~25次。化疗方案包括FOLFOX6、XELOX及单药希罗达等,术前化疗2~4周期。放疗结束后3~8周手术,遵循全直肠系膜切除术原则。134例患者术后接受了辅助化疗。Kaplan-Meier法计算OS、DFS、RFS和DMFS等,Logrank法检验和单因素预后分析,Cox模型多因素预后分析。结果 全组均完成术前新辅助放化疗及手术。R0切除率为98.9%,保肛率为53.6%。T降期73.1%,N降期83.6%,临床分期降期79.4%。pCR率为26.8%,3级血液系统反应为7.9%,3级腹泻为7.2%,3级放射性皮炎为2.7%。术后会阴部疼痛占12.3%,伤口延迟愈合占8.2%。随访率94.5%,5年样本量为95例。5年OS、DFS、RFS和DMFS分别为76.6%、72.1%、88.8%和79.7%,5年LR率为7.5%,远处转移率为15.8%。术后病理分期是预后影响因素。结论 术前新辅助放化疗提高了LARC的R0切除率及保肛率,并使肿瘤显著降期,不良反应较轻且未增加手术并发症,LR率低且远期生存率得到改善。术前新辅助放化疗作为LARC标准治疗策略宜推广应用。     

分子预测直肠癌新辅助放化疗后pCR的研究进展

摘 要：局部晚期直肠癌（LARC）目前的基本治疗策略是新辅助放化疗（nCRT）和随后的全直肠系膜切除术（TME）。nCRT 后的肿瘤消退在个体间差异显著,病理完全缓解（pCR）是 LARC 的预后因素。明确放化疗反应的预测因素有助于临床医生鉴别可能从多模式治疗中获益的患者,并在早期对其预后进行评估。本文结合近年的相关研究,探讨LARC在新辅助治疗后可能达到pCR的分子预测因子。     

AJCC-TRG联合ypTN分期评价局部进展期直肠癌预后

目的 探讨AJCC-TRG分级联合ypTN分期评估局部进展期直肠癌(LARC)新辅助放化疗后的预后,并筛查预后最差的亚组人群。方法 2004—2012年间中山大学肿瘤防治中心收治LARC 263例,男176例,女87例,中位年龄55岁。所有患者接受术前新辅助放化疗,并于放疗结束后6~8周施行全直肠系膜切除术。根据第7版AJCC-TRG分级标准及ypTNM分期标准对术后组织标本重新评价。生存分析评价不同肿瘤退缩分级(TRG)联合ypTN对各项生存指标的预测情况。Kaplan-Meier法计算OS、DFS、LRFS及DMFS,Logrank法检验和单因素预后分析。结果 中位随访时间为60.1个月,全组5年OS、DFS、LRFS和DMFS分别为80.0%、75.0%、97.0%和81.0%。不同ypT/TRG、ypN/TRG组合间的OS、DFS及DMFS差异均有统计学意义(P均<0.05)。ypT₃—T₄/TRG 2—3、ypN₁—N₂/TRG 2—3亚组预后最差,5年OS,DFS和DMFS分别为66.9%、56.0%,52.2%、41.4%和60.9%、46.0%。结论 AJCC-TRG联合ypTN分期能更准确评估LARC预后,筛查出高危远处转移预后最差亚组人群,对指导LARC个体化术后辅助治疗具有重要临床意义。     

基于脂代谢相关基因预测局部晚期直肠癌新辅助放化疗疗效

目的探讨基于脂代谢相关基因(LMRG)预测局部晚期直肠癌(LARC)新辅助放化疗疗效的价值。方法于基因表达数据库获得接受新辅助放化疗的LARC的全基因组表达数据GSE46862, 进行差异表达分析以获得差异表达基因。于分子标签数据库(MSigDB数据库)搜集LMRG并与差异表达基因取交集获得差异表达的LMRG。基于最小绝对收缩和选择算子(LASSO)回归、支持向量机递归特征消除(SVM-RFE)、随机森林(RF)三种机器学习算法筛选获得候选LMRG。采用基因本体论(GO)与京都基因与基因组百科全书(KEGG)分析进行功能富集分析以获得潜在的功能与作用通路。采用受试者操作特征(ROC)曲线分析评估候选LMRG预测LARC新辅助放化疗疗效的准确性。结果共筛选出8个候选LMRG(ALOX5AP、FADS2、GALC、PLA2G12A、AGPAT1、AACS、DGKG、ACSBG2), 这些LMRG主要涉及脂质代谢相关生物进程, 并参与调控多个重要的脂质代谢相关信号通路。此外, 这8个候选LMRG拥有较高的预测LARC新辅助放化疗疗效的曲线下面积(AUC)值。结论基于3种机器学习算法鉴定出的8...     

基于器官功能保全的局部进展期直肠癌诊治新策略

局部进展期直肠癌（locally advanced rectal cancer, LARC）的治疗进入肿瘤学效果和功能并重的时代，传统“三明治”治疗模式的利弊凸显，通过高分辨率核磁共振成像，可以将LARC按照局部复发风险进一步分成不同危险度组别，从而施行个体化治疗模式，是保障疗效和功能的最优化策略。部分危险度稍低的LARC可以通过直接进行高质量手术、单纯术前化疗来避免术前放疗带来的功能损害。而对于根治性手术可能带来较大功能损害的LARC，通过结合各种不同的术前治疗策略，乃至全程新辅助治疗（TNT）策略，强化肿瘤退缩，甚至获得肿瘤完全缓解来改变原有的手术方式，从不可保肛的根治性腹会阴联合切除术变为可保肛的低位/极低位前切除术、括约肌间切除术等根治性手术，或从全直肠系膜切除术变为经肛局部切除术，乃至最后不需要手术的“观察＆等待”，从而最大限度保全患者的器官功能。     

局部进展期直肠癌新辅助化疗后病理完全缓解及肿瘤降期的预测因素分析

目的:探索局部进展期直肠癌(LARC)经新辅助化疗后病理完全缓解（pCR）和肿瘤降期（ypT0-1）的预测因素。方法:回顾性分析71例经新辅助化疗后进行全直肠系膜切除术的局部进展期直肠癌患者的临床资料,分析其临床特征,筛选经新辅助化疗后达到pCR及肿瘤降期（ypT0-1）的预测因子。结果:单因素分析结果显示肿瘤占肠腔＜1/2周（P＜0.001）、基线CEA≤5 ng/mL（P=0.001）、基线临床N分期为N0期（P=0.019）以及新辅助治疗2周期后影像评估为缓解（P=0.002）与直肠癌新辅助化疗后的高pCR率有关;肿瘤占肠腔＜1/2周（P＜0.001）、基线CEA≤5 ng/mL（P=0.029）以及新辅助治疗2周期后影像评估为缓解（P=0.007）与直肠癌新辅助化疗后的高肿瘤降期率（ypT0-1）有关。多因素Logistic回归分析结果显示,肿瘤占肠腔环周大小（P=0.013）、基线CEA水平（P=0.042）以及基线临床N分期（P=0.038）是影响直肠癌新辅助化疗后pCR的独立预测因子;肿瘤占肠腔环周大小（P=0.001）是影响直肠癌新辅助化疗后肿瘤降期（ypT0-1）的独立预测因子。结论:初始诊断时肿瘤占肠腔环周大小、基线CEA水平及淋巴结是否阳性对局部进展期直肠癌新辅助化疗后pCR有预测作用,肿瘤占肠腔环周大小对局部进展期直肠癌新辅助化疗后肿瘤降期（ypT0-1）有预测作用。     

Biomarkers in Locally Advanced Rectal Cancer: A Review

Locally advanced rectal cancers (LARC) are the subject of a rapidly evolving treatment paradigm. The critical timepoints where management decisions are required during the care of the LARC patient are: prior to the institution of any treatment, post neoadjuvant therapy and post-surgery. This article reviews the clinical, imaging, blood-based, tissue-based, and molecular biomarkers that can assist clinicians at these timepoints in the patient's management, in prognosticating for their LARC patients or in predicting responses to therapy in the multi-modality neoadjuvant treatment era.     

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。     

全程新辅助治疗模式用于局部进展期直肠癌治疗的研究进展

大肠癌在全球范围内是一种发病率较高的实体性肿瘤,直肠癌手术难度大、并发症发生率高、局部复发率比较高，尤其是局部进展期直肠癌(locally rectal cancer，LAＲC)治疗效果较差，随着多学科综合治疗理念在直癌中的应用,特别是新辅助放化疗应用于局部进展期直肠癌的治疗,患者的治疗效果得到改善,局部进展期直肠癌领域是目前研究的重点和热点之一,本文对目前最新的2018年美国NCCN直肠癌肿瘤学临床实践指南中局部进展期直肠癌新辅助同步放化疗、新辅助短程放疗、全程新辅助治疗(total neoadjuvant therapy,TNT)的模式进行综述。     

Improved response rate in patients with prognostically poor locally advanced rectal cancer after treatment with induction chemotherapy and chemoradiotherapy when compared with chemoradiotherapy alone: A matched case-control study

IntroductionThe addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics.MethodsAll LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics.ResultsOf 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013).ConclusionTreatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics.     

The effect of neoadjuvant short-course radiotherapy and delayed surgery versus chemoradiation on postoperative outcomes in locally advanced rectal cancer patients – A propensity score matched nationwide audit-based study

ObjectiveTo investigate differences in postoperative outcomes between short-course radiotherapy and delayed surgery (SCRT-delay) and chemoradiation (CRT) in patients with locally advanced rectal cancer (LARC).BackgroundPrevious trials suggest that SCRT-delay could serve as an adequate neoadjuvant treatment for LARC. Therefore, in frail LARC patients SCRT-delay is recommended as an alternative to CRT. However, data on postoperative outcomes after SCRT-delay in comparison to CRT is scarce.MethodsThis was an observational study with data from the Dutch ColoRectal Audit (DCRA). LARC patients who underwent surgery (2014–2017) after an interval of ≥6 weeks were included. Missing values were replaced by multiple imputation. Propensity score matching (PSM), using age, Charlson Comorbidity Index, cT-stage and surgical procedure, was applied to create comparable groups. Differences in postoperative outcomes were analyzed using Chi-square test for categorical variables, independent sample t-test for continuous variables and Mann-Whitney U test for non-parametric data.Results2926 patients were included. In total, 288 patients received SCRT-delay and 2638 patients underwent CRT. Patients in the SCRT-delay group were older and had more comorbidities. Also, ICU-admissions and permanent colostomies were more common, as well as pulmonic, cardiologic, infectious and neurologic complications. After PSM, both groups comprised 246 patients with equivalent age, comorbidities and tumor stage. There were no differences in postoperative complications.ConclusionPostoperative complications were not increased in LARC patients undergoing SCRT-delay as neoadjuvant treatment. Regarding treatment-related complications, SCRT-delay is a safe alternative neoadjuvant treatment option for frail LARC patients.