直肠癌新辅助放化疗敏感性预测进展

直肠癌是我国最常见的恶性肿瘤之一。近年来,直肠癌的新辅助放疗或放疗联合化疗及全直肠系膜切除的根治术已逐步成为治疗中下段进展期直肠癌的标准模式。目前已经有大量研究证实新辅助治疗的优点,但尚有一部分患者无法在其中受益。在新辅助放化疗前或其早期预测其敏感性,达到肿瘤的“个体化治疗”,目前在这方面已经进行了大量研究。本文将就预测新辅助治疗敏感性的进展进行综述。     

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。     

食管癌新辅助放化疗效应预测的研究进展

食管癌是中国发病率第三的恶性肿瘤,新辅助放化疗后行根治手术是目前治疗局部晚期食管癌的标准方案。肿瘤病灶在放化疗后是否达到病理完全缓解对后续治疗有重要引导意义,现对通过病理评估、影像学方法和生物标记物等方法预测食管癌新辅助放化疗效应的研究进展作综述。     

直肠癌新辅助放化疗抵抗性的基因组学预测研究

目的 基于加权基因共表达网络(WGCNA)从分子水平寻找影响直肠癌放化疗抵抗的枢纽基因。方法 于基因表达数据库获得接受放化疗患者的全基因组表达数据GSE119409,分别构建放化疗病理完全缓解组与未获得病理完全缓解组的加权基因共表达网络。利用NetRep保守性评估方法综合分析网络模块各个节点基因连接度、基因显著性与网络位置属性,确定与直肠癌放化疗抵抗性密切相关的枢纽基因。结果 通过WGCNA方法共获得5个(black、blue、green、yellow、purple)与放化疗抵抗性密切相关的网络模块,筛选出5个(SLC22A14、SIDT2、CABP4、EPHB6、RAB11B)与直肠癌放化疗抵抗性相关的枢纽基因。结论 通过加权基因共表达网络分析方法共筛选出与直肠癌放化疗抵抗性相关的5个基因共表达网络模块及相应的5个枢纽基因,为寻找术前放化疗抵抗性评估分子标志物及潜在的治疗靶点提供了线索。     

局部进展期直肠癌新辅助放化疗的研究进展

术前放化疗联合全系膜切除手术为局部晚期直肠癌患者治疗的标准模式,术前放化疗比术后放化疗提高了肿瘤降期率、保肛率及局部控制率,术前放化疗后达到病理完全缓解患者拥有更好的预后。本文就近年来术前放化疗的研究进展作一综述。     

局部进展期直肠癌新辅助放化疗的研究进展

术前放化疗联合全系膜切除手术为局部晚期直肠癌患者治疗的标准模式,术前放化疗比术后放化疗提高了肿瘤降期率、保肛率及局部控制率,术前放化疗后达到病理完全缓解患者拥有更好的预后。本文就近年来术前放化疗的研究进展作一综述。     

腹腔镜与传统手术联合新辅助放化疗治疗直肠癌的疗效分析

目的比较腹腔镜与传统手术联合新辅助放化疗治疗直肠癌的临床疗效。方法选取2011年6月至2013年6月间治疗的56例直肠癌患者,随机分为腹腔镜手术组和传统手术组,所有患者术前均行新辅助放化疗,新辅助放化疗结束6~8周后,行直肠癌根治术。结果两组患者的手术方式、淋巴结清扫数目及并发症、复发情况等方面差异无统计学意义(P>0.05)。腹腔镜手术组术中出血量、术后恢复时间、住院时间均显著短于传统手术组(P<0.05),手术时间长于传统手术组(P<0.05)。结论腹腔镜联合新辅助放化疗治疗直肠癌与传统手术相比并未增加手术风险,且有同样的疗效,安全可行,可临床推广应用。     

MicroRNA在直肠癌新辅助治疗疗效预测中的作用

新辅助放化疗是局部晚期直肠癌的标准治疗模式,然而并非所有患者均能从中获益,对放化疗不敏感的患者,新辅助治疗可能延误手术时机,降低总生存率。因此,寻找预测直肠癌新辅助治疗疗效的生物标志物,筛选出对新辅助治疗疗效差的患者,及早行手术治疗,对制定个体化的治疗策略具有重要意义。MicroRNA是具有基因表达调节作用的小的非编码RNA,参与多种信号传导途径和DNA损伤修复过程,影响直肠癌细胞的放射敏感性,可能预测新辅助治疗的疗效。本文旨在对近年来有关microRNA在直肠癌新辅助治疗中疗效预测相关的研究进展进行综述,以期进一步明确microRNA在直肠癌新辅助治疗疗效预测中的作用。     

MicroRNA在直肠癌新辅助治疗疗效预测中的作用

新辅助放化疗是局部晚期直肠癌的标准治疗模式,然而并非所有患者均能从中获益,对放化疗不敏感的患者,新辅助治疗可能延误手术时机,降低总生存率。因此,寻找预测直肠癌新辅助治疗疗效的生物标志物,筛选出对新辅助治疗疗效差的患者,及早行手术治疗,对制定个体化的治疗策略具有重要意义。MicroRNA是具有基因表达调节作用的小的非编码RNA,参与多种信号传导途径和DNA损伤修复过程,影响直肠癌细胞的放射敏感性,可能预测新辅助治疗的疗效。本文旨在对近年来有关microRNA在直肠癌新辅助治疗中疗效预测相关的研究进展进行综述,以期进一步明确microRNA在直肠癌新辅助治疗疗效预测中的作用。     

Ku70 和端粒酶及端粒酶逆转录酶预测直肠癌新辅助放化疗的疗效

目的 研究Ku70、端粒酶（telomerase）及端粒酶逆转录酶（hTERT） 3种蛋白预测Ⅱ期和Ⅲ期直肠癌放疗联合XELOX方案化疗的疗效。方法 根据新辅助放化疗前后影像学检查的疗效评价,将入组患者分为有效组27例和无效组18例;采用免疫组化SP法检测两组患者新辅助放化疗前后Ku70、端粒酶及hTERT 蛋白的表达情况,并分析其与疗效的关系。结果 有效组患者hTERT蛋白的表达水平比无效组低,差异具有统计学意义（P〈0.05）。Ku70、端粒酶蛋白在有效组与无效组患者中的表达水平差异无统计学意义（P〉0.05）。Ku70、 端粒酶及hTERT蛋白的表达水平在放化疗前后的差异有统计学意义（P〈0.05）。直肠癌患者新辅助放化疗的疗效与患者KPS评分、性别、年龄和病理类型等无关（P〉0.05）。结论 hTERT蛋白的表达可以反映Ⅱ期和Ⅲ期直肠癌患者予放疗联合XELOX方案化疗的新辅助放化疗的疗效。     

Complete clinical response after neoadjuvant chemoradiation for distal rectal cancer

Multimodality treatment of rectal cancer, with the combination of radiation therapy, chemotherapy, and surgery has become the preferred approach to locally advanced rectal cancer. The use of neoadjuvant chemoradiation therapy (CRT) has resulted in reduced toxicity rates, significant tumor downsizing and downstaging, better chance of sphincter preservation, and improved functional results. A proportion of patients treated with neoadjuvant CRT may ultimately develop complete clinical response. Management of these patients with complete clinical response remains controversial and approaches including radical resection, transanal local excision, and observation alone without immediate surgery have been proposed. The use of strict selection criteria of patients after neoadjuvant CRT has resulted in excellent long-term results with no oncological compromise after observation alone in patients with complete clinical response. Recurrences are detectable by clinical assessment and frequently amenable to salvage procedures.     

Extramural depth of rectal cancer tumor invasion at thin-section MRI: predicting treatment response to neoadjuvant chemoradiation

Objectives

To assess whether the maximal extramural depth (EMD) of T3 tumor spread on magnetic resonance imaging(MRI) correlates with tumor response parameters and whether it can predict tumor response to neoadjuvant chemoradiation.

Methods

111 rectal cancer patients with American Joint Committee on Cancer (AJCC) T3 tumors underwent MRI staging before neoadjuvant chemoradiotherapy were included. Tumor EMD was measured as mm tumor beyond the muscular and compared between the following groups by Kruskal-Wallis test: pathological complete response(pCR) versus nonpCR, good regression versus poor regression, downstage versus nondownstage.

Results

The final study population consisted of the 111 patients (79 male, 32 female). Median age was 56 years (range, 23–75 years). The EMD was significantly higher in nonpCR patients (7.8 ± 3.2 mm) than in pCR patients(6.1 ± 1.8 mm) (p = 0.033). According to good regression (tumor regression grade(TRG) 0–1 vs. TRG 2–3) and downstaging (ypStage 0-I vs. ypStage II–III), the difference was not significant. Receiver operating characteristic curve analysis revealed a good value for the area under the curve (0.775) and the cutoff value for EMD to predict pCR was 5.6 mm. Compared with patients with a EMD ≥ 5 mm, more patients with EMD <5 mm showed pCR (p = 0.019), while there was no correlation between EMD and good regression or downstaged.

Conclusion

EMD value obtained on initial staging MRI may serve as an imaging biomarker which predicts patients that have an incomplete response pathological response after standard neoadjuvant therapy.     

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。     

Aspirin as a neoadjuvant agent during preoperative chemoradiation for rectal cancer

Background:

Recently, many studies have suggested a possible adjuvant role of aspirin in colorectal cancer, reporting a positive prognostic effect with its use in patients with established disease. The aim of this study was to investigate the anticancer effect of aspirin use during preoperative chemoradiation for rectal cancer.

Methods:

Two hundred and forty-one patients with stage II–III rectal cancer and candidates for chemoradiation (CRT) were selected and assigned to two groups: group 1, patients taking aspirin at the time of diagnosis, and group 2, all others. Treatment and oncological outcomes were explored.

Results:

Aspirin use was associated with a higher rate of tumour downstaging (67.6% vs 43.6%, P=0.01), good pathological response (46% vs 19% P<0.001), and a slightly, although not significant, higher rate of complete pathological response (22% vs 13% P=0.196). Aspirin use was also associated with a better 5-year progression-free survival (86.6% vs 67.1% hazard rate (HR)=0.20; 95% CI=0.07–0.60) and overall survival (90.6% vs 73.2% HR=0.21; 95% CI=0.05–0.89). Although chance of local relapse was similar (HR=0.6; 95% CI=0.06–4.5), aspirin use was associated with a lower risk of developing metastasis (HR=0.30; 95% CI=0.10–0.86).

Conclusions:

Aspirin might have anticancer activity against rectal cancer during preoperative CRT. This finding could be clinically relevant and should be further investigated with randomised trials.     

Tumor regression in mesorectal lymphnodes after neoadjuvant chemoradiation for rectal cancer.

AIMS: The histological modification produced by neoadjuvant chemoradiation on primary rectal cancer has been investigated by many authors, and a prognostic value of tumor regression grade (TRG) has been identified. Tumor regression grade on metastatic mesorectal lymphnodes has been never evaluated. The purpose of this study is to analyse the TRG on mesorectal lymphnodes (lymphnode regression grade, LRG) after preoperative chemoradiation in rectal cancer patients and to determine the correlation with TRG of primary tumor. METHODS: Surgical specimens from 35 patients who underwent chemoradiation were included. LRG on mesorectal lymphnodes was assessed by immunohistochemistry. Response to treatment was evaluated by a 5-point LRG based on the ratio of residual tumor to fibrosis. RESULTS: Complete pathologic response (LRG 1) was observed in 18 patients (51%). In 4 patients (11%) no regression was observed (LRG 5). In 4 cases only reactive lymphnodes were found. LRG on lymphnodes significantly correlated with TRG on primary tumor (p<0.05). CONCLUSIONS: Neoadjuvant chemoradiation determines a tumor regression on mesorectal lymphnodes as on primary tumor; further studies are needed to evaluate the prognostic value of LRG.     

Counterpoint: long-course chemoradiation is preferable in the neoadjuvant treatment of rectal cancer

There are 2 approaches to preoperative therapy. Short-course (25 Gy in 5 fractions) radiation and long-course (50.4 Gy in 28 fractions) radiation combined with chemotherapy (CMT). Although short-course radiation therapy is used in some European countries, it is not favored in all European countries or North America. Unlike long-course CMT, it cannot be safely combined with adequate doses of systemic concurrent chemotherapy, and, as currently designed, it does not increase sphincter preservation. Long-course CMT remains the preferred regimen for cT3 and/or node-positive disease. With parallel advances in staging, surgery, systemic therapy, and molecular markers, more selective approaches are being investigated.