局部进展期直肠癌新辅助放化疗后肿瘤退缩的影响因素分析及预测模型构建

背景与目的：局部进展期直肠癌（locally advanced rectal cancer,LARC）的标准治疗策略是新辅助放化疗（neoadjuvant chemoradiotherapy,nCRT）后进行手术治疗,nCRT可以使肿块缩小,实现肿瘤降期,增加R0切除率。但直肠癌个体差异较大,有部分患者对nCRT反应较差,并不能从nCRT中获益。因此,采取有效的筛选措施,以识别nCRT效果不佳的患者很有必要。本研究旨在探讨临床基线指标对LARC nCRT后肿瘤退缩的预测价值并构建肿瘤退缩预测模型。方法：收集2016年1月—2020年12月在空军军医大学第一附属医院接受nCRT治疗且行全直肠系膜切除术的LARC患者,收集入组患者nCRT前的临床基线指标,包括实验室检查、肿瘤标志物和磁共振成像（magnetic resonance imaging,MRI）资料。根据nCRT前后的MRI报告的肿瘤大小,通过实体瘤疗效评价标准（Response Evaluation Criteria in Solid Tumors,RECIST）来评价LARC患者nCRT后肿瘤退缩程度。使用受试者工作特征（r...     

直肠癌新辅助治疗后复发及远处转移的研究进展

结直肠癌是中国常见的恶性肿瘤,位居恶性肿瘤死因的第3位。在2012年诊断的全球1361000例结直肠癌中,中国结直肠癌患者占18.6%。手术是直肠癌的主要治疗手段。多项大型Ⅲ期临床研究结果显示,新辅助放化疗(nCRT)较术后放化疗能有效降低患者的术后5年局部复发率,提高括约肌保存率。nCRT已被美国癌症联合委员会确定为Ⅱ、Ⅲ期直肠癌的标准治疗方法。虽然nCRT能降低患者的局部复发率,但在减少远处转移的发生和延长生存期方面并无获益。本文探讨nCRT后局部进展期直肠癌患者肿瘤复发及远处转移的模式,并探讨患者无生存获益的原因。     

同步放化疗治疗食管癌术后复发的临床效果及预后因素分析

目的:分析同步放化疗治疗食管癌术后复发患者的治疗效果及预后因素。方法:回顾性分析103例食管癌术后复发患者行同步放化疗的治疗结果及预后因素。所有患者行同步放化疗,中位放疗剂量60Gy。治疗后1~3月评价肿瘤的治疗反应。结果:中位随访时间30个月（3~103月）。3年总生存率47.6%,中位存活时间35月。总体反应率70.9%（73/103),完全缓解率41.7%（43/103)。单因素分析显示同步放化疗后肿瘤的反应（P=0.000)、至复发的时间(P=0.028)及ECOG评分(P=0.090),有益于总生存率,多因素分析显示同步放化疗后肿瘤的反应(P=0.000)及ECOG评分(P=0.010)为总生存率的独立预后因素。同步放化疗后,共70例患者出现肿瘤进展,39例局部复发,22例远处转移,9例远处转移伴局部复发。结论:同步放化疗是治疗食管癌术后复发的有效手段,治疗后取得完全缓解的患者预后较好。     

根治术后局部复发性直肠癌的预后因素分析

目的 探讨影响直肠痛根治术后局部复发患者预后因素以及术后联合辅助治疗的疗效.方法 搜集2000年4月至2004年4月间105例局部复发性直肠癌再次治疗患者的病例资料和随访结果,回顾分析17项临床病理因素和患者预后的关系.确定影响局部复发性直肠癌预后的独立因素并对复发后不同治疗方式进行评价.结果 随访率为95.2%,1、3、5年总生存率分别为63%、34%、19%,中位生存时间23个月.手术+放化疗(34例),单纯手术(35例)和放化疗(36例)的1、3、5年生存率分别为79%、55%、32%,68%、40%、14%和64%、36%、11%(χ~2=7.96,P=0.019).单因素分析结果表明原发肿瘤组织学分级、浸润深度、转移淋巴结数、首次术后分期、复发部位、复发时间及复发后治疗方式与预后相关;其中首次术后TNM分期、复发部位、复发时间和复发后治疗方法是影响根治术后局部复发直肠癌患者预后的独立因素.手术联合放化疗的5年生存率明显优于单纯手术及单纯辅助治疗.结论 首次术后TNM分期、复发部位、复发时间和复发后治疗方式是局部复发性直肠癌的独立预后因素,手术联合放化疗可能会给局部复发性直肠癌患者带来长期生存机会.     

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。     

脑胶质瘤术后放化疗复发再手术患者预后的影响因素分析

目的 分析脑胶质瘤术后放化疗复发再手术患者预后的影响因素。方法 选取86例脑胶质瘤术后放化疗复发再手术患者的病历资料,采用卡氏功能状态(KPS)评分评估再手术治疗前及术后6个月的生活质量。脑胶质瘤术后放化疗复发再手术患者预后的影响因素采用Logistic回归分析。结果 再手术后6个月,脑胶质瘤术后放化疗复发再手术患者的KPS评分为(77.16±6.91)分,明显高于再手术前的(58.15±8.33)分,差异有统计学意义(P﹤0.01);且Ⅰ～Ⅱ级脑胶质瘤术后放化疗复发再手术患者的KPS评分为(81.51±6.31)分,高于Ⅲ～Ⅳ级患者的(71.74±8.33)分,差异有统计学意义(P﹤0.01)。随访结束后,86例脑胶质瘤术后放化疗复发再手术患者中,生存56例,死亡30例,生存与死亡脑胶质瘤术后放化疗复发再手术患者年龄、合并基础疾病、饮酒情况、再手术前KPS评分、与初次手术间隔时间、病理分级、肿瘤体积比较,差异均有统计学意义(P﹤0.05)。多因素Logistic回归分析结果显示,年龄≥65岁、合并基础疾病、再手术前KPS评分﹤70分、与初次手术间隔时间﹤1年、病理分级为Ⅲ～Ⅳ级、肿瘤...     

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。     

胸段食管鳞癌手术治疗或根治性放化疗后复发和生存分析北大核心CSCD

目的分析经手术治疗或根治性放化疗的胸段食管鳞癌患者的复发部位和生存时间特征。方法回顾性分析胸段食管鳞癌患者的复发和生存时间,应用Kaplan-Meier法分析生存时间,Cox回归模型进行多因素预后分析。结果本研究纳入586例胸段食管鳞癌患者,其中手术组334例,放化疗组252例。手术组共有129例复发(局部区域复发36例,远处转移93例),放化疗组共有118例复发(局部区域复发79例,远处转移39例),两组复发部位的构成比差异有统计学意义(χ~2=37.75,P<0.01)。手术组和放化疗组的中位总生存时间分别为39.5月和23.5月,两者的差异具有统计学意义(P<0.01)。结论胸段食管鳞癌手术治疗后复发以远处转移为主,根治性放化疗后的复发则以局部区域复发为主。手术治疗的生存结果优于根治性放化疗。     

新辅助同步放化疗联合TME及术后辅助化疗对中低位局部进展期直肠癌的疗效研究

目的探讨新辅助同步放化疗联合全直肠系膜切除（TME）加术后辅助化疗三联疗法治疗中低位局部进展期直肠癌的疗效及安全性.方法选择局部进展期中低位直肠癌Ⅱ、Ⅲ期（T2N＋M0,T3-4N0-2M0期）65例,术前放疗总剂量50～54Gy,术前采用Xelox方案化疗3个疗程,放化疗结束后6～8周根据TME原则行直肠癌根治术.术后采用Forfox4方案辅助化疗6个疗程.结果65例均完成新辅助同步放化疗、手术治疗及术后辅助化疗.其中48例行Dix-on’s手术,17例行mile’s手术,保肛率73.85%,术后并发症发生率23.08%,其中伤口感染延期愈合6例,吻合口瘘4例,吻合口狭窄5例,手术后病理完全缓解（pCR）11例,占16.92%.结论新辅助放化疗＋TME手术治疗＋术后辅助化疗三联疗法治疗中低位进展期直肠癌安全有效,可以降低肿瘤分期,减少局部复发及远处转移,中远期疗效好.     

侧方淋巴结转移的中低位局部晚期直肠癌治疗现状

中低位局部晚期(Ⅱ-Ⅲ期)直肠癌侧方淋巴结转移(LLN)率高、预后差。目前, 关于LLN治疗方案东西方争议较大:以日本为代表的东方学者认为LLN是区域性疾病, 当肿瘤位于腹膜返折下且侵及肌层时无论有无LLN, 均推荐预防性盆腔侧方淋巴结清扫(LPLND);而欧美学者认为LLN是全身性疾病, 推荐新辅助放化疗(nCRT)联合全直肠系膜切除(TME)。然而, 近年来有研究发现, nCRT或LPLND均不能显著降低LLN患者的局部复发率, 而nCRT联合LPLND治疗的预后更好, 也有研究发现增加转移淋巴结放疗剂量可以提高局部控制率。本文综述了该类人群的治疗现状, 以期为临床治疗提供依据。     

The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.     

Optimal Interval to Surgery After Neoadjuvant Chemoradiotherapy in Rectal Cancer: A Systematic Review and Meta-analysis

This study aimed to evaluate the influence of a waiting interval of ≥ 8 weeks between the end of preoperative neoadjuvant chemoradiotherapy (nCRT) and surgery on the outcomes of patients with locally advanced rectal cancer. We conducted a comprehensive literature review of retrospective and prospective studies from PubMed, Embase, and Cochrane Library databases to investigate the length of the preoperative nCRT–surgery waiting interval and outcomes in patients with locally advanced rectal cancer. The primary outcome measure was pathologic complete response (pCR) rate. Secondary outcome measures included overall survival, disease-free survival, operative time, and the incidence of local recurrence, postoperative complications, anastomotic leakage, and sphincter-preserving surgery. Standardized mean differences and risk ratios were calculated. Thirteen studies involving 19,652 patients were included. The meta-analysis demonstrated that pCR was significantly increased in patients with locally advanced rectal cancer and a waiting interval of ≥ 8 weeks between preoperative nCRT and surgery compared to a waiting interval of < 8 weeks, or a waiting interval of > 8 weeks compared to ≤ 8 weeks (risk ratio = 1.25; 95% confidence interval, 1.16-1.35; P < .0001). There were no significant differences in overall survival, disease-free survival, operative time, or incidence of local recurrence, postoperative complications, or sphincter-preserving surgery. This study revealed that performing surgery after a waiting interval of ≥ 8 weeks after the end of preoperative nCRT is safe and efficacious for patients with locally advanced rectal cancer, significantly improving pCR without increasing operative time or incidence of postoperative complications, compared to a waiting interval of ≤ 8 weeks.     

基于深度学习的放射影像组学特征预测局部晚期直肠癌新辅助放化疗反应研究

目的 探讨基于深度学习的方法,从疗前MRI中提取放射影像组学特征预测局部晚期直肠癌新辅助放化疗反应的有效性。方法 2016-2017年纳入43例局部晚期直肠癌新辅助同步放化疗患者。均在疗后6~12周接受全系膜直肠切除术。弥散加权成像(DWI)序列MRI在同步放化疗前获得。根据术后病理、影像学检查或肠镜检查评估新辅助治疗后反应,将患者分为治疗反应组(22例)和治疗无反应组(21例)。分别采用传统的计算机辅助诊断方法和预先训练的卷积神经网络,从DWI序列的表观扩散系数图中提取手工和基于深度学习的影像组学(DLR)特征。利用提取的特征建立最小绝对收缩和选择算子Logistic回归模型,预测治疗反应。使用受试者工作特性曲线,通过重复20次分层4倍交叉验证评估模型性能。结果 使用基于DLR构建模型的平均曲线下面积为0.73(标准误为0.58~0.80)。结论 从疗前MRI中基于深度学习方法提取的影像组学特征在预测局部晚期直肠癌患者新辅助治疗反应方面准确度高。     

Circulating Lymphocytes as Predictors of Sensitivity to Preoperative Chemoradiotherapy in Rectal Cancer Cases

Objective: The objective of this study was to identify clinical predictive factors for tumor response afterneoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Methods: All factors wereevaluated in 88 patients with LARC treated with nCRT. After a long period of 4-8 weeks of chemoradiotherapy,3 patients achieved clinical complete response (cCR) and thus aggressive surgery was avoided, and the remaining85 patients underwent a curative-intent operation. The response to nCRT was evaluated by tumor regressiongrade (TRG) system. Results: There were 32 patients (36.4%) with good tumor regression (TRG 3-4) and 56(63.6%) with poor tumor regression (TRG 0-2). Lymphocyte counts and ratios were higher in good responsecases (P=0.01, 0.03, respectively) while neutrophil ratios and N/L ratios were higher in poor response cases(P=0.04, 0.02, respectively). High lymphocyte ratios before nCRT and good tumor regression (TRG3-4) weresignificantly associated with improved 5-year disease-free survival (P<0.05). Pretreatment nodal status wasalso significantly associated with 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariateanalysis confirmed that the pretreatment lymphocyte ratio and lymph nodal status were independent prognosticfactors. Conclusion: Our study suggested that LARC patients with high lymphocyte ratios before nCRT wouldhave good tumor response and high 5-year DFS and OS.     

直肠癌新辅助治疗中盆腔骨髓保护调强放疗与病理反应的相关性

目的:探讨直肠癌新辅助治疗中盆腔骨髓保护调强放疗与病理反应的相关性。方法:回顾性分析2017年01月至2020年12月于我院接受新辅助放化疗及根治性手术的192例Ⅱ、Ⅲ期直肠癌患者的临床病理资料,其中95例为接受盆腔骨髓保护调强放疗的患者(淋巴细胞保护组),余97例患者来源于本单位回顾性数据库(对照组)。比较两组患者淋巴细胞绝对计数最低值、淋巴细胞下降程度及肿瘤病理反应率差异,分析直肠癌新辅助治疗中盆腔骨髓保护调强放疗与病理反应的相关性。结果:淋巴细胞保护组患者放化疗期间最低淋巴细胞计数、放化疗后淋巴细胞计数及病理反应率均高于对照组,差异有统计学意义。淋巴细胞保护组3-4级淋巴细胞减少症发生率为38.9%,低于对照组的56.8%(P=0.034)。多因素Logistic回归分析结果显示3-4级淋巴细胞减少症、淋巴细胞保护、临床分期及等待手术期间化疗是肿瘤病理反应状态的独立影响因素。结论:直肠癌患者新辅助放化疗期间3-4级淋巴细胞减少症与治疗后肿瘤病理反应状态密切相关,通过盆腔骨髓保护调强放疗可有效保护患者的淋巴细胞,减轻3-4级淋巴细胞减少症发生率,提高肿瘤病理反应。     

Is neoadjuvant chemoradiation with dose-escalation and consolidation chemotherapy sufficient to increase surgery-free and distant metastases-free survival in baseline cT3 rectal cancer?

Patients with cT3 rectal cancer are less likely to develop complete response to neoadjuvant chemoradiation (nCRT) and still face significant risk for systemic relapse. In this setting, radiation (RT) dose-escalation and consolidation chemotherapy in “extended” nCRT regimens have been suggested to improve primary tumor response and decrease the risks of systemic recurrences. For these reasons we compared surgery-free and distant-metastases free survival among cT3 patients undergoing standard or extended nCRT.

Laparoscopic resection for rectal adenocarcinoma

Aims

Laparoscopic surgery for rectal cancer is still under discussion, but there is evidence that minimal access surgery can be feasible and safe also in this field. The aim of this study was to confirm that laparoscopic resection for rectal cancer can afford good results in terms of recurrence rate and survival.

Patients and methods

Since June 1998 through December 2007 as many as 252 patients underwent laparoscopic resection for rectal cancer. Laparoscopic anterior resection (LAR) was performed in 209 and laparoscopic abdominoperineal resection (LAPR) in 43. Neoadjuvant radiochemotherapy (nCRT) was administered in 48 patients with mid-low rectal cancer stage II and III with evidence of nodal involvement in preoperative work up.

Results

Patients who received nCRT showed a significant longer duration of surgery compared to patients who did not (p = 0.004). Conversion to laparotomy was needed in 24 cases, (21 LAR and three LAPR) but no patient receiving nCRT needed conversion. Postoperative surgical complications occurred in 38 patients, 20 of which were represented by anastomotic leak after LAR. Six patients died postoperatively, in half the cases for surgery related causes. Downstaging after nCRT was seen in 40 patients, and complete histological response was observed in six cases. The mean number of lymph nodes harvested was 12, also in patients receiving nCRT. The mean follow-up was 48 ± 33 months (range 0.1–120.4), and 10 patients experienced local recurrence. Cumulative 5 year survival was 73.7%.

Conclusion

Laparoscopic resection for rectal cancer is feasible and safe, with morbidity and long-term results quite acceptable also in patients receiving neoadjuvant treatment.     

Tumour-stroma ratio to predict pathological response to neo-adjuvant treatment in rectal cancer

IntroductionManagement of rectal cancer has advanced, with an increasing use of neoadjuvant chemoradiotherapy (nCRT). This opens options for organ preserving treatment for those with a major response to nCRT. However, the degree of clinical response, based on MRI and post-treatment biopsies, only poorly matches the degree of actual pathological response. In order to select patients with major pathological response without surgical resection, it is of importance to define tumour markers predicting the degree of pathological response to nCRT. The intra-tumoural tumour-stroma ratio (TSR) might be this marker.MethodsTSR in pre-treatment biopsies was estimated according to the method described by van Pelt et al. The degree of pathological response was assessed on the tumour resection according to tumour regression grading (TRG) by Mandard. The primary endpoint of this study was the difference in pathological response to nCRT between TSR-high and TSR-low groups.ResultsWe found that 26.2% of patients with major response was classified as TSR-high, while 73.8% of patients were classified as TSR-low. A high TSR in pre-treatment biopsies was associated with a lower chance of major-response to nCRT (OR = 0.37, 95%CI; 0.19–0.73), p = 0.004), independent of tumour stage and time between nCRT and surgery.ConclusionIn rectal cancer, TSR in pre-treatment biopsies predicts pathologic response to nCRT, with a high TSR bringing twice the risk of poor to no response compared to low TSR. In future, assessment of TSR may fulfil a role in a therapeutic algorithm identifying patients who will or will not respond to nCRT prior to treatment initiation.     

局部晚期直肠癌新辅助放化疗联合免疫治疗的研究进展

对于局部晚期(T3-4/N+M0)直肠癌, 新辅助放化疗联合全直肠系膜切除术的标准治疗模式可以明显减少局部复发、增加肿瘤退缩, 但是远处转移没有得到改善。放疗和免疫治疗相辅相成, 两者联合具有良好的理论基础。近年来, 局部晚期直肠癌新辅助放化疗联合免疫治疗的相关临床试验逐渐展开, 在微卫星不稳定(MSI-H)和微卫星稳定(MSS)患者中均进一步提高肿瘤退缩程度和病理性完全缓解率, 增加器官保留概率, 为"等待观察"策略提供更多可能。新辅助放化疗联合免疫治疗未来仍需要更多的大型临床试验进行验证, 期待能带来更好的生存获益。