局部进展期直肠癌新辅助放化疗后缓解率的准确性评估

新辅助放化疗是局部进展期直肠癌术前的首选辅助治疗,其使肿瘤降期、降级的作用已得到广泛认可.部分局部进展期直肠癌患者经新辅助放化疗后可达到临床完全缓解(cCR),经术后病理证实为病理完全缓解(pCR).而准确评估缓解率对制定局部进展期直肠癌的后续治疗策略有重要指导作用,本文主要对局部进展期直肠癌缓解率的准确性评估予以综述.     

直肠癌术前放化疗完全缓解后的临床策略分析

  目的  探讨直肠癌经新辅助放化疗后获得完全缓解病例的处理办法。  方法  回顾性分析河南大学淮河医院2010年1月至2014年8月收治的直肠癌术前进行新辅助放化疗的84例患者临床资料。  结果  经过新辅助放化疗,33例（39.3%）患者获得临完全床缓解（clinical complete response,cCR）;经术后病理检查,6例患者获得病理完全缓解（pathological complete response,pCR）,占cCR病例的18.2%（6/33）,术后随访12~36个月均未出现肿瘤转移复发情况。  结论  新辅助放化疗能明显降低肿瘤分期,并能使部分患者获得cCR。对于cCR病例,不建议非手术治疗。      

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T 3-T 4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...     

直肠癌新辅助治疗后临床完全缓解的评估

新辅助治疗已成为局部晚期直肠癌的标准治疗模式。新辅助治疗后对肿瘤反应进行评估及再分期对于制定患者后续的治疗策略和预测肿瘤的预后至关重要。有一部分患者在新辅助治疗后能达到临床完全缓解甚至病理完全缓解,而在病理未明确之前如何评估临床缓解一直是目前国内外专家关注的焦点。本文就直肠癌新辅助治疗后的最佳评估时间和评估方法的进展进行综述。     

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。     

辅助化疗对ypⅠ期直肠癌患者术后生存的影响

[目的]比较Ⅰ期直肠癌与新辅助治疗后降期为ypT1-2N0M0的cT3-4或N+的直肠癌患者5年总生存率的差异.[方法]回顾分析105例直肠癌根治术后病理分期为T1～2N0M0的直肠癌患者的临床病理资料及随访资料.按患者是否行新辅助治疗和辅助化疗分为3组.单纯手术组(A组):未经术前新辅助治疗,pT1～2N0M0的早期直肠癌患者(29例).新辅助降期化疗组(B1组):初始诊断为cT3-4或N+,术前行新辅助治疗后降期为ypT1-2N0M0,且术后行辅助化疗的直肠癌患者(54例).新辅助降期非化疗组(B2组):初始诊断为cT3～4或N+,术前行新辅助治疗后降期为ypT1～2N0M0,且术后未行辅助化疗的直肠癌患者(22例).对3组生存情况进行分析.[结果]新辅助治疗后降期为T1～2N0M0的直肠癌患者(B1+B2组)术后5年生存率为94.0％.单纯手术组(A组)患者术后5年生存率为91.0％,新辅助降期化疗组(B1组)为88.9％,新辅助降期非化疗组(B2组)为90.9％.单因素分析提示3组预后差异无统计学意义(P＞0.05).[结论]新辅助治疗后降期为T1-2N0M0的直肠癌患者无论是否行术后化疗都可获得与Ⅰ期直肠癌患者相同的预后.新辅助治疗后降期为T1～2N0M0直肠癌患者术后化疗并未能提高患者5年总生存率.     

局部晚期直肠癌新辅助治疗后病理完全缓解者的预后分析

目的:总结局部晚期直肠癌新辅助治疗后病理完全缓解（pCR）者的长期预后,探讨术后辅助化疗的必要性。方法:回顾性分析2005年至2014年间,323例在我院进行新辅助治疗及根治性手术的局部晚期直肠癌患者的临床资料,分析pCR者的长期预后,同时比较术后辅助化疗组和术后未化疗组的预后。结果:52例（16.1%）获得pCR,其中1例患者失访;全组患者中位随访时间为53个月,全组5年无病生存率和总生存率分别为82.7%和90.9%。其中22例（43.1%）患者接受术后辅助化疗,29例（56.9%）未接受术后化疗。两组患者的性别、年龄、肿瘤临床分期、肿瘤位置、大小、分化程度、术前CEA水平、新辅助化疗的方案、新辅助治疗结束至手术的间隔周期、手术方式、术后并发症、淋巴结清扫的数目以及随访时间均无统计学差异。两组患者的5年无病生存率以及总生存率亦无统计学差异。结论:局部晚期直肠癌新辅助治疗后病理完全缓解者可获得良好的生存预后;对于pCR者,实施术后辅助化疗不会影响其预后。     

中低位局部进展期直肠癌器官保留热点问题

局部进展期直肠癌标准治疗为新辅助放化疗后全直肠系膜切除术。临床上部分患者在新辅助治疗后可以达到临床完全缓解或者近临床完全缓解。对于该类患者，很多研究机构采取等待观察策略或者局部切除来代替传统的全直肠系膜切除术。临床上将该种代替治疗手段称之为器官保留。而器官保留自从诞生之日起，争论不断。作者就器官保留中的热点问题做一述评。     

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。     

局部晚期食管鳞癌新辅助放化疗联合手术治疗的临床疗效分析

目的 探讨新辅助放化疗联合手术治疗局部晚期食管鳞癌的临床疗效,并分析临床完全缓解率(cCR)与病理完全缓解率(pCR)的关系。方法 回顾性选取2001—2013年局部晚期胸段食管鳞癌患者 158例,全组均采用术前同期放化疗联合手术方式,化疗采用以铂类为基础化疗方案,放疗剂量为40 Gy,2.0 Gy/次,5 次/周。Kaplan-Meier法计算OS和DFS,Logrank法检验并单因素预后分析,Cox模型多因素预后分析。结果 全组患者的pCR率为41.1%。新辅助放化疗后 44例cCR患者中 32例(73%)达pCR,114例非cCR患者中 33例(28.9%)达pCR (P=0.000)。cCR预测pCR的敏感性、特异性分别为49.2%、87.1%,阳性、阴性预测值分别为72.7%、71.1%。3年总样本数为 53例。全组 3年OS、DFS分别为53.9%、48.6%,cCR的显著高于非cCR的(P=0.012、P=0.026),pCR的显著高于非pCR的(P=0.000、0.000)。多因素分析显示放化疗后病理反应和化疗方案是影响OS的因素。最常见≥3级急性不良反应为白细胞减少(34.2%)。结论 新辅助放化疗联合手术治疗局部晚期食管鳞癌可获得较高pCR率且不良反应可耐受,放化疗后cCR率与pCR率、OS密切相关。     

三阴性乳腺癌患者的临床特征及新辅助化疗疗效与预后的相关性

 目的　探讨三阴性乳腺癌（TNBC）的临床病理特点及远期生存率。并分析其新辅助化疗的疗效与生存率的相关性。方法　研究对象为535例乳腺癌患者,其中TNBC患者75例,非TNBC患者460例,对其临床和病理资料以及 5年的无病生存（DFS）率及总生存（OS）率进行回顾性分析,并与同期的非TNBC患者进行对比。535例中88例患者接受术前新辅助化疗,TNBC患者26例,非TNBC患者62例,分析其化疗疗效与远期生存的相关性。结果　TNBC患者与非TNBC患者相比,中位年龄轻（35岁比44岁）,绝经前患者居多（88.0 % 比67.2 %,P＝0.009）;浸润性导管癌多见（92. 0 % 比80.4 %,P＝0.020）,组织学分级Ⅱ级者居多（56.0 %比17.2 %,P＝0.000）;淋巴结转移阳性者较少（33.3 %比53.9 %,P＝0.001）;TNBC组5年DFS（66.67 %）、OS（80.0 %）明显低于非TNBC组（74.78 %、90.0 %）。接受新辅助化疗的TNBC患者与非TNBC患者相比,化疗的总有效（OR）率（88.46 %比82.26 %）、临床完全缓解（cCR）率（65.38 %比37.10 %）、部分缓解（PR）率（23.08 %比45.16 %）差异均有统计学意义（P＜0.05）。新辅助化疗的TNBC患者与非TNBC患者相比,5年的OS率（73.08 %比80.65 %）差异具有统计学意义（P＝0.049）;5年的DFS率（65.38 %比72.58 %）差异具有统计学意义（P＝0.253）。分层分析发现：获得cCR的TNBC与非TNBC患者的5年DFS及OS差异无统计学意义（P＞0.05）。未获得cCR TNBC患者的5年DFS及OS均显著低于非TNBC患者（P＜0.05）,临床OR对两组的5年DFS及OS无影响（P＞0.05）。结论　TNBC多见于年轻的绝经前妇女,主要病理类型为浸润性导管癌,核分级高,淋巴结转移少见,但相对非TNBC患者有较低的DFS率和OS率,TNBC患者对新辅助化疗更敏感,更易获得cCR,获得cCR的TNBC患者预后好,未获得cCR的TNBC患者远期生存率明显低于非TNBC患者     

直肠癌新辅助放化疗后cCR患者不同治疗方法随访观察

目的 通过比较新辅助放化疗后cCR的直肠癌患者采用非手术治疗和TME治疗的效果,旨在探讨非手术治疗策略的可行性。方法 选取2006—2016年中山大学肿瘤防治中心接受术前放化疗并获得cCR的135例Ⅱ、Ⅲ期直肠癌患者,根据治疗方法的不同将其分为非手术组(43例NOM组)和标准手术组(92例SOM组)。比较2组患者的局部复发率、挽救性治疗后的累计LC率、DFS、OS以及保肛率等。Kaplan-Meier法计算LC、OS、DFS并Logrank法检验,χ²检验保肛率。结果 中位随访39个月(10~127个月)。135例患者的局部复发率及远处转移率分别为3.7%和11.1%,术后3年DFS和OS分别为90.5%和97.0%。NOM组与SOM组术后3、5年DFS率分别为87%与93%、73%与87%(P=0.089),OS率分别为98%与99%、98%与97%(P=0.578)。NOM组局部复发5例(12%),80%患者得到挽救性治疗,累计LC率为98%;SOM组无局部复发病例;两组差异有统计学意义(P=0.010)。NOM组保肛率为93%,显著高于SOM组的70%(P=0.030)。结论 新辅助放化疗后获得cCR的直肠癌患者采取非手术治疗策略是可行的,部分局部复发患者仍可通过及时的挽救性治疗痊愈,从而有效避免了TME及其并发症,提高了患者的生活质量。     

Oestrogen receptor status, pathological complete response and prognosis in patients receiving neoadjuvant chemotherapy for early breast cancer

The aim of this study was to ascertain if oestrogen receptor (ER) status predicts for pathological complete response (pCR) to neoadjuvant chemotherapy in operable breast cancer, and the effects of pCR on survival. Using a single-institution database, 435 patients were identified, who received neoadjuvant chemotherapy for operable breast cancer and were eligible for the analysis. Patients whose tumours were ER negative were more likely to achieve a pCR than patients who were ER positive (21.6 vs 8.1%, P<0.001). Owing to a strong correlation between ER status and grade, these variables were not shown to be independent predictors of pCR. Overall survival (OS) was better in those patients who achieved a pCR compared to those who did not (5-year OS 91 vs 73%; P=0.02). This was still the case when only patients with ER-negative tumours were examined (5-year OS 90 vs 52%, P=0.005), but not in the subset of patients with ER-positive tumours (5-year OS 93 vs 79%; P=0.3). Therefore, patients with ER-negative tumours were found to be more likely to achieve a pCR to neoadjuvant chemotherapy than those with ER-positive tumours, and pathological response did not have prognostic significance in patients with ER-positive tumours.     

Association between Pathological Complete Response and Outcome Following Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients

Purpose

We aimed to determine the rate of pathological complete response (pCR), clinicopathological factors associated with pCR, and clinical outcomes following neoadjuvant chemotherapy in locally advanced breast cancer.

Methods

Medical records of patients who had undergone neoadjuvant chemotherapy for breast cancer between January 2007 and September 2011 were retrospectively reviewed, and the pCR rates were calculated according to three sets of criteria: the National Surgical Adjuvant Breast and Bowel Project (NSABP), the MD Anderson Cancer Center (MDACC), and the German Breast Group (GBG). Tumors were classified as luminal A like, luminal B like, human epidermal growth factor receptor 2 (HER2), or triple-negative. pCR and clinical outcome, including overall survival (OS) and disease-free survival (DFS) rates were analyzed at the median follow-up of 54.2 months.

Results

Of a total of 179 patients who had received neoadjuvant chemotherapy, 167 patients (93.3%) had locally advanced breast cancer and 12 patients (6.7%) had early-stage breast cancer. The majority of patients (152 patients, 89.4%) received anthracycline-based neoadjuvant chemotherapy. The objective clinical response rate was 61.5%, comprising clinical partial response in 5.5% and clinical complete response in 3.9% of patients. Twenty-one (11.7%), 20 (11.2%), and 17 patients (9.5%) achieved pCR according to NSABP, MDACC, and GBG definitions, respectively. pCR rates, as defined by NSABP, according to breast cancer subtype were 4.4%, 9.7%, 24.2%, and 19.2% in luminal A like, luminal B like, HER2, and triple-negative subtypes, respectively. Patients who achieved pCR had significantly better DFS (5-year DFS rates, 80% vs. 53%, p=0.030) and OS (5-year OS rates, 86% vs. 54%, p=0.042) than those who did not.

Conclusion

The pCR rate following neoadjuvant chemotherapy for breast cancer in Thai women attending our institution was 11.7%; pCR was more frequently observed in HER2 and triple-negative breast tumor subtypes. Patients who achieved pCR had significantly improved survival.     

直肠癌新辅助放化疗后临床完全缓解等待观察策略可行性的Meta分析

目的:比较直肠癌新辅助放化疗后达到临床完全缓解（clinical complete response,cCR）采取等待观察策略和手术切除治疗策略在肿瘤控制及生存期方面的差异,以此阐述等待观察策略的可行性。方法:在国外数据库中检索关于直肠癌新辅助放化疗（nCRT）达到cCR关于等待观察策略和手术切除对比试验的相关文献,按照纳入和排除标准进行文献筛选和质量评估,使用STATA 12.0软件进行Meta分析,对比两组在局部复发、远处转移、肿瘤相关死亡、2年及5年无疾病进展生存期和总体生存期之间的差异。结果:本研究总共纳入9篇文献,Meta分析结果显示:等待观察组相比手术组有着较高的局部复发率（LR）（RR=5.05;95%CI:2.22~11.51;P<0.001),但是两组在远处转移（RR=0.93;95%CI:0.51~1.68;P=0.805）、肿瘤相关死亡（RR=0.83;95%CI:0.37~1.87;P=0.658）、2年无疾病进展生存期（RR=0.97;95%CI:0.91~1.03;P=0.277）、2年总体生存期（RR=1.03;95%CI:0.97~1.10;P=0.346）、5年无疾病进展生存期（RR=0.95,95%CI:0.83~1.08;P=0.406）、5年总体生存期（RR=1.03;95%CI:0.95~1.11;P=0.534）并无统计学差异。结论:对于部分nCRT后达到cCR的患者采用等待观察策略是可行的,但需要制定严格的筛选标准以及规范的随访。     

Wait-and-see or radical surgery for rectal cancer patients with a clinical complete response after neoadjuvant chemoradiotherapy: a cohort study

A wait-and-see policy might be considered instead of surgery for rectal cancer patients with no residual tumor or involved lymph nodes on imaging or endoscopy after neoadjuvant chemoradiotherapy (clinical complete response, cCR). In this cohort study, we compared the oncologic outcomes of rectal cancer patients with a cCR who were managed according to a wait-and-see policy (observation group) or with surgery (surgery group). In the observation group, follow-up was performed every 3 months for the first year and consisted of MRI, endoscopy with biopsy, computed tomography and transrectal ultrasonography. In the surgery group, patients received radical surgery. Long-term oncologic outcomes were estimated using Kaplan-Meier curves. Thirty patients were enrolled in the observation group (median follow-up, 60 months; range, 18-100 months), and 92 patients were enrolled in the surgery group (median follow-up, 58 months; range, 18-109 months). The 5-year disease free survival and overall survival rates were similar in the two groups: 90.0% vs. 94.3% (P = 0.932) and 100.0% vs. 95.6% (P = 0.912), respectively. We conclude that for rectal cancer patients with a cCR after neoadjuvant chemoradiotherapy, a wait-and-see policy with strict selection criteria, follow-up and salvage treatments achieves outcomes at least as good as radical surgery. Additionally, we declare that the pCR (pathologic complete regression) and non-pCR subgroups of patients with a cCR have similar long-term failure (local recurrence and/or distant metastasis) rate.     

乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用

目的:探讨乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用.方法:收集漯河市中心医院收治的236例接受新辅助化疗患者的临床病理资料,分为Luminal A、Luminal B、Her-2阳性和三阴乳腺癌4种分子分型,分析分子分型与临床病理因素、新辅助化疗疗效及 5 年生存率的相关性.结果:236例患者中,107例(45.3%)为Luminal A亚型,47例(19.9%)为Luminal B亚型,27例(11.4%)为Her-2阳性亚型,55例(23.3%)为三阴乳腺癌亚型.Her-2阳性(25.9%)及三阴乳腺癌亚型(30.9%)的病理完全缓解(pCR)率明显高于Luminal亚型(Luminal A亚型 4.7%及Luminal B亚型 8.5%),差异有统计学意义(P<0.05).与Luminal亚型相比,Her-2阳性及三阴乳腺癌亚型具有更差的5年无病生存和总生存(P<0.01);获得pCR的乳腺癌患者的5年无病生存和总生存明显高于化疗后仍有癌残留的患者(P<0.05).结论:相对于Luminal亚型,Her-2 阳性和三阴乳腺癌亚型对新辅助化疗更为敏感,更易达到pCR;但是Her-2阳性和三阴乳腺癌亚型预后反而更差.     

原发性乳腺癌分子分型与新辅助化疗疗效及预后的相关性

目的 探讨原发性乳腺癌分子分型与新辅助化疗疗效及预后之间的相关性。方法 回顾性分析河南省肿瘤医院收治的204例接受新辅助化疗患者的临床病理资料,分为Luminal A、LuminalB、HER2阳性和三阴乳腺癌4种亚型,分析乳腺癌分子分型对新辅助化疗疗效及预后的预测作用。结果 204例患者中,40例（19.6％）为Luminal A亚型,46例（22.5％）为Luminal B亚型,36例（17.6％）为HER2阳性亚型,82例（40.2％）为三阴乳腺癌亚型。HER2阳性（22.2%）及三阴乳腺癌亚型（22.4%）的病理完全缓解（pCR）率明显高于Luminal A亚型（2.5％）及Luminal B亚型（6.5％）,差异有统计学意义（P=0.03）。与Luminal亚型相比,HER2阳性及三阴乳腺癌亚型具有更差的无病生存期（DFS）（P=0.001）和OS（P=0.002）;剔除获得pCR的患者,单独评价存在肿瘤残留的患者,我们发现HER2阳性及三阴乳腺癌亚型比Luminal亚型具有更差的DFS（P<0.001）和OS（P<0.001）。获得pCR的乳腺癌患者的5年DFS和总生存期（OS）均明显高于化疗后仍有癌残留的患者（P=0.002, P=0.012）。结论 相对于Luminal亚型,HER2 阳性和三阴乳腺癌亚型对新辅助化疗更为敏感,更易达到pCR;但是HER2阳性和三阴乳腺癌亚型预后反而更差。     

Salvage surgery for local regrowths in Watch & Wait - Are we harming our patients by deferring the surgery?

BackgroundRectal cancer surgery conveys significant morbidity/mortality, long-term functional impairment and urinary & sexual dysfunction, especially if associated with neoadjuvant chemoradiotherapy (ChRT). Watch & Wait (W&W) is gaining momentum as an option for patients with clinical complete response (cCR) after ChRT. Approximately 30% will develop a local regrowth (RG) and need deferred surgery. Our study aimed to assess the short-term clinical outcomes after surgery for regrowths.Patients and methodsConsecutive rectal cancer patients from a tertiary institution who underwent neoadjuvant ChRT, between January 2013 and October 2018, were identified from a prospectively maintained database. Patients with RG under W&W surveillance were operated - regrowth deferred surgery (RDS) group - and compared to those with persistent disease after ChRT who did undergo surgery - non-deferred surgery (NDS) group.ResultsTotal of 124 patients received neoadjuvant treatment: 46 (37%) underwent surgery for persistent disease; 78 (63%) with cCR entered W&W. Twenty three developed RG and underwent surgery, while 55 remain under surveillance. RDS group had lower tumors than NDS group (2.3 cm ± 2 vs 4.5 cm ± 3, p = 0.002). All RG underwent minimally invasive surgery (MIS). Anastomotic leaks, 30-day morbidity, reintervention and readmission rates were similar. Pathology features and 3-year oncological outcomes were identical between groups.ConclusionPatients with initial cCR and local regrowth may be safely managed by deferred surgery. Short-term outcomes suggest equivalent results to patients with incomplete clinical response and immediate radical surgery. Delayed MIS appears to have no negative impact on oncological outcomes.