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。     

Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure

BACKGROUNDFor locally advanced rectal cancer (LARC), standard therapy [consisting of neoadjuvant chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (ChT)] achieves excellent local control. Unfortunately, survival is still poor due to distant metastases, which remains the leading cause of death among these patients. In recent years, the concept of total neoadjuvant treatment (TNT) has been developed, whereby all systemic ChT-mainly affecting micrometastases-is applied prior to surgery.AIMTo compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for failure.METHODSIn a retrospective study, we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with TNT. High-risk for failure was defined according to the presence of at least one of the following factors: T4 stage; N2 stage; positive mesorectal fascia; extramural vascular invasion; positive lateral lymph node. TNT consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin, CRT with capecitabine, and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin prior to surgery. The primary endpoint was pathological complete response (pCR). In total, 72 patients treated with standard therapy and 89 patients treated with TNT were included in the analysis.RESULTSCompared to standard therapy, TNT showed a higher proportion of pCR (23% vs 7%; P = 0.01), a lower neoadjuvant rectal score (median: 8.43 vs 14.98; P < 0.05), higher T-and N-downstaging (70% and 94% vs 51% and 86%), equivalent R0 resection (95% vs 93%), shorter time to stoma closure (mean: 20 vs 33 wk; P < 0.05), higher compliance during systemic ChT (completed all cycles 87% vs 76%; P < 0.05), lower proportion of acute toxicity grade ≥ 3 during ChT (3% vs 14%, P < 0.05), and equivalent acute toxicity and compliance during CRT and in the postoperative period. The pCR rate in patients treated with TNT was significantly higher in patients irradiated with intensity-modulated radiotherapy/volumetric-modulated arc radiotherapy than with 3D conformal radiotherapy (32% vs 9%; P < 0.05).CONCLUSIONCompared to standard therapy, TNT provides better outcome for LARC patients with high-risk factors for failure, in terms of pCR and neoadjuvant rectal score.     

直肠癌新辅助放化疗后病理完全缓解的临床因素分析

目的 评估影响直肠癌新辅助放化疗后pCR的临床因素。方法 回顾分析2009—2012年间接受新辅助放化疗随后行根治性手术的116例直肠癌患者临床资料。所有患者术前接受盆腔调强放疗50 Gy分25次,同期氟尿嘧啶为基础化疗,完成治疗休息4~8周后行根治性手术。应用 Logistic法分析影响pCR和非pCR的临床因素。结果 共20例患者经新辅助放化疗后达pCR,pCR率为17.2%。单因素分析表明肿瘤侵犯直肠管腔周径范围达75%以上(全周肿瘤)、治疗前血清CEA水平、T分期、N分期、肛缘距离、分化程度、肿瘤最大直径与直肠癌新辅助放化疗后肿瘤pCR水平相关。多因素分析结果显示全周肿瘤、治疗前血清CEA水平和T分期是影响放化疗后肿瘤pCR预测因素。结论 非全周肿瘤、低CEA水平和早T分期等治疗前临床因素可能是获得pCR的重要决定因素。     

The impact of circumferential tumour location on the clinical outcome of rectal cancer patients managed with neoadjuvant chemoradiotherapy followed by total mesorectal excision

AimTo investigate the impact of circumferential tumour location on neoadjuvant chemoradiotherapy (CRT) response and its prognostic value for locally advanced rectal cancer (LARC) patients after CRT and surgery.MethodsA retrospective study was performed on 486 patients with LARC who received neoadjuvant CRT and surgical treatment. The rate of pathological complete response (pCR) and survival among patients with anteriorly, laterally, and posteriorly located tumours were compared. Logistic regression was performed to identify pCR predictors.ResultsThe anterior tumours exhibited the highest pCR rate of 26.7%, which was slightly higher than the 20.0% and 12.3% for lateral and posterior tumours, respectively (P = 0.006). The 5-year Overall survival (OS) rates after CRT were similar among the anterior, lateral, and posterior groups (anterior vs lateral vs posterior: 81.1% vs 89.9% vs 84.1%, P = 0.6368). Multivariate analysis revealed that the circumferential tumour location, post-CRT serum CEA and post-CRT tumour thickness measured by MRI were independently correlated with achieving pCR.ConclusionThis study is the first, to the best of our knowledge, to show that anterior LARC exhibited the highest pCR rate after neoadjuvant CRT. Patients with anterior rectal cancers do not have different prognoses from those with non-anterior cancers if they undergo neoadjuvant CRT.     

局部晚期胃癌全新辅助治疗Ⅱ期临床研究中期分析

目的 探讨“新辅助同步放化疗+巩固化疗+手术”的全新辅助治疗模式在局部晚期胃癌治疗中的安全性和疗效。方法 2018—2020年间前瞻性纳入局部晚期胃腺癌或Siewert Ⅱ/Ⅲ型胃食管结合部腺癌患者 28例,首先接受同步放化疗(CCRT),放疗剂量为45Gy,1.8 Gy/次,同步口服替吉奥 40~60mg,2 次/d。CCRT后3周接受 4~6周期SOX方案巩固化疗(CNCT)。CNCT结束后 4~6周完成胃 癌D2根治术。结果 28例患者均完成新辅助治疗,治疗中≥3级不良反应在CCRT期间出现 3例(11%),分别为血小板下降、白细胞下降、食欲下降;在CNCT期间出现白细胞下降 2例(7%)、血小板下降 3例(11%)。共 20例(71%)完成手术,达病理完全缓解者占50%。3例手术并发症分别为吻合口瘘、吻合口狭窄、感染,对症处理后好转。结论 中期分析结果示局部晚期胃癌接受全新辅助治疗可获得显著的降期,治疗不良反应及手术并发症可耐受。     

Comparative Effectiveness of Total Neoadjuvant Therapy Versus Standard Adjuvant Chemotherapy for Locally Advanced Rectal Cancer

IntroductionThe use of total neoadjuvant therapy (TNT) for locally advanced rectal cancer has been increasing in recent years, but the long-term overall survival characteristics of this approach is currently unknown.MethodsWe performed a retrospective study of patients with clinical stage II/III rectal cancer within the National Cancer Database. Patients who received TNT (defined as chemotherapy, followed by CRT, followed by surgery) were propensity score matched to patients who received adjuvant therapy (defined as CRT, followed by surgery, followed by chemotherapy). We compared overall survival (OS) and rates of pathologic complete response (pCR) between the 2 arms.ResultsOf the 4300 patients in our cohort, 3502 (81%) received adjuvant therapy and 798 (19%) received TNT. At baseline, patients who received TNT were more likely to have higher clinical T and N stages (P< .001). The 5-year OS was 77% for both TNT and adjuvant therapy patients (hazard ratio [HR] 1.06, 95% confidence interval [CI], 0.88-1.28, P = .57). After propensity score matching and adjusting for potential confounders, there were no significant differences in OS (HR_adj 1.00, 95% CI, 0.71-1.40, P = .99). After propensity score matching, there were higher pCR rates among TNT patients (16.1%) compared to adjuvant therapy patients (12.0%) (P = .037).ConclusionIn this observational study, we found TNT was not associated with a lower OS compared to standard adjuvant chemotherapy. This finding potentially reassures clinicians choosing TNT as an alternative to adjuvant chemotherapy. However, future prospective data are needed to confirm these findings.     

体素内不相干运动扩散加权成像在预测局部进展期直肠癌新辅助放化疗疗效中的初步研究

背景与目的：弥散加权成像(diffusion-weighted imaging,DWI)是目前检查活体组织中水分子扩散运动的理想方法,常规DWI使用单指数拟合函数得到表观扩散系数(apparent diffusion coefficient,ADC)值,而体素内不相干运动扩散加权磁共振成像(intravoxel incoherent motion MR imaging,IVIM-MRI)则采用足够多的低b值和高b值并使用双指数拟合函数,可获取更丰富的生物信息,因此本研究欲探讨IVIM-MRI的单、双指数模型在预测局部进展期直肠癌新辅助放化疗疗效中的应用价值。方法：纳入32例接受新辅助放化疗的局部进展期直肠癌并在新辅助治疗前、后行常规MR序列及IVIM序列扫描的患者。IVIM序列包括9个b值(0~800 s/ mm²),所得IVIM序列原始数据经单、双指数模型处理,得到单、双指数模型衰减曲线,并生成对应参数图。测量新辅助治疗前、后肿瘤实质区单指数模型ADC值和双指数模型D值、灌注系数D^*值、灌注分数f值,采用配对样本t检验进行分析;并比较病理完全缓解(pathological complete response,pCR)组和非pCR组新辅助治疗前、后参数差异。组间比较采用两独立样本t检验,P<0.05为差异有统计学意义。结果：IVIM的单指数模型中,治疗前肿瘤平均ADC值［(133.2±21.5)×10^-5 mm/s］较治疗后［(166.9±29.7)×10^-5 mm/s］小且差异有统计学意义(P<0.05);双指数模型中,新辅助放化疗前pCR组肿瘤D*值［(4 471±1 271)×10^-5 mm/ s］低于非pCR组［(5 749±1 722)×10^-5mm/s］,差异有统计学意义(P<0.05);新辅助放化疗后pCR组肿瘤D值［(97.0±14.6)×10^-5 mm/s］低于非pCR组［(113.4±22.6)×10^-5 mm/s］,且差异有统计学意义(P<0.05)。结论：基于常规DWI序列,IVIM双指数模型可更加详细补充描述肿瘤扩散信息。     

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。     

Total neoadjuvant therapy for pancreatic adenocarcinoma increases probability for a complete pathologic response

BackgroundMultiple neoadjuvant therapy protocols have been proposed in the treatment of pancreatic adenocarcinoma, including chemotherapy (CT), chemoradiation (CRT), and total neoadjuvant therapy (TNT), defined as a CT plus CRT. A pathologic complete response (pCR) can be achieved in a minority of cases. We hypothesize that TNT is more likely to confer pCR than other neoadjuvant therapies, which may improve overall survival (OS).MethodsA retrospective review of the National Cancer Database (NCDB) from 2006 to 2016 was performed, identifying patients who underwent any neoadjuvant therapy followed by definitive pancreatic resection for locally advanced or borderline resectable pancreatic adenocarcinoma. A pathologic complete response was defined as down-staging from any clinical stage to pathologic stage 0.ResultsA total of 5402 patients who received neoadjuvant therapy followed by resection were identified. 177 patients (3.3%) achieved a pCR. Of the patients who achieved a pCR, 57 received CT, 41 CRT and 79 received TNT. On multivariate analysis, TNT was more likely to confer a pCR than CRT (OR 1.67, CI 1.13–2.46, p = 0.0103) or CT (OR 2.61, CI 1.83–3.71, p < 0.0001). Patients who achieved pCR had a significantly higher OS, with median survival of 64.9 months, compared to 21.6 months in patients who did not achieve pCR (p < 0.0001).ConclusionTNT may be more likely to achieve a pCR than CT or CRT. Patients who achieve a pCR have a significant OS benefit as compared to those who have residual disease. TNT should be considered for patients requiring neoadjuvant therapy, as it may increase the likelihood of achieving a pCR, thus potentially improving OS.     

Neoadjuvant FOLFIRINOX followed by Chemoradiotherapy for Middle and Lower Rectal Cancer

Objective: Neoadjuvant concomitant chemoradiotherapy followed by surgical resection is the standard of care in the treatment of rectal cancer. We are investigating the value of adding combination chemotherapy oxaliplatin, irinotecan, leucovorin and fluorouracil (FOLFIRINOX) before neoadjuvant chemoradiotherapy. Methods: Forty-one patients with middle and lower rectal cancer were included. FOLFORINOX were given every 2 weeks over 2 months (4 cycles) followed by concomitant chemoradiotherapy (CRT). Surgery was done 6-8 weeks after CRT and then adjuvant 4 months of FOLFOX or XELOX were given. The primary end point was sphincter preservation rate. Results: All patients received the four cycles of neoadjuvant chemotherapy FOLFORINOX, 38 patients completed CRT and only 29 patients underwent surgery. 32 patients were available for assessment (29 patients who underwent surgery and three patients who refuse surgery because of no evidence of disease by endoscopy, imaging and biopsy). Sphincter preservation was achieved in twenty-one patients (51.2%). Pathological complete response rate was 24.1%. After a median follow up of 24 months. Median PFS was 20 months and 2-years PFS was 62.3%. The median overall survival of all patients was not reached, while 2-years OS was 76.5%. Conclusion: Neoadjuvant FOLFIRINOX followed by CRT for middle and lower rectal cancer is feasible, tolerable with satisfactory sphincter preservation rate.     

局部晚期直肠癌新辅助治疗pCR相关因素研究

目的 评价局部晚期直肠癌新辅助治疗后pCR的相关影响因素。方法 回顾分析2011—2013年间收治的265例AJCC分期Ⅱ、Ⅲ期直肠癌患者资料。所有患者均接受新辅助治疗±等待手术间期化疗, 而后手术。运用单因素和二元Logistic回归多因素分析影响pCR的预测因素, 并根据预测危险因素进行归类后分为无风险组(无因素)、低风险组(1个因素)、高风险组(2个因素)。建立临床风险评估模型。因素分析运用二元Logistic回归模型。结果 达pCR者50例(18.9%)。单因素分析中新辅助治疗前CEA、放化疗前T分期、同期放化疗结束至手术间隔时间和放化疗前肿瘤最大厚度对pCR有影响(P=0.017、0.001、0.000、0.040), 多因素分析显示新辅助治疗前CEA水平和同期放化疗结束至手术间隔时间是pCR影响因素(P=0.021、0.001), 进一步分层分析表明只有非吸烟组中新辅助治疗前低水平CEA对pCR有影响(P=0.044)。临床风险评估模型诊断pCR的敏感性为80.5%, 特异性为46.0%, AUC为0.690, 阳性预测值为35.49%, 阴性预测值为86.5%, 准确性为73.9%。结论 新辅助治疗能使部分局部晚期直肠癌患者达pCR。新辅助治疗前低水平CEA和更长的同期放化疗结束至手术间隔时间是局部晚期直肠癌新辅助治疗pCR的预测因素, 而新辅助治疗前低水平CEA对pCR预测只在非吸烟人群中有效。根据新辅助治疗前CEA>5 ng/ml和同期放化疗结束至手术间隔时间≤8周的危险因素建立的临床风险评估模型可用于预测局部晚期直肠癌新辅助治疗pCR率。     

The effectiveness of planned esophagectomy after neoadjuvant chemoradiotherapy for advanced esophageal carcinomas

BACKGROUND: The best treatment option for patients with locally advanced esophageal carcinoma has not yet been determined, especially because the benefits of esophagectomy after neoadjuvant chemoradiotherapy are still controversial. We report the results of a retrospective cohort comparison of definitive chemoradiotherapy without surgery (CRT) versus neoadjuvant chemoradiotherapy followed by planned surgery (CRTS) in patients with advanced esophageal squamous cell carcinoma (SCC). MATERIALS AND METHODS: Between January 1991 and December 2002, 67 patients were enrolled in this study. Fifty of the 67 patients were considered to have inoperable tumors due to distant organ metastasis, distant lymph node metastasis, severe organ dysfunction or rejection of surgery by the patient and received CRT, while the remaining 17 patients were treated with CRTS. The clinical responses of the primary tumors were evaluated. RESULTS: In the 50 CRT patients, the one- and 2-year survival rates were 33.8% and 20.2%, respectively, and the median survival time (MST) was 13.5 months. In the 17 CRTS patients, the response rate (CR + PR) was 76.5%, and the pathological complete response (pCR) rate was 29.4%. Their one- and 2-year survival rates were 61.6% and 35.9%, respectively, and the MST was 24.4 months. The survival rates of the CRT patients were lower than those of the CRTS patients (p = 0.1288). When the 12 patients with distant organ metastases were removed from the CRT group, the one- and 2-year survival rates of the remaining 38 patients were 36.5% and 24.1%, respectively, and the MST was 14.7 months. The survival rates of these 38 CRT patients without distant organ metastases were similar to those of the 12 CRTS patients in the pathological partial response (pPR) group (p = 0.6279). CONCLUSION: This retrospective cohort comparison of CRT versus CRTS demonstrated that there may not be any survival benefit from the addition of surgery in the pPR group for advanced esophageal carcinomas. For patients with a poor response to neoadjuvant chemoradiotherapy, we suggest that the addition of chemoradiotherapy, instead of planned esophagectomy, may show a similar survival rate to definitive CRT. Thus, a large series of a randomized control study will be required to confirm the benefit of surgery after chemoradiotherapy.     

New standard in locally advanced rectal cancer

In the following review we intend to ascertain the optimal neoadjuvant therapy in patients with locally advanced rectal cancer. In 2004, a study revealed that chemoradiotherapy (CRT) resulted in better local control when performed preoperatively rather than postoperatively, thus neoadjuvant treatment was established as a standard treatment. Subsequently, the Polish study and the Trans-Tasman Radiation Oncology Group showed no statistically significant difference between concomitant CRT over 5 wk vs short-course radiotherapy (RT). Therefore, both were established as standard neoadjuvant treatments. Later, the Stockholm III study demonstrated that short-course RT had a higher complete pathological response than long-course RT. It also showed that a delay between RT and surgery presented fewer complications. This opened a window of time to provide an early and effective systemic treatment to prevent distant metastases. Studies show that short-course RT plus oxaliplatin-based chemotherapy could achieve this. When comparing this total neoadjuvant treatment (TNT) vs concomitant CRT, the former showed greater complete pathological response and lower acute toxicity. Studies presented during 2020 have also shown the benefits of TNT in terms of complete pathological response, as well as disease and metastasis-free survival. Our review suggests that probably TNT should be the new standard treatment for these patients. However, we will have to wait for the full text publications of these studies to confirm this statement.     

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。     

系统免疫炎症指数对激素受体阴性乳腺癌新辅助化疗后病理完全缓解的预测价值

目的:探讨化疗前系统免疫炎症指数（systemic immune-inflammation index,SII）与激素受体阴性乳腺癌新辅助化疗（neoadjuvant chemotherapy,NAC）后病理完全缓解（pathological complete response,pCR）的关系。方法:回顾性分析2013年1月-2017年1月在我院接受新辅助化疗并行手术的278例女性乳腺癌临床病理资料,组间分析通过Pearson's χ2进行评估。使用Logistic回归模型进行单因素和多因素分析。结果:本研究共91例（32.7%）患者接受新辅助化疗后获得pCR,其中低SII组55例,高SII组36例,SII与pCR相关（P=0.015）。单因素分析显示:T1+T2组（pCR率37.10%）较T3+T4组（pCR率15.79%）更易获得pCR(P=0.003);低SII组（pCR率39.57%）较高SII组（pCR率25.90%）更易获得pCR(P=0.016);将单因素分析中差异具有统计学意义的临床病理特征纳入多因素分析显示:与T1+T2组相比,T3+T4组更难获得pCR(P=0.005);与低SII组相比,高SII组更难获得pCR(P=0.031)。结论:SII、临床T分期是乳腺癌新辅助化疗后pCR的独立预测因素,低SII且T1+T2组患者更易获得pCR。     

Delaying surgery after neoadjuvant chemoradiotherapy in rectal cancer has no influence in surgical approach or short-term clinical outcomes

Aims

In rectal cancer, increasing the interval between the end of neoadjuvant chemoradiotherapy (CRT) and surgery could improve the pathological complete response (pCR) rates, allow full-dose neoadjuvant chemotherapy, and select patients with a clinical complete response (cCR) for inclusion in a “watch & wait” program (W&W). However, controversy arises from waiting more than 8–12 weeks after CRT, as it might increase fibrosis around the total mesorectal excision (TME) plane potentially leading to technical difficulties and higher surgical morbidity. This study evaluates the type of surgical approach and short term post-operative outcomes in patients with rectal cancer that were operated before and after 12 weeks post CRT.

Microsatellite instability and response to neoadjuvant chemoradiotherapy in rectal cancer: A systematic review and meta-analysis

BackgroundResponse to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer is variable. Identification of biomarkers to predict response is desirable in order to provide prognostic information and targeted therapy. Several studies have investigated microsatellite instability (MSI) as a predictor of response to CRT with contradictory results. This study aims to clarify the effect of MSI status on response to CRT in locally advanced rectal cancer through systematic review and meta-analysis.MethodsA systematic search of PubMed, Embase and Cochrane databases was performed for all studies relating to MSI and response to CRT in rectal cancer using the search algorithm (Microsatellite Instability) AND (Chemoradiotherapy) AND (Rectal Cancer). From each included study the number of patients with MSI tumors and Microsatellite Stable (MSS) tumors and the numbers achieving pathological complete response (pCR) were recorded. Pooled outcome measures were determined using a random effects model and the odds ratio estimated with variance and 95% confidence interval.ResultsNine published studies were identified reporting data on MSI and its effect on outcome after CRT for locally advanced rectal cancer. Five studies describing 5,877 patients included data on MSI and the number of patients achieving pCR. There was no significant association between MSI and pCR (MSI Vs MSS: 10.1% Vs 6.6%, OR 1.38, 95% CI: 0.7–2.72, p = 0.35).ConclusionThis meta-analysis concludes that there appears to be no significant difference in pCR rate following CRT in patients with MSI versus MSS rectal tumors.     

Intensified Total Neoadjuvant Therapy in Patients With Locally Advanced Rectal Cancer: A Phase II Trial

AimsWe assessed the efficacy and safety of total neoadjuvant therapy, including targeted agent plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified chemoradiotherapy (CRT) and surgical resection, in patients with locally advanced rectal cancer.Materials and methodsThis was a single-arm, single-centre phase II trial. Eligible patients had non-metastatic locally advanced rectal adenocarcinoma. Based on Ras-BRAF status, patients were treated with bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) plus FOLFOXIRI regimen followed by oxaliplatin–5-fluorouracil-based CRT and surgery. The primary end point was pathological complete response rate. Secondary end points were toxicity, compliance, tumour downstaging, complete resection, surgical complications, local and distant failures and overall survival. The sample size was planned to expect an absolute 20% improvement in pathological complete response rate over historical literature data with an α error of 0.05 and a power of 80%.ResultsBetween October 2015 and September 2019, 28 patients (median age 66 years) were enrolled. All patients had regional lymph node involvement at diagnosis. FOLFOXIRI plus bevacizumab was administered in 11 mutated Ras-BRAF patients, whereas the 17 wild-type Ras-BRAF patients received FOLFOXIRI plus panitumumab/cetuximab. Overall, total neoadjuvant therapy was well tolerated and 26 patients (92.9%) completed the programmed strategy. A complete response was achieved in nine cases (32.1%) and a nearly pathological complete response (ypT1 ypN0) in two patients (7.2%). There was no evidence of febrile neutropenia and no grade 4 adverse events were recorded. Radical resection was achieved in all cases.ConclusionFOLFOXIRI plus targeted agent-based induction chemotherapy and intensified CRT before surgery showed promising clinical activity and was well tolerated in locally advanced rectal cancer patients. This phase II trial provides a strong rationale for phase III studies.     

Predictive Factors for Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer

Background: An accurate assessment of potential pathologic complete response(pCR) following neoadjuvant chemoradiotherapy(NCRT) is important for the appropriate treatment of rectal cancer. However, the factors that predict the response to neoadjuvant chemoradiotherapy have not been well defined. Therefore, this study analyzed the predictive factors on the development of pCR after neoadjuvant chemoradiation for rectal cancer. Methods: From January 2008 to January 2018, a total of 432 consecutive patients from a single institution patients who underwent a long-course neoadjuvant chemoradiotherapy were reviewed in this study. The clinicopathological features were analyzed to identify predictive factors for pathologic complete response in rectal cancer after neoadjuvant chemoradiation. Results: The rate of pathologic complete response in rectal cancer after neoadjuvant chemoradiation was 20.8%, patients were divided into the pCR and non-pCR groups. The two groups were well balanced in terms of age, gender, body mass index, ASA score, tumor stage, tumor differentiation, tumor location, surgical procedure, chemotherapy regimen and radiation dose. The multivariate analysis revealed that a pretreatment carcinoembryonic antigen (CEA) level of ≤5 ng/mL and an interval of ≥8 weeks between the completion of chemoradiation and surgical resection were independent risk factors of an increased rate of pCR. Conclusions: Pretreatment carcinoembryonic antigen (CEA) level of ≤5 ng/mL and an interval of ≥8 weeks between the completion of chemoradiation and surgical resection are predictive factors for pathologic complete response in rectal cancer after neoadjuvant chemoradiation. Using these predictive factors, we can predict the prognosis of patients and develop adaptive treatment strategies. A wait-and-see policy might be possible in highly selective cases.     

Stepwise neoadjuvant chemoradiotherapy in the management of mid-low locally advanced rectal cancer

BackgroundThis study aimed to compare the treatment response, complications and prognosis in mid-low locally advanced rectal cancer (LARC) patients who underwent stepwise neoadjuvant chemoradiotherapy (SCRT) or traditional neoadjuvant chemoradiotherapy (CRT).MethodsThe medical records of patients with mid-low rectal cancer who underwent SCRT or CRT were retrospectively analyzed. Differences in the treatment response, pathologic complete response (pCR), R0 resection, local recurrence, anastomotic leakage, presacral infection, anal preservation, defunctioning stoma, treatment-emergent adverse events (TEAEs), overall survival (OS) and disease-free survival (DFS) between patients who underwent SCRT and CRT were compared.ResultsA total of 430 medical records were investigated, including 194 patients in the SCRT group and 236 patients in the CRT group. There was no significant difference in the rates of treatment response, pCR, R0 resection, local recurrence, anastomotic leakage, presacral infection, anal preservation or TEAEs between the two groups. However, the rate of defunctioning stoma in the SCRT group was significantly lower than that in the CRT group (20.1% vs. 44.1%, respectively, P < 0.01). Moreover, the median OS time of the SCRT and CRT groups was 44.0 and 50.5 months, respectively (P = 0.17). The median DFS time of the SCRT and CRT groups was 41.0 and 46.8 months, respectively (P = 0.32).ConclusionCompared with the CRT group, the SCRT group had a similar treatment response, local control and long-term prognosis, and more importantly, a portion of the patients in the SCRT group were exempted from excessive radiation.