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。     

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。     

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。     

直肠腺癌新辅助放化疗疗效影响因素及病理完全缓解对预后的影响

  目的  探讨直肠腺癌新辅助放化疗（neoadjuvant chemoradiotherapy,NCRT）后病理完全缓解（pathologic complete response,pCR）的影响因素及pCR对生存的影响。  方法  回顾性分析2014年1月至2017年12月郑州大学附属肿瘤医院收治的98例直肠腺癌NCRT患者的临床病理资料,分析临床病理特征与pCR的关系以及pCR对预后的影响。  结果  98例患者NCRT后19例（19.4%）获得pCR。单因素分析显示,术前淋巴结转移情况、治疗前CEA水平、肿瘤大小、肿瘤侵犯肠壁周径程度以及KRAS基因状态与直肠腺癌NCRT后pCR相关。Logistic回归多因素分析显示,治疗前CEA≤5 μg/L（OR=4.095,95%CI:1.131~14.823,P=0.032）和肿瘤侵犯肠壁周径（≤1/2）（OR=3.268,95%CI:1.015~10.527,P=0.047）是影响直肠腺癌NCRT后pCR的独立因素。生存分析显示非pCR患者的3年无病生存率（disease-free survival,DFS）为71.1%,显著低于pCR患者100%（P < 0.05）;两者3年总生存率（overall survival,OS）分别为100%和88.5%,差异无统计学意义（P>0.05）。  结论  治疗前检测CEA以及评估肿瘤侵犯肠壁周径程度有助于预测直肠腺癌NCRT后pCR率,提示两者可作为新辅助放化疗疗效的评价指标,并指导临床进行个体化治疗。与pCR患者相比,非pCR直肠癌患者DFS较短。      

局部晚期直肠癌术前同期放化疗达pCR者预后分析

目的 分析与局部晚期直肠癌患者术前放化疗后达pCR相关的临床因素。方法 搜集2005—2012年间经活检证实并neo-CRT (放疗采用3DCRT、VMAT)及根治性切除的临床资料完整的局部晚期直肠癌297例,采用Logistic回归模型多因素分析年龄、性别、肿瘤距肛门距离、疗前血清CEA水平、疗前血红蛋白、cT分期、cN分期与pCR是否相关。结果 全组疗后达pCR者78例(26.7%),T₁—T₃期者达42例(34.4%),T₄期者达37例(21.1%)。疗前CEA≤5.33 ng/ml疗后达pCR者55例(36.4%),CEA>5.33 ng/ml仅24例(16.4%)。单因素分析年龄、性别、肿瘤距肛门距离、疗前是否贫血和cN分期与pCR无关。多因素分析cT₁—T₃期、疗前CEA≤5.33 ng/ml是影响局部晚期直肠癌neo-CRT后是否达pCR的影响因素(P=0.031、0.000)。结论 临床分期、疗前血清CEA水平是影响局部晚期直肠癌neo-CRT后是否达pCR的影响因素;疗前血清CEA水平可作为局部晚期直肠癌neo-CRT后是否达pCR的筛选指标之一。     

直肠癌新辅助放化疗前后LGR5基因表达的变化及其与疗效的关系

目的：探讨肿瘤干细胞标记基因LGR5在局部晚期直肠癌新辅助放化疗（放疗同时口服卡培他滨）前后表达的变化,及其对新辅助放化疗效果预测的作用。方法：收集2014年1月-2016年2月在新疆医科大学附属肿瘤医院接受新辅助放化疗并手术治疗的94例局部晚期直肠癌患者临床资料,对其新辅助放化疗前肠镜活检组织及新辅助放化疗后手术切除组织标本采用荧光定量PCR（qPCR）法检测LGR5 mRNA的表达,分析其在新辅助放化疗前后表达水平的变化及其与疗效的关系,采用Kaplan-Meier法进行生存分析,Log-rank法进行单因素预后分析和Cox回归进行多因素预后分析。结果：直肠癌患者接受新辅助放化疗后肿瘤病理退缩反应良好,肿瘤退缩有效率达87.2%,其中病理完全缓解率为18.1%。直肠癌癌组织中LGR5 mRNA的相对表达水平从新辅助放化疗前的14.396±9.924减少到手术后的8.847±6.664,总体表达水平显著下降（P < 0.05）。放化疗后LGR5 mRNA表达上调者27例,表达下调者67例,表达下调组肿瘤病理退缩程度（TRG）和1、2年生存率均明显优于表达上调组（P < 0.05）。单因素生存分析结果显示放化疗前血清CA19-9水平、临床分期、TRG分级和LGR5 mRNA表达差异为直肠癌预后的影响因素（P均 < 0.05）;多因素分析表明放化疗前CA19-9水平和放化疗前后LGR5 mRNA表达差异是直肠癌预后的影响因素（P分别为0.013和0.015）。结论：新辅助放化疗可以诱导LGR5 mRNA表达的改变,检测其表达对于判断直肠癌预后及指导治疗具有参考价值,新辅助放化疗前后LGR5 mRNA表达变化和放化疗前CA19-9水平有可能成为预测局部晚期直肠癌新辅助放化疗效果的参考指标。     

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。     

进展期胃癌新辅助治疗后病理完全缓解相关因素分析及风险预测模型建立

  目的  探讨局部进展期胃癌新辅助治疗后病理完全缓解（pathological complete response，pCR）的临床相关因素。  方法  回顾性分析2011年6月至2018年3月河北医科大学第四医院收治的452例局部进展期胃癌患者cT3~4N+~M0新辅助治疗及手术的临床资料，采用单因素分析及Logistic多因素回归分析法研究pCR的临床相关因素。  结果  452例患者全部完成新辅助治疗及根治性手术，其中44例（9.7%）患者达到pCR。治疗前T分期为T3期、肿瘤最长径 < 4 cm、治疗前CA199≤30 U/mL、治疗结束与手术时间间隔≥6周、同步放化疗或联合靶向治疗方案与进展期胃癌新辅助治疗后高pCR率有关（均P < 0.05）。治疗前T分期为T3期、CA199≤30 U/mL、肿瘤最长径 < 4 cm、新辅助同步放化疗或联合靶向治疗是影响进展期胃癌新辅助治疗后出现pCR的独立因素（均P < 0.05）。以上每项指标出现pCR的预测评分均为1分。评分>2分患者出现pCR的概率为34.48%，评分≤2分患者出现pCR的概率为6.09%。  结论  治疗前临床分期、CA199水平、肿瘤最长径及治疗模式是进展期胃癌新辅助治疗后达到pCR的影响因素，通过预测评分模型能有效识别其发生率。      

Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer

BACKGROUND: The objective of this study was to identify predictive factors for pathologic complete response and tumor downstaging after preoperative chemoradiation for rectal cancer. METHODS: Between 1989 and 2004, 562 patients with nonmetastatic rectal adenocarcinoma received preoperative chemoradiation and underwent mesorectal excision. The median radiation dose was 45 Gray (Gy) (range, 19.8-58.6 Gy), 77% of patients received concurrent infusional 5-fluorouracil, 20% of patients received concurrent capecitabine, and 3% of patients received other regimens. RESULTS: Nineteen percent of patients achieved a pathologic complete response (CR), whereas 20% of patients had only microscopic residual disease at surgery, and 61% of patients had macroscopic residual disease at surgery. Downstaging of the tumor stage occurred in 57% of patients. The results from a univariate analysis indicated that tumor circumferential extent>60% (P=.033) and pretreatment carcinoembryonic antigen (CEA) level>2.5 ng/mL (P=.015) were associated significantly with lower pathologic CR rates. The univariate analysis also indicated that tumor circumferential extent>60% (P=.001), pretreatment CEA level>2.5 ng/mL (P=.006), and distance from the anal verge>5 cm (P=.035) were associated significantly with lower downstaging rates. The results from a multivariate logistic regression analysis indicated that greater circumferential extent of tumor (odds ratio [OR], 0.43; P=.033) independently predicted a lower pathologic CR rate. The multivariate logistic regression analysis also indicated that greater circumferential extent of tumor (OR, 0.49; P=.020) and greater distance from the anal verge (OR, 0.46; P=.010) independently predicted a lower downstaging rate. CONCLUSIONS: Circumferential extent of tumor, CEA level, and distance from the anal verge predicted for the pathologic response to preoperative chemoradiation for patients with rectal cancer. Therefore, these factors may be used to predict outcomes for patients, to develop risk-adapted treatment strategies, and to target patients who participate in trials of newer therapies.     

Outcomes of neoadjuvant chemoradiotherapy followed by radical resection for T4 colorectal cancer

BACKGROUNDPatients with clinical T4 colorectal cancer (CRC) have a poor prognosis because of compromised surgical margins. Neoadjuvant therapy may be effective in downstaging tumors, thereby rendering possible radical resection with clear margins. AIMTo evaluate tumor downsizing and resection with clear margins in T4 CRC patients undergoing neoadjuvant concurrent chemoradiotherapy followed by surgery.METHODSThis study retrospectively included 86 eligible patients with clinical T4 CRC who underwent neoadjuvant concurrent chemoradiotherapy followed by radical resection. Neoadjuvant therapy consisted of radiation therapy at a dose of 45-50.4 Gy and chemotherapy agents, either FOLFOX or capecitabine. A circumferential resection margin (CRM) of < 1 mm was considered to be a positive margin. We defined pathological complete response (pCR) as the absence of any malignant cells in a specimen, including the primary tumor and lymph nodes. A multivariate logistic regression model was used to identify independent predictive factors for pCR.RESULTSFor 86 patients who underwent neoadjuvant chemoradiotherapy and surgery, the rate of pCR was 14%, and the R0 resection rate was 91.9%. Of the 61 patients with rectal cancer, 7 (11.5%) achieved pCR and 5 (8.2%) had positive CRMs. Of the 25 patients with colon cancer, 5 (20%) achieved pCR and 2 (8%) had positive CRMs. We observed that the FOLFOX regimen was an independent predictor of pCR (P = 0.046). After a median follow-up of 47 mo, the estimated 5-year overall survival (OS) and disease-free survival (DFS) rates were 70.8% and 61.4%, respectively. Multivariate analysis revealed that a tumor with a negative resection margin was associated with improved DFS (P = 0.014) and OS (P = 0.001). Patients who achieved pCR exhibited longer DFS (P = 0.042) and OS (P = 0.003) than those who did not.CONCLUSIONNeoadjuvant concurrent chemoradiotherapy engenders favorable pCR and R0 resection rates among patients with T4 CRC. The R0 resection rate and pCR are independent prognostic factors for patients with T4 CRC.     

Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

PURPOSE: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. METHODS AND MATERIALS: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-fluorouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. RESULTS: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. CONCLUSION: In multivariate analysis, statin use is associated with an improved pCR rate after neoadjuvant chemoradiation for rectal cancer. The low prevalence of statin use limits the power to detect a significant difference at a type I error threshold of p = 0.05 in this analysis. Although no definitive conclusions can be drawn on the basis of this retrospective study, the unusually high incidence of pCR after chemoradiation suggests that the use of statins in the treatment of rectal cancer warrants further evaluation.     

FDG-PET in the prediction of pathologic response after neoadjuvant chemoradiotherapy in locally advanced, resectable esophageal cancer

PURPOSE: To assess the efficacy of 18Fluorodeoxyglucose-positron emission tomography (FDG-PET) for predicting a pathologic response in locally advanced esophageal cancer after neoadjuvant chemoradiotherapy. METHODS AND MATERIALS: All enrolled patients were treated with neoadjuvant chemoradiotherapy followed by esophagectomy and underwent two FDG-PET scans, before and after neoadjuvant chemoradiotherapy. We compared the results of the preoperative FDG-PET scans with the pathologic results. RESULTS: From July 2001 to July 2004, 32 patients (29 men and 3 women) were enrolled in this study. Pathologic complete response (pCR) in the esophagus was achieved in 21 of 32 patients (66%). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in the primary tumors of the preoperative FDG-PET were 27%, 95%, 75%, and 71%, respectively. In regional lymph nodes, these values were 16%, 98%, 36%, and 93%, respectively. The mean standardized uptake value (SUV) of primary tumors was initially 5.6 +/- 3.6 and changed to 1.5 +/- 1.3 after neoadjuvant chemoradiotherapy (p < 0.05). If analysis of metabolic response (SUV decrease, DeltaSUV) was limited to initially highly metabolic primary tumors (SUV > or =4.0), pathologic response was correlated with metabolic response (p = 0.006). CONCLUSIONS: This study suggested that the pathologic response of an initially highly metabolic tumor after neoadjuvant chemoradiotherapy could be correlated with the metabolic response, and FDG-PET can provide additional information on tumor response to chemoradiotherapy.     

The predictive value of clinical evaluation of response to neoadjuvant chemoradiation therapy for rectal cancer

INTRODUCTION: Multimodality therapy has become the standard treatment for patients with locally advanced (T3 and T4) rectal carcinoma. Accurate preoperative staging of the patients with rectal cancer has increased in importance because the selection of patients with transmural rectal cancer (T3 or T4) or node-positive disease leads to a previous nonsurgical neoadjuvant treatment. The purpose of this study was to evaluate the predictive value of the clinical response to neoadjuvant therapy on the basis of pathological results obtained on rectal cancer patients treated by chemoradiotherapy and surgery. METHODS: From 1994 to 2003, 58 patients with a primary diagnosis of rectal cancer were studied at our department and enrolled in a neoadjuvant protocol of chemoradiotherapy followed by surgery. All patients were treated by 30 days of chemoradiotherapy. At the end of the chemoradiotherapy, each patient underwent clinical examination, including digital rectal examination, proctoscopy and abdominal-pelvic computerized tomography to define the clinical response to the chemoradiotherapy. Surgical resection was performed in all patients three weeks after the end of chemoradiotherapy, and histological analysis was performed on all resected specimens. RESULTS: The clinical complete response rate corresponded to the pathological complete response rate, whereas the clinical evaluation overestimated partial response and stable disease. The pathologic examination revealed that 3.5% of clinical partial responses and 3.4% of clinical stable disease were really pathological progressive disease. Clinical partial response and clinical stable disease positive predictive values were 92.8% and 90.9%, respectively, whereas the clinical progressive disease negative predictive value was 20%. Then, 6.9% of patients believed to have responded to the therapy, or not to have responded or worsened, actually had worsened by the end of the chemoradiotherapy. CONCLUSIONS: Positive and negative predictive values, in particular for partial response and stable disease, of clinical evaluation of the response to chemoradiotherapy were not high enough to consider clinical evaluation accurate enough to make treatment decisions.     

Clinical implications of initial FDG-PET/CT in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

Purpose

The present study evaluated the predictive and prognostic impact of initial fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with locally advanced rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT).

Methods

Eighty-one consecutive patients with locally advanced rectal cancer (cT3-T4 N?/N+) treated with neoadjuvant CCRT were enrolled. The FDG-PET/CT parameters, including the SUVmax, metabolic tumor volume (MTV, 50 % of SUVmax), and multiplication of the SUVmean and MTV (total lesion glycolysis, TLG), were analyzed in relation to the pathologic response and disease recurrence.

Results

Five patients (6.2 %) achieved a pathologic complete response (pCR) after CCRT followed by surgery. None of the FDG-PET/CT parameters was identified as a predictive factor for pCR. After a median follow-up period of 26.7 (range 10.9–63.3) months, 19 patients (23.5 %) presented a local and/or distant recurrence. In a multivariate analysis including the clinicopathologic parameters, the TLG of the primary tumor was associated with a worse disease-free survival after neoadjuvant CCRT (HR 20.035, 95 % CI 1.726–232.559; P = 00.017).

Conclusions

The TLG of the primary tumor in the initial FDG-PET/CT can be considered as a prognostic factor for patients with locally advanced rectal cancer treated with neoadjuvant CCRT.     

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。      

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.     

Clinical parameters predicting pathologic tumor response after preoperative chemoradiotherapy for rectal cancer

PURPOSE: To identify pretreatment clinical parameters that could predict pathologic tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer. METHODS AND MATERIALS: The study involved 351 patients who underwent preoperative CRT followed by surgery between October 2001 and July 2006. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and tumor regression. Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. RESULTS: Tumor downstaging (defined as ypT2 or less) was observed in 167 patients (47.6%), whereas tumor regression (defined as Dworak's Regression Grades 3 or 4) was observed in 103 patients (29.3%) and complete regression in 51 patients (14.5%). Multivariate analysis found that predictors of downstaging were pretreatment hemoglobin level (p = 0.045), cN0 classification (p < 0.001), and serum carcinoembryonic antigen (CEA) level (p < 0.001), that predictors of tumor regression were cN0 classification (p = 0.044) and CEA level (p < 0.001), and that the predictor of complete regression was CEA level (p = 0.004). CONCLUSIONS: The data suggest that pretreatment CEA level is the most important clinical predictor of pathologic tumor response. It may be of benefit in the selection of treatment options as well as the assessment of individual prognosis.     

A Panel of Tumor Biomarkers to Predict Complete Pathological Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer

Pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients is related to a favorable prognosis. The identification of early biomarkers predictive of pathological complete response would help optimize the multimodality management of the patients. A panel of 11 tumor-related proteins was investigated by immunohistochemistry in the pretreatment biopsy of a group of locally advanced rectal cancer patients to identify early biomarkers of pathological complete response to neoadjuvant chemoradiotherapy. A mono-institutional retrospective cohort of 95 stage II/III locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy and surgery was selected based on clinical–pathological characteristics and the availability of a pretreatment tumor biopsy. Eleven selected protein marker expression (MLH1, GLUT1, Ki67, CA-IX, CXCR4, COX2, CXCL12, HIF1α, VEGF, CD44, and RAD51) was investigated. The optimal cutoff values were calculated by receiver operating characteristic curve analysis. Classification and regression tree analysis was performed to investigate the biomarker interaction. Patients presenting either Ki-67 or HIF1α or RAD51 below the cutoff value, or CXCR4 or COX2 above the cutoff value, were more likely to get a pathological complete response. Classification and regression tree analysis identified three groups of patients resulting from the combination of Ki-67 and CXCR4 expression. Patients with high expression of Ki-67 had the lowest chance to get a pathological complete response (18%), as compared to patients with low expression of both Ki-67 and CXCR4 (29%), and patients with low Ki-67 and high CXCR4 expression (70%). Pretreatment Ki-67, CXCR4, COX2, HIF1α, and RAD51 in tumor biopsies are associated with pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. A combined evaluation of Ki-67 and CXCR4 would increase their predictive potential. If validated, their optimal cutoff could be used to select patients for a tailored multimodality treatment.Key words: Rectal cancer, Neoadjuvant chemoradiotherapy (nCRT), Pathological complete response (pCR), Predictive biomarkers, Immunohistochemistry (IHC)     

Predictors of Pathological Complete Response to Neoadjuvant Chemotherapy in Iranian Breast Cancer Patients

Background: Achievement of pathologic complete response (pCR) in breast cancer patients receiving neoadjuvant chemotherapy (NAC) is associated with both overall survival and disease-free survival. The aim of present study was to identify clinical and pathological factors associated with achieving pCR in Iranian breast cancer patients receiving NAC. Methods: A retrospective review of all breast cancer patients treated with neoadjuvant chemotherapy between April 2012 and September 2016 at our institution was performed; 207 cases were evaluable for analysis. pCR was defined as having no residual invasive tumor in the breast surgical specimen removed following neoadjuvant therapy. Results: In univariate analysis, factors associated with pCR were age less than 35 years (p = 0.03), absence of Lymphovascular invasion (LVI) (p = 0.002) and negative hormone receptor status (p = 0.003). Hormone receptor status (P = 0.01; OR, 2.45; CI, 1.20 - 4.99) and LVI (P = 0.001; OR, 0.22; CI, 0.10 - 0.46) remained predictive variables in multivariate analysis after correction for the other variables. Conclusions: In conclusion, the results of this study suggests that presence of Lymphovascular invasion and positive hormone receptor status are associated with poorer response to neoadjuvant chemotherapy in breast cancer patients.     

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。