Diagnostic accuracy of MRI in assessing tumor regression and identifying complete response in patients with locally advanced rectal cancer after neoadjuvant treatment

Background

The diagnostic accuracy of Magnetic Resonance Imaging (MRI) in restaging locally advanced rectal cancers (LARC) after neoadjuvant chemo-radio therapy (NCRT) has been under recent scrutiny. There is limited data on the accuracy of MRI and its timing in assessing tumor regression grade (TRG) and in identifying patients with complete response (CR). NCRT seems to cause tissue inflammation and oedema which renders reading the scans difficult for radiologist.

Aim

This study aims to assess the accuracy of MRI at different time intervals after NCRT in staging TRG and in identifying CR. Inter-observer agreement between 2 blinded radiologists will also be assessed.

Method

In this retrospective analysis, all patients diagnosed with LARC between January 2003 and 2014, who underwent long-course NCRT, who had at least one post-treatment MRI scan, and who underwent surgery with available pathology results are included. Histopathology staging is considered the reference standard. Accuracy of MRI in T staging and in TRG staging is assessed using weighted kappa. Accuracy, sensitivity, and specificity in identifying CR are calculated from a 2 × 2 contingency table. Inter-observer agreement between two-staging blinded radiologists is calculated using weighted kappa. These are calculated at 2 different time intervals after completion of NCRT.

Results

114 patients were identified who had a first post-treatment MRI scan at an average of 6.2 weeks after completion of NCRT. A subgroup of 68 patients had a second post-treatment MRI at an average of 10.4 weeks. Pathology results were available for 103 patients. By the second post-treatment scan, an additional 25% of patients experienced downstaging; accuracy in T staging increased from 43% to 57.4%; accuracy in TRG staging rose from 28.2% to 38.1%; accuracy in identifying CR rose from 83.4% to 84.1%. Inter-observer agreement in T staging rose from 0.1 for first post-treatment MRI to 0.206 for second post-treatment MRI.

Conclusion

This study advocates that restaging should occur at 10 weeks rather than the standard 6 weeks. This results in higher complete response rates and higher concordance with pathological specimens. Our results also showed that it is easier for radiologists to stage the MRI scans, resulting in higher inter-rater agreements.

     

影像学评价局部进展期直肠癌新辅助治疗后病理完全缓解的研究进展

局部进展期直肠癌治疗的国际标准为新辅助治疗联合手术。对于局部进展期直肠癌新辅助治疗后能否达到病理完全缓解(pCR),需要通过术后病理得知,但通过组织学评价pCR无法为术前治疗方案的调整提供依据。目前,关于影像学技术评价局部进展期直肠癌新辅助治疗后的pCR成为研究热点,本文对相关研究进展进行综述。     

3.0T磁共振扩散加权成像评估进展期直肠癌新辅助放化疗疗效

目的 探讨应用3.0T MR DWI评价进展期直肠癌新辅助放化疗疗效的价值。方法 回顾分析54例接受新辅助放化疗的进展期直肠癌患者影像资料。所有患者均经术后病理证实为直肠癌且术前MR分期为T3、T4期;均于新辅助放化疗前及治疗后术前1周接受DWI联合常规MR序列扫描;根据Dworak's肿瘤消退分级标准,其中敏感组(TRG 3~4级)21例(21/54,38.89%)、不敏感组(TRG 0~2级)33例(33/54,61.11%)。测量直肠癌病变区治疗前后长度、厚度及ADC值,计算治疗前后的差值(Δ长度、Δ厚度、ΔACD)及变化率(长度%、厚度%、ACD%)。结果 54例患者新辅助放化疗后病变区较治疗前长度缩短、厚度减低、ADC值升高(P均<0.01)。新辅助放化疗后敏感组ADC值、ΔADC值及ADC%均高于不敏感组(P均<0.05)。结论 新辅助放化疗对进展期直肠癌有效,治疗后病变区ADC值、ΔADC及ADC%指标对疗效有评价预测作用。     

新辅助放化疗对局部进展期直肠癌近期疗效的影响

目的：探讨术前新辅助放化疗（NCRT）对低位局部进展期直肠癌围手术期及近期疗效的影响。方法回顾性分析138例低位局部进展期直肠癌患者的临床资料,分为NCRT组和直接手术治疗组各69例,观察NCRT组的毒副反应、治疗效果,比较两组在围手术期并发症发生情况。结果 NRCT组的急性毒副反应较小,主要为Ⅰ～Ⅱ度,如乏力、放射性皮炎、骨髓抑制、胃肠反应、泌尿系急性毒性反应等,有5例患者出现Ⅲ度反应。 NRCT组患者降期39例（56.52％）,术后证实为病理完全缓解者14例（20.29％）,其手术保肛率为55.07％,明显高于直接手术组的36.23％（χ2=4.94,P＜0.05）。 NRCT组术中出血量较直接手术组少,差异有统计学意义（χ2=5.71,P＜0.05）,但围手术期并发症发生率比较均无明显差异（P＞0.05）。结论 NCRT的毒副反应较轻,可明显降低局部进展期直肠癌的病理分期,提高保肛率,同时并不增加术后并发症。     

How to use magnetic resonance imaging following neoadjuvant chemotherapy in locally advanced breast cancer

Magnetic resonance imaging(MRI) is highly sensitive in identifying residual breast cancer following neoadjuvant chemotherapy(NAC), and consequently is a commonly used imaging modality in locally advanced breast cancer patients. In these patients, tumor response is an important prognostic indicator. However, discrepancies between MRI findings and surgical pathology are well documented. Overestimation of residual disease by MRI may result in greater surgery than is actually required while underestimation may result in insufficient surgery. Thus, it is important to understand when MRI findings are reliable and when they are less accurate. MRI most accurately predicts pathology in triple negative, Her2 positive and hormone receptor negative tumors, especially if they are of a solid imaging phenotype. In these cases, post-NAC MRI is highly reliable for surgical planning. Hormone receptor positive cancers and those demonstrating non mass enhancement show lower concordance with surgical pathology, making surgical guidance more nebulous in these cases. Radiologists and surgeons must assess MRI response to NAC in the context of tumor subtype. Indiscriminate interpretations will prevent MRI from achieving its maximum potential in the pre-operative setting.     

Impact factors of lymph node retrieval on survival in locally advanced rectal cancer with neoadjuvant therapy

BACKGROUNDConventional clinical guidelines recommend that at least 12 lymph nodes should be removed during radical rectal cancer surgery to achieve accurate staging. The current application of neoadjuvant therapy has changed the number of lymph node dissection.AIMTo investigate factors affecting the number of lymph nodes dissected after neoadjuvant chemoradiotherapy in locally advanced rectal cancer and to evaluate the relationship of the total number of retrieved lymph nodes (TLN) with disease-free survival (DFS) and overall survival (OS).METHODSA total of 231 patients with locally advanced rectal cancer from 2015 to 2017 were included in this study. According to the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) classification system and the NCCN guidelines for rectal cancer, the patients were divided into two groups: group A (TLN ≥ 12, n = 177) and group B (TLN < 12, n = 54). Factors influencing lymph node retrieval were analyzed by univariate and binary logistic regression analysis. DFS and OS were evaluated by Kaplan-Meier curves and Cox regression models.RESULTSThe median number of lymph nodes dissected was 18 (range, 12-45) in group A and 8 (range, 2-11) in group B. The lymph node ratio (number of positive lymph nodes/total number of lymph nodes) (P = 0.039) and the interval between neoadjuvant therapy and radical surgery (P = 0.002) were independent factors of the TLN. However,TLN was not associated with sex, age, ASA score, clinical T or N stage, pathological T stage, tumor response grade (Dworak), downstaging, pathological complete response, radiotherapy dose, preoperative concurrent chemotherapy regimen, tumor distance from anal verge, multivisceral resection, preoperative carcinoembryonic antigen level, perineural invasion, intravascular tumor embolus or degree of differentiation. The pathological T stage (P < 0.001) and TLN (P < 0.001) were independent factors of DFS, and pathological T stage (P = 0.011) and perineural invasion (P = 0.002) were independent factors of OS. In addition, the risk of distant recurrence was greater for TLN < 12 (P = 0.009).CONCLUSIONA shorter interval to surgery after neoadjuvant chemoradiotherapy for rectal cancer under indications may cause increased number of lymph nodes harvested. Tumor shrinkage and more extensive lymph node retrieval may lead to a more favorable prognosis.     

体素内不相干运动成像评估局部进展期直肠癌新辅助化疗后病理完全缓解

目的 探讨体素内不相干运动（IVIM）成像在诊断局部进展期直肠癌新辅助化疗后病理完全缓解（pCR）中的价值。方法 61例经手术病理证实为直肠腺癌患者于新辅助化疗前后分别行常规MR及多b值DWI IVIM检查,由2名医师独立测量肿瘤的ADC值及IVIM参数[真实扩散系数（D值）、灌注相关假扩散系数（D^*值）、灌注分数（f值）]。将患者分为pCR组（14例）和非pCR组（47例）。采用独立样本t检验比较两组所有参数及其新辅助化疗前后变化的百分数（Δ_ratio）,采用ROC曲线下面积评价各参数诊断pCR的效能。结果 与非pCR组比较,pCR组化疗前ADC值（P=0.002）和D值（P=0.007）更低,Δ_ratioADC值（P < 0.001）和Δ_ratioD值（P=0.002）更高;两组化疗前和化疗后D^*、f值及其Δ_ratio差异均无统计学意义（P均>0.05）。Δ_ratioD值诊断pCR的ROC曲线下面积最高（0.786,P < 0.01）。结论 D值有助于预测和鉴别新辅助化疗后达到pCR的局部进展期直肠癌。     

Locally advanced rectal cancer: qualitative and quantitative evaluation of diffusion-weighted magnetic resonance imaging in restaging after neoadjuvant chemo-radiotherapy

Abdominal Radiology - To determine the added value of qualitative and quantitative evaluation of diffusion-weighted magnetic resonance imaging (DWI) in locally advanced rectal cancer (LARC)...     

中低位局部进展期直肠癌术前采用新辅助放化疗和全程新辅助治疗的近期疗效与安全性

目的 观察中低位局部进展期直肠癌术前采用新辅助放化疗(nCRT)与全程新辅助治疗(TNT)的近期疗效及安全性.方法 前瞻性选取2016年12月至2018年10月河北北方学院附属第一医院收治的100例中低位局部进展期直肠癌患者为研究对象,按照随机数字表法将其分为nCRT组(放疗期予以口服卡培他滨治疗)和TNT组(放疗前予...     

Response to neoadjuvant therapy in locally advanced rectal cancer: assessment with diffusion-weighted MR imaging and 18FDG PET/CT

The aim of this study was to evaluate the correlation between the changes of SUV_max and of apparent diffusion coefficient (ADC) before and after neoadjuvant therapy, to enable us predict the therapy response, in patients with locally advanced rectal cancer (LARC). A total of 30 patients with LARC who underwent CRT were recruited for our study. All the patients underwent a whole body 18F-FDG-PET/CT scan and a pelvic MR examination including DW imaging for staging (PET/CT1 and RM1), and after the chemoradiation therapy (PET/CT2, and RM2). Histopathologic analysis of rectal specimen, according to tumor regression grade (Mandard??s criteria) was used as the standard reference. MR and PET-CT images were analyzed, and measurements of ADC values and SUV_max were taken. Diagnostic performance for selection of complete responders (TRG1?C2) and overall diagnostic accuracy for each item were calculated. After neoadjuvant therapy, all patients were submitted to surgery. According to Mandard??s criteria, 21 tumors showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders; nine tumors were classified as non responders (TRG3, 4, and 5). In all the patients, mean value of SUV_max in PET/CT1 was higher than those in PET/CT2 (P?<?0.001), whereas mean ADC value was lower in RM1 than RM2 (P?<?0.001), with a significant percentage decrease of values after the treatment (P?<?0.005).The best predictors cut-off values for TRG response were SUV_max of 4.4 and ADC of 1.28?×?10³?mm²/s with sensitivity, specificity accuracy, negative predictive value, and positive predictive values of 77.3%, 88.9%, 80.7%, 61.5%, and 94.4%, respectively. We conclude from the overall data of this study that the absolute values of SUV_max and ADC of rectal lesion after CRT were the best parameters to define the response to treatment, by differentiating fibrosis from viable tumor tissue.     

Robotic radical hysterectomy after neoadjuvant chemotherapy in locally advanced cervical cancer

Neoadjuvant platinum-based chemotherapy (NACT) plus radical hysterectomy and pelvic lymphadenectomy has been demonstrated to be a valid alternative to chemoradiation in patients with advanced cervical cancer. Several publications have reported on the feasibility of robot-assisted laparoscopy in early cervical cancer. Herein is reported the case of a woman with locally advanced cervical cancer that was successfully treated using neoadjuvant chemotherapy followed by total robotic type C1 radical hysterectomy (TRRH) plus pelvic lymphadenectomy. The success of this approach, which is not the standard of care in this disease, suggests that additional studies should be performed in a selected population.     

Robotic radical hysterectomy after neoadjuvant chemotherapy in locally advanced cervical cancer

Abstract

Neoadjuvant platinum-based chemotherapy (NACT) plus radical hysterectomy and pelvic lymphadenectomy has been demonstrated to be a valid alternative to chemoradiation in patients with advanced cervical cancer. Several publications have reported on the feasibility of robot-assisted laparoscopy in early cervical cancer. Herein is reported the case of a woman with locally advanced cervical cancer that was successfully treated using neoadjuvant chemotherapy followed by total robotic type C1 radical hysterectomy (TRRH) plus pelvic lymphadenectomy. The success of this approach, which is not the standard of care in this disease, suggests that additional studies should be performed in a selected population.     

Pre- and postoperative adjuvant therapy for locally advanced rectal cancer

The conventional therapy for locally advanced rectal cancer involves surgery and adjuvant therapy. The standard adjuvant therapy is combined modality treatment, including 5-fluorouracil chemotherapy and radiation. The standard of care in terms of timing of adjuvant therapy, whether pre- or postoperative, continues to evolve, and potential advantages and disadvantages exist for both neoadjuvant and adjuvant combined modality therapy. Newer modalities of assessment, such as endoscopic ultrasound, have had an impact on more accurate staging of locally advanced rectal cancer, thus impacting the choice of therapy. Continued emphasis on improving survival, decreasing local recurrence, and minimizing treatment toxicity to improve quality of life are the goals of ongoing research in the field of rectal cancer.     

Value of diffusion-weighted MRI and apparent diffusion coefficient measurements for predicting the response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

Purpose

The aim of our study was to assess the performance value of magnetic resonance imaging (MRI) in the restaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy (CRT) and in the identification of good vs. poor responders to neoadjuvant therapy.

Materials and Methods

A total of 34 patients with locally advanced rectal cancer underwent MRI prior to and after CRT. T stage and tumor regression grade (TRG) on post-CRT MRI was compared with the pathological staging ypT and TRG. Tumor volume and the apparent diffusion coefficient (ADC) were measured using diffusion-weighted imaging (DWI) before and after neoadjuvant CRT; the percentage of tumor volume reduction and the change of ADC (ΔADC) was also calculated. ADC parameters and the percentage of tumor volume reduction were correlated to histopathological results. The diagnostic performance of ADC and volume reduction to assess tumor response was evaluated by calculating the area under the ROC curve and the optimal cut-off values.

Results

A significant correlation between the T stage and the TRG defined in DW-MRI after CRT and the ypT and the TRG observed on the surgical specimens was found (p = 0.001; p < 0.001). The mean post-CRT ADC and ΔADC in responder patients was significantly higher compared to non-responder ones (p = 0.001; p = 0.01). Furthermore, the mean post-CRT ADC values were significantly higher in tumors with T-downstage (p = 0.01).

Conclusion

DW-MRI may have a significant role in the restaging and in the evaluation of post-CRT response of locally advanced rectal cancer. Quantitative analysis of DWI through ADC map may result in a promising noninvasive tool to evaluate the response to therapy.

     

新辅助化疗在局部晚期宫颈癌治疗中的作用

宫颈癌在全世界是女性第二大恶性肿瘤。同步放化疗是局部晚期宫颈癌的标准治疗方法。然而,由于放疗设备的缺乏,尤其在发展中国家、放疗后长期并发症以及转移性疾病的控制不良,使得不同的治疗方法得到进一步发展,例如新辅助化疗后手术治疗。本文通过文献复习进一步了解新辅助化疗在局部晚期宫颈癌中的临床作用。     

经直肠三维超声在局部晚期直肠癌新辅助放化疗后病理完全缓解评估中的应用价值

目的：探讨经直肠三维超声（3D-ERUS）在局部晚期直肠癌新辅助放化疗后病理完全缓解评估中的应用价值。 方法：回顾分析我院局部晚期直肠癌患者98例,所有患者均行标准新辅助放化疗方案后行全直肠系膜切除术,在首次入院一周内和术前放化疗后一周内分别行3D-ERUS,记录相关超声参数,将其分为病理完全缓解组（pCR组）和非缓解组（non-pCR组）,比较两组中3D-ERUS参数的差异,采用 Spearman 相关系数法分析各参数与 TRG分级的相关性;采用 ROC 曲线计算各参数对疗效评估的截断值并评价其诊断效能。 结果： NCRT后病变累及长径（r=0.336）、累及最厚径（r=0.403）、累及肠圈（r=0.339）与TRG分级呈正相关（均P＜0.05）,累及长径变化率（r=-0.407）、最厚径变化率（r=-0.435）、肠圈变化率（r=-0.408）、血流分级变化率（r=-0.235）与TRG分级呈负相关（均P＜0.05）。ROC曲线显示3D-ERUS预测pCR的诊断性能,其中累及长径变化率的截断值为29％,敏感性为70.0％,特异性为76.9％,累及最厚变化率的截断值为44％,敏感性为80.0％,特异性为76.9％,累及肠圈变化率的截断值为33％,敏感性为70.0％,特异性为79.5％,累及血流分级变化率的截断值为0％,敏感性为70.0％,特异性为57.7％,NCRT后累及长径的截断值为39mm,敏感性为95.0％,特异性为39.7％,NCRT后累及最厚径的截断值为10mm,敏感性为100.0％,特异性为47.7％,NCRT后累及肠圈的截断值为25％,敏感性为70.0％,特异性为70.5％。 结论：3D-ERUS在局部晚期直肠癌新辅助放化疗后pCR评估中具有重要价值,其所测量的NCRT后累及长径、累及最厚径、累及肠圈,累及长径变化率、最厚径变化率、肠圈变化率、血流分级变化率具有较高的准确性。     

胃癌新辅助治疗后不同肿瘤退缩分级系统的预后预测价值

目的 探讨不同肿瘤退缩分级（tumor regression grade，TRG）标准（Mandard-TRG、Becker-TRG及JGCA-TRG）与局部进展期胃癌患者新辅助治疗术后病理特征的关系，并比较其预后预测价值。方法 回顾性收集行新辅助治疗及胃癌根治术的局部进展期胃癌患者，根据Mandard-TRG、Becker-TRG及JGCA-TRG对术后组织标本进行重新评价，分析各肿瘤退缩分级标准与临床病理特征的关系及对预后的预测价值。结果 共纳入198例接受过新辅助治疗的局部进展期胃癌患者，其中男性152例，女性46例。三种TRG标准划分的不同肿瘤退缩分级间肿瘤直径、ypT、ypN、脉管浸润、神经侵犯的构成比例均具有统计学差异。Kaplan-Meier分析显示不同Becker分级或JGCA分级之间的OS具有统计学差异（p=0.019，p=0.035），而不同Mandard分级之间的OS差异不显著（p=0.146）。进一步比较Becker 1a-2级和Becker 3级患者的生存情况，Becker 1a-2级患者的预后显著优于Becker 3级患者（p=0.002），JGCA 2-3级患者的预后亦显著优于JGCA 0-1b级患者（p=0.006）。COX回归分析显示三种肿瘤退缩分级均非新辅助治疗后胃癌患者的独立预后因子。三种分级预测5年生存状态的ROC曲线下面积分别为0.608、0.624和0.611。结论 Becker-TRG对于接受新辅助治疗的胃癌患者的预后预测价值略优于JGCA-TRG和Mandard-TRG，仍需探索更加全面精准的胃癌新辅助治疗后病理评价标准。     

影响局部进展期直肠癌新辅助放化疗疗效的临床因素分析

目的:探讨影响局部进展期直肠癌(locally advanced rectal cancer,LARC)患者新辅助放化疗(neoadjuvant chemoradiotherapy,nCRT)的疗效及预后的临床因素。方法:回顾性分析辽宁省肿瘤医院335例接受nCRT后并进行根治性手术的LARC患者的临床资料。通过单因素...     

Evaluation of diffusion kurtosis and diffusivity from baseline staging MRI as predictive biomarkers for response to neoadjuvant chemoradiation in locally advanced rectal cancer

Abdominal Radiology - To evaluate the role of diffusion kurtosis and diffusivity as potential imaging biomarkers to predict response to neoadjuvant chemoradiation therapy (CRT) from baseline...