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.     

功能成像技术对局部晚期直肠癌新辅助治疗预测与评估价值

对于局部晚期直肠癌,新辅助放化疗后行手术切除,再行术后辅助化疗,已发展为标准治疗模式。新辅助治疗可使肿瘤病灶发生不同程度的退缩,部分患者术后病理证实达到完全缓解,有助于增加直肠癌患者根治性手术概率,并降低复发率,改善患者的远期预后。近年来,新辅助治疗疗效的预测和评估,成为临床医生关注的焦点。在影像学方面,常规的形态成像技术,不能够准确反映新辅助放化疗后肿瘤治疗效果,而DWI-MRI、DCE-MRI、PET-CT等功能成像技术不仅能够反映肿瘤退缩程度,还可以反映治疗前后肿瘤功能代谢方面的变化,因而更为准确。现对直肠癌新辅助放化疗影像学疗效评价方法的应用现状进行综述。     

直肠癌新辅助放化疗后等待观察策略疗效分析

目的:比较局部进展期直肠癌新辅助治疗后临床完全缓解(cCR)的患者等待观察(W&W)与直肠癌全系膜切除术(TME)后病理完全缓解(pCR)患者的疗效。方法:回顾性队列研究,收集2014—2019年中国医学科学院肿瘤医院收治的新辅助放化疗Ⅱ-Ⅲ期直肠癌患者,纳入标准为完成新辅助治疗后规律随访≥1年且达到cCR者(W&W组...     

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。     

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。     

直肠癌新辅助放化疗疗效预测指标研究进展

 目前新辅助放化疗联合手术逐渐成为局部进展期直肠癌的推荐治疗或标准治疗方案。但直肠癌患者对术前同步放化疗敏感性存在明显差异,部分患者可获得病理完全缓解（pCR）,而部分患者对治疗不敏感,导致肿瘤进展,延误手术时机。因此,对直肠癌患者新辅助治疗敏感性预测指标的相关研究成为热点。本文就局部晚期直肠癌患者新辅助放化疗疗效预测评价指标研究进展作一综述,为临床个体化方案制定提供参考。     

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。     

直肠癌新辅助放化疗后的非手术治疗

新辅助放化疗目前已成为临床Ⅱ、Ⅲ期直肠癌的标准辅助治疗方式。接受新辅助治疗的患者部分可达到病理完全缓解,即切除的样本中不存在癌细胞。达到临床完全缓解的患者,取消手术治疗后仍获得较好的生存率。临床是否可以通过筛选取消部分患者的手术治疗,以避免术中及术后可能存在的风险及不良反应成为值得探讨的问题。     

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。      

直肠癌经新辅助治疗后达到临床完全缓解的评估策略及观察和等待策略

术前新辅助放化疗联合全直肠系膜切除术已成为局部晚期直肠癌患者治疗的金标准。临床上部分患者经放化疗治疗后达到病理完全缓解,并与不全缓解患者相比局部复发率显著降低,生存期延长。为了避免手术相关并发症、改善患者生活质量（造瘘和保肛问题）,一些机构尝试对放化疗后临床完全缓解患者采用非手术方案—“观察和等待策略”。然而,临床完全缓解并不总是预示病理完全缓解,需要综合评估策略更准确地预测哪些患者已经达到病理完全缓解来安全行“观察和等待策略”。本文就目前关于非手术方案的数据作一综述并讨论与此方案相关的持续争议。     

直肠癌新辅助治疗进展

近年来新辅助治疗已成为局部晚期中低位直肠癌的标准治疗,目前常用的方案为长程同步放化疗与短程放疗。全新辅助治疗也是可行的新辅助治疗方案,临床完全缓解后等待观察的临床研究也在进行中。本文就直肠癌新辅助治疗的现状与研究进展进行综述。     

Complete clinical response after neoadjuvant chemoradiation for distal rectal cancer

Multimodality treatment of rectal cancer, with the combination of radiation therapy, chemotherapy, and surgery has become the preferred approach to locally advanced rectal cancer. The use of neoadjuvant chemoradiation therapy (CRT) has resulted in reduced toxicity rates, significant tumor downsizing and downstaging, better chance of sphincter preservation, and improved functional results. A proportion of patients treated with neoadjuvant CRT may ultimately develop complete clinical response. Management of these patients with complete clinical response remains controversial and approaches including radical resection, transanal local excision, and observation alone without immediate surgery have been proposed. The use of strict selection criteria of patients after neoadjuvant CRT has resulted in excellent long-term results with no oncological compromise after observation alone in patients with complete clinical response. Recurrences are detectable by clinical assessment and frequently amenable to salvage procedures.     

直肠癌的新辅助治疗

局部晚期直肠癌单纯手术后局部复发率高,近年的随机对照Ⅲ期临床研究提示,局部晚期直肠癌的新辅助治疗可明显提高局部控制率,对于治疗后病理完全缓解者还可提高生存率,在欧美国家已成为局部晚期直肠癌的标准治疗.但化疗药物的选择、热疗等的应用等尚需进一步临床研究.     

Nonoperative approach to locally advanced rectal cancer after neoadjuvant combined modality therapy: challenges and opportunities from a surgical perspective

This review contains a surgical perspective on the evolution of the nonoperative approach to patients with locally advanced rectal cancer who have a clinical complete response after neoadjuvant combined modality therapy, including accuracy of pathologic complete response identification, the timing between neoadjuvant combined modality therapy and assessment of response, the extent of long-term follow-up, and the likelihood of surgical salvage after an initial nonoperative approach.     

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.     

Nonoperative approaches to rectal cancer: a critical evaluation

A neoadjuvant multimodality approach with chemoradiation therapy (CRT) is the preferred treatment strategy for most distal rectal cancers. Significant downstaging and complete pathologic response may develop after this strategy, and there is still controversy regarding the management of these patients. In this setting, a nonoperative approach has been suggested in select patients with complete clinical response after thorough clinical, endoscopic, and radiologic assessment. However, the assessment of these patients is not straightforward and remains complex. Available data regarding this approach are limited to a single institution's experience from retrospective analyses. Standardization of the assessment of tumor response and the development of radiological/molecular tools may clarify the role of no immediate surgery in patients with complete clinical response after neoadjuvant CRT. Advances in radiation and medical oncology could potentially lead to significant improvements in complete tumor regression rates, leading to an increase in importance of a minimally invasive approach in patients with rectal cancer.     

Can We Reliably Predict a Clinical Complete Response in Rectal Cancer? Current Trends and Future Strategies

Purpose of Review

Prediction of clinical complete response is pivotal in the management of patients with rectal cancer. The ability to determine tumor response to neoadjuvant therapy in rectal cancer might guide subsequent treatment modalities. We review the current literature on predictors of complete response after neoadjuvant for rectal cancer with an emphasis of clinical complete response rather than pathological complete response.

Recent Findings

Clinical and radiological findings have been used to predict response, as well as a myriad of biomarkers. There is limited evidence validating most of these strategies. The role of imaging in defining tumor response has been assessed retrospectively. The TRIGGER trial is a randomized trial that will evaluate stratified management of rectal cancer based on their tumor regression grade.

Summary

The management of locally advanced rectal cancer is evolving. The ability to predict clinical complete response in patients that have undergone neoadjuvant chemoradiation will allow us to select potential patients that can benefit from a “watch and wait” strategy. Identifying patients that will have a complete response will result in decreased surgical overtreatment, favoring organ-sparing strategies. Treatment individualization will require further research. Emphasis should be made in validating prediction markers; these should be cost-effective and of minimally invasive retrieval. Surveillance protocols to assess for tumor regrowth are yet to be determined.

     

Clinical and biochemical predictors of tumor response after neoadjuvant therapy in rectal cancer

Background

Patients who have a good clinical and/or pathologic response to neoadjuvant chemoradiotherapy (nCRT) for rectal cancer have better long-term outcomes and can potentially be spared morbid surgery. This study aimed to identify pretreatment clinical and biochemical predictors of response to neoadjuvant treatment for rectal cancer.

Methods

Patients undergoing neoadjuvant therapy for rectal cancer between 2007 and 2022 were retrospectively included. Those patients who achieved a complete clinical response were offered a nonoperative management strategy and the remaining patients underwent surgical resection. The primary endpoint was tumor regression grade (TRG) based on radiological imaging (mrTRG) or pathology (pTRG). Patient response was classified as good (mrTRG 1–2 or pTRG 0–1) versus poor (mrTRG 3–4 or pTRG 2–3). Logistic regression was performed to determine predictors of TRG.

Results

A total of 984 patients with rectal cancer were identified of which 274 met the inclusion criteria. Of 274 patients, 228 (83%) underwent surgical resection. A good TRG response was observed in 119 (41%) patients, and a complete response was achieved in 53 (17%) patients. On univariable and multivariable logistic regression, clinical T2 stage and body mass index of ≥25 kg/m² were significant predictors of a good TRG. Clinical T2 stage and a personalised total neoadjuvant therapy regimen were significant predictors of complete response.

Conclusion

Clinical T2 stage and a BMI≥25 kg/m² were predictors of good response to neoadjuvant therapy for rectal cancer. Future prospective studies are required to confirm these findings and evaluate their potential use in better targeting of nCRT.     

Significance of tumor‐infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer

Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly common. However, biomarkers predicting the response to neoadjuvant therapy have not been established. Tumor‐infiltrating lymphocytes (TILs) have a crucial effect on tumor progression and survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of TILs before and after neoadjuvant treatment and the change in the density of those TILs. Sixty‐four patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of TIL subsets was examined using immunohistochemical staining of pretreatment biopsy samples and post‐treatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of CD8⁺ TILs in pretreatment biopsy samples was associated with a poor response, and a low density of CD8⁺ TILs in post‐treatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the density of CD8⁺ TILs in post‐treatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte‐mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of TILs in pretreatment biopsy samples might be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, could induce the activation of the local immune status.