Clinical colorectal cancer最新文献_第3页

Adjuvant Anti-Inflammatory Therapy in Postoperative Colorectal Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials 结直肠癌术后辅助抗炎治疗：随机对照试验的系统回顾和荟萃分析。

IF 3.2 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2025-12-01 Epub Date: 2025-08-21 DOI: 10.1016/j.clcc.2025.08.003

Gabriel Lenz , Rafael Alvim Pereira , Gabriel Valagni , Tiago Biachi de Castria

Colorectal cancer (CRC) recurrence remains a major challenge in postsurgery. Chronic inflammation driven by cyclooxygenase (COX-2) and prostaglandin pathways promotes tumor recurrence, encouraging interest in nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin (acetylsalicylic acid, ASA) and COX-2 inhibitors. While observational studies suggest a benefit in reducing recurrence, randomized controlled trial (RCT) evidence is controversial. This meta-analysis evaluates the efficacy and safety of adjuvant NSAIDs in nonmetastatic resected CRC. We systematically searched PubMed, Scopus, and Cochrane Central for RCTs comparing anti-inflammatory agents to placebo in postoperative CRC patients. Primary outcomes included overall survival (OS) and disease-free survival (DFS); secondary outcomes were time to recurrence (TTR), recurrence rate, and adverse events. Subgroup analyses focused on aspirin use and the presence of PI3K pathway mutations were performed. Five RCTs (7246 patients) were included. Anti-inflammatory therapy improved DFS (HR = 0.85; 95% CI: 0.76-0.96; P = .008) and TTR (HR = 0.61; 95% CI: 0.44-0.84; P = .003) but not OS (HR = 0.90; P = .07) or recurrence rates (RR = 0.90; P = .06). Aspirin demonstrated superior DFS benefit (HR = 0.70; P = .03) and patients with PI3K mutations had markedly reduced recurrence risk (HR = 0.56; P < .0001). Serious cardiac events, gastrointestinal bleeding, and infections showed no significant differences. Adjuvant anti-inflammatory therapy improves DFS and delays recurrence in postoperative CRC, with pronounced benefit in PIK3CA mutant tumors. These findings support biomarker-driven strategies and highlight the need for ongoing trials to validate long-term efficacy and safety.

结直肠癌（CRC）术后复发仍然是一个主要的挑战。环氧化酶（COX-2）和前列腺素途径驱动的慢性炎症促进肿瘤复发，鼓励对非甾体抗炎药（NSAIDs）的兴趣，如阿司匹林（乙酰水杨酸，ASA）和COX-2抑制剂。虽然观察性研究表明在减少复发方面有好处，随机对照试验（RCT）的证据是有争议的。本荟萃分析评估了非转移性切除结直肠癌中辅助非甾体抗炎药的疗效和安全性。我们系统地检索了PubMed、Scopus和Cochrane Central，以比较术后结直肠癌患者中抗炎药与安慰剂的rct。主要结局包括总生存期（OS）和无病生存期（DFS）；次要终点为复发时间（TTR）、复发率和不良事件。亚组分析集中在阿司匹林的使用和PI3K通路突变的存在。纳入5项随机对照试验（7246例患者）。抗炎治疗改善了DFS （HR = 0.85; 95% CI: 0.76-0.96; P = 0.008）和TTR (HR = 0.61; 95% CI: 0.44-0.84; P = 0.003)，但没有改善OS （HR = 0.90; P = 0.07）或复发率（RR = 0.90; P = 0.06）。阿司匹林显示出优越的DFS益处（HR = 0.70; P = 0.03）， PI3K突变患者的复发风险显著降低（HR = 0.56; P < 0.0001）。严重心脏事件、胃肠道出血和感染无显著差异。辅助抗炎治疗可改善术后结直肠癌的DFS并延缓复发，对PIK3CA突变肿瘤有明显的益处。这些发现支持生物标志物驱动的策略，并强调需要进行持续的试验来验证长期疗效和安全性。

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引用次数: 0

Machine Learning-Based Prediction Model for Early-Onset Colorectal Cancer Risk: A Systematic Review and Meta-Analysis 基于机器学习的早发性结直肠癌风险预测模型：系统综述和荟萃分析。

IF 3.2 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2025-12-01 Epub Date: 2025-10-03 DOI: 10.1016/j.clcc.2025.09.003

Wenting Chai , Siyue Fan , Yanni Lin , Nengtong Zheng , Yuanfang Xiong , Yuan Chen , Zhaoxia Zhang , Lijuan Chen

Through systematic review and meta-analysis, we explored the performance of machine learning (ML) risk prediction models for early-onset colorectal cancer (EOCRC) to enhance model development and application. Following preregistration of the study protocol in PROSPERO (CRD42024606785), we searched PubMed, Embase, Web of Science, Cochrane Library, WanFang Data, VIP, SinoMed, and the CNKI databases for studies on constructing predictive EOCRC based on ML methods. The prediction model Risk of Bias Assessment Tool + Artificial Intelligence (PROBAST + AI) tool was used to evaluate the quality, bias risk, and applicability of the included studies. The Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis + Artificial Intelligence (TRIPOD + AI) reporting standard was applied to assess the reporting quality of these studies. We conducted subgroup analysis and sensitivity analysis. This study followed the PRISMA reporting guidelines. A total of 2809 studies were retrieved, and 7 studies were included. The training set size ranged from 987 to 21,700 patients, with an average of 5037 per model. XGBoost was the most frequently used modelling method. Overall TRIPOD + AI compliance was 70.5%. In model development, 5 studies were rated as high-quality concerns (2 unclear), and 5 studies were rated as high adaptability concerns (2 unclear). In model evaluation, 6 studies were rated as high-risk bias (1 unclear), and 5 studies were of concern for high adaptability (2 unclear). The top 5 most common predictors include age, gender, BMI, diabetes and smoking. Meta-analysis showed a pooled AUC of 0.84 (95% CI, 0.77-0.90; I² = 99.3%, P < .001). Pooled sensitivity and specificity were 0.75 (95% CI, 0.59-0.86; I² = 94.8%) and 0.87 (95% CI, 0.71-0.94; I² = 95.6%), respectively (both P < .001 for heterogeneity). This study demonstrates that ML models show outstanding discriminatory capabilities in predicting the risk of EOCRC, supporting their potential application in identifying high-risk individuals for targeted prevention and monitoring. In the future, prospective design and standardized reporting are needed to enhance reliability and clinical translation.

通过系统综述和荟萃分析，探讨机器学习（ML）早发性结直肠癌（EOCRC）风险预测模型的性能，以促进模型的开发和应用。在PROSPERO预注册研究方案（CRD42024606785）后，我们检索PubMed、Embase、Web of Science、Cochrane Library、万方数据、VIP、中国医学信息网（SinoMed）和CNKI数据库，查找基于ML方法构建预测EOCRC的研究。采用预测模型偏倚风险评估工具+人工智能（PROBAST + AI）工具评估纳入研究的质量、偏倚风险和适用性。采用个体预后或诊断多变量预测模型透明报告+人工智能（TRIPOD + AI）报告标准评估这些研究的报告质量。进行亚组分析和敏感性分析。本研究遵循PRISMA报告指南。共检索2809项研究，纳入7项研究。训练集的大小从987到21,700个患者，平均每个模型为5037个。XGBoost是最常用的建模方法。总体TRIPOD + AI依从性为70.5%。在模型开发中，5项研究被评为高质量关注（2项不清楚），5项研究被评为高适应性关注（2项不清楚）。在模型评价中，6项研究被评为高危偏倚（1项不清楚），5项研究被评为高适应性关注（2项不清楚）。最常见的5个预测因素包括年龄、性别、身体质量指数、糖尿病和吸烟。meta分析显示合并AUC为0.84 （95% CI, 0.77-0.90; I²= 99.3%,P < .001）。合并敏感性和特异性分别为0.75 （95% CI, 0.59-0.86; I²= 94.8%）和0.87 (95% CI, 0.71-0.94; I²= 95.6%)（异质性均P < 0.001）。该研究表明，ML模型在预测EOCRC风险方面表现出出色的区分能力，支持其在识别高风险个体以进行针对性预防和监测方面的潜在应用。在未来，需要前瞻性设计和标准化报告，以提高可靠性和临床翻译。

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引用次数: 0

Impact of distal resection margin on survival after tumour-specific mesorectal excision for rectal cancer: retrospective cohort study 远端切除缘对肿瘤特异性直肠癌肠系膜切除术后生存率的影响：回顾性队列研究。

IF 3.2 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2025-12-01 Epub Date: 2025-08-20 DOI: 10.1016/j.clcc.2025.08.001

Fabio Carbone , Roberto Santalucia , Simona Borin , Davide Ciardiello , Luca Bottiglieri , Stefano de Pascale , Emilio Bertani , Uberto Fumagalli Romario

Background

The safe oncological distal resection margin (DRM) after anterior resection (AR) with tumour-specific mesorectal excision (TSME) for rectal cancer is still debated. This study aims to clarify the impact of DRM on survival outcomes.

Methods

Patients who underwent an intention-to-treat AR-TSME for a non-metastatic rectal adenocarcinoma within 15 cm from the anal verge from September 2018 to February 2024 were included. Those with locally advanced rectal cancer underwent neoadjuvant treatment. Patients were divided into 3 groups according to the DRM: < 1 cm, 1 to 4.9 cm, and ≥ 5 cm, and compared for overall survival (OS) and disease-free survival (DFS).

Results

A total of 268 patients were included: 29 with DRM < 1 cm (11%), 208 with DRM 1 to 4.9 cm (78%), and 31 with DRM ≥ 5 cm (11%). Median follow-up was 27 months. Three-year OS was 93%, 97%, and 100% in the respective groups (P = .36); DFS was 85%, 76%, and 75% (P = .51). Multivariable analysis did not identify DRM as an independent risk factor for OS or DFS. Circumferential resection margin (CRM) involvement (HR 4.68, 95%CI 1.78-12.31) and R1 resections (HR 5.66, 95%CI 2.31-13.87) were significantly associated with disease recurrence. Subgroup analysis showed no significant impact of DRM on the survival of patients undergoing neoadjuvant therapy.

Conclusions

Short DRM does not compromise oncological outcomes, provided that complete (R0) resection is achieved. These findings support a more individualised surgical approach, with emphasis on CRM status over arbitrary DRM thresholds.

背景：直肠癌前切除术（AR）联合肿瘤特异性肠系膜切除术（TSME）后的安全肿瘤远端切除边缘（DRM）仍存在争议。本研究旨在阐明DRM对生存结果的影响。方法：纳入2018年9月至2024年2月期间在肛门边缘15 cm范围内接受有意治疗的非转移性直肠腺癌AR-TSME的患者。局部晚期直肠癌患者接受新辅助治疗。将患者按DRM < 1 cm、1 ~ 4.9 cm和≥5 cm分为3组，比较总生存期（OS）和无病生存期（DFS）。结果：共纳入268例患者：DRM < 1 cm 29例（11%），DRM 1 ~ 4.9 cm 208例（78%），DRM≥5 cm 31例（11%）。中位随访时间为27个月。3年OS分别为93%、97%和100% (P = 0.36)；DFS分别为85%、76%和75% （P = 0.51）。多变量分析未发现DRM是OS或DFS的独立危险因素。环切缘（CRM）受累（HR 4.68, 95%CI 1.78-12.31）和R1切除（HR 5.66, 95%CI 2.31-13.87）与疾病复发显著相关。亚组分析显示，DRM对接受新辅助治疗的患者的生存无显著影响。结论：短DRM不会影响肿瘤预后，前提是完全切除（R0）。这些发现支持更个性化的手术方法，强调CRM状态而不是任意DRM阈值。

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引用次数: 0

Incidence of Mismatch Repair Deficiency in Rectal Cancer and Response to Neoadjuvant Treatment 直肠癌错配修复缺陷的发生率及对新辅助治疗的反应。

IF 3.2 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2025-12-01 Epub Date: 2025-09-15 DOI: 10.1016/j.clcc.2025.09.001

Jelle A. Nieuwstraten , Eline G.M. van Geffen , Martijn W.H. Leenders , Pieter J. Tanis , Miranda Kusters , Tjeerd S. Aukema

Introduction

The role of mismatch repair deficiency (dMMR) in colon cancer has gained increasing attention due to its association with response to neoadjuvant therapy. In contrast, its significance in rectal cancer remains less comprehensively explored. The influence of dMMR on pathological response following neoadjuvant (chemo)radiotherapy ((C)RT) in rectal cancer is not well understood. This study aimed to compare pathological response to neoadjuvant treatment between dMMR and proficient mismatch repair (pMMR) rectal cancer.

Methods

A retrospective cohort study was conducted using data from the Dutch ColoRectal Cancer Audit database, including patients who underwent rectal cancer resection between 2018 and 2021. Primary outcomes of this study were the incidence of dMMR and pathological complete response (pCR). A multinomial logistic regression analysis was performed to determine if MMR-status was an independent predictor of pCR.

Results

Out of 8570 patients, MMR-status was determined in 4659 (54.4%) patients, of whom 4516 (96.9%) were pMMR and 143 (3.1%) dMMR. A total of 1562 patients with known MMR-status underwent neoadjuvant treatment. 1514 (96.9%) had pMMR tumors and 48 (3.1%) dMMR tumors. The pCR rate was significantly higher in dMMR patients (29.2%) compared to pMMR patients (13.5%, P = .008). Multivariable logistic regression analysis showed that MMR-status was independently associated with pCR (OR 2.422 [95% CI, 1.236-4.746], P = .010).

Conclusion

In this cross-sectional national rectal cancer cohort, the incidence of dMMR was 3.1%, and dMMR appeared to be an independent predictor for higher chance of pathological complete response after neoadjuvant (chemo)radiotherapy.

错配修复缺陷（dMMR）在结肠癌中的作用越来越受到关注，因为它与新辅助治疗的反应有关。相比之下，其在直肠癌中的意义尚未得到全面探讨。dMMR对直肠癌新辅助（化疗）放疗（(C)RT）后病理反应的影响尚不清楚。本研究旨在比较dMMR和熟练错配修复（pMMR）直肠癌新辅助治疗的病理反应。方法：使用荷兰结直肠癌审计数据库的数据进行回顾性队列研究，包括2018年至2021年期间接受直肠癌切除术的患者。本研究的主要结果是dMMR的发生率和病理完全缓解（pCR）。进行多项逻辑回归分析以确定mmr状态是否为pCR的独立预测因子。结果：在8570例患者中，4659例（54.4%）患者确定了mmr状态，其中4516例（96.9%）为pMMR， 143例（3.1%）为dMMR。共有1562例已知mmr状态的患者接受了新辅助治疗。pMMR肿瘤1514例（96.9%），dMMR肿瘤48例（3.1%）。dMMR患者的pCR率（29.2%）明显高于pMMR患者（13.5%,P = 0.008）。多变量logistic回归分析显示，mmr状态与pCR独立相关（OR 2.422 [95% CI, 1.236 ~ 4.746], P = 0.010）。结论：在这个横断面的全国直肠癌队列中，dMMR的发病率为3.1%，dMMR似乎是新辅助（化疗）放疗后病理完全缓解几率较高的独立预测因子。

{"title":"Incidence of Mismatch Repair Deficiency in Rectal Cancer and Response to Neoadjuvant Treatment","authors":"Jelle A. Nieuwstraten , Eline G.M. van Geffen , Martijn W.H. Leenders , Pieter J. Tanis , Miranda Kusters , Tjeerd S. Aukema","doi":"10.1016/j.clcc.2025.09.001","DOIUrl":"10.1016/j.clcc.2025.09.001","url":null,"abstract":"<div><h3>Introduction</h3><div>The role of mismatch repair deficiency (dMMR) in colon cancer has gained increasing attention due to its association with response to neoadjuvant therapy. In contrast, its significance in rectal cancer remains less comprehensively explored. The influence of dMMR on pathological response following neoadjuvant (chemo)radiotherapy ((C)RT) in rectal cancer is not well understood. This study aimed to compare pathological response to neoadjuvant treatment between dMMR and proficient mismatch repair (pMMR) rectal cancer.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted using data from the Dutch ColoRectal Cancer Audit database, including patients who underwent rectal cancer resection between 2018 and 2021. Primary outcomes of this study were the incidence of dMMR and pathological complete response (pCR). A multinomial logistic regression analysis was performed to determine if MMR-status was an independent predictor of pCR.</div></div><div><h3>Results</h3><div>Out of 8570 patients, MMR-status was determined in 4659 (54.4%) patients, of whom 4516 (96.9%) were pMMR and 143 (3.1%) dMMR. A total of 1562 patients with known MMR-status underwent neoadjuvant treatment. 1514 (96.9%) had pMMR tumors and 48 (3.1%) dMMR tumors. The pCR rate was significantly higher in dMMR patients (29.2%) compared to pMMR patients (13.5%, <em>P</em> = .008). Multivariable logistic regression analysis showed that MMR-status was independently associated with pCR (OR 2.422 [95% CI, 1.236-4.746], <em>P</em> = .010).</div></div><div><h3>Conclusion</h3><div>In this cross-sectional national rectal cancer cohort, the incidence of dMMR was 3.1%, and dMMR appeared to be an independent predictor for higher chance of pathological complete response after neoadjuvant (chemo)radiotherapy.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 4","pages":"Pages 483-491"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of Neoadjuvant Immunotherapy in Localized Rectal Cancer. A Systematic Review 新辅助免疫治疗对局部直肠癌的影响。系统评价。

IF 3.2 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2025-12-01 Epub Date: 2025-08-26 DOI: 10.1016/j.clcc.2025.08.005

Florian Salihu , Claudia Corro , Frédéric Ris , Guillaume Meurette , André Durham , Vassilis Genoud , Aurélie Bornand , Jeremy Meyer , Thibaud Koessler

Current treatments for locally advanced rectal cancer (LARC) include preoperative radiotherapy, chemotherapy and chemoradiotherapy followed by total mesorectal excision (TME), which can severely impact quality of life. Recently, anti-PD1 immunotherapy in microsatellite instability high (MSI-H) LARC has shown 100% clinical complete responses, allowing patients to avoid surgery with minimal toxicity. This review assesses the safety, toxicity, pathological impact, and long-term benefits of incorporating immunotherapy into the neoadjuvant treatment of microsatellite stable (MSS) and MSI-H LARC.

This systematic review, conducted following PRISMA guidelines, investigates neoadjuvant immunotherapy in LARC. Data on study characteristics, treatment protocols, and outcomes were extracted. Quality assessment was conducted by using the Methodological Index for nonrandomized studies (MINORS) and the RoB2 tool. Patients were categorized into MSI-H, MSS, and unknown microsatellite status cohorts.

We found twelve published studies including 547 patients. In the MSS cohort, postneoadjuvant surgery rates ranged from 57.6% to 100%, with a watch-and-wait approach adopted in up to 27.1% of cases. For MSI-H patients, surgery and watch-and-wait rates varied widely (0%-100%), reflecting heterogeneity in management. R0 resection rates were high across cohorts (70%-100% MSS, 80%-100% MSI-H). Pathological complete response (pCR) rates were 25% to 50% in MSS and 50% to 60% in MSI-H cohorts. Grade 3–4 adverse events ranged from 3.9% to 45.2% (MSS), 0% to 60% (MSI-H), with immune-related events generally below 10%.

The role of immunotherapy in MSS rectal cancer remains unclear; phase III trials and translational research are needed urgently for guidance

局部晚期直肠癌（LARC）目前的治疗方法包括术前放疗、化疗和放化疗，然后进行全肠系膜切除术（TME），这可能严重影响患者的生活质量。最近，抗pd1免疫治疗在微卫星不稳定性高（MSI-H） LARC中显示出100%的临床完全缓解，使患者避免手术且毒性最小。本综述评估了将免疫治疗纳入微卫星稳定型（MSS）和MSI-H LARC新辅助治疗的安全性、毒性、病理影响和长期益处。本系统综述遵循PRISMA指南，研究LARC的新辅助免疫治疗。提取有关研究特征、治疗方案和结果的数据。采用非随机研究方法学指数（Methodological Index for non - random studies，未成年人）和RoB2工具进行质量评价。患者被分为MSI-H、MSS和未知微卫星状态组。我们找到了12项已发表的研究，包括547名患者。在MSS队列中，新辅助手术后的发生率从57.6%到100%不等，27.1%的病例采用观察和等待方法。对于MSI-H患者，手术和观察等待率差异很大（0%-100%），反映了治疗的异质性。R0切除率在所有队列中都很高（70%-100% MSS, 80%-100% MSI-H）。病理完全缓解（pCR）率在MSS组为25%至50%，在MSI-H组为50%至60%。3-4级不良事件范围为3.9% - 45.2% (MSS), 0% - 60% (MSI-H)，免疫相关事件一般低于10%。免疫治疗在MSS直肠癌中的作用尚不清楚；迫切需要III期试验和转化研究的指导。

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引用次数: 0

B7-H3 in Colorectal Adenocarcinoma: Are We Focusing on the Right Target? B7-H3在结直肠癌中的作用：我们是否关注正确的靶点？

IF 3.2 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2025-12-01 Epub Date: 2025-10-03 DOI: 10.1016/j.clcc.2025.09.005

Paola Parente , Davide Ciardiello , Valentina Angerilli , Jessica Gasparello , Matteo Fassan

Introduction

B7-H3 belongs to B7 protein family which comprises molecules located on the cell surface, that play a crucial role in the modulation of immune response. Emerging data suggest that B7-H3 could promote cancer progression by coinhibitory effects on T cell responses, allowing cancer cells to avoid immune response, favoring invasion, metastatic spread, and drug resistance. Nevertheless, conflicting data regarding B7-H3 tumor expression, clinical correlation, and therapy response are reported. This is mainly due to (1) different investigated populations, (2) methods employed to assess its expression, and (3) the lack of standardized guidelines for B7-H3 expression scoring.

Materials and Methods

We investigated, on the whole sections, the immunohistochemical expression of B7-H3 (clone D9M2L) in a cohort of 87 patients affected by localized colorectal cancer (CRC, stage I-III), retrospectively selected to be representative of the different CRC histotypes, according to WHO, 2019 edition.

Results

Positive B7-H3 staining was documented in 68/89 cases (76.5%). All 68 cases showed immunostaining in neoplastic stroma, whereas non-neoplastic tissue was unstained in all 55 cases with normal mucosa and in 5 cases of dysplasia (100%). The highest frequency of B7-H3 positivity was observed in the CRC, NOS histotype (86%). The positivity rate in NOS histotype is even higher (90.5%), when only low-grade cases are considered, whereas lower rates (73.3%) were reported in the high-grade subgroup.

Conclusion

The presented data provide further evidence on the role of B7-H3 in CRC with particular reference to the tumor microenvironment and histotype, with a possible implication for the CRC therapy. Further studies are required to both confirm these data and elucidate the role of B7-H3 as a potential target to unleash the response to immunotherapy in CRC.

B7- h3属于B7蛋白家族，B7蛋白家族由位于细胞表面的分子组成，在免疫应答的调节中起着至关重要的作用。新出现的数据表明B7-H3可能通过对T细胞反应的共抑制作用来促进癌症进展，使癌细胞避免免疫反应，有利于侵袭、转移性扩散和耐药性。然而，关于B7-H3肿瘤表达、临床相关性和治疗反应的数据相互矛盾。这主要是由于(1)调查人群不同，(2)评估其表达的方法不同，以及(3)缺乏B7-H3表达评分的标准化指南。材料和方法：我们回顾性选择87例局限性结直肠癌（CRC， I-III期）患者，在整个切片上研究B7-H3（克隆D9M2L）的免疫组织化学表达，以代表不同的CRC组织类型，根据WHO， 2019版。结果：68/89例（76.5%）B7-H3染色阳性。68例肿瘤间质均显示免疫染色，而55例正常粘膜和5例不典型增生的非肿瘤组织均未染色（100%）。B7-H3阳性率在CRC、NOS组织型中最高（86%）。当仅考虑低级别病例时，NOS组织型的阳性率甚至更高（90.5%），而高级别亚组的阳性率较低（73.3%）。结论：本研究为B7-H3在结直肠癌中的作用提供了进一步的证据，特别是在肿瘤微环境和组织类型方面，可能对结直肠癌的治疗具有指导意义。需要进一步的研究来证实这些数据，并阐明B7-H3作为CRC中释放免疫治疗应答的潜在靶点的作用。

{"title":"B7-H3 in Colorectal Adenocarcinoma: Are We Focusing on the Right Target?","authors":"Paola Parente , Davide Ciardiello , Valentina Angerilli , Jessica Gasparello , Matteo Fassan","doi":"10.1016/j.clcc.2025.09.005","DOIUrl":"10.1016/j.clcc.2025.09.005","url":null,"abstract":"<div><h3>Introduction</h3><div>B7-H3 belongs to B7 protein family which comprises molecules located on the cell surface, that play a crucial role in the modulation of immune response. Emerging data suggest that B7-H3 could promote cancer progression by coinhibitory effects on T cell responses, allowing cancer cells to avoid immune response, favoring invasion, metastatic spread, and drug resistance. Nevertheless, conflicting data regarding B7-H3 tumor expression, clinical correlation, and therapy response are reported. This is mainly due to (1) different investigated populations, (2) methods employed to assess its expression, and (3) the lack of standardized guidelines for B7-H3 expression scoring.</div></div><div><h3>Materials and Methods</h3><div>We investigated, on the whole sections, the immunohistochemical expression of B7-H3 (clone D9M2L) in a cohort of 87 patients affected by localized colorectal cancer (CRC, stage I-III), retrospectively selected to be representative of the different CRC histotypes, according to WHO, 2019 edition.</div></div><div><h3>Results</h3><div>Positive B7-H3 staining was documented in 68/89 cases (76.5%). All 68 cases showed immunostaining in neoplastic stroma, whereas non-neoplastic tissue was unstained in all 55 cases with normal mucosa and in 5 cases of dysplasia (100%). The highest frequency of B7-H3 positivity was observed in the CRC, NOS histotype (86%). The positivity rate in NOS histotype is even higher (90.5%), when only low-grade cases are considered, whereas lower rates (73.3%) were reported in the high-grade subgroup.</div></div><div><h3>Conclusion</h3><div>The presented data provide further evidence on the role of B7-H3 in CRC with particular reference to the tumor microenvironment and histotype, with a possible implication for the CRC therapy. Further studies are required to both confirm these data and elucidate the role of B7-H3 as a potential target to unleash the response to immunotherapy in CRC.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 4","pages":"Pages 492-497"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Effect of Total Neoadjuvant Treatment on Pathological Response and Survival in Locally Advanced Rectal Cancer: A Single Center Experience 全新辅助治疗对局部晚期直肠癌病理反应和生存的影响：单中心经验。

IF 3.2 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2025-09-01 Epub Date: 2025-05-22 DOI: 10.1016/j.clcc.2025.05.001

Okan Aydın , Ahmet Emin Öztürk , Mert Erciyestepe , Şermin Dinç Sonuşen , Zehra Sucuoğlu İşleyen , Selvi Tabak Dinçer , Emir Çelik , Kayhan Ertürk , Muhammed Mustafa Atcı

Background

Total neoadjuvant therapy (TNT) has emerged as a promising approach in the treatment of locally advanced rectal cancer (LARC), aiming to improve pathological complete response (pCR) and survival by eradicating micrometastases.

Purpose

We aimed to evaluate the effect of TNT, which has been applied to patients with LARC in our clinic since 2019, on pathological response and survival and to present real-life data.

Methods

The medical records of 116 patients with stage 3 locally advanced rectal cancer who were followed at our clinic between March 2019 and March 2024 and who received TNT were retrospectively analyzed. Patients with pCR and non-pCR and TRG 0-1 and 2-3 were compared.

Results

The median follow-up period was 24.5. All of these 116 patients, were stage 3 (mostly stage 3B). Surgery was performed in 106 patients after TNT and 10 patients (8.6%) were followed with nonoperative management (NOM). Pathological complete response (pCR) was achieved in 28 (26.5%) of these 106 patients. The number of CAP-TRG 1 patients (near-pCR) was 35 (33%) and the number of CAP-TRG 2-3 patients was 43 (40.5%). Complete and near-complete responses (pCR and near-pCR) were achieved in approximately 60% of patients. Two parameters showed statistical significance in the univariate analysis of factors affecting pCR; tumor distance from the anal verge > 10 cm increased pCR 7.2-fold (P = .02) and CEA level at diagnosis ≤ 5 ng/ml increased pCR 4.4-fold (P = .008). During follow-up, 10 patients developed recurrence and/or metastasis and 5 of these 10 patients died. The majority of treatment-related toxicities were manageable grade 1-2 toxicities.

Conclusion

These single center, real-world data provide a perspective on the impact of TNT on pathological response and survival in patients with LARC. TNT is an effective and safe treatment and has become the standard of care with increased pathological complete response rates.

背景：全新辅助治疗（TNT）已成为治疗局部晚期直肠癌（LARC）的一种很有前景的方法，旨在通过根除微转移来提高病理完全缓解（pCR）和生存率。目的：我们旨在评估TNT自2019年以来在我诊所应用于LARC患者的病理反应和生存的影响，并提供现实数据。方法：回顾性分析2019年3月~ 2024年3月在我院随访并接受TNT治疗的116例3期局部晚期直肠癌患者病历。比较pCR与非pCR患者及TRG 0-1、2-3。结果：中位随访时间为24.5。所有116例患者均为3期（大部分为3B期）。106例患者行手术治疗，10例（8.6%）患者行非手术治疗。106例患者中28例（26.5%）达到病理完全缓解（pCR）。CAP-TRG 1患者（近pcr） 35例（33%），CAP-TRG 2-3患者43例（40.5%）。在大约60%的患者中实现了完全和接近完全的反应（pCR和近pCR）。单因素分析中有两个参数有统计学意义；肿瘤距离肛门边缘bbb10 cm时pCR增加7.2倍（P = 0.02），诊断时CEA水平≤5 ng/ml时pCR增加4.4倍（P = 0.008）。随访期间，10例患者复发和/或转移，其中5例死亡。大多数治疗相关的毒性是可控的1-2级毒性。结论：这些单中心、真实世界的数据为TNT对LARC患者病理反应和生存的影响提供了视角。TNT是一种有效且安全的治疗方法，已成为病理完全缓解率提高的标准治疗方法。

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引用次数: 0

MRI Monitoring of Locally Advanced Rectal Cancer in Watch and Wait Patients 局部进展期直肠癌观察等待患者的MRI监测。

IF 3.2 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2025-09-01 Epub Date: 2025-06-06 DOI: 10.1016/j.clcc.2025.05.003

Jian Zhao , Kanghua Huang , Akao Zhu , Jinghan Zhu , Yimin Fang , Xiaofeng Zhou , Hao Jiang , Li Shen , Haiyan Chen

Background

Watch and wait (W&W) is an alternative strategy for locally advanced rectal cancer (LARC) (T3-4/N+) patients. MRI-based evaluation of clinical complete response (cCR) and post-cCR disease monitoring remain uncertain. This study aims to investigate the association between MRI feature changes and survival outcomes in these patients.

Methods

LARC Patients achieving cCR after neoadjuvant chemoradiotherapy and opting for W&W were included. MRI features were recorded from pretreatment to the follow-up period, including tumor bed scarring on post-treatment T2-weighted imaging (T2WI), magnetic resonance tumor regression grade (mrTRG), and high-signal areas on diffusion-weighted imaging (DWI). The relationship between follow-up data and MRI feature changes over time was analyzed.

Results

41 patients were included, and 5-year PFS and OS were 64.1% and 90.9%. For the 11 patients without cCR at the initial assessment, tumor signals decreased over time on both T2WI and DWI, with an increasing trend in scar formation on T2WI. Cumulative cCR rates at 7 weeks (± 1 week), 16 weeks (± 3 weeks), 24 weeks (± 4 weeks), and 32 weeks (± 3 weeks) were 72.5%, 80.5%, 95.1%, and 100.0%. Seven patients (17.1%) had a recurrence, with a disruption of the scar and the appearance of intermediate-intensity signals within the low-signal fibrotic area of the original tumor bed on T2WI. A newly developed high-signal area was observed on DWI.

Conclusions

The cCR rate increased over time. The scar sign on T2WI was more prevalent in patients with cCR, increased over time. MRI surveillance is essential for W&W patients but remains dynamic and challenging.

背景：观察和等待（W&W）是局部晚期直肠癌（LARC）（T3-4/N+）患者的替代策略。基于mri的临床完全缓解（cCR）评估和cCR后疾病监测仍不确定。本研究旨在探讨这些患者的MRI特征变化与生存结果之间的关系。方法：纳入经新辅助放化疗后达到cCR并选择W&W的LARC患者。记录从治疗前到随访期间的MRI特征，包括治疗后t2加权成像（T2WI）上的肿瘤床瘢痕、磁共振肿瘤消退分级（mrTRG）、弥散加权成像（DWI）上的高信号区。分析随访数据与MRI特征随时间变化的关系。结果：纳入41例患者，5年PFS和OS分别为64.1%和90.9%。在初步评估时无cCR的11例患者中，T2WI和DWI上的肿瘤信号随时间的推移而减弱，T2WI上的疤痕形成呈增加趋势。7周（±1周）、16周（±3周）、24周（±4周）和32周（±3周）的累积cCR率分别为72.5%、80.5%、95.1%和100.0%。7例（17.1%）复发，T2WI表现为瘢痕破坏，原肿瘤床低信号纤维化区出现中强度信号。在DWI上观察到一个新形成的高信号区。结论：cCR率随着时间的推移而增加。T2WI上疤痕征像在cCR患者中更为普遍，随着时间的推移而增加。MRI监测对W&W患者至关重要，但仍然是动态的和具有挑战性的。

{"title":"MRI Monitoring of Locally Advanced Rectal Cancer in Watch and Wait Patients","authors":"Jian Zhao , Kanghua Huang , Akao Zhu , Jinghan Zhu , Yimin Fang , Xiaofeng Zhou , Hao Jiang , Li Shen , Haiyan Chen","doi":"10.1016/j.clcc.2025.05.003","DOIUrl":"10.1016/j.clcc.2025.05.003","url":null,"abstract":"<div><h3>Background</h3><div>Watch and wait (W&W) is an alternative strategy for locally advanced rectal cancer (LARC) (T3-4/N+) patients. MRI-based evaluation of clinical complete response (cCR) and post-cCR disease monitoring remain uncertain. This study aims to investigate the association between MRI feature changes and survival outcomes in these patients.</div></div><div><h3>Methods</h3><div>LARC Patients achieving cCR after neoadjuvant chemoradiotherapy and opting for W&W were included. MRI features were recorded from pretreatment to the follow-up period, including tumor bed scarring on post-treatment T2-weighted imaging (T2WI), magnetic resonance tumor regression grade (mrTRG), and high-signal areas on diffusion-weighted imaging (DWI). The relationship between follow-up data and MRI feature changes over time was analyzed.</div></div><div><h3>Results</h3><div>41 patients were included, and 5-year PFS and OS were 64.1% and 90.9%. For the 11 patients without cCR at the initial assessment, tumor signals decreased over time on both T2WI and DWI, with an increasing trend in scar formation on T2WI. Cumulative cCR rates at 7 weeks (± 1 week), 16 weeks (± 3 weeks), 24 weeks (± 4 weeks), and 32 weeks (± 3 weeks) were 72.5%, 80.5%, 95.1%, and 100.0%. Seven patients (17.1%) had a recurrence, with a disruption of the scar and the appearance of intermediate-intensity signals within the low-signal fibrotic area of the original tumor bed on T2WI. A newly developed high-signal area was observed on DWI.</div></div><div><h3>Conclusions</h3><div>The cCR rate increased over time. The scar sign on T2WI was more prevalent in patients with cCR, increased over time. MRI surveillance is essential for W&W patients but remains dynamic and challenging.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 378-388.e5"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Treatment of Oligometastatic BRAFV600E Mutant Colorectal Cancer: Learning From a Clinical Case 少转移性BRAFV600E突变型结直肠癌的治疗：从一个临床病例的学习。

IF 3.2 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2025-09-01 Epub Date: 2025-03-25 DOI: 10.1016/j.clcc.2025.03.003

Renato Maria Marsicano , Luca Boscolo Bielo , Elena Guerini Rocco , Mariano Lombardi , Emilio Bertani , Filippo Maria Bassi , Giuseppe Curigliano , Davide Ciardiello , Nicola Fazio , Maria Giulia Zampino

•
Treatment with Encorafenib plus Cetuximab is one standard option of care in patients with BRAF V600E-mutated (MT) metastatic colorectal cancer (mCRC).
•
Treatment of oligometastatic disease in BRAFV600E MT CRC remains a topic of debate.
•
Here, we present the case of a patient with oligometastatic lymph nodes-only involvement treated with target therapy and loco-regional treatment.

•对于BRAF v600e突变（MT）转移性结直肠癌（mCRC）患者，恩科非尼加西妥昔单抗治疗是一种标准的治疗选择。•BRAFV600E MT结直肠癌低转移性疾病的治疗仍然是一个有争议的话题。•在这里，我们报告了一例仅涉及少转移淋巴结的患者，接受了靶向治疗和局部区域治疗。

引用次数: 0

Role of Neoadjuvant Chemotherapy Before Simultaneous Resection of Colon Cancer and Liver Metastases: A Propensity-Score Matched Analysis 结肠癌和肝转移同时切除前新辅助化疗的作用：倾向评分匹配分析。

IF 3.2 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2025-09-01 Epub Date: 2025-05-29 DOI: 10.1016/j.clcc.2025.05.005

Sameh Hany Emile , Zoe Garoufalia , Rachel Gefen , Justin Dourado , Ebram Salama , Steven D. Wexner

Background

There has been a controversy about the optimal management of colorectal liver metastases (CLM). Both upfront surgery and neoadjuvant chemotherapy are viable options for CLM. The present study aimed to assess the short-term and survival outcomes of neoadjuvant chemotherapy before simultaneous resection of primary colon cancer and liver metastases.

Methods

This retrospective cohort study used data from the National Cancer Database (2015-2019) on patients with primary colon cancer and synchronous liver metastases. The main exposure was neoadjuvant chemotherapy before simultaneous resection of colon cancer and hepatic metastases. Propensity-score matching was used to match patients who had upfront surgery without neoadjuvant chemotherapy with patients who received neoadjuvant chemotherapy. The primary outcome was 5-year overall survival (OS). Secondary outcomes included hospital stay, 30-day and 90-day mortality, 30-day unplanned readmission, conversion to open surgery, surgical margins, and disease downstaging.

Results

Overall, neoadjuvant chemotherapy was given to 38.3% of 4060 patients. After matching, 1446 patients (53% male) were included; 482 were in the neoadjuvant group and 964 were in the no-neoadjuvant group. Neoadjuvant chemotherapy was associated with a longer restricted mean OS (46.7 vs. 40.6 months, P < .001) and significantly lower rates of 90-day mortality (3% vs. 6.5%, P = .008), 30-day unplanned readmission (4.8% vs. 8.8%, P = .002), positive surgical margins (6.5% vs. 15.1%, P < .001), and administration of adjuvant therapy (47.3% vs. 79.5%, P < .001). The 2 groups were comparable in hospital stay, 30-day mortality, and number of examined lymph nodes.

Conclusions

Giving neoadjuvant chemotherapy before simultaneous resection of colon cancer and hepatic metastases was associated with extended mean OS and reduced rates of 90-day mortality, 30-day unplanned readmission, and positive surgical margins.

背景：关于结肠直肠肝转移（CLM）的最佳治疗一直存在争议。前期手术和新辅助化疗都是CLM的可行选择。本研究旨在评估原发性结肠癌和肝转移同时切除前新辅助化疗的短期和生存结果。方法：本回顾性队列研究使用国家癌症数据库（2015-2019）的原发性结肠癌合并同步肝转移患者数据。主要暴露于结肠癌和肝转移同时切除前的新辅助化疗。倾向评分匹配用于将术前未进行新辅助化疗的患者与接受新辅助化疗的患者进行匹配。主要终点为5年总生存期（OS）。次要结局包括住院时间、30天和90天死亡率、30天意外再入院、转为开放手术、手术切缘和疾病分期降低。结果：4060例患者中，38.3%的患者接受了新辅助化疗。匹配后纳入1446例患者，其中男性53%；新辅助组482例，非新辅助组964例。新辅助化疗与更长的受限平均生存期（46.7个月对40.6个月，P < 0.001）、显著降低的90天死亡率（3%对6.5%,P = 0.008）、30天计划外再入院（4.8%对8.8%,P = 0.002）、阳性手术切缘（6.5%对15.1%,P < 0.001）和辅助治疗的实施（47.3%对79.5%,P < 0.001）相关。两组在住院时间、30天死亡率和检查淋巴结数量方面具有可比性。结论：在结肠癌和肝转移同时切除前给予新辅助化疗可延长平均总生存期，降低90天死亡率、30天意外再入院率和手术切缘阳性。

{"title":"Role of Neoadjuvant Chemotherapy Before Simultaneous Resection of Colon Cancer and Liver Metastases: A Propensity-Score Matched Analysis","authors":"Sameh Hany Emile , Zoe Garoufalia , Rachel Gefen , Justin Dourado , Ebram Salama , Steven D. Wexner","doi":"10.1016/j.clcc.2025.05.005","DOIUrl":"10.1016/j.clcc.2025.05.005","url":null,"abstract":"<div><h3>Background</h3><div><span>There has been a controversy about the optimal management of colorectal liver metastases<span> (CLM). Both upfront surgery and neoadjuvant chemotherapy are viable options for CLM. The present study aimed to assess the short-term and survival outcomes of neoadjuvant chemotherapy before simultaneous resection of primary </span></span>colon cancer and liver metastases.</div></div><div><h3>Methods</h3><div>This retrospective cohort study<span> used data from the National Cancer Database (2015-2019) on patients with primary colon cancer and synchronous liver metastases. The main exposure was neoadjuvant chemotherapy before simultaneous resection of colon cancer and hepatic metastases. Propensity-score matching was used to match patients who had upfront surgery without neoadjuvant chemotherapy with patients who received neoadjuvant chemotherapy. The primary outcome was 5-year overall survival (OS). Secondary outcomes included hospital stay, 30-day and 90-day mortality, 30-day unplanned readmission, conversion to open surgery, surgical margins, and disease downstaging.</span></div></div><div><h3>Results</h3><div>Overall, neoadjuvant chemotherapy was given to 38.3% of 4060 patients. After matching, 1446 patients (53% male) were included; 482 were in the neoadjuvant group and 964 were in the no-neoadjuvant group. Neoadjuvant chemotherapy was associated with a longer restricted mean OS (46.7 vs. 40.6 months, <em>P</em> < .001) and significantly lower rates of 90-day mortality (3% vs. 6.5%, <em>P</em> = .008), 30-day unplanned readmission (4.8% vs. 8.8%, <em>P</em> = .002), positive surgical margins (6.5% vs. 15.1%, <em>P</em> < .001), and administration of adjuvant therapy (47.3% vs. 79.5%, <em>P</em> < .001). The 2 groups were comparable in hospital stay, 30-day mortality, and number of examined lymph nodes.</div></div><div><h3>Conclusions</h3><div>Giving neoadjuvant chemotherapy before simultaneous resection of colon cancer and hepatic metastases was associated with extended mean OS and reduced rates of 90-day mortality, 30-day unplanned readmission, and positive surgical margins.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 400-409.e1"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0