Clinical colorectal cancer最新文献_第7页

Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer 巴西-TNT：新辅助化疗后 FOLFIRINOX 与化疗治疗 II/III 期直肠癌的随机 2 期试验

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-09-01 DOI: 10.1016/j.clcc.2024.03.003

Background

Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy—TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW.

Methods

This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)—TNT-arm—or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR).

Results

Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns).

Conclusions

TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).

背景新辅助放疗和以奥沙利铂为基础的全身治疗（全新辅助治疗-TNT）已被证明可提高局部直肠癌的反应率和器官保留率。然而，有关治疗方案的试验各不相同，很少有试验对完全应答者采用观察和等待（WW）方法。本试验评估了传统的长期化疗后巩固FOLFIRINOX是否能提高完全反应率，以及采用观察-等待（WW）方法治疗的患者人数。这是一项在巴西两家癌症中心进行的实用随机II期试验，纳入了T3+或N+直肠腺癌患者。患者在完成卡培他滨长疗程54 Gy化放疗后，按1:1随机分配到4个周期的mFOLFIRINOX（奥沙利铂85、伊立替康150、5-FU 2400）- TNT-治疗组或对照组，后者不包括进一步的新辅助治疗。所有患者均在放射治疗结束 12 周后接受专门的盆腔磁共振成像和乙状结肠镜检查，重新分期。临床完全反应患者采用WW方案进行随访。主要终点是完全反应：临床完全反应（cCR）或病理反应（pCR）。结果在2021年4月至2023年6月期间，55名患者随机接受了TNT治疗，53名患者接受了对照组治疗。74%的肿瘤为3期，距离肛门边缘的中位距离为6厘米，63%的肿瘤周缘有风险，33%的肿瘤累及括约肌。TNT 的 cCR + pCR 率为（31%），而对照组为（17%）（几率比 2.19，CI 95% 0.8-6.22 P = .091），WW 率分别为 16% 和 9%（P = ns）。中位随访时间为 8.1 个月，TNT 和对照组的复发率分别为 16% 和 21% (P = ns)。该试验得到了巴西政府的资助（PROADI-SUS - NUP 25000.164382/2020-81）。

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引用次数: 0

Potential for Metastasis and Recurrence in Colorectal Carcinoma In Situ: A Retrospective Analysis of 1069 Patients 结直肠原位癌转移和复发的可能性：对 1069 例患者的回顾性分析

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-09-01 DOI: 10.1016/j.clcc.2024.04.003

Background

Colorectal carcinoma in situ, characterized by cancer limited to the intramucosal layer or known as intraepithelial carcinoma, has conventionally considered to be without any risk of regional lymph node metastasis. However, isolated cases of regional lymph node metastasis, local recurrence, and distant metastasis challenge this assumption. This study aimed to assess the occurrence of regional lymph node metastasis and recurrence of colorectal carcinoma in situ.

Methods

A retrospective analysis was conducted in 1069 patients who underwent full-thickness local excision or radical surgery for colorectal carcinoma in situ between January 1994 and December 2020. Histopathological features were assessed by 2 experienced pathologists. In cases of suspected recurrence, evaluation involved abdomen-pelvis and chest computed tomography, or PET-CT.

Results

The recurrence rate of colorectal carcinoma in situ patients was 0.46%. Among the patients, 9 were diagnosed with regional lymph node metastasis or cancer recurrence. Of these, 4 patients were diagnosed with lymph node metastasis during primary surgery; 2 exhibited regional lymph node metastasis, and 2 presented with both regional and distant lymph node metastases. Regional lymph node metastasis occurred in additional 2 patients after radical surgery for the primary tumor. Distant metastasis was observed in 3 patients: hepatic metastasis in 1, hepatic and pulmonary metastases in another, and small bowel metastasis in the third patient. Among the 5 patients experiencing cancer recurrence, 1 expired due to cancer progression.

Conclusion

Contrary to previous assumptions, colorectal carcinoma in situ can potentially metastasize to lymph nodes and recur. Therefore, careful assessment at the time of diagnosis is crucial, recognizing the possibility of lymph node metastasis or recurrence. This approach is essential for accurately identifying instances of cancer recurrence and ensuring optimal oncological outcomes.

背景大肠原位癌的特点是癌变局限于粘膜内层，或称为上皮内癌，传统上认为这种癌没有区域淋巴结转移的风险。然而，区域淋巴结转移、局部复发和远处转移的个别病例挑战了这一假设。本研究旨在评估结直肠原位癌区域淋巴结转移和复发的发生率。方法对 1994 年 1 月至 2020 年 12 月间因结直肠原位癌接受全层局部切除术或根治术的 1069 例患者进行了回顾性分析。组织病理学特征由两名经验丰富的病理学家进行评估。对疑似复发病例的评估包括腹部-盆腔和胸部计算机断层扫描或 PET-CT。其中，9 名患者被诊断为区域淋巴结转移或癌症复发。其中，4 名患者在初次手术中被诊断为淋巴结转移；2 名患者出现区域淋巴结转移，2 名患者同时出现区域和远处淋巴结转移。另有 2 名患者在原发肿瘤根治术后出现区域淋巴结转移。3 名患者出现了远处转移：1 名患者出现了肝转移，另一名患者出现了肝和肺转移，第三名患者出现了小肠转移。结论与之前的假设相反，结直肠原位癌有可能转移到淋巴结并复发。因此，在诊断时进行仔细评估至关重要，要认识到淋巴结转移或复发的可能性。这种方法对于准确识别癌症复发和确保最佳肿瘤治疗效果至关重要。

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引用次数: 0

An Evolving Landscape: New Therapies for Metastatic Colorectal Cancer 不断演变的格局：转移性结直肠癌的新疗法

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-08-24 DOI: 10.1016/j.clcc.2024.08.003

Christiana Mo , Bhawneet Chadha , Chaoyuan Kuang

Substantial progress is being made in the development of novel therapies directed against colorectal cancer. The discovery of various molecular markers and advances in tumor profiling have facilitated the development of new targeted agents and immunotherapy. Not only have these drugs improved progression-free survival and even overall survival in some cases, but their related outcomes have also raised questions as to how to best combine or sequence therapies for even greater efficacy. Furthermore, we are beginning to understand how these combination therapies may yield for greater therapeutic response for patients with microsatellite stable colorectal cancer for which there is much need for improvement. In this article, we review recent trial data and explore the outcomes of various targeted therapies and immunotherapies for patient with advanced colorectal cancer.

在开发针对结直肠癌的新型疗法方面正在取得重大进展。各种分子标记物的发现和肿瘤图谱分析的进步促进了新型靶向药物和免疫疗法的开发。这些药物不仅改善了无进展生存期，甚至在某些病例中改善了总生存期，而且其相关结果也提出了如何最佳组合或排序疗法以获得更大疗效的问题。此外，我们也开始了解这些联合疗法如何为微卫星稳定型结直肠癌患者带来更大的治疗反应，在这方面还有很多需要改进的地方。在本文中，我们将回顾最近的试验数据，并探讨各种靶向疗法和免疫疗法对晚期结直肠癌患者的治疗效果。

引用次数: 0

Clinical Outcomes of Elective Early Discontinuation of Immunotherapy Based on Objective Response in Microsatellite Instability-High Metastatic Colorectal Cancer 微卫星不稳定性高的转移性结直肠癌患者根据客观反应选择性提前终止免疫疗法的临床结果

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-08-18 DOI: 10.1016/j.clcc.2024.08.001

Annie Xiao , Xiaochen Li , Chongkai Wang , Marwan Fakih

Background

Patients with microsatellite-high (MSI-H) metastatic colorectal cancers (CRC) may experience long-lasting benefit from immune checkpoint inhibitors (ICI) upon stopping therapy. However, optimal timing and patient selection criteria for early treatment withdrawal remain undefined. In this single-center retrospective study, we characterized the clinical response and associated survival outcomes of patients who received elective early versus late treatment discontinuation.

Methods

We retrospectively analyzed patients with MSI-H metastatic CRC treated with ICI therapy from May 2015 to April 2024. Early ICI discontinuation was defined as treatment withdrawal before 2 years, and late ICI discontinuation as after 2 years. Response was assessed using Response Evaluation Criteria in Solid Tumors. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. Efficacy outcomes between early and late ICI discontinuation groups were compared using a log-rank test.

Results

Of 36 patients with MSI-H metastatic CRC, 12 underwent elective early ICI discontinuation and 9 experienced late ICI discontinuation. After a median follow-up of 32 months post-treatment, 91.7% (11/12) in the early discontinuation group remain off therapy without progression. PFS and OS outcomes between the early and late discontinuation groups were similarly favorable (P = .88 and P = .85, respectively), despite a 12-month difference in median duration of ICI therapy (13.3 and 25.6 months, respectively). The most common reason for elective early treatment discontinuation was clinical remission (n = 10), defined as a complete response, or a partial response with negative PET and/or ctDNA testing.

Conclusions

Early ICI discontinuation guided by response criteria resulted in low rates of recurrence. Survival outcomes between early and late ICI discontinuation groups were comparable, suggesting that treatment duration can be individualized based on clinical response without compromising favorable long-term prognosis.

微卫星高（MSI-H）转移性结直肠癌（CRC）患者在停止治疗后可能会从免疫检查点抑制剂（ICI）中获得长期获益。然而，早期停药的最佳时机和患者选择标准仍未确定。在这项单中心回顾性研究中，我们描述了选择性早期停药与晚期停药患者的临床反应和相关生存结果。我们回顾性分析了 2015 年 5 月至 2024 年 4 月期间接受 ICI 治疗的 MSI-H 转移性 CRC 患者。早期 ICI 停药定义为 2 年前停止治疗，晚期 ICI 停药定义为 2 年后停止治疗。反应采用实体瘤反应评估标准进行评估。无进展生存期（PFS）和总生存期（OS）采用卡普兰-麦尔法估算。采用对数秩检验比较了早期和晚期停用 ICI 组的疗效。在36例MSI-H转移性CRC患者中，12例选择了早期停用ICI，9例经历了晚期停用ICI。在治疗后中位随访32个月后，早期停药组中91.7%（11/12）的患者仍在接受治疗，且未出现病情进展。尽管 ICI 治疗的中位持续时间相差 12 个月（分别为 13.3 个月和 25.6 个月），但早期停药组和晚期停药组的 PFS 和 OS 结果同样良好（分别为 = .88 和 = .85）。选择性早期停药的最常见原因是临床缓解（10 例），即完全缓解或 PET 和/或 ctDNA 检测阴性的部分缓解。在应答标准指导下早期中断 ICI 治疗的复发率较低。早期停用 ICI 组和晚期停用 ICI 组的生存结果相当，这表明治疗时间可根据临床反应进行个体化，而不会影响良好的长期预后。

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引用次数: 0

The Site of Checkpoint in a Continuous Oncological Evolving Course of Colon Cancer to an Obstruction Phenotype Decides the Effects of “Incomplete” Obstruction 在结肠癌向梗阻表型的连续肿瘤学演变过程中，检查点的位置决定了 "不完全 "梗阻的效果

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-08-17 DOI: 10.1016/j.clcc.2024.08.002

Shenghe Deng, Falong Zou, Kailin Cai

引用次数: 0

Adaptive Immune Receptor Distinctions Along the Colorectal Polyp-Tumor Timelapse 大肠息肉-肿瘤时间推移过程中适应性免疫受体的区别

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-07-26 DOI: 10.1016/j.clcc.2024.07.002

Taha I. Huda , Diep Nguyen , Arpan Sahoo , Joanna J. Song , Alexander F. Gutierrez , Boris I. Chobrutskiy , George Blanck

Introduction

Colorectal cancer (CRC) is the third-most common cancer diagnosed worldwide, with 1.85 million new cases per year. While mortality has significantly decreased due to preventive colonoscopy, only 5% of polyps identified progress to cancer. Studies have found that immunological alterations in other solid tumor microenvironments are associated with worse prognoses.

Methods

We applied an immunogenomics approach to assess adaptive immune receptor gene expression changes that were associated with development of adenocarcinoma, utilizing 79 samples that represented normal, tubular, villous, and tumor colorectal tissue for 32 patients.

Results

Results indicated that the number of productive TRD and TRG recombination reads, representing gamma-delta (γδ) T-cells, significantly decreased with progression from normal to tumor tissue. A further assessment of two independent CRC datasets was consistent with a decrease in TRD recombination reads with progression to CRC. Further, we identified three physicochemical parameters for immunoglobulin, complementarity determining region-3 (CDR3) amino acids associated with progression from normal to tumor tissue.

Conclusions

Overall, this study points towards a need for further investigation of γδ T-cells in relation to CRC development; and indicates immunoglobulin CDR3 physicochemical features as potential CRC biomarkers.

导言：大肠癌（CRC）是全球第三大常见癌症，每年新增病例 185 万。虽然预防性结肠镜检查使死亡率大幅下降，但发现的息肉中只有 5%会发展为癌症。研究发现，其他实体瘤微环境中的免疫学改变与较差的预后有关。研究结果表明，代表γ-δ（γδ）T细胞的有成效TRD和TRG重组读数的数量随着从正常组织到肿瘤组织的进展而明显减少。对两个独立的 CRC 数据集进行的进一步评估表明，TRD 重组读数随着 CRC 的进展而减少。此外，我们还发现了免疫球蛋白的三个理化参数，即互补决定区-3（CDR3）氨基酸与肿瘤组织从正常发展到肿瘤的过程有关。结论总之，这项研究表明有必要进一步研究γδ T 细胞与 CRC 发展的关系；并指出免疫球蛋白 CDR3 理化特征是潜在的 CRC 生物标记物。

{"title":"Adaptive Immune Receptor Distinctions Along the Colorectal Polyp-Tumor Timelapse","authors":"Taha I. Huda , Diep Nguyen , Arpan Sahoo , Joanna J. Song , Alexander F. Gutierrez , Boris I. Chobrutskiy , George Blanck","doi":"10.1016/j.clcc.2024.07.002","DOIUrl":"10.1016/j.clcc.2024.07.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Colorectal cancer (CRC) is the third-most common cancer diagnosed worldwide, with 1.85 million new cases per year. While mortality has significantly decreased due to preventive colonoscopy, only 5% of polyps identified progress to cancer. Studies have found that immunological alterations in other solid tumor microenvironments are associated with worse prognoses.</div></div><div><h3>Methods</h3><div>We applied an immunogenomics approach to assess adaptive immune receptor gene expression changes that were associated with development of adenocarcinoma, utilizing 79 samples that represented normal, tubular, villous, and tumor colorectal tissue for 32 patients.</div></div><div><h3>Results</h3><div>Results indicated that the number of productive TRD and TRG recombination reads, representing gamma-delta (γδ) T-cells, significantly decreased with progression from normal to tumor tissue. A further assessment of two independent CRC datasets was consistent with a decrease in TRD recombination reads with progression to CRC. Further, we identified three physicochemical parameters for immunoglobulin, complementarity determining region-3 (CDR3) amino acids associated with progression from normal to tumor tissue.</div></div><div><h3>Conclusions</h3><div>Overall, this study points towards a need for further investigation of γδ T-cells in relation to CRC development; and indicates immunoglobulin CDR3 physicochemical features as potential CRC biomarkers.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 402-411"},"PeriodicalIF":3.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841467","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

Neoadjuvant Immunotherapy for Patients With Microsatellite Instability-High or POLE-Mutated Locally Advanced Colorectal Cancer With Bulky Tumors: New Optimization Strategy 针对微卫星不稳定性高或 POLE 突变的大块肿瘤局部晚期结直肠癌患者的新辅助免疫疗法：新的优化策略

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-07-09 DOI: 10.1016/j.clcc.2024.07.001

Yingjie Li , Fei Liang , Zhongwu Li , Xiaoyan Zhang , Aiwen Wu

Objective

To evaluate the efficacy and safety of neoadjuvant immunotherapy for patients with microsatellite instability-high (MSI-H) or DNA polymerase ε (POLE)-mutated locally advanced colorectal cancer (LACRC) with bulky tumors. 

Patients

We retrospectively reviewed 22 consecutive patients with MSI-H or POLE-mutated LACRC with bulky tumors (>8 cm in diameter) who received preoperative programmed death-1 blockade, with or without CapOx chemotherapy. 

Main Outcome Measures

Pathological complete response (pCR), clinical complete response (cCR), toxicity, R0 resection rate, and complications were evaluated. Survival outcomes were analyzed using the Kaplan-Meier method. Multiplex immunofluorescence analysis were performed before and after treatment. 

Results

The incidence of immune-related adverse events (irAEs) was 36.4% (8/22). Five of 22 patients presented with surgical emergencies, most commonly perforation or obstruction. The 22 patients underwent a median 4 (1-8) cycles. Two patients were evaluated as cCR and underwent a watch and wait strategy. The R0 resection rate was 100.0% (20/20) and pCR rate was 70.0% (14/20). Twelve of 14 cT4b patients (85.7%) avoided multivisceral resection, and 10 of them achieved pCR or cCR. In the two patients with POLE mutations, one each achieved pCR and cCR. No Grade III/IV postoperative complications occurred. The median follow-up was 16.0 months. Two-year event-free and overall survival for the whole cohort was both 100%. 

Conclusions

Preoperative immunotherapy is the optimal option for MSI-H or POLE-mutated LACRC with bulky tumors, especially cT4b. Preoperative immunotherapy in patients with T4b CRC can reduce multivisceral resection and achieve high CR rate.

目的评价微卫星不稳定性高（MSI-H）或DNA聚合酶ε (POLE)突变局部晚期结直肠癌（LACRC）伴大体积肿瘤患者新辅助免疫治疗的疗效和安全性。 患者我们回顾性分析了22例连续的MSI-H或pole突变LACRC患者，这些患者伴有大体积肿瘤（直径8cm），术前接受程序性死亡-1阻断，伴或不伴CapOx化疗。 主要观察指标评估病理完全缓解（pCR）、临床完全缓解（cCR）、毒性、R0切除率、并发症。生存结果采用Kaplan-Meier法进行分析。治疗前后进行多重免疫荧光分析。 结果免疫相关不良事件（irAEs）发生率为36.4%（8/22）。22例患者中有5例出现手术紧急情况，最常见的是穿孔或梗阻。22例患者的平均周期为4（1-8）个周期。2例患者被评估为cCR，并接受观察和等待策略。R0切除率为100.0% (20/20)，pCR率为70.0%（14/20）。14例cT4b患者中有12例（85.7%）避免了多脏器切除，其中10例实现了pCR或cCR。在2例POLE突变患者中，各有1例实现了pCR和cCR。无III/IV级术后并发症发生。中位随访时间为16.0个月。整个队列的2年无事件生存率和总生存率均为100%。 结论对于体积较大的肿瘤，尤其是cT4b， MSI-H或pole突变的LACRC，术前免疫治疗是最佳选择。T4b结直肠癌患者术前免疫治疗可减少多脏器切除，达到较高的CR率。

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引用次数: 0

Trifluridine/Tipiracil Based Chemoradiation in locally Advanced Rectal Cancer: The Phase I/II TARC Trial 基于三氟啶/替吡拉西尔的局部晚期直肠癌化疗：I/II 期 TARC 试验

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-06-22 DOI: 10.1016/j.clcc.2024.06.003

Benjamin Thiele , Alexander Stein , Christoph Schultheiß , Lisa Paschold , Hanna Jonas , Eray Goekkurt , Jörn Rüssel , Gunter Schuch , Jan Wierecky , Marianne Sinn , Joseph Tintelnot , Cordula Petersen , Kai Rothkamm , Eik Vettorazzi , Mascha Binder

Background

Optimizing functional outcomes and securing long-term remissions are key goals in managing patients with locally advanced rectal cancer. In this proof-of-concept study, we set out to further optimize neoadjuvant therapy by integrating the radiosensitizer trifluridine/tipiracil and explore the potential of cell free tumor DNA (ctDNA) to monitor residual disease.

Methods

About 10 patients were enrolled in the phase I dose finding part which followed a 3 + 3 dose escalation design. Tipiracil/trifluridine was administered concomitantly to radiotherapy. ctDNA monitoring was performed before and after chemoradiation with patient-individualized digital droplet PCRs.

Results

No dose-limiting toxicities were observed at the maximum tolerated dose level of 2 × 35 mg/m² trifluridine/tipiracil. There were 9 grade 3 adverse events, of which 8 were hematologic with anemia and leukopenia. Chemoradiation yielded a pathological complete response in 1 out of 8 assessable patients, downstaging in nearly all patients, and 1 clinical complete response referred for watchful waiting. Three of 4 assessable patients with residual tumor cells at pathological assessment remained liquid biopsy positive after chemoradiation, but 1 turned negative.

Conclusion

In this exploratory phase I trial, the novel combination of neoadjuvant trifluridine/tipiracil and radiotherapy proved to be feasible, tolerable, and effective. However, the application of liquid biopsy as a potential marker for therapeutic de-escalation in the neoadjuvant setting requires additional research and prospective validation.

The trial was registered at ClinicalTrials.gov: NCT04177602.

优化功能结果和确保长期缓解是治疗局部晚期直肠癌患者的关键目标。在这项概念验证研究中，我们通过整合放射增敏剂三氟尿苷/替比拉西，进一步优化新辅助治疗，并探索细胞游离肿瘤DNA（ctDNA）监测残留疾病的潜力。约有10名患者参加了I期剂量发现部分，该部分采用3+3剂量递增设计。化疗前后使用患者个体化数字液滴PCR对ctDNA进行监测。在 2 × 35 mg/m² 三氟尿苷/替比拉西最大耐受剂量水平下，未观察到剂量限制性毒性。共发生了9起3级不良反应，其中8起为血液学不良反应，包括贫血和白细胞减少。在 8 例可评估的患者中，化疗使 1 例患者获得了病理完全反应，几乎所有患者都进行了降期治疗，1 例临床完全反应患者转为观察等待。在病理评估时有残留肿瘤细胞的 4 名可评估患者中，有 3 人在化疗后液体活检仍为阳性，但有 1 人转为阴性。在这项探索性 I 期试验中，新辅助三氟啶/替比拉西和放疗的新型组合被证明是可行、可耐受和有效的。然而，将液体活检作为新辅助治疗中治疗降级的潜在标志物还需要更多的研究和前瞻性验证。

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引用次数: 0

Minimally Invasive Surgery for Colorectal Cancer: Benchmarking Uptake for a Regional Improvement Programme 结直肠癌微创手术：以地区改进计划的接受率为基准

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-06-18 DOI: 10.1016/j.clcc.2024.05.013

John C. Taylor , Dermot Burke , Lene H. Iversen , Rebecca J. Birch , Paul J. Finan , Mark M. Iles , Philip Quirke , Eva J.A. Morris , YCR BCIP Study Group

Background

The uptake of minimally invasive surgery (MIS) for patients with colorectal cancer has progressed at differing rates, both across countries, and within countries. This study aimed to investigate uptake for a regional colorectal cancer improvement programme in England.

Method

We calculated the proportion of patients receiving elective laparoscopic and robot-assisted surgery amongst those diagnosed with colorectal cancer over 3 time periods (2007-2011, 2012-2016 and 2017-2021) in hospitals participating in the Yorkshire Cancer Research Bowel Cancer Improvement Programme (YCR BCIP). These were benchmarked against national rates. Regression analysis and funnel plots were used to develop a data driven approach for analysing trends in the use of MIS at hospitals in the programme.

Results

In England, resections performed by MIS increased from 34.9% to 72.9% for colon cancer and from 28.8% to 72.5% for rectal cancer. Robot-assisted surgery increased from 0.1% to 2.7% for colon cancer and from 0.2% to 7.9% for rectal cancer. Wide variation in the uptake of MIS was observed at a hospital level. Detailed analysis of the YCR BCIP region identified a decreasing number of surgical departments, since the start of the programme, as potential outliers for MIS when compared to the English national average.

Conclusion

Wide variation in use of MIS for colorectal cancer exists within the English National Health Service and a data-driven approach can help identify outlying hospitals. Addressing some of the challenges behind the uptake of MIS, such as ensuring adequate provision of surgical training and equipment, could help increase its use.

在不同国家和国家内部，结直肠癌患者接受微创手术（MIS）的进度各不相同。本研究旨在调查英格兰地区结直肠癌改善计划的接受率。我们计算了参与约克郡癌症研究肠癌改善计划（YCR BCIP）的医院在三个时间段（2007-2011 年、2012-2016 年和 2017-2021 年）内确诊为结直肠癌的患者中接受选择性腹腔镜手术和机器人辅助手术的比例。这些数据以全国比率为基准。利用回归分析和漏斗图开发出一种数据驱动型方法，用于分析参与计划的医院使用 MIS 的趋势。在英格兰，结肠癌的 MIS 切除率从 34.9% 增加到 72.9%，直肠癌的 MIS 切除率从 28.8% 增加到 72.5%。结肠癌的机器人辅助手术从0.1%增加到2.7%，直肠癌的机器人辅助手术从0.2%增加到7.9%。在医院层面，MIS的使用率差异很大。对YCR BCIP地区进行的详细分析发现，与英国全国平均水平相比，自该计划启动以来，作为MIS潜在异常值的外科部门数量不断减少。在英国国家医疗服务机构中，结直肠癌 MIS 的使用情况存在很大差异，而数据驱动方法可以帮助确定离群医院。解决 MIS 使用率背后的一些挑战，如确保提供充足的手术培训和设备，将有助于提高其使用率。

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引用次数: 0

A Comparison of Cellular Immune Response and Immunological Biomarkers in Laparoscopic Surgery for Colorectal Cancer and Benign Disorders 腹腔镜手术治疗结直肠癌和良性疾病时细胞免疫反应和免疫生物标志物的比较

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-06-18 DOI: 10.1016/j.clcc.2024.05.012

Line Nederby , Natacha Dencker Trabjerg , Anja Bjørnskov Andersen , Jan Lindebjerg , Torben Frøstrup Hansen , Hans Bjarke Rahr

Background

Surgical trauma causes immune impairment, but it is largely unknown whether surgery for cancer and benign diseases instigate comparable levels of immune inhibition. Here, we compared the impact of laparoscopic surgery on immunological biomarkers in patients with colorectal cancer (CRC) and ventral hernia (VH).

Methods

Natural Killer cell activity (NKA), leukocyte subsets, and soluble programmed death ligand 1 (sPD-L1) were measured in blood samples collected from CRC (n = 29) and VH (n = 9) patients preoperatively (PREOP) and on postoperative day (POD) 1, 3-6, 2 weeks and 3 months. NKA was evaluated by the NK Vue assay that uses the level of IFNγ as a surrogate marker of NKA. Normal NKA was defined as IFNγ > 250 pg/mL and low NKA was defined as IFNγ < 250 pg/mL.

Results

The CRC cohort was classified into either PREOP_LOW having preoperative low NKA or PREOP_HIGH having preoperative normal NKA. The median NKA of the PREOP_LOW subset was only in the normal range in the POD3 months sample, whereas median NKA of the PREOP_HIGH subset and the VH cohort were only low in the POD1 sample. While PREOP_LOW differed from VH in the PREOP-, POD1-, and POD3-6 samples (P =.0006, P = .0181, and P = .0021), NKA in PREOP_HIGH and VH differed in the POD1 samples (P = .0226). There were no apparent differences in the distribution of leukocyte subsets in the perioperative period between the cohorts.

Conclusion

CRC patients with preoperative normal NKA and VH patients showed the same pattern of recovery in NKA, while the CRC subset with preoperative low NKA seemed to experience prolonged NK cell impairment. As low NKA is associated with recurrence, preoperative level of NKA may identify patients who will benefit from immune-enhancing therapy in the perioperative period.

手术创伤会导致免疫功能受损，但癌症手术和良性疾病手术是否会引起同等程度的免疫抑制，目前还不得而知。在这里，我们比较了腹腔镜手术对结直肠癌（CRC）和腹股沟疝（VH）患者免疫生物标志物的影响。我们在 CRC（29 人）和 VH（9 人）患者术前（PREOP）和术后第 1 天、第 3-6 天、第 2 周和第 3 个月采集的血液样本中测量了自然杀伤细胞活性（NKA）、白细胞亚群和可溶性程序性死亡配体 1（sPD-L1）。NKA 通过 NK Vue 检测法进行评估，该检测法使用 IFNγ 水平作为 NKA 的替代标记物。正常 NKA 的定义是 IFNγ > 250 pg/mL，低 NKA 的定义是 IFNγ < 250 pg/mL。CRC 组群被分为术前 NKA 偏低的 PREOP 和术前 NKA 正常的 PREOP。PREOP 子群的 NKA 中位数仅在 POD3 个月样本中处于正常范围，而 PREOP 子群和 VH 队列的 NKA 中位数仅在 POD1 样本中偏低。在 PREOP-、POD1- 和 POD3-6 样本中，PREOP 与 VH 存在差异（=.0006、=.0181 和 =.0021），而在 POD1 样本中，PREOP 和 VH 的 NKA 存在差异（=.0226）。两组患者围手术期的白细胞亚群分布无明显差异。术前 NKA 正常的 CRC 患者和 VH 患者的 NKA 恢复模式相同，而术前 NKA 偏低的 CRC 亚群似乎经历了长时间的 NK 细胞损伤。由于低 NKA 与复发有关，因此术前 NKA 水平可确定哪些患者将在围手术期受益于免疫增强疗法。

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