Clinical colorectal cancer最新文献_第3页

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。

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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.

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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。

{"title":"Minimally Invasive Surgery for Colorectal Cancer: Benchmarking Uptake for a Regional Improvement Programme","authors":"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","doi":"10.1016/j.clcc.2024.05.013","DOIUrl":"10.1016/j.clcc.2024.05.013","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Method</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 382-391.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141574540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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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引用次数: 0

Effects of Adjuvant Chemotherapy on Oncologic Outcomes in Patients With Stage ⅡA Rectal Cancer Above the Peritoneal Reflection Who Did Not Undergo Preoperative Chemoradiotherapy 辅助化疗对未接受术前放化疗的腹膜反光以上ⅡA期直肠癌患者肿瘤预后的影响

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-06-18 DOI: 10.1016/j.clcc.2024.05.011

Hyo Seon Ryu , Jong Lyul Lee , Chan Wook Kim , Yong Sik Yoon , In Ja Park , Seok-Byung Lim , Yong Sang Hong , Tae Won Kim , Chang Sik Yu

Purpose

This study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper rectal cancer and to investigate whether AC is associated with improved survival outcomes.

Methods

This retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative chemoradiotherapy between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, perineural invasion, resection margin involvement, and < 12 lymph nodes harvested.

Results

Among the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs. 84.6%, P = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs. 64.1%, P = .01) and 5-year OS (88.8% vs. 69.0%, P = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged > 65 years.

Conclusion

AC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors.

本研究旨在评估辅助化疗（AC）对IIA期上段直肠癌患者肿瘤预后的影响，并探讨辅助化疗是否与生存预后的改善相关。这项回顾性研究纳入了2008年至2016年期间接受根治性切除术但未进行术前化疗的432例腹膜反射以上直肠癌患者。该研究队列根据是否接受化疗（化疗组）进行了划分（无化疗组）。风险因素包括梗阻、穿孔、肿瘤分化差、淋巴管侵犯、神经周围侵犯、切除边缘受累以及摘除的淋巴结少于12个。在432名患者中，279人（64.6%）接受了前列腺癌根治术。接受 AC 治疗组的 5 年总生存率（OS）明显高于未接受 AC 治疗组（93.2% vs 84.6%，=0.001）。在风险因素≥1的患者中，AC组（n = 123）的5年无复发生存率（RFS）（81.6% vs 64.1%，= .01）和5年OS（88.8% vs 69.0%，= .001）明显高于无AC组（n = 59）。在年龄大于 65 岁的患者中，两组的生存结果无明显差异。对于未接受术前放化疗的腹膜反射以上的IIA期直肠癌患者，尤其是危险因素≥1的患者，AC与更好的5年RFS和5年OS率明显相关。

{"title":"Effects of Adjuvant Chemotherapy on Oncologic Outcomes in Patients With Stage ⅡA Rectal Cancer Above the Peritoneal Reflection Who Did Not Undergo Preoperative Chemoradiotherapy","authors":"Hyo Seon Ryu , Jong Lyul Lee , Chan Wook Kim , Yong Sik Yoon , In Ja Park , Seok-Byung Lim , Yong Sang Hong , Tae Won Kim , Chang Sik Yu","doi":"10.1016/j.clcc.2024.05.011","DOIUrl":"10.1016/j.clcc.2024.05.011","url":null,"abstract":"<div><h3>Purpose</h3><div><span>This study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper </span>rectal cancer and to investigate whether AC is associated with improved survival outcomes.</div></div><div><h3>Methods</h3><div><span>This retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative </span>chemoradiotherapy<span><span> between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, </span>perineural invasion, resection margin involvement, and < 12 lymph nodes harvested.</span></div></div><div><h3>Results</h3><div><span>Among the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs</span><em>.</em> 84.6%, <em>P</em> = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs<em>.</em> 64.1%, <em>P</em> = .01) and 5-year OS (88.8% vs<em>.</em> 69.0%, <em>P</em> = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged > 65 years.</div></div><div><h3>Conclusion</h3><div>AC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 392-401"},"PeriodicalIF":3.3,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141574541","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

Chemotherapy Rechallenge or Reintroduction Compared to Regorafenib or Trifluridine/Tipiracil for Pretreated Metastatic Colorectal Cancer Patients: A Propensity Score Analysis of Treatment Beyond Second Line (Proserpyna Study) 化疗再挑战或再引入与瑞戈非尼或曲氟尿苷/替吡拉西钠治疗预处理转移性结直肠癌患者的比较：二线治疗后疗效的密度扫描分析（PROSERpYNa 研究）

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-06-12 DOI: 10.1016/j.clcc.2024.06.002

M.A. Calegari , I.V. Zurlo , E. Dell'Aquila , M. Basso , A. Orlandi , M. Bensi , F. Camarda , A. Anghelone , C. Pozzo , I. Sperduti , L. Salvatore , D. Santini , D.C. Corsi , E. Bria , G. Tortora

Background

The optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated.

Patients and methods

PROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses.

Results

Data referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 vs. 6.5 months), PFS (6.1 vs. 3.5 months) and RR (28.6% vs. 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses.

Conclusions

Although the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity.

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引用次数: 0

Oncological Outcomes and Response Rate After Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Network Meta-Analysis Comparing Induction vs. Consolidation Chemotherapy vs. Standard Chemoradiation 局部晚期直肠癌新辅助治疗后的肿瘤预后和反应率：比较诱导化疗和巩固化疗与标准化疗放疗的网络荟萃分析

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer

Pub Date : 2024-06-11 DOI: 10.1016/j.clcc.2024.06.001

Sergei Bedrikovetski , Luke Traeger , Warren Seow , Nagendra N. Dudi-Venkata , Sudarsha Selva-Nayagam , Michael Penniment , Tarik Sammour

TNT is now considered the preferred option for stage II-III locally advanced rectal cancer (LARC). However, the prognostic benefit and optimal sequence of TNT remains unclear. This network meta-analysis (NMA) compared short- and long-term outcomes amongst patients with LARC receiving total neoadjuvant therapy (TNT) as induction (iTNT) or consolidation chemotherapy (cTNT) with those receiving neoadjuvant chemoradiation (nCRT) alone. A systematic literature search was performed between 2012 and 2023. A Bayesian NMA was conducted using a Markov Chain Monte Carlo method with a random-effects model and vague prior distribution to calculate odds ratios (OR) with 95% credible intervals (CrI). The surface under the cumulative ranking (SUCRA) curves were used to rank treatment(s) for each outcome. In total, 11 cohorts involving 8360 patients with LARC were included. There was no significant difference in disease-free survival (DFS) and overall survival (OS) amongst the 3 treatments. Compared with nCRT, both cTNT (OR 2.36; 95% CrI, 1.57-3.66) and iTNT (OR 1.99; 95% CrI, 1.44-2.95) significantly improved complete response (CR) rate. Notably, cTNT ranked as the best treatment for CR (SUCRA 0.90) and iTNT as the best treatment for 3-year DFS and OS (SUCRA 0.72 and 0.87, respectively). Both iTNT and cTNT strategies significantly improved CR rates compared with nCRT. cTNT was ranked highest for CR rates, while iTNT was ranked highest for 3-year survival outcomes. However, no other significant differences in DFS, OS, sphincter-saving surgery, R0 resection and postoperative complications were found amongst the treatment groups.

TNT目前被认为是治疗II-III期局部晚期直肠癌（LARC）的首选方案。然而，TNT的预后益处和最佳治疗顺序仍不明确。这项网络荟萃分析（NMA）比较了接受作为诱导（iTNT）或巩固化疗（cTNT）的全新辅助治疗（TNT）和单独接受新辅助化放疗（nCRT）的 LARC 患者的短期和长期预后。我们对 2012 年至 2023 年间的文献进行了系统检索。采用随机效应模型和模糊先验分布的 Markov Chain Monte Carlo 方法进行了贝叶斯 NMA，计算出带有 95% 可信区间 (CrI) 的几率比 (OR)。累积排名（SUCRA）曲线下表面用于对每种结果的治疗方法进行排名。共纳入了 11 个队列，涉及 8360 名 LARC 患者。三种治疗方法的无病生存期（DFS）和总生存期（OS）无明显差异。与 nCRT 相比，cTNT（OR 2.36；95% CrI，1.57-3.66）和 iTNT（OR 1.99；95% CrI，1.44-2.95）均显著提高了完全缓解率（CR）。值得注意的是，cTNT 是获得 CR 的最佳治疗方法（SUCRA 0.90），iTNT 是获得 3 年 DFS 和 OS 的最佳治疗方法（SUCRA 分别为 0.72 和 0.87）。与 nCRT 相比，iTNT 和 cTNT 策略都能显著提高 CR 率。cTNT 的 CR 率排名最高，而 iTNT 的 3 年生存率排名最高。不过，各治疗组在 DFS、OS、括约肌挽救手术、R0 切除术和术后并发症方面均无其他明显差异。

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