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Escalated Segmental and Modified Radiation Lobectomy Dosing for Yttrium-90 Radioembolization of Liver-Dominant Metastatic Colorectal Cancer: 10-year Outcomes 肝主导型转移性结直肠癌的放射栓塞治疗中，渐进式节段放疗和改良放射肺叶切除术剂量：10年结果。
IF 3.3 3区 医学 Q2 ONCOLOGY
Clinical colorectal cancer
Pub Date : 2025-06-01 Epub Date: 2025-02-28 DOI: 10.1016/j.clcc.2025.02.005
Andrew C Gordon , Saad Abu Zahra , Muhamad Serhal , Sheetal M Kircher , Aparna Kalyan , Kent Sato , Ahsun Riaz , Elias Hohlastos , Riad Salem , Robert J Lewandowski

Purpose

This study evaluates the safety and efficacy of escalated-dosing Yttrium-90 transarterial radioembolization (TARE) for unresectable, unablatable metastatic colorectal cancer (mCRC) to the liver.

Materials and Methods

A retrospective review (September 2009 to March 2020) included 45 patients with liver-dominant mCRC treated with segmental Y90 or modified radiation lobectomy. Patient demographics, treatment details, adverse events, imaging response, and overall survival (OS) were analyzed. OS Prognosticators were examined using log-rank test and Cox proportional hazards regression.

Results

45 patients (median age 61.4 years; 60% male) were included, with 96% ECOG 0-1. Prior treatments included primary site resection (93%), liver resection (65%), chemotherapy (60%), and ablation (27%). Extrahepatic disease was present in 51%. 71% of patients had < 25% liver tumor burden (mean tumor size = 4.8 cm). Treatment was technically successful in all cases, with 4% 30-day mortality. Adverse events were mostly low-grade, including fatigue (58%) and abdominal pain (20%). Mean neutrophil-to-lymphocyte ratio (NLR) increase was 2.9, and 33% of patients showed 50% reduction in CEA. Imaging responses (RECIST) included SD (80%), PR (18%), PD (2%), and CR (0%), with PET/CT showing 39% objective response after 4.2 months. Median OS was 41.9 months (95% CI 15.4-NE). Extrahepatic disease significantly reduced OS (15.7 vs. 44.4 months, P = .0033). Both pre- and post-NLR (HR:1.42, P = .007; HR 1.12, P = .027) were associated with worse OS. In the multivariable analysis, Pre-NLR and extrahepatic disease remained adverse prognosticators.

Conclusion

Y90 TARE with escalated dosing demonstrated an acceptable safety profile in heavily pretreated mCRC patients. Extrahepatic disease and pre-NLR were significant adverse prognosticators. Future studies should explore Y90 TARE dosing in mCRC patients.
目的：本研究评估增大剂量钇-90经动脉放射栓塞（TARE）治疗不可切除、不可治愈的肝转移性结直肠癌（mCRC）的安全性和有效性。材料和方法：一项回顾性研究（2009年9月至2020年3月）包括45例肝为主的mCRC患者，他们接受了节段性Y90或改良的放射线肺叶切除术。分析患者人口统计学、治疗细节、不良事件、影像学反应和总生存期（OS）。采用log-rank检验和Cox比例风险回归对OS预后者进行检验。结果：45例患者(中位年龄61.4岁；60%为男性)，96%为ECOG 0-1。既往治疗包括原发部位切除（93%）、肝切除（65%）、化疗（60%）和消融（27%）。肝外疾病占51%。71%的患者肝脏肿瘤负荷< 25%（平均肿瘤大小= 4.8 cm）。所有病例的治疗在技术上都是成功的，30天死亡率为4%。不良事件大多为轻度，包括疲劳（58%）和腹痛（20%）。平均中性粒细胞与淋巴细胞比值（NLR）增加2.9,33%的患者CEA降低50%。影像学反应（RECIST）包括SD（80%）、PR（18%）、PD（2%）和CR(0%)， 4.2个月后PET/CT显示39%的客观反应。中位生存期为41.9个月（95% CI 15.4-NE）。肝外疾病显著降低OS（15.7个月vs. 44.4个月，P = 0.0033）。nlr前后(HR:1.42, P = .007；HR 1.12, P = 0.027)与较差的OS相关。在多变量分析中，前nlr和肝外疾病仍然是不良预后因素。结论：递增剂量的Y90 TARE在重度预处理的mCRC患者中显示出可接受的安全性。肝外疾病和nlr前是显著的不良预后因素。未来的研究应该探索Y90 TARE在mCRC患者中的剂量。
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引用次数: 0
A Phase Two, Single-Arm, Open-Label Study With Dostarlimab Monotherapy in Participants With Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer (AZUR-1) 多斯塔利单抗单药治疗未治疗的II/III期dMMR/MSI-H局部晚期直肠癌（AZUR-1）的2期单臂开放标签研究
IF 3.3 3区 医学 Q2 ONCOLOGY
Clinical colorectal cancer
Pub Date : 2025-06-01 Epub Date: 2025-02-21 DOI: 10.1016/j.clcc.2025.02.003
Andrea Cercek , Jean-Baptiste Bachet , Jaume Capdevila , Naureen Starling , Eric Chen , Lisa Salvatore , Hideaki Bando , Sean O'Donnell , Lauren Harfst , Zsolt Szijgyarto , Volker Heinemann

Background

Colorectal cancer (CRC) had the second highest cancer mortality worldwide in 2020; nearly a third of CRCs were rectal cancers (RC). A recent study demonstrated that dostarlimab, an immune-checkpoint inhibitor, was highly effective in treating mismatch repair deficient (dMMR) locally advanced RC as all included patients had a clinical complete response (cCR) without radiation or chemotherapy. This study's objective is to evaluate the efficacy and safety of dostarlimab monotherapy in patients with previously untreated locally advanced dMMR RC.

Patients/Methods

AZUR-1 (NCT05723562) is a multicenter, open-label, nonrandomized, single-arm phase 2 study enrolling approximately 150 patients across 10 countries. Key eligibility criteria include dMMR status or microsatellite instability-high (MSI-H) phenotype. Dostarlimab 500 mg will be administered intravenously every 3 weeks for 9 cycles. The primary endpoint is cCR by independent central review (ICR) at 12 months. Key secondary endpoints include cCR by ICR at 24 and 36 months, and 3-year event-free survival by investigator assessment. Additional secondary endpoints include organ preservation rate at 3 years and disease-specific survival and overall survival at 5 years. Efficacy and safety will be assessed in all patients who receive ≥1 dose of dostarlimab. All patients will be followed for 5 years (unless consent is withdrawn).

Conclusions

AZUR-1 will evaluate the efficacy of dostarlimab immunotherapy in dMMR/MSI-H RC. Utilizing novel aspects including long follow-up of all patients and standardization of clinical response assessment, this study will provide international multicentric data to evaluate tumor response in an immunotherapy setting and new evidence on long-term outcomes.
背景：2020年，结直肠癌（CRC）是全球第二高的癌症死亡率；近三分之一的crc是直肠癌（RC）。最近的一项研究表明，dostarlimab是一种免疫检查点抑制剂，对于治疗局部晚期RC （dMMR）非常有效，因为所有纳入的患者在没有放疗或化疗的情况下都有临床完全缓解（cCR）。本研究的目的是评估多司达单抗单药治疗先前未治疗的局部晚期dMMR RC患者的疗效和安全性。患者/方法：AZUR-1 （NCT05723562）是一项多中心、开放标签、非随机、单臂2期研究，在10个国家招募了约150名患者。关键资格标准包括dMMR状态或微卫星不稳定性高（MSI-H）表型。Dostarlimab 500mg每3周静脉给药，共9个周期。主要终点是12个月时独立中心审查（ICR）的cCR。关键次要终点包括24个月和36个月ICR的cCR，以及研究者评估的3年无事件生存期。其他次要终点包括3年的器官保存率、5年的疾病特异性生存和总生存。将对所有接受≥1剂量dostarlimab的患者的疗效和安全性进行评估。所有患者将被随访5年（除非撤回同意）。结论：AZUR-1将评估多斯塔利单抗免疫治疗dMMR/MSI-H RC的疗效。利用新颖的方面，包括所有患者的长期随访和临床反应评估的标准化，本研究将提供国际多中心数据来评估免疫治疗环境下的肿瘤反应，并为长期结果提供新的证据。
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引用次数: 0
The Impact of a Multidisciplinary Tumor Board (MDTB) in the Management of Colorectal Cancer (CRC) 多学科肿瘤委员会（MDTB）在结直肠癌（CRC）管理中的影响。
IF 3.3 3区 医学 Q2 ONCOLOGY
Clinical colorectal cancer
Pub Date : 2025-06-01 Epub Date: 2025-01-10 DOI: 10.1016/j.clcc.2025.01.002
Francesco Schietroma , Maria Bensi , Maria Alessandra Calegari , Carmelo Pozzo , Michele Basso , Giustina Valente , Giulia Caira , Giovanni Trovato , Alexia Spring , Viria Beccia , Anna Ceccarelli , Serena Perazzo , Laura Chiofalo , Brunella Barbaro , Giulia Tatulli , Sergio Alfieri , Davide De Sio , Laura Lorenzon , Roberto Persiani , Filippo Lococo , Lisa Salvatore

Background

The management of colorectal cancer (CRC) is a complex process. Defining the disease burden, assessing the radiological response and identifying the right time for surgery or other locoregional treatments are crucial factors which can require the involvement of a multidisciplinary tumor board (MDTB) comprising several specialists. This study investigates the impact of MDTB on management of CRC in our institution.

Methods

We retrospectively assessed all cases discussed by our MDTB between September 2019 and April 2023. In particular, we collected data concerning radiology, surgery and radiotherapy indication before and after MDTB meetings. The primary endpoint was the overall rate of discrepancy between pre- and post-discussion evaluations.

Results

Our analysis involved 1150 cases. Median age was 64 years (16-90), 629 patients (54.7%) were male and 915 (79.5%) had metastatic disease at the time of the relevant MDTB discussion. After the meetings, 325 treatment decisions were modified, producing an overall discrepancy rate of 28.3%. In particular: (1) of 648 cases discussed for radiological assessment, 156 decisions (24.1%) were altered after a central imaging review; (2) of 327 cases considered for surgical approach, treatment strategy changed in 118 (36.1%); and (3) of the 160 cases discussed regarding radiotherapy, the treatment strategy changed in 51 of them (31.9%).

Conclusions

Our analysis shows significant discrepancies between the radiology and locoregional evaluations from both before and after the MDTB meetings. Our results highlight that the discussions of a MDTB can considerably change the management of CRC, maximizing the treatment strategy.
背景：结直肠癌（CRC）的治疗是一个复杂的过程。确定疾病负担、评估放射反应和确定手术或其他局部治疗的合适时间是关键因素，可能需要由几位专家组成的多学科肿瘤委员会（MDTB）的参与。本研究探讨耐多药结核对我院结直肠癌管理的影响。方法：我们回顾性评估了2019年9月至2023年4月期间MDTB讨论的所有病例。特别是，我们收集了MDTB会议前后有关放射学、手术和放疗指征的数据。主要终点是讨论前后评估之间的总体差异率。结果：我们分析了1150例病例。中位年龄为64岁（16-90岁），629例（54.7%）为男性，915例（79.5%）在相关的MDTB讨论时已经转移。会议结束后，325项治疗决定被修改，总体差异率为28.3%。特别是：(1)在648例放射学评估病例中，156例（24.1%）在中央影像学检查后改变了决定；(2)在327例考虑手术入路的患者中，改变治疗策略的118例（36.1%）；(3)在讨论的160例放疗病例中，有51例（31.9%）改变了治疗策略。结论：我们的分析显示，在MDTB会议前后的放射学和局部区域评估之间存在显著差异。我们的研究结果强调，讨论耐多药结核可以显著改变结直肠癌的管理，最大限度地提高治疗策略。
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引用次数: 0
AGITG MONARCC: A Randomized Phase 2 Study of Panitumumab Monotherapy and Panitumumab Plus 5-Fluorouracil as First-Line Therapy for Older Patients With RAS and BRAF Wild Type Metastatic Colorectal Cancer. A Study by the Australasian Gastro-Intestinal Trials Group (AGITG) AGITG MONARCC：帕尼单抗单药和帕尼单抗加5-氟尿嘧啶作为RAS和BRAF野生型转移性结直肠癌老年患者一线治疗的随机2期研究澳大利亚胃肠试验组（AGITG）的研究。
IF 3.3 3区 医学 Q2 ONCOLOGY
Clinical colorectal cancer
Pub Date : 2025-06-01 Epub Date: 2024-12-12 DOI: 10.1016/j.clcc.2024.11.003
Matthew E. Burge , David Espinoza , Katrin Marie Sjoquist , Derrick Ho Siu , Rebecca Mercieca-Bebber , Lorraine A. Chantrill , Christos Stelios Karapetis , Christopher B. Steer , Sonia Yip , Jeff Cuff , Stephanie Winata , Jeanne Tie , Darshit Arunbhai Thaker , Ratnesh Srivastav , Ehtesham Abdi , Andrew Strickland , Eva Segelov , Alessandra Francesconi , Timothy Price , Rahul Ladwa , Niall C. Tebbutt

Background

Panitumumab (pan) plus chemotherapy is a preferred first-line therapy for unresectable RAS and BRAF wild type metastatic colorectal cancer (mCRC). Older patients may not be suitable for combination regimens. We investigated 2 lower intensity pan-containing regimens.

Methods

Prospective, noncomparative, randomized (1:1) phase 2 study of pan alone (Arm A) or pan plus FU (Arm B). Previously untreated mCRC were ≥70 years; RAS/BRAF wild type. Primary endpoint: 6-month progression-free survival (PFS). Secondary endpoints included: overall survival (OS), response rate (RR), feasibility of geriatric assessments and overall treatment utility (OTU)—a composite measure based on radiological response, clinical progress, toxicity and patient-reported treatment worth. Planned sample size was 40 patients per arm.

Results

36 patients (Arm A n = 19, Arm B n = 17) were randomized between June 2018 and June 2021. Median age was 79 and 80 years respectively. 6-month PFS 63% (95% CI 38%-80%) arm A 82% (95%CI 55%-94%) Arm B. Median OS 21 months Arm A (95%CI 13-31) 28 (95%CI 14-39) months Arm B. RR 47% and 65% Arms A and B respectively. Baseline comprehensive geriatric assessments were completed in >80% of patients. At week 16, OTU was categorized as good in 92% (Arm A) and 90% (Arm B). No unexpected adverse events were seen.

Conclusions

Six-month PFS in both arms was consistent with that achieved with FU/bev, whilst the rate was numerically higher for Arm B. Baseline comprehensive geriatric assessments were feasible and OTU was high. Both treatment arms might be suitable in appropriately selected patients.
背景：帕尼珠单抗（Panitumumab, pan）联合化疗是不可切除的RAS和BRAF野生型转移性结直肠癌（mCRC）的首选一线治疗方法。老年患者可能不适合联合用药。我们研究了2种低强度的泛含方案。方法：前瞻性，非比较，随机（1:1）2期研究，pan单独（A组）或pan加FU （B组）。先前未治疗的mCRC≥70年；RAS/BRAF野生型。主要终点：6个月无进展生存（PFS）。次要终点包括：总生存期（OS）、缓解率（RR）、老年评估的可行性和总治疗效用（OTU）——一种基于放射反应、临床进展、毒性和患者报告的治疗价值的综合指标。计划样本量为每组40例患者。结果：在2018年6月至2021年6月期间，36例患者（A组n = 19， B组n = 17）被随机分组。中位年龄分别为79岁和80岁。6个月PFS 63% (95%CI 38%-80%) A组82% (95%CI 55%-94%) B组中位OS 21个月A组（95%CI 13-31） 28个月（95%CI 14-39） B组RR分别为47%和65% A组和B组。80%的患者完成了基线综合老年评估。在第16周，92% （A组）和90% （B组）的OTU被归类为良好。未见意外不良事件。结论：两个组的6个月PFS与FU/bev组一致，而b组的比率更高。基线综合老年评估是可行的，OTU很高。两种治疗方法可能都适用于适当选择的患者。
{"title":"AGITG MONARCC: A Randomized Phase 2 Study of Panitumumab Monotherapy and Panitumumab Plus 5-Fluorouracil as First-Line Therapy for Older Patients With RAS and BRAF Wild Type Metastatic Colorectal Cancer. A Study by the Australasian Gastro-Intestinal Trials Group (AGITG)","authors":"Matthew E. Burge ,&nbsp;David Espinoza ,&nbsp;Katrin Marie Sjoquist ,&nbsp;Derrick Ho Siu ,&nbsp;Rebecca Mercieca-Bebber ,&nbsp;Lorraine A. Chantrill ,&nbsp;Christos Stelios Karapetis ,&nbsp;Christopher B. Steer ,&nbsp;Sonia Yip ,&nbsp;Jeff Cuff ,&nbsp;Stephanie Winata ,&nbsp;Jeanne Tie ,&nbsp;Darshit Arunbhai Thaker ,&nbsp;Ratnesh Srivastav ,&nbsp;Ehtesham Abdi ,&nbsp;Andrew Strickland ,&nbsp;Eva Segelov ,&nbsp;Alessandra Francesconi ,&nbsp;Timothy Price ,&nbsp;Rahul Ladwa ,&nbsp;Niall C. Tebbutt","doi":"10.1016/j.clcc.2024.11.003","DOIUrl":"10.1016/j.clcc.2024.11.003","url":null,"abstract":"<div><h3>Background</h3><div>Panitumumab (pan) plus chemotherapy is a preferred first-line therapy for unresectable RAS and BRAF wild type metastatic colorectal cancer (mCRC). Older patients may not be suitable for combination regimens. We investigated 2 lower intensity pan-containing regimens.</div></div><div><h3>Methods</h3><div>Prospective, noncomparative, randomized (1:1) phase 2 study of pan alone (Arm A) or pan plus FU (Arm B). Previously untreated mCRC were ≥70 years; RAS/BRAF wild type. Primary endpoint: 6-month progression-free survival (PFS). Secondary endpoints included: overall survival (OS), response rate (RR), feasibility of geriatric assessments and overall treatment utility (OTU)—a composite measure based on radiological response, clinical progress, toxicity and patient-reported treatment worth. Planned sample size was 40 patients per arm.</div></div><div><h3>Results</h3><div>36 patients (Arm A n <em>=</em> 19, Arm B n <em>=</em> 17) were randomized between June 2018 and June 2021. Median age was 79 and 80 years respectively. 6-month PFS 63% (95% CI 38%-80%) arm A 82% (95%CI 55%-94%) Arm B. Median OS 21 months Arm A (95%CI 13-31) 28 (95%CI 14-39) months Arm B. RR 47% and 65% Arms A and B respectively. Baseline comprehensive geriatric assessments were completed in &gt;80% of patients. At week 16, OTU was categorized as good in 92% (Arm A) and 90% (Arm B). No unexpected adverse events were seen.</div></div><div><h3>Conclusions</h3><div>Six-month PFS in both arms was consistent with that achieved with FU/bev, whilst the rate was numerically higher for Arm B. Baseline comprehensive geriatric assessments were feasible and OTU was high. Both treatment arms might be suitable in appropriately selected patients.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 2","pages":"Pages 120-128"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960182","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 Upfront DPYD Genotyping on Fluoropyrimidine Adjuvant Therapy in Colorectal Cancer: A Real-World Data 前期DPYD基因分型对结直肠癌氟嘧啶辅助治疗的影响：真实世界数据
IF 3.3 3区 医学 Q2 ONCOLOGY
Clinical colorectal cancer
Pub Date : 2025-06-01 Epub Date: 2025-02-04 DOI: 10.1016/j.clcc.2025.02.001
Jatta Saarenheimo , Hugo Willför , Nesna Wahid , Antti Jekunen , Heidi Andersén

Background

The application of fluoropyrimidine-based chemotherapy in colorectal cancer treatment is known to pose significant toxicity risks, which can be mitigated by tailoring treatment according to DPYD gene variants. This study evaluates the impact of DPYD genotype-guided dosing on treatment-related toxicities and patient outcomes.

Methods

A retrospective analysis was conducted on CRC patients treated with fluoropyrimidines in adjuvant setting at The Wellbeing Services County of Ostrobothnia. Patients were divided into two cohorts based on the implementation of routine DPYD genotyping: pregenotyping (2016-2018) (n = 80) and postgenotyping (2020-2022) (n = 69). The incidence of side effects, treatment discontinuation, hospitalization, and 90-day mortality were compared between groups.

Results

The study revealed a reduction in 90-day mortality rates among patients who underwent DPYD genotyping before treatment. Patients with pathogenic DPYD variants received ≥50% reduced doses initially, leading to no severe toxicities (grade ≥3). Class 3 variants showed similar side effect profiles and hospitalization rates as untested patients but had a lower rate of treatment discontinuation.

Conclusions

Upfront DPYD genotyping appears to improve patient safety in CRC patients treated with adjuvant fluoropyrimidines, leading to personalized dosing that reduces severe toxicities and early mortality. These findings underscore the importance of integrating pharmacogenetic testing in clinical oncology to optimize treatment regimens and enhance patient care.
背景：以氟嘧啶为基础的化疗在结直肠癌治疗中的应用具有明显的毒性风险，可以根据DPYD基因变异进行定制治疗来减轻毒性风险。本研究评估了DPYD基因型指导给药对治疗相关毒性和患者预后的影响。方法：回顾性分析在促进健康服务县接受氟嘧啶辅助治疗的结直肠癌患者。根据DPYD常规基因分型的实施，将患者分为两组：基因前分型（2016-2018）（n = 80）和基因后分型（2020-2022）（n = 69）。比较两组的副作用发生率、停药率、住院率和90天死亡率。结果：该研究显示，治疗前接受DPYD基因分型的患者90天死亡率降低。致病性DPYD变体患者最初接受≥50%的剂量减少，导致没有严重毒性（等级≥3）。3类变体显示出与未测试患者相似的副作用概况和住院率，但停药率较低。结论：前期DPYD基因分型似乎提高了接受辅助氟嘧啶治疗的结直肠癌患者的安全性，导致个性化给药，减少严重毒性和早期死亡率。这些发现强调了在临床肿瘤学中整合药物遗传学检测以优化治疗方案和加强患者护理的重要性。
{"title":"Impact of Upfront DPYD Genotyping on Fluoropyrimidine Adjuvant Therapy in Colorectal Cancer: A Real-World Data","authors":"Jatta Saarenheimo ,&nbsp;Hugo Willför ,&nbsp;Nesna Wahid ,&nbsp;Antti Jekunen ,&nbsp;Heidi Andersén","doi":"10.1016/j.clcc.2025.02.001","DOIUrl":"10.1016/j.clcc.2025.02.001","url":null,"abstract":"<div><h3>Background</h3><div>The application of fluoropyrimidine-based chemotherapy in colorectal cancer treatment is known to pose significant toxicity risks, which can be mitigated by tailoring treatment according to <em>DPYD</em> gene variants. This study evaluates the impact of <em>DPYD</em> genotype-guided dosing on treatment-related toxicities and patient outcomes.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on CRC patients treated with fluoropyrimidines in adjuvant setting at The Wellbeing Services County of Ostrobothnia. Patients were divided into two cohorts based on the implementation of routine <em>DPYD</em> genotyping: pregenotyping (2016-2018) (<em>n</em> = 80) and postgenotyping (2020-2022) (<em>n</em> = 69). The incidence of side effects, treatment discontinuation, hospitalization, and 90-day mortality were compared between groups.</div></div><div><h3>Results</h3><div>The study revealed a reduction in 90-day mortality rates among patients who underwent <em>DPYD</em> genotyping before treatment. Patients with pathogenic <em>DPYD</em> variants received ≥50% reduced doses initially, leading to no severe toxicities (grade ≥3). Class 3 variants showed similar side effect profiles and hospitalization rates as untested patients but had a lower rate of treatment discontinuation.</div></div><div><h3>Conclusions</h3><div>Upfront <em>DPYD</em> genotyping appears to improve patient safety in CRC patients treated with adjuvant fluoropyrimidines, leading to personalized dosing that reduces severe toxicities and early mortality. These findings underscore the importance of integrating pharmacogenetic testing in clinical oncology to optimize treatment regimens and enhance patient care.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 2","pages":"Pages 264-271"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506603","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
Association Between Colorectal Cancer Primary Features and Liver Metastases Histological Growth Patterns: Inflammation on the Primary Tumor is Associated with Desmoplastic Growth Pattern 结直肠癌原发特征与肝转移组织学生长模式的关系：原发肿瘤的炎症与结缔组织增生生长模式相关。
IF 3.3 3区 医学 Q2 ONCOLOGY
Clinical colorectal cancer
Pub Date : 2025-06-01 Epub Date: 2025-02-07 DOI: 10.1016/j.clcc.2025.01.004
Ana Margarida Abrantes , Rui Caetano-Oliveira , Bárbara Oliveiros , Maria Augusta Cipriano , José Guilherme Tralhão

Background

More than 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastases (CRCLM), which is the main cause of death for more than 60% of these patients. The aim of this study was to correlate the clinical and pathological characteristics of the primary CRC and CRCLM, with emphasis in predicting the histological growth pattern of the CRCLM.

Methods

Cohort of 73 patients with CRC. Analysis of clinical data and blinded pathological review was performed related with primary tumor and CRCLM features. The analysis was performed in SPSS (version 27) with a significance level of 5%.

Results

A statistically significant association was found between tumor size and metastasis growth pattern (P = .002), with larger tumors giving rise to metastases with a nondesmoplastic growth pattern. Lymphovascular invasion (LVI) was associated with metachronous CRCLM (P = .043). In the absence of LVI, the time required for CRCLM to appear was significantly longer (P = .011). The number of metastases was significantly higher (P = .049) in tumors without LVI when compared to tumors with LVI. There was a statistically significant association between CRC high-grade inflammation and the desmoplastic metastases growth pattern of the CRCLM (P = .017).

Conclusion

The possibility of predicting the CRCLM histological growth pattern resorting to primary CRC characteristics would be useful for proper patient selection for surgery and adapting biological therapies.
背景：超过50%的结直肠癌（CRC）患者会发展为肝转移（CRCLM），这是超过60%的结直肠癌患者死亡的主要原因。本研究的目的是将原发性结直肠癌和CRCLM的临床和病理特征联系起来，重点是预测CRCLM的组织学生长模式。方法：对73例结直肠癌患者进行队列研究。对原发肿瘤及CRCLM特征进行临床资料分析及病理盲法检查。采用SPSS （version 27）进行分析，显著性水平为5%。结果：在肿瘤大小和转移生长模式之间发现了统计学上显著的关联（P = 0.002），更大的肿瘤引起转移，而非结缔组织增生模式。淋巴血管侵袭（LVI）与异时性CRCLM相关（P = 0.043）。在没有LVI的情况下，CRCLM出现所需的时间明显更长（P = 0.011）。与有LVI的肿瘤相比，无LVI的肿瘤转移数量显著增加（P = 0.049）。CRC高级别炎症与CRCLM的结缔组织增生转移生长模式有统计学意义（P = 0.017）。结论：根据原发性结直肠癌的特征来预测CRCLM的组织学生长模式，将有助于正确选择患者的手术和适应生物治疗。
{"title":"Association Between Colorectal Cancer Primary Features and Liver Metastases Histological Growth Patterns: Inflammation on the Primary Tumor is Associated with Desmoplastic Growth Pattern","authors":"Ana Margarida Abrantes ,&nbsp;Rui Caetano-Oliveira ,&nbsp;Bárbara Oliveiros ,&nbsp;Maria Augusta Cipriano ,&nbsp;José Guilherme Tralhão","doi":"10.1016/j.clcc.2025.01.004","DOIUrl":"10.1016/j.clcc.2025.01.004","url":null,"abstract":"<div><h3>Background</h3><div>More than 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastases (CRCLM), which is the main cause of death for more than 60% of these patients. The aim of this study was to correlate the clinical and pathological characteristics of the primary CRC and CRCLM, with emphasis in predicting the histological growth pattern of the CRCLM.</div></div><div><h3>Methods</h3><div>Cohort of 73 patients with CRC. Analysis of clinical data and blinded pathological review was performed related with primary tumor and CRCLM features. The analysis was performed in SPSS (version 27) with a significance level of 5%.</div></div><div><h3>Results</h3><div>A statistically significant association was found between tumor size and metastasis growth pattern (<em>P</em> = .002), with larger tumors giving rise to metastases with a nondesmoplastic growth pattern. Lymphovascular invasion (LVI) was associated with metachronous CRCLM (<em>P</em> = .043). In the absence of LVI, the time required for CRCLM to appear was significantly longer (<em>P</em> = .011). The number of metastases was significantly higher (<em>P</em> = .049) in tumors without LVI when compared to tumors with LVI. There was a statistically significant association between CRC high-grade inflammation and the desmoplastic metastases growth pattern of the CRCLM (<em>P</em> = .017).</div></div><div><h3>Conclusion</h3><div>The possibility of predicting the CRCLM histological growth pattern resorting to primary CRC characteristics would be useful for proper patient selection for surgery and adapting biological therapies.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 2","pages":"Pages 239-247"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532242","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
Multidisciplinary Team Meeting Significantly Enhances Disease-Free Survival in Stage II-III Rectal Cancer 多学科团队会议显著提高II-III期直肠癌的无病生存率。
IF 3.3 3区 医学 Q2 ONCOLOGY
Clinical colorectal cancer
Pub Date : 2025-06-01 Epub Date: 2024-12-28 DOI: 10.1016/j.clcc.2024.12.006
Wenheng Jiang , Xue Dou , Nan Zhang , Jinming Yu , Lei Zhao , Jinbo Yue

Background

Multidisciplinary team (MDT) meetings have been increasingly recognized for enhancing cancer treatment outcomes; however, their specific impact on stage II-III rectal cancer remains to be fully elucidated.

Materials and Methods

This retrospective cohort study investigated the influence of MDT meeting on disease-free survival (DFS) and overall survival (OS) in patients with stage II-III rectal cancer. Propensity score matching (PSM) was used to minimize selection bias. Kaplan-Meier survival analysis and Cox proportional hazards models were used to compare DFS and OS between groups.

Results

A total of 502 patients were included, with 176 whose cases were discussed in MDT meetings and 326 who did not undergo MDT discussions. After PSM, 173 patients were matched in each group. The MDT group exhibited a significantly improved DFS compared to the non-MDT group, both before PSM (HR = 0.618, P = .037) and after PSM (HR = 0.545, P = .012). Subgroup analysis indicated notable benefits of MDT discussions for patients with T3 to 4 tumors, low to mid tumor locations, and node-positive tumors. While there was a trend towards improved OS in the MDT group, this did not reach statistical significance. More MDT group patients received MRI staging and neoadjuvant therapy compared to non-MDT group.

Conclusions

Discussion in MDT meetings is associated with improved DFS in stage II-III rectal cancer, particularly among patients with locally advanced, low to mid rectal cancer. These findings underscore the importance of incorporating MDT discussions into routine clinical practice to optimize outcomes for rectal cancer patients.
背景：多学科团队（MDT）会议在提高癌症治疗效果方面越来越得到认可；然而，它们对II-III期直肠癌的具体影响仍有待充分阐明。材料与方法：本回顾性队列研究探讨了MDT治疗对II-III期直肠癌患者无病生存期（DFS）和总生存期（OS）的影响。倾向评分匹配（PSM）用于最小化选择偏差。采用Kaplan-Meier生存分析和Cox比例风险模型比较各组间的DFS和OS。结果：共纳入502例患者，其中176例在MDT会议上讨论，326例未进行MDT讨论。经PSM后，每组配对173例。与非MDT组相比，MDT组在PSM前（HR = 0.618, P = 0.037）和PSM后（HR = 0.545, P = 0.012）均表现出显著改善的DFS。亚组分析显示，对于T3至4期肿瘤、低至中位肿瘤和淋巴结阳性肿瘤患者，MDT讨论有显著的益处。虽然MDT组有改善OS的趋势，但没有达到统计学意义。与非MDT组相比，MDT组接受MRI分期和新辅助治疗的患者较多。结论：MDT会议上的讨论与II-III期直肠癌的DFS改善有关，特别是在局部晚期、低至中期直肠癌患者中。这些发现强调了将MDT讨论纳入常规临床实践以优化直肠癌患者预后的重要性。
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引用次数: 0
Does Extramural Vascular Invasion Predict Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer? 外血管侵袭能预测局部晚期直肠癌新辅助治疗的疗效吗？
IF 3.3 3区 医学 Q2 ONCOLOGY
Clinical colorectal cancer
Pub Date : 2025-06-01 Epub Date: 2025-02-07 DOI: 10.1016/j.clcc.2025.02.002
Neal Bhutiani , Mahmoud MG Yousef , Abdelrahman MG Yousef , Emaan U. Haque , George J. Chang , Tsuyoshi Konishi , Brian K. Bednarski , Y. Nancy You , John Paul Shen , Abhineet Uppal

Introduction

Extramural vascular invasion (EMVI) is associated with distant recurrence after treatment of locogionally advanced rectal adenocarcinomas (LARCs), but its use as a marker for response to neoadjuvant therapy is less well understood. We examined the relationship between EMVI and tumor or nodal category downstaging after treatment of LARCs with neoadjuvant therapy.

Methods

Patients with EMVI categorized on initial staging pelvic MRI for LARC who underwent curative-intent surgery after neoadjuvant therapy at MD Anderson Cancer Center from 2016 to 2022 were identified. Patients received either preoperative chemoradiation or total neoadjuvant therapy (TNT). Associations between EMVI and demographic, radiologic, and clinicopathologic variables were analyzed.

Results

EMVI was associated with higher rates of lymphovascular invasion (LVI) (46.2% vs. 27.8%, P = .001) and perineural invasion (PNI) (51.9% vs. 28.4%, P < .001) on final pathology. Patients with EMVI were more likely to have cT4 tumors (31.7% vs. 16.3%, P = .004) and cN+ status (86.8% vs. 66.3%, P = .001) and more likely to be treated with TNT rather than chemoradiation alone (62.3% vs. 41.9%, P = .005). EMVI was associated with a lower rate of pathologic complete or near-complete response (20.1% vs. 34.2%, P = .018), downstaging to ypT0-2 from cT3/4 tumors (14.9% vs. 44.4%, P = .0001), and downstaging to ypN0 from cN+ status (47.9% vs. 66.4%, P = .015).

Conclusions

Rectal tumors with EMVI are more likely to have higher clinical stage, less likely to respond to neoadjuvant therapy despite increased use of TNT, and more likely to have high-risk features for recurrence. This suggests EMVI is a marker of disease with poorer response to neoadjuvant therapy. Disease biology should be strongly considered in treatment decision-making, and new treatment strategies are needed to improve disease response.
外膜血管侵犯（EMVI）与局部进展期直肠腺癌（LARCs）治疗后远处复发有关，但其作为新辅助治疗反应的标志尚不清楚。我们研究了EMVI与LARCs接受新辅助治疗后肿瘤或淋巴结分期降低的关系。方法：选取2016年至2022年在MD安德森癌症中心接受新辅助治疗后进行治愈意图手术的EMVI患者，这些患者在LARC的初始期骨盆MRI分类。患者接受术前放化疗或全新辅助治疗（TNT）。分析EMVI与人口统计学、放射学和临床病理变量之间的关系。结果：EMVI与淋巴血管侵袭（LVI） （46.2% vs. 27.8%, P = 0.001）和周围神经侵袭（PNI） （51.9% vs. 28.4%, P < 0.001）相关。EMVI患者更容易出现cT4肿瘤（31.7% vs. 16.3%, P = 0.004）和cN+状态（86.8% vs. 66.3%, P = 0.001），更容易接受TNT治疗而不是单独放化疗（62.3% vs. 41.9%, P = 0.005）。EMVI与较低的病理完全或接近完全缓解率（20.1%对34.2%,P = 0.018）、从cT3/4肿瘤降期为ypT0-2（14.9%对44.4%,P = 0.0001）和从cN+状态降期为ypN0（47.9%对66.4%,P = 0.015）相关。结论：直肠EMVI肿瘤临床分期较高，尽管增加了TNT的使用，但对新辅助治疗的反应较低，更有可能具有复发的高危特征。这表明EMVI是对新辅助治疗反应较差的疾病的标志。在治疗决策中应充分考虑疾病生物学，并需要新的治疗策略来提高疾病反应。
{"title":"Does Extramural Vascular Invasion Predict Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer?","authors":"Neal Bhutiani ,&nbsp;Mahmoud MG Yousef ,&nbsp;Abdelrahman MG Yousef ,&nbsp;Emaan U. Haque ,&nbsp;George J. Chang ,&nbsp;Tsuyoshi Konishi ,&nbsp;Brian K. Bednarski ,&nbsp;Y. Nancy You ,&nbsp;John Paul Shen ,&nbsp;Abhineet Uppal","doi":"10.1016/j.clcc.2025.02.002","DOIUrl":"10.1016/j.clcc.2025.02.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Extramural vascular invasion (EMVI) is associated with distant recurrence after treatment of locogionally advanced rectal adenocarcinomas (LARCs), but its use as a marker for response to neoadjuvant therapy is less well understood. We examined the relationship between EMVI and tumor or nodal category downstaging after treatment of LARCs with neoadjuvant therapy.</div></div><div><h3>Methods</h3><div>Patients with EMVI categorized on initial staging pelvic MRI for LARC who underwent curative-intent surgery after neoadjuvant therapy at MD Anderson Cancer Center from 2016 to 2022 were identified. Patients received either preoperative chemoradiation or total neoadjuvant therapy (TNT). Associations between EMVI and demographic, radiologic, and clinicopathologic variables were analyzed.</div></div><div><h3>Results</h3><div>EMVI was associated with higher rates of lymphovascular invasion (LVI) (46.2% vs. 27.8%, <em>P</em> = .001) and perineural invasion (PNI) (51.9% vs. 28.4%, <em>P</em> &lt; .001) on final pathology. Patients with EMVI were more likely to have cT4 tumors (31.7% vs. 16.3%, <em>P</em> = .004) and cN+ status (86.8% vs. 66.3%, <em>P</em> = .001) and more likely to be treated with TNT rather than chemoradiation alone (62.3% vs. 41.9%, <em>P</em> = .005). EMVI was associated with a lower rate of pathologic complete or near-complete response (20.1% vs. 34.2%, <em>P</em> = .018), downstaging to ypT0-2 from cT3/4 tumors (14.9% vs. 44.4%, <em>P</em> = .0001), and downstaging to ypN0 from cN+ status (47.9% vs. 66.4%, <em>P</em> = .015).</div></div><div><h3>Conclusions</h3><div>Rectal tumors with EMVI are more likely to have higher clinical stage, less likely to respond to neoadjuvant therapy despite increased use of TNT, and more likely to have high-risk features for recurrence. This suggests EMVI is a marker of disease with poorer response to neoadjuvant therapy. Disease biology should be strongly considered in treatment decision-making, and new treatment strategies are needed to improve disease response.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 2","pages":"Pages 272-279.e2"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560326","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
Oncological Outcomes From Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Colorectal Cancer Peritoneal Metastases 结直肠癌腹膜转移的细胞减少手术和腹腔加热化疗的肿瘤预后。
IF 3.3 3区 医学 Q2 ONCOLOGY
Clinical colorectal cancer
Pub Date : 2025-06-01 Epub Date: 2024-12-12 DOI: 10.1016/j.clcc.2024.12.001
Nadina Tinsley , Sarah T. O'Dwyer , Raghavendar Nagaraju , Michael Braun , Saifee Mullamitha , Konstantinos Kamposioras , F.E. Marti Marti , Mark Saunders , Hamish Clouston , Chelliah Selvasekar , Jonathan Wild , Malcolm Wilson , Andrew Renehan , Omer Aziz , Jorge Barriuso

Background

Cytoreductive surgery (CRS) is effective for colorectal cancer peritoneal metastases (CRPM) at increasing overall survival (OS) compared to systemic anticancer treatment (SACT) alone. The addition of Oxaliplatin heated intraperitoneal chemotherapy (HIPEC) has been shown in a randomized controlled trial to result in increased complications without significant OS benefit. This study evaluates outcomes for CRPM patients undergoing CRS+HIPEC with Oxaliplatin (Ox) 368mg/m2 (30 min), versus Mitomycin C (MMC) 35mg/m2 (90min). 

Methods

A prospective CRPM real-world database was used to collect outcomes for patients undergoing CRS+HIPEC at a single center. OS, recurrence-free (RFS), peritoneal RFS (PeRFS) were compared amongst all patients with histologically proven CRPM, those with completeness of cytoreduction (CC) score =0/1, and those with CC score=0/1 who were SACT naïve. 

Results

Between April 2005 and April 2021, 409 patients underwent CRS+HIPEC: 271 (66%) had MMC, 138 (34%) Ox. Of these, 395 (97%) had histologically confirmed CRPM, 336 (85%) achieved CC=0/1, 188 (47%) were SACT naïve; median OS =39.5, 44.4, and 47.2 months respectively. MMC versus Ox median OS in CC0/1=43.7 (95% CI 35.9-48.3) versus 50.1 (39.7-70.2) months, P = .28; Median OS in SACT naïve=45.7 (39.4-65.9) versus 59.9 (38.3-82.0) months, P = .31; multivariable analysis for CC0/1, SACT naïve patients showed Ox was comparable to MMC: HR=0.90, (0.64-1.27) P = .55 versus HR=0.88, (0.53-1.44) P = .60, respectively. Ox resulted in a significantly improved PeRFS in CC0/1 patients (MMC=9.0 versus Ox=12.6months, P = .01). A multivariable model for PeRFS showed a HR=0.63, (0.43-0.95), P = .03 for Ox. 

Conclusion

This study suggests a role for Ox HIPEC in CRPM which should be explored further in clinical trials.
背景：与单纯全身抗癌治疗（SACT）相比，腹腔镜手术（CRS）能有效提高结直肠癌腹膜转移（CRPM）患者的总生存率（OS）。一项随机对照试验显示，加用奥沙利铂腹腔内加温化疗（HIPEC）会导致并发症增加，但对 OS 却无明显益处。本研究评估了接受奥沙利铂（Ox）368mg/m2（30 分钟）与丝裂霉素 C（MMC）35mg/m2（90 分钟）CRS+HIPEC 的 CRPM 患者的疗效。方法：使用前瞻性 CRPM 真实世界数据库收集在单个中心接受 CRS+HIPEC 治疗的患者的疗效。在所有经组织学证实的CRPM患者、细胞减灭完全性（CC）评分=0/1的患者和CC评分=0/1但未接受SACT的患者中比较了OS、无复发（RFS）和腹膜RFS（PeRFS）。结果：2005年4月至2021年4月，409名患者接受了CRS+HIPEC治疗：271人（66%）接受了MMC治疗，138人（34%）接受了Ox治疗。其中，395 例（97%）经组织学证实为 CRPM，336 例（85%）达到 CC=0/1，188 例（47%）为 SACT 天真患者；中位 OS 分别为 39.5、44.4 和 47.2 个月。MMC与Ox相比，CC0/1的中位OS=43.7（95% CI 35.9-48.3）个月对50.1（39.7-70.2）个月，P = .28；SACT新患者的中位OS=45.7（39.4-65.9）个月对59.9（38.3-82.0）个月，P = .31；对CC0/1、SACT新患者的多变量分析显示，Ox与MMC的疗效相当：HR=0.90，（0.64-1.27）P=.55对HR=0.88，（0.53-1.44）P=.60。Ox可明显改善CC0/1患者的PeRFS（MMC=9.0个月对Ox=12.6个月，P = .01）。PeRFS的多变量模型显示，Ox的HR=0.63，(0.43-0.95)，P=0.03。结论：本研究表明，Ox HIPEC 可在 CRPM 中发挥作用，应在临床试验中进一步探讨。
{"title":"Oncological Outcomes From Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Colorectal Cancer Peritoneal Metastases","authors":"Nadina Tinsley ,&nbsp;Sarah T. O'Dwyer ,&nbsp;Raghavendar Nagaraju ,&nbsp;Michael Braun ,&nbsp;Saifee Mullamitha ,&nbsp;Konstantinos Kamposioras ,&nbsp;F.E. Marti Marti ,&nbsp;Mark Saunders ,&nbsp;Hamish Clouston ,&nbsp;Chelliah Selvasekar ,&nbsp;Jonathan Wild ,&nbsp;Malcolm Wilson ,&nbsp;Andrew Renehan ,&nbsp;Omer Aziz ,&nbsp;Jorge Barriuso","doi":"10.1016/j.clcc.2024.12.001","DOIUrl":"10.1016/j.clcc.2024.12.001","url":null,"abstract":"<div><h3>Background</h3><div>Cytoreductive surgery (CRS) is effective for colorectal cancer peritoneal metastases (CRPM) at increasing overall survival (OS) compared to systemic anticancer treatment (SACT) alone. The addition of Oxaliplatin heated intraperitoneal chemotherapy (HIPEC) has been shown in a randomized controlled trial to result in increased complications without significant OS benefit. This study evaluates outcomes for CRPM patients undergoing CRS+HIPEC with Oxaliplatin (Ox) 368mg/m<sup>2</sup> (30 min), versus Mitomycin C (MMC) 35mg/m<sup>2</sup> (90min). </div></div><div><h3>Methods</h3><div>A prospective CRPM real-world database was used to collect outcomes for patients undergoing CRS+HIPEC at a single center. OS, recurrence-free (RFS), peritoneal RFS (PeRFS) were compared amongst all patients with histologically proven CRPM, those with completeness of cytoreduction (CC) score =0/1, and those with CC score=0/1 who were SACT naïve. </div></div><div><h3>Results</h3><div>Between April 2005 and April 2021, 409 patients underwent CRS+HIPEC: 271 (66%) had MMC, 138 (34%) Ox. Of these, 395 (97%) had histologically confirmed CRPM, 336 (85%) achieved CC=0/1, 188 (47%) were SACT naïve; median OS =39.5, 44.4, and 47.2 months respectively. MMC versus Ox median OS in CC0/1=43.7 (95% CI 35.9-48.3) versus 50.1 (39.7-70.2) months, <em>P = .</em>28; Median OS in SACT naïve=45.7 (39.4-65.9) versus 59.9 (38.3-82.0) months, <em>P = .</em>31; multivariable analysis for CC0/1, SACT naïve patients showed Ox was comparable to MMC: HR=0.90, (0.64-1.27) <em>P = .</em>55 versus HR=0.88, (0.53-1.44) <em>P = .</em>60, respectively. Ox resulted in a significantly improved PeRFS in CC0/1 patients (MMC=9.0 versus Ox=12.6months, <em>P = .</em>01). A multivariable model for PeRFS showed a HR=0.63, (0.43-0.95), <em>P = .</em>03 for Ox. </div></div><div><h3>Conclusion</h3><div>This study suggests a role for Ox HIPEC in CRPM which should be explored further in clinical trials.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 2","pages":"Pages 166-179"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973824","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
Organ Preservation After Immune Checkpoint Inhibition for Locally Advanced Rectal Cancer 局部晚期直肠癌免疫检查点抑制后的器官保存。
IF 3.3 3区 医学 Q2 ONCOLOGY
Clinical colorectal cancer
Pub Date : 2025-06-01 Epub Date: 2024-12-15 DOI: 10.1016/j.clcc.2024.12.005
Charlotte Claeys , Antoon Billiet , Karin Haustermans , Albert Wolthuis , Gabriele Bislenghi , André D'Hoore , Raphaëla Dresen , Gertjan Rasschaert , Eric Van Cutsem , Filip Van Herpe , Jeroen Dekervel
  • •
    Immune checkpoint inhibition (ICI) targeting PD-1 (programmed cell death protein 1) is the standard treatment for metastatic microsatellite instable (MSI-H)/mismatch repair deficient (dMMR) colorectal cancer, producing long-lasting responses. Emerging evidence suggests an important role for neoadjuvant ICI in local and locoregional disease, especially in anatomical regions associated with high surgical morbidity.
  • •
    We report single-center data of the clinical course and outcome of 6 eligible patients with dMMR locally advanced rectal cancer (LARC) treated with off-label ICI as part of their initial treatment.
  • •
    Meaningful clinical responses were noted in all evaluable patients. Four patients had a complete clinical response, followed by active surveillance. Two patients had a partial response and underwent surgery. After a median follow-up of 25.8 months, no local or distant recurrences were noted.
  • •
    The role of immunotherapy in dMMR LARC is promising, although more prospective clinical trials with a longer follow-up are required.
•针对PD-1（程序性细胞死亡蛋白1）的免疫检查点抑制（ICI）是转移性微卫星不稳定(MSI-H)/错配修复缺陷（dMMR）结直肠癌的标准治疗方法，可产生持久的应答。越来越多的证据表明，新辅助ICI在局部和局部疾病中发挥重要作用，特别是在与高手术发病率相关的解剖区域。•我们报告了6例符合条件的dMMR局部晚期直肠癌（LARC）患者的临床过程和结果的单中心数据，这些患者接受了说明书外ICI治疗，作为初始治疗的一部分。•在所有可评估的患者中都注意到有意义的临床反应。4例患者有完全的临床反应，随后进行了主动监测。两名患者有部分反应并接受了手术。中位随访25.8个月后，未发现局部或远处复发。•免疫治疗在dMMR LARC中的作用是有希望的，尽管需要更多的前瞻性临床试验和更长的随访时间。
{"title":"Organ Preservation After Immune Checkpoint Inhibition for Locally Advanced Rectal Cancer","authors":"Charlotte Claeys ,&nbsp;Antoon Billiet ,&nbsp;Karin Haustermans ,&nbsp;Albert Wolthuis ,&nbsp;Gabriele Bislenghi ,&nbsp;André D'Hoore ,&nbsp;Raphaëla Dresen ,&nbsp;Gertjan Rasschaert ,&nbsp;Eric Van Cutsem ,&nbsp;Filip Van Herpe ,&nbsp;Jeroen Dekervel","doi":"10.1016/j.clcc.2024.12.005","DOIUrl":"10.1016/j.clcc.2024.12.005","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Immune checkpoint inhibition (ICI) targeting PD-1 (programmed cell death protein 1) is the standard treatment for metastatic microsatellite instable (MSI-H)/mismatch repair deficient (dMMR) colorectal cancer, producing long-lasting responses. Emerging evidence suggests an important role for neoadjuvant ICI in local and locoregional disease, especially in anatomical regions associated with high surgical morbidity.</div></span></li><li><span>•</span><span><div>We report single-center data of the clinical course and outcome of 6 eligible patients with dMMR locally advanced rectal cancer (LARC) treated with off-label ICI as part of their initial treatment.</div></span></li><li><span>•</span><span><div>Meaningful clinical responses were noted in all evaluable patients. Four patients had a complete clinical response, followed by active surveillance. Two patients had a partial response and underwent surgery. After a median follow-up of 25.8 months, no local or distant recurrences were noted.</div></span></li><li><span>•</span><span><div>The role of immunotherapy in dMMR LARC is promising, although more prospective clinical trials with a longer follow-up are required.</div></span></li></ul></div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 2","pages":"Pages 320-324"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967367","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}
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