Pub Date : 2025-09-01Epub Date: 2025-04-30DOI: 10.1016/j.clcc.2025.04.001
Jane McKenzie , Vanessa Wong , Shehara Mendis , Rachel Wong , Suzanne Kosmider , Yat Hang To , Louise Nott , Jeremy Shapiro , Javier Torres , Belinda Lee , Azim Jalali , Stephanie Hui-Su Lim , Susan Caird , Adnan Khattak , Peter Gibbs
Background
Epidermal growth factor receptor inhibitors (EGFRi), most commonly cetuximab and panitumumab, are first-line options for patients with left-sided, RAS wildtype (RASwt) metastatic colorectal cancer. Limited data is available comparing EGFRi outcomes.
Methods
Data for patients diagnosed January 2015 to October 2024 was reviewed from TRACC, a prospective, multi-site Australasian colorectal cancer registry. Patients with left-sided, RASwt disease treated with an EGFRi as first-line (1 L) therapy were identified. Survival outcomes were calculated using Kaplan-Meir methods.
Results
We identified 747 patients with RASwt, left-sided, metastatic colorectal cancer. Of these, 287 (38%) received 1 L therapy that included cetuximab (n = 210, 73%) or panitumumab (n = 77, 27%). A switch from one to the other agent occurred in seven patients, all due to skin toxicity, including six patients (7.8%) initially treated with panitumumab and 1 (0.5%) initially treated with cetuximab. After switching, median time on the second EGFRi agent was 212 days. For 242 patients treated with an EGFRi in combination with doublet chemotherapy, toxicity contributed to treatment cessation more often in patients treated with panitumumab (32% vs. 13%, P = .003). For the subset of patients treated with palliative intent (n = 156), median progression-free (P = .43) and overall survival (P = .98) were similar for both EGFRi.
Conclusion
In this real-world analysis, a switch from one EGFRi agent to the other in the presence of skin toxicity led to durable treatment benefit with the alternate EGFRi. For patients receiving first-line cetuximab or panitumumab in combination with doublet chemotherapy, toxicity-related treatment cessation rates differed between EGFRi agents. No differences were seen in survival outcomes.
{"title":"Exploring Real-World Outcomes of First Line EGFR Inhibitor Use, Cetuximab Versus Panitumumab, in Patients with Left-Sided, RAS Wild-Type, Metastatic Colorectal Cancer","authors":"Jane McKenzie , Vanessa Wong , Shehara Mendis , Rachel Wong , Suzanne Kosmider , Yat Hang To , Louise Nott , Jeremy Shapiro , Javier Torres , Belinda Lee , Azim Jalali , Stephanie Hui-Su Lim , Susan Caird , Adnan Khattak , Peter Gibbs","doi":"10.1016/j.clcc.2025.04.001","DOIUrl":"10.1016/j.clcc.2025.04.001","url":null,"abstract":"<div><h3>Background</h3><div><span>Epidermal growth factor receptor inhibitors<span> (EGFRi), most commonly cetuximab<span> and panitumumab, are first-line options for patients with left-sided, RAS wildtype (RASwt) </span></span></span>metastatic colorectal cancer. Limited data is available comparing EGFRi outcomes.</div></div><div><h3>Methods</h3><div>Data for patients diagnosed January 2015 to October 2024 was reviewed from TRACC, a prospective, multi-site Australasian colorectal cancer registry. Patients with left-sided, RASwt disease treated with an EGFRi as first-line (1 L) therapy were identified. Survival outcomes were calculated using Kaplan-Meir methods.</div></div><div><h3>Results</h3><div><span><span>We identified 747 patients with RASwt, left-sided, metastatic colorectal cancer. Of these, 287 (38%) received 1 L therapy that included </span>cetuximab (</span><em>n</em><span> = 210, 73%) or panitumumab (</span><em>n</em><span> = 77, 27%). A switch from one to the other agent occurred in seven patients, all due to skin toxicity, including six patients (7.8%) initially treated with panitumumab and 1 (0.5%) initially treated with cetuximab. After switching, median time on the second EGFRi agent was 212 days. For 242 patients treated with an EGFRi in combination with doublet chemotherapy, toxicity contributed to treatment cessation more often in patients treated with panitumumab (32% vs. 13%, </span><em>P</em> = .003). For the subset of patients treated with palliative intent (<em>n</em> = 156), median progression-free (<em>P</em><span> = .43) and overall survival (</span><em>P</em> = .98) were similar for both EGFRi.</div></div><div><h3>Conclusion</h3><div>In this real-world analysis, a switch from one EGFRi agent to the other in the presence of skin toxicity led to durable treatment benefit with the alternate EGFRi. For patients receiving first-line cetuximab or panitumumab in combination with doublet chemotherapy, toxicity-related treatment cessation rates differed between EGFRi agents. No differences were seen in survival outcomes.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 362-368"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144988","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}
Pub Date : 2025-09-01Epub Date: 2025-03-19DOI: 10.1016/j.clcc.2025.03.002
Seong-Eun Kim , Ji Sung Lee , Sun Young Kim , Jeong Eun Kim , Yong Sang Hong , Tae Won Kim
Background
RAS mutations are important biomarkers for predicting the efficacy of anti-EGFR treatment in metastatic colorectal cancer (mCRC). The emergence of RAS mutations is a known resistance mechanism. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) RAS mutations in patients with mCRC treated with cetuximab, focusing on the temporal dynamics of RAS mutation emergence.
Patients and Methods
Patients with tissue-confirmed RAS wild-type mCRC were included in the study. ctDNA samples were collected at baseline, every 8 weeks during treatment, and after the final cetuximab dose. Cetuximab, combined with FOLFOX or FOLFIRI, was administered as first-line therapy. The primary objective was to assess the impact of emergent ctDNA RAS mutations on progression-free survival (PFS) during cetuximab-based treatment in the first-line setting.
Results
A total of 49 patients contributed at least 1 ctDNA sample, with 320 samples collected in total. The baseline concordance rate between ctDNA and tissue RAS status was 89.1% (41/46). Among 41 baseline RAS wild-type cases, 22 (53.7%) demonstrated emergent RAS mutations. The median time to RAS emergence was 12.8 months, and the median PFS was 12.7 months. Temporal analysis revealed that a single detection of RAS mutation was not consistently associated with poor PFS and could resolve in subsequent tests. However, time-dependent analysis indicated that the presence of ctDNA RAS mutations at any time point was significantly associated with poorer PFS (adjusted HR = 2.24, P = .02).
Conclusion
The emergence of ctDNA RAS mutations during cetuximab-based first-line therapy exhibits temporal variability. Nevertheless, the presence of ctDNA RAS mutations at any time point is collectively associated with reduced PFS.
{"title":"Prognostic Relevance of ctDNA RAS Mutation in Patients With Metastatic Colorectal Cancer Treated With Cetuximab","authors":"Seong-Eun Kim , Ji Sung Lee , Sun Young Kim , Jeong Eun Kim , Yong Sang Hong , Tae Won Kim","doi":"10.1016/j.clcc.2025.03.002","DOIUrl":"10.1016/j.clcc.2025.03.002","url":null,"abstract":"<div><h3>Background</h3><div>RAS mutations are important biomarkers for predicting the efficacy of anti-EGFR treatment in metastatic colorectal cancer (mCRC). The emergence of RAS mutations is a known resistance mechanism. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) RAS mutations in patients with mCRC treated with cetuximab, focusing on the temporal dynamics of RAS mutation emergence.</div></div><div><h3>Patients and Methods</h3><div>Patients with tissue-confirmed RAS wild-type mCRC were included in the study. ctDNA samples were collected at baseline, every 8 weeks during treatment, and after the final cetuximab dose. Cetuximab, combined with FOLFOX or FOLFIRI, was administered as first-line therapy. The primary objective was to assess the impact of emergent ctDNA RAS mutations on progression-free survival (PFS) during cetuximab-based treatment in the first-line setting.</div></div><div><h3>Results</h3><div>A total of 49 patients contributed at least 1 ctDNA sample, with 320 samples collected in total. The baseline concordance rate between ctDNA and tissue RAS status was 89.1% (41/46). Among 41 baseline RAS wild-type cases, 22 (53.7%) demonstrated emergent RAS mutations. The median time to RAS emergence was 12.8 months, and the median PFS was 12.7 months. Temporal analysis revealed that a single detection of RAS mutation was not consistently associated with poor PFS and could resolve in subsequent tests. However, time-dependent analysis indicated that the presence of ctDNA RAS mutations at any time point was significantly associated with poorer PFS (adjusted HR = 2.24, <em>P</em> = .02).</div></div><div><h3>Conclusion</h3><div>The emergence of ctDNA RAS mutations during cetuximab-based first-line therapy exhibits temporal variability. Nevertheless, the presence of ctDNA RAS mutations at any time point is collectively associated with reduced PFS.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 341-351.e5"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045834","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}
Pub Date : 2025-09-01Epub Date: 2025-05-28DOI: 10.1016/j.clcc.2025.05.002
Janine Wieser , Michael Hoffmeister , Hermann Brenner , Ute Mons
The incidence of early-onset CRC (EOCRC) has lately been increasing. We aimed to synthesize findings on the association of smoking and alcohol consumption with EOCRC in a systematic review and meta-analysis. Following preregistration of the study protocol in PROSPERO (CRD42023424149), we searched PubMed and Web of Science for observational studies on the association of smoking or alcohol consumption with EOCRC. We performed meta-analyses, including several subgroup analyses, to examine the association of alcohol consumption and smoking, respectively, with the risk of EOCRC. Generally, random effects models were calculated, with fixed effect models employed for analyses including only a small number of studies. We included eleven studies for alcohol consumption and twelve for smoking. Alcohol use was found to be a risk factor for EOCRC, with a pooled odds ratio (OR) of 1.39 (95 % confidence interval (CI) 1.14-1.69). A dose-response model revealed a positive association between the amount of ethanol consumed and the risk of EOCRC (OR per 10 g/d ethanol increase 1.02, 95 % CI, 1.01-1.08). Smoking (ever or current combined) was also found to be a significant risk factor for EOCRC (OR 1.39, 95 % CI, 1.20-1.59). Alcohol consumption and smoking are significant risk factors for EOCRC and should be addressed in the context of prevention.
{"title":"Associations of Alcohol Use and Smoking With Early-Onset Colorectal Cancer—A Systematic Review and Meta-Analysis","authors":"Janine Wieser , Michael Hoffmeister , Hermann Brenner , Ute Mons","doi":"10.1016/j.clcc.2025.05.002","DOIUrl":"10.1016/j.clcc.2025.05.002","url":null,"abstract":"<div><div>The incidence of early-onset CRC (EOCRC) has lately been increasing. We aimed to synthesize findings on the association of smoking and alcohol consumption with EOCRC in a systematic review and meta-analysis. Following preregistration of the study protocol in PROSPERO (CRD42023424149), we searched PubMed and Web of Science for observational studies on the association of smoking or alcohol consumption with EOCRC. We performed meta-analyses, including several subgroup analyses, to examine the association of alcohol consumption and smoking, respectively, with the risk of EOCRC. Generally, random effects models were calculated, with fixed effect models employed for analyses including only a small number of studies. We included eleven studies for alcohol consumption and twelve for smoking. Alcohol use was found to be a risk factor for EOCRC, with a pooled odds ratio (OR) of 1.39 (95 % confidence interval (CI) 1.14-1.69). A dose-response model revealed a positive association between the amount of ethanol consumed and the risk of EOCRC (OR per 10 g/d ethanol increase 1.02, 95 % CI, 1.01-1.08). Smoking (ever or current combined) was also found to be a significant risk factor for EOCRC (OR 1.39, 95 % CI, 1.20-1.59). Alcohol consumption and smoking are significant risk factors for EOCRC and should be addressed in the context of prevention.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 331-340.e15"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340694","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}
Pub Date : 2025-09-01Epub Date: 2025-03-26DOI: 10.1016/j.clcc.2025.03.004
Peter Gibbs , Khalid Abubaker , Danyi Wang , Zheng Feng , Jawad Hamad , Jiemin Liao , Christopher Stroh , Soetkin Vlassak , Kathrin Heinrich , Adnan Khattak , Juergen Scheuenpflug
Introduction
Colorectal cancer (CRC), a global health concern, requires effective treatments. Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies are used for RAS wild-type and BRAFV600 mutation-negative metastatic CRC (mCRC) but are not indicated for RAS mutant CRC. Evidence suggests CRC patients with sub-clonal RAS/BRAF mutations in tumor tissue may benefit from anti-EGFRs. We assessed the outcomes of patients with sub-clonal RAS/BRAF mutated advanced/mCRC receiving anti-EGFRs using liquid-based GuardantINFORM real-world clinical-genomic analysis.
Patients and Methods
GuardantINFORM analyzed US patients with advanced CRC with BRAFV600/KRAS/NRAS mutations who received anti-EGFR therapies within 90 days after a Guardant360 test. Primary endpoints were time-to-next treatment (TTNT) and overall survival (OS) (compared across RAS/BRAF mutation clonality cut-offs of 0.3–0.8 using the Cox proportional hazards model).
Results
In GuardantINFORM, 446 patients initiated anti-EGFR therapy within 90 days after the Guardant360 test, and 11%, 9%, and 1% had BRAFV600E, KRAS, or NRAS mutations, respectively; median distribution of RAS/BRAF clonality was 0.84 (IQR, 0.57-1.00). The data show that patients harboring sub-clonal RAS/BRAF mutations benefited from anti-EGFR therapy to a degree similar to patients without RAS/BRAF mutations. For cut-offs of 0.3 to 0.8, sub-clonal RAS/BRAF had similar TTNT to patients without RAS/BRAF mutations, while clonal RAS/BRAF had a significantly shorter TTNT. For cut-offs of 0.3 to 0.7, sub-clonal RAS/BRAF had similar OS to RAS/BRAF mutations not detected, while clonal RAS/BRAF had a significantly shorter OS.
Conclusion
Consistent with tumor tissue biopsy data, patients with CRC harboring sub-clonal RAS/BRAF mutations as assessed by liquid biopsy may derive benefit from anti-EGFR therapy, warranting further investigation.
{"title":"Clinical Impact of Sub-Clonal RAS/BRAF Alterations in Liquid Biopsies From Patients With Advanced or Metastatic CRC","authors":"Peter Gibbs , Khalid Abubaker , Danyi Wang , Zheng Feng , Jawad Hamad , Jiemin Liao , Christopher Stroh , Soetkin Vlassak , Kathrin Heinrich , Adnan Khattak , Juergen Scheuenpflug","doi":"10.1016/j.clcc.2025.03.004","DOIUrl":"10.1016/j.clcc.2025.03.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Colorectal cancer (CRC), a global health concern, requires effective treatments. Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies are used for <em>RAS</em> wild-type and <em>BRAF<sup>V600</sup></em> mutation-negative metastatic CRC (mCRC) but are not indicated for <em>RAS</em> mutant CRC. Evidence suggests CRC patients with sub-clonal <em>RAS/BRAF</em> mutations in tumor tissue may benefit from anti-EGFRs. We assessed the outcomes of patients with sub-clonal <em>RAS</em>/<em>BRAF</em> mutated advanced/mCRC receiving anti-EGFRs using liquid-based GuardantINFORM real-world clinical-genomic analysis.</div></div><div><h3>Patients and Methods</h3><div>GuardantINFORM analyzed US patients with advanced CRC with <em>BRAF<sup>V600</sup>/KRAS/NRAS</em> mutations who received anti-EGFR therapies within 90 days after a Guardant360 test. Primary endpoints were time-to-next treatment (TTNT) and overall survival (OS) (compared across <em>RAS/BRAF</em> mutation clonality cut-offs of 0.3–0.8 using the Cox proportional hazards model).</div></div><div><h3>Results</h3><div>In GuardantINFORM, 446 patients initiated anti-EGFR therapy within 90 days after the Guardant360 test, and 11%, 9%, and 1% had <em>BRAF<sup>V600E</sup>, KRAS</em>, or <em>NRAS</em> mutations, respectively; median distribution of <em>RAS/BRAF</em> clonality was 0.84 (IQR, 0.57-1.00). The data show that patients harboring sub-clonal <em>RAS</em>/<em>BRAF</em> mutations benefited from anti-EGFR therapy to a degree similar to patients without <em>RAS/BRAF</em> mutations. For cut-offs of 0.3 to 0.8, sub-clonal <em>RAS/BRAF</em> had similar TTNT to patients without <em>RAS/BRAF</em> mutations, while clonal <em>RAS/BRAF</em> had a significantly shorter TTNT. For cut-offs of 0.3 to 0.7, sub-clonal <em>RAS/BRAF</em> had similar OS to <em>RAS/BRAF</em> mutations not detected, while clonal <em>RAS/BRAF</em> had a significantly shorter OS.</div></div><div><h3>Conclusion</h3><div>Consistent with tumor tissue biopsy data, patients with CRC harboring sub-clonal <em>RAS/BRAF</em> mutations as assessed by liquid biopsy may derive benefit from anti-EGFR therapy, warranting further investigation.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 352-361.e14"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082768","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}
Pub Date : 2025-09-01Epub Date: 2025-06-03DOI: 10.1016/j.clcc.2025.05.004
Hyeon Kyeong Kim, Jong Lyul Lee, Chan Wook Kim, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu
Introduction
Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC), which differs in carcinogenesis from sporadic CRC (S-CRC). This study aimed to compare the clinical features and oncologic outcomes between UCCRC and S-CRC groups.
Patients and methods
A retrospective cohort of patients who underwent surgery at Asan Medical Center, Seoul, Korea, between January 2010 to December 2020 comprised 46 patients with UCCRC and 9717 patients with S-CRC. Before propensity score matching (PSM), several variables significantly differed between the 2 groups. PSM was performed at a 1:2 ratio.
Results
Of the 126 analyzed patients after PSM, 42 and 84 patients were in the UCCRC and S-CRC groups, respectively. Five-year overall survival (OS) (82.2% ± 6.1% vs. 81.7% ± 5.2%), 5-year disease-free survival (DFS) (70.9% ± 10.1% vs. 76.1 ± 5.7%), and stage-by-stage survival outcomes were not significantly different between the UCCRC and S-CRC groups. Among stage III patients, the 5-year OS and DFS rates in the UCCRC group were lower than those in the S-CRC group without reaching significance (OS: 33.3% ± 19.2% vs. 68.4% ± 13.1%, P=.078; DFS: 33.3% ± 19.2% vs. 69.2% ± 12.8%, P=.053). Regarding adjuvant chemotherapy, the UCCRC group had more chemotherapy-induced complications than the S-CRC group (21.2% vs. 0%, P=.026).
Conclusion
This study demonstrates that 5-year OS and DFS are equivalent in UCCRC and S-CRC groups, even in stage-by-stage analyses. As the chemotherapy-induced complications differed, this may have affected the oncologic outcomes in stage III CRC.
溃疡性结肠炎（UC）患者发生结直肠癌（CRC）的风险增加，其癌变与散发性结直肠癌（S-CRC）不同。本研究旨在比较UCCRC组和S-CRC组的临床特征和肿瘤预后。患者和方法：2010年1月至2020年12月在韩国首尔牙山医疗中心接受手术的患者进行回顾性队列研究，包括46例UCCRC患者和9717例S-CRC患者。在倾向评分匹配（PSM）之前，两组之间的一些变量存在显著差异。PSM以1:2的比例进行。结果：在126例PSM后分析的患者中，UCCRC组和S-CRC组分别为42例和84例。5年总生存率（OS）（82.2%±6.1% vs. 81.7%±5.2%）、5年无病生存率（DFS）（70.9%±10.1% vs. 76.1±5.7%）和分期生存率在UCCRC组和S-CRC组之间无显著差异。在III期患者中，UCCRC组5年OS和DFS率均低于S-CRC组，但无显著性差异(OS: 33.3%±19.2% vs 68.4%±13.1%，P= 0.078；DFS: 33.3%±19.2% vs. 69.2%±12.8%，P= 0.053)。在辅助化疗方面，UCCRC组化疗并发症发生率高于S-CRC组（21.2% vs. 0%， P= 0.026）。结论：本研究表明，UCCRC组和S-CRC组的5年OS和DFS是相等的，即使在分期分析中也是如此。由于化疗引起的并发症不同，这可能影响了III期结直肠癌的肿瘤预后。
{"title":"Stage-by-stage comparison of clinical and oncologic outcomes in ulcerative colitis-associated versus sporadic colorectal cancer: A propensity-matched analysis","authors":"Hyeon Kyeong Kim, Jong Lyul Lee, Chan Wook Kim, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu","doi":"10.1016/j.clcc.2025.05.004","DOIUrl":"10.1016/j.clcc.2025.05.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC), which differs in carcinogenesis from sporadic CRC (S-CRC). This study aimed to compare the clinical features and oncologic outcomes between UC<img>CRC and S-CRC groups.</div></div><div><h3>Patients and methods</h3><div>A retrospective cohort of patients who underwent surgery at Asan Medical Center, Seoul, Korea, between January 2010 to December 2020 comprised 46 patients with UC<img>CRC and 9717 patients with S-CRC. Before propensity score matching (PSM), several variables significantly differed between the 2 groups. PSM was performed at a 1:2 ratio.</div></div><div><h3>Results</h3><div>Of the 126 analyzed patients after PSM, 42 and 84 patients were in the UC<img>CRC and S-CRC groups, respectively. Five-year overall survival (OS) (82.2% ± 6.1% <em>vs.</em> 81.7% ± 5.2%), 5-year disease-free survival (DFS) (70.9% ± 10.1% <em>vs.</em> 76.1 ± 5.7%), and stage-by-stage survival outcomes were not significantly different between the UC<img>CRC and S-CRC groups. Among stage III patients, the 5-year OS and DFS rates in the UC<img>CRC group were lower than those in the S-CRC group without reaching significance (OS: 33.3% ± 19.2% <em>vs.</em> 68.4% ± 13.1%, <em>P</em> <em>=</em> <em>.078</em>; DFS: 33.3% ± 19.2% <em>vs.</em> 69.2% ± 12.8%, <em>P</em> <em>=</em> <em>.053</em>). Regarding adjuvant chemotherapy, the UC<img>CRC group had more chemotherapy-induced complications than the S-CRC group (21.2% <em>vs.</em> 0%, <em>P</em> <em>=</em> <em>.026</em>).</div></div><div><h3>Conclusion</h3><div>This study demonstrates that 5-year OS and DFS are equivalent in UC<img>CRC and S-CRC groups, even in stage-by-stage analyses. As the chemotherapy-induced complications differed, this may have affected the oncologic outcomes in stage III CRC.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 3","pages":"Pages 389-399"},"PeriodicalIF":3.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531649","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}
Pub Date : 2025-06-01Epub Date: 2025-03-19DOI: 10.1016/j.clcc.2025.03.001
Caroline L. Kahn , Mathias M. Petersen , Jakob Kleif , Mees S.E. Mansvelders , Morten Rasmussen , Lars N. Jørgensen , Jesper Vilandt , Jakob B. Seidelin , Claudia Jaensch , Peter Bondeven , Kåre A. Gotschalck , Uffe S. Løve , Berit Andersen , Ib J. Christensen , Lawrence C. LaPoint , Christina Therkildsen
Background
Early detection is paramount when reducing incidence and mortality of colorectal cancer (CRC). Current population-based screening programs primarily use fecal immunochemical test (FIT) to allocate individuals for colonoscopy although low specificity challenges colonoscopy capacities. We aimed to assess the potential of circulating tumor (ct)DNA markers for early CRC detection in a dual-test CRC screening approach among FIT positive individuals.
Methods
Plasma samples from 774 FIT positive (≥100 ng Hemoglobin/mL) individuals from the Danish CRC screening program were analyzed for hypermethylated DNA in the genes Branched Chain Amino-acid Transaminase 1 (BCAT1), Ikaros-Family Zinc Finger transcription 1 (IKZF1), and Interferon Regulator Factor 4 (IRF4). Multivariate logistic regression models were generated adding the ctDNA markers and age to the FIT value. The dual-test approach was benchmarked to FIT at specific thresholds.
Results
The dual-test approach improved CRC detection compared to the FIT alone (AUC of 87.2 [95% CI, 82.9-91.4] vs AUC of 72.5 [95% CI, 67.0-77.9]). This was also seen when adding advanced adenomas to the outcome resulting in AUCs of 71.8 [95% CI, 67.8-75.8] for the dual-test approach compared to 65.5 [95% CI, 61.3-69.7] for the FIT model alone. Benchmarking the dual-test approach at FIT cut-offs between 100 and 600 ng Hb/mL showed a potential for either reducing the colonoscopy requirement by up to 56% or increasing CRC detection by up to 28%.
Conclusions
As increasing FIT cutoff will decrease CRC detection rate, application of the ctDNA panel can increase the sensitivity and specificity in a dual-test approach among asymptomatic individuals.
{"title":"Circulating Tumor DNA in Addition to Fecal Immunochemical Test in a Dual-Test Colorectal Cancer Screening Approach","authors":"Caroline L. Kahn , Mathias M. Petersen , Jakob Kleif , Mees S.E. Mansvelders , Morten Rasmussen , Lars N. Jørgensen , Jesper Vilandt , Jakob B. Seidelin , Claudia Jaensch , Peter Bondeven , Kåre A. Gotschalck , Uffe S. Løve , Berit Andersen , Ib J. Christensen , Lawrence C. LaPoint , Christina Therkildsen","doi":"10.1016/j.clcc.2025.03.001","DOIUrl":"10.1016/j.clcc.2025.03.001","url":null,"abstract":"<div><h3>Background</h3><div>Early detection is paramount when reducing incidence and mortality of colorectal cancer (CRC). Current population-based screening programs primarily use fecal immunochemical test (FIT) to allocate individuals for colonoscopy although low specificity challenges colonoscopy capacities. We aimed to assess the potential of circulating tumor (ct)DNA markers for early CRC detection in a dual-test CRC screening approach among FIT positive individuals.</div></div><div><h3>Methods</h3><div>Plasma samples from 774 FIT positive (≥100 ng Hemoglobin/mL) individuals from the Danish CRC screening program were analyzed for hypermethylated DNA in the genes Branched Chain Amino-acid Transaminase 1 (<em>BCAT1</em>), Ikaros-Family Zinc Finger transcription 1 (<em>IKZF1</em>), and Interferon Regulator Factor 4 (<em>IRF4</em>). Multivariate logistic regression models were generated adding the ctDNA markers and age to the FIT value. The dual-test approach was benchmarked to FIT at specific thresholds.</div></div><div><h3>Results</h3><div>The dual-test approach improved CRC detection compared to the FIT alone (AUC of 87.2 [95% CI, 82.9-91.4] vs AUC of 72.5 [95% CI, 67.0-77.9]). This was also seen when adding advanced adenomas to the outcome resulting in AUCs of 71.8 [95% CI, 67.8-75.8] for the dual-test approach compared to 65.5 [95% CI, 61.3-69.7] for the FIT model alone. Benchmarking the dual-test approach at FIT cut-offs between 100 and 600 ng Hb/mL showed a potential for either reducing the colonoscopy requirement by up to 56% or increasing CRC detection by up to 28%.</div></div><div><h3>Conclusions</h3><div>As increasing FIT cutoff will decrease CRC detection rate, application of the ctDNA panel can increase the sensitivity and specificity in a dual-test approach among asymptomatic individuals.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 2","pages":"Pages 310-319.e1"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044968","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}
Pub Date : 2025-06-01Epub Date: 2025-01-02DOI: 10.1016/j.clcc.2024.12.007
Jessica Lucchetti , Lorenzo Angotti , Alessandro Parisi , Michele Basso , Mariam Grazia Polito , Federica Zoratto , Emanuela Di Giacomo , Daniele Nitti , Alessandro Minelli , Lisa Salvatore , Maria Alessandra Calegari , Federica Lo Prinzi , Donatello Gemma , Carlo Signorelli , Margherita Veroli , Annunziato Anghelone , Luca Galbato Muscio , Barbara Di Cocco , Giorgio Trombetta , Cristina Morelli , Giuseppe Tonini
Background
Both aflibercept and bevacizumab-based regimens are available II-line treatment options for patients with metastatic colorectal cancer (mCRC). However, no head-to-head trials established the optimal anti-angiogenic strategy for this setting.
Methods
We launched a multicenter, retrospective, observational study to assess and compare clinical efficacy of II-line treatments for patients with mCRC. Patients with KRAS/NRAS/BRAF-wild type and KRAS/NRAS mutant tumors were also analyzed separately.
Findings
348 patients were included, of whom 153 and 195 were treated with bevacizumab- and aflibercept-based regimens, respectively. Patients treated with aflibercept showed an increased risk of death (corrected [co]-HR 1.92, 95 %CI: 1.37–2.68), of disease progression/death (co-HR 1.43, 95 %CI: 1.12–1.82) and a decreased objective response rate (ORR) (21.5 % vs 34.7 %, p=0.007) in comparison to bevacizumab. Patients treated with II-line bevacizumab were more frequently treated in the third line setting after disease progression (91.1 % vs 68.5 %, p<0.0001). In the KRAS/NRAS mutant cohort, treatment with bevacizumab was associated with longer overall survival (OS) (18.0 months vs 12.5 months, p=0.0069), but similar progression free survival (PFS) (p=0.32) and ORR (p=0.57). In the KRAS/NRAS, BRAF wild type cohort, patients treated with bevacizumab achieved longer OS (20.2 months vs 10.6 months, p=0.013), PFS (8.4 months vs 3.7 months, p=0.0002), and higher ORR (48.6 % vs 15.0 %, p=0.0016), compared to those treated with aflibercept. The results were independently confirmed with inverse probability of treatment weighting and with fixed multivariable Cox-regressions.
Conclusion
These findings support the use of bevacizumab-based over aflibercept-based regimens as II-line treatment in mCRC, especially in KRAS/NRAS and BRAF wild type tumors.
背景：对于转移性结直肠癌（mCRC）患者，阿非利西普和贝伐单抗方案都是可用的二线治疗方案。然而，在这种情况下，没有正面试验确定最佳的抗血管生成策略。方法：我们开展了一项多中心、回顾性、观察性研究，以评估和比较ii线治疗对mCRC患者的临床疗效。KRAS/NRAS/ braf -野生型和KRAS/NRAS突变型肿瘤患者也分别进行了分析。研究结果：纳入348例患者，其中分别有153例和195例患者接受了基于贝伐单抗和阿普利赛的治疗方案。与贝伐单抗相比，阿非利西普治疗的患者死亡风险（校正[co]-HR 1.92, 95 %CI: 1.37-2.68）、疾病进展/死亡风险（校正[co]-HR 1.43, 95 %CI: 1.12-1.82）增加，客观缓解率（ORR）降低（21.5% % vs 34.7 %,p=0.007）。接受贝伐单抗ii线治疗的患者在疾病进展后更频繁地接受三线治疗（91.1 % vs 68.5 %）。结论：这些发现支持使用基于贝伐单抗的方案作为mCRC的ii线治疗，特别是在KRAS/NRAS和BRAF野生型肿瘤中。
{"title":"Aflibercept-Based and Bevacizumab-Based Second Line Regimens in Patients with Metastatic Colorectal Cancer: Propensity Score Weighted-Analysis from a Multicenter Cohort","authors":"Jessica Lucchetti , Lorenzo Angotti , Alessandro Parisi , Michele Basso , Mariam Grazia Polito , Federica Zoratto , Emanuela Di Giacomo , Daniele Nitti , Alessandro Minelli , Lisa Salvatore , Maria Alessandra Calegari , Federica Lo Prinzi , Donatello Gemma , Carlo Signorelli , Margherita Veroli , Annunziato Anghelone , Luca Galbato Muscio , Barbara Di Cocco , Giorgio Trombetta , Cristina Morelli , Giuseppe Tonini","doi":"10.1016/j.clcc.2024.12.007","DOIUrl":"10.1016/j.clcc.2024.12.007","url":null,"abstract":"<div><h3>Background</h3><div>Both aflibercept and bevacizumab-based regimens are available II-line treatment options for patients with metastatic colorectal cancer (mCRC). However, no head-to-head trials established the optimal anti-angiogenic strategy for this setting.</div></div><div><h3>Methods</h3><div>We launched a multicenter, retrospective, observational study to assess and compare clinical efficacy of II-line treatments for patients with mCRC. Patients with <em>KRAS/NRAS/BRAF</em>-wild type and <em>KRAS/NRAS</em> mutant tumors were also analyzed separately.</div></div><div><h3>Findings</h3><div>348 patients were included, of whom 153 and 195 were treated with bevacizumab- and aflibercept-based regimens, respectively. Patients treated with aflibercept showed an increased risk of death (corrected [co]-HR 1.92, 95 %CI: 1.37–2.68), of disease progression/death (co-HR 1.43, 95 %CI: 1.12–1.82) and a decreased objective response rate (ORR) (21.5 % vs 34.7 %, p=0.007) in comparison to bevacizumab. Patients treated with II-line bevacizumab were more frequently treated in the third line setting after disease progression (91.1 % vs 68.5 %, p<0.0001). In the <em>KRAS/NRAS</em> mutant cohort, treatment with bevacizumab was associated with longer overall survival (OS) (18.0 months vs 12.5 months, p=0.0069), but similar progression free survival (PFS) (p=0.32) and ORR (p=0.57). In the <em>KRAS/NRAS, BRAF</em> wild type cohort, patients treated with bevacizumab achieved longer OS (20.2 months vs 10.6 months, p=0.013), PFS (8.4 months vs 3.7 months, p=0.0002), and higher ORR (48.6 % vs 15.0 %, p=0.0016), compared to those treated with aflibercept. The results were independently confirmed with inverse probability of treatment weighting and with fixed multivariable Cox-regressions.</div></div><div><h3>Conclusion</h3><div>These findings support the use of bevacizumab-based over aflibercept-based regimens as II-line treatment in mCRC, especially in <em>KRAS/NRAS</em> and <em>BRAF</em> wild type tumors.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 2","pages":"Pages 207-217.e5"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044044","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}
Pub Date : 2025-06-01Epub Date: 2024-12-10DOI: 10.1016/j.clcc.2024.12.003
Eline G.M. van Geffen , Cornelis R.C. Hogewoning , Sanne-Marije J.A. Hazen , Tania C. Sluckin , Marilyne M. Lange , Petur Snaebjornsson , Regina G.H. Beets-Tan , Corrie A.M. Marijnen , Cornelis Verhoef , Myriam Chalabi , Pieter J. Tanis , Miranda Kusters , Tjeerd S. Aukema , behalf of the Dutch Snapshot Research Group
Introduction
Data regarding the incidence and outcomes of mismatch repair deficient (dMMR) rectal cancer is limited. This study characterizes dMMR rectal cancer patients, comparing response after neoadjuvant radiotherapy and oncological outcomes to mismatch repair proficient (pMMR) rectal cancer patients.
Method
A retrospective cross-sectional cohort study was conducted in 67 Dutch centers. Data including patient and tumor characteristics, radiological and pathological reports and oncological follow-up outcomes were gathered from documentation in electronic patient files for patients who underwent a curative resection for primary rectal cancer in 2016. MMR-status was verified in pathology reports from immunohistochemistry or PCR microsatellite instability testing.
Results
MMR-status was determined in 1645 (54.9%) of 3001 stage I-IV rectal cancer patients, of which 46 (2.8%) were dMMR. Median follow up was 50 months (IQR 38-55). MMR-status was determined more often in younger patients. DMMR tumors were more locally advanced (cT4 23.9% vs. 8.8%, P = .010), and more distally located (mean distance to anorectal junction 3.6 cm vs. 5.3 cm, P = .004) than pMMR tumors. While radiological response after neoadjuvant (chemo)radiotherapy was similar, pathological complete response was significantly higher in dMMR compared to pMMR tumors (24.0% vs. 10.0%, P = .039). Four-year local recurrence, distant metastases, cancer-specific or overall survival rate between patients with dMMR or pMMR tumors were similar.
Conclusion
In this population-based cohort, 2.8% of rectal cancers in which MMR-status was determined were subtyped as dMMR. Surprisingly, dMMR was associated with higher pathological complete response rate to neoadjuvant (chemo) radiotherapy than pMMR. MMR-status did not impact oncological outcomes.
关于错配修复缺陷（dMMR）直肠癌的发病率和预后的数据有限。本研究描述了dMMR直肠癌患者的特征，比较了错配修复熟练（pMMR）直肠癌患者在新辅助放疗后的反应和肿瘤预后。方法：在荷兰67个中心进行回顾性横断面队列研究。数据包括患者和肿瘤特征、放射学和病理学报告以及肿瘤随访结果，收集自2016年接受根治性直肠癌切除术患者的电子患者档案文件。免疫组织化学或PCR微卫星不稳定性检测的病理报告证实了核磁共振状态。结果：3001例I-IV期直肠癌患者中有1645例（54.9%）检测到mmr状态，其中46例（2.8%）为dMMR。中位随访50个月（IQR 38-55）。mmr状态在年轻患者中更为常见。DMMR肿瘤比pMMR肿瘤更局部进展（cT4 23.9%比8.8%,P = 0.010），更远端定位（平均距离肛门直肠结3.6 cm比5.3 cm, P = 0.004）。虽然新辅助（化疗）放疗后的放射学反应相似，但dMMR肿瘤的病理完全缓解率明显高于pMMR肿瘤（24.0%比10.0%,P = 0.039）。dMMR或pMMR肿瘤患者的四年局部复发率、远处转移率、癌症特异性生存率或总生存率相似。结论：在这个以人群为基础的队列中，确定mmr状态的2.8%的直肠癌亚型为dMMR。令人惊讶的是，与pMMR相比，dMMR对新辅助（化疗）放疗的病理完全缓解率更高。mmr状态不影响肿瘤预后。
{"title":"Incidence and Outcomes of Patients With Mismatch Repair Deficient Rectal Cancer Operated in 2016: A Nationwide Cohort From The Netherlands","authors":"Eline G.M. van Geffen , Cornelis R.C. Hogewoning , Sanne-Marije J.A. Hazen , Tania C. Sluckin , Marilyne M. Lange , Petur Snaebjornsson , Regina G.H. Beets-Tan , Corrie A.M. Marijnen , Cornelis Verhoef , Myriam Chalabi , Pieter J. Tanis , Miranda Kusters , Tjeerd S. Aukema , behalf of the Dutch Snapshot Research Group","doi":"10.1016/j.clcc.2024.12.003","DOIUrl":"10.1016/j.clcc.2024.12.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Data regarding the incidence and outcomes of mismatch repair deficient (dMMR) rectal cancer is limited. This study characterizes dMMR rectal cancer patients, comparing response after neoadjuvant radiotherapy and oncological outcomes to mismatch repair proficient (pMMR) rectal cancer patients.</div></div><div><h3>Method</h3><div>A retrospective cross-sectional cohort study was conducted in 67 Dutch centers. Data including patient and tumor characteristics, radiological and pathological reports and oncological follow-up outcomes were gathered from documentation in electronic patient files for patients who underwent a curative resection for primary rectal cancer in 2016. MMR-status was verified in pathology reports from immunohistochemistry or PCR microsatellite instability testing.</div></div><div><h3>Results</h3><div>MMR-status was determined in 1645 (54.9%) of 3001 stage I-IV rectal cancer patients, of which 46 (2.8%) were dMMR. Median follow up was 50 months (IQR 38-55). MMR-status was determined more often in younger patients. DMMR tumors were more locally advanced (cT4 23.9% vs. 8.8%, <em>P =</em> .010), and more distally located (mean distance to anorectal junction 3.6 cm vs. 5.3 cm, <em>P =</em> .004) than pMMR tumors. While radiological response after neoadjuvant (chemo)radiotherapy was similar, pathological complete response was significantly higher in dMMR compared to pMMR tumors (24.0% vs. 10.0%, <em>P =</em> .039). Four-year local recurrence, distant metastases, cancer-specific or overall survival rate between patients with dMMR or pMMR tumors were similar.</div></div><div><h3>Conclusion</h3><div>In this population-based cohort, 2.8% of rectal cancers in which MMR-status was determined were subtyped as dMMR. Surprisingly, dMMR was associated with higher pathological complete response rate to neoadjuvant (chemo) radiotherapy than pMMR. MMR-status did not impact oncological outcomes.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 2","pages":"Pages 188-197.e1"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911404","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}
Pub Date : 2025-06-01Epub Date: 2024-12-18DOI: 10.1016/j.clcc.2024.12.004
Barry Maguire , Batuhan Kisakol , Jochen H.M. Prehn , John P. Burke
Background
Special AT-rich binding protein-2 (SATB2) is a nuclear matrix associated protein regulating gene expression which is normally expressed in colonic tissue. Loss of SATB2 expression in colorectal cancer (CRC) has negative implications for prognosis and has been associated with chemotherapy resistance. Furthermore, recent evidence suggests SATB2 may influence immune checkpoint (IC) expression. We hypothesized that SATB2 expression may be associated with altered expression of chemotherapy resistance associated and IC genes.
Methods
Clinicopathologic and gene expression data were extracted from The Cancer Genome Atlas PanCancer Atlas. SATB2 expression was compared by clinicopathologic characteristic and by using multivariate regression analysis to explore associations with chemotherapy and IC gene expression.
Results
About 553 patients were included for analysis. Lower quartile SATB2 expression was associated with worse disease specific survival (P = .04). MSI (P < .001) and mucinous (P < .001) tumors were associated with reduced SATB2 expression independently. SATB2 varied by consensus molecular subtype (P < .001) and was lowest in CMS1. On multivariate analysis, SATB2 was negatively associated with 5-FU related metabolism genes, while more complex but significant relationships were seen with oxaliplatin and irinotecan related genes. Low SATB2 expression was associated with increased expression of PD-1, PD-L1, TIM-3 and CTLA-4 IC genes.
Conclusion
The positive prognostic influence of SATB2 expression is reaffirmed in this study. This effect may be explained by the negative association between SATB2 and 5-FU-resistance related gene expression. Enhanced IC gene expression in SATB2 low cases suggests a potential role for IC inhibition in this setting, but further study is required.
{"title":"SATB2 Expression Affects Chemotherapy Metabolism and Immune Checkpoint Gene Expression in Colorectal Cancer","authors":"Barry Maguire , Batuhan Kisakol , Jochen H.M. Prehn , John P. Burke","doi":"10.1016/j.clcc.2024.12.004","DOIUrl":"10.1016/j.clcc.2024.12.004","url":null,"abstract":"<div><h3>Background</h3><div>Special AT-rich binding protein-2 (SATB2) is a nuclear matrix associated protein regulating gene expression which is normally expressed in colonic tissue. Loss of SATB2 expression in colorectal cancer (CRC) has negative implications for prognosis and has been associated with chemotherapy resistance. Furthermore, recent evidence suggests SATB2 may influence immune checkpoint (IC) expression. We hypothesized that SATB2 expression may be associated with altered expression of chemotherapy resistance associated and IC genes.</div></div><div><h3>Methods</h3><div>Clinicopathologic and gene expression data were extracted from The Cancer Genome Atlas PanCancer Atlas. SATB2 expression was compared by clinicopathologic characteristic and by using multivariate regression analysis to explore associations with chemotherapy and IC gene expression.</div></div><div><h3>Results</h3><div>About 553 patients were included for analysis. Lower quartile SATB2 expression was associated with worse disease specific survival (<em>P</em> = .04). MSI (<em>P</em> < .001) and mucinous (<em>P</em> < .001) tumors were associated with reduced SATB2 expression independently. SATB2 varied by consensus molecular subtype (<em>P</em> < .001) and was lowest in CMS1. On multivariate analysis, SATB2 was negatively associated with 5-FU related metabolism genes, while more complex but significant relationships were seen with oxaliplatin and irinotecan related genes. Low SATB2 expression was associated with increased expression of PD-1, PD-L1, TIM-3 and CTLA-4 IC genes.</div></div><div><h3>Conclusion</h3><div>The positive prognostic influence of SATB2 expression is reaffirmed in this study. This effect may be explained by the negative association between SATB2 and 5-FU-resistance related gene expression. Enhanced IC gene expression in SATB2 low cases suggests a potential role for IC inhibition in this setting, but further study is required.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 2","pages":"Pages 129-134.e7"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967478","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}
Liquid biopsies offer the possibility to evaluate cancer patients using noninvasive approaches. Circulating cell-free DNA (ccfDNA) is 1 of the most used and promising sources. Detecting tumor DNA among ccfDNA (ctDNA) can be used for early cancer detection, treatment response assessment, prognosis, and predictive evaluations. Providing analyses that can increase the quality of patient treatment is very much a joint effort between laboratory scientists and clinicians. With its use approaching clinical practice, it is important for clinicians to be familiar with the basic concepts and analyses behind ctDNA results in a similar way as laboratory scientists should have knowledge of the clinical needs to provide relevant analyses. In this Perspective, we describe the whole process of ctDNA analyses, from the preanalytical standards to reporting/analyzing results, and highlight some important factors that need to be addressed in the process of implementing them to clinical practice.
{"title":"What the Clinician Needs to Know About Laboratory Analyses of Circulating Tumor DNA","authors":"Cecilie Mondrup Jacobsen , Luisa Matos do Canto , Søren Kahns , Torben Frøstrup Hansen , Rikke Fredslund Andersen","doi":"10.1016/j.clcc.2025.01.003","DOIUrl":"10.1016/j.clcc.2025.01.003","url":null,"abstract":"<div><div>Liquid biopsies offer the possibility to evaluate cancer patients using noninvasive approaches. Circulating cell-free DNA (ccfDNA) is 1 of the most used and promising sources. Detecting tumor DNA among ccfDNA (ctDNA) can be used for early cancer detection, treatment response assessment, prognosis, and predictive evaluations. Providing analyses that can increase the quality of patient treatment is very much a joint effort between laboratory scientists and clinicians. With its use approaching clinical practice, it is important for clinicians to be familiar with the basic concepts and analyses behind ctDNA results in a similar way as laboratory scientists should have knowledge of the clinical needs to provide relevant analyses. In this Perspective, we describe the whole process of ctDNA analyses, from the preanalytical standards to reporting/analyzing results, and highlight some important factors that need to be addressed in the process of implementing them to clinical practice.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 2","pages":"Pages 109-119"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434701","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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