Clinical colorectal cancer最新文献

{"title":"A National Cancer Database Analysis of the Characteristics and Outcome of Colon Cancer According to Type of Preexisting Adenoma","authors":"Sameh Hany Emile ,&nbsp;Nir Horesh ,&nbsp;Victor Strassmann ,&nbsp;Zoe Garoufalia ,&nbsp;Rachel Gefen ,&nbsp;Peige Zhou ,&nbsp;Steven D. Wexner","doi":"10.1016/j.clcc.2024.09.002","DOIUrl":"10.1016/j.clcc.2024.09.002","url":null,"abstract":"<div><h3>Background</h3><div>The vast majority of colon cancers occur in pre-existing adenomas. Little is known about the impact of adenoma type on behavior and outcome of subsequent carcinomas. The present study aimed to assess characteristics, behavior, and outcome of colon adenocarcinoma based on histologic type of pre-existing adenoma.</div></div><div><h3>Methods</h3><div>US-National Cancer Database was searched between 2005 and 2019 for patients with colonic adenocarcinoma with known adenoma type who underwent colectomy. Patients were divided into 3 groups according to type of adenoma in which carcinoma developed: tubular adenoma (TA), villous adenoma (VA), and tubulovillous adenoma (TVA)-associated carcinomas. The main outcome of the study was 5-year overall survival (OS).</div></div><div><h3>Results</h3><div>66,854 patients were included. 79.3% of carcinomas originated from TVA, 10.2% from VA, and 0.5% from TA. Patients with adenocarcinoma in VA were more often female whereas carcinomas in TA affected patients of Asian race more often. Approximately one-third of carcinomas in villous and tubulovillous adenomas were in the cecum whereas one-third of carcinomas in tubular adenomas were in the sigmoid colon. More TA-associated carcinomas were of clinical T1-2 stage (30.2% vs. 20.8%; <em>P</em> &lt; .001), clinical N0 stage (69% vs. 62.2%, <em>P</em> &lt; .001), and high grade (15.9% vs. 11.5%, <em>P</em> &lt; .001) compared to VA-associated carcinomas. Patients with TA-associated carcinomas had longer mean OS than patients with VA and TVA-associated carcinomas (130.1 vs. 116.9 vs. 123.5 months, <em>P</em> &lt; .0001).</div></div><div><h3>Conclusions</h3><div>Adenocarcinomas that arose in TA had more T1-2 stage and N0 stage, higher grade, and longer OS than did adenocarcinomas that arose in VA and TVA.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 56-63"},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different Metabolic Associations of Hepatitis C With Colon and Rectal Cancers: A 9-Year Nationwide Population-Based Cohort Study","authors":"Chun-Wei Chen ,&nbsp;Jur- Shan Cheng ,&nbsp;Tsung-Hsing Chen ,&nbsp;Chia-Jung Kuo ,&nbsp;Hsin-Ping Ku ,&nbsp;Rong-Nan Chien ,&nbsp;Ming-Ling Chang","doi":"10.1016/j.clcc.2024.08.005","DOIUrl":"10.1016/j.clcc.2024.08.005","url":null,"abstract":"<div><h3>Background</h3><div>Whether HCV infection is associated with colorectal cancer (CRC) development remains inconclusive.</div></div><div><h3>Methods</h3><div>A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database was conducted.</div></div><div><h3>Results</h3><div>From 2003 to 2012, 1:2:2 propensity score-matched HCV-treated [interferon-based therapy ≥ 6 months, surveys for CRC (n = 9017), colon cancer (CC) (n = 9,022) and rectal cancer (RC) (n = 9,033), HCV-untreated and HCV-uninfected cohorts CRC (n = 18034), CC (n = 18,044) and RC (n = 18,066) were enrolled. The HCV-uninfected cohort had the lowest cumulative incidence of CRC (0.117%; 95% CI: 0.062%-0.207%), whereas the HCV-treated (0.966%; 0.375-2.122%) and HCV-untreated (0.807%; 0.485%-1.280%) cohorts had similar incidences (<em>P</em> = <em>.</em>0662); HCV infection [reference: HCV-untreated cohort, HCV-treated: hazard ratio (HR): 0.598; 95% CI HR: 0.337-1.059; HCV-uninfected: 0.250; 0.138-0.456] and age ≥ 49 years (3.128;1.751-5.59) were associated with CRC development. The HCV-untreated cohort had the highest cumulative incidence of CC (0.883%; 0.371-1.839%), while HCV-treated (0.478%; 0.110-1.518%) and HCV-uninfected cohorts (0.147%; 0.071-0.284%) had similar incidences (<em>P</em> = .4853); HCV infection (HCV-treated: 0.474; 0.232-0.971; HCV-uninfected: 0.338; 0.184-0.62), male sex (2.18; 1.301-3.654), age≥ 49 years (4.818; 2.123-10.936) and diabetes (1.983; 1.205-3.262) were associated with CC development. A higher RC cumulative incidence was noted in the HCV-untreated cohort (0.332%; 0.151-0.664%) than in the HCV-uninfected cohort (0.116%; 0.054-0.232%) (<em>P</em> = .0352); HCV infection (HCV-treated: 0.691; 0.295-1.617; HCV-uninfected: 0.424; 0.207-0.867), age ≥ 49 years (3.745, 1.576-8.898) and stroke (3.162; 1.366-7.322) were associated with RC development.</div></div><div><h3>Conclusions</h3><div>The baseline associations were HCV infection and age ≥ 49 years with CRC; male sex and diabetes with CC; and stroke with RC. Anti-HCV therapy might reverse the risk of HCV-related CC but not RC.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 39-47.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334386","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}

{"title":"Rationale and Design of the COPERNIC Trial: A Study of On-treatment ctDNA Changes in Chemo-refractory Colorectal Cancer Patients","authors":"Irene Assaf ,&nbsp;Giacomo Bregni ,&nbsp;Geraldine Anthoine ,&nbsp;Thomas Aparicio ,&nbsp;Pascal Artru ,&nbsp;Meher Ben Abdelghani ,&nbsp;Marc Buyse ,&nbsp;Benoist Chibaudel ,&nbsp;Elisabeth Coart ,&nbsp;Marie Diaz ,&nbsp;Camille Evrard ,&nbsp;Karen Geboes ,&nbsp;François Ghiringhelli ,&nbsp;Francesco Puleo ,&nbsp;Judith Raimbourg ,&nbsp;Timon Vandamme ,&nbsp;Marc Van den Eynde ,&nbsp;Alain Hendlisz ,&nbsp;Francesco Sclafani","doi":"10.1016/j.clcc.2024.08.004","DOIUrl":"10.1016/j.clcc.2024.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Evidence suggests that ctDNA may be a reliable biomarker to monitor metastatic colorectal cancer (CRC) evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies.</div></div><div><h3>Methods</h3><div>COPERNIC is an international, multicenter clinical trial. The pilot study aims to confirm the predictive potential of early on-treatment ctDNA dynamics, and inform the design of a larger ctDNA-driven trial. Advanced CRC patients who are candidates for ≥3rd lines of systemic therapy undergo longitudinal blood sample collection during treatment (day 1, 15 and 29 for 2- or 4-weekly treatment regimens; day 1, 22 and 43 for 3-weekly treatment regimens) and at each imaging assessment. ctDNA analyses are carried out with the FoundationOne Liquid CDx and FoundationOneMonitor assays, and ctDNA changes during treatment are correlated with radiologic response (as assessed every 8-12 weeks by RECIST v1.1). The primary objective is to select the optimal timepoint and cut-off value for early ctDNA changes (at day 15/22) to predict progressive disease as best radiological response with a high positive predictive value. The cut-off value for ctDNA will be defined based on nonparametric ROC-curves with bootstrapping. Based on the expected rate of progressive disease and statistical assumptions, 109 patients are needed to be screened to have 87 assessable patients. COPERNIC is sponsored by the Institut Jules Bordet, and supported by Roche and Foundation Medicine. Recruitment is open in 13 centres across Belgium and France. The study is registered with clinicaltrials.gov (NCT05487248).</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 101-105"},"PeriodicalIF":3.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334388","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}

{"title":"Fruquintinib-Associated Posterior Reversible Encephalopathy Syndrome in a Patient With Multiply Metastatic Rectal Cancer","authors":"Caroline B. Ledet ,&nbsp;Ugur Sener ,&nbsp;Derek R. Johnson ,&nbsp;Kimberly Ku ,&nbsp;Thorvardur R. Halfdanarson","doi":"10.1016/j.clcc.2024.08.006","DOIUrl":"10.1016/j.clcc.2024.08.006","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Antiangiogenic agents are frequently used in the treatment of malignancies, such as colorectal cancer. Posterior reversible encephalopathy syndrome (PRES), a clinicoradiographic syndrome characterized by headache, encephalopathy, seizures, and characteristic magnetic resonance imaging (MRI) changes, is a rare but known complication of antiangiogenic therapies.</div></span></li><li><span>•</span><span><div>Fruquintinb is a tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF) receptors and has been recently approved for the treatment of colorectal cancer refractory to prior standard of care therapies. To date, only 1 other case of PRES associated with fruquintinib has been described. Our case highlights the possibility of PRES association with this novel antiangiogenic and emphasizes the importance of early recognition and management of this rare but potentially life-threatening treatment complication.</div></span></li><li><span>•</span><span><div>Our case underscores that prior tolerance of 1 antiangiogenic does not preclude occurrence of PRES associated with another agent from the same class.</div></span></li></ul></div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 98-100"},"PeriodicalIF":3.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334387","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}

{"title":"KRAS G12C Inhibitors in the Treatment of Metastatic Colorectal Cancer","authors":"","doi":"10.1016/j.clcc.2024.05.004","DOIUrl":"10.1016/j.clcc.2024.05.004","url":null,"abstract":"<div><p><span>KRAS mutations contribute substantially to the overall colorectal cancer burden and have long been a focus of </span>drug development<span><span> efforts. After a lengthy preclinical road, KRAS inhibition via the G12C allele has finally become a therapeutic reality. Unlike in NSCLC, early studies of KRAS inhibitors in CRC struggled to demonstrate single agent activity. Investigation into these tissue-specific treatment differences has led to a deeper understanding of the complexities of MAPK signaling and the diverse adaptive feedback responses to KRAS inhibition. EGFR reactivation has emerged as a principal resistance mechanism to KRAS inhibitor </span>monotherapy. Thus, the field has pivoted to dual EGFR/KRAS blockade with promising efficacy. Despite significant strides in the treatment of KRAS G12C mutated CRC, new challenges are on the horizon. Alternative RTK reactivation and countless acquired molecular resistance mechanisms have shifted the treatment goalpost. This review focuses on the historical and contemporary clinical strategies of targeting KRAS G12C alterations in CRC and highlights future directions to overcome treatment challenges.</span></p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 3","pages":"Pages 199-206"},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141031570","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}

{"title":"Clinical and Molecular Variables Associated With Early Progression to Checkpoint Inhibitors in MSI-High Metastatic Colorectal Cancer: A Retrospective Cohort Study","authors":"L. Hulst,&nbsp;S. Cappuyns,&nbsp;F. Peeters,&nbsp;F. Vulsteke,&nbsp;F. Van Herpe,&nbsp;E. Van Cutsem,&nbsp;J. Dekervel","doi":"10.1016/j.clcc.2024.06.004","DOIUrl":"10.1016/j.clcc.2024.06.004","url":null,"abstract":"<div><h3>Background</h3><p>About one third of patients with deficient mismatch repair/microsatellite instability-high metastatic colorectal cancer (dMMR/MSI-H mCRC) experience primary resistance or early progression on immune checkpoint inhibitors (ICI), while others benefit from exceptionally long-lasting responses. In this single-centre retrospective study, we aimed to identify variables associated with improved overall survival (OS) as well as early disease progression.</p></div><div><h3>Methods</h3><p>All dMMR/MSI-H mCRC patients treated with ICI between 2014 and 2022 were included. Baseline patient demographics, tumour characteristics as well response and outcome data were recorded. OS was estimated using the Kaplan–Meier method. Uni- and multivariate cox regression analysis was used to identify parameters associated with improved OS. Clinicopathological factors associated with early progression (≤ 12 months after treatment initiation) were assessed using uni- and multivariate logistic regression analysis.</p></div><div><h3>Results</h3><p>About 84 ICI-treated dMMR/MSI-H mCRC patients were included. Progressive disease occurred in 37 (44%) patients, but only in 11 (19%) patients with disease control at 12 months. Median OS was 80 months and improved outcome was associated with a lower neutrophile-to-lymphocyte ratio (NLR) (<em>P</em> = .004) and the presence of immune-related adverse events (irAEs) (<em>P</em> = .015). Early progression was associated with poor performance status (<em>P</em> = .036), a higher blood CRP level (<em>P</em> = .033) and absence of irAEs (<em>P</em> = .002).</p></div><div><h3>Conclusion</h3><p>Disease progression in ICI-treated dMMR/MSI-H mCRC rarely occurs in patients experiencing disease control for at least 12 months. Performance status, presence of immune-related adverse events, CRP levels, CEA levels and NLR can be helpful to identify those patients that may benefit from ICI treatment, guiding clinicians in therapeutic decisions.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 3","pages":"Pages 230-237.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696877","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}

{"title":"Clinical Outcomes in T4 and/or N2 Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy: A Retrospective Study","authors":"","doi":"10.1016/j.clcc.2024.04.005","DOIUrl":"10.1016/j.clcc.2024.04.005","url":null,"abstract":"<div><h3>Introduction</h3><p><span>Total neoadjuvant therapy (TNT) in the management of locally advanced </span>rectal cancer<span> (LARC) did not show survival benefit over the standard long course chemoradiotherapy. Trials of TNT did not address the impact of each risk feature in isolation from other high-risk features.</span></p></div><div><h3>Methodology</h3><p>In this retrospective study, we describe the clinical outcomes of patients with T4 and/or N2 rectal adenocarcinoma<span> who were treated with chemoradiotherapy<span> followed by total mesorectal excision (TME). After obtaining the local regulatory approvals, demographic and clinical data were collected for patients in Manitoba between January 2007 and December 2019.</span></span></p></div><div><h3>Results</h3><p><span><span>The cohort included 331 patients. 61 patients had T4-only disease and 218 had N2-only disease. Mean age was 59.65 years. 74.3% received adjuvant chemotherapy (ACT), but only 56.5% completed the planned course. R0 resection was achieved in 93.4% of patients (78.7% and 97.2% in T4 and N2, respectively). Median follow up was 4.93 years. 3-year overall recurrence rate was 29%. 3-year locoregional recurrence (LRR) rate was 8% (16% and 6% in T4 and N2, respectively). 3-year </span>overall survival<span> (OS) rate was 84% in the whole cohort (72.6% and 87.1% in T4 and N2, respectively). Incomplete surgical resection was a poor prognostic factor for both OS and LRR. ACT was associated with a survival benefit in the whole cohort (</span></span><em>P</em> = .001) and in the N2 sub-cohort (<em>P</em> = 003) but there was no survival benefit observed in T4 sub-cohort. ACT did not have an impact on LRR.</p></div><div><h3>Conclusions</h3><p>Achieving R0 resection in LARC with neoadjuvant therapy improves recurrence and survival rates. T4 disease carries a worse clinical outcome than N2 and consideration should be given to upstage T4 to stage III. Different high-risk features in LARC predict different clinical outcomes. In the era of TNT, personalization of treatment strategy based on these factors could potentially improve outcomes.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 3","pages":"Pages 251-257"},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141139045","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}

{"title":"A Phase II, Open-Label, Randomized Trial of Durvalumab With Olaparib or Cediranib in Patients With Mismatch Repair—Proficient Colorectal or Pancreatic Cancer","authors":"","doi":"10.1016/j.clcc.2024.05.002","DOIUrl":"10.1016/j.clcc.2024.05.002","url":null,"abstract":"<div><h3>Background</h3><p>The use of immunotherapy in mismatch repair proficient colorectal cancer (pMMR-CRC) or pancreatic adenocarcinoma (PDAC) is associated with limited efficacy. DAPPER (NCT03851614) is a phase 2, basket study randomizing patients with pMMR CRC or PDAC to durvalumab with olaparib (durvalumab + olaparib) or durvalumab with cediranib (durvalumab + cediranib).</p></div><div><h3>Methods</h3><p>PDAC or pMMR-CRC patients were randomized to either durvalumab+olaparib (arm A), or durvalumab + cediranib (arm B). Co-primary endpoints included pharmacodynamic immune changes in the tumor microenvironment (TME) and safety. Objective response rate, progression-free survival (PFS) and overall survival (OS) were determined. Paired tumor samples were analyzed by multiplexed immunohistochemistry and RNA-sequencing.</p></div><div><h3>Results</h3><p>A total of 31 metastatic pMMR-CRC patients were randomized to arm A (n = 16) or B (n = 15). In 28 evaluable patients, 3 patients had stable disease (SD) (2 patients treated with durvalumab + olaparib and 1 patient treated with durvalumab + cediranib) while 25 had progressive disease (PD). Among patients with PDAC (n = 19), 9 patients were randomized to arm A and 10 patients were randomized to arm B. In 18 evaluable patients, 1 patient had a partial response (unconfirmed) with durvalumab + cediranib, 1 patient had SD with durvalumab + olaparib while 16 had PD. Safety profile was manageable and no grade 4-5 treatment-related adverse events were observed in either arm A or B. No significant changes were observed for CD3+/CD8+ immune infiltration in on-treatment biopsies as compared to baseline for pMMR-CRC and PDAC independent of treatment arms. Increased tumor-infiltrating lymphocytes at baseline, low baseline CD68+ cells and different immune gene expression signatures at baseline were associated with outcomes.</p></div><div><h3>Conclusions</h3><p>In patients with pMMR-CRC or PDAC, durvalumab + olaparib and durvalumab + cediranib showed limited antitumor activity. Different immune components of the TME were associated with treatment outcomes.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 3","pages":"Pages 272-284.e9"},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S153300282400032X/pdfft?md5=cb2ff5fb09d59f492d2512c0d4a0d319&pid=1-s2.0-S153300282400032X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141042333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRAFV600E-Mutant Metastatic Colorectal Cancer: Current Evidence, Future Directions, and Research Priorities","authors":"","doi":"10.1016/j.clcc.2024.04.004","DOIUrl":"10.1016/j.clcc.2024.04.004","url":null,"abstract":"<div><p><em>BRAF^V600E</em><span>-mutant metastatic colorectal cancer<span> represents a distinct molecular phenotype known for its aggressive biological behavior, resistance to standard therapies, and poor survival rates. Improved understanding of the biology of the </span></span><em>BRAF</em><span> oncogene has led to the development of targeted therapies that have paved the way for a paradigm shift in managing this disease. However, despite significant recent advancements, responses to targeted therapies are short-lived, and several challenges remain. In this review, we discuss how progress in treating </span><em>BRAF^V600E</em><span><span>-mutant metastatic colorectal cancer has been made through a better understanding of its unique biological and </span>clinical features. We provide an overview of the evidence to support current treatment approaches and discuss critical areas of need and future research strategies that hold the potential to refine clinical practice further. We also discuss some challenging aspects of managing this disease, particularly the complexity of acquired resistance mechanisms that develop under the selective pressure of targeted therapies and rational strategies being investigated to overcome them.</span></p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 3","pages":"Pages 215-229"},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141060240","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}

{"title":"Use of FOLFOXIRI Plus Bevacizumab and Subsequent Therapies in Metastatic Colorectal Cancer: An Age-Stratified Analysis","authors":"","doi":"10.1016/j.clcc.2024.05.001","DOIUrl":"10.1016/j.clcc.2024.05.001","url":null,"abstract":"<div><h3>Background</h3><p>Treatment recommendations for metastatic colorectal cancer (mCRC) do not differ by age group; nevertheless, aggressive multiagent chemotherapy comprising FOLFOXIRI+bevacizumab (triplet+bev) is routinely administered in younger patients. This study analyzed real-world data on index triplet+bev use and subsequent systemic therapies.</p></div><div><h3>Materials and Methods</h3><p>This retrospective, observational cohort study was conducted in patients aged ≥ 18 years with mCRC, who were initiated on triplet+bev. Data were derived from the Optum de-identified electronic health record dataset.</p></div><div><h3>Results</h3><p>Of 36,056 patients, 14%, 36%, and 50% were aged 18-49, 50-64, and ≥ 65 years, respectively. During the study period (2010-2021), triplet+bev use increased in patients aged 18-49 years (1%-4%) but remained at approximately 3% and 1% in patients aged 50-64 and ≥ 65 years, respectively. Patient demographics and clinical characteristics varied slightly; of patients receiving triplet+bev (n = 921) versus nontriplet+bev (n = 35,132) most were male (57% vs. 52%), resided in the Midwest (54% vs. 49%) and Northeast (18% vs. 14%) US regions, and had secondary malignancies (86% vs. 73%). Following triplet+bev, most patients received subsequent therapies (including continued triplet component therapies; 97%) or subsequent “new” therapies (therapies that did not include any agents comprising triplet+bev; 57%), most frequently EGFR inhibitors (28%) and regorafenib (21%), with a similar trend among all age groups.</p></div><div><h3>Conclusions</h3><p>Overall, this study shows that younger patients with mCRC are more likely to receive first-line triplet+bev. These results also reveal that nonchemotherapy options are often used beyond first-line triplet chemotherapy for patients with mCRC.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 3","pages":"Pages 258-271.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1533002824000318/pdfft?md5=e861cd6529b5d79baa26e8835e2140a2&pid=1-s2.0-S1533002824000318-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141036632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}