Clinical colorectal cancer最新文献

{"title":"Colorectal Cancer Screening at Younger Ages: A Multicutoff Analysis of FIT Performance","authors":"Julia Hibbert,&nbsp;Teresa Seum,&nbsp;Michael Hoffmeister,&nbsp;Hermann Brenner MD MPH","doi":"10.1016/j.clcc.2026.07.001","DOIUrl":"10.1016/j.clcc.2026.07.001","url":null,"abstract":"<div><h3>Background</h3><div>Due to rising early-onset colorectal cancer (CRC) incidence, lowering the starting age for CRC screening is considered in many countries. However, data on diagnostic performance of fecal immunochemical tests (FIT), the most commonly employed CRC screening test, in younger populations remain limited. This study assessed FIT diagnostic performance for detecting advanced neoplasia (AN) at various cutoffs of fecal hemoglobin (Hb) concentrations in individuals aged 55 years or younger.</div></div><div><h3>Methods</h3><div>A total of 1724 participants aged 55 years or younger who underwent screening colonoscopy were recruited in a cross-sectional study conducted in Germany. Fecal Hb concentrations were measured in all participants using FIT (Sentinel FOB Gold) prior to colonoscopy. AN prevalence was determined by screening colonoscopy. FIT performance was evaluated based on positivity rate, sensitivity, specificity, and predictive values at various Hb concentration thresholds.</div></div><div><h3>Results</h3><div>AN was detected in 139 participants (8.1%), including 5 participants (0.3%) with CRC. At the manufacturer-recommended cut off of 17 µg Hb/g stool, positivity rate was 7.7%, yielding a sensitivity of 26.6% (95% confidence interval [CI], 20.0-34.5), specificity of 94.0% (95% CI, 92.7-95.1), positive predictive value (PPV) of 28.0% (95% CI, 21.1-36.2), and negative predictive value (NPV) of 93.6% (95% CI, 92.3-94.7) for AN detection. These measures strongly varied across the range of cutoffs employed in FIT-based screening programs. Men showed higher AN prevalence, positivity rate, sensitivity, and PPV across the investigated Hb range, whereas sex differences in specificity and NPV were minimal.</div></div><div><h3>Conclusion</h3><div>Our study provides detailed quantitative information on diagnostic performance characteristics of FIT in a younger CRC screening population, which may inform and optimize effectiveness and cost-efficiency of CRC screening at younger ages.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 3","pages":"Pages 414-421"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611014","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":"Optimizing Systemic Therapy in Advanced Gastrointestinal Malignancies: Strategies to Minimize Toxicity and Maximize Tolerability","authors":"Sabrina Bulancea,&nbsp;Udhayvir S. Grewal,&nbsp;Marta Wronska,&nbsp;Deepak Vadehra,&nbsp;Nicholas Hornstein,&nbsp;Timothy J. Brown,&nbsp;Michael Shusterman","doi":"10.1016/j.clcc.2026.05.004","DOIUrl":"10.1016/j.clcc.2026.05.004","url":null,"abstract":"<div><div>Advanced gastrointestinal cancers remain a major global health challenge, with rising incidence especially among younger populations. Systemic chemotherapy continues to be the mainstay of care for most patients, but balancing treatment benefit with tolerability is an ongoing concern. Many patients, especially older adults and those with significant medical comorbidities, may struggle with standard dosing due to side effects, yet they are often underrepresented in clinical trials. As a result, real-world practice often relies on adjusting drug doses and schedules to reduce toxicity without compromising outcomes. Personalizing systemic therapy based on patient factors like age, fitness, and individual response can help improve tolerability and maintain quality of life. Emerging evidence supports the use of modified dosing and frequency, but prospective data remain limited. In this review, we discuss current approaches to optimizing systemic therapy for advanced gastrointestinal cancers and the need for practical, patient-centered care pathways.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 3","pages":"Pages 311-320"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221242","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":"Resource Use and Costs of the Low-risk Arm of a Risk-stratified Colorectal Cancer Screening Approach Based on Previous Negative FIT Values: Comparative Analyses With the Standard Approach","authors":"Andrea Buron,&nbsp;Merce Comas,&nbsp;Carmen Guirado-Fuentes,&nbsp;Cristina Barrufet,&nbsp;Cristina Alvarez-Urturi,&nbsp;Xavier Bessa,&nbsp;Josep M. Auge,&nbsp;Isabel Torá-Rocamora,&nbsp;Jaume Grau,&nbsp;Oswaldo Ortiz,&nbsp;Teresa Puig,&nbsp;Monica Pardo,&nbsp;Xavier Castells,&nbsp;Carlo Senore,&nbsp;Maria Sala","doi":"10.1016/j.clcc.2026.05.005","DOIUrl":"10.1016/j.clcc.2026.05.005","url":null,"abstract":"<div><h3>Background</h3><div>Risk-stratified colorectal cancer (CRC) screening may improve benefit-risk ratios and alleviate colonoscopy demands. Utilizing previous faecal immunochemical tests (FIT) values below positivity thresholds is promising due to its high predictive value and availability. This study aims to estimate and compare resources and costs between standard screening (SS and 2-year interval) and risk-stratified protocol (RS and 4-year interval) among low-risk participants (cumulative f-Hb ≤ 3.8 µg/g in 2 consecutive episodes) using retrospective data.</div></div><div><h3>Methods</h3><div>The Barcelona colorectal cancer screening programme biennially invites people aged 50 to 69 years to a FIT (cut-off point 20 µg/g). Negative results lead to reinvitation in 2 years; positive results prompt a colonoscopy appointment. Low-risk participants who underwent 2 additional screenings from 2009-2019 were considered. The SS scenario utilized real resources and costs, whereas the RS simulated outcomes using natural history probabilities. Direct screening and stage-specific CRC treatment costs were obtained.</div></div><div><h3>Results</h3><div>Compared to SS, RS showed a 50% reduction in invitation letters and FITs, less than 4% reduction in nurse visits and colonoscopies, and 49 fewer low-risk and 24 fewer high-risk lesions per 100,000 screenees, with an increase in local CRC and interval cancers. The RS protocol was estimated to generate a 17.4% decrease in screening costs and a 22.6% increase in treatment costs compared to the SS, resulting in an excess cost of 8.5%.</div></div><div><h3>Conclusions</h3><div>These findings will inform the results of experimental studies, and need to be assessed in the context of the entire strategy, since the high-risk group could notably reduce treatment costs through earlier detection.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 3","pages":"Pages 370-378"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284775","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":"The Impact of Lesion Morphology and Resection Strategy on Curative Outcomes in Colorectal Malignant Polyps","authors":"João C. Gonçalves,&nbsp;Ana I. Ferreira,&nbsp;Mariana Souto,&nbsp;Raquel Barros,&nbsp;Sofia Xavier,&nbsp;Pedro B. Carvalho,&nbsp;Joana Magalhães,&nbsp;José Cotter","doi":"10.1016/j.clcc.2026.06.001","DOIUrl":"10.1016/j.clcc.2026.06.001","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal malignant polyps (MPs) appear benign endoscopically but display cancer cell invasion beyond the muscularis mucosae. Their recognition is challenging, as most lack overt signs of submucosal invasion (SMI) despite advances in optical diagnosis. This study aimed to identify the endoscopic features associated with curative resection of MPs.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of patients undergoing colonoscopy at our institution, and those with resected MPs were included.</div></div><div><h3>Results</h3><div>A total of 165 patients were analyzed, 57.6% males, with a mean age of 65 ± 10 years. A total of 170 MPs were resected with a global curative resection rate of 33.5%. Pedunculated polyps demonstrated a significantly higher curative resection rate (50.8%) compared with nonpedunculated lesions (23.4%; <em>P</em> &lt; .001; OR 3.4, 95% CI, 1.74-6.6). On multivariate analysis, piecemeal resection was independently associated with noncurative outcomes for both pedunculated (<em>P</em> = .027) and nonpedunculated polyps (<em>P</em> = .013). In the latter group, indirect signs of deep SMI were also significantly associated with a noncurative resection (<em>P</em> = .01). Supporting these results, the major causes for a noncurative resection were specimen fragmentation (35.5% in pedunculated, 57% in nonpedunculated polyps) and insufficient margins, defined as a vertical margin &lt; 1 mm or R1 resection (41.9% in pedunculated, 36.7% in nonpedunculated polyps).</div></div><div><h3>Conclusions</h3><div>Polyp morphology and resection strategy are key determinants of curative outcomes in MPs. <em>En bloc</em> resection should be achieved in lesions suspected of SMI, as piecemeal removal is a leading cause of noncurative outcomes.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 3","pages":"Pages 396-402.e1"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400125","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":"The Impact of Surgical Resection in Early Onset Colorectal Cancer Patients With Liver Limited Disease","authors":"Andrea Pretta ,&nbsp;Pina Ziranu ,&nbsp;Francesca Bergamo ,&nbsp;Andrea Bottelli ,&nbsp;Federica Marmorino ,&nbsp;Mariapaola Masiello ,&nbsp;Stefano Mariani ,&nbsp;Krisida Cerma ,&nbsp;Filippo Ghelardi ,&nbsp;Paolo Ciracì ,&nbsp;Alessia Lancianese ,&nbsp;Valeria Pusceddu ,&nbsp;Eleonora Perissinotto ,&nbsp;Alberto Giovanni Leone ,&nbsp;Ada Taravella ,&nbsp;Erika Cimbro ,&nbsp;Gianluca Pretta ,&nbsp;Riccardo Cerantola ,&nbsp;Luca Papini ,&nbsp;Clelia Donisi ,&nbsp;Mario Scartozzi","doi":"10.1016/j.clcc.2026.02.002","DOIUrl":"10.1016/j.clcc.2026.02.002","url":null,"abstract":"<div><h3>Background</h3><div>Recent studies have shown an increased incidence of early-onset CRC (EO-CRC), particularly in advanced stages and with metastatic disease. Our study aimed to evaluate the role of metastasectomies related to the clinical and molecular characteristics of EO-CRC patients with liver metastases compared to average-onset CRC (AO-CRC) patients.</div></div><div><h3>Methods</h3><div>We retrospectively collected data from 1123 stage IV colorectal cancers, including 782 with liver metastases, from 5 different Italian institutions. The main objective of the study was to compare the overall survival of liver metastatic EO-CRC and AO-CRC patients who underwent metastasectomy versus those who were not resected.</div></div><div><h3>Results</h3><div>Liver resected EO-CRCs patients showed a statistically significant lower mOS than liver resected AO-CRCs (44.0 vs. 64.0 months, <em>P &lt; .0001</em>). mPFS was also statistically significant lower in EO-CRCs (13.0 vs. 17.0, <em>P &lt; .0001</em>). Same outcomes were found in RAS mut subgroup (37.0 vs. 52.0 months, <em>P</em> &lt; .0001) and in RAS/BRAF wild-type subgroup (50.0 vs. 81.0 months, <em>P</em> &lt; .0001).</div><div>EO-CRC patients showed a higher prevalence of TP53 alterations (56.2%) and a lower of APC mutation (29.9%). EO-CRCs presented a higher frequency of ARID1A (4.4%) and CTNNB1 (3.0%) alterations.</div></div><div><h3>Conclusion</h3><div>The results indicate a worse overall prognosis for EO-CRC patients undergoing metastasectomy compared to average-onset patients. This outcome appears to occur independently of the molecular status. These observations could have a considerable impact on clinical practice and research.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 2","pages":"Pages 258-270"},"PeriodicalIF":3.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461505","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":"Randomized phase III Study of Adding Paclitaxel to Chemoradiotherapy With Capecitabine and Mitomycin C in Squamous Cell Anal Carcinoma","authors":"Sergey S. Gordeyev ,&nbsp;Marina V. Chernykh ,&nbsp;Mikhail Yu. Fedyanin ,&nbsp;Evgeny G. Rybakov ,&nbsp;Nataliya S. Besova ,&nbsp;Valerii A. Ivanov ,&nbsp;Zaman Z. Mamedli","doi":"10.1016/j.clcc.2026.01.002","DOIUrl":"10.1016/j.clcc.2026.01.002","url":null,"abstract":"<div><h3>Purpose</h3><div>In our pilot study adding paclitaxel to chemoradiotherapy (CRT) with capecitabine and mitomycin C (MMC) showed promising efficacy and we aimed to determine whether it could improve progression-free survival (PFS) in a randomized clinical trial setting.</div></div><div><h3>Methods</h3><div>We performed a randomized phase III trial at 2 centers. Enrolled patients with stage I-IIIB SCAC were randomly (1:1) allocated to either CRT with capecitabine and MMC (CRT-CM arm) or CRT with capecitabine, MMC and paclitaxel (CRT-CMP arm). The CRT-CMP regimen comprised 52 to 58 Gy IMRT, paclitaxel 45 mg/m² on days 3, 10, 17, 24, 31, capecitabine 625 mg/m² bid on treatment days and mitomycin C 10 g/m² on day 1. The primary endpoint was PFS. Secondary endpoints were toxicity, overall survival (OS), complete clinical response (cCR) at 12 and 26 weeks.</div></div><div><h3>Results</h3><div>Between January 2016 and February 2020, 87 patients were enrolled in the CRT-CMP arm and 86 patients in the CRT-CM arm. The trial was stopped prematurely because MMC was no longer available in the country. Median follow-up was 50.3 months. Three-year PFS was 84.8% in the CRT-CMP arm and 66.9% in the CRM-CM arm (<em>P</em> = .009). Grade 3 or worse adverse events were observed in 45 (51.7%) patients in the CRT-CMP arm and in 20 (23.3%) patients in the CRT-CM arm (<em>P</em> &lt; .0001). Seventy seven (89.5%) patients in the CRT-CMP arm and 63 (75.9%) patients in the CRM-CM arm had a cCR at 26 weeks (<em>P</em> = .024).</div></div><div><h3>Conclusion</h3><div>Adding paclitaxel to CRT with capecitabine and MMC improves cCR rate and long-term outcomes in SCAC at the cost of higher toxicity.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 2","pages":"Pages 216-224"},"PeriodicalIF":3.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146196237","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":"Circulating Tumor DNA as a Biomarker for Recurrence After Curative Resection of Colorectal Cancer Liver Metastases: A Systematic Review and Meta-Analysis","authors":"Atta Ullah Khan ,&nbsp;Abdul Ahad Mehboob ,&nbsp;Asraa Abdulsahib Yousif ,&nbsp;Awais Ali ,&nbsp;Mustafa Jawad Kadham","doi":"10.1016/j.clcc.2026.01.006","DOIUrl":"10.1016/j.clcc.2026.01.006","url":null,"abstract":"<div><div>Colorectal liver metastases (CRLM) remain a leading cause of cancer-related mortality, with recurrence rates of 50 to 70% following curative-intent hepatic resection. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for minimal residual disease (MRD) detection, yet its prognostic value in resected CRLM has not been systematically quantified. A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines (PROSPERO: CRD420251177140). MEDLINE, Embase, Web of Science, Cochrane CENTRAL, and Scopus were searched through October 2025. Studies evaluating ctDNA as a prognostic biomarker in adults with resected CRLM were included. Hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival (OS) were pooled using random-effects models. Evidence certainty was assessed using GRADE methodology. Ten studies (1034 patients) were included. Postoperative ctDNA positivity was significantly associated with inferior RFS in the MRD window (HR 3.28, 995% CI, 2.58-4.17; I² = 10%) and after adjuvant chemotherapy (HR 8.69, 995% CI, 5.43-13.90; I² = 0%). ctDNA positivity was also associated with reduced OS (HR 7.11, 995% CI, 3.87-13.09). ctDNA detection preceded radiological recurrence by 3.5 to 6.1 months. Preoperative ctDNA was not a statistically significant predictor. ctDNA is a promising prognostic biomarker in resected CRLM, strongly associated with recurrence and mortality. However, prospective randomized trials are needed before routine clinical implementation.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 2","pages":"Pages 181-190.e1"},"PeriodicalIF":3.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146777046","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":"Incidence and Risk Factors of Non-neutropenic Enterocolitis With Adjuvant Capecitabine and Oxaliplatin Chemotherapy in Colorectal Cancer","authors":"Guillaume Roy ,&nbsp;Rakan Okde ,&nbsp;Olivia Cull ,&nbsp;Giulia Pool ,&nbsp;Mélina Boutin","doi":"10.1016/j.clcc.2026.03.002","DOIUrl":"10.1016/j.clcc.2026.03.002","url":null,"abstract":"<div><h3>Background</h3><div>Following the IDEA collaboration, the use of capecitabine and oxaliplatin (CAPOX regimen) for adjuvant colorectal cancer treatment has increased. While CAPOX is associated with higher rates of diarrhea, non-neutropenic enterocolitis (NNE) and related hospitalizations have not been well described.</div></div><div><h3>Patients and Methods</h3><div>We performed a retrospective cohort study of patients treated with adjuvant CAPOX, mFOLFOX6 (infusional 5-fluorouracil, leucovorin, and oxaliplatin), and capecitabine between 2015 and 2023 at 2 hospitals in Quebec, Canada. Data on demographics, oncologic treatments, and complications, including NNE (defined as grade ≥ 2 diarrhea with radiologic ileocolitis) were extracted.</div></div><div><h3>Results</h3><div>A total of 223 patients were included, 82.9% of patients had stage III colorectal cancer, 54.3% received CAPOX, and 40.8% mFOLFOX6. NNE occurred in 12.4% of patients treated with CAPOX versus 1.1% with mFOLFOX6 (odds ratio [OR] 12.736, <em>P</em> = .002). All NNE were grade 3 to 4 events and required hospitalization. The median time to CAPOX-induced NNE onset was 36 days after the first chemotherapy dose. Risk factors for NNE included CAPOX use (OR [vs. mFOLFOX6] OR 12.736, <em>P</em> = .002) and age over 65 years (OR 4.214, <em>P</em> = .006). No difference in relapse-free survival was observed for stage III patients with versus without NNE (hazard ratio 0.247, <em>P</em> = .167).</div></div><div><h3>Conclusion</h3><div>NNE is a significant complication of CAPOX, particularly in patients over 65 years. It occurs early in the treatment course, leads to a high rate of hospitalization, and necessitates careful patient selection and close monitoring during early cycles.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 2","pages":"Pages 283-290"},"PeriodicalIF":3.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719252","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":"Lenvatinib Plus Pembrolizumab for Patients With Previously Treated Advanced Colorectal Cancer: Results From the Phase II LEAP-005 Study","authors":"Iván Victoria Ruiz ,&nbsp;Nataliya V. Uboha ,&nbsp;Rahima Jamal ,&nbsp;Fernando Contreras Mejía ,&nbsp;Mónica Ahumada ,&nbsp;Seock-Ah Im ,&nbsp;Carlos Gomez-Roca ,&nbsp;Ronnie Shapira-Frommer ,&nbsp;Ruth Perets ,&nbsp;Eduardo Yañez ,&nbsp;Corina Dutcus ,&nbsp;Chinyere E. Okpara ,&nbsp;Razi Ghori ,&nbsp;Fan Jin ,&nbsp;Roman Groisberg ,&nbsp;Eduardo Castanon","doi":"10.1016/j.clcc.2026.01.003","DOIUrl":"10.1016/j.clcc.2026.01.003","url":null,"abstract":"<div><h3>Background</h3><div>Current treatments for patients with previously treated metastatic colorectal cancer (CRC) have poor outcomes. LEAP-005 (ClinicalTrials.gov, NCT03797326) was a multicohort, open-label phase II study evaluating the efficacy and safety of lenvatinib plus pembrolizumab in participants with previously treated selected solid tumors. We report findings from the LEAP-005 CRC cohort.</div></div><div><h3>Patients and Methods</h3><div>Participants aged ≥ 18 years with advanced (metastatic and/or unresectable) CRC with 2 prior lines of systemic therapy were eligible for the CRC cohort of LEAP-005. Participants received oral lenvatinib (20 mg/day) plus intravenous pembrolizumab (200 mg Q3W) combination therapy (Arm 1) or lenvatinib (24 mg/day) monotherapy (Arm 2). Dual primary endpoints were objective response rate (ORR) per RECIST version 1.1 and safety. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), and overall survival (OS).</div></div><div><h3>Results</h3><div>135 participants were enrolled in the CRC cohort (Arm 1, <em>n</em> = 105; Arm 2, <em>n</em> = 35). In Arm 1, ORR was 14% (95% CI, 8-23), median PFS was 3.4 (95% CI, 2.1-4.1) months, and OS was 8.7 (95% CI, 7.0-10.0) months. In Arm 2, ORR was 7% (95% CI, 1-22), median PFS was 3.4 (95% CI, 2.1-4.2) months, and OS was 7.7 (95% CI, 5.6-14.8) months. Treatment-related AEs occurred in 96% of participants (grade 3/4, 63%) in Arm 1 and 97% (grade 3/4, 63%) in Arm 2. One participant in Arm 1 died due to treatment-related intestinal perforation.</div></div><div><h3>Conclusion</h3><div>Lenvatinib plus pembrolizumab demonstrated antitumor activity in participants with advanced CRC with 2 prior lines of treatment. No new safety signals were identified.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 2","pages":"Pages 225-238.e2"},"PeriodicalIF":3.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322781","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":"Consistency of Radiological Staging in Resectable Mismatch-Repair Proficient Colon Cancer: An Interobserver Agreement Study","authors":"Vincenzo Nasca ,&nbsp;Gabriele Tinè ,&nbsp;Marta Vaiani ,&nbsp;Raffaella Vigorito ,&nbsp;Francesca Gabriella Greco ,&nbsp;Alessandra Casale ,&nbsp;Gaetano Ramondo ,&nbsp;Alessandro Rago ,&nbsp;Luigi Asmundo ,&nbsp;Cristiano Sgrazzutti ,&nbsp;Dania Cioni ,&nbsp;Roberto Francischello ,&nbsp;Emanuele Neri ,&nbsp;Marco Calandri ,&nbsp;Carolina Sciortino ,&nbsp;Laura Sanchez ,&nbsp;Margherita Ambrosini ,&nbsp;Isacco Montroni ,&nbsp;Federica Marmorino ,&nbsp;Chiara Cremolini ,&nbsp;Giovanni Randon","doi":"10.1016/j.clcc.2026.01.007","DOIUrl":"10.1016/j.clcc.2026.01.007","url":null,"abstract":"<div><h3>Background</h3><div>Reproducibility and accuracy of radiological classification with CT imaging is crucial for selecting patients with resectable, nonmetastatic colon cancer (CC) who may benefit from neoadjuvant strategies.</div></div><div><h3>Methods</h3><div>We evaluated interobserver agreement among 4 independent radiology equipes in classifying patients with resectable, nonmetastatic, mismatch repair proficient CC with available preoperative CT imaging. Radiology equipes were blinded to clinical and pathological data, and categorized tumors according to FOxTROT and Node-RADS criteria, classifying T (T1/2, T3, T4, including stratification by extramural invasion [EMI]) and N status. The primary endpoint was interobserver agreement (Cohen’s κw); secondary endpoints included concordance with pathological staging and diagnostic performance metrics. Bayesian and cross-validation analyses assessed robustness.</div></div><div><h3>Results</h3><div>Among 109 patients (32.1% pT2, 33.9% pT3, 33.9% pT4; 45.9% pN0/1c, 54.1% pN1-2), overall interobserver agreement indicated inadequate concordance for both cT (κw = 0.56; 95% CI, 0.43-0.68) and cN category (κw = 0.51; 95% CI, 0.36-0.66). Of 109 patients, 38 (35%) were classified identically for T stage by all 4 Radiology groups, while 74 (68%) showed some disagreement. When considering risk stratification into high risk (cT3 with EMI ≥5 mm or cT4) versus low risk (cT1/cT2 or cT3 with EMI &lt;5 mm) 56 patients (51%) received the same classification all 4 groups, and 95 patients (87%) were classified consistently by at least 3 groups. Overall concordance between radiology and pathological staging was inadequate for both T (κw = 0.47; 95% CI, 0.35-0.57) and N staging (κw = 0.16; 95% CI, 0.07-0.33). The mean sensitivity and specificity of CT scan for pT3/T4 and pT4 were 72%/78% and 33%/93%.</div></div><div><h3>Conclusions</h3><div>Identification of high-risk features in resectable CC by CT scan should be implemented to guide patients’ selection for neoadjuvant therapies.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 2","pages":"Pages 239-248.e6"},"PeriodicalIF":3.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446501","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}