Clinical colorectal cancer最新文献

{"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":"2025-03-01","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":"Chemotherapy Rechallenge or Reintroduction Compared to Regorafenib or Trifluridine/Tipiracil for Pretreated Metastatic Colorectal Cancer Patients: A Propensity Score Analysis of Treatment Beyond Second Line (Proserpyna Study)","authors":"M.A. Calegari ,&nbsp;I.V. Zurlo ,&nbsp;E. Dell'Aquila ,&nbsp;M. Basso ,&nbsp;A. Orlandi ,&nbsp;M. Bensi ,&nbsp;F. Camarda ,&nbsp;A. Anghelone ,&nbsp;C. Pozzo ,&nbsp;I. Sperduti ,&nbsp;L. Salvatore ,&nbsp;D. Santini ,&nbsp;D.C. Corsi ,&nbsp;E. Bria ,&nbsp;G. Tortora","doi":"10.1016/j.clcc.2024.06.002","DOIUrl":"10.1016/j.clcc.2024.06.002","url":null,"abstract":"<div><h3>Background</h3><div><span>The optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, </span>REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated.</div></div><div><h3>Patients and methods</h3><div>PROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses.</div></div><div><h3>Results</h3><div>Data referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 <em>vs.</em> 6.5 months), PFS (6.1 <em>vs.</em> 3.5 months) and RR (28.6% <em>vs.</em> 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses.</div></div><div><h3>Conclusions</h3><div>Although the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 1-10.e4"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141405704","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 of Elective Early Discontinuation of Immunotherapy Based on Objective Response in Microsatellite Instability-High Metastatic Colorectal Cancer","authors":"Annie Xiao ,&nbsp;Xiaochen Li ,&nbsp;Chongkai Wang ,&nbsp;Marwan Fakih","doi":"10.1016/j.clcc.2024.08.001","DOIUrl":"10.1016/j.clcc.2024.08.001","url":null,"abstract":"<div><h3>Background</h3><div>Patients with microsatellite-high (MSI-H) metastatic colorectal cancers (CRC) may experience long-lasting benefit from immune checkpoint inhibitors (ICI) upon stopping therapy. However, optimal timing and patient selection criteria for early treatment withdrawal remain undefined. In this single-center retrospective study, we characterized the clinical response and associated survival outcomes of patients who received elective early versus late treatment discontinuation.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed patients with MSI-H metastatic CRC treated with ICI therapy from May 2015 to April 2024. Early ICI discontinuation was defined as treatment withdrawal before 2 years, and late ICI discontinuation as after 2 years. Response was assessed using Response Evaluation Criteria in Solid Tumors. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. Efficacy outcomes between early and late ICI discontinuation groups were compared using a log-rank test.</div></div><div><h3>Results</h3><div>Of 36 patients with MSI-H metastatic CRC, 12 underwent elective early ICI discontinuation and 9 experienced late ICI discontinuation. After a median follow-up of 32 months post-treatment, 91.7% (11/12) in the early discontinuation group remain off therapy without progression. PFS and OS outcomes between the early and late discontinuation groups were similarly favorable (<em>P</em> = .88 and <em>P</em> = .85, respectively), despite a 12-month difference in median duration of ICI therapy (13.3 and 25.6 months, respectively). The most common reason for elective early treatment discontinuation was clinical remission (n = 10), defined as a complete response, or a partial response with negative PET and/or ctDNA testing.</div></div><div><h3>Conclusions</h3><div>Early ICI discontinuation guided by response criteria resulted in low rates of recurrence. Survival outcomes between early and late ICI discontinuation groups were comparable, suggesting that treatment duration can be individualized based on clinical response without compromising favorable long-term prognosis.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 32-38.e1"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209166","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":"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":"2025-03-01","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":"Trifluridine/Tipiracil Based Chemoradiation in locally Advanced Rectal Cancer: The Phase I/II TARC Trial","authors":"Benjamin Thiele ,&nbsp;Alexander Stein ,&nbsp;Christoph Schultheiß ,&nbsp;Lisa Paschold ,&nbsp;Hanna Jonas ,&nbsp;Eray Goekkurt ,&nbsp;Jörn Rüssel ,&nbsp;Gunter Schuch ,&nbsp;Jan Wierecky ,&nbsp;Marianne Sinn ,&nbsp;Joseph Tintelnot ,&nbsp;Cordula Petersen ,&nbsp;Kai Rothkamm ,&nbsp;Eik Vettorazzi ,&nbsp;Mascha Binder","doi":"10.1016/j.clcc.2024.06.003","DOIUrl":"10.1016/j.clcc.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><div>Optimizing functional outcomes and securing long-term remissions are key goals in managing patients with locally advanced rectal cancer. In this proof-of-concept study, we set out to further optimize neoadjuvant therapy by integrating the radiosensitizer trifluridine/tipiracil and explore the potential of cell free tumor DNA (ctDNA) to monitor residual disease.</div></div><div><h3>Methods</h3><div>About 10 patients were enrolled in the phase I dose finding part which followed a 3 + 3 dose escalation design. Tipiracil/trifluridine was administered concomitantly to radiotherapy. ctDNA monitoring was performed before and after chemoradiation with patient-individualized digital droplet PCRs.</div></div><div><h3>Results</h3><div>No dose-limiting toxicities were observed at the maximum tolerated dose level of 2 × 35 mg/m² trifluridine/tipiracil. There were 9 grade 3 adverse events, of which 8 were hematologic with anemia and leukopenia. Chemoradiation yielded a pathological complete response in 1 out of 8 assessable patients, downstaging in nearly all patients, and 1 clinical complete response referred for watchful waiting. Three of 4 assessable patients with residual tumor cells at pathological assessment remained liquid biopsy positive after chemoradiation, but 1 turned negative.</div></div><div><h3>Conclusion</h3><div>In this exploratory phase I trial, the novel combination of neoadjuvant trifluridine/tipiracil and radiotherapy proved to be feasible, tolerable, and effective. However, the application of liquid biopsy as a potential marker for therapeutic de-escalation in the neoadjuvant setting requires additional research and prospective validation.</div><div>The trial was registered at ClinicalTrials.gov: NCT04177602.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 11-17"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141574539","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":"Neoadjuvant Immunotherapy for Patients With Microsatellite Instability-High or POLE-Mutated Locally Advanced Colorectal Cancer With Bulky Tumors: New Optimization Strategy","authors":"Yingjie Li ,&nbsp;Fei Liang ,&nbsp;Zhongwu Li ,&nbsp;Xiaoyan Zhang ,&nbsp;Aiwen Wu","doi":"10.1016/j.clcc.2024.07.001","DOIUrl":"10.1016/j.clcc.2024.07.001","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the efficacy and safety of neoadjuvant immunotherapy for patients with microsatellite instability-high (MSI-H) or DNA polymerase ε (POLE)-mutated locally advanced colorectal cancer (LACRC) with bulky tumors. </div></div><div><h3>Patients</h3><div>We retrospectively reviewed 22 consecutive patients with MSI-H or POLE-mutated LACRC with bulky tumors (&gt;8 cm in diameter) who received preoperative programmed death-1 blockade, with or without CapOx chemotherapy. </div></div><div><h3>Main Outcome Measures</h3><div>Pathological complete response (pCR), clinical complete response (cCR), toxicity, R0 resection rate, and complications were evaluated. Survival outcomes were analyzed using the Kaplan-Meier method. Multiplex immunofluorescence analysis were performed before and after treatment. </div></div><div><h3>Results</h3><div>The incidence of immune-related adverse events (irAEs) was 36.4% (8/22). Five of 22 patients presented with surgical emergencies, most commonly perforation or obstruction. The 22 patients underwent a median 4 (1-8) cycles. Two patients were evaluated as cCR and underwent a watch and wait strategy. The R0 resection rate was 100.0% (20/20) and pCR rate was 70.0% (14/20). Twelve of 14 cT4b patients (85.7%) avoided multivisceral resection, and 10 of them achieved pCR or cCR. In the two patients with POLE mutations, one each achieved pCR and cCR. No Grade III/IV postoperative complications occurred. The median follow-up was 16.0 months. Two-year event-free and overall survival for the whole cohort was both 100%. </div></div><div><h3>Conclusions</h3><div>Preoperative immunotherapy is the optimal option for MSI-H or POLE-mutated LACRC with bulky tumors, especially cT4b. Preoperative immunotherapy in patients with T4b CRC can reduce multivisceral resection and achieve high CR rate.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 18-31.e2"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141714317","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":"Initial Assessment of Resectability of Colorectal Cancer Liver Metastases Versus Clinical Outcome","authors":"Grace Y. Kim ,&nbsp;Azim Jalali ,&nbsp;Grace Gard ,&nbsp;Justin M. Yeung ,&nbsp;Hieu Chau ,&nbsp;Lucy Gately ,&nbsp;Nezor Houli ,&nbsp;Ian T. Jones ,&nbsp;Suzanne Kosmider ,&nbsp;Belinda Lee ,&nbsp;Margaret Lee ,&nbsp;Louise Nott ,&nbsp;Jeremy D. Shapiro ,&nbsp;Jeanne Tie ,&nbsp;Benjamin Thomson ,&nbsp;Yat Hang To ,&nbsp;Vanessa Wong ,&nbsp;Rachel Wong ,&nbsp;Catherine Dunn ,&nbsp;Julie Johns ,&nbsp;Peter Gibbs","doi":"10.1016/j.clcc.2024.10.001","DOIUrl":"10.1016/j.clcc.2024.10.001","url":null,"abstract":"<div><h3>Background</h3><div>Surgery improves long-term survival for resectable, liver-only metastatic colorectal cancer (mCRC). With no consensus definition of “resectable” disease, decisions regarding resectability are reliant on the expertise and judgement of the treating clinician working in consultation with a multidisciplinary team (MDT). This study examines the clinical outcome versus initial assessment of resectability in an Australian population with mCRC.</div></div><div><h3>Patients and Methods</h3><div>Patients with liver-only mCRC diagnosed January 2009 to December 2022 were identified from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry. Patients were classified based on prospectively documented treatment assessment as “resectable,” “potentially resectable,” or “unresectable.” The correlation between initial assessment of resectability and clinical outcome, and any impact of clinicopathologic factors were examined. Kaplan-Meier analysis assessed overall survival based on initial resectability assessment and resection status.</div></div><div><h3>Results</h3><div>Of 4437 patients with mCRC identified through TRACC, 1250 (28%) had liver-only disease at presentation, with 497 (43%), 277 (24%), and 374 (33%) classified as “unresectable,” “potentially resectable,” and “resectable,” respectively. In total, 516 (41%) ultimately underwent surgical resection, including 30 (6%) of the “initially unresectable,” 148 (53%) of the “potentially resectable,” and 338 (90%) of the “resectable” at a median of 9.5, 5.9, and 2.4 months from the diagnosis of liver metastases, respectively. Resection in the “unresectable” patient population was associated with younger age (mean age 63 vs. 69, <em>P</em> = .0006), better performance status (ECOG 0-1 100% vs. 74%, <em>P</em> = .0017), and fewer comorbidities (Charlson index 0-3 in 73% vs. 53%, <em>P</em> = .0296) compared with no resection. Median overall survival was longer for resected versus nonresected patients across all categories: “unresectable” (59.2 vs. 17.6 months, <em>P</em> &lt; .0001), “potentially resectable” (57.2 vs. 22.8 months, <em>P</em> &lt; .0001), and “resectable” (108 vs. 55 months, <em>P</em> &lt; .0001).</div></div><div><h3>Conclusions</h3><div>This real-world study demonstrates the potential for “initially unresectable” patients to become surgical candidates following systemic therapy, more likely in younger and fitter patients, with overall excellent survival outcomes in resected patients. This highlights the value of routine, repeated MDT assessments for patients with liver-only disease who are continuing to respond to systemic therapy, even for those initially considered never to be surgical candidates.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 72-81"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634575","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":"Prognostic Impact of Para-Aortic Lymph Node Dissection in Colorectal Cancer Patients Suspected of Para-Aortic Lymph Node Metastasis: A Retrospective Cohort Study","authors":"Yingqian Zhou ,&nbsp;Xiaoyu Xie ,&nbsp;Xi Chen ,&nbsp;Qiongwei Tang ,&nbsp;Zerong Cai ,&nbsp;Yifeng Zou ,&nbsp;Zhaoliang Yu ,&nbsp;Yufeng Chen","doi":"10.1016/j.clcc.2024.09.001","DOIUrl":"10.1016/j.clcc.2024.09.001","url":null,"abstract":"<div><h3>Background</h3><div>Para-aortic lymph node metastasis (PALNM) is a rare occurrence in colorectal cancer (CRC), and the high risk of radical lymphadenectomy leads to persistent debate about the best treatment strategy. This study aims to evaluate the predictor for PALNM and the clinical value of para-aortic lymph node dissection (PALND) in CRC patients with radiologically suspected synchronous PALNM.</div></div><div><h3>Methods</h3><div>Patients who have synchronous radiologically suspected PALNM and underwent primary tumor resection were included. Logistic regression and receiver operating characteristic curve analysis were used to assess the predictive value of lymph node short axis in preoperative CT, identifying the optimal cut-off value. Propensity score matching and Cox regression explored factors affecting overall and disease-free survival, while Kaplan-Meier curves and decision tree models identified patient characteristics suitable for synchronous para-aortic lymph node dissection.</div></div><div><h3>Results</h3><div>A total of 578 patients were enrolled, and 125 patients received synchronous PALND. We found that simultaneous PALND significantly improved overall survival (HR, 0.56; 95% CI, 0.35-0.91; <em>P</em> = .019) in multivariate analysis, while disease-free survival showed no significant difference (<em>P</em> = .41). The short axis diameter of PALN on preoperative CT is a crucial predictor of PALNM (<em>P</em> &lt; .001, AUC = 0.759) with a threshold of &gt; 7 mm. N-stage and distant metastasis were included as independent predictors in the diagnostic model to enhance accuracy. A larger short axis diameter of PALN correlated with advanced tumor stage and poorer prognosis. Subgroup analysis revealed that PALND offers survival benefits for colorectal cancer patients at all stages with a short axis diameter &gt;10 mm on preoperative CT (<em>P</em> = .037) and for stage III patients with a diameter between 7 to10 mm (<em>P</em> &lt; .001, AUC = 0.810).</div></div><div><h3>Conclusion</h3><div>Synchronous PALND can improve overall survival in CRC patients with suspected PALNM, with the maximum short axis diameter of PALN serving as a key criterion for selecting patients for surgery.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 48-55.e4"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483187","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":"Neoadjuvant Treatment With Regorafenib and Capecitabine Combined With Radiotherapy in Locally Advanced Rectal Cancer: A Multicenter Phase Ib Trial (RECAP)–SAKK 41/16","authors":"Sara Bastian ,&nbsp;Markus Joerger ,&nbsp;Lisa Holer ,&nbsp;Daniela Bärtschi ,&nbsp;Matthias Guckenberger ,&nbsp;Wolfram Jochum ,&nbsp;Dieter Koeberle ,&nbsp;Alexander R. Siebenhüner ,&nbsp;Andreas Wicki ,&nbsp;Martin D. Berger ,&nbsp;Ralph C. Winterhalder ,&nbsp;Carlo R. Largiadèr ,&nbsp;Melanie Löffler ,&nbsp;Katarzyna Mosna-Firlejczyk ,&nbsp;Angela Fischer Maranta ,&nbsp;Bernhard C. Pestalozzi ,&nbsp;Chantal Csajka ,&nbsp;Roger von Moos ,&nbsp;Swiss Group for Clinical Cancer Research (SAKK)","doi":"10.1016/j.clcc.2024.10.002","DOIUrl":"10.1016/j.clcc.2024.10.002","url":null,"abstract":"<div><h3>Background</h3><div>The multi tyrosine kinase inhibitor regorafenib is active in metastatic colorectal cancer. Improvement in clinical outcome by adding regorafenib to long-course chemoradiotherapy (LcCRT) was investigated in molecularly undefined LARC.</div></div><div><h3>Methods</h3><div>Patients with T3-4 and/or N+ but M0 rectal cancer were included. Neoadjuvant LcRCT consisted in capecitabine (C) 825mg/m² d1-d38 and 28 fractions of 1.8Gy (50.4Gy). Regorafenib was added d1-14 and d22-35 in 3 dose escalation (DE) cohorts (40mg/80mg/120mg). The recommended dose (RD) was used for the expansion (EXP) cohort. Primary endpoints were dose-limiting toxicity (DLT) for DE and pathological response (near-complete regression [npCR] or complete regression [pCR]) for EXP.</div></div><div><h3>Results</h3><div>Overall, 25 patients were included. Two DLTs occurred at the regorafenib dose level of 120 mg, thereby establishing the RD at 80mg daily. Among the 19 patients who were treated at the RD, 8 (42.1%; 1-sided 80% confidence interval [CI] (lower bound): 30.7%; 95% CI, 20.3%-66.5%) reached the primary endpoint (5 [26.3%] had npCR and 3 [15.8%] pCR). One additional patient received no surgery due to clinical complete response. All patients had R0 resections and clear circumferential margins. Postoperative complications occurred in 6 patients (35.3%). The most common grade ≥ 3 treatment-related adverse event in the EXP cohort was diarrhea (2 patients).</div></div><div><h3>Conclusion</h3><div>Adding regorafenib 80 mg to LcCRT in LARC resulted in both primary endpoints being met and yielded an expected pathological response rate. Toxicity was manageable, and postoperative complications were as expected.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 82-88.e1"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634584","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":"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":"2025-03-01","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}