Clinical colorectal cancer最新文献

{"title":"An Evolving Landscape: New Therapies for Metastatic Colorectal Cancer","authors":"Christiana Mo, Bhawneet Chadha, Chaoyuan Kuang","doi":"10.1016/j.clcc.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.clcc.2024.08.003","url":null,"abstract":"Substantial progress is being made in the development of novel therapies directed against colorectal cancer. The discovery of various molecular markers and advances in tumor profiling have facilitated the development of new targeted agents and immunotherapy. Not only have these drugs improved progression-free survival and even overall survival in some cases, but their related outcomes have also raised questions as to how to best combine or sequence therapies for even greater efficacy. Furthermore, we are beginning to understand how these combination therapies may yield for greater therapeutic response for patients with microsatellite stable colorectal cancer for which there is much need for improvement. In this article, we review recent trial data and explore the outcomes of various targeted therapies and immunotherapies for patient with advanced colorectal cancer.","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249647","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, Xiaochen Li, Chongkai Wang, Marwan Fakih","doi":"10.1016/j.clcc.2024.08.001","DOIUrl":"https://doi.org/10.1016/j.clcc.2024.08.001","url":null,"abstract":"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. 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. 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 ( = .88 and = .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. 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.","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-18","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":"The Site of Checkpoint in a Continuous Oncological Evolving Course of Colon Cancer to an Obstruction Phenotype Decides the Effects of “Incomplete” Obstruction","authors":"Shenghe Deng, Falong Zou, Kailin Cai","doi":"10.1016/j.clcc.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.clcc.2024.08.002","url":null,"abstract":"","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209167","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, Alexander Stein, Christoph Schultheiß, Lisa Paschold, Hanna Jonas, Eray Goekkurt, Jörn Rüssel, Gunter Schuch, Jan Wierecky, Marianne Sinn, Joseph Tintelnot, Cordula Petersen, Kai Rothkamm, Eik Vettorazzi, Mascha Binder","doi":"10.1016/j.clcc.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.clcc.2024.06.003","url":null,"abstract":"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. 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. 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. 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.","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-22","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimally Invasive Surgery for Colorectal Cancer: Benchmarking Uptake for a Regional Improvement Programme","authors":"John C. Taylor, Dermot Burke, Lene H. Iversen, Rebecca J. Birch, Paul J. Finan, Mark M. Iles, Philip Quirke, Eva J.A. Morris, YCR BCIP Study Group","doi":"10.1016/j.clcc.2024.05.013","DOIUrl":"https://doi.org/10.1016/j.clcc.2024.05.013","url":null,"abstract":"The uptake of minimally invasive surgery (MIS) for patients with colorectal cancer has progressed at differing rates, both across countries, and within countries. This study aimed to investigate uptake for a regional colorectal cancer improvement programme in England. We calculated the proportion of patients receiving elective laparoscopic and robot-assisted surgery amongst those diagnosed with colorectal cancer over 3 time periods (2007-2011, 2012-2016 and 2017-2021) in hospitals participating in the Yorkshire Cancer Research Bowel Cancer Improvement Programme (YCR BCIP). These were benchmarked against national rates. Regression analysis and funnel plots were used to develop a data driven approach for analysing trends in the use of MIS at hospitals in the programme. In England, resections performed by MIS increased from 34.9% to 72.9% for colon cancer and from 28.8% to 72.5% for rectal cancer. Robot-assisted surgery increased from 0.1% to 2.7% for colon cancer and from 0.2% to 7.9% for rectal cancer. Wide variation in the uptake of MIS was observed at a hospital level. Detailed analysis of the YCR BCIP region identified a decreasing number of surgical departments, since the start of the programme, as potential outliers for MIS when compared to the English national average. Wide variation in use of MIS for colorectal cancer exists within the English National Health Service and a data-driven approach can help identify outlying hospitals. Addressing some of the challenges behind the uptake of MIS, such as ensuring adequate provision of surgical training and equipment, could help increase its use.","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141574540","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 Comparison of Cellular Immune Response and Immunological Biomarkers in Laparoscopic Surgery for Colorectal Cancer and Benign Disorders","authors":"Line Nederby, Natacha Dencker Trabjerg, Anja Bjørnskov Andersen, Jan Lindebjerg, Torben Frøstrup Hansen, Hans Bjarke Rahr","doi":"10.1016/j.clcc.2024.05.012","DOIUrl":"https://doi.org/10.1016/j.clcc.2024.05.012","url":null,"abstract":"Surgical trauma causes immune impairment, but it is largely unknown whether surgery for cancer and benign diseases instigate comparable levels of immune inhibition. Here, we compared the impact of laparoscopic surgery on immunological biomarkers in patients with colorectal cancer (CRC) and ventral hernia (VH). Natural Killer cell activity (NKA), leukocyte subsets, and soluble programmed death ligand 1 (sPD-L1) were measured in blood samples collected from CRC (n = 29) and VH (n = 9) patients preoperatively (PREOP) and on postoperative day (POD) 1, 3-6, 2 weeks and 3 months. NKA was evaluated by the NK Vue assay that uses the level of IFNγ as a surrogate marker of NKA. Normal NKA was defined as IFNγ > 250 pg/mL and low NKA was defined as IFNγ < 250 pg/mL. The CRC cohort was classified into either PREOP having preoperative low NKA or PREOP having preoperative normal NKA. The median NKA of the PREOP subset was only in the normal range in the POD3 months sample, whereas median NKA of the PREOP subset and the VH cohort were only low in the POD1 sample. While PREOP differed from VH in the PREOP-, POD1-, and POD3-6 samples ( =.0006, = .0181, and = .0021), NKA in PREOP and VH differed in the POD1 samples ( = .0226). There were no apparent differences in the distribution of leukocyte subsets in the perioperative period between the cohorts. CRC patients with preoperative normal NKA and VH patients showed the same pattern of recovery in NKA, while the CRC subset with preoperative low NKA seemed to experience prolonged NK cell impairment. As low NKA is associated with recurrence, preoperative level of NKA may identify patients who will benefit from immune-enhancing therapy in the perioperative period.","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141574542","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":"Effects of Adjuvant Chemotherapy on Oncologic Outcomes in Patients With Stage ⅡA Rectal Cancer Above the Peritoneal Reflection Who Did Not Undergo Preoperative Chemoradiotherapy","authors":"Hyo Seon Ryu, Jong Lyul Lee, Chan Wook Kim, Yoon Yong Sik, In Ja Park, Seok-Byung Lim, Yong Sang Hong, Tae Won Kim, Chang Sik Yu","doi":"10.1016/j.clcc.2024.05.011","DOIUrl":"https://doi.org/10.1016/j.clcc.2024.05.011","url":null,"abstract":"This study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper rectal cancer and to investigate whether AC is associated with improved survival outcomes. This retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative chemoradiotherapy between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, perineural invasion, resection margin involvement, and < 12 lymph nodes harvested. Among the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs 84.6%, = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs 64.1%, = .01) and 5-year OS (88.8% vs 69.0%, = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged > 65 years. AC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors.","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141574541","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":"Pembrolizumab Plus mFOLFOX7 or FOLFIRI for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer: KEYNOTE-651 Cohorts B and D","authors":"Richard Kim ,&nbsp;Mustapha Tehfe ,&nbsp;Petr Kavan ,&nbsp;Jorge Chaves ,&nbsp;Jeremy S. Kortmansky ,&nbsp;Eric X. Chen ,&nbsp;Christopher H. Lieu ,&nbsp;Lucas Wong ,&nbsp;Marwan Fakih ,&nbsp;Kristen Spencer ,&nbsp;Qing Zhao ,&nbsp;Raluca Predoiu ,&nbsp;Chenxiang Li ,&nbsp;Pierre Leconte ,&nbsp;David Adelberg ,&nbsp;E. Gabriela Chiorean","doi":"10.1016/j.clcc.2024.03.001","DOIUrl":"10.1016/j.clcc.2024.03.001","url":null,"abstract":"<div><h3>Background</h3><p>The phase 1b KEYNOTE-651 study evaluated pembrolizumab plus chemotherapy in microsatellite stable or mismatch repair-proficient metastatic colorectal cancer.</p></div><div><h3>Patients and Methods</h3><p>Patients with microsatellite stable or mismatch repair-proficient metastatic colorectal cancer received pembrolizumab 200 mg every 3 weeks plus 5-fluorouracil, leucovorin, oxaliplatin (previously untreated; cohort B) or 5-fluorouracil, leucovorin, irinotecan (previously treated with fluoropyrimidine plus oxaliplatin; cohort D) every 2 weeks. Primary end point was safety; investigator-assessed objective response rate per RECIST v1.1 was secondary and biomarker analysis was exploratory.</p></div><div><h3>Results</h3><p>Thirty-one patients were enrolled in cohort B and 32 in cohort D; median follow-up was 30.2 and 33.5 months, respectively. One dose-limiting toxicity (grade 3 small intestine obstruction) occurred in cohort D. In cohort B, grade 3 or 4 treatment-related adverse events (AEs) occurred in 18 patients (58%), most commonly neutropenia and decreased neutrophil count (n = 5 each). In cohort D, grade 3 or 4 treatment-related AEs occurred in 17 patients (53%), most commonly neutropenia (n = 7). No grade 5 treatment-related AEs occurred. Objective response rate was 61% in cohort B (<em>KRAS</em> wildtype: 71%; <em>KRAS</em> mutant: 53%) and 25% in cohort D (<em>KRAS</em> wildtype: 47%; <em>KRAS</em> mutant: 6%). In both cohorts, PD-L1 combined positive score and T-cell-inflamed gene expression profiles were higher and HER2 expression was lower in responders than nonresponders. No association between tumor mutational burden and response was observed.</p></div><div><h3>Conclusion</h3><p>Pembrolizumab plus 5-fluorouracil, leucovorin, oxaliplatin/5-fluorouracil, leucovorin, irinotecan demonstrated an acceptable AE profile. Efficacy data appeared comparable with current standard of care (including by <em>KRAS</em> mutation status). Biomarker analyses were hypothesis-generating, warranting further exploration.</p></div><div><h3>ClinicalTrials.gov Identifier</h3><p>ClinicalTrials.gov; NCT03374254</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613984","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":"MA Calegari, I. Zurlo, E. Dell'Aquila, M. Basso, A. Orlandi, M. Bensi, F. Camarda, A. Anghelone, C. Pozzo, I. Sperduti, L. Salvatore, D. Santini, DC Corsi, E. Bria, G. Tortora","doi":"10.1016/j.clcc.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.clcc.2024.06.002","url":null,"abstract":"","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","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":"Consideration of Metastasis-Directed Therapy for Patients With Metastatic Colorectal Cancer: Expert Survey and Systematic Review","authors":"Eric D. Miller ,&nbsp;Brett G. Klamer ,&nbsp;Jordan M. Cloyd ,&nbsp;Timothy M. Pawlik ,&nbsp;Terence M. Williams ,&nbsp;Kathryn E. Hitchcock ,&nbsp;Paul B. Romesser ,&nbsp;Harvey J. Mamon ,&nbsp;Kimmie Ng ,&nbsp;Sepideh Gholami ,&nbsp;George J. Chang ,&nbsp;Christopher J. Anker","doi":"10.1016/j.clcc.2024.01.004","DOIUrl":"10.1016/j.clcc.2024.01.004","url":null,"abstract":"<div><h3>Background</h3><p>A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT).</p></div><div><h3>Materials and Methods</h3><p>An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions.</p></div><div><h3>Results</h3><p>Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT.</p></div><div><h3>Conclusions</h3><p>Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1533002824000045/pdfft?md5=b73b78ab7b7a93a7f10dda6c37cb59c4&pid=1-s2.0-S1533002824000045-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139646133","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}