Clinical colorectal cancer最新文献

{"title":"First Report of a Noncomplete Clinical Response to Dostarlimab in Locally Advanced Rectal Cancer: Insights into Patient-Related Factors and Implications for Future Therapeutic Management","authors":"Marco Lorenzo Bonù ,&nbsp;Giuseppina Arcangeli ,&nbsp;Giovanni Rangoni ,&nbsp;Marco Bergamini ,&nbsp;Andrea Guerini ,&nbsp;Salvatore Grisanti ,&nbsp;Stefano Maria Magrini ,&nbsp;Barbara Frittoli ,&nbsp;Carla Baronchelli ,&nbsp;Gianpaolo Cengia ,&nbsp;Sarah Molfino ,&nbsp;Marco Ramera ,&nbsp;Silvia Casiraghi ,&nbsp;Jacopo Andreuccetti ,&nbsp;Luca Triggiani ,&nbsp;Mattia Bertoli ,&nbsp;Michela Buglione","doi":"10.1016/j.clcc.2025.11.002","DOIUrl":"10.1016/j.clcc.2025.11.002","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>In this case report, we present the first documented case of noncomplete clinical remission (ncCR) following 9 cycles of Dostarlimab for mismatch repair deficient (MMRd) locally advanced rectal cancer. This occurred in a patient with cT3cN1bM0 rectal adenocarcinoma living with HIV, with high adherence to HAART and a normal CD4+ count. Relapse was diagnosed by magnetic resonance imaging (MRI) and confirmed histologically via biopsy. Our report examines both tumor-related and patient-related factors that may have contributed to the ncCR and discusses possible management strategies for treatment failure in the potentially curable setting of LARC.</div></span></li><li><span>•</span><span><div>We believe this unprecedented case—representing the first documented evidence of noncomplete clinical remission after dostarlimab in MMRd LARC—holds significant relevance for the scientific and clinical community. It underscores that even the most promising therapeutic breakthroughs may encounter exceptions that challenge prevailing expectations. By reporting this observation, we aim to stimulate further research into resistance mechanisms, foster critical discussion, and contribute to the refinement of surveillance and treatment strategies for this rare yet clinically meaningful patient subgroup.</div></span></li></ul></div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 1","pages":"Pages 164-167"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770247","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":"Very Early-Onset Colorectal Cancer: Need for a Sub-Category Based on Differences in Tumor Biology, Metastatic and Survival Patterns? A Population-Based Cohort Study","authors":"Abdul Qahar K. Yasinzai ,&nbsp;Qaidar Alizai ,&nbsp;Danish Ali ,&nbsp;Muhammad B. Mirza ,&nbsp;Imran K. Kakar ,&nbsp;Asad Ullah ,&nbsp;Thomas J. George ,&nbsp;Kamran Idrees ,&nbsp;Aimal Khan","doi":"10.1016/j.clcc.2025.11.004","DOIUrl":"10.1016/j.clcc.2025.11.004","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of early-onset colorectal cancer (eoCRC)—diagnosed before age 50—has been increasing annually. Notably, there is significant heterogeneity in the biology within the eoCRC group, yet the specific metastatic patterns and survival characteristics of these subgroups remain poorly understood. This study aims to investigate tumor biology, metastatic patterns, and cancer-specific survival among very-early onset CRC (VeoCRC) (20-34), eoCRC (35-49), and late-onset CRC (LoCRC) (≥ 50).</div></div><div><h3>Methods</h3><div>We utilized the Surveillance, Epidemiology, and End Results (SEER) database (2000-2018). Patients aged 20 and older diagnosed with primary CRC were included. The primary outcome was cancer-specific survival, assessed using Kaplan–Meier survival curves and multivariable Cox proportional hazard regression.</div></div><div><h3>Results</h3><div>Of the 537,494 patients included in the study, 6307 (1.2%) were classified as VeoCRC, 50,179 (9.3%) as eoCRC, and 481,008 (89.5%) as LoCRC patients. The VeoCRC cohort had significantly higher rates of mucinous (10.3%) and signet-ring type adenocarcinomas (4.5%) than the eoCRC and LoCRC cohorts (<em>P</em> &lt; .05). Early age of onset of CRC was associated with higher rates of positive lymph nodal status at the time of diagnosis (VeoCRC 43.4% vs. eoCRC 38.5% vs. LoCRC 28.2%) (<em>P</em> &lt; .05). While the VeoCRC and eoCRC had similar 1-year survival, the VeoCRC cohort had a similar 5-year survival to that of LoCRC patients. On the multivariable Cox regression model, VeoCRC (HR = 1.049, [95% CI, 1.001-1.098]) and LoCRC (HR = 1.360 [95% CI, 1.337-1.383]) were associated with significantly lower survival compared to eoCRC.</div></div><div><h3>Conclusion</h3><div>VeoCRC patients have a distinct tumor biology as noted by their higher rates of signet ring cell cancers, mucinous cancers, worse tumor grades, nodal involvement and distant metastases compared to eoCRC patients. This is associated with worse 5-year cancer-specific survival compared to eoCRC, and is more consistent with the LoCRC cohort.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 1","pages":"Pages 125-134"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044414","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":"Therapy-Induced Metastatic Melanoma During Treatment With Encorafenib and Cetuximab for BRAF-Mutated Colorectal Cancer: A Case Report and Short Literature Review","authors":"Nerina Denaro ,&nbsp;Renato M. Marsicano ,&nbsp;Barbara Galassi ,&nbsp;Sveva Mortellaro ,&nbsp;Giulia Murgia ,&nbsp;Emanuela Passoni ,&nbsp;Ornella Garrone ,&nbsp;Michele Ghidini","doi":"10.1016/j.clcc.2025.10.005","DOIUrl":"10.1016/j.clcc.2025.10.005","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>BRAF inhibitor therapy, due to paradoxical activation of the MAPK pathway (RAS-RAF-MEK-ERK), can lead to the development of melanomas and new nevi.</div></span></li><li><span>•</span><span><div>Patients with BRAF-mutated metastatic colorectal cancer may benefit from combined BRAF and MEK inhibitor therapy.</div></span></li><li><span>•</span><span><div>A pretreatment dermatologic evaluation is recommended for all patients.</div></span></li><li><span>•</span><span><div>Patients at high risk for melanoma (eg, positive family history, Fitzpatrick skin phototype I-II, or presence of atypical nevi) may benefit from a preventive surgical approach.</div></span></li></ul></div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 1","pages":"Pages 152-159"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524582","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":"Predicting Pathologic Response in Locally Advanced Rectal Cancer Using Inflammatory, Nutritional, and Sarcopenia-Based Markers: A Regression and AI-Based Analysis (CINR-AI Study)","authors":"Galip Can Uyar ,&nbsp;Beyza Nur Başaran ,&nbsp;Kadriye Başkurt ,&nbsp;Enes Yeşilbaş ,&nbsp;Erdem Özkan ,&nbsp;Kadriye Bir Yücel ,&nbsp;Mustafa Altınbaş ,&nbsp;Şehnaz Evrimler ,&nbsp;Ömür Berna Çakmak Öksüzoğlu ,&nbsp;Osman Sütcüoğlu","doi":"10.1016/j.clcc.2025.10.002","DOIUrl":"10.1016/j.clcc.2025.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Total neoadjuvant therapy (TNT) is the standard approach for locally advanced rectal cancer (LARC), yet pathological complete response (pCR) is achieved in only a subset. Systemic inflammation, nutritional status, and sarcopenia influence outcomes, yet integrated predictive models are lacking. We aimed to develop clinical, laboratory, and AI-based models to predict pathological response.</div></div><div><h3>Methods</h3><div>This retrospective study included stage II to III LARC patients treated at Ankara Etlik City Hospital (Nov 2022-Dec 2024). Eligible patients received ≥ 12 weeks of TNT followed by curative surgery. Sarcopenia was assessed using CT-based skeletal muscle area at the third lumbar vertebra (L3). C-reactive protein/albumin ratio (CAR) and systemic immune-inflammation index (SII) were used to assess inflammatory and nutritional status. Composite scores (CINR-pCR, CINR-Ryan) were calculated using z-transformed CAR and SII weighted by regression coefficients. Outcomes included pCR and good pathological response, defined as tumor regression grade (TRG) 0 to 1 per the modified Ryan grading system. Logistic regression and Random Forest (RF) models were used. ClinicalTrials.gov: NCT07049627.</div></div><div><h3>Results</h3><div>Among 136 patients, 93 met the inclusion criteria. pCR and TRG 0 to 1 was achieved in 20 (21.5%) and 43 (46.2%) patients, respectively. Independent predictors of pCR included absence of post-TNT sarcopenia (OR 0.30, 95% CI, 0.09-0.95, <em>P =</em> .007), low CAR (OR 0.14, 95% CI, 0.03-0.70, <em>P =</em> .008), low SII (OR 0.28, 95% CI, 0.08-0.96, <em>P =</em> .042), low LDH (OR 0.10, 95% CI, 0.02-0.70, <em>P =</em> .020), and metformin use (OR 2.52, 95% CI, 1.40-3.78, <em>P =</em> .031). For TRG 0 to 1, significant predictors included low CAR (OR 0.42, 95% CI, 0.23-0.76, <em>P =</em> .005), low SII (OR 0.13, 95% CI, 0.03-0.56, <em>P =</em> .006), absence of ≥ 10% weight loss (OR 0.12, 95% CI, 0.02-0.66, <em>P =</em> .016), absence of post-TNT sarcopenia (OR 0.18, 95% CI, 0.05-0.70, <em>P =</em> .014), and shorter RT-to-surgery interval (OR 3.14, 95% CI, 1.17-6.43, <em>P =</em> .004). CINR scores showed strong predictive value (AUCs: 0.868 and 0.846), and RF models showed excellent performance (AUCs: 0.933 and 0.910, respectively).</div></div><div><h3>Conclusions</h3><div>Inflammatory, nutritional, and sarcopenia-based markers, including CINR scores and AI models, accurately predict pathological response in LARC. Importantly, the ROC-derived cut-off values (CINR-pCR: 1.58; CINR-Ryan: 0.45) stratified patients into low- and high-risk groups, supporting clinical decision-making in organ-preservation strategies and surgical timing. Prospective multicenter validation is warranted.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 1","pages":"Pages 51-67.e7"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460905","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 Value of Circulating Tumor DNA for Recurrence Risk in Stage III Colorectal Cancer: A Systematic Review and Meta-Analysis","authors":"Turkan Aliyeva ,&nbsp;Hiba Siddiqui ,&nbsp;Julia Natche ,&nbsp;Yumna Ahmad Al-Wraikat ,&nbsp;Farah Mahzabin Hossain ,&nbsp;Imane El-Amri","doi":"10.1016/j.clcc.2025.10.004","DOIUrl":"10.1016/j.clcc.2025.10.004","url":null,"abstract":"<div><h3>Background</h3><div>Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for minimal residual disease (MRD) detection and recurrence risk stratification in colorectal cancer (CRC). However, its prognostic significance in stage III CRC remains incompletely defined. This meta-analysis aimed to evaluate the association between postoperative ctDNA positivity and recurrence risk in patients with stage III CRC.</div></div><div><h3>Methods</h3><div>PubMed, Embase, and the Cochrane Library were searched for potentially eligible studies published up to April 2025. Pooled risk ratio (RR) and pooled hazard ratio (HR) were calculated to evaluate recurrence rate and the prognosis of recurrence-free survival (RFS) following CRC surgery and ACT. Meta-analysis was performed using a random-effects model.</div></div><div><h3>Results</h3><div>A total of ten studies involving 2461 stage III CRC patients were included. Postoperative ctDNA positivity was significantly associated with an increased risk of recurrence (RR = 4.39, 95% CI, 3.45-5.58, <em>P</em> &lt; .00001) and a poorer RFS (HR = 6.56, 95% CI, 4.80-8.98, <em>P</em> &lt; .00001). The pooled analysis showed that ctDNA-positive patients had a significantly higher risk of recurrence following ACT (RR = 4.80, 95% CI, 3.17-7.26, <em>P</em> &lt; .00001) and a worse RFS (HR = 10.00, 95% CI, 4.84-20.66, <em>P</em> &lt; .00001).</div></div><div><h3>Conclusion</h3><div>Postoperative ctDNA positivity is a strong prognostic marker of recurrence in patients with stage III CRC and could guide individualized surveillance and adjuvant therapy decisions. Further prospective studies are warranted to validate its routine clinical use.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 1","pages":"Pages 77-86"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566499","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":"Dietary Diabetes Risk Reduction Score (DDRRS) and the Risk of Colorectal Cancer and Adenoma: A Case-Control Study","authors":"Niayesh Naghshi ,&nbsp;Milad Mohammadzadeh ,&nbsp;Fatemeh Babaee Kiadehi ,&nbsp;Alireza Bahrami ,&nbsp;Fatemeh Abdi ,&nbsp;Mohammad Gholizadeh ,&nbsp;Ehsan Hejazi","doi":"10.1016/j.clcc.2025.08.006","DOIUrl":"10.1016/j.clcc.2025.08.006","url":null,"abstract":"<div><h3>Background</h3><div>Given the role of insulin resistance in several cancers, we hypothesized that the risk of colorectal cancer and colorectal adenoma may be lessened by following a diet that improves insulin resistance. Therefore, we conducted the current study to examine the association between dietary diabetes risk reduction and the odds of colorectal cancer and colorectal adenoma.</div></div><div><h3>Method</h3><div>This hospital-based case-control study was conducted on 129 newly diagnosed colorectal cancer patients, 130 newly diagnosed colorectal adenoma cases, and 240 healthy age- and sex-matched hospitalized controls. We used a valid and reliable 148-item food frequency questionnaire (FFQ) to collect the dietary intake of subjects. Multivariate logistic regression was used to estimate the association between DDRRS and the odds of colorectal cancer and adenoma.</div></div><div><h3>Results</h3><div>After adjusting for confounding variables, individuals in the highest tertile of the DDRRS were 0.13 and 0.22 times less likely to have colorectal cancer (OR = 0.13, 95% CI: 0.06-0.25) and adenoma (OR = 0.22, 95% CI: 0.12-0.41) respectively.</div></div><div><h3>Conclusion</h3><div>Current results demonstrated that a high DDRRS was associated with a lower risk of colorectal cancer and adenoma.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 4","pages":"Pages 477-482"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076899","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":"Age as a Modifier of the Effects of Sarcopenia on Survival Among Colon Cancer Patients Receiving Chemotherapy","authors":"Wen-Li Lin ,&nbsp;Li‐Min Wu ,&nbsp;Wen-Tsung Huang ,&nbsp;Yu-Pao Chen","doi":"10.1016/j.clcc.2025.08.002","DOIUrl":"10.1016/j.clcc.2025.08.002","url":null,"abstract":"<div><h3>Background</h3><div>Sarcopenia is common among older adults and is associated with poor prognosis in several malignancies. This study evaluated whether sarcopenia serves as a survival risk factor among patients with colon cancer treated with chemotherapy, alongside the effects of age and visceral adiposity (VA).</div></div><div><h3>Patients and methods</h3><div>We retrospectively recruited 133 patients diagnosed with resectable colon cancer who received chemotherapy between January 2014 and December 2017 at a teaching hospital. Computed tomography images were analyzed to assess body composition, and Kaplan–Meier survival curves and Cox proportional hazards regression models were used to assess survival.</div></div><div><h3>Results</h3><div>Patients receiving chemotherapy who were diagnosed with sarcopenia were associated with worse 5-year overall survival (OS: 87.3% vs. 65.4%) and longer hospital stay (19.1 vs. 15 days) compared with patients without sarcopenia. VA was not associated with OS or the length of hospital stay. There was a significant association between sarcopenia and OS, with a hazard ratio (HR) of 2.77 (95% confidence interval [CI]:1.42-5.38). The association remained after adjustment for other independent risk factors, including age &gt; 70 years (adjusted HR: 1.98, 95% CI: 0.99-3.95) and alcohol consumption (adjusted HR: 8.96, 95% CI: 1.22-65.77). In age-stratified analyses, sarcopenia was an independent risk factor for worse OS (adjusted HR: 7.85, 95% CI: 1.05-58.91) among patients &gt; 70 years but not among patients ≤ 70 years (adjusted HR: 2.01, 95% CI: 0.75-5.93).</div></div><div><h3>Conclusion</h3><div>Sarcopenia is associated with improved OS, particularly in patients aged ≥ 70 years who underwent chemotherapy after resection of colorectal cancer.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 4","pages":"Pages 454-465"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103105","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":"Adjuvant Anti-Inflammatory Therapy in Postoperative Colorectal Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials","authors":"Gabriel Lenz ,&nbsp;Rafael Alvim Pereira ,&nbsp;Gabriel Valagni ,&nbsp;Tiago Biachi de Castria","doi":"10.1016/j.clcc.2025.08.003","DOIUrl":"10.1016/j.clcc.2025.08.003","url":null,"abstract":"<div><div>Colorectal cancer (CRC) recurrence remains a major challenge in postsurgery. Chronic inflammation driven by cyclooxygenase (COX-2) and prostaglandin pathways promotes tumor recurrence, encouraging interest in nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin (acetylsalicylic acid, ASA) and COX-2 inhibitors. While observational studies suggest a benefit in reducing recurrence, randomized controlled trial (RCT) evidence is controversial. This meta-analysis evaluates the efficacy and safety of adjuvant NSAIDs in nonmetastatic resected CRC. We systematically searched PubMed, Scopus, and Cochrane Central for RCTs comparing anti-inflammatory agents to placebo in postoperative CRC patients. Primary outcomes included overall survival (OS) and disease-free survival (DFS); secondary outcomes were time to recurrence (TTR), recurrence rate, and adverse events. Subgroup analyses focused on aspirin use and the presence of PI3K pathway mutations were performed. Five RCTs (7246 patients) were included. Anti-inflammatory therapy improved DFS (HR = 0.85; 95% CI: 0.76-0.96; <em>P</em> = .008) and TTR (HR = 0.61; 95% CI: 0.44-0.84; <em>P</em> = .003) but not OS (HR = 0.90; <em>P</em> = .07) or recurrence rates (RR = 0.90; <em>P</em> = .06). Aspirin demonstrated superior DFS benefit (HR = 0.70; <em>P</em> = .03) and patients with PI3K mutations had markedly reduced recurrence risk (HR = 0.56; <em>P</em> &lt; .0001). Serious cardiac events, gastrointestinal bleeding, and infections showed no significant differences. Adjuvant anti-inflammatory therapy improves DFS and delays recurrence in postoperative CRC, with pronounced benefit in PIK3CA mutant tumors. These findings support biomarker-driven strategies and highlight the need for ongoing trials to validate long-term efficacy and safety.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 4","pages":"Pages 415-424.e2"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056465","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":"Characterization of the Tumor Immune Microenvironment in HER2-Positive Colorectal Cancer: Association With Prognostic and Therapeutic Implications","authors":"Wen-Wen Huang MD ,&nbsp;Yan-Jun Cheng MSc ,&nbsp;Sha-Sha Yuan MD ,&nbsp;Yu Liu MSc ,&nbsp;Fu-Rong Liu MD","doi":"10.1016/j.clcc.2025.08.004","DOIUrl":"10.1016/j.clcc.2025.08.004","url":null,"abstract":"<div><h3>Background</h3><div>The human epidermal growth factor receptor 2 (HER2) status has been proposed as a biomarker to identify colorectal cancer (CRC) patients suitable for anti-HER2 treatment. However, response varies from HER2-negative CRC, influenced by factors such as the tumors immune microenvironment (TIME) in HER2-positive CRC patients. We aimed to characterize the TIME of HER2-positive CRC by assessing the associations of inflammatory cells and prognosis.</div></div><div><h3>Methods</h3><div>TIME was characterized through immunostaining for CD3, CD4, CD8, CD20, CD68, Forkhead box protein P3 (Foxp3), and programmed death-ligand 1 (PD-L1) cell densities in 36 HER2-positive and 72 HER2-negative CRC patients. HER2 positivity was evaluated by the HERACLES criteria. PD-L1 expression was evaluated by the tumor proportion score (TPS) and combined proportion score (CPS).</div></div><div><h3>Results</h3><div>In our study, the densities of CD3, CD4, CD8, CD20, CD68, Foxp3 cells and PD-L1 expression showed no statistic differences in HER2-positive CRC patients compared to HER2-negative patients. There was a greater proportion of Foxp3+ cells (≥ 10%) among patients with HER2-positive CRC (<em>P</em> = .023). Although the PD-L1 CPS was correlated with sex (<em>P</em> = .012), inflammatory cells and the PD-L1 TPS were not correlated with clinicopathological parameters. Additionally, CRC patients with PD-L1 CPSs ≥ 1 had significantly better event-free survival (EFS) than patients with PD-L1 CPSs &lt; 1 (<em>P</em> = .029). For patients with HER2-positive CRC, higher CD68 indicated better EFS (<em>P</em> = .047).</div></div><div><h3>Conclusions</h3><div>This study characterized a preliminary immune microenvironment profile and indicated CD68 increased correlation with EFS for HER2-positive CRC patients. These immune microenvironment profiles and prognostic implications could serve as potential biomarkers for stratifying patients with HER-2 positive for clinical trials.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 4","pages":"Pages 466-476.e3"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066422","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":"Machine Learning-Based Prediction Model for Early-Onset Colorectal Cancer Risk: A Systematic Review and Meta-Analysis","authors":"Wenting Chai ,&nbsp;Siyue Fan ,&nbsp;Yanni Lin ,&nbsp;Nengtong Zheng ,&nbsp;Yuanfang Xiong ,&nbsp;Yuan Chen ,&nbsp;Zhaoxia Zhang ,&nbsp;Lijuan Chen","doi":"10.1016/j.clcc.2025.09.003","DOIUrl":"10.1016/j.clcc.2025.09.003","url":null,"abstract":"<div><div>Through systematic review and meta-analysis, we explored the performance of machine learning (ML) risk prediction models for early-onset colorectal cancer (EOCRC) to enhance model development and application. Following preregistration of the study protocol in PROSPERO (CRD42024606785), we searched PubMed, Embase, Web of Science, Cochrane Library, WanFang Data, VIP, SinoMed, and the CNKI databases for studies on constructing predictive EOCRC based on ML methods. The prediction model Risk of Bias Assessment Tool + Artificial Intelligence (PROBAST + AI) tool was used to evaluate the quality, bias risk, and applicability of the included studies. The Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis + Artificial Intelligence (TRIPOD + AI) reporting standard was applied to assess the reporting quality of these studies. We conducted subgroup analysis and sensitivity analysis. This study followed the PRISMA reporting guidelines. A total of 2809 studies were retrieved, and 7 studies were included. The training set size ranged from 987 to 21,700 patients, with an average of 5037 per model. XGBoost was the most frequently used modelling method. Overall TRIPOD + AI compliance was 70.5%. In model development, 5 studies were rated as high-quality concerns (2 unclear), and 5 studies were rated as high adaptability concerns (2 unclear). In model evaluation, 6 studies were rated as high-risk bias (1 unclear), and 5 studies were of concern for high adaptability (2 unclear). The top 5 most common predictors include age, gender, BMI, diabetes and smoking. Meta-analysis showed a pooled AUC of 0.84 (95% CI, 0.77-0.90; <em>I</em>² = 99.3%, <em>P</em> &lt; .001). Pooled sensitivity and specificity were 0.75 (95% CI, 0.59-0.86; <em>I</em>² = 94.8%) and 0.87 (95% CI, 0.71-0.94; <em>I</em>² = 95.6%), respectively (both <em>P</em> &lt; .001 for heterogeneity). This study demonstrates that ML models show outstanding discriminatory capabilities in predicting the risk of EOCRC, supporting their potential application in identifying high-risk individuals for targeted prevention and monitoring. In the future, prospective design and standardized reporting are needed to enhance reliability and clinical translation.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 4","pages":"Pages 432-445"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373389","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}