Pub Date : 2026-03-01Epub Date: 2025-09-24DOI: 10.1016/j.clcc.2025.09.002
Bobby Zamaray , Jan Willem B. de Groot , Jeanin E. van Hooft , Niels F.M. Kok , Peter D. Siersema , Esther C.J. Consten , Pieter J. Tanis , Henderik L. van Westreenen , Dutch Snapshot Research Group and the Dutch Complex Colon Cancer Initiative (DCCCI)
Background
Bowel obstruction is considered a poor prognostic factor in colon cancer. Therefore, these patients are generally treated with adjuvant chemotherapy following resection of the primary tumour. However, the benefit of adjuvant chemotherapy in stage II obstructive colon cancer, and the impact of bridge-to-surgery strategies are insufficiently known.
Methods
This was a nationwide cohort study of patients who underwent resection of left-sided obstructive colon cancer (LSOCC) with curative intent in 75 hospitals between 2009 and 2016. Potential predictors for receiving adjuvant chemotherapy were included in a multivariable model. The impact of adjuvant chemotherapy on disease-free survival (DFS) and overall survival (OS), corrected for age, ASA-score, and 30-day postoperative complications, was determined using Cox regression analyses, with pTN stratification.
Results
Of 2151 included patients, 39.7% received adjuvant chemotherapy. Independent predictors of receiving adjuvant chemotherapy were age, ASA score, pT and pN1-2 categories, and Clavien-Dindo grade III-IV postoperative complications, but not a bridge-to-surgery strategy. Adjuvant chemotherapy was independently associated with better DFS (HR: 0.61; 95% CI, 0.51-0.72) and OS (HR: 0.49; 95% CI, 0.40-0.61) in the overall population. In pT3N0 LSOCC, adjuvant chemotherapy was not associated with DFS or OS. In patients with pT4N0 LSOCC however, adjuvant chemotherapy was associated with improved DFS (HR: 0.53, 95% CI, 0.29-0.95) and OS (HR: 0.42, 95% CI, 0.20-0.86). No differences in DFS or OS were observed between patients who received single-agent versus doublet chemotherapy were found.
Conclusion
A bridge-to-surgery strategy did not influence adjuvant chemotherapy receipt in patients with LSOCC. Obstruction is considered a risk factor in stage II, but no survival benefit of adjuvant chemotherapy is seen for the pT3N0 subgroup.
{"title":"Real-World Evidence on Adjuvant Chemotherapy After Resection of Left-Sided Obstructive Colon Cancer","authors":"Bobby Zamaray , Jan Willem B. de Groot , Jeanin E. van Hooft , Niels F.M. Kok , Peter D. Siersema , Esther C.J. Consten , Pieter J. Tanis , Henderik L. van Westreenen , Dutch Snapshot Research Group and the Dutch Complex Colon Cancer Initiative (DCCCI)","doi":"10.1016/j.clcc.2025.09.002","DOIUrl":"10.1016/j.clcc.2025.09.002","url":null,"abstract":"<div><h3>Background</h3><div>Bowel obstruction is considered a poor prognostic factor in colon cancer. Therefore, these patients are generally treated with adjuvant chemotherapy following resection of the primary tumour. However, the benefit of adjuvant chemotherapy in stage II obstructive colon cancer, and the impact of bridge-to-surgery strategies are insufficiently known.</div></div><div><h3>Methods</h3><div>This was a nationwide cohort study of patients who underwent resection of left-sided obstructive colon cancer (LSOCC) with curative intent in 75 hospitals between 2009 and 2016. Potential predictors for receiving adjuvant chemotherapy were included in a multivariable model. The impact of adjuvant chemotherapy on disease-free survival (DFS) and overall survival (OS), corrected for age, ASA-score, and 30-day postoperative complications, was determined using Cox regression analyses, with pTN stratification.</div></div><div><h3>Results</h3><div>Of 2151 included patients, 39.7% received adjuvant chemotherapy. Independent predictors of receiving adjuvant chemotherapy were age, ASA score, pT and pN1-2 categories, and Clavien-Dindo grade III-IV postoperative complications, but not a bridge-to-surgery strategy. Adjuvant chemotherapy was independently associated with better DFS (HR: 0.61; 95% CI, 0.51-0.72) and OS (HR: 0.49; 95% CI, 0.40-0.61) in the overall population. In pT3N0 LSOCC, adjuvant chemotherapy was not associated with DFS or OS. In patients with pT4N0 LSOCC however, adjuvant chemotherapy was associated with improved DFS (HR: 0.53, 95% CI, 0.29-0.95) and OS (HR: 0.42, 95% CI, 0.20-0.86). No differences in DFS or OS were observed between patients who received single-agent versus doublet chemotherapy were found.</div></div><div><h3>Conclusion</h3><div>A bridge-to-surgery strategy did not influence adjuvant chemotherapy receipt in patients with LSOCC. Obstruction is considered a risk factor in stage II, but no survival benefit of adjuvant chemotherapy is seen for the pT3N0 subgroup.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 1","pages":"Pages 21-32"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411037","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}
Pub Date : 2026-03-01Epub Date: 2025-10-30DOI: 10.1016/j.clcc.2025.10.009
Brendan P. Stewart , Rachel L. Atkinson , Herbert Downton Ramos , Jonathan Chang , Andrew C. Raissis
•
We recommend always obtaining a thorough history and physical exam to elucidate potential undiagnosed malignancies in patients presenting with lower GI symptoms
•
In patients with HIV, ART is important in preventing both infectious and malignant complications
•
Although rare, visceral Kaposi sarcoma is a known disease associated with advanced and untreated HIV
{"title":"Misdiagnosed: A Sigmoid Perforation Secondary to Visceral Kaposi Sarcoma","authors":"Brendan P. Stewart , Rachel L. Atkinson , Herbert Downton Ramos , Jonathan Chang , Andrew C. Raissis","doi":"10.1016/j.clcc.2025.10.009","DOIUrl":"10.1016/j.clcc.2025.10.009","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>We recommend always obtaining a thorough history and physical exam to elucidate potential undiagnosed malignancies in patients presenting with lower GI symptoms</div></span></li><li><span>•</span><span><div>In patients with HIV, ART is important in preventing both infectious and malignant complications</div></span></li><li><span>•</span><span><div>Although rare, visceral Kaposi sarcoma is a known disease associated with advanced and untreated HIV</div></span></li></ul></div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"25 1","pages":"Pages 160-163"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575079","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}
Pub Date : 2026-03-01Epub Date: 2025-12-21DOI: 10.1016/j.clcc.2025.11.004
Abdul Qahar K. Yasinzai , Qaidar Alizai , Danish Ali , Muhammad B. Mirza , Imran K. Kakar , Asad Ullah , Thomas J. George , Kamran Idrees , Aimal Khan
Background
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).
Methods
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.
Results
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 (P < .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%) (P < .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.
Conclusion
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.
{"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 , Qaidar Alizai , Danish Ali , Muhammad B. Mirza , Imran K. Kakar , Asad Ullah , Thomas J. George , Kamran Idrees , 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> < .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> < .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}
Pub Date : 2026-03-01Epub Date: 2025-11-21DOI: 10.1016/j.clcc.2025.11.002
Marco Lorenzo Bonù , Giuseppina Arcangeli , Giovanni Rangoni , Marco Bergamini , Andrea Guerini , Salvatore Grisanti , Stefano Maria Magrini , Barbara Frittoli , Carla Baronchelli , Gianpaolo Cengia , Sarah Molfino , Marco Ramera , Silvia Casiraghi , Jacopo Andreuccetti , Luca Triggiani , Mattia Bertoli , Michela Buglione
•
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.
•
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.
{"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 , Giuseppina Arcangeli , Giovanni Rangoni , Marco Bergamini , Andrea Guerini , Salvatore Grisanti , Stefano Maria Magrini , Barbara Frittoli , Carla Baronchelli , Gianpaolo Cengia , Sarah Molfino , Marco Ramera , Silvia Casiraghi , Jacopo Andreuccetti , Luca Triggiani , Mattia Bertoli , 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}
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.
•
Patients with BRAF-mutated metastatic colorectal cancer may benefit from combined BRAF and MEK inhibitor therapy.
•
A pretreatment dermatologic evaluation is recommended for all patients.
•
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.
{"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 , Renato M. Marsicano , Barbara Galassi , Sveva Mortellaro , Giulia Murgia , Emanuela Passoni , Ornella Garrone , 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}
Pub Date : 2026-03-01Epub Date: 2025-10-16DOI: 10.1016/j.clcc.2025.10.002
Galip Can Uyar , Beyza Nur Başaran , Kadriye Başkurt , Enes Yeşilbaş , Erdem Özkan , Kadriye Bir Yücel , Mustafa Altınbaş , Şehnaz Evrimler , Ömür Berna Çakmak Öksüzoğlu , Osman Sütcüoğlu
Background
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.
Methods
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.
Results
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, P = .007), low CAR (OR 0.14, 95% CI, 0.03-0.70, P = .008), low SII (OR 0.28, 95% CI, 0.08-0.96, P = .042), low LDH (OR 0.10, 95% CI, 0.02-0.70, P = .020), and metformin use (OR 2.52, 95% CI, 1.40-3.78, P = .031). For TRG 0 to 1, significant predictors included low CAR (OR 0.42, 95% CI, 0.23-0.76, P = .005), low SII (OR 0.13, 95% CI, 0.03-0.56, P = .006), absence of ≥ 10% weight loss (OR 0.12, 95% CI, 0.02-0.66, P = .016), absence of post-TNT sarcopenia (OR 0.18, 95% CI, 0.05-0.70, P = .014), and shorter RT-to-surgery interval (OR 3.14, 95% CI, 1.17-6.43, P = .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).
Conclusions
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.
背景：全面新辅助治疗（TNT）是局部晚期直肠癌（LARC）的标准治疗方法，但病理完全缓解（pCR）仅在一小部分患者中实现。全身性炎症、营养状况和肌肉减少症影响预后，但缺乏综合预测模型。我们的目标是开发临床、实验室和基于人工智能的模型来预测病理反应。方法：本回顾性研究纳入了2022年11月至2024年12月在安卡拉埃特利克市医院治疗的II至III期LARC患者。符合条件的患者接受≥12周TNT治疗，随后进行根治性手术。在第三腰椎（L3）使用基于ct的骨骼肌面积评估骨骼肌减少症。用c反应蛋白/白蛋白比（CAR）和全身免疫炎症指数（SII）评估炎症和营养状况。综合评分（CINR-pCR, CINR-Ryan）计算使用z转换CAR和SII加权回归系数。结果包括pCR和良好的病理反应，根据改进的Ryan分级系统定义为肿瘤消退等级（TRG） 0至1。采用Logistic回归和随机森林（RF）模型。Clinicaltrials: gov: NCT07049627。结果：136例患者中，93例符合纳入标准。20例（21.5%）和43例（46.2%）患者分别达到pCR和TRG 0 ~ 1。pCR的独立预测因子包括没有tnt后肌肉减少症（OR 0.30, 95% CI, 0.09-0.95, P = 0.007）、低CAR （OR 0.14, 95% CI, 0.03-0.70, P = 0.008）、低SII （OR 0.28, 95% CI, 0.08-0.96, P = 0.042）、低LDH （OR 0.10, 95% CI, 0.02-0.70, P = 0.020）和二甲双胍使用（OR 2.52, 95% CI, 1.40-3.78, P = 0.031）。对于TRG 0至1，重要的预测因素包括低CAR （OR 0.42, 95% CI, 0.23-0.76, P = 0.005）、低SII （OR 0.13, 95% CI, 0.03-0.56, P = 0.006）、没有体重减轻≥10% （OR 0.12, 95% CI, 0.02-0.66, P = 0.016）、没有tnt后肌肉减少（OR 0.18, 95% CI, 0.05-0.70, P = 0.014）和较短的rt -to-手术间隔（OR 3.14, 95% CI, 1.17-6.43, P = 0.004）。CINR评分具有较强的预测价值（auc分别为0.868和0.846），RF模型表现优异（auc分别为0.933和0.910）。结论：炎症、营养和基于肌肉减少的标志物，包括CINR评分和AI模型，可以准确预测LARC的病理反应。重要的是，roc衍生的临界值（CINR-pCR: 1.58; CINR-Ryan: 0.45）将患者分为低危组和高危组，为器官保存策略和手术时机的临床决策提供支持。前瞻性多中心验证是必要的。
{"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 , Beyza Nur Başaran , Kadriye Başkurt , Enes Yeşilbaş , Erdem Özkan , Kadriye Bir Yücel , Mustafa Altınbaş , Şehnaz Evrimler , Ömür Berna Çakmak Öksüzoğlu , 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}
Pub Date : 2026-03-01Epub Date: 2025-10-27DOI: 10.1016/j.clcc.2025.10.004
Turkan Aliyeva , Hiba Siddiqui , Julia Natche , Yumna Ahmad Al-Wraikat , Farah Mahzabin Hossain , Imane El-Amri
Background
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.
Methods
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.
Results
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, P < .00001) and a poorer RFS (HR = 6.56, 95% CI, 4.80-8.98, P < .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, P < .00001) and a worse RFS (HR = 10.00, 95% CI, 4.84-20.66, P < .00001).
Conclusion
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.
背景：循环肿瘤DNA （ctDNA）已成为结直肠癌（CRC）最小残留病（MRD）检测和复发风险分层的有希望的生物标志物。然而，其在III期CRC中的预后意义仍不完全明确。本荟萃分析旨在评估III期CRC患者术后ctDNA阳性与复发风险之间的关系。方法：检索PubMed、Embase和Cochrane图书馆，检索截至2025年4月发表的潜在符合条件的研究。计算合并风险比（RR）和合并危险比（HR），评价结直肠癌手术和ACT后的复发率和无复发生存（RFS）预后。采用随机效应模型进行meta分析。结果：共纳入10项研究，涉及2461例III期CRC患者。术后ctDNA阳性与复发风险增加（RR = 4.39, 95% CI, 3.45-5.58, P < 0.00001）和较差的RFS （HR = 6.56, 95% CI, 4.80-8.98, P < 0.00001）显著相关。合并分析显示，ctdna阳性患者ACT术后复发风险显著增高（RR = 4.80, 95% CI, 3.17 ~ 7.26, P < 0.00001）， RFS较差（HR = 10.00, 95% CI, 4.84 ~ 20.66, P < 0.00001）。结论：术后ctDNA阳性是III期结直肠癌患者复发的重要预后指标，可指导个体化监测和辅助治疗决策。需要进一步的前瞻性研究来验证其常规临床应用。
{"title":"Prognostic Value of Circulating Tumor DNA for Recurrence Risk in Stage III Colorectal Cancer: A Systematic Review and Meta-Analysis","authors":"Turkan Aliyeva , Hiba Siddiqui , Julia Natche , Yumna Ahmad Al-Wraikat , Farah Mahzabin Hossain , 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> < .00001) and a poorer RFS (HR = 6.56, 95% CI, 4.80-8.98, <em>P</em> < .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> < .00001) and a worse RFS (HR = 10.00, 95% CI, 4.84-20.66, <em>P</em> < .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}
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.
Method
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.
Results
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.
Conclusion
Current results demonstrated that a high DDRRS was associated with a lower risk of colorectal cancer and adenoma.
{"title":"Dietary Diabetes Risk Reduction Score (DDRRS) and the Risk of Colorectal Cancer and Adenoma: A Case-Control Study","authors":"Niayesh Naghshi , Milad Mohammadzadeh , Fatemeh Babaee Kiadehi , Alireza Bahrami , Fatemeh Abdi , Mohammad Gholizadeh , 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}
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).
Patients and methods
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.
Results
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 > 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 > 70 years but not among patients ≤ 70 years (adjusted HR: 2.01, 95% CI: 0.75-5.93).
Conclusion
Sarcopenia is associated with improved OS, particularly in patients aged ≥ 70 years who underwent chemotherapy after resection of colorectal cancer.
{"title":"Age as a Modifier of the Effects of Sarcopenia on Survival Among Colon Cancer Patients Receiving Chemotherapy","authors":"Wen-Li Lin , Li‐Min Wu , Wen-Tsung Huang , 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 > 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 > 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}
Pub Date : 2025-12-01Epub Date: 2025-08-20DOI: 10.1016/j.clcc.2025.08.004
Wen-Wen Huang MD , Yan-Jun Cheng MSc , Sha-Sha Yuan MD , Yu Liu MSc , Fu-Rong Liu MD
Background
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.
Methods
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).
Results
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 (P = .023). Although the PD-L1 CPS was correlated with sex (P = .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 < 1 (P = .029). For patients with HER2-positive CRC, higher CD68 indicated better EFS (P = .047).
Conclusions
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.
{"title":"Characterization of the Tumor Immune Microenvironment in HER2-Positive Colorectal Cancer: Association With Prognostic and Therapeutic Implications","authors":"Wen-Wen Huang MD , Yan-Jun Cheng MSc , Sha-Sha Yuan MD , Yu Liu MSc , 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 < 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}
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