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Bae SU, Lee JL, Yang CS, Park EJ, Park SY, Kim CW, Ji WB, Son GM, Han YD, Kim SH, Kim MS, Park YY, Lee KH, Kim CH, Ha GW, Lee J, Kim KE, Jeong WK, Kim DW, Baek SK. Survival benefit of adjuvant chemotherapy in high-risk patients with colon cancer regardless of microsatellite instability. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109674. [PMID: 40043595 DOI: 10.1016/j.ejso.2025.109674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 12/20/2024] [Accepted: 02/01/2025] [Indexed: 05/26/2025]
Abstract
INTRODUCTION The predictive utility of high-risk features (HRFs) and microsatellite instability (MSI) status for adjuvant chemotherapy (ACT) in patients with stage II colon cancer remains unclear. We examined the impact of HRFs and MSI in predicting the benefits of adjuvant ACT in patients with stage II colon cancer. MATERIALS AND METHODS We included 1801 patients with resected stage II colon cancer who underwent ACT (5-fluorouracil [FU] and oxaliplatin) or surgery alone between January 2010 and December 2017. The primary outcomes were overall survival (OS) and disease-free survival (DFS). RESULTS Among MSI-high patients with HRFs, patients who received 5- FU and oxaliplatin-based ACT had significantly higher OS and DFS than patients who did not, with no significant difference between those who received 5-FU and oxaliplatin as ACT. Among MSI-low/microsatellite stable patients with HRFs, patients who received 5-FU and oxaliplatin as ACT had significantly higher OS and DFS than patients who did not, with no significant differences between those who received 5-FU and oxaliplatin as ACT. Among patients who did not receive ACT, OS and DFS were 95.0 % and 91.2 % for patients without HRFs, respectively, and 84.4 % and 75.0 % for patients with HRFs, respectively. ACT improved the survival rates of patients with HRFs (OS: 84.4 %→95.9 %, DFS: 75.0 %→88.9 %). CONCLUSIONS ACT can be recommended for patients having stage II colon cancer with one or more HRF(s) for recurrence, regardless of the MSI status. In patients with HRFs, we observed no significant difference regarding survival between those who received 5-FU and oxaliplatin-based ACT.
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Affiliation(s)
- Sung Uk Bae
- Department of Surgery, School of Medicine, Keimyung University and Dongsan Hospital, 1035 Dalgubeol-daero Dalseo-gu, Daegu, 42601, Republic of Korea
| | - Jong Lyul Lee
- Divsion of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center and University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Chun-Seok Yang
- Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, Daegu, 42472, Republic of Korea
| | - Eun Jung Park
- Divsion of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center and University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea; Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 06273, Republic of Korea
| | - Soo Yeun Park
- Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, 807 Hogukro Buk-gu, Daegu, 40414, Republic of Korea
| | - Chang Woo Kim
- Department of Surgery, Ajou University School of Medicine, Suwon, 16499, Republic of Korea
| | - Woong Bae Ji
- Department of Surgery, Korea University Ansan Hospital, Ansan, 15355, Republic of Korea
| | - Gyung Mo Son
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, 50612, Republic of Korea
| | - Yoon Dae Han
- Division of Colorectal Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro Seodaemun-Gu, Seoul, 03722, Republic of Korea
| | - So Hyun Kim
- Department of Surgery, Yeungnam University College of Medicine, Daegu, 42415, Republic of Korea
| | - Min Sung Kim
- Department of Surgery, Eulji General Hospital, Eulji University School of Medicine, Seoul, 01830, Republic of Korea
| | - Youn Young Park
- Department of Surgery, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, 05278, Republic of Korea
| | - Kyung Ha Lee
- Department of Surgery, Chungnam National University College of Medicine, Daejeon, 35015, Republic of Korea
| | - Chang Hyun Kim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun, 58128, Republic of Korea
| | - Gi Won Ha
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, 54907, Republic of Korea
| | - JaeIm Lee
- Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, 11765, Republic of Korea
| | - Kyeong Eui Kim
- Department of Surgery, School of Medicine, Keimyung University and Dongsan Hospital, 1035 Dalgubeol-daero Dalseo-gu, Daegu, 42601, Republic of Korea
| | - Woon Kyung Jeong
- Department of Surgery, School of Medicine, Keimyung University and Dongsan Hospital, 1035 Dalgubeol-daero Dalseo-gu, Daegu, 42601, Republic of Korea
| | - Duck-Woo Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 Beon-gil Bundang-gu, Seongnam, 13620, Republic of Korea.
| | - Seong Kyu Baek
- Department of Surgery, School of Medicine, Keimyung University and Dongsan Hospital, 1035 Dalgubeol-daero Dalseo-gu, Daegu, 42601, Republic of Korea.
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Tie J, Wang Y, Lo SN, Lahouel K, Cohen JD, Wong R, Shapiro JD, Harris SJ, Khattak A, Burge ME, Lee M, Harris M, McLachlan SA, Horvath L, Karapetis C, Shannon J, Singh M, Yip D, Ananda S, Underhill C, Ptak J, Silliman N, Dobbyn L, Popoli M, Papadopoulos N, Tomasetti C, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial. Nat Med 2025; 31:1509-1518. [PMID: 40055522 DOI: 10.1038/s41591-025-03579-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 02/07/2025] [Indexed: 04/30/2025]
Abstract
Early data from the DYNAMIC study of circulating tumor DNA (ctDNA)-guided adjuvant chemotherapy (ACT) versus standard approach met its primary outcome demonstrating reduced ACT use without compromising 2-year recurrence-free survival (RFS) for stage II colon cancer. We report here other prespecified analyses of overall survival, ctDNA clearance and ctDNA level. At a median follow-up of 59.7 months, 5-year RFS was 88% and 87% with ctDNA-guided and standard management, respectively (difference 1.1%, 95% confidence interval -5.8% to 8.0%), and 5-year overall survival is similar (93.8% versus 93.3%, hazard ratio (HR) 1.05; P = 0.887). For treated ctDNA-positive patients, ctDNA clearance was observed at the end of ACT (EOT) in 35 out of 40 patients (87.5%). A higher than median postoperative tumor-derived mutant molecules per milliliter plasma was associated with worse 5-year RFS (HR 10.62; P = 0.005). For treated ctDNA-positive patients, post hoc analysis of ctDNA clearance at EOT assessed by a new assay that evaluated an average of 29 tumor-derived mutations per patient predicted for a favorable 5-year recurrence-free probability of 97% versus 0% for ctDNA persistence (P < 0.001). Mature DYNAMIC outcome data support a ctDNA-guided approach to ACT for stage II colon cancer, with potential to further risk stratify ctDNA-positive patients based on ctDNA burden and EOT results. Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615000381583 .
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Affiliation(s)
- Jeanne Tie
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
- Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
| | - Yuxuan Wang
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Serigne N Lo
- Research and Biostatistics, Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Kamel Lahouel
- Center for Cancer Prevention, Early Detection and Monitoring, City of Hope, Duarte, CA, USA
- Division of Integrated Cancer Genomics, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Joshua D Cohen
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Rachel Wong
- Department of Medical Oncology, Eastern Health, Melbourne, Victoria, Australia
- Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - Jeremy D Shapiro
- Department of Medical Oncology, Cabrini Health, Melbourne, Victoria, Australia
| | - Samuel J Harris
- Department of Medical Oncology, Bendigo Health, Bendigo, Victoria, Australia
| | - Adnan Khattak
- Department of Medical Oncology, Fiona Stanley Hospital, Perth, Western Australia, Australia
- Edith Cowan University, Perth, Western Australia, Australia
| | - Matthew E Burge
- Department of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Margaret Lee
- Department of Medical Oncology, Eastern Health, Melbourne, Victoria, Australia
- Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia
| | - Marion Harris
- Department of Medical Oncology, Monash Health, Melbourne, Victoria, Australia
| | - Sue-Anne McLachlan
- Department of Medical Oncology, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - Lisa Horvath
- Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia
| | - Christos Karapetis
- Department of Medical Oncology, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Jenny Shannon
- Department of Medical Oncology, Nepean Cancer Care Centre, Kingswood, New South Wales, Australia
| | - Madhu Singh
- Department of Medical Oncology, Barwon Health, Geelong, Victoria, Australia
| | - Desmond Yip
- Department of Medical Oncology, Canberra Hospital, Canberra, Australian Capital Territory, Australia
| | - Sumitra Ananda
- Epworth Freemasons, Richmond, Melbourne, Victoria, Australia
| | - Craig Underhill
- Border Medical Oncology, Albury, New South Wales, Australia
- Rural Medical School, Albury Campus, University of NSW, Albury, New South Wales, Australia
| | - Janine Ptak
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Natalie Silliman
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Lisa Dobbyn
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Maria Popoli
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Nickolas Papadopoulos
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Cristian Tomasetti
- Center for Cancer Prevention, Early Detection and Monitoring, City of Hope, Duarte, CA, USA
- Division of Integrated Cancer Genomics, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Kenneth W Kinzler
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Bert Vogelstein
- Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Peter Gibbs
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
- Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
- Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia
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Zengin M, Işıkçı ÖT. Tumour Budding Is a Useful Predictor to Identify High-Risk Stage II Colon Cancer Patients After Curative Surgery. Int J Surg Pathol 2025; 33:363-374. [PMID: 39094576 DOI: 10.1177/10668969241265017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
Aim. Although it is now accepted in the literature that tumour budding (TB) is a useful survival indicator in colon cancer (CC), there are still uncertainties about daily use. Here we methodologically examined the role of TB on survival in CC. Methods. In our study, we examined colon cancer patients who had surgery up to 15 years before presentation. TB was calculated separately using different comprehensive methodological methods. Results. We first investigated an optimal evaluation method. Relationship with prognostic factors was better (Venous invasion [p = .001], advanced pT [p = .003], perineural invasion [p = .040], MSS [p = .016], advanced size [p = .001], tumour obstruction [p = .005], margin involvement [p = .043], and nodal involvement [p = .028]) in Method-1. Similarly, with the same method, the success of the cut-off value, the correlation of TB data (r = .724), and the repeatability of the method (Κappa = .53-.75) were quite good (ROC = .816 [.707-.925]). Then, survival analysis was performed using the best three methods, including this method. In univariate analysis using Method-1, survival analyses were worse in high TB patients (RFS: 81%, p < .001; OS: 84%, p < .001). Multivariate analyses using the same method confirmed that high TB for RFS and OS was an independent poor prognostic parameter for survival (p = .002, Hazard ratio [HR]: 1.42 [1.13-1.80]) and OS (p = .014, HR: 1.38 [1.07-1.79]). Conclusions. With our study, we showed that tumour budding calculated by the standard method is a very valuable prognostic parameter in stage II CC and can contribute to the detection of patients with poor prognosis in stage II CC.
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Affiliation(s)
- Mehmet Zengin
- Department of Pathology, Kırıkkale University, Kırıkkale, Turkey
| | - Özlem Tanas Işıkçı
- Department of Pathology, Ankara Training and Research Hospital, Ankara, Turkey
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Negro S, Pulvirenti A, Trento C, Indraccolo S, Ferrari S, Scarpa M, Urso EDL, Bergamo F, Pucciarelli S, Deidda S, Restivo A, Lonardi S, Spolverato G. Circulating Tumor DNA as a Real-Time Biomarker for Minimal Residual Disease and Recurrence Prediction in Stage II Colorectal Cancer: A Systematic Review and Meta-Analysis. Int J Mol Sci 2025; 26:2486. [PMID: 40141130 PMCID: PMC11942625 DOI: 10.3390/ijms26062486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 03/05/2025] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
The role of adjuvant chemotherapy (adj-CT) in stage II colon cancer remains controversial. Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual disease (MRD) and predicting recurrence. This systematic review and meta-analysis evaluated the prognostic value of ctDNA in stage II colorectal cancer (CRC), focusing on postoperative detection, post adj-CT outcomes, and dynamic surveillance. A literature search identified studies correlating ctDNA positivity in stage II CRC with recurrence risk, recurrence-free survival (RFS), and disease-free survival (DFS). Seven studies met the inclusion criteria. Postoperative ctDNA positivity significantly increased the risk of recurrence (pooled risk ratio [RR:] 3.66; 95% confidence interval [CI]: 1.25-10.72; p = 0.002). CtDNA positivity after adj-CT was strongly associated with poor survival, while dynamic ctDNA monitoring detected recurrence earlier than conventional methods, including carcinoembryonic antigen (CEA) and imaging. CtDNA is a robust prognostic biomarker in stage II CRC, enabling personalized treatment. High-risk ctDNA-positive patients may benefit from intensified therapy, while ctDNA-negative patients could avoid unnecessary treatments. However, the standardization of detection methods and large-scale validation studies are needed before integrating ctDNA into routine clinical practice as a non-invasive, dynamic tool for personalized care.
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Affiliation(s)
- Silvia Negro
- Third Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, 35128 Padova, Italy; (A.P.); (S.F.); (M.S.); (E.D.L.U.); (S.P.); (G.S.)
| | - Alessandra Pulvirenti
- Third Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, 35128 Padova, Italy; (A.P.); (S.F.); (M.S.); (E.D.L.U.); (S.P.); (G.S.)
| | - Chiara Trento
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (C.T.); (S.I.)
| | - Stefano Indraccolo
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (C.T.); (S.I.)
- Basic and Translational Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy
| | - Stefania Ferrari
- Third Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, 35128 Padova, Italy; (A.P.); (S.F.); (M.S.); (E.D.L.U.); (S.P.); (G.S.)
| | - Marco Scarpa
- Third Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, 35128 Padova, Italy; (A.P.); (S.F.); (M.S.); (E.D.L.U.); (S.P.); (G.S.)
| | - Emanuele Damiano Luca Urso
- Third Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, 35128 Padova, Italy; (A.P.); (S.F.); (M.S.); (E.D.L.U.); (S.P.); (G.S.)
| | - Francesca Bergamo
- Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy; (F.B.); (S.L.)
| | - Salvatore Pucciarelli
- Third Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, 35128 Padova, Italy; (A.P.); (S.F.); (M.S.); (E.D.L.U.); (S.P.); (G.S.)
| | - Simona Deidda
- Colorectal Surgery Unit, A.O.U. Cagliari, Department of Surgical Science, University of Cagliari, 09042 Cagliari, Italy; (S.D.); (A.R.)
| | - Angelo Restivo
- Colorectal Surgery Unit, A.O.U. Cagliari, Department of Surgical Science, University of Cagliari, 09042 Cagliari, Italy; (S.D.); (A.R.)
| | - Sara Lonardi
- Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy; (F.B.); (S.L.)
| | - Gaya Spolverato
- Third Surgical Clinic, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, 35128 Padova, Italy; (A.P.); (S.F.); (M.S.); (E.D.L.U.); (S.P.); (G.S.)
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Fan S, Wang J, Hou Y, Cui X, Feng Z, Qi L, Liu J, Bian K, Liang J, Ye Z, Zheng S, Ma W. MRI-based multiregional radiomics for desmoplastic reaction classification and prognosis stratification in stage II rectal cancer: A bicenter study. Eur J Radiol 2025; 183:111888. [PMID: 39705910 DOI: 10.1016/j.ejrad.2024.111888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 11/22/2024] [Accepted: 12/11/2024] [Indexed: 12/23/2024]
Abstract
PURPOSE To develop an MRI-based multiregional radiomics model for the noninvasive desmoplastic reaction (DR) classification and prognosis stratification in stage II rectal cancer (RC) patients. MATERIALS AND METHODS This study retrospectively involved 336 patients with RC from two centers, with 239 from Center 1 divided into training (n = 191) and internal validation (n = 48) datasets at an 8:2 ratio, and 97 from Center 2 serving as external validation dataset. Radiomics features were extracted, and a multiregional radiomics DR (M-RDR) signature was established using multi-level feature selection procedure. The cut-off value for M-RDR was determined using Youden's index. We further evaluated the predictive values of M-RDR on prognosis and adjuvant chemotherapy stratification. The primary outcome was 3-year disease-free survival (DFS), and cox model performance was assessed using AUCs and 95 % confidence intervals. RESULTS M-RDR demonstrated a high accuracy in DR classification with AUCs of 0.778 and 0.798 in the training and internal validation datasets. Multivariable analysis confirmed M-RDR as an independent prognostic factor after adjusting for clinicopathological factors.The combined model incorporating M-RDR and clinicopathological factors showed good performance in predicting 3-year DFS, with AUCs of 0.923, 0.908, and 0.891 in the training, internal validation and external validation datasets, respectively. Additionally, patients in the M-RDR-high group who received adjuvant chemotherapy had significantly better DFS compared with those who did not (P < 0.05). CONCLUSION The MRI-based multiregional radiomics model could effectively improve non-invasive DR classification, and was able to enhance postoperative risk stratification and treatment decision-making in stage II RC patients.
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Affiliation(s)
- Shuxuan Fan
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Jing Wang
- School of Public Health, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yan Hou
- Department of Radiology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Precise Imaging of Inflammation - Related Tumors, Hebei, China
| | - Xiaonan Cui
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Ziwei Feng
- Department of Epidemiology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China
| | - Lisha Qi
- Department of Pathology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China
| | - Jiaxin Liu
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Keyi Bian
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Jing Liang
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Zhaoxiang Ye
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Sunyi Zheng
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
| | - Wenjuan Ma
- Department of Breast Imaging, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China.
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Fang H, Han L, Xu Y, Gu R, Cai G, Xia Z, Dai W, Wang R. High expression of PAX8-AS1 correlates with poor prognosis and response to fluorouracil-based chemotherapy in stage II colon cancer. Transl Oncol 2024; 50:102128. [PMID: 39303358 PMCID: PMC11437868 DOI: 10.1016/j.tranon.2024.102128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/27/2024] [Accepted: 09/14/2024] [Indexed: 09/22/2024] Open
Abstract
Decisions regarding adjuvant therapy in patients with stage II colon cancer remains controversial and challenging. We aimed to determine novel biomarkers that help to predict relapse free survival (RFS) and identify a subset of patients with stage II colon cancer who could gain survival benefits from adjuvant chemotherapy. Public microarray datasets of stage II colon cancer samples were extracted from Gene Expression Omnibus database. Global gene expression changes were then analyzed between the paired early relapse and long-term survival group to identify the differentially expressed mRNAs and lncRNAs. Based on Lasso Cox regression modeling analysis, a total of 30 mRNAs and 2 lncRNAs were finally identified. With specific formula, stage II patients in training and validation sets were divided into low and risk groups with significantly different RFS. PAX8-AS1 is the novel lncRNA which showed the highest upregulation in early relapse group. Patients with high PAX8-AS1 expression level showed notably poorer RFS in both meta GEO cohort (P = 0.04, Figure 4B) and FUSCC cohort (P < 0.001, Figure 4C). Among the stage II patients with high PAX8-AS1 level, administration of fluorouracil-based adjuvant chemotherapy provided a substantial improvement in RFS (P = 0.002, Figure 3C). Further mechanistic study unveiled that PAX8-AS1 increases the response of CRC cells to chemotherapy in vitro and in vivo by maintaining the mRNA stability of PAX8. In conclusion, PAX8-AS1 as a novel and reliable biomarker for predicting prognosis and identification of patients with stage II disease who could gain survival benefit from fluorouracil-based adjuvant chemotherapy.
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Affiliation(s)
- Hongsheng Fang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, Shanghai, PR China
| | - Lingyu Han
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, Shanghai, PR China
| | - Yun Xu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, Shanghai, PR China
| | - Ruiqi Gu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, Shanghai, PR China
| | - Guoxiang Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, Shanghai, PR China
| | - Zuguang Xia
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, Shanghai, PR China; Department of lymphoma, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, PR China.
| | - Weixing Dai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, Shanghai, PR China.
| | - Renjie Wang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, Shanghai, PR China.
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Li GG, Chu XF, Xing YM, Xue X, Ihtisham B, Liang XF, Xu JX, Mi Y, Zheng PY. Baicalin Prevents Colon Cancer by Suppressing CDKN2A Protein Expression. Chin J Integr Med 2024; 30:1007-1017. [PMID: 38941045 DOI: 10.1007/s11655-024-4109-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2024] [Indexed: 06/29/2024]
Abstract
OBJECTIVE To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. METHODS The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. RESULTS Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G0/G1 phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). CONCLUSION Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.
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Affiliation(s)
- Gang-Gang Li
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancers, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 400015, China
| | - Xiu-Feng Chu
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancers, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 400015, China
| | - Ya-Min Xing
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancers, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 400015, China
| | - Xia Xue
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancers, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 400015, China
| | - Bukhari Ihtisham
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancers, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 400015, China
| | - Xin-Feng Liang
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancers, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 400015, China
| | - Ji-Xuan Xu
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancers, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 400015, China
| | - Yang Mi
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancers, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 400015, China
| | - Peng-Yuan Zheng
- Henan Key Laboratory of Helicobacter pylori, Microbiota and Gastrointestinal Cancers, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 400015, China.
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8
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Montcusí B, Madrid-Gambin F, Marin S, Mayol X, Pascual M, Cascante M, Pozo ÓJ, Pera M. Circulating Metabolic Markers Identify Patients at Risk for Tumor Recurrence: A Prospective Cohort Study in Colorectal Cancer Surgery. Ann Surg 2024; 280:842-849. [PMID: 39087328 DOI: 10.1097/sla.0000000000006463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
OBJECTIVE To investigate the spermidine pathway capability to predict patients at risk for tumor recurrence following colorectal cancer (CRC) surgery. BACKGROUND Recurrence rates after CRC surgery remain at about 20% despite an optimal technique and adjuvant therapy when necessary. Identification of risk biomarkers of recurrence is an unmet need. The spermidine pathway is indispensable for cell proliferation and differentiation, and is suggested to accelerate tumor spread. METHODS This was a prospective cohort study of patients undergoing CRC surgery from 2015 to 2018. Plasma samples were collected before surgery and on postoperative day 4, and the spermidine pathway was assessed through mass spectrometry. Oncological outcomes were registered. RESULTS A total of 146 patients were included and 24 (16.4%) developed tumor recurrence. Higher levels of preoperative spermidine pathway components (spermidine, spermine, spermidine synthase enzyme, and spermine/arginine balance) were positively associated with recurrence. Surgery promoted a decrease in these pathway elements. The greater the decline was, the lower the risk of recurrence. Preoperative spermidine over the cut-off of 0.198 µM displayed a 4.69-fold higher risk of recurrence. The spermine synthase enzyme behaved in the opposite direction. CONCLUSIONS The spermidine pathway is associated with tumor recurrence following CRC surgery and, after confirmation in larger cohorts, could be translated as a risk biomarker of recurrence into clinical practice.
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Affiliation(s)
- Blanca Montcusí
- Department of Surgery, Section of Colon and Rectal Surgery, Hospital del Mar, Barcelona, Spain
- Colorectal Neoplasms Clinical and Translational Research Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain
- Applied Metabolomics Research Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain
- Department of Surgery, University of Barcelona (UB), Barcelona, Spain
| | - Francisco Madrid-Gambin
- Applied Metabolomics Research Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain
- Signal and Information Processing for Sensing Systems, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Silvia Marin
- Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona (UB), Barcelona, Spain
- Institute of Biomedicine, University of Barcelona (UB), Barcelona, Spain
- CIBER of Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III (ISCIII), Madrid, Spain
| | - Xavier Mayol
- Colorectal Neoplasms Clinical and Translational Research Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain
| | - Marta Pascual
- Department of Surgery, Section of Colon and Rectal Surgery, Hospital del Mar, Barcelona, Spain
- Colorectal Neoplasms Clinical and Translational Research Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain
| | - Marta Cascante
- Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona (UB), Barcelona, Spain
- Institute of Biomedicine, University of Barcelona (UB), Barcelona, Spain
- CIBER of Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III (ISCIII), Madrid, Spain
| | - Óscar J Pozo
- Applied Metabolomics Research Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain
| | - Miguel Pera
- Department of Surgery, University of Barcelona (UB), Barcelona, Spain
- CIBER of Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III (ISCIII), Madrid, Spain
- Gastrointestinal and Pancreatic Oncology Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
- Department of General and Digestive Surgery, Institute of Digestive and Metabolic Diseases, Hospital Clínic, Barcelona, Spain
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9
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Hsieh RW, Symonds LK, Siu J, Cohen SA. Identification of circulating tumor DNA as a biomarker for diagnosis and response to therapies in cancer patients. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2024; 391:43-93. [PMID: 39939078 DOI: 10.1016/bs.ircmb.2024.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/14/2025]
Abstract
The sampling of circulating biomarkers provides an opportunity for non-invasive evaluation and monitoring of cancer activity. In modern day practice, this has typically been in the form of circulating tumor DNA (ctDNA) detected in plasma. The field of ctDNA has been a burgeoning technology, with prominent applications for blood-based cancer screening and in disease status assessment, especially after curative-intent surgery to evaluate for minimal residual disease (MRD). Clinical applications for the latter show an incredibly high sensitivity in certain cancer types with a need for additional studies to determine how much clinical decision-making should be adapted based on ctDNA results and which cancer types, stages, and treatments are best informed by ctDNA results. This chapter provides an overview of ctDNA detection as tool for cancer screening, detecting MRD, and/or molecularly characterizing a cancer, highlighting the rapidly amassing research as a prognostic biomarker and emerging data on ctDNA as a predictive biomarker.
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Affiliation(s)
- Ronan W Hsieh
- Division of Hematology/Oncology, University of Washington, Seattle, WA, United States; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Lynn K Symonds
- Division of Hematology/Oncology, University of Washington, Seattle, WA, United States; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Jason Siu
- Department of Laboratory Medicine, University of Washington, Seattle, WA, United States
| | - Stacey A Cohen
- Division of Hematology/Oncology, University of Washington, Seattle, WA, United States; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
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10
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Ogata Y, Sadahiro S, Sakamoto K, Tsuchiya T, Takahashi T, Ohge H, Sato T, Kondo K, Baba H, Itabashi M, Ikeda M, Hamada M, Maeda K, Masuko H, Takahashi K, Kusano M, Hyodo I, Sakamoto J, Taguri M, Morita S. Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201). Int J Clin Oncol 2024; 29:1284-1292. [PMID: 38833114 PMCID: PMC11347494 DOI: 10.1007/s10147-024-02565-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 05/28/2024] [Indexed: 06/06/2024]
Abstract
BACKGROUND The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. METHODS In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. RESULTS Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. CONCLUSION The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. TRIAL REGISTRATION Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).
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Affiliation(s)
- Yutaka Ogata
- Department of Surgery, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, Fukuoka, 830-0011, Japan.
| | - Sotaro Sadahiro
- Department of Surgery, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Kazuhiro Sakamoto
- Department of Coloproctological Surgery, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Takashi Tsuchiya
- Department of Surgery, Sendai City Medical Center, 5-22-1 Tsurugaya, Miyagino-Ku, Sendai, Miyagi, 983-0824, Japan
| | - Takao Takahashi
- Department of Digestive Surgery, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan
- Department of Surgery, Seino Kosei Hospital, 293-1 Shimoiso Ono-Cho, Ibi-Gun, Gifu, 501-0532, Japan
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Toshihiko Sato
- Department of Surgery, Yamagata Prefectural Central Hospital, 1800 Aoyagi, Yamagata, 990-2292, Japan
| | - Ken Kondo
- Department of Surgery, Nagoya Medical Center, 4-1-1 Sannomaru, Naka-Ku, Nagoya, Aichi, 460-0001, Japan
| | - Hideo Baba
- Department of Gastroen- Terological Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Michio Itabashi
- Department of Surgery, Division of Inflammatory Bowel Disease Surgery, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan
| | - Masataka Ikeda
- Department of Gastroenterological Surgery, Division of Lower GI, Hyogo Medical University, 1-1 Mukogawa-Cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Madoka Hamada
- Department of Gastrointestinal Surgery, Kansai Medical University Hospital, 2-3-1 Shinmachi Hirakata, Osaka, 573-1191, Japan
| | - Kiyoshi Maeda
- Department of Gastroenterological Surgery, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
| | - Hiroyuki Masuko
- Department of Surgery, Nikko Memorial Hospital, 1-5-13 Shintomi-Cho, Muroran, Hokkaido, 051-8501, Japan
| | - Keiichi Takahashi
- Tokyo Metropolitan Health and Hospitals Corporation Ohkubo Hospital, 2-44-1 Kabuki-Cho, Shinjuku-Ku, Tokyo, 160-8488, Japan
| | - Mitsuo Kusano
- Department of Physical Medicine, Yoichi Hospital, 19-1-1 Kurokawa-Cho Yoichi, Hokkaido, 046-0003, Japan
| | - Ichinosuke Hyodo
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto, Matsuyama, Ehime, 791-0280, Japan
| | - Junichi Sakamoto
- Tokai Central Hospital, 4-6-2 Sohara Higashijima-Cho, Kakamigahara, Gifu, 504-8601, Japan
| | - Masataka Taguri
- Department of Health Data Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-Ku, Tokyo, 160-8402, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan
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11
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Akdag G, Isik D, Dogan A, Yildirim S, Kinikoglu O, Topal A, Oksuz S, Turkoglu E, Surmeli H, Basoglu T, Sever ON, Odabas H, Yildirim ME, Turan N. Does Adjuvant Chemotherapy Benefit Patients with T4 N0 Colon Cancer? MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1372. [PMID: 39202652 PMCID: PMC11356621 DOI: 10.3390/medicina60081372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 08/11/2024] [Accepted: 08/20/2024] [Indexed: 09/03/2024]
Abstract
Background and Objectives: Colorectal cancer (CRC) poses a major global health challenge, with high incidence rates and ongoing treatment debates. Adjuvant chemotherapy benefits for high-risk subgroups, particularly stage II disease, remain controversial. This study seeks to clarify this issue by specifically examining the impact of adjuvant chemotherapy on disease-free survival (DFS) and overall survival (OS) in patients diagnosed with T4 colon cancer. Materials and Methods: This retrospective study analyzed patients undergoing radical surgery for T4 colon cancer between 2002 and 2023. Results: Our study of 184 pT4 pN0 colon cancer patients revealed that 79.3% received adjuvant chemotherapy. Multivariate analysis demonstrated significant DFS improvement: a 60% reduction in risk for those who received adjuvant therapy (0.40 95% CI: 0.25-0.62, p < 0.001). Lymphovascular invasion (LVI) and adjuvant treatment were also significantly associated with OS. Adjuvant treatment reduced mortality by 60% (HR: 0.40, 95% CI: 0.23-0.68, p = 0.001). Patients with LVI had a 1.9-fold increase in mortality (HR: 1.94, 95% CI: 1.17-3.20, p = 0.011). These findings underscore the potential value of adjuvant chemotherapy and highlight the importance of treatment completion in managing T4 colon cancer. Conclusions: Our study identifies LVI and adjuvant chemotherapy as key prognostic factors in T4 colon cancer patients. These results support the consideration of adjuvant chemotherapy in this patient population.
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Affiliation(s)
- Goncagul Akdag
- Dr Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi, 34865 Istanbul, Turkey; (D.I.); (A.D.); (S.Y.); (O.K.); (A.T.); (S.O.); (E.T.); (H.S.); (T.B.); (O.N.S.); (H.O.); (M.E.Y.); (N.T.)
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12
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Korsgaard U, García-Rodríguez JL, Jakobsen T, Ahmadov U, Dietrich KG, Vissing SM, Paasch TP, Lindebjerg J, Kjems J, Hager H, Kristensen LS. The Transcriptional Landscape of Coding and Noncoding RNAs in Recurrent and Nonrecurrent Colon Cancer. THE AMERICAN JOURNAL OF PATHOLOGY 2024; 194:1424-1442. [PMID: 38704091 DOI: 10.1016/j.ajpath.2024.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 03/15/2024] [Accepted: 04/05/2024] [Indexed: 05/06/2024]
Abstract
A number of patients with colon cancer with local or local advanced disease suffer from recurrence and there is an urgent need for better prognostic biomarkers in this setting. Here, the transcriptomic landscape of mRNAs, long noncoding RNAs, snRNAs, small nucleolar RNAs (snoRNAs), small Cajal body-specific RNAs, pseudogenes, and circular RNAs, as well as RNAs denoted as miscellaneous RNAs, was profiled by total RNA sequencing. In addition to well-known coding and noncoding RNAs, differential expression analysis also uncovered transcripts that have not been implicated previously in colon cancer, such as RNA5SP149, RNU4-2, and SNORD3A. Moreover, there was a profound global up-regulation of snRNA pseudogenes, snoRNAs, and rRNA pseudogenes in more advanced tumors. A global down-regulation of circular RNAs in tumors relative to normal tissues was observed, although only a few were expressed differentially between tumor stages. Many previously undescribed transcripts, including RNU6-620P, RNU2-20P, VTRNA1-3, and RNA5SP60, indicated strong prognostic biomarker potential in receiver operating characteristics analyses. In summary, this study unveiled numerous differentially expressed RNAs across various classes between recurrent and nonrecurrent colon cancer. Notably, there was a significant global up-regulation of snRNA pseudogenes, snoRNAs, and rRNA pseudogenes in advanced tumors. Many of these newly discovered candidates demonstrate a strong prognostic potential for stage II colon cancer.
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Affiliation(s)
- Ulrik Korsgaard
- Department of Clinical Pathology, Vejle Hospital, Vejle, Denmark; Danish Colorectal Cancer Center South, Vejle Hospital, Vejle, Denmark
| | | | | | - Ulvi Ahmadov
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | | | - Stine M Vissing
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Thea P Paasch
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Jan Lindebjerg
- Department of Clinical Pathology, Vejle Hospital, Vejle, Denmark; Danish Colorectal Cancer Center South, Vejle Hospital, Vejle, Denmark
| | - Jørgen Kjems
- Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark; Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, Denmark
| | - Henrik Hager
- Department of Clinical Pathology, Vejle Hospital, Vejle, Denmark; Danish Colorectal Cancer Center South, Vejle Hospital, Vejle, Denmark; Department of Pathology, Aarhus University Hospital, Aarhus, Denmark
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13
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Zheng P, Xu G, Qin Z, Zhou S, Huang H, Ma D, Gao X. The Causes Behind the Survival Paradox in Non-Metastatic Colorectal Cancer Patients and its Impact on the Treatment Regimen: A Retrospective Cohort Study. Surgery 2024; 176:310-318. [PMID: 38760234 DOI: 10.1016/j.surg.2024.03.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/07/2024] [Accepted: 03/25/2024] [Indexed: 05/19/2024]
Abstract
BACKGROUND The survival paradox (ie, the prognosis of the population at earlier tumor stages is worse than that of the population at later stages) has been observed in colorectal cancer based on the American Joint Committee on Cancer Tumor-Nodes-Metastases staging system. We aimed to clarify the reason for the survival paradox and its impact on patient treatment. METHODS We conducted a retrospective study analyzing eligible patients with colorectal cancer from the Surveillance, Epidemiology, and End Results database and Zhejiang Cancer Hospital between 2010 and 2019. Adjusting for confounders using propensity score matching allowed confirmation of the effect of staging on the survival paradox. RESULTS Based on the Surveillance, Epidemiology, and End Results database, the subgroups with survival paradox might be IIB/C versus IIIA, IIA versus IIIA, and T4N0 (IIB/C) versus T3N1 (IIIB). After propensity score matching, stage IIB/C still had a worse prognosis than stage IIIA (5-year overall survival: 69.3% vs 78.5%, P < .001). Interestingly, the proportion of stage IIIA people receiving chemotherapy was higher than that of stage IIB/C (P < .001), and logistic regression models showed that staging was the reason for deciding whether a patient receives chemotherapy or not. These phenomena between stage IIB/C and IIIA were verified in the local database. CONCLUSION These results suggested that the survival paradox was mainly due to underestimation of stage T4 weights or overestimation of stage N1 weights, and the low proportion of chemotherapy in patients with T4N0M0 colorectal cancer (proven to be more malignant than stage IIIA) might be related to the assignment to earlier stages, resulting in a lack of attention and poor compliance to chemotherapy in these patients.
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Affiliation(s)
- Pengwen Zheng
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
| | - Guohui Xu
- Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
| | - Zhaofu Qin
- Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
| | - Shiqi Zhou
- Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
| | - Hai Huang
- Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
| | - Dening Ma
- Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
| | - Xinyi Gao
- Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
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14
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Chien H, Chu YD, Hsu YP, Yeh CT, Lai MW, Chang ML, Lim SN, Chen CW, Lin WR. An SNP Marker Predicts Colorectal Cancer Outcomes with 5-Fluorouracil-Based Adjuvant Chemotherapy Post-Resection. Int J Mol Sci 2024; 25:6642. [PMID: 38928347 PMCID: PMC11203489 DOI: 10.3390/ijms25126642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 06/04/2024] [Accepted: 06/14/2024] [Indexed: 06/28/2024] Open
Abstract
Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly in intermediate-stage patients. However, existing therapeutic disparities highlight the need for biomarker-guided adjuvant chemotherapy to achieve better CRC inhibition. This study explores the molecular mechanisms underlying the inhibition of CRC through a genome-wide association study (GWAS) focused on 5-fluorouracil (5-FU)-based adjuvant therapy in intermediate-stage CRC patients, a domain previously unexplored. We retrospectively included 226 intermediate-stage CRC patients undergoing surgical resection followed by 5-FU-based adjuvant chemotherapy. The exploration cohort comprised 31 patients, and the validation cohort included 195 individuals. Genotyping was carried out using either Axiom Genome-Wide TWB 2.0 Array Plate-based or polymerase chain reaction-based methods on genomic DNA derived from collected tissue samples. Statistical analyses involved descriptive statistics, Kaplan-Meier analyses, and Cox proportional hazard analyses. From the GWAS, potential genetic predictors, GALNT14-rs62139523 and DNMBP-rs10786578 genotypes, of 5-FU-based adjuvant therapy following surgery in intermediate-stage CRC patients were identified. Validation in a larger cohort of 195 patients emphasized the predictive significance of GALNT14-rs62139523 genotypes, especially the "A/G" genotype, for improved overall and progression-free survival. This predictive association remained robust across various subgroups, with exceptions for specific demographic and clinical parameters such as age < 58 years old, CEA ≤ 2.5 ng/mL, tumor diameter > 44.0 mm, and tumor-free margin ≥ 50 mm. This study identifies that the GALNT14-rs62139523 "A/G" genotype modulates therapeutic outcomes, establishing it as a promising biomarker for predicting favorable responses to 5-FU-based adjuvant chemotherapy in intermediate-stage CRC patients, although further investigations are needed to detail these mechanisms.
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Affiliation(s)
- Hao Chien
- Department of Hepatology and Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (H.C.); (C.-T.Y.); (M.-L.C.)
| | - Yu-De Chu
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (Y.-D.C.); (Y.-P.H.); (M.-W.L.)
| | - Yi-Ping Hsu
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (Y.-D.C.); (Y.-P.H.); (M.-W.L.)
| | - Chau-Ting Yeh
- Department of Hepatology and Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (H.C.); (C.-T.Y.); (M.-L.C.)
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (Y.-D.C.); (Y.-P.H.); (M.-W.L.)
- Institute of Stem Cell and Translational Cancer Research, Linkou Chang Gung Memorial Hospital, Taoyuan 333323, Taiwan
| | - Ming-Wei Lai
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (Y.-D.C.); (Y.-P.H.); (M.-W.L.)
- Division of Pediatric Gastroenterology, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
| | - Ming-Ling Chang
- Department of Hepatology and Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (H.C.); (C.-T.Y.); (M.-L.C.)
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (Y.-D.C.); (Y.-P.H.); (M.-W.L.)
| | - Siew-Na Lim
- Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan;
| | - Chun-Wei Chen
- Department of Hepatology and Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (H.C.); (C.-T.Y.); (M.-L.C.)
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (Y.-D.C.); (Y.-P.H.); (M.-W.L.)
| | - Wey-Ran Lin
- Department of Hepatology and Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (H.C.); (C.-T.Y.); (M.-L.C.)
- Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; (Y.-D.C.); (Y.-P.H.); (M.-W.L.)
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15
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Chen S, Li G, Pan R, Zhou K, Wen W, Tao J, Wang F, Han RPS, Pan H, Tu Y. Novel Near-Infrared Fluorescent Probe for Hepatocyte Growth Factor in Vivo Imaging in Surgical Navigation of Colorectal Cancer. Anal Chem 2024; 96:9016-9025. [PMID: 38780636 DOI: 10.1021/acs.analchem.4c00350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Abstract
Despite recent advancements in colorectal cancer (CRC) treatment, the prognosis remains unfavorable primarily due to high recurrence and liver metastasis rates. Fluorescence molecular imaging technologies, combined with specific probes, have gained prominence in facilitating real-time tumor resection guided by fluorescence. Hepatocyte growth factor (HGF) is overexpressed in CRC, but the advancement of HGF fluorescent probes has been impeded by the absence of effective HGF-targeting small-molecular ligands. Herein, we present the targeted capabilities of the novel V-1-GGGK-MPA probe labeled with a near-infrared fluorescent dye, which targets HGF in CRC. The V-1-GGGK peptide exhibits high specificity and selectivity for HGF-positive in vitro tumor cells and in vivo tumors. Biodistribution analysis of V-1-GGGK-MPA revealed tumor-specific accumulation with low background uptake, yielding signal-to-noise ratio (SNR) values of tumor-to-colorectal >6 in multiple subcutaneous CRC models 12 h postinjection. Quantitative analysis confirmed the probe's high uptake in SW480 and HT29 orthotopic and liver metastatic models, with SNR values of tumor-to-colorectal and -liver being 5.6 ± 0.4, 4.6 ± 0.5, and 2.1 ± 0.3, 2.0 ± 0.5, respectively, enabling precise tumor visualization for surgical navigation. Pathological analysis demonstrated the excellent tumor boundaries discrimination capacity of the V-1-GGGK-MPA probe at the molecular level. With its rapid tumor targeting, sustained tumor retention, and precise tumor boundary delineation, V-1-GGGK-MPA merges as a promising HGF imaging agent, enriching the toolbox of intraoperative navigational fluorescent probes for CRC.
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Affiliation(s)
- Shuying Chen
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Gang Li
- Department of Ecology and Environment, Yuzhang Normal University, Nanchang 330103, China
| | - Rongbin Pan
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Kuncheng Zhou
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Weijie Wen
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Ji Tao
- Human Phenome Institute, Fudan University, Shanghai 201203, China
| | - Fang Wang
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Ray P S Han
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Huaping Pan
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Yuanbiao Tu
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, China
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16
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Oh SY, Kim CW, Kim S, Kim MH, Kim YI, Lee JL, Yoon YS, Park IJ, Lim SB, Yu CS. Complete Obstruction, a Real Risk Factor: A Comprehensive Study on Obstruction in Stage IIA Colon Cancer With Propensity Score Matching Analysis. Clin Colorectal Cancer 2024; 23:135-146.e3. [PMID: 38749791 DOI: 10.1016/j.clcc.2024.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 04/03/2024] [Accepted: 04/06/2024] [Indexed: 06/04/2024]
Abstract
MICROABSTRACT This study evaluates the prognostic significance of obstructions in stage IIA colon cancer, distinguishing between partial and complete obstructions. It employs a retrospective review of 1914 patients with propensity score matching to analyze oncologic outcomes. Findings reveal complete obstruction as a significant risk factor for poorer outcomes, emphasizing the necessity for further research to refine treatment strategies, particularly regarding the efficacy of adjuvant chemotherapy across obstruction types. BACKGROUND This study examined the prognostic impact of obstructions in stage IIA colon cancer. The analysis specifically differentiated partial and complete obstructions, analyzing their distinct influences of both on oncologic outcomes. MATERIALS AND METHODS A retrospective review was conducted of stage IIA colon cancer cases with the presence of an obstruction. Patients were stratified by whether it was partial or complete based on the severity of obstruction. Propensity score matching was employed to control for confounders. RESULTS Among 1914 consecutive patients diagnosed with stage IIA colon cancer, 758 patients (597 patients with partial obstruction, 161 patients with complete obstruction) exhibited obstruction, while 1156 patients had no obstruction. The median follow-up period was 126 months. Complete obstruction was associated with poorer disease-free survival (Hazard ratio (HR) = 1.785, P < .001) and overall survival (HR = 1.853, P = .001). This trend persisted after propensity score matching, patients with complete obstruction showing a worsened disease-free survival (HR = 1.666, P = .028) and overall survival (HR = 1.732, P = .041). Adjuvant chemotherapy showed improved outcomes overall, but its efficacy varied across obstruction types. CONCLUSION Differentiating between complete and partial obstructions in stage IIA colon cancer is an important clinical distinction, as our findings suggest that complete obstruction is a significant risk factor for poorer oncologic outcomes. While adjuvant chemotherapy generally improves prognosis in stage IIA colon cancer, the correlation of obstruction type with its efficacy remains uncertain, necessitating further research to refine treatment strategies.
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Affiliation(s)
- Soo Young Oh
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea; Department of Surgery, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chan Wook Kim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea.
| | - Seonok Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul, Republic of Korea
| | - Min Hyun Kim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Young Il Kim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Jong Lyul Lee
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Yong Sik Yoon
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - In Ja Park
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Seok-Byung Lim
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
| | - Chang Sik Yu
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea
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Pathak PS, Chan G, Deming DA, Chee CE. State-of-the-Art Management of Colorectal Cancer: Treatment Advances and Innovation. Am Soc Clin Oncol Educ Book 2024; 44:e438466. [PMID: 38768405 DOI: 10.1200/edbk_438466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
Colorectal cancer (CRC) remains a significant global health challenge, ranking among the leading causes of cancer-related morbidity and mortality worldwide. Recent advancements in molecular characterization have revolutionized our understanding of the heterogeneity within colorectal tumors, particularly in the context of tumor sidedness. Tumor sidedness, referring to the location of the primary tumor in either the right or left colon, has emerged as a critical factor influencing prognosis and treatment responses in metastatic CRC. Molecular underpinnings of CRC, the impact of tumor sidedness, and how this knowledge guides therapeutic decisions in the era of precision medicine have led to improved outcomes and better quality of life in patients. The emergence of circulating tumor DNA as a prognostic and predictive tool in CRC heralds promising advancements in the diagnosis and monitoring of the disease. This innovation facilitates better patient selection for exploration of additional treatment options. As the field progresses, with investigational agents demonstrating potential as future treatments for refractory metastatic CRC, new avenues for enhancing outcomes in this challenging disease are emerging.
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Affiliation(s)
- Priyadarshini S Pathak
- Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Gloria Chan
- Department of Hematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore
| | - Dustin A Deming
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI
- University of Wisconsin Carbone Cancer Center, Madison, WI
- McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI
| | - Cheng Ean Chee
- Department of Hematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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18
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Tan C, Wang Q, Yao S. Effects of Adjuvant Chemotherapy on Early-onset Stage II Colon Cancer at Different Tumor Sites. Am J Clin Oncol 2024; 47:253-258. [PMID: 38251762 DOI: 10.1097/coc.0000000000001084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]
Abstract
OBJECTIVES Left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) have shown distinct clinical and prognostic features. We investigated the effect of adjuvant chemotherapy (ACT) on cause-specific survival (CSS) in patients with stage II LSCC and RSCC. METHODS Using the Surveillance, Epidemiology and End Results (SEER) database, a cohort of patients with stage II colon cancer, aged between 20 and 49 years was identified. Both Cox proportional hazards regression and Kaplan-Meier survival analysis as well as propensity score matching were used. RESULTS Overall, 5633 patients were eligible. Patients with RSCC were more likely to be male, black, and younger, with a poor grade and histologic type, and were more likely to have more regional nodes examined and larger tumor size. After propensity score matching, CSS was significantly superior in patients with RSCC compared to those with LSCC (Hazard Ratio (HR): 0.80, 95% CI: 0.68-0.95, P =0.01). However, no survival benefit was observed for patients with LSCC after ACT (HR: 1.10, 95% CI: 0.90-1.35, P =0.35), and surprisingly, ACT was found to do more harm than good in patients with RSCC (HR: 1.31, 95% CI: 1.05-1.63, P =0.02). Even among patients with high-risk features such as T4 stage and regional nodes examined<12 in both groups, ACT still did not improve CSS except for T4 stage LSCC (HR: 0.65, 95% CI: 0.44-0.97, P =0.02). CONCLUSIONS The results of this analysis indicate that the prognosis of RSCC is better than that of LSCC in stage II colon cancer, and ACT did not improve CSS in patients with either LSCC or RSCC. Even in patients with parts of high-risk features, ACT still did not improve CSS, except for T4 stage LSCC.
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Affiliation(s)
- Chang Tan
- Graduate School, Peking University China-Japan Friendship School of Clinical Medicine
| | - Qianqian Wang
- Graduate School, Peking University China-Japan Friendship School of Clinical Medicine
| | - Shukun Yao
- Graduate School, Peking University China-Japan Friendship School of Clinical Medicine
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
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19
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Shkurupii B, Zakhartseva L. PROGNOSTIC VALUE OF THE DENSITY OF TUMOR-INFILTRATING LYMPHOCYTES AND ITS ASSOCIATION WITH CLINICAL-MORPHOLOGICAL FEATURES OF COLON ADENOCARCINOMAS. Exp Oncol 2024; 46:45-52. [PMID: 38852053 DOI: 10.15407/exp-oncology.2024.01.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Indexed: 06/10/2024]
Abstract
AIM To study the prognostic value of the density of tumor-infiltrating lymphocytes (TILs) and its association with other clinical-morphological parameters in colon adenocarcinomas (CAC). MATERIALS AND METHODS 236 CAC samples were examined. TILs density was estimated as the percentage of tumor stromal area occupied by TILs. By the index of TILs density, the patients were divided into 3 groups: TILs 0-9% (n = 88); TILs 10-39% (n = 106); TILs > 40% (n = 42). Dependent on this index, their overall survival (OS) was analyzed. RESULTS Kaplan - Meier curves revealed a significant (p < 0.001) difference in the OS for patients with different TILs infiltration intensities. Multivariate Cox's proportional hazard regression model analysis has confirmed that patients with moderate TILs density (HR 0.57, 95% CI 0.34-0.96, p = 0.035) had better OS rates compared to low TILs density. TILs were associated with the stage (p < 0.001), lymph node metastasis pN (p < 0.001), distant metastasis M (p < 0.001), and the patient's outcome (p < 0.001). CONCLUSION TILs can be considered an additional prognostic tool during regular histological examination and are strongly associated with the most significant clinical-morphological features of CAC.
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Affiliation(s)
- B Shkurupii
- Bogomolets National Medical University, Kyiv, Ukraine
| | - L Zakhartseva
- Bogomolets National Medical University, Kyiv, Ukraine
- Kyiv City Oncology Hospital, Kyiv, Ukraine
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20
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Zhou K, Li G, Pan R, Xin S, Wen W, Wang H, Luo C, Han RPS, Gu Y, Tu Y. Preclinical evaluation of AGTR1-Targeting molecular probe for colorectal cancer imaging in orthotopic and liver metastasis mouse models. Eur J Med Chem 2024; 271:116452. [PMID: 38685142 DOI: 10.1016/j.ejmech.2024.116452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 04/20/2024] [Accepted: 04/24/2024] [Indexed: 05/02/2024]
Abstract
Despite advancements in colorectal cancer (CRC) treatment, the prognosis remains unfavorable for patients with distant liver metastasis. Fluorescence molecular imaging with specific probes is increasingly used to guide CRC surgical resection in real-time and treatment planning. Here, we demonstrate the targeted imaging capacity of an MPA-PEG4-N3-Ang II probe labeled with near-infrared (NIR) fluorescent dye targeting the angiotensin II (Ang II) type 1 receptor (AGTR1) that is significantly upregulated in CRC. MPA-PEG4-N3-Ang II was highly selective and specific to in vitro tumor cells and in vivo tumors in a mouse CRC xenograft model. The favorable ex vivo imaging and in vivo biodistribution of MPA-PEG4-N3-Ang II afforded tumor-specific accumulation with low background and >10 contrast tumor-to-colorectal values in multiple subcutaneous CRC models at 8 h following injection. Biodistribution analysis confirmed the probe's high uptake in HT29 and HCT116 orthotopic and liver metastatic models of CRC with signal-to-noise ratio (SNR) values of tumor-to-colorectal and -liver fluorescence of 5.8 ± 0.6, 5.3 ± 0.7, and 2.7 ± 0.5, 2.6 ± 0.5, respectively, enabling high-contrast intraoperative tumor visualization for surgical navigation. Given its rapid tumor targeting, precise tumor boundary delineation, durable tumor retention and docking study, MPA-PEG4-N3-Ang II is a promising high-contrast imaging agent for the clinical detection of CRC.
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Affiliation(s)
- Kuncheng Zhou
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang, 330004, China
| | - Gang Li
- Department of Ecology and Environment, Yuzhang Normal University, Nanchang, 330103, China
| | - Rongbin Pan
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang, 330004, China
| | - Sulin Xin
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang, 330004, China
| | - Weijie Wen
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang, 330004, China
| | - Huiyi Wang
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang, 330004, China
| | - Chao Luo
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang, 330004, China
| | - Ray P S Han
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang, 330004, China.
| | - Yueqing Gu
- State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing, 210009, China.
| | - Yuanbiao Tu
- Cancer Research Center, the Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang, 330004, China.
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21
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Hijazi A, Galon J. Principles of risk assessment in colon cancer: immunity is key. Oncoimmunology 2024; 13:2347441. [PMID: 38694625 PMCID: PMC11062361 DOI: 10.1080/2162402x.2024.2347441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 04/16/2024] [Indexed: 05/04/2024] Open
Abstract
In clinical practice, the administration of adjuvant chemotherapy (ACT) following tumor surgical resection raises a critical dilemma for stage II colon cancer (CC) patients. The prognostic features used to identify high-risk CC patients rely on the pathological assessment of tumor cells. Currently, these factors are considered for stratifying patients who may benefit from ACT at early CC stages. However, the extent to which these factors predict clinical outcomes (i.e. recurrence, survival) remains highly controversial, also uncertainty persists regarding patients' response to treatment, necessitating further investigation. Therefore, an imperious need is to explore novel biomarkers that can reliably stratify patients at risk, to optimize adjuvant treatment decisions. Recently, we evaluated the prognostic and predictive value of Immunoscore (IS), an immune digital-pathology assay, in stage II CC patients. IS emerged as the sole significant parameter for predicting disease-free survival (DFS) in high-risk patients. Moreover, IS effectively stratified patients who would benefit most from ACT based on their risk of recurrence, thus predicting their outcomes. Notably, our findings revealed that digital IS outperformed the visual quantitative assessment of the immune response conducted by expert pathologists. The latest edition of the WHO classification for digestive tumor has introduced the evaluation of the immune response, as assessed by IS, as desirable and essential diagnostic criterion. This supports the revision of current cancer guidelines and strongly recommends the implementation of IS into clinical practice as a patient stratification tool, to guide CC treatment decisions. This approach may provide appropriate personalized therapeutic decisions that could critically impact early-stage CC patient care.
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Affiliation(s)
- Assia Hijazi
- INSERM, Laboratory of Integrative Cancer Immunology, Paris, France
- Equipe Labellisée Ligue Contre le Cancer, Paris, France
- Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France
| | - Jérôme Galon
- INSERM, Laboratory of Integrative Cancer Immunology, Paris, France
- Equipe Labellisée Ligue Contre le Cancer, Paris, France
- Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France
- Veracyte, Marseille, France
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22
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Ryu HS, Kim HJ, Ji WB, Kim BC, Kim JH, Moon SK, Kang SI, Kwak HD, Kim ES, Kim CH, Kim TH, Noh GT, Park BS, Park HM, Bae JM, Bae JH, Seo NE, Song CH, Ahn MS, Eo JS, Yoon YC, Yoon JK, Lee KH, Lee KH, Lee KY, Lee MS, Lee SH, Lee JM, Lee JE, Lee HH, Ihn MH, Jang JH, Jeon SK, Chae KJ, Choi JH, Pyo DH, Ha GW, Han KS, Hong YK, Hong CW, Kwak JM, Korean Colon Cancer Multidisciplinary Committee. Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment. Ann Coloproctol 2024; 40:89-113. [PMID: 38712437 PMCID: PMC11082542 DOI: 10.3393/ac.2024.00059.0008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 03/11/2024] [Accepted: 03/18/2024] [Indexed: 05/08/2024] Open
Abstract
Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.
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Affiliation(s)
- Hyo Seon Ryu
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Hyun Jung Kim
- Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea
- Institute for Evidence-based Medicine, Cochrane Collaboration, Seoul, Korea
| | - Woong Bae Ji
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Ansan Hospital, Ansan, Korea
| | - Byung Chang Kim
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Ji Hun Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Kyung Moon
- Department of Radiology, Kyung Hee University Hospital, Seoul, Korea
| | - Sung Il Kang
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Han Deok Kwak
- Department of Surgery, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
| | - Eun Sun Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Chang Hyun Kim
- Department of Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
| | - Tae Hyung Kim
- Department of Radiation Oncology, Nowon Eulji Medical Center, Eulji University, Seoul, Korea
| | - Gyoung Tae Noh
- Department of Surgery, Ewha Womans University College of Medicine, Seoul, Korea
| | - Byung-Soo Park
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - Hyeung-Min Park
- Department of Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
| | - Jeong Mo Bae
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Jung Hoon Bae
- Division of Colorectal Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ni Eun Seo
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Chang Hoon Song
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Mi Sun Ahn
- Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea
| | - Jae Seon Eo
- Department of Nuclear Medicine and Molecular Imaging, Korea University College of Medicine, Seoul, Korea
| | - Young Chul Yoon
- Department of General Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Joon-Kee Yoon
- Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Korea
| | - Kyung Ha Lee
- Department of Surgery, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea
| | - Kyung Hee Lee
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kil-Yong Lee
- Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Myung Su Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Sung Hak Lee
- Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jong Min Lee
- Department of Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Ji Eun Lee
- Department of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Han Hee Lee
- Division of Gastroenterology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Myong Hoon Ihn
- Department of Surgery, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Je-Ho Jang
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University, Daejeon, Korea
| | - Sun Kyung Jeon
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Kum Ju Chae
- Department of Radiology, Jeonbuk National University Medical School, Jeonju, Korea
| | - Jin-Ho Choi
- Center for Lung Cancer, Department of Thoracic Surgery, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Dae Hee Pyo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gi Won Ha
- Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
| | - Kyung Su Han
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Young Ki Hong
- Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Chang Won Hong
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Jung-Myun Kwak
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Korean Colon Cancer Multidisciplinary Committee
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea
- Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea
- Institute for Evidence-based Medicine, Cochrane Collaboration, Seoul, Korea
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Ansan Hospital, Ansan, Korea
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Radiology, Kyung Hee University Hospital, Seoul, Korea
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
- Department of Surgery, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
- Department of Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
- Department of Radiation Oncology, Nowon Eulji Medical Center, Eulji University, Seoul, Korea
- Department of Surgery, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
- Division of Colorectal Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea
- Department of Nuclear Medicine and Molecular Imaging, Korea University College of Medicine, Seoul, Korea
- Department of General Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Korea
- Department of Surgery, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
- Department of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Division of Gastroenterology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Surgery, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University, Daejeon, Korea
- Department of Radiology, Jeonbuk National University Medical School, Jeonju, Korea
- Center for Lung Cancer, Department of Thoracic Surgery, Research Institute and Hospital, National Cancer Center, Goyang, Korea
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
- Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea
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23
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Pihlmann Kristensen M, Korsgaard U, Timm S, Hansen TF, Zlobec I, Hager H, Kjær-Frifeldt S. The prognostic value of tumor budding in a thoroughly characterized stage II colon cancer population in the context of a national screening program. Hum Pathol 2024; 146:15-22. [PMID: 38428823 DOI: 10.1016/j.humpath.2024.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 02/20/2024] [Accepted: 02/26/2024] [Indexed: 03/03/2024]
Abstract
Tumor budding as a prognostic marker in colorectal cancer has not previously been investigated in a cohort of screened stage II colon cancer patients. We assessed the prognostic significance of tumor budding in a thoroughly characterized stage II colon cancer population comprising surgically resected patients in the Region of Southern Denmark from 2014 to 2016. Tumors were re-staged according to the 8th edition of UICC TNM Classification, undergoing detailed histopathological evaluation and tumor budding assessment following guidelines from the International Tumor Budding Consensus Conference. Prognostic evaluation utilized Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models for time to recurrence (TTR), recurrence-free survival (RFS), and overall survival (OS). Out of 497 patients, 20% were diagnosed through the national colorectal cancer screening program. High-grade tumor budding (Bd3) was found in 19% of tumors and was associated with glandular subtype, perineural invasion, mismatch repair proficient tumors, and tumor recurrence (p < 0.001, p < 0.001, p = 0.045, and p = 0.007 respectively). In multivariable Cox regression, high-grade budding was a significant prognostic factor for TTR compared to low-grade (Bd3 HR 2.617; p = 0.007). An association between tumor budding groups and RFS was observed, and the difference was significant in univariable analysis for high-grade compared to low-grade tumor budding (Bd3 HR 1.461; p = 0.041). No significant differences were observed between tumor budding groups and OS. High-grade tumor budding is a predictor of recurrence in a screened population of patients with stage II colon cancer and should be considered a high-risk factor in a shared decision-making process when stratifying patients to adjuvant chemotherapy.
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Affiliation(s)
- Maria Pihlmann Kristensen
- Department of Pathology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, 5230 Odense M, Denmark; Colorectal Cancer Center South, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark.
| | - Ulrik Korsgaard
- Department of Pathology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, 5230 Odense M, Denmark; Colorectal Cancer Center South, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark
| | - Signe Timm
- Institute of Regional Health Research, University of Southern Denmark, 5230 Odense M, Denmark; Colorectal Cancer Center South, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark; Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark
| | - Torben Frøstrup Hansen
- Institute of Regional Health Research, University of Southern Denmark, 5230 Odense M, Denmark; Colorectal Cancer Center South, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark; Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark
| | - Inti Zlobec
- Institute of Tissue Medicine and Pathology, University of Bern, 3008 Bern, Switzerland
| | - Henrik Hager
- Department of Pathology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, 5230 Odense M, Denmark; Colorectal Cancer Center South, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark; Department of Pathology, Aarhus University Hospital, 8200 Aarhus N, Denmark
| | - Sanne Kjær-Frifeldt
- Department of Pathology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, 5230 Odense M, Denmark; Colorectal Cancer Center South, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark
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24
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Egger ME, Feygin Y, Kong M, Poddar T, Ghosh I, Xu Q, McCabe RM, McMasters KM, Ellis CT. Variation in Lymph Node Assessment for Colon Cancer at the Tumor, Surgeon, and Hospital Level. J Am Coll Surg 2024; 238:520-528. [PMID: 38205923 DOI: 10.1097/xcs.0000000000000963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024]
Abstract
BACKGROUND We hypothesized that tumor- and hospital-level factors, compared with surgeon characteristics, are associated with the majority of variation in the 12 or more lymph nodes (LNs) examined quality standard for resected colon cancer. STUDY DESIGN A dataset containing an anonymized surgeon identifier was obtained from the National Cancer Database for stage I to III colon cancers from 2010 to 2017. Multilevel logistic regression models were built to assign a proportion of variance in achievement of the 12 LNs standard among the following: (1) tumor factors (demographic and pathologic characteristics), (2) surgeon factors (volume, approach, and margin status), and (3) facility factors (volume and facility type). RESULTS There were 283,192 unique patient records with 15,358 unique surgeons across 1,258 facilities in our cohort. Achievement of the 12 LNs standard was high (90.3%). Achievement of the 12 LNs standard by surgeon volume was 88.1% and 90.7% in the lowest and highest quartiles, and 86.8% and 91.6% at the facility level for high and low annual volume quartiles, respectively. In multivariate analysis, the following tumor factors were associated with meeting the 12 LNs standard: age, sex, primary tumor site, tumor grade, T stage, and comorbidities (all p < 0.001). Tumor factors were responsible for 71% of the variation in 12 LNs yield, whereas surgeon and facility characteristics contributed 17% and 12%, respectively. CONCLUSIONS Twenty-nine percent of the variation in the 12 LNs standard is linked to modifiable factors. The majority of variation in this quality metric is associated with non-modifiable tumor-level factors.
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Affiliation(s)
| | | | - Maiying Kong
- Biostatistics and Bioinformatics, School of Public Health and Information Sciences (Kong, Poddar, Ghosh, Xu), University of Louisville, Louisville, KY
| | - Triparna Poddar
- Biostatistics and Bioinformatics, School of Public Health and Information Sciences (Kong, Poddar, Ghosh, Xu), University of Louisville, Louisville, KY
| | - Indranil Ghosh
- Biostatistics and Bioinformatics, School of Public Health and Information Sciences (Kong, Poddar, Ghosh, Xu), University of Louisville, Louisville, KY
| | - Qian Xu
- Biostatistics and Bioinformatics, School of Public Health and Information Sciences (Kong, Poddar, Ghosh, Xu), University of Louisville, Louisville, KY
| | - Ryan M McCabe
- National Cancer Database, Commission on Cancer, American College of Surgeons (McCabe)
| | | | - C Tyler Ellis
- From the Departments of Surgery (Egger, McMasters, Ellis)
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25
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Yu G, Wei R, Liu H, Liu Y, Guan X, Wang X, Jiang Z. Prognostic model for predicting the survival benefit of adjuvant chemotherapy for elderly patients with stage II colon cancer: a population-based study. Eur J Cancer Prev 2024; 33:105-114. [PMID: 38299664 DOI: 10.1097/cej.0000000000000836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2024]
Abstract
OBJECTIVES Adjuvant chemotherapy benefits in elderly patients with stage II colon cancer (CC) remain controversial. We aimed to construct a nomogram to estimate the chemotherapy survival benefits in elderly patients. METHODS The training and testing cohort were patients with stage II CC older than 70 years from the Surveillance, Epidemiology, and End Results (SEER) database, while the external validation cohort included patients from the National Cancer Center (NCC). Cox proportional hazard models were used to determine the covariates associated with overall survival (OS). Using the risk factors identified by Cox proportional hazards regression, a nomogram was developed to predict OS. Nomogram precision was assessed using receiver operating characteristic and calibration curves. RESULTS The present study recruited 42 097 and 504 patients from the SEER database and NCC, respectively. The OS of patients who underwent surgery plus adjuvant chemotherapy was considerably longer than patients who underwent surgery alone. The nomogram included variables related to OS, including age, year of diagnosis, sex, AJCC T stage, tumor location, tumor size, harvested lymph nodes, and chemotherapy. According to the nomogram score, the elderly patients were separated into high- and low-risk groups, with high-risk group nomogram scores being greater than the median value, and vice versa. Patients in the high-risk group witnessed worse prognosis and were more likely to benefit from postoperative chemotherapy. CONCLUSION This nomogram can be regarded as a useful clinical tool for assessing the potential adjuvant chemotherapy benefits and for predicting survival in elderly patients with stage II CC.
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Affiliation(s)
- Guanhua Yu
- Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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26
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Alnakli AAA, Mohamedali A, Heng B, Chan C, Shin JS, Solomon M, Chapuis P, Guillemin GJ, Baker MS, Ahn SB. Protein prognostic biomarkers in stage II colorectal cancer: implications for post-operative management. BJC REPORTS 2024; 2:13. [PMID: 39516345 PMCID: PMC11523985 DOI: 10.1038/s44276-024-00043-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 01/13/2024] [Accepted: 01/20/2024] [Indexed: 11/16/2024]
Abstract
Colorectal cancer (CRC) poses a significant threat to many human lives worldwide and survival following resection is predominantly stage dependent. For early-stage cancer, patients are not routinely advised to undergo additional post-operative adjuvant chemotherapy. Acceptable clinical management guidelines are well established for patients in pTNM stages I, III and IV. However, recommendations for managing CRC stage II patients remain controversial and many studies have been conducted to segregate stage II patients into low- and high-risk of recurrence using genomic, transcriptomic and proteomic molecular markers. As proteins provide valuable insights into cellular functions and disease state and have a relatively easy translation to the clinic, this review aims to discuss potential prognostic protein biomarkers proposed for predicting tumour relapse in early-stage II CRC. It is suggested that a panel of markers may be more effective than a single marker and further evaluation is required to translate these into clinical practice.
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Affiliation(s)
- Aziz A A Alnakli
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, North Ryde, Sydney, NSW, Australia
| | - Abidali Mohamedali
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, North Ryde, Sydney, NSW, Australia
- School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, North Ryde, Sydney, NSW, Australia
| | - Benjamin Heng
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, North Ryde, Sydney, NSW, Australia
| | - Charles Chan
- Department of Anatomical Pathology, NSW Health Pathology, Concord Hospital, Sydney, NSW, Australia
- Concord Institute of Academic Surgery, Concord Clinical School, Faculty of Medicine and Health, Concord Hospital, University of Sydney, Sydney, NSW, Australia
| | - Joo-Shik Shin
- Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia
| | - Michael Solomon
- Department of Colorectal Surgery RPAH & Institute of Academic Surgery at Sydney Medical School, University of Sydney, Sydney, Australia
| | - Pierre Chapuis
- Concord Institute of Academic Surgery, Concord Clinical School, Faculty of Medicine and Health, Concord Hospital, University of Sydney, Sydney, NSW, Australia
| | | | - Mark S Baker
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, North Ryde, Sydney, NSW, Australia
| | - Seong Beom Ahn
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, North Ryde, Sydney, NSW, Australia.
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Abstract
Importance Liquid biopsy is an emerging tool with the potential to change oncologic care practices. Optimal clinical applications for its use are currently undefined for surgical patients. Observations Liquid biopsy analytes such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been the most clinically studied assays and were initially limited to advanced-stage disease. In the metastatic setting, CTCs and ctDNA levels are prognostic. Although their levels correlate with treatment response, CTC-guided systemic regimen switches for nonresponders have not been shown to improve clinical outcomes. ctDNA genomic profiling has succeeded, and there are now multiple plasma-based assays approved by the US Food and Drug Administration that can detect actionable mutations to guide systemic therapy. Technological advancements in assay sensitivity have expanded the use of ctDNA to early-stage and resectable disease, allowing for detection of minimal residual disease. Postoperative ctDNA levels are a strong predictor of disease recurrence, and ctDNA detection often precedes serum carcinoembryonic antigen elevation and radiographic changes. However, its use for surveillance has not been shown to improve clinical outcomes. A promising application of ctDNA is for adjuvant therapy escalation and de-escalation. A phase 2 clinical trial demonstrated that treatment de-escalation for patients with high-risk stage II colorectal cancer and negative postoperative ctDNA had similar recurrence-free survival as patients receiving standard-of-care chemotherapy. These results suggest that ctDNA may help select patients who will benefit from adjuvant chemotherapy, and multiple clinical trials are actively underway. Conclusions and Relevance Although uncertainties regarding the optimal use of liquid biopsy remain, it has the potential to significantly improve care for patients with cancer at all stages of disease. It is critical that surgeons understand how to use and interpret these assays, and they should be active participants in clinical trials to advance the field.
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Affiliation(s)
- Kelly M Mahuron
- Department of Surgery, City of Hope National Medical Center, Duarte, California
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, California
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28
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Zheng P, Ye C, Liu H, Gao X, Huang H. Adjuvant chemotherapy decision-making in stage II colon adenocarcinoma associated with patients' age and high-risk factors. Int J Colorectal Dis 2023; 39:3. [PMID: 38091096 DOI: 10.1007/s00384-023-04581-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/11/2023] [Indexed: 12/18/2023]
Abstract
PURPOSE To clarify whether the combination of age and high-risk factors (HRFs) was preferable for adjuvant chemotherapy (AC) decision-making in patients with stage II colon adenocarcinoma. METHODS We conducted a retrospective study analyzing eligible colon cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. A nomogram was used to predict patient prognosis. Decision curve analysis (DCA) predicted model clinical benefit. Restricted cubic spline calculated the optimal cut-off value. RESULTS A total of 8570 patients with stage II colon adenocarcinoma were included in this study; 25.2% received AC. A nomogram predicting the prognosis of patients with stage II colon adenocarcinoma was constructed with age and HRFs, and scores were assigned to the relevant variables. DCA showed that age combined with HRFs was superior to treatment decision-making based on HRFs alone. Patients were grouped according to their total score with the cut-off value of 100. AC did not significantly improve overall survival (OS) in low-score group (hazard ratios (HRs) 1.01, 95% confidence intervals (CIs) 0.86-1.18, p = 0.918). In high-score group, AC improved 5-year OS by about 7.6% (HR 0.73, 95% CI 0.61-0.88, p = 0.001). And high-score group mainly included patients aged < 50 years with two or more HRFs and patients aged ≥ 50 years with at least one HRF. CONCLUSION Age and HRFs could be preferable for determining the group of stage II colon adenocarcinoma patients who would benefit from AC. Patients aged < 50 years with two or more HRFs might be a potential benefit population for AC.
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Affiliation(s)
- Pengwen Zheng
- Department of General Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, 310007, Hangzhou, China
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, 310022, Hangzhou, China
- Zhejiang Chinese Medical University, 310053, Hangzhou, China
| | - Chao Ye
- Department of General Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, 310007, Hangzhou, China
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, 310022, Hangzhou, China
- Zhejiang Chinese Medical University, 310053, Hangzhou, China
| | - Hui Liu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, 310022, Hangzhou, China
- Zhejiang Chinese Medical University, 310053, Hangzhou, China
| | - Xinyi Gao
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, 310022, Hangzhou, China.
- Department of Radiology, Zhejiang Cancer Hospital, 1 Banshan East Road, Hangzhou, 310022, China.
| | - Hai Huang
- Department of General Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, 310007, Hangzhou, China.
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29
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Yu J, Bai Y, Jin L, Zhang Z, Yang Y. A Prospective Long-Term Follow-Up Study: The Application of Circulating Tumor Cells Analysis to Guide Adjuvant Therapy in Stage II Colorectal Cancer. Ann Surg Oncol 2023; 30:8495-8500. [PMID: 37598121 DOI: 10.1245/s10434-023-14168-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 08/03/2023] [Indexed: 08/21/2023]
Abstract
BACKGROUND The efficacy of circulating tumor cells (CTCs) in the selection of stage II colorectal cancer (CRC) patients for adjuvant chemotherapy remains inconclusive. OBJECTIVE The aim of this study was to validate the necessity of adjuvant chemotherapy for stage II CRC patients with positive postoperative CTCs. METHODS The clinicopathological features and overall survival (OS) of a cohort of 70 patients with confirmed CRC were collected and analyzed. RESULTS The total rate of positive CTCs was 55.7%, while the average OS was 70.8 months and the OS rate was 75.7% (53/70). These 70 patients were divided into four subgroups, including a CTC-negative group with non-adjuvant chemotherapy (CHEMO-/CTC-) versus a CTC-positive group with non-adjuvant chemotherapy (CHEMO-/CTC+), CHEMO+/CTC- versus CHEMO+/CTC+, CHEMO-/CTC- versus CHEMO+/CTC-, and CHEMO+/CTC+ versus CHEMO-/CTC+; the total numbers in each subgroup were 25 versus 32, 6 versus 7, 25 versus 6, and 7 versus 32, respectively. The average OS of the CHEMO-/CTC- and CHEMO-/CTC+ groups was 82.0 and 68.1 months, respectively (p = 0.020); the average OS of the CHEMO+/CTC- and CHEMO+/CTC+ groups was 83.6 months and 76.4 months, respectively (p = 0.963); the average OS of the CHEMO-/CTC- and CHEMO+/CTC- groups was 82.0 months and 83.6 months, respectively (p = 0.999); and the average OS of the CHEMO+/CTC+ and CHEMO-/CTC+ groups was 76.4 months and 68.1 months, respectively (p = 0.247). CONCLUSIONS Positive CTCs are a potential prognostic marker for stage II CRC.
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Affiliation(s)
- Junhui Yu
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive Disease, Beijing, People's Republic of China
| | - Yanyan Bai
- Department of Cadre Synthesis, Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Lan Jin
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive Disease, Beijing, People's Republic of China
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive Disease, Beijing, People's Republic of China.
| | - Yingchi Yang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive Disease, Beijing, People's Republic of China.
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30
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Zambeli-Ljepović A, Hoffman D, Barnes KE, Romero-Hernandez F, Ashraf Ganjouei A, Adam MA, Sarin A. Inadequate Lymph Node Yield: An Inadequate Indication for Adjuvant Chemotherapy in Stage II Colon Cancer. ANNALS OF SURGERY OPEN 2023; 4:e338. [PMID: 38144492 PMCID: PMC10735076 DOI: 10.1097/as9.0000000000000338] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 08/11/2023] [Indexed: 12/26/2023] Open
Abstract
Background Optimal therapy for stage II colon cancer remains unclear, and national guidelines recommend "consideration" of adjuvant chemotherapy (ACT) in the presence of high-risk features, including inadequate lymph node yield (LNY, <12 nodes). This study aims to determine whether the survival benefit of ACT in stage II disease varies based on the adequacy of LNY. Methods We used the National Cancer Database (NCDB) to identify adults who underwent resection for a single primary T3 or T4 colon cancer between 2006 and 2018. Multivariable logistic regression tested for associations between ACT and prespecified demographic and clinical characteristics, including the adequacy of LNY. We used Cox proportional hazards models to assess overall survival and restricted cubic splines to estimate the optimal LNY threshold to dichotomize patients based on overall survival. Results Unadjusted 5- and 10-year survival rates were 84% and 75%, respectively, among patients who received ACT and 70% and 50% among patients who did not (log-rank P < 0.01). Inadequate LNY was independently associated with both receipt of ACT (odds ratios, 1.50; P < 0.01) and decreased overall survival [hazard ratio (HR), 1.56; P < 0.01]. ACT was independently associated with improved survival (HR, 0.67; P < 0.01); this effect size did not change based on the adequacy of LNY (interaction P = 0.41). Results were robust to re-analysis with our cohort-optimized threshold of 18 lymph nodes. Conclusions Consistent with contemporary guidelines, patients with inadequate LNY are more likely to receive ACT. LNY adequacy is an independent prognostic factor but, in isolation, should not dictate whether patients receive ACT.
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Affiliation(s)
- Alan Zambeli-Ljepović
- From the Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Daniel Hoffman
- From the Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Katherine E. Barnes
- From the Department of Surgery, University of California, San Francisco, San Francisco, CA
| | | | - Amir Ashraf Ganjouei
- From the Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Mohamed A. Adam
- From the Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Ankit Sarin
- Department of Surgery, University of California Davis, Sacramento, CA
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31
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Ying H, Shao J, Liao N, Xu X, Yu W, Hong W. The effect of adjuvant chemotherapy on survival in node negative colorectal cancer with or without perineural invasion: a systematic review and meta-analysis. Front Surg 2023; 10:1308757. [PMID: 38033531 PMCID: PMC10687374 DOI: 10.3389/fsurg.2023.1308757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 10/31/2023] [Indexed: 12/02/2023] Open
Abstract
Purpose It was aimed at assessing the benefits of adjuvant chemotherapy (ACT) for patients with node-negative colorectal cancer (CRC) either with or without perineural invasion (PNI). Methods We systematically searched PubMed, Cochrane Library, Embase, and Web of Science from database inception through October 1, 2023. Survival outcomes were analyzed using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The methodological quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Heterogeneity for the descriptive meta-analyses was quantified using the I2 statistic. Results Ten studies included in this review. ACT improved overall survival (OS) (HR 0.52, 95% CI 0.40-0.69) and disease-free survival (DFS) (HR 0.53, 95% CI 0.35-0.82) in PNI + patients but did not affect DFS (HR 1.13, 95% CI 0.72-1.77) in PNI- patients. A disease-specific survival (DSS) benefit with chemotherapy was observed in PNI + (HR 0.76, 95% CI 0.58-0.99) and PNI- patients (HR 0.76, 95% CI 0.57-1.00). And PNI decreased DFS (HR 1.94, 95% CI 1.52-2.47) and OS (HR 1.75, 95% CI 0.96-3.17) in node-negative CRC. Conclusions In conclusion, chemotherapy appears most beneficial for survival outcomes in node-negative patients with PNI, but may also confer some advantage in those without PNI. Systematic Review Registration Identifier INPLASY2021120103.
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Affiliation(s)
- Hongan Ying
- Department of Geriatrics, Taizhou First People’s Hospital, Taizhou, China
| | - Jinfan Shao
- Department of Anus & Intestine Surgery, Taizhou First People’s Hospital, Taizhou, China
| | - Nansheng Liao
- Department of General Surgery, Taizhou First People’s Hospital, Taizhou, China
| | - Xijuan Xu
- Department of Anus & Intestine Surgery, Taizhou First People’s Hospital, Taizhou, China
| | - Wenfeng Yu
- Department of Anus & Intestine Surgery, Taizhou First People’s Hospital, Taizhou, China
| | - Weiwen Hong
- Department of Anus & Intestine Surgery, Taizhou First People’s Hospital, Taizhou, China
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To YH, Gibbs P, Tie J, Loree J, Glyn T, Degeling K. Circulating Tumour DNA Guided Adjuvant Chemotherapy Decision Making in Stage II Colon Cancer-A Clinical Vignette Study. Cancers (Basel) 2023; 15:5227. [PMID: 37958401 PMCID: PMC10648421 DOI: 10.3390/cancers15215227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 10/23/2023] [Accepted: 10/25/2023] [Indexed: 11/15/2023] Open
Abstract
Circulating tumour DNA (ctDNA) is a promising biomarker that may better identify stage II colon cancer (CC) patients who will benefit from adjuvant chemotherapy (AC) compared to standard clinicopathological parameters. The DYNAMIC study demonstrated that ctDNA-informed treatment decreased AC utilisation without compromising recurrence free survival, but medical oncologists' willingness to utilise ctDNA results to inform AC decision is unknown. Medical oncologists from Australia, Canada and New Zealand were presented with clinical vignettes for stage II CC comprised of two variables with three levels each (age: ≤50, 52-69, ≥70 years; and clinicopathological risk of recurrence: low, intermediate, high) and were queried about ctDNA testing and treatment recommendations based on results. Sixty-four colorectal oncologists completed at least one vignette (all vignettes, n = 59). The majority of oncologist were Australian (70%; Canada: n = 13; New Zealand: n = 6) and had over 10 years of clinical experience (n = 41; 64%). The proportion of oncologists requesting ctDNA testing exceeded 80% for all vignettes, except for age ≥ 70 and low-risk disease (63%). Following a positive ctDNA result, the proportion of oncologists recommending AC (p < 0.01) and recommending oxaliplatin-based doublet (p < 0.01) increased in all vignettes. Following a negative result, the proportion recommending AC decreased in all intermediate and high-risk vignettes (p < 0.01).
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Affiliation(s)
- Yat Hang To
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3000, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
| | - Peter Gibbs
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3000, Australia
- Department of Medical Oncology, Western Health, St Albans, VIC 3091, Australia
- Faculty of Medicine & Health Sciences, University of Melbourne, Melbourne, VIC 3000, Australia
| | - Jeanne Tie
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3000, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
- Faculty of Medicine & Health Sciences, University of Melbourne, Melbourne, VIC 3000, Australia
| | - Jonathan Loree
- Division of Medical Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada
| | - Tamara Glyn
- Department of Surgery, University of Otago, Christchurch 8011, New Zealand;
- Department of Surgery, Te Whatu Ora Health New Zealand Waitaha Canterbury, Christchurch 8140, New Zealand
| | - Koen Degeling
- Cancer Health Services Research, Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC 3000, Australia
- Cancer Health Services Research, Centre for Health Policy, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC 3000, Australia
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Appiah D, Goodart CR, Kothari GK, Ebong IA, Nwabuo CC. Reduced Risk of All-Cause, Cancer-, and Cardiovascular Disease-Related Mortality among Patients with Primary Malignant Cardiac Tumors Receiving Chemotherapy in the United States. Curr Oncol 2023; 30:8488-8500. [PMID: 37754533 PMCID: PMC10529023 DOI: 10.3390/curroncol30090618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Revised: 09/12/2023] [Accepted: 09/14/2023] [Indexed: 09/28/2023] Open
Abstract
Primary malignant cardiac tumors (PMCTs) are rare but lethal neoplasms. There are limited evidence-based treatment guidelines for PMCTs. We evaluated the relation of chemotherapy with mortality outcomes in patients with PMCTs in the United States. Data were from patients aged ≥ 20 years from the Surveillance, Epidemiology, and End Results program who were diagnosed with PMCTs from 2000 to 2020. Cox regression, competing risk, and propensity score analyses were performed to estimate hazard ratios (HR) and confidence intervals (CI). About 53% of the 563 patients with PMCTs received chemotherapy as the first course of treatment. During a mean follow-up of 24.7 months (median: 10), 458 deaths occurred with 81.7% and 9.4% due to cancer and cardiovascular disease (CVD), respectively. In models adjusted for sociodemographic and clinico-pathophysiological factors including histology, receipt of chemotherapy was associated with low risk for all-cause (HR: 0.56, 95%CI: 0.45-0.69), cancer (HR: 0.63, 95%CI: 0.50-0.80) and CVD mortality (HR: 0.27, 95%CI: 0.12-0.58). Patients who had both chemotherapy and surgery had the lowest risk for all-cause and cancer mortality. This study suggests that the subpopulations of patients with PMCTs who receive chemotherapy may have better prognosis than those who do not receive this therapy regardless of histology.
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Affiliation(s)
- Duke Appiah
- Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Carina R. Goodart
- School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Grishma K. Kothari
- Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Imo A. Ebong
- Division of Cardiovascular Medicine, University of California, Davis, Sacramento, CA 95616, USA
| | - Chike C. Nwabuo
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;
- Ronin Institute, Montclair, NJ 07043, USA
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Ginesi MC, Bliggenstorfer JT, Kwesiga DM, Xu SH, Jodeh D, Eva Selfridge J, Stein SL, Steinhagen EF. Factors Associated with Receipt of Adjuvant Chemotherapy in Stage II Colon Cancer. Ann Surg Oncol 2023; 30:5511-5518. [PMID: 37249722 DOI: 10.1245/s10434-023-13631-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 04/24/2023] [Indexed: 05/31/2023]
Abstract
BACKGROUND The benefits of chemotherapy in stage II colon cancer remain unclear, but it is recommended for high-risk stage II disease. Which patients receive chemotherapy and its impact on survival remains undetermined. METHODS The National Cancer Database was surveyed between 2004 and 2016 for stage II colon cancer patients. Patients were categorized as high- or average-risk as defined by the National Comprehensive Cancer Network. The demographic characteristics of high- and average-risk patients who did and did not receive chemotherapy were compared using univariate and multivariable analyses. The survival of high- and average-risk patients was compared based on receipt of chemotherapy with Cox hazard ratios and Kaplan-Meier curves. RESULTS Overall, 84,424 patients met the inclusion criteria. A total of 34,868 patients were high-risk and 49,556 were average-risk. In high-risk patients, the risk factors for not receiving chemotherapy included increasing age, distance from the treatment facility, Charlson-Deyo score, and lack of insurance. In average-risk patients, factors associated with receipt of chemotherapy were decreasing age, distance from the treatment facility, Charlson-Deyo score, and non-academic association of the treatment facility. In both, chemotherapy was significantly associated with increased survival on the Kaplan-Meier curve. In the Cox hazard ratio, only high-risk patients benefited from chemotherapy (hazard ratio 1.183, confidence interval 1.116-1.254). CONCLUSIONS Factors associated with not receiving chemotherapy in high-risk stage II colon cancers included increasing age, medical comorbidities, increasing distance from the treatment facility, and lack of insurance. Chemotherapy is associated with improved overall survival in high-risk patients.
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Affiliation(s)
- Meridith C Ginesi
- Department of Surgery, University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jonathan T Bliggenstorfer
- Department of Surgery, University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Daphine M Kwesiga
- Department of Surgery, University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Samantha H Xu
- Department of Surgery, University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Diana Jodeh
- Department of Surgery, University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - J Eva Selfridge
- Department of Surgery, University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Sharon L Stein
- Department of Surgery, University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Emily F Steinhagen
- Department of Surgery, University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
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Zhu H, Hu M, Ma Y, Yao X, Lin X, Li M, Li Y, Wu Z, Shi D, Tong T, Chen H. Multi-center evaluation of machine learning-based radiomic model in predicting disease free survival and adjuvant chemotherapy benefit in stage II colorectal cancer patients. Cancer Imaging 2023; 23:74. [PMID: 37537659 PMCID: PMC10401876 DOI: 10.1186/s40644-023-00588-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 07/02/2023] [Indexed: 08/05/2023] Open
Abstract
BACKGROUND Our study aimed to explore the potential of radiomics features derived from CT images in predicting the prognosis and response to adjuvant chemotherapy (ACT) in patients with Stage II colorectal cancer (CRC). METHODS A total of 478 patients with confirmed stage II CRC, with 313 from Shanghai (Training set) and 165 from Beijing (Validation set) were enrolled. Optimized features were selected using GridSearchCV and Iterative Feature Elimination (IFE) algorithm. Subsequently, we developed an ensemble random forest classifier to predict the probability of disease relapse.We evaluated the performance of the model using the concordance index (C-index), precision-recall curves, and area under the precision-recall curves (AUCPR). RESULTS A radiomic model (namely the RF5 model) consisting of four radiomics features and T stage were developed. The RF5 model performed better than simple radiomics features or T stage alone, with higher C-index and AUCPR, as well as better sensitivity and specificity (C-indexRF5: 0.836; AUCPR = 0.711; Sensitivity = 0.610; Specificity = 0.935). We identified an optimal cutoff value of 0.1215 to split patients into high- or low-score subgroups, with those in the low-score group having better disease-free survival (DFS) (Training Set: P = 1.4e-11; Validation Set: P = 0.015). Furthermore, patients in the high-score group who received ACT had better DFS compared to those who did not receive ACT (P = 0.04). However, no statistical difference was found in low-score patients (P = 0.17). CONCLUSION The radiomic model can serve as a reliable tool for assessing prognosis and identifying the optimal candidates for ACT in Stage II CRC patients. TRIAL REGISTRATION Retrospectively registered.
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Affiliation(s)
- Hui Zhu
- Department of Diagnostic Radiology, Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 DongAn Road, Shanghai, 200032, China
| | - Muni Hu
- State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Yanru Ma
- State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Xun Yao
- Department of Radiology, Peking University People's Hospital, 11 Xizhimen South St, Beijing, 100044, China
| | - Xiaozhu Lin
- Department of Radiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Rui Jin Er Rd, Shanghai, 200025, China
| | - Menglei Li
- Department of Diagnostic Radiology, Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 DongAn Road, Shanghai, 200032, China
| | - Yue Li
- Department of Diagnostic Radiology, Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 DongAn Road, Shanghai, 200032, China
| | - Zhiyuan Wu
- Department of Radiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Rui Jin Er Rd, Shanghai, 200025, China.
| | - Debing Shi
- Department of Colorectal Surgery, Department of Oncology, Fudan University Shanghai Cancer Center; Shanghai Medical College, Fudan University, 270 DongAn Road, Shanghai, 200032, China.
| | - Tong Tong
- Department of Diagnostic Radiology, Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 DongAn Road, Shanghai, 200032, China.
| | - Haoyan Chen
- State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
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Tirendi S, Marengo B, Domenicotti C, Bassi AM, Almonti V, Vernazza S. Colorectal cancer and therapy response: a focus on the main mechanisms involved. Front Oncol 2023; 13:1208140. [PMID: 37538108 PMCID: PMC10396348 DOI: 10.3389/fonc.2023.1208140] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/19/2023] [Indexed: 08/05/2023] Open
Abstract
Introduction The latest GLOBOCAN 2021 reports that colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Most CRC cases are sporadic and associated with several risk factors, including lifestyle habits, gut dysbiosis, chronic inflammation, and oxidative stress. Aim To summarize the biology of CRC and discuss current therapeutic interventions designed to counteract CRC development and to overcome chemoresistance. Methods Literature searches were conducted using PubMed and focusing the attention on the keywords such as "Current treatment of CRC" or "chemoresistance and CRC" or "oxidative stress and CRC" or "novel drug delivery approaches in cancer" or "immunotherapy in CRC" or "gut microbiota in CRC" or "systematic review and meta-analysis of randomized controlled trials" or "CSCs and CRC". The citations included in the search ranged from September 1988 to December 2022. An additional search was carried out using the clinical trial database. Results Rounds of adjuvant therapies, including radiotherapy, chemotherapy, and immunotherapy are commonly planned to reduce cancer recurrence after surgery (stage II and stage III CRC patients) and to improve overall survival (stage IV). 5-fluorouracil-based chemotherapy in combination with other cytotoxic drugs, is the mainstay to treat CRC. However, the onset of the inherent or acquired resistance and the presence of chemoresistant cancer stem cells drastically reduce the efficacy. On the other hand, the genetic-molecular heterogeneity of CRC often precludes also the efficacy of new therapeutic approaches such as immunotherapies. Therefore, the CRC complexity made of natural or acquired multidrug resistance has made it necessary the search for new druggable targets and new delivery systems. Conclusion Further knowledge of the underlying CRC mechanisms and a comprehensive overview of current therapeutic opportunities can provide the basis for identifying pharmacological and biological barriers that render therapies ineffective and for identifying new potential biomarkers and therapeutic targets for advanced and aggressive CRC.
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Affiliation(s)
- Sara Tirendi
- Department of Experimental Medicine, University of Genoa, Genoa, Italy
- Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research (Centro 3R), Genoa, Italy
| | - Barbara Marengo
- Department of Experimental Medicine, University of Genoa, Genoa, Italy
- Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research (Centro 3R), Genoa, Italy
| | - Cinzia Domenicotti
- Department of Experimental Medicine, University of Genoa, Genoa, Italy
- Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research (Centro 3R), Genoa, Italy
| | - Anna M. Bassi
- Department of Experimental Medicine, University of Genoa, Genoa, Italy
- Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research (Centro 3R), Genoa, Italy
| | - Vanessa Almonti
- Department of Experimental Medicine, University of Genoa, Genoa, Italy
| | - Stefania Vernazza
- Department of Experimental Medicine, University of Genoa, Genoa, Italy
- Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research (Centro 3R), Genoa, Italy
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Xu G, Mo Y, Li J, Wei Q, Zhou F, Chen J. Two tripartite classification systems of CD86 + and CD206 + macrophages are significantly associated with tumor recurrence in stage II-III colorectal cancer. Front Immunol 2023; 14:1136875. [PMID: 37342343 PMCID: PMC10277500 DOI: 10.3389/fimmu.2023.1136875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 05/22/2023] [Indexed: 06/22/2023] Open
Abstract
Introduction The prognostic value of tumor-associated macrophages remains unclear in colorectal cancer (CRC). Two tripartite classification systems, namely, ratio and quantity subgroups, were investigated as the prognostic stratification tools for stage II-III CRC. Methods We assessed the infiltration intensity of CD86+ and CD206+ macrophages in 449 cases with stage II-III disease by immunohistochemical staining. Ratio subgroups were defined by the lower- and upper-quartile points of CD206+/(CD86++CD206+) macrophage ratio, including the low-, moderate-, and high-ratio subgroups. Quantity subgroups were defined by the median points of CD86+ and CD206+ macrophages and included the low-, moderate-, and high-risk subgroups. The main analysis was recurrence-free survival (RFS) and overall survival (OS). Results Ratio subgroups (RFS/OS: HR=2.677/2.708, all p<0.001) and quantity subgroups (RFS/OS: HR=3.137/3.250, all p<0.001) could serve as independent prognostic indicators that effectively predicted survival outcomes. More importantly, log-rank test revealed that patients in the high-ratio (RFS/OS: HR=2.950/3.151, all p<0.001) or high-risk (RFS/OS: HR=3.453/3.711, all p<0.001) subgroup exhibited decreased survival outcomes after adjuvant chemotherapy. The predictive accuracy of the quantity subgroups within 48 months was higher than that of the ratio subgroups and tumor stage (all p<0.05). Conclusions Ratio and quantity subgroups could serve as independent prognostic indicators that could potentially be incorporated into the tumor staging algorithm to improve prognostic stratification and provide better predictions of survival outcomes in stage II-III CRC after adjuvant chemotherapy.
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Affiliation(s)
- Guozeng Xu
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei, China
- Department of Oncology, Liuzhou People’s Hospital of Guangxi Medical University, Guangxi, China
| | - Yuzhen Mo
- Department of Radiation Oncology, Guangzhou Red Cross Hospital of Jinan University, Guangdong, China
| | - Jing Li
- Department of Oncology, Liuzhou People’s Hospital of Guangxi Medical University, Guangxi, China
| | - Qingqing Wei
- Department of Oncology, Liuzhou People’s Hospital of Guangxi Medical University, Guangxi, China
| | - Fuxiang Zhou
- Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei, China
| | - Jian Chen
- Department of Medical Oncology, Yantai Yuhuangding Hospital of Qingdao University, Shandong, China
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Chen Y, Shankaran V, Hahn EE, Haupt EC, Bansal A. Underutilization or appropriate care? Assessing adjuvant chemotherapy use and survival in 3 heterogenous subpopulations with stage II/III colorectal cancer within a large integrated health system. J Manag Care Spec Pharm 2023; 29:635-646. [PMID: 37276035 PMCID: PMC10387960 DOI: 10.18553/jmcp.2023.29.6.635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
BACKGROUND: Clinical guidelines have recommended adjuvant chemotherapy (ACT) for patients with high-risk stage II colon cancer, although the survival benefit is unclear. ACT is also recommended for patients with stage III colon cancer to reduce the risk of recurrence and mortality. For stage II/III rectal cancer, however, the role of perioperative chemotherapy (PCT, adjuvant or neoadjuvant) remains controversial, resulting in substantial variation in its use in clinical practice. OBJECTIVES: To understand real-world use and predictors of ACT or PCT use and survival outcomes in 3 heterogeneous patient groups with colorectal cancer (CRC), and to inform the evidence gap between guideline-based care and clinical practice. METHODS: This retrospective cohort study included patients with an initial stage II/III CRC diagnosis between 2008 and 2013 identified from Kaiser Permanente Southern California electronic health record databases. Patients were eligible if they were aged 18-74 years at diagnosis and received primary curative surgery. We fitted mixed effects logistic regression models to evaluate predictors of ACT receipt and Cox proportional hazards models on propensity score-matched (PS-matched) samples to assess the association between ACT/PCT receipt and survival. RESULTS: We included 1,690 patients with colon cancer (stage II: 820 and stage III: 870) and 587 patients with rectal cancer (stage II: 241 and stage III: 346). We found that 65% of patients with high-risk stage II colon cancer, 15% of those with stage III colon, and 15% of those with stage II/III rectal cancer did not receive ACT/PCT. Patients with stage II colon cancer with T4 stage (odds ratio [OR] = 5.79, 95% CI = 3.33 - 10.06) and a lower comorbidity score were more likely to receive ACT (high vs low Charlson score: OR = 0.69, 95% CI = 0.55 - 0.87). Patients with stage III rectal cancer were more likely to receive PCT than those with stage II disease (OR = 7.85, 95% CI = 2.07 - 29.74). Patients with another cancer diagnosis prior to CRC diagnosis were less likely to receive PCT (OR = 0.37, 95% CI = 0.16 - 0.85). ACT/PCT use was associated with improved overall survival among patients with high-risk stage II colon cancer (PS-matched hazard ratio [HR] = 0.42, 95% CI = 0.25 - 0.70) and those with stage III CRC (stage III colon: PS-matched HR = 0.3, 95% CI = 0.25 - 0.36; stage III rectal: PS-matched HR = 0.2, 95% CI = 0.13 - 0.31). CONCLUSIONS: We found potential underuse of appropriate chemotherapy treatment in patients with high-risk stage II colon cancer and stage III CRC. Clinicians' and providers' decisions on ACT administration may not be fully guided by the risk of recurrence and 5-year survival benefits in stage II colon cancer. DISCLOSURES: This research was supported by the National Cancer Institute of the National Institutes of Health (NIH) (under R37-CA218413). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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Affiliation(s)
- Yilin Chen
- CHOICE Institute, School of Pharmacy, University of Washington, Seattle
| | - Veena Shankaran
- Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, and Division of Medical Oncology, University of Washington, Seattle
| | - Erin E Hahn
- Department of Health Systems Sciences, Bernard J. Tyson School of Medicine, Kaiser Permanente, Pasadena, CA
- Department of Research and Evaluation, Kaiser Permanente, Pasadena, CA
| | - Eric C Haupt
- Department of Research and Evaluation, Kaiser Permanente, Pasadena, CA
| | - Aasthaa Bansal
- CHOICE Institute, School of Pharmacy, University of Washington, Seattle
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Hu Q, Wang Y, Yao S, Mao Y, Liu L, Li Z, Chen Y, Zhang S, Li Q, Zhao Y, Fan X, Cui Y, Zhao K, Liu Z. Desmoplastic Reaction Associates with Prognosis and Adjuvant Chemotherapy Response in Colorectal Cancer: A Multicenter Retrospective Study. CANCER RESEARCH COMMUNICATIONS 2023; 3:1057-1066. [PMID: 37377615 PMCID: PMC10269709 DOI: 10.1158/2767-9764.crc-23-0073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 04/26/2023] [Accepted: 05/23/2023] [Indexed: 06/29/2023]
Abstract
Desmoplastic reaction (DR) is one of many tumor-host interactions and is associated with the overall survival (OS) of patients with colorectal cancer. However, the clinical significance of DR requires further study in large multicenter cohorts and its predictive value in adjuvant chemotherapy (ACT) response remains unclear. Here, a total of 2,225 patients with colorectal cancer from five independent institutions were divided into primary (N = 1,012 from two centers) and validation (N = 1,213 from three centers) cohorts. DR was classified as immature, middle, or mature depending on the presence of myxoid stroma and hyalinized collagen bundles at the invasive front of the primary tumor. OS among different subgroups were compared, and the correlations of DR type with tumor-infiltrating lymphocytes (TILs) within stroma, tumor stroma ratio (TSR), and Stroma AReactive Invasion Front Areas (SARIFA) were also analyzed. In the primary cohort, patients with mature DR had the highest 5-year survival rate. These findings were confirmed in validation cohort. In addition, for stage II colorectal cancer, patients classified as non-mature DR would benefit from ACT compared with surgery alone. Furthermore, immature and middle DR were more associated with high TSR, less distribution of TILs within stroma and positive SARIFA compared with mature. Taken together, these data suggest that DR is a robust-independent prognostic factor for patients with colorectal cancer. For patients with stage II colorectal cancer, non-mature DR could be a potential marker for recognizing high-risk patients who may benefit from ACT. Significance DR has the potential to identify patients with high-risk colorectal cancer and predict the efficacy of adjuvant chemotherapy in patients with stage II colorectal cancer. Our findings support reporting DR types as additional pathologic parameters in clinical practice for more precise risk stratification.
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Affiliation(s)
- Qingru Hu
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, P.R. China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, P.R. China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, P.R. China
| | - Yiting Wang
- Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China
| | - Su Yao
- Department of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, P.R. China
| | - Yun Mao
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China
| | - Liu Liu
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China
| | - Zhenhui Li
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, P.R. China
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China
- Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, P.R. China
| | - Yonghe Chen
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
| | - Shenyan Zhang
- Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China
| | - Qian Li
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, P.R. China
- School of Medicine, South China University of Technology, Guangzhou, P.R. China
| | - Yingnan Zhao
- School of Computer Science and Cyber Engineering, Guangzhou University, Guangzhou, P.R. China
| | - Xinjuan Fan
- Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China
| | - Yanfen Cui
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, P.R. China
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China
- Department of Radiology, Shanxi Cancer Hospital, Shanxi Medical University, Taiyuan, P.R. China
| | - Ke Zhao
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, P.R. China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, P.R. China
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China
| | - Zaiyi Liu
- Department of Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, P.R. China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, P.R. China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, P.R. China
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Li M, Zhu C, Xue Y, Miao C, He R, Li W, Zhang B, Yu W, Huang X, Lv M, Xu Y, Huang Q. A DNA methylation signature for the prediction of tumour recurrence in stage II colorectal cancer. Br J Cancer 2023; 128:1681-1689. [PMID: 36828869 PMCID: PMC10133253 DOI: 10.1038/s41416-023-02155-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 01/05/2023] [Accepted: 01/11/2023] [Indexed: 02/26/2023] Open
Abstract
BACKGROUND A major challenge in stage II colorectal carcinoma is to identify patients with increased risk of recurrence. Biomarkers that distinguish patients with poor prognosis from patients without recurrence are currently lacking. This study aims to develop a robust DNA methylation classifier that allows the prediction of recurrence and chemotherapy benefit in patients with stage II colorectal cancer. We performed a genome-wide DNA methylation capture sequencing in 243 stage II colorectal carcinoma samples and identified a relapse-specific DNA methylation signature consisting of eight CpG sites. METHODS Two hundred and forty-three patients with stage II CRC were enrolled in this study. In order to select differential methylation sites among recurrence and non-recurrence stage II CRC samples, DNA methylation profiles of 62 tumour samples including 31 recurrence and 31 nonrecurrence samples were analysed using the Agilent SureSelectXT Human Methyl-Seq, a comprehensive target enrichment system to analyse CpG methylation. Pyrosequencing was applied to quantify the methylation level of candidate DNA methylation sites in 243 patients. Least absolute shrinkage and selection operator (LASSO) method was employed to build the disease recurrence prediction classifier. RESULTS We identified a relapse-related DNA methylation signature consisting of eight CpG sites in stage II CRC by DNA methylation capture sequencing. The classifier showed significantly higher prognostic accuracy than any clinicopathological risk factors. The Kaplan-Meier survival curve showed an association of high-risk score with poor prognosis. In multivariate analysis, the signature was the most significant prognosis factor, with an HR of 2.80 (95% CI, 1.71-4.58, P < 0.001). The signature could identify patients who are suitable candidates for adjuvant chemotherapy. CONCLUSIONS An eight-CpG DNA methylation signature is a reliable prognostic and predictive tool for disease recurrence in patients with stage II CRC.
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Affiliation(s)
- Min Li
- Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China
- Institute of Clinical Sciences, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China
| | - Congcong Zhu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, 200032, Shanghai, P. R. China
- Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, 200032, Shanghai, P. R. China
| | - Ying Xue
- Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China
- Institute of Clinical Sciences, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China
| | - Changhong Miao
- Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China
| | - Ruiping He
- Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China
- Institute of Clinical Sciences, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China
| | - Wei Li
- Laboratory of RNA Epigenetics, Institute of Biomedical Sciences, Fudan University, 130 Dong'An Road, 200032, Shanghai, P. R. China
| | - Baolong Zhang
- Laboratory of RNA Epigenetics, Institute of Biomedical Sciences, Fudan University, 130 Dong'An Road, 200032, Shanghai, P. R. China
| | - Wenqiang Yu
- Laboratory of RNA Epigenetics, Institute of Biomedical Sciences, Fudan University, 130 Dong'An Road, 200032, Shanghai, P. R. China
| | - Xingxu Huang
- School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, P. R. China
| | - Minzhi Lv
- Institute of Clinical Sciences, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China.
- Department of Biostatistics, Clinical Research Unit, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China.
| | - Ye Xu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, 200032, Shanghai, P. R. China.
- Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'An Road, 200032, Shanghai, P. R. China.
| | - Qihong Huang
- Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China.
- Institute of Clinical Sciences, Zhongshan Hospital, Fudan University, 180 Fenglin Road, 200032, Shanghai, P. R. China.
- Shanghai Respiratory Research Institute, 180 Fenglin Road, 200032, Shanghai, P. R. China.
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Davey MG, O'Neill M, Regan M, Meshkat B, Nugent E, Joyce M, Hogan AM. Impact of the 12-gene recurrence score in influencing adjuvant chemotherapy prescription in mismatch repair proficient stage II/III colonic carcinoma-a systematic review and meta-analysis. Int J Colorectal Dis 2023; 38:71. [PMID: 36912973 PMCID: PMC10011316 DOI: 10.1007/s00384-023-04364-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/03/2023] [Indexed: 03/14/2023]
Abstract
INTRODUCTION The 12-gene recurrence score (RS) is a clinically validated assay which predicts recurrence risk in patients with stage II/III colon cancer. Decisions regarding adjuvant chemotherapy may be guided using this assay or based on the judgement of tumour board. AIMS To assess the concordance between the RS and MDT decisions regarding adjuvant chemotherapy in colon cancer. METHODS A systematic review was performed in accordance with PRISMA guidelines. Meta-analyses were performed using the Mantel-Haenszel method using the Review Manager version 5.4 software. RESULTS Four studies including 855 patients with a mean age of 68 years (range: 25-90 years) met inclusion criteria. Overall, 79.2% had stage II disease (677/855) and 20.8% had stage III disease (178/855). For the entire cohort, concordant results between the 12-gene assay and MDT were more likely than discordant (odds ratio (OR): 0.38, 95% confidence interval (CI): 0.25-0.56, P < 0.001). Patients were more likely to have chemotherapy omitted than escalated when using the RS (OR: 9.76, 95% CI: 6.72-14.18, P < 0.001). For those with stage II disease, concordant results between the 12-gene assay and MDT were more likely than discordant (OR: 0.30, 95% CI: 0.17-0.53, P < 0.001). In stage II disease, patients were more likely to have chemotherapy omitted than escalated when using the RS (OR: 7.39, 95% CI: 4.85-11.26, P < 0.001). CONCLUSIONS The use of the 12-gene signature refutes the decision of tumour board in 25% of cases, with 75% of discordant decisions resulting in omission of adjuvant chemotherapy. Therefore, it is possible that a proportion of such patients are being overtreated when relying on tumour board decisions alone.
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Affiliation(s)
- Matthew G Davey
- Department of Surgery, Galway University Hospitals, Galway, H91 YRY71, Ireland.
| | - Maeve O'Neill
- Department of Surgery, Galway University Hospitals, Galway, H91 YRY71, Ireland
| | - Mark Regan
- Department of Surgery, Galway University Hospitals, Galway, H91 YRY71, Ireland
| | - Babak Meshkat
- Department of Surgery, Galway University Hospitals, Galway, H91 YRY71, Ireland
| | - Emmeline Nugent
- Department of Surgery, Galway University Hospitals, Galway, H91 YRY71, Ireland
| | - Myles Joyce
- Department of Surgery, Galway University Hospitals, Galway, H91 YRY71, Ireland
| | - Aisling M Hogan
- Department of Surgery, Galway University Hospitals, Galway, H91 YRY71, Ireland
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Zhou J, Lin G. Ready for ctDNA-guided treatment decisions in colorectal cancer? JOURNAL OF THE NATIONAL CANCER CENTER 2023; 3:1-3. [PMID: 39036306 PMCID: PMC11256668 DOI: 10.1016/j.jncc.2022.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 10/16/2022] [Accepted: 10/24/2022] [Indexed: 11/11/2022] Open
Affiliation(s)
- Jiaolin Zhou
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Guole Lin
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Li J, Mo Y, Wei Q, Chen J, Xu G. High Infiltration of CD203c + Mast Cells Reflects Immunosuppression and Hinders Prognostic Benefit in Stage II-III Colorectal Cancer. J Inflamm Res 2023; 16:723-735. [PMID: 36852299 PMCID: PMC9961162 DOI: 10.2147/jir.s400233] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
Background Activated mast cells (AMCs) have been fully researched in inflammation and allergic reactions. However, the protumoral role of AMCs and their biomarker CD203c has not yet been investigated in colorectal cancer (CRC). Methods We retrospectively collected 449 postoperative patients with stage II-III CRC at two different hospitals as the training (n=310) and validation (n=139) cohorts. These findings were further validated in the independent cohort (Integration of GSE39582 and GSE17536, n=489). The AMC density was assessed using CD203c staining or the CIBERSORT method. The main analysis was recurrence-free survival (RFS) and overall survival (OS). Results As an independent factor, high AMC infiltration was associated with worse RFS/OS in the training (hazard ratio [HR]=3.437/3.014, all p<0.001) and validation (HR=3.537/2.382, all p<0.001) cohorts. We developed and validated an AMC-based nomogram for better stratification for postoperative recurrence in these two cohorts. The role of AMC density was further validated in the independent cohort. High AMC infiltration was associated with decreased RFS/OS after adjuvant chemotherapy (all p<0.05). Approximately 74.2% of intramural CD203c+ AMCs expressed a high level of PD-L1. Multiple immunosuppressive pathways were enriched in high AMC infiltration tumors, including upregulation of the TNF-α/NF-κB and angiogenesis pathways and downregulation of the IFN-γ and IFN-α responses. AMC infiltration was reversely associated with CD8+ T-cell infiltration (all p<0.05). Conclusion High AMC infiltration is associated with worse survival outcomes in stages II-III CRC. AMC density may serve as a potential biomarker for survival benefit in patients receiving adjuvant chemotherapy. This AMC-based nomogram could provide better recurrence stratification. Immunosuppression in tumors with high AMC infiltration might contribute to promoting tumor progression.
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Affiliation(s)
- Jing Li
- Department of Oncology, Liuzhou People’s Hospital of Guangxi Medical University, Liuzhou, Guangxi, People’s Republic of China
| | - Yuzhen Mo
- Department of Radiation Oncology, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China
| | - Qingqing Wei
- Department of Oncology, Liuzhou People’s Hospital of Guangxi Medical University, Liuzhou, Guangxi, People’s Republic of China
| | - Jian Chen
- Department of Medical Oncology, Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, People’s Republic of China
| | - Guozeng Xu
- Department of Oncology, Liuzhou People’s Hospital of Guangxi Medical University, Liuzhou, Guangxi, People’s Republic of China,Correspondence: Guozeng Xu; Jian Chen, Email ;
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Lee HG, Kim YIL, Park IJ, Lim SB, Yu CS. Can clinicopathologic high-risk features in T3N0 colon cancer be reliable prognostic factors? Ann Surg Treat Res 2023; 104:109-118. [PMID: 36816734 PMCID: PMC9929437 DOI: 10.4174/astr.2023.104.2.109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/03/2022] [Accepted: 12/02/2022] [Indexed: 02/10/2023] Open
Abstract
Purpose The purpose of this study was to assess the reliability and prognostic significance of the high-risk feature (HRF) in patients with T3N0 colon cancer. Methods We included 1,205 patients with pT3N0 colon cancer treated with curative radical resection between 2012 and 2016. HRF was defined as lymphovascular invasion, perineural invasion, poorly/undifferentiated histology, margin involvement, and preoperative obstruction. We investigated the relationships between the number and type of HRF and recurrence-free survival (RFS) and overall survival (OS), as well as the effect of adjuvant treatment. Results A total of 751 of the patients (62.3%) had more than 1 HRF and 515 of the patients (42.7%) underwent adjuvant treatment. Patients who had more than 2 HRFs had a significantly worse 5-year RFS and OS compared to patients who had neither HRF nor even one HRF. According to the findings of the multivariate analysis, the presence of multiple HRFs was a risk factor for a lower RFS and OS. When the quantity and type of HRF were taken into consideration in the multivariate analysis, adjuvant chemotherapy was not found to be linked with RFS or OS in patients with pT3N0 colon cancer. Conclusion In the present study, adjuvant treatment based on the current guideline of treatment indication was unable to enhance the prognosis of patients with pT3N0 colon cancer. The role of adjuvant treatment in T3N0 colon cancer must be examined with the HRF count in mind.
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Affiliation(s)
- Hyun Gu Lee
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young IL Kim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In Ja Park
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seok-Byung Lim
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chang Sik Yu
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Chan HT, Nagayama S, Otaki M, Chin YM, Fukunaga Y, Ueno M, Nakamura Y, Low SK. Tumor-informed or tumor-agnostic circulating tumor DNA as a biomarker for risk of recurrence in resected colorectal cancer patients. Front Oncol 2023; 12:1055968. [PMID: 36776372 PMCID: PMC9909342 DOI: 10.3389/fonc.2022.1055968] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 11/30/2022] [Indexed: 01/28/2023] Open
Abstract
Introduction Circulating tumor DNA (ctDNA) has been increasingly recognized as a promising minimally-invasive biomarker that could identify patients with minimal residual disease and a high risk of recurrence after definitive treatment. In this study, we've compared the clinical utility and sensitivity of 2 different approaches to ctDNA analyses: tumor-informed and tumor-agnostic in the management of colorectal (CRC) patients. The clinical benefits of a single timepoint ctDNA analysis compared to serial ctDNA monitoring after definitive treatment were also evaluated to uncover the ideal surveillance protocol. Methods Patient-paired resected tumor tissues, peripheral blood cells, and a total of 127 pre-operative and serial plasma cell-free DNA (cfDNA) samples after definitive treatment from 38 CRC patients that had undergone curative intent surgery were analyzed using a commercial NGS cfDNA panel. Results Up to 84% (32/38) of the recruited patients were detected with at least 1 genomic alteration from the tumor tissues that could be monitored using the tumor-informed ctDNA approach and none of the detected alterations were clonal hematopoiesis (CH) related. In contrast, 37% (14/38) of patients were detected with at least 1 monitoring alteration after exclusion of CH mutations using the tumor-agnostic approach. Serial plasma samples after definitive therapy were available for 31 patients. In the landmark ctDNA analysis, 24% (7/29) of patients had detectable ctDNA and were more likely to relapse than ctDNA-negative patients (p < 0.05). The landmark analysis sensitivity and specificity for recurrence were 67% and 87%, respectively. The incorporation of longitudinal ctDNA analysis at 6-months intervals improved the sensitivity to 100%. The median variant allele frequency (VAF) of the ctDNA mutations detected during surveillance was 0.028% (range: 0.018-0.783), where up to 80% (8/10) of the mutations were detected at VAF lower than the tumor-agnostic detection limit of 0.1%. Utilizing the tumor-agnostic approach reduced the recurrence detection sensitivity to 67% (4/6). Serial ctDNA analyses predicted disease recurrence at a median of 5 months ahead of radiological imaging. Conclusion Longitudinal monitoring using tumor-informed ctDNA testing shows high analytical sensitivity, low probability of false-positive results due to CH mutations, and improved sensitivity in detecting recurrence which may modify the clinical management of CRC.
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Affiliation(s)
- Hiu Ting Chan
- Project for Development of Liquid Biopsy Diagnosis, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Satoshi Nagayama
- Department of Gastroenterological and Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan,Department of Surgery, Uji-Tokushukai Medical Center, Kyoto, Japan
| | - Masumi Otaki
- Department of Medical Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan,Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoon Ming Chin
- Project for Development of Liquid Biopsy Diagnosis, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan,Department of Research and Development, Cancer Precision Medicine, Inc., Kawasaki, Japan
| | - Yosuke Fukunaga
- Department of Gastroenterological and Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masashi Ueno
- Department of Gastroenterological and Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yusuke Nakamura
- Project for Development of Liquid Biopsy Diagnosis, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan,National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
| | - Siew-Kee Low
- Project for Development of Liquid Biopsy Diagnosis, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan,*Correspondence: Siew-Kee Low,
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Futoh Y, Kumagai Y, Miyato H, Ozawa H, Kanamaru R, Sadatomo A, Ohnishi Y, Koinuma K, Horie H, Yamaguchi H, Lefor AK, Sata N, Kitayama J. Peripheral low-density granulocytes after colorectal cancer surgery in predicting recurrence. BJS Open 2023; 7:6991922. [PMID: 36655328 PMCID: PMC9849843 DOI: 10.1093/bjsopen/zrac154] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 10/13/2022] [Accepted: 10/20/2022] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Low-density granulocytes (LDGs) have been shown to be increased in the peripheral blood of patients with inflammatory and malignant diseases. This study evaluated LDGs in patients who underwent radical surgery for colorectal cancer (CRC) and their impact on survival. METHODS Patients who underwent radical colectomy between 2017 to 2021 were screened for enrolment in the study. Peripheral blood was obtained in the operating room before and after surgery and cells were recovered from the mononuclear layer after density gradient preparations. The ratio of CD66b(+) LDG to CD45(+) leukocytes was determined with flow cytometry, and the association of the ratios with patient outcomes was examined. The main outcome of interest was recurrence-free survival (RFS). RESULTS Out of 228 patients treated, 176 were enrolled, including 108 colonic and 68 rectal cancers. Overall, 38 patients were stage I, 30 were stage II, 72 were stage 3, and 36 were stage IV. The number of LDGs was markedly increased immediately after surgery and the proportion of LDGs correlated positively with operating time (r = 0.2806, P < 0.001) and intraoperative blood loss (r = 0.1838, P = 0.014). Purified LDGs produced high amounts of neutrophil extracellular traps after short-term culture and efficiently trapped tumour cells in vitro. The proportion of postoperative LDGs was significantly higher in 13 patients who developed recurrence (median 9 (range 1.63-47.0)) per cent versus median 2.93 ((range 0.035-59.45) per cent, P = 0.013). When cut-off values were set at 4.9 per cent, a higher proportion of LDGs was strongly and independently associated with decreased RFS (P = 0.005). In patients with stage III disease, adjuvant chemotherapy significantly improved RFS of patients with high ratios of LDGs, but not low LDGs. CONCLUSION LDGs are recruited to circulating blood by surgical stress early in the postoperative interval after colectomy for colonic cancer and their postoperative proportion is correlated with recurrence.
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Affiliation(s)
- Yurie Futoh
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Yuko Kumagai
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Hideyo Miyato
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Hideyuki Ozawa
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Rihito Kanamaru
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Ai Sadatomo
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Yasuharu Ohnishi
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Koji Koinuma
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Hisanaga Horie
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Hironori Yamaguchi
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Alan Kawarai Lefor
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Naohiro Sata
- Department of Gastrointestinal Surgery, Jichi Medical University,Shimotsuke, Japan
| | - Joji Kitayama
- Correspondence to: Joji Kitayama, Department of Gastrointestinal Surgery, Jichi Medical University, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan (e-mail: )
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Wang F, Lu S, Cao D, Qian J, Li C, Zhang R, Wang F, Wu M, Liu Y, Pan Z, Wu X, Lu Z, Ding P, Li L, Lin J, Catteau A, Galon J, Chen G. Prognostic and predictive value of Immunoscore and its correlation with ctDNA in stage II colorectal cancer. Oncoimmunology 2023; 12:2161167. [PMID: 36632564 PMCID: PMC9828598 DOI: 10.1080/2162402x.2022.2161167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
This study aimed to validate the prognostic value of Immunoscore (IS) in stage II colorectal cancer (CRC), and explore the roles of IS and circulating tumor DNA (ctDNA) in the adjuvant treatment for early-stage CRC. Resected tumor samples from stage II CRC patients were collected from the Sun Yat-sen University Cancer Center. The densities of CD3+ and CD8+ lymphocytes were quantified and converted to IS and classified into Low, Intermediate (Int), and High groups according to predefined cutoffs. A total of 113 patients were included in the study. Patients with IS-High, Int, and Low were 43 (38%), 62 (55%), and 8 (7%), respectively. Patients with IS-High had an excellent clinical outcome, with none recurring during a median follow-up of 3 years, including 15 (35%) clinical high-risk patients. The 3-year disease-free survival (DFS) was 100% for IS-High, 76% for IS-Int, and 47% for IS-Low (P < .001). In the multivariate Cox analysis, IS was the only significant parameter associated with DFS. IS-Int and IS-Low patients with adjuvant chemotherapy had improved DFS compared to those who did not receive adjuvant chemotherapy (HR = 0.3; 95% CI 0.1-0.92; P = .026). Among the 49 patients with postoperative ctDNA data, IS-High patients had the lowest ctDNA positivity rate, suggesting that they were most eligible for chemotherapy-free treatment. IS had a strong prognostic value in Chinese patients with stage II CRC and demonstrates its clinical utility. IS and ctDNA will jointly optimize the adjuvant treatment strategies for early-stage CRC.
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Affiliation(s)
- Fulong Wang
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Shixun Lu
- Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Di Cao
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Juanjuan Qian
- Department of Medicine, Genecast Biotechnology Co., Ltd, Beijing, China
| | - Cong Li
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Rongxin Zhang
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Feng Wang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Miaoqing Wu
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Yifan Liu
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Zhizhong Pan
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Xiaojun Wu
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Zhenhai Lu
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Peirong Ding
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Liren Li
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | - Junzhong Lin
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
| | | | - Jérôme Galon
- Veracyte, Marseille, France,INSERM, Laboratory of Integrative Cancer Immunology, Paris, France,Equipe Labellisée Ligue Contre le Cancer, Paris, France,Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France,CONTACT Jérôme Galon INSERM, Laboratory of Integrative Cancer Immunology. Cordeliers Research Centre. 15 rue de l’école de médecine, Paris75006, France
| | - Gong Chen
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Hong Kong, China
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Yu H, Wang X, Bai L, Tang G, Carter KT, Cui J, Huang P, Liang L, Ding Y, Cai M, Huang M, Liu H, Cao G, Gallinger S, Pai RK, Buchanan DD, Win AK, Newcomb PA, Wang J, Grady WM, Luo Y. DNA methylation profile in CpG-depleted regions uncovers a high-risk subtype of early-stage colorectal cancer. J Natl Cancer Inst 2023; 115:52-61. [PMID: 36171645 PMCID: PMC10089593 DOI: 10.1093/jnci/djac183] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/27/2022] [Accepted: 08/23/2022] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND The current risk stratification system defined by clinicopathological features does not identify the risk of recurrence in early-stage (stage I-II) colorectal cancer (CRC) with sufficient accuracy. We aimed to investigate whether DNA methylation could serve as a novel biomarker for predicting prognosis in early-stage CRC patients. METHODS We analyzed the genome-wide methylation status of CpG loci using Infinium MethylationEPIC array run on primary tumor tissues and normal mucosa of early-stage CRC patients to identify potential methylation markers for prognosis. The machine-learning approach was applied to construct a DNA methylation-based prognostic classifier for early-stage CRC (MePEC) using the 4 gene methylation markers FAT3, KAZN, TLE4, and DUSP3. The prognostic value of the classifier was evaluated in 2 independent cohorts (n = 438 and 359, respectively). RESULTS The comprehensive analysis identified an epigenetic subtype with high risk of recurrence based on a group of CpG loci in the CpG-depleted region. In multivariable analysis, the MePEC classifier was independently and statistically significantly associated with time to recurrence in validation cohort 1 (hazard ratio = 2.35, 95% confidence interval = 1.47 to 3.76, P < .001) and cohort 2 (hazard ratio = 3.20, 95% confidence interval = 1.92 to 5.33, P < .001). All results were further confirmed after each cohort was stratified by clinicopathological variables and molecular subtypes. CONCLUSIONS We demonstrated the prognostic statistical significance of a DNA methylation profile in the CpG-depleted region, which may serve as a valuable source for tumor biomarkers. MePEC could identify an epigenetic subtype with high risk of recurrence and improve the prognostic accuracy of current clinical variables in early-stage CRC.
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Affiliation(s)
- Huichuan Yu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
| | - Xiaolin Wang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
| | - Liangliang Bai
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
| | - Guannan Tang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
| | - Kelly T Carter
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
| | - Ji Cui
- Departments of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Pinzhu Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Li Liang
- Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
- Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China
| | - Yanqing Ding
- Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
- Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China
| | - Muyan Cai
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Meijin Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
| | - Huanliang Liu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
| | - Guangwen Cao
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Steven Gallinger
- Wallace McCain Centre for Pancreatic Cancer, Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada
- PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
- Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, ON, Canada
| | - Rish K Pai
- Department of laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Daniel D Buchanan
- Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia
- Genomic Medicine and Familial Cancer Centre, The Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Aung Ko Win
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
| | - Polly A Newcomb
- Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Jianping Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
| | - William M Grady
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
| | - Yanxin Luo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
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49
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Chang JS, Cheng HH, Huang SC, Lin HH, Chang SC, Lin CC. The impact of inflammatory markers on prognosis of stage II colon cancers depends on tumour sidedness. ANZ J Surg 2023; 93:182-195. [PMID: 36097407 DOI: 10.1111/ans.18014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 08/10/2022] [Accepted: 08/16/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUNDS Accumulating evidence has reported a high correlation between inflammatory markers and oncological outcomes in colorectal cancer. In the present study, we aimed to assess the prognostic values of five inflammatory markers in stage II colon cancer patients with different tumour locations. METHODS The consecutive stage II colon adenocarcinoma patients undergoing curative resection were analysed retrospectively. ROC curves and the area under the curve (AUCs) via bootstrap method were used to analyse the prognostic impact of various inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII) and prognostic nutrition index (PNI). RESULTS A total of 768 patients were enrolled for analysis. In univariate analysis, right-sided colon cancer (RCC) patients have significantly higher mean levels of all inflammatory markers than left-sided colon cancer (LCC) patients. In multivariate analyses, high NLR in LCC (P = 0.025) and low PNI in both RCC (P = 0.049) and LCC (P = 0.027) were significantly associated with a worse OS while none of the inflammatory markers was found to have a significant impact on DFS or CSS. CONCLUSIONS The profiles and prognostic impact of inflammatory markers are significantly different between stage II RCC and LCC patients. Researchers should take sidedness into consideration when addressing survival analysis of inflammatory markers.
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Affiliation(s)
- Jui-Shen Chang
- Department of Surgery, Veterans General Hospital, Taipei, Taiwan
| | - Hou-Hsuan Cheng
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Sheng-Chieh Huang
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Hung-Hsin Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Shih-Ching Chang
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chi Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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50
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Postoperative circulating tumor DNA could guide CRC adjuvant treatment. Nat Med 2023; 29:39-40. [PMID: 36646801 DOI: 10.1038/s41591-022-02119-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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