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Hooda Z, Eisenberg M, Antonoff MB. Role of Pulmonary Metastasectomy in Colorectal Cancer. Thorac Surg Clin 2025; 35:143-153. [PMID: 40246404 DOI: 10.1016/j.thorsurg.2024.11.002] [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] [Indexed: 04/19/2025]
Abstract
Pulmonary metastasectomy serves as the most efficacious local therapeutic option for stage IV colorectal cancer that has spread to the lungs. In order to properly select patients who will benefit most from pulmonary metastasectomy over other therapeutic options, a multidisciplinary approach should be utilized. The ideal technique is parenchymal-sparing, especially given that there is a high recurrence rate with the most common location being the remainder of the lung. While benefits of pulmonary metastatsectomy are well-documented, further studies are warranted to continue to refine patient selection, timing of surgery, and interplay with other treatment modalities.
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Affiliation(s)
- Zamaan Hooda
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
| | - Michael Eisenberg
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
| | - Mara B Antonoff
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
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Wang F, Chen G, Zhang Z, Yuan Y, Wang Y, Gao Y, Sheng W, Wang Z, Li X, Yuan X, Cai S, Ren L, Liu Y, Xu J, Zhang Y, Liang H, Wang X, Zhou A, Ying J, Li G, Cai M, Ji G, Li T, Wang J, Hu H, Nan K, Wang L, Zhang S, Li J, Xu R. The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update. Cancer Commun (Lond) 2025; 45:332-379. [PMID: 39739441 PMCID: PMC11947620 DOI: 10.1002/cac2.12639] [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: 11/27/2024] [Accepted: 12/02/2024] [Indexed: 01/02/2025] Open
Abstract
The 2024 updates of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China, highlighting the latest advancements in evidence-based medicine, healthcare resource access, and precision medicine in oncology. These updates address disparities in epidemiological trends, clinicopathological characteristics, tumor biology, treatment approaches, and drug selection for colorectal cancer patients across diverse regions and backgrounds. Key revisions include adjustments to evidence levels for intensive treatment strategies, updates to regimens for deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) patients, proficient mismatch repair (pMMR)/ microsatellite stability (MSS) patients who have failed standard therapies, and rectal cancer patients with low recurrence risk. Additionally, recommendations for digital rectal examination and DNA polymerase epsilon (POLE)/ DNA polymerase delta 1 (POLD1) gene mutation testing have been strengthened. The 2024 CSCO Guidelines are based on both Chinese and international clinical research, as well as expert consensus, ensuring their relevance and applicability in clinical practice, while maintaining a commitment to scientific rigor, impartiality, and timely updates.
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Affiliation(s)
- Feng Wang
- Department of Medical OncologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical SciencesGuangzhouGuangdongP. R. China
| | - Gong Chen
- Department of Colorectal SurgerySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerGuangzhouGuangdongP. R. China
| | - Zhen Zhang
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Ying Yuan
- Department of Medical OncologyThe Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Yi Wang
- Department of RadiologyPeking University People's HospitalBeijingP. R. China
| | - Yuan‐Hong Gao
- Department of Radiation OncologySun Yat‐sen University Cancer Centre, The State Key Laboratory of Oncology in South ChinaGuangzhouGuangdongP. R. China
| | - Weiqi Sheng
- Department of PathologyFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Zixian Wang
- Department of Medical OncologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical SciencesGuangzhouGuangdongP. R. China
| | - Xinxiang Li
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Xianglin Yuan
- Department of OncologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanHubeiP. R. China
| | - Sanjun Cai
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Li Ren
- Department of General SurgeryZhongshan HospitalFudan UniversityShanghaiP. R. China
| | - Yunpeng Liu
- Department of Medical OncologyThe First Hospital of China Medical UniversityShenyangLiaoningP. R. China
| | - Jianmin Xu
- Department of General SurgeryZhongshan HospitalFudan UniversityShanghaiP. R. China
| | - Yanqiao Zhang
- Department of OncologyHarbin Medical University Cancer HospitalHarbinHeilongjiangP. R. China
| | - Houjie Liang
- Department of OncologySouthwest HospitalThird Military Medical University (Army Medical University)ChongqingP. R. China
| | - Xicheng Wang
- Department of Gastrointestinal OncologyCancer Medical Center, Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina
| | - Aiping Zhou
- Department of Medical OncologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Jianming Ying
- Department of PathologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Guichao Li
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiP. R. China
| | - Muyan Cai
- Department of PathologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South ChinaGuangzhouGuangdongP. R. China
| | - Gang Ji
- Department of Gastrointestinal SurgeryXijing HospitalAir Force Military Medical UniversityXi'anShaanxiP. R. China
| | - Taiyuan Li
- Department of General SurgeryThe First Affiliated Hospital of Nanchang UniversityNanchangJiangxiP. R. China
| | - Jingyu Wang
- Department of RadiologyThe First Hospital of Jilin UniversityChangchunJilinP. R. China
| | - Hanguang Hu
- Department of Medical OncologyThe Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Kejun Nan
- Department of Medical OncologyThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiP. R. China
| | - Liuhong Wang
- Department of RadiologySecond Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Suzhan Zhang
- Department of Colorectal SurgeryThe Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP. R. China
| | - Jin Li
- Department of Medical OncologyShanghai GoBroad Cancer HospitalChina Pharmaceutical UniversityShanghaiP. R. China
| | - Rui‐Hua Xu
- Department of Medical OncologySun Yat‐sen University Cancer Center, The State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat‐sen University, Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical SciencesGuangzhouGuangdongP. R. China
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3
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Biondo S, Frago R, Kreisler E. Primary tumor resection for asymptomatic colorectal cancer with unresectable metastasis: the end of the dilemma. Ann Oncol 2024; 35:757-759. [PMID: 38969010 DOI: 10.1016/j.annonc.2024.06.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 06/21/2024] [Indexed: 07/07/2024] Open
Affiliation(s)
- S Biondo
- Department of General and Digestive Surgery, Colorectal Unit, Bellvitge University Hospital, and Bellvitge Biomedical Investigation Institute (IDIBELL), Barcelona; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
| | - R Frago
- Department of General and Digestive Surgery, Colorectal Unit, Bellvitge University Hospital, and Bellvitge Biomedical Investigation Institute (IDIBELL), Barcelona; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
| | - E Kreisler
- Department of General and Digestive Surgery, Colorectal Unit, Bellvitge University Hospital, and Bellvitge Biomedical Investigation Institute (IDIBELL), Barcelona; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
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van der Kruijssen DEW, Elias SG, van de Ven PM, van Rooijen KL, Lam-Boer J', Mol L, Punt CJA, Sommeijer DW, Tanis PJ, Nielsen JD, Yilmaz MK, van Riel JMGH, Wasowiz-Kemps DK, Loosveld OJL, van der Schelling GP, de Groot JWB, van Westreenen HL, Jakobsen HL, Fromm AL, Hamberg P, Verseveld M, Jaensch C, Liposits GI, van Duijvendijk P, Oulad Hadj J, van der Hoeven JAB, Trajkovic M, de Wilt JHW, Koopman M. Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group. Ann Oncol 2024; 35:769-779. [PMID: 38852675 DOI: 10.1016/j.annonc.2024.06.001] [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: 02/05/2024] [Revised: 05/11/2024] [Accepted: 06/02/2024] [Indexed: 06/11/2024] Open
Abstract
BACKGROUND Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.
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Affiliation(s)
- D E W van der Kruijssen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht
| | - S G Elias
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - P M van de Ven
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - K L van Rooijen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht
| | - J 't Lam-Boer
- Department of Surgery, Radboud University Medical Center, Nijmegen; Department of Surgery, Netherlands Cancer Institute, Amsterdam
| | - L Mol
- Clinical Research Department, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht
| | - C J A Punt
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - D W Sommeijer
- Department of Medical Oncology, Amsterdam University Medical Center, Amsterdam; Department of Medical Oncology, Flevo Hospital, Almere
| | - P J Tanis
- Department of Surgery, Amsterdam University Medical Center, Amsterdam; Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
| | - J D Nielsen
- Department of Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - M K Yilmaz
- Department of Medical Oncology, Aalborg University Hospital, Aalborg, Denmark
| | - J M G H van Riel
- Department of Medical Oncology, Elisabeth-TweeSteden Hospital, Tilburg
| | | | | | | | - J W B de Groot
- Department of Medical Oncology, Isala Hospital, Zwolle, The Netherlands
| | | | - H L Jakobsen
- Department of Surgery, Herlev and Gentofte Hospital, Herlev, Denmark
| | - A L Fromm
- Department of Medical Oncology, Herlev and Gentofte Hospital, Herlev, Denmark
| | - P Hamberg
- Department of Medical Oncology, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - M Verseveld
- Department of Surgery, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - C Jaensch
- Department of Surgery, Regional Hospital Gødstrup, Herning, Denmark
| | - G I Liposits
- Department of Medical Oncology, Regional Hospital Gødstrup, Herning, Denmark
| | | | - J Oulad Hadj
- Department of Medical Oncology, Gelre Hospital, Apeldoorn
| | | | - M Trajkovic
- Department of Medical Oncology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - J H W de Wilt
- Department of Surgery, Radboud University Medical Center, Nijmegen
| | - M Koopman
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht.
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Rahbari NN, Biondo S, Frago R, Feißt M, Kreisler E, Rossion I, Serrano M, Jäger D, Lehmann M, Sommer F, Dignass A, Bolling C, Vogel I, Bork U, Büchler MW, Folprecht G, Kieser M, Lordick F, Weitz J. Primary Tumor Resection Before Systemic Therapy in Patients With Colon Cancer and Unresectable Metastases: Combined Results of the SYNCHRONOUS and CCRe-IV Trials. J Clin Oncol 2024; 42:1531-1541. [PMID: 38412408 DOI: 10.1200/jco.23.01540] [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: 07/20/2023] [Revised: 11/13/2023] [Accepted: 12/21/2023] [Indexed: 02/29/2024] Open
Abstract
PURPOSE Chemotherapy is established as primary treatment in patients with stage IV colorectal cancer and unresectable metastases. Data from nonrandomized clinical trials have fueled persistent uncertainty if primary tumor resection (PTR) before chemotherapy prolongs survival. We investigated the prognostic value of PTR in patients with newly diagnosed stage IV colon cancer who were not amenable to curative treatment. PATIENTS AND METHODS Patients enrolled in the multicenter, randomized SYNCHRONOUS and CCRe-IV trials were included in the analysis. Patients with colon cancer with synchronous unresectable metastases were randomly assigned at 100 sites in Austria, Germany, and Spain to undergo PTR or up-front chemotherapy (No PTR group). The chemotherapy regimen was left at discretion of the local team. Patients with tumor-related symptoms, inability to tolerate surgery and/or systemic chemotherapy, and history of another cancer were excluded. The primary end point was overall survival (OS), and the analyses were performed with intention-to-treat. RESULTS A total of 393 patients were randomly assigned to undergo PTR (n = 187) or no PTR (n = 206) between November 2011 and March 2017. Chemotherapy was not administered to 6.4% in the No PTR group and 24.1% in the PTR group. The median follow-up time was 36.7 months (95% CI, 36.6 to 37.3). The median OS was 16.7 months (95% CI, 13.2 to 19.2) in the PTR group and 18.6 months (95% CI, 16.2 to 22.3) in the No PTR group (P = .191). Comparable OS between the study groups was further confirmed on multivariate analysis (hazard ratio, 0.944 [95% CI, 0.738 to 1.209], P = .65) and across all subgroups. Patients with serious adverse events were more common in the No PTR group (10.2% v 18.0%; P = .027). CONCLUSION Among patients with colon cancer and synchronous unresectable metastases, PTR before systemic chemotherapy was not associated with prolonged OS.
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Affiliation(s)
- Nuh N Rahbari
- Department of Surgery, Ulm University hospital, Ulm, Germany
| | - Sebastiano Biondo
- Department of General and Digestive Surgery-Colorectal Unit, Bellvitge University Hospital, University of Barcelona and IDIBELL, Barcelona, Spain
| | - Ricardo Frago
- Department of General and Digestive Surgery-Colorectal Unit, Bellvitge University Hospital, University of Barcelona and IDIBELL, Barcelona, Spain
| | - Manuel Feißt
- Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany
| | - Esther Kreisler
- Department of General and Digestive Surgery-Colorectal Unit, Bellvitge University Hospital, University of Barcelona and IDIBELL, Barcelona, Spain
| | - Inga Rossion
- The Study Center of the German Society of Surgery (SDGC), University of Heidelberg, Heidelberg, Germany
| | - Monica Serrano
- Department of General and Digestive Surgery-Colorectal Unit, Bellvitge University Hospital, University of Barcelona and IDIBELL, Barcelona, Spain
| | - Dirk Jäger
- Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany
| | - Monika Lehmann
- Coordination Centre for Clinical Trials (KKS), University Hospital Heidelberg, Heidelberg, Germany
| | - Florian Sommer
- Department of General, Visceral and Transplantation Surgery, University Hospital Augsburg, Augsburg, Germany
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe-University, Frankfurt am Main, Germany
| | - Claus Bolling
- Department of Medicine I, Agaplesion Markus Hospital, Goethe-University, Frankfurt am Main, Germany
| | - Ilka Vogel
- Department of Surgery, Community Hospital Kiel, Kiel, Germany
| | - Ulrich Bork
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, Medical Faculty Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Gunnar Folprecht
- Department of Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Meinhard Kieser
- Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany
| | - Florian Lordick
- Department of Oncology, Gastroenterology, Hepatology, and Pulmonology, Comprehensive Cancer Center Central Germany (CCCG), University of Leipzig Medical Center, Leipzig, Germany
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany
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Ciocan RA, Ciocan A, Mihăileanu FV, Ursu CP, Ursu Ș, Bodea C, Cordoș AA, Chiș BA, Al Hajjar N, Dîrzu N, Dîrzu DS. Metabolic Signatures: Pioneering the Frontier of Rectal Cancer Diagnosis and Response to Neoadjuvant Treatment with Biomarkers-A Systematic Review. Int J Mol Sci 2024; 25:2381. [PMID: 38397058 PMCID: PMC10889270 DOI: 10.3390/ijms25042381] [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: 01/06/2024] [Revised: 02/06/2024] [Accepted: 02/13/2024] [Indexed: 02/25/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most aggressive, heterogenous, and fatal types of human cancer for which screening, and more effective therapeutic drugs are urgently needed. Early-stage detection and treatment greatly improve the 5-year survival rate. In the era of targeted therapies for all types of cancer, a complete metabolomic profile is mandatory before neoadjuvant therapy to assign the correct drugs and check the response to the treatment given. The aim of this study is to discover specific metabolic biomarkers or a sequence of metabolomic indicators that possess precise diagnostic capabilities in predicting the efficacy of neoadjuvant therapy. After searching the keywords, a total of 108 articles were identified during a timeframe of 10 years (2013-2023). Within this set, one article was excluded due to the use of non-English language. Six scientific papers were qualified for this investigation after eliminating all duplicates, publications not referring to the subject matter, open access restriction papers, and those not applicable to humans. Biomolecular analysis found a correlation between metabolomic analysis of colorectal cancer samples and poor progression-free survival rates. Biomarkers are instrumental in predicting a patient's response to specific treatments, guiding the selection of targeted therapies, and indicating resistance to certain drugs.
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Affiliation(s)
- Răzvan Alexandru Ciocan
- Department of Surgery-Practical Abilities, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania;
| | - Andra Ciocan
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (F.V.M.); (C.-P.U.); (Ș.U.); (C.B.); (N.A.H.)
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Florin Vasile Mihăileanu
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (F.V.M.); (C.-P.U.); (Ș.U.); (C.B.); (N.A.H.)
| | - Cristina-Paula Ursu
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (F.V.M.); (C.-P.U.); (Ș.U.); (C.B.); (N.A.H.)
| | - Ștefan Ursu
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (F.V.M.); (C.-P.U.); (Ș.U.); (C.B.); (N.A.H.)
| | - Cătălin Bodea
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (F.V.M.); (C.-P.U.); (Ș.U.); (C.B.); (N.A.H.)
| | | | - Bogdan Augustin Chiș
- Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania;
| | - Nadim Al Hajjar
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (F.V.M.); (C.-P.U.); (Ș.U.); (C.B.); (N.A.H.)
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Noemi Dîrzu
- Clinical Laboratory Department, Transilvania Hospital, 400486 Cluj-Napoca, Romania
| | - Dan-Sebastian Dîrzu
- Emergency County Hospital Cluj, 400006 Cluj-Napoca, Romania;
- STAR—UBB Institute, Babeș Bolyai University, 400084 Cluj-Napoca, Romania
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7
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Liao SW, Zhan JQ, Liu CT, Yu HT, Wen MJ. Survival Benefit of Primary Tumor Resection Combined With Chemotherapy in Patients With Unresectable Colorectal Mucinous Adenocarcinoma With Liver Metastasis. Am J Clin Oncol 2024; 47:30-39. [PMID: 38148710 PMCID: PMC10743404 DOI: 10.1097/coc.0000000000001055] [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] [Indexed: 12/28/2023]
Abstract
OBJECTIVE To evaluate the survival benefit of combining primary tumor resection (PTR) and chemotherapy in patients with unresectable colorectal mucinous adenocarcinoma with liver metastasis (UCR-MAC-LM). METHODS We obtained data from the surveillance, epidemiology, and end results database for patients with UCR-MAC-LM from 2010 to 2017. Clinicopathological characteristics were analyzed using the χ2 test. Propensity score matching was performed to balance baseline characteristics. Kaplan-Meier analysis and log-rank tests were used to estimate and compare survival outcomes. Univariate and multivariate Cox regression analyses were conducted to identify the prognostic factors. RESULTS A total of 10,178 patients with unresectable colorectal adenocarcinoma with liver metastasis were included, of whom 6.01% (n=612) had UCR-MAC-LM. The UCR-MAC-LM group had a higher proportion of female patients, a greater number of elderly patients, an increased incidence of right colon localization, larger tumor size, and higher T and N staging than the unresectable colorectal non-mucinous adenocarcinoma with liver metastasis group (P<0.05). Multivariate analysis identified several independent prognostic factors (P<0.05). Patients with unresectable colorectal adenocarcinoma with liver metastasis who underwent PTR+C had superior survival rates compared with those who received PTR/C alone or no treatment (cancer-specific survival, P<0.05; overall survival, P<0.05). Subgroup analysis revealed that 17 of 22 groups of patients with UCR-MAC-LM who received PTR+C had significantly prolonged long-term survival compared with those who received PTR/C alone. CONCLUSIONS This surveillance, epidemiology, and end results-based study indicates that PTR+C may offer a survival advantage for a specific subgroup of patients with UCR-MAC-LM compared with PTR/C alone. Nonetheless, additional clinical trials are necessary to validate these findings.
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Affiliation(s)
- Shu-wen Liao
- Department of General Surgery, Guangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology
- Departments of General Surgery
| | - Jie-qun Zhan
- Physical Examination Center, Guangzhou Nansha Central Hospital Affiliated to Guangzhou First People’s Hospital, Guangzhou, Guangdong, China
| | - Chu-tian Liu
- Department of General Surgery, Guangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology
- Departments of General Surgery
| | - Hai-tao Yu
- Department of General Surgery, Guangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology
- Departments of General Surgery
| | - Min-jie Wen
- Department of General Surgery, Guangzhou First People’s Hospital, the Second Affiliated Hospital of South China University of Technology
- Departments of General Surgery
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8
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Fanotto V, Rossini D, Casagrande M, Bergamo F, Spagnoletti A, Santini D, Antoniotti C, Cupini S, Daniel F, Nasca V, Vetere G, Zaniboni A, Borelli B, Carullo M, Conca V, Passardi A, Tamburini E, Masi G, Pella N, Cremolini C. Primary Tumor Resection in Synchronous Metastatic Colorectal Cancer Patients Treated with Upfront Chemotherapy plus Bevacizumab: A Pooled Analysis of TRIBE and TRIBE2 Studies. Cancers (Basel) 2023; 15:5451. [PMID: 38001711 PMCID: PMC10670103 DOI: 10.3390/cancers15225451] [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: 10/07/2023] [Revised: 11/08/2023] [Accepted: 11/11/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND The decision to resect or not the primary tumor in asymptomatic patients with synchronous metastatic colorectal cancer (mCRC) is a complex and challenging issue for oncologists, especially when an antiangiogenic-based therapy is planned. METHODS Patients enrolled in the phase III TRIBE and TRIBE2 studies that compared upfront FOLFOXIRI + bevacizumab to FOLFIRI or FOLFOX + bevacizumab, respectively, were included. We assessed the association of primary tumor resection (PTR) with progression-free survival (PFS), overall survival (OS), response rate (ORR), rate of grade > 2 adverse events (AEs), and serious gastrointestinal and surgical AEs in the overall population and according to the treatment arm. RESULTS Of the 999 patients included, 513 (51%) underwent PTR at baseline. Longer PFS and OS were observed in resected patients compared to those with unresected primary tumors: 11.2 vs. 10.0 months (p < 0.001) and 26.6 vs. 22.5 (p < 0.001), respectively. In multivariate models, PTR was confirmed as an independent prognostic factor for better PFS (p = 0.032) and OS (p = 0.018). Patients with PTR experienced a higher incidence of grade 3 or 4 diarrhea (p = 0.055) and lower incidence of anemia (p = 0.053), perforation (p = 0.015), and serious gastrointestinal and surgical AEs (p < 0.001). No statistically significant differences were noted in incidence of bleeding (p = 0.39). The benefit of FOLFOXIRI + bevacizumab in terms of PFS (p for interaction: 0.46), OS (p for interaction: 0.80), ORR (p for interaction: 0.36), and incidence of grade 3 or 4 AEs was independent of PTR. CONCLUSIONS PTR at baseline was independently associated with good prognosis in synchronous mCRC patients and with lower incidence of serious gastrointestinal and surgical AEs during upfront chemotherapy plus bevacizumab. The benefit and toxicity profile of FOLFOXIRI plus bevacizumab was independent of PTR.
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Affiliation(s)
- Valentina Fanotto
- Department of Oncology, Academic Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; (V.F.); (M.C.); (N.P.)
| | - Daniele Rossini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Mariaelena Casagrande
- Department of Oncology, Academic Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; (V.F.); (M.C.); (N.P.)
| | - Francesca Bergamo
- Medical Oncology 1, Veneto Institute of Oncology IOV—IRCCS, 35128 Padua, Italy; (F.B.); (F.D.)
| | - Andrea Spagnoletti
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, 20133 Milan, Italy; (A.S.); (V.N.)
| | - Daniele Santini
- Medical Oncology Unit A, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy;
| | - Carlotta Antoniotti
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Samanta Cupini
- Department of Oncology, Division of Medical Oncology, Azienda USL Toscana Nord Ovest, 57124 Livorno, Italy;
| | - Francesca Daniel
- Medical Oncology 1, Veneto Institute of Oncology IOV—IRCCS, 35128 Padua, Italy; (F.B.); (F.D.)
| | - Vincenzo Nasca
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, 20133 Milan, Italy; (A.S.); (V.N.)
| | - Guglielmo Vetere
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Alberto Zaniboni
- Oncology Department, Istituto Ospedaliero Fondazione Poliambulanza, 25124 Brescia, Italy;
| | - Beatrice Borelli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Martina Carullo
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Veronica Conca
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Alessandro Passardi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy;
| | - Emiliano Tamburini
- Oncology Department and Palliative Care, Cardinale Panico Tricase City Hospital, 73039 Tricase, Italy;
| | - Gianluca Masi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Nicoletta Pella
- Department of Oncology, Academic Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy; (V.F.); (M.C.); (N.P.)
| | - Chiara Cremolini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Savi 10, 56126 Pisa, Italy; (D.R.); (C.A.); (G.V.); (B.B.); (M.C.); (V.C.); (G.M.)
- UO Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
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Xing P, Wang S, Cao Y, Liu B, Zheng F, Guo W, Huang J, Zhao Z, Yang Z, Lin X, Sang L, Liu Z. Treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs. Drug Resist Updat 2023; 71:101002. [PMID: 37678078 DOI: 10.1016/j.drup.2023.101002] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 08/11/2023] [Accepted: 08/12/2023] [Indexed: 09/09/2023]
Abstract
Adenocarcinoma is a common type of malignant tumor, originating from glandular epithelial cells in various organs, such as pancreas, breast, lung, stomach, colon, rectus, and prostate. For patients who lose the opportunity for radical surgery, medication is available to provide potential clinical benefits. However, drug resistance is a big obstacle to obtain desired clinical prognosis. In this review, we provide a summary of treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs, including pancreatic cancer, gastric adenocarcinoma, colorectal adenocarcinoma, lung adenocarcinoma, and prostate cancer. Although the underlying molecular mechanisms involved in drug resistance of adenocarcinoma vary from one organ to the other, there are several targets that are universal for drug resistance in adenocarcinoma, and targeting these molecules could potentially reverse drug resistance in the treatment of adenocarcinomas.
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Affiliation(s)
- Peng Xing
- Department of Surgical Oncology, Breast Surgery, General Surgery,The First Hospital of China Medical University, Shenyang, China
| | - Shuo Wang
- Department of Surgical Oncology, Breast Surgery, General Surgery,The First Hospital of China Medical University, Shenyang, China
| | - Yu Cao
- Department of Surgical Oncology, Breast Surgery, General Surgery,The First Hospital of China Medical University, Shenyang, China
| | - Bo Liu
- Department of Cardiac Surgery,The First Hospital of China Medical University, Shenyang, China
| | - Feifei Zheng
- Department of Laboratory Medicine, the Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Wei Guo
- Department of Pancreatic-Biliary Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Junhao Huang
- Department of Pancreatic-Biliary Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Zimo Zhao
- Department of Ultrasound, The First Hospital of China Medical University, Shenyang, China
| | - Ziyi Yang
- Department of Pancreatic-Biliary Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Xingda Lin
- Department of Pancreatic-Biliary Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Liang Sang
- Department of Ultrasound, The First Hospital of China Medical University, Shenyang, China.
| | - Zhe Liu
- Department of Pancreatic-Biliary Surgery, The First Hospital of China Medical University, Shenyang, China.
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10
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Bong JW, Kang S, Park P. Multicenter study of prognostic factors in paraaortic lymph node dissection for metastatic colorectal cancer. Ann Surg Treat Res 2023; 105:271-280. [PMID: 38023439 PMCID: PMC10648615 DOI: 10.4174/astr.2023.105.5.271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 09/06/2023] [Accepted: 09/06/2023] [Indexed: 12/01/2023] Open
Abstract
Purpose The role of paraaortic lymph node dissection (PALND) in colorectal cancer (CRC) has been less evaluated than surgical treatments for other distant metastases. We evaluated surgical outcomes after PALND and identified prognostic factors. Methods The medical records of patients who underwent PALND for paraaortic lymph node metastasis (PALNM) were reviewed retrospectively. All patients were categorized into the M1a group (isolated PALNM, n = 27), and the M1bc group (distant metastases other than PALNM, n = 26). Three severity factors (PALNM-SF: number of harvested paraaortic lymph nodes [hLN], ≥14; number of metastatic paraaortic lymph nodes [mLN], ≥5; and lymph nodes ratio [mLN/hLN], ≥0.5) were defined to determine their effects on survival. Results The 5-year overall survival (OS) of the M1a and M1bc groups were 61.1% and 6.4%, respectively (P = 0.0013). The 5-year disease-free survival (DFS) of the M1a group was 47.4%, and the 3-year DFS of the M1bc group was 9.1% (P < 0.001). Patients with 2 or more PALNM-SFs showed worse OS than those with 1 PALNM-SF (P = 0.017). In multivariate analysis, M1bc (non-isolated PALNM) was the only significant factor for survival. In the M1a group, patients with 2 or more PALNM-SFs showed significantly worse survival than those with a single PALNM-SF. In multivariate analysis, 2 or more PALNM-SF was a significant factor for survival. Conclusion PALND for CRC provided favorable outcomes in the survival of an isolated PALNM, although this was uncertain for non-isolated PALNMs. The PALNM-SFs helped assess the prognosis after PALND.
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Affiliation(s)
- Jun Woo Bong
- Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Sanghee Kang
- Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Pyoungjae Park
- Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
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11
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Jin R, Ogbomo AS, Accortt NA, Lal LS, Bishi G, Sandschafer D, Goldschmidt JH. Real-world outcomes among patients with metastatic colorectal cancer treated first line with a bevacizumab biosimilar (bevacizumab-awwb). Ther Adv Med Oncol 2023; 15:17588359231182386. [PMID: 37360769 PMCID: PMC10288425 DOI: 10.1177/17588359231182386] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 05/30/2023] [Indexed: 06/28/2023] Open
Abstract
Background Bevacizumab-awwb (MVASI®) was the first U.S. Food and Drug Administration-approved biosimilar to Avastin® (reference product [RP]) for the treatment of several different types of cancers, including metastatic colorectal cancer (mCRC), an indication approved based on extrapolation. Objectives Evaluate treatment outcomes in mCRC patients who received first-line (1L) bevacizumab-awwb at treatment initiation or as continuing bevacizumab therapy (switched from RP). Design A retrospective chart review study. Methods Adult patients who had a confirmed diagnosis of mCRC (initial presentation of CRC on or after 01 January 2018) and initiated 1L bevacizumab-awwb between 19 July 2019 and 30 April 2020 were identified from the ConcertAI Oncology Dataset. A chart review was conducted to evaluate patient baseline clinical characteristics and effectiveness and tolerability outcomes during the follow-up. Study measures were reported stratified by prior use of RP: (1) naïve patients and (2) switchers (patients who switched to bevacizumab-awwb from RP without advancing the line of therapy). Results At the end of study period, naïve patients (n = 129) had a median 1L progression-free survival (PFS) of 8.6 months [95% confidence interval (CI), 7.6-9.9] and a 12-month overall survival (OS) probability of 71.4% (95% CI, 61.0-79.5%). Switchers (n = 105) had a median 1L PFS of 14.1 months (95% CI, 12.1-15.8) and a 12-month OS probability of 87.6% (95% CI, 79.1-92.8%). During treatment with bevacizumab-awwb, 20 events of interest (EOIs) were reported in 18 naïve patients (14.0%) and 4 EOIs reported in 4 switchers (3.8%), of which the most commonly reported events were thromboembolic and hemorrhagic events. Most EOIs resulted in emergency department visit and/or treatment hold/discontinuation/switch. None of the EOIs resulted in death. Conclusion In this real-world cohort of mCRC patients who were treated 1L with a bevacizumab biosimilar (bevacizumab-awwb), the clinical effectiveness and tolerability data were as expected and consistent with previously published findings from real-world studies of bevacizumab RP in mCRC patients.
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Affiliation(s)
- Ran Jin
- Amgen Inc., 1 Amgen Center Dr, Thousand Oaks, CA 91320, USA
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12
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He M, Jia Z, Hu L, Wu H. Development and validation of a nomogram to predict which patients with colorectal cancer liver metastases would benefit from primary tumor resection. Int J Colorectal Dis 2023; 38:144. [PMID: 37237238 DOI: 10.1007/s00384-023-04426-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/01/2023] [Indexed: 05/28/2023]
Abstract
PURPOSE The use of primary tumor resection (PTR) in the treatment of colorectal cancer liver metastases (CRLM) patients has become increasingly controversial. Our goal is to establish a nomogram to screen for the candidates that would benefit from PTR in CRLM patients. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was searched for 8366 patients with colorectal liver cancer metastases (CRLM) from 2010 to 2015. Overall survival (OS) rates were calculated using the Kaplan-Meier curve. After propensity score matching (PSM), predictors were analyzed by logistic regression analysis, and a nomogram was created to predict for survival benefit of PTR using R software. RESULTS After PSM, there were 814 patients in both PTR group and non-PTR group, respectively. The median OS time in the PTR group was 26 months (95%CI = 23.33 ~ 28.67) and the median OS time in the non-PTR group was 15 months (95%CI = 13.36 ~ 16.64). The Cox regression analysis found that PTR was an independent predictive factor (HR = 0.46, 0.41 ~ 0.52) for OS. Additionally, logistic regression was used to study the factors impacting PTR benefit, and the results showed that CEA (P = 0.016), chemotherapy (P < 0.001), N stage (P < 0.001), histological grade (P < 0.001), and lung metastasis (P = 0.001) are independent predictive factors affecting the therapeutic outcome of PTR in patients with CRLM. The developed nomogram displayed good discriminative ability in predicting the beneficial probability of PTR surgery, with the area under the curve (AUC) values of 0.801 in training set and 0.739 in validation set respectively. CONCLUSION We developed a nomogram that predicts the survival benefits of PTR in CRLM patients with relatively high accuracy, and quantifies the predictive factors for PTR-related benefits.
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Affiliation(s)
- Mingming He
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China
| | - Zhenya Jia
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Lei Hu
- Department of General Surgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230001, China.
| | - Huo Wu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China.
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Rijken A, van de Vlasakker VCJ, Simkens GA, Rovers KP, van Erning FN, Koopman M, Verhoef C, de Wilt JHW, de Hingh IHJT. Primary tumor resection or systemic treatment as palliative treatment for patients with isolated synchronous colorectal cancer peritoneal metastases in a nationwide cohort study. Clin Exp Metastasis 2023:10.1007/s10585-023-10212-y. [PMID: 37209222 DOI: 10.1007/s10585-023-10212-y] [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: 12/29/2022] [Accepted: 05/15/2023] [Indexed: 05/22/2023]
Abstract
Limited data are available to guide the decision-making process for clinicians and their patients regarding palliative treatment options for patients with isolated synchronous colorectal cancer peritoneal metastases (CRC-PM). Therefore, the aim of this study is to analyze the outcome of the different palliative treatments for these patients. All patients diagnosed with isolated synchronous CRC-PM between 2009 and 2020 (Netherlands Cancer Registry) who underwent palliative treatment were included. Patients who underwent emergency surgery or curative intent treatment were excluded. Patients were categorized into upfront palliative primary tumor resection (with or without additional systemic treatment) or palliative systemic treatment only. Overall survival (OS) was compared between both groups and multivariable cox regression analysis was performed. Of 1031 included patients, 364 (35%) patients underwent primary tumor resection and 667 (65%) patients received systemic treatment only. Sixty-day mortality was 9% in the primary tumor resection group and 5% in the systemic treatment group (P = 0.007). OS was 13.8 months in the primary tumor resection group and 10.3 months in the systemic treatment group (P < 0.001). Multivariable analysis showed that primary tumor resection was associated with improved OS (HR 0.68; 95%CI 0.57-0.81; P < 0.001). Palliative primary tumor resection appeared to be associated with improved survival compared to palliative systemic treatment alone in patients with isolated synchronous CRC-PM despite a higher 60-day mortality. This finding must be interpreted with care as residual bias probably played a significant role. Nevertheless, this option may be considered in the decision-making process by clinicians and their patients.
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Affiliation(s)
- Anouk Rijken
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | | | - Geert A Simkens
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - Koen P Rovers
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - Felice N van Erning
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Cornelis Verhoef
- Department of Surgery, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Ignace H J T de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands.
- GROW- School for Oncology and Development Biology, Maastricht University, Maastricht, the Netherlands.
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14
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Bai J, Yang M, Liu Z, Efetov S, Kayaalp C, Dulskas A, Shaw D, Wang X. Primary tumor resection in colorectal cancer patients with unresectable distant metastases: a minireview. Front Oncol 2023; 13:1138407. [PMID: 37182188 PMCID: PMC10172590 DOI: 10.3389/fonc.2023.1138407] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 04/12/2023] [Indexed: 05/16/2023] Open
Abstract
Colorectal cancer (CRC) is the second most common cause of cancer-related death among both men and women worldwide and the third most common cancer overall. About 20% of patients diagnosed with CRC were discovered to have distant metastatic lesions, the majority of which were located in the liver. For the optimum treatment of CRC patients with hepatic metastases, interventional radiologists, medical oncologists, and surgeons must all collaborate. The surgical excision of the primary tumor is an important part of CRC treatment since it has been found to be curative in cases of CRC with minimal metastases. However, given the evidence to date was gathered from retrospective data, there is still controversy over the effectiveness of primary tumor resection (PTR) in improving the median overall survival (OS) and quality of life. Patients who have hepatic metastases make up a very tiny fraction of those who are candidates for resection. With a focus on the PTR, this minireview attempted to review the current advancements in the treatment options for hepatic colorectal metastatic illness. This evaluation also included information on PTR's risks when performed on individuals with stage IV CRC.
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Affiliation(s)
- Junge Bai
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming Yang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zheng Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sergey Efetov
- Clinic of Coloproctology and Minimally Invasive Surgery, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Cuneyt Kayaalp
- Department of Gastrointestinal Surgery, Yeditepe University, Istanbul, Türkiye
| | - Audrius Dulskas
- Department of Abdominal and General Surgery and Oncology, National Cancer Institute, Vilnius, Lithuania
- Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, Vilnius, Lithuania
| | - Darcy Shaw
- Colorectal Surgery Associates, Kansas City University, Kansas, MO, United States
| | - Xishan Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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15
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Zhao J, Zhu J, Huang C, Yuan R, Zhu Z. Impact of primary tumor resection on the survival of patients with unresectable colon cancer liver metastasis at different colonic subsites: a propensity score matching analysis. Acta Chir Belg 2023; 123:132-147. [PMID: 34278951 DOI: 10.1080/00015458.2021.1956799] [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: 01/14/2021] [Accepted: 07/13/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVE To investigate the effect of primary tumor resection (PTR) on the prognosis of patients with unresectable colon cancer liver metastasis (UCCLM) at seven colonic subsites using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS Propensity score matching (PSM) was performed to balance selection bias using all available variables that could be of potential relevance. After matching, the groups were redefined in a 1:1 ratio using the nearest method. Cancer-specific survival (CSS) was compared among the patients of PTR and non-PTR groups. Cox regression models were used to identify the prognostic factors for CSS. RESULTS CSS was significantly different between all groups. Cox regression analysis showed that PTR was an independent prognostic factor for all groups. After PSM, PTR significantly prolonged CSS for all groups. Subgroup analysis showed that PTR did not improve the prognosis of N2 stage patients in the cecum, ascending colon, and descending colon groups; T1 + T2 stage patients in the hepatic flexure group; and patients with a tumor size ≤5 cm in the splenic flexure group. Segmental colectomy could prolong CSS of patients in the cecum, ascending colon, transverse colon, splenic flexure, and sigmoid colon groups, while extended colectomy could prolong CSS of patients in the hepatic flexure and descending colon groups. CONCLUSION At different colonic subsites, UCCLM patients had different CSS. PTR could improve their prognosis, however, N stage, T stage, and tumor size are important reference indicators. In addition to patients in the hepatic flexure and descending colon groups, we suggested that patients in other groups should choose segmental colectomy.
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Affiliation(s)
- Jiefeng Zhao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jinfeng Zhu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Chao Huang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Rongfa Yuan
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhengming Zhu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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The Resection Rate of Synchronously Detected Liver and Lung Metastasis from Colorectal Cancer Is Low-A National Registry-Based Study. Cancers (Basel) 2023; 15:cancers15051434. [PMID: 36900225 PMCID: PMC10000535 DOI: 10.3390/cancers15051434] [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: 01/27/2023] [Revised: 02/21/2023] [Accepted: 02/22/2023] [Indexed: 03/02/2023] Open
Abstract
Population-based data on the incidence and surgical treatment of patients with colorectal cancer (CRC) and synchronous liver and lung metastases are lacking as are real-life data on the frequency of metastasectomy for both sites and outcomes in this setting. This is a nationwide population-based study of all patients having liver and lung metastases diagnosed within 6 months of CRC between 2008 and 2016 in Sweden identified through the merging of data from the National Quality Registries on CRC, liver and thoracic surgery and the National Patient Registry. Among 60,734 patients diagnosed with CRC, 1923 (3.2%) had synchronous liver and lung metastases, of which 44 patients had complete metastasectomy. Surgery of liver and lung metastases yielded a 5-year OS of 74% (95% CI 57-85%) compared to 29% (95% CI 19-40%) if liver metastases were resected but not the lung metastases and 2.6% (95% CI 1.5-4%) if non-resected, p < 0.001. Complete resection rates ranged from 0.7% to 3.8% between the six healthcare regions of Sweden, p = 0.007. Synchronous liver and lung CRC metastases are rare, and a minority undergo the resection of both metastatic sites but with excellent survival. The reasons for differences in regional treatment approaches and the potential of increased resection rates should be studied further.
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Survival Outcomes after Elective or Emergency Surgery for Synchronous Stage IV Colorectal Cancer. Biomedicines 2022; 10:biomedicines10123114. [PMID: 36551870 PMCID: PMC9775222 DOI: 10.3390/biomedicines10123114] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/29/2022] [Accepted: 11/29/2022] [Indexed: 12/12/2022] Open
Abstract
Patients with stage IV colorectal cancer (CRC) who have not undergone primary tumor resection (PTR) are at risk of sudden medical emergencies. Despite the ongoing controversy over the necessity and timing of PTR in patients with stage IV CRC, studies comparing the survival outcomes of elective and emergency surgery in this population are scarce. This is a retrospective study conducted at a single institute. The patients were divided into two groups: the elective surgery (ELS) group (n = 46) and the emergency surgery (EMS) group (n = 26). The primary outcome was 2-year overall survival (OS). During a median follow-up period of 27.0 months, the 2-year OS was significantly better in the ELS group (80% vs. 42.9%, p = 0.002). No significant differences were observed in the 2-year relapse-free survival and 30-day postoperative complication rates. Planning and performing elective surgery could help increase the survival rate of patients with synchronous stage IV CRC, especially those that undergo simultaneous or staged metastasectomy.
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Liu LL, Sun JD, Xiang ZL. Survival nomograms for colorectal carcinoma patients with lung metastasis and lung-only metastasis, based on the SEER database and a single-center external validation cohort. BMC Gastroenterol 2022; 22:446. [PMID: 36335295 PMCID: PMC9636633 DOI: 10.1186/s12876-022-02547-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 10/19/2022] [Indexed: 11/06/2022] Open
Abstract
Background We analysed the survival of colorectal cancer (CRC) patients with lung metastasis and lung-only metastasis and determined the risk factors for lung metastasis in CRC patients. Methods Data from colorectal cancer patients with lung metastasis diagnosed from 2010 to 2015 were obtained from the SEER database. Survival was analysed using the Kaplan–Meier method and log-rank test, the Cox proportional hazards regression model, and a competing risk model. The predictive ability of the nomgram was assessed by the concordance index (C-index) and calibration curves. The data from the SEER database for the period 2016–2019 was used as an external validation set. The characteristics of 70 CRC patients treated at Shanghai East Hospital between 2016 and 2019 were retrospectively analysed and data from China was chosen as an external validation set. Results The median survival time for colorectal cancer patients with lung metastasis was 12 months, while this value was 24 months in patients with lung-only metastasis. Among all CRC patients with lung metastasis, age, grade, T stage, N stage, presence of liver, brain or bone metastasis, anatomic site and surgery were related to overall survival (OS). In CRC patients with lung-only metastasis, age, T stage, marital status, chemotherapy and surgery were independent prognostic factors affecting OS. Two nomograms predicting OS were established, with great discrimination (C-index between 0.67 and 0.81) and excellent calibration. Factors including age, race, sex, tumour grade, T stage, N stage, presence of liver, brain or bone metastasis, marital status, insurance status and anatomic location were related to the occurrence of lung metastasis in CRC patients. Conclusion We developed two reliable clinical prediction models among CRC patients to predict the OS rates in patients with lung metastasis and lung metastasis only. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02547-9.
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Park EJ, Baik SH. Recent Advance in the Surgical Treatment of Metastatic Colorectal Cancer-An English Version. J Anus Rectum Colon 2022; 6:213-220. [PMID: 36348943 PMCID: PMC9613413 DOI: 10.23922/jarc.2022-048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 09/04/2022] [Indexed: 11/06/2022] Open
Abstract
Stage IV colorectal cancer (CRC) has heterogeneous characteristics in tumor extent and biology. The overall survival of patients with metastatic CRC has improved with the development of multimodal treatments and new chemotherapeutic drugs. Resection of metastatic CRC is performed for liver, lung, or peritoneal metastases. Conversion surgeries to resect oligometastatic lesions have been developed with tumor regression using chemotherapeutic agents. Two-stage hepatectomy has extended the surgical indications for patients with metastatic CRC. Synchronous liver and primary tumor resection can be considered in patients with adequate conditions. Local ablation with radiotherapy can be used to treat lung metastasis. In the treatment of patients with CRC with peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy can be considered. Surgical treatments should be performed in patients with symptomatic primary tumors with unresectable metastasis. However, primary tumor resection in patients with asymptomatic CRC with synchronous, unresectable metastases did not show overall survival benefits in recent studies. Therefore, the treatment of metastatic CRC is challenging due to the variable tumor extent and heterogenous characteristics. Tailored surgical treatments and multidisciplinary approaches may improve survival and the quality of life in patients with metastatic CRC.
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Affiliation(s)
- Eun Jung Park
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine
| | - Seung Hyuk Baik
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine
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Park EJ, Baik SH. Surgical treatment for metastatic colorectal cancer. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2022. [DOI: 10.5124/jkma.2022.65.9.568] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Background: Stage IV colorectal cancer (CRC) exhibits heterogeneous characteristics in tumor extent and biology. The overall survival of patients with metastatic CRC has improved with the development of multimodal treatments and new chemotherapeutic drugs.Current Concepts: Resection of metastatic CRC is performed for liver, lung, or peritoneal metastases. Conversion surgeries to resect oligometastatic lesions have been developed with tumor regression using chemotherapeutic agents. Two-stage hepatectomy has extended the surgical indications for patients with metastatic CRC. Synchronous liver and primary tumor resection can be considered in patients with adequate conditions. Local ablation with radiotherapy can be used to treat lung metastasis. Meanwhile, for treating patients with CRC with peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy can be considered. Surgical treatments should be performed in patients with symptomatic primary tumors with unresectable metastasis. However, in recent studies, primary tumor resection in patients with asymptomatic CRC with synchronous, unresectable metastases did not show overall survival benefits.Discussion and Conclusion: The treatment of metastatic CRC is challenging because of the variable tumor extent and heterogenous characteristics. Tailored surgical treatments and multidisciplinary approaches may improve the survival and quality of life of patients with metastatic CRC.
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Colloca GA, Venturino A, Guarneri D. Primary tumor resection in patients with unresectable colorectal cancer with synchronous metastases could improve the activity of poly-chemotherapy: A trial-level meta-analysis. Surg Oncol 2022; 44:101820. [DOI: 10.1016/j.suronc.2022.101820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 06/12/2022] [Accepted: 07/11/2022] [Indexed: 12/24/2022]
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Qiao Y, Qiao Y, Li H, Fu J, You S. Survival benefit of primary and metastatic tumor resection for colon cancer with liver metastases: A population based, propensity score-matched study. Front Surg 2022; 9:959826. [PMID: 36111222 PMCID: PMC9468248 DOI: 10.3389/fsurg.2022.959826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 08/08/2022] [Indexed: 11/16/2022] Open
Abstract
Background Colon cancer remains one of the most common malignancies and we aimed to evaluate whether surgery has an effect on the survival of metastatic colon patients. Methods We analyzed 7,583 metastatic colon patients from the Surveillance, Epidemiology, between January 2010 and December 2015. Using Cox proportional hazards models and Kaplan-Meier curves, the overall survival rate (OS) and cancer-specific survival rate and End Results (SEER) registry (CSS) months (m) were evaluated with corresponding 95% confidence intervals (95% CIs). Propensity score matching (PSM) was performed to adjust for potential baseline confounding of all comparison groups. Results In general, receiving both primary and metastatic tumor resection (PMTR) remarkably improved OS and CSS compared with only primary tumor resection (PTR) after PS matching (PSM) (P < 0.05), with a significantly improved OS (HR = 0.74, 95%CI = 0.69–0.80) and CSS (HR = 0.71, 95%CI = 0.66–0.76) in all stage M1 colon patients. The stratification analysis indicated a significant difference between OS and CSS in M1a and M1b stages. After PSM, PMTR was found to be associated with remarkably improved OS and CSS for patients with liver metastases but not associated with OS and CSS of patients with lung metastases in both M1a and M1b stage. Conclusions The results from this large SEER cohort supported PMTR might improve the survival of colon patients with liver metastases on the basis of chemotherapy.
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Affiliation(s)
- Yunfeng Qiao
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yunfeng Qiao
- Cancer Center, Faculty of Health Sciences, University of Macau, Macau, China
| | - Huijun Li
- Department of Imaging Medicine, Taikang Tongji (Wuhan) Hospital, Wuhan, China
| | - Jinge Fu
- Department of Anorectal Surgery, Weishi Central Hospital, Kaifeng, China
| | - Shuping You
- Department of Anus and Bowel Surgery, Jingmen No. 2 People's Hospital, Jingmen, China
- Correspondence: Shuping You
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Combined Primary Resection with Hepatic Artery Infusion Pump Implantation Is Safe for Unresectable Colorectal Liver Metastases. J Gastrointest Surg 2022; 26:764-771. [PMID: 34820727 DOI: 10.1007/s11605-021-05195-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 10/02/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Colorectal liver metastases (CRLM) are the most common cause of disease-specific mortality in patients with colorectal cancer. Hepatic artery infusion (HAI) combined with systemic chemotherapy improves survival for these patients. The safety of colorectal resection at the time of HAI pump placement has not been well established. METHODS Patients with CRLM who underwent combined HAI pump placement and colorectal (primary) resection or HAI pump placement alone were evaluated for perioperative outcomes, pump-specific complications, infectious complications, and time to treatment initiation. These outcomes were compared using comparative statistics. RESULTS Patients who underwent combined HAI pump placement and primary resection (n = 19) vs HAI pump placement alone (n = 13) had similar demographics and rates of combined hepatectomy. Combined HAI pump placement and primary resection group had similar operative time and blood loss (both p = NS), but longer length of stay (6 vs 4 days, p = 0.02) compared to pump placement alone. Overall postoperative complications (21% vs 8%) and pump-specific complications (16% vs 31%) were similar (both p = NS). Infection rates were not different between groups, nor was time to initiation of HAI therapy (19 vs 16 days p = NS), or systemic therapy (34 vs 35 days p = NS). CONCLUSION Combining colorectal resection with HAI pump implantation is a safe surgical approach for management of unresectable CRLM. Postoperative complications, specifically infectious complications, were not increased, nor was there a delay to initiation of HAI or systemic chemotherapy. Investigation of long-term oncologic outcomes for HAI pump placement and primary tumor resection in patients with unresectable CRLM is ongoing.
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Huang L, Wei G, Chen N, Liu J, Wang Z, Yu Y, Qiu M. Impact of Upfront Chemotherapy on the Effect of Primary Tumour Resection for Asymptomatic Synchronous Colorectal Cancer With Unresectable Metastases: A Propensity-Score-Matched Cohort Analysis. Clin Med Insights Oncol 2022; 16:11795549221085054. [PMID: 35355515 PMCID: PMC8958687 DOI: 10.1177/11795549221085054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 02/05/2022] [Indexed: 02/05/2023] Open
Abstract
Background: It is controversial whether primary tumour resection (PTR) and the sequencing of chemotherapy and PTR are associated with the survival of patients with incurable stage IV colorectal cancer. This study aimed to explore the effects of PTR and the sequencing of chemotherapy and PTR on asymptomatic colorectal cancer with synchronous unresectable metastases (asmCRC). Patients and Methods: Patients with asmCRC were retrospectively identified from a single centre and categorised into 3 groups: PTR followed by chemotherapy (POC), upfront chemotherapy followed by PTR (UFC), and palliative chemotherapy (PC). The primary end points included median overall survival (OS) and progression-free survival (PFS). Clinical features were analysed using χ2 test, while survival curves were generated using the Kaplan-Meier test. Propensity-score matching (PSM) was performed when comparing survival between POC and UFC groups. Results: From 2008 to 2014, 255 patients were identified and included into the POC (n = 101), UFC (n = 40), and PC (n = 114) groups. The UFC and POC groups had significantly better median OS compared with the PC group (40.7 vs 16.3 months, P < .0001; 39.7 vs 16.3 months, P < .0001). Before PSM, the UFC group had better median PFS than the POC and PC groups (18.5 vs 9.7 months, P = .038; 18.5 vs 6.1 months, P < .0001). After PSM, UFC has better PFS than POC (P = .038). And the UFC group did not have higher postoperative or preoperative morbidity compared with the POC group (P = .235). Conclusions: Primary tumour resection could improve the survival of patients with asmCRC. Compared with POC or PC, UFC was associated with a better median PFS without significantly increasing preoperative or postoperative morbidity.
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Affiliation(s)
- Lin Huang
- Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Guixia Wei
- Department of Abdominal Cancer, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Nan Chen
- Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jiewei Liu
- Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Ziqiang Wang
- Department of Gastrointestinal Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Yongyang Yu
- Department of Gastrointestinal Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Meng Qiu
- Department of Abdominal Cancer, West China Hospital of Sichuan University, Chengdu, Sichuan, China
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Yao YC, Chen JQ, Yin L, Lin WH, Peng JH, Fan WH. Primary tumor resection with or without metastasectomy for left- and right-sided stage IV colorectal cancer: an instrumental variable analysis. BMC Gastroenterol 2022; 22:114. [PMID: 35264117 PMCID: PMC8908621 DOI: 10.1186/s12876-022-02184-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 02/21/2022] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Whether primary tumor location (PTL) is predictive of survival benefits following primary tumor resection plus metastasectomy (PMTR) and primary tumor resection (PTR) alone in stage IV colorectal cancer patients is not known. We sought to address this issue by employing instrumental variable analysis to evaluate the efficacy of PMTR and PTR with stratification for primary tumor location in stage IV colorectal cancer patients. PATIENTS AND METHODS Stage IV colorectal cancer patients diagnosed between January 1, 2005 and December 31, 2015 were identified from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. To account for both measured and unmeasured confounders, the efficacy of PMTR and PTR in the left- and right-sided subgroups was evaluated using instrumental variable analysis, with the health service area as the instrument variable. Overall survival (OS) was the primary outcome of interest. RESULTS A total of 50,333 eligible patients were analyzed (left-sided, n = 29,402 and right-sided, n = 20,931). OS was significantly better with PMTR than with other treatments (PTR, metastasectomy only, or no surgery) in patients with left-sided tumors (hazard ratio [HR] = 0.37 [95% CI 0.24-0.58], P < 0.001), but not in patients with right-sided tumors (HR = 0.98 [95% CI 0.65-1.47], P = 0.910; interaction test P < 0.001). OS was comparable in patients treated with PTR and those treated with no surgery in both the left-sided (HR = 1.11 [95% CI 0.68-1.81], P = 0.690) and right-sided (HR = 0.85 [95% CI 0.50-1.43], P = 0.530; interaction test P = 0.466) subgroups. CONCLUSIONS PMTR appears to only benefit patients with left-sided stage IV colorectal cancer but not those with right-sided tumors. PTR does not improve OS, regardless of primary tumor location. When selecting patients for PMTR, primary tumor location should be considered. Overuse of PTR should be avoided.
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Affiliation(s)
- Yi-Chen Yao
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Jun-Quan Chen
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Ling Yin
- Department of Clinical Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Wu-Hao Lin
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Jian-Hong Peng
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, People's Republic of China.
| | - Wen-Hua Fan
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, People's Republic of China.
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Hedrick TL, Zaydfudim VM. Management of Synchronous Colorectal Cancer Metastases. Surg Oncol Clin N Am 2022; 31:265-278. [DOI: 10.1016/j.soc.2021.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Huang JH, Liu HS, Hu T, Zhang ZJ, He XW, Mo TW, Wen XF, Lan P, Lian L, Wu XR. OUP accepted manuscript. Gastroenterol Rep (Oxf) 2022; 10:goac020. [PMID: 35711715 PMCID: PMC9196102 DOI: 10.1093/gastro/goac020] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 04/16/2022] [Accepted: 04/30/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Jun-Hua Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Hua-Shan Liu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Tuo Hu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Zong-Jin Zhang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Xiao-Wen He
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Tai-Wei Mo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Xiao-Feng Wen
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Ping Lan
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Lei Lian
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
- Department of Gastric Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Xian-Rui Wu
- Corresponding author. The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong 510655, P. R. China. Tel: +86-20-38254009; Fax: +86-20-38254159;
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Benavides M, Gómez-España A, García-Alfonso P, González CG, Viéitez JM, Rivera F, Safont MJ, Abad A, Sastre J, Valladares-Ayerbes M, Carrato A, González-Flores E, Robles L, Salud A, Alonso-Orduña V, Montagut C, Asensio E, Díaz-Rubio E, Aranda E. Upfront primary tumour resection and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD). Eur J Surg Oncol 2021; 48:1123-1132. [PMID: 34872775 DOI: 10.1016/j.ejso.2021.11.122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 09/14/2021] [Accepted: 11/17/2021] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION Retrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy. PATIENTS AND METHODS Survival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling. RESULTS Of 1334 eligible patients, 642 (48%) had undergone UPTR. UPTR was associated with significantly longer overall survival (OS; 25.0 vs 20.3 months; HR 1.30, 95%CI 1.15-1.48; p < 0.0001). UPTR was associated with significant OS benefit in both left-sided (HR 1.38, 95%CI 1.13-1.69; p = 0.002) and right-sided (HR 1.39, 95%CI 1.00-1.94; p = 0.049) tumours, RASwt (HR 1.29, 95%CI 1.05-1.60; p = 0.016) and BRAFwt (HR 1.49, 95%CI 1.21-1.84; p = 0.0002) tumours, and treatment with anti-EGFRs (HR 1.47, 95%CI 1.13-1.92; p = 0.004) and anti-VEGFs (HR 1.25, 95%CI 1.08-1.44; p = 0.003). Multivariate analysis identified number of metastatic sites, RAS status, primary tumour location and UPTR as independent prognostic factors for OS. CONCLUSION Considering the selection bias inherent to this study, our results support UPTR before first-line anti-EGFR or anti-VEGF targeted therapy in right and left-sided asymptomatic unresectable synchronous mCRC patients. RAS/BRAF mutational status may also influence UPTR function.
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Affiliation(s)
- Manuel Benavides
- UGC Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain.
| | - Auxiliadora Gómez-España
- Department of Medical Oncology, IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - Pilar García-Alfonso
- Department of Medical Oncology, Hospital Universitario Gregorio Marañón, Madrid, Spain
| | - Cristina García González
- UGC Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain
| | - Jose María Viéitez
- Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Fernando Rivera
- Department of Medical Oncology, University Hospital Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - María José Safont
- Department of Medical Oncology, Hospital General Universitario Valencia, Universidad de Valencia, CIBERONC, Valencia, Spain
| | - Albert Abad
- Department of Medical Oncology, Instituto Oncológico Dr. Rosell, Barcelona, Spain
| | - Javier Sastre
- Department of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clínico San Carlos (IdISSC), University Complutense, CIBERONC, Madrid, Spain
| | | | - Alfredo Carrato
- Department of Medical Oncology, IRYCIS, CIBERONC, Alcalá University, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | - Luis Robles
- Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain
| | - Antonieta Salud
- Department of Medical Oncology, Hospital de Lleida Arnau de Vilanova, Lérida, Spain
| | - Vicente Alonso-Orduña
- Department of Medical Oncology, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISA), Zaragoza, Spain
| | - Clara Montagut
- Department of Medical Oncology, Hospital del Mar Medical Research Institute, CIBERONC, Barcelona, Spain
| | - Elena Asensio
- Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain
| | - Eduardo Díaz-Rubio
- Department of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clínico San Carlos (IdISSC), University Complutense, CIBERONC, Madrid, Spain
| | - Enrique Aranda
- Department of Medical Oncology, IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain
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Shida D, Boku N, Nakamura Y, Yoshida T, Tanabe T, Yasui K, Takashima A, Kanemitsu Y. Comparison of model fit and discriminatory ability of M category as defined by the 7th and 8th editions of the tumor-node-metastasis classification of colorectal cancer and the 9th edition of the Japanese classification. Cancer Med 2021; 10:6937-6946. [PMID: 34587374 PMCID: PMC8525077 DOI: 10.1002/cam4.3972] [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: 11/01/2020] [Revised: 03/18/2021] [Accepted: 04/21/2021] [Indexed: 11/28/2022] Open
Abstract
Background In transitioning from the 7th edition of the tumor‐node‐metastasis classification (TNM‐7) to the 8th edition (TNM‐8), colorectal cancer with peritoneal metastasis was newly categorized as M1c. In the 9th edition of the Japanese Classification of colorectal, appendiceal, and anal carcinoma (JPC‐9), M1c is further subdivided into M1c1 (without other organ involvement) and M1c2 (with other organ involvement). This study aimed to compare the model fit and discriminatory ability of the M category of these three classification systems, as no study to date has made this comparison. Methods The study population consisted of stage IV colorectal cancer patients who were referred to the National Cancer Center Hospital from 2000 to 2017. The Akaike information criterion (AIC), Harrell's concordance index (C‐index), and time‐dependent receiver operating characteristic (ROC) curves were used to compare the three classification systems. Subgroup analyses, stratified by initial treatment year, were also performed. Results According to TNM‐8, 670 (55%) patients had M1a, 273 (22%) had M1b, and 279 (23%) had M1c (87 M1c1 and 192 M1c2 using JPC‐9) tumors. Among the three classification systems, JPC‐9 had the lowest AIC value (JPC‐9: 10546.3; TNM‐7: 10555.9; TNM‐8: 10585.5), highest C‐index (JPC‐9: 0.608; TNM‐7: 0.598; TNM‐8: 0.599), and superior time‐dependent ROC curves throughout the observation period. Subgroup analyses were consistent with these results. Conclusions While the revised M category definition did not improve model fit and discriminatory ability from TNM‐7 to TNM‐8, further subdivision of M1c in JPC‐9 improved these parameters. These results support further revisions to M1 subcategories in future editions of the TNM classification system.
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Affiliation(s)
- Dai Shida
- Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan.,Division of Frontier Surgery, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Narikazu Boku
- Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yuya Nakamura
- Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takefumi Yoshida
- Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Taro Tanabe
- Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan.,Division of Frontier Surgery, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Kohei Yasui
- Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Atsuo Takashima
- Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yukihide Kanemitsu
- Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan
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30
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Gao X, Kahl AR, Goffredo P, Lin AY, Vikas P, Hassan I, Charlton ME. Treatment of Stage IV Colon Cancer in the United States: A Patterns-of-Care Analysis. J Natl Compr Canc Netw 2021; 18:689-699. [PMID: 32502984 DOI: 10.6004/jnccn.2020.7533] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 01/10/2020] [Indexed: 11/17/2022]
Abstract
BACKGROUND National guidelines recommend chemotherapy as the mainstay of treatment for stage IV colon cancer, with primary tumor resection (PTR) reserved for patients with symptomatic primary or curable disease. The aims of this study were to characterize the treatment modalities received by patients with stage IV colon cancer and to determine the patient-, tumor-, and hospital-level factors associated with those treatments. METHODS Patients diagnosed with stage IV colon cancer in 2014 were extracted from the SEER Patterns of Care initiative. Treatments were categorized into chemotherapy only, PTR only, PTR + chemotherapy, and none/unknown. RESULTS The total weighted number of cases was 3,336; 17% of patients received PTR only, 23% received chemotherapy only, 41% received PTR + chemotherapy, and 17% received no treatment. In multivariable analyses, compared with chemotherapy only, PTR + chemotherapy was associated with being married (odds ratio [OR], 1.9), having bowel obstruction (OR, 2.55), and having perforation (OR, 2.29), whereas older age (OR, 5.95), Medicaid coverage (OR, 2.46), higher T stage (OR, 3.51), and higher N stage (OR, 6.77) were associated with PTR only. Patients who received no treatment did not have more comorbidities or more severe disease burden but were more likely to be older (OR, 3.91) and non-Hispanic African American (OR, 2.92; all P<.05). Treatment at smaller, nonacademic hospitals was associated with PTR (± chemotherapy). CONCLUSIONS PTR was included in the treatment regimen for most patients with stage IV colon cancer and was associated with smaller, nonacademic hospitals. Efforts to improve guideline implementation may be beneficial in these hospitals and also in non-Hispanic African American and older populations.
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Affiliation(s)
- Xiang Gao
- 1Department of Surgery, Carver College of Medicine, and
| | - Amanda R Kahl
- 2Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
| | | | - Albert Y Lin
- 3Division of Oncology, Department of Medicine, VA Palo Alto Health Care System, Palo Alto, California.,4Department of Medicine, Stanford University, Stanford, California; and
| | - Praveen Vikas
- 5Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa
| | - Imran Hassan
- 1Department of Surgery, Carver College of Medicine, and
| | - Mary E Charlton
- 2Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
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van der Kruijssen DEW, Brouwer NPM, van der Kuil AJS, Verhoeven RHA, Elias SG, Vink GR, Punt CJA, de Wilt JHW, Koopman M. Interaction Between Primary Tumor Resection, Primary Tumor Location, and Survival in Synchronous Metastatic Colorectal Cancer: A Population-Based Study. Am J Clin Oncol 2021; 44:315-324. [PMID: 33899807 DOI: 10.1097/coc.0000000000000823] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVES Location of the primary tumor has prognostic value and predicts the effect of certain therapeutics in synchronous metastatic colorectal cancer. We investigated whether the association between primary tumor resection (PTR) and overall survival (OS) also depends on tumor location. METHODS Data on synchronous metastatic colorectal cancer patients from the Netherlands Cancer Registry (n=16,106) and Surveillance, Epidemiology, and End Results (SEER) registry (n=19,584) were extracted. Cox models using time-varying covariates were implemented. Median OS for right-sided colon cancer (RCC), left-sided colon cancer, and rectal cancer was calculated using inverse probability weighting and a landmark point of 6 months after diagnosis as reference. RESULTS The association between PTR and OS was dependent on tumor location (P<0.05), with a higher median OS of upfront PTR versus upfront systemic therapy in Netherlands Cancer Registry (NCR) of 1.9 (95% confidence interval: 0.9-2.8), 4.3 (3.3-5.6), and 3.4 (0.6-7.6) months in RCC, left-sided colon cancer and rectal cancer, respectively. In SEER data, the difference was 6.0 (4.0-8.0), 8.0 (5.0-10.0), and 10.0 (7.0-13.0) months, respectively. Hazard plots indicate a higher hazard of death 2 to 3 months after PTR in RCC. CONCLUSION Upfront PTR is associated with improved survival regardless of primary tumor location. Patients with RCC appear to have less benefit because of higher mortality during 2 to 3 months after PTR.
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Affiliation(s)
| | - Nelleke P M Brouwer
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - Rob H A Verhoeven
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL)
| | - Sjoerd G Elias
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - Geraldine R Vink
- Department of Medical Oncology, University Medical Center Utrecht
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL)
| | - Cornelis J A Punt
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Center Utrecht
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Hermanowicz JM, Szymanowska A, Sieklucka B, Czarnomysy R, Pawlak K, Bielawska A, Bielawski K, Kalafut J, Przybyszewska A, Surazynski A, Rivero-Muller A, Mojzych M, Pawlak D. Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer. J Enzyme Inhib Med Chem 2021; 36:535-548. [PMID: 33522320 PMCID: PMC7850456 DOI: 10.1080/14756366.2021.1879803] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in men and in women. The impact of the new pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide (MM-129) was evaluated against human colon cancer in vitro and in zebrafish xenografts. Our results show that this new synthesised compound effectively inhibits cell survival in BTK-dependent mechanism. Its effectiveness is much higher at a relatively low concentration as compared with the standard chemotherapy used for CRC, i.e. 5-fluorouracil (5-FU). Flow cytometry analysis after annexin V-FITC and propidium iodide staining revealed that apoptosis was the main response of CRC cells to MM-129 treatment. We also found that MM-129 effectively inhibits tumour development in zebrafish embryo xenograft model, where it showed a markedly synergistic anticancer effect when used in combination with 5-FU. The above results suggest that this novel heterofused 1,2,4-triazine derivative may be a promising candidate for further evaluation as chemotherapeutic agent against CRC.
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Affiliation(s)
- Justyna Magdalena Hermanowicz
- Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland.,Department of Clinical Pharmacy, Medical University of Bialystok, Bialystok, Poland
| | - Anna Szymanowska
- Department of Biotechnology, Medical University of Bialystok, Bialystok, Poland
| | - Beata Sieklucka
- Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland
| | - Robert Czarnomysy
- Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Bialystok, Poland
| | - Krystyna Pawlak
- Department of Monitored Pharmacotherapy, Medical University of Bialystok, Bialystok, Poland
| | - Anna Bielawska
- Department of Biotechnology, Medical University of Bialystok, Bialystok, Poland
| | - Krzysztof Bielawski
- Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Bialystok, Poland
| | - Joanna Kalafut
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland
| | - Alicja Przybyszewska
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland
| | - Arkadiusz Surazynski
- Department of Medicinal Chemistry, Medical University of Bialystok, Bialystok, Poland
| | - Adolfo Rivero-Muller
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland
| | - Mariusz Mojzych
- Department of Chemistry, Siedlce University of Natural Sciences and Humanities, Siedlce, Poland
| | - Dariusz Pawlak
- Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland.,Department of Pharmacology and Toxicology, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland
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Zhai S, Sun X, Du L, Chen K, Zhang S, Shi Y, Yuan F. Role of Surgical Approach to Synchronous Colorectal Liver Metastases: A Retrospective Analysis. Cancer Manag Res 2021; 13:3699-3711. [PMID: 33994810 PMCID: PMC8112857 DOI: 10.2147/cmar.s300890] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 04/07/2021] [Indexed: 12/16/2022] Open
Abstract
PURPOSE This study is a retrospective analysis of exploring the efficiency of surgical management on patients with synchronous colorectal liver metastasis (SCLM). PATIENTS AND METHODS Nine hundred fifty-three consecutive patients with SCLM from Weifang People's Hospital of Shandong Province between January 2006 and December 2015 were reviewed. The values of different factors were analyzed, such as different surgical indications of liver metastases, simultaneous or staged resection of primary colorectal cancer and liver metastases, and primary tumor resection (PTR) of asymptomatic patients with unresectable liver metastases. RESULTS Median survival time (47.3 months) and 5-year survival rate (31%) for patients with resected liver metastases were significantly superior to that of with nonoperative treatment (17.2 months, 4%, P<0.001); enlarging the standard of liver metastases resection can improve the resection rates (31.0% vs 13.6%, P<0.001); for patients with resectable liver metastases, the in-hospital cost for simultaneous resection group was lower than that in the staged resection group (36,698 vs 45,134 RMB, P<0.001); for patients of the asymptomatic primary tumor with unresectable liver metastases, PTR was associated with improved median survival (18.0 vs 15.0 months, P=0.006). CONCLUSION For patients with SCLM, liver resection is considered the best treatment; expanding indications of liver resection can improve the resection rates. Simultaneous resection of the primary tumor and liver metastases were indicated in patients with resectable SCLM; PTR was recommended for asymptomatic patients with unresectable hepatic metastases.
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Affiliation(s)
- Shengyong Zhai
- Department of Oncology Surgery, Weifang People’ s Hospital, Weifang Medical College, Weifang City, Shandong Province, 261041, People’s Republic of China
| | - Xiaojing Sun
- School of Management and Information, Shandong Transport Vocational College, Weifang City, Shandong Province, 261041, People’s Republic of China
| | - Longfeng Du
- Department of Oncology Surgery, Weifang People’ s Hospital, Weifang Medical College, Weifang City, Shandong Province, 261041, People’s Republic of China
| | - Kai Chen
- Department of Oncology Surgery, Weifang People’ s Hospital, Weifang Medical College, Weifang City, Shandong Province, 261041, People’s Republic of China
| | - Shanshan Zhang
- School of Management and Information, Shandong Transport Vocational College, Weifang City, Shandong Province, 261041, People’s Republic of China
| | - Yiran Shi
- Department of Oncology Surgery, Weifang People’ s Hospital, Weifang Medical College, Weifang City, Shandong Province, 261041, People’s Republic of China
| | - Fei Yuan
- Department of Oncology Surgery, Weifang People’ s Hospital, Weifang Medical College, Weifang City, Shandong Province, 261041, People’s Republic of China
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Doah KY, Shin US, Jeon BH, Cho SS, Moon SM. The Impact of Primary Tumor Resection on Survival in Asymptomatic Colorectal Cancer Patients With Unresectable Metastases. Ann Coloproctol 2021; 37:94-100. [PMID: 33979907 PMCID: PMC8134925 DOI: 10.3393/ac.2020.09.15.1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 09/15/2020] [Indexed: 12/16/2022] Open
Abstract
Purpose This study was conducted to evaluate the effectiveness of primary tumor resection (PTR) in asymptomatic colorectal cancer (CRC) patients with unresectable metastases using the inverse probability of treatment weighting (IPTW) method to minimize selection bias. Methods We selected 146 patients diagnosed with stage IV CRC with unresectable metastasis between 2001 and 2018 from our institutional database. In a multivariate logistic regression model using the patients’ baseline covariates associated with PTR, we applied the IPTW method based on a propensity score and performed a weighted Cox proportional regression analysis to estimate survival according to PTR. Results Upfront PTR was performed in 98 patients, and no significant differences in baseline factors were detected. The upweighted median survival of the PTR group was 18 months and that of the non-PTR group was 15 months (P = 0.15). After applying the IPTW, the PTR was still insignificant in the univariate Cox regression (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.5–1.21). However, in the multivariate weighted Cox regression with adjustment for other covariates, the PTR showed a significantly decreased risk of cancer-related death (HR, 0.61; 95% CI, 0.40–0.94). Conclusion In this study, we showed that asymptomatic CRC patients with unresectable metastases could gain a survival benefit from upfront PTR by analysis with the IPTW method. However, randomized controlled trials are mandatory.
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Affiliation(s)
- Ki Yoon Doah
- Department of Surgery, Korea Institute of Radiological & Medical Sciences, Korea Cancer Center Hospital, Seoul, Korea
| | - Ui Sup Shin
- Department of Surgery, Korea Institute of Radiological & Medical Sciences, Korea Cancer Center Hospital, Seoul, Korea
| | - Byong Ho Jeon
- Department of Surgery, Korea Institute of Radiological & Medical Sciences, Korea Cancer Center Hospital, Seoul, Korea
| | - Sang Sik Cho
- Department of Surgery, Korea Institute of Radiological & Medical Sciences, Korea Cancer Center Hospital, Seoul, Korea
| | - Sun Mi Moon
- Department of Surgery, Korea Institute of Radiological & Medical Sciences, Korea Cancer Center Hospital, Seoul, Korea
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Ihn MH. Primary Tumor Resection in Asymptomatic Colorectal Cancer Patients With Unresectable Metastases: Can It Improve Survival? Ann Coloproctol 2021; 37:71-72. [PMID: 33979905 PMCID: PMC8134923 DOI: 10.3393/ac.2021.04.14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/29/2022] Open
Affiliation(s)
- Myong Hoon Ihn
- Department of Surgery, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
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36
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Chen JN, Shoucair S, Wang Z, Habib JR, Zhao FQ, Yu J, Liu Z, Liu Q. Primary Tumor Resection for Rectal Cancer With Unresectable Liver Metastases: A Chance to Cut Is a Chance for Improved Survival. Front Oncol 2021; 11:628715. [PMID: 33791215 PMCID: PMC8006931 DOI: 10.3389/fonc.2021.628715] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 02/22/2021] [Indexed: 01/05/2023] Open
Abstract
Background: About half of the patients with rectal cancer will develop liver metastasis during the course of their illness. Unfortunately, a large proportion of these metastases are unresectable. Surgical resection of the primary tumor vs. palliative treatment in patients with unresectable synchronous liver metastases remains controversial. Methods: Patients with rectal cancer with surgically unresectable liver metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2015. According to different treatment modalities, patients were divided into a primary tumor resection group and a non-resection group. Rates of primary tumor resection and survival were calculated for each year. Kaplan-Meier methods and Cox regression models were used to assess long-term survival. Multivariable logistic regression models were used to evaluate factors potentially associated with primary tumor resection. Results: Among 1,957 patients, 494 (25.2%) had undergone primary tumor resection. Patients with primary tumor resection had significantly better 5-year survival rate (27.2 vs. 5.6%, P < 0.001) compared to the non-resection group. Chemoradiotherapy with primary site resection was associated with the longest mean and 5-year OS (44.7 months, 32.4%). The Cox regression analyses of the subgroup indicated that patients who underwent primary tumor resection had improved survival compared with those who did not undergo resection in all 25 subgroups. Factors associated with primary tumor resection were well or moderately differentiated tumor grade, undergoing radiation, and primary tumor size <5 cm. Conclusions: The majority of patients with rectal cancer with unresectable liver metastases did not undergo primary tumor resection. Our results indicate that resection of the primary tumor appears to offer the greatest chance of survival. Prospective studies are needed to confirm these results.
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Affiliation(s)
- Jia-nan Chen
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Sami Shoucair
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Zheng Wang
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Joseph R. Habib
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Fu-qiang Zhao
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Yu
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Zheng Liu
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qian Liu
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Díez-Alonso M, Mendoza-Moreno F, Jiménez-Álvarez L, Nuñez O, Blazquez-Martín A, Sanchez-Gollarte A, Matías-García B, Molina R, San-Juan A, Gutierrez-Calvo A. Prognostic factors of survival in stage IV colorectal cancer with synchronous liver metastasis: Negative effect of the KRAS mutation. Mol Clin Oncol 2021; 14:93. [PMID: 33767862 PMCID: PMC7976435 DOI: 10.3892/mco.2021.2255] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 02/09/2021] [Indexed: 01/07/2023] Open
Abstract
The aim of the present study was to identify predictive parameters of survival in patients affected by stage IV colorectal cancer with synchronous and bilateral liver metastases. A retrospective cohort study was performed. Patients diagnosed between January 2013 and December 2018 were included in the present study. Data on the histopathological, clinical and treatment factors (chemotherapy as the first measure or resection of the primary tumor) were collected. The effect of each variable on survival was evaluated using Cox regression analysis. A total of 104 patients were included [43 women (41.3%) and 61 men (58.7%); mean age, 63 years]. The long-term survival rate at 36 months was 29% (median, 25 months). Kaplan-Meier analysis was used to estimate that survival was higher in patients with wild-type KRAS tumors (42%) than in patients with mutated KRAS tumors (9%; P=0.001). In the multivariate analysis, KRAS mutation (HR, 2.484; 95% CI, 1.472-4.192), T4 tumors (HR, 1.795; 95% CI, 1.045-3.084), resection/local treatment of hepatic metastases (HR, 0.447; 95% CI, 0.222-0.901), Eastern Cooperative Oncology Group performance status (HR, 1.632; 95% CI, 1.182-2.254), were revealed to have independent predictive value. The type of treatment (chemotherapy or resection of the primary tumor) did not influence the survival. The results indicated that mutation of the KRAS gene was an important prognostic factor and associated with survival.
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Affiliation(s)
- Manuel Díez-Alonso
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid 28805, Spain
| | - Fernando Mendoza-Moreno
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid 28805, Spain
| | - Laura Jiménez-Álvarez
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid 28805, Spain
| | - Oscar Nuñez
- National Center for Epidemiology, Carlos III Health Institute, Madrid 28029, Spain
| | - Alma Blazquez-Martín
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid 28805, Spain
| | - Ana Sanchez-Gollarte
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid 28805, Spain
| | - Belén Matías-García
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid 28805, Spain
| | - Raquel Molina
- Department of Oncology, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid 28805, Spain
| | - Alberto San-Juan
- Department of Oncology, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid 28805, Spain
| | - Alberto Gutierrez-Calvo
- Department of General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, Alcalá de Henares, Madrid 28805, Spain
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Matsuda A, Yamada T, Matsumoto S, Shinji S, Ohta R, Sonoda H, Takahashi G, Iwai T, Takeda K, Sekiguchi K, Yoshida H. Systemic Chemotherapy is a Promising Treatment Option for Patients with Colonic Stents: A Review. J Anus Rectum Colon 2021; 5:1-10. [PMID: 33537495 PMCID: PMC7843144 DOI: 10.23922/jarc.2020-061] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 09/15/2020] [Indexed: 02/08/2023] Open
Abstract
Approximately 10% of patients with colorectal cancer (CRC) develop malignant large bowel obstruction (MLBO) at diagnosis. Furthermore, for 35% of patients with MLBO, curative primary tumor resection is unfeasible because of locally advanced disease and comorbidities. The practice of placing a self-expandable metallic stent (SEMS) has dramatically increased as an effective palliative treatment. Recent advances in systemic chemotherapy for metastatic CRC have significantly contributed to prolonging patients' prognosis and expanding the indications. However, the safety and efficacy of systemic chemotherapy in patients with SEMS have not been established. This review outlines the current status of this relatively new therapeutic strategy and future perspectives. Some reports on this topic have demonstrated that 1) systemic chemotherapy and the addition of molecular targeted agents contribute to prolonged survival in patients with SEMS; 2) delayed SEMS-related complications are a major concern, and this requires strict patient monitoring; however, primary tumor control by chemotherapy might result in decreased complications, especially regarding re-obstruction; and 3) using bevacizumab could be a risk factor for SEMS-related perforation, which may be lethal. Although this relatively new approach for unresectable stage IV obstructive CRC requires a well-planned clinical trial, this therapy could be promising for patients who are unideal candidates for emergency surgery and require immediate systemic chemotherapy.
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Affiliation(s)
- Akihisa Matsuda
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Takeshi Yamada
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Satoshi Matsumoto
- Department of Surgery, Nippon Medical School Chiba Hokusoh Hospital, Kamagari, Inzai, Japan
| | - Seiichi Shinji
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Ryo Ohta
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Hiromichi Sonoda
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Goro Takahashi
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Takuma Iwai
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Kohki Takeda
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Kumiko Sekiguchi
- Department of Surgery, Nippon Medical School Tama Nagayama Hospital, Tokyo, Japan
| | - Hiroshi Yoshida
- Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
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Tan WJ, Patil S, Guillem JG, Paty PB, Weiser MR, Nash GM, Smith JJ, Pappou EP, Wei IH, Garcia-Aguilar J. Primary Tumor-Related Complications and Salvage Outcomes in Patients with Metastatic Rectal Cancer and an Untreated Primary Tumor. Dis Colon Rectum 2021; 64:45-52. [PMID: 33306531 PMCID: PMC7931667 DOI: 10.1097/dcr.0000000000001803] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND For rectal cancer with unresectable metastases, current practice favors omitting interventions directed at the primary tumor in asymptomatic patients. OBJECTIVE This study aimed to determine the proportion of patients with primary tumor-related complications, characterize salvage outcomes, and measure survival in patients with metastatic rectal cancer who did not undergo upfront intervention for their primary tumor. DESIGN This is a retrospective analysis. SETTING This study was conducted at a comprehensive cancer center. PATIENTS Patients who presented between January 1, 2008, and December 31, 2015, with synchronous stage IV rectal cancer, an unresected primary tumor, and no prior primary tumor-directed intervention were selected. MAIN OUTCOME MEASURES The main outcome measured was the rate of primary tumor-related complications in the cohort that did not receive any primary tumor-directed intervention. The Kaplan-Meier method and Cox regression analysis were used to determine whether complications are associated with survival. RESULTS The cohort comprised 358 patients with a median age of 56 years (22-92). Median follow-up was 26 months (range, 1-93 months). Among the 168 patients (46.9%) who eventually underwent elective resection of the primary tumor, the surgery was performed with curative intent in 66 patients (18.4%) and preemptive intent in 102 patients (28.5%). Of the 190 patients who did not undergo an upfront or elective intervention for the primary tumor, 68 (35.8%) experienced complications. Nonsurgical intervention for complications was attempted in 34 patients with an overall success rate of 61.8% (21/34). Surgical intervention was performed in 47 patients (including 13 patients for whom nonsurgical intervention failed): diversion in 26 patients and resection in 21 patients. Of those 47 patients, 42 (89.4%) ended up with a colostomy or ileostomy. LIMITATIONS This study was conducted at a single center. CONCLUSION A significant proportion of patients with metastatic rectal cancer and untreated primary tumor experience primary tumor-related complications. These patients should be followed closely, and preemptive intervention (resection, diversion, or radiation) should be considered if the primary tumor progresses despite systemic therapy. See Video Abstract at http://links.lww.com/DCR/B400. COMPLICACIONES RELACIONADAS CON EL TUMOR PRIMARIO Y RESULTADOS DE RESCATE EN PACIENTES CON CÁNCER DE RECTO METASTÁSICO Y UN TUMOR PRIMARIO NO TRATADO: Para el cáncer de recto con metástasis no resecables, la práctica actual favorece la omisión de las intervenciones dirigidas al tumor primario en pacientes asintomáticos.Determinar la proporción de pacientes con complicaciones relacionadas con el tumor primario, caracterizar los resultados de rescate y medir la supervivencia en pacientes con cáncer rectal metastásico que no se sometieron a una intervención inicial para su tumor primario.Análisis retrospectivo.Centro oncológico integral.Pacientes que se presentaron entre el 1 de enero de 2008 y el 31 de diciembre de 2015 con cáncer de recto en estadio IV sincrónico, un tumor primario no resecado y sin intervención previa dirigida al tumor primario.Tasa de complicaciones relacionadas con el tumor primario en la cohorte que no recibió ninguna intervención dirigida al tumor primario. Se utilizó el método de Kaplan-Meier y el análisis de regresión de Cox para determinar si las complicaciones están asociadas con la supervivencia.La cohorte estuvo compuesta por 358 pacientes con una mediana de edad de 56 años (22-92). La mediana de seguimiento fue de 26 meses (rango, 1 a 93 meses). Entre los 168 pacientes (46,9%) que finalmente se sometieron a resección electiva del tumor primario, la cirugía se realizó con intención curativa en 66 pacientes (18,4%) y con intención preventiva en 102 pacientes (28,5%). De los 190 pacientes que no se sometieron a una intervención inicial o electiva para el tumor primario, 68 (35,8%) experimentaron complicaciones. Se intentó una intervención no quirúrgica para las complicaciones en 34 pacientes con una tasa de éxito global del 61,8% (21 de 34). La intervención quirúrgica se realizó en 47 pacientes (incluidos 13 pacientes en los que falló la intervención no quirúrgica): derivación en 26 pacientes y resección en 21 pacientes. De esos 47 pacientes, 42 (89,4%) terminaron con una colostomía o ileostomía.Único centro.Una proporción significativa de pacientes con cáncer de recto metastásico y primario no tratado experimentan complicaciones relacionadas con el tumor primario. Se debe hacer un seguimiento estrecho de estos pacientes y considerar la posibilidad de una intervención preventiva (resección, derivación o radiación) si el tumor primario progresa a pesar de la terapia sistémica. Consulte Video Resumen en http://links.lww.com/DCR/B400.
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Affiliation(s)
- Winson J. Tan
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
- Department of General Surgery, Sengkang General Hospital, Singapore
| | - Sujata Patil
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jose G. Guillem
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Philip B. Paty
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Martin R. Weiser
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Garrett M. Nash
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - J. Joshua Smith
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Emmanouil P. Pappou
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Iris H. Wei
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Julio Garcia-Aguilar
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, New York
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Jácome AA, Kee B, Fogelman D, Dasari A, Shureiqi I, Raghav K, Morris V, Johnson B, Overman M, Wolff R, Kopetz S, Rogers J, Ahmed SU, Mehdizadeh A, Rothschild N, Eng C. FOLFOXIRI Versus Doublet Regimens in Right-Sided Metastatic Colorectal Cancer: Focus on Subsequent Therapies and Impact on Overall Survival. Clin Colorectal Cancer 2020; 19:248-255.e6. [DOI: 10.1016/j.clcc.2020.05.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 05/14/2020] [Accepted: 05/26/2020] [Indexed: 12/14/2022]
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Baxter NN, Sutradhar R, Dossa F, Fu L, Rochon P, Wei AC, Kennedy ED, Earle CC. Does the presence of an intact primary increase the risk of nonelective colorectal surgery in patients treated with bevacizumab? Colorectal Dis 2020; 22:1974-1983. [PMID: 32767608 DOI: 10.1111/codi.15294] [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: 05/31/2020] [Accepted: 07/25/2020] [Indexed: 02/08/2023]
Abstract
AIM In patients with incurable metastatic colorectal cancer (mCRC), resection of the primary tumour is debated; however, patients with intact primaries may be at a higher risk of complications requiring surgery when receiving treatment with bevacizumab. Our aim was to estimate the risk of nonelective colorectal surgery in patients undergoing bevacizumab therapy for mCRC and evaluate the association between intact primary tumours and risk of nonelective surgery. METHOD We designed a population-based, retrospective cohort study using administrative and cancer registry data in Ontario, Canada. We included patients with mCRC who received bevacizumab from 1 January 2008 to 31 December 2014. The primary outcome was nonelective colorectal surgery after initiation of bevacizumab. We determined the cumulative incidence of nonelective colorectal surgery among patients with previously resected and unresected primaries, accounting for the competing risk of death. We explored the relationship between previous resection of the primary and need for nonelective surgery using a cause-specific hazards model, controlling for patient, tumour and treatment factors. RESULTS We identified 1840 (32.7%) patients with intact primaries and 3784 (67.3%) patients with prior resection. The cumulative incidence of nonelective surgery 1 year after initiating bevacizumab for all patients was 3.9% (95% CI 3.4-4.5%). One-year cumulative incidence was higher in those with intact primaries than in those with resected primaries (6.1% vs 2.9%, P < 0.0001). After adjustment, an intact primary remained strongly associated with nonelective colorectal surgery (hazard ratio = 2.89, 95% CI 2.32-3.61; P < 0.0001). CONCLUSION Bevacizumab is associated with a low but meaningful risk for serious gastrointestinal complications, necessitating vigilance, particularly among patients with an intact primary tumour.
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Affiliation(s)
- N N Baxter
- Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.,Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.,Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - R Sutradhar
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.,Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - F Dossa
- Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.,Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - L Fu
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
| | - P Rochon
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,Ontario Institute for Cancer Research, Toronto, Ontario, Canada
| | - A C Wei
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,Memorial Sloan Kettering Cancer Center, New York City, New York, USA
| | - E D Kennedy
- Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,Sinai Health System, Toronto, Ontario, Canada
| | - C C Earle
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.,Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
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Rumpold H, Niedersüß-Beke D, Heiler C, Falch D, Wundsam HV, Metz-Gercek S, Piringer G, Thaler J. Prediction of mortality in metastatic colorectal cancer in a real-life population: a multicenter explorative analysis. BMC Cancer 2020; 20:1149. [PMID: 33238958 PMCID: PMC7691098 DOI: 10.1186/s12885-020-07656-w] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 11/17/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Metastatic colorectal cancer (mCRC) remains a lethal disease. Survival, however, is increasing due to a growing number of treatment options. Yet due to the number of prognostic factors and their interactions, prediction of mortality is difficult. The aim of this study is to provide a clinical model supporting prognostication of mCRC mortality in daily practice. METHODS Data from 1104 patients with mCRC in three prospective cancer datasets were used to construct and validate Cox models. Input factors for stepwise backward method variable selection were sex, RAS/BRAF-status, microsatellite status, treatment type (no treatment, systemic treatment with or without resection of metastasis), tumor load, location of primary tumor, metastatic patterns and synchronous or metachronous disease. The final prognostic model for prediction of survival at two and 3 years was validated via bootstrapping to obtain calibration and discrimination C-indices and dynamic time dependent AUC. RESULTS Age, sidedness, number of organs with metastases, lung as only site of metastasis, BRAF mutation status and treatment type were selected for the model. Treatment type had the most prominent influence on survival (resection of metastasis HR 0.26, CI 0.21-0.32; any treatment vs no treatment HR 0.31, CI 0.21-0.32), followed by BRAF mutational status (HR 2.58, CI 1.19-1.59). Validation showed high accuracy with C-indices of 72.2 and 71.4%, and dynamic time dependent AUC's of 76.7 ± 1.53% (both at 2 or 3 years), respectively. CONCLUSION The mCRC mortality prediction model is well calibrated and internally valid. It has the potential to support both, clinical prognostication for treatment decisions and patient communication.
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Affiliation(s)
- Holger Rumpold
- Gastrointestinal Cancer Center, Ordensklinikum Linz, Seilerstaette 4, 4010, Linz, Austria.
| | | | - Cordula Heiler
- Department of Internal Medicine I, Wilhelminenspital, Vienna, Austria
| | - David Falch
- Department of Internal Medicine I, Wilhelminenspital, Vienna, Austria
| | | | | | - Gudrun Piringer
- Department of Internal Medicine IV, Hospital Wels-Grieskirchen, Wels, Austria
| | - Josef Thaler
- Department of Internal Medicine IV, Hospital Wels-Grieskirchen, Wels, Austria
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DeYoreo M, Lansdorp-Vogelaar I, Knudsen AB, Kuntz KM, Zauber AG, Rutter CM. Validation of Colorectal Cancer Models on Long-term Outcomes from a Randomized Controlled Trial. Med Decis Making 2020; 40:1034-1040. [PMID: 33078673 PMCID: PMC7665984 DOI: 10.1177/0272989x20961095] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Microsimulation models are often used to predict long-term outcomes and guide policy decisions regarding cancer screening. The United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial examines a one-time intervention of flexible sigmoidoscopy that was implemented before a colorectal cancer (CRC) screening program was established. Long-term study outcomes, now a full 17 y following randomization, have been published. We use the outcomes from this trial to validate 3 microsimulation models for CRC to long-term study outcomes. We find that 2 of 3 models accurately predict the relative effect of screening (the hazard ratios) on CRC-specific incidence 17 y after screening. We find that all 3 models yield predictions of the relative effect of screening on CRC incidence and mortality (i.e., the hazard ratios) that are reasonably close to the UKFSS results. Two of the 3 models accurately predict the relative reduction in CRC incidence 17 y after screening. One model accurately predicted the absolute incidence and mortality rates in the screened group. The models differ in their estimates related to adenoma detection at screening. Although high-quality screening results help to inform models, trials are expensive, last many years, and can be complicated by ethical issues and technological changes across the duration of the trial. Thus, well-calibrated and validated models are necessary to predict outcomes for which data are not available. The results from this validation demonstrate the utility of models in predicting long-term outcomes and in collaborative modeling to account for uncertainty.
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Affiliation(s)
| | | | - Amy B Knudsen
- Institute for Technology Assessment and Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
| | - Karen M Kuntz
- Department of Health Policy and Management, University of Minnesota, School of Public Health, Minneapolis, MN, USA
| | - Ann G Zauber
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY, USA
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Park EJ, Baek JH, Choi GS, Park WC, Yu CS, Kang SB, Min BS, Kim JH, Kim HR, Lee BH, Oh JH, Jeong SY, Jung M, Ahn JB, Baik SH. The Role of Primary Tumor Resection in Colorectal Cancer Patients with Asymptomatic, Synchronous, Unresectable Metastasis: A Multicenter Randomized Controlled Trial. Cancers (Basel) 2020; 12:cancers12082306. [PMID: 32824392 PMCID: PMC7464811 DOI: 10.3390/cancers12082306] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/07/2020] [Accepted: 08/13/2020] [Indexed: 12/13/2022] Open
Abstract
We aimed to assess the survival benefits of primary tumor resection (PTR) followed by chemotherapy in patients with asymptomatic stage IV colorectal cancer with asymptomatic, synchronous, unresectable metastases compared to those of upfront chemotherapy alone. This was an open-label, prospective, randomized controlled trial (ClnicalTrials.gov Identifier: NCT01978249). From May 2013 to April 2016, 48 patients (PTR, n = 26; upfront chemotherapy, n = 22) diagnosed with asymptomatic colorectal cancer with unresectable metastases in 12 tertiary hospitals were randomized (1:1). The primary endpoint was two-year overall survival. The secondary endpoints were primary tumor-related complications, PTR-related complications, and rate of conversion to resectable status. The two-year cancer-specific survival was significantly higher in the PTR group than in the upfront chemotherapy group (72.3% vs. 47.1%; p = 0.049). However, the two-year overall survival rate was not significantly different between the PTR and upfront chemotherapy groups (69.5% vs. 44.8%, p = 0.058). The primary tumor-related complication rate was 22.7%. The PTR-related complication rate was 19.2%, with a major complication rate of 3.8%. The rates of conversion to resectable status were 15.3% and 18.2% in the PTR and upfront chemotherapy groups. While PTR followed by chemotherapy resulted in better two-year cancer-specific survival than upfront chemotherapy, the improvement in the two-year overall survival was not significant.
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Affiliation(s)
- Eun Jung Park
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea;
| | - Jeong-Heum Baek
- Department of Surgery, Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Korea;
| | - Gyu-Seog Choi
- Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu 41404, Korea;
| | - Won Cheol Park
- Department of Surgery, Wonkwang University School of Medicine, Iksan 54538, Korea;
| | - Chang Sik Yu
- Department of Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea;
| | - Sung-Bum Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea;
| | - Byung Soh Min
- Division of Colon and Rectal Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea;
| | - Jae Hwang Kim
- Department of Surgery, Yeungnam University College of Medicine, Daegu 42415, Korea;
| | - Hyeong Rok Kim
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun 58128, Korea;
| | - Bong Hwa Lee
- Department of Surgery, Hallym University Sacred Heart Hospital, Anyang 14068, Korea;
| | - Jae Hwan Oh
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang 10408, Korea;
| | - Seung-Yong Jeong
- Department of Surgery, Seoul National University College of Medicine, Colorectal Cancer Center, Seoul National University Cancer Hospital, Seoul 03080, Korea;
| | - Minkyu Jung
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul 03722, Korea; (M.J.); (J.B.A.)
| | - Joong Bae Ahn
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul 03722, Korea; (M.J.); (J.B.A.)
| | - Seung Hyuk Baik
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea;
- Correspondence: ; Tel.: +82-2-2019-3378; Fax: +82-2-3462-5994
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Namba Y, Hirata Y, Mukai S, Nishida T, Ishikawa S, Kai A, Kohata A, Okimoto S, Fujisaki S, Fukuda S, Takahashi M, Fukuda T. Multiple peritoneal dissemination of T2 colorectal cancer without lymph node metastases: a case report. J Surg Case Rep 2020; 2020:rjaa118. [PMID: 32760481 PMCID: PMC7394141 DOI: 10.1093/jscr/rjaa118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 03/29/2020] [Accepted: 06/15/2020] [Indexed: 11/24/2022] Open
Abstract
Most cases of peritoneal dissemination of colorectal cancers are from T3 or T4 tumors. A 61-year-old woman was admitted for examination of a positive fecal occult blood test. Colonoscopy showed an ascending colon tumor that was diagnosed as an adenocarcinoma with massive submucosal invasion. Imaging modality revealed numerous nodules throughout the abdominal cavity. Peritoneal dissemination of the ascending colon or ovarian cancer and pseudomyxoma peritonei were considered in the preoperative differential diagnoses, and laparoscopic ileocecal resection was performed. Intraperitoneal observation revealed numerous white nodules in the peritoneum, omentum and Douglas fossa. Both the nodules and tumor were diagnosed as mucinous carcinoma based on a pathology report. The tumor invasion depth was limited to muscularis propria, and no regional lymph node metastasis was detected. Peritoneal dissemination of the ascending colon cancer was considered. We report a rare case of multiple peritoneal dissemination of T2 colorectal cancer without lymph node metastases.
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Affiliation(s)
- Yosuke Namba
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan
| | - Yuzo Hirata
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan.,Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shoichiro Mukai
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan.,Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Toshihiro Nishida
- Department of Pathology Clinical Laboratory, Chugoku Rosai Hospital, Kure, Japan
| | - Syo Ishikawa
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan
| | - Azusa Kai
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan
| | - Akihiro Kohata
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan
| | - Syo Okimoto
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan.,Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Seiji Fujisaki
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan.,Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Saburo Fukuda
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan.,Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Mamoru Takahashi
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan.,Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Toshikatsu Fukuda
- Department of Surgery, Chugoku Rosai Hospital, Kure, Japan.,Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Abstract
BACKGROUND Patients seeking second opinions are a challenge for the colorectal cancer provider because of complexity, failed therapeutic relationship with another provider, need for reassurance, and desire for exploration of treatment options. OBJECTIVE The purpose of this study was to describe the patient and treatment characteristics of patients seeking initial and second opinions in colorectal cancer care at a multidisciplinary colorectal cancer clinic. DESIGN This was a retrospective cohort study. SETTINGS A prospectively collected clinical registry of a multidisciplinary colorectal cancer clinic was included. PATIENTS The study included patients with colon or rectal cancer seen from 2012 to 2017. MAIN OUTCOME MEASURES Data were analyzed for initial versus second opinion and demographic and clinical characteristics. RESULTS Of 1711 patients with colorectal cancer, 1008 (58.9%) sought an initial opinion and 700 (40.9%) sought a second opinion. As compared with initial-opinion patients, second-opinion patients were more likely to have stage IV disease (OR = 1.94 (95% CI, 1.47-2.58)), recurrent disease (OR = 1.67 (95% CI, 1.13-2.46)), and be ages 40 to 49 years (OR = 1.47 (95% CI, 1.02-2.12)). Initial- and second-opinion cohorts were similar in terms of sex, race, and proportion of colon versus rectal cancer. Among second-opinion patients, 246 (35%) transitioned their care to the multidisciplinary colorectal cancer clinic. LIMITATIONS We were unable to capture the final treatment plan for those patients who did not transfer care to the multidisciplinary colorectal cancer clinic. CONCLUSIONS Patients seeking a second opinion represent a unique subset of patients with colorectal cancer. In general, they are younger and more likely to have stage IV or recurrent disease than patients seeking an initial opinion. Although transfer of care to a multidisciplinary colorectal cancer clinic after second opinion is lower than for initial consultations, multidisciplinary colorectal cancer clinics provide an important role for patients with complex disease characteristics and treatment needs. See Video Abstract at http://links.lww.com/DCR/B192. CARACTERíSTICAS DE LOS PACIENTES QUE BUSCAN UNA SEGUNDA OPINIóN EN CLíNICAS MULTIDISCIPLINARIAS ESPECIALIZADAS EN CáNCER COLORECTAL: Los pacientes que buscan una segunda opinión son un desafío para el médico que trata el cáncer colorrectal debido a la complejidad de la situación, a la relación terapéutica fallida con otro especialista, a la necesidad de tranquilidad y el deseo de explorar otras opciones del tratamiento.El describir las características y el tratamiento de los pacientes que buscan opiniones iniciales y secundarias en la atención del cáncer colorrectal en una clínica especializada de manera multidisciplinaria en cáncer colorrectal.Este es un estudio de cohortes retrospectivo.Registro clínico de casos obtenidos prospectivamente en una clínica especializada de manera multidisciplinaria en cáncer colorrectal.Todos aquellos pacientes con cáncer de colon o recto examinados entre 2012-2017.Se analizaron los datos obtenidos en la opinión inicial y se compararon con la segunda opinión, se revisaron tanto sus características demográficas como clínicas.De 1711 pacientes con cáncer colorrectal, 1008 (58.9%) buscaron una opinión inicial, 700 (40.9%) buscaron una segunda opinión. En comparación con los pacientes de opinión inicial, los pacientes de segunda opinión presentaron más probabilidades de tener enfermedad en estadio IV (OR 1.94, IC 95% 1.47-2.58), enfermedad recurrente (OR 1.67, IC 95% 1.13-2.46) y tener edades entre 40 y 49 (O 1.47, IC 95% 1.02-2.12). Las cohortes iniciales y de segunda opinión fueron similares en términos de género, raza y proporción del cáncer de colon versus cáncer de recto. Entre los pacientes de segunda opinión, 246 (35%) transfirieron su tratamiento hacia una clínica multidisplinaria especializada en cáncer colorrectal.No se obtuvieron los planes del tratamiento final de aquellos pacientes que no transfirieron sus cuidados hacia una la clínica especializada en cáncer colorrectal.Los pacientes que buscan una segunda opinión representan un subconjunto único de personas con cáncer colorrectal. En general, son más jóvenes y tienen más probabilidades de tener enfermedad en estadio IV o recurrente, con relación a aquellos pacientes que buscan una opinión inicial. Aunque la transferencia de los cuidados hacia una clínica multidisciplinaria especializada en cáncer colorrectal después de una segunda opinión es menor que para las consultas iniciales. Las clínicas multidisciplinarias especializadas en cáncer colorrectal juegan un papel importante con los pacientes que tienen características complejas de enfermedad y necesidades particulares en el tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/B192. (Traducción-Dr Xavier Delgadillo).
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Breugom A, Bastiaannet E, Guren M, Kørner H, Boelens P, Dekker F, Kapiteijn E, Gelderblom H, Larsen I, Liefers G, van de Velde C. Treatment strategies and overall survival for incurable metastatic colorectal cancer – A EURECCA international comparison including 21,196 patients from the Netherlands and Norway. Eur J Surg Oncol 2020; 46:1167-1173. [DOI: 10.1016/j.ejso.2020.02.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 01/15/2020] [Accepted: 02/10/2020] [Indexed: 12/26/2022] Open
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Zhang J, Guo Y, Pan G, Wang P, Li Y, Zhu X, Zhang C. Injectable Drug-Conjugated DNA Hydrogel for Local Chemotherapy to Prevent Tumor Recurrence. ACS APPLIED MATERIALS & INTERFACES 2020; 12:21441-21449. [PMID: 32314901 DOI: 10.1021/acsami.0c03360] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Considering the high rate of postsurgical tumor recurrence due to the possible residual cancer cells and the non-negligible toxicity of postsurgical systemic chemotherapy, we designed an injectable DNA hydrogel assembled by chemodrug-grafted DNA strands for localized chemotherapy. First, a multitude of camptothecin was successfully grafted on backbones of the phosphorothioate DNAs, which could be assembled into two types of Y-shaped building blocks and then hierarchically associated together to form drug-containing hydrogels. The injectable feature of drug-containing DNA hydrogels enables a minimally invasive approach for local drug administration. Owing to the enzymatic degradation, the hydrogel can gradually disassemble into nanosized particles, allowing its good permeation into the residual tumor tissue and efficient uptake by cells. Together with its sustained and responsive drug release behaviors, the drug-containing DNA hydrogel can significantly inhibit the regrowth of tumor cells and prevent cancer recurrence. Compared to the control groups, mice treated with our drug-containing DNA hydrogel show the lowest tumor relapse rate (1/3) and substantial slow tumor progression. Despite the long-term local embedding, negligible systemic toxicity and organ damages are observed after the treatment with our drug-grafted DNA hydrogel. With excellent antitumor efficacy and low side effects in vivo, our DNA-drug conjugate (DDC)-based hydrogel represents a promising candidate for local adjuvant therapy in cancer treatment.
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Affiliation(s)
- Jiao Zhang
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Yuanyuan Guo
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Gaifang Pan
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Ping Wang
- Weigao Research Center, 304, Building 2, Lane 720, Cailun Road, Shanghai 201203, China
| | - Yuehua Li
- Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yi Shan Road, Shanghai 200233, China
| | - Xinyuan Zhu
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Chuan Zhang
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China
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Tominaga T, Nonaka T, Shiraisi T, Hamada K, Noda K, Takeshita H, Maruyama K, Fukuoka H, Wada H, Hashimoto S, Sawai T, Nagayasu T. Factors related to short-term outcomes and delayed systemic treatment following primary tumor resection for asymptomatic stage IV colorectal cancer. Int J Colorectal Dis 2020; 35:837-846. [PMID: 32103325 DOI: 10.1007/s00384-020-03550-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/18/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND The effectiveness of primary tumor resection (PTR) for asymptomatic stage IV colorectal cancer patients to continue prolonged and safe systemic chemotherapy has recently been re-evaluated. However, postoperative complications lead to a prolonged hospital stay and delay systemic treatment, which could result in a poor oncologic outcome. The objective of this study was to identify the risk factors for morbidity and delay of systemic chemotherapy in such patients. METHODS Between April 2016 and March 2018, 115 consecutive colorectal cancer patients with distant metastasis who had no clinical symptoms and underwent PTR in all participating hospitals were retrospectively reviewed. The patients were divided into two groups according to the presence (CD ≥ 2, n = 23) or absence (CD < 2, n = 92) of postoperative complications. RESULTS The proportion of combined resection of adjacent organs was significantly higher in the postoperative complication group (p = 0.014). Complications were significantly correlated with longer hospital stay (p < 0.001) and delay of first postoperative treatment (p = 0.005). Univariate and multivariate analyses showed that combined resection (odds ratio 4.593, p = 0.010) was the independent predictor for postoperative complications. Median survival time was 8.5 months. Postoperative complications were not associated with overall survival, but four patients (3.5%) could not receive systemic chemotherapy because of prolonged postoperative complications. CONCLUSIONS Although PTR for asymptomatic stage IV CRC patients showed an acceptable prognosis, appropriate patient selection is needed to obtain its true benefit.
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Affiliation(s)
- Tetsuro Tominaga
- Departments of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. .,Department of Surgical Oncology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
| | - Takashi Nonaka
- Departments of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Toshio Shiraisi
- Department of Surgery, Sasebo City General Hospital, Sasebo, Japan
| | - Kiyoaki Hamada
- Department of Surgery, Sasebo City General Hospital, Sasebo, Japan
| | - Keisuke Noda
- Department of Surgery, Sasebo City General Hospital, Sasebo, Japan
| | - Hiroaki Takeshita
- Department of Surgery, National Hospital Organization Nagasaki Medical Center, Ōmura, Japan
| | | | | | - Hideo Wada
- Department of Surgery, Ureshino Medical Center, Saga, Japan
| | | | - Terumitsu Sawai
- Departments of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Takeshi Nagayasu
- Departments of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
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Xu J, Ma T, Ye Y, Pan Z, Lu D, Pan F, Peng W, Sun G. Surgery on primary tumor shows survival benefit in selected stage IV colon cancer patients: A real-world study based on SEER database. J Cancer 2020; 11:3567-3579. [PMID: 32284753 PMCID: PMC7150453 DOI: 10.7150/jca.43518] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 03/02/2020] [Indexed: 12/16/2022] Open
Abstract
Objectives: Most patients with stage IV colon cancer did not have the opportunity for curative surgery, only selected patients could benefit from surgery. This study aimed to determine whether surgery on the primary tumor (SPT) should be performed in patients with stage IV colon cancer and how to select patients for SPT. Methods: This study included 48,933 patients with stage IV colon cancer who were identified in the Surveillance, Epidemiology and End Results (SEER) database between 1998 and 2015. Propensity score matching (PSM) analysis was adopted to balance baseline differences between SPT and non-surgery groups. Kaplan-Meier (K-M) curves were utilized to compare the overall survival (OS). Prognostic nomograms were generated to predict survival based on pre- and post-operative risk factors. Patients were divided into low, middle, and high mortality risk subsets for OS by X-tile analyses based on scores derived from above nomograms. Results: Patients with SPT had a significantly longer OS than those without surgery, regardless of the metastatic sites and diagnostic years. Nomograms, according to the pre- and post-operative risk factors, showed moderate discrimination (all C-indexes above 0.7). Based on X-tile analyses, low mortality risk subset (post-operative score ≤ 22.3, preoperative score ≤ 9.7) recommended for SPT, and high mortality risk was not. Conclusions: SPT led to prolonged survival in stage IV colon cancer. Our nomograms would help to select suitable patients for SPT.
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Affiliation(s)
- Jing Xu
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Tai Ma
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Yuanzi Ye
- Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Zhipeng Pan
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Donghui Lu
- Department of Radiology, The 901st Hospital of the Joint Logistics Support Force of PLA, Hefei, Anhui Province 230031, China
| | - Faming Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Wanren Peng
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Guoping Sun
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
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