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Raunkilde L, Andersen RF, Thomsen CB, Hansen TF, Jensen LH. A prospective study of methylated ctDNA in patients undergoing treatment for liver metastases from colorectal cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109586. [PMID: 39847896 DOI: 10.1016/j.ejso.2025.109586] [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: 06/21/2024] [Revised: 12/12/2024] [Accepted: 01/06/2025] [Indexed: 01/25/2025]
Abstract
BACKGROUND Decision regarding local treatment of colorectal liver metastases (CRLM) is a multidisciplinary assessment, and liver intervention should be performed when the metastases are deemed resectable. There is no standard biomarker to aid neither this decision nor the postoperative treatment decisions. The present prospective, observational study aimed to investigate the potential clinical utility of a combined tumor-specific and organ-specific methylated circulating DNA assay in the perioperative setting of CRLM. MATERIAL AND METHODS The study included 56 cases with CRLM. Blood samples were drawn preoperatively and postoperatively. Multiplex methylation analysis of the markers NPY, KANK1, and GAL3ST3 (meth-ctDNA) was performed using droplet digital PCR. RESULTS The assay detected preoperative and postoperative meth-ctDNA in 37 % and 46 % of patients, respectively. Patients with negative preoperative meth-ctDNA had a longer median PFS compared to those with positive preoperative meth-ctDNA (HR = 2.2, 95 % CI 1.2-3.9, p < 0.01). In a multivariate analysis, preoperative negative meth-ctDNA was identified as a strong independent predictor of PFS (HR = 3.3, 95 % CI 1.5-7.2, p < 0.01). Similarly, patients with negative postoperative meth-ctDNA had longer median PFS (HR = 3.0, 95 % CI = 1.6-5.6, p < 0.001) and OS (HR = 4.1, 95 % CI 1.9-9.1, p < 0.001) compared to those with positive postoperative meth-ctDNA. CONCLUSION Preoperative meth-ctDNA may serve as an important biomarker to inform the multidisciplinary assessment and treatment planning of CRLM. Negative meth-ctDNA may indicate the optimal timing for liver intervention, whereas positive meth-ctDNA may indicate initiation or re-orientation of chemotherapy, or immediate local intervention. Our results confirm postoperative negative meth-ctDNA as a strong prognostic marker of survival.
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Affiliation(s)
- Louise Raunkilde
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark; Danish Colorectal Cancer Center South, Vejle Hospital, Beriderbakken 4, 7100, Vejle, Denmark; Department of Regional Health Research, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.
| | - Rikke Fredslund Andersen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark; Danish Colorectal Cancer Center South, Vejle Hospital, Beriderbakken 4, 7100, Vejle, Denmark; Department of Clinical Biochemistry and Immunology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark
| | - Caroline Brenner Thomsen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark; Danish Colorectal Cancer Center South, Vejle Hospital, Beriderbakken 4, 7100, Vejle, Denmark
| | - Torben Frøstrup Hansen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark; Danish Colorectal Cancer Center South, Vejle Hospital, Beriderbakken 4, 7100, Vejle, Denmark; Department of Regional Health Research, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark
| | - Lars Henrik Jensen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark; Danish Colorectal Cancer Center South, Vejle Hospital, Beriderbakken 4, 7100, Vejle, Denmark; Department of Regional Health Research, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark
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Xue JS, Maimaitiming N, Zhang BL, Xu BW, Yin X, Huang Z, Che X, Zhao H, Cai JQ. Prognostic analysis of patients with CRLM based on CRS score: a single-center retrospective study. BMC Cancer 2025; 25:718. [PMID: 40247181 PMCID: PMC12004860 DOI: 10.1186/s12885-025-14135-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 04/10/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND To improve prognosis of patients with synchronous colorectal liver metastasis (CRLM), we constructed a nomogram model to improve outcome through risk stratification and decision support. METHODS The 389 CRLM patients (273 training set and 116 validation set at a ratio of 7: 3) receiving systematic chemotherapy and synchronously resection with/without radiofrequency ablation (RFA) were retrospectively investigated. Overall survival (OS) and recurrence free survival (RFS) were mainly endpoint. A normo-gram model was conduct. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), C-index and calibration curve were performed to assess stablity and efficacy of model. The prognosis was evaluated based on Kaplan-Meier (KM) curve. RESULTS A total of 389 CRLM patients were included. The median OS and RFS times were 70.20 months (95% CIs: 57.73, 82.68) and 11.70 months (95% CIs: 9.75, 13.65), respectively. These patients were divided into training set and validation set at a ratio of 7: 3. In training set, 1, 3, and 5-year survival rate of OS was 97.38%, 71.18%, and 54.56% as well as RFS was 52.57%, 22.65%, and 21.12%, respectively. Cox model showed that hospital day, R0 resection, RFA, only neoadjuvant chemotherapy and CRS score were independent prognostic factors for CRLM patients. The patients were divided into high-risk group and low-risk group based on cut-off value of score calculated by model. The KM curves were statistically different between two groups (P < 0.01). The ROC curve, DCA and calibration curve showed a good prediction efficacy. the C-index of OS and RFS were 0.72 and 0.68, respectively, which were also verified in the validation set (OS, 0.71; RFS, 0.65). CONCLUSIONS A good prediction model was developed and validated to assess the prognoses of CRLM patients. Systematic chemotherapy and R0 resection could benefit patients' survival and improve prognosis.
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Affiliation(s)
- Jun-Shuai Xue
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Nuersimanguli Maimaitiming
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Bo-Lun Zhang
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Bo-Wen Xu
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xin Yin
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhen Huang
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xu Che
- Department of Hepatobiliary Surgery, Shenzhen Center, Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen, 518000, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jian-Qiang Cai
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Xin H, Lai Q, Liu Y, Liao N, Wang Y, Liao B, Zhou K, Zhou Y, Bai Y, Chen Z, Zhou Y. Integrative radiomics analyses identify universal signature for predicting prognosis and therapeutic vulnerabilities across primary and secondary liver cancers: A multi-cohort study. Pharmacol Res 2024; 210:107535. [PMID: 39626849 DOI: 10.1016/j.phrs.2024.107535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 10/22/2024] [Accepted: 11/29/2024] [Indexed: 12/06/2024]
Abstract
As the hallmark of cancer, genetic and phenotypic heterogeneity leads to biomarkers that are typically tailored to specific cancer type or subtype. This specificity introduces complexities in facilitating streamlined evaluations across diverse cancer types and optimizing therapeutic outcomes. In this study, we comprehensively characterized the radiological patterns underlying liver cancer (LC) by integrating radiomics profiles from computed tomography (CT) images of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and colorectal cancer liver metastases (CRLM) through unsupervised clustering analysis. We identified three distinct radiomics clusters, displaying heterogeneity in prognosis. Subsequently, we formulated a shared prognosticator, the liver cancer radiomics signature (LCRS), by discovering and manifesting connectivity among radiomics phenotypes using GGI strategy. We validated that the LCRS is independent prognostic factor after adjusting for clinic-pathologic variables (all P < 0.05), with the LCRS-High group consistently associated with worse survival outcomes across HCC, ICC, and CRLM. However, the LCRS-High group showed clinical benefit from adjuvant chemotherapy, leading to reduced disease recurrence risk and improved survival. By contrast, the LCRS-Low group, including a subset of gastric cancer liver metastases (GCLM), exhibited more favorable response to immune checkpoint inhibitors (ICIs)-based combinational therapy (P = 0.02, hazard ratio (HR): 0.34 [95 % confidence interval (CI): 0.13-0.88]). Further analysis revealed that Notch signaling pathway was enriched in LCRS-High tumors, while LCRS-Low tumors exhibited higher infiltration of natural killer cell. These findings highlight the promise of this universal scoring model to personalize management strategies for patients with LC.
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Affiliation(s)
- Hongjie Xin
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qianwei Lai
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yanping Liu
- Department of Gastroenterology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Naying Liao
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ying Wang
- Department of Gastroenterology, The Fourth Hospital of Changsha, Hunan Normal University, Changsha, China
| | - Bihong Liao
- Department of Radiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Keyang Zhou
- Department of Radiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Yuchen Zhou
- Department of General Surgery, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Yang Bai
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Zhihua Chen
- Department of Radiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
| | - Yuanping Zhou
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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Wong GYM, Li J, McKay M, Castaneda M, Bhimani N, Diakos C, Hugh TJ, Molloy MP. Proteogenomic Characterization of Early Intrahepatic Recurrence after Curative-Intent Treatment of Colorectal Liver Metastases. J Proteome Res 2024; 23:4523-4537. [PMID: 39264718 DOI: 10.1021/acs.jproteome.4c00440] [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: 09/14/2024]
Abstract
Clinical and pathological factors are insufficient to accurately identify patients at risk of early recurrence after curative-intent treatment of colorectal liver metastases (CRLM). This study aimed to identify candidate prognostic proteogenomic biomarkers for early intrahepatic recurrence after curative-intent resection of CRLM. Patients diagnosed with intrahepatic recurrence within 6 months of liver resection were categorized as the "early recurrence" group, while those who achieved a recurrence-free status for 10 years were designated as "durable remission". Comprehensive genomic and proteomic profiling of fresh frozen samples from these prognostically distinct groups was performed using the TruSight Oncology 500 assay and label-free data-dependent acquisition liquid chromatography-mass spectrometry. Genetic alterations were identified in 117 of the 523 profiled genes in patients with early recurrence. The most common somatic mutations linked to early recurrence were TP53 (88%), APC (71%), KRAS (38%), and SMAD4 (21%). SMAD4 alterations were absent in samples from patients with a durable remission. Calponin-2, versican core protein, glutathione peroxidase 3, fibulin-5, and amyloid-β precursor protein were upregulated more than 2-fold in early recurrence. Exploratory analysis of these proteogenomic biomarkers suggests that SMAD4, calponin-2, and glutathione peroxidase 3 may have the potential to predict early recurrence, enabling improved prognostication and precision oncology in CRLM.
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Affiliation(s)
- Geoffrey Yuet Mun Wong
- Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia
- Northern Clinical School, The University of Sydney, Sydney, New South Wales 2065, Australia
- Bowel Cancer and Biomarker Research Laboratory, Kolling Institute, St Leonards, New South Wales 2065, Australia
| | - Jun Li
- Bowel Cancer and Biomarker Research Laboratory, Kolling Institute, St Leonards, New South Wales 2065, Australia
| | - Matthew McKay
- Bowel Cancer and Biomarker Research Laboratory, Kolling Institute, St Leonards, New South Wales 2065, Australia
| | - Miguel Castaneda
- Bowel Cancer and Biomarker Research Laboratory, Kolling Institute, St Leonards, New South Wales 2065, Australia
| | - Nazim Bhimani
- Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia
- Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales 2050, Australia
| | - Connie Diakos
- Northern Clinical School, The University of Sydney, Sydney, New South Wales 2065, Australia
- Department of Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia
| | - Thomas J Hugh
- Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia
- Northern Clinical School, The University of Sydney, Sydney, New South Wales 2065, Australia
| | - Mark P Molloy
- Bowel Cancer and Biomarker Research Laboratory, Kolling Institute, St Leonards, New South Wales 2065, Australia
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Deyrat J, Fuks D, Murris J, Lanoy E, Nassar A, Dhote A, Marchese U, Mallet V, Katsahian S, Gaillard M, Tzedakis S. Evolution of minimally invasive liver surgery in France over the last decade. Surg Endosc 2024:10.1007/s00464-024-10951-3. [PMID: 38902411 DOI: 10.1007/s00464-024-10951-3] [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: 02/22/2024] [Accepted: 05/23/2024] [Indexed: 06/22/2024]
Abstract
BACKGROUND Despite evidence of benefits on postoperative outcomes, minimally invasive liver surgery (MILS) had a very low diffusion up to 2014, and recent evolution is unknown. Our aim was to analyze the recent diffusion and adoption of MILS and compare the trends in indications, extent of resection, and institutional practice with open liver surgery (OLS). METHODS We analyzed the French nationwide, exhaustive cohort of all patients undergoing a liver resection in France between January 1, 2013 and December 31, 2022. Average annual percentage changes (AAPC) in the incidence of MILS and OLS were compared using mixed-effects log-linear regression models. Time trends were analyzed in terms of extent of resection, indication, and institutional practice. RESULTS MILS represented 25.2% of 74,671 liver resections and year incidence doubled from 16.5% in 2013 to 35.4% in 2022. The highest AAPC were observed among major liver resections [+ 22.2% (19.5; 24.9) per year], primary [+ 10.2% (8.5; 12.0) per year], and secondary malignant tumors [+ 9.9% (8.2; 11.6) per year]. The highest increase in MILS was observed in university hospitals [+ 14.7% (7.7; 22.2) per year] performing 48.8% of MILS and in very high-volume (> 150 procedures/year) hospitals [+ 12.1% (9.0; 15.3) per year] performing 19.7% of MILS. OLS AAPC decreased for all indications and institutions and accelerated over time from - 1.8% (- 3.9; - 0.3) per year in 2013-2018 to - 5.9% (- 7.9; - 3.9) per year in 2018-2022 (p = 0.013). CONCLUSIONS This is the first reported trend reversal between MILS and OLS. MILS has considerably increased at a national scale, crossing the 20% tipping point of adoption rate as defined by the IDEAL framework.
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Affiliation(s)
- Julie Deyrat
- AP-HP Centre, Groupe Hospitalier Cochin Port-Royal, DMU Cancérologie et Spécialités Médico-Chirurgicales, Service de Chirurgie Hépatobiliaire, Digestive et Endocrinienne, Paris, France
- Université Paris Cité, 75006, Paris, France
| | - David Fuks
- AP-HP Centre, Groupe Hospitalier Cochin Port-Royal, DMU Cancérologie et Spécialités Médico-Chirurgicales, Service de Chirurgie Hépatobiliaire, Digestive et Endocrinienne, Paris, France
- Université Paris Cité, 75006, Paris, France
| | - Juliette Murris
- Université Paris Cité, 75006, Paris, France
- INSERM, UMR 1138, Centre de Recherche des Cordeliers, Centre Inria de Paris, Équipe, HeKA, Paris, France
| | - Emilie Lanoy
- Université Paris Cité, 75006, Paris, France
- AP-HP Centre, Hôpital Européen Georges-Pompidou, Service d'Épidémiologie et de Biostatistiques, Paris, France
| | - Alexandra Nassar
- AP-HP Centre, Groupe Hospitalier Cochin Port-Royal, DMU Cancérologie et Spécialités Médico-Chirurgicales, Service de Chirurgie Hépatobiliaire, Digestive et Endocrinienne, Paris, France
- Université Paris Cité, 75006, Paris, France
| | - Alix Dhote
- AP-HP Centre, Groupe Hospitalier Cochin Port-Royal, DMU Cancérologie et Spécialités Médico-Chirurgicales, Service de Chirurgie Hépatobiliaire, Digestive et Endocrinienne, Paris, France
- Université Paris Cité, 75006, Paris, France
| | - Ugo Marchese
- AP-HP Centre, Groupe Hospitalier Cochin Port-Royal, DMU Cancérologie et Spécialités Médico-Chirurgicales, Service de Chirurgie Hépatobiliaire, Digestive et Endocrinienne, Paris, France
- Université Paris Cité, 75006, Paris, France
| | - Vincent Mallet
- AP-HP Centre, Groupe Hospitalier Cochin Port-Royal, DMU Cancérologie et Spécialités Médico-Chirurgicales, Service de Chirurgie Hépatobiliaire, Digestive et Endocrinienne, Paris, France
- Université Paris Cité, 75006, Paris, France
| | - Sandrine Katsahian
- Université Paris Cité, 75006, Paris, France
- INSERM, UMR 1138, Centre de Recherche des Cordeliers, Centre Inria de Paris, Équipe, HeKA, Paris, France
- AP-HP Centre, Hôpital Européen Georges-Pompidou, Service d'Épidémiologie et de Biostatistiques, Paris, France
| | - Martin Gaillard
- AP-HP Centre, Groupe Hospitalier Cochin Port-Royal, DMU Cancérologie et Spécialités Médico-Chirurgicales, Service de Chirurgie Hépatobiliaire, Digestive et Endocrinienne, Paris, France
- Université Paris Cité, 75006, Paris, France
| | - Stylianos Tzedakis
- AP-HP Centre, Groupe Hospitalier Cochin Port-Royal, DMU Cancérologie et Spécialités Médico-Chirurgicales, Service de Chirurgie Hépatobiliaire, Digestive et Endocrinienne, Paris, France.
- Université Paris Cité, 75006, Paris, France.
- INSERM, UMR 1138, Centre de Recherche des Cordeliers, Centre Inria de Paris, Équipe, HeKA, Paris, France.
- Department of Hepato-Biliary, Digestive and Endocrine Surgery, Cochin Hospital, AP-HP, University of Paris, 27, Rue du Faubourg Saint Jacques, 75014, Paris, France.
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Zhai M, Wu P, Liao Y, Wu L, Zhao Y. Polymer Microspheres and Their Application in Cancer Diagnosis and Treatment. Int J Mol Sci 2024; 25:6556. [PMID: 38928262 PMCID: PMC11204375 DOI: 10.3390/ijms25126556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 06/05/2024] [Accepted: 06/11/2024] [Indexed: 06/28/2024] Open
Abstract
Cancer is a significant global public health issue with increasing morbidity and mortality rates. To address this challenge, novel drug carriers such as nano-materials, liposomes, hydrogels, fibers, and microspheres have been extensively researched and utilized in oncology. Among them, polymer microspheres are gaining popularity due to their ease of preparation, excellent performance, biocompatibility, and drug-release capabilities. This paper categorizes commonly used materials for polymer microsphere preparation, summarizes various preparation methods (emulsification, phase separation, spray drying, electrospray, microfluidics, and membrane emulsification), and reviews the applications of polymer microspheres in cancer diagnosis, therapy, and postoperative care. The current status and future development directions of polymer microspheres in cancer treatment are analyzed, highlighting their importance and potential for improving patient outcomes.
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Affiliation(s)
| | | | | | | | - Yongxiang Zhao
- State Key Laboratory of Targeting Oncology, National Center for International Research of Bio-Targeting Theranostics, Guangxi Key Laboratory of Bio-Targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning 530021, China; (M.Z.); (P.W.); (Y.L.); (L.W.)
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Liu Z, Wang D, Cao Q, Li J. The treatment efficacy of three-layered functional polymer materials as drug carrier for orthotopic colon cancer. Drug Deliv 2022; 29:2971-2983. [PMID: 36101475 PMCID: PMC9487963 DOI: 10.1080/10717544.2022.2122633] [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] [Indexed: 11/10/2022] Open
Abstract
Colorectal cancer (CRC) is a worldwide disease posing serious threats to people’s life. Surgery and postsurgical chemotherapy are still the first choices to control the rapid progression of cancer. However, tumor recurrence and even distant metastasis are prone to occur. As a result, it is in urgent demand to find a new method to control CRC progression while inhibiting distant metastasis. On this basis, this study developed the three-layered functionalized hydrogel-fibrous membrane-hydrogel composite materials. The Chinese traditional drugs 20 (S)-ginsenoside Rg3 (Rg3) and chemotherapeutic agent 5-fluorouracil (5-Fu) were loaded in the inner hydrogel and middle fibrous membrane and could be constantly released at the same time and space. The outer hydrogel was decorated with phenylboronic acid (PA) to interact with sialic acid expressed on the CRC cell surface. The composite materials possessed biocompatibility and showed no toxicity to normal human intestinal mucosa endothelial cells HIEC. According to the results, the cell viability of CT26 could be significantly decreased in vitro. The three-layered functionalized materials inhibited the original tumor progression and distant tumor metastasis to the liver in an orthotopic colon cancer mouse model by increasing the caspase3 expression and inhibiting the expressions of Bcl-2, Ki-67, and VEGF. In addition, the functions of major organs were not significantly damaged. Our study provides a safe and efficacious method of this three-layered functionalized hydrogel-fibrous membrane-hydrogel composite materials for CRC treatment.
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Affiliation(s)
- Zhuo Liu
- Department of Gastrointestinal Colorectal & Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Dongxin Wang
- Department of Anesthesiology, Jilin Cancer Hospital, Changchun, China
| | - Qian Cao
- Department of Education, The Second Hospital of Jilin University, Changchun, China
| | - Jiannan Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun, China
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Mo S, Tang P, Luo W, Zhang L, Li Y, Hu X, Ma X, Chen Y, Bao Y, He X, Fu G, Xu X, Rao X, Li X, Guan R, Chen S, Deng Y, Lv T, Mu P, Zheng Q, Wang S, Liu F, Li Y, Sheng W, Huang D, Hu C, Gao J, Zhang Z, Cai S, Clevers H, Peng J, Hua G. Patient-Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 9:e2204097. [PMID: 36058001 PMCID: PMC9631073 DOI: 10.1002/advs.202204097] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 08/18/2022] [Indexed: 05/19/2023]
Abstract
There is no effective method to predict chemotherapy response and postoperative prognosis of colorectal cancer liver metastasis (CRLM) patients. Patient-derived organoid (PDO) has become an important preclinical model. Herein, a living biobank with 50 CRLM organoids derived from primary tumors and paired liver metastatic lesions is successfully constructed. CRLM PDOs from the multiomics levels (histopathology, genome, transcriptome and single-cell sequencing) are comprehensively analyzed and confirmed that this organoid platform for CRLM could capture intra- and interpatient heterogeneity. The chemosensitivity data in vitro reveal the potential value of clinical application for PDOs to predict chemotherapy response (FOLFOX or FOLFIRI) and clinical prognosis of CRLM patients. Taken together, CRLM PDOs can be utilized to deliver a potential application for personalized medicine.
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Tajima T, Mukai M, Uda S, Izumi H, Yokoyama D, Hasegawa S, Makuuchi H. Conversion surgery by hand-assisted laparoscopic surgery following chemotherapy for rectal cancer with H3 liver metastases: a case report. J Gastrointest Oncol 2022; 13:2639-2646. [PMID: 36388681 PMCID: PMC9660080 DOI: 10.21037/jgo-22-245] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 07/20/2022] [Indexed: 07/28/2023] Open
Abstract
Background Recent advancements in molecularly targeted chemotherapy for stage IV colorectal cancer have enabled the possibility of complete resection in primary colorectal cancer, which often involves distant liver or lung metastases, by aggressive surgical resection followed by multi-combination chemotherapy. Case description A 73-year-old man treated previously for hyperuricemia, hypertension, and a dissecting abdominal aortic aneurysm was referred to us after an incidental finding of multiple liver masses on abdominal ultrasound during follow-up for the aneurysm. A detailed examination by contrast-enhanced computed tomography revealed a ring-enhancing mass larger than 5 cm in diameter in segment 3 of the liver and more than 6 low-density areas with total diameter of 1 to 2 cm in both lobes. A barium enema examination revealed a Borrmann type 2 lesion covering two-thirds of the circumference of the colon, with a 5-cm major axis in the rectosigmoid colon. Biopsy revealed a well-differentiated adenocarcinoma. The patient was diagnosed with stage IV rectal cancer. Because there was no intestinal obstruction, we administered 9 cycles of bevacizumab with capecitabine and oxaliplatin as chemotherapy. Subsequent diagnostic imaging revealed the metastatic lesions in liver segment 3 had reduced to 2 low-density areas with a diameter of 8 mm, and the other hepatic metastases had disappeared; the main tumor had flattened and shrunk. Therefore, we used hand-assisted laparoscopic surgery (HALS) to perform anterior resection of the rectosigmoid colon and partial resection of liver segment 3 as conversion therapy. The patient was discharged 10 days after surgery. The rectal lesion was a well-differentiated adenocarcinoma with a depth of invasion of p-MP and a spread of L0, V0, and pN0. The partial hepatectomy did not indicate viable cancer cells; only necrotic, lysed tissue was observed. Postoperative chemotherapy involved 4 cycles of bevacizumab with capecitabine and oxaliplatin. At more than 42 months postoperatively, no metastasis or recurrence has been observed. Conclusions This rare case demonstrates that conversion surgery can be a viable option following systemic chemotherapy in patients with advanced colon cancer and H3 liver metastases.
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Affiliation(s)
- Takayuki Tajima
- Department of Surgery, Tokai University Tokyo Hospital, Tokyo, Japan
| | - Masaya Mukai
- Department of Surgery, Tokai University Hachioji Hospital, Tokyo, Japan
| | - Shuji Uda
- Department of Surgery, Tokai University Hachioji Hospital, Tokyo, Japan
| | - Hideki Izumi
- Department of Surgery, Tokai University Hachioji Hospital, Tokyo, Japan
| | - Daiki Yokoyama
- Department of Surgery, Tokai University Hachioji Hospital, Tokyo, Japan
| | - Sayuri Hasegawa
- Department of Surgery, Tokai University Hachioji Hospital, Tokyo, Japan
| | - Hiroyasu Makuuchi
- Department of Surgery, Tokai University Hachioji Hospital, Tokyo, Japan
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10
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Chiorean EG, Nandakumar G, Fadelu T, Temin S, Alarcon-Rozas AE, Bejarano S, Croitoru AE, Grover S, Lohar PV, Odhiambo A, Park SH, Garcia ER, Teh C, Rose A, Zaki B, Chamberlin MD. Treatment of Patients With Late-Stage Colorectal Cancer: ASCO Resource-Stratified Guideline. JCO Glob Oncol 2021; 6:414-438. [PMID: 32150483 PMCID: PMC7124947 DOI: 10.1200/jgo.19.00367] [Citation(s) in RCA: 113] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
PURPOSE To provide expert guidance to clinicians and policymakers in resource-constrained settings on the management of patients with late-stage colorectal cancer. METHODS ASCO convened a multidisciplinary, multinational Expert Panel that reviewed existing guidelines, conducted a modified ADAPTE process, and used a formal consensus process with additional experts for two rounds of formal ratings. RESULTS Existing sets of guidelines from four guideline developers were identified and reviewed; adapted recommendations from five guidelines form the evidence base and provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75% on all recommendations. RECOMMENDATIONS Common elements of symptom management include addressing clinically acute situations. Diagnosis should involve the primary tumor and, in some cases, endoscopy, and staging should involve digital rectal exam and/or imaging, depending on resources available. Most patients receive treatment with chemotherapy, where chemotherapy is available. If, after a period of chemotherapy, patients become candidates for surgical resection with curative intent of both primary tumor and liver or lung metastatic lesions on the basis of evaluation in multidisciplinary tumor boards, the guidelines recommend patients undergo surgery in centers of expertise if possible. On-treatment surveillance includes a combination of taking medical history, performing physical examinations, blood work, and imaging; specifics, including frequency, depend on resource-based setting. Additional information is available at www.asco.org/resource-stratified-guidelines.
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Affiliation(s)
- E Gabriela Chiorean
- University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Govind Nandakumar
- Columbia Asia Hospitals, Bangalore, India.,Weill Cornell Medical College, New York, NY
| | | | - Sarah Temin
- American Society of Clinical Oncology, Alexandria, VA
| | | | - Suyapa Bejarano
- Excelmedica, Liga Contra el Cancer Honduras, San Pedro Sulal, Honduras
| | | | | | | | - Andrew Odhiambo
- University of Nairobi, College of Health Sciences, Nairobi, Kenya
| | | | | | - Catherine Teh
- Philippine Association of HPB Surgeons/Makati Medical Center, Makati City, Philippines
| | - Azmina Rose
- Independent Colorectal Patient Representative, London, United Kingdom
| | - Bassem Zaki
- Dartmouth-Hitchcock Medical Center, Lebanon, NH
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11
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A novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers for postoperative rapid hemostasis and prevention of tumor recurrence. Int J Biol Macromol 2021; 182:1339-1350. [PMID: 34000316 DOI: 10.1016/j.ijbiomac.2021.05.074] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/29/2021] [Accepted: 05/11/2021] [Indexed: 12/16/2022]
Abstract
Surgical resection of the tumor remains the preferred treatment for most solid tumors at an early stage, but surgical treatment often leads to massive bleeding and residual tumor cells. Therefore, a novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers (CFAGS) for rapid hemostasis and prevention of tumor recurrence was prepared by using an electrospinning and interpenetrating polymer network (IPN) strategy. The present results show that alginate/gelatin sponge display excellent hemostatic properties and possess more advantages than commercial gelatin hemostasis sponge. More importantly, CFAGS could control the release of curcumin, inducing curcumin to accumulate at the surgical site of the tumor, thereby inhibiting local tumor recurrence in the subcutaneous postoperative recurrence model. In addition, the sponge was safe to implant in the body and did not cause toxicity to normal tissues and organs. This approach represents a new strategy to implant a dual functional sponge at the postoperative site as an adjuvant to the surgical treatment of cancer.
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12
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Srouji RM, Narayan RR, Boerner T, Buisman FE, Seier K, Gonen M, Balachandran VP, Drebin JA, Jarnagin WR, Kingham TP, Wei A, Kemeny NE, D'Angelica MI. Extrahepatic recurrence rates in patients receiving adjuvant hepatic artery infusion and systemic chemotherapy after complete resection of colorectal liver metastases. J Surg Oncol 2020; 122:1536-1542. [PMID: 32976666 DOI: 10.1002/jso.26221] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 09/02/2020] [Accepted: 09/06/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study investigated the effect of the reduced dose of systemic chemotherapy (SYS) on recurrence patterns in patients receiving adjuvant hepatic artery infusion (HAI) chemotherapy after complete colorectal liver metastases (CRLM) resection. METHODS Patients undergoing complete CRLM resection between 2000 and 2007 were selected from a prospectively maintained database and categorized as receiving SYS or HAI + SYS. Those with pre and/or intraoperative extrahepatic disease, documented death, or recurrence within 30 days of CRLM resection were excluded. Competing risk, Fine and Gray's tests were used to compare SYS versus HAI + SYS for time-to-organ recurrence. RESULTS Of 361 study patients, 153 (42.4%) received SYS and 208 (57.6%) received HAI + SYS. The median follow-up for survivors was 100 (range = 12-185) and 156 months (range = 18-217) for SYS and HAI + SYS, respectively. The 5-year cumulative incidence (CI) of any liver recurrence was greater for those receiving SYS (SYS = 41.9% vs. HAI + SYS = 28.6%, p = .005). The 5-year CI of developing any lung or extrahepatic recurrence for SYS patients was 36.2% and 47.9% compared with 44.5% (p = .242) and 51.7% (p = .551), respectively, in patients receiving HAI + SYS. CONCLUSION Despite the reduced dose of SYS, adjuvant HAI + SYS after CRLM resection is not associated with a significantly increased risk of extrahepatic recurrence.
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Affiliation(s)
- Rami M Srouji
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.,Department of Surgery, Barnes Jewish Hospital, Washington University, St. Louis, Missouri, USA
| | - Raja R Narayan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.,Department of Surgery, School of Medicine, Stanford University, Stanford, California, USA
| | - Thomas Boerner
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Florian E Buisman
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.,Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Kenneth Seier
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Jeffrey A Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Alice Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Nancy E Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Michael I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
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13
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Paulatto L, Dioguardi Burgio M, Sartoris R, Beaufrère A, Cauchy F, Paradis V, Vilgrain V, Ronot M. Colorectal liver metastases: radiopathological correlation. Insights Imaging 2020; 11:99. [PMID: 32844319 PMCID: PMC7447704 DOI: 10.1186/s13244-020-00904-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/04/2020] [Indexed: 02/07/2023] Open
Abstract
With the development of chemotherapy regimens, targeted therapies, and hepatic surgery, the survival of patients with colorectal liver metastases (CRLM) has dramatically improved. Imaging plays a central role for the diagnosis, staging, and treatment allocation in these patients. To interpret CRLM on imaging, radiologists must be familiar with the main imaging features of untreated tumors as well as the modifications induced by systemic therapies, and their meaning in relation to pathological tumor response and tumor biology. CRLM have the same histological features as the primary tumor. Most are “non-otherwise specified” (NOS) adenocarcinomas. The mucinous tumor is the most common of the rare subtypes. In NOS tumors, imaging usually differentiates central areas of necrosis from peripheral proliferating tumors and desmoplastic reaction. Areas of mucin mixed with fibrosis are seen in mucinous subtypes to help differentiate the metastases from other tumors cysts or hemangiomas. After treatment, the viable tumor is gradually replaced by ischemic-like necrosis and fibrosis, and remnants cells are mainly located on the periphery of tumors. Imaging can help predict the degree of tumor response, but changes can be difficult to differentiate from the pretherapeutic appearance. When chemotherapy is interrupted or in case of resistance to treatment, a peripheral infiltrating halo of tumor growth may appear. The purpose of the article is to illustrate the significance of the imaging features of colorectal liver metastases during systemic therapy, using radiopathological correlations.
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Affiliation(s)
- Luisa Paulatto
- Department of Radiology, University Hospitals Paris Nord Val de Seine, Beaujon, Hauts-de-Seine, Clichy, France
| | - Marco Dioguardi Burgio
- Department of Radiology, University Hospitals Paris Nord Val de Seine, Beaujon, Hauts-de-Seine, Clichy, France.,Université de Paris, Paris, France.,INSERM U1149, CRI, Paris, France
| | - Riccardo Sartoris
- Department of Radiology, University Hospitals Paris Nord Val de Seine, Beaujon, Hauts-de-Seine, Clichy, France.,Université de Paris, Paris, France.,INSERM U1149, CRI, Paris, France
| | - Aurélie Beaufrère
- INSERM U1149, CRI, Paris, France.,Department of Pathology, University Hospitals Paris Nord Val de Seine, Beaujon, Hauts-de-Seine, Clichy, France
| | - François Cauchy
- Department of HPB Surgery, University Hospitals Paris Nord Val de Seine, Beaujon, Hauts-de-Seine, Clichy, France
| | - Valérie Paradis
- INSERM U1149, CRI, Paris, France.,Department of Pathology, University Hospitals Paris Nord Val de Seine, Beaujon, Hauts-de-Seine, Clichy, France
| | - Valérie Vilgrain
- Department of Radiology, University Hospitals Paris Nord Val de Seine, Beaujon, Hauts-de-Seine, Clichy, France.,Université de Paris, Paris, France.,INSERM U1149, CRI, Paris, France
| | - Maxime Ronot
- Department of Radiology, University Hospitals Paris Nord Val de Seine, Beaujon, Hauts-de-Seine, Clichy, France. .,Université de Paris, Paris, France. .,INSERM U1149, CRI, Paris, France.
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14
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Shi Y, Liu Z. Serum miR-92a-1 is a novel diagnostic biomarker for colorectal cancer. J Cell Mol Med 2020; 24:8363-8367. [PMID: 32562465 PMCID: PMC7412696 DOI: 10.1111/jcmm.15282] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 02/25/2020] [Accepted: 03/27/2020] [Indexed: 12/15/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide, with high mortality. Abnormally expressed microRNAs (miRNAs) are considered novel biomarkers in cancer diagnosis. The aim of this study was to investigate the diagnostic value of miR‐92a‐1 in patients with CRC. Serum samples were collected from 148 patients pathologically diagnosed with CRC and 68 gender‐ and age‐matched healthy volunteers. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to measure serum miR‐92a‐1 level. Relationship between miR‐92a‐1 and clinicopathological features of CRC cases was analysed via chi‐square test. Receiver operating characteristic (ROC) curve was plotted to estimate the diagnostic value of miR‐92a‐1 in CRC. Serum miR‐92a‐1 was significantly up‐regulated in CRC patients compared with healthy individuals (P < .001). Moreover, miR‐92a‐1 expression was correlated with TNM stage (P = .02), histological stage (P = .003), lymph node metastasis (P = .003) and distant metastasis (P < .001). ROC analysis showed that the area under the ROC curve (AUC) was 0.914, suggesting high diagnostic accuracy of miR‐92a‐1 in ROC. The optimal cut‐off value was 1.485, with a sensitivity of 81.8% and a specificity of 95.6%. MiR‐92a‐1 is increased in CRC patients and correlated with aggressive clinical characteristics. Serum miR‐92a‐1 may be a potential diagnostic biomarker for CRC.
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Affiliation(s)
- Ying Shi
- Department of Oncology, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Zhibao Liu
- Department of Oncology, Cangzhou Central Hospital, Cangzhou, Hebei, China
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15
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Ren L, Zhu D, Benson AB, Nordlinger B, Koehne CH, Delaney CP, Kerr D, Lenz HJ, Fan J, Wang J, Gu J, Li J, Shen L, Tsarkov P, Tejpar S, Zheng S, Zhang S, Gruenberger T, Qin X, Wang X, Zhang Z, Poston GJ, Xu J. Shanghai international consensus on diagnosis and comprehensive treatment of colorectal liver metastases (version 2019). EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:955-966. [PMID: 32147426 DOI: 10.1016/j.ejso.2020.02.019] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Accepted: 02/17/2020] [Indexed: 12/17/2022]
Abstract
The liver is the most common anatomical site for hematogenous metastases from colorectal cancer. Therefore effective treatment of liver metastases is one of the most challenging elements in the management of colorectal cancer. However, there is rare available clinical consensus or guideline only focusing on colorectal liver metastases. After six rounds of discussion by 195 clinical experts of the Shanghai International Consensus Expert Group on Colorectal Liver Metastases (SINCE) from 29 countries or regions, the Shanghai Consensus has been finally completed, based on current research and expert experience. The consensus emphasized the principle of multidisciplinary team, provided detailed diagnosis approaches, and guided precise local and systemic treatments. This Shanghai Consensus might be of great significance to standardized diagnosis and treatment of colorectal liver metastases all over the world.
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Affiliation(s)
- Li Ren
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dexiang Zhu
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Al B Benson
- Division of Hematology/Oncology, Northwestern Medical Group, Chicago, USA
| | - Bernard Nordlinger
- Surgery Department, Hospital Ambroise-Pare, Boulogne-Billancourt, France
| | | | - Conor P Delaney
- Department of Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - David Kerr
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Heinz-Josef Lenz
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, China
| | - Jianping Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jin Gu
- Department of Colorectal Surgery, Peking University Cancer Hospital, Beijing, China; Department of Colorectal Surgery, Peking University Shougang Hospital, Beijing, China
| | - Jin Li
- Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China
| | - Petrv Tsarkov
- Clinic of Colorectal and Minimally Invasive Surgery, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Sabine Tejpar
- Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium
| | - Shu Zheng
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Suzhan Zhang
- Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | | | - Xinyu Qin
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - 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
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Graeme John Poston
- Surgery Department, Aintree University Hospital, School of Translational Studies, University of Liverpool, Liverpool, UK.
| | - Jianmin Xu
- Department of Colorectal Surgery, Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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16
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Srouji R, Narayan R, Boerner T, Buisman F, Seier K, Gonen M, Balachandran VP, Drebin J, Jarnagin WR, Kingham TP, Wei A, Kemeny NE, D'Angelica M. Addition of adjuvant hepatic artery infusion to systemic chemotherapy following resection of colorectal liver metastases is associated with reduced liver-related mortality. J Surg Oncol 2020; 121:1314-1319. [PMID: 32236970 DOI: 10.1002/jso.25916] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 03/07/2020] [Accepted: 03/09/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND After resection of colorectal liver metastases (CRLM), recurrent disease in the liver is a major cause of death but may be reduced with the addition of adjuvant hepatic arterial infusion (HAI) chemotherapy to systemic chemotherapy (SYS). OBJECTIVE This study investigates organ-specific causes of death in patients receiving adjuvant HAI and SYS compared to adjuvant SYS alone. METHODS Between 2000 and 2007, patients undergoing complete CRLM resection were identified from a prospectively maintained liver resection database and categorized as receiving HAI + SYS or SYS only. Using newly constructed definitions, mortality was attributed to specific organs (liver, lung, peritoneum, and brain) or infection. Univariate models and cumulative incidence functions were generated using competing risk methods. RESULTS Of 361 eligible patients, 208 (57.6%) received HAI + SYS and 153 (42.4%) received SYS. The median follow up among survivors was 142 months (range = 12-217 months). Ten-year overall survival was 50.6% in the HAI + SYS group compared to 30.9% in those receiving SYS (P = .004). The 5-year cumulative incidence of liver-related mortality was 6.8% in the HAI + SYS group compared to 14.3% in the SYS group (P = .007). CONCLUSION The addition of HAI to SYS after CRLM resection is associated with a 50% reduction in liver-related mortality at 5 years.
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Affiliation(s)
- Rami Srouji
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York.,Department of Surgery, Washington University, St. Louis, Missouri
| | - Raja Narayan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York.,Department of Surgery, Stanford University, Stanford, California
| | - Thomas Boerner
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - Florian Buisman
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - Ken Seier
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - Jeffrey Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - Alice Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - Nancy E Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York
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17
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18
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Huang C, Huang J, Luo H, Zong Z, Zhu Z. Comparative Efficacy of Preoperative, Postoperative, and Perioperative Treatments for Resectable Colorectal Liver Metastases: A Network Meta-Analysis. Front Pharmacol 2019; 10:1052. [PMID: 31619998 PMCID: PMC6759603 DOI: 10.3389/fphar.2019.01052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 08/20/2019] [Indexed: 12/24/2022] Open
Abstract
Background: Several treatment strategies are used for management of resectable colorectal liver metastases. We performed a Bayesian network meta-analysis to compare preoperative, postoperative, or perioperative treatments, identifying the optimal approach. Methods: We searched reports of randomized controlled trials through the relevant databases. The primary outcome criterion was overall survival (OS). The secondary outcome measure was disease-free survival (DFS). We calculated the hazard ratio (HR) with the 95% credible interval (Crl) of the time-to-event data. Rank probabilities were evaluated by the probability of treatment rankings. Multiple treatment comparisons based on a Bayesian network integrated the efficacy of all included approaches. Results: Twenty-two eligible randomized controlled trials with 6,115 patients were included in the network meta-analysis. One treatment that resulted in a significant improvement in OS compared with surgery alone was hepatic arterial infusion (HAI) plus postoperative chemotherapy (CT) [HR = 0.74 with 95% Crl: (0.60, 0.94)]. With regard to the secondary outcome measure, three approaches that led to a significant improvement in DFS compared with surgery alone were HAI plus postoperative CT [HR = 1.44 with 95% Crl: (1.19, 1.75)], postoperative CT [HR = 1.14 with 95% Crl: (1.01, 1.29)], preoperative hepatic and regional arterial chemotherapy (PHRAC) plus preoperative CT [HR = 1.41 with 95% Crl: (1.03, 1.89)]. According to the results for the rank probabilities of the 11 treatments, the combination of HAI and bevacizumab plus postoperative CT showed the highest probability of benefitting OS, and PHRAC plus preoperative CT was most likely to benefit DFS. Conclusions: The combination of HAI and bevacizumab plus postoperative CT exhibited the greatest odds of being the most effective treatment for improving OS, and PHRAC plus preoperative CT exhibited the greatest odds of improving DFS. Further clinical studies are needed and justified.
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Affiliation(s)
| | | | | | | | - Zhengming Zhu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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19
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Shigematsu Y, Inamura K, Yamamoto N, Mise Y, Saiura A, Ishikawa Y, Takahashi S, Kanda H. Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis. BMC Cancer 2018; 18:980. [PMID: 30326864 PMCID: PMC6192098 DOI: 10.1186/s12885-018-4902-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 10/04/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The prognostic biomarker for patients undergoing curative liver metastasectomy for colorectal cancer (CRC) is lacking. The purpose was to investigate the prognostic role of a lack of CDX2 expression, which has been proposed as a potential biomarker for high-risk relapse in early-stage CRC, in patients undergoing curative liver metastasectomy. METHODS A total of 396 consecutive patients with CRC liver metastasis who underwent potentially curative liver metastasectomy at a single center in Japan between 2005 and 2015 were included. For the immunohistochemical analysis of nuclear CDX2 expression, we adopted the tissue microarray approach using the resected metastatic liver CRCs. Patient subgroups were compared with respect to disease-free survival (DFS) and overall survival (OS) by applying the Kaplan-Meier curve, log-rank tests, and multivariate analyses based on the Cox proportional hazards method. OS is defined as the period from the date of curative liver resection for metastatic CRC until death. DFS is defined as the length of time from curative liver resection to either the first recurrence or death. In patients without recurrence, the latest imaging inspection date was used as the censored date. RESULTS Thirty-six of the 396 CRCs (9.1%) reduced CDX2 expression. The reduced expression of CDX2 was associated with poor differentiation (P = 0.02). DFS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median DFS: 245 days versus 420 days; hazard ratio for disease recurrence: 1.64; 95% confidence interval: 1.08-2.38; P = 0.02). OS in days was lower in the patients with CDX2-low CRC than in the patients with CDX2-high CRC (median OS: 1024 days versus 3145 days; hazard ratio: 2.41; 95% confidence interval: 1.52-3.85; P < 0.001). In patients with CDX2-low CRC, both DFS and OS were similar between the with and without pre- or post-operative chemotherapy groups (median DFS: 243 versus 247 days; P = 0.73, median OS: 1016 versus 1363 days; P = 0.69). CONCLUSIONS Reduced expression of CDX2 indicates poor DFS and OS, however, it might not represent chemosensitivity in patients undergoing curative liver metastasectomy. (339/350).
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Affiliation(s)
- Yasuyuki Shigematsu
- Department of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research (JFCR), 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan.
| | - Kentaro Inamura
- Department of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research (JFCR), 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
| | - Noriko Yamamoto
- Department of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research (JFCR), 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
| | - Yoshihiro Mise
- Division of Gastroenterology Center, The Cancer Institute Hospital, JFCR, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
| | - Akio Saiura
- Division of Gastroenterology Center, The Cancer Institute Hospital, JFCR, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
| | - Yuichi Ishikawa
- Department of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research (JFCR), 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
| | - Shunji Takahashi
- Division of General Oncology, The Cancer Institute Hospital, JFCR, 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan
| | - Hiroaki Kanda
- Department of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research (JFCR), 3-8-31 Ariake, Koto, Tokyo, 135-8550, Japan.,Department of Pathology, Saitama Cancer Center, 780 Komuro, Ina, Kita-adachi-gun, Saitama, 362-0806, Japan
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20
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Lin J, Peng J, Zhao Y, Luo B, Zhao Y, Deng Y, Sui Q, Gao Y, Zeng Z, Lu Z, Pan Z. Early recurrence in patients undergoing curative resection of colorectal liver oligometastases: identification of its clinical characteristics, risk factors, and prognosis. J Cancer Res Clin Oncol 2017; 144:359-369. [PMID: 29128882 PMCID: PMC5794819 DOI: 10.1007/s00432-017-2538-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 10/24/2017] [Indexed: 12/18/2022]
Abstract
PURPOSE Oligometastatic disease can potentially be cured when an optimal approach is performed. Early recurrence after liver resection is an intractable problem, and the clinical implications remain unknown in colorectal liver oligometastases (CLOM) patients. This study aimed to investigate the clinical characteristics, risk factors, and prognosis related to early recurrence in these patients. METHODS A total of 307 consecutive patients with CLOM undergoing curative liver resection were retrospectively reviewed between September 1999 and June 2016. Early recurrence was defined as any recurrence or death from CLOM that occurred within 6 months of liver resection. RESULTS With a median follow-up time of 31.7 months, the 3-year overall survival (OS) and recurrence-free survival rates were 68.7 and 42.5%, respectively. Forty-nine (16.0%) patients developed early recurrence and showed a poorer 3-year OS than those with non-early recurrence (22.3 vs. 75.8%, P < 0.001) or later recurrence (22.3 vs. 52.8 vs. 63.2%, P < 0.001). Moreover, early recurrence was identified as an independent predictor of 3-year OS [hazard ratio (HR) 6.282; 95% confidence interval (CI) 3.980-9.915, P < 0.001]. In multivariate analysis, a node-positive primary tumor [odds ratio (OR) 2.316; 95% CI 1.097-4.892, P = 0.028) and metastatic diameter > 3 cm (OR 2.560; 95% CI 1.290-5.078; P = 0.007) were shown to be risk factors for early recurrence. The salvage liver resection rate for patients with early recurrence was significantly lower than that for patients with later recurrence (4.1 vs. 19.7%, P = 0.010). CONCLUSIONS Early recurrence should be investigated in routine clinical practice, even in patients with CLOM after curative liver resection. Detailed preoperative comprehensive measurements might help stratify high-risk patients, and a non-surgical treatment for early recurrence might represent an effective alternative.
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Affiliation(s)
- Junzhong Lin
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Jianhong Peng
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Yixin Zhao
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Baojia Luo
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Yujie Zhao
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Yuxiang Deng
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Qiaoqi Sui
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Yuanhong Gao
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.,Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Zhifan Zeng
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.,Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Zhenhai Lu
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
| | - Zhizhong Pan
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
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21
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Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases. CHINESE JOURNAL OF CANCER 2017; 36:78. [PMID: 28969708 PMCID: PMC5625647 DOI: 10.1186/s40880-017-0244-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 09/17/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorectal cancer patients with liver metastases who underwent hepatectomy. However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients. PATIENTS AND METHODS In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients. The pathologic response was evaluated according to the tumor regression grade (TRG). The prognostic role of pathologic response in recurrence-free survival (RFS) and overall survival (OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests. RESULTS Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy (median RFS: 9.9 vs. 6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors, and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases (all P < 0.05). A decrease in the serum carcinoembryonic antigen (CEA) level after preoperative chemotherapy predicted an increased pathologic response rate (P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemotherapy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens. CONCLUSIONS We found that the evaluation of pathologic response may predict the prognosis of Chinese colorectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.
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22
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Appleman LJ, Maranchie JK. Systemic therapy following metastasectomy for renal cell carcinoma: Using insights from other clinical settings to address unanswered questions. Urol Oncol 2017; 36:17-22. [PMID: 28736252 DOI: 10.1016/j.urolonc.2017.06.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 06/02/2017] [Accepted: 06/07/2017] [Indexed: 12/12/2022]
Abstract
Surgical resection for metastatic renal cell carcinoma (RCC) was first described several decades ago, but the appropriate role for surgery in coordinated multidisciplinary care has not been well-defined. The explosive development of new therapies for advanced RCC over the past 10 years has improved the outlook for patients, and there is now renewed interest in surgical metastasectomy for selected patients with metastatic RCC, moving away from the conventional dichotomy between surgery for local disease and systemic therapy for metastatic disease. Patients rendered disease-free after metastasectomy are at high risk of recurrence, but to date no postoperative medical treatment has been shown to be beneficial. Ongoing studies and relevant data will be reviewed to frame the multidisciplinary approach to patients with oligometastatic RCC and to outline future challenges and opportunities for advancing their care.
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Affiliation(s)
- Leonard J Appleman
- Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA.
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23
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Fiorentini G, Sarti D, Aliberti C, Carandina R, Mambrini A, Guadagni S. Multidisciplinary approach of colorectal cancer liver metastases. World J Clin Oncol 2017; 8:190-202. [PMID: 28638789 PMCID: PMC5465009 DOI: 10.5306/wjco.v8.i3.190] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 04/27/2017] [Accepted: 05/03/2017] [Indexed: 02/06/2023] Open
Abstract
Large bowel cancer is a worldwide public health challenge. More than one third of patients present an advanced stage of disease at diagnosis and the liver is the most common site of metastases. Selection criteria for early diagnosis, chemotherapy and surgery have been recently expanded. The definition of resectability remains unclear. The presence of metastases is the most significant prognostic factor. For this reason the surgical resection of hepatic metastases is the leading treatment. The most appropriate resection approach remains to be defined. The two step and simultaneous resection processes of both primary and metastases have comparable survival long-term outcomes. The advent of targeted biological chemotherapeutic agents and the development of loco-regional therapies (chemoembolization, thermal ablation, arterial infusion chemotherapy) contribute to extend favorable results. Standardized evidence-based protocols are missing, hence optimal management of hepatic metastases should be single patient tailored and decided by a multidisciplinary team. This article reviews the outcomes of resection, systemic and loco-regional therapies of liver metastases originating from large bowel cancer.
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24
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Wang Y, Wang ZQ, Wang FH, Yuan YF, Li BK, Ding PR, Chen G, Wu XJ, Lu ZH, Pan ZZ, Wan DS, Sun P, Yan SM, Xu RH, Li YH. The Role of Adjuvant Chemotherapy for Colorectal Liver Metastasectomy after Pre-Operative Chemotherapy: Is the Treatment Worthwhile? J Cancer 2017; 8:1179-1186. [PMID: 28607592 PMCID: PMC5463432 DOI: 10.7150/jca.18091] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Accepted: 01/12/2017] [Indexed: 12/13/2022] Open
Abstract
Peri-operative chemotherapy has been proposed to improve the survival of patients with colorectal cancer hepatic metastases (CRCHM). However, the role of the adjuvant chemotherapy post-metastasectomy for CRCHM patients who have undergone pre-operative chemotherapy is still undetermined. We retrospectively analyzed the role of adjuvant chemotherapy post-metastasectomy on relapse-free survival (RFS) and overall survival (OS) in 163 CRCHM patients who received pre-operative chemotherapy using a Kaplan-Meier curve and univariate/multiple Cox model. Ten patients with rapidly progressing disease were further excluded in a sensitivity analysis. Seven risk factors (metachronous/synchronous metastases, differentiated grade of the primary tumor, number of metastases, size of the max metastasis, duration of pre-operative chemotherapy, radiologic response and pathologic regression) were used to stratify patients and investigate the beneficial features of adjuvant chemotherapy post-metastasectomy. The results indicated that adjuvant chemotherapy post-metastasectomy prolonged both RFS (median RFS: 3.3 vs. 10.2 m, P = 0.002) and OS (median OS: 28.1 vs. 40.7 m, P = 0.005) in CRCHM patients who received pre-operative chemotherapy. After adjusting for other risk factors in a multiple Cox model, the adjuvant chemotherapy group was estimated to have a 54.0 % relapse-free survival (hazard ratio (HR) = 0.46, 95 % confidence interval (CI) 0.31 - 0.69, P < 0.001) and a 55.0 % overall survival (HR [95 % CI]: 0.45 [0.26 - 0.78], P = 0.005) advantage compared to patients without adjuvant chemotherapy. Additionally, the benefit of adjuvant chemotherapy post-liver resection remained in sensitivity analysis. After the risk stratification, patients with synchronous metastases, poor differentiation, ≥ 3 metastases per patient, size of the maximum metastasis >3 cm, a short duration of pre-operative chemotherapy, radiologic response and poor pathologic regression seem to benefit more from adjuvant chemotherapy. To sum up, adjuvant chemotherapy post-metastasectomy might be considered for CRCHM patients who have received preoperative chemotherapy, especially for those with high-risk factors.
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Affiliation(s)
- Yun Wang
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Zhi-Qiang Wang
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Feng-Hua Wang
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Yun-Fei Yuan
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of hepatobiliary surgery, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Bin-Kui Li
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of hepatobiliary surgery, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Pei-Rong Ding
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of colorectal surgery, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Gong Chen
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of colorectal surgery, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Xiao-Jun Wu
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of colorectal surgery, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Zhen-Hai Lu
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of colorectal surgery, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Zhi-Zhong Pan
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of colorectal surgery, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - De-Sen Wan
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of colorectal surgery, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Peng Sun
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Shu-Mei Yan
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Rui-Hua Xu
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
| | - Yu-Hong Li
- Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P.R. China.,Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
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25
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Passot G, Denbo JW, Yamashita S, Kopetz SE, Chun YS, Maru D, Overman MJ, Brudvik KW, Conrad C, Aloia TA, Vauthey JN. Is hepatectomy justified for patients with RAS mutant colorectal liver metastases? An analysis of 524 patients undergoing curative liver resection. Surgery 2016; 161:332-340. [PMID: 27592215 DOI: 10.1016/j.surg.2016.07.032] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 06/24/2016] [Accepted: 07/18/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND RAS mutations are associated with limited overall survival after resection of colorectal liver metastases. Our aim was to determine criteria for considering hepatectomy for patients with RAS mutant colorectal liver metastases. METHODS Of 1,163 patients who underwent liver resection for colorectal liver metastases during 2005-2014, all patients operated on with curative intent who had known RAS mutation status were included. Factors associated with overall survival were determined using multivariate analysis. RESULTS A total of 524 patients met the inclusion criteria; 212 (40%) had mutated RAS. Mutations were located on codon 12 in 128 patients (60%) and codon 13 in 29 (14%). At median follow-up of 38 months, median overall survival was 72.6 months for wild-type RAS and 50.9 months for mutated RAS (P < .001). Median overall survival for patients with codon 12 and 13 mutations was 51.9 and 50.9 months, respectively (P = .839), significantly worse than for patients with wild-type RAS (P = .005, and P = .038 for codon 12 and 13, respectively). For patients with RAS mutation, factors associated independently with worse overall survival were node-positive primary tumor, tumor >3 cm, and >7 cycles of preoperative chemotherapy. Major and 2-stage hepatectomy were not associated independently with overall survival. Median overall survival was 57, 41, and 21.5 months for patients with 1, 2, and 3 risk factors, respectively. There were no 4-year survivors in the highest-risk group. CONCLUSION Patients with multiple risk factors had poor overall survival after curative resection of RAS mutant colorectal liver metastases. For such patients, hepatectomy may be ill advised, and alternative therapies or further systemic therapy should be considered.
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Affiliation(s)
- Guillaume Passot
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Jason W Denbo
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Suguru Yamashita
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Scott E Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Yun S Chun
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Dipen Maru
- Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | | | - Claudius Conrad
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
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26
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Siriwardana PN, Luong TV, Watkins J, Turley H, Ghazaley M, Gatter K, Harris AL, Hochhauser D, Davidson BR. Biological and Prognostic Significance of the Morphological Types and Vascular Patterns in Colorectal Liver Metastases (CRLM): Looking Beyond the Tumor Margin. Medicine (Baltimore) 2016; 95:e2924. [PMID: 26937938 PMCID: PMC4779035 DOI: 10.1097/md.0000000000002924] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2015] [Revised: 01/29/2016] [Accepted: 01/31/2016] [Indexed: 01/06/2023] Open
Abstract
Patients with encapsulated colorectal liver metastases (CRLM) have a better prognosis than those without a capsule. The reason for the encapsulation is unknown. Hypoxia inducible factor-1α (HIF-1α) increases tumor angiogenesis and tumor tissue expression is associated with reduced survival. Our aim was to determine whether the good prognosis of encapsulated CRLM is associated with reduced HIF-1α expression by the cancer.The study selected only patients who had not undergone neoadjuvant chemotherapy prior to a potentially curative hepatectomy for CRLM. From 30 selected patients, serial sections were cut from a single randomly selected metastasis. Morphology was assessed following H&E staining. Tumor hypoxia, vascular endothelial growth factor (VEGF), proliferation, and microvascular density (MVD) were assessed by immunostaining for HIF-1α and carbonic anhydrase-9 (CA-9), VEGF, Ki67, and cluster of differentiation-31, respectively. MVD was calculated in the vascular hot spots. Pathology was reported without clinical outcome information. Actual long-term survival was recorded.Thirteen (43%) of the cancers were encapsulated CRLM containing glands which were large, complex, and cribriform. Thirteen (43%) were infiltrative CRLM and their glands were small, closely packed, and rounded with vessels in the interglandular fibrous tissue with no capsule; 3 (10%) had a mixed picture. Encapsulated CRLM had a higher expression of HIF-1α (58% vs 8%, P = 0.03), CA-9 (42% vs 0%, P = 0.04), and VEGF (92% vs 25%, P = 0.02). MVD was lower in the encapsulated CRLM group (37 mm vs 143 mm, P < 0.001). The median follow-up was 115 months. The encapsulated CRLM group had a better overall and 5-year survival (relative hazard: 0.58, P = 0.057 and hazard ratio: 0.52, P = 0.044).There are 2 main morphological appearances of CRLM which have very different long-term survival following liver resection surgery. The morphology is associated with differences in expression of HIF-1α, CA-9, VEGF, and angiogenesis.
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Affiliation(s)
- Pulathis N Siriwardana
- From the Hepatopancreatobiliary and Liver Transplant Surgery Unit, University Department of Surgery, Royal Free London NHS Foundation Trust (MG) and University College London Medical School (PNS, BRD); Department of Cellular Pathology, Royal Free London NHS Foundation Trust (TVL, JW); Department of Oncology, UCL Cancer Institute (DH), London, UK; Nuffield Department of Clinical Laboratory Sciences, Tumor Pathology Group (HT) and Nuffield Division of Clinical Laboratory Sciences, Department of Medicine (KG), John Radcliffe Hospital, University of Oxford; and Department of Oncology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University (ALH), Oxford, UK
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27
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Leal JN, Bressan AK, Vachharajani N, Gonen M, Kingham TP, D'Angelica MI, Allen PJ, DeMatteo RP, Doyle MBM, Bathe OF, Greig PD, Wei A, Chapman WC, Dixon E, Jarnagin WR. Time-to-Surgery and Survival Outcomes in Resectable Colorectal Liver Metastases: A Multi-Institutional Evaluation. J Am Coll Surg 2016; 222:766-79. [PMID: 27113514 DOI: 10.1016/j.jamcollsurg.2016.01.046] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Revised: 01/18/2016] [Accepted: 01/19/2016] [Indexed: 12/21/2022]
Abstract
BACKGROUND Resection of colorectal liver metastases (CRLM) is associated with improved survival; however, the impact of time to resection on survival is unknown. The current multi-institutional study sought to evaluate the influence of time from diagnosis (Dx) to resection (Rx) on survival outcomes among patients with resectable, metachronous CRLM and to compare practice patterns across hospitals. STUDY DESIGN Medical records of patients with ≤4 metachronous CRLM treated with surgery were reviewed and analyzed retrospectively. Time from Dx to Rx was analyzed as a continuous variable and also dichotomized into 2 groups (group 1: Dx to Rx <3 months and group 2: Dx to Rx ≥3 months) for additional analysis. Survival time distributions after resection were estimated using the Kaplan-Meier method. Between-group univariate comparisons were based on the log-rank test and multivariable analysis was done using Cox proportional hazards model. RESULTS From 2000 to 2010, six hundred and twenty-six patients were identified. Type of initial referral (p < 0.0001) and use of neoadjuvant (p = 0.04) and/or adjuvant (p < 0.0001) chemotherapy were significantly different among hospitals. Patients treated with neoadjuvant chemotherapy (n = 108) and those with unresectable disease at laparotomy (n = 5) were excluded from final evaluation. Median overall survival and recurrence-free survival were 74 months (range 63.8 to 84.2 months) and 29 months (range 23.9 to 34.1 months), respectively. For the entire cohort, longer time from Dx to Rx was independently associated with shorter overall survival (hazard ratio = 1.12; 95% CI, 1.06-1.18; p < 0.0001), but not recurrence-free survival. Median overall survival for group 1 was 76 months (range 62.0 to 89.2 months) vs 58 months (range 34.3 to 81.7 months) in group 2 (p = 0.10). Among patients with available data pertaining to adjuvant chemotherapy (N = 457; 318 treated and 139 untreated), overall survival (87 months [range 71.2 to 102.8 months] vs 48 months [range 25.3 to 70.7 months]; p <0.0001), and recurrence-free survival (33 months [range 25.3 to 40.7 months] vs 22 months [range 14.5 to 29.5 months]; p = 0.05) were improved significantly. CONCLUSIONS In select patients undergoing initial resection for CRLM, longer time from Dx to Rx is independently associated with worse overall survival. In addition, despite uniform disease characteristics, practice patterns related to definitely resectable CRLM vary significantly across hospitals.
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Affiliation(s)
- Julie N Leal
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Alexsander K Bressan
- Department of Surgery, University of Calgary and Foothills Medical Center, Calgary, Alberta, Canada
| | | | - Mithat Gonen
- Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Peter J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Ronald P DeMatteo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Majella B M Doyle
- Department of Surgery, Washington University in St Louis, St Louis, MO
| | - Oliver F Bathe
- Department of Surgery, University of Calgary and Foothills Medical Center, Calgary, Alberta, Canada
| | - Paul D Greig
- Department of Surgery, Hepatobiliary and Pancreatic Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Alice Wei
- Department of Surgery, Hepatobiliary and Pancreatic Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - William C Chapman
- Department of Surgery, Washington University in St Louis, St Louis, MO
| | - Elijah Dixon
- Department of Surgery, University of Calgary and Foothills Medical Center, Calgary, Alberta, Canada
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
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28
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Subramanian M, Choti MA, Yopp AC. Hepatic Arterial Infusion Pump Chemotherapy for Colorectal Liver Metastases: Making a Comeback? CURRENT COLORECTAL CANCER REPORTS 2015. [DOI: 10.1007/s11888-015-0277-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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29
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Zhu GQ, You J, Shi KQ, He SY, Wang LR, Chen YP, Braddock M, Zheng MH. Systematic review with network meta-analysis: adjuvant chemotherapy for resected colorectal liver metastases. Medicine (Baltimore) 2015; 94:e379. [PMID: 25569666 PMCID: PMC4602852 DOI: 10.1097/md.0000000000000379] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Revised: 11/24/2014] [Accepted: 11/25/2014] [Indexed: 12/29/2022] Open
Abstract
There are 5 major adjuvant chemotherapies (ACTs) for hepatic metastases for colorectal cancer; however, the optimal treatment regimen remains inconclusive. Here, we aim to compare these therapies in terms of patient survival rate, intrahepatic recurrence rate, and adverse events.Different databases were searched for controlled trials up to June 30, 2014. The pooled hazards ratios for death and odds ratios (ORs) for intrahepatic recurrence and adverse events were estimated. A mean ranking and the probability of optimal therapeutic regime was obtained for each treatment analyzed in the network meta-analysis.Eleven eligible articles were included. Systemic chemotherapy (SCT) was ranked the most efficacious intervention among ACTs in both 1-year and 5-year survival; however, no statistical difference could be determined. Combination of bevacizumab (BEV) and hepatic arterial infusion (HAI) plus SCT was the most effective in preventing intrahepatic recurrence when compared with HAI alone (OR 1.21, 95% confidence interval [CI] 0.01-131.12), SCT (OR 2.37, 95% CI 0.03-234.16), HAI plus SCT (OR 0.97, 95% CI 0.03-35.30), SCT plus irinotecan (OR 1.01, 95% CI 0.00-278.14) and observation alone (OR 0.83, 95% CI 0.01-59.53). BEV and HAI plus SCT provided the least survival benefit after both 1 and 5 years compared with remaining therapies, and also was ranked the regiment with the least favorable adverse event profile among ACTs.SCT may be the most efficacious intervention, however, the potential benefit should be carefully considered with the regime's associated toxicities. Combination of BEV and HAI plus SCT was effective in preventing intrahepatic relapse but was associated with the highest risk for adverse events in patients with resected hepatic metastases for colorectal cancer.
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Affiliation(s)
- Gui-Qi Zhu
- From the Department of Infection and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University (GQZ, KQS, SYH, LRW, YPC, MHZ); School of the First Clinical Medical Sciences, Wenzhou Medical University (GQZ, SYH, LRW); Department of Oncological Surgery, the First Affiliated Hospital of Wenzhou Medical University (JY); Institute of Hepatology, Wenzhou Medical University, Wenzhou, China (KQS, YPC, MHZ); and Global Medicines Development, AstraZeneca R&D, Loughborough, United Kingdom (MB)
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Oba M, Hasegawa K, Matsuyama Y, Shindoh J, Mise Y, Aoki T, Sakamoto Y, Sugawara Y, Makuuchi M, Kokudo N. Discrepancy between recurrence-free survival and overall survival in patients with resectable colorectal liver metastases: a potential surrogate endpoint for time to surgical failure. Ann Surg Oncol 2014; 21:1817-1824. [PMID: 24499828 DOI: 10.1245/s10434-014-3504-1] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Indexed: 02/19/2025]
Abstract
BACKGROUND Recurrence-free survival (RFS) may not be a surrogate for overall survival (OS) in patients with resectable colorectal liver metastases (CLM). We investigated whether a new composite tool-time to surgical failure (TSF)-is a suitable endpoint. METHODS The medical records of consecutive patients who underwent curative resection for CLM at our center over a 17-year period were reviewed. Patients with liver-limited tumors (n = 371) who had not received previous treatment for metastasis were eligible for analysis. TSF was defined as the time until unresectable relapse or death. The correlations between TSF and OS, and between RFS and OS, were assessed for all the eligible patients. RESULTS The median OS, TSF, and RFS were 5.7, 2.7, and 0.7 years, respectively, and the 5-year OS, TSF, and RFS rates were 52.6, 39.8, and 23.7 %, respectively, for all patients. The rates of first, second, and third relapse were 75.5, 77.6, and 70.8 %, respectively, and repeat resections were performed in 54.3 % (first relapses), 40.7 % (second relapses), and 47.1 % (third relapses) of patients. The concordance proportions of TSF and RFS for OS events were 0.83 and 0.65, respectively. The correlation between TSF and OS was stronger than that between RFS and OS in terms of the predicted probabilities. CONCLUSIONS The correlation between TSF and OS was stronger than that between RFS and OS after curative hepatic resection. TSF could be a suitable endpoint for CLM overall management.
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Affiliation(s)
- Masaru Oba
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Zhu D, Zhong Y, Wei Y, Ye L, Lin Q, Ren L, Ye Q, Liu T, Xu J, Qin X. Effect of neoadjuvant chemotherapy in patients with resectable colorectal liver metastases. PLoS One 2014; 9:e86543. [PMID: 24466143 PMCID: PMC3897724 DOI: 10.1371/journal.pone.0086543] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2013] [Accepted: 12/13/2013] [Indexed: 12/21/2022] Open
Abstract
Background Whether patients with resectable colorectal liver metastases (CRLM) receive survival benefit from neoadjuvant chemotherapy remains controversial. Methods We retrospectively analyzed 466 patients with resectable CRLM between 2000 and 2010. Patient characteristics and survival data were recorded. Results The patients were divided into one group with neoadjuvant chemotherapy (group NC, n = 121) and another without (group WN, n = 345). There was no difference in 5-year survival (52% vs. 48%) between the two groups. No significant differences were identified between the two groups in terms of 30-day mortality (1.7% vs. 1.2%) or morbidity (33.9% vs. 25.8%). A primary tumor at stage T4, ≥4 liver metastases, the largest liver metastasis ≥5 cm in diameter, and a serum CEA level ≥5 ng/ml were independent prognostic factors. By assigning one point to each, the patients were divided into a low-risk group (0–2) and a high-risk (3–4). The patients in the low-risk group received no survival benefit from neoadjuvant chemotherapy, whereas those in the high-risk group received survival benefit (5-year survival, 39% vs. 33%, P = 0.028). Conclusions Preoperative neoadjuvant chemotherapy did not increase mortality or complications. Not all resectable patients, only those with >2 independent risk factors, received survival benefit from neoadjuvant chemotherapy.
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Affiliation(s)
- Dexiang Zhu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yunshi Zhong
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ye Wei
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lechi Ye
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qi Lin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Li Ren
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qinghai Ye
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tianshu Liu
- Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jianmin Xu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- * E-mail:
| | - Xinyu Qin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Mauer M, Tanis E, Van Cutsem E, Scheithauer W, Gruenberger T. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 2013; 14:1208-15. [PMID: 24120480 DOI: 10.1016/s1470-2045(13)70447-9] [Citation(s) in RCA: 910] [Impact Index Per Article: 75.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Previous results of the EORTC intergroup trial 40983 showed that perioperative chemotherapy with FOLFOX4 (folinic acid, fluorouracil, and oxaliplatin) increases progression-free survival (PFS) compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Here we present overall survival data after long-term follow-up. METHODS This randomised, controlled, parallel-group, phase 3 study recruited patients from 78 hospitals across Europe, Australia, and Hong Kong. Eligible patients aged 18-80 years who had histologically proven colorectal cancer and up to four liver metastases were randomly assigned (1:1) to either perioperative FOLFOX4 or surgery alone. Perioperative FOLFOX4 consisted of six 14-day cycles of oxaliplatin 85mg/m(2), folinic acid 200 mg/m(2) (DL form) or 100 mg/m(2) (L form) on days 1-2 plus bolus, and fluorouracil 400 mg/m(2) (bolus) and 600 mg/m(2) (continuous 22 h infusion), before and after surgery. Patients were centrally randomised by minimisation, adjusting for centre and risk score and previous adjuvant chemotherapy to primary surgery for colorectal cancer, and the trial was open label. Analysis of overall survival was by intention to treat in all randomly assigned patients. FINDINGS Between Oct 10, 2000, and July 5, 2004, 364 patients were randomly assigned to a treatment group (182 patients in each group, of which 171 per group were eligible and 152 per group underwent resection). At a median follow-up of 8·5 years (IQR 7·6-9·5), 107 (59%) patients in the perioperative chemotherapy group had died versus 114 (63%) in the surgery-only group (HR 0·88, 95% CI 0·68-1·14; p=0·34). In all randomly assigned patients, median overall survival was 61·3 months (95% CI 51·0-83·4) in the perioperative chemotherapy group and 54·3 months (41·9-79·4) in the surgery alone group. 5-year overall survival was 51·2% (95% CI 43·6-58·3) in the perioperative chemotherapy group versus 47·8% (40·3-55·0) in the surgery-only group. Two patients in the perioperative chemotherapy group and three in the surgery-only group died from complications of protocol surgery, and one patient in the perioperative chemotherapy group died possibly as a result of toxicity of protocol treatment. INTERPRETATION We found no difference in overall survival with the addition of perioperative chemotherapy with FOLFOX4 compared with surgery alone for patients with resectable liver metastases from colorectal cancer. However, the previously observed benefit in PFS means that perioperative chemotherapy with FOLFOX4 should remain the reference treatment for this population of patients. FUNDING Norwegian and Swedish Cancer Societies, Cancer Research UK, Ligue Nationale Contre Cancer, US National Cancer Institute, Sanofi-Aventis.
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Affiliation(s)
- Bernard Nordlinger
- Department of Surgery and Oncology, Centre Hospitalier Universitaire Ambroise Paré, Assistance Publique-Hôpitaux de Paris, Université de Versailles, Boulogne-Billancourt, France.
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Luu C, Arrington AK, Schoellhammer HF, Singh G, Kim J. Targeted therapies in colorectal cancer: surgical considerations. J Gastrointest Oncol 2013; 4:328-36. [PMID: 23997944 DOI: 10.3978/j.issn.2078-6891.2013.032] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2013] [Accepted: 05/13/2013] [Indexed: 12/27/2022] Open
Abstract
Colorectal cancer (CRC) is a leading worldwide health concern that is responsible for thousands of deaths each year. The primary source of mortality for patients with CRC is the development and subsequent progression of metastatic disease. The most common site for distant metastatic disease is the liver. Although patients with metastatic disease to the liver have several effective treatment options, the only one for cure remains surgical resection of the liver metastases. Historically, most patients with liver metastases have had unresectable disease, and only a small percentage of patients have undergone complete curative resection. However, improved systemic therapies have led to an evolution in strategies to treat metastatic CRC to the liver. Under most conditions the management of these patients remains complex; and as chemotherapy options and new targeted therapies continue to improve outcomes, it is clear that a multidisciplinary approach must be the foundation on which advanced surgical and medical techniques are employed. Here, in this review, we highlight the role of targeted therapies in the surgical management of patients with metastatic CRC to the liver.
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Affiliation(s)
- Carrie Luu
- Division of Surgical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
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Matsuda A, Matsumoto S, Seya T, Matsutani T, Kishi T, Yokoi K, Wang P, Uchida E. Does postoperative complication have a negative impact on long-term outcomes following hepatic resection for colorectal liver metastasis?: a meta-analysis. Ann Surg Oncol 2013; 20:2485-2492. [PMID: 23620215 DOI: 10.1245/s10434-013-2972-z] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2012] [Indexed: 12/31/2022]
Abstract
BACKGROUND The negative impact of postoperative complications (POCs) on long-term outcomes is well documented for several cancer surgeries, but conclusive evidence has yet to be provided on the influence of POCs on long-term oncological outcomes after hepatic resection for colorectal liver metastasis (CRLM). METHODS Studies published through February 2012 evaluating the oncological impact of POCs after hepatectomy for CRLM were identified by an electronic literature search. Finally, 4 studies were identified and included in the meta-analysis. The main outcome measures were 5-year disease-free survival (DFS) and overall survival (OS). A meta-analysis was performed using the DerSimonian-Laird random-effects models to compute odds ratio (OR) along with 95 % confidence intervals (95 % CI). RESULTS The outcomes of 2,280 patients were studied. Meta-analysis of 5-year DFS data extracted from three studies demonstrated a significant reduction in 5-year DFS after POCs, with an OR of 1.98 (95 % CI = 1.33-2.96; P = .0008). Meta-analysis of 5-year OS data extracted from four studies demonstrated a significant reduction in 5-year OS after POCs, with an OR of 1.68 (95 % CI = 1.25-2.27; P = .0006). No differences between study heterogeneity were observed in either the DFS or the OS analyses. CONCLUSIONS This study provides persuasive evidence that POCs following hepatic resection for CRLM have significant adverse oncological outcomes. These findings emphasize the need for meticulous surgical technique and careful perioperative management to minimize POCs.
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Affiliation(s)
- Akihisa Matsuda
- Department of Surgery, Nippon Medical School Chiba-Hokuso Hospital, Chiba, Japan.
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Benhaim L, Goéré D, Deschamps F, Dumont F, Bonnet S, Honoré C, Malka D, Boige V, De Baere T, Elias D. Placement of an arterial hepatic catheter after a major hepatectomy for colorectal liver metastases: Is this safe? EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2013; 39:640-7. [DOI: 10.1016/j.ejso.2013.02.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Revised: 12/20/2012] [Accepted: 02/01/2013] [Indexed: 11/25/2022]
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Qi J, Fong Y, Saltz L, D'Angelica MI, Kemeny NE, Gonen M, Shia J, Shukla-Dave A, Jarnagin WM, Do RKG, Schwartz LH, Koutcher JA, Zakian KL. Serial measurement of hepatic lipids during chemotherapy in patients with colorectal cancer: a 1 H MRS study. NMR IN BIOMEDICINE 2013; 26:204-12. [PMID: 22961714 PMCID: PMC3519948 DOI: 10.1002/nbm.2837] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2012] [Revised: 06/20/2012] [Accepted: 06/21/2012] [Indexed: 05/12/2023]
Abstract
Hepatic steatosis is a hallmark of chemotherapy-induced liver injury. We made serial (1) H MRS measurements of hepatic lipids in patients over the time course of a 24-week chemotherapeutic regimen to determine whether (1) H MRS could be used to monitor the progression of chemotherapy-induced steatosis. Thirty-four patients with stage III or IV colorectal cancer receiving 5-fluorouracil, folinic acid and oxaliplatin (n=21) or hepatic arterial infusion of floxuridine with systemic irinotecan (n=13) were studied prospectively. (1) H MRS studies were performed at baseline and after 6 and 24 weeks of treatment. A (1) H MR spectrum was acquired from the liver during a breath hold and the ratio of fat to fat+water (FFW) was calculated to give a measure of hepatic triglycerides (HTGCs). The methodology was histologically validated in 18 patients and the reproducibility was assessed in 16 normal volunteers. Twenty-seven patients completed baseline, 6-week and 24-week (1) H MRS examinations and one was censored. Thirteen of 26 patients (50%) showed an increase in FFW after completion of treatment. Six patients (23%) developed hepatic steatosis and two patients converted from steatosis to nonsteatotic liver. Patients whose 6-week hepatic lipid levels had increased significantly relative to baseline also had a high probability of lipid elevation relative to baseline at the completion of treatment. Serial (1) H MRS is effective for the monitoring of HTGC changes during chemotherapy and for the detection of chemotherapy-associated steatosis. Six of 26 patients developed steatosis during chemotherapy. Lipid changes were observable at 6 weeks.
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Affiliation(s)
- Jing Qi
- Memorial Sloan-Kettering Cancer Center, New York, New York, USA
| | - Yuman Fong
- Memorial Sloan-Kettering Cancer Center, New York, New York, USA
| | - Leonard Saltz
- Memorial Sloan-Kettering Cancer Center, New York, New York, USA
| | | | - Nancy E. Kemeny
- Memorial Sloan-Kettering Cancer Center, New York, New York, USA
| | - Mithat Gonen
- Memorial Sloan-Kettering Cancer Center, New York, New York, USA
| | - Jinru Shia
- Memorial Sloan-Kettering Cancer Center, New York, New York, USA
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Behl AS, Goddard KAB, Flottemesch TJ, Veenstra D, Meenan RT, Lin JS, Maciosek MV. Cost-effectiveness analysis of screening for KRAS and BRAF mutations in metastatic colorectal cancer. J Natl Cancer Inst 2012. [PMID: 23197490 DOI: 10.1093/jnci/djs433] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND In 2009, the American Society of Clinical Oncology recommended that patients with metastatic colorectal cancer (mCRC) who are candidates for anti-epidermal growth factor receptor (EGFR) therapy have their tumors tested for KRAS mutations because tumors with such mutations do not respond to anti-EGFR therapy. Limiting anti-EGFR therapy to those without KRAS mutations will reserve treatment for those likely to benefit while avoiding unnecessary costs and harm to those who would not. Similarly, tumors with BRAF genetic mutations may not respond to anti-EGFR therapy, though this is less clear. Economic analyses of mutation testing have not fully explored the roles of alternative therapies and resection of metastases. METHODS This paper is based on a decision analytic framework that forms the basis of a cost-effectiveness analysis of screening for KRAS and BRAF mutations in mCRC in the context of treatment with cetuximab. A cohort of 50 000 patients with mCRC is simulated 10 000 times, with attributes randomly assigned on the basis of distributions from randomized controlled trials. RESULTS Screening for both KRAS and BRAF mutations compared with the base strategy (of no anti-EGFR therapy) increases expected overall survival by 0.034 years at a cost of $22 033, yielding an incremental cost-effectiveness ratio of approximately $650 000 per additional year of life. Compared with anti-EGFR therapy without screening, adding KRAS testing saves approximately $7500 per patient; adding BRAF testing saves another $1023, with little reduction in expected survival. CONCLUSIONS Screening for KRAS and BFAF mutation improves the cost-effectiveness of anti-EGFR therapy, but the incremental cost effectiveness ratio remains above the generally accepted threshold for acceptable cost effectiveness ratio of $100 000/quality adjusted life year.
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Affiliation(s)
- Ajay S Behl
- HealthPartners Research Foundation, 8170 33rd Ave. S., Mail Stop 21111R, Bloomington, MN 55425, USA.
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Eveno C, Pocard M. VEGF levels and the angiogenic potential of the microenvironment can affect surgical strategy for colorectal liver metastasis. Cell Adh Migr 2012; 6:569-73. [PMID: 23257830 DOI: 10.4161/cam.23247] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The hypotheses emerging from basic research on colorectal liver metastases must be tested in clinical situations for the adaptation of current treatment strategies. Pre-metastatic niches have been shown to exist in human colorectal synchronous metastases, with the liver parenchyma adjacent to the synchronous liver metastases providing a favorable, angiogenic environment for metastatic tumor growth. The role of the VEGF signaling pathway in liver regeneration and tumor growth remains unclear, but the use of antiangiogenic agents in combination with surgical treatment is almost certainly beneficial.
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Affiliation(s)
- Clarisse Eveno
- INSERM U965 Angiogenesis and Translational Research; Paris-Diderot Paris 7 University, Hôpital Lariboisière, Paris, France
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Turan N, Benekli M, Koca D, Ustaalioglu BO, Dane F, Ozdemir N, Ulas A, Oztop I, Gumus M, Ozturk MA, Berk V, Kucukoner M, Uner A, Balakan O, Helvaci K, Ozkan S, Yilmaz U, Buyukberber S. Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected liver metastases from colorectal cancer. Oncology 2012; 84:14-21. [PMID: 23076023 DOI: 10.1159/000342429] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2012] [Accepted: 08/02/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND We aimed to investigate the impact of adjuvant systemic therapy with modern chemotherapy combinations on survival outcomes in patients with resected liver-confined metastases from colorectal carcinomas, and whether addition of bevacizumab (BEV) provides further benefit. METHODS A total of 229 consecutive patients who underwent resection for liver-confined colorectal liver metastases were retrospectively analyzed. RESULTS Of 229 patients, 204 who received chemotherapy with fluoropyrimidine-based (n = 27), irinotecan-based (n = 84) and oxaliplatin-based (n = 93) combinations were analyzed. Among these, 87 patients received BEV while 117 did not (NoBEV). With a median follow-up of 27 months after metastasectomy, the median recurrence-free survival (RFS) and overall survival (OS) were 17 and 53 months, respectively. OS rates at 3 and 5 years were 71% and 40%, respectively. No significant differences were found in the median RFS (p = 0.744) and OS (p = 0.440) among different chemotherapy regimens. The median RFS (p = 0.375) and OS (p = 0.251) were similar in BEV and NoBEV arms. In multivariate analysis, having 4 liver metastases was the only negative independent factor on both RFS and OS, while positive surgical margin was another negative independent factor for RFS. CONCLUSION Chemotherapy type and addition of BEV have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal liver metastases.
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Affiliation(s)
- Nedim Turan
- Department of Medical Oncology, Gazi University Faculty of Medicine, Ankara, Turkey.
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Wanebo HJ, LeGolvan M, Paty PB, Saha S, Zuber M, D’Angelica MI, Kemeny NE. Meeting the biologic challenge of colorectal metastases. Clin Exp Metastasis 2012; 29:821-39. [DOI: 10.1007/s10585-012-9517-x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Accepted: 07/09/2012] [Indexed: 12/20/2022]
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Fornaro L, Masi G, Caparello C, Vivaldi C, Falcone A. Resectable liver metastases from colorectal cancer: where we are now and where do we go from here? COLORECTAL CANCER 2012. [DOI: 10.2217/crc.12.47] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
SUMMARY Liver metastases from colorectal cancer represent a peculiar clinical scenario in everyday practice, since treatment should achieve long-term survival or even a cure in selected patients. Presentation may vary between single cases, ranging from easily resectable lesions to more advanced metastatic spreading for which surgery can only be considered after major tumor shrinkage. For resectable liver metastases, surgery remains the essential step in the curative approach to the disease, even though different ablative procedures may be considered as valuable alternatives in certain subsets. Postoperative or perioperative chemotherapy may further improve long-term outcome, even though treatment benefits and harms related to liver toxicity should be carefully balanced in each patient. A comprehensive multidisciplinary assessment of patient- and tumor-related features remains the key to complement the clinical aspects with the biological characterization in the framework of a personalized therapeutic approach.
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Affiliation(s)
- Lorenzo Fornaro
- Istituto di Scienze della Vita, Scuola Superiore di Studi Universitari e di Perfezionamento Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
| | - Gianluca Masi
- UO Oncologia Medica 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Chiara Caparello
- UO Oncologia Medica 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Caterina Vivaldi
- UO Oncologia Medica 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
| | - Alfredo Falcone
- UO Oncologia Medica 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy
- Dipartimento di Oncologia, dei Trapianti e delle Nuove Tecnologie in Medicina, Università di Pisa, Via Roma 55, 56126 Pisa, Italy
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Sperling J, Ziemann C, Schuld J, Laschke MW, Schilling MK, Menger MD, Kollmar O. A comparative evaluation of ablations produced by high-frequency coagulation-, argon plasma coagulation-, and cryotherapy devices in porcine liver. Int J Colorectal Dis 2012; 27:1229-35. [PMID: 22648175 DOI: 10.1007/s00384-012-1504-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/10/2012] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Hepatic resection is the only curative treatment option for primary or metastatic malignancies of the liver. Although R1 resections can also lead to prolonged survival, the main surgical goal is complete tumor resection (R0). To achieve this, additional treatment of the resection margin with ablation devices is discussed. Using a porcine in vivo model, we therefore analyzed the effect of different ablation devices on depth and completeness of hepatic parenchymal cell destruction. METHODS Swabian-Hall strain pigs underwent ablation on the surface of the right, middle, or left liver lobe using seven different types of high-frequency (HF)-, cryotherapy (Cryo)-, or argon plasma coagulation (APC) devices. Penetration depth and volume were analyzed from histological sections. Severity of parenchymal cell destruction was assessed by a histomorphological score. RESULTS The greatest penetration depth was achieved with Cryo (10.4 ± 1.7 mm), whereas HF and APC exhibited a smaller penetration depth. However, HF and APC compared to Cryo achieved complete destruction of the intralobular architecture and hepatocellular morphology depending on the application time and the adjusted power. CONCLUSION HF, APC, and Cryo applied to the liver surface induce different parenchymal penetration depth and cell destruction. HF and APC are considered to be standard surgical instruments and therefore recommended as standard treatment, whereas Cryo may be used only if particularly deep penetration is required.
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Affiliation(s)
- J Sperling
- Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany.
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Kanat O, Gewirtz A, Kemeny N. What is the potential role of hepatic arterial infusion chemo-therapy in the current armamentorium against colorectal cancer. J Gastrointest Oncol 2012; 3:130-138. [PMID: 22811880 PMCID: PMC3397645 DOI: 10.3978/j.issn.2078-6891.2011.025] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2011] [Accepted: 06/30/2011] [Indexed: 12/30/2022] Open
Abstract
The management of colorectal cancer patients with liver metastases is a common clinical problem. If patients can undergo resection of liver metastases, long-term survival can be achieved. Converting a patient from unresectable to resectable, however, remains a major challenge. The majority of patients who undergo liver resection for colorectal metastases recur; therefore, adjuvant treatment following resection should be considered. Emerging literature suggests that hepatic arterial infusion (HAI) can be combined with systemic chemotherapy. Both therapies can be given at nearly full doses, thus improving resectability and outcomes for patients with colorectal liver metastases. HAI plus systemic can also be a useful option for adjuvant treatment after hepatic resection.
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Affiliation(s)
- Ozkän Kanat
- Memorial Sloan Kettering Cancer Center, GI Medicine, New York, New York, USA
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Shimada Y. Chemotherapy and molecular-targeted treatment for unresectable hepatic metastases: a Japanese perspective. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2012; 19:515-22. [PMID: 22588204 DOI: 10.1007/s00534-012-0517-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
Liver metastasis from colorectal cancer has become a common disease associated with the increase of primary colorectal cancer in Japan. The standard treatment for resectable liver metastases is still complete liver resection. Recent advances in systemic chemotherapy have introduced another strategy, i.e., conversion chemotherapy, for patients with initially diagnosed unresectable liver metastases. The conversion rate after neo-adjuvant chemotherapy is increasing with multidisciplinary approaches. Long-term clinical data have not been established yet. Indications for liver resection after neo-adjuvant chemotherapy; optimal chemotherapy regimens; and histological changes in the normal liver are important research issues for the future.
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Affiliation(s)
- Yasuhiro Shimada
- Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
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Shin SJ, Ahn JB, Choi JS, Choi GH, Lee KY, Baik SH, Min BS, Hur H, Roh JK, Kim NK. Implications of clinical risk score to predict outcomes of liver-confined metastasis of colorectal cancer. Surg Oncol 2012; 21:e125-30. [PMID: 22560405 DOI: 10.1016/j.suronc.2012.04.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2012] [Revised: 04/04/2012] [Accepted: 04/05/2012] [Indexed: 12/11/2022]
Abstract
OBJECTIVE/BACKGROUND We investigated the usefulness of a clinical risk scoring system (CRS) for guiding management and defining prognosis for patients with colorectal liver met"astases (CLM). METHOD We retrospectively analyzed data about the correlation between outcomes and Fong's CRS from 1989 to 2010 for patients treated for CLM at the Severance Hospital. RESULTS Of 566 patients, 232 received adjuvant treatment after liver resection. Of these patients, 185 (81%) had a low CRS (0-2) and 47 (19%) had a high CRS (3-5). Stratification into high and low CRS allowed significant distinction between Kaplan-Meier curves for outcome. The 5-year survival rate was 88.5% and 11.5% among patients with a low and high CRS, respectively (P < 0.001). Seventy patients with initially unresectable CLM underwent liver resection after tumor downsizing by induction chemotherapy. Shifting of the CRS from high to low (8 patients; 11.4%) improved disease-free survival and overall survival. CONCLUSION High CRS is associated with worse survival after resection in resectable and unresectable disease. The CRS may be used for risk assessment when recommending oncological surgical timing in initially unresectable disease and treatment options for perioperative or adjuvant treatment in resectable disease.
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Affiliation(s)
- Sang Joon Shin
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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Cucchetti A, Ercolani G, Cescon M, Bigonzi E, Peri E, Ravaioli M, Pinna AD. Impact of subcentimeter margin on outcome after hepatic resection for colorectal metastases: A meta-regression approach. Surgery 2012; 151:691-9. [DOI: 10.1016/j.surg.2011.12.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2011] [Accepted: 12/09/2011] [Indexed: 10/14/2022]
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Predictive factors for the benefit of perioperative FOLFOX for resectable liver metastasis in colorectal cancer patients (EORTC Intergroup Trial 40983). Ann Surg 2012; 255:534-9. [PMID: 22314329 DOI: 10.1097/sla.0b013e3182456aa2] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE In EORTC study 40983, perioperative FOLFOX increased progression-free survival (PFS) compared with surgery alone for patients with initially 1 to 4 resectable liver metastases from colorectal cancer (CRC). We conducted an exploratory retrospective analysis to identify baseline factors possibly predictive for a benefit of perioperative FOLFOX on PFS. METHODS The analysis was based on 237 events from 342 eligible patients. Cox proportional hazards regression models with a significance level of 0.1 were used to build up univariate and multivariate models. RESULTS After adjustment for identified prognostic factors, moderately (5.1-30 ng/mL) and highly (>30 ng/mL) elevated carcinoembryonic antigen (CEA) serum levels were both predictive for the benefit of perioperative chemotherapy (interaction P = 0.07; hazard ratio [HR] = 0.58 and HR = 0.52 for treatment benefit). For patients with moderately or highly elevated CEA (>5 ng/mL), the 3-year PFS was 35% with perioperative chemotherapy compared to 20% with surgery alone. Performance status (PS) 0 and BMI lower than 30 were also predictive for the benefit of perioperative chemotherapy (interaction P = 0.04 and P = 0.02). However, the number of patients with PS 1 and BMI 30 or higher were limited. The benefit of perioperative therapy was not influenced by the number of metastatic lesions (1 vs 2-4, interaction HR = 0.98). CONCLUSIONS Perioperative FOLFOX seems to benefit in particular patients with resectable liver metastases from CRC when CEA is elevated and when PS is unaffected, regardless of the number of metastatic lesions.ClinicalTrials.gov number NCT00006479.
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Schirin-Sokhan R, Winograd R, Roderburg C, Bubenzer J, Ó NCD, Guggenberger D, Hecker H, Trautwein C, Tischendorf JJW. Response evaluation of chemotherapy in metastatic colorectal cancer by contrast enhanced ultrasound. World J Gastroenterol 2012; 18:541-5. [PMID: 22363120 PMCID: PMC3280399 DOI: 10.3748/wjg.v18.i6.541] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2010] [Revised: 10/26/2010] [Accepted: 11/09/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate whether contrast enhanced ultrasound (CEUS) might also be used for response prediction and early response evaluation in patients receiving bevacizumab based chemotherapy for metastasized colorectal cancer.
METHODS: Thirty consecutive patients with non primary resectable liver metastases from colorectal cancer underwent CEUS before treatment (CEUS date 1) and before the second (CEUS date 2) and fourth (CEUS date 3) cycle of bevacizumab based chemotherapy. Three parameters [PEAK, Time to peak (TTP) and RISE RATE]were correlated with radiological response.
RESULTS: For neoadjuvant purpose a reduction of tumour mass was required to assume clinical response. Based on these response criteria there was a significant (P < 0.001) correlation in TTP between metastases of responders (9.08 s) and non-responders (14.76 s) archived on CEUS date 1. By calculating a standardized quotient (metastases divided by normal liver tissue) we were able to define a cut off, predicting response with a sensitivity of 92.3 % and a specificity of 100 %. To reflect a palliative intention only those patients with progressive disease were classified as non-responders. In this stetting TTP was also significantly (P < 0.01) different between responders and non-responders. In contrast, Peak and Rise rate did not show any significant difference between responder and non-responder.
CONCLUSION: CEUS might serve as a surrogate marker to predict treatment response in patients with metastasized colorectal cancer who receive antiangiogenic therapy.
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Nishida N, Yamashita S, Mimori K, Sudo T, Tanaka F, Shibata K, Yamamoto H, Ishii H, Doki Y, Mori M. MicroRNA-10b is a prognostic indicator in colorectal cancer and confers resistance to the chemotherapeutic agent 5-fluorouracil in colorectal cancer cells. Ann Surg Oncol 2012; 19:3065-71. [PMID: 22322955 DOI: 10.1245/s10434-012-2246-1] [Citation(s) in RCA: 127] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2011] [Indexed: 12/19/2022]
Abstract
PURPOSE Recent evidence has shown that altered patterns of microRNA (miRNA) expression correlate with various human cancers. We investigated the clinical significance of miR-10b and its involvement in chemotherapeutic resistance to 5-fluorouracil (5-FU), which is a key component of common chemotherapy regimens in colorectal cancer. METHODS Quantitative RT-PCR was used to evaluate the clinicopathologic significance of miR-10b expression in 88 colorectal cancer cases. We also investigated the chemotherapeutic sensitivity to 5-FU in miR-10b-overexpressing colorectal cancer cells. To explore the mechanism of chemoresistance in miR-10b transfected cells, we examined whether miR-10b inhibits the pro-apoptotic BH3-only Bcl-2 family member BIM(BCL2L11), a key mediator of chemotherapy-induced cell death. RESULTS High level miR-10b expression was found to be significantly associated with high incidence of lymphatic invasion (P = 0.0257) and poor prognosis (P = 0.0057). Multivariate analysis indicated that high miR-10b expression is an independent prognostic factor for survival. In vitro studies revealed that miR-10b directly inhibits pro-apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU. CONCLUSIONS MiR-10b is a novel prognostic marker in colorectal cancer. Moreover, the expression of miR-10b is a potential indicator of chemosensitivity to the common 5-FU-based chemotherapy regimen.
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Affiliation(s)
- Naohiro Nishida
- Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Oita, Japan
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Parikh AA, Ellis LM. Circulating angiogenic factors, tumor cells, and outcome after resection of metastatic colorectal cancer--what does it mean? Ann Surg Oncol 2011; 18:2111-3. [PMID: 21626082 DOI: 10.1245/s10434-011-1765-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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