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Phillips MJ, Alese OB, Horvat NK, Greene E, Gbolahan OB, Coleman K, Doxie DB, Parihar V, Mahdi ZK, McCook-Veal A, Switchenko JM, Diab M, Herting CJ, Paulos CM, El-Rayes BF, Lesinski GB. XL888 and pembrolizumab modulate the immune landscape of colorectal tumors in a phase Ib/II clinical trial. Oncoimmunology 2025; 14:2475620. [PMID: 40079916 PMCID: PMC11913390 DOI: 10.1080/2162402x.2025.2475620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 02/17/2025] [Accepted: 03/02/2025] [Indexed: 03/15/2025] Open
Abstract
We conducted a phase Ib/II clinical trial to evaluate the safety, feasibility, and clinical activity of combining pembrolizumab (anti-PD-1) with XL888 (Hsp90 inhibitor) in patients with advanced colorectal cancer (CRC). We hypothesized that this regimen would modulate soluble and cellular immune mediators and enhance clinical outcomes. The trial employed a 3 + 3 open-label design, with an expansion cohort at the recommended phase II dose (RP2D) in treatment-refractory, mismatch repair-proficient CRC patients. Comprehensive analyses of plasma cytokines, peripheral blood mononuclear cells (PBMCs), and spatial immune cell patterns in liver biopsies were performed to identify unique immune signatures resulting from the combined therapy. The combination of pembrolizumab and XL888 proved to be safe and feasible, with a subset of patients achieving stable disease, although no objective responses were observed in this heavily pre-treated population. Correlative studies revealed immunomodulatory effects in tumors and circulation, including a reduction in IL6+ cells and macrophages (CD68+) within metastatic liver tissue, alterations in blood CD3+ cells, and upregulation of numerous inflammatory plasma cytokines. These findings suggest local and systemic immune activation by the combination of pembrolizumab and XL888. While clinical activity was modest in treatment-refractory CRC patients, there were notable effects on the tumor immune environment and systemic immune modulation.
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Affiliation(s)
- Maggie J. Phillips
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Olatunji B. Alese
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Natalie K. Horvat
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Emily Greene
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Olumide B. Gbolahan
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | | | - Deon B. Doxie
- Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Vaunita Parihar
- Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Zaid K. Mahdi
- Department of Pathology, Emory University, Atlanta, GA, USA
| | - Ashley McCook-Veal
- Department of Biostatistics & Bioinformatics, Emory University, Atlanta, GA, USA
| | | | - Maria Diab
- Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, USA
| | - Cameron J. Herting
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Chrystal M. Paulos
- Department of Surgery, Emory University, Atlanta, GA, USA
- Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA
| | - Bassel F. El-Rayes
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Gregory B. Lesinski
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
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Shi X, Huang C, Lu S, Luo T, Qin Z, Zhu P, Zhang Q, Wu H, Wang X, Chen J, Tang W. Simultaneous curative resection may improve the long-term survival of patients diagnosed with colorectal liver metastases: A propensity score-matching study. Surgery 2025; 181:109144. [PMID: 39891967 DOI: 10.1016/j.surg.2024.109144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 12/07/2024] [Accepted: 12/13/2024] [Indexed: 02/03/2025]
Abstract
BACKGROUND The benefit of simultaneous curative resection in patients with colorectal liver metastases has been unclear. Adjuvant chemotherapy is still considered an effective and priority treatment for advanced-stage colorectal patients. METHODS We retrospectively collected patients with colorectal liver metastases from January 2012 to October 2023 at the Guangxi Medical University Cancer Hospital. The baseline information was compared between a simultaneous curative resection group and a palliative treatment group. Propensity score matching with a 1:1 ratio was applied to develop comparable cohorts of curative resection and palliative treatment resection. Kaplan-Meier survival and Cox regression analyses were performed to determine the impact of curative resection on survival of colorectal liver metastasis patients. Prognostic nomogram and a web-version calculator were developed based on the multivariate Cox regression method. Then, the concordance index (C-index), receiver operating characteristic, calibration plots, and decision curves analysis were applied to evaluate the prognostic performance of the nomogram. RESULTS A total of 716 patients with colorectal liver metastases were enrolled in the study, of whom 131 patients received curative resection. There was no significant difference in terms of baseline information between the curative resection group and the palliative treatment group after propensity score matching. Multivariable Cox regression analysis showed that curative resection was an independent prognostic factor affecting overall survival (P = .001, hazard ratio = 1.95, 95% confidence interval 1.30-2.91). Compared with patients who did not receive curative resection, patients who received simultaneous curative resection had a significant improvement in overall survival before and after propensity score matching (P < .0001 and P = .0047, respectively). Overall survival nomogram showed excellent predictive performance with the C-indexes of 0.686 (95% confidence interval 0.556-0.792). The areas under the receiver operating characteristic curves were 0.75 (95% confidence interval 64.43-96.05), 0.75 (67.22-82.58), and 0.76 (66.10-85.98) for predicting 1-, 3-, and 5-year survival, respectively. The calibration plots and decision curves analysis also indicated the good predictability of the predictive nomogram. Finally, subgroup analysis further demonstrated a favorable impact of curative resection on overall survival in colorectal liver metastasis patients after propensity score matching. CONCLUSIONS Simultaneous curative resection may improve the overall survival of patients with colorectal liver metastases and is an independent and effective indicator for predicting overall survival. The nomogram may provide a personalized treatment strategy.
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Affiliation(s)
- Xianmao Shi
- Division of Colorectal and Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, China; Guangxi Key Laboratory of Basic and Translational Research for Colorectal Cancer, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Chunliu Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Shaolong Lu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Tao Luo
- Division of Colorectal and Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, China; Guangxi Key Laboratory of Basic and Translational Research for Colorectal Cancer, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Zhengjun Qin
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Peng Zhu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Qingyuan Zhang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Hualin Wu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xiaobo Wang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jie Chen
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Weizhong Tang
- Division of Colorectal and Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, China; Guangxi Key Laboratory of Basic and Translational Research for Colorectal Cancer, Guangxi Medical University Cancer Hospital, Nanning, China.
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Sawano H, Matsuoka H, Mizuno T, Kamiya T, Chong Y, Iwama H, Takahara T, Hiro J, Otsuka K, Ishihara T, Hayashi T, Suda K. Risk factors for residual liver recurrence of colorectal cancer after resection of liver metastases and significance of adjuvant chemotherapy. Asian J Surg 2024; 47:5124-5130. [PMID: 39034242 DOI: 10.1016/j.asjsur.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 04/05/2024] [Accepted: 07/04/2024] [Indexed: 07/23/2024] Open
Abstract
OBJECTIVE The risk factors for residual liver recurrence after resection of colorectal cancer liver metastases were analyzed separately for synchronous and metachronous metastases. METHODS This retrospective study included 236 patients (139 with synchronous and 97 with metachronous lesions) who underwent initial surgery for colorectal cancer liver metastases from April 2010 to December 2021 at the Fujita Health University Hospital. We performed univariate and multivariate analyses of risk factors for recurrence based on clinical background. RESULTS Univariate analysis of synchronous liver metastases identified three risk factors: positive lymph nodes (p = 0.018, HR = 2.067), ≥3 liver metastases (p < 0.001, HR = 2.382), and use of adjuvant chemotherapy (p = 0.013, HR = 0.560). Multivariate analysis identified the same three factors. For metachronous liver metastases, univariate and multivariate analysis identified ≥3 liver metastases as a risk factor (p = 0.002, HR = 2.988); however, use of adjuvant chemotherapy after hepatic resection was not associated with a lower risk of recurrence for metachronous lesions. Inverse probability of treatment weighting analysis of patients with these lesions with or without adjuvant chemotherapy after primary resection showed that patients with metachronous liver metastases who did not receive this treatment had fewer recurrences when adjuvant therapy was administered after subsequent liver resection, although the difference was not significant. Patients who received adjuvant chemotherapy after hepatic resection had less recurrence but less benefit from this treatment. CONCLUSION Risk factors for liver recurrence after resection of synchronous liver metastases were positive lymph nodes, ≥3 liver metastases, and no postoperative adjuvant chemotherapy. Adjuvant chemotherapy is recommended after hepatic resection of synchronous liver metastases.
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Affiliation(s)
- Hiroko Sawano
- College of Pharmacy, Kinjo Gakuin University, Nagoya, Japan
| | - Hiroshi Matsuoka
- Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan.
| | - Tomohiro Mizuno
- Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine, Toyoake, Japan
| | - Tadahiro Kamiya
- Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan
| | - Yongchol Chong
- Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan
| | - Hideaki Iwama
- Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan
| | - Takeshi Takahara
- Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan
| | - Junichiro Hiro
- Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan
| | - Koki Otsuka
- Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan
| | - Takuma Ishihara
- Innovative and Clinical Research Promotion Center, Gifu University Hospital, Yanagido, Gifu, Japan
| | | | - Kouichi Suda
- Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan
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Wu X, Liu W, Wang Y, Wang K, Xing B. Association of various RAS codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomy. Cancer Med 2024; 13:e70168. [PMID: 39377605 PMCID: PMC11459679 DOI: 10.1002/cam4.70168] [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: 06/27/2023] [Revised: 11/14/2023] [Accepted: 08/19/2024] [Indexed: 10/09/2024] Open
Abstract
PURPOSE The prognostic and predictive value of RAS mutations in patients with colorectal liver metastases (CRLM) who have undergone hepatectomy holds substantial importance. The present study aimed to investigate the impact of different RAS codon mutations on long-term survival in CRLM patients. METHODS A retrospective analysis was conducted on clinicopathological data from 399 CRLM patients with RAS mutations who underwent hepatectomy between January 2000 and December 2020. The RAS mutation gene status was assessed in KRAS codons (G12, G13, Q61, and A146) and NRAS codons (G12, G13, and Q61). Survival curves were generated using the Kaplan-Meier plotter and compared using the log-rank test. Univariate and multivariate analyses were performed to analyze the clinicopathological data. RESULTS In the entire cohort, patients with KRAS G12 mutations exhibited the most favorable prognosis (p = 0.018). Comparatively, patients harboring KRAS Q61 mutations experienced poorer overall survival (OS) with a median of 15 months versus 33 months (p = 0.011) when compared to those with KRAS G12 mutations. Moreover, patients with NRAS Q61 mutations also showed decreased OS with a median of 26 months versus 33 months (p = 0.020) in comparison to KRAS G12 mutation patients. The results of multivariate analysis showed that both KRAS Q61 mutation (HR 2.130; 95% CI 1.088-4.168; p = 0.027) and NRAS Q61 mutation (HR 2.877; 95% CI 1.398-5.922; p = 0.004) were independent influencing factors of OS. Based on all identified risk factors, patients with RAS mutation were divided into high-risk and low-risk groups. Notably, in the high-risk group, the incorporation of postoperative chemotherapy was associated with longer OS, while it did not improve the survival of patients in the low-risk group. CONCLUSIONS KRAS Q61 and NRAS Q61 mutations are promising predictors for OS in CRLM patients after hepatectomy. Postoperative chemotherapy may significantly benefit CRLM patients with RAS mutations, particularly those identified as high-risk.
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Affiliation(s)
- Xiao‐Gang Wu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department IPeking University Cancer Hospital & InstituteBeijingChina
| | - Wei Liu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department IPeking University Cancer Hospital & InstituteBeijingChina
| | - Yan‐Yan Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department IPeking University Cancer Hospital & InstituteBeijingChina
| | - Kun Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department IPeking University Cancer Hospital & InstituteBeijingChina
| | - Bao‐Cai Xing
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department IPeking University Cancer Hospital & InstituteBeijingChina
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Beppu T, Yamamura K, Imai K, Hayashi H, Miyamoto Y. Recurrence-risk stratification using the Beppu score and selection of perioperative chemotherapy for colorectal liver metastases. J Surg Oncol 2024; 129:893-900. [PMID: 38239092 DOI: 10.1002/jso.27590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 01/06/2024] [Indexed: 04/02/2024]
Abstract
The annual postoperative disease-free survival for colorectal liver metastases can be easily estimated by weighting six preoperative clinical parameters (Beppu score). We identified three recurrence-risk stratification groups: the low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). For low-, moderate-, and high-risk patients, hepatectomy alone, hepatectomy with adjuvant chemotherapy, and hepatectomy with preoperative chemotherapy are recommended, respectively. The Beppu score enables the decision on the necessity and timing of perioperative chemotherapy.
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Affiliation(s)
- Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Yamaga, Japan
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Kensuke Yamamura
- Department of Surgery, Yamaga City Medical Center, Yamaga, Japan
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
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Bernardi L, Roesel R, Aghayan DL, Majno-Hurst PE, De Dosso S, Cristaudi A. Preoperative chemotherapy in upfront resectable colorectal liver metastases: New elements for an old dilemma? Cancer Treat Rev 2024; 124:102696. [PMID: 38335813 DOI: 10.1016/j.ctrv.2024.102696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 02/01/2024] [Indexed: 02/12/2024]
Abstract
The use of preoperative or "neoadjuvant" chemotherapy (NAC) has long been controversial for resectable colorectal liver metastases (CRLM). The European Society of Medical Oncology (ESMO) 2023 guidelines on metastatic colorectal cancer (CRC) indicate a combination of surgical/technical and oncologic/prognostic criteria as the two determinants for allocating patients to NAC or upfront hepatectomy. However, surgical and technical criteria have evolved, and oncologic prognostic criteria date from the pre-modern chemotherapy era and lack prospective validation. The traditional literature is interpreted as not supporting the use of NAC because several studies fail to demonstrate a benefit in overall survival (OS) compared to upfront surgery; however, OS may not be the most appropriate endpoint to consider. Moreover, the commonly quoted studies against NAC contain many limitations that may explain why NAC failed to demonstrate its value. The query of the recent literature focused primarily on other aspects than OS, such as surgical technique, the impact of side effects of chemotherapy, the histological growth pattern of metastases, or the detection of circulating tumor DNA, shows data that support a more widespread use of NAC. These should prompt a critical reappraisal of the use of NAC, leading to a more precise selection of patients who could benefit from it.
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Affiliation(s)
- Lorenzo Bernardi
- Department of Surgery, Lugano Regional Hospital, Ente Ospedaliero Cantonale (EOC), Via Tesserete 46, 6900 Lugano, Switzerland
| | - Raffaello Roesel
- Department of Surgery, Lugano Regional Hospital, Ente Ospedaliero Cantonale (EOC), Via Tesserete 46, 6900 Lugano, Switzerland
| | - Davit L Aghayan
- Department of Surgery, Ringerike Hospital, Vestre Viken Hospital Trust, Drammen, Norway
| | - Pietro E Majno-Hurst
- Department of Surgery, Lugano Regional Hospital, Ente Ospedaliero Cantonale (EOC), Via Tesserete 46, 6900 Lugano, Switzerland; Faculty of Biomedical Sciences, University of Southern Switzerland (USI), Via Buffi 13, 6900 Lugano, Switzerland
| | - Sara De Dosso
- Faculty of Biomedical Sciences, University of Southern Switzerland (USI), Via Buffi 13, 6900 Lugano, Switzerland; Medical Oncology Department, Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Via A. Gallino 12, 6500 Bellinzona, Switzerland.
| | - Alessandra Cristaudi
- Department of Surgery, Lugano Regional Hospital, Ente Ospedaliero Cantonale (EOC), Via Tesserete 46, 6900 Lugano, Switzerland; Faculty of Biomedical Sciences, University of Southern Switzerland (USI), Via Buffi 13, 6900 Lugano, Switzerland
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Done JZ, Papanikolaou A, Stem M, Radomski SN, Chen SY, Atallah C, Efron JE, Safar B. Impact of preoperative chemotherapy on perioperative morbidity in combined resection of colon cancer and liver metastases. J Gastrointest Surg 2023; 27:2380-2387. [PMID: 37468732 DOI: 10.1007/s11605-023-05758-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 06/11/2023] [Indexed: 07/21/2023]
Abstract
BACKGROUND Preoperative chemotherapy, or neoadjuvant therapy (NAC) can be used to improve resectability but can also have hepatotoxic effects on the future liver remnant. The purpose of this study was to investigate the impact of NAC on 30-day morbidity among patients undergoing a resection of primary colon cancer and synchronous liver metastases (sLM). METHODS This was a retrospective study using the National Surgical Quality Improvement Program database (2012-2020). The association between NAC and 30-day overall morbidity, the primary outcome, was assessed. Subgroup analyses for low and high-risk procedures were performed. RESULTS Among 968 patients who underwent the combined resection, 571 (58.99%) received NAC. There was a lower rate of 30-day overall morbidity among patients who received NAC (34.50% vs. 41.56%, p = 0.026) and no difference in rates of postoperative liver failure, bile leak, need for invasive intervention for hepatic procedure, and anastomotic leak. On adjusted analyses, patients who received NAC had decreased odds of overall morbidity (OR 0.73, 95% CI 0.55-0.97, p = 0.031) compared to patients who did not receive NAC. On subgroup analyses, patients who received NAC prior to a low risk combined resection had lower rates of overall morbidity on both adjusted and unadjusted analyses. Among those undergoing high-risk combined resections, there was no difference in overall morbidity. DISCUSSION AND CONCLUSION Patients who are deemed to be candidates for preoperative chemotherapy can proceed with planned neoadjuvant chemotherapy prior to combined resection of primary colon cancer and sLM as preoperative neoadjuvant chemotherapy does not appear to be associated with increased postoperative morbidity.
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Affiliation(s)
- Joy Z Done
- Colorectal Research Unit, Department of Surgery, Johns Hopkins University, Baltimore, USA
| | - Angelos Papanikolaou
- Colorectal Research Unit, Department of Surgery, Johns Hopkins University, Baltimore, USA
| | - Miloslawa Stem
- Colorectal Research Unit, Department of Surgery, Johns Hopkins University, Baltimore, USA
| | - Shannon N Radomski
- Colorectal Research Unit, Department of Surgery, Johns Hopkins University, Baltimore, USA
| | - Sophia Y Chen
- Colorectal Research Unit, Department of Surgery, Johns Hopkins University, Baltimore, USA
| | - Chady Atallah
- Colorectal Research Unit, Department of Surgery, Johns Hopkins University, Baltimore, USA
| | - Jonathan E Efron
- Colorectal Research Unit, Department of Surgery, Johns Hopkins University, Baltimore, USA
| | - Bashar Safar
- Colorectal Research Unit, Department of Surgery, Johns Hopkins University, Baltimore, USA.
- Division of Colon and Rectal Surgery, Department of Surgery, New York University Grossman School of Medicine, NYU Langone Health, 530 First Ave, Suite 7V, New York, NY, 10016, USA.
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Berardi G, Chou J, Gonen M, Balachandran VP, Drebin J, Jarnagin WR, Kingham TP, Soares KC, Wei A, D'Angelica M. A Model to Predict Treatment Failure in Patients Undergoing Upfront Surgery for Resectable Colorectal Liver Metastases. Ann Surg Oncol 2023; 30:2820-2827. [PMID: 36692613 PMCID: PMC10089972 DOI: 10.1245/s10434-023-13113-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 12/07/2022] [Indexed: 01/25/2023]
Abstract
INTRODUCTION Patients who recur in the first year after resection of colorectal liver metastases (CRLM) do poorly. The aim of our study was to predict treatment failure in patients undergoing upfront resection with a nomogram. METHODS Data from patients resected between 1991 and 2019 were randomly split (70:30) into two cohorts. Treatment failure was defined as any recurrence or death within 12 months. A nomogram was constructed using multivariable logistic regression on the training cohort and validated using the testing cohort. RESULTS Overall, 783 patients were included. Primary tumor characteristics included 50% left-sided: 75.2% T3/4 and 56.5% node-positive. The median disease-free interval was 10 months, median number of metastases was 1 (1-50), and with a median size of 3.6 cm (0.2-22); 222 (28.3%) patients recurred within 1 year. Recurrence was mostly extrahepatic with or without liver involvement (150/222, 67.6%). Curative-intent treatment was possible in 37.8% of these patients. Primary location, T-stage and node status, disease-free interval, and number and size of metastases were associated with treatment failure. The area under the curve from the validation of the model was 0.6 (95% confidence interval 0.52-0.68). Patients with a high-risk of treatment failure (≥40%) had a worse survival from the landmark time of 12 months from surgery compared with those with low-risk (2-years: 82% vs. 70%; p = 0.0002). CONCLUSIONS Primary location, T stage, node status, disease-free interval, and number and size of metastases are associated with treatment failure. The survival of patients with a probability of treatment failure ≥40% is unfavorable. Future trials investigating the role of neoadjuvant therapy in these high-risk patients are warranted.
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Affiliation(s)
- Giammauro Berardi
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Joanne Chou
- Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mithat Gonen
- Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jeffrey Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kevin C Soares
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alice Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Dumarco RB, Fonseca GM, Coelho FF, Jeismann VB, Makdissi FF, Kruger JAP, Nahas SC, Herman P. Multiple colorectal liver metastases resection can offer long-term survival: The concept of a chronic neoplastic disease. Surgery 2023; 173:983-990. [PMID: 36220666 DOI: 10.1016/j.surg.2022.08.032] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 08/25/2022] [Accepted: 08/27/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Resection for colorectal liver metastases has evolved significantly and, currently, there are no limits to the number of resected nodules. This study aimed to evaluate the outcomes and prognostic factors after liver resection for patients with ≥4 colorectal liver metastases, emphasizing long-term survival. METHODS The study population consisted of 137 patients with ≥4 colorectal liver metastases out of a total of 597 patients with colorectal liver metastases who underwent curative intent liver resection from January 2010 to July 2019 in a single hepatobiliary center. RESULTS The probability of overall and disease-free survival at 1, 3, and 5 years was 90.8%, 64.5%, 40.6%, and 37.7%, 19.3%, 18.1%, respectively. In a multivariate analysis for overall survival, the size of the largest metastatic nodule was the only unfavorable factor (P = .001). For disease-free survival, complete pathological response was a favorable factor (P = .04), and the following were negative factors: number of nodules ≥7 (P = .034), radiofrequency ablation during surgery (P = .04), positive primary tumor lymph nodes (P = .034), R1 resection (P = .011), and preoperative carcinoembryonic antigen >20 ng/mL (P = .015). After the first and second years of follow-up, 59 patients (45.3%) and 45 patients (34.6%), respectively, were not receiving chemotherapy. After 5 years of follow-up, 21 (16.1%) multimetastatic patients were chemotherapy-free. CONCLUSION A significant number of patients with multiple colorectal liver metastases will present long-term survival and should not be denied surgery. The long-term survival rates, even in the presence of recurrence, characterize a chronic neoplastic disease.
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Affiliation(s)
- Rodrigo Blanco Dumarco
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Gilton Marques Fonseca
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil. https://twitter.com/medgilton
| | - Fabricio Ferreira Coelho
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Vagner Birk Jeismann
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil. https://twitter.com/vjeismann
| | - Fabio Ferrari Makdissi
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Jaime Arthur Pirolla Kruger
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil
| | - Sergio Carlos Nahas
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil. https://twitter.com/SergioNahasDr
| | - Paulo Herman
- Liver Surgery Unit, Digestive Surgery Division, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil.
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10
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Plúa-Muñiz K, Bailón-Cuadrado M, Pérez-Saborido B, Pacheco-Sánchez D, Pinto P, Asensio-Díaz E. Survival analysis and identification of prognostic factors in colorectal liver metastasis after liver resection. Cir Esp 2023; 101:160-169. [PMID: 36108955 DOI: 10.1016/j.cireng.2022.09.023] [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: 08/29/2021] [Accepted: 01/25/2022] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Liver resection is the only curative treatment for colorectal liver metastasis. The identification of predictive factors leads to personalize patient management to enhance their long-term outcomes. This population-based study aimed to characterize factors associated with, and survival impact of patients who received hepatectomy for colorectal liver metastasis. METHODS A retrospective cohort study of all the hepatectomies for colorectal liver metastasis performed at third-level hospital of Spain (2010-2018) was conducted. The Kaplan-Meier method was used for survival analyses. Multivariable Cox and regression models were used to determine prognostic factors associated with overall survival. RESULTS The 5-year overall survival and disease-free survival were 42 and 33%, respectively. Survival analysis showed that metastasis features (number, largest size, distribution, and extrahepatic disease) and postsurgical factors (transfusion, major complications, and positive margin resection), as well as non-mutated KRAS, showed a significant association with survival. Otherwise, on multivariate analysis, only 5 independent risk factors were identified: major size metastasis >4 cm, RAS mutation, positive margin resection, intraoperative transfusion, and major complications. CONCLUSIONS According to our findings, major size metastasis >4 cm, intraoperative transfusion, and major postoperative complications continue to be traditional prognostic factors. Meanwhile, the KRAS biomarker has a powerful impact as a survival prognostic factor.
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Affiliation(s)
- Katherine Plúa-Muñiz
- Unidad de Cirugía Hepatobiliopancréatica, Hospital Universitario Río Hortega, Valladolid, Spain.
| | - Martín Bailón-Cuadrado
- Unidad de Cirugía Hepatobiliopancréatica, Hospital Universitario Río Hortega, Valladolid, Spain
| | - Baltasar Pérez-Saborido
- Unidad de Cirugía Hepatobiliopancréatica, Hospital Universitario Río Hortega, Valladolid, Spain
| | - David Pacheco-Sánchez
- Unidad de Cirugía Hepatobiliopancréatica, Hospital Universitario Río Hortega, Valladolid, Spain
| | - Pilar Pinto
- Unidad de Cirugía Hepatobiliopancréatica, Hospital Universitario Río Hortega, Valladolid, Spain
| | - Enrique Asensio-Díaz
- Unidad de Cirugía Hepatobiliopancréatica, Hospital Universitario Río Hortega, Valladolid, Spain
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11
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Frühling P, Urdzik J, Isaksson B. Chemotherapy in patients with a solitary colorectal liver metastasis – A nationwide propensity score matched study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:2188-2194. [DOI: 10.1016/j.ejso.2022.05.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 05/06/2022] [Accepted: 05/20/2022] [Indexed: 11/26/2022]
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12
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Julio C, Benoist S, Allard MA, Navarro F, Pessaux P, Sa Cunha A, Brouquet A. Treatment strategies to resectable metachronous colorectal liver metastases after adjuvant oxaliplatin-based chemotherapy for primary colorectal cancer. J Surg Oncol 2022; 126:330-338. [PMID: 35397122 DOI: 10.1002/jso.26885] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 03/28/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND outcome of patients who develop resectable metachronous colorectal liver metastases (CLM) after adjuvant oxaliplatin-based chemotherapy for Stage III colorectal cancer (CRC) is not well defined and the value of preoperative chemotherapy is controversial. METHODS From 2006 to 2013, all patients undergoing liver resection for Class I metachronous CLM after adjuvant oxaliplatin-based chemotherapy for CRC, across 32 French academic centers, were included. RESULTS Sixty-two patients with an average of 2 ± 1 CLM were included. Thirty-two (52%) patients received preoperative chemotherapy. There was no significant difference in the characteristics of CLM between patients with or without preoperative chemotherapy. After a median follow-up of 29 months, 3-year overall and disease-free survival rates were 79.8% and 34.6%, respectively. The median disease-free survival was not different in patients with or without preoperative chemotherapy (17 vs. 35 months respectively, p = 0.112). In multivariate analysis, only CEA level > 200 ng/ml was associated with the risk of recurrence (p = 0.027; OR = 4.7, 95% CI = 1.2-18.7). CONCLUSION Liver resection provides a good outcome in patients with limited metachronous CLM after adjuvant oxaliplatin-based chemotherapy for CRC. The interest of preoperative chemotherapy is not obvious and should be tested in a prospective controlled study.
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Affiliation(s)
- Camille Julio
- The Department of Digestive and Oncologic Surgery, Bicêtre Hospital, APHP, Paris-Sud, University, Le Kremlin Bicêtre, France
| | - Stephane Benoist
- The Department of Digestive and Oncologic Surgery, Bicêtre Hospital, APHP, Paris-Sud, University, Le Kremlin Bicêtre, France.,Faculté de Médecine, Paris-Sud University, Le Kremlin Bicêtre, France
| | - Marc-Antoine Allard
- Faculté de Médecine, Paris-Sud University, Le Kremlin Bicêtre, France.,Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Paul Brousse Hospital, Villejuif, France
| | - Francis Navarro
- The Department of Digestive Surgery and Transplantation, Saint Eloi University Hospital, Montpellier, France
| | - Patrick Pessaux
- Department of General, Digestive, and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France
| | - Antonio Sa Cunha
- Faculté de Médecine, Paris-Sud University, Le Kremlin Bicêtre, France.,Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Paul Brousse Hospital, Villejuif, France
| | - Antoine Brouquet
- The Department of Digestive and Oncologic Surgery, Bicêtre Hospital, APHP, Paris-Sud, University, Le Kremlin Bicêtre, France.,Faculté de Médecine, Paris-Sud University, Le Kremlin Bicêtre, France
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13
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Mishina T, Uehara K, Ogura A, Murata Y, Aiba T, Mizuno T, Yokoyama Y, Ebata T. Role of resection for extrahepatopulmonary metastases of colon cancer. Jpn J Clin Oncol 2022; 52:735-741. [PMID: 35393617 DOI: 10.1093/jjco/hyac045] [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: 11/04/2021] [Accepted: 03/17/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Although surgical resection for liver or lung metastases of colorectal cancer has been widely accepted, the use of this approach for extrahepatopulmonary metastases remains debatable due to the systemic nature of the disease. The aim of this study was to clarify the utility of resection along with perioperative chemotherapy for patients with extrahepatopulmonary metastases of colon cancer. METHODS This is a retrospective single-arm study at a single institution. Forty-two patients with resectable extrahepatopulmonary metastases who underwent metastasectomy with curative intent between 2009 and 2018 at Nagoya University Hospital were retrospectively analyzed. The primary outcomes measured were overall and relapse-free survival. RESULTS The most common metastatic site was the peritoneum (n = 31), followed by the distant lymph nodes (n = 10), ovary (n = 1) and spleen (n = 1), with overlaps. Preoperative and postoperative chemotherapies were administered to 22 and 8 patients, respectively; the remaining 14 patients received surgery alone. R0 resection was achieved in 36 patients (85.7%). The 5-year overall survival and 3-year relapse-free survival rates were 58.6% and 33.8%, respectively. In the univariate analysis, R1 resection was associated with a poor relapse-free survival rate (P = 0.02). In the multivariate analysis, the absence of perioperative chemotherapy was an independent risk factor for poor overall survival rates (P = 0.02). CONCLUSIONS Surgical resection benefited selected patients with extrahepatopulmonary metastases with favorable long-term survival outcomes. Surgery alone without systemic chemotherapy is likely to bring poor outcome; therefore, preoperative induction might be promising to keep up with chemotherapy.
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Affiliation(s)
- Takuya Mishina
- Division of Surgical Oncology, Department of Surgery, Nagoya Graduate School of Medicine, Nagoya, Japan
| | - Kay Uehara
- Division of Surgical Oncology, Department of Surgery, Nagoya Graduate School of Medicine, Nagoya, Japan
| | - Atsushi Ogura
- Division of Surgical Oncology, Department of Surgery, Nagoya Graduate School of Medicine, Nagoya, Japan
| | - Yuki Murata
- Division of Surgical Oncology, Department of Surgery, Nagoya Graduate School of Medicine, Nagoya, Japan
| | - Toshisada Aiba
- Division of Surgical Oncology, Department of Surgery, Nagoya Graduate School of Medicine, Nagoya, Japan
| | - Takashi Mizuno
- Division of Surgical Oncology, Department of Surgery, Nagoya Graduate School of Medicine, Nagoya, Japan
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya Graduate School of Medicine, Nagoya, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya Graduate School of Medicine, Nagoya, Japan
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14
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Plúa-Muñiz K, Bailón-Cuadrado M, Pérez-Saborido B, Pacheco-Sánchez D, Pinto P, Asensio-Díaz E. Análisis de supervivencia e identificación de factores pronósticos de metástasis hepáticas de cáncer colorrectal tras resección hepática. Cir Esp 2022. [DOI: 10.1016/j.ciresp.2022.01.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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15
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Cassar N, Geoghegan J, Hoti E. Shifting concepts in the management of colorectal liver metastases. Surgeon 2022; 20:363-372. [PMID: 34998701 DOI: 10.1016/j.surge.2021.12.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 11/21/2021] [Accepted: 12/14/2021] [Indexed: 02/07/2023]
Abstract
Management of patients with colorectal liver metastases has evolved considerably due to a better understanding of the biology of the disease with concurrent improvements in surgical techniques, oncological strategies and radiological interventions. This review article examines the factors that have contributed to this radical change. Management will be discussed in relation to chemotherapy, surgery and interventional radiology. The addition of chemotherapy and biological agents has greatly extended the reach and scope of surgery. Parenchymal sparing resections, repeat resections, two stage hepatectomy and Associating Liver Partition and Portal Vein ligation are all available to the hepatobiliary surgeon who deals with colorectal liver metastases. Interventional radiology techniques like liver venous deprivation may also replace established surgical practice. Whilst traditionally it was thought that only a few liver metastases could be treated effectively, nowadays tumour number is no longer a limiting factor provided enough functioning liver can be spared and the patient can tolerate the operation.
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Affiliation(s)
- Noel Cassar
- Department of Hepatobiliary Surgery and Liver Transplantation, St Vincent's University Hospital, Elm Park, Dublin 4 D04 T6F4, Ireland.
| | - Justin Geoghegan
- Department of Hepatobiliary Surgery and Liver Transplantation, St Vincent's University Hospital, Elm Park, Dublin 4 D04 T6F4, Ireland
| | - Emir Hoti
- Department of Hepatobiliary Surgery and Liver Transplantation, St Vincent's University Hospital, Elm Park, Dublin 4 D04 T6F4, Ireland
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16
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Takeda Y, Mise Y, Takahashi Y, Ito H, Inoue Y, Yoshioka R, Ono Y, Saiura A. Limited Prognostic Value of KRAS in Patients Undergoing Hepatectomy for Colorectal Liver Metastases. Ann Surg Oncol 2021; 29:2383-2391. [PMID: 34851437 DOI: 10.1245/s10434-021-11015-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 10/11/2021] [Indexed: 01/22/2023]
Abstract
BACKGROUND RAS mutation status is considered a powerful prognostic factor in patients undergoing hepatectomy for colorectal liver metastases (CLM). However, whether its prognostic power is robust regardless of administration of preoperative chemotherapy or tumor burden remains unclear. METHODS Consecutive patients who underwent initial hepatectomy for CLM from April 2010 through March 2017 in two hospitals were included. The prognostic value of KRAS was compared based on whether patients received preoperative chemotherapy and their tumor burden score (TBS). RESULTS We included 409 patients (median follow-up 38 months). In the preoperative chemotherapy group, patients with mutant KRAS (mt-KRAS) CLM had poorer overall survival (OS) than those with wild KRAS (wt-KRAS; 5-year OS: 37.7% vs 53.8%, p = 0.024), although their OS was not different from patients undergoing upfront surgery. Similarly, patients with mt-KRAS had poorer OS than those with wt-KRAS in TBS of 3-9 (5-year OS: 33.1% vs 63.2%, p = 0.001), although their OS was not different from patients with TBS < 3 or ≥ 9. In multivariate analysis, mt-KRAS was an independent prognostic factor of OS among patients receiving preoperative chemotherapy (hazard ratio [HR] 1.61, 95% confidence interval [CI]: 1.034-2.491; p = 0.035) and patients with TBS of 3-9 (HR 1.836, 95% CI 1.176-2.866; p = 0.008). However, it was not a prognostic factor in patients who underwent upfront surgery or with TBS > 3 or ≥ 9. CONCLUSIONS In patients undergoing hepatectomy for CLM, the prognostic value of KRAS depends on their history of preoperative chemotherapy or tumor burden.
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Affiliation(s)
- Yoshinori Takeda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan.,Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Yoshihiro Mise
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan.,Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Yu Takahashi
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Hiromichi Ito
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Yosuke Inoue
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Ryuji Yoshioka
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yoshihiro Ono
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Akio Saiura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan. .,Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan.
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17
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Di Martino M, Primavesi F, Syn N, Dorcaratto D, de la Hoz Rodríguez Á, Dupré A, Piardi T, Rhaiem R, Blanco Fernández G, Prada Villaverde A, Rodríguez Sanjuán JC, Fernández Santiago R, Fernández-Moreno MC, Ferret G, López Ben S, Suárez Muñoz MÁ, Perez-Alonso AJ, Koh YX, Jones R, Martín-Pérez E. Perioperative chemotherapy versus surgery alone for resectable colorectal liver metastases: an international multicentre propensity score matched analysis on long-term outcomes according to established prognostic risk scores. HPB (Oxford) 2021; 23:1873-1885. [PMID: 34103246 DOI: 10.1016/j.hpb.2021.04.026] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 03/10/2021] [Accepted: 04/26/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND There is still uncertainty regarding the role of perioperative chemotherapy (CTx) in patients with resectable colorectal liver metastases (CRLM), especially in those with a low-risk of recurrence. METHODS Multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010-2015. Patients were divided into two groups according to whether they received perioperative CTx or not and were compared using propensity score matching (PSM) analysis. Then, they were stratified according to prognostic risk scores, including: Clinical Risk Score (CRS), Tumour Burden Score (TBS) and Genetic And Morphological Evaluation (GAME) score. RESULTS The study included 967 patients with a median follow-up of 68 months. After PSM analysis, patients with perioperative CTx presented prolonged overall survival (OS) in comparison with the surgery alone group (82.8 vs 52.5 months, p = 0.017). On multivariable analysis perioperative CTx was an independent predictor of increased OS (HR 0.705, 95%CI 0.705-0.516, p = 0.029). The benefits of perioperative CTx on survival were confirmed in patients with CRS and TBS scores ≤2 (p = 0.022 and p = 0.020, respectively) and in patients with a GAME score ≤1 (p = 0.006). CONCLUSION Perioperative CTx demonstrated an increase in OS in patients with CRLM. Patients with a low-risk of recurrence seem to benefit from systemic treatment.
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Affiliation(s)
- Marcello Di Martino
- HPB Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain.
| | - Florian Primavesi
- Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; Salzkammergutklinikum Vöcklabruck, Vöcklabruck, Austria
| | - Nicholas Syn
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Dimitri Dorcaratto
- Department of Surgery, Liver, Biliary, and Pancreatic Unit, Biomedical Research Institute INCLIVA, Hospital Clínico University of Valencia, Valencia, Spain
| | - Ángela de la Hoz Rodríguez
- HPB Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - Aurélien Dupré
- Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Tullio Piardi
- Department of HBP and Digestive Oncological Surgery, Robert Debré University Hospital, Reims, France; Department of Surgery, HPB Unit, Simone Veil Hospital, Troyes, France
| | - Rami Rhaiem
- Department of HBP and Digestive Oncological Surgery, Robert Debré University Hospital, Reims, France
| | - Gerardo Blanco Fernández
- Department of HBP and Liver Transplantation Surgery, University Hospital of Badajoz, INUBE (Instituto Universitario de Investigación Biosanitaria de Extremadura), University of Extremadura, Badajoz, Spain
| | - Arancha Prada Villaverde
- Department of HBP and Liver Transplantation Surgery, University Hospital of Badajoz, INUBE (Instituto Universitario de Investigación Biosanitaria de Extremadura), University of Extremadura, Badajoz, Spain
| | | | | | - María-Carmen Fernández-Moreno
- Department of Surgery, Liver, Biliary, and Pancreatic Unit, Biomedical Research Institute INCLIVA, Hospital Clínico University of Valencia, Valencia, Spain
| | - Georgina Ferret
- Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain
| | | | | | - Alejandro J Perez-Alonso
- Unidad de Cirugia HBP y Trasplante Hepático, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - Ye-Xin Koh
- Salzkammergutklinikum Vöcklabruck, Vöcklabruck, Austria
| | - Robert Jones
- Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom
| | - Elena Martín-Pérez
- HPB Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain
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18
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Zhang Y, Ge L, Weng J, Tuo WY, Liu B, Ma SX, Yang KH, Cai H. Neoadjuvant chemotherapy for patients with resectable colorectal cancer liver metastases: A systematic review and meta-analysis. World J Clin Cases 2021; 9:6357-6379. [PMID: 34435001 PMCID: PMC8362587 DOI: 10.12998/wjcc.v9.i22.6357] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 04/14/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In recent years, neoadjuvant chemotherapy (NAC) has been increasingly used in patients with resectable colorectal liver metastases. However, the efficacy and safety of NAC in the treatment of resectable colorectal liver metastases (CRLM) are still controversial.
AIM To assess the efficacy and application value of NAC in patients with resectable CRLM.
METHODS We searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to December 2020 to collect clinical studies comparing NAC with non-NAC. Data processing and statistical analyses were performed using Stata V.15.0 and Review Manager 5.0 software.
RESULTS In total, 32 studies involving 11236 patients were included in this analysis. We divided the patients into two groups, the NAC group (that received neoadjuvant chemotherapy) and the non-NAC group (that received no neoadjuvant chemotherapy). The meta-analysis outcome showed a statistically significant difference in the 5-year overall survival and 5-year disease-free survival between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) were HR = 0.49, 95%CI: 0.39-0.61, P = 0.000 and HR = 0.48 95%CI: 0.36-0.63, P = 0.000. The duration of surgery in the NAC group was longer than that of the non-NAC group [standardized mean difference (SMD) = 0.41, 95%CI: 0.01-0.82, P = 0.044)]. The meta-analysis showed that the number of liver metastases in the NAC group was significantly higher than that in the non-NAC group (SMD = 0.73, 95%CI: 0.02-1.43, P = 0.043). The lymph node metastasis in the NAC group was significantly higher than that in the non-NAC group (SMD = 1.24, 95%CI: 1.07-1.43, P = 0.004).
CONCLUSION We found that NAC could improve the long-term prognosis of patients with resectable CRLM. At the same time, the NAC group did not increase the risk of any adverse event compared to the non-NAC group.
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Affiliation(s)
- Yue Zhang
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Long Ge
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Jun Weng
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Wen-Yu Tuo
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Bin Liu
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Shi-Xun Ma
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Ke-Hu Yang
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Hui Cai
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
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19
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Konishi T, Yoshidome H, Shida T, Furukawa K, Takayashiki T, Kuboki S, Takano S, Miyazaki M, Ohtsuka M. Phosphorylated mTOR expression as a predictor of survival after liver resection for colorectal liver metastases. J Surg Oncol 2021; 124:598-606. [PMID: 34061356 DOI: 10.1002/jso.26551] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 04/18/2021] [Accepted: 05/17/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND Phosphorylated mammalian target of rapamycin (p-mTOR) plays a crucial role in the process of cancer progression. Common gene mutations of colorectal cancer lead to the activation of the PI3k/Akt/mTOR pathway. In this study, we determined whether p-mTOR expression in colorectal liver metastases is a predictive marker of prognosis following liver resection. METHODS Eighty-one patients with colorectal liver metastases who had undergone curative resection were evaluated using immunohistochemistry of p-mTOR. Data regarding clinicopathological features and patient survival were analyzed. RESULTS The p-mTOR expression in colorectal liver metastases was detected in 55 (67.9%) patients. Patients whose metastases had high p-mTOR expression showed a significantly lower overall survival rate after resection as compared to patients with low p-mTOR expression (p = 0.016), while there was no significant difference in the disease-free survival between the two groups. Repeat resection for recurrence was performed more frequently in patients with p-mTOR positive than others (p = 0.024). Multivariate analysis showed that p-mTOR expression was an independent prognostic factor of overall survival after liver resection (p = 0.019). CONCLUSIONS mTOR was frequently activated in colorectal liver metastases, and the p-mTOR expression was a biological marker for predicting the overall survival of patients with colorectal liver metastases following liver resection.
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Affiliation(s)
- Takanori Konishi
- Department of General Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan
| | - Hiroyuki Yoshidome
- Department of General Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan.,Department of Surgery, Oami Municipal Hospital, Oami-Shirasato-shi, Chiba, Japan
| | - Takashi Shida
- Department of General Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan
| | - Katsunori Furukawa
- Department of General Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan
| | - Tsukasa Takayashiki
- Department of General Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan
| | - Satoshi Kuboki
- Department of General Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan
| | - Shigetsugu Takano
- Department of General Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan
| | - Masaru Miyazaki
- Department of General Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan
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20
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Kelm M, Schollbach J, Anger F, Wiegering A, Klein I, Germer CT, Schlegel N, Kunzmann V, Löb S. Prognostic impact of additive chemotherapy after curative resection of metachronous colorectal liver metastasis: a single-centre retrospective study. BMC Cancer 2021; 21:490. [PMID: 33941104 PMCID: PMC8091534 DOI: 10.1186/s12885-021-07941-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 02/21/2021] [Indexed: 01/05/2023] Open
Abstract
Background A prognostic benefit of additive chemotherapy in patients following resection of metachronous colorectal liver metastases (CRLM) remains controversial. Therefore, the goal of this retrospective study was to investigate the impact of perioperative chemotherapy on disease-free survival (DFS) and overall survival (OS) of patients after curative resection of metachronous CRLM. Methods In a retrospective single-centre study, patients after curative resection of metachronous CRLM were included and analysed for DFS and OS with regard to the administration of additive chemotherapy. The Kaplan-Meier method was applied to compare DFS and OS while Cox regression models were used to identify independent prognostic variables. Results Thirty-four of 75 patients were treated with additive 5-FU based chemotherapy. OS was significantly prolonged in this patient subgroup (62 vs 57 months; p = 0.032). Additive chemotherapy significantly improved 10-year survival rates (42% vs 0%, p = 0.023), but not 5-year survival (58% vs 42%, p = 0.24). Multivariate analysis identified additive chemotherapy (p = 0.016, HR 0.44, 95% CI 0.23–0.86), more than five CRLM (p = 0.026, HR 2.46, 95% CI 1.16–10.32) and disease recurrence (0.009, HR 2.70, 95% CI 1.29–5.65) as independent risk factors for OS. Conclusion Additive chemotherapy significantly prolonged OS and 10-year survival in patients after curative resection of metachronous CRLM. Randomized clinical trials are needed in the future to identify optimal chemotherapy regimens for those patients.
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Affiliation(s)
- Matthias Kelm
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.
| | - Julia Schollbach
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany
| | - Friedrich Anger
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany
| | - Armin Wiegering
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.,Theodor-Boveri-Institute, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany.,Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str. 6, 97080, Würzburg, Germany
| | - Ingo Klein
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.,Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str. 6, 97080, Würzburg, Germany
| | - Christoph-Thomas Germer
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.,Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str. 6, 97080, Würzburg, Germany
| | - Nicolas Schlegel
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany
| | - Volker Kunzmann
- Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str. 6, 97080, Würzburg, Germany.,Department of Internal Medicine II, University of Würzburg, Würzburg, Germany
| | - Stefan Löb
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.,Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str. 6, 97080, Würzburg, Germany
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21
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Ono K, Abe T, Oshita A, Sumi Y, Yano T, Okuda H, Kurayoshi M, Kobayashi T, Ohdan H, Noriyuki T, Nakahara M. Efficacy of upfront hepatectomy without neoadjuvant chemotherapy for resectable colorectal liver metastasis. World J Surg Oncol 2021; 19:97. [PMID: 33820549 PMCID: PMC8022388 DOI: 10.1186/s12957-021-02210-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 03/22/2021] [Indexed: 12/17/2022] Open
Abstract
Background Hepatectomy for resectable colorectal liver metastasis (CRLM) is recommended. However, the efficacy of upfront hepatectomy without neoadjuvant chemotherapy (NAC) is unclear due to the uncertainty of perioperative systemic chemotherapy. Moreover, it is crucial to predict the prognosis when considering perioperative chemotherapy. This study evaluated the impact of neoadjuvant chemotherapy on the prognosis of patients with resectable CRLM and assessed the usefulness of Beppu’s nomogram for predicting prognosis. Methods This retrospective study identified 88 consecutive inpatients who underwent primary hepatic resection for CRLM; 58 received neoadjuvant chemotherapy and 30 underwent upfront surgery. Factors associated with recurrence-free survival were identified via univariate and multivariate analysis. Furthermore, propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. Results On univariate analysis, poor recurrence-free survival was associated with multiple tumors, advanced primary tumor stage, vascular invasion by the primary tumor, a Beppu’s nomogram score ≥ 6, and neoadjuvant chemotherapy. On multivariate analysis, a Beppu’s nomogram score ≥ 6 and neoadjuvant chemotherapy were independent risk factors for recurrence. Neoadjuvant chemotherapy recipients had a higher incidence of lymph node metastasis and vascular invasion than non-recipients. Propensity score analysis revealed no significant difference in the recurrence-free survival rate between these groups. Conclusions Our results show that upfront hepatectomy without neoadjuvant chemotherapy can be considered for resectable CRLM treatment. Beppu’s nomogram score can be a tool for predicting the prognosis of patients with CRLM.
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Affiliation(s)
- Kosuke Ono
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara Onomichi, Hiroshima, 722-8508, Japan
| | - Tomoyuki Abe
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara Onomichi, Hiroshima, 722-8508, Japan.
| | - Akihiko Oshita
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara Onomichi, Hiroshima, 722-8508, Japan.,Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima, 734-8551, Japan
| | - Yusuke Sumi
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara Onomichi, Hiroshima, 722-8508, Japan
| | - Takuya Yano
- Department of Surgery, Hiroshima Citizens Hospital, 7-33 Motomachi, Hiroshima, 730-8518, Japan
| | - Hiroshi Okuda
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara Onomichi, Hiroshima, 722-8508, Japan
| | - Manabu Kurayoshi
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara Onomichi, Hiroshima, 722-8508, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima, 734-8551, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima, 734-8551, Japan
| | - Toshio Noriyuki
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara Onomichi, Hiroshima, 722-8508, Japan.,Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima, 734-8551, Japan
| | - Masahiro Nakahara
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara Onomichi, Hiroshima, 722-8508, Japan
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22
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Kovács A, Bischoff P, Haddad H, Kovács G, Schaefer A, Zhou W, Pinkawa M. Personalized Image-Guided Therapies for Local Malignencies: Interdisciplinary Options for Interventional Radiology and Interventional Radiotherapy. Front Oncol 2021; 11:616058. [PMID: 33869002 PMCID: PMC8047426 DOI: 10.3389/fonc.2021.616058] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 03/09/2021] [Indexed: 12/19/2022] Open
Abstract
Minimal-invasive interventions considerably extend the therapeutic spectrum in oncology and open new dimensions in terms of survival, tolerability and patient-friendliness. Through the influence of image-guided interventions, many interdisciplinary therapy concepts have significantly evolved, and this process is by far not yet over. The rapid progression of minimal-invasive technologies offers hope for new therapeutic concepts in the short, medium and long term. Image-guided hybrid-technologies complement and even replace in selected cases classic surgery. In this newly begun era of immune-oncology, interdisciplinary collaboration and the focus on individualized and patient-friendly therapies are crucial.
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Affiliation(s)
- Attila Kovács
- Clinic for Diagnostic and Interventional Radiology and Neuroradiology, MediClin Robert Janker Klinik, Bonn, Germany
| | - Peter Bischoff
- Clinic for Diagnostic and Interventional Radiology and Neuroradiology, MediClin Robert Janker Klinik, Bonn, Germany
| | - Hathal Haddad
- Clinic for Radiotherapy and Radiooncology, MediClin Robert Janker Klinik, Bonn, Germany
| | - György Kovács
- Gemelli-INTERACTS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Andreas Schaefer
- Clinic for Diagnostic and Interventional Radiology and Neuroradiology, MediClin Robert Janker Klinik, Bonn, Germany
| | - Willi Zhou
- Clinic for Diagnostic and Interventional Radiology and Neuroradiology, MediClin Robert Janker Klinik, Bonn, Germany
| | - Michael Pinkawa
- Clinic for Radiotherapy and Radiooncology, MediClin Robert Janker Klinik, Bonn, Germany
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23
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Kamphues C, Andreatos N, Kruppa J, Buettner S, Wang J, Sasaki K, Wagner D, Morioka D, Fitschek F, Løes IM, Imai K, Sun J, Poultsides G, Kaczirek K, Lønning PE, Endo I, Baba H, Kornprat P, Aucejo FN, Wolfgang CL, Kreis ME, Weiss MJ, Margonis GA. The optimal cut-off values for tumor size, number of lesions, and CEA levels in patients with surgically treated colorectal cancer liver metastases: An international, multi-institutional study. J Surg Oncol 2021; 123:939-948. [PMID: 33400818 DOI: 10.1002/jso.26361] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 12/18/2020] [Accepted: 12/18/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES Despite the long-standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen (CEA) levels as predictors of long-term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut-offs for these variables have not been established. METHODS Patients who underwent curative-intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi-institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut-offs. The concordance probability estimates (CPEs) for these optimal cut offs were calculated and compared to CPEs for the most widely used cut-offs in the surgical literature. RESULTS A total of 1643 patients who met eligibility criteria were identified. Following recursive partitioning analysis in the training dataset, the following cut-offs were identified: 2.95 cm for tumor size, 1.5 for tumor number and 6.15 ng/ml for CEA levels. In the entire dataset, the calculated CPEs for the new tumor size (0.52), tumor number (0.56) and CEA (0.53) cut offs exceeded CPEs for other commonly employed cut-offs. CONCLUSION The current study was able to identify optimal cut-offs for the three most commonly employed prognostic factors in CRLM. While the per variable gains in discriminatory power are modest, these novel cut-offs may help produce appreciable increases in prognostic performance when combined in the context of future risk scores.
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Affiliation(s)
- Carsten Kamphues
- Department of General, Visceral, and Vascular Surgery, Charité, University Medicine, Campus Benjamin Franklin, Berlin, Germany
| | | | - Jochen Kruppa
- Department of General, Visceral, and Vascular Surgery, Charité, University Medicine, Campus Benjamin Franklin, Berlin, Germany
| | - Stefan Buettner
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jaeyun Wang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kazunari Sasaki
- Department of Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - Doris Wagner
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | - Daisuke Morioka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Fabian Fitschek
- Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Inger Marie Løes
- Department of Clinical Science and Oncology, Haukeland University Hospital, University of Bergen, Bergen, Norway
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
| | - Jinger Sun
- Department of Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - George Poultsides
- Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Klaus Kaczirek
- Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Per Eystein Lønning
- Department of Clinical Science and Oncology, Haukeland University Hospital, University of Bergen, Bergen, Norway
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
| | - Peter Kornprat
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | | | - Christopher L Wolfgang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Martin E Kreis
- Department of General, Visceral, and Vascular Surgery, Charité, University Medicine, Campus Benjamin Franklin, Berlin, Germany
| | - Matthew J Weiss
- Department of Surgery, Zucker School of Medicine at Hofstra, Northwell Health Cancer Institute, Lake Success, New York, USA
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24
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Martin J, Petrillo A, Smyth EC, Shaida N, Khwaja S, Cheow HK, Duckworth A, Heister P, Praseedom R, Jah A, Balakrishnan A, Harper S, Liau S, Kosmoliaptsis V, Huguet E. Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol 2020; 11:761-808. [PMID: 33200074 PMCID: PMC7643190 DOI: 10.5306/wjco.v11.i10.761] [Citation(s) in RCA: 131] [Impact Index Per Article: 26.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/14/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation.
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Affiliation(s)
- Jack Martin
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Angelica Petrillo
- Department of Precision Medicine, Division of Medical Oncology, University of Campania "L. Vanvitelli", Napoli 80131, Italy, & Medical Oncology Unit, Ospedale del Mare, 80147 Napoli Italy
| | - Elizabeth C Smyth
- Department of Oncology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Nadeem Shaida
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - Samir Khwaja
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - HK Cheow
- Department of Nuclear Medicine, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Adam Duckworth
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Paula Heister
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Raaj Praseedom
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Asif Jah
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Anita Balakrishnan
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Simon Harper
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Siong Liau
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Vasilis Kosmoliaptsis
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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25
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Chun YJ, Kim SG, Lee KW, Cho SH, Kim TW, Baek JY, Park YS, Hong S, Chu CW, Beom SH, Jung M, Shin SJ, Ahn JB. A Randomized Phase II Study of Perioperative Chemotherapy Plus Bevacizumab Versus Postoperative Chemotherapy Plus Bevacizumab in Patients With Upfront Resectable Hepatic Colorectal Metastases. Clin Colorectal Cancer 2020; 19:e140-e150. [DOI: 10.1016/j.clcc.2020.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 02/23/2020] [Accepted: 03/22/2020] [Indexed: 12/15/2022]
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26
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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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27
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Yang D, Zhuang B, Lin M, Xu M, Lv M, Kuang M, Xie X, Xie X. Primary tumour location is an important prognostic factor in colorectal cancer liver metastases following radiofrequency ablation. Clin Radiol 2020; 75:961.e1-961.e9. [PMID: 32859384 DOI: 10.1016/j.crad.2020.07.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 07/09/2020] [Indexed: 01/27/2023]
Abstract
AIM To examine the outcomes and different prognoses for colorectal cancer patients with liver metastases (CRCLM) treated with radiofrequency ablation (RFA) based on the origin of the primary tumour (rectum versus colon). MATERIALS AND METHODS Patients diagnosed with CRCLM from July 2011 to June 2018 were assessed in the study. The study included 114 patients with 176 lesions. All of the patients underwent RFA of their CRCLM. The overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier survival function estimate curves and Cox regression analysis between the group of patients with rectal cancer liver metastases (RCLM) and colon cancer liver metastases (CCLM). RESULTS Patients with RCLM exhibited worse OS and PFS than those with CCLM. The 1-, 2-, and 3-year OS rates were 87.5%, 75%, and 54.2% in the RCLM group and 93.9%, 87.8%, and 81.8% in the CCLM group (p=0.001), respectively. The 1-, 2-, and 3-year PFS rates were 43.7%, 22.9%, and 20.8% in the RCLM group and 57.6%, 45.4%, and 36.5% in the CCLM group (p=0.001), respectively. Multivariate analysis showed that primary tumour location, carcinoembryonic antigen (CEA), and response to pre-ablation chemotherapy were independent variables for OS and PFS. The N state of the primary tumour also had a significant impact on OS. CONCLUSION This study showed that patients with CCLM had better prognoses than those with RCLM following RFA treatment. If patients intend to undergo RFA for CRCLM, the location of the primary tumour should be considered in the assessment of long-term therapeutic effects.
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Affiliation(s)
- D Yang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - B Zhuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - M Lin
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - M Xu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - M Lv
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - M Kuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - X Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
| | - X Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
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28
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Yang DP, Zhuang BW, Wang YZ, Lin MX, Xu M, Kuang M, Lei YY, Xie XY, Xie XH. Thermal ablation versus hepatic resection for the treatment of liver metastases from gastrointestinal stromal tumors: a retrospective study. Int J Hyperthermia 2020; 37:592-599. [PMID: 32484012 DOI: 10.1080/02656736.2020.1772513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
Objective: The study aimed to compare effectiveness and safety of thermal ablation and hepatic resection in patients with liver metastases of gastrointestinal stromal tumors (GISTs).Method: A total of 55 patients (27 in the ablation group and 28 in the surgery group) with liver metastases were included. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier's survival estimate curves. Univariate and multivariate regression analyses were carried out to identify potential prognostic factors.Results: The median OS was 102.0 months in the ablation group and 117.0 months in the surgery group (p = .875). The 1-, 3- and 5-year OS rates were 100%, 88.9% and 74.1% in the ablation group and 92.8%, 82.1% and 78.6% in the surgery group, respectively. The 1-, 3- and 5-year PFS rates were 48.1%, 25.9% and 18.5% in the ablation group and 67.8%, 64.3% and 64.3% in the surgery group, respectively. Multivariate analysis showed that preoperative tyrosine kinase inhibitor (TKI) treatment (progressive disease, PD) (HR, 13.985; 95% CI, 1.791-109.187; p = .012) was the only significant independent prognostic factor for OS. Tumor number (HR, 1.318; 95% CI, 1.021-1.702; p = .034) was identified as an independent predictor for PFS in multivariate analysis. There were fewer postoperative complications (18.5% vs. 78.6%, p = .001) and shorter lengths of hospital stay (8.0 vs. 16.5 days, p = .001) in the ablation group.Conclusion: Compared with resection, thermal ablation offered comparable OS for liver metastases of GISTs. Furthermore, thermal ablation had the advantages of fewer complications and shorter lengths of hospital stay.
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Affiliation(s)
- Dao-Peng Yang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Bo-Wen Zhuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yu-Zhao Wang
- Sun Yat-Sen University School of Medicine, Guangzhou, China
| | - Man-Xia Lin
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming Xu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming Kuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yang-Yang Lei
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Hua Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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Smedman TM, Line P, Hagness M, Syversveen T, Grut H, Dueland S. Liver transplantation for unresectable colorectal liver metastases in patients and donors with extended criteria (SECA-II arm D study). BJS Open 2020; 4:467-477. [PMID: 32333527 PMCID: PMC7260412 DOI: 10.1002/bjs5.50278] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 02/06/2020] [Accepted: 02/07/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Patients with metastatic colorectal cancer receiving palliative chemotherapy have a 5-year survival rate of approximately 10 per cent. Liver transplantation using strict selection criteria in patients with colorectal cancer and unresectable liver-only disease will result in a 5-year survival rate of 56-83 per cent. The aim of this study was to evaluate survival of patients with colorectal liver metastases (CRLM) after liver transplantation using extended criteria for both patients and donors. METHODS This was a prospective single-arm study. Patients with synchronous unresectable CRLM who were not suitable for arms A, B or C of the SEcondary CAncer (SECA) II study who had undergone radical resection of the primary tumour and received chemotherapy were included; they underwent liver transplantation with extended criteria donor grafts. Patients who had resectable pulmonary metastases were eligible for inclusion. The main exclusion criteria were BMI above 30 kg/m2 and liver metastases larger than 10 cm. Survival was estimated using Kaplan-Meier analysis. RESULTS Ten patients (median age 54 years; 3 women) were included. They had an extensive liver tumour load with a median of 20 (range 1-45) lesions; the median size of the largest lesion was 59 (range 15-94) mm. Eight patients had (y)pN2 disease, six had poorly differentiated or signet ring cell-differentiated primary tumours, and five had primary tumour in the ascending colon. The median Fong clinical risk score was 3 (range 2-5) and the median Oslo score was 1 (range 1-4). The median plasma carcinoembryonic antigen level was 4·3 (range 2-4346) μg/l. Median disease-free and overall survival was 4 and 18 months respectively. CONCLUSION Patients with unresectable liver-only CRLM undergoing liver transplantation with extended patient and donor criteria have relatively short overall survival.
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Affiliation(s)
- T. M. Smedman
- Department of OncologyOsloNorway
- Institute of Clinical MedicineUniversity of OsloOsloNorway
| | - P.‐D. Line
- Department of Transplantation MedicineOsloNorway
- Institute of Clinical MedicineUniversity of OsloOsloNorway
| | - M. Hagness
- Department of Transplantation MedicineOsloNorway
| | | | - H. Grut
- Radiology and Nuclear MedicineOsloNorway
- Institute of Clinical MedicineUniversity of OsloOsloNorway
| | - S. Dueland
- Department of OncologyOsloNorway
- Experimental Transplantation and Malignancy Research Group, Division of Surgery, Inflammatory Diseases and TransplantationOslo University HospitalOsloNorway
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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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Kobayashi S, Beppu T, Honda G, Yamamoto M, Takahashi K, Endo I, Hasegawa K, Kotake K, Itabashi M, Hashiguchi Y, Kotera Y, Sakamoto K, Yamaguchi T, Morita S, Tabuchi K, Miyazaki M, Sugihara K. Survival Benefit of and Indications for Adjuvant Chemotherapy for Resected Colorectal Liver Metastases-a Japanese Nationwide Survey. J Gastrointest Surg 2020; 24:1244-1260. [PMID: 31197683 DOI: 10.1007/s11605-019-04250-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Accepted: 04/24/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND The survival benefit of and indications for adjuvant chemotherapy (AC) for colorectal liver metastases (CRLM) remain unclear. METHODS Patients who were diagnosed with liver-limited CRLM between 2005 and 2007 and subsequently underwent R0 resection without preoperative chemotherapy were identified in a Japanese nationwide survey. This overall cohort was divided into synchronous and metachronous CRLM cohorts. In each of the three cohorts, the patients that were given AC were matched with those treated with surgery alone via 1:1 propensity score (PS) matching. Recurrence-free survival (RFS) and overall survival (OS) after the initial hepatectomy were compared. RESULTS The median follow-up period was 79.4 months and the overall, synchronous, and metachronous cohorts included 1145, 498, and 647 patients, respectively. After the PS matching, the patients' demographics were well balanced. AC was effective in terms of both RFS and OS in the overall cohort (RFS hazard ratio [HR] 0.784, p = 0.045; OS HR 0.716, p = 0.028) and synchronous cohort (RFS HR 0.677, p = 0.027; OS HR 0.642, p = 0.036), whereas AC was not effective in the metachronous cohort (RFS HR 0.875, p = 0.378; OS HR 0.881, p = 0.496). However, in the metachronous cohort, AC was effective in terms of OS in the subgroup that exhibited disease-free intervals of ≤ 1 year after primary tumor resection (RFS HR 0.667, p = 0.068; OS HR 0.572, p = 0.042). CONCLUSION Adjuvant chemotherapy has a survival benefit for patients with resected CRLM. Synchronous CRLM is a favorable indication for AC, whereas in metachronous CRLM, the use of AC should be individualized according to each patient's risk factors.
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Affiliation(s)
- Shin Kobayashi
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Toru Beppu
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
| | - Goro Honda
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Gastroenterological Surgery, New Tokyo Hospital, Chiba, Japan
| | - Masakazu Yamamoto
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Keiichi Takahashi
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan.
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo, Tokyo, 1138677, Japan.
| | - Itaru Endo
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Gastrointestinal Surgery, Graduate School of Medicine, Yokohama City University, Kanagawa, Japan
| | - Kiyoshi Hasegawa
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Surgery, Graduate School of Medicine Hepato-Biliary-Pancreatic Surgery Division, University of Tokyo, Tokyo, Japan
| | - Kenjiro Kotake
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Surgery, Sano City Hospital, Tochigi, Japan
| | - Michio Itabashi
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Yojiro Hashiguchi
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Yoshihito Kotera
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Katsunori Sakamoto
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Surgery, Ehime University Hospital, Ehime, Japan
| | - Tatsuro Yamaguchi
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo, Tokyo, 1138677, Japan
| | - Satoshi Morita
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ken Tabuchi
- The Joint Committee for Nationwide Survey on Colorectal Liver Metastasis, Tokyo, Japan
- Department of Pediatrics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Masaru Miyazaki
- Mita Hospital, International University of Health and Welfare, Tokyo, Japan
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Prognostic Value of Poorly Differentiated Clusters in Liver Metastatic Lesions of Colorectal Carcinoma. Am J Surg Pathol 2020; 43:1341-1348. [PMID: 31318710 DOI: 10.1097/pas.0000000000001329] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Colorectal liver metastasis (CRLM) is the most common pattern of metastases or recurrence in colorectal carcinoma; however, no robust pathologic prognostic factors have been identified. This study aimed to verify the prognostic value of poorly differentiated clusters (PDC) in liver metastatic lesions and to clarify the correlation between PDC in liver metastatic lesions (PDC) and the primary tumor histology. Consecutive patients who underwent resection for CRLM were pathologically reviewed. PDC was defined as cancer clusters comprising ≥5 cancer cells and lacking glandular formation and was quantifiably graded as G1 (<5 clusters), G2 (5 to 9 clusters), and G3 (≥10 clusters) based on the highest number of clusters observed under ×20 magnification. The cohort comprised 204 patients. PDC was classified as G1, G2, and G3 for 68, 69, and 67 patients, respectively, and it was significantly associated with PDC grade in the primary tumor (P<0.001). Among the potential prognostic factors, tumor budding in the primary tumor, PDC in the primary tumor, the number of liver metastases, extrahepatic metastasis, and PDC significantly influenced overall survival (OS) after CRLM resection. According to the PDC grade, the 5-year OS rates were 68.9%, 48.3%, and 39.5% for G1, G2, and G3 (P<0.001), respectively. Multivariate analysis for OS showed that PDC grade, tumor budding in the primary tumor, the number of liver metastasis and extrahepatic metastasis were independent prognostic factors. In conclusion, there is a correlation in the PDC grade between the primary tumor and liver metastatic lesion, and PDC grade could be a promising new prognostic factor after CRLM resection.
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Elfrink AKE, Kok NFM, van der Werf LR, Krul MF, Marra E, Wouters MWJM, Verhoef C, Kuhlmann KFD, den Dulk M, Swijnenburg RJ, Te Riele WW, van den Boezem PB, Leclercq WKG, Lips DJ, Nieuwenhuijs VB, Gobardhan PD, Hartgrink HH, Buis CI, Grünhagen DJ, Klaase JM. Population-based study on practice variation regarding preoperative systemic chemotherapy in patients with colorectal liver metastases and impact on short-term outcomes. Eur J Surg Oncol 2020; 46:1742-1755. [PMID: 32303416 DOI: 10.1016/j.ejso.2020.03.221] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 03/09/2020] [Accepted: 03/25/2020] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Definitions regarding resectability and hence indications for preoperative chemotherapy vary. Use of preoperative chemotherapy may influence postoperative outcomes. This study aimed to assess the variation in use of preoperative chemotherapy for CRLM and related postoperative outcomes in the Netherlands. MATERIALS AND METHODS All patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were included from a national database. Case-mix factors contributing to the use of preoperative chemotherapy, hospital variation and postoperative outcomes were assessed using multivariable logistic regression. Postoperative outcomes were postoperative complicated course (PCC), 30-day morbidity and 30-day mortality. RESULTS In total, 4469 patients were included of whom 1314 patients received preoperative chemotherapy and 3155 patients did not. Patients receiving chemotherapy were significantly younger (mean age (+SD) 66.3 (10.4) versus 63.2 (10.2) p < 0.001) and had less comorbidity (Charlson scores 2+ (24% versus 29%, p = 0.010). Unadjusted hospital variation concerning administration of preoperative chemotherapy ranged between 2% and 55%. After adjusting for case-mix factors, three hospitals administered significantly more preoperative chemotherapy than expected and six administered significantly less preoperative chemotherapy than expected. PCC was 12.1%, 30-day morbidity was 8.8% and 30-day mortality was 1.5%. No association between preoperative chemotherapy and PCC (OR 1.24, 0.98-1.55, p = 0.065), 30-day morbidity (OR 1.05, 0.81-1.39, p = 0.703) or with 30-day mortality (OR 1.22, 0.75-2.09, p = 0.467) was found. CONCLUSION Significant hospital variation in the use of preoperative chemotherapy for CRLM was present in the Netherlands. No association between postoperative outcomes and use of preoperative chemotherapy was found.
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Affiliation(s)
- Arthur K E Elfrink
- Dutch Institute for Clinical Auditing, Scientific Bureau, Leiden, the Netherlands; Department of Surgery, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Niels F M Kok
- Department of Surgery, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Leonie R van der Werf
- Dutch Institute for Clinical Auditing, Scientific Bureau, Leiden, the Netherlands; Department of Surgical Oncology, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands
| | - Myrtle F Krul
- Department of Surgery, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Elske Marra
- Dutch Institute for Clinical Auditing, Scientific Bureau, Leiden, the Netherlands
| | - Michel W J M Wouters
- Dutch Institute for Clinical Auditing, Scientific Bureau, Leiden, the Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands
| | - Koert F D Kuhlmann
- Department of Surgery, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Marcel den Dulk
- Department of Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Rutger-Jan Swijnenburg
- Department of Surgery, Cancer Centre Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Wouter W Te Riele
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands
| | | | - Wouter K G Leclercq
- Department of Surgery, Máxima Medical Centre, Eindhoven / Veldhoven, the Netherlands
| | - Daan J Lips
- Department of Surgery, Medical Spectrum Twente, Enschede, the Netherlands
| | | | | | - Henk H Hartgrink
- Department of Surgery, Leiden University Medical Centre, Leiden, the Netherlands
| | - Carlijn I Buis
- Department of Surgery, University Medical Centre Groningen, Groningen, the Netherlands
| | - Dirk J Grünhagen
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Erasmus University, Rotterdam, the Netherlands
| | - Joost M Klaase
- Department of Surgery, University Medical Centre Groningen, Groningen, the Netherlands
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Makhloufi S, Turpin A, el Amrani M, André T, Truant S, Bachet JB, Vernerey D, Hebbar M. Fong’s Score in the Era of Modern Perioperative Chemotherapy for Metastatic Colorectal Cancer: A Post Hoc Analysis of the GERCOR-MIROX Phase III Trial. Ann Surg Oncol 2019; 27:877-885. [DOI: 10.1245/s10434-019-07976-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Indexed: 01/04/2023]
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Barresi V, Fioravanzo A, Pecori S, Tomezzoli A, Reggiani Bonetti L. The histopathologic report of surgically resected colorectal liver metastases: What is clinically relevant? Pathol Res Pract 2019; 215:152547. [PMID: 31371210 DOI: 10.1016/j.prp.2019.152547] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 07/12/2019] [Accepted: 07/17/2019] [Indexed: 02/08/2023]
Abstract
Colorectal carcinoma (CRC) is one of the most common malignancies and a major cause of cancer-related death worldwide. The liver is the most frequent site of metastatic spread, so that about half of the patients with CRC have or develop liver metastases (LM) during the clinical course of the disease. Colorectal LM can potentially be cured by surgery, but most patients still experience disease progression and recurrence after the surgical treatment. Prediction of a patient's post-surgical clinical course is mainly based on clinical parameters or the histopathological features of the primary tumor, while little attention is given to the pathological characteristics of the LM. In this paper, we review the prognostic relevance of the gross and microscopic pathological features observed in surgically resected LM and propose which information should be included in the histopathological report to guide surgeons and oncologists for the subsequent therapeutic management.
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Affiliation(s)
- Valeria Barresi
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy.
| | - Adele Fioravanzo
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy
| | - Sara Pecori
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy
| | - Anna Tomezzoli
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy
| | - Luca Reggiani Bonetti
- Department of Laboratory Integrated Activities, Anatomic Pathology and Legal Medicine, University of Modena and Reggio Emilia, Modena, Italy
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Garlipp B, Gibbs P, Van Hazel GA, Jeyarajah R, Martin RCG, Bruns CJ, Lang H, Manas DM, Ettorre GM, Pardo F, Donckier V, Benckert C, van Gulik TM, Goéré D, Schoen M, Pratschke J, Bechstein WO, de la Cuesta AM, Adeyemi S, Ricke J, Seidensticker M. Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial. Br J Surg 2019; 106:1837-1846. [PMID: 31424576 PMCID: PMC6899564 DOI: 10.1002/bjs.11283] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 05/22/2019] [Accepted: 05/23/2019] [Indexed: 12/12/2022]
Abstract
Background Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX‐based chemotherapy. Methods Baseline and follow‐up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium‐90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. Results Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow‐up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). Conclusion Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM.
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Affiliation(s)
- B Garlipp
- Otto-von-Guericke-University Hospital, Magdeburg, Germany
| | - P Gibbs
- Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia
| | - G A Van Hazel
- Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - R Jeyarajah
- Methodist Richardson Medical Center, Dallas, Texas, USA
| | - R C G Martin
- Division of Surgical Oncology, University of Louisville, Louisville, Kentucky, USA
| | - C J Bruns
- University Hospital Cologne, Cologne, Germany
| | - H Lang
- General, Visceral and Transplant Surgery, University Medical Centre of Johannes Gutenberg University, Mainz, Germany
| | - D M Manas
- Department of Hepato-Pancreato-Biliary Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK
| | | | - F Pardo
- Hepato-Pancreatico-Biliary Surgery and Oncology, Clinica Universidad de Navarra, Pamplona, Spain.,Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain
| | - V Donckier
- Jules Bordet Institute, Brussels, Belgium
| | - C Benckert
- Vivantes Klinikum Am Friedrichshain, Berlin, Germany
| | | | - D Goéré
- Institut Gustave Roussy, Villejuif, France
| | - M Schoen
- Städtisches Klinikum Karlsruhe, Karlsruhe, Germany
| | - J Pratschke
- Charité Universitätsmedizin Berlin, Berlin, Germany
| | - W O Bechstein
- Department of General and Visceral Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | | | - S Adeyemi
- Statsxperts Consulting Limited, Hemel Hempstead, UK
| | - J Ricke
- Deutsche Akademie für Mikrotherapie, Magdeburg, Germany.,Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany
| | - M Seidensticker
- Otto-von-Guericke-University Hospital, Magdeburg, Germany.,Deutsche Akademie für Mikrotherapie, Magdeburg, Germany.,Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany
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Ichida H, Mise Y, Ito H, Ishizawa T, Inoue Y, Takahashi Y, Shinozaki E, Yamaguchi K, Saiura A. Optimal indication criteria for neoadjuvant chemotherapy in patients with resectable colorectal liver metastases. World J Surg Oncol 2019; 17:100. [PMID: 31196104 PMCID: PMC6567619 DOI: 10.1186/s12957-019-1641-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 06/03/2019] [Indexed: 02/07/2023] Open
Abstract
Background There are no optimal indication criteria for neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastases (CLM). The aim of this study was to prospectively assess the survival benefit of selective NAC administration in this patient population based on tumor characteristics. Methods Borderline resectable CLM (BR-CLM) were defined as four or more liver metastases, CLM larger than 5 cm, or CLM with concomitant resectable extrahepatic metastases. From 2010 to 2015, NAC was administered to BR-CLM patients. Upfront surgery without NAC was performed to patients having clearly resectable CLM (less than 3 lesions, smaller than 5 cm, and no extrahepatic metastases: CR-US group). Survival outcomes of the two groups were assessed. Results The BR-NAC group comprised 73 patients and the CR-US group 172. All patients in the BR-NAC group underwent subsequent resection, as none showed disease progression or chemotherapy-associated liver damage. The 3- and 5-year overall survival rates of the CR-US group were 83.0% and 74.0%, while patients in the BR-NAC group had comparable 3-year and 5-year overall survivals (80.5% and 66.6%, P = 0.397). Conclusion Defining BR-CLM based on tumor characteristics optimizes patient selection for NAC. Favorable overall survival can be achieved by upfront surgery in patients with clearly resectable CLM and by NAC in patients with BR-CLM.
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Affiliation(s)
- Hirofumi Ichida
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Yoshihiro Mise
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Hiromichi Ito
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Takeaki Ishizawa
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Yosuke Inoue
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Yu Takahashi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Eiji Shinozaki
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Akio Saiura
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
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Imai K, Yamashita YI, Miyamoto Y, Nakao Y, Yusa T, Itoyama R, Nakagawa S, Okabe H, Hiyoshi Y, Nitta H, Chikamoto A, Baba H. Implication of primary tumor location for the indication of preoperative chemotherapy in patients with colorectal liver metastases. HPB (Oxford) 2019; 21:405-412. [PMID: 30266494 DOI: 10.1016/j.hpb.2018.08.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 08/04/2018] [Accepted: 08/12/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND The benefit of preoperative chemotherapy for colorectal liver metastases (CRLM) remains uncertain. The aim was to clarify the effect of preoperative chemotherapy on CRLM according to the primary tumor location. METHODS Among a total cohort of 163 patients who underwent curative hepatectomy for CRLM, 36 patients had a right-sided and 127 had a left-sided primary tumor. According to the performance of preoperative chemotherapy, survival analysis was conducted and prognostic factors were identified. RESULTS Preoperative chemotherapy was administered to 17 patients (47.2%) with a right-sided and 74 (58.3%) with a left-sided primary tumor (P = 0.24). Among the patients who received preoperative chemotherapy, overall survival (OS) and disease-free survival (DFS) were similar between patients with right- and left-sided primary tumors (P = 0.36 and P = 0.44, respectively). Among the patients who underwent upfront hepatectomy, the OS and DFS of patients with a right-sided primary tumor were worse than those with a left-sided primary tumor (P = 0.02 and P = 0.025, respectively). Among the patients who underwent upfront surgery, the right-sided primary tumor was identified as an independent poor prognostic factor for OS (hazard ratio 3.44, P = 0.021). CONCLUSION The existence of a right-sided primary tumor may be an indication of preoperative chemotherapy for patients with CRLM.
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Affiliation(s)
- Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.
| | - Yo-Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yosuke Nakao
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Toshihiko Yusa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Rumi Itoyama
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yukiharu Hiyoshi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hidetoshi Nitta
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
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Impact of Neoadjuvant Chemotherapy on the Postoperative Outcomes of Patients Undergoing Liver Resection for Colorectal Liver Metastases: A Population-Based Propensity-Matched Analysis. J Am Coll Surg 2019; 229:69-77.e2. [PMID: 30905856 DOI: 10.1016/j.jamcollsurg.2019.03.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 02/26/2019] [Accepted: 03/11/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND The role of neoadjuvant chemotherapy in the management of colorectal liver metastases remains controversial. We sought to investigate whether neoadjuvant systemic chemotherapy contributes to clinically significant increases in postoperative morbidity and mortality using a population-based cohort. STUDY DESIGN The American College of Surgeons NSQIP Targeted Hepatectomy Participant Use Files were queried from 2014 to 2016 to identify patients with colorectal liver metastases who underwent liver resection. Patients were stratified by receipt of neoadjuvant chemotherapy using propensity score matching. Univariate and multivariable analyses were used to characterize the effect of neoadjuvant chemotherapy on perioperative morbidity and mortality. RESULTS After propensity score matching, 1,416 (50%) patients received neoadjuvant chemotherapy before hepatectomy and 1,416 (50%) underwent liver resection without neoadjuvant chemotherapy. There were no differences in age (60 vs 61 years), maximum tumor size (≤5 cm: 79% vs 80%, >5 cm: 21% vs 20%), resection type (partial hepatectomy: 69% vs 70%), simultaneous colectomy (9% vs 9%), or use of preoperative portal vein embolization (5% vs 5%) in those undergoing neoadjuvant chemotherapy compared with those who did not (all, p > 0.05). Overall 30-day postoperative morbidity (34% vs 33%), including rates of biliary fistula (6% vs 5%), post-hepatectomy liver failure (5% vs 5%), and mortality rates (0.8% vs 0.7%), were similar among patients who received neoadjuvant chemotherapy vs those who did not (all, p > 0.05). On multivariable analysis, receipt of neoadjuvant chemotherapy was not associated with increased morbidity (odds ratio 1.07; 95% CI 0.90 to 1.27; p = 0.43) or mortality (odds ratio 1.09; 95% CI 0.44 to 2.72; p = 0.85). CONCLUSIONS In this propensity-matched population-based cohort study, the use of neoadjuvant systemic chemotherapy was not associated with higher rates of complications, biliary fistula, post-hepatectomy liver failure, or mortality among patients with colorectal liver metastases undergoing liver resection.
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Adam R, Kitano Y. Multidisciplinary approach of liver metastases from colorectal cancer. Ann Gastroenterol Surg 2019; 3:50-56. [PMID: 30697610 PMCID: PMC6345652 DOI: 10.1002/ags3.12227] [Citation(s) in RCA: 118] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 12/10/2018] [Accepted: 12/16/2018] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer liver metastases (CRLM) represent most of the causes of death in patients with colorectal cancer. Surgical resection is the only treatment that can provide the possibility of prolonged survival, or even cure, for patients with CRLM. Over the last few decades, survival of these patients has improved dramatically thanks to more effective chemotherapy, extension of surgical indications, and development of new surgical procedures. In particular, patients with initially unresectable CRLM can achieve downsizing of the tumor by using various chemotherapies and the tumor can become resectable. It has been shown that such patients have a 33% 5‐year survival and a 23% 10‐year survival rate after surgery, which is a little bit lower than that of patents with resectable CRLM but significantly higher than patients without surgery. However, a decision‐making strategy for patients with CRLM is difficult because there is a wide variety of treatments and no definitive consensus. As an example, much variation among institutions exists on the resectability rate in patients with unresectable CRLM. Also, it is recommended that all patients with CRLM be managed by a multidisciplinary approach (MDA) to select the best strategy. In the future, new treatment procedures (e.g. immune checkpoint blockade, liver transplantation) may contribute to improve prognosis; hence, the necessity for MDA for the treatment of CRLM will further increase.
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Affiliation(s)
- René Adam
- AP-HP Paul Brousse Hospital, Hepato-Biliary Center Paris Sud University Inserm U 935 Villejuif France
| | - Yuki Kitano
- AP-HP Paul Brousse Hospital, Hepato-Biliary Center Paris Sud University Inserm U 935 Villejuif France.,Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
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Shin H, Kim CW, Lee JL, Yoon YS, Park IJ, Lim SB, Yu CS, Kim JC. Solitary colorectal liver metastasis after curative intent surgery: prognostic factors affecting outcomes and survival. ANZ J Surg 2019; 89:61-67. [PMID: 30484933 DOI: 10.1111/ans.14933] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 09/16/2018] [Accepted: 10/02/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of this study was to identify the prognostic factors affecting recurrence and survival in patients who underwent curative intent surgery for colorectal cancer (CRC) with a single liver metastasis. METHODS Between January 2006 and August 2012, we retrospectively evaluated 141 patients for CRC with single liver metastasis underwent curative intent surgery for colon and liver simultaneously. Some patients (11.3%) had radiofrequency ablation as an option. RESULTS The 5-year disease-free and overall survival (OS) rates were 38.9% and 59.6%, respectively. Recurrence occurred in 77 (54.6%) patients after surgery. Multivariate analysis identified node positivity and no adjuvant chemotherapy as independent risk factors for OS. We analyzed the OS risk factors in 76 recurred patients from the time of recurrence. Multivariate analysis revealed the following significant risk factors for OS after recurrence: a high serum carcinoembryonic antigen concentration at the time of recurrence, the treatment type after recurrence (chemotherapy or no treatment) and a left hepatic metastasis. CONCLUSION Patients who underwent a curative resection for CRC with a single liver metastasis had a relatively favourable prognosis; in these patients, node positivity and no adjuvant chemotherapy were independent prognostic factors for OS. Furthermore, a high serum carcinoembryonic antigen concentration at the time of recurrence, the treatment type after recurrence (chemotherapy or no treatment) and a left hepatic metastasis may be independent prognostic factors for OS in patients with recurrence. The left hepatic metastasis group tended to have a multiple hepatic relapse more frequently than the right hepatic metastasis group in cases of isolated hepatic relapse.
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Affiliation(s)
- Heeji Shin
- Department of Surgery, University of Ulsan College of Medicine, Institute of Innovative Cancer Research, and Asan Medical Center, Seoul, South Korea
| | - Chan Wook Kim
- Department of Surgery, University of Ulsan College of Medicine, Institute of Innovative Cancer Research, and Asan Medical Center, Seoul, South Korea
| | - Jong Lyul Lee
- Department of Surgery, University of Ulsan College of Medicine, Institute of Innovative Cancer Research, and Asan Medical Center, Seoul, South Korea
| | - Yong Sik Yoon
- Department of Surgery, University of Ulsan College of Medicine, Institute of Innovative Cancer Research, and Asan Medical Center, Seoul, South Korea
| | - In Ja Park
- Department of Surgery, University of Ulsan College of Medicine, Institute of Innovative Cancer Research, and Asan Medical Center, Seoul, South Korea
| | - Seok-Byung Lim
- Department of Surgery, University of Ulsan College of Medicine, Institute of Innovative Cancer Research, and Asan Medical Center, Seoul, South Korea
| | - Chang Sik Yu
- Department of Surgery, University of Ulsan College of Medicine, Institute of Innovative Cancer Research, and Asan Medical Center, Seoul, South Korea
| | - Jin Cheon Kim
- Department of Surgery, University of Ulsan College of Medicine, Institute of Innovative Cancer Research, and Asan Medical Center, Seoul, South Korea
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Cetin B, Bilgetekin I, Cengiz M, Ozet A. Managing Synchronous Liver Metastases in Colorectal Cancer. Indian J Surg Oncol 2018; 9:461-471. [PMID: 30538373 PMCID: PMC6265172 DOI: 10.1007/s13193-018-0765-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Accepted: 05/08/2018] [Indexed: 02/06/2023] Open
Abstract
The most common site of blood-borne metastases from colorectal cancers (CRC) is the liver. Resection of (liver) metastases is a part of standard treatment of metastatic colorectal cancer. Hepatic resection is the first-line treatment of liver metastases, with 5-year survival rates between 25 and 58%. The enhanced efficacy of systemic chemotherapeutic regimens has increased tumor response rates and improved the progression-free and overall survival of patients with these malignancies. In approximately 20% of patients with initially unresectable liver metastases, the metastases may become resectable after administration of neoadjuvant chemotherapy. Unresectable liver metastases can be managed with systemic therapy and/or a variety of liver-directed techniques such as radiofrequency ablation, hepatic artery infusion, or yttrium-90 radioembolization. Our examination of the literature led us to propose a new patient-oriented algorithm to guide clinicians' decisions on the best choice of upfront therapy for CRC and synchronous liver metastases. The need for multidisciplinary consensus has become especially important for metastatic CRC.
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Affiliation(s)
- Bulent Cetin
- Department of Internal Medicine, Division of Medical Oncology, Recep Tayyip Erdogan University Faculty of Medicine, 53200 Rize, Turkey
| | - Irem Bilgetekin
- Department of Internal Medicine, Division of Medical Oncology, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Mustafa Cengiz
- Department of Internal Medicine, Division of Gastroenterology, Dr. A. Y. Ankara Oncology Training and Research Hospital, Ankara, Turkey
| | - Ahmet Ozet
- Department of Internal Medicine, Division of Medical Oncology, Gazi University Faculty of Medicine, Ankara, Turkey
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Evrard S, Torzilli G, Caballero C, Bonhomme B. Parenchymal sparing surgery brings treatment of colorectal liver metastases into the precision medicine era. Eur J Cancer 2018; 104:195-200. [PMID: 30380461 DOI: 10.1016/j.ejca.2018.09.030] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 09/11/2018] [Accepted: 09/26/2018] [Indexed: 12/30/2022]
Abstract
The treatment of advanced colorectal liver metastases (CRLMs) follows the biphasic pattern characteristic of oncological surgery. A phase of escalation-the therapeutic aggressiveness-is followed by a phase of de-escalation aimed at decreasing the morbidity, while preserving the gains in survival. From a maximum of three lesions, the rule no longer limits the number, provided the intervention does not cause lethal liver failure. Technically feasible non-anatomical resections, two-stage hepatectomies, portal vein obliteration and so forth, have pushed the boundaries of surgery far. However, the impact and the biology of metastatic processes have been long ignored. Parenchymal sparing surgery (PSS) is a de-escalation strategy that targets only metastasis by minimising the risk of stimulating tumour growth, while enabling iterative interventions. Reducing the loss of healthy parenchyma increases the tolerance of the liver to interval chemotherapy. Technically, PSS could use any type of hepatectomy, providing it is centred on the metastatic load alongside intraoperative ablation. The PSS concept sometimes wrongly comes across as a debate between minor versus major hepatectomies. Hence, we propose a clear definition, both quantitative and qualitative, of what PSS is and what it is not. Conversely, the degree of selectivity of PSS as a percentage of the volume of resected metastases versus the volume of total liver removed has not been stopped to date and should be the subject of prospective studies. Ultimately, the treatment of advanced CRLMs, of which PSS is a part, needs to be personalised by the multidisciplinary team by adapting its response to each new recurrence.
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Affiliation(s)
- Serge Evrard
- Institut Bergonié, 229 Cours de L'Argonne, 33076 Bordeaux, Cedex, France.
| | - Guido Torzilli
- Department of Surgery, Division of Hepatobiliary and General Surgery, Humanitas Research Hospital & Humanitas University, Via A Manzoni 56, 20089 Rozzano-Milano, Italy
| | | | - Benjamin Bonhomme
- Department of Biopathology, Institut Bergonié, 229 Cours de L'Argonne, 33076 Bordeaux, Cedex, France
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Viganò L, Costa G, Cimino MM, Procopio F, Donadon M, Del Fabbro D, Belghiti J, Kokudo N, Makuuchi M, Vauthey JN, Torzilli G. R1 Resection for Colorectal Liver Metastases: a Survey Questioning Surgeons about Its Incidence, Clinical Impact, and Management. J Gastrointest Surg 2018; 22:1752-1763. [PMID: 29948554 DOI: 10.1007/s11605-018-3820-z] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 05/15/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND A ≥ 1-mm margin is standard for resection of colorectal liver metastases (CLM). However, R1 resection is not rare (10-30%), and chemotherapy could mitigate its impact. The possibility of detaching CLM from vessels (R1 vascular margin) has been described. A reappraisal of R1 resection is needed. METHODS A 19-question survey regarding R1 resection for CLM was sent to hepatobiliary surgeons worldwide. Seven clinical cases were included. RESULTS In total, 276 surgeons from 52 countries completed the survey. Ninety percent reported a negative impact of R1 resection (74% local recurrence, 31% hepatic recurrence, and 36% survival), but 50% considered it sometimes required for resectability. Ninety-one percent of responders suggested that the impact of R1 resection is modulated by the response to chemotherapy and/or CLM characteristics. Half considered the risk of R1 resection to be an indication for preoperative chemotherapy in patients who otherwise underwent upfront resection, and 40% modified the chemotherapy regimen when the tumor response did not guarantee R0 resection. Nevertheless, 80% scheduled R1 resection for multiple bilobar CLM that responded to chemotherapy. Forty-five percent considered the vascular margin equivalent to R0 resection. However, for lesions in contact with the right hepatic vein, right hepatectomy remained the standard. Detachment from the vein was rarely considered (10%), but 27% considered detachment in the presence of multiple bilobar CLM. CONCLUSIONS A negative margin is still standard for CLM, but R1 resection is no longer just a technical error. R1 resection should be part of the modern multidisciplinary, aggressive approach to CLM.
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Affiliation(s)
- Luca Viganò
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
| | - Guido Costa
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Matteo Maria Cimino
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Fabio Procopio
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Matteo Donadon
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
| | - Daniele Del Fabbro
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Jacques Belghiti
- Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital Beaujon, Assistance Publique des Hôpitaux de Paris, Clichy, France
| | - Norihiro Kokudo
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masatoshi Makuuchi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, Hepato-Pancreato-Biliary Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. .,Department of Biomedical Sciences, Humanitas University, Rozzano, Italy.
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Madkhali A, Alalem F, Aljuhani G, Alsharaabi A, Alsaif F, Hassanain M. Preoperative Selection and Optimization for Liver Resection in Colorectal Cancer Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2018. [DOI: 10.1007/s11888-018-0405-x] [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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Lionti S, Reggiani Bonetti L, Bettelli S, Spallanzani A, Gelsomino F, Barresi V. Histopathological variables in liver metastases of patients with stage IV colorectal cancer: potential prognostic relevance of poorly differentiated clusters. Hum Pathol 2018; 78:115-124. [PMID: 29715463 DOI: 10.1016/j.humpath.2018.04.019] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 04/08/2018] [Accepted: 04/12/2018] [Indexed: 02/07/2023]
Abstract
The prognosis of patients with colorectal liver metastases (LMs) is mostly established on clinical variables or on the anatomic extent of colorectal cancer (CRC). Histopathological factors of LMs which may actually reflect the biological aggressiveness of the tumor are not routinely considered to define the risk of worse clinical outcome in those patients. The number of poorly differentiated clusters (PDCs) of neoplastic cells in primary CRC is associated with metastatic risk and bad prognosis, but PDC presence in LMs has been barely analyzed thus far. We assessed PDC presence in the histological slides of surgically resected and synchronous LMs in 63 patients with CRC who had been not submitted to any neoadjuvant treatments. Then, we analyzed its association with patients' cancer-specific survival (CSS) or progression-free survival. The presence of PDCs (P = .016) and PDC localization at tumor edge of LMs (P = .0004) were significantly associated with shorter CSS. PDC presence at the periphery of LMs and positive resection margin were independent prognostic variables for CSS. PDC localization at the tumor edge of LMs was a significant (P = .0079) and independent prognosticator of shorter progression-free survival. Our data suggest that PDC presence and peripheral localization in LMs may be relevant to predict outcome and useful for clinical decision making in patients with colorectal synchronous LMs.
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Affiliation(s)
- Simona Lionti
- Department of Pathology in Evolutive Age and Adulthood "Gaetano Barresi," University of Messina, 98125, Messina, Italy
| | - Luca Reggiani Bonetti
- Department of Laboratory Integrated Activities, Anatomic Pathology and Legal Medicine, University of Modena and Reggio Emilia, 41125, Modena, Italy
| | - Stefania Bettelli
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, 41124, Modena, Italy
| | - Andrea Spallanzani
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, 41124, Modena, Italy
| | - Fabio Gelsomino
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, 41124, Modena, Italy
| | - Valeria Barresi
- Department of Pathology in Evolutive Age and Adulthood "Gaetano Barresi," University of Messina, 98125, Messina, Italy.
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Acciuffi S, Meyer F, Bauschke A, Settmacher U, Lippert H, Croner R, Altendorf-Hofmann A. Analysis of prognostic factors after resection of solitary liver metastasis in colorectal cancer: a 22-year bicentre study. J Cancer Res Clin Oncol 2018; 144:593-599. [PMID: 29340767 DOI: 10.1007/s00432-018-2583-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Accepted: 01/11/2018] [Indexed: 02/08/2023]
Abstract
PURPOSE The investigation of the predictors of outcome after hepatic resection for solitary colorectal liver metastasis. METHODS We recruited 350 patients with solitary colorectal liver metastasis at the University Hospitals of Jena and Magdeburg, who underwent curative liver resection between 1993 and 2014. All patients had follow-up until death or till summer 2016. RESULTS The follow-up data concern 96.6% of observed patients. The 5- and 10-year overall survival rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival rates were 30 and 20%, respectively. The analysis of the prognostic factors revealed that the pT category of primary tumour, size and grade of the metastasis and extension of the liver resection had no statistically significant impact on survival and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant predictors for the prognosis. Moreover, patients with rectal cancer had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence rate. CONCLUSION The long-term follow-up of patients with R0-resected liver metastasis is multifactorially influenced. Age and comorbidity have a role only in the overall survival. More than three lymph node metastasis reduced both the overall and disease-free survival. Extrahepatic tumour had a negative influence on the extrahepatic recurrence and on the overall survival. Neither overall survival nor recurrence rates was improved using neoadjuvant chemotherapy.
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Affiliation(s)
- Sara Acciuffi
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Frank Meyer
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Astrid Bauschke
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - Utz Settmacher
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - Hans Lippert
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Roland Croner
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Annelore Altendorf-Hofmann
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany.
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Liu W, Zhou JG, Sun Y, Zhang L, Xing BC. The role of neoadjuvant chemotherapy for resectable colorectal liver metastases: a systematic review and meta-analysis. Oncotarget 2018; 7:37277-37287. [PMID: 27074564 PMCID: PMC5095075 DOI: 10.18632/oncotarget.8671] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 03/28/2016] [Indexed: 12/17/2022] Open
Abstract
Neoadjuvant chemotherapy is being increasingly accepted as an effective treatment of resectable colorectal liver metastases (CRLM), but it may also damage the hepatic parenchyma. We performed a meta-analysis to compare the outcomes of patients who received neoadjuvant chemotherapy (NEO) prior to hepatic resection with hepatic resection without neoadjuvant chemotherapy (SG). Eligible trials were identified from Embase, PubMed, the Web of Science and the Cochrane library. Hazard ratios (HRs) with a 95% confidence intervals (CIs) were used to measure the pooled effect using a random-effects model. Statistical heterogeneity was detected by I2 test. Sensitivity analyses and publication bias were also assessed. The study outcomes included 3-year, 5-year disease-free and overall survival rate, respectively. Eighteen studies involving 6,254 patients were included. The pooled HRs for 5-year DFS and 5-year OS for NEO in the included studies calculated using the random-effects model were 1.38 (95 % CI; 1.26-1.51, p=0.00; I2=9.6%, p=0.36) and 1.19 (95% CI: 1.02-1.38; p=0.03; I2=49.2%, p=0.03), respectively. For CRLM patients with factors indicating a high risk of recurrence, the pooled HR for 5-year OS of NEO in the included studies calculated using the random-effects model was 0.69 (95% CI: 0.55-0.87; p=0.00; I2=0.0%, p=0.48). These results suggest neoadjuvant chemotherapy improved survival of patients with initially resectable CRLM and a high risk of disease recurrence.
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Affiliation(s)
- Wei Liu
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing , PR China
| | - Jian-Guo Zhou
- Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi Medical University, Zunyi, China
| | - Yi Sun
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing , PR China
| | - Lei Zhang
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing , PR China
| | - Bao-Cai Xing
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing , PR China
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Abstract
Surgical treatment of metastatic colorectal cancer offers a chance for cure or prolonged survival, particularly for those with more favorable prognostic factors and limited tumor burden. The treatment plan requires multidisciplinary evaluation because multiple therapy options exist. Advanced surgical techniques, adjuncts to resection, and modern chemotherapy all contribute to best outcomes for patients with hepatic metastases. Although cure is less common for patients with metastasis to lung or peritoneum, surgical resection for the former and cytoreduction and intraperitoneal chemotherapy for the latter may help to achieve cancer control in selected patients.
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Affiliation(s)
- Jeffery Chakedis
- Division of Surgical Oncology, Department of Surgery, Complex General Surgical Oncology, The Ohio State University Wexner Medical Center, Arthur G. James Cancer Hospital and Solove Research Institute, 395 West 12th Avenue, Suite 670, Columbus, OH 43210-1267, USA
| | - Carl R Schmidt
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Arthur G. James Cancer Hospital and Solove Research Institute, 395 West 12th Avenue, Suite 670, Columbus, OH 43210-1267, USA.
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Mukai T, Uehara K, Goto H, Hiramatsu K, Kobayashi S, Sakamoto E, Maeda A, Takeuchi E, Okada Y, Ebata T, Nagino M. Phase II trial of neoadjuvant chemotherapy with S-1 and oxaliplatin plus bevacizumab for colorectal liver metastasis (N-SOG 05 trial). Jpn J Clin Oncol 2017; 47:597-603. [PMID: 28398493 DOI: 10.1093/jjco/hyx048] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Accepted: 03/21/2017] [Indexed: 01/01/2023] Open
Abstract
Purpose This Phase II trial evaluated the safety and efficacy of neoadjuvant chemotherapy (NAC) with S-1 and oxaliplatin (SOX) plus bevacizumab (Bev) in patients with colorectal liver metastasis (CRLM). Methods Patients with initially resectable CRLM received four cycles of SOX plus Bev as NAC. We adopted the R0 resection rate as the primary endpoint, and the threshold R0 resection rate was set at 80%. Results Between December 2010 and August 2014, 61 patients were enrolled in this study and all started NAC. The completion rate of NAC was 82.0%. Three patients (4.9%) developed severe liver dysfunction caused by NAC and one patient finally decided against resection. Three patients (4.9%) were judged as having progressive disease during or after NAC and did not undergo liver resection. Among 57 patients who underwent liver resection after NAC, three patients were diagnosed with CRLM by pre-treatment imaging modalities and received NAC although a final pathological diagnosis was another malignant disease or benign condition. Finally, 47 of the 54 patients (87.0%) with resected CRLM achieved R0 resection. The pathological complete response rate of the 54 patients was 13.0%, and 31.5% were judged as pathological responders. However, the R0 resection rate of 77.0% in the entire cohort did not meet the endpoint. Conclusions NAC with SOX plus Bev has an acceptable toxicity profile and achieved a satisfactory pathological response. However, accuracy of pre-operative diagnoses and liver dysfunction caused by NAC were serious problems. Easy introduction of NAC for initially resectable CRLM should not be performed.
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Affiliation(s)
- Toshiki Mukai
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya
| | - Keisuke Uehara
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya
| | | | | | | | - Eiji Sakamoto
- Department of Surgery, Nagoya Daini Red Cross Hospital, Nagoya
| | | | - Eiji Takeuchi
- Department of Surgery, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya
| | - Yoshito Okada
- Department of Surgery, Handa City Hospital, Aichi, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya
| | - Masato Nagino
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya
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