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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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Zhong C, Jiang WJ, Yao Y, Li Z, Li Y, Wang S, Wang X, Zhu W, Wu S, Wang J, Fan S, Ma S, Liu Y, Zhang H, Zhao W, Zhao L, Feng Y, Li Z, Guo R, Yu L, Pei F, Hu J, Feng X, Yang Z, Yang Z, Yang X, Hou Y, Zhang D, Xu D, Sheng R, Li Y, Liu L, Wu HJ, Huang J, Fei T. CRISPR screens reveal convergent targeting strategies against evolutionarily distinct chemoresistance in cancer. Nat Commun 2024; 15:5502. [PMID: 38951519 PMCID: PMC11217446 DOI: 10.1038/s41467-024-49673-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 06/17/2024] [Indexed: 07/03/2024] Open
Abstract
Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.
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Affiliation(s)
- Chunge Zhong
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
- Foshan Graduate School of Innovation, Northeastern University, Foshan, 528311, China
| | - Wen-Jie Jiang
- Peking University Third Hospital, Beijing, 100191, China
| | - Yingjia Yao
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Zexu Li
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - You Li
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Shengnan Wang
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Xiaofeng Wang
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Wenjuan Zhu
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Siqi Wu
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
| | - Jing Wang
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
| | - Shuangshuang Fan
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Shixin Ma
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Yeshu Liu
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
| | - Han Zhang
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Wenchang Zhao
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Lu Zhao
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Yi Feng
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Zihan Li
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China
| | - Ruifang Guo
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
| | - Li Yu
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
| | - Fengyun Pei
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jun Hu
- Clinical Research Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Institute of Gastroenterology, Guangzhou, China
| | - Xingzhi Feng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Institute of Gastroenterology, Guangzhou, China
| | - Zihuan Yang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Institute of Gastroenterology, Guangzhou, China
| | - Zhengjia Yang
- Department of Cardiothoracic Surgery, Jinqiu Hospital of Liaoning Province, Shenyang, China
| | - Xueying Yang
- Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Yue Hou
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
| | - Danni Zhang
- Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), School of Materials Science and Engineering, Northeastern University, Shenyang, China
| | - Dake Xu
- Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), School of Materials Science and Engineering, Northeastern University, Shenyang, China
| | - Ren Sheng
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
| | - Yihao Li
- BeiGene Institute, BeiGene (Shanghai) Research & Development Co., Ltd, 200131, Shanghai, China
| | - Lijun Liu
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China
| | - Hua-Jun Wu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, 100142, China.
- Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
- Center for Precision Medicine Multi-Omics Research, Institute of Advanced Clinical Medicine, Peking University, Beijing, 100191, China.
| | - Jun Huang
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- Clinical Research Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- Guangdong Institute of Gastroenterology, Guangzhou, China.
| | - Teng Fei
- Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
- National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Northeastern University, Shenyang, 110819, China.
- Key Laboratory of Data Analytics and Optimization for Smart Industry (Northeastern University), Ministry of Education, Shenyang, 110819, China.
- Foshan Graduate School of Innovation, Northeastern University, Foshan, 528311, China.
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Zhang XL, Wang HT, Tang Y, Lu Q, Yuan HX, Wang X, Liu LH, Zhu DX, Wang WP. Colorectal liver metastases: Correlations of contrast-enhanced ultrasound features with tumor clinicopathological factors and clinical outcomes following conversion therapy. Clin Hemorheol Microcirc 2024; 86:339-356. [PMID: 37927253 DOI: 10.3233/ch-231963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2023]
Abstract
OBJECTIVE To explore the prognostic impact of contrast-enhanced ultrasound (CEUS) features for initially unresectable colorectal liver metastases (CLMs) in a clinical setting of conversion therapy. METHODS Between March 2015 and November 2020, consecutive patients with CLMs who received conversion treatment were prospectively enrolled. All participants underwent liver CEUS at baseline. The primary endpoint was conversion resection rate (R0 and overall resection). Secondary endpoints were objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). RESULTS 104 participants who completed conversion treatment were included. CEUS enhancement pattern was correlated with index lesion (size and echogenicity), primary (site, differentiation, perineural invasion, and RAS genotype) and serum (CA19-9 level) characteristics (P = <0.001-0.016). CEUS enhancement pattern was significantly associated with R0 resection rate, ORR, PFS, and OS (P = 0.001-0.049), whereas enhancement degree was associated with PFS and OS (P = 0.043 and 0.045). Multivariate analysis showed that heterogeneous enhancement independently predicted R0 and overall resection (P = 0.028 and 0.024) while rim-like enhancement independently predicted ORR and OS (P = 0.009 and 0.026). CONCLUSION CEUS enhancement pattern was significantly associated with tumor characteristics and clinical outcomes following conversion therapy, and thus might be of prognosis impact for initially unresectable CLMs.
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Affiliation(s)
- Xiao-Long Zhang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hang-Tao Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yang Tang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qing Lu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hai-Xia Yuan
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xi Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Li-Heng Liu
- Department of Radiology and Multi-Disciplinary Team of Colorectal Cancer, Zhongshan Hospital, Fudan University, Shanghai, China
| | - De-Xiang Zhu
- Department of General Surgery and Multi-Disciplinary Team of Colorectal Cancer, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wen-Ping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
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Choi SH, Yang G, Koom WS, Yang SY, Kim S, Lim JS, Kim HS, Shin SJ, Chang JS. Active involvement of patients, radiation oncologists, and surgeons in a multidisciplinary team approach: Guiding local therapy in recurrent, metastatic rectal cancer. Cancer Med 2023; 12:21057-21067. [PMID: 37909227 PMCID: PMC10709736 DOI: 10.1002/cam4.6667] [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] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 09/11/2023] [Accepted: 09/27/2023] [Indexed: 11/02/2023] Open
Abstract
BACKGROUND Despite the extensive implementation of an organized multidisciplinary team (MDT) approach in cancer treatment, there is little evidence regarding the optimal format of MDT. We aimed to investigate the impact of patient participation in MDT care on the actual application rate of metastasis-directed local therapy. METHODS We identified all 1211 patients with locally advanced rectal cancer treated with neoadjuvant radiochemotherapy at a single institution from 2006 to 2018. Practice patterns, tumor burden and OMD state were analyzed in recurrent, metastatic cases. RESULTS With a median follow-up of 60.7 months, 281 patients developed metastases, and 96 (34.2%), 92 (32.7%), and 93 (33.1%) patients had 1, 2-5, and >5 lesions, respectively. In our study, 27.1% were managed in the MDT clinic that mandated the participation of at least four to five board-certified multidisciplinary experts and patients in decision-making processes, while the rest were managed through diverse MDT approaches such as conferences, tumor board meetings, and discussions conducted via phone calls or email. Management in MDT clinic was significantly associated with more use of radiotherapy (p = 0.003) and more sessions of local therapy (p < 0.001). At the time of MDT clinic, the number of lesions was 1, 2-5, and >5 in 9 (13.6%), 35 (53.1%), and 19 (28.8%) patients, respectively. The most common states were repeat OMD (28.8%) and de novo OMD (27.3%), followed by oligoprogression (15%) and induced OMD (10.6%). CONCLUSION Our findings suggest that active involvement of patients and radiation oncologists, and surgeons in MDT care has boosted the probability of using local therapies for various types of OMD throughout the course of the disease.
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Affiliation(s)
- Seo Hee Choi
- Department of Radiation OncologyYonsei University College of MedicineSeoulKorea
| | - Gowoon Yang
- Department of Radiation OncologyYonsei University College of MedicineSeoulKorea
| | - Woong Sub Koom
- Department of Radiation OncologyYonsei University College of MedicineSeoulKorea
| | - Seung Yoon Yang
- Department of SurgeryYonsei University College of MedicineSeoulKorea
| | - Seung‐Seob Kim
- Department of RadiologyYonsei University College of MedicineSeoulKorea
| | - Joon Seok Lim
- Department of RadiologyYonsei University College of MedicineSeoulKorea
| | - Han Sang Kim
- Division of Medical Oncology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
| | - Sang Joon Shin
- Division of Medical Oncology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
| | - Jee Suk Chang
- Department of Radiation OncologyYonsei University College of MedicineSeoulKorea
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Wang YY, Xin ZC, Wang K. Impact of Molecular Status on Metastasectomy of Colorectal Cancer Liver Metastases. Clin Colon Rectal Surg 2023; 36:423-429. [PMID: 37795466 PMCID: PMC10547543 DOI: 10.1055/s-0043-1767700] [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: 10/06/2023]
Abstract
Although surgical resection could provide better survival for patients with colorectal cancer liver metastases (CRLM), the recurrence rate after resection of CRLM remains high. The progress of genome sequencing technologies has greatly improved the molecular understanding of colorectal cancer. In the era of genomics and targeted therapy, genetic mutation analysis is of great significance to guide systemic treatment and identify patients who can benefit from resection of CRLM. RAS and BRAF mutations and microsatellite instability/deficient deoxyribonucleic acid (DNA) mismatch repair status have been incorporated into current clinical practice. Other promising molecular biomarkers such as coexisting gene mutations and circulating tumor DNA are under active investigation. This study aimed to review the prognostic significance of molecular biomarkers in patients with CRLM undergoing metastasectomy based on the current evidence.
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Affiliation(s)
- Yan-Yan Wang
- 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, China
| | - Ze-Chang Xin
- 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, China
| | - Kun Wang
- 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, China
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Deng Y, Chen Q, Chen J, Zhang Y, Zhao J, Bi X, Li Z, Zhang Y, Huang Z, Cai J, Zhao H. An elevated preoperative cholesterol-to-lymphocyte ratio predicts unfavourable outcomes in colorectal cancer liver metastasis patients receiving simultaneous resections: a retrospective study. BMC Surg 2023; 23:131. [PMID: 37194000 DOI: 10.1186/s12893-023-01988-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 04/04/2023] [Indexed: 05/18/2023] Open
Abstract
BACKGROUND To explore the clinical prognostic utility of the preoperative cholesterol-to-lymphocyte ratio (CLR) in outcomes for colorectal cancer liver metastasis (CRLM) patients receiving simultaneous resection of the primary lesion and liver metastases. METHODS A total of 444 CRLM patients receiving simultaneous resections were enrolled. The optimal cut-off value for CLR was determined using the highest Youden's index. Patients were divided into the CLR < 3.06 group and the CLR≥3.06 group. Propensity score matching analysis (PSM) and the inverse probability of treatment weighting (IPTW) method were conducted to eliminate bias between the two groups. The outcomes included short-term outcomes and long-term outcomes. Kaplan-Meier curves and log-rank tests were used to analyse progression-free survival (PFS) and overall survival (OS). RESULTS In the short-term outcome analysis, after 1:1 PSM, 137 patients were distributed to the CLR < 3.06 group and CLR≥3.06 group. No significant difference was noted between the two groups (P > 0.1). Compared with patients with CLR < 3.06, patients with CLR≥3.06 had comparable operation times (320.0 [272.5-421.0] vs. 360.0 [292.5-434.5], P = 0.088), blood loss (200.0 [100.0-400.0] vs. 200.0 [150.0-450.0], P = 0.831), postoperative complication rates (50.4% vs. 46.7%, P = 0.546) and postoperative ICU rates (5.8% vs. 11.7%, P = 0.087). In the long-term outcome analysis, Kaplan-Meier analysis showed that compared with patients with CLR < 3.06, patients with CLR≥3.06 had worse PFS (P = 0.005, median: 10.2 months vs. 13.0 months) and OS (P = 0.002, median: 41.0 months vs. 70.9 months). IPTW-adjusted Kaplan-Meier analysis showed that the CLR≥3.06 group had worse PFS (P = 0.027) and OS (P = 0.010) than the CLR < 3.06 group. In the IPTW-adjusted Cox proportional hazards regression analysis, CLR≥3.06 was an independent factor for PFS (HR = 1.376, 95% CI 1.097-1.726, P = 0.006) and OS (HR = 1.723, 95% CI 1.218-2.439, P = 0.002). IPTW-adjusted Cox proportional hazards regression analysis including postoperative complications, operation time, intraoperative blood loss, intraoperative blood transfusion and postoperative chemotherapy revealed that CLR≥3.06 was an independent factor for PFS (HR = 1.617, 95% CI 1.252-2.090, P < 0.001) and OS (HR = 1.823, 95% CI 1.258-2.643, P = 0.002). CONCLUSIONS The preoperative CLR level predicts unfavourable outcomes in CRLM patients receiving simultaneous resection of the primary lesion and liver metastases and should be taken into consideration when developing treatment and monitoring strategies.
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Affiliation(s)
- Yiqiao Deng
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Qichen Chen
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jinghua Chen
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yizhou Zhang
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jianjun Zhao
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xinyu Bi
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhiyu Li
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yefan Zhang
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhen Huang
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Galli R, Siciliano T, Aust D, Korn S, Kirsche K, Baretton GB, Weitz J, Koch E, Riediger C. Label-free multiphoton microscopy enables histopathological assessment of colorectal liver metastases and supports automated classification of neoplastic tissue. Sci Rep 2023; 13:4274. [PMID: 36922643 PMCID: PMC10017791 DOI: 10.1038/s41598-023-31401-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/10/2023] [Indexed: 03/18/2023] Open
Abstract
As the state of resection margins is an important prognostic factor after extirpation of colorectal liver metastases, surgeons aim to obtain negative margins, sometimes elaborated by resections of the positive resection plane after intraoperative frozen sections. However, this is time consuming and results sometimes remain unclear during surgery. Label-free multimodal multiphoton microscopy (MPM) is an optical technique that retrieves morpho-chemical information avoiding all staining and that can potentially be performed in real-time. Here, we investigated colorectal liver metastases and hepatic tissue using a combination of three endogenous nonlinear signals, namely: coherent anti-Stokes Raman scattering (CARS) to visualize lipids, two-photon excited fluorescence (TPEF) to visualize cellular patterns, and second harmonic generation (SHG) to visualize collagen fibers. We acquired and analyzed over forty thousand MPM images of metastatic and normal liver tissue of 106 patients. The morphological information with biochemical specificity produced by MPM allowed discriminating normal liver from metastatic tissue and discerning the tumor borders on cryosections as well as formalin-fixed bulk tissue. Furthermore, automated tissue type classification with a correct rate close to 95% was possible using a simple approach based on discriminant analysis of texture parameters. Therefore, MPM has the potential to increase the precision of resection margins in hepatic surgery of metastases without prolonging surgical intervention.
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Affiliation(s)
- Roberta Galli
- Department of Medical Physics and Biomedical Engineering, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
| | - Tiziana Siciliano
- Center for Regenerative Therapies (CRTD), Technische Universität Dresden, Fetscherstr. 105, 01307, Dresden, Germany
| | - Daniela Aust
- Institute of Pathology, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
| | - Sandra Korn
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Katrin Kirsche
- Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Gustavo B Baretton
- Institute of Pathology, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
| | - Jürgen Weitz
- National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.,Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Edmund Koch
- Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Carina Riediger
- National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.,Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
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8
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Liu Y, Zhou B, Tang W, Xu D, Yan Z, Ren L, Zhu D, He G, Wei Y, Chang W, Xu J. Preoperative transarterial chemoembolization with drug-eluting beads (DEB-TACE) in patients undergoing conversional hepatectomy: a propensity-score matching analysis. Eur Radiol 2023; 33:1022-1030. [PMID: 36066736 DOI: 10.1007/s00330-022-09063-0] [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: 03/12/2022] [Revised: 06/30/2022] [Accepted: 07/24/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVES Patients with colorectal liver metastases (CRLM) who underwent hepatic resection after conversion therapy had a high recurrence rate of nearly 90%. Preoperative DEB-TACE has the potential to prevent postoperative recurrence which has not been elucidated. The objective of this study was to evaluate the safety and efficacy of preoperative DEB-TACE. MATERIALS AND METHODS Patients with CRLM who underwent liver resection from June 1, 2016, to June 30, 2021, were collected and those who received conversional hepatectomy were included in this study. Patients with preoperative DEB-TACE were propensity-score matched in a 1:1 ratio to patients without preoperative DEB-TACE. Short-term outcomes and recurrence-free survival (RFS) were compared between the two groups. RESULTS After PSM, 44 patients were included in each group. The toxicities of DEB-TACE were mild and could be managed by conservative treatment. Overall response rate (ORR) of conversion therapy (75.0% vs. 81.2%, p = 0.437) and postoperative complication of hepatic resection (27.3% vs. 20.5%, p = 0.453) were similar between the two groups. The median RFS of the DEB-TACE group (10.7 months, 95%CI: 6.6-14.8 months) was significantly longer than that of the control group (8.1 months, 95%CI: 3.4-12.8 months) (HR: 0.60, 95%CI: 0.37-0.95, p = 0.027). CONCLUSIONS In patients who became resectable after conversion therapy, preoperative DEB-TACE might be a safe option to achieve longer RFS. KEY POINTS • This is a propensity-score matching study comparing patients who underwent conversional hepatectomy with or without preoperative DEB-TACE. • The preoperative DEB-TACE was safe and with mild toxicities (without toxicities more than CTCAE grade 3). • The preoperative DEB-TACE significantly prolonged the RFS of those patients who underwent conversional hepatectomy (10.7 vs. 8.1 months, p = 0.027).
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Affiliation(s)
- Yu Liu
- Colorectal Cancer Centre, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Engineering Research Centre of Colorectal Cancer Minimally Invasive, Shanghai, China
| | - Bo Zhou
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wentao Tang
- Colorectal Cancer Centre, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Engineering Research Centre of Colorectal Cancer Minimally Invasive, Shanghai, China
| | - Donghao Xu
- Colorectal Cancer Centre, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhiping Yan
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Li Ren
- Colorectal Cancer Centre, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Engineering Research Centre of Colorectal Cancer Minimally Invasive, Shanghai, China
| | - Dexiang Zhu
- Colorectal Cancer Centre, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Engineering Research Centre of Colorectal Cancer Minimally Invasive, Shanghai, China
| | - Guodong He
- Colorectal Cancer Centre, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Engineering Research Centre of Colorectal Cancer Minimally Invasive, Shanghai, China
| | - Ye Wei
- Colorectal Cancer Centre, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Engineering Research Centre of Colorectal Cancer Minimally Invasive, Shanghai, China
| | - Wenju Chang
- Colorectal Cancer Centre, Zhongshan Hospital, Fudan University, Shanghai, China. .,Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. .,Shanghai Engineering Research Centre of Colorectal Cancer Minimally Invasive, Shanghai, China.
| | - Jianmin Xu
- Colorectal Cancer Centre, Zhongshan Hospital, Fudan University, Shanghai, China. .,Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. .,Shanghai Engineering Research Centre of Colorectal Cancer Minimally Invasive, Shanghai, China.
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9
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Takamizawa Y, Inoue M, Moritani K, Tsukamoto S, Esaki M, Shimada K, Kanemitsu Y. Prognostic impact of conversion hepatectomy for initially unresectable colorectal liver metastasis. Langenbecks Arch Surg 2022; 407:2893-2903. [PMID: 36068379 DOI: 10.1007/s00423-022-02666-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 08/25/2022] [Indexed: 11/25/2022]
Abstract
PURPOSE This study aimed to evaluate the prognostic impact of conversion hepatectomy in patients with initially unresectable colorectal liver metastasis (CRLM) and to identify prognostic factors after conversion hepatectomy. METHODS Correlations of conversion hepatectomy with relapse-free survival (RFS) and overall survival (OS) were retrospectively investigated in 554 consecutive patients who underwent hepatectomy for CRLM in 2000-2017. Prognostic factors after conversion hepatectomy were examined in multivariable analysis. RESULTS Five hundred and nine patients (92%) had initially resectable CRLM at diagnosis and underwent hepatectomy (primary resection group) and 45 (8%) underwent conversion hepatectomy following chemotherapy (conversion group). The 5-year RFS was 30.0% in the primary resection group and 19.8% in the conversion group (p = 0.042); the respective 5-year OS rates were 62.0% and 52.4% (p = 0.253). Multivariable analysis did not identify conversion hepatectomy as a significant prognostic factor for RFS (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.64-1.37, p = 0.796) or OS (HR 1.12, 95% CI 0.67-1.79, p = 0.667). In the conversion group, multivariable analysis identified the following independent prognostic factors: timing of liver metastases for RFS (synchronous: HR 3.14, 95% CI 1.20-8.24, p = 0.020) and preoperative CEA level for RFS (> 5 ng/ml: HR 3.10, 95% CI 1.45-6.61, p = 0.003) and OS (> 5 ng/ml: HR 3.29, 95% CI 1.18-9.17, p = 0.023). CONCLUSIONS RFS and OS rates after conversion hepatectomy were not inferior to those after primary resection in patients with CRLM. Patients with a normal CEA level before hepatectomy can be expected to have good long-term prognosis after conversion hepatectomy.
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Affiliation(s)
- Yasuyuki Takamizawa
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
| | - Manabu Inoue
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Konosuke Moritani
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Shunsuke Tsukamoto
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yukihide Kanemitsu
- Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
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10
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Wu R, Gogineni K, Meisel J, Szabo S, Thirunavu M, Friend S, Bercu Z, Sethi I, Natarajan N, Switchenko J, Levy J, Abdalla E, Weakland L, Kalinsky K, Kokabi N. Study Protocol: Efficacy and Safety of Radioembolization (REM) as an Early Modality (EM) Therapy for Metastatic Breast Cancer (BR) to the Liver with Y90 (REMEMBR Y90). Cardiovasc Intervent Radiol 2022; 45:1725-1734. [PMID: 36008574 DOI: 10.1007/s00270-022-03254-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 08/09/2022] [Indexed: 11/27/2022]
Abstract
PURPOSE The primary objective of the REMEMBR Y90 study is to evaluate the efficacy of Yttrium-90 (Y90) radioembolization in patients with breast cancer metastases to the liver as a 2nd or 3rd line treatment option with systemic therapy by assessing liver-specific and overall progression-free survival. Secondary objectives include quality of life, overall survival benefit, and toxicity in relation to patients' tumor biology. MATERIALS AND METHODS This trial is a multi-center, prospective, Phase 2, open-label, IRB-approved, randomized control trial in the final phases of activation. Eligible patients include those over 18 years of age with metastatic breast cancer to the liver with liver-only or liver-dominant disease, and history of tumor progression on 1-2 lines of chemotherapy. 60 patients will be randomized to radioembolization with chemotherapy versus chemotherapy alone. Permissible regimens include capecitabine, eribulin, vinorelbine, and gemcitabine within 2 weeks of enrollment for every patient. Patients receiving radioembolization will receive lobar or segmental treatment within 1-6 weeks of enrollment depending on their lesion. After final radioembolization, patients will receive clinical and imaging follow-up every 12-16 weeks for two years, including contrast-enhanced computed tomography or magnetic resonance imaging of the abdomen and whole-body positron emission tomography/computed tomography. DISCUSSION This study seeks to elucidate the clinical benefit and toxicity of Y90 in patients with metastatic breast cancer to the liver who are receiving minimal chemotherapy. Given previous data, it is anticipated that the use of Y90 and chemotherapy earlier in the metastatic disease course would improve survival outcomes and reduce toxicity. LEVEL OF EVIDENCE Level 1b, Randomized Controlled Trial. TRIAL REGISTRATION NUMBER NCT05315687 on clinicaltrials.gov.
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Affiliation(s)
- Richard Wu
- School of Medicine, Emory University, Atlanta, GA, USA
| | - Keerthi Gogineni
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Jane Meisel
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Stephen Szabo
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Meenakshi Thirunavu
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Sarah Friend
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Zachary Bercu
- Division of Interventional Radiology and Image Guided Medicine, Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, USA
| | - Ila Sethi
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, USA
| | - Neela Natarajan
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Jeffrey Switchenko
- Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA
| | - Jason Levy
- Northside Hospital Cancer Institute, Atlanta, GA, USA
| | - Eddie Abdalla
- Northside Hospital Cancer Institute, Atlanta, GA, USA
| | | | - Kevin Kalinsky
- Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
| | - Nima Kokabi
- Division of Interventional Radiology and Image Guided Medicine, Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA, USA.
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11
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Xu W, Zhao D, Huang X, Zhang M, Yin M, Liu L, Wu H, Weng Z, Xu C. The prognostic value and clinical significance of mitophagy-related genes in hepatocellular carcinoma. Front Genet 2022; 13:917584. [PMID: 35991574 PMCID: PMC9388833 DOI: 10.3389/fgene.2022.917584] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 06/30/2022] [Indexed: 12/21/2022] Open
Abstract
Background: Mitophagy has been found to play a significant part in the cancer process in a growing number of studies in recent years. However, there is still a lack of study on mitophagy-related genes' (MRGs) prognostic potential and clinical significance in hepatocellular carcinoma (HCC). Methods: We employed bioinformatics and statistical knowledge to examine the transcriptome data of HCC patients in the TCGA and GEO databases, with the goal of constructing a multigene predictive model. Then, we separated the patients into high- and low-risk groups based on the score. The model's dependability was determined using principal components analysis (PCA), survival analysis, independent prognostic analysis, and receiver operating characteristic (ROC) analysis. Following that, we examined the clinical correlations, pharmacological treatment sensitivity, immune checkpoint expression, and immunological correlations between patients in high and low risk groups. Finally, we evaluated the variations in gene expression between high- and low-risk groups and further analyzed the network core genes using protein-protein interaction network analysis. Results: Prognostic models were built using eight genes (OPTN, ATG12, CSNK2A2, MFN1, PGAM5, SQSTM1, TOMM22, TOMM5). During validation, the prognostic model demonstrated high reliability, indicating that it could accurately predict the prognosis of HCC patients. Additionally, we discovered that typical HCC treatment medicines had varying impacts on patients classified as high or low risk, and that individuals classified as high risk are more likely to fail immunotherapy. Additionally, the high-risk group expressed more immunological checkpoints. The immunological status of patients in different risk categories varies as well, and patients with a high-risk score have a diminished ability to fight cancer. Finally, PPI analysis identified ten related genes with potential for research. Conclusion: Our prognostic model had good and reliable predictive ability, as well as clinical diagnosis and treatment guiding significance. Eight prognostic MRGs and ten network core genes merited further investigation.
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Affiliation(s)
- Wei Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Dongxu Zhao
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiaowei Huang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Man Zhang
- Department of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Minyue Yin
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Lu Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Hongyu Wu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhen Weng
- Cyrus Tang Hematology Center and Ministry of Education Engineering Center of Hematological Disease, and the Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
| | - Chunfang Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
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12
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SegChaNet: A Novel Model for Lung Cancer Segmentation in CT Scans. Appl Bionics Biomech 2022; 2022:1139587. [PMID: 35607427 PMCID: PMC9124150 DOI: 10.1155/2022/1139587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 05/02/2022] [Indexed: 11/17/2022] Open
Abstract
Accurate lung tumor identification is crucial for radiation treatment planning. Due to the low contrast of the lung tumor in computed tomography (CT) images, segmentation of the tumor in CT images is challenging. This paper effectively integrates the U-Net with the channel attention module (CAM) to segment the malignant lung area from the surrounding chest region. The SegChaNet method encodes CT slices of the input lung into feature maps utilizing the trail of encoders. Finally, we explicitly developed a multiscale, dense-feature extraction module to extract multiscale features from the collection of encoded feature maps. We have identified the segmentation map of the lungs by employing the decoders and compared SegChaNet with the state-of-the-art. The model has learned the dense-feature extraction in lung abnormalities, while iterative downsampling followed by iterative upsampling causes the network to remain invariant to the size of the dense abnormality. Experimental results show that the proposed method is accurate and efficient and directly provides explicit lung regions in complex circumstances without postprocessing.
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13
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Synthesis of diaryl urea derivatives and evaluation of their antiproliferative activities in colon adenocarcinoma. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2021.132318] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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14
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Vogl TJ, Lahrsow M. The Role of Conventional TACE (cTACE) and DEBIRI-TACE in Colorectal Cancer Liver Metastases. Cancers (Basel) 2022; 14:1503. [PMID: 35326651 PMCID: PMC8946099 DOI: 10.3390/cancers14061503] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 03/11/2022] [Accepted: 03/12/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common tumor entities worldwide and a common cause of cancer-associated death. Colorectal cancer liver metastases (CRLM) thereby constitute a severe life-limiting factor. The therapy of CRLM presents a major challenge and surgical resection as well as systemic chemotherapy remain the first-line treatment options. Over the years several locoregional, vascular- and image-based treatments offered by interventional radiologists have emerged when conventional therapies fail, or metastases recurrence occurs. Among such options is the conventional/traditional transarterial chemoembolization (cTACE) by local injection of a combination of chemotherapeutic- and embolic-agents. A similar treatment is the more recent irinotecan-loaded drug-eluting beads TACE (DEBIRI-TACE), which are administered using the same approach. Numerous studies have shown that these different types of chemoembolization can be applied in different clinical settings safely. Furthermore, such treatments can also be combined with other local or systemic therapies. Unfortunately, due to the incoherent patient populations of studies investigating TACE in CRLM, critics state that the definite evidence supporting positive patient outcomes is still lacking. In the following article we review studies on conventional and DEBIRI-TACE. Although highly dependent on the clinical setting, prior therapies and generally the study population, cTACE and DEBIRI-TACE show comparable results. We present the most representative studies on the different chemoembolization procedures and compare the results. Although there is compelling evidence for both approaches, further studies are necessary to determine which patients profit most from these therapies. In conclusion, we determine TACE to be a viable option in CRLM in different clinical settings. Nevertheless, a multidisciplinary approach is desired to offer patients the best possible care.
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Affiliation(s)
| | - Maximilian Lahrsow
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany;
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15
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Umeda Y, Nagasaka T, Takagi K, Yoshida R, Yoshida K, Fuji T, Matsuda T, Yasui K, Kumano K, Sato H, Yagi T, Fujiwara T. Technique of vessel-skeletonized parenchyma-sparing hepatectomy for the oncological treatment of bilobar colorectal liver metastases. Langenbecks Arch Surg 2021; 407:685-697. [PMID: 34839388 PMCID: PMC8933371 DOI: 10.1007/s00423-021-02373-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 10/30/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND To aid in the oncological management of multiple bilobar colorectal liver metastases (CRLMs), we describe a new surgical procedure, VEssel-Skeletonized PArenchyma-sparing Hepatectomy (VESPAH). STUDY DESIGN Of 152 patients with CRLMs treated with hepatectomy, 33 patients had multiple bilobar liver metastases (≥8 liver metastases); their surgical procedures and clinical outcomes were retrospectively summarized and compared between those who underwent VESPAH and those who underwent major hepatectomy (Major Hx). RESULTS Of the 33 patients, 20 patients were resected by VESPAH (the VESPAH group) and 13 patients by major hepatectomy (Major Hx group). The median number of CRLMs was 13 (range, 8-53) in the VESPAH group and 10 (range, 8-41) in the Major Hx group (P=0.511). No operative mortality nor severe morbidity was observed in either group. The VESPAH group showed earlier recovery of remnant liver function after surgery than the Major Hx group; the incidence of grade B/C post hepatectomy liver failure was 5% in the VESPAH group and 38% in the Major Hx group, P=0.048). Intrahepatic tumor recurrence was confirmed in 14 (70%) and 7 (54%) patients in the VESPAH and Major Hx groups, respectively (P=0.416). There was no significant difference in median overall survival (OS) after hepatectomy between the two groups; the median OS was 47 months in the VESPAH group and 33 months in the Major Hx group (P=0.481). The VESPAH group showed the higher induction rate of adjuvant chemotherapy within 2 months after surgery (P=0.002) and total number of repeat hepatectomy for intrahepatic recurrence (P=0.060) than the Major Hx group. CONCLUSIONS VESPAH enables us to clear surgical navigation by hepatic vessel skeletonization and may enhance patient tolerability of not only adjuvant chemotherapy but also repeat hepatectomies during the patients' lifetimes.
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Affiliation(s)
- Yuzo Umeda
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan.
| | - Takeshi Nagasaka
- Department of Clinical Oncology, Kawasaki Medical School, Kurashiki, Okayama, 701-0192, Japan
| | - Kosei Takagi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan
| | - Ryuichi Yoshida
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan
| | - Kazuhiro Yoshida
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan
| | - Tomokazu Fuji
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan
| | - Tatsuo Matsuda
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan
| | - Kazuya Yasui
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan
| | - Kenjiro Kumano
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan
| | - Hiroki Sato
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan
| | - Takahito Yagi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan
| | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan
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Gao X, Kahl AR, Goffredo P, Lin AY, Vikas P, Hassan I, Charlton ME. Treatment of Stage IV Colon Cancer in the United States: A Patterns-of-Care Analysis. J Natl Compr Canc Netw 2021; 18:689-699. [PMID: 32502984 DOI: 10.6004/jnccn.2020.7533] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 01/10/2020] [Indexed: 11/17/2022]
Abstract
BACKGROUND National guidelines recommend chemotherapy as the mainstay of treatment for stage IV colon cancer, with primary tumor resection (PTR) reserved for patients with symptomatic primary or curable disease. The aims of this study were to characterize the treatment modalities received by patients with stage IV colon cancer and to determine the patient-, tumor-, and hospital-level factors associated with those treatments. METHODS Patients diagnosed with stage IV colon cancer in 2014 were extracted from the SEER Patterns of Care initiative. Treatments were categorized into chemotherapy only, PTR only, PTR + chemotherapy, and none/unknown. RESULTS The total weighted number of cases was 3,336; 17% of patients received PTR only, 23% received chemotherapy only, 41% received PTR + chemotherapy, and 17% received no treatment. In multivariable analyses, compared with chemotherapy only, PTR + chemotherapy was associated with being married (odds ratio [OR], 1.9), having bowel obstruction (OR, 2.55), and having perforation (OR, 2.29), whereas older age (OR, 5.95), Medicaid coverage (OR, 2.46), higher T stage (OR, 3.51), and higher N stage (OR, 6.77) were associated with PTR only. Patients who received no treatment did not have more comorbidities or more severe disease burden but were more likely to be older (OR, 3.91) and non-Hispanic African American (OR, 2.92; all P<.05). Treatment at smaller, nonacademic hospitals was associated with PTR (± chemotherapy). CONCLUSIONS PTR was included in the treatment regimen for most patients with stage IV colon cancer and was associated with smaller, nonacademic hospitals. Efforts to improve guideline implementation may be beneficial in these hospitals and also in non-Hispanic African American and older populations.
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Affiliation(s)
- Xiang Gao
- 1Department of Surgery, Carver College of Medicine, and
| | - Amanda R Kahl
- 2Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
| | | | - Albert Y Lin
- 3Division of Oncology, Department of Medicine, VA Palo Alto Health Care System, Palo Alto, California.,4Department of Medicine, Stanford University, Stanford, California; and
| | - Praveen Vikas
- 5Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa
| | - Imran Hassan
- 1Department of Surgery, Carver College of Medicine, and
| | - Mary E Charlton
- 2Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
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17
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Chen JN, Shoucair S, Wang Z, Habib JR, Zhao FQ, Yu J, Liu Z, Liu Q. Primary Tumor Resection for Rectal Cancer With Unresectable Liver Metastases: A Chance to Cut Is a Chance for Improved Survival. Front Oncol 2021; 11:628715. [PMID: 33791215 PMCID: PMC8006931 DOI: 10.3389/fonc.2021.628715] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 02/22/2021] [Indexed: 01/05/2023] Open
Abstract
Background: About half of the patients with rectal cancer will develop liver metastasis during the course of their illness. Unfortunately, a large proportion of these metastases are unresectable. Surgical resection of the primary tumor vs. palliative treatment in patients with unresectable synchronous liver metastases remains controversial. Methods: Patients with rectal cancer with surgically unresectable liver metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2015. According to different treatment modalities, patients were divided into a primary tumor resection group and a non-resection group. Rates of primary tumor resection and survival were calculated for each year. Kaplan-Meier methods and Cox regression models were used to assess long-term survival. Multivariable logistic regression models were used to evaluate factors potentially associated with primary tumor resection. Results: Among 1,957 patients, 494 (25.2%) had undergone primary tumor resection. Patients with primary tumor resection had significantly better 5-year survival rate (27.2 vs. 5.6%, P < 0.001) compared to the non-resection group. Chemoradiotherapy with primary site resection was associated with the longest mean and 5-year OS (44.7 months, 32.4%). The Cox regression analyses of the subgroup indicated that patients who underwent primary tumor resection had improved survival compared with those who did not undergo resection in all 25 subgroups. Factors associated with primary tumor resection were well or moderately differentiated tumor grade, undergoing radiation, and primary tumor size <5 cm. Conclusions: The majority of patients with rectal cancer with unresectable liver metastases did not undergo primary tumor resection. Our results indicate that resection of the primary tumor appears to offer the greatest chance of survival. Prospective studies are needed to confirm these results.
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Affiliation(s)
- Jia-nan Chen
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Sami Shoucair
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Zheng Wang
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Joseph R. Habib
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Fu-qiang Zhao
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Yu
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Zheng Liu
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qian Liu
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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18
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Dijkstra M, Nieuwenhuizen S, Puijk RS, Geboers B, Timmer FEF, Schouten EAC, Scheffer HJ, de Vries JJJ, Ket JCF, Versteeg KS, Meijerink MR, van den Tol MP. The Role of Neoadjuvant Chemotherapy in Repeat Local Treatment of Recurrent Colorectal Liver Metastases: A Systematic Review and Meta-Analysis. Cancers (Basel) 2021; 13:378. [PMID: 33561088 PMCID: PMC7864163 DOI: 10.3390/cancers13030378] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/15/2021] [Accepted: 01/18/2021] [Indexed: 12/15/2022] Open
Abstract
The additive value of neoadjuvant chemotherapy (NAC) prior to repeat local treatment of patients with recurrent colorectal liver metastases (CRLM) is unclear. A systematic search was performed in PubMed, Embase, Web of Science, and an additional search in Google Scholar to find articles comparing repeat local treatment by partial hepatectomy and/or thermal ablation with versus without NAC. The search included randomized trials and comparative observational studies with univariate/multivariate analysis and/or matching as well as (inter)national guidelines assessed using the AGREE II instrument. The search identified 21,832 records; 172 were selected for full-text review; 20 were included: 20 comparative observational studies were evaluated. Literature to evaluate the additive value of NAC prior to repeat local treatment was limited. Outcomes of NAC were often reported as subgroup analyses and reporting of results was frequently unclear. Assessment of the seven studies that qualified for inclusion in the meta-analysis showed conflicting results. Only one study reported a significant difference in overall survival (OS) favoring NAC prior to repeat local treatment. However, further analysis revealed a high risk for residual bias, because only a selected group of chemo-responders qualified for repeat local treatment, disregarding the non-responders who did not qualify. All guidelines that specifically mention recurrent disease (3/3) recommend repeat local treatment; none provide recommendations about the role of NAC. The inconclusive findings of this meta-analysis do not support recommendations to routinely favor NAC prior to repeat local treatment. This emphasizes the need to investigate the additive value of NAC prior to repeat local treatment of patients with recurrent CRLM in a future phase 3 randomized controlled trial (RCT).
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Affiliation(s)
- Madelon Dijkstra
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, VU Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; (S.N.); (R.S.P.); (B.G.); (F.E.F.T.); (E.A.C.S.); (H.J.S.); (J.J.J.d.V.); (M.R.M.)
| | - Sanne Nieuwenhuizen
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, VU Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; (S.N.); (R.S.P.); (B.G.); (F.E.F.T.); (E.A.C.S.); (H.J.S.); (J.J.J.d.V.); (M.R.M.)
| | - Robbert S. Puijk
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, VU Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; (S.N.); (R.S.P.); (B.G.); (F.E.F.T.); (E.A.C.S.); (H.J.S.); (J.J.J.d.V.); (M.R.M.)
| | - Bart Geboers
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, VU Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; (S.N.); (R.S.P.); (B.G.); (F.E.F.T.); (E.A.C.S.); (H.J.S.); (J.J.J.d.V.); (M.R.M.)
| | - Florentine E. F. Timmer
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, VU Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; (S.N.); (R.S.P.); (B.G.); (F.E.F.T.); (E.A.C.S.); (H.J.S.); (J.J.J.d.V.); (M.R.M.)
| | - Evelien A. C. Schouten
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, VU Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; (S.N.); (R.S.P.); (B.G.); (F.E.F.T.); (E.A.C.S.); (H.J.S.); (J.J.J.d.V.); (M.R.M.)
| | - Hester J. Scheffer
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, VU Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; (S.N.); (R.S.P.); (B.G.); (F.E.F.T.); (E.A.C.S.); (H.J.S.); (J.J.J.d.V.); (M.R.M.)
| | - Jan J. J. de Vries
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, VU Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; (S.N.); (R.S.P.); (B.G.); (F.E.F.T.); (E.A.C.S.); (H.J.S.); (J.J.J.d.V.); (M.R.M.)
| | - Johannes C. F. Ket
- Medical Library, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands;
| | - Kathelijn S. Versteeg
- Department of Medical Oncology, Amsterdam University Medical Center, VU Medical Center Amsterdam Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands;
| | - Martijn R. Meijerink
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, VU Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; (S.N.); (R.S.P.); (B.G.); (F.E.F.T.); (E.A.C.S.); (H.J.S.); (J.J.J.d.V.); (M.R.M.)
| | - M. Petrousjka van den Tol
- Department of Surgery, Amsterdam University Medical Center, location VU Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands;
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19
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Muaddi H, D'Angelica M, Wiseman JT, Dillhoff M, Latchana N, Roke R, Ko YJ, Carpizo D, Spencer K, Fields RC, Williams G, Aucejo F, Acevedo-Moreno LA, Billingsley KG, Walker BS, Mayo SC, Karanicolas PJ. Safety and feasibility of initiating a hepatic artery infusion pump chemotherapy program for unresectable colorectal liver metastases: A multicenter, retrospective cohort study. J Surg Oncol 2020; 123:252-260. [PMID: 33095919 DOI: 10.1002/jso.26270] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 10/06/2020] [Accepted: 10/08/2020] [Indexed: 01/20/2023]
Abstract
INTRODUCTION Hepatic artery infusion pump (HAIP) chemotherapy is a specialized therapy for patients with unresectable colorectal liver metastases (uCRLM). Its effectiveness was demonstrated from a high volume center, with uncertainty regarding the feasibility and safety at other centers. Therefore, we sought to assess the safety and feasibility of HAIP for the management of uCRLM at other centers. METHODS We conducted a multicenter retrospective cohort study of patients with uCRLM treated with HAIP from January 2003 to December 2017 at six North American centers initiating the HAIP program. Outcomes included the safety and feasibility of HAIP chemotherapy. RESULTS We identified 154 patients with HAIP insertion and the median age of 54 (48-61) years. The burden of disease was >10 intra-hepatic metastatic foci in 59 (38.3%) patients. Patients received at least one cycle of systemic chemotherapy before HAIP insertion. Major complications occurred in 7 (4.6%) patients during their hospitalization and 13 (8.4%) patients developed biliary sclerosis during follow-up. A total of 148 patients (96.1%) received at least one-dose of HAIP chemotherapy with a median of 5 (4-7) cycles. 78 patients (56.5%) had a complete or partial response and 12 (7.8%) received a curative liver resection. CONCLUSION HAIP programs can be safely and effectively initiated in previously inexperienced centers with good response.
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Affiliation(s)
- Hala Muaddi
- Division of General Surgery, Sunnybrook Health Science Centre, Toronto, Ontario, Canada
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Jason T Wiseman
- Arthur G. James Comprehensive Cancer Center Cancer Cachexia Program, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Mary Dillhoff
- Arthur G. James Comprehensive Cancer Center Cancer Cachexia Program, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Nicholas Latchana
- Department of Surgery, Novant Health Carolina Surgical, Charlotte, North Carolina, USA
| | - Rachel Roke
- Division of General Surgery, Sunnybrook Health Science Centre, Toronto, Ontario, Canada
| | - Yoo-Joung Ko
- Division of General Surgery, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.,St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Darren Carpizo
- Department of Surgery, Division of Surgical Oncology, Rochester's School of Medicine and Dentistry and Wilmot Cancer Center, Rochester, New York, USA
| | - Kristen Spencer
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
| | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine and the Alvin J. Siteman Comprehensive Cancer Center, St. Louis, Missouri, USA
| | - Gregory Williams
- Department of Surgery, Washington University School of Medicine and the Alvin J. Siteman Comprehensive Cancer Center, St. Louis, Missouri, USA
| | - Federico Aucejo
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Lou-Anne Acevedo-Moreno
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Kevin G Billingsley
- Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland, Oregon, USA
| | - Brett S Walker
- Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland, Oregon, USA
| | - Skye C Mayo
- Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland, Oregon, USA
| | - Paul J Karanicolas
- Division of General Surgery, Sunnybrook Health Science Centre, Toronto, Ontario, Canada
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20
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Mismatch repair status between primary colorectal tumor and metastatic tumor, a retrospective consistent study. Biosci Rep 2020; 39:221418. [PMID: 31804673 PMCID: PMC6911159 DOI: 10.1042/bsr20190730] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 10/07/2019] [Accepted: 12/04/2019] [Indexed: 12/30/2022] Open
Abstract
Objectives Mismatch repair (MMR) and Microsatellite instability (MSI) are critical when considering immunotherapy and chemotherapeutic drugs an option for patients with colorectal cancer (CRC). We investigated the consistence of MMR status as well as MSI between primary CRC and metastatic tumor to see if the expression of four MMR proteins and the status of MSI are congruent in primary tumor and metastatic tumor. With the results of the study and future more relevant studies, the sites of MMR testing may be more precise for individualized treatment. Study design Patients with clear diagnosis of sporadic CRC and distal organ metastasis were identified from a prospectively established database. The status of MMR and MSI was evaluated by immunohistochemistry (IHC) and Polymerase Chain Reaction (PCR) respectively of synchronously obtained tissue samples. Results Forty patients with complete clinical date were enrolled. For primary tumor, 36/40 samples were tested as MMR-proficient (pMMR) and 4 were MMR-deficient (dMMR). For metastatic samples, 30 samples were tested as pMMR while 10 samples were dMMR. Six out of forty patients were tested as inconsistent status of MMR and MSI. After statistical analysis, the expression status of MMR was not statistically significant between primary and metastatic tumors (P=0.1405, larger than 0.05). Conclusion Based on our samples, the status of MMR between primary CRC and metastatic tumor was consistent, thus test of MMR status can be performed at both sites. However, due to the limited samples enrolled in our study, the results should be interpreted carefully.
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21
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Tang W, Ren L, Liu T, Ye Q, Wei Y, He G, Lin Q, Wang X, Wang M, Liang F, Cui Y, Xu J. Bevacizumab Plus mFOLFOX6 Versus mFOLFOX6 Alone as First-Line Treatment for RAS Mutant Unresectable Colorectal Liver-Limited Metastases: The BECOME Randomized Controlled Trial. J Clin Oncol 2020; 38:3175-3184. [PMID: 32749938 DOI: 10.1200/jco.20.00174] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
PURPOSE To assess the effects of bevacizumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) as first-line treatment of RAS mutant unresectable colorectal liver metastases. METHODS From October 2013 to December 2017, patients with RAS mutant unresectable liver-limited metastases from colorectal cancer were randomly assigned to receive mFOLFOX6 plus bevacizumab (arm A) or mFOLFOX6 alone (arm B). The resectability of liver metastases was determined by a local multidisciplinary team. The primary end point was the actual rate of patients converted to R0 resection for liver metastases. Secondary end points included tumor response, survival, and toxicity. The block randomization method was used. RESULTS The intention-to-treat population comprised 241 patients. A total of 121 patients were randomly assigned to arm A and 120 to arm B. The median follow-up time was 37.0 months for all patients. The R0 resection rates for liver metastases were 22.3% (27 of 121 patients) in arm A and 5.8% (7 of 120 patients) in arm B, with a significant difference (P < .01). Patients in arm A had significantly better objective response rates (54.5% v 36.7%; P < .01), median progression-free survival (9.5 v 5.6 months; P < .01) and median overall survival (25.7 v 20.5 months; P = .03) compared with those in arm B. The addition of bevacizumab was associated with more frequent proteinuria (9.9% v 3.3%; P = .04) and hypertension (8.3% v 2.5%; P < .05). CONCLUSION For patients with initially unresectable RAS mutant colorectal liver metastases, bevacizumab combined with mFOLFOX6 increased the resectability of liver metastases and improved response rates and survival compared with mFOLFOX6 alone.
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Affiliation(s)
- Wentao Tang
- Department of General Surgery, Zhongshan Hospital, Fudan University, and Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
| | - Li Ren
- Department of General Surgery, Zhongshan Hospital, Fudan University, and Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
| | - Tianshu Liu
- Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Qinghai Ye
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Ye Wei
- Department of General Surgery, Zhongshan Hospital, Fudan University, and Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
| | - Guodong He
- Department of General Surgery, Zhongshan Hospital, Fudan University, and Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
| | - Qi Lin
- Department of General Surgery, Zhongshan Hospital, Fudan University, and Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
| | - Xiaoying Wang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Mingliang Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Fei Liang
- Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Yuehong Cui
- Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Jianmin Xu
- Department of General Surgery, Zhongshan Hospital, Fudan University, and Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
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22
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Brajcich BC, Bentrem DJ, Yang AD, Cohen ME, Ellis RJ, Mahalingam D, Mulcahy MF, Lidsky ME, Allen PJ, Merkow RP. Short-Term Risk of Performing Concurrent Procedures with Hepatic Artery Infusion Pump Placement. Ann Surg Oncol 2020; 27:5098-5106. [PMID: 32740732 DOI: 10.1245/s10434-020-08938-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 07/14/2020] [Indexed: 01/12/2023]
Abstract
BACKGROUND Hepatic artery infusion pump (HAIP) chemotherapy is an advanced cancer therapy for primary and secondary hepatic malignancies. The risk of concurrent hepatic and/or colorectal operations with HAIP placement is unknown. Our objective was to characterize the short-term outcomes of concurrent surgery with HAIP placement. METHODS The 2005-2017 ACS NSQIP dataset was queried for patients undergoing hepatic and colorectal operations with or without HAIP placement. Outcomes were compared for HAIP placement with different combined procedures. Patients who underwent procedures without HAIP placement were propensity score matched with those with HAIP placement. The primary outcome was 30-day death or serious morbidity (DSM). Secondary outcomes included infectious complications, wound complications, length of stay (LOS), and operative time. RESULTS Of 467 patients who underwent HAIP placement, 83.9% had concurrent surgery. The rate of DSM was 10.7% for HAIP placement alone, 19.2% with concurrent minor hepatic procedures, 22.1% with concurrent colorectal resection, 23.2% with concurrent minor hepatic plus colorectal procedures, 28.4% with concurrent major hepatic resection, and 41.7% with concurrent major hepatic plus colorectal resection. On matched analyses, there was no difference in DSM, infectious, or wound complications for procedures with HAIP placement compared with the additional procedure alone, but operative time (294.7 vs 239.8 min, difference 54.9, 95% CI 42.8-67.0) and LOS (6 vs 5, IRR 1.20, 95% CI 1.08-1.33) were increased. CONCLUSIONS HAIP placement is not associated with additional morbidity when performed with hepatic and/or colorectal surgery. Decisions regarding HAIP placement should consider the risks of concurrent operations, and patient- and disease-specific factors.
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Affiliation(s)
- Brian C Brajcich
- Department of Surgery, Feinberg School of Medicine, Surgical Outcomes and Quality Improvement Center, Northwestern University, Chicago, IL, USA.,American College of Surgeons, Chicago, IL, USA
| | - David J Bentrem
- Department of Surgery, Feinberg School of Medicine, Surgical Outcomes and Quality Improvement Center, Northwestern University, Chicago, IL, USA.,Department of Surgery, Jesse Brown Veterans' Affairs Medical Center, Chicago, IL, USA
| | - Anthony D Yang
- Department of Surgery, Feinberg School of Medicine, Surgical Outcomes and Quality Improvement Center, Northwestern University, Chicago, IL, USA
| | | | - Ryan J Ellis
- Department of Surgery, Feinberg School of Medicine, Surgical Outcomes and Quality Improvement Center, Northwestern University, Chicago, IL, USA.,American College of Surgeons, Chicago, IL, USA
| | - Devalingam Mahalingam
- Department of Medicine, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Mary F Mulcahy
- Department of Medicine, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Michael E Lidsky
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Peter J Allen
- Department of Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Ryan P Merkow
- Department of Surgery, Feinberg School of Medicine, Surgical Outcomes and Quality Improvement Center, Northwestern University, Chicago, IL, USA. .,American College of Surgeons, Chicago, IL, USA.
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23
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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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Vaz da Silva DG, Ribeiro HSC, Arra DASM, Torres SM, Diniz AL, Godoy AL, Farias IC, Costa WL, Coimbra FJF. Predictors of long-term survival in patients with hepatic resection of colorectal metastases: Analysis of a Brazilian Cancer Center Cohort. J Surg Oncol 2020; 121:893-900. [PMID: 32153041 DOI: 10.1002/jso.25893] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 02/22/2020] [Indexed: 11/09/2022]
Abstract
BACKGROUND Hepatic metastases are a major cause of death in patients with colorectal cancer. A comprehensive assessment of the prognostic factors associated with long-term survival could improve patient selection for surgical approaches and decrease morbidity and futile locoregional treatments. METHODS We performed a retrospective analysis of patients who underwent hepatectomy for colorectal liver metastases at a single center from 2000 to 2012. RESULTS To identify factors associated with 5- and 10-year overall (OS) and disease-free survival (DFS), we analyzed 280 patients and 150 patients in the 5- and 10-year cohorts, respectively. Only seven relapses occurred after 5 years of follow-up, and no relapses occurred after 10 years. Multivariable analysis indicated that bilobar disease and extra-hepatic disease before hepatectomy were independent 5- and 10-year predictors of OS, and major postoperative complications predicted OS in the 5-year survival cohort only. Our analysis indicated that prognostic factors associated with DFS included some confounders and was therefore inconclusive. CONCLUSIONS Taken together, our results suggest that the predictors of 5- and 10-year OS rates of colorectal cancer patients with hepatic metastases are similar, differing only by postoperative complications that influenced exclusively 5-year survival. Since no relapse occurred 10 years after hepatic resection, oncological remission is likely.
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Affiliation(s)
| | - Heber S C Ribeiro
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Dante A S M Arra
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Silvio M Torres
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Alessandro L Diniz
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - André L Godoy
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Igor C Farias
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Wilson L Costa
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil.,Department of Medicine, Epidemiology, and Population Sciences, Dan L Duncan Comprehensive, Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Felipe J F Coimbra
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
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Albertsmeier M, Riedl K, Stephan AJ, Drefs M, Schiergens TS, Engel J, Angele MK, Werner J, Guba M. Improved survival after resection of colorectal liver metastases in patients with unresectable lung metastases. HPB (Oxford) 2020; 22:368-375. [PMID: 31399325 DOI: 10.1016/j.hpb.2019.07.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 05/19/2019] [Accepted: 07/09/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Modern systemic therapies considerably improve tumour control and thus open the possibility of new surgical approaches in metastatic colorectal cancer. In this retrospective clinical cohort with a comparison group, we investigated whether liver resection in a combined liver-lung-metastasised stage is justified if pulmonary disease is not resected. METHODS From 283 patients treated in our institution between 2000 and 2014 for combined colorectal liver- and lung metastases, 35 patients had their pulmonary metastases left in situ while they were eligible for both treatment options: resection versus non-resection of liver metastases. Effectively, 15 of these patients received whereas 20 did not receive a liver resection. In these patients, we compared overall survival and determined risk factors that are associated with poor survival, applying a Cox-Proportional Hazards model. RESULTS Patients whose liver metastases were resected showed significantly longer median survival compared to patients who did not undergo hepatic surgery (median 2.6 vs 1.5 years, P = 0.0182). The Cox-Proportional Hazards model revealed hepatic metastasectomy to be the strongest determinant of patient survival (HR 5.27; CI: (1.89, 14.65)). CONCLUSION Our results suggest that surgical removal of liver metastases may be beneficial in selected patients even if concomitant lung metastases cannot be resected.
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Affiliation(s)
- Markus Albertsmeier
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany.
| | - Kathrin Riedl
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Anna-Janina Stephan
- Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Moritz Drefs
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Tobias S Schiergens
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Jutta Engel
- Munich Cancer Registry (MCR), Bavarian Cancer Registry - Regional Centre Munich (LGL) at the University Hospital of Munich, Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Martin K Angele
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Jens Werner
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Markus Guba
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
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Wang J, Xing Y, Wang Y, He Y, Wang L, Peng S, Yang L, Xie J, Li X, Qiu W, Yi Z, Liu M. A novel BMI-1 inhibitor QW24 for the treatment of stem-like colorectal cancer. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2019; 38:422. [PMID: 31640758 PMCID: PMC6805542 DOI: 10.1186/s13046-019-1392-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 08/26/2019] [Indexed: 02/06/2023]
Abstract
Background Cancer-initiating cell (CIC), a functionally homogeneous stem-like cell population, is resonsible for driving the tumor maintenance and metastasis, and is a source of chemotherapy and radiation-therapy resistance within tumors. Targeting CICs self-renewal has been proposed as a therapeutic goal and an effective approach to control tumor growth. BMI-1, a critical regulator of self-renewal in the maintenance of CICs, is identified as a potential target for colorectal cancer therapy. Methods Colorectal cancer stem-like cell lines HCT116 and HT29 were used for screening more than 500 synthetic compounds by sulforhodamine B (SRB) cell proliferation assay. The candidate compound was studied in vitro by SRB cell proliferation assay, western blotting, cell colony formation assay, quantitative real-time PCR, flow cytometry analysis, and transwell migration assay. Sphere formation assay and limiting dilution analysis (LDA) were performed for measuring the effect of compound on stemness properties. In vivo subcutaneous tumor growth xenograft model and liver metastasis model were performed to test the efficacy of the compound treatment. Student’s t test was applied for statistical analysis. Results We report the development and characterization of a small molecule inhibitor QW24 against BMI-1. QW24 potently down-regulates BMI-1 protein level through autophagy-lysosome degradation pathway without affecting the BMI-1 mRNA level. Moreover, QW24 significantly inhibits the self-renewal of colorectal CICs in stem-like colorectal cancer cell lines, resulting in the abrogation of their proliferation and metastasis. Notably, QW24 significantly suppresses the colorectal tumor growth without obvious toxicity in the subcutaneous xenograft model, as well as decreases the tumor metastasis and increases mice survival in the liver metastasis model. Moreover, QW24 exerts a better efficiency than the previously reported BMI-1 inhibitor PTC-209. Conclusions Our preclinical data show that QW24 exerts potent anti-tumor activity by down-regulating BMI-1 and abrogating colorectal CICs self-renewal without obvious toxicity in vivo, suggesting that QW24 could potentially be used as an effective therapeutic agent for clinical colorectal cancer treatment. Electronic supplementary material The online version of this article (10.1186/s13046-019-1392-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Jinhua Wang
- East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Yajing Xing
- East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Yingying Wang
- Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China
| | - Yundong He
- East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Liting Wang
- Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China
| | - Shihong Peng
- East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Lianfang Yang
- Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China
| | - Jiuqing Xie
- East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Xiaotao Li
- Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Wenwei Qiu
- Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.
| | - Zhengfang Yi
- East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China. .,Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.
| | - Mingyao Liu
- East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
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Symonds LK, Cohen SA. Use of perioperative chemotherapy in colorectal cancer metastatic to the liver. Gastroenterol Rep (Oxf) 2019; 7:301-311. [PMID: 31687149 PMCID: PMC6821343 DOI: 10.1093/gastro/goz035] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 06/06/2019] [Accepted: 07/18/2019] [Indexed: 12/22/2022] Open
Abstract
A curative-intent approach may improve survival in carefully selected patients with oligometastatic colorectal cancer. Aggressive treatments are most frequently administered to patients with isolated liver metastasis, though they may be judiciously considered for other sites of metastasis. To be considered for curative intent with surgery, patients must have disease that can be definitively treated while leaving a sufficient functional liver remnant. Neoadjuvant chemotherapy may be used for upfront resectable disease as a test of tumor biology and/or for upfront unresectable disease to increase the likelihood of resectability (so-called 'conversion' chemotherapy). While conversion chemotherapy in this setting aims to improve survival, the choice of a regimen remains a complex and highly individualized decision. In this review, we discuss the role of RAS status, primary site, sidedness, and other clinical features that affect chemotherapy treatment selection as well as key factors of patients that guide individualized patient-treatment recommendations for colorectal-cancer patients being considered for definitive treatment with metastasectomy.
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Affiliation(s)
- Lynn K Symonds
- Division of Oncology, University of Washington, Seattle, WA, USA
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Stacey A Cohen
- Division of Oncology, University of Washington, Seattle, WA, USA
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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28
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Huiskens J, Bolhuis K, Engelbrecht MR, De Jong KP, Kazemier G, Liem MS, Verhoef C, de Wilt JH, Punt CJ, van Gulik TM. Outcomes of Resectability Assessment of the Dutch Colorectal Cancer Group Liver Metastases Expert Panel. J Am Coll Surg 2019; 229:523-532.e2. [PMID: 31520695 DOI: 10.1016/j.jamcollsurg.2019.08.1445] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 08/20/2019] [Accepted: 08/20/2019] [Indexed: 01/18/2023]
Abstract
BACKGROUND Decision making on optimal treatment strategy in patients with initially unresectable colorectal cancer liver metastases (CRLM) remains complex because uniform criteria for (un)resectability are lacking. This study reports on the feasibility and short-term outcomes of The Dutch Colorectal Cancer Group Liver Expert Panel. STUDY DESIGN The Expert Panel consists of 13 hepatobiliary surgeons and 4 radiologists. Resectability assessment is performed independently by 3 randomly assigned surgeons, and CRLM are scored as resectable, potentially resectable, or permanently unresectable. In absence of consensus, 2 additional surgeons are invited for a majority consensus. Patients with potentially resectable or unresectable CRLM at baseline are evaluated every 2 months of systemic therapy. Once CRLM are considered resectable, a treatment strategy is proposed. RESULTS Overall, 398 panel evaluations in 183 patients were analyzed. The median time to panel conclusion was 7 days (interquartile range [IQR] 5-11 days). Intersurgeon disagreement was observed in 205 (52%) evaluations, with major disagreement (resectable vs permanently unresectable) in 42 (11%) evaluations. After systemic treatment, 106 patients were considered to have resectable CRLM, 84 of whom (79%) underwent a curative procedure. R0 resection (n = 41), R0 resection in combination with ablative treatment (n = 26), or ablative treatment only (n = 4) was achieved in 67 of 84 (80%) patients. CONCLUSIONS This study analyzed prospective resectability evaluation of patients with CRLM by a panel of radiologists and liver surgeons. The high rate of disagreement among experienced liver surgeons reflects the complexity in defining treatment strategies for CRLM and supports the use of a panel rather than a single-surgeon decision.
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Affiliation(s)
- Joost Huiskens
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Karen Bolhuis
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
| | - Marc Rw Engelbrecht
- Department of Radiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Koert P De Jong
- Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Geert Kazemier
- Department of Surgery, Amsterdam UMC, VU University, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Mike Sl Liem
- Department of Surgery, Medical Spectrum Twente, Enschede, The Netherlands
| | - Cornelis Verhoef
- Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
| | | | - Cornelis Ja Punt
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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29
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Zhou Y, Zhang HX, Zhang XS, Sun YF, He KB, Sang XQ, Zhu YM, Kuai ZX. Non-mono-exponential diffusion models for assessing early response of liver metastases to chemotherapy in colorectal Cancer. Cancer Imaging 2019; 19:39. [PMID: 31217036 PMCID: PMC6585014 DOI: 10.1186/s40644-019-0228-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 06/13/2019] [Indexed: 02/08/2023] Open
Abstract
Background Preoperative chemotherapy is becoming standard therapy for liver metastasis from colorectal cancer, so early assessment of treatment response is crucial to make a reasonable therapeutic regimen and avoid overtreatment, especially for patients with severe side effects. The role of three non-mono-exponential diffusion models, such as the kurtosis model, the stretched exponential model and the statistical model, were explored in this study to early assess the response to chemotherapy in patients with liver metastasis from colorectal cancer. Methods Thirty-three patients diagnosed as colorectal liver metastasis were evaluated in this study. Diffusion-weighted images with b values (0, 200, 500, 1000, 1500, 2000 s/mm2) were acquired at 3.0 T. The parameters (ADCk, K, DDC,α, Dsand σ) were derived from three non-mono-exponential models (the kurtosis, stretched exponential and statistical models) as well as their corresponding percentage changes before and after chemotherapy. The difference in above parameters between the response and non-response groups were analyzed with independent-samples T-test (normality) and Mann–Whitney U-test (non-normality). Meanwhile, receiver operating characteristic curve (ROC) analyses were performed to assess the response to chemotherapy. Results Significantly lower values of K (the kurtosis coefficient derived from the kurtosis model) and σ (the width of diffusion coefficient distribution in the statistical model) (P < 0.05) were observed in the respond group before treatment, as well as higher ΔK and Δσ values (P < 0.05) after the first cycle of chemotherapy were also found compared with the non-respond group. ROC analyses showed the K value acquired before treatment had the highest diagnostic performance (0.746) in distinguishing responders from non-responders. Furthermore, the high sensitivity (100%) and accuracy (76.3%) from the K value before treatment was found in assessing the response of colorectal liver metastasis to chemotherapy. Conclusions The non-mono-exponential diffusion models may be able to predict early response to chemotherapy in patients with colorectal liver metastasis.
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Affiliation(s)
- Yang Zhou
- Imaging Center, Harbin Medical University Cancer Hospital, Haping Road No.150, Nangang District, Harbin, 150081, China
| | - Hong-Xia Zhang
- Imaging Center, Harbin Medical University Cancer Hospital, Haping Road No.150, Nangang District, Harbin, 150081, China
| | - Xiu-Shi Zhang
- Imaging Center, Harbin Medical University Cancer Hospital, Haping Road No.150, Nangang District, Harbin, 150081, China
| | - Yun-Feng Sun
- Imaging Center, Harbin Medical University Cancer Hospital, Haping Road No.150, Nangang District, Harbin, 150081, China
| | - Kuang-Bang He
- Imaging Center, Harbin Medical University Cancer Hospital, Haping Road No.150, Nangang District, Harbin, 150081, China
| | - Xi-Qiao Sang
- Division of Respiratory Disease, The Fourth Hospital of Harbin Medical University, Harbin, 150001, China
| | - Yue-Min Zhu
- CREATIS, CNRS UMR 5220-INSERM U1206, University Lyon 1-INSA Lyon-University Jean Monnet Saint-Etienne, 69621, Lyon, France
| | - Zi-Xiang Kuai
- Imaging Center, Harbin Medical University Cancer Hospital, Haping Road No.150, Nangang District, Harbin, 150081, China.
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A Mechatronic Platform for Computer Aided Detection of Nodules in Anatomopathological Analyses via Stiffness and Ultrasound Measurements. SENSORS 2019; 19:s19112512. [PMID: 31159334 PMCID: PMC6603638 DOI: 10.3390/s19112512] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Revised: 05/11/2019] [Accepted: 05/29/2019] [Indexed: 11/17/2022]
Abstract
This study presents a platform for ex-vivo detection of cancer nodules, addressing automation of medical diagnoses in surgery and associated histological analyses. The proposed approach takes advantage of the property of cancer to alter the mechanical and acoustical properties of tissues, because of changes in stiffness and density. A force sensor and an ultrasound probe were combined to detect such alterations during force-regulated indentations. To explore the specimens, regardless of their orientation and shape, a scanned area of the test sample was defined using shape recognition applying optical background subtraction to the images captured by a camera. The motorized platform was validated using seven phantom tissues, simulating the mechanical and acoustical properties of ex-vivo diseased tissues, including stiffer nodules that can be encountered in pathological conditions during histological analyses. Results demonstrated the platform’s ability to automatically explore and identify the inclusions in the phantom. Overall, the system was able to correctly identify up to 90.3% of the inclusions by means of stiffness in combination with ultrasound measurements, paving pathways towards robotic palpation during intraoperative examinations.
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31
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Gao H, Meng XY, Wang HQ, Zhu FF, Guo AL, Zhu M, Song JC, Yu WF. Association between Anaesthetic Technique and Oncological Outcomes after Colorectal Carcinoma Liver Metastasis Resection. Int J Med Sci 2019; 16:337-342. [PMID: 30745816 PMCID: PMC6367527 DOI: 10.7150/ijms.28016] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 12/22/2018] [Indexed: 12/17/2022] Open
Abstract
Background: Recently published studies suggest that the anaesthetic technique used during oncologic surgery can improve patient outcomes. Therefore, the authors evaluated the survival of patients with resected colorectal carcinoma liver metastases (CRCLMs) who received either EGA (general anaesthesia [GA] combined with epidural anaesthesia [EA]) or GA alone. Methods: We conducted an ambispective cohort study including 225 post-surgical CRCLM patients between May 2007 and July 2012 and performed a follow-up investigation of survival in July 2017. Results: The basic characteristics in the two groups were largely similar. The median (quartiles) recurrence interval for all patients was 10 (2.5, 23) months, and the median (quartiles) survival for CRCLM patients post-surgically was 37 (30.5, 51.5) months. Perioperative EA was associated with survival (P =0.039, log-rank test), with an estimated hazard ratio of 0.737 (95% CI 0.551-0.985) in the univariate analysis. Kaplan-Meier estimates of survival for GA and EGA suggested that GA might provide better outcomes than EGA [P=0.028, hazard ratio of 0.7328 (95% CI 0.5433-0.9884)]. Significant differences in anaesthesia techniques were found (P=0.048), with an adjusted estimated hazard ratio of 0.741 (95% CI 0.550-0.998) in the multivariate analysis. Subgroup analyses of patients in different age groups (< 40, ≥ 40 but <60, and ≥ 60 years old) suggested that no significant differences existed among all three subgroups. Conclusions: Compared with EGA, GA may provide a better survival outcome for CRCLM patients. The benefits of anaesthetic techniques in oncological surgery are most likely related to certain cancer types.
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Affiliation(s)
- Hao Gao
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
- Department of Anesthesiology, Shanghai Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, China
| | - Xiao-Yan Meng
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Hong-Qian Wang
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Feng-Feng Zhu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of the University of South China, 69 Chuanshan Road, Hunan, China
| | - Ai-Ling Guo
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Mei Zhu
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Jin-Chao Song
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Wei-Feng Yu
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
- Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pudian Road, Shanghai, China
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Recent Strategies and Paradigm Shift in Management of Hepatic Metastasis from Colorectal Cancer. Indian J Surg Oncol 2018; 9:456-460. [PMID: 30538372 DOI: 10.1007/s13193-018-0766-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Accepted: 05/08/2018] [Indexed: 10/16/2022] Open
Abstract
The liver is the most common site for metastasis from colorectal cancers (CRCs). There are so many new armamentarium, which have increased the life expectancy and progression-free survival. There are various available guidelines, such as NCCN, ESMO, and ASCO, which provide an insight into the latest modalities and new protocols. We have tried to elucidate into paradigm shift of the management.
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Zhang W, Wang F, Hu X, Liang J, Liu B, Guan Q, Liu S. Inhibition of colorectal cancer liver metastasis in BALB/c mice following intratumoral injection of oncolytic herpes simplex virus type 2 for the induction of specific antitumor immunity. Oncol Lett 2018; 17:815-822. [PMID: 30655834 PMCID: PMC6313052 DOI: 10.3892/ol.2018.9720] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 09/05/2018] [Indexed: 02/06/2023] Open
Abstract
Liver metastasis represents the most prominent metastasis of colorectal cancer (CRC) and is the leading cause of CRC mortality, making the early prevention of this event very important. While current CRC therapies include surgery, radiotherapy and chemotherapy, no effective treatment option for CRC liver metastasis (CRLM) exists. Furthermore, the effects of currently available metastatic CRC drugs are frequently limited by their toxicity and side effects. Oncolytic herpes simplex virus type 2 (oHSV2) selectively infects tumor cells and also induces an antitumor immune response. The present study investigated the cytopathic effects of oHSV2 on CT-26 cells in vitro and tested its inhibitory effect on CRLM. In vitro experimental data demonstrated that oHSV2 effectively inhibited the growth of CT-26 cells. In vivo study data demonstrated that treatment with oHSV2 alone slowed the growth of subcutaneous xenograft tumors without inducing weight loss and also inhibited CRLM by increasing the numbers of cluster of differentiation (CD)4+ T, CD8+ T and natural killer cells. In summary, oHSV2 shows potential as a safe and effective therapeutic agent for inhibiting the metastasis of CT-26 CRC cells to the liver.
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Affiliation(s)
- Wen Zhang
- Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Feifei Wang
- Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.,Inner Mongolia University For Nationalities, Tongliao, Inner Mongolia 028000, P.R. China
| | - Xiao Hu
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Jing Liang
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Binlei Liu
- Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.,Hubei Provincial Cooperative, Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan, Hubei 30068, P.R. China
| | - Qi Guan
- Department of Hematology and Oncology, The Second Clinical Medical School of Inner Mongolia University for Nationalities, Yakeshi, Inner Mongolia 022150, P.R. China
| | - Shangmei Liu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
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Bolaños-Díaz R, Sanabria-Montañez C, Farfán-Tello C, Calderón-Cahua M. Cost-effectiveness of Cetuximab as a treatment strategy for metastatic colon cancer in Peru: chemotherapy/Cetuximab versus chemotherapy alone. JOURNAL OF PHARMACEUTICAL HEALTH SERVICES RESEARCH 2018. [DOI: 10.1111/jphs.12262] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Vogl TJ, Lahrsow M, Albrecht MH, Hammerstingl R, Thompson ZM, Gruber-Rouh T. Survival of patients with non-resectable, chemotherapy-resistant colorectal cancer liver metastases undergoing conventional lipiodol-based transarterial chemoembolization (cTACE) palliatively versus neoadjuvantly prior to percutaneous thermal ablation. Eur J Radiol 2018; 102:138-145. [PMID: 29685527 DOI: 10.1016/j.ejrad.2018.03.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 02/19/2018] [Accepted: 03/09/2018] [Indexed: 12/23/2022]
Abstract
PURPOSE To determine overall (OS) and progression-free survival (PFS) for cTACE alone and in combination with percutaneous thermal ablation in patients with non-resectable, chemotherapy-resistant colorectal cancer liver metastases (CRLM). MATERIAL AND METHODS The study included 452 patients undergoing 2654 repetitive cTACE treatments of CRLM. 233 patients were treated palliatively using only cTACE, whereas 219 patients were treated with cTACE in a neoadjuvant intend with subsequent thermal ablation (either microwave ablation or laser-induced thermotherapy). The chemotherapeutics agents used, in either single-, double-, or triple-combinations, included MitomycinC, Gemcitabine, Irinotecan, and Cisplatin. Several factors were analysed to determine their prognostic value in terms of OS and PFS. RESULTS Palliative use of cTACE resulted in a median OS and PFS of 12.6 and 5.9 months, whereas the neoadjuvant use of cTACE showed a median OS and PFS of 25.8 and 10.8 months. The differences in OS and PFS between the two groups were statistically significant (p < 0.001). Extrahepatic metastases were a significant prognostic factor in the OS and PFS analysis of the palliative and neoadjuvant group. In addition, number, location, and mean size of metastases were significant prognostic factors for OS and PFS in the neoadjuvant group. Sex, primary tumor location, T- and N-parameters of the TNM staging system, time of liver metastases appearance, ablation method, and patient age did not significantly impact OS and PFS in either patient group. The most distinct response to cTACE was observed in metastases that were treated with a triple-combination of chemotherapeutics (p = 0.021). CONCLUSION cTACE is an effective treatment option in advanced non-resectable CRLM. Chemoembolization followed by ablation further increases survival rates. A triple combination of chemotherapeutics improves response to cTACE.
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Affiliation(s)
- Thomas J Vogl
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Maximilian Lahrsow
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Moritz H Albrecht
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Renate Hammerstingl
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
| | - Zachary M Thompson
- Department of Radiology and Radiological Science, Medical University of South Carolina, 25 Courtenay Drive, 29425 Charleston, USA.
| | - Tatjana Gruber-Rouh
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
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Obinu A, Gavini E, Rassu G, Maestri M, Bonferoni MC, Giunchedi P. Lymph node metastases: importance of detection and treatment strategies. Expert Opin Drug Deliv 2018; 15:459-467. [PMID: 29504430 DOI: 10.1080/17425247.2018.1446937] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Lymphatic vessels are the preferential route of most solid tumors to spread their metastases in the body. The onset of metastatic nests in draining lymph nodes (LNs) are a significant indicator of cancer progression and a dismaying sign of worsen staging. Therefore, the individuation and elimination of cancer cells within the lymphatic system (LS) are an important goal. Nevertheless, the targeting of the LS with traditional contrast agents and/or chemotherapeutics is difficult, due to its anatomical structure. For this reason, many studies on new lymphatic delivery systems have been carried out, both to improve lymphatic imaging and to selectively carry chemotherapeutics to LNs, reducing the exposure of healthy tissues to the cytotoxic substances. This is an overview of the present situation in the field of detection and treatment strategies of lymphatic metastases, taking into account the use of nano-drug delivery systems. Nanocarriers, thanks to their small size and other physicochemical characteristics, are suitable vectors for imaging and chemotherapy of the LS. AREAS COVERED The role of the LS in tumor progression and importance of treatment and imaging strategies of lymphatic metastases. EXPERT OPINION The nanoparticles are a promising approach for treatment and detection of lymphatic metastases. However further studies are necessary in order to evaluate their efficacy in human clinical application.
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Affiliation(s)
- Antonella Obinu
- a PhD in Experimental Medicine, Department of Clinical-Surgical, Diagnostic and Paediatric Sciences , University of Pavia , Pavia , Italy
| | - Elisabetta Gavini
- b Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy
| | - Giovanna Rassu
- b Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy
| | - Marcello Maestri
- a PhD in Experimental Medicine, Department of Clinical-Surgical, Diagnostic and Paediatric Sciences , University of Pavia , Pavia , Italy.,c Department of Surgery , IRCCS Policlinico San Matteo Foundation , Pavia , Italy
| | | | - Paolo Giunchedi
- b Department of Chemistry and Pharmacy , University of Sassari , Sassari , Italy
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Fiorentini G, Del Conte A, De Simone M, Guadagni S, Mambrini A, D'Alessandro M, Aliberti C, Rossi G, Cantore M. Complete Response of Colorectal Liver Metastases after Intra-Arterial Chemotherapy. TUMORI JOURNAL 2018; 94:489-92. [DOI: 10.1177/030089160809400408] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Aims and Background We demonstrated that colorectal liver metastases considered in complete response after intra-arterial floxuridine-based chemotherapy had recurred in situ. Methods and Study Design One hundred and six colorectal liver metastases disappeared after intra-arterial chemotherapy. Persistent macroscopic disease was observed at surgery at the site of 52 of 106 liver metastases, even though computerized tomography scan and ultrasound showed a complete response. The sites of 35 initial liver metastases that were not visible at surgery were resected. Pathologic examination of these sites, considered in complete response, showed viable cancer cells in 22 of 35 cases. Results After 1 year of follow-up, 33 of 106 liver metastases considered in complete response had recurred in situ. After 2 years of follow-up, persistent macroscopic or microscopic residual disease or recurrence was observed in 86 (81%) of the 106 liver metastases. Conclusions Nevertheless, 19% of the patients had a long-lasting response. This means that floxuridine given as intra-arterial hepatic chemotherapy can still be considered an interesting option of cure in the treatment of colorectal liver metastases. When feasible, the site of the lesion that disappeared after intra-arterial chemotherapy should be resected at surgery. The best palliative cure of liver metastases should be the combination of local-regional strategies like intra-arterial chemotherapy, surgery or radiofrequency ablation with the systemic approach.
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Affiliation(s)
| | | | - Michele De Simone
- Department of Surgical Oncology, San Giuseppe Hospital, Empoli (Florence)
| | | | | | | | | | - Giuseppe Rossi
- Interventional Radiology Unit, Istituto Ortopedico Rizzoli, Bologna, Italy
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Prognostic Significance of Surgical Margin Size After Neoadjuvant FOLFOX and/or FOLFIRI for Colorectal Liver Metastases. J Gastrointest Surg 2017; 21:1831-1840. [PMID: 28884391 DOI: 10.1007/s11605-017-3557-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Accepted: 08/18/2017] [Indexed: 02/08/2023]
Abstract
PURPOSE Optimal margin size when resecting colorectal liver metastases (CRLM) remains unclear, particularly in the setting of perioperative chemotherapy. We evaluated the prognostic significance of margin size in patients who received neoadjuvant FOLFOX and/or FOLFIRI prior to resection of CRLM. METHODS Clinicopathologic factors were collected for patients who underwent curative liver resections for CRLM between 4/2004-1/2016 and received neoadjuvant oxaliplatin and/or irinotecan and 5-FU (FOLFOX, FOLFIRI). Margins were categorized as < 1, ≥ 1-< 5, ≥ 5-< 10, or ≥ 10 mm and evaluated for association with overall survival (OS) and disease-free survival (DFS) by Cox multiple regression analysis. Margin status was classified as positive (< 1 mm) or negative (≥ 1 mm) and similarly evaluated. RESULTS Of 227 patients, the median age was 58 years and most had synchronous (80%) lesions. The majority had colon cancers (75%). Margin sizes were 13% < 1 mm, 27% ≥ 1-< 5 mm, 23% ≥ 5-< 10 mm, 36% ≥ 10 mm. Most (63%) received chemotherapy post-liver resection. Five-year OS and DFS were 54% (95% CI 46-62%) and 22% (95% CI 16-28%), respectively. Positive margins significantly increased the risk of death without post-liver resection chemotherapy (HR = 3.32, p = 0.0077), but not with post-liver resection chemotherapy (HR = 1.00, p = 0.99). Negative margin sizes of ≥ 1-< 5, ≥ 5-< 10, and ≥ 10 mm were not significant predictors of OS (p > 0.05). CONCLUSION Patients undergoing liver resection for CRLM should receive post-resection chemotherapy if negative margins (≥ 1 mm) cannot be achieved. For patients receiving FOLFOX and/or FOLFIRI chemotherapy, wider margins did not improve OS.
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Li XF, Tan YN, Zhong CH, Zhu LZ, Fang XF, Li J, Ding KF, Yuan Y. Left-sided primary tumor is a favorable prognostic factor for metastatic colorectal cancer patients receiving surgery. Oncotarget 2017; 8:79618-79628. [PMID: 29108341 PMCID: PMC5668074 DOI: 10.18632/oncotarget.18896] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 06/12/2017] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE The role of surgery in metastatic colorectal cancer (mCRC) remains controversial. This study was performed to assess the impact of surgery on survival in metastatic colorectal cancer. MATERIALS AND METHODS Information of mCRC patients diagnosed between January 1, 2004, and December 31, 2013, was retrieved from the Surveillance, Epidemiology, and End Results Program database. Patients were classified in three groups: patients undergoing resection of both primary and distant metastatic tumors (group 'PMTR'), patients receiving primary tumor resection alone (group 'PTR') and patients not undergoing any surgery (group 'No resection'). Kaplan-Meier method and multivariate Cox proportional hazard regression analysis were applied to estimate disease specific survival time (DSS) and determine prognostic factors. RESULTS A total of 38,591 mCRC patients were eligible. Overall, median DSS of group 'PMTR' was significantly longer compared with group 'PTR' and group 'No resection' (28.0 vs 21.0 vs 11.0 months, P < 0.001). Stratified analysis observed that primary tumor in left-sided colorectal cancer (LCRC) was a favorable prognostic factor compared with right-sided colorectal cancer (RCRC) (median DSS of LCRC: PMTR, 34 months, PTR, 25 months, No resection, 13 months; median DSS of RCRC: PMTR, 20 months, PTR, 16 months, No resection, 8 months; P < 0.001). Multivariate analysis demonstrated that surgery was an independent prognostic factor for better survival (PMTR, HR = 0.403, 95% CI 0.384-0.423, P < 0.001; PTR, HR = 0.515, 95% CI 0.496-0.534, P < 0.001). Furthermore, in patients undergoing surgery, patients with younger age, female, married status, LCRC and lower CEA level were prone to receiving PMTR. CONCLUSIONS This analysis demonstrated that surgery was an independent prognostic factor for improved survival in mCRC. Patients with LCRC had better survival than patients with RCRC after surgery.
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Affiliation(s)
- Xiao-Fen Li
- Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yi-Nuo Tan
- Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chen-Han Zhong
- Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Li-Zhen Zhu
- Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xue-Feng Fang
- Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jun Li
- Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ke-Feng Ding
- Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Cancer Prevention and Intervention of Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ying Yuan
- Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Cancer Prevention and Intervention of Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Labala S, Jose A, Chawla SR, Khan MS, Bhatnagar S, Kulkarni OP, Venuganti VVK. Effective melanoma cancer suppression by iontophoretic co-delivery of STAT3 siRNA and imatinib using gold nanoparticles. Int J Pharm 2017; 525:407-417. [PMID: 28373100 DOI: 10.1016/j.ijpharm.2017.03.087] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 03/12/2017] [Accepted: 03/31/2017] [Indexed: 01/06/2023]
Abstract
Co-delivery of chemotherapeutic agents improve anti-tumor efficacy and reduce cancer resistance. Here, we report development of layer-by-layer assembled gold nanoparticles (LbL-AuNP) containing anti-STAT3 siRNA and imatinib mesylate (IM) to treat melanoma. The combination treatment with STAT3 siRNA and IM in B16F10 melanoma cells showed greater suppression of STAT3 protein, decreased cell viability and increased apoptotic events compared with LbL-AuNP containing either STAT3 siRNA or IM. In vivo efficacy studies in melanoma tumor bearing mice showed that non-invasive topical iontophoretic administration (0.5mA/cm2) of LbL-AuNP was comparable with intratumoral administration. Co-delivery of STAT3 siRNA and IM using LbL-AuNP showed significant (p<0.05) reduction in percentage tumor volume, tumor weight and suppressed STAT3 protein expression compared with either STAT3 siRNA or IM loaded LbL-AuNP. Taken together, LbL-AuNP can be developed as nanocarrier system for co-delivery of siRNA and small molecule drugs for topical iontophoretic delivery.
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Affiliation(s)
- Suman Labala
- Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Shameerpet, Hyderabad 500078, India
| | - Anup Jose
- Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Shameerpet, Hyderabad 500078, India
| | - Sumeet Rajesh Chawla
- Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Shameerpet, Hyderabad 500078, India
| | - Mohammed Shareef Khan
- Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Shameerpet, Hyderabad 500078, India
| | - Shubhmita Bhatnagar
- Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Shameerpet, Hyderabad 500078, India
| | - Onkar Prakash Kulkarni
- Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Shameerpet, Hyderabad 500078, India
| | - Venkata Vamsi Krishna Venuganti
- Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Shameerpet, Hyderabad 500078, India.
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Al Bandar MH, Kim NK. Current status and future perspectives on treatment of liver metastasis in colorectal cancer (Review). Oncol Rep 2017; 37:2553-2564. [PMID: 28350137 DOI: 10.3892/or.2017.5531] [Citation(s) in RCA: 89] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2016] [Accepted: 03/13/2017] [Indexed: 12/29/2022] Open
Abstract
Liver metastasis is the most common site of colorectal cancer (CRC) metastasis. Approximately half of all colorectal cancer patients will develop liver metastases. Although radical surgery is the standard treatment modality, only 10-20% of patients are deemed eligible for resection. Despite advances in survival with chemotherapy, surgical resection is still considered the only curative option for patients with liver metastases. Much effort has been expended to address patients with metastatic liver disease. The majority of evidence stated a significant survival benefit with surgical resection to reach an overall 5-year survival rate of 35-55% after hepatic resection. However, still majority of patients will experience disease recurrence even after a successful resection. In this review, we describe current status and controversies related to treatment options for CRC liver metastases and its potential for enhancing oncologic outcomes and improving quality of life.
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Affiliation(s)
- Mahdi Hussain Al Bandar
- Department of Surgery, Yonsei University, College of Medicine, Seoul 120-752, Republic of Korea
| | - Nam Kyu Kim
- Department of Surgery, Yonsei University, College of Medicine, Seoul 120-752, Republic of Korea
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Imai K, Allard MA, Castro Benitez C, Vibert E, Sa Cunha A, Cherqui D, Castaing D, Baba H, Adam R. Long-term outcomes of radiofrequency ablation combined with hepatectomy compared with hepatectomy alone for colorectal liver metastases. Br J Surg 2017; 104:570-579. [DOI: 10.1002/bjs.10447] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Revised: 10/23/2016] [Accepted: 10/31/2016] [Indexed: 12/15/2022]
Abstract
Abstract
Background
Combining radiofrequency ablation (RFA) with hepatectomy may enable treatment with curative intent for patients with colorectal liver metastasis (CRLM). However, the oncological outcomes in comparison with resection alone remain to be clarified.
Methods
Patients who underwent a first hepatectomy between 2001 and 2012 for CRLM were enrolled. Short- and long-term outcomes of patients who underwent hepatectomy plus RFA were compared with those of patients who had hepatectomy alone using propensity score matching.
Results
Of a total of 553 patients, hepatectomy + RFA and hepatectomy alone were performed in 37 and 516 respectively. Before matching, patients in the hepatectomy + RFA group were characterized primarily by a larger tumour burden. After matching of 31 patients who underwent hepatectomy + RFA with 93 who had hepatectomy alone, background characteristics were well balanced. In the matched cohort, overall and disease-free survival in the hepatectomy + RFA group were no different from those among patients who had hepatectomy alone (5-year overall survival rate 57 versus 61 per cent, P = 0·649; 5-year disease-free survival rate 19 versus 17 per cent, P = 0·865). Local recurrence at the ablated site was observed in four of 31 patients (13 per cent). Although overall local recurrence (ablated site and/or cut surface) was more frequent in the hepatectomy + RFA group (9 of 31 (29 per cent) versus 11 of 93 (12 per cent); P = 0·032), there was no difference in intrahepatic disease-free survival between the two groups (P = 0·705).
Conclusion
Hepatectomy + RFA achieved outcomes comparable to hepatectomy alone. Combining RFA with hepatectomy should be considered as an option to achieve cure.
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Affiliation(s)
- K Imai
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - M-A Allard
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - C Castro Benitez
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - E Vibert
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- INSERM Unité 785, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - A Sa Cunha
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - D Cherqui
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- INSERM Unité 785, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - D Castaing
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- INSERM Unité 785, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - H Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - R Adam
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France
- Université Paris-Sud, Villejuif, France
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Laurent C, Adam JP, Denost Q, Smith D, Saric J, Chiche L. Significance of R1 Resection for Advanced Colorectal Liver Metastases in the Era of Modern Effective Chemotherapy. World J Surg 2016; 40:1191-9. [PMID: 26757718 DOI: 10.1007/s00268-016-3404-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The prognosis impact of positive margins after resection of colorectal liver metastases (CLM) in patients treated with modern effective chemotherapy has not been elucidated. The objective was to compare oncologic outcomes after R0 and R1 resections in the era of modern effective chemotherapy. METHODS Between 1999 and 2010, all consecutive patients undergoing liver resection for CLM were analyzed retrospectively. Patients with extrahepatic metastases, macroscopic residual tumor, treated with combined radiofrequency, or not treated with chemotherapy were excluded. Survival and recurrence after R0 (tumor-free margin >0 mm) and R1 resections were analyzed. RESULTS Among 466 patients undergoing hepatectomy for CLM, 191 were eligible. Of them, 164 (86 %) received preoperative chemotherapy and 105 (55 %) received postoperative chemotherapy. R1 resection (10 %) was comparable in patients treated or not by preoperative chemotherapy. R1 status was associated with more intrahepatic recurrences. Overall survival (OS) (44 vs. 61 %; p = 0.047) and disease-free survival (DFS) (8 vs. 26 %; p = 0.082) were lower in patients after R1 compared to R0 resection (32 months of median follow-up). Preoperative chemotherapy and major hepatectomy were prognostic factors of survival, whereas postoperative chemotherapy was a protective factor from recurrences. In patients treated with preoperative chemotherapy, OS and DFS were similar between R1 and R0 resections (40 vs. 55 %, p = 0.104 and 9 vs. 22 %, p = 0.174, respectively). CONCLUSION In the era of modern effective chemotherapy, R1 resection leads to more intrahepatic recurrences but did not affect OS in selected patient responders to neoadjuvant chemotherapy. Postoperative chemotherapy protects from recurrences whatever the margin resection status.
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Affiliation(s)
- Christophe Laurent
- University of Bordeaux Segalen, 33076, Bordeaux, France. .,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France.
| | - Jean-Philippe Adam
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Quentin Denost
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Denis Smith
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Digestive Oncology, CHU Bordeaux, Saint André Hospital, 33075, Bordeaux, France
| | - Jean Saric
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Laurence Chiche
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Haut-Lévèque Hospital, 33600, Pessac, France
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Kilburn DJ, Chiow AKH, Lewin J, Kienzle N, Cavallucci DJ, Bryant R, O'Rourke N. Laparoscopic approach to a planned two-stage hepatectomy for bilobar colorectal liver metastases. ANZ J Surg 2016; 86:811-815. [DOI: 10.1111/ans.12748] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Affiliation(s)
- Daniel James Kilburn
- Hepatopancreatobiliary Unit; Department of Surgery; Royal Brisbane and Women's Hospital, Queensland Health; Herston Queensland Australia
| | - Adrian Kah Heng Chiow
- Hepatopancreatobiliary Unit; Department of Surgery; Royal Brisbane and Women's Hospital, Queensland Health; Herston Queensland Australia
| | - Joel Lewin
- Hepatopancreatobiliary Unit; Department of Surgery; Royal Brisbane and Women's Hospital, Queensland Health; Herston Queensland Australia
| | - Nicholas Kienzle
- Department of Medical Imaging; Royal Brisbane and Women's Hospital, Queensland Health; Herston Queensland Australia
| | - David Joseph Cavallucci
- Hepatopancreatobiliary Unit; Department of Surgery; Royal Brisbane and Women's Hospital, Queensland Health; Herston Queensland Australia
| | - Richard Bryant
- Hepatopancreatobiliary Unit; Department of Surgery; Royal Brisbane and Women's Hospital, Queensland Health; Herston Queensland Australia
| | - Nicholas O'Rourke
- Hepatopancreatobiliary Unit; Department of Surgery; Royal Brisbane and Women's Hospital, Queensland Health; Herston Queensland Australia
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Li W, Chang J, Wang S, Liu X, Peng J, Huang D, Sun M, Chen Z, Zhang W, Guo W, Li J. miRNA-99b-5p suppresses liver metastasis of colorectal cancer by down-regulating mTOR. Oncotarget 2016; 6:24448-62. [PMID: 26259252 PMCID: PMC4695197 DOI: 10.18632/oncotarget.4423] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2015] [Accepted: 05/30/2015] [Indexed: 12/13/2022] Open
Abstract
Liver metastasis is common in patients diagnosed with colorectal cancer (CRC), and is also correlated with poor outcome. In this study we screened the different expression profiles of microRNAs (miRNAs) on the development of liver metastasis in CRC patients. miR-99b-5p was found to be more than 6-fold higher in primary tumors than in matched liver metastases (P = 0.007). Expression of miR-99b-5p in primary tumors of patients with stage III CRC without liver metastases was higher than in CRC patients with liver metastases (P = 0.028). Up-regulated miR-99b-5p was associated with longer overall survival (P = 0.01). Besides, miR-99b-5p silencing in miR-99b-5p-positive CRC cell lines promoted cell migration and up-regulated mTOR, and vice versa. In addition, luciferase assays demonstrated that miR-99b-5p functioned as a tumor suppressor by targeting mTOR. Taken together, our results demonstrate thatmiR-99b-5p is differently expressed in primary CRC and liver metastasis and functions as a tumor-suppressive microRNA in metastatic CRC. The miR-99b-5p–mTOR axis may serve as a prognostic factor and therapeutic target for anti-metastatic therapy in CRC patients.
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Affiliation(s)
- Wenhua Li
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jinjia Chang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shanshan Wang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xinyang Liu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Junjie Peng
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Dan Huang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Menghong Sun
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhiyu Chen
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wen Zhang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Weijian Guo
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jin Li
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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46
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Tobi M, Thomas P, Ezekwudo D. Avoiding hepatic metastasis naturally: Lessons from the cotton top tamarin (Saguinus oedipus). World J Gastroenterol 2016; 22:5479-94. [PMID: 27350726 PMCID: PMC4917608 DOI: 10.3748/wjg.v22.i24.5479] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Revised: 04/26/2016] [Accepted: 05/21/2016] [Indexed: 02/06/2023] Open
Abstract
Much has been written about hepatic metastasis and animal models abound. In terms of the human experience, progress in treating this final common pathway, a terminal event of many human malignancies has been relatively slow. The current thinking is that primary prevention is best served by early detection of cancer and eradication of early stage cancers by screening. Some cancers spread early in their course and the role of screening may be limited. Until relatively recently there has not been a pathfinder model that makes the evasion of this unfortunate event a reality. This review discusses such an animal model and attempts to relate it to human disease in terms of intervention. Concrete proposals are also offered on how scientists may be able to intervene to prevent this deadly progression of the cancer process.
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47
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Diffusion-Related MRI Parameters for Assessing Early Treatment Response of Liver Metastases to Cytotoxic Therapy in Colorectal Cancer. AJR Am J Roentgenol 2016; 207:W26-32. [PMID: 27303858 DOI: 10.2214/ajr.15.15683] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The objective of our study was to evaluate early therapeutic response after cytotoxic chemotherapy in patients with liver metastasis from colorectal cancer (CRC) using intravoxel incoherent motion (IVIM) DWI and dynamic contrast-enhanced MRI (DCE-MRI). SUBJECTS AND METHODS Nineteen patients with liver metastasis from CRC underwent DCE-MRI and IVIM DWI at baseline and after the first cycle of chemotherapy. IVIM DWI parameters including the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) and DCE-MRI perfusion parameters including the volume transfer constant (K(trans)), reverse volume transfer constant (Kep), extravascular extracellular volume fraction (Ve), and initial area under the concentration curve in 60 seconds (iAUC) were calculated. The response evaluation was based on Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS There were eight responding and 11 nonresponding patients. ADC (baseline value vs value after first cycle of chemotherapy [mean ± SD]: 1191.9 ± 232.2 vs 1263.5 ± 266.4 × 10(-3) mm(2)/s; p = 0.012), D (1085.9 ± 232.9 vs 1173.5 ± 248.9 × 10(-3) mm(2)/s; p = 0.012), and f (173.7% ± 39.8% vs 133.5% ± 28.3%; p = 0.017) showed a significant change after the first cycle of chemotherapy in the response group, whereas ADC and D showed no significant change in the nonresponse group. In addition, DCE-MRI perfusion parameters showed no significant changes. A correlation was found between each of perfusion-related IVIM parameters and the DCE-MRI parameters before chemotherapy (r = 1.33, p > 0.05). CONCLUSION Diffusion-related MRI parameters are useful for the early prediction of therapeutic response after cytotoxic chemotherapy for liver metastasis from CRC.
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48
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Mehrzad V, Roayaei M, Peikar MS, Nouranian E, Mokarian F, Khani M, Farzannia S. Bevacizumab plus FOLFOX or FOLFIRI regimens on patients with unresectable liver-only metastases of metastatic colorectal cancer. Adv Biomed Res 2016; 5:10. [PMID: 26962512 PMCID: PMC4770632 DOI: 10.4103/2277-9175.175243] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2013] [Accepted: 08/21/2013] [Indexed: 12/27/2022] Open
Abstract
Background: The present study was aimed to evaluate the efficacy and safety of at least three cycles of Bevacizumab in combination with chemotherapy regimens, FOLFIRI or FOLFOX to treat liver metastatic colorectal cancer and improved response rates in these patients. Materials and Methods: In this non-randomized clinical trial, 38 patients were enrolled and followed for 12-weeks period of chemotherapy. Fifteen patients under treated with FOLOFX (Group I), 15 patients under treated with FOLOFIRI (Group II), 4 patients under treated with FOLOFX + Bevacizumab (Group III), and 34 patients under treated with FOLOFIRI + Bevacizumab (Group IV). Response to treatment was assessed in all patients as main endpoint. Patients in groups I and II, who did not response to treatment after 12 weeks of chemotherapy, were followed by groups III and IV regimens, respectively, for 12 weeks. Results: Overall response rate was 35% (19 of 54), and complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD) rates in all patients were 18%, 17%, 35%, and 30%. PR, SD, and PD were different among groups, but no statistical significance was noted among groups (P-value >0.05). No patient achieved a CR in groups III and IV, although CR was observed in 4 patients (27%) and 6 patients (40%) in groups I and II, respectively. The rare of CR was statistically significant among studied groups (P-value = 0.013). Conclusion: Results showed that adding Bevacizumab to chemotherapy regimens, in patients who did not response to FOLFIRI or FOLFOX regimen, did not increase CR in these patients.
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Affiliation(s)
- Valiollah Mehrzad
- Department of Clinical Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahnaz Roayaei
- Department of Radiation Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Saleh Peikar
- Department of Clinical Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Elham Nouranian
- Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fariborz Mokarian
- Department of Radiation Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohsen Khani
- Department of Clinical Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Somaieh Farzannia
- Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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49
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Imai K, Allard MA, Castro Benitez C, Vibert E, Sa Cunha A, Cherqui D, Castaing D, Bismuth H, Baba H, Adam R. Nomogram for prediction of prognosis in patients with initially unresectable colorectal liver metastases. Br J Surg 2016; 103:590-9. [PMID: 26780341 DOI: 10.1002/bjs.10073] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Revised: 10/31/2015] [Accepted: 11/05/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Although recent advances in surgery and chemotherapy have increasingly enabled hepatectomy in patients with initially unresectable colorectal liver metastases (CRLM), not all such patients benefit from surgery. The aim of this study was to develop a nomogram to predict survival after hepatectomy for initially unresectable CRLM. METHODS Patients with initially unresectable CRLM treated with chemotherapy followed by hepatectomy between 1990 and 2012 were included in the study. A nomogram to predict survival was developed based on a multivariable Cox model. The predictive performance of the model was assessed according to the C-statistic, Kaplan-Meier curve and calibration plots. RESULTS Of a total of 439 patients, liver and globally completed surgery was achieved in 380 (86·6 per cent) and 335 (76·3 per cent) patients respectively. The 5-year overall and disease-free survival rates were 39·9 and 10·0 per cent respectively. Based on the Cox model, the following five factors were selected for the nomogram and assigned specific scores: node-positive primary, 5; more than six metastases at hepatectomy, 7; carbohydrate antigen 19-9 level at hepatectomy above 37 units/ml, 10; disease progression during first-line chemotherapy, 9; and presence of extrahepatic disease, 4. The model achieved relatively good discrimination and calibration, with a C-statistic of 0·66. The overall survival rate for patients with a score greater than 16 was significantly worse than that for patients with a score of 16 or less (5-year survival rate 4 versus 46·3 per cent respectively; P < 0·001). CONCLUSION The nomogram facilitates personalized assessment of prognosis for patients with initially unresectable CRLM treated with chemotherapy and with planned resection.
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Affiliation(s)
- K Imai
- Centre Hépato-Biliaire, Assistance Publique - Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France.,Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France.,Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - M-A Allard
- Centre Hépato-Biliaire, Assistance Publique - Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France.,Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France.,Université Paris-Sud, Villejuif, France
| | - C Castro Benitez
- Centre Hépato-Biliaire, Assistance Publique - Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France.,Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France.,Université Paris-Sud, Villejuif, France
| | - E Vibert
- Centre Hépato-Biliaire, Assistance Publique - Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France.,INSERM, Unité 785, Villejuif, France.,Université Paris-Sud, Villejuif, France
| | - A Sa Cunha
- Centre Hépato-Biliaire, Assistance Publique - Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France.,Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France.,Université Paris-Sud, Villejuif, France
| | - D Cherqui
- Centre Hépato-Biliaire, Assistance Publique - Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France.,INSERM, Unité 785, Villejuif, France.,Université Paris-Sud, Villejuif, France
| | - D Castaing
- Centre Hépato-Biliaire, Assistance Publique - Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France.,INSERM, Unité 785, Villejuif, France.,Université Paris-Sud, Villejuif, France
| | - H Bismuth
- Centre Hépato-Biliaire, Assistance Publique - Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
| | - H Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - R Adam
- Centre Hépato-Biliaire, Assistance Publique - Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France.,Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France.,Université Paris-Sud, Villejuif, France
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50
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Bagni O, Filippi L, Pelle G, Cianni R, Schillaci O. Total Lesion Glycolysis and Sequential (90)Y-Selective Internal Radiation Therapy in Breast Cancer Liver Metastases: Preliminary Results. Cancer Biother Radiopharm 2015; 30:421-6. [PMID: 26594900 DOI: 10.1089/cbr.2015.1877] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
To assess the prognostic role of total lesion glycolysis (TLG) in patients with breast cancer liver metastases (BCLM) after sequential lobar (90)Y-radioembolization ((90)Y-RE). Seventeen patients with bilobar BCLM underwent FDG PET/CT and TLG calculation before (90)Y-RE. The hepatic lobe with the highest TLG was treated in the first session. PET was performed 6 weeks postprocedure and decrease in TLG (ΔTLG) in the treated lobe was calculated before the second (90)Y administration. Subjects were divided in two groups (group 1: ΔTLG >50%, group 2: ΔTLG <50%). After the two consecutive (90)Y-therapies, patients underwent follow-up until death. Statistical analysis was performed to identify prognostic factors on overall survival (OS). After the first (90)Y administration, 10 cases showed a ΔTLG >50% and seven had a ΔTLG value <50%. After the two consecutive procedures, the mean OS for all patients was 13.5 ± 0.8 months. Subjects with a ΔTLG >50% and ΔTLG <50% had a mean OS of 16.4 ± 0.6 and 10.3 ± 0.4 months, respectively (p < 0.001). Cox regression analysis demonstrated hepatic tumor load (p = 0.048) and ΔTLG as the only significant (p = 0.005) predictors of survival. ΔTLG after the first (90)Y administration agrees with final outcome in BCLM patients after separate sequential lobar (90)Y-RE.
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Affiliation(s)
- Oreste Bagni
- 1 Department of Nuclear Medicine, Santa Maria Goretti Hospital , Latina, Italy
| | - Luca Filippi
- 1 Department of Nuclear Medicine, Santa Maria Goretti Hospital , Latina, Italy
| | - Giuseppe Pelle
- 2 Department of Interventional Radiology, Santa Maria Goretti Hospital , Latina, Italy
| | - Roberto Cianni
- 2 Department of Interventional Radiology, Santa Maria Goretti Hospital , Latina, Italy
| | - Orazio Schillaci
- 3 Department of Biomedicine and Prevention, University Tor Vergata , Rome, Italy
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