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Wang LJ, Bao Q, Zhang JQ, Li ZW, Xing BC. ASO Author Reflections: Toward Precision Chemotherapy in Colorectal Liver Metastases: Integrating Genomics into Predictive Modeling. Ann Surg Oncol 2025:10.1245/s10434-025-17533-0. [PMID: 40419715 DOI: 10.1245/s10434-025-17533-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2025] [Accepted: 05/03/2025] [Indexed: 05/28/2025]
Affiliation(s)
- Li-Jun Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery Unit I, Peking University Cancer Hospital & Institute, Beijing, China
| | - Quan Bao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery Unit I, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jing-Qing Zhang
- Research Institute, GloriousMed Clinical Laboratory Co., Ltd., Shanghai, China
| | - Zhong-Wu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.
| | - Bao-Cai Xing
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery Unit I, Peking University Cancer Hospital & Institute, Beijing, China.
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Wang LJ, Bao Q, Wang HW, Huang LF, Zhang JQ, Zhao TT, Jin KM, Liu XF, Wang K, Li ZW, Xing BC. Predictive Factors for Chemotherapy Response in Colorectal Liver Metastasis: A Retrospective Study Utilizing Next-Generation Sequencing. Ann Surg Oncol 2025:10.1245/s10434-025-17320-x. [PMID: 40342004 DOI: 10.1245/s10434-025-17320-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 03/30/2025] [Indexed: 05/11/2025]
Abstract
BACKGROUND This study aimed to identify predictive factors for chemotherapy response in colorectal liver metastasis (CRLM) patients. METHODS Eligible participants with CRLM who had undergone at least two systemic chemotherapy cycles postdiagnosis were retrospectively analyzed. They were categorized as responders and nonresponders based on tumor size reduction. DNA extracted from tumor tissues was subjected to sequencing. Additionally, a comparative analysis of oncogenic pathways was conducted. Logistic regression analysis was conducted to determine predictive factors for chemotherapy response. RESULTS A total of 230 Chinese patients were analyzed. Significant differences in mutation distribution were found, particularly in the KRAS gene and several specific rare gene mutations (EP300, PTPRK, KMT2A, and ACVR1B), as well as in the PI3K and RTK-RAS pathways between the two groups. Gender, utilization of biological targeted agents (BTAs), KRAS gene mutations, PI3K pathway alterations, and specific rare gene mutations were used to construct a specific efficacy prediction model, achieving an area under the curve (AUC) of 0.73. Approximately 75% (87/116) of patients could potentially avoid BTAs based on the model's predictions. In a subgroup of 52 patients not using BTAs, simulation indicated that 10 patients could benefit by including BTAs, representing 32% (10 of 31) of initially nonresponsive patients. CONCLUSIONS Gender, utilization of BTAs, and specific gene and pathway mutations may be significant predictors of chemotherapy response in CRLM patients. These findings highlight the role of genetic profiling in refining treatment strategies.
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Affiliation(s)
- Li-Jun Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery Unit I, Peking University Cancer Hospital and Institute, Beijing, China
| | - Quan Bao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery Unit I, Peking University Cancer Hospital and Institute, Beijing, China
| | - Hong-Wei Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery Unit I, Peking University Cancer Hospital and Institute, Beijing, China
| | - Long-Fei Huang
- GloriousMed Clinical Laboratory Co., Ltd., Research Institute, Shanghai, China
| | - Jing-Qing Zhang
- GloriousMed Clinical Laboratory Co., Ltd., Research Institute, Shanghai, China
| | - Ting-Ting Zhao
- GloriousMed Clinical Laboratory Co., Ltd., Research Institute, Shanghai, China
| | - Ke-Min Jin
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery Unit I, Peking University Cancer Hospital and Institute, Beijing, China
| | - Xiao-Feng Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery Unit I, Peking University Cancer Hospital and Institute, Beijing, China
| | - Kun Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery Unit I, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhong-Wu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
| | - Bao-Cai Xing
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery Unit I, Peking University Cancer Hospital and Institute, Beijing, China.
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Lakha AS, Sud V, Alemour Y, Perera NJ, McGivern H, Smith C, Gordon-Weeks A. Simultaneous versus delayed resection of synchronous colorectal liver metastases: A systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109732. [PMID: 40048802 DOI: 10.1016/j.ejso.2025.109732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/23/2025] [Accepted: 02/26/2025] [Indexed: 05/13/2025]
Abstract
Colorectal cancer is a leading malignancy, with synchronous colorectal liver metastases (CRLM) presenting in 20 % of patients. Resection remains the gold standard treatment for CRLMs, significantly improving survival outcomes. However, the optimal timing of resection of these synchronous lesions - simultaneous versus staged - remains controversial. This systematic review and meta-analysis synthesises data exclusively from propensity-score-matched and prospective studies. A comprehensive search of five databases identified 11 eligible studies, encompassing 2884 patients. Of these, 1453 underwent simultaneous resection, and 1431 underwent staged procedures. The primary outcome was 5-year overall survival (OS), with secondary outcomes including disease-free survival (DFS), surgical morbidity, operating time, and length of hospital stay. Meta-analysis demonstrated no significant difference in 5-year OS between simultaneous and staged resection groups (odds ratio [OR] 1.10, 95 % CI 0.75-1.61; p = 0.83). However, simultaneous resection was associated with significantly higher 3-year DFS (OR 1.67, 95 % CI 1.28-2.17; p = 0.0001) but also increased major surgical complications (Clavien-Dindo ≥ III: OR 1.32, 95 % CI 1.03-1.68; p = 0.03). This review highlights a lack of oncological advantage for simultaneous resection, coupled with higher morbidity, suggesting its use should be limited to select patients with low surgical risk. The findings underscore the need for well-powered, randomised trials to confirm these conclusions, as well as assess quality of life and economic outcomes, however delivering such trials in this patient cohort brings unique challenges. Until such data are available, clinical decision-making should remain individualised, guided by multidisciplinary discussion and available local expertise.
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Affiliation(s)
- Adil S Lakha
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom; Oxford Hepatobiliary and Pancreatic Surgery Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
| | - Vikas Sud
- Oxford Hepatobiliary and Pancreatic Surgery Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Younis Alemour
- Faculty of Medicine, Al-Quds University, Al-Azhar Branch, Gaza, Palestine
| | - Nikhil J Perera
- First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Hannah McGivern
- Bodleian Healthcare Libraries, University of Oxford, United Kingdom
| | - Carolyn Smith
- Bodleian Healthcare Libraries, University of Oxford, United Kingdom
| | - Alex Gordon-Weeks
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom; Oxford Hepatobiliary and Pancreatic Surgery Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
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Dossa F, Weiser MR. The Ugly: Metastatic Colon Cancer-Surgical Options. Clin Colon Rectal Surg 2025; 38:219-228. [PMID: 40291995 PMCID: PMC12020648 DOI: 10.1055/s-0044-1787825] [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: 04/30/2025]
Abstract
Over 50% of patients with colorectal cancer develop metastatic disease. Although systemic therapy remains the backbone of palliative treatment, select patients may be candidates for surgical resection with curative intent. Given increasing evidence of the association between metastasectomy and prolonged survival, surgery has acquired an increasingly central role in the management of liver, lung, and peritoneal metastases. This is compounded by accumulating advances in local and systemic treatments that have allowed for expansion of the resectability pool, bringing the potential for curative surgical treatment to increasing numbers of patients with stage IV disease. However, as the boundaries of resectability are pushed, patient selection and consideration of tumor-related and technical factors are imperative to the identification of patients for whom surgery would be of the greatest benefit.
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Affiliation(s)
- Fahima Dossa
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Martin R. Weiser
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
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Uysal M, Wehrle CJ, Satish S, Knott E, Hong H, Allkushi E, Schlegel A, Berber E, Aucejo F, Kim J, Kwon DCH. Histotripsy of Liver Tumors: Patient Selection, Ethical Discussions, and How We Do It. Cancers (Basel) 2025; 17:1100. [PMID: 40227626 PMCID: PMC11987918 DOI: 10.3390/cancers17071100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 03/09/2025] [Accepted: 03/21/2025] [Indexed: 04/15/2025] Open
Abstract
Liver malignancies, both primary and metastatic tumors, are a major cause of cancer-related mortality. Colorectal cancer alone results in liver metastases in nearly 50% of patients, with approximately 85% presenting with unresectable disease. Similarly, hepatocellular carcinoma and intrahepatic cholangiocarcinoma frequently present at advanced stages, limiting curative options. Systemic therapies provide modest survival benefits, underscoring the need for alternative treatments. Locoregional approaches, such as thermal ablation and chemoembolization, while effective, have notable limitations, including invasiveness, peri-procedural risks, and the requirement to interrupt systemic treatments. Histotripsy is a novel, non-invasive method that uses focused ultrasound-induced cavitation to enable precise tumor ablation without heat or radiation. Our institution utilizes a multidisciplinary tumor board approach to evaluate patients for histotripsy, particularly in cases involving unresectable disease, complex surgical candidacy, palliative intent related to disease control and symptom management, or as bridging therapy for transplantation. Early results, including preclinical data and the THERESA and #HOPE4LIVER trials, highlight its efficacy in treating liver tumors with minimal complications. This review outlines institutional protocols for histotripsy, covering pre- and post-procedural management, along with ethical considerations of current treatment paradigms. As a patient-centered approach, histotripsy offers a novel treatment option with a favorable safety profile and compatibility with systemic therapies.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - David C. H. Kwon
- Cleveland Clinic, Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland, OH 44120, USA; (M.U.); (C.J.W.); (S.S.); (A.S.); (F.A.); (J.K.)
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Lyadov VK, Moskalenko AN, Magomedov MM, Galkin VN. [Laparoscopic ALPPS procedure: a series of cases]. Khirurgiia (Mosk) 2025:20-26. [PMID: 39918799 DOI: 10.17116/hirurgia202502120] [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: 02/09/2025]
Abstract
The combination of liver resection and chemotherapy is the most effective way to treat primary and secondary malignant liver tumors. One of the methods for increasing resectability is the use of two-stage liver resection (associated liver partition and portal vein ligation for staged hepatectomy - ALPPS). OBJECTIVE To demonstrate the feasibility of laparoscopic ALPPS with good short-term and long-term results. MATERIAL AND METHODS From 2020 to 2021, in the oncology department No. 4 of the State Budgetary Healthcare Institution "GKOB 1 DZM" 6 laparoscopic ALPPS were performed for metastases of colorectal cancer in the liver in 4 patients and cholangiocellular cancer in two in the presence of an insufficient volume of remaining liver parenchyma (13-32.1%). RESULTS All patients underwent the first stage of ALPPS laparoscopically without conversions or intraoperative complications. The duration of the operation ranged from 300 to 470 minutes (average 347.5±74 minutes), blood loss - from 100 to 300 ml (average 175±88 ml). The duration of the second stage is from 165 to 470 minutes (average 281.5±132.9 minutes) with blood loss from 100 to 850 ml (average 484.5±392.3 ml). The increase in the volume of residual liver parenchyma was 36-68%. The period between the ALPPS stages ranged from 13 to 22 days. Final resection to the extent of R0 was performed in 4 of 6 patients. The second stage of ALPPS was complicated in two patients by the formation of an external biliary fistula and in another two by right-sided hydrothorax. The median follow-up was 25 months, during which time 3 patients died: two patients with incomplete second stage ALPPS due to cancer progression and one patient from coronavirus infection. CONCLUSION ALPPS can be performed entirely laparoscopically with good short-term and long-term results, but should be performed in high-volume liver surgery centers by an experienced surgical team.
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Affiliation(s)
- V K Lyadov
- Yudin Moscow City Clinical Hospital, Moscow, Russia
- Russian Medical Academy of Continuous Professional Education, Moscow, Russia
- Novokuznetsk State Institute for Advanced Medical Studies, Novokuznetsk, Russia
| | | | | | - V N Galkin
- Yudin Moscow City Clinical Hospital, Moscow, Russia
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Signorelli C, Calegari MA, Anghelone A, Passardi A, Frassineti GL, Bittoni A, Lucchetti J, Angotti L, Di Giacomo E, Zurlo IV, Morelli C, Dell'Aquila E, Artemi A, Gemma D, Corsi DC, Emiliani A, Ribelli M, Mazzuca F, Arrivi G, Zoratto F, Chilelli MG, Schirripa M, Morandi MG, Santamaria F, Dettori M, Cosimati A, Saltarelli R, Minelli A, Lucci-Cordisco E, Basso M. Survival Outcomes with Regorafenib and/or Trifluridine/Tipiracil Sequencing to Rechallenge with Third-Line Regimens in Metastatic Colorectal Cancer: A Multicenter Retrospective Real-World Subgroup Comparison from the ReTrITA Study. Curr Oncol 2024; 31:7793-7808. [PMID: 39727697 DOI: 10.3390/curroncol31120574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 11/26/2024] [Accepted: 11/30/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND There is ongoing discussion around the optimal course of treatment for metastatic colorectal cancer (mCRC) following the second line. Trifluridine/tipiracil (T) and regorafenib (R) have been the mainstay of therapy in this situation, as they both increased overall survival (OS) in comparison to a placebo. Despite the paucity of evidence, therapy rechallenge is also recognized as an option for practical use. In the third-line scenario of mCRC, we planned to investigate the survival outcomes using (T) and (R), both with and without prior rechallenge treatment. MATERIALS AND METHODS Between 2012 and 2023, we examined the medical records of 1156 patients with refractory mCRC who were enrolled in the multicenter retrospective ReTrITA study. We then separated the patients into two cohorts based on the rechallenge therapy that was given before regorafenib and/or trifluridine/tipiracil at 17 Italian centres. RESULTS A total of 981 patients underwent T and/or R therapy, while 175 patients had therapy rechallenge before T and/or R. The median overall survival (mOS) for patients treated with T/R and R/T sequences in the rechallenge therapy cohort was 14.5 months and 17.6 months, respectively (p = 0.1955). A statistically significant survival benefit was observed in patients who received monotheraphy with R (mOS: 6 months) compared to the T group (mOS: 4.2 months) (p = 0.0332). In the same cohort, a median progression-free survival (mPFS) benefit was demonstrated in favour of the R/T group (11.3 months) vs. 9 months of the reverse sequence (p = 0.4004). In the no-rechallenge cohort, the mOS was statistically longer in the R/T sequence than in the T/R sequence (16.2 months vs. 12.3 months, respectively; p = 0.0014). In terms of the mPFS, we saw the same significant result for the adoption of R/T treatment (11.5 months vs. 8.4 months, respectively; p < 0.0001). The two monotherapy groups did not reveal any significant differences. CONCLUSIONS This study suggests that rechallenge therapy may improve survival rates in the third-line treatment of mCRC, particularly if it is administered before sequential R/T treatment. This could allow for the extension of mCRC treatment choices until prospective studies are finished or randomised trials are performed.
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Affiliation(s)
- Carlo Signorelli
- Medical Oncology Unit, Belcolle Hospital, ASL Viterbo, 01100 Viterbo, Italy
| | - Maria Alessandra Calegari
- Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, 00168 Rome, Italy
| | - Annunziato Anghelone
- Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, 00168 Rome, Italy
| | - Alessandro Passardi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy
| | - Giovanni Luca Frassineti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy
| | - Alessandro Bittoni
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy
| | - Jessica Lucchetti
- Division of Medical Oncology, Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Lorenzo Angotti
- Division of Medical Oncology, Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Emanuela Di Giacomo
- Division of Medical Oncology, Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | | | - Cristina Morelli
- Medical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, 00133 Rome, Italy
| | | | - Adele Artemi
- IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
| | | | | | | | - Marta Ribelli
- Medical Oncology, Isola Tiberina Hospital, Gemelli Isola, 00186 Rome, Italy
| | - Federica Mazzuca
- Oncology Unit, Department of Clinical and Molecular Medicine, Sant' Andrea University Hospital, Sapienza University of Rome, 00189 Rome, Italy
| | - Giulia Arrivi
- Oncology Unit, Department of Clinical and Molecular Medicine, Sant' Andrea University Hospital, Sapienza University of Rome, 00189 Rome, Italy
| | - Federica Zoratto
- UOC Oncologia, Ospedale Santa Maria Goretti, ASL Latina, 04100 Latina, Italy
| | | | - Marta Schirripa
- Medical Oncology Unit, Belcolle Hospital, ASL Viterbo, 01100 Viterbo, Italy
| | - Maria Grazia Morandi
- Medical Oncology Unit, San Camillo de Lellis Hospital, ASL Rieti, 02100 Rieti, Italy
| | - Fiorenza Santamaria
- UOC Oncology A, Policlinico Umberto I, 00161 Rome, Italy
- Experimental Medicine, Network Oncology and Precision Medicine, Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Manuela Dettori
- Medical Oncology Department, Ospedale Oncologico Armando Businco, 09121 Cagliari, Italy
| | - Antonella Cosimati
- Medical Oncology Department, UO Oncologia Universitaria della Casa della Salute di Aprilia, 04011 Aprilia, Italy
| | - Rosa Saltarelli
- UOC Oncology, San Giovanni Evangelista Hospital, ASL RM5, 00019 Tivoli, Italy
| | - Alessandro Minelli
- Medical Oncology Department, UO Oncologia, Ospedale San Paolo, ASL RM4, 00053 Civitavecchia, Italy
| | - Emanuela Lucci-Cordisco
- UOC Genetica Medica, Dipartimento di Scienze della Vita e Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy
- Medical Oncology Department, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, 00168 Rome, Italy
| | - Michele Basso
- Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, 00168 Rome, Italy
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Cui F, Chen Y, Wu X, Zhao W. Mesenchymal stem cell-derived exosomes carrying miR-486-5p inhibit glycolysis and cell stemness in colorectal cancer by targeting NEK2. BMC Cancer 2024; 24:1356. [PMID: 39506654 PMCID: PMC11539302 DOI: 10.1186/s12885-024-13086-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 10/22/2024] [Indexed: 11/08/2024] Open
Abstract
Colorectal cancer (CRC) is a major global concern. Mesenchymal stem cell-derived exosomes (MSC-EXOs) have demonstrated efficacy as a therapeutic approach for colorectal cancer. However, the precise mechanism by which MSC-EXOs treat colorectal cancer remains unclear. Human umbilical cord (hUC)-MSC-EXOs were isolated and identified. Cell Counting Kit-8 (CCK-8), Transwell, and colony formation assays were used to assess the activity of CRC cells. Glucose consumption, lactic acid production, and extracellular acidification rate (ECAR) were measured to assess glycolytic activity. Cell stemness was assessed using a sphere-formation assay. Furthermore, MSC-exosomal microRNAs (miRNAs) in CRC tissues were analyzed using the EVmiRNA database, and aberrantly expressed miRNAs in CRC cells were obtained from the Gene Expression Omnibus (GEO) database. The binding relationship between miR-486-5p and the never in mitosis gene A-related kinase 2 (NEK2) was predicted using the Starbase database and validated through RNA binding protein immunoprecipitation (RIP) and dual luciferase assays. These results showed that hUC-MSC-EXOs inhibited the proliferation and metastasis of CRC cells. Moreover, glycolysis and stemness abilities of CRC cells also decreased after treatment with hUC-MSC-EXOs. miR-486-5p was found to be enriched in hUC-MSC-EXOs and significantly downregulated in CRC cells. miR-486-5p directly bound to NEK2. Overexpression of NEK2 reversed the inhibitory effect of miR-486-5p on CRC cell glycolysis and stemness. Our study highlights that hUC-MSC-EXO miR-486-5p inhibits glycolysis and cell stemness in CRC by targeting NEK2. This finding offers compelling evidence supporting the potential application of hUC-MSC-EXOs in the treatment of CRC.
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Affiliation(s)
- Facai Cui
- Department of Clinical Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Jinshui District, Zhengzhou City, 450003, Henan, China.
| | - Yu Chen
- Department of Pathology, Affiliated Tumor Hospital of Zhengzhou University, No. 127 Dongming Road, Jinshui District, Zhengzhou City, 450003, Henan, China
| | - Xiaoyu Wu
- Department of Clinical Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Jinshui District, Zhengzhou City, 450003, Henan, China
| | - Weifeng Zhao
- Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Jinshui District, Zhengzhou City, 450003, Henan, China
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Li Z, Yan T, Cai X. Comparative efficacy of microwave ablation and radiofrequency ablation for treating metastatic liver cancer: a systematic review and meta-analysis. Front Oncol 2024; 14:1473780. [PMID: 39540156 PMCID: PMC11557459 DOI: 10.3389/fonc.2024.1473780] [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: 07/31/2024] [Accepted: 09/30/2024] [Indexed: 11/16/2024] Open
Abstract
Objective This study aims at evaluating and juxtaposing the efficacy of radiofrequency ablation (RFA) and microwave ablation (MWA) for hepatic metastases treatment. Methods We undertook an extensive literature search across the Cochrane Library, Web of Science, Embase, PubMed, CNKI, and databases for studies published up to December 2023, assessing the outcomes of RFA versus MWA in hepatic metastases treatment. Studies were included or excluded based on established criteria. Continuous variables were analyzed with the aid of the weighted mean difference (WMD) and its 95% confidence interval (CI), while the odds ratio (OR) with its 95% CI was utilized for dichotomous variables. Data were processed by use of STATA 17.0 software. Key outcomes assessed included ablation time, post-operative local tumor progression (LTP), disease-free survival (DFS), and post-operative complications (POCs). Results Seven studies, comprising 357 patients undergoing MWA and 452 patients undergoing RFA, fulfilled the inclusion criteria. As unveiled by the meta-analysis, RFA and MWA did not significantly differ in ablation time, DFS, and POCs. Nonetheless, MWA resulted in a strikingly reduced rate of post-operative LTP versus RFA. Conclusion MWA offers superior control over post-operative LTP, suggesting better overall efficacy in hepatic metastases treatment compared with RFA. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD42023385201.
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Affiliation(s)
- Zheng Li
- Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tingting Yan
- Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiujun Cai
- Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments, Hangzhou, China
- Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Hangzhou, China
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Krzywoń L, Lazaris A, Petrillo SK, Zlotnik O, Gao ZH, Metrakos P. Histopathological Growth Patterns Determine the Outcomes of Colorectal Cancer Liver Metastasis Following Liver Resection. Cancers (Basel) 2024; 16:3148. [PMID: 39335120 PMCID: PMC11430747 DOI: 10.3390/cancers16183148] [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: 07/23/2024] [Revised: 08/14/2024] [Accepted: 08/17/2024] [Indexed: 09/30/2024] Open
Abstract
INTRODUCTION Colorectal cancer liver metastasis (CRCLM) remains a lethal diagnosis, with an overall 5-year survival rate of 5-10%. Two distinct histopathological growth patterns (HGPs) of CRCLM are known to have significantly differing rates of patient survival and response to treatment. We set out to review the results of 275 patients who underwent liver resection for CRCLM at the McGill University Health Center (MUHC) and analyze their clinical outcome, mutational burden, and pattern of cancer progression in light of their HGPs, and to consider their potential effect on surgical decision making. METHODS We performed a retrospective multivariate analysis on clinical data from patients with CRCLM (n = 275) who underwent liver resection at the McGill University Health Center (MUHC). All tumors were scored using international consensus guidelines by pathologists trained in HGP scoring. RESULTS A total of 109 patients (42.2%) were classified as desmoplastic and angiogenic, whereas 149 patients (57.7%) were non-desmoplastic and vessel co-opting. The 5-year survival rates for angiogenic patients compared with vessel co-opting patients were 47.1% and 13%, respectively (p < 0.0001). Multivariate analysis showed patients with vessel co-opting CRCLM had a higher incidence of extrahepatic metastatic disease (p = 0.0215) compared with angiogenic CRCLM. Additionally, KRAS mutation status was a marker of increased likelihood of disease recurrence (p = 0.0434), as was increased number of liver tumors (p = 0.0071) and multiple sites of extrahepatic metastatic disease (p < 0.0001). CONCLUSIONS Multivariate analysis identified key clinical prognostic and molecular features correlating with the two HGPs. Determining liver tumor HGPs is essential for patient prognostication and treatment optimization.
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Affiliation(s)
- Lucyna Krzywoń
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
- Department of Experimental Surgery, McGill University, 1650 Cedar Ave., Room A7.117, Montreal, QC H4A 3J1, Canada
| | - Anthoula Lazaris
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
| | - Stephanie K Petrillo
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
| | - Oran Zlotnik
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
- Department of Experimental Surgery, McGill University, 1650 Cedar Ave., Room A7.117, Montreal, QC H4A 3J1, Canada
| | - Zu-Hua Gao
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
- Department of Pathology and Labaratory Medicine, University of British Columbia, Rm. G227-2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada
- McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada
| | - Peter Metrakos
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
- McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada
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11
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Toyota N, Tsuruta M, Tajima Y, Shigeta K, Okabayashi K, Hasegawa H, Fujita S, Yoshimatsu Y, Ozawa I, Kondo T, Kitagawa Y. Profilin 2 isoform expression is associated with lung metastasis of colorectal cancer according to a comprehensive gene expression study using a mouse model. Oncol Lett 2024; 28:381. [PMID: 38939626 PMCID: PMC11209866 DOI: 10.3892/ol.2024.14514] [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: 01/23/2024] [Accepted: 05/30/2024] [Indexed: 06/29/2024] Open
Abstract
Lung metastasis is the second most common type of metastasis in colorectal cancer. Specific treatments for lung metastasis have not been developed since the underlying mechanisms are poorly understood. The present study aimed to elucidate the molecular basis of lung metastasis in colorectal cancer. In a mouse model, cell lines that were highly metastatic to the lungs were established by injecting colorectal cancer cells through the tail vein and removing them from the lungs. Differential gene expression comparing the transfected cells with their parental cells was investigated using DNA microarrays. The results were functionally interpreted using gene enrichment analysis and validated using reverse transcription-quantitative PCR (RT-qPCR). The isoforms of the identified genes were examined by melting curve analysis. The present study established colorectal cancer cell lines that were highly metastatic to the lungs. DNA microarray experiments revealed that genes (N-cadherin, VE-cadherin, Six4, Akt and VCAM1) involved in motility, proliferation and adhesion were upregulated, and genes (tissue inhibitor of metalloproteinase-3 and PAX6) with tumor-suppressive functions were downregulated in metastatic cells. Profilin 2 (PFN2) expression was upregulated in multiple metastatic cell lines using RT-qPCR. Two PFN2 isoforms were overexpressed in metastatic cells. In vitro and in vivo models were established and genes associated with lung metastasis were identified to overcome the heterogeneity of the disease. Overall, aberrant PFN2 expression is unreported in lung metastasis in colorectal cancer. In the present study, two PFN2 isoforms with differential tissue distribution were upregulated in metastatic cells, suggesting that they promote lung metastasis in colorectal cancer.
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Affiliation(s)
- Naoyuki Toyota
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
- Department of Colorectal Surgery, Tochigi Cancer Center, Utsunomiya, Tochigi 320-0834, Japan
| | - Masashi Tsuruta
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery and Welfare, School of Medicine, International University of Health, Narita, Chiba 286-8520, Japan
| | - Yuki Tajima
- Department of Surgery, Hiratsuka City Hospital, Hiratsuka, Kanagawa 254-0065, Japan
| | - Kohei Shigeta
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Koji Okabayashi
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Hirotoshi Hasegawa
- Department of Surgery, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Chiba 272-8513, Japan
| | - Shin Fujita
- Department of Colorectal Surgery, Tochigi Cancer Center, Utsunomiya, Tochigi 320-0834, Japan
| | - Yuki Yoshimatsu
- Department of Patient-Derived Cancer Model, Tochigi Cancer Center, Utsunomiya, Tochigi 320-0834, Japan
| | - Iwao Ozawa
- Department of Patient-Derived Cancer Model, Tochigi Cancer Center, Utsunomiya, Tochigi 320-0834, Japan
- Department of Cancer Proteogenomics, Tochigi Cancer Center, Utsunomiya, Tochigi 320-0834, Japan
| | - Tadashi Kondo
- Department of Cancer Proteogenomics, Tochigi Cancer Center, Utsunomiya, Tochigi 320-0834, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
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12
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Jeong JU, Rim CH, Yoo GS, Cho WK, Chie EK, Ahn YC, Lee JH, on behalf of Korean Oligometastasis Working Group, Korean Cancer Association. The Clinical Efficacy of Colorectal Cancer Patients with Pulmonary Oligometastases by Sterotactic Body Ablative Radiotherapy: A Meta-Analysis. Cancer Res Treat 2024; 56:809-824. [PMID: 38097919 PMCID: PMC11261202 DOI: 10.4143/crt.2023.920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 12/13/2023] [Indexed: 07/18/2024] Open
Abstract
PURPOSE There is increasing interest in the efficacy of stereotactic ablative radiotherapy (SABR) for treating colorectal cancer (CRC) patients with oligometastases (OM), recently. The purpose of this meta-analysis was to evaluate local control (LC), progression-free survival (PFS), and overall survival (OS) of CRC patients with pulmonary OM treated with SABR and toxicities. MATERIALS AND METHODS Studies that reported SABR for CRC patients with pulmonary OM were searched from MEDLINE and Embase. Treatment outcomes including LC, PFS, OS, and toxicities of grade 3 or higher were assessed. RESULTS A total of 19 studies with 1,668 patients were chosen for this meta-analysis. Pooled 1-, 2-, and 3-year LC rates were 83.1%, 69.3%, and 63.9%, respectively. PFS rates were 44.8%, 26.5%, and 21.5% at 1, 2, and 3 years, respectively. OS rates at 1-, 2-, and 3-year were 87.5%, 69.9%, and 60.5%, respectively. The toxicity rate of grade 3 or higher was 3.6%. The effect of dose escalation was meta-analyzed using available studies. CONCLUSION Application of SABR to CRC patients with pulmonary OM achieved modest local control with acceptable toxicity according to the present meta-analysis. Further studies establishing the clinical efficacy of SABR are guaranteed.
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Affiliation(s)
- Jae-Uk Jeong
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University College of Medicine, Hwasun, Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Gyu Sang Yoo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Kyung Cho
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Yong Chan Ahn
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Hoon Lee
- Department of Radiation Oncology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - on behalf of Korean Oligometastasis Working Group, Korean Cancer Association
- Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University College of Medicine, Hwasun, Korea
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiation Oncology, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
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Lee J, Ku G. State of the art and upcoming trends in HER2-directed therapies in gastrointestinal malignancies. Curr Opin Oncol 2024; 36:326-331. [PMID: 38726843 PMCID: PMC11611523 DOI: 10.1097/cco.0000000000001043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2024]
Abstract
PURPOSE OF REVIEW This review critically evaluates the evolution and current status of human epidermal growth factor receptor 2 (HER2)-directed therapies in upper gastrointestinal (GI) malignancies, a timely and relevant inquiry given the dynamic shifts in therapeutic strategies over the past decade. Initial enthusiasm following the Trastuzumab for Gastric Cancer (ToGA) study's demonstration of trastuzumab's efficacy, however, encountered hurdles due to subsequent trials showing limited progress, underscoring the necessity for a reevaluation of therapeutic approaches and the exploration of novel agents. RECENT FINDINGS The review highlights significant breakthroughs in the form of immune checkpoint inhibitors and innovative therapeutic technologies, which have redefined treatment paradigms and shown promising efficacy in HER2-positive cases. Emerging treatments such as trastuzumab deruxtecan (T-DXd), zanidatamab and evorpacept further illustrate the ongoing efforts to leverage unique mechanisms of action for improved HER2-positive antitumor activity. SUMMARY The advancements in HER2-directed therapies underscore a pivotal era in the management of upper GI malignancies. These developments not only reflect the profound impact of integrating novel therapeutic combinations but also highlight the critical role of ongoing research in overcoming resistance mechanisms and tailoring treatment to individual disease profiles.
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Affiliation(s)
- Jaeyop Lee
- Medical Oncology Fellow, Medicine, Memorial Sloan Kettering Cancer Center New York, NY, USA
| | - Geoffrey Ku
- Associate Attending Physician, Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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14
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Dong T, Fan H, Lyu J, Shi Y, Hu P, Wu X, Sun J. A retrospective study comparing the efficacy of microwave ablation and stereotactic body radiotherapy in colorectal cancer lung metastases. Oncol Lett 2024; 28:322. [PMID: 38807676 PMCID: PMC11130612 DOI: 10.3892/ol.2024.14455] [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: 02/08/2024] [Accepted: 04/24/2024] [Indexed: 05/30/2024] Open
Abstract
The purpose of the present study was to assess and compare the efficacy of microwave ablation (MWA) and stereotactic body radiotherapy (SBRT) in the treatment of lung metastases from patients with colorectal cancer (CRC) and to identify the preferable treatment modality based on patient and tumor characteristics. Records of 118 patients with CRC with a total of 307 lung metastases who underwent SBRT or MWA between January 2015 and December 2022 were retrospectively analyzed, including the essential clinicopathological information on patients (age, sex and underlying diseases), diagnosis and treatment information [primary tumor site, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9], imaging data [diameter of lung metastasis, location of the metastasis (i.e., whether or not the tumor was adjacent to the vessel or bronchus) and internal features] and follow-up data (postoperative therapy, complications or adverse effects and survival outcomes). For statistical analysis of the local tumor progression (LTP), disease-free survival and overall survival (OS) rates, Cox regression analysis, along with the Kaplan-Meier method adjusted using inverse probability of treatment weighting (IPTW), were performed. The median follow-up duration in the present study was 31.5 months. Multivariable Cox regression analysis revealed that the CEA level, metastasis diameter and internal features were independent predictors of OS. In the IPTW-adjusted analysis, no significant difference in the 1-year OS rate was observed between the SBRT and MWA groups (92.9 vs. 93.9%; P=0.483); however, a notable discrepancy in the treatment modalities was noted, leading to significant differences in the 2- and 3-year OS rates (65.9 vs. 57.6%, P=0.001, and 44.7 vs. 36.4%, P<0.001, respectively). A significant interaction effect for the treatment modality was observed for LTP (P=0.021). In conclusion, the present study revealed that SBRT and MWA have similar therapeutic effects in terms of prolonging the survival of patients with CRC with lung metastases; however, regarding the local control of lung metastases, MWA is associated with a number of significant advantages.
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Affiliation(s)
- Tianjie Dong
- School of Medicine, Shaoxing University, Shaoxing, Zhejiang 312000, P.R. China
| | - Hongjie Fan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Jiali Lyu
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China
| | - Yuting Shi
- School of Medicine, Shaoxing University, Shaoxing, Zhejiang 312000, P.R. China
| | - Peng Hu
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China
| | - Xia Wu
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China
| | - Jihong Sun
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China
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15
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Lee J, Ku G. Advances in Human Epidermal Growth Factor Receptor 2-Targeted Therapy in Upper Gastrointestinal Cancers. Hematol Oncol Clin North Am 2024; 38:585-598. [PMID: 38521686 DOI: 10.1016/j.hoc.2024.02.005] [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: 03/25/2024]
Abstract
The Trastuzumab for Gastric Cancer (ToGA) trial marked a pivotal moment in the adoption of trastuzumab for treating advanced human epidermal growth factor receptor 2 (HER2)-positive esophagogastric (EG) cancer. The KEYNOTE-811 trial brought to light the synergistic effect of immune modulation and HER2 targeting. Additionally, the emergence of trastuzumab deruxtecan (T-DXd) highlighted the potential of new pharmaceutical technologies to extend response, particularly for patients who have advanced beyond initial HER2-targeted therapies. This review aims to navigate through both the successes and challenges encountered historically, as well as promising current trials on innovative and transformative therapeutic strategies, including promising first-in-class and novel first-in-human agents.
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Affiliation(s)
- Jaeyop Lee
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Geoffrey Ku
- Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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16
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Sljivic M, Sever M, Ocvirk J, Mesti T, Brecelj E, Popovic P. Prognostic factors for overall survival and safety of trans-arterial chemoembolization (TACE) with irinotecan-loaded drug-eluting beads (DEBIRI) in patients with colorectal liver metastases. Radiol Oncol 2024; 58:214-220. [PMID: 38553252 PMCID: PMC11165976 DOI: 10.2478/raon-2024-0023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 03/06/2024] [Indexed: 06/12/2024] Open
Abstract
BACKGROUND Transarterial chemoembolisation with irinotecan-loaded drug-eluting beads (DEBIRI TACE) can be considered in patients with unresectable colorectal cancer liver metastases (CRLM) who progress after all approved standard therapies or in patients unsuitable for systemic therapy. PATIENTS AND METHODS Between September 2010 and March 2020, thirty patients (22 men and 8 women; mean age 66.8 ± 13.2) were included in this retrospective study. DEBIRI TACE was conducted in 43% of patients unsuitable for systemic therapy as a first-line treatment and 57% as salvage therapy after the progression of systemic therapy. All the patients had liver-limited disease. In the case of unilobar disease, two treatments were performed at four-week intervals, and in the case of bilobar disease, four treatments were performed at two-week intervals. All patients were premedicated and monitored after the procedure. Adverse events were graded according to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) classification system for complications. RESULTS The median overall survival (OS) from the beginning of DEBIRI TACE in the salvage group was 17.4 months; in the group without prior systemic therapy, it was 21.6 months. The median overall survival of all patients was 17.4 months (95% confidence interval [CI]: 10.0-24.7 months), and progression-free survival (PFS) was 4.2 months (95% CI: 0.9-7.4 months). The one-year survival rate after the procedure was 61%, and the two-year rate was 25%. Univariate analysis showed better survival of patients with four or fewer liver metastases (p = 0.002). There were no treatment-related deaths or grade 4 and 5 adverse events. Nonserious adverse events (Grades 1 and 2) were present in 53% of patients, and Grade 3 adverse events were present in 6% of the patients. CONCLUSIONS DEBIRI TACE is a well-tolerated treatment option for patients with liver metastases of colorectal cancer. Patients with four or fewer liver metastases correlated with better survival.
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Affiliation(s)
- Maja Sljivic
- Faculty of Medicine Ljubljana, Ljubljana, Slovenia
- Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | | | - Janja Ocvirk
- Faculty of Medicine Ljubljana, Ljubljana, Slovenia
- Institute of Oncology, Ljubljana, Slovenia
- University of Primorska, Faculty of Health Sciences, Isola, Slovenia
| | - Tanja Mesti
- Faculty of Medicine Ljubljana, Ljubljana, Slovenia
- Institute of Oncology, Ljubljana, Slovenia
| | - Erik Brecelj
- Faculty of Medicine Ljubljana, Ljubljana, Slovenia
- Institute of Oncology, Ljubljana, Slovenia
| | - Peter Popovic
- Faculty of Medicine Ljubljana, Ljubljana, Slovenia
- Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
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17
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Yang J, Wei Y, Gao L, Li Z, Yang X. Thermosensitive methyl-cellulose-based injectable hydrogel carrying oxaliplatin for the treatment of peritoneal metastasis in colorectal cancer. J Mater Chem B 2024; 12:5171-5180. [PMID: 38687592 DOI: 10.1039/d4tb00210e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2024]
Abstract
Advanced colorectal cancer (CRC) with peritoneal metastasis (PM) is a highly aggressive malignancy with poor prognosis. Systematic chemotherapy and local treatments are the primary therapeutic approaches. However, systemic chemotherapy is limited by low accumulation of drugs at the tumor site and systemic toxicity. Local treatments include cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). However, CRS faces challenges related to incomplete tumor resection, while HIPEC is restricted by the uneven distribution of drugs and potential complications. Herein, a thermosensitive methyl-cellulose-based injectable hydrogel carrying oxaliplatin (OXA) was synthesized to improve this situation. Specifically, methyl cellulose (MC) coagulated into a hydrogel, and OXA was loaded into the MC hydrogel to construct the OXA-MC hydrogel. We explored the OXA-MC hydrogel for the treatment of PM in CRC. The results demonstrated that the OXA-MC hydrogel had favorable biocompatibility and thermo-sensitivity and could act as a local slow-release drug carrier. Moreover, in a CT-26 tumor-bearing model, it showed a remarkable anti-tumor effect by inhibiting proliferation and promoting apoptosis. Additionally, transcriptome analysis indicated that the OXA-MC hydrogel might be involved in the regulation of the PI3K-AKT signaling pathway. In summary, we successfully prepared the OXA-MC hydrogel and provided a valid approach in the treatment of PM in CRC, which lays a foundation for other PM treatments.
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Affiliation(s)
- Ju Yang
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Yuanfeng Wei
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Ling Gao
- Department of Health Ward, The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou 510095, China
| | - Zhaojun Li
- Department of Radiation Oncology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou 570311, China
| | - Xi Yang
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
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18
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Cheng DX, Xu KD, Liu HB, Liu Y. Prognostic value of a nomogram model for postoperative liver metastasis of colon cancer. World J Gastrointest Surg 2024; 16:1055-1065. [PMID: 38690047 PMCID: PMC11056678 DOI: 10.4240/wjgs.v16.i4.1055] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/18/2024] [Accepted: 03/07/2024] [Indexed: 04/22/2024] Open
Abstract
BACKGROUND Colon cancer is one of the most common malignant tumors of the digestive system. Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer. AIM To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery. METHODS We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People's Hospital from December 2019 to December 2022. Patients were divided into liver metastasis and non-liver metastasis groups. Sex, age, and other general and clinicopathological data (preoperative blood routine and biochemical test indexes) were compared. The risk factors for liver metastasis were analyzed using single-factor and multifactorial logistic regression. A predictive model was then constructed and evaluated for efficacy. RESULTS Systemic inflammatory index (SII), C-reactive protein/albumin ratio (CAR), red blood cell distribution width (RDW), alanine aminotransferase, preoperative carcinoembryonic antigen level, and lymphatic metastasis were different between groups (P < 0.05). SII, CAR, and RDW were risk factors for liver metastasis after colon cancer surgery (P < 0.05). The area under the curve was 0.93 for the column-line diagram prediction model constructed based on these risk factors to distinguish whether liver metastasis occurred postoperatively. The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve, with good agreement. The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases, indicating that the model is safer. CONCLUSION Liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the SII, CAR, and RDW.
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Affiliation(s)
- De-Xin Cheng
- Cancer Center, Department of Interventional Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou 310014, Zhejiang Province, China
| | - Kang-Di Xu
- General Surgery, Cancer Center, Department of Vascular Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou 310014, Zhejiang Province, China
| | - Han-Bo Liu
- Cancer Center, Department of Interventional Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou 310014, Zhejiang Province, China
| | - Yi Liu
- General Surgery, Cancer Center, Department of Vascular Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou 310014, Zhejiang Province, China
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19
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Numata K, Ono Y, Ju M, Onuma S, Tanaka A, Kawabe T, Sawazaki S, Higuchi A, Yamanaka K, Hatori S, Saeki H, Matsukawa H, Rino Y, Tani K. Evaluating prognostic significance of preoperative C-reactive protein to albumin ratio in older patients with pathological stage II or III colorectal cancer. Ann Coloproctol 2024; 40:161-168. [PMID: 36217812 PMCID: PMC11082553 DOI: 10.3393/ac.2022.00367.0052] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 06/19/2022] [Accepted: 06/23/2022] [Indexed: 10/17/2022] Open
Abstract
PURPOSE This study was performed to evaluate the prognostic value of preoperative C-reactive protein to albumin ratio (CAR) in older patients with colorectal cancer (CRC) undergoing curative resection. METHODS We retrospectively analyzed 244 older patients (aged 75 years or higher) with pathological stage II or III CRC who underwent curative surgery between 2008 and 2016. The optimal value of CAR was calculated and its correlation with the clinicopathological factors and prognosis was examined. RESULTS The optimal cutoff value of the CAR was 0.085. High preoperative CAR was significantly associated with high carcinoembryonic antigen levels (P=0.001), larger tumor size (P<0.001), and pT factor (P=0.001). On multivariate analysis, high CAR was independent prognostic factor for relapse-free survival (P=0.042) and overall survival (P=0.001). CONCLUSION Preoperative elevated CAR could be considered as an adverse predictor of both relapse-free survival and overall survival in older patients with CRC undergoing curative surgery.
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Affiliation(s)
- Koji Numata
- Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan
| | - Yukari Ono
- Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan
| | - Mihwa Ju
- Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan
| | - Shizune Onuma
- Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan
| | - Ayano Tanaka
- Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan
| | - Taichi Kawabe
- Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan
| | - Sho Sawazaki
- Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan
| | - Akio Higuchi
- Department of Surgery, Yokohama Minami Kyosai Hospital, Yokohama, Japan
| | - Kazuki Yamanaka
- Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan
| | - Shinsuke Hatori
- Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan
| | - Hiroyuki Saeki
- Department of Surgery, Yokohama Minami Kyosai Hospital, Yokohama, Japan
| | - Hiroshi Matsukawa
- Department of Surgery, Yokohama Minami Kyosai Hospital, Yokohama, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Kazuyuki Tani
- Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan
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20
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Numata K, Shiozawa M, Ono Y, Iguchi K, Uchiyama M, Asari M, Rino Y, Saito A. Clinical Significance of the Post/Preoperative Anti-p53 Antibody Ratio in Predicting the Prognosis of Patients with Colorectal Cancer after Curative Surgery and Its Usefulness in Combination with Carcinoembryonic Antigen. Oncology 2024; 102:841-849. [PMID: 38382488 DOI: 10.1159/000537963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 02/07/2024] [Indexed: 02/23/2024]
Abstract
INTRODUCTION Anti-p53 antibody (p53Ab) is useful for monitoring colorectal cancer (CRC) recurrence. We retrospectively analyzed the clinical impact of p53Ab ratio (p53R) before and after surgery to predict recurrence in patients with CRC. METHODS In total, 1,223 patients with stage I-III CRC who underwent curative surgery between January 2005 and December 2019 were enrolled in this retrospective study. In patients with elevated p53Ab levels, p53R was calculated by measuring p53Ab levels within 1 month preoperatively and 3 months postoperatively. The optimal p53R level was determined, and its relationship with clinicopathological factors and prognosis was examined. We also evaluated the efficacy of the combination of p53R and preoperative carcinoembryonic antigen (CEA) values. RESULTS Overall, 341 patients (27.9%) showed elevated p53Ab levels. Preoperative p53Ab levels were significantly associated with tumor location, lymphatic invasion, and venous invasion. The p53R level was significantly higher in patients with recurrent disease. Patients with high p53R levels had significantly shorter relapse-free survival than those with low p53R levels (p < 0.001). When p53R was combined with preoperative CEA values, specificity improved to 0.97, with an accuracy of 0.88. CONCLUSION In patients with CRC and elevated preoperative p53Ab levels, p53R expression may be prognostically useful after radical resection. Furthermore, the combination of p53R and preoperative CEA levels may be useful for postoperative follow-ups.
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Affiliation(s)
- Koji Numata
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Manabu Shiozawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Yukari Ono
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Kenta Iguchi
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Mamoru Uchiyama
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Masahiro Asari
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Aya Saito
- Department of Surgery, Yokohama City University, Yokohama, Japan
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21
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Yokoi R, Tajima JY, Fukada M, Hayashi H, Kuno M, Asai R, Sato Y, Yasufuku I, Kiyama S, Tanaka Y, Murase K, Matsuhashi N. Optimizing Treatment Strategy for Oligometastases/Oligo-Recurrence of Colorectal Cancer. Cancers (Basel) 2023; 16:142. [PMID: 38201569 PMCID: PMC10777959 DOI: 10.3390/cancers16010142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 12/25/2023] [Accepted: 12/26/2023] [Indexed: 01/12/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer, and nearly half of CRC patients experience metastases. Oligometastatic CRC represents a distinct clinical state characterized by limited metastatic involvement, demonstrating a less aggressive nature and potentially improved survival with multidisciplinary treatment. However, the varied clinical scenarios giving rise to oligometastases necessitate a precise definition, considering primary tumor status and oncological factors, to optimize treatment strategies. This review delineates the concepts of oligometastatic CRC, encompassing oligo-recurrence, where the primary tumor is under control, resulting in a more favorable prognosis. A comprehensive examination of multidisciplinary treatment with local treatments and systemic therapy is provided. The overarching objective in managing oligometastatic CRC is the complete eradication of metastases, offering prospects of a cure. Essential to this management approach are local treatments, with surgical resection serving as the standard of care. Percutaneous ablation and stereotactic body radiotherapy present less invasive alternatives for lesions unsuitable for surgery, demonstrating efficacy in select cases. Perioperative systemic therapy, aiming to control micrometastatic disease and enhance local treatment effectiveness, has shown improvements in progression-free survival through clinical trials. However, the extension of overall survival remains variable. The review emphasizes the need for further prospective trials to establish a cohesive definition and an optimized treatment strategy for oligometastatic CRC.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Nobuhisa Matsuhashi
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu, Japan; (R.Y.); (K.M.)
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Petretta M, Nappi C, Cuocolo A. Editorial: Insights in PET and SPECT: 2023. FRONTIERS IN NUCLEAR MEDICINE (LAUSANNE, SWITZERLAND) 2023; 3:1342672. [PMID: 39355025 PMCID: PMC11440878 DOI: 10.3389/fnume.2023.1342672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 12/11/2023] [Indexed: 10/03/2024]
Affiliation(s)
- Mario Petretta
- Department of Nuclear Medicine, IRCCS SYNLAB SDN, Naples, Italy
| | - Carmela Nappi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Alberto Cuocolo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
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23
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Krell M, Llera B, Brown ZJ. Circulating Tumor DNA and Management of Colorectal Cancer. Cancers (Basel) 2023; 16:21. [PMID: 38201448 PMCID: PMC10778183 DOI: 10.3390/cancers16010021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 12/05/2023] [Accepted: 12/12/2023] [Indexed: 01/12/2024] Open
Abstract
Although the incidence of colorectal cancer (CRC) has decreased as a result of increased screening and awareness, it still remains a major cause of cancer-related death. Additionally, early detection of CRC recurrence by conventional means such as CT, endoscopy, and CEA has not translated into an improvement in survival. Liquid biopsies, such as the detection circulating tumor DNA (ctDNA), have been investigated as a biomarker for patients with CRC in terms of prognosis and recurrence, as well as their use to guide therapy. In this manuscript, we provide an overview of ctDNA as well as its utility in providing prognostic information, using it to guide therapy, and monitoring for recurrence in patients with CRC. In addition, we discuss the influence the site of disease may have on the ability to detect ctDNA in patients with metastatic CRC.
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Affiliation(s)
| | | | - Zachary J. Brown
- Department of Surgery, Division of Surgical Oncology, NYU Langone Health, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (M.K.); (B.L.)
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24
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Simmons K, Thomas JV, Ludford K, Willis JA, Higbie VS, Raghav KP, Johnson B, Dasari A, Kee BK, Parseghian CM, Lee MS, Le PH, Morelli MP, Shen JP, Bent A, Vilar E, Wolff RA, Kopetz S, Overman MJ, Morris VK. Sustained Disease Control in Immune Checkpoint Blockade Responders with Microsatellite Instability-high Colorectal Cancer after Treatment Termination. CANCER RESEARCH COMMUNICATIONS 2023; 3:2510-2517. [PMID: 38085001 PMCID: PMC10712284 DOI: 10.1158/2767-9764.crc-23-0340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/11/2023] [Accepted: 11/07/2023] [Indexed: 12/18/2023]
Abstract
Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas - MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed. Median progression-free and overall survival were estimated. Associations between the event of recurrence and coexisting mutations (KRAS/NRAS, BRAFV600E), metastatic organ involvement (lung, liver, lymph node, or peritoneum), metastatic timing (synchronous vs. metachronous), prior immunotherapy [anti-PD-(L)1 alone or in combination with anti-CTLA antibodies], etiology of MSI status (sporadic vs. hereditary non-polyposis colorectal cancer), and duration of immunotherapy were assessed. Sixty-four patients with MSI-H colorectal cancer without progression on immunotherapy were reviewed. Of these 48 and 16 received anti-PD(L)1 antibody alone or in combination with anti-CTLA-4 antibody, respectively. Median exposure to immunotherapy was 17.6 months (range, 1.3-51.9). After a median follow-up of 22.6 months (range, 0.3-71.7) after stopping immunotherapy, 56 of 64 patients (88%) remained without disease progression. Lung metastases were associated with recurrence/progression (OR, 6.1; P = 0.04), but coexisting mutation, primary tumor sidedness, and immunotherapy were not. These data provide a retrospective, single-institution analysis that showed that most patients with advanced MSI-H colorectal cancer do not recur after treatment cessation, regardless of the reason for stopping treatment or a variety of patient and disease features, supporting an optimistic prognosis of sustained disease control. SIGNIFICANCE Outcomes for patients with MSI-H colorectal cancer stopping immunotherapy after disease control remain unknown. Sixty-four patients with MSI-H colorectal cancer from our institution stopping treatment for sustained benefit or toxicity were retrospectively assessed. After median follow up of 22 months and median immunotherapy exposure of 18 months, 88% patients remained without progression. All patients who recurred or progressed and were rechallenged with immunotherapy have continued to experience disease control.
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Affiliation(s)
- Kristen Simmons
- Department of Hematology/Oncology, Baylor College of Medicine, Houston, Texas
| | - Jane V. Thomas
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Kaysia Ludford
- Department of General Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Jason A. Willis
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Victoria S. Higbie
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Kanwal P.S. Raghav
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Benny Johnson
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Arvind Dasari
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Bryan K. Kee
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Christine M. Parseghian
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Michael S. Lee
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Phat H. Le
- Department of General Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Maria P. Morelli
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - John Paul Shen
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Alisha Bent
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Eduardo Vilar
- Clinical Cancer Prevention, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Robert A. Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Michael J. Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
| | - Van Karlyle Morris
- Department of Gastrointestinal Medical Oncology, The University of Texas – MD Anderson Cancer Center, Houston, Texas
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Tsai HL, Huang CW, Chen YC, Su WC, Chang TK, Chen PJ, Li CC, Chang YT, Wang JY. Real-World Outcomes of First-Line FOLFIRI Plus Bevacizumab with Irinotecan Dose Escalation versus FOLFOXIRI Plus Bevacizumab in BRAFV600E-Mutant Metastatic Colorectal Cancer: The Preliminary Data from a Single-Center Observational Study. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:2108. [PMID: 38138211 PMCID: PMC10745094 DOI: 10.3390/medicina59122108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Revised: 11/17/2023] [Accepted: 11/21/2023] [Indexed: 12/24/2023]
Abstract
Background and Objectives: Approximately 5-10% of all patients with metastatic colorectal cancer (mCRC) harbor a BRAFV600E mutation. These patients exhibit distinct metastatic patterns, poor prognosis, and heterogenous survival outcomes. The findings from the TRIBE study indicated that the administration of FOLFOXIRI plus bevacizumab as first-line treatment extended the median duration of overall survival (OS). In this study, we explored the effects of UGT1A1 polymorphism on the outcomes of irinotecan dose escalation versus FOLFOXIRI plus bevacizumab in patients with BRAFV600E-mutant mCRC. Materials and Methods: We retrospectively reviewed the medical records of 25 patients who had received a diagnosis of BRAFV600E-mutant mCRC between October 2015 and August 2022. All patients underwent UGT1A1 genotyping before receiving bevacizumab plus FOLFIRI. The primary end point was progression-free survival (PFS), and secondary endpoints were OS and adverse events (AEs). The two treatment arms were compared in terms of 6-month PFS and 12-month OS. Results: Over a median follow-up duration of 15.0 (interquartile range, 10.0-30.5) months, no significant differences were noted between the treatment arms in severe AEs (SAEs), 6-month PFS, or 12-month OS (all p < 0.05). Regarding AEs, the FOLFIRI plus bevacizumab regimen was associated with a lower incidence of anorexia than was the FOLFOXIRI plus bevacizumab regimen (p = 0.042). Conclusions: Our findings indicate that FOLFIRI plus bevacizumab with irinotecan dose escalation is an effective first-line treatment regimen for patients with BRAFV600E-mutant mCRC. This regimen leads to acceptable clinical outcomes with manageable AEs. However, the effects on survival and safety outcomes could only be speculated, and further studies are needed because of the sample size, the follow-up for the OS evaluation, and the non-uniformity in all the variables considered in the two groups.
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Affiliation(s)
- Hsiang-Lin Tsai
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (H.-L.T.); (C.-W.H.); (Y.-C.C.); (W.-C.S.); (T.-K.C.); (P.-J.C.); (C.-C.L.); (Y.-T.C.)
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ching-Wen Huang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (H.-L.T.); (C.-W.H.); (Y.-C.C.); (W.-C.S.); (T.-K.C.); (P.-J.C.); (C.-C.L.); (Y.-T.C.)
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Yen-Cheng Chen
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (H.-L.T.); (C.-W.H.); (Y.-C.C.); (W.-C.S.); (T.-K.C.); (P.-J.C.); (C.-C.L.); (Y.-T.C.)
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Wei-Chih Su
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (H.-L.T.); (C.-W.H.); (Y.-C.C.); (W.-C.S.); (T.-K.C.); (P.-J.C.); (C.-C.L.); (Y.-T.C.)
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Surgery, Faculty of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Tsung-Kun Chang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (H.-L.T.); (C.-W.H.); (Y.-C.C.); (W.-C.S.); (T.-K.C.); (P.-J.C.); (C.-C.L.); (Y.-T.C.)
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Surgery, Faculty of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Po-Jung Chen
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (H.-L.T.); (C.-W.H.); (Y.-C.C.); (W.-C.S.); (T.-K.C.); (P.-J.C.); (C.-C.L.); (Y.-T.C.)
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ching-Chun Li
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (H.-L.T.); (C.-W.H.); (Y.-C.C.); (W.-C.S.); (T.-K.C.); (P.-J.C.); (C.-C.L.); (Y.-T.C.)
| | - Yu-Tang Chang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (H.-L.T.); (C.-W.H.); (Y.-C.C.); (W.-C.S.); (T.-K.C.); (P.-J.C.); (C.-C.L.); (Y.-T.C.)
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Division of Pediatric Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Jaw-Yuan Wang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (H.-L.T.); (C.-W.H.); (Y.-C.C.); (W.-C.S.); (T.-K.C.); (P.-J.C.); (C.-C.L.); (Y.-T.C.)
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Qu W, Sun Y, Zhang W, Jiang Z, Han Y, Jin J, Xue Q, Zhou A. Less aggressive treatment for less aggressive disease? A retrospective single-center study of pulmonary-limited metastases associated with colorectal cancer. Asia Pac J Clin Oncol 2023; 19:664-671. [PMID: 36693818 DOI: 10.1111/ajco.13918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 12/11/2022] [Accepted: 12/26/2022] [Indexed: 01/26/2023]
Abstract
OBJECTIVE To explore the appropriate treatment strategies, clinical outcomes, and prognostic factors of patients with pulmonary-limited metastases derived from colorectal cancer (CRC), usually manifested as a less aggressive course. METHODS A retrospective review was conducted in 331 CRC patients diagnosed with pulmonary-limited metastases at a single institution between January 2011 and November 2017. The Kaplan-Meier method was used to calculate the overall survival (OS). Further analysis was conducted according to treatment modalities. Univariate and multivariate analyses were used to determine potential prognostic factors influencing OS. RESULTS With a median follow-up time of 38.6 months, the median OS in all patients was 45.2 months. A total of 163 patients received intensive local treatment with a median OS of 76.4 months, whereas 168 patients received palliative systemic treatment with a median OS of 29.7 months. The median OS was 68.9 months for patients treated with radiotherapy/radiofrequency ablation, with similar efficacy compared to surgery group, whose OS had not reached yet. No survival benefits were observed from the additional targeted therapy in systemic treatment group. The prognostic analysis demonstrated unilateral/bilateral lesions, synchronous/metachronous metastases, intensive local treatment, and resection of primary lesion that were significantly associated with survival of patients. CONCLUSIONS Intensive local treatment alone for pulmonary lesions was associated with excellent survival in certain patients with CRC presented with metastases confined to lungs. Doublet systemic chemotherapy as the first-line treatment also revealed satisfied efficacy and safety.
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Affiliation(s)
- Wang Qu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongkun Sun
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhichao Jiang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yue Han
- Department of Interventional Radiography, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jing Jin
- Department of Radiotherapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qi Xue
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Aiping Zhou
- Department of Medical Oncology, 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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27
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Horkaew P, Chansangrat J, Keeratibharat N, Le DC. Recent advances in computerized imaging and its vital roles in liver disease diagnosis, preoperative planning, and interventional liver surgery: A review. World J Gastrointest Surg 2023; 15:2382-2397. [PMID: 38111769 PMCID: PMC10725533 DOI: 10.4240/wjgs.v15.i11.2382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 08/30/2023] [Accepted: 09/27/2023] [Indexed: 11/26/2023] Open
Abstract
The earliest and most accurate detection of the pathological manifestations of hepatic diseases ensures effective treatments and thus positive prognostic outcomes. In clinical settings, screening and determining the extent of a pathology are prominent factors in preparing remedial agents and administering appropriate therapeutic procedures. Moreover, in a patient undergoing liver resection, a realistic preoperative simulation of the subject-specific anatomy and physiology also plays a vital part in conducting initial assessments, making surgical decisions during the procedure, and anticipating postoperative results. Conventionally, various medical imaging modalities, e.g., computed tomography, magnetic resonance imaging, and positron emission tomography, have been employed to assist in these tasks. In fact, several standardized procedures, such as lesion detection and liver segmentation, are also incorporated into prominent commercial software packages. Thus far, most integrated software as a medical device typically involves tedious interactions from the physician, such as manual delineation and empirical adjustments, as per a given patient. With the rapid progress in digital health approaches, especially medical image analysis, a wide range of computer algorithms have been proposed to facilitate those procedures. They include pattern recognition of a liver, its periphery, and lesion, as well as pre- and postoperative simulations. Prior to clinical adoption, however, software must conform to regulatory requirements set by the governing agency, for instance, valid clinical association and analytical and clinical validation. Therefore, this paper provides a detailed account and discussion of the state-of-the-art methods for liver image analyses, visualization, and simulation in the literature. Emphasis is placed upon their concepts, algorithmic classifications, merits, limitations, clinical considerations, and future research trends.
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Affiliation(s)
- Paramate Horkaew
- School of Computer Engineering, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand
| | - Jirapa Chansangrat
- School of Radiology, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand
| | - Nattawut Keeratibharat
- School of Surgery, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand
| | - Doan Cong Le
- Faculty of Information Technology, An Giang University, Vietnam National University (Ho Chi Minh City), An Giang 90000, Vietnam
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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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29
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Tsai HL, Lin CC, Sung YC, Chen SH, Chen LT, Jiang JK, Wang JY. The emergence of RAS mutations in patients with RAS wild-type mCRC receiving cetuximab as first-line treatment: a noninterventional, uncontrolled multicenter study. Br J Cancer 2023; 129:947-955. [PMID: 37488448 PMCID: PMC10491612 DOI: 10.1038/s41416-023-02366-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 06/30/2023] [Accepted: 07/11/2023] [Indexed: 07/26/2023] Open
Abstract
ABSRTACT BACKGROUND: Patients treated with anti-epidermal growth factor receptor (anti-EGFR) will ultimately develop acquired resistance promoted by clonal selection, mainly the emergence of mutations in the MAPK pathway (mostly RAS mutations). Baseline assessment of RAS mutations in the blood of patients correlates well with RAS tumour tissue testing and is currently an alternative option in routine clinical practice to guide first-line therapy. The aim of this study was the prevalence of acquired genomic alterations detected in the auxiliary tool of ctDNA testing and investigated the role of RAS ctDNA status for detecting tumour response and predicting benefit to anti-EGFR therapy. METHODS Only patients with concordant wild-type formalin-fixed, paraffin-embedded (FFPE) tumour tissue and baseline ctDNA RAS wild-type were included. RAS mutations in plasma were evaluated using MassARRAY platform. Blood samples were collected at baseline, every 3 months during first-line treatment, and at disease progression. The primary endpoint was the detection rate of RAS mutations during cetuximab treatment. The correlation between response and survival outcomes and the emergence of circulating RAS mutations was also analysed. RESULTS The detection rate of RAS mutations during treatment was 9.3% (10/108). RAS mutations detection occurred a median of 3 months prior to radiologic documentation. The subgroup of patients with RAS mutations exhibited significantly inferior progression-free survival and overall survival (P = 0.002 and 0.027, respectively) but the baseline characteristics, response rates, disease control rates, and metastatectomy were not significant (all P > 0.05). CONCLUSIONS We demonstrated that RAS ctDNA status might be a valuable biomarker for detecting early tumour response and predicting benefit to anti-EGFR therapy. CLINICAL TRIAL REGISTRATION NCT03401957 (January 17, 2018).
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Affiliation(s)
- Hsiang-Lin Tsai
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chun-Chi Lin
- Division of Colorectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yung-Chung Sung
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
- Division of Hematology/Oncology, Internal Medicine, Cathay General Hospital, Taipei, Taiwan
| | - Shang-Hung Chen
- Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- Division of Medical Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jeng-Kai Jiang
- Division of Colorectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Jaw-Yuan Wang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan.
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Keogh C, O’Sullivan NJ, Temperley HC, Flood MP, Ting P, Walsh C, Waters P, Ryan ÉJ, Conneely JB, Edmundson A, Larkin JO, McCormick JJ, Mehigan BJ, Taylor D, Warrier S, McCormick PH, Soucisse ML, Harris CA, Heriot AG, Kelly ME. Redo Pelvic Surgery and Combined Metastectomy for Locally Recurrent Rectal Cancer with Known Oligometastatic Disease: A Multicentre Review. Cancers (Basel) 2023; 15:4469. [PMID: 37760439 PMCID: PMC10527388 DOI: 10.3390/cancers15184469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/29/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023] Open
Abstract
INTRODUCTION Historically, surgical resection for patients with locally recurrent rectal cancer (LRRC) had been reserved for those without metastatic disease. 'Selective' patients with limited oligometastatic disease (OMD) (involving the liver and/or lung) are now increasingly being considered for resection, with favourable five-year survival rates. METHODS A retrospective analysis of consecutive patients undergoing multi-visceral pelvic resection of LRRC with their oligometastatic disease between 1 January 2015 and 31 August 2021 across four centres worldwide was performed. The data collected included disease characteristics, neoadjuvant therapy details, perioperative and oncological outcomes. RESULTS Fourteen participants with a mean age of 59 years were included. There was a female preponderance (n = 9). Nine patients had liver metastases, four had lung metastases and one had both lung and liver disease. The mean number of metastatic tumours was 1.5 +/- 0.85. R0 margins were obtained in 71.4% (n = 10) and 100% (n = 14) of pelvic exenteration and oligometastatic disease surgeries, respectively. Mean lymph node yield was 11.6 +/- 6.9 nodes, with positive nodes being found in 28.6% (n = 4) of cases. A single major morbidity was reported, with no perioperative deaths. At follow-up, the median disease-free survival and overall survival were 12.3 months (IQR 4.5-17.5 months) and 25.9 months (IQR 6.2-39.7 months), respectively. CONCLUSIONS Performing radical multi-visceral surgery for LRRC and distant oligometastatic disease appears to be feasible in appropriately selected patients that underwent good perioperative counselling.
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Affiliation(s)
- Cian Keogh
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
- Department of Surgery, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
- School of Medicine, University of Queensland, Brisbane 4072, Australia
| | - Niall J. O’Sullivan
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - Hugo C. Temperley
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - Michael P. Flood
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
| | - Pascallina Ting
- Department of Surgery, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
| | - Camille Walsh
- Department of Surgery, Hôpital Maisonneuve-Rosemont, Montreal, QC H1T 2M4, Canada
| | - Peadar Waters
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
| | - Éanna J. Ryan
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - John B. Conneely
- Department of Surgery, Mater Misericordiae University Hospital, D07 R2WY Dublin, Ireland
| | - Aleksandra Edmundson
- Department of Surgery, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
| | - John O. Larkin
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - Jacob J. McCormick
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
| | - Brian J. Mehigan
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - David Taylor
- Department of Surgery, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
| | - Satish Warrier
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
| | - Paul H. McCormick
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
| | - Mikael L. Soucisse
- Department of Surgery, Hôpital Maisonneuve-Rosemont, Montreal, QC H1T 2M4, Canada
| | - Craig A. Harris
- Department of Surgery, Royal Brisbane and Women’s Hospital, Brisbane 4029, Australia
| | - Alexander G. Heriot
- Department of Surgery, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
| | - Michael E. Kelly
- Department of Surgery, St. James’s Hospital, School of Medicine, Trinity College Dublin, D02 R590 Dublin, Ireland
- Trinity St. James Cancer Institute, D08 W9RT Dublin, Ireland
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Gao J, Zhuang L, He C, Xu X, Zhu Z, Chen W. Risk and prognostic factors in patients with colon cancer with liver metastasis. J Int Med Res 2023; 51:3000605231191580. [PMID: 37737100 PMCID: PMC10517611 DOI: 10.1177/03000605231191580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 07/11/2023] [Indexed: 09/23/2023] Open
Abstract
OBJECTIVE The most common site of metastasis in patients with colon cancer is the liver. This study aimed to identify patients with colon cancer at high risk of developing liver metastasis and to explore their prognosis. METHODS The clinical characteristics, treatment methods and survival outcomes of patients diagnosed with colon cancer from 2010 to 2015 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Patients were divided into two groups according to the presence of liver metastasis, and multivariate logistic and Cox regression models were used to identify risk and prognostic factors. RESULTS A total of 60,018 patients with colon cancer were selected from the SEER database. The incidence of liver metastasis was 9.2%. African American ethnicity, poor differentiation, higher tumor stage, higher lymph node ratio, and lung metastases were common factors associated with both liver metastasis risk and prognosis. CONCLUSIONS Metastasectomy might improve survival among patients with colon cancer with resectable liver metastasis lesions and no other organ involvement.
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Affiliation(s)
- Jiawei Gao
- Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Linjun Zhuang
- Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Chenxin He
- Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Xiangrong Xu
- Department of General Surgery, The First People's Hospital of Kunshan, Suzhou, P.R. China
| | - Zhaobi Zhu
- Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Wei Chen
- Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, P.R. China
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Huang Z, Kaller M, Hermeking H. CRISPR/Cas9-mediated inactivation of miR-34a and miR-34b/c in HCT116 colorectal cancer cells: comprehensive characterization after exposure to 5-FU reveals EMT and autophagy as key processes regulated by miR-34. Cell Death Differ 2023; 30:2017-2034. [PMID: 37488217 PMCID: PMC10406948 DOI: 10.1038/s41418-023-01193-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 07/06/2023] [Accepted: 07/12/2023] [Indexed: 07/26/2023] Open
Abstract
The miR-34a and miR-34b/c encoding genes represent direct targets of the p53 transcription factor, and presumably mediate part of the tumor suppressive effects of p53. Here, we sought to determine their functional relevance by inactivating miR-34a and/or miR-34b/c using a CRISPR/Cas9 approach in the colorectal cancer (CRC) cell line HCT116. Concomitant deletion of miR-34a and miR-34b/c resulted in significantly reduced suppression of proliferation after p53 activation, enhanced migration, invasion and EMT, as well as reduced sensitivity to chemotherapeutics, increased stress-induced autophagic flux, decreased apoptosis and upregulation of autophagy-related genes after 5-FU treatment. However, inactivation of singular miR-34a or miR-34b/c had little effects on the aforementioned processes. RNA-Seq analysis revealed that concomitant deletion of miR-34a/b/c caused EMT signature enrichment, impaired gene repression by the p53-DREAM pathway and elevated autophagy after 5-FU treatment. A gene signature comprised of mRNAs significantly upregulated after combined inactivation of miR-34a and miR-34b/c showed a significant association with the invasive colon cancer subtype CMS4 and poor overall survival in two CRC patient cohorts, and with 5-FU resistance in CRC cell lines. In miR-34a/b/c-deficient cells the upregulated miR-34 target FOXM1 directly induced p62 and ATG9A, which increased autophagy and consequently attenuated apoptosis and rendered the miR-34a/b/c-KO cells more resistant to 5-FU. Inhibition of autophagy by depletion of ATG9A or chloroquine re-sensitized miR-34a/b/c-deficient HCT116 cells to 5-FU. In summary, our findings show a complementary role of miR-34a and miR-34b/c in the regulation of EMT and autophagy which may be relevant for CRC therapy in the future.
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Affiliation(s)
- Zekai Huang
- Experimental and Molecular Pathology, Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Thalkirchner Str. 36, D-80337, Munich, Germany
| | - Markus Kaller
- Experimental and Molecular Pathology, Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Thalkirchner Str. 36, D-80337, Munich, Germany
| | - Heiko Hermeking
- Experimental and Molecular Pathology, Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Thalkirchner Str. 36, D-80337, Munich, Germany.
- German Cancer Consortium (DKTK), Partner Site Munich, D-80336, Munich, Germany.
- German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.
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Lin Z, Zheng Y, Yang J, Jin W, Wang J, Wang W, Li S. Prognostic Analysis of Lymphovascular Invasion in Stages I-III Colorectal Cancer: A Retrospective Study Based on Propensity Score Match. Am J Clin Oncol 2023; 46:366-373. [PMID: 37219364 DOI: 10.1097/coc.0000000000001015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
INTRODUCTION Lymphovascular invasion (LVI) is a micropathological tumor factor believed to increase the risk of tumor metastasis and spread. Propensity score matching (PSM) is a statistical method that can control confounding factors. Current research rarely considers the confounding relationship between LVI and other factors that may influence prognosis. This study aimed to investigate the relationship between LVI and prognosis in patients with stage I-III colorectal cancer (CRC) by using propensity score matching (PSM). METHODS This was a retrospective study involving 610 patients. PSM was used to adjust for baseline differences between the groups. The survival rates were calculated. A nomogram was constructed based on the Cox proportional hazards model before matching. The C-index, receiver operating characteristic curve (ROC), and calibration curve were used to evaluate the nomogram. RESULTS A total of 150 patients tested positive for LVI, accounting for 24.6% of the total, and 120 couples of patients were identified after PSM. The survival curve and Cox proportional hazards model after matching confirmed the adverse effects of LVI on tumor prognosis. The Cox proportional hazards model before matching showed that age, carcinoembryonic antigen level, T stage, N stage, histologic grade and LVI were independent prognostic factors. The C-index of the nomogram established based on the Cox proportional hazards model was 0.787 (95% CI=0.728-0.845). The areas under the curve were 0.796 in the 3-year ROC. CONCLUSIONS LVI is an adverse prognostic factor in patients with stage I-III colorectal cancer.
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Affiliation(s)
- Zhuoqun Lin
- Department of Colorectal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
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Shannon AH, Ruff SM, Schenk AD, Washburn K, Pawlik TM. Updates and Expert Opinions on Liver Transplantation for Gastrointestinal Malignancies. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1290. [PMID: 37512101 PMCID: PMC10383519 DOI: 10.3390/medicina59071290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/12/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023]
Abstract
Transplant oncology is a relatively new field in which transplantation is used to treat patients who would otherwise be unresectable. New anticancer treatment paradigms using tumor and transplant immunology and cancer immunogenomics are emerging. In turn, liver transplantation (LT) has become a potential therapy for certain patients with colorectal cancer (CRC) with liver metastasis, hepatocellular (HCC), cholangiocarcinoma (CCA), and metastatic neuroendocrine tumor (NET) of the liver. Although there are established criteria for LT in HCC, evidence regarding LT as a treatment modality for certain gastrointestinal malignancies is still debated. The aim of this review is to highlight updates in the role of LT for certain malignancies, including HCC, metastatic CRC, hilar CCA, and neuroendocrine tumor (NET), as well as contextualize LT use and discuss controversies in transplant oncology.
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Selvaggi F, Catalano T, Lattanzio R, Cotellese R, Aceto GM. Wingless/It/β-catenin signaling in liver metastasis from colorectal cancer: A focus on biological mechanisms and therapeutic opportunities. World J Gastroenterol 2023; 29:2764-2783. [PMID: 37274070 PMCID: PMC10237106 DOI: 10.3748/wjg.v29.i18.2764] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/28/2023] [Accepted: 04/17/2023] [Indexed: 05/11/2023] Open
Abstract
The liver is the most common site of metastases in patients with colorectal cancer. Colorectal liver metastases (CRLMs) are the result of molecular mechanisms that involve different cells of the liver microenvironment. The aberrant activation of Wingless/It (Wnt)/β-catenin signals downstream of Wnt ligands initially drives the oncogenic transformation of the colon epithelium, but also the progression of metastatization through the epithelial-mesenchymal transition/mesenchymal-epithelial transition interactions. In liver microenvironment, metastatic cells can also survive and adapt through dormancy, which makes them less susceptible to pro-apoptotic signals and therapies. Treatment of CRLMs is challenging due to its variability and heterogeneity. Advances in surgery and oncology have been made in the last decade and a pivotal role for Wnt/β-catenin pathway has been re-cognized in chemoresistance. At the state of art, there is a lack of clear understanding of why and how this occurs and thus where exactly the opportunities for developing anti-CRLMs therapies may lie. In this review, current knowledge on the involvement of Wnt signaling in the development of CRLMs was considered. In addition, an overview of useful biomarkers with a revision of surgical and non-surgical therapies currently accepted in the clinical practice for colorectal liver metastasis patients were provided.
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Affiliation(s)
- Federico Selvaggi
- Department of Surgical, ASL2 Lanciano-Vasto-Chieti, Ospedale Clinicizzato SS Annunziata of Chieti, Chieti 66100, Italy
| | - Teresa Catalano
- Department of Clinical and Experimental Medicine, University of Messina, Messina 98125, Italy
| | - Rossano Lattanzio
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, Chieti 66100, Italy
| | - Roberto Cotellese
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Chieti 66100, Italy
- Villa Serena Foundation for Research, Villa Serena - Del Dott. L. Petruzzi, Città Sant’Angelo 65013, Pescara, Italy
| | - Gitana Maria Aceto
- Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, Chieti 66100, Italy
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Impact of neoadjuvant chemotherapy on post-hepatectomy regeneration for patients with colorectal cancer liver metastasis - Systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:533-541. [PMID: 36631347 DOI: 10.1016/j.ejso.2022.12.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 12/18/2022] [Accepted: 12/30/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND Today, there is still debate on the impact of neoadjuvant chemotherapy (NeoChem) on liver regeneration (LivReg). The objectives of this study were to assess the impact of NeoChem and its characteristics (addition of bevacizumab, number of cycles and time from end of NeoChem) on post-hepatectomy LivReg. MATERIAL & METHODS Studies reporting LivReg in patients submitted to liver resection were included. Pubmed, Scopus, Web of Science, Embase, and Cochrane databases were searched. Only studies comparing NeoChem vs no chemotherapy or comparing chemotherapy characteristics from 1990 to present were included. Two researchers individually screened the identified records registered in a predesigned database. Primary outcome was future liver remnant regeneration rate (FLR3). Bias of the studies was evaluated with the ROBINS-I tool, and quality of evidence with the GRADE system. Data was presented as mean difference or standard mean difference. RESULTS Eight studies with a total of 681 patients were selected. Seven were retrospective and one prospective comparative cohort studies. In patients submitted to major hepatectomy, NeoChem did not have an impact on LivReg (MD 3.12, 95% CI -2,12-8.36, p 0,24). Adding bevacizumab to standard NeoChem was associated with better FLR3 (SMD 0.45, 95% CI 0.19-0.71, p 0.0006). DISCUSSION The main drawback of this review is the retrospective nature of the available studies. NeoChem does not have a negative impact on postoperative LivReg in patients submitted to liver resection. Regimens with bevacizumab seem to be associated with better postoperative LivReg rates when compared to standard NeoChem.
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Kim HR, Kim SH, Nam KH. Association between Dynamic Contrast-Enhanced MRI Parameters and Prognostic Factors in Patients with Primary Rectal Cancer. Curr Oncol 2023; 30:2543-2554. [PMID: 36826155 PMCID: PMC9955503 DOI: 10.3390/curroncol30020194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/09/2023] [Accepted: 02/18/2023] [Indexed: 02/22/2023] Open
Abstract
BACKGROUND To evaluate the association between perfusion parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with prognostic factors in primary rectal cancer patients. METHODS A sample of 51 patients with pathologically proven rectal adenocarcinoma through surgery were retrospectively enrolled. All the patients underwent preoperative DCE-MRI including 3D-spoiled gradient echo. Two radiologists determined the tumor border after radiologic-pathologic correlation and drew regions of interest. The perfusion parameters, including the volume transfer constant (Ktrans), were calculated under the extended Toft model. The prognostic factors included TN stage, circumferential resection margin, extramural venous invasion, Kirsten-ras mutation, tumor size, carcinoembryonic antigen, and tumor differentiation. The association was assessed via correlation or t-test. For significant prognostic factors, receiver operating characteristic (ROC) curve analyses were performed to estimate the diagnostic predictive values. RESULTS Ktrans only showed a significant difference according to tumor differentiation, between the well-differentiated (n = 6) and moderately differentiated (n = 45) groups (0.127 ± 0.032, 0.084 ± 0.036, p = 0.036). The AUC was 0.838 (95% CI, 0.702-0.929), and the estimated accuracy, sensitivity, and specificity were 87%, 90%, and 60%, respectively. CONCLUSIONS Ktrans showed a significant difference based on tumor differentiation, which may be conducive to prediction of prognosis in primary rectal cancer.
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Affiliation(s)
- Hye Ri Kim
- Department of Radiology, Inje University College of Medicine, Haeundae Paik Hospital, Busan 48108, Republic of Korea
| | - Seung Ho Kim
- Department of Radiology, Inje University College of Medicine, Haeundae Paik Hospital, Busan 48108, Republic of Korea
- Correspondence: ; Tel.: +82-51-797-0382
| | - Kyung Han Nam
- Department of Pathology, Inje University College of Medicine, Haeundae Paik Hospital, Busan 48108, Republic of Korea
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Miao Z, Zhao X, Li X. [18F]FDG PET/CT versus [18F]FDG PET/MRI for the diagnosis of colorectal liver metastasis: A systematic review and meta-analysis. Front Oncol 2023; 13:1114059. [PMID: 36860315 PMCID: PMC9969139 DOI: 10.3389/fonc.2023.1114059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 01/31/2023] [Indexed: 02/16/2023] Open
Abstract
Purpose The purpose of our meta-analysis and systematic review was to compare the diagnostic performance of [18F]FDG PET/CT and [18F]FDG PET/MRI in colorectal liver metastasis. Methods We searched PubMed, Embase, and Web of Science for eligible articles until November 2022. Studies focusing on the diagnostic value of [18F]FDG PET/CT or PET/MRI for colorectal liver metastasis were included. Using a bivariate random-effect model, the pooled sensitivity and specificity for [18F]FDG PET/CT and [18F]FDG PET/MRI were reported as estimates with 95% confidence intervals (CIs). Heterogeneity among pooled studies was assessed using the I2 statistic. The Quality Assessment of Diagnostic Performance Studies (QUADAS-2) method was used to evaluate the quality of the studies that were included. Results There were a total of 2743 publications identified in the initial search, finally, a total of 21 studies comprising 1036 patients were included. The pooled sensitivity, specificity, and AUC of [18F]FDG PET/CT in were 0.86 (95% CI: 0.76-0.92), 0.89 (95% CI: 0.83-0.94), and 0.92(95% CI: 0.90-0.94). [18F]FDG PET/MRI were 0.84 (95% CI: 0.77-0.89), 1.00 (95% CI: 0.32-1.00), and 0.89(95% CI: 0.86-0.92), respectively. Conclusion [18F]FDG PET/CT shows similar performance compared to [18F]FDG PET/MRI in detecting colorectal liver metastasis. However, pathological results were not obtained for all patients in the included studies and PET/MRI results were derived from studies with small sample sizes. There is a need for additional, larger prospective studies on this issue. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier (CRD42023390949).
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Affiliation(s)
- Zhi Miao
- Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, China,School of Chemical Engineering and Technology, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, China,*Correspondence: Zhi Miao,
| | - Xiaomeng Zhao
- Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, China,School of Chemical Engineering and Technology, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, China
| | - Xuanwen Li
- Graduate School of Health Science, Suzuka University of Medical Science, Suzuka, Japan
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Zhang C, Wang XY, Zuo JL, Wang XF, Feng XW, Zhang B, Li YT, Yi CH, Zhang P, Ma XC, Chen ZM, Ma Y, Han JH, Tao BR, Zhang R, Wang TQ, Tong L, Gu W, Wang SY, Zheng XF, Yuan WK, Kan ZJ, Fan J, Hu XY, Li J, Zhang C, Chen JH. Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases. J Immunother Cancer 2023; 11:jitc-2022-006425. [PMID: 36759015 PMCID: PMC9923349 DOI: 10.1136/jitc-2022-006425] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2023] [Indexed: 02/11/2023] Open
Abstract
BACKGROUND Tertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM). METHODS 603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients. RESULTS T score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p=0.029, p=0.047 and p=0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts. CONCLUSIONS The distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.
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Affiliation(s)
- Chong Zhang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Xiang-Yu Wang
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
| | - Jie-Liang Zuo
- Department of General Surgery, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China
| | - Xue-Fu Wang
- School of Pharmacy, Anhui Medical University, Hefei, China,Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, China
| | - Xiao-Wen Feng
- School of Pharmacy, Anhui Medical University, Hefei, China,Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, China
| | - Bo Zhang
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
| | - Yi-Tong Li
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
| | - Chen-He Yi
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
| | - Peng Zhang
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
| | - Xiao-Chen Ma
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
| | - Zhen-Mei Chen
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
| | - Yue Ma
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
| | - Jia-Hao Han
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
| | - Bao-Rui Tao
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
| | - Rui Zhang
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
| | - Tian-Qi Wang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Li Tong
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Wang Gu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Si-Yu Wang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Xiao-Fei Zheng
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Wen-Kang Yuan
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Zi-Jie Kan
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Jie Fan
- Department of Pathology, Huashan Hospital Fudan University, Shanghai, China
| | - Xiang-Yang Hu
- Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Jun Li
- Department of General Surgery, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China
| | - Chao Zhang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Jin-Hong Chen
- Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China
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Oncotherapeutic Strategies in Early Onset Colorectal Cancer. Cancers (Basel) 2023; 15:cancers15020552. [PMID: 36672501 PMCID: PMC9856676 DOI: 10.3390/cancers15020552] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/09/2023] [Accepted: 01/10/2023] [Indexed: 01/18/2023] Open
Abstract
Early onset colorectal cancer (EOCRC), defined as colorectal cancers in patients aged less than 50 years, is becoming an increasingly common issue, globally. Since 1994, the incidence of this condition has been rising by 2% annually. Approximately one in five patients under 50 years of age diagnosed with colorectal cancer have an underlying genetic predisposition syndrome. The detection of cancer among the other 80% of patients poses a considerable task, as there is no family history to advocate for commencing early screening in this group. Patients with EOCRC have distinct social, spiritual, fertility, and financial needs from their older counterparts that need to be addressed. This review discusses the risk factors associated with the development of EOCRC and current best practice for the management of this disease.
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The Impact of Molecular Biology in the Seeding, Treatment Choices and Follow-Up of Colorectal Cancer Liver Metastases-A Narrative Review. Int J Mol Sci 2023; 24:ijms24021127. [PMID: 36674640 PMCID: PMC9863977 DOI: 10.3390/ijms24021127] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 12/27/2022] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
There is a clear association between the molecular profile of colorectal cancer liver metastases (CRCLM) and the degree to which aggressive progression of the disease impacts patient survival. However, much of our knowledge of the molecular behaviour of colorectal cancer cells comes from experimental studies with, as yet, limited application in clinical practice. In this article, we review the current advances in the understanding of the molecular behaviour of CRCLM and present possible future therapeutic applications. This review focuses on three important steps in CRCLM development, progression and treatment: (1) the dissemination of malignant cells from primary tumours and the seeding to metastatic sites; (2) the response to modern regimens of chemotherapy; and (3) the possibility of predicting early progression and recurrence patterns by molecular analysis in liquid biopsy.
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Liu X, Ma X, Ou K, Wang Q, Gao L, Yang L. Real-World Results of Raltitrexed Combined with S-1 and Bevacizumab in Heavily Pretreated Metastatic Colorectal Cancer. Cancer Manag Res 2023; 15:277-289. [PMID: 36969545 PMCID: PMC10038009 DOI: 10.2147/cmar.s398539] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 03/14/2023] [Indexed: 03/29/2023] Open
Abstract
Purpose Treatment options for refractory metastatic colorectal cancer (CRC) are scarce. This retrospective study aimed to evaluate the efficacy and safety of raltitrexed combined with S-1 and bevacizumab in patients with heavily pretreated metastatic CRC in a clinical real-world setting. Patients and Methods Records of patients with metastatic CRC refractory to standard therapies who initiated raltitrexed plus S-1 and bevacizumab from October 2017 to December 2021 were retrospectively reviewed at our institution. The study endpoints included median overall survival (OS), overall response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs). Results Forty-four patients with metastatic CRC, who had previously undergone standard chemotherapy received the regimen comprising raltitrexed plus S-1 and bevacizumab. As of March 2022, the median follow-up was 23.2 months (95% confidence interval 15.8-30.6). The median OS and median PFS were 13.5 (95% CI 9.9-17.1) and 4.7 months (95% CI 3.6-5.8), respectively, with a 16-week PFS rate of 60.9%. Among 43 patients with measurable lesions, the ORR and DCR were 7.0% (3/43) and 65.1% (28/43), respectively. Patients without peritoneal metastases (P = 0.003, hazard ratio 0.160, 95% CI 0.048-0.531), lower carcinoembryonic antigen level (≤42.8 ng/mL) (P = 0.039, HR 0.382, 95% CI 0.153-0.952), and no previous treatment with both vascular endothelial growth factor inhibitors (VEGF) and S-1 (P = 0.020, HR 0.215, 95% CI 0.059-0.785) had better OS. The incidence of any grade of treatment-related AEs was 88.6%, most of which were mild to moderate, and no treatment-related deaths occurred. Conclusion Raltitrexed combined with S-1 and bevacizumab shows promising antitumor activity and safety and could be an alternative for patients with metastatic CRC who are refractory or intolerant to standard therapy.
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Affiliation(s)
- Xiu Liu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Xiaoting Ma
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Kai Ou
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Qi Wang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
- Department of Medical Oncology, Beijing Chaoyang District Sanhuan Cancer Hospital, Beijing, People’s Republic of China
| | - Lizhen Gao
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
- Department of Medical Oncology, Beijing Chaoyang Huanxing Cancer Hospital, Beijing, People’s Republic of China
| | - Lin Yang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
- Correspondence: Lin Yang, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiyuanninli, Beijing, 10021, People’s Republic of China, Tel +86-10-87788118, Email
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A comparison of the simultaneous, liver-first, and colorectal-first strategies for surgical treatment of synchronous colorectal liver metastases at two major liver-surgery institutions in Sweden. HPB (Oxford) 2023; 25:26-36. [PMID: 36167765 DOI: 10.1016/j.hpb.2022.09.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 05/29/2022] [Accepted: 09/04/2022] [Indexed: 01/18/2023]
Abstract
BACKGROUND The optimal treatment strategy for patients with synchronous colorectal liver metastases (CRLM) is unclear. The aim of this study was to compare the outcome of the simultaneous, liver-first, and colorectal-first surgical approaches. METHODS All consecutive patients who had been resected with curative intent for CRLM were included. A Cox regression model was constructed, and an intention-to-treat analysis was performed between the liver-first and the simultaneous approaches, after propensity score matching. RESULTS 658 patients were included in the analysis. 92 patients had a simultaneous resection, 163 patients had liver-first, and 403 patients had a colorectal-first approach. Overall survival was 54.9 months (95% CI 39.2-70.4) in the liver-first group, 54.5 months (95% CI 46.8-62.3) in colorectal-first group, and 59.6 months (95% CI 42.2-77.0) in the simultaneous group (log-rank p =0.850). In the matched cohort there were no differences in Clavien-Dindo 3a (p = 0.992) or 3b and greater (p = 0.999). Median overall survival was for liver-first group 42.2 months (95% CI 26.3-58.2), and for the simultaneous group 56.2 months (95% CI 47.1-65.4) (stratified log-rank p = 0.455). CONCLUSION A simultaneous approach was not associated with worse overall survival or morbidity compared to a liver-first approach.
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Yeo M, Masuda Y, Calvo MP, Di Martino M, Ielpo B, Ye-Xin K. Surgery for liver metastases from primary melanoma: a systematic review and meta-analysis. Langenbecks Arch Surg 2022; 407:3235-3247. [PMID: 36201022 DOI: 10.1007/s00423-022-02658-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 08/12/2022] [Indexed: 10/10/2022]
Abstract
BACKGROUND Historically , liver metastases due to melanoma have been associated with dismal prognosis. Moreover, the actual survival benefit from the treatment of melanoma liver metastases is still controversial. Hence, this study aims to evaluate the difference in surgical versus non-surgical options for melanoma liver metastases. METHODS Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to July 17, 2022. Studies were included if they compared outcomes between surgical and non-surgical treatment for patients with liver metastases from resectable melanoma. Meta-analyses were performed for the outcomes of 1-year, 2-year, 3-year and 5-year OS. Sensitivity analyses were performed for outcomes with substantial statistical heterogeneity. To account for possible moderators that might contribute to statistical heterogeneity, univariate meta-regression with mixed-effects models and subgroup analyses were conducted for the outcome of 2-year OS. RESULTS The search yielded 6610 articles; 13 studies were included in our analysis. Meta-analyses showed that survival outcomes were in favour of patients undergoing surgery as compared to non-surgery: 1-year OS (HR = 0.29, 95%CI 0.19-0.44, p < 0.00001), 2-year OS (HR = 0.19, 95%CI 0.09-0.38, p < 0.00001), 3-year OS (HR = 0.07, 95%CI 0.03-0.19, p < 0.00001) and 5-year OS (HR = 0.07, 95%CI 0.02-0.22, p < 0.00001). All included studies were of high quality. There was moderate-to-high statistical heterogeneity. Findings were robust to sensitivity analyses. Subgroup analyses and univariate meta-regression revealed neoadjuvant therapy and age as statistically significant subgroup and moderator respectively. CONCLUSIONS This study suggests that surgical treatment of melanoma liver metastases could offer better OS outcomes compared with non-surgical treatment.
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Affiliation(s)
- Mark Yeo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yoshio Masuda
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Mikel-Prieto Calvo
- Hepatobiliary Surgery and Liver Transplantation Unit, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, University of the Basque Country, Bilbao, Spain
| | - Marcello Di Martino
- Department of Hepatobiliary and Liver Transplant Surgery, A.O.R.N. Cardarelli, Naples, Italy
| | - Benedetto Ielpo
- Hepatopancreatobiliary Unit, Parc Salut Mar University Hospital, Barcelona, Spain
- Pompeu Fabra University, Barcelona, Spain
| | - Koh Ye-Xin
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, 1 Outram Road, Singapore, 169608, Singapore.
- Duke-National University of Singapore Medical School, Singapore, Singapore.
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Park EJ, Baik SH. Recent Advance in the Surgical Treatment of Metastatic Colorectal Cancer-An English Version. J Anus Rectum Colon 2022; 6:213-220. [PMID: 36348943 PMCID: PMC9613413 DOI: 10.23922/jarc.2022-048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 09/04/2022] [Indexed: 11/06/2022] Open
Abstract
Stage IV colorectal cancer (CRC) has heterogeneous characteristics in tumor extent and biology. The overall survival of patients with metastatic CRC has improved with the development of multimodal treatments and new chemotherapeutic drugs. Resection of metastatic CRC is performed for liver, lung, or peritoneal metastases. Conversion surgeries to resect oligometastatic lesions have been developed with tumor regression using chemotherapeutic agents. Two-stage hepatectomy has extended the surgical indications for patients with metastatic CRC. Synchronous liver and primary tumor resection can be considered in patients with adequate conditions. Local ablation with radiotherapy can be used to treat lung metastasis. In the treatment of patients with CRC with peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy can be considered. Surgical treatments should be performed in patients with symptomatic primary tumors with unresectable metastasis. However, primary tumor resection in patients with asymptomatic CRC with synchronous, unresectable metastases did not show overall survival benefits in recent studies. Therefore, the treatment of metastatic CRC is challenging due to the variable tumor extent and heterogenous characteristics. Tailored surgical treatments and multidisciplinary approaches may improve survival and the quality of life in patients with metastatic CRC.
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Affiliation(s)
- Eun Jung Park
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine
| | - Seung Hyuk Baik
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine
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Hao Z, Parasramka S, Chen Q, Jacob A, Huang B, Mullett T, Benson AB. Neoadjuvant Versus Adjuvant Chemotherapy for Resectable Metastatic Colon Cancer in Non-academic and Academic Programs. Oncologist 2022; 28:48-58. [PMID: 36200844 PMCID: PMC9847538 DOI: 10.1093/oncolo/oyac209] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 09/09/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Overall survival advantage of chemotherapy before versus after metastasectomy of liver or lung lesion is not clear for colon cancer with synchronous liver or lung metastasis. MATERIALS AND METHODS Adults 20 years or older with primary colon cancer and single organ metastatic disease either in the liver or lung at diagnosis were identified between 2010 and 2015 through the National Cancer Database (NCDB). Patients were categorized into 2 cohorts: pre-operative/peri-operative chemotherapy (neoadjuvant -[NAC]) or post-operative chemotherapy (adjuvant [AC]). Survivals and factors associated with were compared between the 2 groups. RESULTS A total of 3038 patients with colon cancer with liver or lung metastases were identified. The percentage of patients receiving NAC had steadily increased from 12.29% to 28.31%, mostly in academic programs. On multivariate analysis, patients who received NAC had an overall survival advantage in the non-academic setting whereas no advantage is seen in the patients treated in the academic settings. The median overall survival for patients receiving NAC and AC was 47.24 months and 38.08 months, respectively. Factors associated with overall survival advantage in NAC patients treated in non-academic programs included age 20-49 years, CEA value of >30, right-sided colon primary, liver metastasis, and clear resection margins. CONCLUSIONS Metastatic colon cancer with single organ liver or lung lesions benefits from neoadjuvant chemotherapy, especially in -non-academic settings. The overall survival advantage in this setting has not been shown before.
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Affiliation(s)
- Zhonglin Hao
- Corresponding author: Zhonglin Hao, MD, PhD, Department of Internal Medicine, Markey Cancer Center, University of Kentucky; 800 Rose Street, Lexington, KY 40536, USA;
| | - Saurabh Parasramka
- Department of Internal Medicine, Markey Cancer Center, University of Kentucky, Lexington, KY, USA
| | - Quan Chen
- Biostatistics and Bioinformatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, KY, USA
| | - Aasems Jacob
- Department of Internal Medicine, Markey Cancer Center, University of Kentucky, Lexington, KY, USA
| | - Bin Huang
- Biostatistics and Bioinformatics Shared Resource Facility, Markey Cancer Center, University of Kentucky, Lexington, KY, USA,Division of Cancer Biostatistics, Department of Internal Medicine, University of Kentucky, Lexington, KY, USA
| | - Timothy Mullett
- Department of Surgery, Markey Cancer Center, University of Kentucky, Lexington, KY, USA
| | - Al B Benson
- Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
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Wang HW, Jin KM, Li J, Wang K, Xing BC. Postoperative complications predict poor outcomes only in patients with a low modified clinical score after resection of colorectal liver metastases: a retrospective cohort study. Updates Surg 2022; 74:1601-1610. [PMID: 35859226 PMCID: PMC9481509 DOI: 10.1007/s13304-022-01312-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 06/06/2022] [Indexed: 01/04/2023]
Abstract
The aim was to identify the optimal criteria of postoperative complications (POCs) for predicting oncological outcomes after hepatectomy for colorectal liver metastases (CRLMs) and to investigate the variable prognostic implications of POCs according to the modified clinical score (M-CS). We identified 751 patients who underwent curative hepatic resection for CRLM between 2007 and 2018. Patients were categorized based on the M-CS. The impact of the severity [≥ Clavien-Dindo grade (C-D) III or comprehensive complication index (CCI) ≥ 26.2] or type [any infectious complications of POC (Inf-poc)] of POC on overall survival (OS) and recurrence-free survival (RFS) was assessed by univariate and multivariable analyses in different groups. Patients with a major or infectious complication were not associated with either RFS or OS in multivariable analysis of the whole cohort. However, patients with a high CCI had a worse OS (HR 1.51, P = 0.004). Among patients with low M-CS, patients with high CCI had worse OS (HR 1.49, P = 0.035) and RFS (HR 1.32, P = 0.048) than those without high CCI. In contrast, the survival disadvantage of a high CCI was not present in patients with a high M-CS. Compared to Inf-poc or major complications, a high CCI decreased long-term OS in patients treated with hepatectomy for CRLM. High CCI has a variable prognostic impact after hepatic resection for CRLM depending on the M-CS. POC is not a decisive factor to justify the use of hepatectomy for CRLM in patients with high M-CS.
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Affiliation(s)
- Hong-Wei 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, Haidian District, Beijing, China
| | - Ke-Min Jin
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Haidian District, Beijing, China
| | - Juan Li
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Haidian District, 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, Haidian District, Beijing, China
| | - Bao-Cai Xing
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Haidian District, Beijing, China.
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Hewitt DB, Brown ZJ, Pawlik TM. The Role of Biomarkers in the Management of Colorectal Liver Metastases. Cancers (Basel) 2022; 14:cancers14194602. [PMID: 36230522 PMCID: PMC9559307 DOI: 10.3390/cancers14194602] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 09/17/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Colorectal cancer remains one of the most significant sources of cancer-related morbidity and mortality worldwide. The liver is the most common site of metastatic spread. Multiple modalities exist to manage and potentially cure patients with metastatic colorectal cancer. However, reliable biomarkers to assist with clinical decision-making are limited. Recent advances in genomic sequencing technology have greatly expanded our knowledge of colorectal cancer carcinogenesis and significantly reduced the cost and timing of the investigation. In this article, we discuss the current utility of biomarkers in the management of colorectal cancer liver metastases. Abstract Surgical management combined with improved systemic therapies have extended 5-year overall survival beyond 50% among patients with colorectal liver metastases (CRLM). Furthermore, a multitude of liver-directed therapies has improved local disease control for patients with unresectable CRLM. Unfortunately, a significant portion of patients treated with curative-intent hepatectomy develops disease recurrence. Traditional markers fail to risk-stratify and prognosticate patients with CRLM appropriately. Over the last few decades, advances in molecular sequencing technology have greatly expanded our knowledge of the pathophysiology and tumor microenvironment characteristics of CRLM. These investigations have revealed biomarkers with the potential to better inform management decisions in patients with CRLM. Actionable biomarkers such as RAS and BRAF mutations, microsatellite instability/mismatch repair status, and tumor mutational burden have been incorporated into national and societal guidelines. Other biomarkers, including circulating tumor DNA and radiomic features, are under active investigation to evaluate their clinical utility. Given the plethora of therapeutic modalities and lack of evidence on timing and sequence, reliable biomarkers are needed to assist clinicians with the development of patient-tailored management plans. In this review, we discuss the current evidence regarding biomarkers for patients with CRLM.
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Park EJ, Baik SH. Surgical treatment for metastatic colorectal cancer. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2022. [DOI: 10.5124/jkma.2022.65.9.568] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Background: Stage IV colorectal cancer (CRC) exhibits heterogeneous characteristics in tumor extent and biology. The overall survival of patients with metastatic CRC has improved with the development of multimodal treatments and new chemotherapeutic drugs.Current Concepts: Resection of metastatic CRC is performed for liver, lung, or peritoneal metastases. Conversion surgeries to resect oligometastatic lesions have been developed with tumor regression using chemotherapeutic agents. Two-stage hepatectomy has extended the surgical indications for patients with metastatic CRC. Synchronous liver and primary tumor resection can be considered in patients with adequate conditions. Local ablation with radiotherapy can be used to treat lung metastasis. Meanwhile, for treating patients with CRC with peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy can be considered. Surgical treatments should be performed in patients with symptomatic primary tumors with unresectable metastasis. However, in recent studies, primary tumor resection in patients with asymptomatic CRC with synchronous, unresectable metastases did not show overall survival benefits.Discussion and Conclusion: The treatment of metastatic CRC is challenging because of the variable tumor extent and heterogenous characteristics. Tailored surgical treatments and multidisciplinary approaches may improve the survival and quality of life of patients with metastatic CRC.
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Xu Y, He J, Li W, Zhang W, Liu S, He J, Pan Z, Lu Z, Peng J, Lin J. The Pathologic Complete Response Ratio of Liver Metastases Represents a Valuable Prognostic Indicator. Pathol Oncol Res 2022; 28:1610663. [PMID: 36147656 PMCID: PMC9485473 DOI: 10.3389/pore.2022.1610663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/17/2022] [Indexed: 11/13/2022]
Abstract
Background and Objectives: The aim of this study was to evaluate the role of the pathologic complete response ratio of liver metastases (PCRRLM) in predicting the prognosis and recurrence of colorectal cancer liver metastases (CRLM). Methods: A total of 305 CRLM patients who underwent preoperative chemotherapy followed by hepatectomy were included. PCRRLM was defined as the number of liver metastases exhibiting pathologic complete response (PCR) divided by the number of total resected liver metastases. The Kaplan–Meier method was used to calculate survival, and differences were examined by the log-rank test. Univariate and multivariate analyses were performed to identify the predictors of PCRRLM, recurrence-free survival (RFS) and overall survival (OS). Results: Among the 305 included patients, 44 (14.4%) achieved a PCRRLM ≥0.50 (including PCRRLM = 1), and 261 (85.6%) achieved a PCRRLM <0.50 (including PCRRLM = 0). Patients of an older age (≥55 years old) and those with higher carcinoembryonic antigen (CEA) levels (≥5 ng/ml) were less likely to achieve a PCRRLM ≥0.50. In the multivariate analysis, PCRRLM≥ 0.50 (vs. < 0.50, HR [95% CI]: 0.67 [0.46–0.99], p = 0.043) was associated with better RFS. Positive lymph node status (vs. negative, HR [95% CI]: 1.46 [1.04–2.05], p = 0.028) and TBS ≥5 (vs. < 5, HR [95% CI]: 1.44 [1.02–2.04], p = 0.038) were associated with worse RFS. Conclusion: PCRRLM was significantly associated with long-term RFS after preoperative chemotherapy and CRLM resection. Thus, it may be a valuable indicator of recurrence in CRLM patients.
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