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Hernández-Yagüe X, López-Ben S, Martínez-Sancho J, Ortíz-Durán MR, Casellas-Robert M, Aula-Olivar A, Meléndez-Muñoz C, Pujolràs MB, Queralt-Merino B, Felip JFI. The Prognostic Value of Tumor Fibrosis in Patients Undergoing Hepatic Metastasectomy for Colorectal Cancer: A Retrospective Pooled Analysis. Cancers (Basel) 2025; 17:1870. [PMID: 40507350 PMCID: PMC12153617 DOI: 10.3390/cancers17111870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2025] [Revised: 05/29/2025] [Accepted: 05/30/2025] [Indexed: 06/16/2025] Open
Abstract
Background: Colorectal cancer (CRC) is a significant global health burden, with liver metastases representing a key prognostic factor. Neoadjuvant chemotherapy (NAC) has improved outcomes in metastatic CRC (mCRC), and tumor regression is commonly assessed using the Rubbia-Brandt classification. The Poultsides classification defines ≥40% fibrosis as an independent prognostic factor, particularly in patients treated with cetuximab (45.71%). However, the predictive value of this threshold remains under debate, warranting further investigation. Methods: This study evaluates the extent of fibrosis (≥40%) induced by NAC plus anti-epidermal growth factor receptor (anti-EGFR) therapy vs. NAC plus anti-vascular endothelial growth factor (anti-VEGF) therapy in mCRC patients. It also examines the prognostic relevance of the Poultsides and Rubbia-Brandt classifications. A total of 108 patients undergoing liver resection for CRC metastases were included. Statistical analyses were performed using SPSS 28.0 version and R software 4.5 version to compare fibrosis rates and survival outcomes. Results: From September 2005 to January 2023, 108 patients were analyzed: 54 received chemotherapy plus anti-EGFR (Cohort 1), and 54 received chemotherapy plus anti-VEGF (Cohort 2). Fibrosis was significantly higher in Cohort 1 (median 40.0%, IQR: 25.4-53.2) than in Cohort 2 (median 20.6%, IQR: 8.07-36.9), p < 0.001. Overall survival was similar between both cohorts (p = 0.96), with a median follow-up of 41.6 months. Conclusions: Anti-EGFR therapy is associated with greater fibrosis than anti-VEGF, despite similar survival outcomes. The Poultsides classification may be a useful prognostic tool for resected liver metastases in mCRC.
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Affiliation(s)
- Xavier Hernández-Yagüe
- Department of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Av. França s/n, 17007 Girona, Spain;
| | - Santiago López-Ben
- Hepatobiliary and Pancreatic Surgery Unit, Department of Surgery, Dr. Josep Trueta Hospital, IdIBGi, 17007 Girona, Spain; (S.L.-B.); (M.C.-R.)
| | - Joan Martínez-Sancho
- Unitat de Estadística, Institut de Recerca Biomèdica de Girona (IDIBGi), 17007 Girona, Spain; (J.M.-S.); (M.B.P.)
| | - Maria Rosa Ortíz-Durán
- Pathology Department, Catalan Institute of Health, Hospital Josep Trueta, School of Medicine, University of Girona (UdG), 17007 Girona, Spain; (M.R.O.-D.); (A.A.-O.); (C.M.-M.)
| | - Margarida Casellas-Robert
- Hepatobiliary and Pancreatic Surgery Unit, Department of Surgery, Dr. Josep Trueta Hospital, IdIBGi, 17007 Girona, Spain; (S.L.-B.); (M.C.-R.)
| | - Ana Aula-Olivar
- Pathology Department, Catalan Institute of Health, Hospital Josep Trueta, School of Medicine, University of Girona (UdG), 17007 Girona, Spain; (M.R.O.-D.); (A.A.-O.); (C.M.-M.)
| | - Cristina Meléndez-Muñoz
- Pathology Department, Catalan Institute of Health, Hospital Josep Trueta, School of Medicine, University of Girona (UdG), 17007 Girona, Spain; (M.R.O.-D.); (A.A.-O.); (C.M.-M.)
| | - Maria Buxó Pujolràs
- Unitat de Estadística, Institut de Recerca Biomèdica de Girona (IDIBGi), 17007 Girona, Spain; (J.M.-S.); (M.B.P.)
| | - Bernardo Queralt-Merino
- Department of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Av. França s/n, 17007 Girona, Spain;
| | - Joan Figueras i Felip
- Researcher Affiliated with the Doctoral Program at the University of Girona, 17007 Giona, Spain;
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Dejonckheere CS, Bilski M, Nour Y, Scafa D, Cisek P, Korab K, Ponikowska J, Wojtyna E, Sroka S, Kugel F, Grimmer M, Holz J, Garbe S, Eich P, Gkika E, Renato Sarria G, Philipp Layer J. A dosimetric comparison of different radiotherapy modalities for Non-Resected oligometastatic liver Disease. Clin Transl Radiat Oncol 2025; 52:100947. [PMID: 40144226 PMCID: PMC11937280 DOI: 10.1016/j.ctro.2025.100947] [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: 03/28/2024] [Revised: 02/02/2025] [Accepted: 03/09/2025] [Indexed: 03/28/2025] Open
Abstract
Purpose The role of radiotherapy in the context of limited liver metastases is emerging rapidly with a variety of available technical approaches. Here, we provide a dosimetric comparison of three different radiotherapy modalities for non-resected liver metastases. Methods This multicentric study included 30 patients previously treated for solitary liver metastases. Interstitial high dose-rate brachytherapy (HDR), stereotactic body radiation therapy (SBRT), and kilovoltage electronic brachytherapy (eBT) with a single dwelling point, as an in this context novel modality, were planned with a 25-Gy single fraction and dosimetrically compared. The primary endpoint was difference in healthy liver tissue exposure. Secondary endpoints included target volume coverage, dose to the surrounding organs at risk (OARs), and radiation treatment time. Results The median (range) lesion volume was 9.3 (2.5 - 29.7) cm3. Electronic BT yielded a significantly better OAR dose sparing compared to SBRT. Radiation exposure to the healthy liver was significantly lower with eBT (V9.1 Gy 13.8 [3.4-41.6] cm3) and HDR (49.2 [12.7-116.8] cm3) when compared with SBRT (98.8 [54.3-303.7] cm3; p < 0.001 for both). Mean treatment time was shortest for SBRT (6.1 min vs. 7.8 min for HDR [p = 0.003] vs. 16.1 min for eBT [p < 0.001]). Equally, CTV D90% and D95% were superior for SBRT (p < 0.001 vs. HDR and eBT). Conclusion Minimally invasive single-catheter eBT provides a new potential approach in the context of unresectable liver metastases, with optimal OAR dose sparing, yet suboptimal target volume coverage. Combining the advantages of both modalities, a multi-dwelling eBT approach as in HDR might ease applicability in clinical routine with optimized target coverage while maintaining excellent OAR doses. Future prospective investigations are required to further define its role within well-established liver-directed therapies.
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Affiliation(s)
| | - Mateusz Bilski
- Department of Radiotherapy, Medical University of Lublin 20059 Lublin, Poland
- Department of Brachytherapy, St. John’s Cancer Center, 20090 Lublin, Poland
- Department of Radiotherapy, St. John’s Cancer Center, 20090 Lublin, Poland
| | - Younèss Nour
- Department of Radiation Oncology, University Hospital Bonn 53127 Bonn, Germany
| | - Davide Scafa
- Department of Radiation Oncology, University Hospital Bonn 53127 Bonn, Germany
| | - Paweł Cisek
- Department of Radiotherapy, Medical University of Lublin 20059 Lublin, Poland
- Department of Brachytherapy, St. John’s Cancer Center, 20090 Lublin, Poland
| | - Katarzyna Korab
- Department of Medical Physics, St. John’s Cancer Center, 20090 Lublin, Poland
| | - Julia Ponikowska
- Department of Medical Physics, St. John’s Cancer Center, 20090 Lublin, Poland
| | - Ewa Wojtyna
- Department of Medical Physics, St. John’s Cancer Center, 20090 Lublin, Poland
| | - Sylwia Sroka
- Department of Medical Physics, St. John’s Cancer Center, 20090 Lublin, Poland
| | - Fabian Kugel
- Department of Radiation Oncology, University Hospital Bonn 53127 Bonn, Germany
| | - Molina Grimmer
- Department of Radiation Oncology, University Hospital Bonn 53127 Bonn, Germany
| | - Jasmin Holz
- Department of Radiation Oncology, University Hospital Bonn 53127 Bonn, Germany
| | - Stephan Garbe
- Department of Radiation Oncology, University Hospital Bonn 53127 Bonn, Germany
| | - Patrick Eich
- Department of Radiation Oncology, University Hospital Bonn 53127 Bonn, Germany
| | - Eleni Gkika
- Department of Radiation Oncology, University Hospital Bonn 53127 Bonn, Germany
| | | | - Julian Philipp Layer
- Department of Radiation Oncology, University Hospital Bonn 53127 Bonn, Germany
- Institute of Experimental Oncology, University Hospital Bonn 53127 Bonn, Germany
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Li W, Liu B, Xiang X, Zhang Q, Yang Q, Cao Y, Liu T. Lymphovascular invasion affects prognosis of colorectal cancer liver metastasis underwent primary resection: a propensity score matching analysis. BMC Cancer 2025; 25:793. [PMID: 40296050 PMCID: PMC12039118 DOI: 10.1186/s12885-025-14083-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 04/03/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND Lymphovascular invasion (LVI) is associated with poor prognosis in a variety of malignancies; however, its prognostic value has not been fully defined in patients with colorectal cancer with liver metastases (CRCLM). The aim of this study was to investigate the impact of LVI on long-term postoperative recurrence and survival in patients with CRCLM. METHODS Clinicopathologic data were retrospectively collected from patients who underwent primary resection for CRCLM at Wuhan Union Hospital from 2013 to 2018. To reduce potential confounders and selection bias, we used propensity score matching (PSM) to compare the clinicopathologic characteristics and long-term prognostic outcomes of patients in the LVI (+) and LVI (-) groups. Cox unifactorial and multifactorial analyses were used to screen relevant factors affecting patient prognosis, and Kaplan-Meier curves were plotted to compare differences in patient overall survival (OS) and disease-free survival (DFS). The predictive power of independent factors on patients' long-term prognosis was assessed using receiver operating characteristic ROC) curves and area under the curve (AUC). RESULTS After PSM, 230 patients were enrolled in the study (n = 115 per group). Multifactorial analysis revealed that LVI was an independent prognostic factor for OS and DFS (hazard ratio [HR], 1.424; 95% confidence interval [CI], 1.004-2.022; P = 0.048 and HR, 1.452; 95% CI, 1.020-2.069; p = 0.039, respectively). In the LVI (-) group, postoperative chemotherapy did not significantly improve OS or DFS; however, in the LVI (+) group, those who received chemotherapy had significantly improved OS (HR: 1.593, 95% CI: 1.187 - 2.571; P = 0.044) and DFS (HR: 1.503, 95% CI. 1.033 - 2.422; P = 0.045) compared with patients not treated with chemotherapy. In the LVI (+) group, the AUC for the OS AUROC curves was more favorable compared with after PSM (AUC at 3 years: 0.786 vs. 0.903; AUC at 5 years: 0.744 vs. 0.889). For DFS, the area under the AUROC curve was also better in the LVI (+) subgroup compared with after PSM (AUC at 3 years: 0.825 vs. 0.874; AUC at 5 years: 0.839 vs. 0.863). CONCLUSIONS LVI may significantly impact long-term survival and prognosis in patients with CRCLM undergoing primary resection, potentially serving as an independent prognostic factor for OS and DFS. Additionally, postoperative chemotherapy appears to significantly improve the long-term prognosis of patients with LVI (+).
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Affiliation(s)
- Wei Li
- Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Bo Liu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Xingxing Xiang
- Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qun Zhang
- Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qinglin Yang
- Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yinghao Cao
- Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
- Hubei Key Laboratory of Biological Targeted Therapy, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Tao Liu
- Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Biswas L, Khatun F, Basak T, Biswas B, Biswas K, De S, Mandal S. Clinico-Demographic Profile of Carcinoma Rectum-Experience from a Tertiary Care Centre of Eastern India. Indian J Surg Oncol 2025; 16:595-600. [PMID: 40337036 PMCID: PMC12052635 DOI: 10.1007/s13193-024-02114-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 10/11/2024] [Indexed: 01/05/2025] Open
Abstract
Carcinoma rectum is a major health issue in India as well as the rest of the world. Cases of rectal cancers are often diagnosed late because of mimicking symptoms with haemorrhoids/fissures and lack of awareness. In this study, we analysed the clinico-demographic profile of patients with carcinoma rectum, attending a tertiary care centre of Eastern India over the last 2 years. We analysed the database of radiotherapy OPD of a tertiary care centre of Eastern India, and collected the demographic, clinical and treatment data of rectal carcinoma patients who attended our OPD between 2021 and 2023. The objective was to assess the demographic and clinical profile of these patients and compare with those reported from other parts of the India as well as rest of the world. Data of total 76 patients were analysed in this study. The mean age of the study population was 50.7 (± 13.59) years. A striking 40% of patients were below 50 years of age. Stage III was the most common (43%) TNM stage at presentation. 15.7% presented with metastatic disease with the liver being the most common site of metastasis. 15.7% of patients underwent upfront surgery either as trans-anal resection or trans-abdominal resection of tumour. Most of the patients (56.5%) had gone through surgery after neo-adjuvant therapy (either total neo-adjuvant therapy or neo-adjuvant radiotherapy). Around 64.4% (n = 49) of patients received radiation as part of total neo-adjuvant therapy (TNT). Eight (10.5%) patients received adjuvant therapy after definitive surgery. To conclude, it can be said that this study revealed involvement of younger population, emergence of poor prognostic histologies and presence of disease at an advanced stage, all of which should be counted as warning signs for the picture rectal carcinoma of India. More researches are required in this field for detection of risk factors, prevention and treatment.
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Affiliation(s)
- Linkon Biswas
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
- Department of Medical Oncology, Chittaranjan National Cancer Institute, Kolkata, India
| | - Firdoushi Khatun
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
- Department of Radiotherapy, IPGMER and SSKM Hospital, Kolkata, India
| | - Tanmoy Basak
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
| | - Bidyut Biswas
- Department of Surgery, Raiganj Government Medical College and Hospital, Uttar Dinajpur, Raiganj, West Bengal India
| | - Koustav Biswas
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
| | - Sumitava De
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
| | - Srikrishna Mandal
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
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Kong Y, Huang X, Cao X, Tang F, Zhou X. Early Recurrence of Colorectal Liver Metastasis (Number ≤ 5 and Largest Diameter ≤ 3 cm) after Resection or Thermal Ablation: a Multi-center Study of Patterns, Safety, Survival and Risk Factors. J Gastrointest Cancer 2025; 56:77. [PMID: 40072796 DOI: 10.1007/s12029-025-01200-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/02/2025] [Indexed: 03/14/2025]
Abstract
OBJECTIVE To compare early recurrence patterns, safety, survival and investigate the clinical risk factors of early recurrence (ER) after liver resection or thermal ablation (TA) for patients with colorectal liver metastases (CRLM) with number ≤ 5 and largest diameter ≤ 3 cm. MATERIALS AND METHODS This retrospective study included patients with CRLM who underwent liver resection or TA between January 2016 and December 2021 at two hospitals in China. The Kaplan-Meier method and log-rank test were used to assess recurrence-free survival (RFS) and overall survival (OS). Risk factors for ER were analysed using univariate and multivariate Cox regression analyses. RESULTS 303 patients with 632 liver metastases were enrolled. The most common early recurrence pattern was intrahepatic recurrence (IHR) in resection group and TA group. There was no significant difference in 6-month RFS rate (65.81% vs 66.23%) and median OS (P = 0.10) between two groups. Patients without ER had better OS than those with ER (P < 0.05). The incidence of serious complications (P = 0.013), length of hospitalization (P < 0.01), and albumin-bilirubin (ALBI) score (P = 0.038) in TA group were significantly better than resection group. The diameter of liver metastases (HR: 4.89, 95% CI: 1.16-20.60; P = 0.031) and clinical risk score (CRS) (HR: 1.86, 95% CI: 1.06-3.25; P = 0.029) were independent risk factors for ER. CONCLUSION For CRLM with largest diameter ≤ 3 cm and number ≤ 5, the efficacy of receiving resection or TA is comparable, and the safety of TA is better. TA may be considered as the first-line local treatment option for patients with CRLM.
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Affiliation(s)
- Yaqing Kong
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiaoyu Huang
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiaojing Cao
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Fan Tang
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiang Zhou
- Department of Interventional Therapy, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Yohanathan L, Chopra A, Simo K, Clancy TE, Khithani A, Anaya DA, Maegawa FA, Sheikh M, Raoof M, Jacobs M, Aleassa E, Boff M, Ferguson B, Tan-Tam C, Winslow E, Qadan M, D’Angelica MI. Assessment and treatment considerations for patients with colorectal liver metastases: AHPBA consensus guideline and update for surgeons. HPB (Oxford) 2025; 27:263-278. [PMID: 39828468 DOI: 10.1016/j.hpb.2024.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 11/20/2024] [Accepted: 12/09/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND Colorectal cancer most commonly metastasizes to the liver. While various treatment strategies have been developed, surgical management of these patients has vital implications on the prognosis and survival of this group of patients. There remains a need for a consensus guideline regarding the surgical evaluation and management of patients with colorectal liver metastases (CRLM). METHODS This review article is a consensus guideline established by the members of the AHPBA Professional Standards Committee, as an amalgamation of existent literature and a guide to surgeons managing this complex disease. RESULTS These guidelines reports the benefits and shortcomings of various diagnostic modalities including imaging and next-generation sequencing in the management of patients with CRLM. While surgery has established survival benefits in patients with resectable disease, this report notes the importance of treatment sequencing with non-surgical modalities as well as between colon and liver resection. Finally, the guidelines address the various treatment modalities for patients with unresectable disease, that may have significant impact on survival. CONCLUSION CRLM is a complex diagnosis which warrants multidisciplinary approach with early surgical involvement in both assessment and management of the disease, to optimize patient outcomes and survival.
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Ng WH, Machado C, Rooney A, Jones R, Rees J, Pathak S. Ablative techniques in colorectal liver metastases: A systematic review, descriptive summary of practice, and recommendations for optimal data reporting. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109487. [PMID: 39637740 DOI: 10.1016/j.ejso.2024.109487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 10/13/2024] [Accepted: 11/21/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND Radiofrequency Ablation (RFA) and Microwave Ablation (MWA) are alternative treatments for colorectal liver metastasis (CRLM) patients that are unsuitable for resection. However, consensus is lacking regarding selection criteria, tumour characteristics, ablation technique delivery, and device settings. This study aims to summarise current evidence to inform future prospective studies. METHODS A systematic review was conducted following PRISMA guidelines. Studies assessing RFA and MWA treatment of CRLM were identified in Medline, Embase, Web of Science and the Cochrane database of systematic reviews, from inception until 31st August 2024. RESULTS Fifty-two studies were included (retrospective cohort n = 45, prospective cohort n = 5, non-randomized comparative studies n = 2). Fifty-four inclusion criteria were used across 45 studies and were not stated in 7 studies. Tumours varied in mean number [1-8] and diameter (1.54-4.35 cm). Neoadjuvant chemotherapy use (10-100 % of patients), ablation delivery approach (open n = 4, laparoscopic n = 11, percutaneous n = 26, mixed n = 5), anaesthetic mode (GA n = 18, LA n = 11, mixed n = 2) and delivering clinician (radiologist n = 11, surgeon n = 16, both n = 1) all varied. Thirty-two studies lacked complete ablation device settings. Six studies followed a standardized ablation algorithm and 14 studies had specific settings. Five-year survival ranged from 0 to 69.7 % for ablation. CONCLUSIONS There is significant heterogeneity in the reporting of study design, patient selection, and ablation techniques for CRLM. The lack of standardized approaches and inconsistent reporting of methodology and outcomes make it challenging to determine the optimal ablative treatment for CRLM. We recommend that future research should focus on clearly defining selection and treatment criteria, as well as treatment delivery.
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Affiliation(s)
- Wee Han Ng
- Bristol Medical School, University of Bristol, Bristol, UK.
| | | | - Alice Rooney
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Robert Jones
- Hepatobiliary Surgery Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Jonathan Rees
- Bristol Medical School, University of Bristol, Bristol, UK; Department of Pancreatic and Hepatobiliary Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.
| | - Samir Pathak
- Department of Pancreatic Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Liu X, Li D, Zhang Y, Liu H, Chen P, Zhao Y, Sun G, Zhao W, Dong G. Multi-Algorithm-Integrated Tertiary Lymphoid Structure Gene Signature for Immune Landscape Characterization and Prognosis in Colorectal Cancer Patients. Biomedicines 2024; 12:2644. [PMID: 39595209 PMCID: PMC11592260 DOI: 10.3390/biomedicines12112644] [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: 09/27/2024] [Revised: 11/12/2024] [Accepted: 11/15/2024] [Indexed: 11/28/2024] Open
Abstract
PURPOSE Colorectal cancer (CRC) is a common malignancy with a low survival rate as well as a low response rate to immunotherapy. This study aims to develop a risk model based on tertiary lymphoid structure (TLS)-associated gene signatures to enhance predictions of prognosis and immunotherapy response. METHODS TLS-associated gene data were obtained from TCGA-CRC and GEO cohorts. A comprehensive analysis using univariate Cox regression identified TLS-associated genes with significant prognostic implications. Subsequently, multiple algorithms were employed to select the most influential genes, and a stepwise Cox regression model was constructed. The model's predictive performance was validated using independent datasets (GSE39582, GSE17536, and GSE38832). To further investigate the immune microenvironment, immune cell infiltration in high-risk (HRG) and low-risk (LRG) groups was assessed using the CIBERSORT and ssGSEA algorithms. Additionally, we evaluated the model's potential to predict immune checkpoint blockade therapy response using data from The Cancer Imaging Archive, the TIDE algorithm, and external immunotherapy cohorts (GSE35640, GSE78200, and PRJEB23709). Immunohistochemistry (IHC) was employed to characterize TLS presence and CCL2 gene expression. RESULTS A three-gene (CCL2, PDCD1, and ICOS) TLS-associated model was identified as strongly associated with prognosis and demonstrated predictive power for CRC patient outcomes and immunotherapy efficacy. Notably, patients in the low-risk group (LRG) had a higher overall survival rate as well as a higher re-response rate to immunotherapy compared to the high-risk group (HRG). Finally, IHC results confirmed significantly elevated CCL2 expression in the TLS regions. CONCLUSIONS The multi-algorithm-integrated model demonstrated robust performance in predicting patient prognosis and immunotherapy response, offering a novel perspective for assessing immunotherapy efficacy. CCL2 may function as a TLS modulator and holds potential as a therapeutic target in CRC.
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Affiliation(s)
- Xianqiang Liu
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Dingchang Li
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Yue Zhang
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
| | - Hao Liu
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Peng Chen
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Yingjie Zhao
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Guanchao Sun
- Medical School of Chinese PLA, Beijing 100853, China; (X.L.)
| | - Wen Zhao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Guanglong Dong
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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Seo N, Ryu HS, Lee M, Jeon SK, Chae KJ, Yoon JK, Han KS, Lee JE, Eo JS, Yoon YC, Moon SK, Kim HJ, Kwak JM. 2023 Korean Multidisciplinary Guidelines for Colon Cancer Management: Summary of Radiological Points. Korean J Radiol 2024; 25:769-772. [PMID: 39197822 PMCID: PMC11361801 DOI: 10.3348/kjr.2024.0575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 06/20/2024] [Indexed: 09/01/2024] Open
Affiliation(s)
- Nieun Seo
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
| | - Hyo Seon Ryu
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Myungsu Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Sun Kyung Jeon
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Kum Ju Chae
- Department of Radiology, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Joon-Kee Yoon
- Department of Nuclear Medicine & Molecular Imaging, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Kyung Su Han
- Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Ji Eun Lee
- Department of Radiology, Soonchunhyang University, Bucheon Hospital, Bucheon, Republic of Korea
| | - Jae Seon Eo
- Department of Nuclear Medicine and Molecular Imaging, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young Chul Yoon
- Department of General Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Kyung Moon
- Department of Radiology, Kyung Hee University Hospital, Seoul, Republic of Korea
| | - Hyun Jung Kim
- Department of Preventive Medicine, Korea University College of Medicine, Seoul, Republic of Korea
- Institute for Evidence-based Medicine, Cochrane Collaboration, Seoul, Republic of Korea
| | - Jung-Myun Kwak
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
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10
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Haddad A, Odisio BC, Vauthey JN. Invited Commentary: Should Patients with Colorectal Liver Metastases Undergo Ablation? J Am Coll Surg 2024; 239:285-287. [PMID: 38690836 DOI: 10.1097/xcs.0000000000001108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2024]
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11
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Li J, Pang C, Liu G, Xie X, Zhang DZ, Li K, Li Z, He G, Xu E, Zhong H, Yang H, Lu M, Lou K, Xie X, Lan S, Li Q, Dai G, Yu J, Liang P. Thermal ablation with and without adjuvant systemic therapy: a nationwide multicenter observational cohort study of solitary colorectal liver metastases. Int J Surg 2024; 110:4240-4248. [PMID: 38597399 PMCID: PMC11254207 DOI: 10.1097/js9.0000000000001397] [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: 10/19/2023] [Accepted: 03/11/2024] [Indexed: 04/11/2024]
Abstract
BACKGROUND Thermal ablation is routinely used for solitary colorectal liver metastases (SCLM), but the added value of adjuvant systemic therapy in SCLM remains unclear. This study aimed to compare the long-term outcomes for SCLM treated by ablation alone (AB) versus ablation plus systemic therapy (AS). METHODS This multicenter retrospective study using nationwide data from fourteen institutions between October 2010 and May 2023, 369 patients with initial SCLM smaller than 5 cm, no extrahepatic metastases, and colorectal cancer R0 resection treated by thermal ablation were included. The crude analysis was used to analyze eligible cases between the two groups. The propensity score matching to control for potential confounders in each matched group. Subgroup analyses were performed to identify specific survival benefits. RESULTS 61.2% (226/369) of eligible patients were treated with AS and 38.8% (143/369) with AB. During the median follow-up period of 8.8 years, 1-/3-/5-year DFS/OS rates did not differ between the two groups, when analyzed via propensity score matching ( P =0.52/0.08). Subgroup analysis revealed that AS was significantly associated with better OS than AB in patients with plasma CEA >5 ug/l ( P =0.036), T (III-IV) category of primary cancer ( P =0.034), or clinical risk score (1-2) ( P =0.041). In each matched group, the authors did find a significant difference in drug-related adverse events ( P <0.001) between AS group (24.1%, 28/116) and AB group (0.0%, 0/116). CONCLUSIONS For patients with plasma CEA >5 ug/l, T (III-IV) category of primary cancer, or clinical risk score (1-2), thermal ablation plus systemic therapy appeared to be associated with improved overall survival. Thermal ablation was equally effective in disease-free survival for treating SCLM, whether with or without adjuvant systemic therapy.
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Affiliation(s)
- Jianming Li
- Department of Interventional Ultrasound PLA Medical College The Fifth Medical Center of Chinese PLA General Hospital, Beijing
| | - Chuan Pang
- Department of Interventional Ultrasound PLA Medical College The Fifth Medical Center of Chinese PLA General Hospital, Beijing
| | - Guangjian Liu
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital of Sun Yat-Sen University Guangzhou
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University Guangzhou
| | - De-zhi Zhang
- Department of Abdominal Ultrasound, The First Affiliated Hospital of Jilin University, Chaoyang District, Changchun, People’s Republic of China
| | - Kai Li
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou
| | - Zhishuai Li
- Biliary Tract Surgery Department I, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai
| | - Guangbin He
- Department of Ultrasound, Xijing Hospital, The Fourth Military Medical University, Xian
| | - Erjiao Xu
- Department of Medical Ultrasonics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen
| | - Huage Zhong
- Department of Gastrointestinal Surgery, Guangxi Clinical Research Center for CRC, Guangxi Medical University Cancer HospitalNanning, Guangxi Zhuang Autonomous Region
| | - Hong Yang
- Department of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region
| | - Man Lu
- Department of Ultrasound Medicine and Laboratory of Translational Research in Ultrasound Theranostics, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu
| | - Kexin Lou
- Department of Medical Ultrasound, Xuzhou Central Hospital, Xuzhou
| | - Xiang Xie
- Department of Interventional Ultrasound, The Second Hospital of Anhui Medical University, Hefei
| | - Sirong Lan
- Department of Ultrasound, Meizhou People’s Hospital, Meizhou
| | - Qian Li
- Department of Ultrasound, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan
| | - Guanghai Dai
- Department of Medical Oncology, PLA Medical College and Fifth Medical Center of Chinese PLA General Hospital, Beijing
| | - Jie Yu
- Department of Interventional Ultrasound PLA Medical College The Fifth Medical Center of Chinese PLA General Hospital, Beijing
| | - Ping Liang
- Department of Interventional Ultrasound PLA Medical College The Fifth Medical Center of Chinese PLA General Hospital, Beijing
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12
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Karaoğlan BB, Öz DK, Araz MS, Akyol C, Utkan G. Advancements in the Management of Synchronous Colorectal Liver Metastases: A Comprehensive Review of Surgical, Systemic, and Local Treatment Modalities. Curr Oncol Rep 2024; 26:791-803. [PMID: 38776011 PMCID: PMC11224077 DOI: 10.1007/s11912-024-01548-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/11/2024] [Indexed: 07/05/2024]
Abstract
PURPOSE OF REVIEW This review addresses the current landscape of colorectal cancer (CRC) with a focus on liver metastases, the third most common cancer globally. It explores recent findings in treatment strategies, emphasizing the dynamic interplay between surgery, systemic chemotherapy, and local therapies for synchronous colorectal liver metastases (CRLMs). RECENT FINDINGS Highlighting the role of advanced imaging, the review underscores the significance of contrast-enhanced MRI in surgical planning for CRLMs. Surgical resection remains a primary choice for resectable cases, with considerations for oncologic scoring systems and tumor biology. Perioperative systemic chemotherapy plays a pivotal role, especially in conversion therapy for initially unresectable CRLMs. The review also explores various local therapies, including radiofrequency ablation, microwave ablation, stereotactic body radiotherapy, hepatic arterial infusional chemotherapy, selective internal radiation therapy, and transarterial chemoembolization for unresectable cases. A comprehensive approach, integrating surgery, systemic chemotherapy, and local therapies, is crucial for managing synchronous CRLMs. Surgical resection and perioperative chemotherapy are key players, guided by considerations of tumor biology and scoring systems. For unresectable cases, local therapies offer viable alternatives, emphasizing the need for tailored treatments. Multidisciplinary collaboration among medical oncologists, surgeons, and radiologists is essential. Ongoing research will refine treatment approaches, while emerging technologies hold promise for further advancements in managing colorectal liver metastases.
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Affiliation(s)
- Beliz Bahar Karaoğlan
- Department of Medical Oncology, Faculty of Medicine, Ankara University, 06100, Ankara, Turkey.
| | - Diğdem Kuru Öz
- Department of Radiology, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Mine Soylu Araz
- Department of Nuclear Medicine, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Cihangir Akyol
- Department of General Surgery, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Güngör Utkan
- Department of Medical Oncology, Faculty of Medicine, Ankara University, 06100, Ankara, Turkey
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13
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Ryu HS, Kim HJ, Ji WB, Kim BC, Kim JH, Moon SK, Kang SI, Kwak HD, Kim ES, Kim CH, Kim TH, Noh GT, Park BS, Park HM, Bae JM, Bae JH, Seo NE, Song CH, Ahn MS, Eo JS, Yoon YC, Yoon JK, Lee KH, Lee KH, Lee KY, Lee MS, Lee SH, Lee JM, Lee JE, Lee HH, Ihn MH, Jang JH, Jeon SK, Chae KJ, Choi JH, Pyo DH, Ha GW, Han KS, Hong YK, Hong CW, Kwak JM, Korean Colon Cancer Multidisciplinary Committee. Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment. Ann Coloproctol 2024; 40:89-113. [PMID: 38712437 PMCID: PMC11082542 DOI: 10.3393/ac.2024.00059.0008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 03/11/2024] [Accepted: 03/18/2024] [Indexed: 05/08/2024] Open
Abstract
Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.
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Affiliation(s)
- Hyo Seon Ryu
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Hyun Jung Kim
- Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea
- Institute for Evidence-based Medicine, Cochrane Collaboration, Seoul, Korea
| | - Woong Bae Ji
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Ansan Hospital, Ansan, Korea
| | - Byung Chang Kim
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Ji Hun Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Kyung Moon
- Department of Radiology, Kyung Hee University Hospital, Seoul, Korea
| | - Sung Il Kang
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Han Deok Kwak
- Department of Surgery, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
| | - Eun Sun Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Chang Hyun Kim
- Department of Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
| | - Tae Hyung Kim
- Department of Radiation Oncology, Nowon Eulji Medical Center, Eulji University, Seoul, Korea
| | - Gyoung Tae Noh
- Department of Surgery, Ewha Womans University College of Medicine, Seoul, Korea
| | - Byung-Soo Park
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - Hyeung-Min Park
- Department of Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
| | - Jeong Mo Bae
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Jung Hoon Bae
- Division of Colorectal Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ni Eun Seo
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Chang Hoon Song
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Mi Sun Ahn
- Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea
| | - Jae Seon Eo
- Department of Nuclear Medicine and Molecular Imaging, Korea University College of Medicine, Seoul, Korea
| | - Young Chul Yoon
- Department of General Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Joon-Kee Yoon
- Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Korea
| | - Kyung Ha Lee
- Department of Surgery, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea
| | - Kyung Hee Lee
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kil-Yong Lee
- Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
| | - Myung Su Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Sung Hak Lee
- Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jong Min Lee
- Department of Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Ji Eun Lee
- Department of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Han Hee Lee
- Division of Gastroenterology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Myong Hoon Ihn
- Department of Surgery, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Je-Ho Jang
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University, Daejeon, Korea
| | - Sun Kyung Jeon
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Kum Ju Chae
- Department of Radiology, Jeonbuk National University Medical School, Jeonju, Korea
| | - Jin-Ho Choi
- Center for Lung Cancer, Department of Thoracic Surgery, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Dae Hee Pyo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gi Won Ha
- Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
| | - Kyung Su Han
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Young Ki Hong
- Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Chang Won Hong
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Jung-Myun Kwak
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Korean Colon Cancer Multidisciplinary Committee
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea
- Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea
- Institute for Evidence-based Medicine, Cochrane Collaboration, Seoul, Korea
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Ansan Hospital, Ansan, Korea
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Radiology, Kyung Hee University Hospital, Seoul, Korea
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
- Department of Surgery, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
- Department of Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
- Department of Radiation Oncology, Nowon Eulji Medical Center, Eulji University, Seoul, Korea
- Department of Surgery, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
- Division of Colorectal Surgery, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea
- Department of Nuclear Medicine and Molecular Imaging, Korea University College of Medicine, Seoul, Korea
- Department of General Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Korea
- Department of Surgery, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Surgery, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
- Department of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Division of Gastroenterology, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Surgery, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University, Daejeon, Korea
- Department of Radiology, Jeonbuk National University Medical School, Jeonju, Korea
- Center for Lung Cancer, Department of Thoracic Surgery, Research Institute and Hospital, National Cancer Center, Goyang, Korea
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
- Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea
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14
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Asai M, Dobesh KD. Combined Resection Approaches: Decision Making for Synchronous Resection, Timing of Staged Intervention to Optimize Outcome. Clin Colon Rectal Surg 2024; 37:96-101. [PMID: 38322604 PMCID: PMC10843888 DOI: 10.1055/s-0043-1761475] [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: 02/08/2024]
Abstract
Advancement in systemic and regional radiation therapy, surgical technique, and anesthesia has provided a path for increased long-term survival and potential cure for more patients with stage IV rectal cancer in recent years. When patients have resectable disease, the sequence for surgical resection is classified in three strategies: classic, simultaneous, or combined, and reversed. The classic approach consists of rectal cancer resection followed by metastatic disease at a subsequent operation. Simultaneous resection addresses both rectal and metastatic disease in a single surgery. The reversed approach treats metastatic disease first, followed by the primary tumor in several months. Simultaneous resection is appropriate for selected patients to avoid delay of definitive surgery, and reduce number of surgeries, hospital stay, and cost to the health care system. It may also improve patients' psychological effect. Multidisciplinary discussions including colorectal and liver surgeons to review patients' baseline medical conditions, tumor biology and behavior, and disease burden and distribution is imperative to guide proper patient selection for simultaneous resection and perioperative treatments.
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Affiliation(s)
- Megumi Asai
- Division of Colon and Rectal Surgery, Henry Ford Hospital, Detroit, Michigan
| | - Kaitlyn D. Dobesh
- Division of Colon and Rectal Surgery, Henry Ford Hospital, Detroit, Michigan
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15
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Abstract
Colorectal cancer is one of the most common cancers diagnosed worldwide. While the incidence of colorectal cancer has been declining since the adoption of screening colonoscopy, the findings of liver metastasis are still found in up to 25% of patients at diagnosis. The management of liver metastasis has evolved over the past two to three decades, and survival rates have improved secondary to improved systemic therapy, surgical options, and local therapies. In this article, we aim to review the available surgical and ablative options for management of colorectal liver metastasis, as well as appropriate imaging and patient selection.
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Affiliation(s)
- Edwin R. Itenberg
- Division of Colon and Rectal Surgery, Henry Ford Hospital, Detroit, Michigan
| | - Ana M. Lozano
- Department of General Surgery, Henry Ford Macomb Hospital, Clinton Township, Michigan
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16
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Liu LP, Pua R, Rosario-Berrios DN, Sandvold OF, Perkins AE, Cormode DP, Shapira N, Soulen MC, Noël PB. Reproducible spectral CT thermometry with liver-mimicking phantoms for image-guided thermal ablation. Phys Med Biol 2024; 69:045009. [PMID: 38252974 PMCID: PMC10839467 DOI: 10.1088/1361-6560/ad2124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 01/02/2024] [Accepted: 01/22/2024] [Indexed: 01/24/2024]
Abstract
Objectives. Evaluate the reproducibility, temperature tolerance, and radiation dose requirements of spectral CT thermometry in tissue-mimicking phantoms to establish its utility for non-invasive temperature monitoring of thermal ablations.Methods. Three liver mimicking phantoms embedded with temperature sensors were individually scanned with a dual-layer spectral CT at different radiation dose levels during heating (35 °C-80 °C). Physical density maps were reconstructed from spectral results using varying reconstruction parameters. Thermal volumetric expansion was then measured at each temperature sensor every 5 °C in order to establish a correlation between physical density and temperature. Linear regressions were applied based on thermal volumetric expansion for each phantom, and coefficient of variation for fit parameters was calculated to characterize reproducibility of spectral CT thermometry. Additionally, temperature tolerance was determined to evaluate effects of acquisition and reconstruction parameters. The resulting minimum radiation dose to meet the clinical temperature accuracy requirement was determined for each slice thickness with and without additional denoising.Results. Thermal volumetric expansion was robustly replicated in all three phantoms, with a correlation coefficient variation of only 0.43%. Similarly, the coefficient of variation for the slope and intercept were 9.6% and 0.08%, respectively, indicating reproducibility of the spectral CT thermometry. Temperature tolerance ranged from 2 °C to 23 °C, decreasing with increased radiation dose, slice thickness, and iterative reconstruction level. To meet the clinical requirement for temperature tolerance, the minimum required radiation dose ranged from 20, 30, and 57 mGy for slice thickness of 2, 3, and 5 mm, respectively, but was reduced to 2 mGy with additional denoising.Conclusions. Spectral CT thermometry demonstrated reproducibility across three liver-mimicking phantoms and illustrated the clinical requirement for temperature tolerance can be met for different slice thicknesses. The reproducibility and temperature accuracy of spectral CT thermometry enable its clinical application for non-invasive temperature monitoring of thermal ablation.
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Affiliation(s)
- Leening P Liu
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States of America
| | - Rizza Pua
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America
| | - Derick N Rosario-Berrios
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America
- Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, United States of America
| | - Olivia F Sandvold
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States of America
| | - Amy E Perkins
- Philips Healthcare, Orange Village, OH, United States of America
| | - David P Cormode
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America
- Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States of America
| | - Nadav Shapira
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America
| | - Michael C Soulen
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America
| | - Peter B Noël
- Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States of America
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17
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Jaksic N, Modesto A, Meillan N, Bordron A, Michalet M, Riou O, Lisbona A, Huguet F. Stereotactic body radiation therapy for liver metastases in oligometastatic disease. Cancer Radiother 2024; 28:75-82. [PMID: 37865603 DOI: 10.1016/j.canrad.2023.04.008] [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: 01/30/2023] [Revised: 04/07/2023] [Accepted: 04/25/2023] [Indexed: 10/23/2023]
Abstract
Oligometastatic cancers designate cancers in which the number of metastases is less than five, corresponding to a particular biological entity whose prognosis is situated between a localized and metastatic disease. The liver is one of the main sites of metastases. When patients are not suitable for surgery, stereotactic body radiotherapy provides high local control rate, although these data come mainly from retrospective studies, with no phase III study results. The need for a high therapeutic dose (biologically effective dose greater than 100Gy) while respecting the constraints on the organs at risk, and the management of respiratory movements require expertise and sufficient technical prerequisites. The emergence of new techniques such as MRI-guided radiotherapy could further increase the effectiveness of stereotactic radiotherapy of liver metastases, and thus improve the prognosis of these oligometastatic cancers.
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Affiliation(s)
- N Jaksic
- Institut de cancérologie et radiothérapie Brétillien, 35400 Saint-Malo, France.
| | - A Modesto
- Département de radiothérapie, institut régional du cancer, 31100 Toulouse, France
| | - N Meillan
- Département de radiothérapie, centre hospitalier d'Argenteuil, 95107 Argenteuil, France
| | - A Bordron
- Département de radiothérapie, centre hospitalier universitaire de Brest, 29200 Brest, France
| | - M Michalet
- Département de radiothérapie, institut régional du cancer, 34000 Montpellier, France
| | - O Riou
- Département de radiothérapie, institut régional du cancer, 34000 Montpellier, France
| | - A Lisbona
- Département de radiothérapie, institut régional du cancer, 44800 Saint-Herblain, France
| | - F Huguet
- Service d'oncologie radiothérapie, hôpital Tenon, hôpitaux universitaires Est Parisien, Sorbonne université, 75020 Paris, France
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Tawara S, Miyazaki T, Kiyota R, Maegawa Y, Shimizu T, Yamai T, Kawai S, Inoue T, Komatsu H, Tomokuni A, Motoori M, Yakushijin T. Comparison of percutaneous ablation and hepatectomy for liver metastasis: A single center retrospective study. Cancer Med 2024; 13:e6957. [PMID: 38379325 PMCID: PMC10831916 DOI: 10.1002/cam4.6957] [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: 10/11/2023] [Revised: 12/18/2023] [Accepted: 01/12/2024] [Indexed: 02/22/2024] Open
Abstract
AIM To investigate the current treatment for liver metastasis and clarify the indications for percutaneous thermal ablation for liver metastasis. METHODS Ninety-two patients were enrolled and retrospectively analyzed. The patients underwent hepatectomy and/or percutaneous thermal ablation for liver metastases between January 2012 and December 2018. Twenty-six patients who underwent ablation treatment and seven patients who underwent both ablation and hepatectomy were included in the ablation treatment group (group A). We compared these patients with 59 patients who underwent hepatectomy only (group H). Subgroup analyses were performed between ablation (group AC) for colorectal liver metastasis and hepatectomy (group HC) for colorectal liver metastasis in 17 and 53 patients, respectively. RESULTS The percentage of liver metastases other than colorectal cancer in group A was higher than that in the group H. Maximum tumor size in group A was significantly smaller than that in group H. Similarly, the patients in group AC were significantly older and demonstrated higher total bilirubin, lower serum albumin, and lower platelet counts than those in group HC. Overall survival was poorer in the AC group than that in the HC group. However, no differences were observed at metastasis ≤2 cm in size. CONCLUSIONS Percutaneous thermal ablation was performed for many cancer types than hepatectomy. It is performed in elderly patients. We suggested that ablation for colorectal liver metastasis sized ≤2 cm is a suitable indication.
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Affiliation(s)
- Seiichi Tawara
- Department of Gastroenterology and HepatologyOsaka General Medical CenterOsakaJapan
| | - Tetsuro Miyazaki
- Department of Gastroenterology and HepatologyOsaka General Medical CenterOsakaJapan
| | - Ryosuke Kiyota
- Department of Gastroenterology and HepatologyOsaka General Medical CenterOsakaJapan
| | - Yuki Maegawa
- Department of Gastroenterology and HepatologyOsaka General Medical CenterOsakaJapan
| | - Takeshi Shimizu
- Department of Gastroenterology and HepatologyOsaka General Medical CenterOsakaJapan
| | - Takuo Yamai
- Department of Gastroenterology and HepatologyOsaka General Medical CenterOsakaJapan
| | - Shoichiro Kawai
- Department of Gastroenterology and HepatologyOsaka General Medical CenterOsakaJapan
| | - Takuya Inoue
- Department of Gastroenterology and HepatologyOsaka General Medical CenterOsakaJapan
| | - Hisateru Komatsu
- Department of Gastrointestinal SurgeryOsaka General Medical CenterOsakaJapan
| | - Akira Tomokuni
- Department of Gastrointestinal SurgeryOsaka General Medical CenterOsakaJapan
| | - Masaaki Motoori
- Department of Gastrointestinal SurgeryOsaka General Medical CenterOsakaJapan
| | - Takayuki Yakushijin
- Department of Gastroenterology and HepatologyOsaka General Medical CenterOsakaJapan
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19
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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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20
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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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21
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Naganuma H, Ishida H. Hepatocellular Carcinoma in Non-Fibrotic Liver: A Narrative Review. Diagnostics (Basel) 2023; 13:3426. [PMID: 37998562 PMCID: PMC10670297 DOI: 10.3390/diagnostics13223426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/08/2023] [Accepted: 11/09/2023] [Indexed: 11/25/2023] Open
Abstract
Hepatocellular carcinoma (HCC) in a non-fibrotic liver (F0) is considered to be rare, and there is a marked paucity of studies in the literature on this HCC type. A review of the literature shows some important clinical and tumor characteristics: (a) it occurs mainly in young female and elder male patients; (b) clinically, under normal hepatic function, alpha-fetoprotein level is often normal, and there are no risk factors; (c) associated with metabolic disease; (d) macroscopically, single large lesions are noted; and (e) microscopically, the lesions are well-differentiated and encapsulated. Radiological imaging results are straightforward, showing arterial hyperenhancement and later wash-out. The combined use of B-mode and contrast-enhanced (CE) ultrasound (US) is the most reliable and cost-effective diagnostic method. Few peri-and post-operative complications are noted and 5-year survival is not inferior to patients with HCC on fibrosis liver despite the lesion's large size. Most clinicians believe that HCC is unlikely to occur if patients have no symptoms and normal hepatic function. Although detailed clinical data are very limited, we expect that this review will help to improve the clinical management of HCC in non-fibrotic livers.
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Affiliation(s)
- Hiroko Naganuma
- Department of Gastroenterology, Yokote Municipal Hospital, Negishi-cho 5-31, Yokote City 013-8602, Japan
| | - Hideaki Ishida
- Department of Gastroenterology, Akita Red Cross Hospital, Kamikitate Saruta aza Naeshirosawa 222-1, Akita City 010-1495, Japan
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22
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Jung JM, Park IJ, Park EJ, Son GM, on behalf of Image-Guided Surgery Study Group of Korean Society of Coloproctology. Fluorescence-guided colorectal surgery: applications, clinical results, and protocols. Ann Surg Treat Res 2023; 105:252-263. [PMID: 38023438 PMCID: PMC10648611 DOI: 10.4174/astr.2023.105.5.252] [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: 09/29/2023] [Revised: 10/09/2023] [Accepted: 10/10/2023] [Indexed: 12/01/2023] Open
Abstract
In recent years, the rise of minimally invasive surgery has driven the development of surgical devices. Indocyanine green (ICG) fluorescence imaging is receiving increased attention in colorectal surgery for improved intraoperative visualization and decision-making. ICG, approved by the U.S. Food and Drug Administration in 1959, rapidly binds to plasma proteins and is primarily intravascular. ICG absorption of near-infrared light (750-800 nm) and emission as fluorescence (830 nm) when bound to tissue proteins enhances deep tissue visualization. Applications include assessing anastomotic perfusion, identifying sentinel lymph nodes, and detecting colorectal cancer metastasis. However, standardized protocols and research on clinical outcomes remain limited. This study explores ICG's role, advantages, disadvantages, and potential clinical impact in colorectal surgery.
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Affiliation(s)
- Jin-Min Jung
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In Ja Park
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Jung Park
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Gyung Mo Son
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
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23
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Turner MA, Amirfakhri S, Nishino H, Neel NC, Hosseini M, Cox KE, Lwin TM, Li L, Hong T, Sherman A, Shively JE, Hoffman RM, Yazaki PJ, Bouvet M. PEGylated Fluorescent Anti-carcinoembryonic Antigen Antibody Labels Colorectal Cancer Tumors in Orthotopic Mouse Models. J Surg Res 2023; 291:596-602. [PMID: 37540977 DOI: 10.1016/j.jss.2023.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 05/29/2023] [Accepted: 06/19/2023] [Indexed: 08/06/2023]
Abstract
INTRODUCTION Colorectal cancer (CRC) patients often develop liver metastasis. However, curative resection of liver metastasis is not always possible due to poor visualization of tumor margins. The present study reports the characterization of a humanized anti-carcinoembryonic antigen monoclonal antibody conjugated to a PEGylated near-infrared dye, that targets and brightly labels human CRC tumors in metastatic orthotopic mouse models. METHODS The hT84.66-M5A (M5A) monoclonal antibody was conjugated with a polyethylene glycol (PEG) chain that incorporated a near infrared (NIR) IR800 dye to establish M5A-IR800 Sidewinder (M5A-IR800-SW). Nude mice with CRC orthotopic primary tumors and liver metastasis both developed from a human CRC cell line, were injected with M5A-IR800-SW and imaged with the Pearl Trilogy Imaging System. RESULTS M5A-IR800-SW targeted and brightly labeled CRC tumors, both in primary-tumor and liver-metastasis models. M5A-IR800-SW at 75 μg exhibited highly-specific tumor labeling in a primary-tumor orthotopic model with a median tumor-to-background ratio of 9.77 and in a liver-metastasis orthotopic model with a median tumor-to-background ratio of 7.23 at 96 h. The precise labeling of the liver metastasis was due to lack of hepatic accumulation of M5A-IR800-SW in the liver. CONCLUSIONS M5A-IR800-SW provided bright and targeted NIR images of human CRC in orthotopic primary-tumor and liver-metastasis mouse models. The results of the present study suggest the clinical potential of M5A-IR800-SW for fluorescence-guided surgery including metastasectomies for CRC. The lack of hepatic NIR signal is of critical importance to allow for precise labeling of liver tumors.
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Affiliation(s)
- Michael A Turner
- Department of Surgery, School of Medicine, University of California San Diego, La Jolla, California; VA San Diego Healthcare System, La Jolla, California
| | - Siamak Amirfakhri
- Department of Surgery, School of Medicine, University of California San Diego, La Jolla, California; VA San Diego Healthcare System, La Jolla, California
| | - Hiroto Nishino
- Department of Surgery, School of Medicine, University of California San Diego, La Jolla, California; VA San Diego Healthcare System, La Jolla, California
| | - Nicholas C Neel
- Department of Surgery, School of Medicine, University of California San Diego, La Jolla, California; School of Medicine, University of California San Diego, La Jolla, California
| | - Mojgan Hosseini
- Department of Pathology, School of Medicine, University of California San Diego, La Jolla, California
| | - Kristin E Cox
- Department of Surgery, School of Medicine, University of California San Diego, La Jolla, California; VA San Diego Healthcare System, La Jolla, California
| | - Thinzar M Lwin
- Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, California
| | - Lin Li
- Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, California
| | - Teresa Hong
- Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, California
| | - Anakim Sherman
- Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, California
| | - John E Shively
- Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, California
| | - Robert M Hoffman
- Department of Surgery, School of Medicine, University of California San Diego, La Jolla, California; VA San Diego Healthcare System, La Jolla, California; AntiCancer, Inc., San Diego, California
| | - Paul J Yazaki
- Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, California
| | - Michael Bouvet
- Department of Surgery, School of Medicine, University of California San Diego, La Jolla, California; VA San Diego Healthcare System, La Jolla, California.
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24
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Hallemeier CL, Sharma N, Anker C, Selfridge JE, Lee P, Jabbour S, Williams V, Liu D, Kennedy T, Jethwa KR, Kim E, Kumar R, Small W, Tchelebi L, Russo S. American Radium Society Appropriate Use Criteria for the use of liver-directed therapies for nonsurgical management of liver metastases: Systematic review and guidelines. Cancer 2023; 129:3193-3212. [PMID: 37409678 DOI: 10.1002/cncr.34931] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 05/09/2023] [Accepted: 05/24/2023] [Indexed: 07/07/2023]
Abstract
The liver is a common site of cancer metastases. Systemic therapy is widely accepted as the standard treatment for liver metastases (LM), although select patients with liver oligometastases may be candidates for potentially curative liver resection. Recent data support the role of nonsurgical local therapies such as ablation, external beam radiotherapy, embolization, and hepatic artery infusion therapy for management of LM. Additionally, for patients with advanced, symptomatic LM, local therapies may provide palliative benefit. The American Radium Society gastrointestinal expert panel, including members representing radiation oncology, interventional radiology, surgical oncology, and medical oncology, performed a systemic review and developed Appropriate Use Criteria for the use of nonsurgical local therapies for LM. Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology was used. These studies were used to inform the expert panel, which then rated the appropriateness of various treatments in seven representative clinical scenarios through a well-established consensus methodology (modified Delphi). A summary of recommendations is outlined to guide practitioners on the use of nonsurgical local therapies for patients with LM.
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Affiliation(s)
| | - Navesh Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, York, Pennsylvania, USA
| | - Christopher Anker
- Division of Radiation Oncology, University of Vermont Larner College of Medicine, Burlington, Vermont, USA
| | - J Eva Selfridge
- Department of Medical Oncology, University Hospitals Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Percy Lee
- Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, California, USA
| | - Salma Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, New Jersey, USA
| | - Vonetta Williams
- Department of Radiation Oncology, Memorial Sloan Kettering, New York, New York, USA
| | - David Liu
- Department of Radiology, University of British Columbia, Vancouver, Birth Columbia, Canada
| | - Timothy Kennedy
- Department of Surgery, Rutgers Cancer Institute, New Brunswick, New Jersey, USA
| | - Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Ed Kim
- Department of Radiation Oncology, University of Washington, Seattle, Washington, USA
| | - Rachit Kumar
- Department of Radiation Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Sibley Memorial Hospital, Washington, District of Columbia, USA
| | - William Small
- Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, Illinois, USA
| | - Leila Tchelebi
- Department of Radiation Oncology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
| | - Suzanne Russo
- Department of Radiation Oncology, University Hospitals Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
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Liu LP, Pua R, Rosario-Berrios DN, Sandvold OF, Perkins AE, Cormode DP, Shapira N, Soulen MC, Noël PB. Reproducible spectral CT thermometry with liver-mimicking phantoms for image-guided thermal ablation. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.10.04.23296423. [PMID: 37873236 PMCID: PMC10593007 DOI: 10.1101/2023.10.04.23296423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2023]
Abstract
Objectives Evaluate the reproducibility, temperature sensitivity, and radiation dose requirements of spectral CT thermometry in tissue-mimicking phantoms to establish its utility for non-invasive temperature monitoring of thermal ablations. Materials and Methods Three liver mimicking phantoms embedded with temperature sensors were individually scanned with a dual-layer spectral CT at different radiation dose levels during heating and cooling (35 to 80 °C). Physical density maps were reconstructed from spectral results using a range of reconstruction parameters. Thermal volumetric expansion was then measured at each temperature sensor every 5°C in order to establish a correlation between physical density and temperature. Linear regressions were applied based on thermal volumetric expansion for each phantom, and coefficient of variation for fit parameters was calculated to characterize reproducibility of spectral CT thermometry. Additionally, temperature sensitivity was determined to evaluate the effect of acquisition parameters, reconstruction parameters, and image denoising. The resulting minimum radiation dose to meet the clinical temperature sensitivity requirement was determined for each slice thickness, both with and without additional denoising. Results Thermal volumetric expansion was robustly replicated in all three phantoms, with a correlation coefficient variation of only 0.43%. Similarly, the coefficient of variation for the slope and intercept were 9.6% and 0.08%, respectively, indicating reproducibility of the spectral CT thermometry. Temperature sensitivity ranged from 2 to 23 °C, decreasing with increased radiation dose, slice thickness, and iterative reconstruction level. To meet the clinical requirement for temperature sensitivity, the minimum required radiation dose ranged from 20, 30, and 57 mGy for slice thickness of 2, 3, and 5 mm, respectively, but was reduced to 2 mGy with additional denoising. Conclusions Spectral CT thermometry demonstrated reproducibility across three liver-mimicking phantoms and illustrated the clinical requirement for temperature sensitivity can be met for different slice thicknesses. Moreover, additional denoising enables the use of more clinically relevant radiation doses, facilitating the clinical translation of spectral CT thermometry. The reproducibility and temperature accuracy of spectral CT thermometry enable its clinical application for non-invasive temperature monitoring of thermal ablation.
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Ghazanfar MA, Abdelhamid A, Aldrighetti L, Sturesson C, Takemura N, Truant S, Fiorentini G, Teh C, Alikhanov R, Ahmed I, Hammond J, Ferrero A, Silva M, Pawlik T, Jones R, Bekheit M. The dilemma of the disappearing colorectal liver metastases: defining international trends in management. HPB (Oxford) 2023; 25:446-453. [PMID: 36775699 DOI: 10.1016/j.hpb.2023.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 12/18/2022] [Accepted: 01/10/2023] [Indexed: 02/14/2023]
Abstract
OBJECTIVE This survey sought to appraise the degree of consistency in the management of disappeared colorectal liver metastases (dCRLM) among liver surgeons in different countries. BACKGROUND Colorectal liver metastases (CRLM) account for half of the deaths secondary to colorectal cancer. Due to the high utilization of chemotherapy before surgery, some or all CRLM can disappear (dCRLM) but management of dCRLMs remains unclear. METHODS Seven simulated scenarios of dCRLM were presented to experienced liver surgeons using an online platform. Treatment decisions were submitted and analysed using the multi-rater kappa method. The effect of the experience, complexity of scenarios, and location and number of dCRLM on treatment decision were analysed. RESULTS Sixty-seven liver surgeons from 25 countries completed the survey. There was no agreement about the therapeutic strategies of dCRLM in all scenarios (kappa 0.12, IQR 0.20-0.32). In scenarios with lower difficulty scores, surgeons tended to offer surgical resection for dCRLM alongside the visible CRLM (vCRLM), however, with poor agreement (kappa 0.32, IQR 0.19-0.51). No agreement was seen for clinical scenario in which all CRLM lesions disappeared (kappa 0.20). CONCLUSION There are clear inconsistencies in the management decisions of dCRLM. Better evidence is required to define optimal management strategies.
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Affiliation(s)
- Mudassar A Ghazanfar
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK
| | - Amir Abdelhamid
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, San Raffaele Hospital, Milan, Italy
| | - Christian Sturesson
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Nobuyuki Takemura
- Department of Surgery, National Center for Global Health and Medicine (NCGM), Tokyo, Japan
| | - Stephanie Truant
- Department of Surgery, Centre Hospitalier Régional Universitaire de Lille: Lille, Nord-Pas-de-Calais, Lille, France
| | - Guido Fiorentini
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic Rochester, Rochester, USA
| | - Catherine Teh
- Department of Surgery, Makati Medical Center, Makati Metro Manila, Philippines; Department of Surgery, National Kidney & Transplant Institute, Quezon, Philippines; Department of Surgery, St Luke's Medical Center, Quezon, Philippines
| | - Ruslan Alikhanov
- Moscow Clinical Scientific Center, Department of Liver and Pancreatic Surgery and Transplantation, Russia
| | - Irfan Ahmed
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK
| | - John Hammond
- Department of HPB and Transplantation, Freeman Hospital, Newcastle Upon Tyne, Newcastle, UK
| | | | - Michael Silva
- Department of Surgery, Oxford University Hospital, Oxford, UK
| | - Timothy Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Ohio, USA
| | - Robert Jones
- Northwest Hepatobiliary Unit, Department of Surgery, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Mohamed Bekheit
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK; HPB Integrated Center of Care, Elite Integrated Centers of Excellence, Alexandria, Egypt.
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Deep learning model based on contrast-enhanced ultrasound for predicting early recurrence after thermal ablation of colorectal cancer liver metastasis. Eur Radiol 2023; 33:1895-1905. [PMID: 36418624 DOI: 10.1007/s00330-022-09203-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 09/19/2022] [Accepted: 09/25/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVES To develop and validate a deep learning (DL) model based on quantitative analysis of contrast-enhanced ultrasound (CEUS) images that predicts early recurrence (ER) after thermal ablation (TA) of colorectal cancer liver metastasis (CRLM). METHODS Between January 2010 and May 2019, a total of 207 consecutive patients with CRLM with 13,248 slice images at three dynamic phases who received CEUS within 2 weeks before TA were retrospectively enrolled in two centres (153 for the training cohort (TC), 32 for the internal test cohort (ITC), and 22 for the external test cohort (ETC)). Clinical and CEUS data were used to develop and validate the clinical model, DL model, and DL combining with clinical (DL-C) model to predict ER after TA. The performance of these models was compared by the receiver operating characteristic curve (ROC) with the DeLong test. RESULTS After a median follow-up of 56 months, 49% (99/207) of patients experienced ER. Three key clinical features (preoperative chemotherapy (PC), lymph node metastasis of the primary colorectal cancer (LMPCC), and T stage) were used to develop the clinical model. The DL model yielded better performance than the clinical model in the ETC (AUC: 0.67 for the clinical model, 0.76 for the DL model). The DL-C model significantly outperformed the clinical model and DL model (AUC: 0.78 for the DL-C model in the ETC; both, p < 0.001). CONCLUSIONS The model based on CEUS can achieve satisfactory prediction and assist physicians during the therapeutic decision-making process in clinical practice. KEY POINTS • This is an exploratory study in which ablation-related contrast-enhanced ultrasound (CEUS) data from consecutive patients with colorectal cancer liver metastasis (CRLM) were collected simultaneously at multiple institutions. • The deep learning combining with clinical (DL-C) model provided desirable performance for the prediction of early recurrence (ER) after thermal ablation (TA). • The DL-C model based on CEUS provides guidance for TA indication selection and making therapeutic decisions.
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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: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [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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Karam E, Tabutin M, Mastier C, Crignis LD, Peyrat P, Martin V, Badon F, Muller X, Meeus P, Rivoire M, Dupré A. Curative-intent treatment of pulmonary metastases from colorectal cancer: A comparison between imaging-guided thermal ablation and surgery. J Surg Oncol 2023; 127:183-191. [PMID: 36169242 DOI: 10.1002/jso.27108] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 08/19/2022] [Accepted: 09/16/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Pulmonary metastases (PM) are the most frequent extra-abdominal metastases from colorectal cancer. Lung resection and imaging-guided thermal ablation (IGTA) are used as curative-intent treatment. We compared the outcomes of patients with PM, treated with resection or ablation. METHODS We retrospectively analyzed data from patients who underwent surgery or IGTA for colorectal PM between April 2011 and November 2020. Surgery was performed for peripheral PM and IGTA for deep-located PM not in contact with major vessels. Patients who had both procedures were excluded. Patients were compared using propensity score matching (PSM) analysis, stratified according to number, size, and unilaterality of PM. RESULTS One hundred and fourty-six patients were included, 65 (44.5%) underwent surgery and 81 (55.5%) underwent IGTA. After PSM analysis, each group contained 46 patients. IGTA patients had a lower morbidity rate (13.1% vs. 15.2%, p = 0.028) and a shorter length of stay (5.13 vs. 2.63 days, p < 0.001). Oncological outcomes were similar in both groups with 5-year OS of 80% and 5-year progression-free survival (PFS) of 30% (p = 0.657 and p = 0.504, respectively) with similar recurrence patterns. CONCLUSION Lung resection and IGTA seem to have similar oncologic outcomes for both OS and PFS. IGTA could be an alternative effective treatment for small PM, whenever technically feasible.
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Affiliation(s)
- Elias Karam
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Mayeul Tabutin
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | | | - Lucas De Crignis
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Patrice Peyrat
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Valentine Martin
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Floriane Badon
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Xavier Muller
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Pierre Meeus
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Michel Rivoire
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France.,Univ Lyon, Université Lyon 1, Centre Léon Bérard, INSERM, LabTAU, Lyon, France
| | - Aurélien Dupré
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France.,Univ Lyon, Université Lyon 1, Centre Léon Bérard, INSERM, LabTAU, Lyon, France
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Yusupov TA, Kostylieva NM. Radiofrequency ablation in treatment of hepatic metastases of colorectal cancer. KLINICHESKAIA KHIRURGIIA 2022. [DOI: 10.26779/2522-1396.2022.7-8.62] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
Radiofrequency ablation in treatment of hepatic metastases of colorectal cancer
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Ratnakumaran R, McDonald F. The Management of Oligometastases in Non-small Cell Lung Cancer - is Stereotactic Ablative Radiotherapy now Standard of Care? Clin Oncol (R Coll Radiol) 2022; 34:753-760. [PMID: 36117126 DOI: 10.1016/j.clon.2022.08.033] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/12/2022] [Accepted: 08/22/2022] [Indexed: 01/31/2023]
Abstract
Oligometastatic non-small cell lung cancer encompasses a number of distinct clinical scenarios with a pattern of limited tumour burden on imaging. Delivering local ablative therapy to individual metastatic lesions may assist in disease modification and contribute to improved outcomes. We review the published randomised clinical trials that support the implementation of stereotactic ablative radiotherapy as a standard of care in certain oligometastatic non-small cell lung cancer clinical scenarios, and highlight the current knowledge gaps and areas of ongoing research.
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Affiliation(s)
- R Ratnakumaran
- The Lung Unit, Royal Marsden NHS Foundation Trust, London, UK; Division of Radiotherapy and Imaging, Institute of Cancer Research, London, UK.
| | - F McDonald
- The Lung Unit, Royal Marsden NHS Foundation Trust, London, UK; Division of Radiotherapy and Imaging, Institute of Cancer Research, London, UK
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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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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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Riesco-Martinez MC, Modrego A, Espinosa-Olarte P, La Salvia A, Garcia-Carbonero R. Perioperative Chemotherapy for Liver Metastasis of Colorectal Cancer: Lessons Learned and Future Perspectives. Curr Treat Options Oncol 2022; 23:1320-1337. [PMID: 35980520 DOI: 10.1007/s11864-022-01008-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2022] [Indexed: 11/27/2022]
Abstract
OPINION STATEMENT Colorectal cancer (CRC) is a major public health problem and the 2nd leading-cause of cancer-related death worldwide. Around 30% of patients present with metastatic disease and 50% of those with early disease will eventually relapse. The metastatic spread occurs mainly to the liver, which is the exclusive site in 30-40% of the cases. Surgery is the main curative option for liver recurrence, but only one out of five patients are eligible for resection. Moreover, even if surgery is feasible, recurrence rate is high, occurring in up to 75% of patients. Therefore, additional treatment to improve these disappointing outcomes has been sought. Adjuvant and perioperative chemotherapy aim to eradicate early micrometastatic disease, decreasing recurrence rates, and improving survival outcomes. Different chemotherapy regimens, mainly extrapolated from the adjuvant experience, have showed conflicting results, with improvements in disease free but not in overall survival. The addition of targeted therapies to chemotherapy has improved response rates and resectability when administered preoperatively, but did not have an impact on survival in the adjuvant setting. There is a need to critically synthetize the available evidence on perioperative and conversion therapy from the past years, and appraise areas of current research and potential future directions.
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Affiliation(s)
- Maria C Riesco-Martinez
- Medical Oncology Department, Hospital Universitario 12 de Octubre, imas 12, UCM, Avda Cordoba km 5.4, 28041, Madrid, Spain
| | - Andrea Modrego
- Medical Oncology Department, Hospital Universitario 12 de Octubre, imas 12, UCM, Avda Cordoba km 5.4, 28041, Madrid, Spain
| | - Paula Espinosa-Olarte
- Medical Oncology Department, Hospital Universitario 12 de Octubre, imas 12, UCM, Avda Cordoba km 5.4, 28041, Madrid, Spain
| | - Anna La Salvia
- Medical Oncology Department, Hospital Universitario 12 de Octubre, imas 12, UCM, Avda Cordoba km 5.4, 28041, Madrid, Spain
| | - Rocio Garcia-Carbonero
- Medical Oncology Department, Hospital Universitario 12 de Octubre, imas 12, UCM, Avda Cordoba km 5.4, 28041, Madrid, Spain.
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Jethwa KR, Jin Z, Hallemeier CL. A Critical Review of the Role of Local Therapy for Oligometastatic Gastrointestinal Cancer. Int J Radiat Oncol Biol Phys 2022; 114:780-791. [DOI: 10.1016/j.ijrobp.2022.06.084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 05/20/2022] [Accepted: 06/22/2022] [Indexed: 10/31/2022]
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Ma WJ, Chen Y, Peng JH, Tang C, Zhang L, Liu M, Hu S, Xu H, Tan H, Gu Y, Pan ZZ, Chen G, Zhou ZG, Zhang RX. Stage IV colon cancer patients without DENND2D expression benefit more from neoadjuvant chemotherapy. Cell Death Dis 2022; 13:439. [PMID: 35523764 PMCID: PMC9076603 DOI: 10.1038/s41419-022-04885-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 04/21/2022] [Accepted: 04/25/2022] [Indexed: 12/14/2022]
Abstract
According to the EPOC study, chemotherapy could improve 5-year disease-free survival of stage IV colon cancer patients by 8.1%. However, more molecular biomarkers are required to identify patients who need neoadjuvant chemotherapy. DENND2D expression was evaluated by immunohistochemistry in 181 stage IV colon cancer patients. The prognosis was better for patients with DENND2D expression than patients without DENND2D expression (5-year overall survival [OS]: 42% vs. 12%, p = 0.038; 5-year disease-free survival: 20% vs. 10%, p = 0.001). Subgroup analysis of the DENND2D-negative group showed that patients treated with neoadjuvant chemotherapy achieved longer OS than patients without neoadjuvant chemotherapy (RR = 0.179; 95% CI = 0.054-0.598; p = 0.003). DENND2D suppressed CRC proliferation in vitro and in vivo. Downregulation of DENND2D also promoted metastasis to distant organs in vivo. Mechanistically, DENND2D suppressed the MAPK pathway in CRC. Colon cancer patients who were DENND2D negative always showed a worse prognosis and were more likely to benefit from neoadjuvant chemotherapy. DENND2D may be a new prognostic factor and a predictor of the need for neoadjuvant chemotherapy in stage IV colon cancer.
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Affiliation(s)
- Wen-juan Ma
- grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in South China, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Intensive Care Unit Department, Sun Yat-Sen University Cancer Centre, Guangzhou, 510060 Guangdong Province People’s Republic of China
| | - Yukun Chen
- grid.12981.330000 0001 2360 039XZhongshan School of Medicine, Sun Yat-Sen University, No. 74, Zhongshan Rd. 2, Guangzhou, 510080 Guangdong Province People’s Republic of China
| | - Jian-hong Peng
- grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in South China, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Department of Colorectal Surgery, Sun Yat-Sen University Cancer Centre, Guangzhou, 510060 Guangdong Province People’s Republic of China
| | - Chaoming Tang
- grid.410737.60000 0000 8653 1072The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, QingYuan, Guangdong Province People’s Republic of China
| | - Ling Zhang
- grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in South China, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Department of Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province People’s Republic of China
| | - Min Liu
- grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in South China, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province People’s Republic of China
| | - Shanshan Hu
- grid.430387.b0000 0004 1936 8796Department of Statistics, Rutgers University, New Brunswick, NJ 08854 USA
| | - Haineng Xu
- grid.25879.310000 0004 1936 8972Ovarian Cancer Research Center, Division of Gynecology Oncology, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104 USA
| | - Hua Tan
- grid.267308.80000 0000 9206 2401School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030 USA
| | - Yangkui Gu
- grid.488530.20000 0004 1803 6191Intervention Department, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province People’s Republic of China
| | - Zhi-zhong Pan
- grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in South China, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Department of Colorectal Surgery, Sun Yat-Sen University Cancer Centre, Guangzhou, 510060 Guangdong Province People’s Republic of China
| | - Gong Chen
- grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in South China, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Department of Colorectal Surgery, Sun Yat-Sen University Cancer Centre, Guangzhou, 510060 Guangdong Province People’s Republic of China
| | - Zhong-guo Zhou
- grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in South China, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province People’s Republic of China
| | - Rong-xin Zhang
- grid.12981.330000 0001 2360 039XState Key Laboratory of Oncology in South China, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060 Guangdong Province People’s Republic of China ,grid.488530.20000 0004 1803 6191Department of Colorectal Surgery, Sun Yat-Sen University Cancer Centre, Guangzhou, 510060 Guangdong Province People’s Republic of China
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Scafa D, Muedder T, Holz JA, Koch D, Nour Y, Garbe S, Gonzalez-Carmona MA, Feldmann G, Vilz TO, Köksal M, Giordano FA, Schmeel LC, Sarria GR. Dosimetric Comparison of Intraoperative Radiotherapy and SRS for Liver Metastases. Front Oncol 2021; 11:767468. [PMID: 34926271 PMCID: PMC8674179 DOI: 10.3389/fonc.2021.767468] [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: 08/30/2021] [Accepted: 11/11/2021] [Indexed: 11/30/2022] Open
Abstract
Purpose/Objectives To perform a dosimetric comparison between kilovoltage intraoperative radiotherapy (IORT) and stereotactic radiosurgery (SRS) simulating both deep-inspiration breath-hold (DIBH) and free-breathing (FB) modalities for patients with liver metastases. Methods/Materials Diagnostic computed tomographies (CT) of patients carrying one or two lesions <4 cm and who underwent surgery were retrospectively screened and randomly selected for the study. For DIBH-SRS, a gross target volume (GTV) plus planning target volume (PTV) were delineated. For FB-SRS, a GTV plus an internal target volume (ITV) and PTV were defined. Accounting for the maximal GTV diameters, a modified GTV (GTV-IORT) was expanded circumferentially to simulate a resection cavity. The best suitable round-applicator size was thereafter selected. All treatment plans were calculated homogeneously to deliver 40 Gy. Doses delivered to organs at risk (OAR) and target volumes were compared for IORT vs. both SRS modalities. Results Eight patients encompassing 10 lesions were included in the study. The mean liver volume was 2,050.97 cm3 (SD, 650.82), and the mean GTV volume was 12.23 cm3 (SD, 12.62). As for target structures, GTV-IORT [19.44 cm3 (SD, 17.26)] were significantly smaller than both PTV DIBH-SRS [30.74 cm3 (SD, 24.64), p = 0.002] and PTV FB-SRS [75.82 cm3 (SD, 45.65), p = 0.002]. The median applicator size was 3 cm (1.5–4.5), and the mean IORT simulated delivery time was 45.45 min (SD, 19.88). All constraints were met in all modalities. Liver V9.1 showed significantly smaller volumes with IORT [63.39 cm3 (SD, 35.67)] when compared to DIBH-SRS [150.12 cm3 (SD, 81.43), p = 0.002] or FB-SRS [306.13 cm3 (SD, 128.75), p = 0.002]. No other statistical or dosimetrically relevant difference was observed for stomach, spinal cord, or biliary tract. Mean IORT D90 was 85.3% (SD, 6.05), whereas D95 for DIBH-SRS and FB-SRS were 99.03% (SD, 1.71; p = 0.042) and 98.04% (SD, 3.46; p = 0.036), respectively. Conclusion Kilovoltage IORT bears the potential as novel add-on treatment for resectable liver metastases, significantly reducing healthy liver exposure to radiation in comparison to SRS. Prospective clinical evidence is required to confirm this hypothesis.
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Affiliation(s)
- Davide Scafa
- Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany
| | - Thomas Muedder
- Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany
| | - Jasmin A Holz
- Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany
| | - David Koch
- Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany
| | - Younéss Nour
- Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany
| | - Stephan Garbe
- Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany
| | | | - Georg Feldmann
- Department of Internal Medicine III, University Hospital Bonn, Bonn, Germany
| | - Tim O Vilz
- Department of Surgery, University Hospital Bonn, Bonn, Germany
| | - Mümtaz Köksal
- Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany
| | - Frank A Giordano
- Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany
| | | | - Gustavo R Sarria
- Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany
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Acciuffi S, Meyer F, Bauschke A, Croner R, Settmacher U, Altendorf-Hofmann A. Solitary colorectal liver metastasis: overview of treatment strategies and role of prognostic factors. J Cancer Res Clin Oncol 2021; 148:657-665. [PMID: 34914005 PMCID: PMC8881245 DOI: 10.1007/s00432-021-03880-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 12/07/2021] [Indexed: 12/09/2022]
Abstract
The following is an overview of the treatment strategies and the prognostic factors to consider in the therapeutic choice of patients characterized by solitary colorectal liver metastasis. Liver resection is the only potential curative option; nevertheless, only 25% of the patients are considered to be eligible for surgery. To expand the potentially resectable pool of patients, surgeons developed multidisciplinary techniques like portal vein embolization, two-stage hepatectomy or associating liver partition and portal vein ligation for staged hepatectomy. Moreover, mini-invasive surgery is gaining support, since it offers lower post-operative complication rates and shorter hospital stay with no differences in long-term outcomes. In case of unresectable disease, various techniques of local ablation have been developed. Radiofrequency ablation is the most commonly used form of thermal ablation: it is widely used for unresectable patients and is trying to find its role in patients with small resectable metastasis. The identification of prognostic factors is crucial in the choice of the treatment strategy. Previous works that focused on patients with solitary colorectal liver metastasis obtained trustable negative predictive factors such as presence of lymph-node metastasis in the primary tumour, synchronous metastasis, R status, right-sided primary colon tumor, and additional presence of extrahepatic tumour lesion. Even the time factor could turn into a predictor of tumour biology as well as further clinical course, and could be helpful to discern patients with worse prognosis.
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Affiliation(s)
- S Acciuffi
- Department of General, Abdominal and Vascular Surgery, University Hospital, Leipziger Str. 44, 39120, Magdeburg, Germany
| | - F Meyer
- Department of General, Abdominal and Vascular Surgery, University Hospital, Leipziger Str. 44, 39120, Magdeburg, Germany
| | - A Bauschke
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - R Croner
- Department of General, Abdominal and Vascular Surgery, University Hospital, Leipziger Str. 44, 39120, Magdeburg, Germany
| | - U Settmacher
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - A Altendorf-Hofmann
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany.
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The Role of Ablative Radiotherapy to Liver Oligometastases from Colorectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2021. [DOI: 10.1007/s11888-021-00472-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Abstract
Purpose of Review
This review describes recent data supporting locoregional ablative radiation in the treatment of oligometastatic colorectal cancer liver metastases.
Recent Findings
Stereotactic body radiotherapy (SBRT) demonstrates high rates of local control in colorectal cancer liver metastases when a biologically equivalent dose of > 100 Gy is delivered. Future innovations to improve the efficacy of SBRT include MRI-guided radiotherapy (MRgRT) to enhance target accuracy, systemic immune activation to treat extrahepatic disease, and genomic customization. Selective internal radiotherapy (SIRT) with y-90 is an intra-arterial therapy that delivers high doses to liver metastases internally which has shown to increase liver disease control in phase 3 trials. Advancements in transarterial radioembolization (TARE) dosimetry could improve local control and decrease toxicity.
Summary
SBRT and SIRT are both promising options in treating unresectable metastatic colorectal cancer liver metastases. Identification of oligometastatic patients who receive long-term disease control from either therapy is essential. Future advancements focusing on improving radiation design and customization could further improve efficacy and toxicity.
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Chansangrat J, Keeratibharat N. Portal vein embolization: rationale, techniques, outcomes and novel strategies. Hepat Oncol 2021; 8:HEP42. [PMID: 34765107 PMCID: PMC8577518 DOI: 10.2217/hep-2021-0006] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 09/08/2021] [Indexed: 12/14/2022] Open
Abstract
The incidence of liver cancer has grown in the past decade, with 905,677 new cases and 830,180 deaths in 2020. According to the highest annual fatality ratio, liver cancer is the third-leading cause of cancer-related deaths worldwide. Surgical resection is the mainstay treatment for long-term survival. However, only 25% of patients are surgical candidates. Recent surgical concepts, techniques and multidisciplinary management were developed, including interventional radiology procedures that improve the management algorithm, expand the indications and limit dropouts from curative treatment. This review summarizes up-to-date information on interventional radiology in the management of liver tumors.
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Affiliation(s)
- Jirapa Chansangrat
- School of Radiology, Institute of Medicine, Suranaree University of Technology, 30000, Thailand
| | - Nattawut Keeratibharat
- School of Surgery, Institute of Medicine, Suranaree University of Technology, 30000, Thailand
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Radiation Therapy in Metastatic Soft Tissue Sarcoma: From Palliation to Ablation. Cancers (Basel) 2021; 13:cancers13194775. [PMID: 34638260 PMCID: PMC8508247 DOI: 10.3390/cancers13194775] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/17/2021] [Accepted: 09/20/2021] [Indexed: 12/20/2022] Open
Abstract
Simple Summary In the United States, over 13,000 patients are diagnosed with soft tissue sarcoma annually leading to over 5000 deaths per year despite aggressive treatments including radiotherapy, surgery, and chemotherapy. Although the majority of patients present with localized disease, unfortunately many will develop metastatic disease, which is generally not curable. There is growing evidence that local ablative therapies may be beneficial in patients with a variety of metastatic malignancies. In this review article, we explore the evolving role of radiotherapy in patients with metastatic soft tissue sarcoma. In particular, we review the growing role of ablative radiotherapy for oligometastatic disease, local control of the primary site, and palliation. Abstract The management of patients with metastatic cancer is rapidly changing. Historically, radiotherapy was utilized for the treatment of localized disease or for palliation. While systemic therapy remains the mainstay of management for patients with metastatic cancer, radiotherapy is becoming increasingly important not only to palliate symptoms, but also to ablate oligometastatic or oligoprogressive disease and improve local control in the primary site. There is emerging evidence in multiple solid malignancies that patients with low volume metastatic disease that undergo local ablative therapy to metastatic sites may have improved progression free survival and potentially overall survival. In addition, there is increasing evidence that select patients with metastatic disease may benefit from aggressive treatment of the primary site. Patients with metastatic soft tissue sarcoma have a poor overall prognosis. However, there may be opportunities in patients with low volume metastatic soft tissue sarcoma to improve outcomes with local therapy including surgery, ablation, embolization, and radiation therapy. Stereotactic body radiation therapy (SBRT) offers a safe, convenient, precise, and non-invasive option for ablation of sites of metastases. In this review article, we explore the limited yet evolving role of radiotherapy to metastatic and primary sites for local control and palliation, particularly in the oligometastatic setting.
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Coffman AR, Sufficool DC, Kang JI, Hsueh CT, Swenson S, McGee PQ, Nagaraj G, Patyal B, Reeves ME, Slater JD, Yang GY. Proton stereotactic body radiation therapy for liver metastases-results of 5-year experience for 81 hepatic lesions. J Gastrointest Oncol 2021; 12:1753-1760. [PMID: 34532125 DOI: 10.21037/jgo-20-424] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 02/01/2021] [Indexed: 12/11/2022] Open
Abstract
Background To report on our institutional experience using Proton stereotactic body radiation therapy (SBRT) for patients with liver metastases. Methods All patients with liver metastases treated with Proton SBRT between September 2012 and December 2017 were retrospectively analyzed. Local control (LC) and overall survival (OS) were estimated using the Kaplan-Meier method calculated from the time of completion of Proton SBRT. LC was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results Forty-six patients with 81 lesions were treated with Proton SBRT. The median age was 65.5 years old (range, 33-86 years) and the median follow up was 15 months (range, 1-54 months). The median size of the gross tumor volume (GTV) was 2.5 cm (range, 0.7-8.9 cm). Two or more lesions were treated in 56.5% of patients, with one patient receiving treatment to a total of five lesions. There were 37 lesions treated with a biologically effective dose (BED) ≤60, 9 lesions with a BED of 61-80, 22 lesions with a BED of 81-100, and 13 lesions with a BED >100. The 1-year and 2-year LC for all lesions was 92.5% (95% CI, 82.7% to 96.8%). The grade 1 and grade 2 toxicity rates were 37% and 6.5%, respectively. There were no grade 3 or higher toxicities and no cases of radiation-induced liver disease (RILD). Conclusions Proton SBRT for the treatment of liver metastases has promising LC rates with the ability to safely treat multiple liver metastases. Accrual continues for our phase II trial treating liver metastases with Proton SBRT to 60 GyE (Gray equivalent) in 3 fractions.
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Affiliation(s)
- Alex R Coffman
- Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Daniel C Sufficool
- Department of Radiation Oncology, Kettering Health Network, Kettering, OH, USA
| | - Joseph I Kang
- Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Chung-Tsen Hsueh
- Department of Medical Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Sasha Swenson
- Loma Linda University School of Medicine, Loma Linda, CA, USA
| | - Patrick Q McGee
- Loma Linda University School of Medicine, Loma Linda, CA, USA
| | - Gayathri Nagaraj
- Department of Medical Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Baldev Patyal
- Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Mark E Reeves
- Department of Surgical Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Jerry D Slater
- Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Gary Y Yang
- Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
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The efficacy of anti-EGFR therapy in treating metastatic colorectal cancer differs between the middle/low rectum and the left-sided colon. Br J Cancer 2021; 125:816-825. [PMID: 34188197 PMCID: PMC8437976 DOI: 10.1038/s41416-021-01470-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 05/20/2021] [Accepted: 06/17/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Clinically, metastatic rectal cancer has been considered a subset of left-sided colon cancer. However, heterogeneity has been proposed to exist between high and middle/low rectal cancers. We aimed to examine the efficacy of anti-epidermal growth factor receptor (EGFR) treatment for middle/low rectal and left-sided colon cancers. METHODS This study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy. They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum. The efficacy of first-line and non-first-line anti-EGFR treatment was analysed. Genomic differences in colorectal cancer data from The Cancer Genome Atlas (TCGA) were investigated and visualised with OncoPrint and a clustered heatmap. RESULTS On first-line anti-EGFR treatment, patients with middle/low rectal tumours had significantly lower progression-free survival, overall survival, and overall response rates (6.8 months, 27.8 months and 43%, respectively) than those with left-sided colon cancer (10.1 months, 38.3 months and 66%, respectively). Similar outcomes were also identified on non-first-line anti-EGFR treatment. In TCGA analysis, rectal tumours displayed genetic heterogeneity and shared features with both left- and right-sided colon cancer. CONCLUSIONS Anti-EGFR treatment has lower efficacy in metastatic middle/low rectal cancer than in left-sided colon cancer.
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Recurrence and survival following microwave, radiofrequency ablation, and hepatic resection of colorectal liver metastases: A systematic review and network meta-analysis. Hepatobiliary Pancreat Dis Int 2021; 20:307-314. [PMID: 34127382 DOI: 10.1016/j.hbpd.2021.05.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 05/20/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Gold standard for colorectal liver metastases (CRLM) remains hepatic resection (HR). However, patients with severe comorbidities, unresectable or deep-situated resectable CRLM are candidates for ablation. The aim of the study was to compare recurrence rate and survival benefit of the microwave ablation (MWA), radiofrequency ablation (RFA) and HR by conducting the first network meta-analysis. DATA SOURCES Systematic search of the literature was conducted in the electronic databases. Both updated traditional and network meta-analyses were conducted and the results were compared between them. RESULTS HR cohort demonstrated significantly less local recurrence rate and better 3- and 5-year disease-free (DFS) and overall survival (OS) compared to MWA and RFA cohorts. HR cohort included significantly younger patients and with significantly lower preoperative carcinoembryonic antigen (CEA) by 10.28 ng/mL compared to RFA cohort. Subgroup analysis of local recurrence and OS of solitary and ≤ 3 cm CRLMs did not demonstrate any discrepancies when compared with the whole sample. CONCLUSIONS For resectable CRLM the treatment of choice still remains HR. MWA and RFA can be used as a single or adjunct treatment in patients with unresectable CRLM and/or prohibitive comorbidities.
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Apers T, Hendrikx B, Bracke B, Hartman V, Roeyen G, Ysebaert D, Op de Beeck B, Chapelle T. Parenchymal-sparing hepatectomy with hepatic vein resection and reconstruction. Acta Chir Belg 2021; 122:334-340. [PMID: 33860723 DOI: 10.1080/00015458.2021.1915021] [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: 10/21/2022]
Abstract
BACKGROUND Hepatectomy remains the most important treatment modality for most malignant liver tumors. Vascular involvement stays a reason for unresectability or major parenchymal resection. A possible way to avoid this is parenchymal-sparing hepatectomy (PSHX) with vascular resection and reconstruction (HVRR). In this article, we aim to demonstrate the specific role of this technique in avoiding post-hepatectomy liver failure (PHLF). METHODS A retrospective analysis of 10 patients who underwent HVRR was conducted. 99mTechnetium-mebrofenin hepatobiliary scintigraphy (HBS) was used to predict the future liver remnant function (FLRF). Calculations were made for each patient to compare HVRR and major hepatectomy (with or without portal vein embolization). RESULTS In our cohort, there was no perioperative mortality. Two patients suffered a Clavien-Dindo grade 3a complication and none had clinically significant PHLF. Estimated FLRF was significantly higher in HVRR compared to major hepatectomy after portal vein embolization (p < .005). CONCLUSIONS Instead of focusing on inducing liver remnant hypertrophy, preserving parenchyma through HVRR can be an interesting treatment strategy. It can be performed with an acceptable operative risk. Calculations of FLRF (using HBS) suggest that this approach is able to reduce the risk for PHLF and related morbidity or mortality.
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Affiliation(s)
- Thomas Apers
- Department of Hepatobiliary and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
| | - Bart Hendrikx
- Department of Hepatobiliary and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
| | - Bart Bracke
- Department of Hepatobiliary and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
| | - Vera Hartman
- Department of Hepatobiliary and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
| | - Geert Roeyen
- Department of Hepatobiliary and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
| | - Dirk Ysebaert
- Department of Hepatobiliary and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
| | - Bart Op de Beeck
- Department of Radiology, Antwerp University Hospital, Edegem, Belgium
| | - Thiery Chapelle
- Department of Hepatobiliary and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
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Chen TH, Chen WS, Jiang JK, Yang SH, Wang HS, Chang SC, Lan YT, Lin CC, Lin HH, Huang SC, Cheng HH, Chau GY, Hsia CY, Lei HJ, Chou SC, Chao Y, Teng HW. Effect of Primary Tumor Location on Postmetastasectomy Survival in Patients with Colorectal Cancer Liver Metastasis. J Gastrointest Surg 2021; 25:650-661. [PMID: 33201458 DOI: 10.1007/s11605-020-04855-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 10/31/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND The effects of primary tumor location on colorectal liver metastasis (CRLM) and post-hepatic-metastasectomy overall survival (OS) are controversial. This study evaluated the difference in post-hepatic-metastasectomy OS among right-sided colon, left-sided colon, and rectal cancer groups. METHODS In total, 381 patients who underwent curative-intent CRLM resection were enrolled. Patients were grouped based on the primary tumor location (right-sided, left-sided, and rectum). The Kaplan-Meier analysis and log-rank test were performed for survival analysis. The univariate and multivariate analyses of clinical and pathological factors were performed using the Cox proportional hazards model. RESULTS Significant OS difference was noted among the three groups (log-rank, p = 0.014). The multivariate analysis revealed a 32% lower death risk in left-sided colon cancer compared with right-sided colon cancer (hazard ratio [HR] 0.68, p = 0.042), whereas no OS difference was noted between the rectal cancer and right-sided colon cancer groups. The left- versus right-sided OS advantage was noted only in the KRAS wild-type subgroup (HR 0.46, p = 0.002), and a rectal versus right-sided OS disadvantage was noted in the KRAS mutant subgroup (HR 1.78, p = 0.03). CONCLUSIONS The CRLM post-hepatic-metastasectomy OS was superior in left-sided colon cancer than in right-sided colon cancer and was similar in rectal and right-sided colon cancer. The OS difference in different primary tumor locations is dependent on KRAS mutation status, with a decreased left- versus right-sided death risk noted only in KRAS wild-type colon cancer and an increased rectal versus right-sided death risk noted only in KRAS mutant colon cancer.
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Affiliation(s)
- Tien-Hua Chen
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Beitou District, Taipei City, Taiwan
| | - Wei-Shone Chen
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jeng-Kai Jiang
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shung-Haur Yang
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Surgery, National Yang-Ming University Hospital, Yilan, Taiwan
| | - Huann-Sheng Wang
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shih-Ching Chang
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yuan-Tzu Lan
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chun-Chi Lin
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hung-Hsin Lin
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Sheng-Chieh Huang
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hou-Hsuan Cheng
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Colon and Rectum Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Gar-Yang Chau
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Cheng-Yuan Hsia
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hao-Jan Lei
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shu-Cheng Chou
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yee Chao
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Beitou District, Taipei City, Taiwan
| | - Hao-Wei Teng
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. .,Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Beitou District, Taipei City, Taiwan. .,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
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Yang G, Wang G, Sun J, Xiong Y, Li W, Tang T, Li J. The prognosis of radiofrequency ablation versus hepatic resection for patients with colorectal liver metastases: A systematic review and meta-analysis based on 22 studies. Int J Surg 2021; 87:105896. [PMID: 33588125 DOI: 10.1016/j.ijsu.2021.105896] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 01/23/2021] [Accepted: 02/02/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Though hepatic resection (HR) is the standard local therapy for patients with colorectal cancer liver metastases (CRLMs), currently, radiofrequency ablation (RFA) may play an alternative role for elderly and vulnerable patients with various organ dysfunctions. This study aims to compare the prognosis of RFA and HR in treatment of CRLMs. METHODS A systematic search of PubMed, Embase, Cochrane Library and Web of Science up to October 1, 2020 was conducted for relevant studies that compared the prognosis of RFA with HR in the treatment of CRLMs. The primary outcomes were 30-day mortality, long-term recurrence, overall survival (OS) and disease-free survival (DFS). The secondary outcomes were various factors of OS, recurrence-free survival (RFS), survival, recurrence and complication. RESULTS A total of 22 studies including 4385 CRLM patients were identified. There was no significant difference between RFA and HR in 30-day mortality, with a pooled OR of 0.88 (95% CI 0.34-2.29; P = 0.80). CRLM patients undergoing RFA experienced significantly higher incidences of marginal and intrahepatic recurrence than HR, with pooled ORs of 7.09 (95% CI 4.56-11.2; 1251 pts) and 2.02 (95% CI 1.24-3.28; 1038 pts). In addition, RFA showed lower 1-, 3- and 5-yr OS rate than HR with pooled ORs of 0.39, 0.40 and 0.60 respectively. A lower 5-yr DFS rate was also found in RFA than HR group, with a pooled OR of 0.74 (95% CI 0.56-0.97; P = 0.03; 1231 pts). Multivariable analysis showed that tumor size, multiple tumors, age, primary node positive and metachronous metastasis were independent factors of OS, and multiple tumors was also an independent factor of RFS. CONCLUSIONS Though the 30-day mortality of RFA was equal to HR, RFA showed a higher recurrence rate and poor long-term survival outcomes for CRLM patients. Tumor size, multiple tumors, age, primary node positive and metachronous metastasis were independent factors of survival. However, the results were limited because of the inequality baseline characteristics between the comparative groups. Randomized or propensity score matching studies should be performed to clarify the effectiveness of RFA and to determine target populations that benefit most from RFA in the future.
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Affiliation(s)
- Gang Yang
- Jinan University, No. 601 Huangpu Avenue West, Guangzhou, 510632, China; Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Guan Wang
- Physical Examination Center, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Ji Sun
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Yongfu Xiong
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China; Institute of Hepato-Biliary-Pancreatic-Intestinal Disease, North Sichuan Medical College, Nanchong, 637000, China
| | - Weinan Li
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Tao Tang
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China
| | - Jingdong Li
- Jinan University, No. 601 Huangpu Avenue West, Guangzhou, 510632, China; Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China; Institute of Hepato-Biliary-Pancreatic-Intestinal Disease, North Sichuan Medical College, Nanchong, 637000, China.
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Srinivasan S, Yee NA, Wu K, Zakharian M, Mahmoodi A, Royzen M, Oneto JMM. SQ3370 Activates Cytotoxic Drug via Click Chemistry at Tumor and Elicits Sustained Responses in Injected & Non-injected Lesions. ADVANCED THERAPEUTICS 2021; 4. [PMID: 33869738 DOI: 10.1002/adtp.202000243] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
While systemic immuno-oncology therapies have shown remarkable success, only a limited subset of patients benefit from them. Our Click Activated Protodrugs Against Cancer (CAPAC™) Platform is a click chemistry-based approach that activates cancer drugs at a specific tumor with minimal systemic toxicity. CAPAC Platform is agnostic to tumor characteristics that can vary across patients and hence applicable to several types of tumors. We describe the benefits of SQ3370 (lead candidate of CAPAC) to achieve systemic anti-tumor responses in mice bearing two tumors. SQ3370 consists of a biopolymer, injected in a single lesion, followed by systemic doses of an attenuated protodrug™ of doxorubicin (Dox). SQ3370 was well-tolerated at 5.9-times the maximum dose of conventional Dox, increased survival by 63% and induced a systemic anti-tumor response against injected and non-injected lesions. The sustained anti-tumor response also correlated with immune activation measured at both lesions. SQ3370 could potentially benefit patients with micro-metastatic lesions.
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Affiliation(s)
- S Srinivasan
- Shasqi, Inc., 665 3 St., Suite 501, San Francisco, CA 94107
| | - N A Yee
- Shasqi, Inc., 665 3 St., Suite 501, San Francisco, CA 94107
| | - K Wu
- University of Albany, 1400 Washington Ave., LS-1136, Albany, NY 12222
| | - M Zakharian
- Shasqi, Inc., 665 3 St., Suite 501, San Francisco, CA 94107
| | - A Mahmoodi
- Shasqi, Inc., 665 3 St., Suite 501, San Francisco, CA 94107
| | - M Royzen
- University of Albany, 1400 Washington Ave., LS-1136, Albany, NY 12222
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Chavez MI, Gholami S, Kim BJ, Margonis GA, Ethun CG, Tsai S, Christians KK, Clarke C, Mogal H, Maithel SK, Pawlik TM, D'Angelica MI, Aloia TA, Eastwood D, Gamblin TC. Two-Stage Hepatectomy for Bilateral Colorectal Liver Metastases: A Multi-institutional Analysis. Ann Surg Oncol 2021; 28:1457-1465. [PMID: 33393036 DOI: 10.1245/s10434-020-09459-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 10/17/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND Two-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management, and outcomes of patients completing TSH in major hepatobiliary centers in the United States (US). METHODS A retrospective review from five liver centers in the US identified patients who completed a TSH procedure for bilateral CRLM. RESULTS From December 2000 to March 2016, a total of 196 patients were identified. The majority of procedures were performed using an open technique (n = 194, 99.5%). The median number of tumors was 7 (range 2-33). One-hundred and twenty-eight (65.3%) patients underwent portal vein embolization. More patients received chemotherapy prior to the first stage than chemotherapy administration preceding the second stage (92% vs. 60%, p = 0.308). Median overall survival (OS) was 50 months, with a median follow-up of 28 months (range 2-143). Hepatic artery infusion chemotherapy was administered to 64 (32.7%) patients with similar OS as those managed without an infusion pump (p = 0.848). Postoperative morbidity following the second-stage resection was 47.4%. Chemotherapy prior to the second stage did not demonstrate an increased complication rate (p = 0.202). Readmission following the second stage was 10.3% and was associated with a decrease in disease-free survival (p = 0.003). OS was significantly decreased by positive resection margins and increased estimated blood loss (EBL; p = 0.036 and p = 0.05, respectively). CONCLUSION This is the largest TSH series in the US and demonstrates evidence of safety and feasibility in the management of bilateral CRLM. Outcomes are influenced by margin status and operative EBL.
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Affiliation(s)
- Mariana I Chavez
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | | | | | | | | | - Susan Tsai
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | | | - Callisia Clarke
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Harveshp Mogal
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | | | - Timothy M Pawlik
- The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | | | | | - Daniel Eastwood
- Division of Biostatistics at Medical College of Wisconsin, Milwaukee, WI, USA
| | - T Clark Gamblin
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
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Halpern AL, Fitz JG, Fujiwara Y, Yi J, Anderson AL, Zhu Y, Schulick RD, El Kasmi KC, Barnett CC. Hepatic thermal injury promotes colorectal cancer engraftment in C57/black 6 mice. Am J Physiol Cell Physiol 2021; 320:C142-C151. [PMID: 33175574 PMCID: PMC7846977 DOI: 10.1152/ajpcell.00071.2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 10/26/2020] [Accepted: 11/02/2020] [Indexed: 11/22/2022]
Abstract
Treatment options for liver metastases (primarily colorectal cancer) are limited by high recurrence rates and persistent tumor progression. Surgical approaches to management of these metastases typically use heat energy including electrocautery, argon beam coagulation, thermal ablation of surgical margins for hemostasis, and preemptive thermal ablation to prevent bleeding or to effect tumor destruction. Based on high rates of local recurrence, these studies assess whether local effects of hepatic thermal injury (HTI) might contribute to poor outcomes by promoting a hepatic microenvironment favorable for tumor engraftment or progression due to induction of procancer cytokines and deleterious immune infiltrates at the site of thermal injury. To test this hypothesis, an immunocompetent mouse model was developed wherein HTI was combined with concomitant intrasplenic injection of cells from a well-characterized MC38 colon carcinoma cell line. In this model, HTI resulted in a significant increase in engraftment and progression of MC38 tumors at the site of thermal injury. Furthermore, there were local increases in expression of messenger ribonucleic acid (mRNA) for hypoxia-inducible factor-1α (HIF1α), arginase-1, and vascular endothelial growth factor α and activation changes in recruited macrophages at the HTI site but not in untreated liver tissue. Inhibition of HIF1α following HTI significantly reduced discreet hepatic tumor development (P = 0.03). Taken together, these findings demonstrate that HTI creates a favorable local environment that is associated with protumorigenic activation of macrophages and implantation of circulating tumors. Discrete targeting of HIF1α signaling or inhibiting macrophages offers potential strategies for improving the outcome of surgical management of hepatic metastases where HTI is used.
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Affiliation(s)
- Alison L Halpern
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - J Gregory Fitz
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
| | - Yuki Fujiwara
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Jeniann Yi
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Aimee L Anderson
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Yuwen Zhu
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Richard D Schulick
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Karim C El Kasmi
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Carlton C Barnett
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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