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1
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Venturino A, Colloca GA. Prognostic Effect of CEA Cut-Off in Patients with Resectable Colorectal Liver Metastases: A Meta-Analysis and Meta-Regression. J Gastrointest Cancer 2025; 56:117. [PMID: 40358861 DOI: 10.1007/s12029-025-01244-6] [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] [Accepted: 05/04/2025] [Indexed: 05/15/2025]
Abstract
BACKGROUND Although preoperative carcinoembryonic antigen (CEA) is a variable used in most prognostic scores assessing the outcome of patients with colorectal liver metastases (CRLM) undergoing resection, it is unclear what the optimal cut-off is or in which patient subgroups CEA is most relevant. The purpose of this study is to evaluate the prognostic effect of CEA in resected CRLM patients and to explore in which subgroups CEA is most closely associated with overall survival (OS). METHODS A systematic literature search was performed, selecting studies that evaluated a relationship between preoperative CEA and OS in patients undergoing CRLM radical surgery. A meta-analysis assessed the overall effect size of the relationship on the selected study cohorts, based on CEA cut-off. An evaluation of 21 baseline variables was performed to explore their possible effect on the relationship between CEA and OS. RESULTS The study confirms a significant negative prognostic effect of increased CEA on OS (HR 1.46, CI 1.30-1.65), but heterogeneity among studies is significant. The effect is consistent for all CEA cut-offs, although the relationship tends to weaken in more recent studies for cut-offs < 10 ng/mL. Meta-regressions also suggest that the prognostic effect may be more pronounced in the elderly. In addition, the effect of CEA ≥ 20 ng/mL on OS appears significantly reduced in the subgroup with mutated RAS carcinoma. CONCLUSIONS For patients with resectable CRLM, the CEA cut-off should be increased to 20 ng/mL, and evaluation in prospective studies of the more pronounced negative prognostic effect of preoperative CEA in the elderly and wild-type RAS CRLM patients is recommended.
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Affiliation(s)
| | - Giuseppe A Colloca
- Oncologia Medica & Innovation, Via Aicardi n. 37, I-18100, Imperia, Italy
- U. O. Oncologia Territoriale, AUSL Bologna, Bologna, Italy
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2
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Atienza ÁV, Iriarte OA, Sarrias OR, Lizundia TZ, Beristain OS, Casajús AE, Gigli LÁ, Sastre FR, García IM, Rodríguez JR. Neoadjuvant Statistical Algorithm to Predict Individual Risk of Relapse in Patients with Resected Liver Metastases from Colorectal Cancer. Biomedicines 2024; 12:1859. [PMID: 39200323 PMCID: PMC11351994 DOI: 10.3390/biomedicines12081859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Revised: 08/10/2024] [Accepted: 08/12/2024] [Indexed: 09/02/2024] Open
Abstract
(1) Background: Liver metastases (LM) are the leading cause of death in colorectal cancer (CRC) patients. Despite advancements, relapse rates remain high and current prognostic nomograms lack accuracy. Our objective is to develop an interpretable neoadjuvant algorithm based on mathematical models to accurately predict individual risk, ensuring mathematical transparency and auditability. (2) Methods: We retrospectively evaluated 86 CRC patients with LM treated with neoadjuvant systemic therapy followed by complete surgical resection. A comprehensive analysis of 155 individual patient variables was performed. Logistic regression (LR) was utilized to develop the predictive model for relapse risk through significance testing and ANOVA analysis. Due to data limitations, gradient boosting machine (GBM) and synthetic data were also used. (3) Results: The model was based on data from 74 patients (12 were excluded). After a median follow-up of 58 months, 5-year relapse-free survival (RFS) rate was 33% and 5-year overall survival (OS) rate was 60.7%. Fifteen key variables were used to train the GBM model, which showed promising accuracy (0.82), sensitivity (0.59), and specificity (0.96) in predicting relapse. Similar results were obtained when external validation was performed as well. (4) Conclusions: This model offers an alternative for predicting individual relapse risk, aiding in personalized adjuvant therapy and follow-up strategies.
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Affiliation(s)
- Ángel Vizcay Atienza
- Department of Medical Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (Á.V.A.); (T.Z.L.)
| | | | - Oskitz Ruiz Sarrias
- Department of Mathematics and Statistic, NNBi, 31110 Noain, Spain; (O.A.I.); (O.R.S.); (O.S.B.)
| | - Teresa Zumárraga Lizundia
- Department of Medical Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (Á.V.A.); (T.Z.L.)
| | - Onintza Sayar Beristain
- Department of Mathematics and Statistic, NNBi, 31110 Noain, Spain; (O.A.I.); (O.R.S.); (O.S.B.)
| | - Ana Ezponda Casajús
- Department of Radiology, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
| | - Laura Álvarez Gigli
- Department of Pathology, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
| | | | - Ignacio Matos García
- Department of Medical Oncology, Clínica Universidad de Navarra, 28027 Madrid, Spain;
| | - Javier Rodríguez Rodríguez
- Department of Medical Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (Á.V.A.); (T.Z.L.)
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3
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Moretto R, Germani MM, Borelli B, Conca V, Rossini D, Boraschi P, Donati F, Urbani L, Lonardi S, Bergamo F, Cerma K, Ramondo G, D'Amico FE, Salvatore L, Valente G, Barbaro B, Giuliante F, Di Maio M, Masi G, Cremolini C. Predicting early recurrence after resection of initially unresectable colorectal liver metastases: the role of baseline and pre-surgery clinical, radiological and molecular factors in a real-life multicentre experience. ESMO Open 2024; 9:102991. [PMID: 38631269 PMCID: PMC11027482 DOI: 10.1016/j.esmoop.2024.102991] [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: 01/04/2024] [Revised: 03/09/2024] [Accepted: 03/11/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND Advances in surgical techniques and systemic treatments have increased the likelihood of achieving radical surgery and long-term survival in metastatic colorectal cancer (mCRC) patients with initially unresectable colorectal liver metastases (CRLMs). Nonetheless, roughly half of the patients resected after an upfront systemic therapy experience disease relapse within 6 months from surgery, thus leading to the question whether surgery is actually beneficial for these patients. MATERIALS AND METHODS A real-world dataset of mCRC patients with initially unresectable liver-limited disease treated with conversion chemotherapy followed by radical resection of CRLMs at three high-volume Italian institutions was retrospectively assessed with the aim of investigating the association of baseline and pre-surgical clinical, radiological and molecular factors with the risk of relapse within 6 or 12 months from surgery. RESULTS Overall, 268 patients were included in the analysis and 207 (77%) experienced recurrence. Ninety-six (46%) of them had disease relapse within 6 months after CRLM resection and in spite of several variables associated with early recurrence at univariate analyses, only primary tumour resection at diagnosis [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.32-0.89, P = 0.02] remained significant in the multivariable model. Among patients with resected primary tumours, pN+ stage was associated with higher risk of disease relapse within 6 months (OR 3.02, 95% CI 1.23-7.41, P = 0.02). One hundred and forty-nine patients (72%) had disease relapse within 12 months after CRLMs resection but none of the analysed variables was independently associated with outcome. CONCLUSIONS Clinical, radiological and molecular factors assessed before and after conversion chemotherapy do not reliably predict early recurrence after secondary resection of initially unresectable CRLMs. While novel markers are needed to optimize the cost/efficacy balance of surgical procedures, CRLM resection should be offered as soon as metastases become resectable during first-line chemotherapy to all patients eligible for surgery.
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Affiliation(s)
- R Moretto
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa
| | - M M Germani
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa; Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa
| | - B Borelli
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa; Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa
| | - V Conca
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa; Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa
| | - D Rossini
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa; Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Pisa
| | - P Boraschi
- Department of Diagnostic and Interventional Radiology, and Nuclear Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa
| | - F Donati
- Department of Diagnostic and Interventional Radiology, and Nuclear Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa
| | - L Urbani
- General Surgery, Azienda Ospedaliero-Universitaria Pisana, Pisa
| | - S Lonardi
- Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua
| | - F Bergamo
- Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua
| | - K Cerma
- Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua
| | - G Ramondo
- Radiology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua
| | - F E D'Amico
- General Surgery 2, Department of Surgical Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua
| | - L Salvatore
- Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome; Medical Oncology Unit, Università Cattolica del Sacro Cuore, Rome
| | - G Valente
- Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome; Medical Oncology Unit, Università Cattolica del Sacro Cuore, Rome
| | - B Barbaro
- Diagnostic and General Interventional Radiology, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome
| | - F Giuliante
- General and Hepatobiliary Surgery, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome
| | - M Di Maio
- Department of Oncology, Università degli Studi di Torino, Turin, Italy
| | - G Masi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa; Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa
| | - C Cremolini
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa; Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa.
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van Nassau SCMW, Bol GM, van der Baan FH, Roodhart JML, Vink GR, Punt CJA, May AM, Koopman M, Derksen JWG. Harnessing the Potential of Real-World Evidence in the Treatment of Colorectal Cancer: Where Do We Stand? Curr Treat Options Oncol 2024; 25:405-426. [PMID: 38367182 PMCID: PMC10997699 DOI: 10.1007/s11864-024-01186-4] [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] [Accepted: 01/17/2024] [Indexed: 02/19/2024]
Abstract
OPINION STATEMENT Treatment guidelines for colorectal cancer (CRC) are primarily based on the results of randomized clinical trials (RCTs), the gold standard methodology to evaluate safety and efficacy of oncological treatments. However, generalizability of trial results is often limited due to stringent eligibility criteria, underrepresentation of specific populations, and more heterogeneity in clinical practice. This may result in an efficacy-effectiveness gap and uncertainty regarding meaningful benefit versus treatment harm. Meanwhile, conduct of traditional RCTs has become increasingly challenging due to identification of a growing number of (small) molecular subtypes. These challenges-combined with the digitalization of health records-have led to growing interest in use of real-world data (RWD) to complement evidence from RCTs. RWD is used to evaluate epidemiological trends, quality of care, treatment effectiveness, long-term (rare) safety, and quality of life (QoL) measures. In addition, RWD is increasingly considered in decision-making by clinicians, regulators, and payers. In this narrative review, we elaborate on these applications in CRC, and provide illustrative examples. As long as the quality of RWD is safeguarded, ongoing developments, such as common data models, federated learning, and predictive modelling, will further unfold its potential. First, whenever possible, we recommend conducting pragmatic trials, such as registry-based RCTs, to optimize generalizability and answer clinical questions that are not addressed in registrational trials. Second, we argue that marketing approval should be conditional for patients who would have been ineligible for the registrational trial, awaiting planned (non) randomized evaluation of outcomes in the real world. Third, high-quality effectiveness results should be incorporated in treatment guidelines to aid in patient counseling. We believe that a coordinated effort from all stakeholders is essential to improve the quality of RWD, create a learning healthcare system with optimal use of trials and real-world evidence (RWE), and ultimately ensure personalized care for every CRC patient.
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Affiliation(s)
- Sietske C M W van Nassau
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, PO Box 85500, Utrecht, 3584 CX, The Netherlands.
| | - Guus M Bol
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, PO Box 85500, Utrecht, 3584 CX, The Netherlands
| | - Frederieke H van der Baan
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, PO Box 85500, Utrecht, 3584 CX, The Netherlands
- Department of Epidemiology & Health Economics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jeanine M L Roodhart
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, PO Box 85500, Utrecht, 3584 CX, The Netherlands
| | - Geraldine R Vink
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, PO Box 85500, Utrecht, 3584 CX, The Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
| | - Cornelis J A Punt
- Department of Epidemiology & Health Economics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Anne M May
- Department of Epidemiology & Health Economics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, PO Box 85500, Utrecht, 3584 CX, The Netherlands
| | - Jeroen W G Derksen
- Department of Epidemiology & Health Economics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
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Kaczmarczyk K, Zakynthinaki M, Barton G, Baran M, Wit A. Biomechanical comparison of two surgical methods for Hallux Valgus deformity: Exploring the use of artificial neural networks as a decision-making tool for orthopedists. PLoS One 2024; 19:e0297504. [PMID: 38349907 PMCID: PMC10863859 DOI: 10.1371/journal.pone.0297504] [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: 07/06/2023] [Accepted: 01/06/2024] [Indexed: 02/15/2024] Open
Abstract
Hallux Valgus foot deformity affects gait performance. Common treatment options include distal oblique metatarsal osteotomy and chevron osteotomy. Nonetheless, the current process of selecting the appropriate osteotomy method poses potential biases and risks, due to its reliance on subjective human judgment and interpretation. The inherent variability among clinicians, the potential influence of individual clinical experiences, or inherent measurement limitations may contribute to inconsistent evaluations. To address this, incorporating objective tools like neural networks, renowned for effective classification and decision-making support, holds promise in identifying optimal surgical approaches. The objective of this cross-sectional study was twofold. Firstly, it aimed to investigate the feasibility of classifying patients based on the type of surgery. Secondly, it sought to explore the development of a decision-making tool to assist orthopedists in selecting the optimal surgical approach. To achieve this, gait parameters of twenty-three women with moderate to severe Hallux Valgus were analyzed. These patients underwent either distal oblique metatarsal osteotomy or chevron osteotomy. The parameters exhibiting differences in preoperative and postoperative values were identified through various statistical tests such as normalization, Shapiro-Wilk, non-parametric Wilcoxon, Student t, and paired difference tests. Two artificial neural networks were constructed for patient classification based on the type of surgery and to simulate an optimal surgery type considering postoperative walking speed. The results of the analysis demonstrated a strong correlation between surgery type and postoperative gait parameters, with the first neural network achieving a remarkable 100% accuracy in classification. Additionally, cases were identified where there was a mismatch with the surgeon's decision. Our findings highlight the potential of artificial neural networks as a complementary tool for surgeons in making informed decisions. Addressing the study's limitations, future research may investigate a wider range of orthopedic procedures, examine additional gait parameters and use more diverse and extensive datasets to enhance statistical robustness.
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Affiliation(s)
- Katarzyna Kaczmarczyk
- Faculty of Rehabilitation, Józef Piłsudski Academy of Physical Education, Warsaw, Poland
| | - Maria Zakynthinaki
- School of Chemical and Environmental Engineering, Technical University of Crete, Chania, Greece
| | - Gabor Barton
- Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom
| | - Mateusz Baran
- Faculty of Rehabilitation, Józef Piłsudski Academy of Physical Education, Warsaw, Poland
| | - Andrzej Wit
- Faculty of Rehabilitation, Józef Piłsudski Academy of Physical Education, Warsaw, Poland
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Lin C, Liang Z, Liu J, Sun W. A machine learning-based prediction model pre-operatively for functional recovery after 1-year of hip fracture surgery in older people. Front Surg 2023; 10:1160085. [PMID: 37351328 PMCID: PMC10282650 DOI: 10.3389/fsurg.2023.1160085] [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: 02/11/2023] [Accepted: 05/22/2023] [Indexed: 06/24/2023] Open
Abstract
Background Machine learning (ML) has been widely utilized for constructing high-performance prediction models. This study aimed to develop a preoperative machine learning-based prediction model to identify functional recovery one year after hip fracture surgery. Methods We collected data from 176 elderly hip fracture patients admitted to the Department of Orthopaedics and Oncology at Shenzhen Second People's Hospital between May 2019 and December 2019, who met the inclusion criteria. Patient's functional recovery was monitored for one year after surgery. We selected 26 factors, comprising 12 preoperative indicators, 8 surgical indicators, and 6 postoperative indicators. Eventually, 77 patients were included based on the exclusion criteria. Random allocation divided them into the training set (70%) and test set (30%) for internal validation. The Lasso method was employed to screen prognostic variables. We conducted comparisons among various common machine learning classifiers to determine the best prediction model. Prediction performance was evaluated using the area under the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis. To identify the importance of the predictor variables, we performed the recursive feature elimination (RFE) algorithm based on Shapley Additive Explanations (SHAP) values. Results The AUCs for the testing dataset were as follows: logistic regression (Logit) model = 0.934, k-nearest neighbors (KNN) model = 0.930, support vector machine (SVM) model = 0.910, Gaussian naive Bayes (GNB) model = 0.926, decision tree (DT) model = 0.730, random forest (RF) model = 0.957, and Extreme Gradient Boosting (XGB) model = 0.902. Among the seven ML-based models tested, the RF model demonstrated the best prediction performance, incorporating four features: postoperative rehabilitation compliance, marital status, age-adjusted Charlson comorbidity score (aCCI), and clinical frailty scale (CFS). Conclusion We developed a prediction model for the functional recovery following hip fracture surgery in elderly patients after one year, based on the Random Forest (RF) algorithm. This model exhibited superior prediction performance (ROC) compared to other models. The software application is available for use. External validation in a larger patient cohort or diverse hospital settings is necessary to assess the clinical utility of this tool.
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Affiliation(s)
- Chun Lin
- Department of Orthopedics, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
- Department of General Medicine and Geriatrics, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, China
| | - Zhen Liang
- Department of Geriatrics, Shenzhen People’s Hospital, Shenzhen, China
| | - Jianfeng Liu
- Department of Cardiology, the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army General Hospital, Beijing, China
| | - Wei Sun
- Department of Orthopedics, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
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Tian Y, Mao Y, Tang Z, Hu M. Current Controversy and Developments Regarding the Cytoreductive Prostatectomy for Oligometastatic Prostate Cancer. Technol Cancer Res Treat 2023; 22:15330338231216011. [PMID: 38105493 PMCID: PMC10729631 DOI: 10.1177/15330338231216011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 09/29/2023] [Accepted: 11/06/2023] [Indexed: 12/19/2023] Open
Abstract
Oligometastatic prostate cancer is a term that is most often used to refer to limited sites of disseminated tumor growth following primary radical prostatectomy (RP) or radiotherapy (RT), while de novo oligometastatic is a term that is used to refer to prostate tumors that have disseminated to limited sites before definitive treatment. In patients with de novo oligometastatic prostate cancer, treatment planning must thus consider the need to manage the primary tumor and the associated distant lesions. Traditionally, resectioning primary metastatic tumors is not thought to offer significant benefits to affected patients while increasing their risk of surgery-related complications. Recent clinical evidence indicates that patients undergoing cytoreductive prostatectomy (CRP) may observe substantial enhancements in overall survival rates while not experiencing a noticeable decline in their quality of life. Nevertheless, based on the current body of evidence, it is deemed inadequate to justify revising clinical guidelines. Consequently, it is not advisable to propose CRP for patients with oligometastatic prostate cancer. The present review was compiled to summarize available data regarding the indications, functional outcomes, and oncological outcomes associated with cytoreductive radical prostatectomy to provide a robust and objective foundation that can be used to better assess the value of this interventional strategy from a clinical perspective.
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Affiliation(s)
- Yuan Tian
- Maoming People's Hospital, Maoming, Guangdong, China
- The First School of Clinical Medicine, Southern Medical University, Gaungzhou, China
| | - Yifeng Mao
- The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Zhizhong Tang
- Maoming People's Hospital, Maoming, Guangdong, China
| | - Mingqiu Hu
- Maoming People's Hospital, Maoming, Guangdong, China
- The First School of Clinical Medicine, Southern Medical University, Gaungzhou, China
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8
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Horak J, Kubecek O, Siskova A, Honkova K, Chvojkova I, Krupova M, Manethova M, Vodenkova S, García-Mulero S, John S, Cecka F, Vodickova L, Petera J, Filip S, Vymetalkova V. Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer. Front Oncol 2023; 13:1133598. [PMID: 37182133 PMCID: PMC10172672 DOI: 10.3389/fonc.2023.1133598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 03/20/2023] [Indexed: 05/16/2023] Open
Abstract
Despite distant metastases being the critical factor affecting patients' survival, they remain poorly understood. Our study thus aimed to molecularly characterize colorectal cancer liver metastases (CRCLMs) and explore whether molecular profiles differ between Synchronous (SmCRC) and Metachronous (MmCRC) colorectal cancer. This characterization was performed by whole exome sequencing, whole transcriptome, whole methylome, and miRNAome. The most frequent somatic mutations were in APC, SYNE1, TP53, and TTN genes. Among the differently methylated and expressed genes were those involved in cell adhesion, extracellular matrix organization and degradation, neuroactive ligand-receptor interaction. The top up-regulated microRNAs were hsa-miR-135b-3p and -5p, and the hsa-miR-200-family while the hsa-miR-548-family belonged to the top down-regulated. MmCRC patients evinced higher tumor mutational burden, a wider median of duplications and deletions, and a heterogeneous mutational signature than SmCRC. Regarding chronicity, a significant down-regulation of SMOC2 and PPP1R9A genes in SmCRC compared to MmCRC was observed. Two miRNAs were deregulated between SmCRC and MmCRC, hsa-miR-625-3p and has-miR-1269-3p. The combined data identified the IPO5 gene. Regardless of miRNA expression levels, the combined analysis resulted in 107 deregulated genes related to relaxin, estrogen, PI3K-Akt, WNT signaling pathways, and intracellular second messenger signaling. The intersection between our and validation sets confirmed the validity of our results. We have identified genes and pathways that may be considered as actionable targets in CRCLMs. Our data also provide a valuable resource for understanding molecular distinctions between SmCRC and MmCRC. They have the potential to enhance the diagnosis, prognostication, and management of CRCLMs by a molecularly targeted approach.
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Affiliation(s)
- Josef Horak
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia
- Department of Medical Genetics, Third Faculty of Medicine, Charles University, Prague, Czechia
| | - Ondrej Kubecek
- Department of Oncology and Radiotherapy, Faculty of Medicine and University Hospital in Hradec Kralove, Charles University, Hradec Kralove, Czechia
| | - Anna Siskova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czechia
| | - Katerina Honkova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia
| | - Irena Chvojkova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia
| | - Marketa Krupova
- The Fingerland Department of Pathology, University Hospital in Hradec Kralove, Hradec Kralove, Czechia
| | - Monika Manethova
- The Fingerland Department of Pathology, University Hospital in Hradec Kralove, Hradec Kralove, Czechia
| | - Sona Vodenkova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Sandra García-Mulero
- Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO)-Oncobell Programme, Bellvitge Biomedical Research Institute Oncobell Programme, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
- Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), Oncobell Programme, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
| | - Stanislav John
- Department of Oncology and Radiotherapy, Faculty of Medicine and University Hospital in Hradec Kralove, Charles University, Hradec Kralove, Czechia
| | - Filip Cecka
- Department of Surgery, Faculty of Medicine and University Hospital in Hradec Kralove, Charles University, Hradec Kralove, Czechia
| | - Ludmila Vodickova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czechia
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
| | - Jiri Petera
- Department of Oncology and Radiotherapy, Faculty of Medicine and University Hospital in Hradec Kralove, Charles University, Hradec Kralove, Czechia
| | - Stanislav Filip
- Department of Oncology and Radiotherapy, Faculty of Medicine and University Hospital in Hradec Kralove, Charles University, Hradec Kralove, Czechia
- *Correspondence: Veronika Vymetalkova, ; Stanislav Filip,
| | - Veronika Vymetalkova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czechia
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia
- *Correspondence: Veronika Vymetalkova, ; Stanislav Filip,
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Bai R, Shi Z, Li D, Zhou D, Ge WT, Zheng S. Gene expression profile of human colorectal cancer identified NKTR as a biomarker for liver metastasis. Aging (Albany NY) 2022; 14:6656-6667. [PMID: 36006421 PMCID: PMC9467399 DOI: 10.18632/aging.204242] [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: 06/30/2020] [Accepted: 07/21/2021] [Indexed: 11/25/2022]
Abstract
Objective: Liver metastasis is one of the prognostic factors of colorectal cancer (CRC). The aim of this study is to identify biomarkers that facilitate easier detection of liver metastasis. Methods: Significance Analysis of Microarrays (SAM) and Array Data Analyzer (ADA) were applied used for the analysis of differentially differently expressed mRNAs. mRNA expression was verified by quantitative real-timer reverse transcriptiontase polymerase chain reaction (qRT-PCR). Immunohistochemistry were was used to show natural killer-tumor recognition (NKTR) expression in CRC. NKTR-knockdown CRC cells were constructed obtained by using short hairpin RNA (shRNA). Followed by CCK-8 assay, plate colony formation test, and transwell assay were used to evaluate the influence of NKTR on cell proliferation, migration, and invasion in vitro. Results: SAM yielded showed 256 up-regulated and 224 down-regulated differentially differently expressed genes. Seven genes were identified by using ADA, tools and four genes were verified by using qRT-PCR. Three genes (metastasis associated lung adenocarcinoma transcript 1 (MALAT1), nuclear factor I/B (NKTR), and nuclear factor I/B (NFIB)) showed a statistically significant considerabley difference between CRC with and liver metastasis and CRC without liver metastasis. Immunohistochemical analysis showed that NKTR expression was much lower in primary CRC with liver metastasis than that in primary CRC without liver metastasis. The NKTR protein plays a role in the lytic function of natural killer (NK) cells and it has been rarely studied in the CRC. The down-regulation of NKTR by shRNA interference in CRC cells increased cell proliferation, migration, and invasion in vitro.
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Affiliation(s)
- Rui Bai
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310002, Zhejiang, China.,Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.,Cancer Center, Zhejiang University, Hangzhou 310058, Zhejiang, China
| | - Zhong Shi
- Department of Medical Oncology, Institute of Cancer and Basic (Medicine ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou 310022, Zhejiang, China
| | - Dan Li
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310002, Zhejiang, China
| | - Donger Zhou
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Wei-Ting Ge
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310002, Zhejiang, China
| | - Shu Zheng
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310002, Zhejiang, China
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10
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Prognostic Models Incorporating RAS Mutation to Predict Survival in Patients with Colorectal Liver Metastases: A Narrative Review. Cancers (Basel) 2022; 14:cancers14133223. [PMID: 35804994 PMCID: PMC9264993 DOI: 10.3390/cancers14133223] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 06/26/2022] [Accepted: 06/26/2022] [Indexed: 02/01/2023] Open
Abstract
Recurrence and survival vary widely among patients who undergo curative-intent resection of colorectal liver metastases (CRLM). Prognostic models provide estimated probabilities of these outcomes and allow the effects of multiple potentially interacting variables to be adjusted and assessed simultaneously. Although many prognostic models based on clinicopathologic factors have been developed since the 1990s to predict survival after resection of CRLM, these models vary in their predictive performance when applied to contemporary cohorts. Rat sarcoma viral oncogene homolog (RAS) mutation status is routinely tested in patients with metastatic colorectal cancer to predict response to anti-epidermal growth factor therapy. In addition, mutations in RAS predict survival and recurrence in patients undergoing hepatectomy for CRLM. Several recent prognostic models have incorporated RAS mutation status as a surrogate of tumor biology and combined revised clinicopathologic variables to improve the prediction of recurrence and survival. This narrative review aims to evaluate the differences between contemporary prognostic models incorporating RAS mutation status and their clinical applicability in patients considered for curative-intent resection of CRLM.
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11
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Germani MM, Borelli B, Boraschi P, Antoniotti C, Ugolini C, Urbani L, Morelli L, Fontanini G, Masi G, Cremolini C, Moretto R. The management of colorectal liver metastases amenable of surgical resection: How to shape treatment strategies according to clinical, radiological, pathological and molecular features. Cancer Treat Rev 2022; 106:102382. [PMID: 35334281 DOI: 10.1016/j.ctrv.2022.102382] [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] [Received: 02/08/2022] [Revised: 03/16/2022] [Accepted: 03/17/2022] [Indexed: 02/05/2023]
Abstract
Metastatic colorectal cancer (mCRC) patients have poor chances of long term survival, being < 15% of them still alive after 5 years from diagnosis. Nonetheless, patients with colorectal liver metastases (CRLM) may be eligible for metastases resection thus being able to achieve long-term disease remission and survival. The likelihood for patients with CRLM of being or becoming eligible for liver metastasectomy is increasing, thanks to the evolution of surgical techniques, the availability of active systemic treatments and the widespread diffusion of experienced multidisciplinary boards to manage these patients. However, disease relapse after liver surgery is common and occurs in two-thirds of resected patients. Therefore, adequate radiological staging and risk stratification is crucial for the optimal selection of patients candidate to surgery in order to maximize the benefit-risk ratio of liver metastasectomy and to individualize the treatment strategy. Based on the multidimensional assessment, three possible approaches are available: upfront liver surgery followed by adjuvant chemotherapy, perioperative chemotherapy preceding and following liver surgery, and an upfront systemic treatment including chemotherapy plus a targeted agent, both chosen according to patients' and tumours' characteristics, then followed by liver surgery if indicated. In this review, we describe the most important factors impacting the therapeutic choices in patients with resectable and potentially resectable CRLM, and we discuss the most promising factors that may reshape the future decision-making process of these patients.
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Affiliation(s)
- Marco Maria Germani
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Beatrice Borelli
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Piero Boraschi
- Department of Diagnostic and Interventional Radiology, and Nuclear Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Carlotta Antoniotti
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Clara Ugolini
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Lucio Urbani
- Unit of General Surgery, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Luca Morelli
- General Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Gabriella Fontanini
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Gianluca Masi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Chiara Cremolini
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Roberto Moretto
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
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12
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Sundaram A, Li Y, Abdel-Khalik H. Denoising Algorithm for Subtle Anomaly Detection. NUCL TECHNOL 2022. [DOI: 10.1080/00295450.2022.2027147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Arvind Sundaram
- Purdue University, 205 Gates Road, West Lafayette, Indiana 47906
| | - Yeni Li
- Purdue University, 205 Gates Road, West Lafayette, Indiana 47906
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13
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Cheng KC, Yip ASM. Prognostic factors of survival and a new scoring system for liver resection of colorectal liver metastasis. World J Hepatol 2022; 14:209-223. [PMID: 35126849 PMCID: PMC8790392 DOI: 10.4254/wjh.v14.i1.209] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 12/03/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatic resection has become the preferred treatment of choice for colorectal liver metastasis (CLM) patients. AIM To identify the prognostic factors and to formulate a new scoring system for management of CLM. METHODS Clinicopathologic and long-term survival data were analyzed to identify the significant predictors of survival by univariate and multivariate analyses with the Cox model. A clinical score was constructed based on the analysis results. RESULTS Three factors of worse overall survival were identified in the multivariate analysis. They were number of liver metastases ≥ 5, size of the largest liver lesion ≥ 4 cm, and the presence of nodal metastasis from the primary tumor. These three factors were chosen as criteria for a clinical risk score for overall survival. The clinical score highly correlated with median overall survival and 5-year survival (P = 0.002). CONCLUSION Priority over surgical resection should be given to the lowest score groups, and alternative oncological treatment should be considered in patients with the highest score.
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Affiliation(s)
- Kai-Chi Cheng
- Department of Surgery, Kwong Wah Hospital, Hong Kong, China.
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14
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Seyedin SN, Parekh KR, Ginader T, Caster JM. The Role of Definitive Radiation and Surgery in Metastatic Esophageal Cancer: An NCDB Investigation. Ann Thorac Surg 2021; 112:459-466. [PMID: 33096068 DOI: 10.1016/j.athoracsur.2020.08.034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 07/29/2020] [Accepted: 08/24/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Approximately 40% of patients with esophageal cancer present with metastatic disease. Survival with palliative treatment is poor, and the benefit of aggressive focal therapies is unclear. This study aimed to identify a subset of patients with metastatic esophageal cancer with favorable outcomes after curative doses of radiation therapy, esophagectomy, or both. METHODS Between 2004 and 2015, the study investigators found 28,101 patients with metastatic esophageal cancer in the National Cancer Database and identified those who underwent chemotherapy and definitive radiation therapy with or without surgery over the study period. The study compared the estimated median overall survival (OS) of all patients with metastatic esophageal cancer with the estimated median OS of patients with metastatic esophageal cancer who underwent radiation therapy with or without surgery. Multivariable analysis was used to examine clinical and pathologic factors associated with OS. RESULTS At a median follow-up of 11.1 months, 3219 patients with a median age of 64 years and a radiation dose of 50.4 Gy were identified. Only 202 (6.2%) patients undergoing definitive-dose radiation therapy underwent esophagectomy, with a median age of 60 years. The median OS durations for all patients, for patients treated with radiation, and for patients treated with radiation therapy in combination with esophagectomy were 6.6, 11.5, and 30.2 months, respectively. Among patients undergoing surgery, median OS after surgery was 23.7 months. Patients with lung, liver, or bone metastases were less likely to undergo esophagectomy. On multivariable analysis, esophagectomy and low tumor grade were associated with higher OS, whereas liver and bone metastases at diagnosis were associated with worse OS. CONCLUSIONS This analysis suggests that select subsets of patients with primarily nonvisceral, nonosseous metastatic esophageal cancer have favorable survival and may potentially benefit from aggressive local therapies.
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Affiliation(s)
- Steven N Seyedin
- Department of Radiation Oncology, University of California, Irvine-Chao Family Comprehensive Cancer Center, Orange, California; Department of Radiation Oncology, University of Iowa Hospital and Clinics, Iowa City, Iowa
| | - Kalpaj R Parekh
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa
| | - Timothy Ginader
- Holden Comprehensive Cancer Center, University of Iowa Hospital and Clinics, Iowa City, Iowa
| | - Joseph M Caster
- Department of Radiation Oncology, University of Iowa Hospital and Clinics, Iowa City, Iowa.
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15
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mSEPT9 Can Monitor the Response and Predict the Prognosis of Stage IV colorectal cancer Patients with Liver Metastasis Undergoing Potentially Curative Surgery. J Surg Res 2021; 267:485-494. [PMID: 34246842 DOI: 10.1016/j.jss.2021.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 05/10/2021] [Accepted: 06/09/2021] [Indexed: 12/07/2022]
Abstract
BACKGROUND Stage IV colorectal cancer (CRC) patients with liver metastasis undergoing potentially curative surgery represent a subgroup of patients with a relatively good prognosis. In this study, we aimed to evaluate the performance of mSEPT9 to monitor response to treatment and predict prognosis. METHODS In total, we recruited 51 stage IV CRC patients with liver metastasis, including 20 patients who underwent simultaneous surgery and 31 patients who underwent staged surgery. We measured the blood levels of mSEPT9 and CEA prior to surgery and then seven days after surgery. RESULTS mSEPT9 and CEA were detected prior to surgery in 92.2% (47/51) and 70.6% (36/51) of patients, respectively. Following simultaneous and staged surgery, levels of mSEPT9 fell significantly by 923-fold (P<0.001) and 11-fold (P<0.001), respectively. Levels of CEA also fell significantly by 17-fold (P<0.001) and 1.7-fold (P<0.01) following simultaneous and staged surgery, respectively. The mean percentage reduction of mSEPT9 levels after simultaneous surgery (12.3%) was significantly lower than that of staged surgery (33.8%) (P<0.001) while the mean percentage reduction of CEA levels after simultaneous surgery (35.5%) were significantly lower than that of staged surgery (64.6%) (P<0.05). The levels of mSEPT9 in the blood were quantitatively correlated with tumor burden. Survival analysis showed that patients who tested negative for mSEPT9 pre- and post-surgery had a better survival rate than those who tested positive, thus suggesting that mSEPT9 can act as a prognostic indicator. CONCLUSIONS mSEPT9 showed good quantitative efficacy, higher applicability, and sensitivity, than CEA in assessing treatment response and prognosis prediction in patients with stage IV CRC and liver metastasis.
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16
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Cheng B, Ye S, Bai P. The efficacy of cytoreductive surgery for oligometastatic prostate cancer: a meta-analysis. World J Surg Oncol 2021; 19:160. [PMID: 34051809 PMCID: PMC8164769 DOI: 10.1186/s12957-021-02265-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 05/12/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUNDS At present, the application of tumor reduction surgery in oligometastatic prostate cancer has aroused extensive discussion among urologists, but clinicians have not reached a consensus on this issue. The purpose of this study was to evaluate the effect of cytoreductive surgery for patients with oligometastatic prostate cancer by meta-analysis. METHODS All relevant studies were systematically searched through The Cochrane Library, PubMed, Web of Science, EMBASE, and China Biomedical Literature Database (CBM) up to December 2019. All the previous clinical studies on the comparison of long-term efficacy between the cytoreductive surgery group and the endocrine therapy group were included in the search. The included studies were analyzed using Stata ver.14.0. The research has been registered on PROSPERO website with the registration number of crd42021224316. The relevant registration information can be obtained from the website: https://www.crd.york.ac.uk/prospero . RESULTS The case presentation is as follows: ten studies were identified that met the conclusion criteria. The total number of samples was 804; 449 patients underwent cytoreductive surgery, and 355 patients underwent endocrine therapy, and we conducted a meta-analysis of studies to compare the prognosis of endocrine therapy and cytoreductive surgery for treating prostate cancer. After all the studies were analyzed, we found that between cytoreductive surgery and endocrine therapy, a significant difference existed in overall survival (HR = 0.635, 95% CI 0.443-0.908, P = 0.013), cancer-specific survival (HR = 0.407, 95% CI 0.243-0.681, P = 0.001), and progression-free survival (HR = 0.489, 95% CI 0.315-0.758, P = 0.001), while there were no significant difference in progresses to castration-resistant prostate cancer (HR = 0.859, 95% CI 0.475-1.554, P = 0.616). CONCLUSION The cytoreductive surgery held advantages in overall survival, cancer-specific survival, and progression-free survival. Therefore, compared with endocrine therapy, cytoreductive surgery could be a more suitable approach in treating oligometastatic prostate cancer.
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Affiliation(s)
- Bisheng Cheng
- Zhongshan Hospital Affiliated to Xiamen University, Xiamen, 361001, China
| | - Shuchao Ye
- Zhongshan Hospital Affiliated to Xiamen University, Xiamen, 361001, China
| | - Peiming Bai
- Zhongshan Hospital Affiliated to Xiamen University, Xiamen, 361001, China.
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17
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Relevance of chemotherapy and margin status in colorectal liver metastasis. Langenbecks Arch Surg 2021; 406:2725-2737. [PMID: 34023941 DOI: 10.1007/s00423-021-02205-w] [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: 04/01/2020] [Accepted: 05/16/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE This retrospective, single-center study aimed to investigate the importance of chemotherapy and to come up with the optimal liver resection margin length for patients with resectable colorectal liver metastasis (CRLM). METHODS Patients who had undergone any form of liver resection for CRLM were reviewed and analyzed. The analyses were broken down into three parts: (1) overall effect of chemotherapy, (2) effect of chemotherapy with positive/negative resection margin, and (3) result of discriminative analysis with optimal margin length analysis. RESULTS In total, 381 patients were studied. Among them, 279 received chemotherapy whereas 102 did not. Survival was significantly better in patients with chemotherapy (5-year, 43.6% vs. 25.8%) (p < 0.001). Patients who received chemotherapy (n = 93) with negative margins had better survival than patients (n = 8) with positive margins (5-year, 28.1% vs. 0%) (p = 0.019). On multivariate analysis, margin involvement was the poor prognostic factor for survival. Patients who had chemotherapy (n = 238) with negative margin showed a trend of better survival than patients (n = 41) with positive margins (5-year, 45.7% vs. 29.3%) (p = 0.085). Patients (n = 93) with negative margin and no chemotherapy and patients (n = 41) with positive margin and chemotherapy had comparable survival at 5 years (p = 0.422). On multivariate analysis, tumor number was the prognostic factor for survival. By the discriminant method, 1.09 cm (sensitivity 0.242, specificity 0.718) was determined as the cut-off for optimal margin length. Patients who had margin ≥ 1.09 cm (n = 81) enjoyed significantly better survival (5-year, 54.3% vs. 33.5%) (p = 0.041). On multivariate analysis, margin length ≥ 1.09 cm was the prognostic factor for favorable survival. CONCLUSION The results demonstrated the important effect of perioperative chemotherapy and negative margin liver resection in management of patients suffered from CRLM.
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Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: A prospective cohort study. PLoS Med 2021; 18:e1003620. [PMID: 33939694 PMCID: PMC8128260 DOI: 10.1371/journal.pmed.1003620] [Citation(s) in RCA: 115] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 05/17/2021] [Accepted: 04/12/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND In patients with resectable colorectal liver metastases (CRLM), the role of pre- and postoperative systemic therapy continues to be debated. Previous studies have shown that circulating tumor DNA (ctDNA) analysis, as a marker of minimal residual disease, is a powerful prognostic factor in patients with nonmetastatic colorectal cancer (CRC). Serial analysis of ctDNA in patients with resectable CRLM could inform the optimal use of perioperative chemotherapy. Here, we performed a validation study to confirm the prognostic impact of postoperative ctDNA in resectable CRLM observed in a previous discovery study. METHODS AND FINDINGS We prospectively collected plasma samples from patients with resectable CRLM, including presurgical and postsurgical samples, serial samples during any pre- or postoperative chemotherapy, and serial samples in follow-up. Via targeted sequencing of 15 genes commonly mutated in CRC, we identified at least 1 somatic mutation in each patient's tumor. We then designed a personalized assay to assess 1 mutation in plasma samples using the Safe-SeqS assay. A total of 380 plasma samples from 54 patients recruited from July 2011 to Dec 2014 were included in our analysis. Twenty-three (43%) patients received neoadjuvant chemotherapy, and 42 patients (78%) received adjuvant chemotherapy after surgery. Median follow-up was 51 months (interquartile range, 31 to 60 months). At least 1 somatic mutation was identified in all patients' tumor tissue. ctDNA was detectable in 46/54 (85%) patients prior to any treatment and 12/49 (24%) patients after surgery. There was a median 40.93-fold (19.10 to 87.73, P < 0.001) decrease in ctDNA mutant allele fraction with neoadjuvant chemotherapy, but ctDNA clearance during neoadjuvant chemotherapy was not associated with a better recurrence-free survival (RFS). Patients with detectable postoperative ctDNA experienced a significantly lower RFS (HR 6.3; 95% CI 2.58 to 15.2; P < 0.001) and overall survival (HR 4.2; 95% CI 1.5 to 11.8; P < 0.001) compared to patients with undetectable ctDNA. For the 11 patients with detectable postoperative ctDNA who had serial ctDNA sampling during adjuvant chemotherapy, ctDNA clearance was observed in 3 patients, 2 of whom remained disease-free. All 8 patients with persistently detectable ctDNA after adjuvant chemotherapy have recurred. End-of-treatment (surgery +/- adjuvant chemotherapy) ctDNA detection was associated with a 5-year RFS of 0% compared to 75.6% for patients with an undetectable end-of-treatment ctDNA (HR 14.9; 95% CI 4.94 to 44.7; P < 0.001). Key limitations of the study include the small sample size and the potential for false-positive findings with multiple hypothesis testing. CONCLUSIONS We confirmed the prognostic impact of postsurgery and posttreatment ctDNA in patients with resected CRLM. The potential utility of serial ctDNA analysis during adjuvant chemotherapy as an early marker of treatment efficacy was also demonstrated. Further studies are required to define how to optimally integrate ctDNA analyses into decision-making regarding the use and timing of adjuvant therapy for resectable CRLM. TRIAL REGISTRATION ACTRN12612000345886.
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Li C, Liu JY, Jiang D, Qiu M. Expression and prognostic value of epithelial-to-mesenchymal transition and cancer stem cellmarkersin primary lesions and liver metastases of colorectal cancers. Oncol Lett 2021; 22:499. [PMID: 33981361 PMCID: PMC8108244 DOI: 10.3892/ol.2021.12760] [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: 05/21/2019] [Accepted: 03/22/2021] [Indexed: 02/05/2023] Open
Abstract
Cancer stem cells (CSCs) and epithelial mesenchymal transition (EMT) markers are considered useful indicators associated with metastasis and prognosis of colorectal cancers (CRCs). However, only a few studies have focused on the expression of these useful markers in metastases. Metastasectomy is widely used in advanced CRCs, and thus the postoperative prognostic factors are worth investigating. The present study investigated the consistency and differences of target proteins between primary and metastatic lesions of colorectal cancer, and discussed the prognostic indicators following resection of colorectal liver metastases. Clinical data of 56 patients with liver metastases from colorectal cancer were collected and the expression levels of target proteins (Ki-67, CD133, CD44, Snail, E-cadherin and β-catenin) were detected in primary tumor and matched liver metastases via immunohistochemistry analysis. Paired comparison between both tissue types was performed. The prognostic values of the target proteins for resectable colorectal cancer liver metastases were assessed. No significant differences were observed between the primary tissues and metastatic tissues. The consistency rates of these protein expression levels ranged from 51.8-78.6%. The maximum diameter of the liver metastases was <5 cm. Low Snail expression in metastases was associated with a longer overall survival (OS) time following resection of colorectal liver metastases. Furthermore, N0 stage and low carcinoembryonic antigen levels were associated with a longer progression-free survival time. Notably, no significant differences were observed in expression levels of the target proteins between the primary tumors and liver metastases. Taken together, the results of the present study suggest that Snail expression in liver metastases may be used as a novel independent prognostic factor for OS following resection of colorectal liver metastases.
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Affiliation(s)
- Cong Li
- Department of Medical Oncology, Cancer Center, The State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.,Department of Radioncology, Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing 400030, P.R. China
| | - Ji-Yan Liu
- Department of Medical Oncology, Cancer Center, The State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Dan Jiang
- Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Meng Qiu
- Department of Medical Oncology, Cancer Center, The State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China
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Abstract
Metastatic lesions are largely responsible for cancer-related deaths and are synonymous with a poor prognosis. However, this is not always true for patients with oligometastases whose disease may be amenable to curative-intent local therapies. It has been proposed that an "intermediate state" (oligometastasis) exists in between locoregional and advanced disease states; however, the clinical definition of oligometastasis varies, and there is limited understanding of how tumor biology differs between oligometastases and polymetastases. There is evidence that local therapies can extend survival in patients with oligometastases, yet patient selection for local intervention and/or systemic therapy remains a challenge. Prognostic and predictive biomarkers of oligometastatic disease are strongly needed to identify patient candidates most likely to gain survival benefit from local therapies and to aid in the incorporation of ablative treatments in the context of existing systemic therapies.
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21
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Outcome of Radical Surgery for Simultaneous Liver and Lung Metastases Synchronous with Primary Colorectal Cancer. Indian J Surg 2021. [DOI: 10.1007/s12262-021-02848-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Abstract
Background
Colorectal cancer (CRC) leads to metastatic disease in approximately 30% of patients. In patients with newly diagnosed CRC with both liver and lung metastases, curative resection is rarely possible. The aim of this study is to evaluate the overall (OS) and relapse-free survival (RFS) rates of these patients after resection with curative intent.
Methods
This study is a retrospective analysis of colorectal cancer patients (n=8, median age 54.3 years) with simultaneous liver and lung metastasis undergoing resection with curative intent between May 1st, 2002, to December 31st, 2016, at our institution.
Results
Colon was the primary tumour site in 2 patients and rectum in 6 patients. The median number of liver and lung metastases was 3 and 2, respectively. Patients received various treatment sequences individualized on tumour disease burden. R0 resection was achieved after all but one procedure. Two severe Clavien-Dindo grade IIIb complications were present. Median hospital stay was 9 (3–24) days per procedure. Tumour relapse was observed in all patients with median RFS of 9 (3–28) months and median OS of 40 (17–52) months. In 4 cases, where repeated resection of recurrent metastases (3 liver and 1 lung) was possible, the median OS was 43 months.
Conclusion
Our data suggests that patients seem to benefit from resection with curative intent, with tendency to prolonged OS and with acceptable complication rate. Tumour recurrence occurred in all patients. Repeated resection was beneficial and led to further prolonged OS.
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Neuroimmune Regulation of Surgery-Associated Metastases. Cells 2021; 10:cells10020454. [PMID: 33672617 PMCID: PMC7924204 DOI: 10.3390/cells10020454] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 02/12/2021] [Accepted: 02/17/2021] [Indexed: 02/06/2023] Open
Abstract
Surgery remains an essential therapeutic approach for most solid malignancies. Although for more than a century accumulating clinical and experimental data have indicated that surgical procedures themselves may promote the appearance and progression of recurrent and metastatic lesions, only in recent years has renewed interest been taken in the mechanism by which metastasizing of cancer occurs following operative procedures. It is well proven now that surgery constitutes a risk factor for the promotion of pre-existing, possibly dormant micrometastases and the acceleration of new metastases through several mechanisms, including the release of neuroendocrine and stress hormones and wound healing pathway-associated immunosuppression, neovascularization, and tissue remodeling. These postoperative consequences synergistically facilitate the establishment of new metastases and the development of pre-existing micrometastases. While only in recent years the role of the peripheral nervous system has been recognized as another contributor to cancer development and metastasis, little is known about the contribution of tumor-associated neuronal and neuroglial elements in the metastatic disease related to surgical trauma and wound healing. Specifically, although numerous clinical and experimental data suggest that biopsy- and surgery-induced wound healing can promote survival and metastatic spread of residual and dormant malignant cells, the involvement of the tumor-associated neuroglial cells in the formation of metastases following tissue injury has not been well understood. Understanding the clinical significance and underlying mechanisms of neuroimmune regulation of surgery-associated metastasis will not only advance the field of neuro–immuno–oncology and contribute to basic science and translational oncology research but will also produce a strong foundation for developing novel mechanism-based therapeutic approaches that may protect patients against the oncologically adverse effects of primary tumor biopsy and excision.
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Varrecchia T, Castiglia SF, Ranavolo A, Conte C, Tatarelli A, Coppola G, Di Lorenzo C, Draicchio F, Pierelli F, Serrao M. An artificial neural network approach to detect presence and severity of Parkinson's disease via gait parameters. PLoS One 2021; 16:e0244396. [PMID: 33606730 PMCID: PMC7894951 DOI: 10.1371/journal.pone.0244396] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 12/08/2020] [Indexed: 01/16/2023] Open
Abstract
Introduction Gait deficits are debilitating in people with Parkinson’s disease (PwPD), which inevitably deteriorate over time. Gait analysis is a valuable method to assess disease-specific gait patterns and their relationship with the clinical features and progression of the disease. Objectives Our study aimed to i) develop an automated diagnostic algorithm based on machine-learning techniques (artificial neural networks [ANNs]) to classify the gait deficits of PwPD according to disease progression in the Hoehn and Yahr (H-Y) staging system, and ii) identify a minimum set of gait classifiers. Methods We evaluated 76 PwPD (H-Y stage 1–4) and 67 healthy controls (HCs) by computerized gait analysis. We computed the time-distance parameters and the ranges of angular motion (RoMs) of the hip, knee, ankle, trunk, and pelvis. Principal component analysis was used to define a subset of features including all gait variables. An ANN approach was used to identify gait deficits according to the H-Y stage. Results We identified a combination of a small number of features that distinguished PwPDs from HCs (one combination of two features: knee and trunk rotation RoMs) and identified the gait patterns between different H-Y stages (two combinations of four features: walking speed and hip, knee, and ankle RoMs; walking speed and hip, knee, and trunk rotation RoMs). Conclusion The ANN approach enabled automated diagnosis of gait deficits in several symptomatic stages of Parkinson’s disease. These results will inspire future studies to test the utility of gait classifiers for the evaluation of treatments that could modify disease progression.
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Affiliation(s)
- Tiwana Varrecchia
- Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone Rome, Rome, Italy
- * E-mail:
| | - Stefano Filippo Castiglia
- Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy
| | - Alberto Ranavolo
- Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone Rome, Rome, Italy
| | | | - Antonella Tatarelli
- Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone Rome, Rome, Italy
- Department of Human Neurosciences, University of Rome Sapienza, Rome, Italy
| | - Gianluca Coppola
- Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy
| | - Cherubino Di Lorenzo
- Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy
| | - Francesco Draicchio
- Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, Monte Porzio Catone Rome, Rome, Italy
| | - Francesco Pierelli
- Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy
| | - Mariano Serrao
- Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy
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Abstract
BACKGROUND Anatomical resection (AR) for colorectal liver metastasis (CLM) is disputable. We investigated the impact of AR on short-term outcomes and survival in CLM patients. METHODS Patients having hepatectomy with AR or nonanatomical resection (NAR) for CLM were reviewed. Comparison was made between AR and NAR groups. Group comparison was performed again after propensity score matching with ratio 1:1. RESULTS AR group (n = 234 vs n = 89 in NAR group) had higher carcinoembryonic antigen level (20 vs 7.8 ng/mL, p ≤ 0.001), more blood loss (0.65 vs 0.2 L, p < 0.001), more transfusions (19.2% vs 3.4%, p = 0.001), longer operation (339.5 vs 180 min, p < 0.001), longer hospital stay (9 vs 6 days, p < 0.001), more tumors (p < 0.001), larger tumors (4 vs 2 cm, p < 0.001), more bilobar involvement (20.9% vs 7.9%, p = 0.006), and comparable survival (overall, p = 0.721; disease-free, p = 0.695). After propensity score matching, each group had 70 patients, with matched tumor number, tumor size, liver function, and tumor marker. AR group had more open resections (85.7% vs 68.6%, p = 0.016), more blood loss (0.556 vs 0.3 L, p = 0.001), more transfusions (17.1% vs 4.3%, p = 0.015), longer operation (310 vs 180 min, p < 0.001), longer hospital stay (8.5 vs 6 days, p = 0.002), comparable overall survival (p = 0.819), and comparable disease-free survival (p = 0.855). CONCLUSION Similar disease-free survival and overall survival of CLM patients were seen with the use of AR and NAR. However, AR may entail a more eventful postoperative course. NAR with margin should be considered whenever feasible.
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Cózar JM, Hernández C, Miñana B, Morote J, Alvarez-Cubero MJ. The role of prostate-specific antigen in light of new scientific evidence: An update in 2020. Actas Urol Esp 2021; 45:21-29. [PMID: 33408046 DOI: 10.1016/j.acuro.2020.09.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 09/23/2020] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To review and update the latest scientific evidence gathered in recent years regarding prostate-specific antigen (PSA) for better implementation into routine clinical practice. EVIDENCE ACQUISITION Analysis of the available evidence on the current role of PSA, based on the experience of an expert panel in the subject under analysis. EVIDENCE SYNTHESIS Currently, PSA cannot be considered only as a guide for the presence or absence of prostate cancer. This determination can also help the urologist to decide on the most convenient treatment for a patient with benign prostatic hypertrophy (BPH) as a criterion for disease progression, and it can also suggest the suspicious existence of a prostatic tumor when there is PSA rise of>0.3 ng/ml over the level reached 6 months after having initiated treatment with 5-alpha-reductase inhibitor. However, the limits of this PSA rise with derivatives of alternative 5-alpha-reductase (5-ARI) inhibitors to dutasteride are controversial. Moreover, PSA is a key factor for the follow-up of patients with prostate adenocarcinoma at any stage who have received treatment (surgery, radiotherapy or focal therapies, hormone therapy), it acts as a guide to identify biochemical recurrence, to suspect the existence of local or distant recurrence, as well as to propose or discard adjuvant treatments. Finally, the role of PSA as a screening tool has been recently reinforced, demonstrating increased mortality rates or the existence of more aggressive cases of prostate cancer in those countries where the use of this tool has declined. CONCLUSIONS We present new data about the current role of PSA in the management of patients treated for BPH and/or prostate cancer that should be implemented into routine clinical practice, with special emphasis on the relevant role of this biomarker in the screening and follow-up of prostate cancer, as well as in the progression of BPH in dutasteride treatment.
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Affiliation(s)
- J M Cózar
- Servicio de Urología, Hospital Universitario Virgen de la Nieves, Granada, España; Servicio de Urología, Hospital General Universitario Gregorio Marañón, Madrid, España.
| | - C Hernández
- Servicio de Urología, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - B Miñana
- Servicio de Urología, Hospital CUN de Madrid, Madrid, España
| | - J Morote
- Servicio de Urología, Hospital Universitario Vall de Hebrón, Barcelona, España
| | - M J Alvarez-Cubero
- Departamento de Bioquímica y Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Granada, Granada, España
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Ren W, Sell NM, Ferrone CR, Tanabe KK, Lillemoe KD, Qadan M. Size of the Largest Colorectal Liver Metastasis Is an Independent Prognostic Factor in the Neoadjuvant Setting. J Surg Res 2020; 259:253-260. [PMID: 33160635 DOI: 10.1016/j.jss.2020.09.039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 07/31/2020] [Accepted: 09/22/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Up to 50% of patients diagnosed with colorectal cancer develop metastases during the course of their disease. Surgical resection remains the only curative treatment option for colorectal liver metastases (CRLM), frequently in conjunction with neoadjuvant chemotherapy. This study sought to determine if the pathologic size of the largest CRLM impacted disease-free survival (DFS) and disease-specific survival (DSS) in the setting of neoadjuvant chemotherapy. METHODS All patients diagnosed with CRLM who underwent neoadjuvant chemotherapy for liver resection at the Massachusetts General Hospital between 2004 and 2016 were reviewed. The median size of the largest liver lesion was used as the cutoff for grouped evaluation. RESULTS A total of 214 patients were included. Median follow-up was 100.0 mo (interquartile range 68.9-133.8 mo). The median size of the largest lesion was 21 mm. Patients with lesions ≥21 mm exhibited significantly worse median DFS (12.5 mo versus 16.6 mo; P = 0.033) and median DSS (71.3 mo versus 103.5 mo; P = 0.038). CRLM lesions ≥21 mm were associated with poorer DFS on univariate analysis (hazard ratio (HR) = 1.42, 95% confidence interval (CI) 1.03-1.95 P = 0.033) and multivariable analysis (HR = 1.58, 95% CI 1.07-2.35, P = 0.023). CRLM lesions ≥21 mm were also independently associated with poorer DSS after liver resection on univariate analysis (HR = 1.51, 95% CI 1.02-2.24; P = 0.037) and multivariable analysis (HR = 1.98, 95% CI: 1.27-3.07; P = 0.002). CONCLUSIONS The size of the largest CRLM is an important prognostic factor for both DFS and DSS after neoadjuvant therapy and serves as a useful indicator of tumor biology.
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Affiliation(s)
- Weizheng Ren
- Department of Hepatopancreatobiliary Surgery, PLA General Hospital, First Medical Center, Beijing, PR China; Harvard Medical School, Boston, Massachusetts
| | - Naomi M Sell
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Cristina R Ferrone
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Kenneth K Tanabe
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Keith D Lillemoe
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Motaz Qadan
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
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Chen H, Louie A, Higginson D, Palma D, Colaco R, Sahgal A. Stereotactic Radiosurgery and Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease. Clin Oncol (R Coll Radiol) 2020; 32:713-727. [DOI: 10.1016/j.clon.2020.06.018] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 06/05/2020] [Accepted: 06/26/2020] [Indexed: 01/29/2023]
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Ma ZH, Wang YP, Zheng WH, Ma J, Bai X, Zhang Y, Wang YH, Chi D, Fu XB, Hua XD. Prognostic factors and therapeutic effects of different treatment modalities for colorectal cancer liver metastases. World J Gastrointest Oncol 2020; 12:1177-1194. [PMID: 33133385 PMCID: PMC7579728 DOI: 10.4251/wjgo.v12.i10.1177] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 08/18/2020] [Accepted: 09/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common malignant tumors in China, and the liver is the most common metastatic site in patients with advanced CRC. Hepatectomy is the gold standard treatment for colorectal liver metastases. For patients who cannot undergo radical resection of liver metastases for various reasons, ablation therapy, interventional therapy, and systemic chemotherapy can be used to improve their quality of life and prolong their survival time.
AIM To explore the prognostic factors and treatments of liver metastases of CRC.
METHODS A retrospective analysis was conducted on 87 patients with liver metastases from CRC treated at the Liaoning Cancer Hospital and Institute between January 2005 and March 2011. According to different treatments, the patients were divided into the following four groups: Surgical resection group (36 patients); ablation group (23 patients); intervention group (15 patients); and drug group (13 patients). The clinicopathological data and postoperative survival of the four groups were analyzed. The Kaplan-Meier method was used for survival analysis, and the Cox proportional hazards regression model was used for multivariate analysis.
RESULTS The median survival time of the 87 patients was 38.747 ± 3.062 mo, and the 1- and 3-year survival rates were 87.5% and 53.1%, respectively. The Cox proportional hazards model showed that the following factors were independent factors affecting prognosis: The degree of tumor differentiation, the number of metastases, the size of metastases, and whether the metastases are close to great vessels. The results of treatment factor analysis showed that the effect of surgical treatment was better than that of drugs, intervention, or ablation alone, and the median survival time was 48.83 ± 4.36 mo. The drug group had the worst prognosis, with a median survival time of only 13.5 ± 0.7 mo (P < 0.05). For patients with liver metastases of CRC near the great vessels, the median survival time (27.3 mo) of patients undergoing surgical resection was better than that of patients using other treatments (20.6 mo) (P < 0.05).
CONCLUSION Patients with a low degree of primary tumor differentiation, multiple liver metastases (number of tumors > 4), and maximum diameter of liver metastases > 5 cm have a poor prognosis. Among drug therapy, intervention, ablation, and surgical treatment options, surgical treatment is the first choice for liver metastases. When liver metastases are close to great vessels, surgical treatment is significantly better than drug therapy, intervention, and ablation alone.
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Affiliation(s)
- Zuo-Hong Ma
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Yong-Peng Wang
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Wen-Heng Zheng
- Department of Medical Imaging, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Ji Ma
- Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Xue Bai
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Yong Zhang
- Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Yuan-He Wang
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Da Chi
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Xi-Bo Fu
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Xiang-Dong Hua
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
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Peltonen R, Gramkow MH, Dehlendorff C, Osterlund PJ, Johansen JS, Isoniemi H. Elevated serum YKL-40, IL-6, CRP, CEA, and CA19-9 combined as a prognostic biomarker panel after resection of colorectal liver metastases. PLoS One 2020; 15:e0236569. [PMID: 32756596 PMCID: PMC7406016 DOI: 10.1371/journal.pone.0236569] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 07/08/2020] [Indexed: 12/17/2022] Open
Abstract
Background The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19–9 (CA19-9) in patients with colorectal liver metastases. Methods Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. Results Patients with 2–5 elevated biomarkers were at an increased risk of relapse compared to those with 0–1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1–1.72) or postoperatively (HR 1.54, 95% CI 1.23–1.92). Patients with 2–5 elevated biomarkers were also at an increased risk of death compared to those with 0–1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39–2.24) or postoperatively (HR 1.83, 95% CI 1.44–2.33). Conclusion The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.
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Affiliation(s)
- Reetta Peltonen
- Transplantation and Liver Surgery, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- * E-mail:
| | - Mathias H. Gramkow
- Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
| | - Christian Dehlendorff
- Statistics and Pharmacoepidemiology, Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen O, Denmark
| | - Pia J. Osterlund
- Department of Oncology, Tampere University Hospital, and University of Tampere, Tampere, Finland
- Helsinki University Hospital, Department of Oncology, and University of Helsinki, Helsinki, Finland
| | - Julia S. Johansen
- Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- Department of Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen K, Denmark
| | - Helena Isoniemi
- Transplantation and Liver Surgery, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Moro A, Mehta R, Tsilimigras DI, Sahara K, Paredes AZ, Bagante F, Guglielmi A, Alexandrescu S, Poultsides GA, Sasaki K, Aucejo FN, Pawlik TM. Prognostic factors differ according to KRAS mutational status: A classification and regression tree model to define prognostic groups after hepatectomy for colorectal liver metastasis. Surgery 2020; 168:497-503. [PMID: 32675031 DOI: 10.1016/j.surg.2020.05.019] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 05/04/2020] [Accepted: 05/11/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although KRAS mutation status is known to affect the prognosis of patients with colorectal liver metastasis, the hierarchical association between other prognostic factors and KRAS status is not fully understood. METHODS Patients who underwent a hepatectomy for colorectal liver metastasis were identified in a multi-institutional international database. A classification and regression tree model was constructed to investigate the hierarchical association between prognostic factors and overall survival relative to KRAS status. RESULTS Among 1,123 patients, 29.9% (n = 336) had a KRAS mutation. Among wtKRAS patients, the classification and regression tree model identified presence of metastatic lymph nodes as the most important prognostic factor, whereas among mtKRAS patients, carcinoembryonic antigen level was identified as the most important prognostic factor. Among patients with wtKRAS, the highest 5-year overall survival (68.5%) was noted among patients with node negative primary colorectal cancer, solitary colorectal liver metastases, size <4.3 cm. In contrast, among patients with mtKRAS colorectal liver metastases, the highest 5-year overall survival (57.5%) was observed among patients with carcinoembryonic antigen <6 mg/mL. The classification and regression tree model had higher prognostic accuracy than the Fong score (wtKRAS [Akaike's Information Criterion]: classification and regression tree model 3334 vs Fong score 3341; mtKRAS [Akaike's Information Criterion]: classification and regression tree model 1356 vs Fong score 1396). CONCLUSION Machine learning methodology outperformed the traditional Fong clinical risk score and identified different factors, based on KRAS mutational status, as predictors of long-term prognosis.
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Affiliation(s)
- Amika Moro
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Rittal Mehta
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Kota Sahara
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Anghela Z Paredes
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH
| | - Fabio Bagante
- Department of Surgery, University of Verona, Verona, Italy
| | | | | | | | - Kazunari Sasaki
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH
| | - Federico N Aucejo
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH.
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Wu L, Fu J, Chen Y, Wang L, Zheng S. Early T Stage Is Associated With Poor Prognosis in Patients With Metastatic Liver Colorectal Cancer. Front Oncol 2020; 10:716. [PMID: 32626650 PMCID: PMC7314979 DOI: 10.3389/fonc.2020.00716] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 04/16/2020] [Indexed: 11/13/2022] Open
Abstract
Clinically, a considerable portion of patients with early T stage who were supposed to have a low distant metastatic probability were diagnosed with metastatic liver colorectal cancer (CRLM). Our study aims to evaluate the prognostic value of the T stage for metastatic patients and establish a convenient individual assessment model for clinicians to explore preoperative predictors. The mRNA profiles of colorectal tumors (N = 19) were obtained by microarray at our clinical center. A total of 5,618 patients with CRLM from 2010 to 2015 were enrolled for the Surveillance, Epidemiology, and End Results (SEER) database. The cDNA microarray analyses showed that gene expression pattern in the T2N0M1 subgroup was significantly different from the T3/4N0M0 subgroup. In the survival analysis, metastatic patients with T1 stage surprisingly had much poorer prognosis than those with T3/T4 stage. Specifically, metastatic patients with early T stage were observed with higher frequency occurring at the rectum, better differentiation, less metastases in the lymph nodes, and a higher CEA level. Further survival analysis indicated that early T classification was an independent prognostic factor for a poor survival. When the lymph node (N) status was taken into consideration, patients with T1/2N+ had better survival than T1/2N0 patients. A clinical nomogram was constructed based on preoperative factors. The calibration curves showed a good concordance between nomogram prediction and actual observation. In conclusion, CRLM with early T stage had a different biological background. The prognosis of patients at T1/2M1 was poorer than at T3/4M1. More attention should be paid to the surveillance of high-risk factors and the screening of early T stage.
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Affiliation(s)
- Lunpo Wu
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.,Institution of Gastroenterology, Zhejiang University, Hangzhou, China
| | - Jianfei Fu
- Department of Medical Oncology, Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Yi Chen
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.,Institution of Gastroenterology, Zhejiang University, Hangzhou, China
| | - Liangjing Wang
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.,Institution of Gastroenterology, Zhejiang University, Hangzhou, China
| | - Shu Zheng
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, Chinese National Ministry of Education and Key Laboratory of Molecular Biology in Medical Sciences), Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Hazhirkarzar B, Khoshpouri P, Shaghaghi M, Ghasabeh MA, Pawlik TM, Kamel IR. Current state of the art imaging approaches for colorectal liver metastasis. Hepatobiliary Surg Nutr 2020; 9:35-48. [PMID: 32140477 DOI: 10.21037/hbsn.2019.05.11] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
One of the most common cancers worldwide, colorectal cancer (CRC) has been associated with significant morbidity and mortality and therefore represents an enormous burden to the health care system. Recent advances in CRC treatments have provided patients with primary and metastatic CRC a better long-term prognosis. The presence of synchronous or metachronous metastasis has been associated, however, with worse survival. The most common site of metastatic disease is the liver. A variety of treatment modalities aimed at targeting colorectal liver metastases (CRLM) has been demonstrated to improve the prognosis of these patients. Loco-regional approaches such as surgical resection and tumor ablation (operative and percutaneous) can provide patients with a chance at long-term disease control and even cure in select populations. Patient selection is important in defining the most suitable treatment option for CRLM in order to provide the best possible survival benefit while avoiding unnecessary interventions and adverse events. Medical imaging plays a crucial role in evaluating the characteristics of CRLMs and disease resectability. Size of tumors, proximity to adjacent anatomical structures, and volume of the unaffected liver are among the most important imaging parameters to determine the suitability of patients for surgical management or other appropriate treatment approaches. We herein provide a comprehensive overview of current-state-of-the-art imaging in the management of CRLM, including staging, treatment planning, response and survival assessment, and post-treatment surveillance. Computed tomography (CT) scan and magnetic resonance imaging (MRI) are two most commonly used techniques, which can be used solely or in combination with functional imaging modalities such as positron emission tomography (PET) and diffusion weighted imaging (DWI). Providing up-to-date evidence on advantages and disadvantages of imaging modalities and tumor assessment criteria, the current review offers a practice guide to assist providers in choosing the most suitable imaging approach for patients with CRLM.
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Affiliation(s)
- Bita Hazhirkarzar
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Pegah Khoshpouri
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mohammadreza Shaghaghi
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mounes Aliyari Ghasabeh
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Ihab R Kamel
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Engstrand J, Strömberg C, Nilsson H, Freedman J, Jonas E. Synchronous and metachronous liver metastases in patients with colorectal cancer-towards a clinically relevant definition. World J Surg Oncol 2019; 17:228. [PMID: 31878952 PMCID: PMC6933908 DOI: 10.1186/s12957-019-1771-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 12/16/2019] [Indexed: 12/17/2022] Open
Abstract
Background Approximately 25% of patients with colorectal cancer (CRC) will have liver metastases classified as synchronous or metachronous. There is no consensus on the defining time point for synchronous/metachronous, and the prognostic implications thereof remain unclear. The aim of the study was to assess the prognostic value of differential detection at various defining time points in a population-based patient cohort and conduct a literature review of the topic. Methods All patients diagnosed with CRC in the counties of Stockholm and Gotland, Sweden, during 2008 were included in the study and followed for 5 years or until death to identify patients diagnosed with liver metastases. Patients with liver metastases were followed from time of diagnosis of liver metastases for at least 5 years or until death. Different time points defining synchronous/metachronous detection, as reported in the literature and identified in a literature search of databases (PubMed, Embase, Cochrane library), were applied to the cohort, and overall survival was calculated using Kaplan-Meier curves and compared with log-rank test. The influence of synchronously or metachronously detected liver metastases on disease-free and overall survival as reported in articles forthcoming from the literature search was also assessed. Results Liver metastases were diagnosed in 272/1026 patients with CRC (26.5%). No statistically significant difference in overall survival for synchronous vs. metachronous detection at any of the defining time points (CRC diagnosis/surgery and 3, 6 and 12 months post-diagnosis/surgery) was demonstrated for operated or non-operated patients. In the literature search, 41 publications met the inclusion criteria. No clear pattern emerged regarding the prognostic significance of synchronous vs. metachronous detection. Conclusion Synchronous vs. metachronous detection of CRC liver metastases lacks prognostic value. Using primary tumour diagnosis/operation as standardized cut-off point to define synchronous/metachronous detection is semantically correct. In synchronous detection, it defines a clinically relevant group of patients where individualized multimodality treatment protocols will apply.
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Affiliation(s)
- Jennie Engstrand
- Division of Surgery, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, 182 88, Stockholm, Sweden.
| | - Cecilia Strömberg
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Henrik Nilsson
- Division of Surgery, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, 182 88, Stockholm, Sweden
| | - Jacob Freedman
- Division of Surgery, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, 182 88, Stockholm, Sweden
| | - Eduard Jonas
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,Surgical Gastroenterology Unit, Department of Surgery, Groote Schuur Hospital, University of Cape Town Health Sciences Faculty, Cape Town, South Africa
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Goto T. Is local consolidative therapy adequate for the treatment of oligometastatic non-small cell lung cancer? J Thorac Dis 2019; 11:E154-E157. [PMID: 31737327 DOI: 10.21037/jtd.2019.09.80] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Taichiro Goto
- Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, Yamanashi, Japan
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35
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Turpin A, Hebbar M. ASO Author Reflections: Fong's Score in the Era of Modern Strategies for Metastatic Colorectal Cancer. Ann Surg Oncol 2019; 27:886. [PMID: 31720930 DOI: 10.1245/s10434-019-08059-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Indexed: 11/18/2022]
Affiliation(s)
- Anthony Turpin
- Department of Medical Oncology, Lille University Hospital, Lille, France. .,University of Lille, Lille, France.
| | - Mohamed Hebbar
- Department of Medical Oncology, Lille University Hospital, Lille, France.,University of Lille, Lille, France
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36
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New concepts in prostate cancer management: the conundrum of managing oligometastatic disease in prostate cancer—through the looking glass darkly. Clin Radiol 2019; 74:865-875. [DOI: 10.1016/j.crad.2019.05.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 05/08/2019] [Indexed: 02/02/2023]
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37
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Makhloufi S, Turpin A, el Amrani M, André T, Truant S, Bachet JB, Vernerey D, Hebbar M. Fong’s Score in the Era of Modern Perioperative Chemotherapy for Metastatic Colorectal Cancer: A Post Hoc Analysis of the GERCOR-MIROX Phase III Trial. Ann Surg Oncol 2019; 27:877-885. [DOI: 10.1245/s10434-019-07976-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Indexed: 01/04/2023]
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38
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Triantafyllidis I, Gayet B, Tsiakyroudi S, Tabchouri N, Beaussier M, Bennamoun M, Sarran A, Lefevre M, Louvet C, Fuks D. Perioperative and long-term outcomes of laparoscopic liver resections for non-colorectal liver metastases. Surg Endosc 2019; 34:3833-3844. [PMID: 31586246 DOI: 10.1007/s00464-019-07148-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 09/24/2019] [Indexed: 01/15/2023]
Abstract
BACKGROUND Liver is a common metastatic site not only of colorectal but of non-colorectal neoplasms, as well. However, resection of non-colorectal liver metastases (NCRLMs) remains controversial. The aim of this retrospective study was to analyze the short- and long-term outcomes of patients undergoing laparoscopic liver resection (LLR) for NCRLMs. METHODS From a prospectively maintained database between 2000 and 2018, patients undergoing LLR for colorectal liver metastases (CRLMs) and NCRLMs were selected. Clinicopathologic, operative, short- and long-term outcome data were collected, analyzed, and compared among patients with CRLMs and NCRLMs. RESULTS The primary tumor was colorectal in 354 (82.1%), neuroendocrine in 21 (4.9%), and non-colorectal, non-neuroendocrine in the remaining 56 (13%) patients. Major postoperative morbidities were 12.7%, 19%, and 3.6%, respectively (p = 0.001), whereas the mortality was 0.6% for patients with CRLMs and zero for patients with NCRLMs. The rate of R1 surgical margin was comparable (p = 0.432) among groups. According to the survival analysis, 3- and 5-year recurrence-free survival (RFS) rates were 76.1% and 64.3% in the CRLM group, 57.1% and 42.3% in the neuroendocrine liver metastase (NELM) group, 33% and 20.8% in the non-colorectal, non-neuroendocrine liver metastase (NCRNNELM) group (p = 0.001), respectively. Three- and 5-year overall survival (OS) rates were 88.3% and 82.7% in the CRLM group, 85.7% and 70.6% in the NELM group, 71.4% and 52.9% in the NCRNNELM group (p = 0.001), respectively. In total, 113 out of 354 (31.9%) patients with CRLMs, 2 out of 21(9.5%) with NELMs, and 8 out of 56 (14.3%) patients with NCRNNELMs underwent repeat LLR for recurrent metastatic tumors. CONCLUSION LLR is safe and feasible in the context of a multimodal management where an aggressive surgical approach, necessitating even complex procedures for bilobar multifocal metastases and repeat hepatectomy for recurrences, is the mainstay and may be of benefit in the long-term survival, in selected patients with NCRNNELMs.
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Affiliation(s)
- Ioannis Triantafyllidis
- Department of Digestive Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Université Paris Descartes, 42 Boulevard Jourdan, 75014, Paris, France.,Department of General Surgery, General Hospital of Veria, 59132, Veria, Greece
| | - Brice Gayet
- Department of Digestive Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Université Paris Descartes, 42 Boulevard Jourdan, 75014, Paris, France
| | - Sofia Tsiakyroudi
- Department of Digestive Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Université Paris Descartes, 42 Boulevard Jourdan, 75014, Paris, France
| | - Nicolas Tabchouri
- Department of Digestive Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Université Paris Descartes, 42 Boulevard Jourdan, 75014, Paris, France
| | - Marc Beaussier
- Department of Digestive Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Université Paris Descartes, 42 Boulevard Jourdan, 75014, Paris, France
| | - Mostefa Bennamoun
- Department of Oncology, Institut Mutualiste Montsouris, 42 Boulevard Jourdan, 75014, Paris, France
| | - Anthony Sarran
- Department of Radiology, Institut Mutualiste Montsouris, 42 Boulevard Jourdan, 75014, Paris, France
| | - Marine Lefevre
- Department of Pathology, Institut Mutualiste Montsouris, 42 Boulevard Jourdan, 75014, Paris, France
| | - Christophe Louvet
- Department of Oncology, Institut Mutualiste Montsouris, 42 Boulevard Jourdan, 75014, Paris, France
| | - David Fuks
- Department of Digestive Oncologic and Metabolic Surgery, Institut Mutualiste Montsouris, Université Paris Descartes, 42 Boulevard Jourdan, 75014, Paris, France.
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Tran BX, Latkin CA, Sharafeldin N, Nguyen K, Vu GT, Tam WWS, Cheung NM, Nguyen HLT, Ho CSH, Ho RCM. Characterizing Artificial Intelligence Applications in Cancer Research: A Latent Dirichlet Allocation Analysis. JMIR Med Inform 2019; 7:e14401. [PMID: 31573929 PMCID: PMC6774235 DOI: 10.2196/14401] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 06/27/2019] [Accepted: 07/19/2019] [Indexed: 01/08/2023] Open
Abstract
Background Artificial intelligence (AI)–based therapeutics, devices, and systems are vital innovations in cancer control; particularly, they allow for diagnosis, screening, precise estimation of survival, informing therapy selection, and scaling up treatment services in a timely manner. Objective The aim of this study was to analyze the global trends, patterns, and development of interdisciplinary landscapes in AI and cancer research. Methods An exploratory factor analysis was conducted to identify research domains emerging from abstract contents. The Jaccard similarity index was utilized to identify the most frequently co-occurring terms. Latent Dirichlet Allocation was used for classifying papers into corresponding topics. Results From 1991 to 2018, the number of studies examining the application of AI in cancer care has grown to 3555 papers covering therapeutics, capacities, and factors associated with outcomes. Topics with the highest volume of publications include (1) machine learning, (2) comparative effectiveness evaluation of AI-assisted medical therapies, and (3) AI-based prediction. Noticeably, this classification has revealed topics examining the incremental effectiveness of AI applications, the quality of life, and functioning of patients receiving these innovations. The growing research productivity and expansion of multidisciplinary approaches are largely driven by machine learning, artificial neural networks, and AI in various clinical practices. Conclusions The research landscapes show that the development of AI in cancer care is focused on not only improving prediction in cancer screening and AI-assisted therapeutics but also on improving other corresponding areas such as precision and personalized medicine and patient-reported outcomes.
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Affiliation(s)
- Bach Xuan Tran
- Institute for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam.,Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States
| | - Carl A Latkin
- Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States
| | - Noha Sharafeldin
- Division of Hematology & Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.,Institute for Cancer Outcomes and Survivorship, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Katherina Nguyen
- Department of Science, Technology, and Society, Stanford University, Palo Alto, CA, United States
| | - Giang Thu Vu
- Center of Excellence in Evidence-based Medicine, Nguyen Tat Thanh University, Ho Chi Minh, Vietnam
| | - Wilson W S Tam
- Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ngai-Man Cheung
- Center of Excellence in Artificial Intelligence in Medicine, Nguyen Tat Thanh University, Ho Chi Minh, Vietnam.,Information Systems Technology and Design, Singapore University of Technology and Design, Singapore, Singapore
| | | | - Cyrus S H Ho
- Department of Psychological Medicine, National University Hospital, Singapore, Singapore
| | - Roger C M Ho
- Center of Excellence in Behavior Medicine, Nguyen Tat Thanh University, Ho Chi Minh, Vietnam.,Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore.,Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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40
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Džunić M, Pejčić B, Andjelković-Apostolović M, Vrbić S, Pejčić I, Petković I. PREDICTORS OF THERAPY RESPONSE AND EARLY RECURRENCE IN PATIENTS WITH POTENTIALLY RESECTABLE COLORECTAL LIVER METASTASES TREATED WITH BEVACIZUMAB AND FOLFOX4 AS A CONVERSION THERAPY. ACTA MEDICA MEDIANAE 2019. [DOI: 10.5633/amm.2019.0310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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41
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Cowan ML. Management of Stage IV rectal disease – How to incorporate radiation therapy, chemotherapy and surgery. SEMINARS IN COLON AND RECTAL SURGERY 2019. [DOI: 10.1053/j.scrs.2019.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Hof J, Kok K, Sijmons RH, de Jong KP. Systematic Review of the Prognostic Role of the Immune System After Surgery of Colorectal Liver Metastases. Front Oncol 2019; 9:148. [PMID: 30941301 PMCID: PMC6433783 DOI: 10.3389/fonc.2019.00148] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 02/21/2019] [Indexed: 12/11/2022] Open
Abstract
Background: The current prognostication of patient survival after surgery for colorectal liver metastases is based on clinical characteristics, but low accuracy makes it difficult to guide treatment for the individual patient. Rapidly evolving technologies have led to the expectation that biomarkers will be able to outperform the current clinical scoring systems and provide more effective personalised treatment. Two main topics prevail in cancer treatment, namely the role of the immune system and the prediction and prognostication by application of high-throughput methodology. The aim of this review is to examine the evidence for prognostic immunological and molecular markers studied in tumour tissue obtained at surgical resection for colorectal liver metastases. Methods: First we analysed immunophenotypical protein markers, that are mainly studied by immunohistochemistry. Second, we review molecular markers by analysing high-throughput studies on tumour mRNA and microRNA expression. Results: CD3, CD4, and CD8 are the most frequently studied protein markers. High intra-tumoural CD3+ T cell infiltration and low CXCR4 expression have the best association with favourable patient survival. Studies that analysed microRNA or mRNA expression data showed very little overlap in prognostic genes. Conclusions: Patient prognostication after surgery for colorectal liver metastases by analysing the immune system remains difficult. Current data are based on diverse and heterogeneous patient populations which prohibits drawing firm conclusions.
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Affiliation(s)
- Joost Hof
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.,Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Klaas Kok
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Rolf H Sijmons
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Koert P de Jong
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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Gao H, Meng XY, Wang HQ, Zhu FF, Guo AL, Zhu M, Song JC, Yu WF. Association between Anaesthetic Technique and Oncological Outcomes after Colorectal Carcinoma Liver Metastasis Resection. Int J Med Sci 2019; 16:337-342. [PMID: 30745816 PMCID: PMC6367527 DOI: 10.7150/ijms.28016] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 12/22/2018] [Indexed: 12/17/2022] Open
Abstract
Background: Recently published studies suggest that the anaesthetic technique used during oncologic surgery can improve patient outcomes. Therefore, the authors evaluated the survival of patients with resected colorectal carcinoma liver metastases (CRCLMs) who received either EGA (general anaesthesia [GA] combined with epidural anaesthesia [EA]) or GA alone. Methods: We conducted an ambispective cohort study including 225 post-surgical CRCLM patients between May 2007 and July 2012 and performed a follow-up investigation of survival in July 2017. Results: The basic characteristics in the two groups were largely similar. The median (quartiles) recurrence interval for all patients was 10 (2.5, 23) months, and the median (quartiles) survival for CRCLM patients post-surgically was 37 (30.5, 51.5) months. Perioperative EA was associated with survival (P =0.039, log-rank test), with an estimated hazard ratio of 0.737 (95% CI 0.551-0.985) in the univariate analysis. Kaplan-Meier estimates of survival for GA and EGA suggested that GA might provide better outcomes than EGA [P=0.028, hazard ratio of 0.7328 (95% CI 0.5433-0.9884)]. Significant differences in anaesthesia techniques were found (P=0.048), with an adjusted estimated hazard ratio of 0.741 (95% CI 0.550-0.998) in the multivariate analysis. Subgroup analyses of patients in different age groups (< 40, ≥ 40 but <60, and ≥ 60 years old) suggested that no significant differences existed among all three subgroups. Conclusions: Compared with EGA, GA may provide a better survival outcome for CRCLM patients. The benefits of anaesthetic techniques in oncological surgery are most likely related to certain cancer types.
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Affiliation(s)
- Hao Gao
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
- Department of Anesthesiology, Shanghai Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, China
| | - Xiao-Yan Meng
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Hong-Qian Wang
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Feng-Feng Zhu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of the University of South China, 69 Chuanshan Road, Hunan, China
| | - Ai-Ling Guo
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Mei Zhu
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Jin-Chao Song
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
| | - Wei-Feng Yu
- Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China
- Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pudian Road, Shanghai, China
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Otake S, Goto T. Stereotactic Radiotherapy for Oligometastasis. Cancers (Basel) 2019; 11:cancers11020133. [PMID: 30678111 PMCID: PMC6407034 DOI: 10.3390/cancers11020133] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 01/17/2019] [Accepted: 01/21/2019] [Indexed: 12/22/2022] Open
Abstract
Oligometastatic disease is defined as “a condition with a few metastases arising from tumors that have not acquired a potential for widespread metastases.” Its behavior suggests a transitional malignant state somewhere between localized and metastatic cancer. Treatment of oligometastatic disease is expected to achieve long-term local control and to improve survival. Historically, patients with oligometastases have often undergone surgical resection since it was anecdotally believed that surgical resection could result in progression-free or overall survival benefits. To date, no prospective randomized trials have demonstrated surgery-related survival benefits. Short courses of highly focused, extremely high-dose radiotherapies (e.g., stereotactic radiosurgery and stereotactic ablative body radiotherapy (SABR)) have frequently been used as alternatives to surgery for treatment of oligometastasis. A randomized study has demonstrated the overall survival benefits of stereotactic radiosurgery for solitary brain metastasis. Following the success of stereotactic radiosurgery, SABR has been widely accepted for treating extracranial metastases, considering its efficacy and minimum invasiveness. In this review, we discuss the history of and rationale for the local treatment of oligometastases and probe into the implementation of SABR for oligometastatic disease.
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Affiliation(s)
- Sotaro Otake
- Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, Kofu 400-8506, Japan.
| | - Taichiro Goto
- Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, Kofu 400-8506, Japan.
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Torén W, Ansari D, Andersson R. Immunohistochemical investigation of prognostic biomarkers in resected colorectal liver metastases: a systematic review and meta-analysis. Cancer Cell Int 2018; 18:217. [PMID: 30602942 PMCID: PMC6307223 DOI: 10.1186/s12935-018-0715-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 12/18/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Many studies have investigated the prognostic role of biomarkers in colorectal liver metastases (CRLM). However, no biomarker has been established in routine clinical practice. The aim of this study was to scrutinize the current literature for biomarkers evaluated by immunohistochemistry as prognostic markers in patients with resected CRLM. METHODS A systematic review was performed according to the PRISMA guidelines. Articles were identified in the PubMed database with selected search terms and by cross-references search. The REMARK quality criteria were applied. Markers were included if they reported the prognostic impact of immunohistochemical markers in a multivariable setting in relation to overall survival (OS). A meta-analysis was conducted when more than one original article provided survival data of a marker. RESULTS In total, 26 biomarkers were identified as independent significant markers for OS in resected CRLM. These biomarkers were found to be involved in multiple oncogenic signalling pathways that control cell growth, apoptosis, angiogenesis and evasion of immune detection. Among these biomarker candidates were Ki-67, EGFR, p53, hTERT, CD34, TSP-1, KISS1, Aurora kinase A and CDX2. CD34 and TSP-1 were reported as significantly associated with survival by more than one study and where therefore pooled in a meta-analysis. CONCLUSION A number of independent prognostic biomarkers for resected CRLM were identified. However, most markers were evaluated in a retrospective setting with small patient cohorts, without external validation. Large, prospective, multicentre studies with standardised methods are needed before biomarkers can translated into the clinic.
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Affiliation(s)
- William Torén
- Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital, SE-221 85 Lund, Sweden
| | - Daniel Ansari
- Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital, SE-221 85 Lund, Sweden
| | - Roland Andersson
- Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital, SE-221 85 Lund, Sweden
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Falcão D, Alexandrino H, Caetano Oliveira R, Martins J, Ferreira L, Martins R, Serôdio M, Martins M, Tralhão JG, Cipriano MA, Castro E Sousa F. Histopathologic patterns as markers of prognosis in patients undergoing hepatectomy for colorectal cancer liver metastases - Pushing growth as an independent risk factor for decreased survival. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2018; 44:1212-1219. [PMID: 29691114 DOI: 10.1016/j.ejso.2018.03.023] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Revised: 03/11/2018] [Accepted: 03/27/2018] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). PATIENTS AND METHODS Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). RESULTS The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis. CONCLUSION The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients.
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Affiliation(s)
- Daniela Falcão
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal
| | - Henrique Alexandrino
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
| | - Rui Caetano Oliveira
- Serviço de Anatomia Patológica - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - João Martins
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal
| | | | - Ricardo Martins
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Marco Serôdio
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Mónica Martins
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - José Guilherme Tralhão
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Maria Augusta Cipriano
- Serviço de Anatomia Patológica - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Francisco Castro E Sousa
- Faculdade de Medicina - Universidade de Coimbra, Coimbra, Portugal; Serviço de Cirurgia A - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
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Shim JR, Lee SD, Han SS, Lee SJ, Lee DE, Kim SK, Kim SH, Park SJ, Oh JH. Prognostic significance of 18F-FDG PET/CT in patients with colorectal cancer liver metastases after hepatectomy. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2018; 44:670-676. [PMID: 29459018 DOI: 10.1016/j.ejso.2018.01.243] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Revised: 01/03/2018] [Accepted: 01/31/2018] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Colorectal cancer liver metastasis (CRLM) can be cured with surgery. To improve survival, optimal selection of CRLM patients should be done cautiously, which may be facilitated by preoperative [F-18] fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). METHODS A total of 245 patients with CRLM between February 2007 and January 2015 were retrospectively studied. All clinical variables, pathological data, and various PET/CT parameters were correlated with disease-free survival (DFS) and overall survival (OS). Metastatic tumor maximum standardized uptake value (SUVmax) and normal liver mean SUV (SUVmean) ratio was selected for group classification. RESULTS The median DFS in months were 24.5 months and median OS were 41.7 months. Multivariate analysis found an increased risk of worse prognosis in DFS for primary colon cancer T3∼T4, N2 stage, neoadjuvant chemotherapy, synchronous metastasis, multiple metastatic tumor number and metastatic tumor SUVmax/normal liver SUVmean ratio >4.3. The DFS rate of each group classified by SUV ratio was 58.1%, 39.0%, and 33.6% vs. 39.3%, 20.8%, and 15.8% at 1, 3, and 5 years (p = 0.017). Patients with multiple tumors and SUV ratio of >4.3 showed worst survival (OS rate: 74.2%, 41.5%, and 24.2%, p = 0.001 at 1, 3, and 5 years, respectively). CONCLUSIONS PET/CT variables can be a valuable prognostic factor in patients with CRLM for the prediction of recurrence. Preoperative PET/CT may improve risk stratification and optimize outcomes of patients with CRLM.
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Affiliation(s)
- Jae-Ryong Shim
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Seung Duk Lee
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
| | - Sung-Sik Han
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
| | - Sang Jae Lee
- Center for Colorectal Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Dong Eun Lee
- Biometric Research Branch, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Seok-Ki Kim
- Department of Nuclear Medicine, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Seong Hoon Kim
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Sang Jae Park
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Jae-Hwan Oh
- Center for Colorectal Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea
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Acciuffi S, Meyer F, Bauschke A, Settmacher U, Lippert H, Croner R, Altendorf-Hofmann A. Analysis of prognostic factors after resection of solitary liver metastasis in colorectal cancer: a 22-year bicentre study. J Cancer Res Clin Oncol 2018; 144:593-599. [PMID: 29340767 DOI: 10.1007/s00432-018-2583-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Accepted: 01/11/2018] [Indexed: 02/08/2023]
Abstract
PURPOSE The investigation of the predictors of outcome after hepatic resection for solitary colorectal liver metastasis. METHODS We recruited 350 patients with solitary colorectal liver metastasis at the University Hospitals of Jena and Magdeburg, who underwent curative liver resection between 1993 and 2014. All patients had follow-up until death or till summer 2016. RESULTS The follow-up data concern 96.6% of observed patients. The 5- and 10-year overall survival rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival rates were 30 and 20%, respectively. The analysis of the prognostic factors revealed that the pT category of primary tumour, size and grade of the metastasis and extension of the liver resection had no statistically significant impact on survival and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant predictors for the prognosis. Moreover, patients with rectal cancer had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence rate. CONCLUSION The long-term follow-up of patients with R0-resected liver metastasis is multifactorially influenced. Age and comorbidity have a role only in the overall survival. More than three lymph node metastasis reduced both the overall and disease-free survival. Extrahepatic tumour had a negative influence on the extrahepatic recurrence and on the overall survival. Neither overall survival nor recurrence rates was improved using neoadjuvant chemotherapy.
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Affiliation(s)
- Sara Acciuffi
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Frank Meyer
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Astrid Bauschke
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - Utz Settmacher
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - Hans Lippert
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Roland Croner
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Annelore Altendorf-Hofmann
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany.
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Gurusamy K, Corrigan N, Croft J, Twiddy M, Morris S, Woodward N, Bandula S, Hochhauser D, Napp V, Pullan A, Jakowiw N, Prasad R, Damink SO, van Laarhoven CJHM, de Wilt JHW, Brown J, Davidson BR. Liver resection surgery versus thermal ablation for colorectal LiVer MetAstases (LAVA): study protocol for a randomised controlled trial. Trials 2018; 19:105. [PMID: 29439711 PMCID: PMC5811975 DOI: 10.1186/s13063-018-2499-5] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Accepted: 01/24/2018] [Indexed: 12/22/2022] Open
Abstract
Background Although surgical resection has been considered the only curative option for colorectal liver metastases (CLM), thermal ablation has recently been suggested as an alternative curative treatment. A prospective randomised trial is required to define the efficacy of resection vs ablation for the treatment of colorectal liver metastases. Methods Design and setting: This is a multicentre, open, randomised controlled non-inferiority trial design with internal pilot and will be performed in tertiary liver centres in UK and The Netherlands. Participants: Eligible patients will be those with colorectal liver metastases at high surgical risk because of their age, co-morbidities or tumour burden and who would be suitable for liver resection or thermal ablation. Intervention: Thermal ablation as per local policy. Control: Surgical liver resection performed as per centre protocol. Co-interventions: Further chemotherapy will be offered to patients as per current practice. Outcomes Pilot study: Same as main study and in addition patients and clinicians’ acceptability of the trial to assist in optimisation of recruitment. Primary outcome: Disease-free survival (DFS) at two years post randomisation. Secondary outcomes: Overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, DFS measured from end of intervention. Follow-up: 24 months from randomisation; five-year follow-up for overall survival. Sample size: 330 patients to demonstrate non-inferiority of thermal ablation. Discussion This trial will determine the effectiveness and cost-effectiveness of thermal ablation vs surgical resection for high-risk people with colorectal liver metastases, and guide the optimal treatment for these patients. Trial registration ISRCTN Registry, ISRCTN52040363. Registered on 9 March 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-2499-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Kurinchi Gurusamy
- Royal Free Campus, Division of Surgery and Interventional Science, University College London, 9th Floor, Royal Free Hospital, Rowland Hill Street, NW3 2PF, London, UK
| | - Neil Corrigan
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Julie Croft
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Maureen Twiddy
- Institute of Clinical and Applied Health Research, University of Hull, Hull, UK
| | - Stephen Morris
- Department of Applied Health Research, University College London, London, UK
| | - Nick Woodward
- Department of Radiology, Royal Free Hospital, London, UK
| | - Steve Bandula
- Department of Radiology, University College London Hospital, London, UK
| | | | - Vicky Napp
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Alison Pullan
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Nicholas Jakowiw
- Royal Free Campus, Division of Surgery and Interventional Science, University College London, 9th Floor, Royal Free Hospital, Rowland Hill Street, NW3 2PF, London, UK
| | - Raj Prasad
- Department of Surgery and Transplantation, Leeds Teaching Hospital, Leeds, UK
| | - Steven Olde Damink
- Department of General Surgery, Maastricht University, Maastricht, The Netherlands
| | | | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Center, Radboud, The Netherlands
| | - Julia Brown
- Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research Unit, University of Leeds, Leeds, UK
| | - Brian R Davidson
- Royal Free Campus, Division of Surgery and Interventional Science, University College London, 9th Floor, Royal Free Hospital, Rowland Hill Street, NW3 2PF, London, UK.
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Oligometastatic recurrent prostate cancer detects by fluorine-18-choline positron emission tomography/computed tomography in patients with prostate-specific antigen levels of up to 5 ng/ml. Nucl Med Commun 2018; 39:260-267. [PMID: 29381584 DOI: 10.1097/mnm.0000000000000808] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
PURPOSE The aim of this study was to assess the ability of fluorine-18-fluorocholine (F-FCH) PET/computed tomography (CT) to detect oligometastatic disease (OMD) in patients with early recurrence of prostate cancer (PC) [prostate-specific antigen (PSA)≤5 ng/ml]. PATIENTS AND METHODS Between 2010 and 2016, 324 patients with PC and PSA levels of less than or equal to 5 ng/ml were recruited. The mean (SD) age of the patients was 71 (10) years. All patients were treated with a radical prostatectomy±lymphadenectomy. One-hundred and twenty-one patients were under hormonal therapy at the time of PET/CT, whereas 203 were not. The mean (SD) PSA at the time of PET/CT was 1.33 (1.19) ng/ml, the mean (SD) PSA doubling time (PSAdt) was 10 (12) months, and the mean (SD) PSA velocity (PSAvel) was 1.94 (3.31) ng/ml/year. The correlation between continuous and categorical data was assessed using Student's t-test or by analysis of variance and by the χ-test, respectively. Univariate and multivariate analysis was carried out for the identification of clinical variables able to predict the presence of OMD. RESULTS One-hundred and ninety-three patients had a negative F-FCH PET/CT, whereas 131 (40.4%) had a positive scan. Of these latter patients, 35 had a significant F-FCH uptake in the prostatic fossae, 59 in the lymph nodes, and 37 in bone. PSA levels were significantly different between patients with a positive than those with a negative scan (P<0.001). F-FCH PET/CT was negative in the majority of patients with a PSA of less than or equal to 1 (63.2%) ng/ml. More than 60% of patients with a PSAdt of less than or equal to 6 months had a positive F-FCH PET/CT scan for OMD. PSAvel was higher in patients with a positive scan than those with a negative finding. At univariate analysis, PSA level, PSAdt, and PSAvel were predictors of a positive F-FCH PET/CT for OMD, whereas on multivariate analysis, only PSA level and PSAdt were independent predictors (both P<0.01). Furthermore, PSAdt was the only independent predictor of OMD at the lymph node level. CONCLUSION In patients with early recurrence of PC, F-FCH PET/CT is able to detect OMD in 40% of cases. This finding has an important impact on the detection of PC recurrent lesions that could be treated by local therapy to achieve long-term survival or cure.
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