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Qi H, Hou Y, Zheng Z, Zheng M, Sun X, Xing L. MRI radiomics predicts the efficacy of EGFR-TKI in EGFR-mutant non-small-cell lung cancer with brain metastasis. Clin Radiol 2024; 79:515-525. [PMID: 38637187 DOI: 10.1016/j.crad.2024.02.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 02/06/2024] [Accepted: 02/13/2024] [Indexed: 04/20/2024]
Abstract
AIM To develop and validate models based on magnetic resonance imaging (MRI) radiomics for predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in EGFR-mutant non-small-cell lung cancer (NSCLC) patients with brain metastases. MATERIALS AND METHODS 117 EGFR-mutant NSCLC patients with brain metastases who received EGFR-TKI treatment were included in this study from January 1, 2014 to December 31, 2021. Patients were randomly divided into training and validation cohorts in a ratio of 2:1. Radiomics features extracted from brain MRI were screened by least absolute shrinkage and selection operator (LASSO) algorithm. Logistic regression analysis and Cox proportional hazard regression analysis were used to screen clinical risk factors. Clinical (C), radiomics (R), and combined (C + R) nomograms were constructed in models predicting short-term efficacy and intracranial progression-free survival (iPFS), respectively. Calibration curves, Harrell's concordance index (C-index), and decision curve analysis (DCA) were used to evaluate the performance of models. RESULTS Overall response rate (ORR) was 57.3% and median iPFS was 12.67 months. The C + R nomograms were more effective. In the short-term efficacy model, the C-indexes of C + R nomograms in training cohort and validation cohort were 0.860 (0.820-0.901, 95%CI) and 0.843 (0.783-0.904, 95%CI). In iPFS model, the C-indexes of C + R nomograms in training cohort and validation cohort were 0.837 (0.751-0.923, 95%CI) and 0.850 (0.763-0.937, 95%CI). CONCLUSION The C + R nomograms were more effective in predicting EGFR-TKI efficacy of EGFR-mutant NSCLC patients with brain metastases than single clinical or radiomics nomograms.
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Affiliation(s)
- H Qi
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Y Hou
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Z Zheng
- Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, Shandong, China
| | - M Zheng
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - X Sun
- Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, Shandong, China
| | - L Xing
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
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Prete AA, Angerilli V, Bergamo F, Vettore V, De Toni C, Intini R, Cerma K, Ricagno G, Cerantola R, Perissinotto E, De Rosa A, Ceccon C, Gasparello J, Denaro L, D'Amico A, Chioffi F, Carcea E, Fassan M, Lonardi S. HER2 expression and genOmic characterization of rESected brain metastases from colorectal cancer: the HEROES study. Br J Cancer 2024; 130:1316-1323. [PMID: 38347094 PMCID: PMC11014920 DOI: 10.1038/s41416-023-02569-4] [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] [Received: 08/02/2023] [Revised: 12/13/2023] [Accepted: 12/21/2023] [Indexed: 04/14/2024] Open
Abstract
BACKGROUND Little is known about prognostic factors of brain metastases (BM) from colorectal cancer (CRC). HER2 amplification/overexpression (HER2+) was previously described; its impact on prognosis remains uncertain. METHODS In the translational study HEROES, extensive molecular analysis was performed on primary CRC (prCRC) and their matched resected BM by means of NGS comprehensive genomic profiling and HER2 status as assessed by immunohistochemical/ in situ hybridization. Count of tumour-infiltrating lymphocytes (TILs) was also performed. PRIMARY OBJECTIVE to describe the molecular landscape of paired BM/prCRC. SECONDARY OBJECTIVES to search for new prognostic biomarkers of outcome after BM resection: intracranial-only Progression-Free Survival (BM-iPFS), Progression-Free Survival (BM-PFS), and Overall Survival (BM-OS). RESULTS Out of 22 patients having paired samples of prCRC and BM, HER2+ was found on 4 (18%) BM, 3 (75%) of which also HER2+ in matched prCRC. Lower tumour mutation burden (HR 3.08; 95%CI 1.06-8.93; p = 0.0386) and HER2-negative BM (HER2neg) (HR 7.75;95%CI 1.97-30.40; p = 0.0033) were associated with longer BM-iPFS; HER2neg BM (HR 3.44; 95%CI 1.03-11.53; p = 0.0449) and KRASmut BM (HR 0.31; 95%CI 0.12-0.80; p = 0.0153) conferred longer BM-PFS. Longer BM-OS was found in pts with TILs-enriched (≥1.6/HPF) BM (HR 0.11; 95%CI0.01-0.91; p = 0.0403). CONCLUSIONS This study shows HER2+ enrichment in both BM and their prCRC. TILs-enriched BM conferred better BM-OS.
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Affiliation(s)
| | - Valentina Angerilli
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | - Francesca Bergamo
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
| | - Valentina Vettore
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Chiara De Toni
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Rossana Intini
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Krisida Cerma
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | | | - Riccardo Cerantola
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | | | - Antonio De Rosa
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Carlotta Ceccon
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | - Jessica Gasparello
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
| | - Luca Denaro
- Academic Neurosurgery, Department of Neurosciences, University of Padua, Padua, Italy
| | - Alberto D'Amico
- Academic Neurosurgery, Department of Neurosciences, University of Padua, Padua, Italy
| | - Franco Chioffi
- Division of Neurosurgery, Azienda Ospedaliera Università di Padova, Padua, Italy
| | - Elena Carcea
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
- Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Sara Lonardi
- Medical Oncology 3, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
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Liu Y, Hu H, Han Y, Li Z, Yang J, Zhang X, Chen L, Chen F, Li W, Huang G. Development and external validation of a novel score for predicting postoperative 30‑day mortality in tumor craniotomy patients: A cross‑sectional diagnostic study. Oncol Lett 2024; 27:205. [PMID: 38516688 PMCID: PMC10956384 DOI: 10.3892/ol.2024.14338] [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: 10/10/2023] [Accepted: 02/15/2024] [Indexed: 03/23/2024] Open
Abstract
The identification of patients with craniotomy at high risk for postoperative 30-day mortality may contribute to achieving targeted delivery of interventions. The present study aimed to develop a personalized nomogram and scoring system for predicting the risk of postoperative 30-day mortality in such patients. In this retrospective cross-sectional study, 18,642 patients with craniotomy were stratified into a training cohort (n=7,800; year of surgery, 2012-2013) and an external validation cohort (n=10,842; year of surgery, 2014-2015). The least absolute shrinkage and selection operator (LASSO) model was used to select the most important variables among the candidate variables. Furthermore, a stepwise logistic regression model was established to screen out the risk factors based on the predictors chosen by the LASSO model. The model and a nomogram were constructed. The area under the receiver operating characteristic (ROC) curve (AUC) and calibration plot analysis were used to assess the model's discrimination ability and accuracy. The associated risk factors were categorized according to clinical cutoff points to create a scoring model for postoperative 30-day mortality. The total score was divided into four risk categories: Extremely high, high, intermediate and low risk. The postoperative 30-day mortality rates were 2.43 and 2.58% in the training and validation cohort, respectively. A simple nomogram and scoring system were developed for predicting the risk of postoperative 30-day mortality according to the white blood cell count; hematocrit and blood urea nitrogen levels; age range; functional health status; and incidence of disseminated cancer cells. The ROC AUC of the nomogram was 0.795 (95% CI: 0.764 to 0.826) in the training cohort and it was 0.738 (95% CI: 0.7091 to 0.7674) in the validation cohort. The calibration demonstrated a perfect fit between the predicted 30-day mortality risk and the observed 30-day mortality risk. Low, intermediate, high and extremely high risk statuses for 30-day mortality were associated with total scores of (-1.5 to -1), (-0.5 to 0.5), (1 to 2) and (2.5 to 9), respectively. A personalized nomogram and scoring system for predicting postoperative 30-day mortality in adult patients who underwent craniotomy were developed and validated, and individuals at high risk of 30-day mortality were able to be identified.
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Affiliation(s)
- Yufei Liu
- Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China
| | - Haofei Hu
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong 518035, P.R. China
| | - Yong Han
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China
- Department of Emergency, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong 518035, P.R. China
| | - Zongyang Li
- Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China
| | - Jihu Yang
- Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China
| | - Xiejun Zhang
- Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China
| | - Lei Chen
- Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China
| | - Fanfan Chen
- Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China
| | - Weiping Li
- Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China
| | - Guodong Huang
- Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China
- Shenzhen University Health Science Center, Shenzhen University, Shenzhen, Guangdong 518000, P.R. China
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Wang H, Shan X, Zhang M, Qian K, Shen Z, Zhou W. Nomograms for predicting overall survival in colorectal cancer patients with metastasis to the liver, lung, bone, and brain. Cancer Causes Control 2023; 34:1059-1072. [PMID: 37486401 DOI: 10.1007/s10552-023-01744-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 06/21/2023] [Indexed: 07/25/2023]
Abstract
BACKGROUND The aim of this study was to identify the heterogeneous and homogeneous prognostic factors associated with distant metastasis to the liver, lung, bone, and brain in colorectal cancer (CRC) patients and then construct nomograms to predict the prognosis. METHODS CRC patients registered in the surveillance, epidemiology, and end results database between 2010 and 2017 were included. A Cox regression model was used to analyse homogeneous and heterogeneous prognostic factors, and Kaplan‒Meier analysis was performed to estimate overall survival (OS). Predictive nomograms were constructed, and their performance was evaluated with C-indexes, calibration curves and the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS A total of 37,641 patients with distant metastasis to the liver, lung, bone, and brain were included. The median survival times of patients with liver metastasis, lung metastasis, bone metastasis, and brain metastasis were 12.00 months (95% CI 11.73-12.27 months), 10.00 months (95% CI 9.60-10.41 months), 5.00 months (95% CI 4.52-5.48 months), and 3.00 months (95% CI 2.28-3.72 months), respectively. An older age, higher N stage, elevated carcinoembryonic antigen level, no surgery at the primary site and no/unknown treatment with chemotherapy were identified as homogeneous prognostic factors for the four types of metastases. The calibration curves, C-indexes and AUCs exhibited good performance for predicting the OS of patients with distant metastases to the liver, lung, bone, and brain. CONCLUSIONS CRC patients with distant metastasis to the liver, lung, bone, and brain exhibited homogeneous and heterogeneous prognostic factors, all of which were associated with shorter survival. The nomograms showed good accuracy and may be used as tools for clinicians to predict the prognosis of CRC patients with distant metastasis.
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Affiliation(s)
- Hongmei Wang
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, 400016, China
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, 400016, China
| | - Xuefeng Shan
- Department of Pharmacy, Bishan Hospital of Chongqing Medical University, Chongqing, 402760, China
| | - Min Zhang
- Department of Epidemiology and Health Statistics, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China
| | - Kun Qian
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Zhengze Shen
- Department of pharmacy, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China.
| | - Weiying Zhou
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, 400016, China.
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, 400016, China.
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Hamed M, Potthoff AL, Heimann M, Schäfer N, Borger V, Radbruch A, Herrlinger U, Vatter H, Schneider M. Survival in patients with surgically treated brain metastases: does infratentorial location matter? Neurosurg Rev 2023; 46:80. [PMID: 36997703 PMCID: PMC10063486 DOI: 10.1007/s10143-023-01986-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 03/09/2023] [Accepted: 03/26/2023] [Indexed: 04/03/2023]
Abstract
Surgical resection is a common treatment modality for brain metastasis (BM). Location of the BM might significantly impact patient survival and therefore might be considered in clinical decision making and patient counseling. In the present study, the authors analyzed infra- and supratentorial BM location for a potential prognostic difference. Between 2013 and 2019, 245 patients with solitary BM received BM resection at the authors' neuro-oncological center. In order to produce a covariate balance for commonly-known prognostic variables (tumor entity, age, preoperative Karnofsky Performance Score, and preoperative Charlson Comorbidity Index), a propensity score matching at a ratio of 1:1 between the cohort of patients with infra- and supratentorial BM location was performed using R. Overall survival (OS) rates were assessed for both matched cohorts of patients with BM. Sixty-one of 245 patients (25%) with solitary BM exhibited an infratentorial tumor location; 184 patients (75%) suffered from supratentorial solitary BM. Patients with infratentorial BM revealed a median OS of 11 months (95% confidence interval (CI) 7.4-14.6 months). Compared with this, median OS for the group of 61 individually matched patients with solitary supratentorial solitary BM was 13 months (95% CI 10.9-15.1 months) (p = 0.32). The present study suggests that the prognostic value of infra- and supratentorial BMs does not significantly differ in patients that undergo surgery for solitary BM. These results might encourage physicians to induce surgical therapy of supra- and infratentorial BM in a similar manner.
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Affiliation(s)
- Motaz Hamed
- Department of Neurosurgery, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
| | - Anna-Laura Potthoff
- Department of Neurosurgery, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Muriel Heimann
- Department of Neurosurgery, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Niklas Schäfer
- Division of Clinical Neuro-Oncology, Department of Neurology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Valeri Borger
- Department of Neurosurgery, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | | | - Ulrich Herrlinger
- Division of Clinical Neuro-Oncology, Department of Neurology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Hartmut Vatter
- Department of Neurosurgery, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Matthias Schneider
- Department of Neurosurgery, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
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Mjahed RB, Astaras C, Roth A, Koessler T. Where Are We Now and Where Might We Be Headed in Understanding and Managing Brain Metastases in Colorectal Cancer Patients? Curr Treat Options Oncol 2022; 23:980-1000. [PMID: 35482170 PMCID: PMC9174111 DOI: 10.1007/s11864-022-00982-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2022] [Indexed: 02/01/2023]
Abstract
OPINION STATEMENT Compared to liver and lung metastases, brain metastases (BMs) from colorectal cancer (CRC) are rare and remain poorly investigated despite the anticipated rise in their incidence. CRC patients bearing BM have a dismal prognosis with a median survival of 3-6 months, significantly lower than that of patients with BM from other primary tumors, and of those with metastatic CRC manifesting extracranially. While liver and lung metastases from CRC have more codified treatment strategies, there is no consensus regarding the treatment of BM in CRC, and their management follows the approaches of BM from other solid tumors. Therapeutic strategies are driven by the number and localisation of the lesion, consisting in local treatments such as surgery, stereotactic radiosurgery, or whole-brain radiotherapy. Novel treatment modalities are slowly finding their way into this shy unconsented armatorium including immunotherapy, monoclonal antibodies, tyrosine kinase inhibitors, or a combination of those, among others.This article reviews the pioneering strategies aiming at understanding, diagnosing, and managing this disease, and discusses future directions, challenges, and potential innovations in each of these domains. HIGHLIGHTS • With the increasing survival in CRC, brain and other rare/late-onset metastases are rising. • Distal colon/rectal primary location, long-standing progressive lung metastases, and longer survival are risk factors for BM development in CRC. • Late diagnosis and lack of consensus treatment strategies make BM-CRC diagnosis very dismal. • Liquid biopsies using circulating tumor cells might offer excellent opportunities in the early diagnosis of BM-CRC and the search for therapeutic options. • Multi-modality treatment including surgical metastatic resection, postoperative SRS with/without WBRT, and chemotherapy is the best current treatment option. • Recent mid-sized clinical trials, case reports, and preclinical models show the potential of unconventional therapeutic approaches as monoclonal antibodies, targeted therapies, and immunotherapy. Graphical abstract.
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Affiliation(s)
- Ribal Bou Mjahed
- Department of Oncology, University hospital of Geneva (HUG), Geneva, Switzerland.
- Département de médecine interne - CHUV, Rue du Bugnon 21, CH-1011, Lausanne, Switzerland.
| | - Christoforos Astaras
- Department of Oncology, University hospital of Geneva (HUG), Geneva, Switzerland
| | - Arnaud Roth
- Department of Oncology, University hospital of Geneva (HUG), Geneva, Switzerland
| | - Thibaud Koessler
- Department of Oncology, University hospital of Geneva (HUG), Geneva, Switzerland
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Zhang S, Zhang R, Li RZ, Wang QX, Chang H, Ding PR, Li LR, Wu XJ, Chen G, Zeng ZF, Xiao WW, Gao YH. Beneficiaries of radical surgery among clinical complete responders to neoadjuvant chemoradiotherapy in rectal cancer. Cancer Sci 2021; 112:3607-3615. [PMID: 34146368 PMCID: PMC8409289 DOI: 10.1111/cas.15039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 06/05/2021] [Accepted: 06/15/2021] [Indexed: 12/24/2022] Open
Abstract
This study aimed to identify patients who benefit from radical surgery among those with rectal cancer who achieved clinical complete response (cCR). Patients with locally advanced rectal cancer (LARC; stage II/III) who achieved cCR after neoadjuvant chemoradiotherapy (nCRT) were included (n = 212). Univariate/multivariate Cox analysis was performed to validate predictors for distant metastasis‐free survival (DMFS). A decision tree was generated using recursive partitioning analysis (RPA) to categorize patients into different risk stratifications. Total mesorectal excision (TME) was compared with the watch‐and‐wait (W&W) strategy in each risk group. Two molecular predicators of CEA and CA19‐9 were selected to establish the RPA‐based risk stratification, categorizing LARC patients into low‐risk (n = 139; CA19‐9 < 35 U/mL and CEA < 5 ng/mL) and high‐risk (n = 73; CA19‐9 ≥ 35 U/mL or CEA ≥5 ng/mL) groups. Superior 5‐y DMFS was observed in the low‐risk group vs. the high‐risk group (92.9% vs. 76.2%, P = .002). Low‐risk LARC patients who underwent TME had significantly improved 5‐y DMFS compared with their counterparts receiving the W&W strategy (95.9% vs. 84.3%; P = .028). No significant survival difference was observed in high‐risk patients receiving the 2 treatment modalities (77.9% vs. 94.1%; P = .143). LARC patients with cCR who had both baseline CA19‐9 < 35 U/mL and CEA < 5 ng/mL may benefit from radical surgery.
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Affiliation(s)
- Shu Zhang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China.,Department of Radiation Oncology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Rong Zhang
- Department of Endoscopy, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | - Rong-Zhen Li
- Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | - Qiao-Xuan Wang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | - Hui Chang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | - Pei-Rong Ding
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | - Li-Ren Li
- Department of Endoscopy, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | - Xiao-Jun Wu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | - Gong Chen
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | - Zhi-Fan Zeng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | - Wei-Wei Xiao
- Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | - Yuan-Hong Gao
- Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
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Hu H, Xu ZY, Zhu Q, Liu X, Jiang SC, Zheng JH. Brain Metastases Status and Immunotherapy Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis. Front Immunol 2021; 12:669398. [PMID: 34335570 PMCID: PMC8316922 DOI: 10.3389/fimmu.2021.669398] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 06/25/2021] [Indexed: 01/22/2023] Open
Abstract
Background Brain metastases (BMs) indicate poor outcomes and are commonly excluded in immunotherapy clinical trials in advanced lung cancer; moreover, the effect of BM status on immunotherapy efficacy is inconsistent and inconclusive. Therefore, we conducted a meta-analysis to assess the influence of BM status on immunotherapy efficacy in advanced lung cancer. Methods Electronic databases and all major conference proceedings were searched without language restrictions according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We extracted randomized clinical trials on lung cancer immunotherapy that had available overall survival (OS) and/or progression-free survival (PFS) data based on the BM status. All analyses were performed using random effects models. Results Fourteen randomized clinical trials with 9,089 patients were identified. Immunotherapy conferred a survival advantage to BM patients [OS-hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58-0.90; P = 0.004; and PFS-HR, 0.68; 95% CI, 0.52-0.87, P = 0.003]. Non-BM patients could also derive a survival benefit from immunotherapy (OS-HR, 0.76; 95% CI, 0.71-0.80; P <0.001; and PFS-HR, 0.68; 95% CI, 0.56-0.82, P <0.001). The pooled ratios of OS-HRs and PFS-HRs reported in BM patients versus non-BM patients were 0.96 (95% CI, 0.78-1.18; P = 0.72) and 0.97 (95% CI, 0.79-1.20; P = 0.78), respectively, indicating no statistically significant difference between them. Subsequent sensitivity analyses did not alter the results. Subgroup analyses according to tumor type, line of therapy, immunotherapy type, study design, and representation of BM patients reconfirmed these findings. Conclusion We demonstrated that BM status did not significantly influence the immunotherapy efficacy in lung cancer, suggesting that both BM and non-BM patients could obtain comparable benefits. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier (CRD42020207446).
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Affiliation(s)
- Hao Hu
- Department of Radiation Therapy, General Hospital of Southern Theater Command, Guangzhou, China
| | - Zhi-Yong Xu
- The Second Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qian Zhu
- Department of Intensive Care Unit, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xi Liu
- Department of Thoracic Surgery, Jiangxi Cancer Hospital of Nanchang University, Nanchang, China
| | - Si-Cong Jiang
- Department of Thoracic Surgery, Jiangxi Cancer Hospital of Nanchang University, Nanchang, China
| | - Ji-Hua Zheng
- Department of Radiation Therapy, General Hospital of Southern Theater Command, Guangzhou, China
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9
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Roussille P, Auvray M, Vansteene D, Lecomte T, Rigault E, Maillet M, Locher C, Dior M, Hautefeuille V, Artru P, Mabro M, Touchefeu Y, Marthey L, Moulin V, Louafi S, Lecaille C, Chautard R, Lièvre A, Zaanan A, Bennouna J, Berger A, Emambux S, Randrian V, Tougeron D. Prognostic factors of colorectal cancer patients with brain metastases. Radiother Oncol 2021; 158:67-73. [PMID: 33600872 DOI: 10.1016/j.radonc.2021.02.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 01/23/2021] [Accepted: 02/02/2021] [Indexed: 02/01/2023]
Abstract
INTRODUCTION Brain metastases (BMs) from colorectal cancer (CRC) are rare (≈2%) but are increasing with the improvement of CRC prognosis. The main objective of this study was to evaluate the prognostic factors of BM from CRC. MATERIALS AND METHODS This multicenter retrospective study included all consecutive patients with BM from CRC diagnosed between 2000 and 2017. THEORY/CALCULATION Prognostic factors of OS were evaluated in univariate (log-rank test) and multivariate analyses (Cox regression model). These prognostic factors could help the management of patients with BM from CRC. RESULTS A total of 358 patients were included with a median age of 65.5 years. Primary tumors were mostly located in the rectum (42.4%) or left colon (37.2%) and frequently KRAS-mutated (56.9%). The median time from metastatic CRC diagnosis to BM diagnosis was 18.5 ± 2.5 months. BMs were predominantly single (56.9%) and only supratentorial (54.4%). BM resection was performed in 33.0% of the cases and 73.2% of patients had brain radiotherapy alone or after surgery. Median OS was 5.1 ± 0.3 months. In multivariate analysis, age under 65 years, ECOG performance status 0-1, single BM and less than 3 chemotherapy lines before BM diagnosis were associated with better OS. Prognostic scores, i.e. recursive partitioning analysis (RPA), Graded Prognostic Assessment (GPA), Disease Specific-Graded Prognostic Assessment (DS-GPA), Gastro-Intestinal-Graded Prognostic Assessment (GI-GPA) and the nomogram were statistically significantly associated with OS but the most relevant prognosis criteria seemed the ECOG performance status 0-1. CONCLUSIONS ECOG performance status, number of BM and number of chemotherapy lines are the most relevant factors in the management of patients with BM from CRC.
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Affiliation(s)
- Pauline Roussille
- Department of Radiotherapy, Poitiers University Hospital, Poitiers, France
| | - Marie Auvray
- Department of Digestive Oncology, European Georges Pompidou Hospital, Paris Descartes University, Paris, France
| | - Damien Vansteene
- Institut de Cancérologie de l'Ouest, site René Gauducheau, Saint-Herblain, France
| | - Thierry Lecomte
- Department of Gastroenterology, Tours University Hospital, Tours, France
| | - Eugénie Rigault
- Department of Gastroenterology, Rennes University Hospital, Rennes, France
| | - Marianne Maillet
- Department of Gastroenterology, Saint Louis Hospital, Paris, France
| | | | - Marie Dior
- Cochin Hospital, Paris Descartes University, Paris, France
| | | | - Pascal Artru
- Department of Gastroenterology, Jean Mermoz Hospital, Lyon, France
| | - May Mabro
- Department of Gastroenterology, Foch Hospital, Suresnes, France
| | - Yann Touchefeu
- Department of Gastroenterology, Nantes University Hospital, Nantes, France
| | - Lysiane Marthey
- Department of Gastroenterology, Antoine-Béclère Hospital, Clamart, France
| | - Valérie Moulin
- Department of Oncology, La Rochelle Hospital, La Rochelle, France
| | | | - Cédric Lecaille
- Department of Gastroenterology, Polyclinique Bordeaux Nord, Bordeaux, France
| | - Romain Chautard
- Department of Gastroenterology, Tours University Hospital, Tours, France
| | - Astrid Lièvre
- Department of Gastroenterology, Rennes University Hospital, Rennes, France
| | - Aziz Zaanan
- Department of Digestive Oncology, European Georges Pompidou Hospital, Paris Descartes University, Paris, France
| | - Jaafar Bennouna
- Department of Gastroenterology, Nantes University Hospital, Nantes, France
| | - Antoine Berger
- Department of Radiotherapy, Poitiers University Hospital, Poitiers, France
| | - Sheik Emambux
- Poitiers University, Poitiers, France; Department of Oncology, Poitiers University Hospital, Poitiers, France
| | - Violaine Randrian
- Poitiers University, Poitiers, France; Department of Gastroenterology, Poitiers University Hospital, Poitiers, France
| | - David Tougeron
- Poitiers University, Poitiers, France; Department of Gastroenterology, Poitiers University Hospital, Poitiers, France.
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10
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Zhang J, Jin J, Ai Y, Zhu K, Xiao C, Xie C, Jin X. Computer Tomography Radiomics-Based Nomogram in the Survival Prediction for Brain Metastases From Non-Small Cell Lung Cancer Underwent Whole Brain Radiotherapy. Front Oncol 2021; 10:610691. [PMID: 33643912 PMCID: PMC7905101 DOI: 10.3389/fonc.2020.610691] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 12/14/2020] [Indexed: 12/25/2022] Open
Abstract
Prognostic parameters and models were believed to be helpful in improving the treatment outcome for patients with brain metastasis (BM). The purpose of this study was to investigate the feasibility of computer tomography (CT) radiomics based nomogram to predict the survival of patients with BM from non-small cell lung cancer (NSCLC) treated with whole brain radiotherapy (WBRT). A total of 195 patients with BM from NSCLC who underwent WBRT from January 2012 to December 2016 were retrospectively reviewed. Radiomics features were extracted and selected from pretherapeutic CT images with least absolute shrinkage and selection operator (LASSO) regression. A nomogram was developed and evaluated by integrating radiomics features and clinical factors to predict the survival of individual patient. Five radiomics features were screened out from 105 radiomics features according to the LASSO Cox regression. According to the optimal cutoff value of radiomics score (Rad-score), patients were stratified into low-risk (Rad-score <= −0.14) and high-risk (Rad-score > −0.14) groups. Multivariable analysis indicated that sex, karnofsky performance score (KPS) and Rad-score were independent predictors for overall survival (OS). The concordance index (C-index) of the nomogram in the training cohort and validation cohort was 0.726 and 0.660, respectively. An area under curve (AUC) of 0.786 and 0.788 was achieved for the short-term and long-term survival prediction, respectively. In conclusion, the nomogram based on radiomics features from CT images and clinical factors was feasible to predict the OS of BM patients from NSCLC who underwent WBRT.
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Affiliation(s)
- Ji Zhang
- Department of Radiotherapy Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Juebin Jin
- Department of Radiotherapy Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yao Ai
- Department of Radiotherapy Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Kecheng Zhu
- Department of Radiotherapy Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Chengjian Xiao
- Department of Radiotherapy Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Congying Xie
- Department of Radiotherapy Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.,Department of Radiation and Medical Oncology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiance Jin
- Department of Radiotherapy Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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11
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Tang M, Wang H, Cao Y, Zeng Z, Shan X, Wang L. Nomogram for predicting occurrence and prognosis of liver metastasis in colorectal cancer: a population-based study. Int J Colorectal Dis 2021; 36:271-282. [PMID: 32965529 DOI: 10.1007/s00384-020-03722-8] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/21/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE This study aimed to investigate the prevalence, risk, and prognostic factors for synchronous liver metastasis (LM) in colorectal cancer (CRC) and to construct nomogram for predicting occurrence and prognosis of synchronous LM. METHODS A total of 203,998 CRC patients who were registered in the SEER database between 2010 and 2016 were included. Logistic regression was used to analyze risk factors and Kaplan-Meier was used to estimate the overall survival of CRC patients with LM. Potential prognostic factors were identified by multivariable Cox regression. For predicting the risk for development and prognosis in CRC patients with LM, we constructed nomogram and the predictive performance was estimated by the receiver operating characteristics cure, the concordance index, and calibration curve. RESULTS In total, 15.3% of the CRC patients (N = 31,288) had synchronous LM. Male gender, black, uninsured status, left colon, T4/T1, and bone and lung metastases were positively associated with synchronous LM risk. The 1-year, 3-year, and 5-year overall survival rate was 49.1%, 18.4%, and 9.2%, respectively. Older age, male gender, black, uninsured status, poor histological differentiation, lymphatic metastasis, T4/T1, positive carcinoembryonic antigen, and lung, bone, and brain metastases were associated with the overall survival. Nomogram was constructed to predict the development and prognosis of synchronous LM and both of them were proved to have good calibration and discrimination. CONCLUSION LM is highly prevalent in CRC patients. Nomogram basing on the risk and prognostic factors for synchronous LM was proved to have good performance for predicting the probability of LM occurrence and prognosis.
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Affiliation(s)
- Mingshuang Tang
- Emergence Department, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China.,Department of Epidemiology and Biostatistics, First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Hongmei Wang
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yitong Cao
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ziqian Zeng
- Department of Epidemiology and Biostatistics, First Affiliated Hospital, Army Medical University, Chongqing, China
| | - Xuefeng Shan
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lihua Wang
- Emergence Department, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China.
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12
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Luo T, Wang Y, Shan X, Bai Y, Huang C, Li G, Wang H. Nomogram based on homogeneous and heterogeneous associated factors for predicting distant metastases in patients with colorectal cancer. World J Surg Oncol 2021; 19:30. [PMID: 33504354 PMCID: PMC7842036 DOI: 10.1186/s12957-021-02140-6] [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: 10/29/2020] [Accepted: 01/19/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The identification of the homogeneous and heterogeneous risk factors for different types of metastases in colorectal cancer (CRC) may shed light on the aetiology and help individualize prophylactic treatment. The present study characterized the incidence differences and identified the homogeneous and heterogeneous risk factors associated with distant metastases in CRC. METHODS CRC patients registered in the SEER database between 2010 and 2016 were included in this study. Logistic regression was used to analyse homogeneous and heterogeneous risk factors for the occurrence of different types of metastases. Nomograms were constructed to predict the risk for developing metastases, and the performance was quantitatively assessed using the receiver operating characteristics (ROC) curve and calibration curve. RESULTS A total of 204,595 eligible CRC patients were included in our study, and 17.07% of them had distant metastases. The overall incidences of liver metastases, lung metastases, bone metastases, and brain metastases were 15.34%, 5.22%, 1.26%, and 0.29%, respectively. The incidence of distant metastases differed by age, gender, and the original CRC sites. Poorly differentiated grade, more lymphatic metastasis, higher carcinoembryonic antigen (CEA), and different metastatic organs were all positively associated with four patterns of metastases. In contrast, age, sex, race, insurance status, position, and T stage were heterogeneously associated with metastases. The calibration and ROC curves exhibited good performance for predicting distant metastases. CONCLUSIONS The incidence of distant metastases in CRC exhibited distinct differences, and the patients had homogeneous and heterogeneous associated risk factors. Although limited risk factors were included in the present study, the established nomogram showed good prediction performance.
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Affiliation(s)
- Tianwen Luo
- Department of Medical and Education Office, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Yutong Wang
- Department of Epidemiology and Biostatistics, The First Affiliated Hospital, Army Medical University, Chongqing, People's Republic of China
| | - Xuefeng Shan
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Ye Bai
- Department of Epidemiology and Health Statistics, School of Public Health and Management, Chongqing Medical University, Chongqing, People's Republic of China
| | - Chun Huang
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Guangcan Li
- Department of Pharmacy, The People's Hospital of Kaizhou District, No. 8, Ankang Road, Hanfeng Street, Kaizhou District, Chongqing, 405400, People's Republic of China.
| | - Hongmei Wang
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People's Republic of China.
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13
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Prognostic factors for survival in colorectal cancer patients with brain metastases undergoing whole brain radiotherapy: multicenter retrospective study. Sci Rep 2020; 10:4340. [PMID: 32152433 PMCID: PMC7062910 DOI: 10.1038/s41598-020-61354-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 02/24/2020] [Indexed: 11/12/2022] Open
Abstract
Whole brain radiotherapy (WBRT) is a mainstay of the treatment for brain metastases (BM). We evaluated prognostic factors in colorectal cancer (CRC) patients undergoing WBRT for BM. The medical records of 106 CRC patients undergoing WBRT for BM between 2000 and 2014 at three institutions were reviewed. Patient and tumor factors were analyzed to identify the prognostic factors for overall survival (OS) calculated from the date of BM diagnosis to the date of death or last follow-up. Surgical resection of BM was performed in six patients. The dose of WBRT was 30 Gy, and boost radiotherapy or stereotactic radiosurgery (8–23 Gy) was given to 15 patients. Systemic therapy for BM was administered in one patient before WBRT and 26 patients after WBRT. The median follow-up time was 3.9 months (range, 0.4–114.1 months). The median OS time was 3.9 months, and the 1-year OS rate was 18.2%. Older age (>65 years), multiple BM (≥3), elevated level of carcinoembryonic antigen (CEA, >5 ng/ml) at BM diagnosis, and extracranial metastases were adverse prognostic factors for OS. Patient with 0–1 factor showed better OS (at 1 year, 76.9%) than patients with 2 factors (16.7%) or 3–4 factors (4.2%; p < 0.001). In conclusion, we evaluated age, the number of BM, CEA level, and extracranial metastases as the prognostic factors for OS in CRC patients undergoing WBRT. Our result might be useful to develop prognostic models predicting survival for patients whom WBRT is intended for.
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14
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Quan JC, Guan X, Ma CX, Liu Z, Yang M, Zhao ZX, Sun P, Zhuang M, Wang S, Jiang Z, Wang XS. Prognostic scoring system for synchronous brain metastasis at diagnosis of colorectal cancer: A population-based study. World J Gastrointest Oncol 2020; 12:195-204. [PMID: 32104550 PMCID: PMC7031150 DOI: 10.4251/wjgo.v12.i2.195] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2019] [Revised: 11/14/2019] [Accepted: 11/28/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Brain metastasis (BM) from colorectal cancer (CRC) is rarely encountered clinically, and its prognosis has not been fully evaluated. AIM To construct a scoring system and accurately predict the survival of patients with synchronous BM at diagnosis of CRC. METHODS A retrospective study of 371 patients with synchronous BM from CRC was performed, using the data from 2010 to 2014 from the Surveillance, Epidemiology, and End Results database. Survival time and prognostic factors were statistically analyzed by the Kaplan-Meier method and Cox proportional hazards models, respectively. A scoring system was developed using the independent prognostic factors, and was used to measure the survival difference among different patients. RESULTS For the 371 patients, the median overall survival was 5 mo, survival rates were 27% at 1 year and 11.2% at 2 years. Prognostic analysis showed that age, carcinoembryonic antigen level and extracranial metastasis to the liver, lung or bone were independent prognostic factors. A scoring system based on these three prognostic factors classified the patients into three prognostic subgroups (scores of 0-1, 2-3, and 4). The median survival of patients with scores of 0-1, 2-3 and 4 was 14, 5 and 2 mo, respectively (P < 0.001). Subgroup analysis showed that there were significant differences in prognosis among the groups. Score 2-3 vs 0-1: hazard ratio (HR) = 2.050, 95%CI: 1.363-3.083; P = 0.001; score 4 vs 0-1: HR = 3.721, 95%CI: 2.225-6.225; P < 0.001; score 2-3 vs 4: HR = 0.551, 95%CI: 0.374-0.812; P = 0.003. CONCLUSION The scoring system effectively distinguishes long-term and short-term survivors with synchronous BM from CRC. These results are helpful in providing a reference for guiding therapy.
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Affiliation(s)
- Ji-Chuan Quan
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xu Guan
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Chen-Xi Ma
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zheng Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ming Yang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zhi-Xun Zhao
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Peng Sun
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China
| | - Meng Zhuang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Song Wang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China
| | - Zheng Jiang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xi-Shan Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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15
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Nieder C, Hintz M, Popp I, Bilger A, Grosu AL. Validation of the graded prognostic assessment for gastrointestinal cancers with brain metastases (GI-GPA). Radiat Oncol 2020; 15:35. [PMID: 32054485 PMCID: PMC7020357 DOI: 10.1186/s13014-020-1484-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 02/04/2020] [Indexed: 02/06/2023] Open
Abstract
PURPOSE The purpose of this study was to validate a new prognostic model (GI-GPA) originally derived from a multi-center database (USA, Canada, Japan). PATIENTS AND METHODS This retrospective study included 92 German and Norwegian patients treated with individualized approaches, always including brain radiotherapy. Information about age, extracranial spread, number of brain metastases, performance status and other variables was collected. The GI-GPA score was calculated as described by Sperduto et al. RESULTS: Median survival was 4 months. The corresponding figures for the 4 different prognostic strata were 2.3, 4.4, 9.4 and 12.7 months, respectively (p = 0.0001). Patients whose management included surgical resection had longer median survival than those who were treated with other approaches (median 11.9 versus 3.0 months, p = 0.002). Comparable results were seen for additional systemic therapy (median 8.5 versus 3.5 months, p = 0.01). CONCLUSION These results confirm the validity of the GI-GPA in an independent dataset from a different geographical region, despite the fact that overall survival was shorter in all prognostic strata, compared to Sperduto et al. Potential explanations include differences in molecular tumor characteristics and treatment selection, both brain metastases-directed and extracranially. Long-term survival beyond 5 years is possible in a small minority of patients.
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Affiliation(s)
- Carsten Nieder
- Department of Oncology and Palliative Medicine, Nordland Hospital, 8092, Bodø, Norway. .,Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, 9037, Tromsø, Norway.
| | - Mandy Hintz
- Department of Radiation Oncology, University Hospital Freiburg, 79106, Freiburg, Germany
| | - Ilinca Popp
- Department of Radiation Oncology, University Hospital Freiburg, 79106, Freiburg, Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
| | - Angelika Bilger
- Department of Radiation Oncology, University Hospital Freiburg, 79106, Freiburg, Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
| | - Anca L Grosu
- Department of Radiation Oncology, University Hospital Freiburg, 79106, Freiburg, Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
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16
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Quan J, Ma C, Sun P, Wang S, Zhuang M, Liu Z, Jiang Z, Chen H, Yang M, Zhao Z, Guan X, Wang X. Brain metastasis from colorectal cancer: clinical characteristics, timing, survival and prognostic factors. Scand J Gastroenterol 2019; 54:1370-1375. [PMID: 31687871 DOI: 10.1080/00365521.2019.1686056] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 10/22/2019] [Accepted: 10/23/2019] [Indexed: 02/04/2023]
Abstract
Background: Brain metastasis (BM) from colorectal cancer (CRC) seriously affects the survival and quality of life of patients. However, this disease is not fully understood. It is not clear when follow-up monitoring should be conducted to achieve early diagnosis. Furthermore, the reported prognostic factors have varied among different studies. Our study aims to determine the clinicopathological, survival and prognostic factors, as well as the timing of BM occurrence.Methods: We retrospectively studied the patients with BM from CRC between January 2000 and July 2017. The clinicopathologic features were assessed, and the time from primary tumor surgery and extracranial metastases (lung, liver and bone) to the occurrence of BM was calculated, respectively. Survival time after BM was statistically analyzed. Multivariate Cox analysis was carried out to determine the independent factors that affected survival.Results: 52 patients were analyzed. Most of the patients (86.5%) had combined extracranial metastases when BM was diagnosed, and lung was the commonest extracranial metastasis location. The median time interval from CRC surgery to the diagnosis of BM was 20.5 months, and the median time interval from lung, liver and bone metastases to BM was 7, 5 and 2 months, respectively. After diagnosis of BM, the median survival was 9 months. Extracranial metastases (p =.012) and Karnofsky performance status (p =.025) were independent prognostic factors based on multivariate analysis.Conclusion: BM from colorectal cancer often occur in the late stage, and has an extremely poor prognosis. Identifying the timing of brain metastasis can help to detect this disease early.
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Affiliation(s)
- Jichuan Quan
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chenxi Ma
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Peng Sun
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Song Wang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Meng Zhuang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zheng Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zheng Jiang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haipeng Chen
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming Yang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhixun Zhao
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xu Guan
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xishan Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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17
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Gilbride L, Siker M, Bovi J, Gore E, Schultz C, Hall WA. Current Predictive Indices and Nomograms To Enable Personalization of Radiation Therapy for Patients With Secondary Malignant Neoplasms of the Central Nervous System: A Review. Neurosurgery 2019; 82:595-603. [PMID: 29669114 DOI: 10.1093/neuros/nyx631] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 02/16/2018] [Indexed: 01/03/2023] Open
Abstract
The proper treatment of brain metastases continues to be a challenge for oncologists given the variability of individual patients' prognoses and the variety of treatment options available to address brain metasteses. There have been efforts since the 1990s to develop prognostic indices and nomograms to help clinicians determine the best approach for individuals with secondary malignant neoplasms of the central nervous system. A literature search was performed to identify the existing prognostic tools published between January 1995 and January 2017. While there have been several reported indices, many are limited by the number of patients analyzed or lack of generalizability. The most robust prognostic tools available are the Disease Specific Graded Prognostic Assessment and the Barnholtz-Sloan nomogram, both of which have online tools available to help clinicians. While these tools are helpful in stratifying different patients' outcomes, they are limited by their retrospective nature and likely underestimate survival in the modern era, where there is a rapidly growing arsenal of systemic agents available to patients with metastatic disease.
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Affiliation(s)
- Lucas Gilbride
- Medical College of Wisconsin, Department of Radiation Oncology
| | - Malika Siker
- Medical College of Wisconsin, Department of Radiation Oncology
| | - Joseph Bovi
- Medical College of Wisconsin, Department of Radiation Oncology
| | - Elizabeth Gore
- Medical College of Wisconsin, Department of Radiation Oncology.,Clement J. Zablocki, VA Medical Center
| | | | - William A Hall
- Medical College of Wisconsin, Department of Radiation Oncology.,Clement J. Zablocki, VA Medical Center
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18
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Kancharla P, Ivanov A, Chan S, Ashamalla H, Huang RY, Yanagihara TK. The effect of brain metastasis location on clinical outcomes: A review of the literature. Neurooncol Adv 2019; 1:vdz017. [PMID: 32642653 PMCID: PMC7212918 DOI: 10.1093/noajnl/vdz017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
It is common clinical practice to consider the location of a brain metastasis when making decisions regarding local therapies and, in some scenarios, estimating clinical outcomes, such as local disease control and patient survival. However, the location of a brain metastasis is not included in any validated prognostic nomogram and it is unclear if this is due to a lack of a relationship or a lack of support from published data. We performed a comprehensive review of the literature focusing on studies that have investigated a relationship between brain metastasis location and clinical outcomes, including patient survival. The vast majority of reports anatomically categorized brain metastases as supratentorial or infratentorial whereas some reports also considered other subdivisions of the brain, including different lobes or with particular areas defined as eloquent cortex. Results were variable across studies, with some finding a relationship between metastasis location and survival, but the majority finding either no relationship or a weak correlation that was not significant in the context of multivariable analysis. Here, we highlight the key findings and limitations of many studies, including how neurosurgical resection might influence the relative importance of metastasis location and in what ways future analyses may improve anatomical categorization and resection status.
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Affiliation(s)
- Pragnan Kancharla
- Department of Medicine, New York Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York
| | - Alexander Ivanov
- Department of Medicine, New York Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York.,Department of Radiation Oncology, New York Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York
| | - Susie Chan
- Department of Radiation Oncology, New York Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York
| | - Hani Ashamalla
- Department of Radiation Oncology, New York Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York
| | - Raymond Y Huang
- Department of Radiology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, Massachusetts
| | - Ted K Yanagihara
- Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina
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19
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Nardone V, Nanni S, Pastina P, Vinciguerra C, Cerase A, Correale P, Guida C, Giordano A, Tini P, Reginelli A, Cappabianca S, Pirtoli L. Role of perilesional edema and tumor volume in the prognosis of non-small cell lung cancer (NSCLC) undergoing radiosurgery (SRS) for brain metastases. Strahlenther Onkol 2019; 195:734-744. [PMID: 31123785 DOI: 10.1007/s00066-019-01475-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 05/10/2019] [Indexed: 12/25/2022]
Abstract
AIM To assess the role of perilesional edema (PE) in non-small cell lung carcinoma (NSCLC) brain metastases (BM) undergoing radiosurgery (SRS). METHODS This series includes 46 patients with 1-2 BM treated with SRS, selected out of all patients referred for radiotherapy (RT) for BMs over 5 years (2013 to 2017). Both the PE and gross tumor volume (GTV) were contoured on MRI images, and the PE/GTV ratio and PE + GTV value (TV, total volume) were calculated. Our clinical endpoints were brain recurrence free-survival, divided into local brain control (in field, LBC) and distant brain control (out of field, DBC) and overall survival (OS). We analyzed the role of the previously described volumetric parameters and of known clinical prognosticators (disease specific GPA, DS-GPA; chemotherapy, CHT) with Cox regression analyses. RESULTS Only four patients (9%) developed in-field progression, whereas 10 patients (22%) showed new out-of-field BM and thirty-eight patients died in the follow up (83%). In univariate analysis, both volumetric parameters and clinical parameters were correlated with DBC and OS, whereas we did not find any correlation with LBC. In the multivariate analysis of DBC, the significant parameters were PE/GTV ratio (HR 0.302), sex (HR 0.131), and DS-GPA (HR 0.261). The OS multivariate analysis showed that the only significant parameters were DS-GPA (HR 0.478) and TV (HR: 1.038). CONCLUSION Our study, although with the limitations of a monocentric retrospective study analyzing a small cohort of patients, suggests the role of PE/GTV ratio for the development of new BMs. TV also seems to be correlated with OS, together with known clinical prognosticators. These findings, if validated in a larger prospective dataset, could help in selecting patients for the most suitable RT modality (or systemic therapy approach).
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Affiliation(s)
- Valerio Nardone
- Unit of Radiation Oncology, Ospedale del Mare, Viale della Metamorfosi, Naples, Italy.
| | - Sara Nanni
- Unit of Radiation Oncology, University Hospital of Siena, Siena, Italy
| | - Pierpaolo Pastina
- Unit of Radiation Oncology, University Hospital of Siena, Siena, Italy
| | - Claudia Vinciguerra
- Department of Medicine, Surgery and Neurosciences (Clinical Neurology and Neuro-metabolic Disorders), University of Siena, Siena, Italy
| | - Alfonso Cerase
- Unit of Neuro-Radiology, University Hospital of Siena, Siena, Italy
| | - Pierpaolo Correale
- Unit of Medical Oncology, Grand Metropolitan Hospital "Bianchi Melacrino Morelli" Reggio Calabria, Reggio Calabria, Italy
| | - Cesare Guida
- Unit of Radiation Oncology, Ospedale del Mare, Viale della Metamorfosi, Naples, Italy
| | - Antonio Giordano
- Sbarro Health Research Organization, Temple University, Philadelphia, PA, USA
- Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA
| | - Paolo Tini
- Unit of Radiation Oncology, University Hospital of Siena, Siena, Italy
- Sbarro Health Research Organization, Temple University, Philadelphia, PA, USA
| | - Alfonso Reginelli
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Salvatore Cappabianca
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Luigi Pirtoli
- Sbarro Health Research Organization, Temple University, Philadelphia, PA, USA
- Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA
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20
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Engelhardt EG, Révész D, Tamminga HJ, Punt CJA, Koopman M, Onwuteaka-Philipsen BD, Steyerberg EW, de Vet HCW, Coupé VMH. Inventory of oncologists' unmet needs for tools to support decision-making about palliative treatment for metastatic colorectal cancer. BMC Med Inform Decis Mak 2018; 18:132. [PMID: 30551735 PMCID: PMC6295030 DOI: 10.1186/s12911-018-0712-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 11/22/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Decision-making about palliative care for metastatic colorectal cancer (mCRC) consists of many different treatment-related decisions, and there generally is no best treatment option. Decision support systems (DSS), e.g., prognostic calculators, can aid oncologists' decision-making. DSS that contain features tailored to the needs of oncologists are more likely to be implemented in clinical practice. Therefore, our aim is to inventory colorectal cancer specialists' unmet decision support needs. METHODS We asked oncologists from the Dutch colorectal cancer group (DCCG), to participate in an online inventory questionnaire on their unmet decision support needs. To get more in-depth insight in required features of the DSS they need, we also conducted semi-structured telephone interviews. RESULTS Forty-one oncologists started the inventory questionnaire, and 27 of them completed all items. Of all respondents, 18 were surgeons (44%), 22 were medical oncologists (54%), and 28 (68%) had more than 10 years of experience treating mCRC. In both the inventory questionnaire and interviews, respondents expressed a need for an overarching DSS incorporating multiple treatment options, and presenting both the treatment benefits and harms. Respondents found it relevant for other outcomes, such as cost-effectiveness of treatment or quality of life, to be incorporated in DSS. There was also a wish for DSS incorporating an up-to-date "personalized" overview of the ongoing trials for which a specific patient is eligible. CONCLUSIONS Experienced oncologists indicate that their treatment advice is currently almost solely based on the available clinical guidelines. They experience a lack of good quality DSS to help them personalize their treatment advice. New tools integrating multiple treatment options and providing a broad range of clinically relevant outcomes are urgently needed to stimulate and safeguard more personalized treatment decision-making.
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Affiliation(s)
- Ellen G Engelhardt
- Department of Epidemiology and Biostatistics, Amsterdam UMC, location VUMC, F-wing Medical Faculty building, PO Box 7057 1007, MB, Amsterdam, The Netherlands.
| | - Dóra Révész
- Department of Epidemiology and Biostatistics, Amsterdam UMC, location VUMC, F-wing Medical Faculty building, PO Box 7057 1007, MB, Amsterdam, The Netherlands
| | - Hans J Tamminga
- Department of Epidemiology and Biostatistics, Amsterdam UMC, location VUMC, F-wing Medical Faculty building, PO Box 7057 1007, MB, Amsterdam, The Netherlands
| | - Cornelis J A Punt
- Department of Medical Oncology, Amsterdam UMC, location AMC, Amsterdam, The Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Center Utrecht and University Utrecht, Utrecht, The Netherlands
| | - Bregje D Onwuteaka-Philipsen
- Department of Public and Occupational Health, and Palliative Care Expertise Centre, VU University Medical Center, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
| | - Ewout W Steyerberg
- Department of Public Health, Centre for Medical Decision Making, Erasmus Medical Center, Rotterdam, The Netherlands and Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
| | - Henrica C W de Vet
- Department of Epidemiology and Biostatistics, Amsterdam UMC, location VUMC, F-wing Medical Faculty building, PO Box 7057 1007, MB, Amsterdam, The Netherlands
| | - Veerle M H Coupé
- Department of Epidemiology and Biostatistics, Amsterdam UMC, location VUMC, F-wing Medical Faculty building, PO Box 7057 1007, MB, Amsterdam, The Netherlands
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21
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Roussille P, Tachon G, Villalva C, Milin S, Frouin E, Godet J, Berger A, Emambux S, Petropoulos C, Wager M, Karayan-Tapon L, Tougeron D. Pathological and Molecular Characteristics of Colorectal Cancer with Brain Metastases. Cancers (Basel) 2018; 10:504. [PMID: 30544743 PMCID: PMC6316286 DOI: 10.3390/cancers10120504] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Revised: 11/30/2018] [Accepted: 12/05/2018] [Indexed: 02/01/2023] Open
Abstract
Background: Colorectal cancers (CRC) with brain metastases (BM) are scarcely described. The main objective of this study was to determine the molecular profile of CRC with BM. Methods: We included 82 CRC patients with BM. KRAS, NRAS, BRAF and mismatch repair (MMR) status were investigated on primary tumors (n = 82) and BM (n = 38). ALK, ROS1, cMET, HER-2, PD-1, PD-L1, CD3 and CD8 status were evaluated by immunohistochemistry, and when recommended, by fluorescence in situ hybridization. Results: In primary tumors, KRAS, NRAS and BRAF mutations were observed in 56%, 6%, and 6% of cases, respectively. No ROS1, ALK and cMET rearrangement was detected. Only one tumor presented HER-2 amplification. Molecular profiles were mostly concordant between BM and paired primary tumors, except for 9% of discordances for RAS mutation. CD3, CD8, PD-1 and PD-L1 expressions presented some discordance between primary tumors and BM. In multivariate analysis, multiple BM, lung metastases and PD-L1+ tumor were predictive of poor overall survival. Conclusions: CRCs with BM are associated with high frequency of RAS mutations and significant discordance for RAS mutational status between BM and paired primary tumors. Multiple BM, lung metastases and PD-L1+ have been identified as prognostic factors and can guide therapeutic decisions for CRC patients with BM.
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Affiliation(s)
- Pauline Roussille
- Department of Radiation Oncology, University Hospital of Poitiers, 86021 Poitiers, France.
- INSERM 1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, 86073 Poitiers, France.
- Faculty of Medicine, University of Poitiers, 86021 Poitiers, France.
| | - Gaelle Tachon
- INSERM 1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, 86073 Poitiers, France.
- Faculty of Medicine, University of Poitiers, 86021 Poitiers, France.
- Cancer Biology Department, University Hospital of Poitiers, 86021 Poitiers, France.
| | - Claire Villalva
- Cancer Biology Department, University Hospital of Poitiers, 86021 Poitiers, France.
| | - Serge Milin
- Pathology Department, University Hospital of Poitiers, 86021 Poitiers, France.
| | - Eric Frouin
- Faculty of Medicine, University of Poitiers, 86021 Poitiers, France.
- Pathology Department, University Hospital of Poitiers, 86021 Poitiers, France.
| | - Julie Godet
- Pathology Department, University Hospital of Poitiers, 86021 Poitiers, France.
| | - Antoine Berger
- Department of Radiation Oncology, University Hospital of Poitiers, 86021 Poitiers, France.
| | - Sheik Emambux
- INSERM 1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, 86073 Poitiers, France.
- Faculty of Medicine, University of Poitiers, 86021 Poitiers, France.
- Cancer Biology Department, University Hospital of Poitiers, 86021 Poitiers, France.
- Medical Oncology Department, University Hospital of Poitiers, 86021 Poitiers, France.
| | - Christos Petropoulos
- INSERM 1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, 86073 Poitiers, France.
- Faculty of Medicine, University of Poitiers, 86021 Poitiers, France.
- Cancer Biology Department, University Hospital of Poitiers, 86021 Poitiers, France.
| | - Michel Wager
- INSERM 1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, 86073 Poitiers, France.
- Faculty of Medicine, University of Poitiers, 86021 Poitiers, France.
- Department of Neurosurgery, University Hospital of Poitiers, 86021 Poitiers, France.
| | - Lucie Karayan-Tapon
- INSERM 1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers, 86073 Poitiers, France.
- Faculty of Medicine, University of Poitiers, 86021 Poitiers, France.
- Cancer Biology Department, University Hospital of Poitiers, 86021 Poitiers, France.
| | - David Tougeron
- Faculty of Medicine, University of Poitiers, 86021 Poitiers, France.
- Medical Oncology Department, University Hospital of Poitiers, 86021 Poitiers, France.
- Department of Gastroenterology, University Hospital of Poitiers, 86021 Poitiers, France.
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22
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Nieder C, Mehta MP, Geinitz H, Grosu AL. Prognostic and predictive factors in patients with brain metastases from solid tumors: A review of published nomograms. Crit Rev Oncol Hematol 2018; 126:13-18. [PMID: 29759555 DOI: 10.1016/j.critrevonc.2018.03.018] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 01/19/2018] [Accepted: 03/25/2018] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE To review published nomograms that predict endpoints such as overall survival (OS) or risk of intracranial relapse in patients with brain metastases from solid tumors. METHODS The methods and results of nomogram studies identified by a systematic search were extracted and compared, stratified by endpoint predicted by the respective nomograms. In particular, validation strategies (external/internal), concordance indices (cut-off 0.75) and comparisons to older models were analyzed. RESULTS Six publications reported on prediction of OS. Most of these analyses focused on one particular primary tumor site, e.g., breast cancer or hepatocellular carcinoma, while the largest study included different primary tumor sites. The median number of patients was 244. Three of six studies included external validation cohorts. With few exceptions, concordance indices <0.75 were reported. In all studies reporting this endpoint, the nomogram outperformed older prognostic scores. Two nomograms focused on development of new brain metastases after radiosurgery (one externally validated), one on survival free from salvage whole brain radiotherapy (WBRT) after radiosurgery, and one on neurologic and non-neurologic death in patients receiving radiosurgery after WBRT failure. All concordance indices of these 4 nomograms were <0.70. CONCLUSION Taking into account concordance indices and comparisons to older prognostic models, the most promising, externally validated nomograms are the breast cancer and the non-small cell lung cancer nomogram predicting OS, and the distant brain failure after radiosurgery nomogram. Additional validation studies as well as continuous monitoring of the models' performance appear necessary to ensure their clinical applicability in the present era of rapidly changing treatment paradigms.
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Affiliation(s)
- Carsten Nieder
- Department of Oncology and Palliative Medicine, Nordland Hospital, 8092 Bodø, Norway; Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
| | - Minesh P Mehta
- Department of Radiation Oncology, Miami Cancer Institute, Miami, FL, USA
| | - Hans Geinitz
- Department of Radiation Oncology, St. Vincent's Hospital, Linz, Austria
| | - Anca L Grosu
- Department of Radiation Oncology, University Medical Center, Medical Faculty, University of Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, Germany
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23
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Chahine G, Ibrahim T, Felefly T, El-Ahmadie A, Freiha P, El-Khoury L, Khalife-Saleh N, Saleh K. Colorectal cancer and brain metastases: An aggressive disease with a different response to treatment. TUMORI JOURNAL 2018; 105:427-433. [PMID: 29714653 DOI: 10.1177/0300891618765541] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
INTRODUCTION Brain metastases (BM) are rare in colorectal cancer (CRC) and are associated with a dismal prognosis. This work aims to report the rate of BM in CRC patients treated in a single institution, along with survival and prognostic factors. METHODS Medical charts for patients with histologically proven CRC were retrospectively reviewed. RESULTS A total of 538 patients were identified, of whom 33% developed any metastatic disease and 4.4% presented BM. Lung was the most frequently associated metastatic site (in 68% of the cases). The only factor independently associated with BM development was the presence of metastatic disease at the time of initial presentation. The median duration from initial diagnosis to BM development was 38.6 months (SD 29.1 months). Median survival after BM development was 62 days (95% confidence interval [CI] 56-68). Patients diagnosed with BM within 1 year of cancer diagnosis responded significantly better to treatment than those who acquired BM later, with a median survival after BM diagnosis of 261 days versus 61 days, respectively (p = .002). Patients with BM who received antiangiogenic therapy had an improved median survival compared to those who did not (151 days vs 59 days, p = 0.02; hazard ratio for death 0.29 [95% CI 0.09-0.94]). CONCLUSION CRC with BM is an aggressive disease resistant to standard treatment and is associated with poor outcomes. Adding antiangiogenic therapy might be of value for those patients. Patients with BM developing early in the disease course might respond better to treatment.
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Affiliation(s)
- Georges Chahine
- Hematology-Oncology Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
| | - Tony Ibrahim
- Hematology-Oncology Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon.,Medical Oncology Department, Gustave Roussy Institute, Villejuif, France
| | - Tony Felefly
- Radiation Oncology Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
| | - Abir El-Ahmadie
- Hematology-Oncology Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
| | - Pamela Freiha
- Hematology-Oncology Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
| | - Lionel El-Khoury
- General Surgery Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
| | - Nadine Khalife-Saleh
- Hematology-Oncology Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon.,Medical Oncology Department, Gustave Roussy Institute, Villejuif, France
| | - Khalil Saleh
- Hematology-Oncology Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon.,Medical Oncology Department, Gustave Roussy Institute, Villejuif, France
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24
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Huang Z, Sun B, Wu S, Meng X, Cong Y, Shen G, Song S. A nomogram for predicting survival in patients with breast cancer brain metastasis. Oncol Lett 2018; 15:7090-7096. [PMID: 29725432 PMCID: PMC5920309 DOI: 10.3892/ol.2018.8259] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 01/18/2018] [Indexed: 12/27/2022] Open
Abstract
Brain metastasis (BM) is common in patients with breast cancer. Predicting patient survival is critical for the clinical management of breast cancer brain metastasis (BCBM). The present study was designed to develop and evaluate a prognostic model for patients with newly diagnosed BCBM. Based on the clinical data of patients with BCBM treated in the Affiliated Hospital of Academy of Military Medical Sciences (Beijing, China) between 2002 and 2014, a nomogram was developed to predict survival using proportional hazards regression analysis. The model was validated internally by bootstrapping, and the concordance index (c-index) was calculated. A calibration curve and c-index were used to evaluate discriminatory and predictive ability, in order to compare the nomogram with widely used models, including recursive partitioning analysis (RPA), graded prognostic assessment (GPA) and breast-graded prognostic assessment (Breast-GPA). A total of 411 patients with BCBM were included in the development of this predictive model. The median overall survival time was 14.1 months. Statistically significant predictors for patient survival included biological subtype, Karnofsky performance score, leptomeningeal metastasis, extracranial metastasis, the number of brain metastases and disease-free survival. A nomogram for predicting 1- and 2-year overall survival rates was constructed, which exhibited good accuracy in predicting overall survival with a concordance index of 0.735. This model outperformed RPA, GPA and Breast-GPA, based on the comparisons of the c-indexes. The nomogram constructed based on a multiple factor analysis was able to more accurately predict the individual survival probability of patients with BCBM, compared with existing models.
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Affiliation(s)
- Zhou Huang
- Department of Radiation Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, P.R. China.,Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, P.R. China
| | - Bing Sun
- Department of Radiation Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, P.R. China
| | - Shikai Wu
- Department of Radiation Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, P.R. China
| | - Xiangying Meng
- Department of Radiation Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, P.R. China
| | - Yang Cong
- Department of Radiation Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, P.R. China
| | - Ge Shen
- Department of Radiation Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, P.R. China
| | - Santai Song
- Department of Breast Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, P.R. China
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25
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Clinical Usefulness of Tools to Support Decision-making for Palliative Treatment of Metastatic Colorectal Cancer: A Systematic Review. Clin Colorectal Cancer 2018; 17:e1-e12. [DOI: 10.1016/j.clcc.2017.06.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 06/16/2017] [Indexed: 12/23/2022]
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26
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Fukuda K, Matsuoka Y, Ota I, Seki H, Ito S, Kato S. Analysis of patients with colorectal cancer and brain metastases. COLORECTAL CANCER 2016. [DOI: 10.2217/crc-2016-0001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Brain metastases from colorectal cancer (CRC) are relatively rare. However, the incidences of brain metastasis have increased. We investigated 516 CRC patients who developed recurrence or metastatic disease. We investigated the primary site, distant metastasis, histological type, clinical features of processes of death and neurological symptoms. Brain metastases were detected in 5.8%. Odds ratios were 6.89 for the lung metastasis (p < 0.001), 0.43 for the liver (p = 0.04). The survival after brain metastasis was significantly poor in multiple brain metastases (hazard ratio: 4.12; p = 0.03) and poor performance status (hazard ratio: 5.38; p = 0.003). Lung metastasis is a higher factor and liver metastasis is a lower factor of brain metastasis. Survival after brain metastasis was poor in multiple brain metastasis and poor performance status.
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Affiliation(s)
- Koji Fukuda
- Department of Clinical Oncology, Iwate Prefectural Central Hospital, Japan
| | | | - Ibuki Ota
- Department of Radiology, Iwate Prefectural Central Hospital, Japan
| | - Hirobumi Seki
- Department of Neurosurgery, Iwate Prefectural Central Hospital, Japan
| | - Shukuei Ito
- Department of Clinical Oncology, Institute of Development, Aging & Cancer, Tohoku University, Iwate Prefectural Central Hospital, Ueda 1-4-1, Morioka, Iwate 020-0066, Japan
| | - Satoshi Kato
- Department of Clinical Oncology, Iwate Prefectural Central Hospital, Japan
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27
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Aprile G, Casagrande M, De Maglio G, Fontanella C, Rihawi K, Bonotto M, Pisa FE, Tuniz F, Pizzolitto S, Fasola G. Comparison of the molecular profile of brain metastases from colorectal cancer and corresponding primary tumors. Future Oncol 2016; 13:135-144. [PMID: 27578453 DOI: 10.2217/fon-2016-0196] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
AIM Little is known about molecular biology of brain metastasis (BM) from colorectal cancer and its concordance with matched primary tumors. MATERIALS & METHODS We identified 56 consecutive colorectal cancer patients who underwent neurosurgical resection of BM. Tumor samples were tested for KRAS, NRAS, BRAF and PIK3CA. The molecular profile of the brain lesion was compared with the corresponding primary tumor. RESULTS The molecular profile concordance rate was 95.1%. Median survival after neurosurgery was 5.5 months (95% CI: 4.7-6.3); median overall survival was 24.0 months (95% CI: 15.6-32.4). CONCLUSION In this cohort, we report a high frequency of KRAS mutations and a very high concordance rate between the molecular status of BM and that of matched primary tumors.
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Affiliation(s)
- Giuseppe Aprile
- Department of Oncology, University & General Hospital, Piazzale S Maria della Misericordia 15, 33100, Udine, Italy
| | - Mariaelena Casagrande
- Department of Oncology, University & General Hospital, Piazzale S Maria della Misericordia 15, 33100, Udine, Italy
| | - Giovanna De Maglio
- Department of Pathology, University & General Hospital, Piazzale S Maria della Misericordia 15, 33100, Udine, Italy
| | - Caterina Fontanella
- Department of Oncology, University & General Hospital, Piazzale S Maria della Misericordia 15, 33100, Udine, Italy
| | - Karim Rihawi
- Department of Oncology, University & General Hospital, Piazzale S Maria della Misericordia 15, 33100, Udine, Italy
| | - Marta Bonotto
- Department of Oncology, University & General Hospital, Piazzale S Maria della Misericordia 15, 33100, Udine, Italy
| | - Federica E Pisa
- Institute of Hygiene & Clinical Epidemiology, University & General Hospital, Piazzale S Maria della Misericordia 15, 33100, Udine, Italy
| | - Francesco Tuniz
- Department of Neurosurgery, University & General Hospital, Piazzale S Maria della Misericordia 15, 33100, Udine, Italy
| | - Stefano Pizzolitto
- Department of Pathology, University & General Hospital, Piazzale S Maria della Misericordia 15, 33100, Udine, Italy
| | - Gianpiero Fasola
- Department of Oncology, University & General Hospital, Piazzale S Maria della Misericordia 15, 33100, Udine, Italy
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Zhang ZY, Luo QF, Yin XW, Dai ZL, Basnet S, Ge HY. Nomograms to predict survival after colorectal cancer resection without preoperative therapy. BMC Cancer 2016; 16:658. [PMID: 27553083 PMCID: PMC4995691 DOI: 10.1186/s12885-016-2684-4] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Accepted: 08/06/2016] [Indexed: 12/14/2022] Open
Abstract
Background The predictive accuracy of the American Joint Committee on Cancer (AJCC) stages of colorectal cancer (CRC) is mediocre. This study aimed to develop postoperative nomograms to predict cancer-specific survival (CSS) and overall survival (OS) after CRC resection without preoperative therapy. Methods Eligible patients with stage I to IV CRC (n = 56072) diagnosed from 2004 to 2010 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were allocated into training (n = 27,700), contemporary (n = 3158), and prospective (n = 25,214) validation cohorts. Clinically important variables were incorporated and selected using the Akaike information criterion in multivariate Cox regressions to derive nomograms with the training cohort. The performance of the nomograms was assessed and externally testified using the concordance index (c-index), bootstrap validation, calibration, time-dependent receiver-operating characteristic curves, Kaplan–Meier curves, mosaic plots, and decision curve analysis (DCA). Performance of the conventional AJCC stages was also compared with the nomograms using similar statistics. Results The nomograms for CSS and OS shared common predictors: sex, age, race, marital status, preoperative carcinoembryonic antigen status, surgical extent, tumor size, location, histology, differentiation, infiltration depth, lymph node count, lymph node ratio, and metastasis. The c-indexes of the nomograms for CSS and OS were 0.816 (95 % CI 0.810–0.822) and 0.777 (95 % CI 0.772–0.782), respectively. Performance evaluations showed that the nomograms achieved considerable predictive accuracy, appreciable reliability, and significant clinical validity with wide practical threshold probabilities, while the results remained reproducible when applied to the validation cohorts. Additionally, model comparisons and DCA proved that the nomograms excelled in stratifying each AJCC stage into three significant prognostic subgroups, allowing for more robust risk classification with an improved net benefit. Conclusions We propose two prognostic nomograms that exhibit improved predictive accuracy and net benefit for patients who have undergone CRC resection. The established nomograms are intended for risk assessment and selection of suitable patients who may benefit from adjuvant therapy and intensified follow-up after surgery. Independent external validations may still be required.
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Affiliation(s)
- Zhen-Yu Zhang
- Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Pudong New District, No. 150, Jimo Road, Shanghai, 200120, China
| | - Qi-Feng Luo
- Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Pudong New District, No. 150, Jimo Road, Shanghai, 200120, China
| | - Xiao-Wei Yin
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhen-Ling Dai
- Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Pudong New District, No. 150, Jimo Road, Shanghai, 200120, China
| | - Shiva Basnet
- Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Pudong New District, No. 150, Jimo Road, Shanghai, 200120, China
| | - Hai-Yan Ge
- Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Pudong New District, No. 150, Jimo Road, Shanghai, 200120, China.
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Nieder C, Hintz M, Grosu AL. Predicted survival in patients with brain metastases from colorectal cancer: Is a current nomogram helpful? Clin Neurol Neurosurg 2016; 143:107-10. [PMID: 26914143 DOI: 10.1016/j.clineuro.2016.02.022] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Revised: 02/15/2016] [Accepted: 02/16/2016] [Indexed: 02/01/2023]
Abstract
OBJECTIVE To examine the clinical applicability of a new nomogram by comparing survival of patients with brain metastases from colorectal cancer treated with surgery and/or radiotherapy in the authors' institutions with nomogram-predicted median survival. METHODS Retrospective analysis of 64 patients treated with comparable approaches and during the same time period as the patients in the nomogram study. Points were assigned for age, performance status, number and site of brain metastases, as required for nomogram use. RESULTS In 46 patients (72%), the observed survival was shorter than the predicted median. The median deviation was -1.4 months. The nomogram underestimated the survival of patients treated with radiosurgery/surgery by a median of 4.2 months, whereas it overestimated the survival of patients treated with whole-brain radiotherapy (WBRT) by a median of 2.1 months (p=0.0001). Nevertheless, all 5 patients with predicted median survival ≤3 months died within 3 months. Among 8 patients with predicted median survival >12 months, 6 (75%) survived for >12 months. Not all prognostic factors in the nomogram correlated with survival. In the multivariate Cox model, only performance status and number of brain metastases were significant, both with p=0.0001. CONCLUSION Despite differences in prognostic factors and survival of many individual patients, especially those with intermediate prognosis, the nomogram performed promising in poor- and good-prognosis patients. Evaluation of separate prediction tools for patients treated with WBRT and more aggressive local approaches appears warranted in order to minimize the influence of better local control of the brain metastases.
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Affiliation(s)
- Carsten Nieder
- Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway; Institute of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
| | - Mandy Hintz
- Department of Radiation Oncology, University Hospital Freiburg, Freiburg, Germany
| | - Anca L Grosu
- Department of Radiation Oncology, University Hospital Freiburg, Freiburg, Germany
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