|
1
|
Ji X, Sun W, Lv C, Huang J, Yu R, Dong W, Zhang H. Survival trends and conditional survival in patients with pulmonary metastases from differentiated thyroid carcinoma. Endocrine 2025; 87:1120-1130. [PMID: 39589684 DOI: 10.1007/s12020-024-04109-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 11/09/2024] [Indexed: 11/27/2024]
Abstract
INTRODUCTION Patients with pulmonary metastases from differentiated thyroid carcinoma (DTC) have a significantly poorer prognosis compared to DTC patients without metastases. This study aimed to establish a nomogram combined with dynamic survival analysis to predict the survival probability of patients with pulmonary metastases from differentiated thyroid carcinoma and compensate for the underestimation of survival in patients with very poor prognosis. PATIENTS AND METHODS Patient data were collected from the Surveillance, Epidemiological, and End Result (SEER) data resource from 2010 to 2019. Multivariate analysis was carried out by the Cox proportional hazards regression to construct a nomogram. Receiver operating characteristic (ROC) curves along with calibration were employed to assess the effectiveness of the model.The life table was used to estimate the conditional cancer-specific survival (CSS). RESULTS In the training set, the AUCs for the CSS nomogram were 0.728, 0.741, and 0.779, with a c-index of 0.682, indicating good predictive performance at 3, 5, and 10 years. In the validation set, the AUCs for the CSS nomogram were 0.706, 0.726, and 0.769, with a c-index of 0.696, while the AUCs for the 8th TNM staging system were 0.521, 0.555, and 0.601, with a c-index of 0.579. The overall 5-year conditional survival rate for patients increased slightly from 63.44 to 70.52%. The survival gap was greatest between patients aged <55 years and those aged ≥55 years. CONCLUSION We established a nomogram combined with dynamic survival analysis, which serve as promising options for prognosis estimation, to enhance personalized evaluation of survival risks and provide the basis for the development of more clinical treatment approaches.
Collapse
Affiliation(s)
- Xiaoyu Ji
- Department of Thyroid Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China
| | - Wei Sun
- Department of Thyroid Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China
| | - Chengzhou Lv
- Department of Thyroid Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China
| | - Jiapeng Huang
- Department of Thyroid Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China
| | - Ruonan Yu
- Department of Thyroid Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China
| | - Wenwu Dong
- Department of Thyroid Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China
| | - Hao Zhang
- Department of Thyroid Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, 110001, China.
| |
Collapse
|
|
2
|
Kusunoki Y, Fukuoka T, Sugimoto A, Tsujio G, Yonemitsu K, Seki Y, Kasashima H, Shibutani M, Maeda K. Impact of Changes in Psoas Muscle Index on Prognosis in Patients With Colorectal Liver Metastases. CANCER DIAGNOSIS & PROGNOSIS 2025; 5:72-82. [PMID: 39758237 PMCID: PMC11696330 DOI: 10.21873/cdp.10414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/02/2024] [Accepted: 12/03/2024] [Indexed: 01/07/2025]
Abstract
Background/Aim Reduction in skeletal muscle mass during chemotherapy is associated with poor outcomes. This study investigated the impact of changes in the psoas muscle index (PMI) on the prognosis of patients with unresectable colorectal liver metastases (CRLM) undergoing chemotherapy, including subgroup analyses based on the initial treatment response assessment. Patients and Methods We evaluated 47 patients with unresectable CRLM who underwent systematic chemotherapy and assessed changes in PMI to determine their prognosis. Results Changes in PMI were significantly associated with the presence or absence of primary tumor resection and the chemotherapeutic responses to first-line chemotherapy. The PMI reduction group was significantly associated with poor prognosis in both overall survival (OS) and progression-free survival (PFS) in patients with CRLM, and in both OS and PFS in the partial response (PR) group at the initial chemotherapy response assessment. Conclusion Skeletal muscle loss at chemotherapy initiation was significantly associated with poorer survival in patients with unresectable CRLM. Maintaining muscle mass could serve as a new indicator for identifying patients with a PR at the initial chemotherapy response assessment for prognosis. Personalized interventions should be investigated to determine whether they can improve muscle mass and lead to better clinical outcomes.
Collapse
Affiliation(s)
- Yukina Kusunoki
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Tatsunari Fukuoka
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Atsushi Sugimoto
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Gen Tsujio
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Ken Yonemitsu
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Yuki Seki
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Hiroaki Kasashima
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Masatsune Shibutani
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| | - Kiyoshi Maeda
- Department of Breast and Endocrine Surgery, Mitsui Memorial Hospital, Tokyo, Japan
| |
Collapse
|
|
3
|
Kawashima J, Endo Y, Woldesenbet S, Chatzipanagiotou OP, Tsilimigras DI, Catalano G, Khan MMM, Rashid Z, Khalil M, Altaf A, Munir MM, Guglielmi A, Ruzzenente A, Aldrighetti L, Alexandrescu S, Kitago M, Poultsides G, Sasaki K, Aucejo F, Endo I, Pawlik TM. Preoperative identification of early extrahepatic recurrence after hepatectomy for colorectal liver metastases: A machine learning approach. World J Surg 2024; 48:2760-2771. [PMID: 39425666 DOI: 10.1002/wjs.12376] [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: 06/27/2024] [Accepted: 10/06/2024] [Indexed: 10/21/2024]
Abstract
BACKGROUND Machine learning (ML) may provide novel insights into data patterns and improve model prediction accuracy. The current study sought to develop and validate an ML model to predict early extra-hepatic recurrence (EEHR) among patients undergoing resection of colorectal liver metastasis (CRLM). METHODS Patients with CRLM who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. An eXtreme gradient boosting (XGBoost) model was developed to estimate the risk of EEHR, defined as extrahepatic recurrence within 12 months after hepatectomy, using clinicopathological factors. The relative importance of factors was determined using Shapley additive explanations (SHAP) values. RESULTS Among 1410 patients undergoing curative-intent resection, 131 (9.3%) patients experienced EEHR. Median OS among patients with and without EEHR was 35.4 months (interquartile range [IQR] 29.9-46.7) versus 120.5 months (IQR 97.2-134.0), respectively (p < 0.001). The ML predictive model had c-index values of 0.77 (95% CI, 0.72-0.81) and 0.77 (95% CI, 0.73-0.80) in the entire dataset and the validation data set with bootstrapping resamples, respectively. The SHAP algorithm demonstrated that T and N primary tumor categories, as well as tumor burden score were the three most important predictors of EEHR. An easy-to-use risk calculator for EEHR was developed and made available online at: https://junkawashima.shinyapps.io/EEHR/. CONCLUSIONS An easy-to-use online calculator was developed using ML to help clinicians predict the chance of EEHR after curative-intent resection for CRLM. This tool may help clinicians in decision-making related to treatment strategies for patients with CRLM.
Collapse
Affiliation(s)
- Jun Kawashima
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Yutaka Endo
- Department of Surgery, University of Rochester, Rochester, New York, USA
| | - Selamawit Woldesenbet
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Odysseas P Chatzipanagiotou
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Diamantis I Tsilimigras
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Giovanni Catalano
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
- Department of Surgery, University of Verona, Verona, Italy
| | - Muhammad Muntazir Mehdi Khan
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Zayed Rashid
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Mujtaba Khalil
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Abdullah Altaf
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Muhammad Musaab Munir
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | | | | | | | | | - Minoru Kitago
- Department of Surgery, Keio University, Tokyo, Japan
| | - George Poultsides
- Department of Surgery, Stanford University, Stanford, California, USA
| | - Kazunari Sasaki
- Department of Surgery, Stanford University, Stanford, California, USA
| | - Federico Aucejo
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| |
Collapse
|
|
4
|
Wach MM, Washburn LA, Alvikas J, Qu LT, Zhang M, Etherington MS, Rieser C, Haykal T, Pingpank JF, Zureikat AH, Geller DA, Hoehn RS, Tohme S. Combined hepatic resection and ablation for high burden of colorectal liver metastases demonstrates safety and durable survival. HPB (Oxford) 2024; 26:362-369. [PMID: 38008683 DOI: 10.1016/j.hpb.2023.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 09/15/2023] [Accepted: 11/03/2023] [Indexed: 11/28/2023]
Abstract
BACKGROUND Hepatic resection (HR) and thermal ablation of Colorectal Liver Metastases (CRLM) have each individually demonstrated safety and survival benefit. We sought to provide our experience with the combination of HR + ablation within one operation for patients with multiple CRLM. METHODS Review of a single institution database of patients who underwent HR + ablation between 2010 and 2019. RESULTS 161 patients were identified who underwent HR + ablation for isolated CRLM (mean age: 59, male 63.4%). 125 (77.6%) patients had bilobar disease and 92 (57.1%) patients had ≥5 tumors. 28 (17.4%) patients experienced minor (grade 1 or 2) complications while 20 (12.4%) had grade 3-5 complications. Patients who underwent simultaneous colon resection with HR + ablation had a higher complication rate (22 of 47, 46.8%) than those undergoing HR + ablation only (26 of 114, 22.8%, p = 0.002). Median and 5-year OS for all patients undergoing HR + ablation was 38.2 months and 33.2%, respectively. 5-year hepatic recurrence free survival was 23.5%. Patients with 5 or more tumors demonstrated no difference in median survival compared to those with fewer than 5 tumors (37.0 months vs 38.4 months, p = 0.326). CONCLUSIONS In this population of CRLM patients with a relatively high burden of disease, HR + ablation demonstrated an acceptable safety profile as well as durable long-term survival.
Collapse
Affiliation(s)
- Michael M Wach
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Laura A Washburn
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Jurgis Alvikas
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Linda T Qu
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Michelle Zhang
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mark S Etherington
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Caroline Rieser
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Tony Haykal
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - James F Pingpank
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - David A Geller
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Richard S Hoehn
- Department of Surgery, University Hospitals, Cleveland, OH, USA
| | - Samer Tohme
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
| |
Collapse
|
|
5
|
Yang YP, Guo CJ, Gu ZX, Hua JJ, Zhang JX, Shi J. Conditional survival probability of distant-metastatic hepatocellular carcinoma: A population-based study. World J Gastrointest Oncol 2023; 15:1874-1890. [DOI: 10.4251/wjgo.v15.i11.1874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 08/20/2023] [Accepted: 09/06/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND The prognosis of many patients with distant metastatic hepatocellular carcinoma (HCC) improved after they survived for several months. Compared with traditional survival analysis, conditional survival (CS) which takes into account changes in survival risk could be used to describe dynamic survival probabilities.
AIM To evaluate CS of distant metastatic HCC patients.
METHODS Patients diagnosed with distant metastatic HCC between 2010 and 2015 were extracted from the Surveillance, Epidemiology and End Results database. Univariate and multivariate Cox regression analysis were used to identify risk factors for overall survival (OS), while competing risk model was used to identify risk factors for cancer-specific survival (CSS). Six-month CS was used to calculate the probability of survival for an additional 6 mo at a specific time after initial diagnosis, and standardized difference (d) was used to evaluate the survival differences between subgroups. Nomograms were constructed to predict CS.
RESULTS Positive α-fetoprotein expression, higher T stage (T3 and T4), N1 stage, non-primary site surgery, non-chemotherapy, non-radiotherapy, and lung metastasis were independent risk factors for actual OS and CSS through univariate and multivariate analysis. Actual survival rates decreased over time, while CS rates gradually increased. As for the 6-month CS, the survival difference caused by chemotherapy and radiotherapy gradually disappeared over time, and the survival difference caused by lung metastasis reversed. Moreover, the influence of age and gender on survival gradually appeared. Nomograms were fitted for patients who have lived for 2, 4 and 6 mo to predict 6-month conditional OS and CSS, respectively. The area under the curve (AUC) of nomograms for conditional OS decreased as time passed, and the AUC for conditional CSS gradually increased.
CONCLUSION CS for distant metastatic HCC patients substantially increased over time. With dynamic risk factors, nomograms constructed at a specific time could predict more accurate survival rates.
Collapse
Affiliation(s)
- Yong-Ping Yang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Cheng-Jun Guo
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Zhao-Xuan Gu
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Jun-Jie Hua
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Jia-Xuan Zhang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Jian Shi
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| |
Collapse
|
|
6
|
Lee SL, Bassetti MF, Rusthoven CG. The Role of Stereotactic Body Radiation Therapy in the Management of Liver Metastases. Semin Radiat Oncol 2023; 33:181-192. [PMID: 36990635 DOI: 10.1016/j.semradonc.2022.11.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
Abstract
The liver is a common site for metastatic spread for various primary tumor histologies. Stereotactic body radiation therapy (SBRT) is a non-invasive treatment technique with broad patient candidacy for the ablation of tumors in the liver and other organs. SBRT involves focused, high-dose radiation therapy delivered in one to several treatments, resulting in high rates of local control. Use of SBRT for ablation of oligometastatic disease has increased in recent years and emerging prospective data have demonstrated improvements in progression free and overall survival in some settings. When delivering SBRT to liver metastases, clinicians must balance the priorities of delivering ablative tumor dosing while respecting dose constraints to surrounding organs at risk (OARs). Motion management techniques are crucial for meeting dose constraints, ensuring low rates of toxicity, maintaining quality of life, and can allow for dose escalation. Advanced radiotherapy delivery approaches including proton therapy, robotic radiotherapy, and real-time MR-guided radiotherapy may further improve the accuracy of liver SBRT. In this article, we review the rationale for oligometastases ablation, the clinical outcomes with liver SBRT, tumor dose and OAR considerations, and evolving strategies to improve liver SBRT delivery.
Collapse
Affiliation(s)
- Sangjune Laurence Lee
- Division of Radiation Oncology, University of Calgary, Tom Baker Cancer Centre, Calgary, AB, Canada.
| | - Michael F Bassetti
- Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison, WI
| | - Chad G Rusthoven
- Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO
| |
Collapse
|
|
7
|
Finotti M, D’Amico FE, Romano M, Brizzolari M, Scopelliti M, Zanus G. Colorectal Liver Metastases: A Literature Review of Viable Surgical Options with a Special Focus on Microwave Liver Thermal Ablation and Mini-Invasive Approach. J Pers Med 2022; 13:33. [PMID: 36675694 PMCID: PMC9866288 DOI: 10.3390/jpm13010033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 11/28/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common tumor worldwide and it is characterized in 20-30% of cases by liver involvement, which strongly affects the long-term patient outcome. There are many available therapies for liver colorectal metastases (CRLMs); the current standard of care is represented by liver resection, and when feasible, associated with systemic chemotherapy. Microwave thermal ablation (MWA) is a viable option in unresectable patients or to achieve treatment with a parenchymal spearing approach. A literature review was performed for studies published between January 2000 and July 2022 through a database search using PUBMED/Medline and the Cochrane Collaboration Library with the following MeSH search terms and keywords: microwave, ablation, liver metastases, colorectal neoplasm, and colon liver rectal metastases. The recurrence rate and overall patients' survival were evaluated, showing that laparoscopic MWA is safe and effective to treat CRLMs when resection is not feasible, or a major hepatectomy in fragile patients is necessary. Considering the low morbidity of this procedure, it is a viable option to treat patients with recurrent diseases in the era of effective chemotherapy and multimodal treatments.
Collapse
Affiliation(s)
- Michele Finotti
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy
- Baylor Scott & White Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical, Dallas, TX 75204, USA
| | | | - Maurizio Romano
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy
| | - Marco Brizzolari
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy
| | - Michele Scopelliti
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy
| | - Giacomo Zanus
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy
| |
Collapse
|
|
8
|
Ye J, Lin Y, Gao X, Lu L, Huang X, Huang S, Bai T, Wu G, Luo X, Li Y, Liang R. Prognosis-Related Molecular Subtypes and Immune Features Associated with Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:cancers14225721. [PMID: 36428813 PMCID: PMC9688639 DOI: 10.3390/cancers14225721] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 10/29/2022] [Accepted: 11/01/2022] [Indexed: 11/23/2022] Open
Abstract
Bioinformatics tools were used to identify prognosis-related molecular subtypes and biomarkers of hepatocellular carcinoma (HCC). Differential expression analysis of four datasets identified 3330 overlapping differentially expressed genes (DEGs) in the same direction in all four datasets. Those genes were involved in the cell cycle, FOXO signaling pathway, as well as complement and coagulation cascades. Based on non-negative matrix decomposition, two molecular subtypes of HCC with different prognoses were identified, with subtype C2 showing better overall survival than subtype C1. Cox regression and Kaplan-Meier analysis showed that 217 of the overlapping DEGs were closely associated with HCC prognosis. The subset of those genes showing an area under the curve >0.80 was used to construct random survival forest and least absolute shrinkage and selection operator models, which identified seven feature genes (SORBS2, DHRS1, SLC16A2, RCL1, IGFALS, GNA14, and FANCI) that may be involved in HCC occurrence and prognosis. Based on the feature genes, risk score and recurrence models were constructed, while a univariate Cox model identified FANCI as a key gene involved mainly in the cell cycle, DNA replication, and mismatch repair. Further analysis showed that FANCI had two mutation sites and that its gene may undergo methylation. Single-sample gene set enrichment analysis showed that Th2 and T helper cells are significantly upregulated in HCC patients compared to controls. Our results identify FANCI as a potential prognostic biomarker for HCC.
Collapse
Affiliation(s)
- Jiazhou Ye
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Yan Lin
- Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Xing Gao
- Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Lu Lu
- Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Xi Huang
- Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Shilin Huang
- Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Tao Bai
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Guobin Wu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Xiaoling Luo
- Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Yongqiang Li
- Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
- Correspondence: (Y.L.); (R.L.); Tel./Fax: +86-771-5335155 (Y.L. & R.L.)
| | - Rong Liang
- Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China
- Correspondence: (Y.L.); (R.L.); Tel./Fax: +86-771-5335155 (Y.L. & R.L.)
| |
Collapse
|
|
9
|
Carpenter EL, Thomas KK, Adams AM, Valdera FA, Chick RC, Kemp Bohan PM, Spitzer HV, Clifton GT, Bader JO, Nelson DW, Vreeland TJ. Modern trends in minimally invasive versus open hepatectomy for colorectal liver metastasis: an analysis of ACS-NSQIP. Surg Endosc 2022:10.1007/s00464-022-09749-y. [DOI: 10.1007/s00464-022-09749-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 10/11/2022] [Indexed: 11/09/2022]
|
|
10
|
Kim K, Yu JI, Park HC, Yoo GS, Lim DH, Noh JM, Jeong WK. A phase II trial of hypofractionated high-dose proton beam therapy for unresectable liver metastases. Radiother Oncol 2022; 176:9-16. [PMID: 36113779 DOI: 10.1016/j.radonc.2022.09.003] [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: 08/03/2022] [Revised: 08/31/2022] [Accepted: 09/05/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND PURPOSE Proton beam therapy (PBT) is an effective treatment option for primary malignant liver disease. However, evidence regarding liver metastasis is insufficient. We aimed to investigate the efficacy and safety of hypofractionated high-dose PBT in the treatment of metastatic liver disease. MATERIALS AND METHODS From January 2019 to January 2021, patients with unresectable liver metastases were enrolled. For PBT, the dose schemes of 60 Gy relative biological effectiveness (GyRBE) in 5 fractions (fx) (biologically effective dose [BED] 132 GyE) or 70 GyRBE in 10 fx (BED 119 GyE) were used. Either a passive scattered beam or pencil beam scanning (PBS)-based intensity-modulated proton therapy (IMPT) was performed with proper respiratory management. The primary endpoint of the study was 6-month freedom from local progression (FFLP) rate; and the Kaplan-Meier method was used to calculate the FFLP and survival rates. RESULTS Of the 49 liver metastases in 46 patients, the colorectum accounted for 60% of the primary cancer sites, followed by the gastrointestinal organs and pancreas/biliary tract. Forty patients presented only 1 liver metastasis, while the other 6 patients had 2 to 4 metastases. The Six-month FFLP rate was 95.2%. The 1-year FFLP rate in patients with <3 cm liver metastasis was 87.4%, while that was 74.1% in patients with > 3 cm group (p = 0.087). With regard to systemic treatment, the 1-year FFLP rate after PBT was better (94.1%) than that without systemic treatment (75.8%; p = 0.051). Regarding PBT-related toxicity, one patient developed a grade 2 gastric ulcer, while none of the patients developed grade ≥3 toxicities. CONCLUSIONS Hypofractionated PBT with a BED > 100 GyRBE for liver metastasis is safe and effective, given the high rate of 6-month FFLP without grade ≥3 treatment-related toxicities. However, further improvements are required for larger tumors and/or those without prior systemic therapy.
Collapse
Affiliation(s)
- Kangpyo Kim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
| | - Gyu Sang Yoo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Do Hoon Lim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jae Myoung Noh
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| |
Collapse
|
|
11
|
A multicenter phase II trial evaluating the efficacy of bevacizumab plus mFOLFOX6 for R0 surgical resection in advanced colorectal liver metastases harboring mutant-type KRAS: NEXTO-mt trial. HPB (Oxford) 2022; 24:1245-1251. [PMID: 35216869 DOI: 10.1016/j.hpb.2022.02.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 01/13/2022] [Accepted: 02/02/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND The effect of bevacizumab plus mFOLFOX6 on downsizing of liver metastases for curative resection has not been well assessed for patients with advanced colorectal liver metastases (CRLMs). This multicenter phase II trial aimed to examine the efficacy and safety of bevacizumab plus mFOLFOX6 for advanced CRLMs harboring mutant-type KRAS. METHODS Patients with advanced CRLMs (tumor number of ≥5 and/or technically unresectable) harboring mutant-type KRAS were included. Surgical indication was evaluated every 4 cycles of bevacizumab plus mFOLFOX6. Liver resection was planned if the CRLMs were resectable. The primary endpoint was R0 resection rate. The secondary endpoints included overall survival (OS), recurrence-free survival, progression-free survival, and safety. RESULTS Between 2013 and 2017, 29 patients from six centers were registered. The rates of complete and partial responses were 0% and 62.1%, respectively. R0 and R1 resections were performed in 19 and 1 patient, respectively (R0 resection rate: 65.5%). No mortality occurred. During the median follow-up of 30.7 months, the 3-year OS rate for all the patients was 64.4% with the median survival of 49.1 months. CONCLUSION For advanced CRLMs harboring mutant-type KRAS, bevacizumab plus mFOLFOX6 achieved a high R0 resection rate, leading to favorable survival.
Collapse
|
|
12
|
Lu W, Hong W, Qiu H, Zhou Z, He Z, Zeng W, Zhong W, Xie J. A novel prognostic time window based on conditional survival and outcomes analyses of primary liver cancer patients. Cancer Med 2022; 11:3873-3885. [PMID: 35460212 PMCID: PMC9582677 DOI: 10.1002/cam4.4762] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/26/2022] [Accepted: 04/09/2022] [Indexed: 11/07/2022] Open
Abstract
Background Liver cancer is one of the most deadly and prevalent cancers. A routine follow‐up plan for liver cancer is crucial but limited. In the present study, we aimed to disclose possible risk factors and critical survival time windows for primary liver cancer. Methods We enrolled 692 liver cancer patients from Sun Yat‐sen University Cancer Center (SYSUCC). Univariate and multivariate logistic regression analyses of cirrhosis and recurrence were conducted. A meta‐analysis was utilized to validate an indication of creatinine (CRE) in recurrence. Conditional survival analysis was performed using the Kaplan–Meier method. The results were further verified by the SYSUCC validation cohort and Surveillance, Epidemiology, and End Results (SEER) validation cohort. Results Our results indicated that A/G, history of hepatitis, history of alcohol consumption and platelet (PLT) might be potential prognostic factors for cirrhosis in liver cancer patients. CRE was significantly correlated with recurrence due to various therapies, especially after transarterial embolization. Moreover, 1.5 years to 2 years may be a critical time window for deterioration in survival rate based on the conditional survival analysis. Conclusion A/G, history of hepatitis, alcohol consumption and PLT may be potential prognostic factors for cirrhosis in liver cancer patients. More attention should be focused on the renal function when treating the patients due to the significant role of CRE. 1.5 years to 2 years is a critical time window for deterioration in survival rate for liver cancer patients that contributes to determining the optimal follow‐up plan in the future.
Collapse
Affiliation(s)
- Weicheng Lu
- State Key Laboratory of Oncology in Southern China, Department of Anesthesiology, Sun Yat-sen University Cancer Center, Collaborative Innovation for Cancer Medicine, Guangzhou, China
| | - Weifeng Hong
- Department of Radiotherapy, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Haibo Qiu
- State Key Laboratory of Oncology in Southern China, Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Collaborative Innovation for Cancer Medicine, Guangzhou, China
| | - Zhongguo Zhou
- State Key Laboratory of Oncology in Southern China, Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Collaborative Innovation for Cancer Medicine, Guangzhou, China
| | - Zhonglian He
- State Key Laboratory of Oncology in Southern China, Information Center, Sun Yat-sen University Cancer Center, Collaborative Innovation for Cancer Medicine, Guangzhou, China
| | - Weian Zeng
- State Key Laboratory of Oncology in Southern China, Department of Anesthesiology, Sun Yat-sen University Cancer Center, Collaborative Innovation for Cancer Medicine, Guangzhou, China
| | - Weiqiang Zhong
- State Key Laboratory of Oncology in Southern China, Department of Anesthesiology, Sun Yat-sen University Cancer Center, Collaborative Innovation for Cancer Medicine, Guangzhou, China
| | - Jingdun Xie
- State Key Laboratory of Oncology in Southern China, Department of Anesthesiology, Sun Yat-sen University Cancer Center, Collaborative Innovation for Cancer Medicine, Guangzhou, China
| |
Collapse
|
|
13
|
Johnson H, El-Schich Z, Ali A, Zhang X, Simoulis A, Wingren AG, Persson JL. Gene-Mutation-Based Algorithm for Prediction of Treatment Response in Colorectal Cancer Patients. Cancers (Basel) 2022; 14:2045. [PMID: 35454952 PMCID: PMC9030299 DOI: 10.3390/cancers14082045] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/14/2022] [Accepted: 04/15/2022] [Indexed: 12/13/2022] Open
Abstract
Purpose: Despite the high mortality of metastatic colorectal cancer (mCRC), no new biomarker tools are available for predicting treatment response. We developed gene-mutation-based algorithms as a biomarker classifier to predict treatment response with better precision than the current predictive factors. Methods: Random forest machine learning (ML) was applied to identify the candidate algorithms using the MSK Cohort (n = 471) as a training set and validated in the TCGA Cohort (n = 221). Logistic regression, progression-free survival (PFS), and univariate/multivariate Cox proportional hazard analyses were performed and the performance of the candidate algorithms was compared with the established risk parameters. Results: A novel 7-Gene Algorithm based on mutation profiles of seven KRAS-associated genes was identified. The algorithm was able to distinguish non-progressed (responder) vs. progressed (non-responder) patients with AUC of 0.97 and had predictive power for PFS with a hazard ratio (HR) of 16.9 (p < 0.001) in the MSK cohort. The predictive power of this algorithm for PFS was more pronounced in mCRC (HR = 16.9, p < 0.001, n = 388). Similarly, in the TCGA validation cohort, the algorithm had AUC of 0.98 and a significant predictive power for PFS (p < 0.001). Conclusion: The novel 7-Gene Algorithm can be further developed as a biomarker model for prediction of treatment response in mCRC patients to improve personalized therapies.
Collapse
Affiliation(s)
| | - Zahra El-Schich
- Department of Biomedical Sciences, Malmö University, SE-206 06 Malmö, Sweden; (Z.E.-S.); (A.G.W.)
| | - Amjad Ali
- Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden;
| | - Xuhui Zhang
- Department of Bio-Diagnosis, Institute of Basic Medical Sciences, Beijing 100005, China;
| | - Athanasios Simoulis
- Department of Clinical Pathology and Cytology, Skåne University Hospital, SE-205 02 Malmö, Sweden;
| | - Anette Gjörloff Wingren
- Department of Biomedical Sciences, Malmö University, SE-206 06 Malmö, Sweden; (Z.E.-S.); (A.G.W.)
| | - Jenny L. Persson
- Department of Biomedical Sciences, Malmö University, SE-206 06 Malmö, Sweden; (Z.E.-S.); (A.G.W.)
- Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden;
| |
Collapse
|
|
14
|
Zhai Y, Bai W, Zhou J, Dong Q, Zhang J. Effect of tumour size ratio on liver recurrence-free survival of patients undergoing hepatic resection for colorectal liver metastases. BMC Cancer 2022; 22:103. [PMID: 35078439 PMCID: PMC8788127 DOI: 10.1186/s12885-022-09199-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 01/14/2022] [Indexed: 11/10/2022] Open
Abstract
Background The study aimed to assess the impact of size differences of multiple liver metastases on liver recurrence-free survival (RFS) in patients undergoing hepatic resection for colorectal liver metastases (CRLMs). Methods Overall, 147 patients with CRLMs who underwent hepatic resection between January 2010 and December 2016 were retrospectively analysed. Tumour size ratio (TSR) was defined as the maximum diameter of the largest liver lesion over the maximum diameter of the smallest liver lesion. The univariate and multivariate analyses were performed to determine independent prognostic risk factors. The prognostic value of the TSR was further explored in each Tumour Burden Score (TBS) zone. Log-rank survival analyses were used to compare liver RFS in the new clinical score and the Fong clinical score. Results Based on the TSR, patients were classified into three groups: TSR < 2, 2 ≤ TSR < 4, and TSR ≥ 4. According to the multivariate analysis, TSR of 2–4 (hazard ratio [HR], 2.580; 95% confidence interval [CI] 1.543–4.312; P < 0.001) and TSR < 2 (HR, 4.435; 95% CI 2.499–7.872; P < 0.001) were associated with worse liver RFS. As TSR decreased, liver RFS worsened. TSR could further stratify patients in zones 1 and 2 into different risk groups according to the TBS criteria (zone 1: median liver RFS, 3.2 and 8.9 months for groups 1 and 2, respectively, P = 0.003; zone 2: median liver RFS, 3.5, 5.0, and 10.9 months for groups 1, 2, and 3, respectively, P < 0.05). The predictive ability of the new clinical score, which includes TSR, was superior to that of the Fong clinical score. Conclusions TSR, as a prognostic tool, could accurately assess the effect of size differences across multiple liver metastases on liver RFS in patients undergoing hepatectomy for CRLMs. Trial registration Retrospectively registered
Collapse
|
|
15
|
Spolverato G, Azzolina D, Paro A, Lorenzoni G, Gregori D, Poultsides G, Fields RC, Weber SM, Votanopoulos K, Maithel SK, Pucciarelli S, Pawlik TM. Dynamic Prediction of Survival after Curative Resection of Gastric Adenocarcinoma: A landmarking-based analysis. Eur J Surg Oncol 2021; 48:1025-1032. [PMID: 34895773 DOI: 10.1016/j.ejso.2021.11.127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 11/17/2021] [Accepted: 11/22/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Accurate estimation of survival and recurrence are important to inform decisions regarding therapy and surveillance. We sought to design and validate a dynamic prognostic model for patients undergoing resection for gastric adenocarcinoma. METHODS Patients who underwent curative-intent surgery for gastric adenocarcinoma between 2000 and 2020 were identified using a multi-institutional database. Landmark analysis was used to create dynamic OS and DFS prediction models. Model performance was internally cross-validated via bootstrap resampling. RESULTS Among 895 patients, 507 (57.2%) patients underwent partial gastrectomy (n = 507, 57.2%) while 380 (42.8%) had total gastrectomy. Median tumor size was 40 mm (IQR: 25-65), most tumors were located in the antrum (n = 344, 39.5%) and infiltrated the subserosa (T3 tumors: n = 283, 31.9%) or serosa (T4 tumors: n = 253, 28.5%); lymph node metastasis occurred in 528 (59.1%) patients. Median OS and DFS were 17.5 (IQR: 7.5-42.8) and 14.3 months (IQR: 6.5-39.9), respectively. The impact of age, sex, preoperative comorbidities, tumor size and location, extent of lymphadenectomy and total number of lymph nodes examined, Lauren class, T and N category, postoperative complications, and tumor recurrence varied over time (all p < 0.05). An online tool to predict dynamic OS and DFS based on patient survival relative to time survived was developed and made available for clinical use. Discrimination ability of OS and DFS was excellent (C-index: 0.84 and 0.86, respectively) and calibration plots revealed good prediction. CONCLUSIONS An online dynamic prognostic tool was developed and validated to predict OS and DFS following resection of gastric adenocarcinoma. Landmark analysis to predict long-term outcomes based on follow-up time may be helpful to surgeons and patients.
Collapse
Affiliation(s)
- Gaya Spolverato
- Department of Surgical Oncological and Gastrointestinal Sciences, University of Padova, Padova, Italy
| | - Danila Azzolina
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Alessandro Paro
- Department of Surgery, The Ohio State Wexner Medical Center, Columbus, OH, USA
| | - Giulia Lorenzoni
- Department of Surgical Oncological and Gastrointestinal Sciences, University of Padova, Padova, Italy
| | - Dario Gregori
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | | | - Ryan C Fields
- Department of Surgery, Washington University, St. Louis, MO, USA
| | - Sharon M Weber
- Department of Surgery, University of Wisconsin, Madison, WI, USA
| | | | | | - Salvatore Pucciarelli
- Department of Surgical Oncological and Gastrointestinal Sciences, University of Padova, Padova, Italy
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State Wexner Medical Center, Columbus, OH, USA.
| |
Collapse
|
|
16
|
Ke B, Cai X, Peng X. Survival prediction and conditional survival of primary central nervous system lymphoma: A population-based study. J Clin Neurosci 2021; 93:188-194. [PMID: 34656246 DOI: 10.1016/j.jocn.2021.09.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 08/18/2021] [Accepted: 09/14/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Primary central nervous system lymphoma is a rare and highly aggressive type of non-Hodgkin lymphoma. This study used population-based data to evaluate the clinical characteristics and prognostic factors of primary central nervous system lymphoma and develop a prediction model to estimate survival. METHODS Patients' data were extracted from the Surveillance, Epidemiology, and End Results database. Significant prognostic factors were identified using univariate and multivariate Cox regression analyses. Conditional survival estimates were calculated as CS(x y) = S(x + y)/S(X), and a nomogram was built to predict patient prognosis. RESULTS In total, 2563 patients with primary central nervous system lymphoma were included. Multivariate Cox analysis showed that age at diagnosis, sex, histology, tumor site, surgery, chemotherapy, and marital status were independent prognostic factors of overall survival. The 1-year conditional survival increased with time, and our nomogram model showed favorable discriminative ability. CONCLUSION At the population level, our study found that gross total resection and chemotherapy improved the prognosis of patients with primary central nervous system lymphoma. However, the prognosis of black patients was poor. Conditional survival provided a more accurate and dynamic survival estimate. Moreover, our nomogram had a good performance and could help predict the overall survival of these patients.
Collapse
Affiliation(s)
- Boxi Ke
- Taizhou Central Hospital (Taizhou University Hospital), Department of Neurology, China
| | - Xueli Cai
- Lishui Municipal Central Hospital, Department of Neurology, China
| | - Xiao Peng
- Lishui Municipal Central Hospital, Department of Neurology, China.
| |
Collapse
|
|
17
|
Bai L, Lin ZY, Lu YX, Chen Q, Zhou H, Meng Q, Lin CP, Huang WL, Wan YL, Pan ZZ, Wang DS. The prognostic value of preoperative serum lactate dehydrogenase levels in patients underwent curative-intent hepatectomy for colorectal liver metastases: A two-center cohort study. Cancer Med 2021; 10:8005-8019. [PMID: 34636145 PMCID: PMC8607270 DOI: 10.1002/cam4.4315] [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: 04/22/2021] [Revised: 08/18/2021] [Accepted: 09/08/2021] [Indexed: 12/13/2022] Open
Abstract
Background The prognostic value of lactate dehydrogenase (LDH) in colorectal cancer patients has remained inconsistent between nonmetastatic and metastatic settings. So far, very few studies have included LDH in the prognostic analysis of curative‐intent surgery for colorectal liver metastases (CRLM). Patients and Methods Five hundred and eighty consecutive metastatic colorectal cancer patients who underwent curative‐intent CRLM resection from Sun Yat‐sen University Cancer Center (434 patients) and Sun Yat‐sen University Sixth Affiliated Hospital (146 patients) in 2000–2019 were retrospectively collected. Overall survival (OS) was the primary end point. Cox regression model was performed to identify the prognostic values of preoperative serum LDH levels and other clinicopathology variables. A modification of the established Fong CRS scoring system comprising LDH was developed within this Chinese population. Results At the median follow‐up time of 60.5 months, median OS was 59.5 months in the pooled cohort. In the multivariate analysis, preoperative LDH >upper limit of normal (250 U/L) was the strongest independent prognostic factor for OS (HR 1.73, 95% confidence interval [CI], 1.22–2.44; p < 0.001). Patients with elevated LDH levels showed impaired OS than patients with normal LDH levels (27.6 months vs. 68.8 months). Five‐year survival rates were 53.7% and 22.5% in the LDH‐normal group and LDH‐high group, respectively. Similar results were also confirmed in each cohort. In the subgroup analysis, LDH could distinguish the survival regardless of most established prognostic factors (number and size of CRLM, surgical margin, extrahepatic metastases, CEA, and CA19‐9 levels, etc.). Integrating LDH into the Fong score contributed to an improvement in the predictive value. Conclusion Our study implicates serum LDH as a reliable and independent laboratory biomarker to predict the clinical outcome of curative‐intent surgery for CRLM. Composite of LDH and Fong score is a potential stratification tool for CRLM resection. Prospective, international studies are needed to validate these results across diverse populations.
Collapse
Affiliation(s)
- Long Bai
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.,Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China.,Department of VIP region, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Ze-Yu Lin
- Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yun-Xin Lu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.,Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China.,Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Qin Chen
- Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Han Zhou
- Department of Medical Administration, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qi Meng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.,Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China.,Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Chun-Ping Lin
- Department of Oncology, Jieyang Affiliated Hospital, Sun Yat-sen University, Jieyang, China
| | - Wan-Lan Huang
- Department of Oncology, Jieyang Affiliated Hospital, Sun Yat-sen University, Jieyang, China
| | - Yun-Le Wan
- Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhi-Zhong Pan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.,Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China.,Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - De-Shen Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.,Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China.,Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| |
Collapse
|
|
18
|
Roles of the Immune/Methylation/Autophagy Landscape on Single-Cell Genotypes and Stroke Risk in Breast Cancer Microenvironment. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:5633514. [PMID: 34457116 PMCID: PMC8397558 DOI: 10.1155/2021/5633514] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 06/29/2021] [Accepted: 07/14/2021] [Indexed: 12/16/2022]
Abstract
This study sought to perform integrative analysis of the immune/methylation/autophagy landscape on breast cancer prognosis and single-cell genotypes. Breast Cancer Recurrence Risk Score (BCRRS) and Breast Cancer Prognostic Risk Score (BCPRS) were determined based on 6 prognostic IMAAGs obtained from the TCGA-BRCA cohort. BCRRS and BCPRS, respectively, were used to construct a risk prediction model of overall survival and progression-free survival. Predictive capacity of the model was evaluated using clinical data. Analysis showed that BCRRS is associated with a high risk of stroke. In addition, PPI and drug-ceRNA networks based on differences in BCPRS were constructed. Single cells were genotyped through integrated scRNA-seq of the TNBC samples based on clustering results of BCPRS-related genes. The findings of this study show the potential regulatory effects of IMAAGs on breast cancer tumor microenvironment. High AUCs of 0.856 and 0.842 were obtained for the OS and PFS prognostic models, respectively. scRNA-seq analysis showed high expression levels of adipocytes and adipose tissue macrophages (ATMs) in high BCPRS clusters. Moreover, analysis of ligand-receptor interactions and potential regulatory mechanisms were performed. The LINC00276&MALAT1/miR-206/FZD4-Wnt7b pathway was also identified which may be useful in future research on targets against breast cancer metastasis and recurrence. Neural network-based deep learning models using BCPRS-related genes showed that these genes can be used to map the tumor microenvironment. In summary, analysis of IMAAGs, BCPRS, and BCRRS provides information on the breast cancer microenvironment at both the macro- and microlevels and provides a basis for development of personalized treatment therapy.
Collapse
|
|
19
|
Nomogram of conditional survival probability of long-term Survival for Metastatic Colorectal Cancer: A Real-World Data Retrospective Cohort Study from SEER database. Int J Surg 2021; 92:106013. [PMID: 34233209 DOI: 10.1016/j.ijsu.2021.106013] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 06/08/2021] [Accepted: 07/02/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Many patients with metastatic colorectal cancer (mCRC) have better prognosis than the prediction at diagnosis. Compared with invariable traditional Kaplan Meier assessment, conditional survival (CS) assessment has become a more accurate and informative assessment method to predict survival time. MATERIALS AND METHODS Patients with mCRC between 2010 and 2015 were extracted from Surveillance, Epidemiology and End Results linked database. CS analysis was applied to depict exact survival for patients who have survived for specific year and standardized difference (d) was used to evaluate the differences between subgroups in CS analysis. Based on variables selected by Lasso analysis, nomograms for each year after diagnosis were fitted to estimate 3-year survival of stage IV CRC, respectively. RESULTS Of 9732 patients, overall actuarial survival (OS) decreased from 24% at 4-year to 16% at 6-year, while corresponding 3-year CS (CS3) increased from 33% at 1-year to 48% at 3-year. Overall, CS3 was higher than corresponding actuarial survival. All clinicopathological characteristics were associated with actuarial survival (p < 0.05). However, in CS3 analysis, survival difference caused by gender, race and tumor size gradually disappeared over time (|d|>0.1→ |d|<0.1). Furthermore, survival difference caused by histological type, brain metastasis and chemotherapy reversed over time (d > 0→d<0 or d<0→d>0). Based on lasso analysis, nomograms for 1st, 2nd and 3rd year after diagnosis were conducted respectively. The AUC of nomogram for 1st year was 0.705, for 2nd year was 0.675, and for 3rd year was 0.648. CONCLUSION Patients with mCRC demonstrated a substantial increase in CS over time. Risk factors collected at diagnosis may change gradually. Nomograms constructed by survival time can predict more accurate survival for patients with mCRC. Conditional survival assessments provide important quantitative information about the probability of survival and are therefore of great value to patients and health care professionals.
Collapse
|
|
20
|
Kang X, Chen Y, Yi B, Yan X, Jiang C, Chen B, Lu L, Sun Y, Shi R. An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes. J Cancer 2021; 12:4148-4171. [PMID: 34093817 PMCID: PMC8176413 DOI: 10.7150/jca.58076] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 04/27/2021] [Indexed: 12/14/2022] Open
Abstract
The effects of methylation/autophagy-related genes (MARGs) and immune infiltration in the tumor microenvironment on the prognosis of laryngeal cancer were comprehensively explored in this study. Survival analysis screened out 126 MARGs and 10 immune cells potentially associated with the prognosis of laryngeal carcinoma. Cox and lasso regression analyses were then used to select 8 MARGs (CAPN10, DAPK2, MBTPS2, ST13, CFLAR, FADD, PEX14 and TSC2) and 2 immune cells (Eosinophil and Mast cell) to obtain the prognostic risk scoring system (pRS). The pRS was used to establish a risk prediction model for the prognosis of laryngeal cancer. The predictive ability of the prediction model was evaluated by GEO datasets and our clinical samples. Further analysis revealed that pRS is highly associated with single nucleotide polymorphism (SNP), copy number variation (CNV), immune checkpoint blockade (ICB) therapy and tumor microenvironment. Moreover, the screened pRS-related ceRNA network and circ_0002951/miR-548k/HAS2 pathway provide potential therapeutic targets and biomarkers of laryngocarcinoma. Based on the clustering results of pRS-related genes, single cells were then genotyped and revealed by integrated scRNA-seq in laryngeal cancer samples. Fibroblasts were found enriched in high risk cell clusters at the scRNA-seq level. Fibroblast-related ligand-receptor interactions were then exposed and a neural network-based deep learning model based on these pRS-related hub gene signatures was also established with a high accuracy in cell type prediction. In conclusion, the combination of single-cell and transcriptome laryngeal carcinoma landscape analyses can investigate the link between the tumor microenvironmental and prognostic characteristics.
Collapse
Affiliation(s)
- Xueran Kang
- Department of Otolaryngology-Head and Neck Surgery, Shanghai ninth people's Hospital, Shanghai Jiao Tong University School of Medicine; Ear Institute, Shanghai JiaoTong University School of Medicine; Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, China
| | - Yisheng Chen
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bin Yi
- Department of Otolaryngology-Head and Neck Surgery, Shanghai ninth people's Hospital, Shanghai Jiao Tong University School of Medicine; Ear Institute, Shanghai JiaoTong University School of Medicine; Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, China
| | - Xiaojun Yan
- Department of Otolaryngology-Head and Neck Surgery, Shanghai ninth people's Hospital, Shanghai Jiao Tong University School of Medicine; Ear Institute, Shanghai JiaoTong University School of Medicine; Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, China
| | - Chenyan Jiang
- Department of Otolaryngology-Head and Neck Surgery, Shanghai ninth people's Hospital, Shanghai Jiao Tong University School of Medicine; Ear Institute, Shanghai JiaoTong University School of Medicine; Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, China
| | - Bin Chen
- Department of Otolaryngology-Head and Neck Surgery, Shanghai ninth people's Hospital, Shanghai Jiao Tong University School of Medicine; Ear Institute, Shanghai JiaoTong University School of Medicine; Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, China
| | - Lixing Lu
- Department of Otolaryngology-Head and Neck Surgery, Shanghai ninth people's Hospital, Shanghai Jiao Tong University School of Medicine; Ear Institute, Shanghai JiaoTong University School of Medicine; Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, China
| | - Yuxing Sun
- Department of Otolaryngology-Head and Neck Surgery, Shanghai ninth people's Hospital, Shanghai Jiao Tong University School of Medicine; Ear Institute, Shanghai JiaoTong University School of Medicine; Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, China
| | - Runjie Shi
- Department of Otolaryngology-Head and Neck Surgery, Shanghai ninth people's Hospital, Shanghai Jiao Tong University School of Medicine; Ear Institute, Shanghai JiaoTong University School of Medicine; Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, China
| |
Collapse
|
|
21
|
Early Recurrence After Initial Hepatectomy for Colorectal Liver Metastases. Int Surg 2021. [DOI: 10.9738/intsurg-d-17-00018.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective
This study investigated the frequency of early recurrence in patients who had undergone hepatectomy for colorectal cancer liver metastasis (CRLM) and assessed the indications for adjuvant chemotherapy in these patients.
Methods
This retrospective analysis included 133 consecutive patients who underwent initial hepatectomy for CRLM between April 2000 and May 2010 and have been followed more than 5 years.
Results
Of the 133 patients, 83 (62%) experienced tumor recurrence, with 14 of the 83 recurrences within 6 months after initial hepatectomy. Overall survival was significantly poorer in patients with recurrences within 6 months than those without any recurrence (P = 0.015). The frequency of adjuvant chemotherapy was significantly lower in patients with recurrences within 6 months than those without recurrences within 6 months. Multivariate analysis showed that H-2 classification was the only independent risk factor for recurrence within 6 months after hepatectomy (P = 0.002). Adjuvant chemotherapy improved prognosis in patients classified as H2.
Conclusions
Patients who experienced tumor recurrence within 6 months after initial hepatectomy for CRLM had a poorer prognosis than patients who experienced recurrence after 6 months. Patients with H2-classification of CRLM should receive preoperative adjuvant chemotherapy.
Collapse
|
|
22
|
de Jong MC, Khan S, Christakis I, Weaver A, Mihai R. Comparative performances of nomograms and conditional survival after resection of adrenocortical cancer. BJS Open 2021; 5:6102899. [PMID: 33609384 PMCID: PMC7893456 DOI: 10.1093/bjsopen/zraa036] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Accepted: 10/08/2020] [Indexed: 11/17/2022] Open
Abstract
Background Adrenocortical carcinomas (ACCs) carry a poor prognosis. This study assessed the comparative performance of existing nomograms in estimating the likelihood of survival, along with the value of conditional survival estimation for patients who had already survived for a given length of time after surgery. Methods This was an observational study based on a prospectively developed departmental database that recorded details of patients operated for ACC in a UK tertiary referral centre. Results Of 74 patients with ACC managed between 2001 and 2020, data were analysed for 62 patients (32 women and 30 men, mean(s.d.) age 51(17) years) who had primary surgical treatment in this unit. Laparoscopic (9) or open adrenalectomies (53) were performed alone or in association with a multivisceral resection (27). Most of the tumours were left-sided (40) and 18 were cortisol-secreting. Overall median survival was 33 months, with 1-, 3- and 5-year survival rates of 79, 49, and 41 per cent respectively. Age over 55 years, higher European Network for Study of Adrenal Tumours stage, and cortisol secretion were associated with poorer survival in univariable analyses. Four published nomograms suggested widely variable outcomes that did not correlate with observed overall survival at 1, 3 or 5 years after operation. The 3-year conditional survival at 2 years (probability of surviving to postoperative year 5) was 65 per cent, compared with a 5-year actuarial survival rate of 41 per cent calculated from the time of surgery. Conclusion Survival of patients with ACC correlates with clinical parameters but not with published nomograms. Conditional survival might provide a more accurate estimate of survival for patients who have already survived for a certain amount of time after resection.
Collapse
Affiliation(s)
- M C de Jong
- Churchill Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - S Khan
- Churchill Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - I Christakis
- Churchill Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - A Weaver
- Churchill Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - R Mihai
- Churchill Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| |
Collapse
|
|
23
|
Chen L, Syn NL, Goh BKP, Cheow PC, Raj P, Koh Y, Chung A, Lee SY, Ooi LL, Chan CY, Teo JY. Impact of multidisciplinary tumour boards (MTB) on the clinicopathological characteristics and outcomes of resected colorectal liver metastases across time. World J Surg Oncol 2020; 18:237. [PMID: 32883292 PMCID: PMC7650267 DOI: 10.1186/s12957-020-01984-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 07/31/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Resection of colorectal liver metastases (CLM) has been established as the standard of care. This study aims to compare the change in clinicopathological characteristics of patients who underwent curative resection of CLM across two time periods-2000 to 2010 (P1) and 2011 to 2016 (P2) and evaluate the prognostic impact of these characteristics on survival outcomes. METHODS Patients who undergo liver resection for CLM at Singapore General Hospital from January 2000 to December 2016 were identified from a prospectively maintained database. The primary end point was overall survival. RESULTS There were 183/318 (57.5%) patients and 135/318 (42.5%) patients in P1 and P2, respectively. There was a lower proportion of patients who had nodal metastases from primary colorectal cancer and clinical risk score (CRS) less than 3 in P2 when compared to P1. There was no difference in survival between both time periods. Independent predictors of survival for the cohort were CEA levels ≥ 200 ng/ml, primary tumour grade and lymph nodal status. Independent predictors of poor survival in P1 were poorly differentiated colorectal cancer and nodal metastases while in P2, independent predictors of poor survival were multiple liver metastases and nodal metastases. CONCLUSION Nodal metastases from primary colorectal cancer are an independent predictor of poor survival across time for resectable CLM. Although there is no difference in survival between the two time periods, patients with multiple liver metastases should be carefully considered prior to surgery as it is also an independent predictor of overall survival.
Collapse
Affiliation(s)
- Lionel Chen
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore.
| | - Nicholas L Syn
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Peng Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Prema Raj
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Yexin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Alexander Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Ser Yee Lee
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - London Lucien Ooi
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Chung Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| | - Jin Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Outram Rd, Singapore, 169856, Singapore
- Duke-NUS Graduate Medical School, Singapore, Singapore
| |
Collapse
|
|
24
|
Conditional Probability of Survival and Prognostic Factors in Long-Term Survivors of High-Grade Serous Ovarian Cancer. Cancers (Basel) 2020; 12:cancers12082184. [PMID: 32764409 PMCID: PMC7465919 DOI: 10.3390/cancers12082184] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/17/2020] [Accepted: 07/28/2020] [Indexed: 12/24/2022] Open
Abstract
Objective: High-grade serous ovarian cancers (HGSOC) are heterogeneous, often diagnosed at an advanced stage, and associated with poor overall survival (OS, 39% at five years). There are few data about the prognostic factors of late relapses in HGSOC patients who survived ≥five years, long-term survivors (LTS). The aim of our study is to assess the probability of survival according to the already survived time from diagnosis. Methods: Data from HGSOC patients treated between 1995 and 2016 were retrospectively collected to estimate the conditional probability of survival (CPS), probability of surviving Y years after diagnosis when the patient had already survived X years, and to determine the LTS prognostic factors. The primary endpoint was OS. Results: 404 patients were included; 120 of them were LTS. Patients were aged 61 years (range: 20–89), WHO performance status 0–1 in 86.9% and 2 in 13.1%, and Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) staging III and IV in 82.7% and 17.3% patients. Breast cancer (BRCA) status was available in 116 patients (33% mutated), including 58 LTS (36% mutated). No macroscopic residual disease was observed in 58.4% patients. First-line platinum-based chemotherapy plus paclitaxel was administered in 80.4% of patients (median: six cycles (range: 1–14)). After a 9 point 3-year follow-up, median OS was four years (95% CI: 3.6–4.5). The CPS at five years after surviving one year was 42.8% (95% CI: 35.3–48.3); it increased to 81.7% (95% CI: 75.5–87.8) after four survived years. Progression-free interval>18 months was the only LTS prognostic factor in the multivariable analysis (hazard ratio (HR) = 0.23; 95% CI: 0.13–0.40; p < 0.001). Conclusion: The CPS provided relevant and encouraging clinical information on the life expectancy of HGSOC patients who already survived a period of time after diagnosis. LTS prognostic factors are useful for clinicians and patients.
Collapse
|
|
25
|
Filip S, Vymetalkova V, Petera J, Vodickova L, Kubecek O, John S, Cecka F, Krupova M, Manethova M, Cervena K, Vodicka P. Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review. Int J Mol Sci 2020; 21:E5255. [PMID: 32722130 PMCID: PMC7432613 DOI: 10.3390/ijms21155255] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) remains a serious health problem worldwide. Approximately half of patients will develop distant metastasis after CRC resection, usually with very poor prognosis afterwards. Because patient performance after distant metastasis surgery remains very heterogeneous, ranging from death within 2 years to a long-term cure, there is a clinical need for a precise risk stratification of patients to aid pre- and post-operative decisions. Furthermore, around 20% of identified CRC cases are at IV stage disease, known as a metastatic CRC (mCRC). In this review, we overview possible molecular and clinicopathological biomarkers that may provide prognostic and predictive information for patients with distant metastasis. These may comprise sidedness of the tumor, molecular profile and epigenetic characteristics of the primary tumor and arising metastatic CRC, and early markers reflecting cancer cell resistance in mCRC and biomarkers identified from transcriptome. This review discusses current stage in employment of these biomarkers in clinical practice as well as summarizes current experience in identifying predictive biomarkers in mCRC treatment.
Collapse
Affiliation(s)
- Stanislav Filip
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Veronika Vymetalkova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 32300 Pilsen, Czech Republic
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
| | - Jiri Petera
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Ludmila Vodickova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 32300 Pilsen, Czech Republic
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
| | - Ondrej Kubecek
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Stanislav John
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Filip Cecka
- Department of Surgery, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic;
| | - Marketa Krupova
- The Fingerland Department of Pathology, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic; (M.K.); (M.M.)
| | - Monika Manethova
- The Fingerland Department of Pathology, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic; (M.K.); (M.M.)
| | - Klara Cervena
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
| | - Pavel Vodicka
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 32300 Pilsen, Czech Republic
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
| |
Collapse
|
|
26
|
Mehta R, Sahara K, Merath K, Hyer JM, Tsilimigras DI, Paredes AZ, Ejaz A, Cloyd JM, Dillhoff M, Tsung A, Pawlik TM. Insurance Coverage Type Impacts Hospitalization Patterns Among Patients with Hepatopancreatic Malignancies. J Gastrointest Surg 2020; 24:1320-1329. [PMID: 31197689 PMCID: PMC7011949 DOI: 10.1007/s11605-019-04288-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 05/26/2019] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Disparities in health and healthcare access remain a major problem in the USA. The current study sought to investigate the relationship between patient insurance status and hospital selection for surgical care. METHODS Patients who underwent liver or pancreatic resection for cancer between 2004 and 2014 were identified in the National Inpatient Sample. The association of insurance status and hospital type was examined. RESULTS In total, 22,254 patients were included in the study. Compared with patients with private insurance, Medicaid patients were less likely to undergo surgery at urban non-teaching hospitals (OR = 0.36, 95%CI 0.22-0.59) and urban teaching hospitals (OR = 0.54, 95%CI 0.34-0.84) than rural hospitals. Medicaid patients were less likely to undergo surgery at private investor-owned hospitals (OR = 0.53, 95%CI 0.38-0.73) than private non-profit hospitals. In contrast, uninsured patients were 2.2-fold more likely to go to government-funded hospitals rather than private non-profit hospitals (OR = 2.19, 95%CI 1.76-2.71). CONCLUSION Insurance status was strongly associated with the type of hospital in which patients underwent surgery for liver and pancreatic cancers. Addressing the reasons for inequitable access to different hospital settings relative to insurance status is essential to ensure that all patients undergoing pancreatic or liver surgery receive high-quality surgical care.
Collapse
Affiliation(s)
- Rittal Mehta
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Kota Sahara
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Katiuscha Merath
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH
| | - J. Madison Hyer
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Diamantis I. Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Anghela Z. Paredes
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Aslam Ejaz
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Mary Dillhoff
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Allan Tsung
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Timothy M. Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH
| |
Collapse
|
|
27
|
Schulz A, Joelsen-Hatlehol ES, Brudvik KW, Aasand KK, Hanekamp B, Viktil E, Johansen CK, Dormagen JB. Preoperative detection of colorectal liver metastases: DWI alone or combined with MDCT is no substitute for Gd-EOB-DTPA-enhanced MRI. Acta Radiol 2020; 61:302-311. [PMID: 31335157 DOI: 10.1177/0284185119864000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Magnetic resonance imaging (MRI) with hepatocyte specific contrast has the highest sensitivity for colorectal liver metastases but comes at high costs and long examination times. Purpose To evaluate if preoperative detection of colorectal liver metastases with less resource-consuming diffusion-weighted imaging (DWI) alone or in combination with multidetector computed tomography (MDCT) can compete with gadolinium-etoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. Material and Methods Forty-four patients with 123 colorectal liver metastases received MDCT and Gd-EOB-DTPA-enhanced MRI including DWI before liver resection for colorectal liver metastases. Five image sets were evaluated by two radiologists. The DWI set consisted of DWI, ADC map, coronal, axial T2-weighted single-shot sequences. The DWI-T2F set contained additionally respiratory-triggered T2-weighted TSE-SPIR sequences. The MDCT set consisted of four-phase MDCT, the MDCT-DWI set also contained DWI. The CE-MRI set contained all MRI sequences including Gd-EOB-DTPA. Reference standards was histopathology and follow-up. Results CE-MRI set had highest sensitivity ( P ≤ 0.013) with 95% compared to 72%, 73%, 73%, and 87% the for DWI set, DWI-T2W-FS set, MDCT set, and MDCT-DWI set, respectively. The CE-MRI set had the highest sensitivity ( P≤0.012) for colorectal liver metastases <10 mm with 87% compared to 55%, 52%, 23%, and 58% for the DWI set, DWI-T2W-FS set, MDCT set, and MDCT-DWI set, respectively. The MDCT-DWI set improved sensitivity overall and in size-dependent subgroup analyses compared to the MDCT set ( P ≤ 0.031). The MDCT-DWI set showed the highest specificity of 98% followed by 98%, 98%, 95%, and 88% for the DWI set, DWI-T2W-FS set, MDCT set, and CE-MRI set, respectively. Conclusion The less resource and time-consuming DWI sets are inferior to Gd-EOB-DTPA-enhanced MRI for the detection of colorectal liver metastases. Gd-EOB-DTPA-enhanced MRI with its excellent sensitivity should be the preferred preoperative modality when meticulous lesion identification is essential. Combination of DWI with MDCT improved significantly sensitivity compared to each modality alone.
Collapse
Affiliation(s)
- Anselm Schulz
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Norway
| | | | | | | | - Bettina Hanekamp
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Norway
| | - Ellen Viktil
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Norway
| | - Cathrine K Johansen
- Department of Radiology and Nuclear Medicine, Oslo University Hospital, Norway
| | | |
Collapse
|
|
28
|
Latenstein AEJ, van Roessel S, van der Geest LGM, Bonsing BA, Dejong CHC, Groot Koerkamp B, de Hingh IHJT, Homs MYV, Klaase JM, Lemmens V, Molenaar IQ, Steyerberg EW, Stommel MWJ, Busch OR, van Eijck CHJ, van Laarhoven HWM, Wilmink JW, Besselink MG. Conditional Survival After Resection for Pancreatic Cancer: A Population-Based Study and Prediction Model. Ann Surg Oncol 2020; 27:2516-2524. [PMID: 32052299 PMCID: PMC7311496 DOI: 10.1245/s10434-020-08235-w] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Indexed: 12/12/2022]
Abstract
Background Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor characteristics. Such prediction models for patients with resected pancreatic cancer are lacking and therefore conditional survival was assessed and a nomogram predicting 5-year survival at a predefined period after resection of pancreatic cancer was developed. Methods This population-based study included patients with resected pancreatic ductal adenocarcinoma from the Netherlands Cancer Registry (2005–2016). Conditional survival was calculated as the median, and the probability of surviving up to 8 years in patients who already survived 0–5 years after resection was calculated using the Kaplan–Meier method. A prediction model was constructed. Results Overall, 3082 patients were included, with a median age of 67 years. Median overall survival was 18 months (95% confidence interval 17–18 months), with a 5-year survival of 15%. The 1-year conditional survival (i.e. probability of surviving the next year) increased from 55 to 74 to 86% at 1, 3, and 5 years after surgery, respectively, while the median overall survival increased from 15 to 40 to 64 months at 1, 3, and 5 years after surgery, respectively. The prediction model demonstrated that the probability of achieving 5-year survival at 1 year after surgery varied from 1 to 58% depending on patient and tumor characteristics. Conclusions This population-based study showed that 1-year conditional survival was 55% 1 year after resection and 74% 3 years after resection in patients with pancreatic cancer. The prediction model is available via www.pancreascalculator.com to inform patients and caregivers. Electronic supplementary material The online version of this article (10.1245/s10434-020-08235-w) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Anouk E J Latenstein
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Stijn van Roessel
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Lydia G M van der Geest
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Cornelis H C Dejong
- Department of Surgery, Maastricht University Medical Centre and NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | | | - Marjolein Y V Homs
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Joost M Klaase
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Valery Lemmens
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands.,Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, St Antonius Hospital Nieuwegein and University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | | | - Martijn W J Stommel
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Olivier R Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | | | - Hanneke W M van Laarhoven
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Johanna W Wilmink
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
| | | |
Collapse
|
|
29
|
Sahara K, Merath K, Tsilimigras DI, Hyer JM, Guglielmi A, Aldrighetti L, Weiss M, Fields RC, Poultsides GA, Maithel SK, Endo I, Pawlik TM, other members of the U.S. Neuroendo. Conditional disease‐free survival after curative‐intent liver resection for neuroendocrine liver metastasis. J Surg Oncol 2019; 120:1087-1095. [PMID: 31550406 DOI: 10.1002/jso.25713] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 09/13/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Kota Sahara
- Department of Surgery, Division of Surgical OncologyThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbus Ohio
- Department of Gastroenterological SurgeryYokohama City University School of MedicineYokohama Japan
| | - Katiuscha Merath
- Department of Surgery, Division of Surgical OncologyThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbus Ohio
| | - Diamantis I. Tsilimigras
- Department of Surgery, Division of Surgical OncologyThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbus Ohio
| | - J. Madison Hyer
- Department of Surgery, Division of Surgical OncologyThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbus Ohio
| | | | | | - Matthew Weiss
- Department of SurgeryJohns Hopkins HospitalBaltimore Maryland
| | - Ryan C. Fields
- Department of SurgeryWashington University School of MedicineSt Louis Missouri
| | | | | | - Itaru Endo
- Department of Gastroenterological SurgeryYokohama City University School of MedicineYokohama Japan
| | - Timothy M. Pawlik
- Department of Surgery, Division of Surgical OncologyThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbus Ohio
| | | |
Collapse
|
|
30
|
Melstrom L. Hepatectomy: more complex operations and improved perioperative outcomes. Hepatobiliary Surg Nutr 2019; 8:389-391. [PMID: 31489310 DOI: 10.21037/hbsn.2019.03.05] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Laleh Melstrom
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| |
Collapse
|
|
31
|
Liang Y, Fan X, Bai Y, Huang D, Yang C. Conditional survival analysis of four treatment strategies for patients with stage I non-small cell lung cancer. Oncol Lett 2019; 18:1089-1098. [PMID: 31423169 PMCID: PMC6607325 DOI: 10.3892/ol.2019.10413] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 04/15/2019] [Indexed: 12/24/2022] Open
Abstract
Conditional survival (CS) is used to describe dynamic survival possibility, taking account of the change in the survival risk that occurs with longevity. The present study aimed to explore the CS of four treatment strategies for stage I non-small cell lung cancer (NSCLC), staged according to the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control NSCLC staging system. Using the Surveillance, Epidemiology and End Results Program cohort obtained between 2004-2014, the current study first extracted data for 27,116 patients with stage I NSCLC. The actuarial cancer-specific survival rates (ACSs) and conditional cancer-specific survival rates of four treatment strategies were then compared. ACS was assessed using the Kaplan-Meier method and a log-rank test. The 3-year conditional cancer-specific survival (CCS3) of patients who had already survived for n years was calculated as CCS3=ACS(n+3)/ACS(n). Cox regression and propensity-score matching (PSM) was applied to adjust confounding factors. The 5-year ACS of patients who underwent lobectomy, sublobar resection, radiation and observation was 80.3, 72.0, 40.8 and 19.6%, respectively. The 5-year CCS3 of patients who underwent lobectomy, sublobar resection, radiation and observation was 91.7, 86.4, 77.0 and 58.2%, respectively. CCS3 increased with an increase in survival time and patients who underwent lobectomy had the highest CCS3 estimates and flattest growth, with the smallest survival gap between CCS3 and ACS. The results were similar in the PSM analysis. In conclusion, CS estimates may provide a more accurate survival prediction for patients with stage I NSCLC, and may assist with treatment decisions and surveillance strategies. In addition, the current study provided evidence that suggests lobectomy may be the optimal treatment strategy for stage I NSCLC compared with sublobar resection.
Collapse
Affiliation(s)
- Yicheng Liang
- Department of Thoracic Surgery, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Xiaoxi Fan
- Department of Thoracic Surgery, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Yunpeng Bai
- Department of Thoracic Surgery, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Dejian Huang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Chunlu Yang
- Department of Thoracic Surgery, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
| |
Collapse
|
|
32
|
Kawaguchi Y, Lillemoe HA, Panettieri E, Chun YS, Tzeng CWD, Aloia TA, Kopetz S, Vauthey JN. Conditional Recurrence-Free Survival after Resection of Colorectal Liver Metastases: Persistent Deleterious Association with RAS and TP53 Co-Mutation. J Am Coll Surg 2019; 229:286-294.e1. [PMID: 31054911 DOI: 10.1016/j.jamcollsurg.2019.04.027] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 03/19/2019] [Accepted: 04/22/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND Conditional recurrence-free survival (RFS) probability, that is, the probability of remaining recurrence-free after a given interval without recurrence, has not been reported after resection of colorectal liver metastases (CLMs). We aimed to estimate conditional RFS and identify factors affecting conditional RFS. STUDY DESIGN Patients undergoing initial resection of CLMs during 2000-2016 with mutation data were identified. The RFS and risk factors for recurrence were evaluated at the time of resection for all patients and at 1 year and 2 years after resection for patients who remained recurrence-free. RESULTS Of 2,118 patients, 485 met the inclusion criteria, of which 225 were recurrence-free at 1 year and 109 were recurrence-free at 2 years. The 5-year RFS rates were 17.3%, 36.8%, and 70.7% for all patients and the 1-year and 2-year recurrence-free groups, respectively, when assessed from the time of initial CLM resection. RAS/TP53 co-mutation was the only factor independently associated with increased risk of recurrence for all groups (all patients, hazard ratio 1.47; 95% CI 1.19 to 1.82; p < 0.001; 1-year recurrence-free, hazard ratio 1.69; 95% CI 1.17 to 2.43; p = 0.005; 2-year recurrence-free, hazard ratio 2.41; 95% CI 1.12 to 5.17; p = 0.024). T category, extrahepatic disease, multiple CLMs, largest CLM diameter, and surgical margin status were risk factors for recurrence in all patients and/or the 1-year recurrence-free group, but not the 2-year recurrence-free group. Median RFS was lower for patients with RAS/TP53 co-mutation than for those with RAS/TP53 wild-type in the 1-year (1.5 vs 2.8 years; p = 0.006) and 2-year recurrence-free groups (3.0 vs 5.9 years; p = 0.024). CONCLUSIONS Conditional RFS is useful for updating prognosis after a given time interval without recurrence after CLM resection. Importantly, RAS/TP53 co-mutation has a persistent deleterious association with recurrence.
Collapse
Affiliation(s)
- Yoshikuni Kawaguchi
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Heather A Lillemoe
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Elena Panettieri
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
| |
Collapse
|
|
33
|
Conditional Survival Analysis of Metastatic Colorectal Cancer Patients Living ≥24 Months: A Single Institutional Study. Am J Clin Oncol 2019; 42:512-518. [PMID: 30973370 DOI: 10.1097/coc.0000000000000535] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES The survival of patients with metastatic colorectal cancer (CRC) has been increasing over recent decades due to improvements in chemotherapy and surgery. There is a need to refine prognostic information to more accurately predict survival as patients survive for any given length of time to assist multidisciplinary cancer management teams in treatment decisions. MATERIALS AND METHODS We performed a single center retrospective analysis of patients treated with metastatic CRC (unresectable and resectable) who survived >24 months between 2005 and 2015 (N=155). Patient tumor and treatment related variables were collected. Overall survival (OS) estimates conditional on surviving >24 months were compared with actuarial survival estimates of a cohort of patients (33,104 resected, 39,382 unresected) from the National Cancer Database (NCDB). RESULTS With a median follow-up of 44.2 months, the median OS of resected patients (n=86) was not reached. The median OS of unresected patients was 75.9 months. The conditional survival probabilities of living 1, 2, or 3 years longer after 24 months of survival are 92%, 72%, and 52%, respectively, in unresectable patients and 98%, 92%, and 89% in patients who were resected. The corresponding NCDB 1, 2, and 3 year actuarial survival was 38%, 20%, and 11% for unresected patients and 68%, 46%, and 32% for resected. CONCLUSIONS These results indicate that CRC patients who survive 24 months with metastatic colorectal cancer have an excellent prognosis and surgery may be appropriate in a subset of patients initially deemed unresectable.
Collapse
|
|
34
|
Lin JX, Lin JP, Xie JW, Wang JB, Lu J, Chen QY, Cao LL, Lin M, Tu RH, Zheng CH, Huang CM, Li P. Is the AJCC TNM staging system still appropriate for gastric cancer patients survival after 5 years? Eur J Surg Oncol 2019; 45:1115-1120. [PMID: 30661920 DOI: 10.1016/j.ejso.2019.01.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 11/18/2018] [Accepted: 01/01/2019] [Indexed: 12/23/2022] Open
Abstract
PURPOSE The aim of this study was to evaluate the prognostic value of the eighth AJCC TNM staging classification for patients with gastric cancer who had already survived for 5 years. PATIENTS AND METHODS Patients who underwent radical gastrectomy at a large eastern center were considered. The prognostic value of staging systems were assessed and compared. Additional external validation was performed using a dataset from the Surveillance, Epidemiology, and End Result (SEER) database. RESULTS The 5-year overall survival (OS) rate for patients in the training set was 59.4%. With the prolongation of the survival time after surgery, the 5-year OS improved significantly (P < 0.05). However, there were no significant differences in survival curves among patients who have survived 5 years after surgery. The AUC and χ2 of the eighth AJCC classification for predicting of 5-year OS decreased gradually after surgery and appeared stable after 5 years. For patients who survived 5 years after surgery, we constructed a new TNM staging system (nTNM) according to the survival curves of T stage and N stage. A 2-step multivariate analysis showed that nTNM, age and sex were independent prognostic factors. The nTNM demonstrated superior prognostic stratification, with higher c-statistic and likelihood ratio chi-square scores and lower AIC values than those of the AJCC classification. Similar results were observed in the external validation set. CONCLUSION The nTNM predicted an additional survival more accurately than did the AJCC classification for patients who have survived 5 years after surgery; this may guide decisions regarding surveillance.
Collapse
Affiliation(s)
- Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Jun-Peng Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China.
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China.
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China.
| |
Collapse
|
|
35
|
Conditional Probability of Survival After Neoadjuvant Chemoradiation and Proctectomy for Rectal Cancer: What Matters and When. Dis Colon Rectum 2019; 62:33-39. [PMID: 30451761 DOI: 10.1097/dcr.0000000000001239] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Disease-free survival estimated from the time of surgery does not account for the changing likelihood of survival based on time already accrued. Conditional disease-free survival is defined as the probability of remaining disease free after reaching a specific time point without recurrence. OBJECTIVE The purpose of this study was to evaluate conditional disease-free survival for patients with rectal cancer who were treated by proctectomy after neoadjuvant chemoradiation. DESIGN Demographics, tumor characteristics, and tumor regression scores were assessed. Three-year conditional disease-free survival was estimated at x year after surgery based on the formula cDFS3 = DFS(x+3)/DFS(x), where DFS is disease-free survival and cDFS is conditional disease-free survival. Analyses were performed using Cox proportional hazards models. SETTING The study was conducted at a single tertiary referral center. PATIENTS A total of 545 patients with rectal cancer who were treated by neoadjuvant chemoradiation and curative intent surgery between 1992 and 2012 were included. MAIN OUTCOME MEASURES Disease-free survival and conditional disease-free survival were measured. RESULTS The median patient age was 57.5 years, and 28.4% were women. Median follow-up was 5.9 years. Disease-free survival at 1, 3, and 5 years was 89%, 71%, and 63%. The probability of remaining disease free for an additional 3 years for patients disease free at 1, 3, and 5 years was 75%, 83%, and 82%. Tumor regression, pathologic stage, margin status, differentiation, and procedure (low anterior versus abdominoperineal resection) were associated with disease-free survival on multivariable analysis (p < 0.05), but their relevance varied over time. R1 resection and differentiation were initially significant but not at 5 years. In contrast, tumor regression after neoadjuvant chemoradiation had a long-lasting impact on survival (at 5 y, conditional disease-free survival for an additional 3 y: 91%, 85%, 76%, and 71% for regression scores 0, 1, 2, and 3; p = 0.002). LIMITATIONS This was a retrospective study over 20 years, with evolution in adjuvant therapies during this time. CONCLUSIONS Conditional disease-free survival estimates improved over time, confirming that most patients will see a recurrence within the first few years. The impact of specific prognostic factors evolves variably over time. This information is useful to patients and providers and can help guide counseling and surveillance. See Video Abstract at http://links.lww.com/DCR/A771.
Collapse
|
|
36
|
Harmon C, Robinson MW, Hand F, Almuaili D, Mentor K, Houlihan DD, Hoti E, Lynch L, Geoghegan J, O'Farrelly C. Lactate-Mediated Acidification of Tumor Microenvironment Induces Apoptosis of Liver-Resident NK Cells in Colorectal Liver Metastasis. Cancer Immunol Res 2018; 7:335-346. [PMID: 30563827 DOI: 10.1158/2326-6066.cir-18-0481] [Citation(s) in RCA: 198] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 10/06/2018] [Accepted: 12/14/2018] [Indexed: 11/16/2022]
Abstract
Colorectal cancer is the third most common malignancy worldwide, with 1.3 million new cases annually. Metastasis to the liver is a leading cause of mortality in these patients. In human liver, metastatic cancer cells must evade populations of liver-resident natural killer (NK) cells with potent cytotoxic capabilities. Here, we investigated how these tumors evade liver NK-cell surveillance. Tissue biopsies were obtained from patients undergoing resection of colorectal liver metastasis (CRLM, n = 18), from the tumor, adjacent tissue, and distal resection margin. The number and phenotype of liver-resident NK cells, at each site, were analyzed by flow cytometry. Tumor-conditioned media (TCM) was generated for cytokine and metabolite quantification and used to treat healthy liver-resident NK cells, isolated from donor liver perfusate during transplantation. Liver-resident NK cells were significantly depleted from CRLM tumors. Healthy liver-resident NK cells exposed to TCM underwent apoptosis in vitro, associated with elevated lactate. Tumor-infiltrating liver-resident NK cells showed signs of mitochondrial stress, which was recapitulated in vitro by treating liver-resident NK cells with lactic acid. Lactic acid induced apoptosis by decreasing the intracellular pH of NK cells, resulting in mitochondrial dysfunction that could be prevented by blocking mitochondrial ROS accumulation. CRLM tumors produced lactate, thus decreasing the pH of the tumor microenvironment. Liver-resident NK cells migrating toward the tumor were unable to regulate intracellular pH resulting in mitochondrial stress and apoptosis. Targeting CRLM metabolism provides a promising therapeutic approach to restoring local NK-cell activity and preventing tumor growth.
Collapse
Affiliation(s)
- Cathal Harmon
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
| | - Mark W Robinson
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.,School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Fiona Hand
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.,Liver Unit, St. Vincent's University Hospital, Dublin, Ireland
| | - Dalal Almuaili
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
| | - Keno Mentor
- Liver Unit, St. Vincent's University Hospital, Dublin, Ireland
| | | | - Emir Hoti
- Liver Unit, St. Vincent's University Hospital, Dublin, Ireland
| | - Lydia Lynch
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.,Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | | | - Cliona O'Farrelly
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. .,School of Medicine, Trinity College Dublin, Dublin, Ireland
| |
Collapse
|
|
37
|
Tian FX, Cai YQ, Zhuang LP, Chen MF, Xiu ZB, Zhang Y, Liu H, Liu ZH, Liu GP, Zeng C, Lin FL, Liu J, Huang ST, Zhang LZ, Lin HY. Clinicopathological features and prognosis of patients with gastric neuroendocrine tumors: A population-based study. Cancer Med 2018; 7:5359-5369. [PMID: 30311450 PMCID: PMC6246951 DOI: 10.1002/cam4.1683] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 06/22/2018] [Indexed: 12/18/2022] Open
Abstract
Background Despite its rarity, studies have shown the incidence of gastric neuroendocrine tumors (G‐NETs) is increasing. This study investigated the risk factors affecting the survival of G‐NETs patients and their prognosis over time. Method A retrospective analysis of 506 G‐NETs patients who underwent surgery for nonmetastatic disease from the Surveillance, Epidemiology and End Result database from 1988 to 2011 was conducted. Multivariate Cox regression analyses identified the prognostic factors affecting overall survival (OS) and disease‐specific survival (DSS). Three‐year conditional survival (COS3 and CDS3) estimates at “x” year after treatment were calculated as follows: COS3 = OS(x + 3)/OS(x) and CDS3 = DSS(x + 3)/DSS(x). Results The 1‐, 3‐, and 5‐year OS rates of all patients after surgery were 90.2%, 77.3%, and 68.8%, respectively. The 1‐, 3‐, and 5‐year DSS rates after surgery were 93.9%, 84.5%, and 80.9%, respectively. In the multivariate analysis, age, tumor grade, and T stage were independent prognostic factors of OS and DSS (all P < 0.05). With 1‐, 3‐, and 5‐year survivorship, the COS3 improved by +5.2 (82.2%), +7.2 (84.4%), and +8.5 (85.5%), respectively, and the CDS3 improved by +4.4 (89.4%), +9.1 (94.1%), and +12.5 (97.5%), respectively. Notably, the CDS3 improved dramatically among patients with advanced stage disease (eg, N0 stage: 93.0%‐98.9%, Δ5.9% vs N1 stage: 52.0%‐95.7%, Δ43.7%). Conclusion For G‐NETs patients, age, tumor grade, T stage, and N stage were the clinicopathological factors significantly associated with prognosis. There were excellent outcomes for most G‐NETs patients, with a CDS3 of greater than 90% across all independent prognostic factors after 5 years of survival.
Collapse
Affiliation(s)
- Fang-Xi Tian
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Union Hospital, Fuzhou, China
| | - Yu-Qing Cai
- Zhejiang University School of Medicine, Hangzhou, China
| | | | - Ming-Fang Chen
- Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Zhong-Biao Xiu
- The Studio of Acupotomology, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Yi Zhang
- The Studio of Acupotomology, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Hong Liu
- The Studio of Acupotomology, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Zhi-Hong Liu
- Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Guo-Ping Liu
- Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Chen Zeng
- Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Fei-Ling Lin
- Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Jing Liu
- The Studio of Acupotomology, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Si-Ting Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.,Fujian Medical University Union Hospital, Fuzhou, China
| | - Liang-Zhi Zhang
- The Studio of Acupotomology, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Hua-Yang Lin
- The Studio of Acupotomology, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China.,Department of Anesthesiology, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| |
Collapse
|
|
38
|
Stewart CL, Warner S, Ito K, Raoof M, Wu GX, Kessler J, Kim JY, Fong Y. Cytoreduction for colorectal metastases: liver, lung, peritoneum, lymph nodes, bone, brain. When does it palliate, prolong survival, and potentially cure? Curr Probl Surg 2018; 55:330-379. [PMID: 30526930 DOI: 10.1067/j.cpsurg.2018.08.004] [Citation(s) in RCA: 147] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 08/28/2018] [Indexed: 12/19/2022]
Affiliation(s)
- Camille L Stewart
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Susanne Warner
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Kaori Ito
- Department of Surgery, Michigan State University, Lansing, MI
| | - Mustafa Raoof
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA
| | - Geena X Wu
- Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, CA
| | - Jonathan Kessler
- Department of Diagnostic Radiology, City of Hope National Medical Center, Duarte, CA
| | - Jae Y Kim
- Division of Thoracic Surgery, City of Hope National Medical Center, Duarte, CA
| | - Yuman Fong
- Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA.
| |
Collapse
|
|
39
|
Hand F, Harmon C, Elliott LA, Caiazza F, Lavelle A, Maguire D, Hoti E, Nolan N, Geoghegan JG, Ryan EJ, O'Farrelly C. Depleted polymorphonuclear leukocytes in human metastatic liver reflect an altered immune microenvironment associated with recurrent metastasis. Cancer Immunol Immunother 2018; 67:1041-1052. [PMID: 29572702 PMCID: PMC11028161 DOI: 10.1007/s00262-018-2149-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 03/09/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Hepatic immunity, normally protective against neoplasia, is subverted in colorectal liver metastasis (CRLM). Here, we compare the inflammatory microenvironment of CRLM-bearing liver tissue to donor liver. METHODS Twenty-five patients undergoing resection for CRLM were recruited, 13 of whom developed intrahepatic recurrence within 18 months. Biopsies were obtained from tumour and normal liver tissue adjacent to and distal from, the tumour. Donor liver biopsies were obtained during transplantation. Biopsies were cultured and conditioned media (CM) screened for 102 inflammatory mediators. Twelve of these were validated by Luminex assay. Transwell assays measured cancer cell chemotaxis. Polymorphonuclear leukocytes (PMN) and lymphocytes were quantified in H&E sections. RESULTS Fewer periportal tissue-resident PMN were present in metastatic liver compared to donor liver. Patients with the fewest PMN in liver tissue distal to their tumour had a shorter time to intrahepatic recurrence (P < 0.001). IL-6, CXCL1, CXCL5, G-CSF, GM-CSF, VEGF, LIF, and CCL3 were higher in liver-bearing CRLM compared to donor tissue. Consequently, cancer cells migrated equally towards CM of all regions of metastatic liver but not towards donor liver CM. CONCLUSIONS The local inflammatory environment may affect both immune cell infiltration and cancer cell migration contributing to recurrence following resection for CRLM.
Collapse
Affiliation(s)
- Fiona Hand
- National Liver Unit, St. Vincent's Hospital, Elm Park, Dublin 4, Ireland
- School of Biochemistry and Immunology and School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, 154-160 Pearse Street, Dublin 2, D02 R590, Ireland
| | - Cathal Harmon
- School of Biochemistry and Immunology and School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, 154-160 Pearse Street, Dublin 2, D02 R590, Ireland
| | - Louise A Elliott
- Centre for Colorectal Disease, School of Medicine, University College Dublin and St. Vincent's Hospital, Elm Park, Dublin 4, Ireland
| | - Francesco Caiazza
- Centre for Colorectal Disease, School of Medicine, University College Dublin and St. Vincent's Hospital, Elm Park, Dublin 4, Ireland
| | - Aonghus Lavelle
- Centre for Colorectal Disease, School of Medicine, University College Dublin and St. Vincent's Hospital, Elm Park, Dublin 4, Ireland
| | - Donal Maguire
- National Liver Unit, St. Vincent's Hospital, Elm Park, Dublin 4, Ireland
| | - Emir Hoti
- National Liver Unit, St. Vincent's Hospital, Elm Park, Dublin 4, Ireland
| | - Niamh Nolan
- National Liver Unit, St. Vincent's Hospital, Elm Park, Dublin 4, Ireland
| | - Justin G Geoghegan
- National Liver Unit, St. Vincent's Hospital, Elm Park, Dublin 4, Ireland
| | - Elizabeth J Ryan
- Centre for Colorectal Disease, School of Medicine, University College Dublin and St. Vincent's Hospital, Elm Park, Dublin 4, Ireland
| | - Cliona O'Farrelly
- School of Biochemistry and Immunology and School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, 154-160 Pearse Street, Dublin 2, D02 R590, Ireland.
| |
Collapse
|
|
40
|
Siddiqui M, Nagtegaal I, Santiago I, Knijn N, Berho M, Mirnezami A, Rao S, Brown G. Session 2: What causes liver metastases - lymph nodes or is it something else? Colorectal Dis 2018; 20 Suppl 1:39-42. [PMID: 29878686 DOI: 10.1111/codi.14077] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The traditional view of progression of disease in cancer is the sequential spread of tumour to locoregional lymph nodes and then to distant metastases. However, this view may need to be challenged and modern pathology techniques such as immunohistochemistry and tumour profiling can provide us with a greater insight into the pathways and mechanisms of distant spread. Professor Nagtegaal discusses the evidence for reconsidering the current paradigm and reflects on the need for further investigation into mechanisms of distant metastatic spread.
Collapse
Affiliation(s)
- M Siddiqui
- Royal Marsden NHS Foundation Trust, London, UK.,Croydon University Hospital, Croydon, UK
| | - I Nagtegaal
- Radboud University Medical Care Academy, Nijmegen, The Netherlands
| | - I Santiago
- Champalimaud Foundation, Lisbon, Portugal
| | - N Knijn
- Radboud University Medical Care Academy, Nijmegen, The Netherlands
| | - M Berho
- Pathology and Laboratory Medicine, Cleveland Clinic, Weston, Florida, USA
| | | | - S Rao
- Royal Marsden NHS Foundation Trust, London, UK
| | - G Brown
- Royal Marsden NHS Foundation Trust, London, UK.,Imperial College London, London, UK
| |
Collapse
|
|
41
|
Margonis GA, Sasaki K, Gholami S, Kim Y, Andreatos N, Rezaee N, Deshwar A, Buettner S, Allen PJ, Kingham TP, Pawlik TM, He J, Cameron JL, Jarnagin WR, Wolfgang CL, D'Angelica MI, Weiss MJ. Genetic And Morphological Evaluation (GAME) score for patients with colorectal liver metastases. Br J Surg 2018; 105:1210-1220. [PMID: 29691844 DOI: 10.1002/bjs.10838] [Citation(s) in RCA: 121] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 12/05/2017] [Accepted: 01/15/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND This study sought to develop a clinical risk score for resectable colorectal liver metastasis (CRLM) by combining clinicopathological and clinically available biological indicators, including KRAS. METHODS A cohort of patients who underwent resection for CRLM at the Johns Hopkins Hospital (JHH) was analysed to identify independent predictors of overall survival (OS) that can be assessed before operation; these factors were combined into the Genetic And Morphological Evaluation (GAME) score. The score was compared with the current standard (Fong score) and validated in an external cohort of patients from the Memorial Sloan Kettering Cancer Center (MSKCC). RESULTS Six preoperative predictors of worse OS were identified on multivariable Cox regression analysis in the JHH cohort (502 patients). The GAME score was calculated by allocating points to each patient according to the presence of these predictive factors: KRAS-mutated tumours (1 point); carcinoembryonic antigen level 20 ng/ml or more (1 point), primary tumour lymph node metastasis (1 point); Tumour Burden Score between 3 and 8 (1 point) or 9 and over (2 points); and extrahepatic disease (2 points). The high-risk group in the JHH cohort (GAME score at least 4 points) had a 5-year OS rate of 11 per cent, compared with 73·4 per cent for those in the low-risk group (score 0-1 point). Importantly, in cohorts from both the JHH and MSKCC (747 patients), the discriminatory capacity of the GAME score was superior to that of the Fong score, as demonstrated by the C-index and the Akaike information criterion. CONCLUSION The GAME score is a preoperative prognostic tool that can be used to inform treatment selection.
Collapse
Affiliation(s)
- G A Margonis
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - K Sasaki
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - S Gholami
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Y Kim
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - N Andreatos
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - N Rezaee
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - A Deshwar
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - S Buettner
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.,Department of Surgery, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
| | - P J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - T P Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - T M Pawlik
- Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - J He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - J L Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - W R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - C L Wolfgang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - M I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - M J Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| |
Collapse
|
|
42
|
Acciuffi S, Meyer F, Bauschke A, Settmacher U, Lippert H, Croner R, Altendorf-Hofmann A. Analysis of prognostic factors after resection of solitary liver metastasis in colorectal cancer: a 22-year bicentre study. J Cancer Res Clin Oncol 2018; 144:593-599. [PMID: 29340767 DOI: 10.1007/s00432-018-2583-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Accepted: 01/11/2018] [Indexed: 02/08/2023]
Abstract
PURPOSE The investigation of the predictors of outcome after hepatic resection for solitary colorectal liver metastasis. METHODS We recruited 350 patients with solitary colorectal liver metastasis at the University Hospitals of Jena and Magdeburg, who underwent curative liver resection between 1993 and 2014. All patients had follow-up until death or till summer 2016. RESULTS The follow-up data concern 96.6% of observed patients. The 5- and 10-year overall survival rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival rates were 30 and 20%, respectively. The analysis of the prognostic factors revealed that the pT category of primary tumour, size and grade of the metastasis and extension of the liver resection had no statistically significant impact on survival and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant predictors for the prognosis. Moreover, patients with rectal cancer had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence rate. CONCLUSION The long-term follow-up of patients with R0-resected liver metastasis is multifactorially influenced. Age and comorbidity have a role only in the overall survival. More than three lymph node metastasis reduced both the overall and disease-free survival. Extrahepatic tumour had a negative influence on the extrahepatic recurrence and on the overall survival. Neither overall survival nor recurrence rates was improved using neoadjuvant chemotherapy.
Collapse
Affiliation(s)
- Sara Acciuffi
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Frank Meyer
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Astrid Bauschke
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - Utz Settmacher
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - Hans Lippert
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Roland Croner
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Annelore Altendorf-Hofmann
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany.
| |
Collapse
|
|
43
|
|
|
44
|
Sabbagh C, Chatelain D, Attencourt C, Joly JP, Chauffert B, Cosse C, Regimbeau JM. Impact of homogeneous pathologic response to preoperative chemotherapy in patients with multiple colorectal liver metastases. World J Gastroenterol 2017; 23:8027-8034. [PMID: 29259378 PMCID: PMC5725297 DOI: 10.3748/wjg.v23.i45.8027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 07/28/2017] [Accepted: 09/05/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze the homogeneity of pathologic response to preoperative chemotherapy (PRPC) after chemotherapy in patients with multiple liver metastases (LM).
METHODS From September 2011 to August 2014, patients with at least two LM undergoing preoperative chemotherapy prior to resection were included in this retrospective, single-center study. The endpoints were PRPC homogeneity (according to both the Rubbia-Brandt and MD Anderson classifications), the impact of PRPC on the MDT decision, factors associated with homogeneous PRPC and overall survival of patients with vs. without homogeneous PRPC.
RESULTS seventy-three patients with a total of 88 liver resections (including 15 two-stage procedures) were included in the study. The homogeneous PRPC rate was 55% according to the Rubbia-Brandt classification and 53% according to the MD Anderson classification. The MDT decision was modified by the PRPC in only 2.7% of patients (n = 2).
CONCLUSION The PRPC was homogeneous in only one half of patients and had very little influence on the MDT decision.
Collapse
Affiliation(s)
- Charles Sabbagh
- Department of Digestive and Oncologic Surgery, Amiens University Medical Center, 80054 Amiens, France
- INSERM U1088, Jules Verne University of Picardie, 80054 Amiens, France
- University of Picardie, 80054 Amiens, France
| | - Denis Chatelain
- University of Picardie, 80054 Amiens, France
- Department of Anatomic Pathology, Amiens University Medical Center, 80054 Amiens, France
| | - Christophe Attencourt
- Department of Anatomic Pathology, Amiens University Medical Center, 80054 Amiens, France
| | - Jean-Paul Joly
- Department of Hepatogastroenterology, Amiens University Medical Center, 80054 Amiens, France
| | - Bruno Chauffert
- University of Picardie, 80054 Amiens, France
- Department of Medical Oncology, Amiens University Medical Center, 80054 Amiens, France
| | - Cyril Cosse
- Department of Digestive and Oncologic Surgery, Amiens University Medical Center, 80054 Amiens, France
- INSERM U1088, Jules Verne University of Picardie, 80054 Amiens, France
| | - Jean-Marc Regimbeau
- Department of Digestive and Oncologic Surgery, Amiens University Medical Center, 80054 Amiens, France
- University of Picardie, 80054 Amiens, France
- EA4294, Jules Verne University of Picardie, 80054 Amiens, France
| |
Collapse
|
|
45
|
Gaspersz MP, Buettner S, van Vugt JLA, Roos E, Coelen RJS, Vugts J, Belt EJ, de Jonge J, Polak WG, Willemssen FEJA, van Gulik TM, IJzermans JNM, Groot Koerkamp B. Conditional survival in patients with unresectable perihilar cholangiocarcinoma. HPB (Oxford) 2017; 19:966-971. [PMID: 28754366 DOI: 10.1016/j.hpb.2017.07.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 06/28/2017] [Accepted: 07/05/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Conditional survival is the life expectancy from a point in time for a patient who has survived a specific period after presentation. The aim of the study was to estimate conditional survival for patients with unresectable perihilar cholangiocarcinoma. METHODS Patients with unresectable perihilar cholangiocarcinoma from two academic hospitals in the Netherlands between 2002 and 2012 were assessed. A multivariable Cox proportional hazards analysis was performed to identify risk factors associated with overall survival. Survival was estimated using the Kaplan-Meier method to evaluate factors associated with overall survival. RESULTS In total, 572 patients were included. Overall survival was 42% at one year and 6% at three years. The conditional chance of surviving three years was 15% at 1 year and increased to 38% at 2 years. Independent poor prognostic factors for overall survival were age ≥65 years, tumor size >3 cm on imaging, bilirubin levels (>250 μmol/L), CA19-9 level at presentation (>1000 U/ml), and suspected distant metastases on imaging. The conditional survival of patients with and without these prognostic factors was comparable after patients survived the first two or more years. CONCLUSION The conditional chance of surviving for patients with unresectable perihilar cholangiocarcinoma increases with time. Poor prognostic factors become less relevant once patients have survived two years.
Collapse
Affiliation(s)
- Marcia P Gaspersz
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
| | - Stefan Buettner
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Jeroen L A van Vugt
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Eva Roos
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Robert J S Coelen
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jaynee Vugts
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Eric J Belt
- Department of Surgery, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Wojciech G Polak
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | | | - Thomas M van Gulik
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Jan N M IJzermans
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| |
Collapse
|
|
46
|
Chakedis J, Squires MH, Beal EW, Hughes T, Lewis H, Paredes A, Al-Mansour M, Sun S, Cloyd JM, Pawlik TM. Update on current problems in colorectal liver metastasis. Curr Probl Surg 2017; 54:554-602. [PMID: 29198365 DOI: 10.1067/j.cpsurg.2017.10.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Jeffrey Chakedis
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Malcolm H Squires
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Eliza W Beal
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Tasha Hughes
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Heather Lewis
- University of Colorado Health System, Fort Collins, CO
| | - Anghela Paredes
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Mazen Al-Mansour
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Steven Sun
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Jordan M Cloyd
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Timothy M Pawlik
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH.
| |
Collapse
|
|
47
|
Wang K, Liu W, Yan XL, Li J, Xing BC. Long-term postoperative survival prediction in patients with colorectal liver metastasis. Oncotarget 2017; 8:79927-79934. [PMID: 29108374 PMCID: PMC5668107 DOI: 10.18632/oncotarget.20322] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 08/05/2017] [Indexed: 12/11/2022] Open
Abstract
Numerous factors affect the prognosis of colorectal liver metastasis (CRLM) patients after hepatic resection. We investigated several factors related to overall survival in patients with CRLM to identify those most likely to benefit from hepatic resection, and produced a rational tumor biology score system. Three hundred CRLM patients treated with preoperative chemotherapy followed by hepatic resection between 2006 and 2016 were enrolled in our study. Clinicopathologic and long-term survival data were collected and assessed. Patient 1-, 3-, and 5-year overall survival rates were 92.7%, 58.3%, and 45.8%, respectively, while 1-, 3-, and 5-year disease-free survival rates were 44.7%, 28.6%, and 24.2%, respectively. Multivariate Cox regression analysis revealed poor preoperative chemotherapy response, Fong clinical risk score > 2, and KRAS mutation to be independent prognostic indicators in CRLM patients. As part of a preoperative staging system in which one point was assigned for each factor, a total score (out of 3) was predictive of long-term survival following surgery. These factors facilitate personalized prognostic assessments in CRLM patients planning for resection.
Collapse
Affiliation(s)
- Kun Wang
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, PR China
| | - Wei Liu
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, PR China
| | - Xiao-Luan Yan
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, PR China
| | - Juan Li
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, PR China
| | - Bao-Cai Xing
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, PR China
| |
Collapse
|
|
48
|
Conditional survival estimate in patients with Barcelona Clinic Liver Cancer stage B/C hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy with/without concurrent radiotherapy. Oncotarget 2017; 8:79914-79926. [PMID: 29108373 PMCID: PMC5668106 DOI: 10.18632/oncotarget.20321] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 08/04/2017] [Indexed: 12/14/2022] Open
Abstract
Conditional survival (CS) provides a prognosis of patients who have already survived several years after treatment. We investigated CS in Barcelona Clinic Liver Cancer (BCLC) stage B/C hepatocellular carcinoma (HCC) patients treated with hepatic arterial infusion chemotherapy (HAIC) with or without concurrent radiotherapy (CRT). A total of 181 patients diagnosed with HCC who were treated with HAIC with or without CRT between 2011 and 2015 were retrospectively reviewed. Overall survival (OS) and CS were calculated and a subgroup analysis was performed. The 1- and 5-year survival rates of all patients were 57.0% and 24.3%. OS was significantly higher in patients with BCLC stage B than BCLC stage C patients. Patients who achieved disease control after treatment also showed longer OS than who did not respond to treatment. Provided that the patient had already survived for 0, 1, 2, and 3 years, the CS estimates of surviving an additional 2 years were 35.6%, 55.1%, 82.0%, and 77.4%, respectively. A subgroup analysis was performed to compare BCLC stage B and C patients and revealed that CS has a tendency to increase and the difference in CS between two groups decreased over time. CS reflects the change of prognosis over time and may provide a more accurate prognosis and hopeful message to patients who have already survived with treatment.
Collapse
|
|
49
|
Meza JM, Hickey EJ, Blackstone EH, Jaquiss RDB, Anderson BR, Williams WG, Cai S, Van Arsdell GS, Karamlou T, McCrindle BW. The Optimal Timing of Stage 2 Palliation for Hypoplastic Left Heart Syndrome: An Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Data Set. Circulation 2017; 136:1737-1748. [PMID: 28687711 DOI: 10.1161/circulationaha.117.028481] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 06/26/2017] [Indexed: 12/24/2022]
Abstract
BACKGROUND In infants requiring 3-stage single-ventricle palliation for hypoplastic left heart syndrome, attrition after the Norwood procedure remains significant. The effect of the timing of stage 2 palliation (S2P), a physician-modifiable factor, on long-term survival is not well understood. We hypothesized that an optimal interval between the Norwood and S2P that both minimizes pre-S2P attrition and maximizes post-S2P survival exists and is associated with individual patient characteristics. METHODS The National Institutes of Health/National Heart, Lung, and Blood Institute Pediatric Heart Network Single Ventricle Reconstruction Trial public data set was used. Transplant-free survival (TFS) was modeled from (1) Norwood to S2P and (2) S2P to 3 years by using parametric hazard analysis. Factors associated with death or heart transplantation were determined for each interval. To account for staged procedures, risk-adjusted, 3-year, post-Norwood TFS (the probability of TFS at 3 years given survival to S2P) was calculated using parametric conditional survival analysis. TFS from the Norwood to S2P was first predicted. TFS after S2P to 3 years was then predicted and adjusted for attrition before S2P by multiplying by the estimate of TFS to S2P. The optimal timing of S2P was determined by generating nomograms of risk-adjusted, 3-year, post-Norwood, TFS versus the interval from the Norwood to S2P. RESULTS Of 547 included patients, 399 survived to S2P (73%). Of the survivors to S2P, 349 (87%) survived to 3-year follow-up. The median interval from the Norwood to S2P was 5.1 (interquartile range, 4.1-6.0) months. The risk-adjusted, 3-year, TFS was 68±7%. A Norwood-S2P interval of 3 to 6 months was associated with greatest 3-year TFS overall and in patients with few risk factors. In patients with multiple risk factors, TFS was severely compromised, regardless of the timing of S2P and most severely when S2P was performed early. No difference in the optimal timing of S2P existed when stratified by shunt type. CONCLUSIONS In infants with few risk factors, progressing to S2P at 3 to 6 months after the Norwood procedure was associated with maximal TFS. Early S2P did not rescue patients with greater risk factor burdens. Instead, referral for heart transplantation may offer their best chance at long-term survival. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT00115934.
Collapse
Affiliation(s)
- James M Meza
- From Division of Cardiovascular Surgery, The Hospital for Sick Children, Toronto, ON, Canada (J.M.M., E.J.H., W.G.W., S.C., G.S.V.A.); Departments of Thoracic and Cardiovascular Surgery and Quantitative Health Sciences, Cleveland Clinic, OH (E.H.B.); Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX (R.D.B.J.); Division of Pediatric Cardiology, New York Presbyterian-Morgan Stanley Children's Hospital, Columbia University Medical Center (B.R.A.); Division of Cardiothoracic Surgery, Phoenix Children's Hospital, Phoenix, AZ (T.K.); and Division of Pediatric Cardiology, The Hospital for Sick Children, University of Toronto, Ontario, Canada (B.W.M.).
| | - Edward J Hickey
- From Division of Cardiovascular Surgery, The Hospital for Sick Children, Toronto, ON, Canada (J.M.M., E.J.H., W.G.W., S.C., G.S.V.A.); Departments of Thoracic and Cardiovascular Surgery and Quantitative Health Sciences, Cleveland Clinic, OH (E.H.B.); Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX (R.D.B.J.); Division of Pediatric Cardiology, New York Presbyterian-Morgan Stanley Children's Hospital, Columbia University Medical Center (B.R.A.); Division of Cardiothoracic Surgery, Phoenix Children's Hospital, Phoenix, AZ (T.K.); and Division of Pediatric Cardiology, The Hospital for Sick Children, University of Toronto, Ontario, Canada (B.W.M.)
| | - Eugene H Blackstone
- From Division of Cardiovascular Surgery, The Hospital for Sick Children, Toronto, ON, Canada (J.M.M., E.J.H., W.G.W., S.C., G.S.V.A.); Departments of Thoracic and Cardiovascular Surgery and Quantitative Health Sciences, Cleveland Clinic, OH (E.H.B.); Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX (R.D.B.J.); Division of Pediatric Cardiology, New York Presbyterian-Morgan Stanley Children's Hospital, Columbia University Medical Center (B.R.A.); Division of Cardiothoracic Surgery, Phoenix Children's Hospital, Phoenix, AZ (T.K.); and Division of Pediatric Cardiology, The Hospital for Sick Children, University of Toronto, Ontario, Canada (B.W.M.)
| | - Robert D B Jaquiss
- From Division of Cardiovascular Surgery, The Hospital for Sick Children, Toronto, ON, Canada (J.M.M., E.J.H., W.G.W., S.C., G.S.V.A.); Departments of Thoracic and Cardiovascular Surgery and Quantitative Health Sciences, Cleveland Clinic, OH (E.H.B.); Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX (R.D.B.J.); Division of Pediatric Cardiology, New York Presbyterian-Morgan Stanley Children's Hospital, Columbia University Medical Center (B.R.A.); Division of Cardiothoracic Surgery, Phoenix Children's Hospital, Phoenix, AZ (T.K.); and Division of Pediatric Cardiology, The Hospital for Sick Children, University of Toronto, Ontario, Canada (B.W.M.)
| | - Brett R Anderson
- From Division of Cardiovascular Surgery, The Hospital for Sick Children, Toronto, ON, Canada (J.M.M., E.J.H., W.G.W., S.C., G.S.V.A.); Departments of Thoracic and Cardiovascular Surgery and Quantitative Health Sciences, Cleveland Clinic, OH (E.H.B.); Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX (R.D.B.J.); Division of Pediatric Cardiology, New York Presbyterian-Morgan Stanley Children's Hospital, Columbia University Medical Center (B.R.A.); Division of Cardiothoracic Surgery, Phoenix Children's Hospital, Phoenix, AZ (T.K.); and Division of Pediatric Cardiology, The Hospital for Sick Children, University of Toronto, Ontario, Canada (B.W.M.)
| | - William G Williams
- From Division of Cardiovascular Surgery, The Hospital for Sick Children, Toronto, ON, Canada (J.M.M., E.J.H., W.G.W., S.C., G.S.V.A.); Departments of Thoracic and Cardiovascular Surgery and Quantitative Health Sciences, Cleveland Clinic, OH (E.H.B.); Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX (R.D.B.J.); Division of Pediatric Cardiology, New York Presbyterian-Morgan Stanley Children's Hospital, Columbia University Medical Center (B.R.A.); Division of Cardiothoracic Surgery, Phoenix Children's Hospital, Phoenix, AZ (T.K.); and Division of Pediatric Cardiology, The Hospital for Sick Children, University of Toronto, Ontario, Canada (B.W.M.)
| | - Sally Cai
- From Division of Cardiovascular Surgery, The Hospital for Sick Children, Toronto, ON, Canada (J.M.M., E.J.H., W.G.W., S.C., G.S.V.A.); Departments of Thoracic and Cardiovascular Surgery and Quantitative Health Sciences, Cleveland Clinic, OH (E.H.B.); Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX (R.D.B.J.); Division of Pediatric Cardiology, New York Presbyterian-Morgan Stanley Children's Hospital, Columbia University Medical Center (B.R.A.); Division of Cardiothoracic Surgery, Phoenix Children's Hospital, Phoenix, AZ (T.K.); and Division of Pediatric Cardiology, The Hospital for Sick Children, University of Toronto, Ontario, Canada (B.W.M.)
| | - Glen S Van Arsdell
- From Division of Cardiovascular Surgery, The Hospital for Sick Children, Toronto, ON, Canada (J.M.M., E.J.H., W.G.W., S.C., G.S.V.A.); Departments of Thoracic and Cardiovascular Surgery and Quantitative Health Sciences, Cleveland Clinic, OH (E.H.B.); Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX (R.D.B.J.); Division of Pediatric Cardiology, New York Presbyterian-Morgan Stanley Children's Hospital, Columbia University Medical Center (B.R.A.); Division of Cardiothoracic Surgery, Phoenix Children's Hospital, Phoenix, AZ (T.K.); and Division of Pediatric Cardiology, The Hospital for Sick Children, University of Toronto, Ontario, Canada (B.W.M.)
| | - Tara Karamlou
- From Division of Cardiovascular Surgery, The Hospital for Sick Children, Toronto, ON, Canada (J.M.M., E.J.H., W.G.W., S.C., G.S.V.A.); Departments of Thoracic and Cardiovascular Surgery and Quantitative Health Sciences, Cleveland Clinic, OH (E.H.B.); Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX (R.D.B.J.); Division of Pediatric Cardiology, New York Presbyterian-Morgan Stanley Children's Hospital, Columbia University Medical Center (B.R.A.); Division of Cardiothoracic Surgery, Phoenix Children's Hospital, Phoenix, AZ (T.K.); and Division of Pediatric Cardiology, The Hospital for Sick Children, University of Toronto, Ontario, Canada (B.W.M.)
| | - Brian W McCrindle
- From Division of Cardiovascular Surgery, The Hospital for Sick Children, Toronto, ON, Canada (J.M.M., E.J.H., W.G.W., S.C., G.S.V.A.); Departments of Thoracic and Cardiovascular Surgery and Quantitative Health Sciences, Cleveland Clinic, OH (E.H.B.); Division of Pediatric Cardiothoracic Surgery, Children's Medical Center, Dallas, TX (R.D.B.J.); Division of Pediatric Cardiology, New York Presbyterian-Morgan Stanley Children's Hospital, Columbia University Medical Center (B.R.A.); Division of Cardiothoracic Surgery, Phoenix Children's Hospital, Phoenix, AZ (T.K.); and Division of Pediatric Cardiology, The Hospital for Sick Children, University of Toronto, Ontario, Canada (B.W.M.)
| |
Collapse
|
|
50
|
Carrato A, Abad A, Massuti B, Grávalos C, Escudero P, Longo-Muñoz F, Manzano JL, Gómez A, Safont MJ, Gallego J, García-Paredes B, Pericay C, Dueñas R, Rivera F, Losa F, Valladares-Ayerbes M, González E, Aranda E. First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD). Eur J Cancer 2017. [PMID: 28633089 DOI: 10.1016/j.ejca.2017.04.024] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations. METHODS Multicentre, open-label study in untreated patients ≥ 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI. The primary end-point was objective response rate (ORR). Secondary end-points included liver metastases resection rate (R0 + R1), progression-free survival (PFS), overall survival (OS), adverse events and perioperative safety. Exploratory end-points were: response by RAS status, early tumour shrinkage (ETS) and depth of response (DpR) in WT-RAS patients. RESULTS Data on 77 patients were analysed (38 Pmab-FOLFOX4; 39 Pmab-FOLFIRI; WT-RAS: 27/26, respectively). ORR was 74% with Pmab-FOLFOX4 and 67% with Pmab-FOLFIRI (WT-RAS: 78%/73%). Out of the above, 45% and 59% underwent surgical resection, respectively (WT-RAS: 37%/69%). The R0-R1 resection rate was 34%/46% (WT-RAS:26%/54%). Median PFS was 13/14 months (hazard ratio [HR] Pmab-FOLFIRI versus Pmab-FOLFOX4: 0.9; 95% confidence interval: [0.6-1.5]; WT-RAS:13/15; HR: 0.7 [0.4-1.3]). Median OS was 37/41 months (HR:1.0 [0.6-1.8]; WT-RAS: 39/49; HR:0.9 [0.4-1.9]). In WT-RAS patients with confirmed response, median DpR was 71%/66%, and 65%/77% of patients showed ETS ≥ 30%/ ≥ 20% at week 8, without significant differences between arms; these patients had longer median PFS and OS and higher resectability rates. Surgery was associated with longer survival. Perioperative and overall safety were similar, except for higher grade 3/4 neutropenia (40%/10%; p = 0.003) and neuropathy (13%/0%; p = 0.025) in the Pmab-FOLFOX4 arm. CONCLUSIONS In patients with WT-KRAS mCRC and LLD, both first-line Pmab-FOLFOX4 and Pmab-FOLFIRI resulted in high ORR and ETS, allowing potentially curative resection. No significant differences in efficacy were observed between the two regimens. (clinicaltrials.gov:NCT00885885).
Collapse
Affiliation(s)
- Alfredo Carrato
- Ramon y Cajal University Hospital, Ramon y Cajal Institute for Health Research - IRYCIS, Alcala University, CIBERONC, Carretera de Colmenar Viejo, km 9.100, ES-28034 Madrid, Spain.
| | - Albert Abad
- Germans Trias i Pujol Hospital-ICO, Carretera de Canyet s/n, ES-08916 Badalona, Spain
| | - Bartomeu Massuti
- Alicante General Hospital, Pintor Baeza, 11, ES-03010 Alicante, Spain
| | - Cristina Grávalos
- Doce de Octubre Hospital, Avenida de Córdoba, s/n, ES-28041 Madrid, Spain
| | - Pilar Escudero
- Clínico Lozano Blesa Hospital, Avenida San Juan Bosco, 15, ES-50009 Zaragoza, Spain
| | - Federico Longo-Muñoz
- Ramon y Cajal University Hospital, Ramon y Cajal Institute for Health Research - IRYCIS, Alcala University, CIBERONC, Carretera de Colmenar Viejo, km 9.100, ES-28034 Madrid, Spain
| | - José-Luis Manzano
- Germans Trias i Pujol Hospital-ICO, Carretera de Canyet s/n, ES-08916 Badalona, Spain
| | - Auxiliadora Gómez
- Maimonides Institute of Biomedical Research, IMIBIC, Spain, Reina Sofía Hospital, University of Córdoba, Spanish Cancer Network, (RTICC), Instituto de Salud Carlos III, Avenida Menéndez Pidal, s/n, ES-14004, Córdoba, Spain
| | - María José Safont
- Valencia General Hospital, Avenida Tres Cruces, 2, ES-46014 Valencia, Spain
| | - Javier Gallego
- Elche General University Hospital, Camí de l'Almazara, 11, ES-03203 Alicante, Spain
| | - Beatriz García-Paredes
- San Carlos Hospital, Calle del Professor Martín Lagos, S/N, ES-28040 Madrid, Center affiliated to the Red Temática de Investigación Cooperativa, RD06/0020/0021, Spain, Instituto Carlos III, Spanish Ministry of Science and Innovation, Madrid, Spain
| | - Carles Pericay
- Sabadell Hospital, Corporación Sanitaria Parc Taulí, Parc del Taulí, 1, ES-08208 Sabadell, Spain
| | - Rosario Dueñas
- Jaén Hospital Complex, Av. del Ejército Español, 10, ES-23007 Jaén, Spain
| | - Fernando Rivera
- Marqués de Valdecilla Hospital, Av. de Valdecilla, s/n, ES-39008 Santander, Spain
| | - Ferrán Losa
- L´Hospitalet General Hospital, Av. Josep Molins, 29, ES-08906 L´Hospitalet de Llobregat, Spain
| | | | - Encarnación González
- Virgen de las Nieves Hospital, Av. de las Fuerzas Armadas, 2, ES-18014 Granada, Spain
| | - Enrique Aranda
- Maimonides Institute of Biomedical Research, IMIBIC, Spain, Reina Sofía Hospital, University of Córdoba, Spanish Cancer Network, (RTICC), Instituto de Salud Carlos III, Avenida Menéndez Pidal, s/n, ES-14004, Córdoba, Spain
| | | |
Collapse
|