Validation and modification of the AJCC 8th TNM staging system for pancreatic ductal adenocarcinoma in a Chinese cohort: A nationwide pancreas data center analysis

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy and its mortality continues to rise globally. Because of its high heterogeneity and complex molecular landscapes, published gene signatures have shown low specificity and robustness. Functional signatures containing a group of genes involved in similar biological functions display a more robust performance. Methods: The present study was designed to excavate potential functional signatures for PDAC by analyzing maximal number of datasets extracted from available databases with a recently developed method of FAIME (Functional Analysis of Individual Microarray Expression) in a comprehensive and integrated way. Results: By using appropriate search strategies, we extracted 11 PDAC datasets from GEO, ICGC and TCGA databases. By systemically analyzing these datasets, we identified a robust functional signature of subpathway (path:00982_1), which belongs to the drug metabolism-cytochrome P450 pathway. The functional signature has displayed a more powerful and robust capacity in predicting prognosis, drug response and chemotherapeutic efficacy for PDAC, particularly for the classical subtype, in comparison with published gene signatures and clinically used TNM staging system. This signature was further verified by meta-analyses and validated in cell line databases and available clinical datasets. Conclusion: This is the first functional signature for PDAC identified from the largest number of datasets by using comprehensive and integrated analyses. The novel signature warrants a further investigation, since it is like to improve the current systems for predicting the prognosis and monitoring drug response, and to serve a potential linkage to therapeutic options for combating PDAC.

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Identification of a robust functional subpathway signature for pancreatic ductal adenocarcinoma by comprehensive and integrated analyses

10.21203/rs.2.17455/v2 ◽

2020 ◽

Author(s):

Ping Wang ◽

chunlong zhang ◽

Weidong Li ◽

Bo Zhai ◽

Xian Jiang ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Drug Response ◽

Staging System ◽

Tnm Staging ◽

Ductal Adenocarcinoma ◽

Gene Signatures ◽

Chemotherapeutic Efficacy ◽

Biological Interpretation ◽

Meta Analyses ◽

Microarray Expression

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy and its mortality continues to rise globally. Because of its high heterogeneity and complex molecular landscapes, published gene signatures have demonstrated low specificity and robustness. Functional signatures containing a group of genes involved in similar biological functions may display a more robust performance. Methods: The present study was designed to excavate potential functional signatures for PDAC by analyzing maximal number of datasets extracted from available databases with a recently developed method of FAIME (Functional Analysis of Individual Microarray Expression) in a comprehensive and integrated way. Results: Eleven PDAC datasets were extracted from GEO, ICGC and TCGA databases. By systemically analyzing these datasets, we identified a robust functional signature of subpathway (path:00982_1), which belongs to the drug metabolism-cytochrome P450 pathway. The signature has displayed a more powerful and robust capacity in predicting prognosis, drug response and chemotherapeutic efficacy for PDAC, particularly for the classical subtype, in comparison with published gene signatures and clinically used TNM staging system. This signature was verified by meta-analyses and validated in available cell line and clinical datasets with chemotherapeutic efficacy. Conclusion: The present study has identified a novel functional signature for PDAC and it is like to improve the current systems for predicting the prognosis and monitoring drug response, and to serve a potential linkage to therapeutic options for combating PDAC. However, the involvement of path:00982_1 subpathway in the metabolism of anti-PDAC chemotherapeutic drugs, particularly its biological interpretation, requires a further investigation.

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Optimized modification of the eighth edition of AJCC TNM staging system for resected pancreatic ductal adenocarcinoma

Future Oncology ◽

10.2217/fon-2019-0264 ◽

2019 ◽

Vol 15 (30) ◽

pp. 3457-3465

Author(s):

Ning Pu ◽

Lingdi Yin ◽

Joseph R Habib ◽

Shanshan Gao ◽

Haijie Hu ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Statistical Significance ◽

Staging System ◽

Tnm Staging ◽

Ductal Adenocarcinoma ◽

Hazard Ratios ◽

Significant Difference ◽

Proposed Modification ◽

Eighth Edition ◽

Ajcc Staging

Aim: To reassess the prognostic performance of the American Joint Committee on Cancer (AJCC) 8th edition for pancreatic ductal adenocarcinoma (PDAC) and optimize the categorization of PDAC staging. Patients & methods: A total of 11,858 patients with resected PDAC from the Surveillance, Epidemiology and End Results database were retrospectively enrolled by sequential analyses. Results: There was no statistical significance between stage IIA and IIB tumors with hazard ratios of 2.065 and 2.184 (p = 0.620) for stages IIA and IIB, respectively. With the proposed modification, there was a significant difference between the hazard ratios of stages IIIA and IIIB which were 2.481 and 2.715, respectively (p = 0.009). The C-index of modified system was 0.609, slightly higher than AJCC 8th staging system 0.604. Conclusion: We proposed a modified eighth edition of the AJCC staging system by combining stage IIA with IIB and further subclassifying stage III patients in order to lead to better discriminative power.

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Mesenterico-portal vein invasion should be an important factor in TNM staging for pancreatic ductal adenocarcinoma: Proposed modification of the 8th edition of the American Joint Committee on Cancer staging system

World Journal of Gastroenterology ◽

10.3748/wjg.v25.i46.6752 ◽

2019 ◽

Vol 25 (46) ◽

pp. 6752-6766

Author(s):

Hong-Yu Chen ◽

Xing Wang ◽

Hao Zhang ◽

Xu-Bao Liu ◽

Chun-Lu Tan

Keyword(s):

Portal Vein ◽

Pancreatic Ductal Adenocarcinoma ◽

Staging System ◽

Cancer Staging ◽

Tnm Staging ◽

Ductal Adenocarcinoma ◽

Portal Vein Invasion ◽

American Joint Committee ◽

Proposed Modification ◽

8Th Edition

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Prognostic nomogram to predict overall survival for patients with perihilar cholangiocarcinoma: A population-based study of SEER database (Preprint)

10.2196/preprints.26118 ◽

2020 ◽

Author(s):

Chendong Wang

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Staging System ◽

Tnm Staging ◽

Survival Outcome ◽

Perihilar Cholangiocarcinoma ◽

Cox Regression Analysis ◽

Calibration Curves ◽

Tnm Staging System ◽

Net Benefits

BACKGROUND Perihilar cholangiocarcinoma (pCCA) is a highly aggressive malignancy with poor prognosis. Accurate prediction is of great significance for patients’ survival outcome. OBJECTIVE The present study aimed to propose a prognostic nomogram for predicting the overall survival (OS) for patients with pCCA. METHODS We conducted a retrospective analysis in a total of 940 patients enrolled from the Surveillance, Epidemiology, and End Results (SEER) program and developed a nomogram based on the prognostic factors identified from the cox regression analysis. Concordance index (C-index), risk group stratification and calibration curves were adopted to test the discrimination and calibration ability of the nomogram with bootstrap method. Decision curves were also plotted to evaluate net benefits in clinical use against TNM staging system. RESULTS On the basis of multivariate analysis, five independent prognostic factors including age, summary stage, surgery, chemotherapy, together with radiation were selected and entered into the nomogram model. The C-index of the model was significantly higher than TNM system in the training set (0.703 vs 0.572, P<0.001), which was also proved in the validation set (0.718 vs 0.588, P<0.001). The calibration curves for 1-, 2-, and 3-year OS probabilities exhibited good agreements between the nomogram-predicted and the actual observation. Decision curves displayed that the nomogram obtained more net benefits than TNM staging system in clinical context. The OS curves of two distinct risk groups stratified by nomogram-predicted survival outcome illustrated statistical difference. CONCLUSIONS We established and validated an easy-to-use prognostic nomogram, which can provide more accurate individualized prediction and assistance in decision making for pCCA patients.

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