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

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.

Proposed Modification of the 8th Edition of the AJCC Staging System for Pancreatic Ductal Adenocarcinoma

2019 ◽  
Vol 269 (5) ◽  
pp. 944-950 ◽  
Author(s):  
Si Shi ◽  
Jie Hua ◽  
Chen Liang ◽  
Qingcai Meng ◽  
Dingkong Liang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Staging System ◽  
Ductal Adenocarcinoma ◽  
Ajcc Staging System ◽  
Proposed Modification ◽  
Ajcc Staging ◽  
8Th Edition

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

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.

scholarly journals Pancreatic Cancer Stem Cells May Define Tumor Stroma Characteristics and Recurrence Patterns in Pancreatic Ductal Adenocarcinoma

2020 ◽  
Author(s):  
Gokce Askan ◽  
Ibrahim Halil Sahin ◽  
Joanne F. Chou ◽  
Aslihan Yavas ◽  
Marinela Capanu ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Statistical Significance ◽  
Specific Antigen ◽  
Tumor Stroma ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Stem Cell Markers ◽  
Significant Difference ◽  
The Impact

Abstract Background: Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients.Methods: PDAC patients who underwent surgical resection between 01/2012 -06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher`s exact test. Results: N= 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA- had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44-/ESA+ (35%), CD44-/ESA- (9%) (p=0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence observed in patients with loose stroma. No statistically significant difference in RFS and OS were observed among subgroups (P=0.089). Conclusions: These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Although not reaching statistical significance, we observed more local recurrences in patients with loose stroma, and no local recurrence was seen in patients with dense stroma suggesting tumor stroma may influence the recurrence pattern in PDAC patients.

scholarly journals Prognostic Validity of the American Joint Committee on Cancer Eighth Edition Staging System for Well-Differentiated Pancreatic Neuroendocrine Tumors: A Retrospective Multinational Multicenter Study

2020 ◽  
Author(s):  
Hebin Wang ◽  
Ding Ding ◽  
Tingting Qin ◽  
Jun Liu ◽  
Hang Zhang ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Staging System ◽  
Tnm Staging ◽  
Stage I ◽  
Pancreatic Neuroendocrine Tumors ◽  
American Joint Committee ◽  
Staging Systems ◽  
Significant Difference ◽  
Well Differentiated ◽  
Eighth Edition

Abstract Background:There is no widely-accepted staging system for pancreatic neuroendocrine tumors (pNETs). The aim of this study was to validate the American Joint Committee on Cancer (AJCC) 8th edition staging system for well-differentiated (G1/G2) pNETs.Methods:A multicenter dataset (n=1086) was used to evaluate the application of the AJCC 7th and 8th, the European Neuroendocrine Tumor Society (ENETS), and the modified ENETS (mENETS) staging systems for well-differentiated pNETs.Results:The proportion of patients with stage III tumors was extremely low (1.1%) according to the AJCC 7th staging system. For the ENETS staging system, patients with stage IIIA disease had worse estimated mean survival than patients with stage IIIB disease (78.9 vs. 107.3 months). When comparing with patients in stage I, the AJCC 7th, ENETS, and mENETS staging systems showed good performance in discriminating between stages; however, there was no significant difference in some stages when the reference was defined as the earlier stage. When the reference was defined as stage I or the earlier stage, there was a significant inter-stage difference in the AJCC 8th staging system.Conclusions:The AJCC 8th staging system is more suitable for pNETs than other TNM staging systems and may be adopted in clinical practice.

scholarly journals Validation and Modification of Staging Systems for Poorly Differentiated Pancreatic Neuroendocrine Carcinoma

2019 ◽  
Author(s):  
Haihong Wang ◽  
Zhenyu Lin ◽  
Guiling Li ◽  
Dejun Zhang ◽  
Dandan Yu ◽  
...  
Keyword(s):  
Stage Iv ◽  
Staging System ◽  
Risk Groups ◽  
Tnm Staging ◽  
7Th Edition ◽  
Staging Systems ◽  
Significant Difference ◽  
Ajcc Staging System ◽  
Poorly Differentiated ◽  
Ajcc Staging

Abstract Background The American Joint Committee on Cancer (AJCC) staging classifications and the European Neuroendocrine Tumor Society (ENETS) are two broadly used systems for pancreatic neuroendocrine tumors. This study aims to identify the most accurate and useful TNM staging system for poorly differentiated pancreatic neuroendocrine carcinomas(pNECs). Methods An analysis was performed to evaluate the application of the ENETS, 7th edition (7th) AJCC and 8th edition (8th) AJCC staging classifications using the Surveillance, Epidemiology, and End Results (SEER) registry (N = 568 patients). A modified system was proposed based on analysis of the 7th AJCC classification. Results In multivariable analyses, only the 7th AJCC staging system allocated patients into four different risk groups, compared with the 8th AJCC staging system and ENETS staging system, although there was no significant difference. We modified the staging classification by maintaining the T and M definitions of the 7th AJCC staging and adopting new staging definitions. An increased hazard ratio (HR) of death was also observed from class I to class IV for the modified 7th (m7th) staging system (compared with stage I disease; HR for stage II =1.23, 95% confidence interval (CI)= 0.73-2.06, P =0.44; HR for stage III =2.20, 95% CI =1.06-4.56, P=0.03; HR for stage IV =4.95, 95% CI =3.20-7.65, P < 0.001).The concordance index (C-index) was higher for local disease with the m7th AJCC staging system than with the 7th AJCC staging system. Conclusions The m7th AJCC staging system for pNECs proposed in this study provides improvements and may be assessed for potential adoption in the next edition.

scholarly journals Validation and Modification of Staging Systems for Poorly Differentiated Pancreatic Neuroendocrine Carcinoma

2020 ◽  
Author(s):  
Haihong Wang ◽  
Zhenyu Lin ◽  
Guiling Li ◽  
Dejun Zhang ◽  
Dandan Yu ◽  
...  
Keyword(s):  
Stage Iv ◽  
Staging System ◽  
Risk Groups ◽  
Tnm Staging ◽  
7Th Edition ◽  
Staging Systems ◽  
Significant Difference ◽  
Ajcc Staging System ◽  
Poorly Differentiated ◽  
Ajcc Staging

Abstract Background: The American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) staging classifications are two broadly used systems for pancreatic neuroendocrine tumors. This study aims to identify the most accurate and useful tumor–node–metastasis (TNM) staging system for poorly differentiated pancreatic neuroendocrine carcinomas(pNECs).Methods: An analysis was performed to evaluate the application of the ENETS, 7th edition (7th) AJCC and 8th edition (8th) AJCC staging classifications using the Surveillance, Epidemiology, and End Results (SEER) registry (N = 568 patients), and a modified system based on the analysis of the 7th AJCC classification was proposed Results: In multivariable analyses, only the 7th AJCC staging system allocated patients into four different risk groups, although there was no significant difference. We modified the staging classification by maintaining the T and M definitions of the 7th AJCC staging and adopting new staging definitions. An increased hazard ratio (HR) of death was also observed from class I to class IV for the modified 7th (m7th) staging system (compared with stage I disease; HR for stage II =1.23, 95% confidence interval (CI)= 0.73-2.06, P =0.44; HR for stage III =2.20, 95% CI =1.06-4.56, P=0.03; HR for stage IV =4.95, 95% CI =3.20-7.65, P < 0.001).The concordance index (C-index) was higher for local disease with the m7th AJCC staging system than with the 7th AJCC staging system. Conclusions: The m7th AJCC staging system for pNECs proposed in this study provides improvements and may be assessed for potential adoption in the next edition.

scholarly journals Validation and Modification of Staging Systems for Poorly Differentiated Pancreatic Neuroendocrine Carcinoma

2020 ◽  
Author(s):  
Haihong Wang ◽  
Zhenyu Lin ◽  
Guiling Li ◽  
Dejun Zhang ◽  
Dandan Yu ◽  
...  
Keyword(s):  
Stage Iv ◽  
Staging System ◽  
Risk Groups ◽  
Tnm Staging ◽  
7Th Edition ◽  
Staging Systems ◽  
Significant Difference ◽  
Ajcc Staging System ◽  
Poorly Differentiated ◽  
Ajcc Staging

Abstract Background: The American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) staging classifications are two broadly used systems for pancreatic neuroendocrine tumors. This study aims to identify the most accurate and useful TNM staging system for poorly differentiated pancreatic neuroendocrine carcinomas(pNECs).Methods: An analysis was performed to evaluate the application of the ENETS, 7th edition (7th) AJCC and 8th edition (8th) AJCC staging classifications using the Surveillance, Epidemiology, and End Results (SEER) registry (N = 568 patients). A modified system was proposed based on analysis of the 7th AJCC classification. Results: In multivariable analyses, only the 7th AJCC staging system allocated patients into four different risk groups, compared with the 8th AJCC staging system and ENETS staging system, although there was no significant difference. We modified the staging classification by maintaining the T and M definitions of the 7th AJCC staging and adopting new staging definitions. An increased hazard ratio (HR) of death was also observed from class I to class IV for the modified 7th (m7th) staging system (compared with stage I disease; HR for stage II =1.23, 95% confidence interval (CI)= 0.73-2.06, P =0.44; HR for stage III =2.20, 95% CI =1.06-4.56, P=0.03; HR for stage IV =4.95, 95% CI =3.20-7.65, P < 0.001).The concordance index (C-index) was higher for local disease with the m7th AJCC staging system than with the 7th AJCC staging system. Conclusions: The m7th AJCC staging system for pNECs proposed in this study provides improvements and may be assessed for potential adoption in the next edition.

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