Proposal of a modified American Joint Committee on Cancer staging scheme for resectable pancreatic ductal adenocarcinoma with a lymph node ratio-based N classification

Li, Huanjun; Chen, Yutong; Yuan, Shuqiang

doi:10.1097/md.0000000000012094

Cited by 11 publications

(15 citation statements)

References 26 publications

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“…Nodal status and quantity are important, and nodal (N) staging is classified based on the number of metastatic lymph nodes, as N0 (0), N1 (1-3), and N2 (≥ 4), in the 8th edition of the American Joint Committee on Cancer [9]. Several other aspects of lymph node metastasis, including the lymph node ratio, are strong prognostic indicators [10]. A minimum of 12 lymph nodes should be examined to properly evaluate the N0 category [11,12].…”

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confidence: 99%

Lymph node size and its association with nodal metastasis in ductal adenocarcinoma of the pancreas

Shin

Lee

et al. 2020

J Pathol Transl Med

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Background: Although lymph node metastasis is a poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC), our understanding of lymph node size in association with PDAC is limited. Increased nodal size in preoperative imaging has been used to detect node metastasis. We evaluated whether lymph node size can be used as a surrogate preoperative marker of lymph node metastasis. Methods: We assessed nodal size and compared it to the nodal metastatic status of 200 patients with surgically resected PDAC. The size of all lymph nodes and metastatic nodal foci were measured along the long and short axis, and the relationships between nodal size and metastatic status were compared at six cutoff points. Results: A total of 4,525 lymph nodes were examined, 9.1% of which were metastatic. The mean size of the metastatic nodes (long axis, 6.9 ± 5.0 mm; short axis, 4.3 ± 3.1 mm) was significantly larger than that of the non-metastatic nodes (long axis, 5.0 ± 4.0 mm; short axis, 3.0 ± 2.0 mm; all p < .001). Using a 10 mm cutoff, the sensitivity, specificity, positive predictive value, overall accuracy, and area under curve was 24.8%, 88.0%, 17.1%, 82.3%, and 0.60 for the long axis and 7.0%, 99.0%, 40.3%, 90.6%, and 0.61 for the short axis, respectively. Conclusions: The metastatic nodes are larger than the non-metastatic nodes in PDAC patients. However, the difference in nodal size was too small to be identified with preoperative imaging. The performance of preoperative radiologic imaging to predict lymph nodal metastasis was not good. Therefore, nodal size cannot be used a surrogate preoperative marker of lymph node metastasis.

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confidence: 99%

Lymph node size and its association with nodal metastasis in ductal adenocarcinoma of the pancreas

Shin

Lee

et al. 2020

J Pathol Transl Med

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“… 20 – 26 Furthermore, a subdivision of N stage based on metastatic lymph node ratio (LNR), accounting for the total number of examined lymph nodes, was suggested for a more accurate prediction of survival. 24 , 27 …”

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confidence: 99%

Nationwide Validation of the 8th American Joint Committee on Cancer TNM Staging System and Five Proposed Modifications for Resected Pancreatic Cancer

et al. 2022

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Background The prognostic value of four proposed modifications to the 8th American Joint Committee on Cancer (AJCC) TNM staging system has yet to be evaluated. This study aimed to validate five proposed modifications. Methods Patients who underwent pancreatic ductal adenocarcinoma resection (2014–2016), as registered in the prospective Dutch Pancreatic Cancer Audit, were included. Stratification and prognostication of TNM staging systems were assessed using Kaplan–Meier curves, Cox proportional hazard analyses, and C-indices. A new modification was composed based on overall survival (OS). Results Overall, 750 patients with a median OS of 18 months (interquartile range 10–32) were included. The 8th edition had an increased discriminative ability compared with the 7th edition {C-index 0.59 (95% confidence interval [CI] 0.56–0.61) vs. 0.56 (95% CI 0.54–0.58)}. Although the 8th edition showed a stepwise decrease in OS with increasing stage, no differences could be demonstrated between all substages; stage IIA vs. IB (hazard ratio [HR] 1.30, 95% CI 0.80–2.09; p = 0.29) and stage IIB vs. IIA (HR 1.17, 95% CI 0.75–1.83; p = 0.48). The four modifications showed comparable prognostic accuracy (C-index 0.59–0.60); however, OS did not differ between all modified TNM stages (ns). The new modification, migrating T3N1 patients to stage III, showed a C-index of 0.59, but did detect significant survival differences between all TNM stages (p < 0.05). Conclusions The 8th TNM staging system still lacks prognostic value for some categories of patients, which was not clearly improved by four previously proposed modifications. The modification suggested in this study allows for better prognostication in patients with all stages of disease.

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“…The TNM staging system is a globally recognized standard for classifying the extent of spread of cancer and is widely accepted for predicting the prognosis and guiding treatment options for PDAC. The N classification of the 8th Edition of the American Joint Committee on Cancer (AJCC) scheme for PDAC, particularly recently proposed LNR (lymph node ratio)-based N classification for respectable PDAC, has been shown to more accurately predict patient response [27][28][29]. Therefore, we employed a multivariate Cox analysis to compare the predicting power of our signature with this clinical system.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, by using multivariate Cox analyses, we found that the path:00982_1 signature was an independent predictive factor as examined in all the available datasets, which included clinical information of age, gender, ethnicity, lymph nodes, grade, maximum tumor dimension, TNM (tumor, lymph nodes & metastasis) stages, N classification, molecular subtype (classical and basal) and history of diabetes [27][28][29] (Analytical data File 4).…”

Section: Identification Of the Path:00982_1 Subpathway Signaturementioning

confidence: 99%

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

Wang

Zhang

et al. 2020

Cell Commun Signal

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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 PDAC signature, which has the potential to improve the current systems for predicting the prognosis and monitoring drug response, and to serve a 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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Proposal of a modified American Joint Committee on Cancer staging scheme for resectable pancreatic ductal adenocarcinoma with a lymph node ratio-based N classification

Cited by 11 publications

References 26 publications

Lymph node size and its association with nodal metastasis in ductal adenocarcinoma of the pancreas

Lymph node size and its association with nodal metastasis in ductal adenocarcinoma of the pancreas

Nationwide Validation of the 8th American Joint Committee on Cancer TNM Staging System and Five Proposed Modifications for Resected Pancreatic Cancer

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

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