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Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and N Staging in Patients With Pancreatic Adenocarcinoma.

ABSTRACT: The aim of this study was to evaluate and validate the proposed 8th edition American Joint Committee on Cancer (AJCC) system for T and N staging of pancreatic adenocarcinoma.Investigators have questioned the clinical relevance and reproducibility of previous AJCC staging for pancreatic adenocarcinoma.Prospective databases at Memorial Sloan Kettering (MSK), Massachusetts General Hospital (MGH), and Johns Hopkins Hospital (JHH) were queried for patients who had undergone resection for pancreatic adenocarcinoma. Patients who underwent a margin-negative (R0) resection, and who had previously undergone pathologic review, were included. Patients were staged according to 7th edition AJCC criteria, as well as the proposed 8th edition system that includes different definitions of tumor size (T) and nodal status (N). The dataset was randomly split into training and test sets.Two thousand three hundred eighteen patients were identified who met inclusion criteria. Recursive partitioning on the training set (n = 1551) identified statistically appropriate cutoffs for tumor size (<2.2?cm, ?4.8?cm,) and nodal status (no positive nodes, 1 to 3 positive nodes, ?4 positive nodes) that supported the proposed 8th edition changes. Median survival in patients staged as T3, N0 by the 7th edition definitions was different between institutions (median Center 1, 24 mo; Center 2, 37 mo; Center 3, 29 mo; P = 0.054). This difference was not observed when patients were staged as T3, N0 by 8th edition criteria. Stage, and stage-specific outcome (7th edition), on the test set revealed a predominance of patients (68%) within the IIB subgroup, and a concordance probability estimate (CPE) of 0.57 for stage-specific survival. When assessed with 8th edition criteria, no stage subgroup had a majority of patients, and the CPE was 0.58.The proposed 8th edition changes for T and N classification were statistically valid and may allow a more reproducible system of T staging. This system also stratifies patients more evenly across stages without sacrificing prognostic accuracy.

SUBMITTER: Allen PJ

PROVIDER: S-EPMC5611666 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and N Staging in Patients With Pancreatic Adenocarcinoma.

Allen Peter J PJ Kuk Deborah D Castillo Carlos Fernandez-Del CF Basturk Olca O Wolfgang Christopher L CL Cameron John L JL Lillemoe Keith D KD Ferrone Cristina R CR Morales-Oyarvide Vicente V He Jin J Weiss Matthew J MJ Hruban Ralph H RH Gönen Mithat M Klimstra David S DS Mino-Kenudson Mari M

Annals of surgery 20170101 1

<h4>Objective</h4>The aim of this study was to evaluate and validate the proposed 8th edition American Joint Committee on Cancer (AJCC) system for T and N staging of pancreatic adenocarcinoma.<h4>Summary of background data</h4>Investigators have questioned the clinical relevance and reproducibility of previous AJCC staging for pancreatic adenocarcinoma.<h4>Methods</h4>Prospective databases at Memorial Sloan Kettering (MSK), Massachusetts General Hospital (MGH), and Johns Hopkins Hospital (JHH) w ...[more]

PMID: 27163957

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Project description:Histologically, the World Health Organization has classified pancreatic neuroendocrine neoplasms (p-NENs) into well-differentiated pancreatic neuroendocrine tumors (G1/G2 p-NETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (G3 p-NECs) based on tumor mitotic counts and Ki-67 index. Recently, the 8th edition of American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging manual has incorporated some major changes in 2017 that the TNM staging system for p-NENs should only be applied to well-differentiated G1/G2 p-NETs, while poorly-differentiated G3 p-NECs be classified according to the new system for pancreatic exocrine adenocarcinomas. However, this new manual for p-NENs has seldom been evaluated.Data of patients with both G1/G2 and G3 non-functional p-NENs (NF-p-NENs) from our institution was retrospectively collected and analyzed using 2 new AJCC 8th staging systems. We also made survival comparisons between the 8th and 7th edition system separately for different subgroups.For G1/G2 NF-p-NETs, there were 52 patients classified in AJCC 8th edition stage I, 40 in stage II, 41 in stage III and 19 in stage IV. As for G3 NF-p-NECs, 17, 19, 24, and 18 patients were respectively defined from AJCC 8th edition stage I to stage IV. In terms of the AJCC 7th staging system, the 230 patients with NF-p-NENs were totally distributed from stage I to stage IV (94, 63, 36, 37, respectively). For the survival analysis of both G1/G2 NF-p-NETs and G3 NF-p-NECs, the AJCC 7th edition system failed to discriminate the survival differences when compared stage III with stage II or stage IV (P > .05), while the 8th edition ones could perfectly allocate patients into 4 statistically different groups (P < .05). The HCIs of AJCC 8th stage for G1/G2 NF-p-NETs [HCI=0.658, 95% confidence interval (CI)=0.602-0.741] and stage for G3 NF-p-NECs (HCI=0.704, 95% CI=0.595-0.813) was both statistically larger than those of AJCC 7th stage for different grading NF-p-NENs [(HCI=0.578, 95% CI=0.557-0.649; P=.031), (HCI=0.546, 95% CI=0.531-0.636; P = .019); respectively], indicating a more accurate predictive ability for the survivals of NF-p-NENs.Our data suggested the 2 new AJCC 8th staging systems were superior to its 7th edition for patients with both G1/G2 NF-p-NETs and G3 NF-p-NECs.

Project description:ImportanceNo previous studies to date have validated the American Joint Committee on Cancer (AJCC) 8th edition of the TNM classification for orbital sarcoma.ObjectivesTo determine the prognostic performance of the most recent TNM classification for orbital sarcoma and to identify other prognostic factors for local recurrence, lymph node metastasis, distant metastasis, and death due to disease.Design, setting, and participantsThis single-center retrospective cohort study included 73 consecutive patients treated for orbital sarcoma from March 1, 2003, through June 30, 2018. Data were analyzed from November 1 to December 31, 2018.Main outcomes and measuresT and N categories at presentation and disease-related outcomes, including local recurrence, lymph node metastasis, distant metastasis (DM), and death due to disease (DD).ResultsThe 73 participants included 43 men (59%), and the median age was 21 (range, 0-77) years. The common histologic types were rhabdomyosarcoma (RMS) (35 [48%]), solitary fibrous tumor/hemangiopericytoma (10 [14%]), and Ewing sarcoma (8 [11%]). The most common TNM designations were T2 N0 M0 (26 [36%]) and T4 N0 M0 (24 [33%]). T category was associated with the risk of all disease-related outcomes, including local recurrence (hazard ratio [HR] for T2 vs T4, 0.22 [95% CI, 0.06-0.81]; HR for T3 vs T4, 0.59 [95% CI, 0.13-2.65]; P = .03), lymph node metastasis by the last follow-up (T1, 1 [14%]; T2, 0; T3, 0; T4, 12 [35%]; P = .001), DM (HR for T2 vs T4, 0.29 [95% CI, 0.08-1.07]; P = .04), and DD (HR of T2 vs T4, 0.16 [95% CI, 0.04-0.73]; HR of T3 vs T4, 0.30 [95% CI, 0.04-2.34]; P = .02). Higher risk of DM and higher risk of DD were associated with disease category of at least T3 (HR for DM, 3.24 [95% CI, 0.89-11.72; P = .06]; HR for DD, 6.32 [95% CI, 1.43-27.95; P = .005]), N1 disease (HR for DM, 13.33 [95% CI, 4.07-43.65; P < .001]; HR for DD, 7.07 [95% CI, 2.45-20.44; P < .001]), tumor size larger than 3 cm (HR for DM, 2.72 [95% CI, 0.92-8.05; P = .06]; HR for DD, 5.79 [95% CI, 1.85-18.14; P < .001]), and age of patient with RMS younger than 1 year or 10 years or older (HR for DM, 6.85 [95% CI, 0.83-56.53; P = .04]; HR for DD, 7.03 [95% CI, 0.85-57.83; P = .04]). Higher risk of local recurrence was associated with disease category of at least T3 (HR for<T3 vs≥T3, 0.20 [95% CI, 0.06-0.71]; P < .01) and tumor size greater than 3 cm (HR for ≤3 cm vs >3 cm, 0.27 [95% CI, 0.09-0.77]; P = .009). Higher risk of lymph node metastasis was associated with disease category of at least T3 (odds ratio [OR], 13.33 [95% CI, 1.77-602.30]; P = .004), alveolar RMS (OR, 9.98 [95% CI, 2.13-51.55]; P = .001), and age of patient with RMS younger than 1 year or 10 years or older (OR, 9.20 [95% CI, 1.01-458.29] P = .03).Conclusions and relevanceIn patients with orbital sarcoma, T and N categories at presentation (defined by the AJCC 8th edition classification) correlate with metastasis and survival. These findings appear to support consideration of strict surveillance testing for regional nodal and systemic metastases in patients with orbital sarcoma with disease category of at least T3 and/or N1 disease.

Project description:ImportanceThe recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international validation.ObjectiveTo validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma.Design, setting, and participantsThis international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018.ExposuresPatients were retrospectively staged according to the seventh and eighth editions of the TNM staging system.Main outcomes and measuresPrognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics.ResultsA total of 1525 consecutive patients were included (median [IQR] age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P < .001) via classification with the seventh edition to 39.2% for patients in stage IA, 33.9% in IB, 27.6% in IIA, 21.0% in IIB, and 10.8% in stage III (log-rank P < .001) with the eighth edition. For patients who were node negative, the T stage was not associated with prognostication of survival in either edition. In the eighth edition, the N stage was associated with 5-year survival rates of 35.6% in N0, 20.8% in N1, and 10.9% in N2 (log-rank P < .001). The C statistic improved from 0.55 (95% CI, 0.53-0.57) for the seventh edition to 0.57 (95% CI, 0.55-0.60) for the eighth edition.Conclusions and relevanceThe eighth edition of the TNM staging system demonstrated a more equal distribution among stages and a modestly increased prognostic accuracy in patients with resected pancreatic ductal adenocarcinoma compared with the seventh edition. The revised T stage remains poorly associated with survival, whereas the revised N stage is highly prognostic.

Dataset Information

Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and N Staging in Patients With Pancreatic Adenocarcinoma.

Publications

Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and N Staging in Patients With Pancreatic Adenocarcinoma.

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