Validation and modification of staging Systems for Poorly Differentiated Pancreatic Neuroendocrine Carcinoma.
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?
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:Background: Considerable modifications have been introduced in the new edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system. Based on the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, this study aimed to compare the 7th and 8th editions of the AJCC/UICC TNM staging system for patients with papillary thyroid microcarcinoma (PTMC) and follicular variant papillary thyroid microcarcinoma (FVPTMC). Methods: A Data from 2004 to 2014 of 39,032 patients registered in the SEER database were included. The 7th and 8th editions of the AJCC/UICC staging system were compared in terms of TNM staging, age cutoff, and clinical staging. Patient survival was evaluated using Kaplan-Meier and multivariable Cox proportional hazards models. The American Thyroid Association (ATA) risk stratification system was integrated with the AJCC/UICC staging system for further investigation. Receiver operating characteristic (ROC) curves, Harrell's C-index, Akaike information criterion (AIC), and the Bayesian information criterion (BIC) were used to assess the models' performances. Results: Revised TNM categories, age cutoff, and clinical staging in the 8th edition resulted in reclassification of the overall stage. Applying the 8th edition, 1,278 stage III and 425 stage IV patients were reclassified as stage I; 950 stage III and 459 stage IV patients were reclassified as stage II; 77 stage IV patients were reclassified as stage III; and only 88 patients remained in stage IV. All patients in stage I, according to the 7th edition, remained in this stage when using the 8th edition. Patients classified into higher stages (III and IV) in the 8th edition showed a worse prognosis than those classified into same stages in the 7th edition. The 8th edition proved to be a better model with higher prognostic efficacy survival (higher AUC and C-index, lower AIC and BIC) than the 7th edition. When integrated with the ATA risk stratification system, the 8th edition still showed better discriminative power for patients in the higher risk group. Conclusion: Based on the SEER database, the 8th edition of the AJCC/UICC staging system has better prognostic efficacy than the 7th edition for patients with PTMC and FVPTMC.
Project description:Purpose:The 8th edition of the American Joint Committee on Cancer (AJCC) staging manual introduced a new prognostic staging system for breast cancer. This study aimed to evaluate the changes in staging distribution and predictive power of the new staging system. Methods:Of the 12,275 patients with breast cancer identified from the Severance Breast Cancer Registry who underwent surgery between 1978 and 2016, 12,125 patients met the inclusion criteria. Results:In both the 7th and 8th staging systems, stage I patients constituted the largest proportion (38.2% and 48.4%). Migration from the 7th to 8th edition of the AJCC manual resulted in a decrease in stage II population and an increase in stage I and III populations. A total of 1,293 (15.4%) patients were upstaged, and 1,201 (14.3%) were downstaged. Downstaged patients had better recurrence-free and overall survival (p < 0.001). Pathologic complete response after neoadjuvant therapy showed good prognosis as p stage 0, and yp stages I and III showed poorer outcomes than the same p stage (p < 0.001). Conclusions:Staging migrations are common in early breast cancer under the prognostic staging system. The prognostic staging system of the 8th edition of the AJCC manual discriminates survival outcomes better than the anatomical staging system of the 7th edition of the AJCC manual.
Project description:Objective:To investigate the validity of the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system for gastric cancer. Methods:The clinicopathologic data of 7371 patients who were diagnosed with gastric cancer and had 16 or more involved lymph nodes (LNs) were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and retrospectively reviewed. Results:Stage migration occurred primarily during stage III between the 7th and 8th edition TNM staging systems. Stages IIIB and IIIC in the 7th edition staging system were divided in the 8th edition and had obvious differences in survival rates (both P < 0.001). The 8th edition TNM stages IIIC and IV showed similar survival rates (P = 0.101). The prognosis of patients with T4aN3bM0 was not different from that of patients with TxNxM1 (P = 0.433), while the prognosis of patients with T4bN3bM0 was significantly poorer than that of patients with TxNxM1 (P = 0.008). A revised TNM system with both T4aN3bM0 and T4bN3bM0 incorporated into stage IV was proposed. Multivariable regression analysis showed that the revised TNM system, but not the 7th and 8th editions, was an independent factor for disease-specific survival (DSS) in the third step of the analysis. Further analyses revealed that the revised TNM system had superior discriminatory ability to the 8th edition staging system, which was also an improvement over the 7th edition staging system. Conclusion:The 8th edition of the AJCC TNM staging system is superior to the 7th edition for predicting the DSS rates of gastric cancer patients. However, for better prognostic stratification, it might be more suitable for T4aN3bM0/T4bN3bM0 to be incorporated into stage IV in the 8th edition TNM staging system.
Project description:Background:The 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor-node-metastasis (TNM) staging system was released with major revisions. The purpose of this retrospective study was to investigate differences between the 7th and 8th editions of the AJCC/UICC TNM staging system and to compare the predictability of prognosis between the two staging systems with patients who underwent thyroidectomy for differentiated thyroid cancer (DTC) at a single institution. Methods:A total of 3238 patients underwent thyroid operation from January 2002 to December 2006 at Yonsei University Hospital (Seoul, Korea), of which 2294 with complete clinical data and sustained follow up were enrolled. Clinicopathologic features and TNM staging by applying the 7th and 8th editions of the AJCC/UICC were analyzed retrospectively by the complete review of medical charts and pathology reports of patients. Mean follow-up duration was 132.9?±?27.9?months. Results:A significant number of T3 patients were downstaged to T1 (838, 36.5%) and T2 (122, 5.3%). After applying the 8th edition of the AJCC/UICC TNM staging system, the number of stage?I patients increased significantly from 1434 (62.5%) to 2058 (89.7%), whereas numbers of stage III and IV patients decreased significantly from 644 (28.1%) to 33 (1.4%) and from 199 (8.7%) to 17 (0.7%), respectively. According to Kaplan-Meier survival analyses and values of the Harrell's c-index and integrated area under the curve (iAUC), the 8th edition has significantly better predictive performance for disease-free survival (DFS) and disease-specific survival (DSS) than the 7th edition. Conclusions:A significant population was downstaged after applying the 8th edition of the AJCC/UICC TNM staging system, and the 8th edition provided significantly better accuracy in predicting DFS and DSS in patients with DTC.
Project description:PURPOSE:Recently, the 8th edition staging system of the American Joint Committee on Cancer (AJCC) for hepatocellular carcinoma (HCC) was released, including a change in T category. We aimed to validate the new AJCC system. Materials and Methods:The predictive value of the new AJCC was validated in comparison to the previous edition, in a total 1,008 patients who underwent curative resection for HCC as initial treatment. RESULTS:The 2-year area under the curve values for recurrence-free survival (RFS) and overall survival (OS) were comparable in the 7th and 8th editions. Stage migration was observed in 63 patients (6.3%); from T2 to T1a for 44 patients and from T3 to T4 for 19 patients. The RFS and OS were not different between T1a and T1b in the 8th edition. For solitary tumors ? 2 cm, those with microvascular invasion had lower RFS and OS values than those without although they were all classified as T1a in the 8th edition. Tumors involving a major branch of the portal or hepatic vein (T4 by the 8th edition and T3b by the 7th edition) had shorter RFS and OS than multifocal tumors, at least one of which was > 5 cm (T3 by the 8th edition and T3a by the 7th edition). CONCLUSION:The AJCC 8th edition staging system for HCC showed comparable predictive performance to the 7th edition. It is desirable in a future revision to consider sub-stratification of solitary tumors ? 2 cm (T1a) depending on the presence of vascular invasion, which is not included in the 8th edition.
Project description:The 8th edition of the TNM was released in 2016 and included major revisions, especially for stage III. We aimed to compare the prognostic value of the 7th and 8th editions of the AJCC TNM classification for stage III gastric cancer. Clinical data from 1557 patients operated on for stage III gastric cancer according to the 7th edition between 2007 and 2014 were analyzed and compared using the 7th and 8th TNM classifications. A proposed staging system was established, and the three systems were compared in terms of prognostic performance. The stage shifted for 669 (42.96%) patients. It shifted from IIIA to IIIB (one patient, 0.06%), IIIB to IIIA (230 patients, 14.8%), IIIB to IIIC (94 patients, 6.0%), and IIIC to IIIB (344 patients, 22.1%). However, the new AJCC subgroupings did not prove distinctive for survival levels between T3N3aM0 (stage IIIB) and T3N3bM0 (stage IIIC) or between T4aN3aM0 (stage IIIB) and T4aN3bM0 (stage IIIC) when <30 lymph nodes (LNs) were resected. The performance of the 8th edition (c-index, 0.614; 95% confidence interval [CI], 0.596-0.633) revealed no relevant improvement compared to the 7th edition (c-index, 0.624; 95% CI, 0.605-0.643). The proposed staging system generated the best prognostic stratification. The 8th TNM edition may not provide better accuracy in predicting the prognosis of stage III gastric cancer. The proposed staging system, comprised of a combination of the number of LNs harvested and the 7th and 8th AJCC classifications, may improve predictive capacities for stage III gastric cancer.
Project description:PURPOSE:The purpose of this study was to compare prognostic differentiation performances of the 7th and the 8th edition of American Joint Commission on Cancer (AJCC) staging system for gastric cancer (GC) patients. Materials and Methods:A total of 1,633 GC patients who underwent curative D2 resection followed by adjuvant chemotherapy alone (CA) or concurrent chemo-radiotherapy (CCRT) from 2004 to 2013 were included. Concordance index (c-index) was applied to compare the discriminatory ability. RESULTS:In the 8th edition, migration of stage was detected in 248 patients (15.2%). Among them, 121 patients were up-staged while 127 patients were down-staged. Overall, there was no statistically significant difference in the discriminatory ability between the 7th and 8th editions. The new edition of staging system, however, showed a trend of better prognostic performance not only in recurrence-free survival (c-index=0.734; 95% confidence interval [CI], 0.706 to 0.762 in the 7th edition vs. c-index=0.740; 95% CI, 0.712 to 0.768 in the 8th edition; p=0.14), but also in overall survival (c-index=0.717; 95% CI, 0.688 to 0.745 in the 7th edition vs. c-index=0.722; 95% CI, 0.694 to 0.751 in the 8th edition; p=0.19), especially in stage III. This finding was repeated in the subgroup analysis regardless of adjuvant CA or CCRT. CONCLUSION:Generally, the 8th edition of AJCC staging system had failed to show a superior discriminatory ability for curatively D2 resected GC patients than the 7th edition, although there was a trend of better prognostic performance of the new edition, regardless of adjuvant treatment method.
Project description:Although several staging systems have been proposed for pancreatic neuroendocrine tumors (pNETs), the optimal staging system remains unclear. Here, we aimed to assess the application of the newly revised 8th edition American Joint Committee on Cancer (AJCC) staging system for exocrine pancreatic carcinoma (EPC) to pNETs, in comparison with that of other staging systems. We identified pNETs patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2014). Overall survival was analyzed using Kaplan-Meier curves with the log-rank test. The predictive accuracy of each staging system was assessed by the concordance index (c-index). Cox proportional hazards regression was conducted to calculate the impact of different stages. In total, 2424 patients with pNETs, including 2350 who underwent resection, were identified using SEER data. Patients with different stages were evenly stratified based on the 8th edition AJCC staging system for EPC. Kaplan-Meier curves were well separated in all patients and patients with resection using the 8th edition AJCC staging system for EPC. Moreover, the hazard ratio increased with worsening disease stage. The c-index of the 8th edition AJCC staging system for EPC was similar to that of the other systems. For pNETs patients, the 8th edition AJCC staging system for EPC exhibits good prognostic discrimination among different stages in both all patients and those with resection.
Project description:<h4>Objective</h4>We assessed the changes that have resulted from the latest breast cancer staging guidelines and the potential impact on prognosis.<h4>Background</h4>Contemporary data suggest that combining anatomic staging and tumor biology yields a predictive synergy for determining breast cancer prognosis. This forms the basis for the American Joint Committee on Cancer's (AJCC) Staging Manual, 8th edition. We assessed the changes that have resulted from the new staging guidelines and the potential impact on prognosis.<h4>Methods</h4>Women with stages I to III breast cancer from 2010 to 2014 in the National Cancer Data Base were pathologically staged according to the 7th and 8th editions of the AJCC Staging Manual. Patient characteristics and restaging outcomes were summarized. Unadjusted overall survival (OS) was estimated, and differences were assessed. Cox proportional-hazards models were utilized to estimate the adjusted association of stage with OS.<h4>Results</h4>After restaging the 493,854 women identified, 6.8% were upstaged and 29.7% were downstaged. The stage changes varied by tumor histology, receptor status, tumor grade, and Oncotype DX scores (all P < 0.0001). Applying the 8th edition criteria yielded an incremental reduction in survival for each increase in stage, which was not consistently seen in the 7th edition. In a subgroup analysis based on hormone receptor (HR) status, those with stages II and III, and HR- disease had a worse OS than those with HR+ disease.<h4>Conclusions</h4>Applying the 8th edition staging criteria resulted in a stage change for >35% of patients diagnosed with invasive breast cancer and refined OS estimates. Overall, the transition to the 8th edition is expected to better drive clinical care, treatment recommendations, and future research.