A comprehensive validation of the novel 8th edition of American Joint Committee on Cancer staging manual for the long-term survivals of patients with non-functional pancreatic neuroendocrine neoplasms.
ABSTRACT: 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?
Project description:Method Data of patients who were surgically treated and clinicopathologically diagnosed as (MH)-NENs secondary to (GEP)-NENs at West China Hospital of Sichuan University from January 2006 to December 2018 were retrospectively collected and analyzed by the grading classification for (GEP)-NENs. Results We identified 150 patients with (MH)-NENs secondary to (GEP)-NENs, including 10 patients with G1 NETs, 26 with G2 NETs, 33 with G3 NETs, and 81 with G3 NECs. There were significant differences between patients with G1/G2/G3 NETs and those with G3 NECs, such as age at diagnosis (P=0.041), synchronous liver lesion (P=0.032), incidental diagnosis (P=0.014), tumor largest diameter (P=0.047), vascular invasion (P=0.017), and extrahepatic metastatic disease (P=0.029). The estimated 3-year overall survival for patients with G1 NETs, G2 NETs, G3 NETs, and G3 NECs was 100%, 79.4%, 49.5%, and 20.7%, respectively (P < 0.001). The survival of G1 NETs or G2 NETs was significantly better than that of G3 NETs (P=0.013, P=0.037, respectively) and G3 NECs (P=0.001, P < 0.001; respectively). Patients with G3 NECs present notably worse survival than those with G3 NETs (P=0.012), while survival comparison between G1 NETs and G2 NETs was not statistically different (P=0.131). The grading classification for (GEP)-NENs was an effective independent predictor of survival for (MH)-NENs secondary to (GEP)-NENs (hazard ratio: 4.234; 95% confidence intervals: 1.984–6.763; P=0.003). Conclusion Our demonstration revealed that the grading classification for (GEP)-NENs could well stratify (MH)-NENs secondary to (GEP)-NENs into prognostic groups and supported its wide use in clinical practice.
Project description:BACKGROUND:Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a complex family of tumors of widely variable clinical behavior. The World Health Organization (WHO) 2010 classification provided a valuable tool to stratify neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the proliferation index. However, substantial heterogeneity remains within these subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic stratification. The purpose of our study was to evaluate the prognostic impact of histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories, and explore additional Ki-67 cutoff values in GEP-NENs. SUBJECTS, MATERIALS, AND METHODS:A total of 2,813 patients from the Spanish National Tumor Registry (RGETNE) were analyzed. Cases were classified by histological differentiation as NETs (neuroendocrine tumors [well differentiated]) or NECs (neuroendocrine carcinomas [poorly differentiated]), and by Ki-67 index as G1 (Ki-67 <2%), G2 (Ki-67 3%-20%), or G3 (Ki-67 >20%). Patients were stratified into five cohorts: NET-G1, NET-G2, NET-G3, NEC-G2, and NEC-G3. RESULTS:Five-year survival was 72%. Age, gender, tumor site, grade, differentiation, and stage were all independent prognostic factors for survival. Further subdivision of the WHO 2010 grading improved prognostic stratification, both within G2 (5-year survival: 81% [Ki-67 3%-5%], 72% [Ki-67 6%-10%], 52% [Ki-67 11%-20%]) and G3 NENs (5-year survival: 35% [Ki-67 21%-50%], 22% [Ki-67 51%-100%]). Five-year survival was significantly greater for NET-G2 versus NEC-G2 (75.5% vs. 58.2%) and NET-G3 versus NEC-G3 (43.7% vs. 25.4%). CONCLUSION:Substantial clinical heterogeneity is observed within G2 and G3 GEP-NENs. The WHO 2010 classification can be improved by including the additive effect of histological differentiation and the proliferation index. IMPLICATIONS FOR PRACTICE:Gastroenteropancreatic neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly stratified by the World Health Organization (WHO) 2010 classification into three subgroups based on proliferation index. Real-world data from 2,813 patients of the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further subdivision of grading substantially improves prognostic stratification of these patients and may help individualize therapy. This combined, additive effect shall be considered in future classifications of neuroendocrine tumors and incorporated for stratification purposes in clinical trials.
Project description:<h4>Background</h4>Although re-assessment of proliferative activity by K67 evaluation during the course of neuroendocrine neoplasms (NENs) is recommended in selected patients, its impact on patients' management is not clear due to the lack of data supporting this practice.<h4>Aim</h4>To investigate Ki67 change at time of progressive disease (PD) in entero-pancreatic NENs (EP-NENs).<h4>Patients and methods</h4>Retrospective analysis of sporadic EP-NENs which received histological re-assessment after PD once radiologically documented.<h4>Results</h4>Forty-three patients were evaluated, including 24 pancreatic NENs (PNENs), and 19 small intestine NENs (SI-NENs). At time of initial histological evaluation, 19 patients had grade 1 (G1) NETs (44.2%), and 24 grade 2 (G2) NETs (55.8%), overall median Ki67 being 3% (range 1%-20%). At time of PD, 13 patients had G1 NETs (30.2%), 26 G2 NETs (60.5%), and 4 had grade 3 (G3) NECs (9.3%), thus resulting in a significant median Ki67 increase (8%, range 1%-70%; p = 0.0006), and a G upgrading in 12 patients (27.9%). A statistically significant Ki67 increase and G grading change at time of PD was observed in PNENs (p = 0.0005 and p = 0.028, respectively). Conversely, no statistically significant change occurred in non-PNENs.<h4>Conclusions</h4>In PNENs with documented PD, Ki67 increase occurs in a significant proportion of patients, providing useful information necessary to choose appropriate therapeutic options.
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: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: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:Background:Preoperative staging of pancreatic cancer determines the choice of treatment. Magnetic resonance imaging (MRI) plays an important role in preoperative staging of pancreatic cancer. The American Joint Committee on Cancer (AJCC) TNM staging system was revised to its 8th version in 2016, there has been no report correlating the 8th edition of the AJCC TNM staging with preoperative MRI examinations and pathological findings. The purpose of our study is to determine the staging accuracy and evaluate the resectability by using MRI about pancreatic cancer compared with intraoperative or pathological findings according to the 8th edition of the AJCC TNM staging system. Methods:One hundred thirty-two patients with a pathological diagnosis of pancreatic cancer who underwent preoperative MRI were identified. The clinical data, MRI findings and pathological findings were analyzed. Preoperative MRI staging and resectability evaluation were compared with pathological findings. The accuracy of MRI for preoperative T and N staging was evaluated, and the sensitivity, specificity and accuracy of MRI in evaluating the resectability were assessed. All the staging and resectability assessments were according to the 8th edition of the AJCC TNM staging system. Results:Analysis showed that the accuracy of MRI for evaluation of the T and N stages was 82.6% (109/132) and 74.2% (98/132), respectively. The sensitivity and specificity of MRI in assessing the resectability were 94.2% and 71.4%, respectively. Integrating the 8th edition of the AJCC TNM stage, no significant differences were identified between the preoperative MRI and pathological results for the staging of pancreatic cancer (P=0.805). Conclusions:MRI is highly accurate for T staging and moderately accurate for N staging. MRI provides important preoperative evaluation of the stage and resectability of pancreatic cancer based on the 8th edition of the AJCC TNM staging system.
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.