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Improving the AJCC/TNM staging for adenocarcinomas of the appendix: the prognostic impact of histological grade.

ABSTRACT: Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas, the prognostic impact of grade in localized disease, and the validity of the American Joint Committee on Cancer AJCC Staging Manual 7th edition's decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known.Patients with adenocarcinoma of the appendix diagnosed between 1988 and 2007 were identified from the SEER database. Cancer-specific survival (CSS) stratified by histological subtype, stage, and grade was calculated, and Cox proportional hazards regression analyses were performed.We analyzed a total of 2469 appendiceal adenocarcinomas, of which 1375 had mucinous histology and 860 had nonmucinous histology. Though overall CSS was similar for mucinous and nonmucinous subtypes, differences in stage distribution and stage-stratified CSS were seen. Female sex, stage IV disease, and well-differentiated histology were more common for mucinous adenocarcinomas. Histological grade had a strong prognostic impact, especially in patients with stage IV mucinous adenocarcinoma. The adjusted hazard ratios for stage IV moderately and poorly differentiated histological grade were 1.63 [95% confidence interval (CI): 1.14-2.34] and 4.94 (95% CI: 3.32-7.35) for mucinous histology, in comparison with 1.44 (95% CI: 0.82-2.52) and 1.90 (95% CI: 0.95-3.80) for nonmucinous histology, respectively.The strong prognostic impact of histological grade for mucinous adenocarcinomas is primarily restricted to stage IV disease. Stage IV moderately and poorly differentiated mucinous adenocarcinomas have distinctly different CSS and these data do not support the combination of these 2 histological grades in the recent AJCC Staging Manual 7th edition.

SUBMITTER: Overman MJ

PROVIDER: S-EPMC3855996 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Improving the AJCC/TNM staging for adenocarcinomas of the appendix: the prognostic impact of histological grade.

Overman Michael J MJ Fournier Keith K Hu Chung-Yuan CY Eng Cathy C Taggart Melissa M Royal Richard R Mansfield Paul P Chang George J GJ

Annals of surgery 20130601 6

<h4>Purpose</h4>Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas, the prognostic impact of grade in localized disease, and the validity of the American Joint Committee on Cancer AJCC Staging Manual 7th edition's decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known.<h4>Methods</h4>Patients with adenocarcinoma of the appendix diagnosed between ...[more]

PMID: 23001080

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Project description:BackgroundIn 2017, the New South Wales Cancer Registry (NSWCR) participated in a project, supported by Cancer Australia, aiming to provide national stage data for melanoma, prostate, colorectal, breast, and lung cancers diagnosed in 2011. Simplified business rules based on the American Joint Committee for Cancer (AJCC) Tumour-Node-Metastasis (TNM) stage were applied to obtain Registry-Derived (RD) stage, defined as the best estimate of TNM stage at diagnosis using routine notifications available within cancer registries. RD-stage was compared with Degree of Spread (DoS), which has been recorded for all applicable cancers in NSWCR at a population-based level since 1972, and a summary AJCC-TNM stage group, which has been collected variably since 2006. For each of the five high incidence cancers, we compared the level of improvements RD-staging provided in terms of completeness and accuracy (alignment to more clinically relevant AJCC-TNM) over DoS.MethodsFor each of the five cancers, stage data were extracted from NSWCR pre- and post- RD-staging to compare data completeness across all three staging systems. The alignment between DoS/RD-stage and AJCC-TNM was compared, as were the expected and observed cross-tabulated frequency distributions using a subset of NSWCR data. To determine differences between use of DoS, RD-stage, and AJCC-TNM in an epidemiological analysis, we compared survival models developed from each of the three stage variables.ResultsWe found RD-staging provided greatest stage data completeness and alignment to AJCC-TNM for prostate cancers, followed by breast, then melanoma and lung cancers. For colorectal cancer, summary stage from DoS was confirmed as an equivalent surrogate staging system to both AJCC-TNM and RD-stage.ConclusionsThis analysis provides an evidence-based approach that can be used to inform decision-making for resource planning and potential implementation of a new stage data field in population-based cancer registries.

Project description:BackgroundThe TNM staging criteria for gastric carcinoma have seen numerous revisions, the most recent of which are reflected in the seventh edition AJCC TNM cancer staging manual.MethodsA retrospective evaluation of the sixth and seventh TNM classification of gastric cancer on a prospective database, regarding patients operated on for primary gastric cancer, was conducted. The end point of the study was prognosis evaluation in terms of overall survival.Patients operated on for primary gastric cancer between September 2003 and March 2012 at our Department of Emergency and General Surgery, were consecutively retrieved in this study; a total of 114 patients were considered. Cardia gastric cancers, gastric lymphomas and gastrointestinal stromal tumors (GIST) were excluded. Median and mean follow-up periods were 22.5 and 27.7 months (range 15 days to 5 years). Both TNM6 and TNM7 were used to evaluate our patients. Overall survival and survival rates at different stages were analyzed using the Kaplan-Meier method and differences were determined using a log-rank test. Cox's proportional hazard model was used to identify significant factors related to prognosis in a multivariate analysis.ResultsOverall survival between the sixth and seventh TNM classification was not significantly different. Both the Kaplan-Meier analysis and the multivariate analysis showed that the major negative prognostic factor was lymphovascular invasion (P<0.001 in the univariate analysis and P=0.035 to 0.048 in the multivariate analysis). Stage distribution and stage-related survival changed from the sixth to the seventh edition, especially in T3 stage where median survival for the sixth edition was 720 days versus 1,200 days for the seventh edition. Moreover, differences were shown in the survival rate of N1 versus N2 stages within the seventh TNM.ConclusionsEven though further studies are needed in order to increase the number of patients studied, the seventh edition seems to provide a more accurate prognosis, especially regarding N1 and N2 tumors, showing that the most important prognostic factor is lymphovascular invasion.

Project description:BackgroundAppendiceal cancer (AC) patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often demonstrate an unpredictable variability in their survival outcomes. Biomarkers predictive of CRS/HIPEC efficacy could better guide treatment decisions. We hypothesized that variation in the transcriptional programming of AC tumors might distinguish molecular subtypes with differential outcomes after CRS/HIPEC.Study designGene expression profiles of 2 AC cohorts were analyzed using Affymetrix whole-genome expression microarrays. Hierarchical clustering methods, Kaplan-Meier analysis, and Cox regression models were used to discover and validate prognostic molecular subtypes of AC. Gene set enrichment analysis was used to infer pathologic attributes of the molecular subtypes.ResultsUnsupervised hierarchical clustering analysis of tumor expression profiles revealed a 139-gene cassette that distinguished 2 molecular subtypes (based on low vs high expression of the gene cassette) with statistically significant survival differences (disease-specific survival, p = 0.0075; progression-free survival, p = 0.0072). In a second AC cohort, the 139-gene cassette reproducibly partitioned tumors into subtypes with significant survival differences. Tumors showing high relative expression of the genes comprising the cassette associated with poor survival outcomes (disease-specific survival, p = 0.047; progression-free survival, p = 0.0079), and exhibited gene expression patterns enriched for oncogenic processes and pathways. The prognostic value of the molecular subtypes was specific for low-grade appendiceal tumors (disease-specific survival, p = 0.028; progression-free survival, p = 0.0016), and remained significant in the presence of conventional prognostic markers, including grade, surgical resection score, Eastern Cooperative Oncology Group status, and age.ConclusionsThe 139-gene cassette can have actionable clinical utility for identifying low-grade appendiceal tumor molecular subtypes predictive of therapeutic efficacy of CRS/HIPEC.

Project description:The aim of our study was to explore the value of the 8th edition TNM staging system on evaluating the prognosis of colorectal carcinoid. Colorectal carcinoid patients between 1988 and 2015 were selected in the Surveillance, Epidemiology, and End Results Program (SEER) database for analysis. About 4286 patients with colorectal carcinoid tumors were identified, of which were carcinoid tumor NOS (n = 1726), neuroendocrine carcinoma (NEC) (n = 1346) and other carcinoid tumor (OCT) (n = 591). Worsening 10-year CSS rates with increasing N status, M status, and SEER historic stage were demonstrated across all three above groups (all P < .05). In carcinoid tumor NOS, significant differences in CSS were found with increasing combined 8th AJCC stages (P < .001), except for that between stage II and stage III (10-year CSS rate: 82.6% vs 84.3%, P = .68). While combined 8th TNM stage in NEC and OTC exhibited greater separations in CSS despite on-going overlaps between groups. For carcinoid tumor NOS, stage II (HR = 3.37; 95% CI: 0.97-11.76), and stage III (HR = 2.09; 95% CI: 0.51-8.66) conferred no significant difference in CSS compared with stage I, while stage IV had an increasing HR of 5.09 (95% CI: 1.08-24.08). Although combined 8th AJCC stage had a good ability to distinguish 10-year CSS of patients with NEC or OCT, detailed 8th AJCC stage did not seem to be applicable. Detailed 8th AJCC categories of advanced stages in all the three groups conferred increased HRs with overlapping CIs. However, in the early and middle status, HRs did not increase with the increase of stages, or there was no difference in HRs between adjacent stages. Combined 8th TNM stage was not practical for judging the survival outcomes of colorectal carcinoid tumor NOS, especially in patients with stages II and III, but it provided useful prognostic information for NEC and OCT. However, for all carcinoid tumors, the prognostic values of detailed 8th AJCC stage were not enough accurate in the clinic. More optimized staging methods should be developed and validated in the future.

Dataset Information

Improving the AJCC/TNM staging for adenocarcinomas of the appendix: the prognostic impact of histological grade.

Publications

Improving the AJCC/TNM staging for adenocarcinomas of the appendix: the prognostic impact of histological grade.

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