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Abstract Context Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors. Metastases develop in 15% to 20%. The American Joint Committee on Cancer (AJCC) established inaugural guidelines for PPGL tumor-node-metastasis (TNM) staging. Objective The objective of this analysis is to investigate the associations between TNM staging and overall survival (OS). Methods We retrospectively applied the TNM staging at the time of diagnosis of the primary tumor. The primary outcome was OS. Unadjusted survival rates were estimated by the Kaplan–Meier method. Cox proportional hazards regression models were used to evaluate the associations between OS and covariates of interest. Results The study included 458 patients. Median OS was 18.0 (95% CI, 15.6-not reached) years. At diagnosis, 126 (27.5%) tumors were stage I, 213 (46.5%) were stage II, 47 (10.3%) were stage III, and 72 (15.7%) were stage IV. The 10-year OS probabilities were 0.844 (95% CI, 0.768-0.928) for patients with stage I tumors, 0.792 (95% CI, 0.726-0.865) for stage II, 0.595 (95% CI, 0.435-0.813) for stage III, and 0.221 (95% CI, 0.127-0.384) for stage IV. Compared with stage I, the hazard ratios (HR) for death were 1.50 (0.87-2.57) for stage II, 2.85 (1.45-5.63) for stage III, and 8.88 (5.16-15.29) for stage IV (P < 0.001). Compared with patients with no germline mutations, those with RET 634/918 had better OS (HR: 0.28; 95% CI, 0.12-0.69). Other germline mutations, including SDHB, did not exhibit worse OS than patients with metastasis and sporadic disease. Conclusion OS rates correlated with the recently developed AJCC TNM staging and were not worse in hereditary disease. Stage IV disease exhibited a significantly shorter OS compared with stages I-III. Future staging systems could be adjusted to better separate stages I and II.

BackgroundThe AJCC 8th edition stratifies stage IV disseminated appendiceal cancer (dAC) patients based on grade and pathology. This study was designed to externally validate the staging system and to identify predictors of long-term survival.MethodsA 12-institution cohort of dAC patients treated with CRS ± HIPEC was retrospectively analyzed. Overall survival (OS) and recurrence-free survival (RFS) were analyzed by using Kaplan-Meier and log-rank tests. Univariate and multivariate cox-regression was performed to assess factors associated with OS and RFS.ResultsAmong 1009 patients, 708 had stage IVA and 301 had stage IVB disease. Median OS (120.4 mo vs. 47.2 mo) and RFS (79.3 mo vs. 19.8 mo) was significantly higher in stage IVA compared with IVB patients (p < 0.0001). RFS was greater among IVA-M1a (acellular mucin only) than IV M1b/G1 (well-differentiated cellular dissemination) patients (NR vs. 64 mo, p = 0.0004). Survival significantly differed between mucinous and nonmucinous tumors (OS 106.1 mo vs. 41.0 mo; RFS 46.7 mo vs. 21.2 mo, p < 0.05), and OS differed between well, moderate, and poorly differentiated (120.4 mo vs. 56.3 mo vs. 32.9 mo, p < 0.05). Both stage and grade were independent predictors of OS and RFS on multivariate analysis. Acellular mucin and mucinous histology were associated with better OS and RFS on univariate analysis only.ConclusionsAJCC 8th edition performed well in predicting outcomes in this large cohort of dAC patients treated with CRS ± HIPEC. Separation of stage IVA patients based on the presence of acellular mucin improved prognostication, which may inform treatment and long-term, follow-up strategies.

BackgroundThe American Joint Committee on Cancer (AJCC) recently released its 8th edition staging system, which created a separate staging system for gastric cancer patients who have undergone preoperative therapy (ypStage). The objective of this retrospective study was to apply the new ypStage to patients who have undergone preoperative therapy and potentially curative gastrectomy.MethodsWe collected data from a prospectively maintained institutional database of gastric cancer patients who underwent potentially curative gastrectomy after preoperative therapy (1995–2015). Kaplan–Meier survival estimations and log-rank tests were performed to compare survival. Univariable and multivariable analyses were performed to determine risk factors for overall survival.ResultsA total of 354 patients met our criteria. Most patients completed planned preoperative therapy (94%; 332/354) and received chemoradiation therapy (75%; 265/354). Although clinical stage (cStage) provided a poor discrimination of survival, postneoadjuvant pathological stage (ypStage) identified significant variation in survival (p < 0.001). Multivariable analysis showed the following factors were associated with survival after adjustment for ypStage: Asian race (HR 0.52; p = 0.028), linitis plastica (HR 1.66; p = 0.037), and R1 resection (HR 1.91; p = 0.016). Survival was not longer in ypT0N0 patients than in ypStage I patients (HR 1.29; p = 0.377).ConclusionsThe AJCC 8th edition staging system for gastric cancer demonstrated reasonable survival prediction by ypStage, but not cStage, in patients who had undergone preoperative therapy. ypT0N0 patients, although not defined in the 8th edition, may be considered for inclusion in the ypStage I group.

BackgroundOur aim was to validate the American Joint Committee on Cancer (AJCC) 8th edition stage system for gastric cancer in the Western world and to compare several modifications between the 7th and 8th edition systems.MethodsEligible patients having undergone surgical resection of gastric cancer during 2004–2011 from the Surveillance, Epidemiology, and End Results (SEER) database were included in the current study. Survival differences were assessed by Kaplan–Meier curve and log-rank tests. The discriminative power of the AJCC 8th and 7th editions was compared by Harrell’s concordance index (c-index).ResultsPatients with pN3a and pN3b presented distinct survival outcomes, especially for cases in which more than 15 lymph nodes were examined. The overall (OS) and cancer-specific survival (CSS) c-indices for the 8th edition were largely comparable with c-indices for the 7th edition throughout the cohort. Notably, the new edition improved the power of discrimination slightly in OS and CSS (c-indices: 0.717, 0.744) compared with the 7th edition (c-indices: 0.712, 0.739) for patients for whom 15 or more lymph nodes were examined. The analysis of stage migration in the new edition revealed nonhomogeneous survival outcomes in stages IIIB and IIIC.ConclusionThe AJCC 8th stage system for gastric cancer performs as well as the AJCC 7th edition in the United States (USA). Importantly, when more than 15 lymph nodes are examined, the discriminatory performance of the new edition is improved.

PurposeThe new eighth edition TNM classification by the AJCC for breast cancer (BC) incorporates biologic factors and gene expression prognostic panels, in addition to traditional anatomic factors. In this study, we evaluated the prognostic value of this new staging system compared to the previous AJCC 7th edition staging system.MethodsWe conducted a retrospective analysis of women with stage I, II, or III BC who underwent curative surgery with/without adjuvant systemic therapy at Samsung Medical Center between July 2004 and December 2008.ResultsOf 3,208 BCs, this study was analyzed using the information of 2,790 BC patients. Hormone receptor-positive (HR+) and human epidermal growth factor 2 (HER2)− BCs were observed in 62.9% of BCs, HR+/ HER2+ in 9.3%, HR−/HER2− in 17.0%, and HR−/HER2+ in 10.8%. In survival analysis, we observed 245 distant recurrences and 198 deaths caused by BC progression. The median follow-up duration was 116.2 months. 10-year disease-specific survival (DSS) rates according to the AJCC 7th edition criteria were 97.2% of stage IA, 100% of IB, 94.9% of IIA, 87.9% of IIB, 86.4% of IIIA, 95.7% of IIIB, and 65.7% of IIIC (p < 0.001). After applying 8th edition criteria, the 10-year DSS rates were 98.1% of stage IA, 97.7% of IB, 93.8% of IIA, 92.7% of IIB, 88.2% of IIIA, 80.8% of IIIB, and 70.3% of IIIC (p < 0.001).ConclusionsThe AJCC 8th edition clinical staging system provides a good prognostic value and addresses the weakness of the AJCC 7th edition, which uses only anatomical pathologic staging.

BackgroundThe eighth edition of AJCC cancer staging manual incorporated biomarker status into the prognostic staging group (PSG). We used data from National Cancer Database (NCDB) to validate and improve the PSG.MethodsAll patients had surgery and at least some systemic treatment (endocrine therapy, chemotherapy or HER2 targeted therapy). Information from 420,520 patients was assessed for potential predictors of overall survival (OS), including age at diagnosis (age), tumor grade (G), hormonal receptor and HER2 status, and presence of lymph vascular invasion (LVI), stratified by stage or sub-stages. Based on the multivariate Cox analyses, we built different point systems to predict OS and evaluated the different point systems by Akaike’s information criterion (AIC), Harrell’s concordance index (C-index), and Uno’s concordance index.ResultsAge, G, hormonal receptor and HER2 status, LVI and being TNBC were significantly associated with OS (all P < 0.0001). Three staging systems were correlated with OS: system 1 was the conventional anatomic TNM staging; system 2 included TNM, age, G, hormonal receptor, HER2, and LVI; system 3 included TNM, age, G, TNBC versus non-TNBC, and LVI. System 3 (C-index; 0.7316; AIC: 488138.91) achieved the best balance between predictive performance and goodness-of-fit to the NCDB data as compared to system 2 (C-index: 0.7325; AIC: 498087.73) and system 1 (C-index: 0.716; AIC: 688536.49).ConclusionsThe new PSG is a better staging system than the conventional anatomic TNM system. Grouping breast cancer into TNBC versus non-TNBC may be simpler while retaining similar accuracy as using ER/PR/HER2 status to predict OS.

Background We retrospectively compared the prognostic value between the AJCC 8th edition anatomic (AS) and prognostic staging (PS) system for triple negative breast cancer (TNBC) in a cohort from two involved institutions and a large population database. Methods Clinicopathological data of TNBCs were identified in two involved institutions (SYSUCC-PWH cohort). Data from SEER database during 2010–2015 was also accessed. We restaged all cases into AS and PS group according to the AJCC 8th staging system. Results A total of 611 and 31,941 TNBCs were identified in two cohorts, with a median follow-up of 53.5 and 27 months respectively. PS upstaged 46.1% of patients in SYSUCC-PWH cohort, and 62.4% in SEER cohort. No significant difference was observed in C index between AS and PS models for disease-specific survival (DSS), progression-free survival (PFS) or overall survival (OS) in either cohort. χ2 statistic and Hazard Ratio for PFS, DSS and OS showed better discrimination between IA and IB, IIB and IIIA, IIIA and IIIB in AS model than PS model. Besides, patients with IIIC unchanged stage showed worse PFS compared to those with AS IIIA or IIIB upstaged to PS IIIC in both cohorts( p  = 0.049, p  < 0.001). Conclusions Our findings demonstrated that prognostic staging system did not provide better discriminatory ability in predicting TNBCs prognosis than anatomic staging system.

One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (≤ 4 cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5 mm and 10 mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2 mm to upstage to T2 and 4 mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12–4.99) and disease-free survival (HR 2.12, 95% CI 1.09–4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27–7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs.

Background Well-differentiated thyroid carcinoma is defined as locally advanced in the presence of an extra thyroid extension, e.g., when the surrounding structures such as the trachea, larynx, esophagus and main blood vessels are invaded by cancer. The 8th edition AJCC Cancer Staging Manual states that this is the main characteristic to evaluate for the staging and consequently for the prognosis in patients over 55 years old. Main body Distinguishing different forms of locally advanced thyroid cancer is essential, and the various anatomical structures and the clinical and therapeutic consequences must be taken into account. An accurate diagnosis of the organs invaded by thyroid cancer is necessary for the planning of surgical treatment, and both aspects are crucial to improving the patients’ survival. Patients affected by thyroid cancer with extra thyroid extension have a poor prognosis and the removal of the entire neoplasm represents a key factor for better disease-free survival. Conclusions We discuss the changes introduced by the 8th edition AJCC Cancer Staging Manual, in terms of the diagnostic and surgical management of extra thyroid extension, in patients affected by papillary and follicular thyroid cancer.

The AJCC 8th edition has included depth of invasion as per the new CAP guidelines as an independent measure of T staging irrespective of tumour size. This aim of this study was to look at the correlation between depth of invasion measured by the new guidelines and neck nodal positivity rate in cases of carcinoma of the tongue. We performed a case series analysis of 131 cases of carcinoma tongue who underwent wide excision and neck dissection at a tertiary cancer care centre in North Kerala, India. Depth of invasion was reported as per the new CAP/AJCC guidelines and its correlation with lymph node positivity rate was assessed. We also looked at the upstaging caused by the addition of depth of invasion to T staging in the AJCC 8th edition. Lymph node positivity correlates well with depth of invasion, and the coefficient of correlation was 0.89 in our study. The lymph node positivity rate exceeded 15% when the depth of invasion exceeded 4 mm. 59.5% of T1 tumours and 28.5% of T2 tumours were upstaged when AJCC 8th edition TNM staging was used instead of 7th edition. Depth of invasion correlates well with lymph node positivity and the addition of depth of invasion in AJCC 8th edition results in upstaging compared to AJCC 7th.