Validation of the AJCC 8th Edition Staging System for Disseminated Appendiceal Cancer Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Multi-institutional Analysis.

BACKGROUND: The 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. METHODS: A 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. RESULTS: Among 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. CONCLUSIONS: AJCC 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.

Definition of prognostic subgroups in the T3 stage of the eighth edition of the American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: Tentative T3 stage subclassification.

BACKGROUND: Although the eighth edition of the American Joint Committee on Cancer staging system (AJCC8) provides improved prognosis stratification of cutaneous squamous cell carcinoma (CSCC) over AJCC7, T3 has a variable prognosis. OBJECTIVE: To define prognostic subgroups in T3-AJCC8 CSCC. METHODS: Retrospective cohort study of 196 primary T3-AJCC8 CSCCs. We conducted multidimensional scaling analysis using the 6 risk factors that define T3 CSCCs. The prognoses of the groups obtained were analyzed by means of competing risk analysis. RESULTS: Group 1 was characterized by a tumor thickness greater than 6 mm (without invasion beyond the subcutaneous fat), alone or in combination with a tumor width of at least 4 cm. Group 2 was characterized by the presence of either invasion beyond the subcutaneous fat or by the involvement of nerves (≥0.1 mm, or deeper than the dermis). Group 3 was characterized by the combination of both T3b risk factors, or of 3 or more risk factors. Group 3 (tentatively named T3c) patients had the worst prognosis for disease-specific poor outcome events and major events, Group 2 (T3b) had intermediate risk, and Group 1 (T3a) had the best prognosis (disease-specific poor outcome events: hazard ratio [HR], 1.94; P = .00009; major events: HR, 2.55; P = .00001; disease-specific death: HR, 10.25; P = .0009). LIMITATIONS: Retrospective study. CONCLUSIONS: There is statistically significant evidence that T3-AJCC8 may be classified into distinct prognostic subgroups.

Performance of Salamanca refinement of the T3-AJCC8 versus the Brigham and Women's Hospital and Tübingen alternative staging systems for high-risk cutaneous squamous cell carcinoma.

INTRODUCTION: The Brigham and Women's Hospital and the Tübingen cutaneous squamous cell carcinoma (SCC) stratification systems propose different criteria from the American Joint Committee on Cancer, eighth edition. Our group identified prognostic subgroups within T3 stage according to the American Joint Committee on Cancer eighth edition's classification, the most common classification for high-risk cutaneous SCCs. OBJECTIVE: To compare the performance and prognostic accuracy of these staging systems in a subset of high-risk cutaneous SCCs. METHODS: Homogeneity, monotonicity, and McNemar tests for pairwise comparisons were assessed. Distinctiveness and relative risk of poor outcome were calculated by stage. Prognostic accuracy was compared with respect to quality (Akaike and Bayesian information criteria), concordance (Harrell C-index and Gönen and Heller concordance probability estimate), and predictive accuracy (sensitivity, specificity, negative predictive value, positive predictive value, and global accuracy). RESULTS: The Brigham and Women's Hospital and Salamanca systems were more distinctive, homogeneous, and monotonic than the Tübingen system. The Tübingen system was the most specific, whereas the Salamanca and Brigham and Women's Hospital systems were more sensitive. Negative predictive value was high in all 3 systems, but positive predictive value and accuracy were low overall. CONCLUSIONS: Alternative staging systems may partially overcome the heterogeneity and low prognostic accuracy of the American Joint Committee on Cancer, eighth edition and enable high-risk cutaneous SCCs to be stratified more reliably, but their prognostic accuracy is still low. Considering the accumulation of risk factors may improve high-risk cutaneous SCC risk stratification.

AJCC 8th edition prognostic staging provides no better discriminatory ability in prognosis than anatomical staging in triple negative breast cancer.

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.

Effectiveness of the AJCC 8th edition staging system for selecting patients with T1-2N1 breast cancer for post-mastectomy radiotherapy: a joint analysis of 1986 patients from two institutions.

BACKGROUND: The role of post-mastectomy radiotherapy (PMRT) in the treatment of patients with T1-2N1 breast cancer is controversial. This study's purpose was to evaluate the risk of recurrence of T1-2N1 breast cancer and the efficacy of PMRT in low-, medium- and high-risk groups of patients. METHODS: Post-mastectomy patients with T1-2N1 breast cancer were restaged according to the American Joint Committee on Cancer Staging Manual, 8th edition (AJCC 8th ed.) staging system. Recurrence scores were generated using prognostic factors identified for loco-regional recurrence and distant metastasis in patients without PMRT, and three risk groups were identified. Rates of loco-regional recurrence and distant metastasis were calculated with a competing risk model and compared using Gray's test. Disease-free survival and overall survival were calculated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards regression model was used for the multivariate analysis. RESULTS: Data from 1986 patients (1521without PMRT; 465 with PMRT) were analyzed. Patients without PMRT were stratified into low-, intermediate- and high-risk groups by age, tumor location, AJCC 8th ed. stage, number of positive nodes and lympho-vascular invasion. The 5-year loco-regional recurrence rate and distant metastasis rates for the three risk groups were significant at 2.5, 5.4 and 16.2% (p <  0.001) respectively, and 4.9, 8.4 and 18.6% (p <  0.001) respectively. In the high-risk group, loco-regional recurrence (p <  0.001), and distant metastasis (p = 0.044) were significantly reduced, and disease free survival (p = 0.004), and overall survival (p = 0.029) were significantly improved after PMRT. In the low- and intermediate-risk groups, PMRT had no significant effect on loco-regional recurrence (p = 0.268), distant metastasis (p = 0.252), disease free survival (p = 0.608) or overall survival (p = 0.986). CONCLUSION: Our results showed no benefits of PMRT in the low-risk group, and thus, omitting PMRT radiotherapy in this population could be considered.

Prognostic value of the AJCC 8th edition staging system for Japanese patients treated with surgery followed by radiotherapy for breast cancer.

BACKGROUND: American Joint Committee on Cancer (AJCC) 8th Edition Breast Cancer Staging System, biological information in addition to anatomical information was added as a basis for prognosis evaluation, but its prognostic impact in Japanese patients treated with postoperative radiotherapy has not been discussed. To determine the applicability of the updated prognostic staging system, we evaluated the prognostic value and confirmed the effectiveness of this system in patients in whom postoperative radiotherapy was performed. MATERIALS AND METHODS: Patients who were treated with postoperative radiotherapy for breast cancer in our institution between January 2011 and December 2015 were restaged by the AJCC 8th pathological prognosis staging system, and then overall survival (OS), disease-free survival (DFS) rates and hazard ratios (HR) were analyzed to compare the predictive fit of the two staging systems. RESULTS: Five hundred and seven patients who in whom postoperative radiotherapy was performed for breast cancer were enrolled in this study. 36.1% patients were downstaged and 5.3% patients were upstaged from the 7th to 8th editions staging system classification. Kaplan-Meier curves and HRs showed differences in OS and DFS rates between the 7th edition and 8th edition staging systems. The AJCC 8th edition prognostic stage system has a better prognostic prediction of OS and DFS than does the 7th edition anatomic stage system. CONCLUSIONS: Compared with the 7th edition in breast cancer, AJCC 8th edition prognostic stage system has more precise stratification and superior prognostic value, providing a more accurate reference for the choice of radiotherapy for patients with breast cancer.

Posterior uveal melanoma in 321 Asian Indian patients: analysis based on the 8th edition of American Joint Committee Cancer classification.

PURPOSE: To evaluate the presenting features, treatment, and outcomes of posterior uveal melanoma (PUM) in Asian Indians based on the 8th edition of American Joint Committee on Cancer (AJCC) classification. METHODS: Retrospective interventional case series of 321 Asian Indian patients with PUM. RESULTS: Based on AJCC, PUM was classified into categories T1 (n = 36; 11%), T2 (n = 74; 23%), T3 (n = 126; 39%), and T4 (n = 85; 27%). Regarding tumor features, T4 was more likely to have pre-equatorial epicenter (vs T1 and T2; p ≤ 0.011), iris abnormalities (vs T2 and T3; p ≤ 0.002), and extraocular tumor extension (vs T3; p = 0.001), whereas T1 was more likely to have macular epicenter (vs T2, T3, T4; p ≤ 0.013), lipofuscin deposits (vs T3 and T4; p ≤ 0.008), and amelanotic tumors (vs. T4; p = 0.003). On multivariate analysis, factors predictive of systemic metastasis were increasing tumor thickness (p = 0.002) and extraocular tumor extension (p = 0.009). The 5-, 10-, and 15-year melanoma-related metastases rates were 0%, 0%, and 0% in T1, 0%, 60%, and 60% in T2, 7%, 40%, and 70% in T3 and 13%, 36%, and 76% in T4, respectively. Risk for metastasis was 1.23 times more for every 1-mm increase in tumor thickness and 9 times more with extraocular tumor extension. CONCLUSION: The AJCC 8th edition provides prognostic classification for PUM in Asian Indian patients. The significant risk factors for metastasis were increasing tumor thickness and extraocular tumor extension.

Validation of the new AJCC eighth edition of the TNM classification for breast cancer with a single-center breast cancer cohort.

PURPOSE: The 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. METHODS: We 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. RESULTS: Of 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). CONCLUSIONS: The 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.

Validation of the newly proposed American Joint Committee on Cancer (AJCC) breast cancer prognostic staging group and proposing a new staging system using the National Cancer Database.

BACKGROUND: The 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. METHODS: All 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. RESULTS: Age, 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). CONCLUSIONS: The 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.

Validation of the American Joint Committee on Cancer (AJCC) 8th edition stage system for gastric cancer patients: a population-based analysis.

BACKGROUND: Our 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. METHODS: Eligible 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). RESULTS: Patients 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. CONCLUSION: The 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.

Evaluation of the American Joint Committee on Cancer 8th edition staging system for gastric cancer patients after preoperative therapy.

BACKGROUND: The 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. METHODS: We 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. RESULTS: A 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). CONCLUSIONS: The 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.

Evaluation of the 8th edition American Joint Commission on Cancer (AJCC) staging system for patients with intrahepatic cholangiocarcinoma: A surveillance, epidemiology, and end results (SEER) analysis.

BACKGROUND: The objective of this study was to assess the prognostic performance of American Joint Committee on Cancer (AJCC) 8th edition in patients with intrahepatic cholangiocarcinoma (ICC) using a cancer registry. METHODS: The Surveillance, Epidemiology, and End Results (SEER) cancer registry was queried to identify 1008 patients who underwent surgical resection of ICC during 1998-2013. Kaplan-Meier method and Cox proportional hazards regression models were used to analyze long-term survival. The relative discriminative abilities were assessed using the Harrell's concordance index. RESULTS: Median patient age was 62 years and 47.6% of the patients were male. Most tumors were T1 or T2 (n = 413, 41.0% and n = 329, 32.6%, respectively) and 22.1% of patients had lymph node (LN) metastasis. Median tumor size was 5.5 cm. With a median follow-up of 18 months, median survival was 27 months and 5-year OS was 30.6%. The OS c-index for the AJCC 8th staging system was 0.669, which was comparable with the c-index for the 7th edition AJCC staging system (c-index: 0.667); the AJCC 8th-edition did provide more discrete stratification of patients. CONCLUSIONS: The new AJCC 8th-edition staging system for ICC was largely comparable to the 7th-edition version and did not provide a marked improvement in overall prognostic discrimination.

Improving accuracy in nodal staging of oral cancer: Proposal of a new system.

BACKGROUND: Despite introduction of extranodal extension (ENE) into the AJCC 8th edition of oral cancer staging, previous criticisms persist, such as limited discrimination between sub-stages and doubtful prognostic value of contralateral nodal disease. The purpose of this study was to compare our novel nodal staging system, based on the number of positive nodes and ENE, to the AJCC staging system in surgically treated patients. METHODS: Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery±adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) and disease specific survival (DSS) as endpoint, the prognostic performance of AJCC 8th and 7th editions were compared using hazard consistency, hazard discrimination, likelihood difference and balance. RESULTS: Our new nodal staging system (PN) a progressive and linear increase in hazard ratio (HR) from pN0 to pN3, with good separation of Kaplan Meier curves. Using the predetermined criteria for evaluation of a staging system, our proposed staging model outperformed AJCC 8th and 7th editions in prediction of OS and DSS. CONCLUSION: PN was the lymph node staging system that provided the most accurate prediction of OS and DSS for patients in our cohort of OSCC. Additionally, it can be easily adopted, addresses the shortcomings of the existing systems and should be considered for future editions of the TNM staging system.

Current status and prospects of diagnosis and treatment for esophageal cancer with supraclavicular lymph node metastasis.

Patients with supraclavicular lymph node (SLN) metastasis from esophageal cancer encounter significant variations in treatment approaches due to differences in pathological subtypes and the lack of a unified regional staging system between East Asian and Western countries. The Tiger study aims to develop an internationally recognized staging system and to delineate the extent of regional lymph node dissection. In the context of esophageal squamous cell carcinoma (SCC) with SLN metastasis, the treatment paradigms from East Asia offer valuable insights. The Japan Esophageal Society (JES) 12th edition staging system guides a tailored comprehensive treatment strategy, emphasizing either radiotherapy and chemotherapy or surgical intervention. In contrast, esophageal adenocarcinoma (AC) predominates in Western countries, where the 8th edition of the American Joint Committee on Cancer (AJCC) staging system classifies SLN metastasis as a distant metastasis, advocating for systemic therapy as the primary treatment modality. Nonetheless, compelling evidence suggests that a multidisciplinary treatment approach, incorporating either radiotherapy and chemotherapy or surgery as the initial treatment, can yield superior outcomes for these patients compared to chemotherapy alone.

Discriminatory Ability and Clinical Utility of the AJCC7 and AJCC8 Staging Systems for Breast Cancer in a Middle-Income Setting.

(1) Background: Differences in access to biomarker testing and cancer treatment in resource-limited settings may affect the clinical utility of the AJCC8 staging system compared to the anatomical AJCC7 system. (2) Methods: A total of 4151 Malaysian women who were newly diagnosed with breast cancer from 2010 to 2020 were followed-up until December 2021. All patients were staged using the AJCC7 and AJCC8 systems. Overall survival (OS) and relative survival (RS) were determined. Concordance-index was used to compare the discriminatory ability between the two systems. (3) Results: Migration from the AJCC7 to AJCC8 staging system resulted in the downstaging of 1494 (36.0%) patients and the upstaging of 289 (7.0%) patients. Approximately 5% of patients could not be staged using the AJCC8 classification. Five-year OS varied between 97% (Stage IA) and 66% (Stage IIIC) for AJCC7, and 96% (Stage IA) and 60% (Stage IIIC) for AJCC8. Concordance-indexes for predicting OS using the AJCC7 and AJCC8 models were 0.720 (0.694-0.747) and 0.745 (0.716-0.774), and for predicting RS they were 0.692 (0.658-0.728) and 0.710 (0.674-0.748), respectively. (4) Conclusions: Given the comparable discriminatory ability between the two staging systems in predicting the stage-specific survival of women with breast cancer in the current study, the continued use of the AJCC7 staging system in resource-limited settings seems pragmatic and justifiable.

The 8th Edition TNM Stage Reclassification of T4 Non-Small Cell Lung Cancer: A Granular Examination of Short and Long-Term Outcomes.

INTRODUCTION: Whilst the American Joint Committee on Cancer 7th edition (AJCC7) classified pT4 non-small-cell lung cancers (NSCLC) as those with extra-pulmonary invasion, the revised 8th edition (AJCC8) included tumors > 7cm regardless of extra-pleural spread. We examined perioperative and long-term outcomes of classical T4 definitions with patients whose tumors were greater than 7cm without extra-pulmonary invasion. MATERIALS AND METHODS: A retrospective single center cohort study was performed. All consecutive patients with pT4 lesions between 2011 and 2018 were identified based on either the AJCC7 or AJCC8 classification. Clinicopathological variables were extracted and compared in a univariate manner. A multivariate Cox regression analysis was performed to assess factors associated with overall survival. RESULTS: Forty patients were allocated to AJCC7 and 118 to AJCC8. Patients in the former were more likely to have positive lymph nodes, synchronous metastasis, multifocal disease and lymphovascular invasion. AJCC7 patients were more likely to undergo pneumonectomy despite significantly more being treated with neoadjuvant therapy. Ninety-day mortality was higher in the AJCC7 group. There was no difference in long-term overall survival. On multivariate analysis male gender, squamous cell histology and increasing tumor size were associated with an increased risk of death. CONCLUSION: Although long-term outcomes were similar, the heterogenicity within the AJCC8 classification emphasizes the need to contextualize the perioperative outcomes for patients with pT4 NSCLC. These data are important for future iterations of the TNM classification in view of emerging neoadjuvant options for patients with cT4 operable NSCLC.

TNM Staging and Overall Survival in Patients With Pheochromocytoma and Sympathetic Paraganglioma.

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.

Lymphocyte subset is more suitable than systemic inflammatory response biomarker and immunoglobulin in constructing prognostic nomogram model for advanced gastric cancer.

The serum factors of inflammation are known to be useful prognostic indicators of gastric cancer (GC). However, few studies have made comparisons to screen out more suitable biomarkers for the construction of Nomogram models. In this study, 566 patients who underwent radical gastrectomy were randomly selected. We evaluated the prognostic value of markers of systemic inflammation, including WBC, NLR, PLR, circulating total T cells, CD4+T cells, CD8+T cells and CD19+B cells, serum IgA, IgM, IgE and IgG, and compared them with traditional tumor markers (CEA, CA19-9, CA72-4 and CA125). Kaplan‒Meier analysis was used to analyze the correlation between biomarkers and overall survival (OS). We used time-dependent ROC analysis to investigate the prognostic accuracy of each biomarker. The risk of death was evaluated by the Cox regression model, and the Nomogram model was constructed by R software. We found that circulating total T cells, CD8+T cells, CEA, and CA125 had statistical significance in predicting advanced GC prognosis. Circulating CD8+T cells and CA125 were continuously superior to circulating total T cells and CEA in the prediction of 5-year OS. Cox regression found that CA125, circulating CD8+T cells, sex, and lymph node metastasis rate were independent risk factors for advanced GC. Furthermore, we combined all these predictors to construct a nomogram, which can supplement the AJCC 8th system. According to the comparison with commonly used serum immune biomarkers, circulating CD8+T cells is more sensitive to advanced GC. The prediction function of the Nomogram will supplement the traditional AJCC system, which contributes to individual survival prediction.

The prognostic value of 11th Japanese classification and 8th AJCC staging systems in Chinese patients with esophageal squamous cell carcinoma.

BACKGROUND: Two staging systems, the 8th staging system by the American Joint Committee on Cancer (AJCC) and the 11th Japanese classification by Japan Esophageal Society (JES), are currently applied in the clinic for predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The differences between the two staging systems have been widely researched. However, little studies focus on the differences in specific staging between the two systems. Therefore, we aimed to compare the performance of different staging in predicting overall survival (OS) of Chinese patients with ESCC. METHODS: This retrospective study included 268 patients who underwent radical esophagectomy and mediastinal lymph node dissection for ESCC between January 2008 and December 2013. Patients were staged by the 8th AJCC and 11th JES staging systems. OS was estimated using the Kaplan-Meier method and compared between N stages and between stage groupings using the log-rank test. Cox proportional hazards regression analysis was performed to identify factors independently related to outcome. Further, we compared the concordance indexes (C-indexes) of the two staging systems. RESULTS: The mean age was 61.25 ± 7.056 years, median follow-up was 44.82 months, and 5-year OS rate was 47%. The OS was well predicted by the 8th AJCC N staging (P < 0.001) and the 11th JES N staging (P < 0.001), with a c-index of 0.638 (95% CI: 0.592-0.683) for AJCC N staging and 0.627 (95% CI: 0.583-0.670) for JES N staging (P = 0.13). In addition, the OS was also well predicted by stage groupings of the 8th AJCC (P < 0.001) and the 11th JES systems (P < 0.001), with a c-index of 0.658 (95% CI: 0.616-0.699) for 8th AJCC stage grouping and 0.629 (95% CI: 0.589-0.668) for the11th JES stage grouping (P = 0.211). CONCLUSIONS: The prognostic effect of 11th JES staging system is comparable with that of AJCC 8th staging system for patients with ESCC. Therefore, both systems are applicable to clinical practice.

Subserosal Layer and/or Pancreatic Invasion Based on Anatomical Features as a Novel Prognostic Indicator in Patients with Distal Cholangiocarcinoma.

The American Joint Committee on Cancer (AJCC) 8th edition T-staging system for distal cholangiocarcinoma (DCC) proposes classification according to the depth of invasion (DOI); nevertheless, DOI measurement is complex and irreproducible. This study focused on the fibromuscular layer and evaluated whether the presence or absence of penetrating fibromuscular invasion of DCC contributes to recurrence and prognosis. In total, 55 patients pathologically diagnosed with DCC who underwent surgical resection from 2002 to 2022 were clinicopathologically examined. Subserosal layer and/or pancreatic (SS/Panc) invasion, defined as penetration of the fibromuscular layer and invasion of the subserosal layer or pancreas by the cancer, was assessed with other clinicopathological prognostic factors to investigate recurrence and prognostic factors. According to the AJCC 8th edition, there were 11 T1, 28 T2, and 16 T3 cases, with 44 (80%) cases of SS/Panc invasion. The DOI was not significantly different for both recurrence and prognostic factors. In the multivariate analysis, only SS/Panc was identified as an independent factor for prognosis (hazard ratio: 16.1; 95% confidence interval: 2.1-118.8, p = 0.006). In conclusion, while the determination of DOI in DCC does not accurately reflect recurrence and prognosis, the presence of SS/Panc invasion may contribute to the T-staging system.