American Joint Committee On Cancer Tumor-node-metastasis Research Articles

Ninth Version of the AJCC and UICC Nasopharyngeal Cancer TNM Staging Classification

Accurate staging is a fundamental step in treating patients with nasopharyngeal carcinoma (NPC) worldwide; this is crucial not only for prognostication, but also for guiding treatment decisions. The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) system is the global language for clinicians, researchers, and cancer registries. Continual improvement that aligns with contemporary pattern of care is essential. To improve the prognostic accuracy and clinical applicability of the eighth edition (TNM-8) for NPC. This multicenter study analyzed patients with NPC with detailed tumor features during January 2014 and December 2015 and was reviewed by experienced radiologists. The data analysis was completed in December 2023. The findings were further confirmed with internal and external validation. Statistical analyses and clinical considerations were reviewed by the AJCC/UICC multidisciplinary head and neck panels and attained consensus. The recommendations were evaluated by the AJCC Evidence-Based Medicine Committee before final endorsement as the ninth version (TNM-9). The primary end point was overall survival. Adjusted hazard ratios of different subgroups were then assessed for confirmation of optimal stage grouping. Of the 4914 patients analyzed, 1264 (25.7%) were female and 3650 (74.3%) were male; the median (SD) age was 48.1 (12.0) years. Advanced radiological extranodal extension (with involvement of adjacent muscles, skin, and/or neurovascular bundles) was identified as an independent adverse factor for all end points: this was added as a criterion for N3. Patients with nonmetastatic disease were regrouped into stages I to III instead of TNM-8 stages I to IVA. Significant hazard discrimination was achieved by grouping T1-2N0-1 as stage I, T3/N2 as stage II, and T4/N3 as stage III. Although the T1-2N0-1 subgroups had comparable 5-year overall survival, subdivisions into IA (T1-T2N0) and IB (T1-T2N1) were recommended due to the distinction in adjusted hazard ratios following adjustment for chemotherapy use. Metastatic disease was exclusively classified as stage IV, and prognostication was further refined by subdivision into IVA (M1a, ≤3 lesions) and IVB (M1b, >3 lesions). TNM-9 demonstrated superiority compared with TNM-8 in major statistical aspects. The results of this diagnostic study suggest that the ninth version of TNM staging for NPC, based on robust analyses and a comprehensive review by the AJCC/UICC staging committees, provides an improved staging system for global application and a framework for future incorporation of nonanatomical factors. This will be launched for global application in January 2025.

Combining lymph node ratio to develop prognostic models for postoperative gastric neuroendocrine neoplasm patients

BACKGROUND Lymph node ratio (LNR) was demonstrated to play a crucial role in the prognosis of many tumors. However, research concerning the prognostic value of LNR in postoperative gastric neuroendocrine neoplasm (NEN) patients was limited. AIM To explore the prognostic value of LNR in postoperative gastric NEN patients and to combine LNR to develop prognostic models. METHODS A total of 286 patients from the Surveillance, Epidemiology, and End Results database were divided into the training set and validation set at a ratio of 8:2. 92 patients from the First Affiliated Hospital of Soochow University in China were designated as a test set. Cox regression analysis was used to explore the relationship between LNR and disease-specific survival (DSS) of gastric NEN patients. Random survival forest (RSF) algorithm and Cox proportional hazards (CoxPH) analysis were applied to develop models to predict DSS respectively, and compared with the 8th edition American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging. RESULTS Multivariate analyses indicated that LNR was an independent prognostic factor for postoperative gastric NEN patients and a higher LNR was accompanied by a higher risk of death. The RSF model exhibited the best performance in predicting DSS, with the C-index in the test set being 0.769 [95% confidence interval (CI): 0.691-0.846] outperforming the CoxPH model (0.744, 95%CI: 0.665-0.822) and the 8th edition AJCC TNM staging (0.723, 95%CI: 0.613-0.833). The calibration curves and decision curve analysis (DCA) demonstrated the RSF model had good calibration and clinical benefits. Furthermore, the RSF model could perform risk stratification and individual prognosis prediction effectively. CONCLUSION A higher LNR indicated a lower DSS in postoperative gastric NEN patients. The RSF model outperformed the CoxPH model and the 8th edition AJCC TNM staging in the test set, showing potential in clinical practice.

Survival benefit of postoperative radioiodine therapy among patients with intermediate-risk differentiated thyroid carcinoma.

The 2015 American Thyroid Association (ATA) guidelines proposed the use of the ATA Risk Stratification System and American Joint Committee on Cancer Tumor-Node-Metastasis (AJCC/TNM) Staging System for postoperative radioiodine decision-making. However, the management of patients with intermediate-risk differentiated thyroid carcinoma (DTC) is not well defined. In this study, we aimed to evaluate the therapeutic efficacy of radioactive iodine therapy (RAIT) among various subgroups of patients with intermediate-risk DTC after surgery. This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). The DTC patients with intermediate risk of recurrence were divided into two groups (treated or not treated with radioactive iodine (RAI)). As the treatment was not randomly assigned, stabilized inverse probability treatment weighting (sIPTW) was used to reduce selection bias. We used the Kaplan-Meier method and log-rank test to analyze overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analysis after sIPTW found a significant difference in OS and CSS between no RAIT and RAIT (log-rank test, P < 0.0001; P = 0.0019, respectively). The Kaplan-Meier curves of CSS in age cutoff of 55 years showed a significant association between no RAIT and RAIT (log-rank test, P = 0.0045). Univariate and multivariate Cox regression showed RAIT was associated with a reduced risk of mortality compared with no RAIT (hazard ratio [HR] 0.59, 95% confidence interval [95% CI 0.44-0.80]). Age (≥ 55) years showed a worse CSS regardless of whether or not a patient was treated or not treated with RAI ([HR] 8.91, 95% confidence interval [95% CI 6.19-12.84]). RAIT improves OS and CSS in patients with intermediate-risk DTC after surgery. 55 years is a more appropriate prognostic age cutoff for the relevant classification systems and is a crucial consideration in RAI decision-making. Therefore, we need individualized treatment plans.

Implications of Pretreatment Serum Carcinoembryonic Antigen Levels and Perineural Invasion with Staging, Prognosis, and Management in Stage I-III Colon Cancer after Surgery: A Retrospective Cohort Study in the SEER Database.

Pretreatment levels of serum carcinoembryonic antigen (CEA) and perineural invasion (PNI) are related to poor prognosis in colon cancer. We analyzed the CEA and PNI (defined as incorporation of carcinoembryonic antigen and perineural invasion (CP)-stage), which are included in the Tumor-Node-Metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC), and evaluated the survival prognosis of patients treated with surgery in I-III stage colon carcinoma. We employed a retrospective study for eligible colon carcinoma patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Kaplan-Meier curve and Multivariate Cox regression analysis were used to analyze different TNM-CP stages for the cancer-specific survival (CSS) probabilities in colon cancer. In our study, CEA levels and PNI were significant prognostic factors (p < 0.05), and the newly proposed CP-stage was an independent prognostic index in stage I-III colon carcinoma after surgery. Multivariate Cox regression analyses indicated that CP1-stage was related to a 63.9% increased risk of cancer-specific mortality (hazard ratio (HR): 1.639, 95% confidence interval (CI): 1.544-1.739, p < 0.001), compared with CP0-stage in colon cancer. In respective TNM stages, the CP0-stage had an advantage over the CP1-stage for CSS (p < 0.001). Moreover, CP1-stage patients with node-negative colon cancer were contacted with similar or worse survival in comparison to CP0-stage patients with node-positive. For postoperative patients with stage I-III colon cancer, our study indicated that the CP stage is a significant prognostic factor for CSS, which deserves more clinical attention. It's worth noting that including the CP stage in the AJCC TNM staging system of colon carcinoma is beneficial to the survival prediction and clinical treatment.

New staging systems for left-sided colon cancer based on the number of retrieved and metastatic lymph nodes provide a more accurate prognosis.

Objectives: We aimed to explore reasonable lymph node classification strategies for left-sided colon cancer (LCC) patients. Methods: 48,425 LCC patients from 2010 to 2015 were identified in the US Surveillance, Epidemiology, and End Results database. We proposed an innovative revised nodal (rN) staging of the 8th American Joint Committee on Cancer (AJCC) Tumor/Node/Metastasis (TNM) classification based on the cut-off value of retrieved lymph nodes and survival analyses in patients with LCC. Log odds of positive lymph nodes (LODDS) stage is a numerical classification strategy obtained by a formula that incorporates the numbers of retrieved and positive lymph nodes. To develop the TrN or TLODDS classification, patients with similar survival rates were grouped by combining T and rN or LODDS stage. The TrN or TLODDS classification was further evaluated in a validation set of 12,436 LCC patients from 2016 to 2017 in the same database and a Chinese application set of 958 LCC patients. Results: We developed novel TrN and TLODDS classifications for LCC patients that incorporated 7 stages with reference to the AJCC staging system. In comparison to the 8th AJCC TNM and TrN classifications, TLODDS classification demonstrated significantly better discrimination (area under the receiver operating characteristic curve, 0.650 vs. 0.656 vs. 0.661, p < 0.001), better model-fitting (Akaike information criteria, 309,287 vs. 308,767 vs. 308,467), and superior net benefits. The predictive performance of the TrN and TLODDS classifications was further verified in the validation and application sets. Conclusion: Both the TrN and TLODDS classifications have better discriminatory ability, model-fitting, and net benefits than the existing TNM classification, and represent an alternative to the current TNM classification for LCC patients.

A Nomogram Based on the Log Odds of Positive Lymph Nodes Predicts the Prognosis of Patients with Colon Neuroendocrine Tumors After Surgery: A Surveillance, Epidemiology, and End Results Population-Based Study.

This work focused on determining the highly efficient nodal classification system from American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) classification (eighth edition), positive lymph node, log odds of positive lymph nodes (LODDS), lymph node ratio, examined lymph node, and establishing the new nomogram for predicting cancer-specific survival in colon neuroendocrine tumors (CNETs). From the Surveillance, Epidemiology, and End Results database, 943 CNET cases undergoing radical operation were enrolled, and randomized as training (n = 663) or validation set (n = 280). For the above 5 lymph node classification systems, their prediction performances were compared with C-index, Akaike information criterion (AIC), and area under the receiver operating characteristic curve. Univariate together with multivariate regression was carried out for identifying independent risk factors. Afterward, this work established 1 nomogram and confirmed its accuracy based on C-index, calibration curves, together with the area under the curve value. Besides, it was compared with the AJCC TNM classification system with regard to model prediction performance. LODSS achieved the greatest area under the curve and C-index, whereas the smallest AIC. Upon multivariate regression, age, histologic grade, T stage, M stage, and LODDS independently predicted the risk of CNETs. For the validation set, the C-index of the nomogram was 0.794, and the area under the curves at 1, 3, and 5 years was 0.826, 0.857, and 0.870, separately. Additionally, as revealed by the C-index, AIC, decision curve analysis, as well as Kaplan-Meier analysis, our nomogram had superior performance to the AJCC TNM classification system. For postoperative patients with CNETs, the LODDS might achieve the best prediction performance. Moreover, the LODDS-based nomograms might show superior survival prediction performance to the AJCC TNM classification system (eighth edition).

Prognostic Nomogram Combining Preoperative Neutrophil to Lymphocyte Ratio and Clinicopathologic Features for Gastric Cancer Patients after Distal Radical Gastrectomy: Based on Propensity Score Matching.

Background: Preoperative inflammatory status has been widely used in assessing the prognosis of malignant tumor. This study aimed to establish a novel nomogram combining preoperative inflammatory factors and clinicopathologic features to predict the prognosis of gastric cancer (GC) patients after distal radical gastrectomy. Methods: A total of 522 GC patients from Fujian Provincial Hospital were retrospectively reviewed. Propensity score matching was performed and Cox regression models were used to analyze the clinical and pathological factors to determine their impact on survival. A prognostic nomogram was established and validated based on these factors. Results: The multivariate analysis indicated that tumor stage, pathological type, and neutrophil to lymphocyte ratio (NLR) were independent risk factors for the prognosis of GC patients. The nomogram was established based on these factors. In the primary cohort, the concordance index (C-index) of the nomogram was 0.753 (95% CI 0.647-0.840), which was higher than that of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) stage. The calibration curve showed the actual overall survival (OS) probabilities were in good keeping with those predicted by the nomogram. Furthermore, we divided the patients into two distinct risk groups for OS according to the nomogram points: low and high risk. The OS rates were significantly different among the subgroups (p ˂ 0.001). Conclusions: We proposed a novel nomogram combining preoperative NLR and clinicopathologic features that is economical, routinely available, and highly predictive of OS in GC patients after distal radical gastrectomy. Compared with the current AJCC TNM staging, this model was more accurate in prognostic prediction.

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

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. The objective of this analysis is to investigate the associations between TNM staging and overall survival (OS). 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. 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. 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.

Novel staging for gastric neuroendocrine neoplasms by incorporating the WHO grading into the TNM staging system.

The 8th tumor-node-metastasis (TNM) classification of the American Joint Committee on Cancer (AJCC) can be used to estimate the prognosis of gastric neuroendocrine tumor (gNET) and gastric neuroendocrine carcinoma (gNEC) patients but not gastric neuroendocrine neoplasms (gNENs). First, in the SEER (training) dataset, a TNMG system was built by combining the WHO G grade (G1-4; NEC grouped into G4) with the 8th AJCC T (T1-4), N (N0-1), and M (M0-1) stage, which was then validated in a Chinese (validation) cohort. In all, 2245 gNENs cases from the training dataset and 280 cases from the validation dataset were eligible. The T stage, M stage, and G grade were independent prognostic factors for OS in both datasets (all p <0.05). The TNMG staging system demonstrated better C-index for predicting OS than the 8th AJCC TNM staging system in both the training (0.87, 95%CI: 0.86-0.88 vs. 0.79, 95%CI: 0.77-0.81) and validation (0.77, 95%CI: 0.73-0.80 vs. 0.75, 95%CI: 0.71-0.79) datasets. The AUC of the 3-year OS for the TNMG staging system was 0.936 and 0.817 in the SEER and validation dataset, respectively; higher than those of the 8th AJCC system (vs. 0.843 and 0.779, respectively). DCA revealed that compared with the 8th AJCC TNM staging system, the TNMG staging system demonstrated superior net prognostic benefit in both the training and validation datasets. The proposed TNMG staging system could more accurately predict the 3- and 5-year OS rate of gNENs patients than the 8th AJCC TNM staging system.

Comparison of the prognostic value of AJCC cancer staging system 7th and 8th editions for differentiated thyroid cancer

BackgroundIn the last American Joint Committee on Cancer/Tumor, Node, Metastasis (AJCC/TNM) 8th edition (TNM8), several changes were introduced to this risk stratification system to improve the prognosis of differentiated thyroid cancer (DTC).AimTo validate the impact of TNM8 vs. TNM 7th edition (TNM7) in DTC in terms of predictive value in two hospitals from Buenos Aires, Argentina.MethodsRetrospective study of DTC patients from two institutions. Reclassification from TNM7 to TNM8, disease-specific survival (DSS), and final clinical outcomes at the end of follow-up (recurrent/persistent structural disease) (median 5 years) were analyzed. The proportion of variation explained (PVE) was used to compare the predictive capability of DSS of both classification systems.ResultsReclassification of 245 patients, aged (mean ± SD) 55 ± 15.36 years, 91% women, to TNM8 from TNM7 showed: 82% vs 57% stage I (SI), 10% vs 8.5% SII, 5% vs 22% SIII, 3% vs 12% SIV (p < 0.01). Forty percent of the population was downstaged with TNM8. Ten-year DSS rates for SI, SII, SIII and SIV in TNM7 were 100, 100, 100 and 74%, respectively and in TNM8: 97.6, 100, 100 and 37.5%, respectively. Out of 4 disease-specific deaths in SIV TNM7, one was subclassified to SI TNM8, corresponding to a 53-year-old patient with structural persistence. PVE for TNM8 (29%) was more than twice that of TNM7 (13%).ConclusionIn this Argentinian DTC patients sample, it was confirmed that the new TNM8 classification is more accurate in predicting survival attributable to cancer than its previous version.

Inclusion of the Number of Metastatic Lymph Nodes in the Staging System for Medullary Thyroid Cancer: Validating a Modified American Joint Committee on Cancer Tumor-Node-Metastasis Staging System.

Background: The current American Joint Committee on Cancer (AJCC) staging system (8th edition) for medullary thyroid cancer (MTC) was originally extrapolated from the staging system for differentiated thyroid cancer. However, the current staging system does not accurately predict the prognosis of patients with MTC. Patients and Methods: The present study was based on data from the Surveillance, Epidemiology, and End Results (SEER) database and validated by multicenter data from the Shanghai Tenth People's Hospital, Tongji University School of Medicine, Xuzhou City Central Hospital, and Suzhou Ninth People's Hospital. Hazard ratio with its 95% confidence interval [CI] was estimated by Cox proportional hazards regression analysis. The concordance index (C-index) was used to evaluate the discrimination accuracy of the current AJCC tumor-node-metastasis (TNM) staging system and the modified AJCC (mAJCC) TNM staging system. Results: A total of 1175 MTC patients were selected from the SEER database and 312 from the three hospitals in China. We redefined the N category according to the number of metastatic lymph nodes (LNs) as follows: N'0 category (0 metastatic LNs), N'1 category (1-9 metastatic LNs), and N'2 category (≥10 metastatic LNs). The four distinct tumor stages were reclassified in the mAJCC staging system as follows: stage I (T1-4N'0M0, T1N'1M0), stage II (T2-3N'1M0, T1N'2M0), stage III (T4N'1M0, T2-4N'2M0), and stage IV (TanyN'anyM1). The C-index of the current AJCC staging system and the mAJCC staging system was 0.72 [CI, 0.67-0.78] and 0.78 [CI, 0.73-0.84], respectively. Similar results were observed in the survival analysis of the multicenter data set. Conclusions: The mAJCC staging system could discriminate the prognosis of MTC patients more effectively than the current AJCC staging system, indicating that it is feasible and appropriate to modify the current AJCC staging system by introducing the number of metastatic LNs instead of the location of LNs. These findings might be adopted in the next edition of the AJCC staging system and be used to guide clinical practice.

Development of a staging system and survival prediction model for advanced gastric cancer patients without adjuvant treatment after curative gastrectomy: A retrospective multicenter cohort study

BackgroundAdjuvant chemotherapy (AC) after curative gastrectomy is the standard treatment for patients with locally advanced gastric adenocarcinoma in East Asia; however, for various reasons, some patients do not receive this treatment. The aim of this study was to develop a system that reflects the survival rate of patients who do not receive AC. Materials and methodsA modified tumor-node-metastasis (TNM) staging system was developed based on the overall survival (OS) of gastric cancer patients after curative gastrectomy without AC at Seoul St. Mary's hospital. A survival prediction model was developed based on the modified staging system and risk factors for OS, which were examined using the Cox proportional hazards regression model. The model was internally validated for the power of prediction and discrimination, compared with the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th edition; it was externally validated using data from two other tertiary teaching hospitals. ResultsOf the 185 patients in the development set, the 5-year OS rates for modified stages IIA, IIB, IIC, IIIA, and IIIB were 80.2%, 74.0%, 56.7%, 50.0%, and 25.0%, respectively; the median OS intervals for modified stages IIIC and IIID were 21.0 and 11.0 months, respectively. Age, American Society of Anesthesiologists physical status, and postoperative complications were significantly associated with OS. The concordance index (0.768 vs. 0.686), Akaike Information Criterion (745.88 vs. 794.84), and estimated area under the curve (0.7567 vs. 0.6655) were all superior for the prediction model, compared with the AJCC TNM stage. For the validation set of 157 patients, the model performed better for the prediction and discrimination of OS. ConclusionThe newly developed survival prediction model improves the accuracy of OS prediction for stage II and III gastric cancer patients without AC after curative gastrectomy.

Early death in supraglottic laryngeal squamous cell carcinoma: A population-based study.

Supraglottic laryngeal squamous cell carcinoma (LSCC) is the second most common type of laryngeal cancer with a poor prognosis. Current population-based estimates of the early death rate and associated factors for early death of supraglottic LSCC are lacking. The purpose of this study was to assess the early death rate and related factors for early death in patients with supraglottic LSCC. We identified 3733 adult patients diagnosed with supraglottic LSCC between 2010 and 2017 for whom the vital status at 3months was known from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were staged according to the seventh edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. The early death (survival time ≤ 3months) rate was calculated. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with the early death rate. 313 (8.38%) of the 3733 patients died within 3months of diagnosis of supraglottic LSCC. Of these, 225 patients died from cancer-specific causes. Multivariate logistic regression analyses confirmed that advanced age, male sex, advanced T stage, advanced N stage, advanced M stage, and not undergoing treatment (surgery, radiotherapy, and chemotherapy) had significant correlations with all-cause early death in supraglottic LSCC. In addition, advanced age, advanced T stage, advanced N stage, advanced M stage, and not undergoing treatment (surgery, radiotherapy, and chemotherapy) were significantly correlated with cancer specificity in supraglottic LSCC. When a tumor is newly diagnosed, we should pay close attention to sex, age, unmarried status and AJCC TNM staging to quickly detect supraglottic LSCC patients with a tendency toward early death. These findings have implications for precise prognosis prediction and individualized and personalized patient counseling and therapy.

Comparison of 4 lymph node staging systems for the prognostic prediction of esophagogastric junction adenocarcinoma with ≤15 retrieved lymph nodes

BackgroundDirectly applying the 8th American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) staging system to evaluate the prognosis of patients with esophagogastric junction adenocarcinoma (AEG) might lead to under-staging, when insufficient lymph nodes were retrieved during surgery. The prognostic value of 4 lymph nodes staging systems, 8th AJCC TNM N stage, lymph node ratio (LNR), log odds of positive lymph nodes (LODDS), and negative lymph nodes (NLN), in AEG patients having ≤15 retrieved lymph nodes were compared. Methods869 AEG patients diagnosed between 2004 and 2012 with ≤15 retrieved lymph nodes were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were conducted to assess the association of cancer-specific survival (CSS) and overall survival (OS) with 8th AJCC TNM N stage, LNR, LODDS, and NLN respectively. Predictive survival ability was assessed and compared using linear trend χ2 score, likelihood ratio (LR) test, Akaike information criterion (AIC), Harrell concordance index (C-index), and Receiver Operative Curve (ROC). ResultsThe N stage, LNR, LODDS, and NLN were all independent prognostic predictors for CSS and OS in multivariate Cox models. Comparatively, LODDS demonstrated higher linear trend χ2 score, LR test score, C-index and integrated area under the curve (iAUC) value, and lower AIC in CSS compared to the other three systems. Moreover, for patients without regional lymph node metastasis, NLN showed higher C-index and lower AIC. ConclusionsLODDS showed better predictive performance than N, LNR, and NLN among patients with node-positive patients while NLN performed better in node-negative patients. A combination of LODDS and NLN has the potential to provide more prognostic information than the current AJCC TNM classification.

Development and validation of a novel classification scheme for combining pathological T stage and log odds of positive lymph nodes for colon cancer

AimLog Odds of Positive Lymph Nodes (LODDS) have a better predictive ability than N stage for colon cancer. However, the prognostic value of developing a novel prognostic classification by combining T stage and LODDS (TLODDS) for colon cancer remains unknown. Therefore, in the present study, we aimed to develop a TLODDS classification for colon cancer, and assess whether or not the novel TLODDS classification could improve survival stratification by comparing its discrimination, model-fitting, and net benefits, with the American Joint Committee on Cancer (AJCC) Tumor/Node/Metastasis (TNM) classification. Methods45,558 Western colon cancers were identified in the Surveillance, Epidemiology, and End Results database as a training set. A novel LODDS stage was established and patients with similar survival rates were grouped by combining T and LODDS stages to develop a novel TLODDS classification. The TLODDS classification was further assessed in a Chinese validation set of 3,515 colon cancers and an application set of 3,053 rectal cancers. ResultsWe developed a novel TLODDS classification that incorporated 7 stages: stage I (T1LODDS1), IIA (T2LODDS1, T1LODDS2, T1LODDS3), IIB (T2LODDS2-3, T3LODDS1, T1LODDS4), IIC (T3LODDS2, T2LODDS4, T4aLODDS1), IIIA (T3LODDS3, T1-2LODDS5, T4bLODDS1, T4aLODDS2), IIIB (T3LODDS4-5, T4aLODDS3-4, T4bLODDS2) and IIIC (T4bLODDS3-5, T4aLODDS5). In the training set, it showed significantly better discrimination (area under the receiver operating characteristic (ROC) curve, 0.691 vs. 0.664, P < 0.001), better model-fitting (Akaike information criteria, 265,644 vs. 267,410), and superior net benefits, than the latest AJCC TNM classification. The predictive performance of the TLODDS classification was further validated in colon cancers and was successfully applied in rectal cancers with regards to both overall and disease-free survival. ConclusionsThe TLODDS classification has better discriminatory ability, model-fitting, and net benefits than the existing TNM classification, and represents an alternative to the current TNM classifications for colon and rectal cancers.

Discrepancies between UICC and AJCC TNM classifications for oral cavity tumors in the 8th editions and following versions.

To underline discrepancies between the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) classifications in oral cavity cancer. Comparison between the UICC and AJCC TNM classifications of oral cavity cancer in their 8th editions and following versions. The most important update was the introduction of the depth of infiltration (DOI), which reflects the proximity of the tumor to the underlying lymphovascular tissues and was associated to the presence of nodal metastases. Since the first publication of the 8th edition of the AJCC Cancer Staging Manual on March 30, 2017, two further versions have been published, while the UICC TNM classification was left unchanged until a document containing modifications to the 8th edition of the UICC TNM Classification of Malignant Tumours was published online on October 6, 2020. Different versions of the TNM classification can be confounding for the scientific community. Citing the 8th edition of the UICC TNM Classification of Malignant Tumours or the AJCC Cancer Staging Manual without specifying the precise version used for classification may be insufficient. Clinicians and researchers are invited to always refer to the latest update of each classification.

Clinical Outcomes of Differentiated Thyroid Cancer With Gross Extrathyroidal Extension Into the Strap Muscles: A Case Control Study

Background: The 8th edition of the American Joint Committee on Cancer/tumor-node-metastasis (AJCC/TNM) staging system for differentiated thyroid cancer (DTC), implemented in January 2018, classifies patients >/= 55 years of age with gross extrathyroidal extension (ETE) of the primary tumor into the overlying strap muscles as prognostic stage II. However, it remains controversial as to whether or not gross ETE into the strap muscles is an independent predictor of recurrence, response to therapy, need for additional therapies, or overall survival. Using a case control study design, we evaluated the prognostic significance of gross ETE among adults. Methods: After obtaining IRB approval, we used the tumor registry at our institution to retrospectively identify 51 AJCC stage II patients with DTC aged >/= 55 years with gross ETE into only the strap muscles (51/2,225 patients). For each of the 51 cases, we identified one control who matched on all of the following important prognostic factors: age at diagnosis (± 5 years), sex, histology, size of tumor (± 1 cm), lymph node metastases, distant metastases, completeness of resection, receipt of radioactive iodine (RAI) therapy, and duration of follow-up (± 5 years). The controls (n=51) had no gross ETE. Results: In the 51 patients with gross ETE into only the strap muscles, the mean age at diagnosis was 64 years, 77% were female, 37% had lymph node metastases, and none had distant metastases. The average tumor size was 2.1 cm with the majority of patients (49/51) demonstrating papillary thyroid carcinoma (1 follicular thyroid carcinoma and 1 Hurthle cell thyroid carcinoma). Only 6% of patients (3/51) had incomplete resections and 92% (47/51) received RAI therapy. The mean duration of follow-up was 8 years.There were no statistically significant differences between the cases and controls on each of the pre-specified prognostic variables described in the methods. In addition, there were no statistically significant differences between the groups in terms of rates of recurrence: cases 18% (9/51) and controls 29% (15/51) (p=0.24), best response to initial therapy (excellent, biochemical incomplete, structural incomplete, or indeterminate response to therapy), and need for subsequent interventions including surgery, RAI, external beam radiation, or systemic therapy. Furthermore, there were no statistically significant differences between the cases and controls with respect to 10-year disease-free survival (cases 83% and controls 68%, p=0.90) and 10-year overall survival (cases 97% and controls 89%, p=0.10). Conclusions: In a case control analysis with a mean follow up of 8 years, the presence of ETE into the strap muscles was not an independent predictor of worse clinical outcomes in adults >/= 55 years old with DTC. These findings can be used to inform the future editions of the AJCC/TNM and American Thyroid Association staging systems for DTC.

Development and validation of a Surveillance, Epidemiology, and End Results (SEER)-based prognostic nomogram for predicting survival in elderly patients with gastric cancer after surgery.

Elderly gastric cancer (ELGC) remains one of the intensively investigated topics during the last decades. To establish a comprehensive nomogram for effective clinical practice and assessment is of significance. This study is designed to develop a prognostic nomogram for ELGC both in overall survival (OS) and cancer-specific survival (CSS). The recruited cases were from the Surveillance, Epidemiology, and End Results (SEER) database and input for the construction of nomogram. A total of 4,414 individuals were recruited for this study, of which 2,208 were randomly in training group and 2,206 were in validation group. In univariate analysis of OS, significant variables (P<0.05) included age, marital status, grade, American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) stage, bone/brain/liver/lung metastasis and tumor size. In univariate analysis of CSS, significant variables (P<0.05) included age, grade, AJCC TNM stage, bone/brain/liver/lung metastasis and tumor size. In multivariate analysis of OS, sex, age, race, grade, TNM stage, lung metastasis and tumor size were considered as the significant variables and subjected to the establishment of nomogram. In multivariable analysis of CSS, age, grade, TNM, tumor size were considered as the significant variables and input to the establishment of nomogram. Sex, age, race, grade, TNM stage, lung metastasis and tumor size were included for the establishment of nomogram in OS while age, grade, TNM, tumor size were included to the establishment of nomogram in CSS. C-index, decision curve analysis (DCA) and the area under the curve (AUC) showed distinct value of newly established nomogram models. Both OS and CSS nomograms showed higher statistic power over the AJCC stage. This study established and validated novel nomogram models of OS and CSS for ELGC based on population dataset.

The new (Version 9) American Joint Committee on Cancer tumor, node, metastasis staging for cervical cancer.

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging for all cancer sites has been periodically updated as a published manual for many years. The last update, the eighth edition AJCC Cancer Staging Manual went into use on January 1, 2018. The AJCC has since restructured and updated its processes, and all AJCC staging-related data are now housed on its new application programming interface. Consequently, the next AJCC TNM staging update, AJCC version 9 TNM staging, will be published electronically and will be released chapter by chapter. The first chapter of version 9 AJCC TNM staging is the updated cervical cancer staging, which is now published. This article highlights the changes to the AJCC TNM cervical cancer staging; these changes align with the International Federation of Gynecology and Obstetrics staging. The most important of the changes are: 1) the incorporation of imaging and surgical findings, 2) the elimination of lateral spread from T1a, 3) the addition of a subcategory to T1b (T1b3), and 4) histopathology is updated to reflect human papillomavirus-associated and human papillomavirus-independent carcinomas.

A Prognostic Model of 15 Immune-Related Gene Pairs Associated With Tumor Mutation Burden for Hepatocellular Carcinoma.

IntroductionTumor mutation burden (TMB) is an emerging biomarker for immunotherapy of hepatocellular carcinoma (HCC), but its value for clinical application has not been fully revealed.Materials and MethodsWe used the Wilcox test to identify the differentially expressed immune-related genes (DEIRGs) in groups with high and low TMB as well as screened the immune gene pairs related to prognosis using univariate Cox regression analysis. A LASSO Cox regression prognostic model was developed by combining The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) with the International Cancer Genome Consortium (ICGC) LIRI-JP cohort, and internal (TCGA, ICGC) and external (GSE14520) validation analyses were conducted on the predictive value of the model. We also explored the relationship between the prognostic model and tumor microenvironment via the ESTIMATE algorithm and performed clinical correlation analysis by the chi-square test, revealing its underlying molecular mechanism with the help of Gene Set Enrichment Analysis (GSEA).ResultsThe prognostic model consisting of 15 immune gene pairs showed high predictive value for short- and long-term survival of HCC in three independent cohorts. Based on univariate multivariate Cox regression analysis, the prognostic model could be used to independently predict the prognosis in each independent cohort. The immune score, stromal score, and estimated score values were lower in the high-risk group than in the low-risk group. As shown by the chi-square test, the prognostic model exhibited an obvious correlation with the tumor stage [American Joint Committee on Cancer tumor–node–metastasis (AJCC-TNM) (p < 0.001), Barcelona Clinic Liver Cancer (BCLC) (p = 0.003)], histopathological grade (p = 0.033), vascular invasion (p = 0.009), maximum tumor diameter (p = 0.013), and background of liver cirrhosis (p < 0.001). GSEA revealed that the high-risk group had an enrichment of many oncology features, including the cell cycle, mismatch repair, DNA replication, RNA degradation, etc.ConclusionOur research developed and validated a reliable prognostic model associated with TMB for HCC, which may help to further enrich the therapeutic targets of HCC.