Combining Molecular Markers With the TNM Staging System to Improve Prognostication in Stage II and III Colon Cancer: Are We Ready Yet?

Abstract Background Lymphovascular invasion (LVI) is defined as the presence of cancer cells in lymphatics or blood vessels. This study aimed to evaluate the prognostic value of LVI in stage II colorectal cancer (CRC) patients with inadequate examination of lymph nodes (ELNs) and further combined LVI with the TNM staging system to determine the predictive efficacy for CRC prognosis. Adjuvant chemotherapy (ACT) was then evaluated for stage II CRC patients with LVI positivity (LVI+). Methods In order to avoid the effects of different ACT regimens, among 409 stage II patients, we chose 121 patients who received FOLFOX regimen and the 144 patients who did not receive ACT as the object of study. LVI was examined by hematoxylin-eosin (HE) staining. Kaplan-Meier analysis followed by a log-rank test was used to analyze survival rates. Univariate and multivariate analyses were performed using a Cox proportional hazards model. Harrell’s concordance index (C-index) was used to evaluate the accuracy of different systems in predicting prognosis. Results The LVI+ status was significantly associated with pT stage, degree of differentiation, tumor stage, serum CEA and CA19-9 levels, perineural invasion (PNI), tumor budding (TB), and KRAS status. The 5-year overall survival (OS) rate of stage II patients with < 12 ELNs and LVI+ was less than stage IIIA. Multivariate analyses showed that LVI, pT-stage, serum CEA and CA19-9 levels, PNI, TB, and KRAS status were significant prognostic factors for stage II patients with < 12 ELNs. The 8th TNM staging system combined with LVI showed a higher C-index than the 8th TNM staging system alone (C-index, 0.895 vs. 0.833). Among patients with LVI+, the ACT group had a significantly higher 5-year OS and 5-year disease-free survival (DFS) than the surgery alone (SA) group (5-year OS, 66.7% vs. 40.9%, P = 0.004; 5-year DFS, 64.1% vs. 36.3%, P = 0.002). Conclusions LVI is an independent prognostic risk factor for stage II CRC patients. Combining LVI with the 8th TNM staging system improved the predictive accuracy for CRC prognosis. ACT in stage II CRC patients with LVI+ is beneficial for survival.

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Masaoka-Koga and TNM Staging System in Thymic Epithelial Tumors: Prognostic Comparison and the Role of the Number of Involved Structures

Cancers ◽

10.3390/cancers13215254 ◽

2021 ◽

Vol 13 (21) ◽

pp. 5254

Author(s):

Marco Chiappetta ◽

Filippo Lococo ◽

Luca Pogliani ◽

Isabella Sperduti ◽

Diomira Tabacco ◽

...

Keyword(s):

Staging System ◽

Tnm Staging ◽

Multiple Organ ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Thymic Epithelial Tumors ◽

Epithelial Tumors ◽

Tnm Staging System ◽

Staging Systems

Background: The aim of this study was to evaluate the Masaoka–Koga and the tumor node metastases (TNM) staging system in thymic epithelial tumors (TET) considering possible improvements. Methods: We reviewed the data of 379 patients who underwent surgical resection for TET from 1 January 1985 to 1 January 2018, collecting and classifying the pathological report according to the Masaoka–Koga and the TMN system. The number of involved organs was also considered as a possible prognostic factor and integrated in the two staging systems to verify its impact. Results: Considering the Masaoka–Koga system, 5- and 10-year overall survival (5–10YOS) was 96.4% and 88.9% in stage I, 95% and 89.5% in stage II and 85.4% and 72.8% in stage III (p = 0.01), with overlapping in stage I and stage II curves. Considering the TNM system, 5–10YOS was 95.5% and 88.8% in T1, 84.8% and 70.7% in T2 and 88% and 76.3% in T3 (p = 0.02), with overlapping T2–T3 curves. Including the number of involved structures, in Masaoka–Koga stage III, patients with singular involved organs had a 100% and 76.6% vs. 87.7% 5–10YOS, which was 76.6% in patients with multiple organ infiltration. Considering the TNM, T3 patients with singular involved structures presented a 5–10YOS of 100% vs. 62.5% and 37.5% in patients with multiple organ involvement (p = 0.07). Conclusion: The two staging systems present limitations due to overlapping curves in early Masaoka–Koga stages and in advanced T stages for TNM. The addition of the number of involved organs seems to be a promising factor for the prognosis stratification in these patients.

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Immunoscore As A Predictor Of Disease Recurrences And Patientsâ€™ Survival in Colon Cancer : A Clinicopathologic Study.

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.3523 ◽

2020 ◽

Vol 8 (E) ◽

pp. 143-149

Author(s):

Reham Shehab El Nemr Esmail ◽

Amr Kamal ◽

Marwa Shabana

Keyword(s):

Colon Cancer ◽

Sensitivity And Specificity ◽

Staging System ◽

Good Prognosis ◽

Tnm Staging ◽

Image Analysis System ◽

Predictive Values ◽

Tnm System ◽

Clinicopathologic Study ◽

Tnm Staging System

BACKGROUND: For years, the American Joint Committee of Cancer/International Union against Cancer TNM staging system was the only accepted staging system for colorectal cancer. Different studies highlighted limitations in this staging system with the need to another staging approach that takes into consideration the individual patient immune response. Recently, the immunoscore was introduced; however, no accurate data regarding its sensitivity and specificity over the routinely used TNM staging system. AIM: We aimed to provide definite sensitivity, septicity, and predictive values for both IS and TNM staging system in prognosis prediction, as evidence-based statistical documentation of its validity to clinical use. METHODS: Fifty-three slides of colon cancer cases were stained for CD3 and CD8 immunohistochemical stains. The density of the stained cells was measured used an image analysis system in the core of the tumor and invasive margin. Immunoscore was calculated and results were compared with TNM in the recurrence-free survival of the patients. The sensitivity and specificity for each test were calculated. RESULTS: High IS was correlated with a good prognosis in the studied cases. IS sensitivity reached 85.7% compared to 28.6% in TNM staging system and the specificity was 78.1% compared to 37.5% in TNM system. CONCLUSION: IS is a promising prognostic estimation tool in colon cancer with better sensitivity and specificity than TNM staging system. The routine use of IS is now becoming a mandatory step.

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P–TNM staging system for colon cancer: combination of P-stage and AJCC TNM staging system for improving prognostic prediction and clinical management

Cancer Management and Research ◽

10.2147/cmar.s165188 ◽

2018 ◽

Vol Volume 10 ◽

pp. 2303-2314 ◽

Cited By ~ 6

Author(s):

Qi Liu ◽

Dakui Luo ◽

Sanjun Cai ◽

Qingguo Li ◽

Xinxiang Li

Keyword(s):

Colon Cancer ◽

Clinical Management ◽

Staging System ◽

Tnm Staging ◽

Tnm Staging System ◽

Prognostic Prediction

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Establishment of a Nomogram by Integrating Molecular Markers and Tumor-Node-Metastasis Staging System for Predicting the Prognosis of Hepatocellular Carcinoma

Digestive Surgery ◽

10.1159/000494219 ◽

2018 ◽

Vol 36 (5) ◽

pp. 426-432 ◽

Cited By ~ 4

Author(s):

Xi-Tai Huang ◽

Liu-Hua Chen ◽

Chen-Song Huang ◽

Jian-Hui Li ◽

Jian-Peng Cai ◽

...

Keyword(s):

Molecular Markers ◽

Validation Cohort ◽

External Validation ◽

Staging System ◽

Tnm Staging ◽

Hazard Ratio ◽

Tumor Node Metastasis ◽

Training Cohort ◽

Tnm Staging System

Aims: This study aimed to develop a valuable nomogram by integrating molecular markers and tumor-node-metastasis (TNM) staging system for predicting the long-term outcome of patients with hepatocellular carcinoma (HCC). Methods: The gene expression profiles of HCC patients undergoing liver resection were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. One hundred and ninety-nine patients from TCGA and 94 patients from GEO were selected to be part of the training cohort and validation cohort respectively. Univariate and multivariate cox analyses were performed to identify genes with independent prognostic values for overall survival (OS) of HCC patients in training cohort. Risk score was calculated based on the coefficients and Z-score of 3 genes for each patient. The nomogram was developed based on the risk score and TNM staging system. Discrimination and predictive accuracy of the nomogram were measured by using the concordance index (C-index) and calibration curve. The efficacy of the nomogram was tested in the external validation cohort. Results: Univariate and multivariate cox analyses revealed that EXT2 (p = 0.035, hazard ratio 13.412), ETV5 (p = 0.010, hazard ratio 4.325), and CHODL (p < 0.001, hazard ratio 6.286) were independent prognostic factors and chosen for further nomogram establishment. The C-index of the nomogram for predicting the OS in the training cohort was superior to that of the TNM staging system (0.77 vs. 0.64, p < 0.01). The calibration curve of predicted 1-, 3-, and 5-year OS showed satisfactory accuracy. The external validation cohort showed good performance of comprehensive nomogram as well. Conclusion: The novel nomogram by integrating the molecular markers and TNM staging system has better performance in predicting long-term prognosis in HCC patients than the TNM staging system alone.

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Addition of V-Stage to Conventional TNM Staging to Create the TNVM Staging System for Accurate Prediction of Prognosis in Colon Cancer: A Multi-Institutional Retrospective Cohort Study

Biomedicines ◽

10.3390/biomedicines9080888 ◽

2021 ◽

Vol 9 (8) ◽

pp. 888

Author(s):

Jung Hoon Bae ◽

Ji Hoon Kim ◽

Jaeim Lee ◽

Bong-Hyeon Kye ◽

Sang Chul Lee ◽

...

Keyword(s):

Colon Cancer ◽

Disease Free Survival ◽

Staging System ◽

Tnm Staging ◽

Stage Ii ◽

Prognostic Impact ◽

Free Survival ◽

N Stage ◽

Prediction Of Prognosis ◽

Study Participants

We evaluated the prognostic impact of vascular invasion (VI) compared with nodal (N) stage and developed a new staging system including VI in colon cancer. Patients who underwent curative resection with stage II-III colon cancer were assigned to VI and non-VI groups; the latter was subclassified as N0, N1, and N2; a new TNVM staging was devised by adding the V-stage. Among the 2243 study participants, the VI group independently showed worse oncological outcomes than the N1 group (disease-free survival (DFS), hazard-ratio (HR) 1.704, 1.267–2.291; overall survival (OS), HR 2.301, 1.582–3.348). The 5-year DFS in the VI group was 63.4% [N1b (74.6%), p = 0.003; N2a (69.7%), p = 0.126; and N2b (56.8%), p = 0.276], and the 5-year OS was 76.6% [N1b (84.9%), p = 0.004; N2a (83.0%), p = 0.047; and N2b (76.1%), p = 0.906]. Thus, we considered VI as N2a in TNVM staging; 78 patients (3.5%) underwent upstaging. The 5-year OS rates of stage IIB and IIC increased from 88.6% and 65.9% in TNM staging to 90.5% and 85.7% in TNVM staging, respectively. In stage II–III colon cancer, VI had a similar prognostic impact as the N2 stage without VI. The incorporation of the V-stage into the conventional TNM staging facilitates better prediction of prognosis.

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Verification of T-plus staging system for colorectal cancer based on nomogram analysis of single center’s 25-year follow-up.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.516 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 516-516

Author(s):

Ke-Feng Ding ◽

Jun Li ◽

Xiang-Xing Kong ◽

Ke-Jun Tang ◽

Di-Kai Bei ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Staging System ◽

Tnm Staging ◽

Information Criteria ◽

Stage Ii ◽

Lymph Node Status ◽

T Stage ◽

Node Status ◽

Tnm Staging System

516 Background: We proposed T-plus staging system which abandon the criterion to discriminate stage II/III by lymph node status and strengthens weighting of the T stage according to cluster analysis of the summary survival data of SEER. In this study, this principle of the T-plus staging system was verified with single center data by nomogram analysis. Methods: The 1,099 patients with colorectal cancer diagnosed before 2005 were analyzed to build a novel staging system based on nomogram (nomo-staging system). The remaining 981 patients diagnosed after 2005 were used to test the performance of nomo-staging system, T-plus staging system and the 7th edition TNM staging system by Akaike information criteria (AIC), Harrell’s c-index and the area under the curve (AUC) of Receiver Operating Characteristic to predict 5-year overall survival. A smaller AIC, higher c-index and higher AUC indicated a better staging system. Results: The nomo-staging system and T-plus staging system were listed in Table 1. The validation found that the 7th edition TNM staging system showed the weakest performance. For AIC, both nomo-staging system and T-plus staging system showed smaller value than the 7th edition TNM staging system (3214.912 vs. 3224.643 vs. 3229.810). For Harrell’s c-index, both the T-plus staging system and nomo-staging system showed higher value than the 7th edition TNM staging system (0.6814 vs. 0.6787 vs. 0.6778). For AUC to predict 5-year OS, the T-plus staging system and nomo-staging system showed slightly higher value than the 7th edition TNM staging system (0.6944 vs. 0.6924 vs. 0.6913). Conclusions: We propose replacement of lymph node status as the criterion to discriminate colorectal cancer stage II/III with greater weighting of the T stage. [Table: see text]

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Construction and validation of a simple-to-use nomogram incorporating clinicopathological parameters into the TNM staging system to predict prognosis for stage II colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.31 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 31-31

Author(s):

Shaobo Mo ◽

Yaqi Li ◽

Junjie Peng ◽

SanJun Cai

Keyword(s):

Colorectal Cancer ◽

Large Population ◽

Disease Free Survival ◽

Staging System ◽

Tnm Staging ◽

Stage Ii ◽

Clinicopathological Parameters ◽

Tnm Staging System ◽

Stage Ii Colorectal Cancer ◽

Validation Set

31 Background: Survival outcomes are significant different in stage II colorectal cancer (CRC) patients with diverse clinicopathological features. Objective of this study is to establish a credible prognostic nomogram incorporating easily obtained parameters for stage II CRC patients. Methods: A total of 1708 stage II CRC patients at Fudan University Shanghai Cancer Center (FUSCC) during 2008 to 2013 were retrospectively analyzed in this study. Cases were randomly separated into training set (n = 1084) and validation set (n = 624). Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors which were subsequently incorporated into a nomogram. The performance of the nomogram was evaluated by C-index and ROC curve to calculate the area under the curve (AUC). The clinical utility of the nomogram was evaluated using decision curve analysis (DCA). Results: In univariate and multivariate analyses, eight parameters were correlated with disease free survival (DFS), which were subsequently selected to draw prognostic nomogram based on DFS. For DFS predictions, the predicted concordance index (C-index) of the nomogram was 0.842 (95% confidence interval (CI), 0.710-0.980), and 0.701 (95% CI, 0.610-0.770) for training and validation set, respectively. The AUC values of ROC predicted 1, 3 and 5-year survival of nomogram in the training and validation groups were 0.869, 0.858, 0.777 and 0.673, 0.714, 0.706, respectively. The recurrence probability calibration curve showed good consistency between actual observations and nomogram-based predictions. DCA showed better clinical application value for the nomogram compared with TNM staging system. Conclusions: A novel nomogram based on a large population study was established and validated, which is a simple-to-use tool for physicians to facilitate the postoperative personalized prognostic evaluation and determine therapeutic strategies for stage II CRC patients.

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