Current TNM Staging Research Articles

Prognostic evaluation of platelet to lymphocyte ratio in patients with colorectal cancer.

Growing evidence indicates that inflammation plays an important role in cancer progression and prognosis; however, the prognostic role of platelet to lymphocyte ratio (PLR) in colorectal cancer (CRC) is unknown. A cohort of 1845 CRC patients from the Department of Surgical Oncology at The First Hospital of China Medical University (CMU-SO) was retrospectively analyzed. Harrell’s concordance index (c-index) was used to determine the optimal cut-off value of PLR and evaluate its predictive ability. Our results from CMU-SO indicated that the overall survival (OS) rate was significantly lower in the high-PLR group compared with the low-PLR group (P = 0.001). A similar result was observed for the cancer-specific survival (CSS) rate between these two groups (P = 0.001). The multivariate analysis indicated that high PLR was an independent prognostic indicator of poor OS (hazard ratio [HR] = 1.356, 95% confidence interval [CI] = 1.117–1.647, P = 0.002) and CSS (HR = 1.364, 95% CI = 1.111–1.675, P = 0.003). In addition, the c-indexes of TNM staging combined with PLR were greater than those of TNM staging alone (OS: 0.768 vs. 0.732; CSS: 0.785 vs. 0.746). In conclusion, elevated PLR is a negative prognostic indicator of CRC and may serve as an additional index of the current TNM staging system for predicting CRC.

Association of O6-Methylguanine-DNA Methyltransferase Protein Expression With Postoperative Prognosis and Adjuvant Chemotherapeutic Benefits Among Patients With Stage II or III Gastric Cancer

Loss of O6-methylguanine-DNA methyltransferase (MGMT) protein expression has been reported in several malignant tumors and predicts dismal survival outcomes. In gastric cancer, existing studies on this topic are limited and the association between MGMT and fluorouracil-based adjuvant chemotherapy remains obscure. To investigate the postoperative prognostic significance of MGMT in patients with resectable gastric cancer and its responsiveness to fluorouracil-based adjuvant chemotherapy. This study recruited 445 consecutive patients with resectable gastric cancer who underwent radical gastrectomy between August 1, 2007, and December 30, 2008, at Zhongshan Hospital at Fudan University in Shanghai, China. Patients were randomly divided into a discovery data set (n = 200) and a validation data set (n = 245), and the range of follow-up time was from 2 to 76 months for the discovery group and 2 to 79 months for the validation group. The immunoreactivity for MGMT in cancer cells was reviewed under a light microscope by 2 pathologists who were blinded to the clinicopathological data. The association of MGMT expression with clinicopathological characteristics and measures and prognosis was inspected. Data and specimens were collected from patients from the date of surgery to April 25, 2014. Data analysis took place from May 9, 2016, to July 15, 2016. Estimates of overall survival on the basis of MGMT expression and hazard ratio (HR) for estimates of overall mortality risk. Of the 445 patients included in the study, 315 (70.8%) were men, and the mean (SD) age of all patients was 60 (12) years. Positive expression of MGMT indicated better overall survival for patients with stage II or III gastric cancer in both the discovery data set (HR, 0.52; 95% CI, 0.32-0.84; P = .003) and the validation data set (HR, 0.63; 95% CI, 0.43-0.93; P = .01). Multivariate analysis identified MGMT expression and TNM stage as 2 independent prognostic factors for overall survival. In stage II disease, the benefit from fluorouracil-based adjuvant chemotherapy was superior among MGMT-positive patients (HR, 0.35; 95% CI, 0.13-0.95; P = .007 for interaction) compared with MGMT-negative patients. Positive expression of MGMT in gastric cancer was identified as an independent, favorable prognostic factor. Incorporating MGMT expression into the current TNM staging system could lead to better prognostic accuracy. These findings should be confirmed within the framework of randomized clinical trials associated with genomic DNA sequencing studies.

Restratification of survival prognosis of N1b papillary thyroid cancer by lateral lymph node ratio and largest lymph node size.

The current 7th TNM staging stratifies N1b papillary thyroid cancer (PTC) patients without distant metastasis into either stage I or stage IV merely by an age threshold (45 years). To date, no studies have adequately quantified the mortality risk of PTC patients with N1b disease. We hypothesized that incorporating lymph node (LN) factors into the staging system would better predict cancer‐specific mortality (CSM). A total of 745 nonmetastatic PTC patients with N1b disease were enrolled. We identified factors related to LNs and cut‐points using Cox regression and time‐dependent ROC analysis. New prognostic groupings were derived based on minimal hazard differences for CSM among the groups stratified by LN risk and age, and prediction of CSM was assessed. Lateral lymph node ratio (LNR) and largest LN size were significant prognostic LN factors at cut‐points of 0.3 and 3 cm. Without LN risk (lateral LNR >0.3 or largest LN size >3 cm), stage IV patients had prognosis [adjusted HR 1.10 (98% CI 0.19–6.20); P = 0.906] similar to stage I patients with LN risk. Patients were restratified into three prognostic groups: Group 1, <45 years without LN risk; Group 2, <45 years with LN risk or ≥45 years without LN risk; and Group 3, ≥45 with LN risk. This system had a lower log‐rank P‐value (<0.001 vs. 0.002) and higher C‐statistics (0.80 vs. 0.71) than the 7th TNM. New prognostic grouping using lateral LNR and largest LN size predicts CSM accurately and distinguishes N1b patients with different prognosis.

Stathmin 1 expression predicts prognosis and benefits from adjuvant chemotherapy in patients with gallbladder carcinoma.

BackgroundAbnormal expression of Stathmin 1(STMN1) plays an important role in the proliferation and migration of gallbladder carcinoma (GBC). The purpose of current study is to investigate the prognostic significance of STMN1 in GBC patients after surgery.MethodsSTMN1 expression was evaluated with immunohistochemistry (IHC) on tissue microarrays from 70 GBC patients from a single institution between 2009 and 2013. The correlation between STMN1 expression and clinicopathological profiles and the prognosis was statistically inspected.ResultsHigh expression of STMN1 in tumoral tissue was associated with poor tumor differentiation (P<0.001), lymph node metastasis (P=0.028), advanced TNM stage (P=0.011) and short overall survival (P<0.001). Cox multivariate analysis identified the STMN1 expression as an independent prognostic factor. Integrating STMN1 expression with current TNM staging system generate a better clinical predictive model for GBC. Moreover, the postoperative adjuvant chemotherapy (ACT) showed significant benefit in TNM III- IV stage patients with low STMN1 expression.ConclusionSTMN1 might be an independent adverse prognostic factor in GBC patients after surgery, which could be combined with TNM staging system to improve the predictive accuracy for overall survival. Low expression of STMN1 stratified a subgroup of advanced GBC patients who could benefit from ACT.

Rethinking the Current American Joint Committee on Cancer TNM Staging System for Medullary Thyroid Cancer

Controversy exists around the American Joint Committee on Cancer (AJCC) TNM staging system for medullary thyroid cancer (MTC). Because of the rarity of the disease and limited available data, the staging system for MTC has been largely extrapolated from staging for differentiated thyroid cancer. To evaluate how well the current (seventh and eighth editions) AJCC TNM staging system correlates with survival for patients with MTC and to suggest a possible revision. This population-based retrospective cohort analysis used the National Cancer Database to select patients aged 18 years or older diagnosed with MTC in the United States between 1998 and 2012. Patient demographic and tumor characteristics were assessed, and pathologic tumor stages were provided as T, N, and M categories. Recursive partitioning with bootstrapping was used to divide patients by TNM stages into groups with similar survival. The newly identified groupings were validated in a Surveillance, Epidemiology, and End Results (SEER) cohort. Data analysis was conducted between July 17, 2016, and November 11, 2016. Overall survival and disease-specific survival. Of the 3315 patients with MTC included in the analysis, 1941 (58.6%) were women. The median (interquartile range) age was 54 (42-65) years, and 2839 (85.6%) self-reported their race/ethnicity as white. The current AJCC TNM staging system classified 941 of these patients (28.4%) as stage I, 907 (27.4%) as stage II, 424 (12.9%) as stage III, and 1043 (31.5%) as stage IV. Recursive partitioning analysis yielded 4 TNM groups: stage I (T1N0-1aM0, T2N0M0), stage II (T1N1bM0, T2N1a-bM0, and T3N0M0), stage III (T3N1a-bM0, T4N0-1bM0), and stage IV (T1-4N0-1bM1). Based on these proposed TNM groupings, 1797 of the 3315 patients (54.2%) were classified as stage I, 684 (20.6%) as stage II, 669 (20.2%) as stage III, and 165 (5.0%) as stage IV. Under the proposed TNM groupings, survival differences across TNM groups were more distinct than under the current AJCC TNM staging system. With stage I as the reference, the hazard ratios of the proposed TNM groupings and the current AJCC TNM staging system were 2.19 (95% CI, 1.37-3.12) vs 1.45 (95% CI, 1.09-1.92) for stage II, 4.20 (95% CI, 2.75-5.75) vs 2.17 (95% CI, 1.59-2.89) for stage III, and 10.97 (95% CI, 5.52-18.57) vs 5.33 (95% CI, 4.13-6.86) for stage IV. In a SEER cohort, the proposed TNM groupings were better at discriminating survival than was the current AJCC TNM staging system. The current AJCC TNM staging system for MTC appears to be less than optimal in distinguishing risk of mortality among stage groups, upstaging a significant number of patients to stage IV. The current AJCC TNM staging system could be improved with the new TNM groupings proposed here for more accurate risk stratification and potential treatment selection.

The Pretreatment Neutrophil-to-Lymphocyte Ratio is a Prognostic Determinant of T3-4 Hypopharyngeal Squamous Cell Carcinoma.

This study aimed to investigate the clinicopathological factors that influence recurrence and survival in patients who undergo operations for T3-4 hypopharyngeal squamous cell carcinomas (SCCs). One hundred and five patients who underwent surgery between 2001 and 2008 for advanced hypopharyngeal SCCs were consecutively enrolled and reviewed. The pretreatment neutrophil-to-lymphocyte ratio (NLR; median 3.22, range 0.62-46.50) was associated with disease recurrence and patient survival. A difference in the 5-year cumulative disease recurrence rate between patients with high (≥3.22) and low (<3.22) NLRs was significant (60.4 and 36.5%, respectively; p=0.004). A multivariate analysis confirmed that an NLR≥3.22 was an independent indicator of a poor prognosis for advanced hypopharyngeal SCC, as per the following parameters: overall survival (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.48-4.30, p=0.001), disease-specific survival (HR 2.45, 95% CI 1.38-4.34, p=0.002), and disease-free survival (HR 2.18, 95% CI 1.24-3.83, p=0.007). Additional prognostic factors per the survival analyses included lymph node density, surgical margin, lymphovascular invasion, and perineural invasion. An NLR≥3.22 is associated with a higher risk of disease recurrence and poor survival in patients with T3-4 hypopharyngeal SCCs. We propose the use of the NLR to broaden the current TNM staging system; the development of a more effective treatment protocol for patients with high NLRs will be essential.

Lymph node ratio as a prognostic factor in gastric cancer patients following D1 resection. Comparison with the current TNM staging system

IntroductionNodal ratio (NR) has been demonstrated to be an independent prognostic factor in patients with gastric cancer. We evaluated the prognostic role of NR comparing it with the current TNM (2010) classification in gastric cancer patients treated with curative (R0) D1 resection. Materials and methodsWe retrospectively reviewed 110 patients who underwent R0 resection for gastric cancer at University Hospital of Larissa between 2002 and 2011. All patients had a D1 lymphadenectomy plus the nodes along the left gastric artery. Factors affecting survival as well as correlations between the N status, NR status and resected nodes were investigated. ResultsIn univariate analysis the N and NR status but not the numbers of retrieved nodes were significant prognostic factors. Inside N1 and N2 categories, patients with different NR groups were present and survival of some of these subpopulations was statistically different at long-rank test. There was a correlation between the nodes retrieved and N status but not with the NR category. In multivariate analysis both N status (HR=1.45; 95% C.I. = 1.19–1.89) and NR (HR=4.53; 95% C.I. = 1.86–11.03) found to be independent prognostic factors of survival. ConclusionPrognostic significance of N status and NR status was comparable. Unlike N status, NR is independent by the number of resected nodes, and therefore it is particularly useful in case of conventional lymphadenectomy.

Abstract P6-09-17: Evaluation of a risk score based on biologic factors to enhance prognostic stratification by the American Joint Committee on Cancer (AJCC) Staging System

Abstract Background: The 7th edition AJCC staging system provides prognostic information based on the anatomic extent of disease determined by the tumor size (T), lymph node status (N), and presence or absence of metastatic disease (M). Tumor biology, including grade, estrogen receptor (ER) status and HER2 status, which are known to have prognostic and predictive value, are not incorporated. This study was undertaken to evaluate a risk score that takes into account the tumor grade and other biomarkers that can be added to the current anatomic TNM staging system to improve stratification of patients with respect to disease specific survival (DSS) and overall survival (OS). Methods: A prospectively maintained database was used to identify 3,327 patients with non-metastatic invasive breast cancer who underwent surgery as a first intervention from January 2007 through December 2013. Clinicopathologic data were recorded including: age, grade, ER status, HER2 status, and pathologic stage. Pathologic stage was determined according to the 7th edition of the AJCC staging guidelines. ER status was recorded as the percentage of cells staining positive by immunohistochemistry (IHC). Prior to 2010, tumors were classified as ER positive if there was &amp;gt;10% staining. A cut-off of 1% was used for patients treated after 2010, consistent with the change in American Society of Clinical Oncology (ASCO) guidelines. HER2 status was defined as positive if 3+ on immunohistochemistry or gene amplification was shown on fluorescence in situ hybridization. A risk score was calculated by assigning one point for each of the following tumor characteristics: ER-negative status, HER2 negative status and grade 3. Univariate survival analyses according to AJCC stage (I, IIA, IIB, IIIA and IIIC) and risk score (0-3) were performed for DSS and OS using the Kaplan Meier method. Results: Median follow-up time was 5.0 years (range, 0.1 to 8.8). Five year DSS for the entire cohort was 97.9% (95% CI: 97.3%-98.4%). The distribution in risk score in the entire cohort was: risk score 0=81 (2.4%), 1=2289 (68.8%), 2=683 (20.5%), and 3= (8.3%). As shown in the table, for all AJCC stages, the 5-yr DSS and 5-yr OS varied according to risk score (p&amp;lt;.01). StageRisk Scoren5-yr DSS (%)95% CI5-yr OS (%)95% CII (IA and IB)036100 9780.4-99.6 1117399.498.7-99.796.795.4-97.6 227498.896.4-00.694.691.0-06.8 311996.691.1-98.793.887.5-97.0IIA031100 96.879.2-99.5 163499.497.5-99.897.194.7-98.4 223697.593.2-99.194.188.7-97.0 39891.081.8-95.788.278.5-93.8IIB011100 100 130996.992.6-98.894.689.6-97.2 210792.983.6-97.189.380.1-94.4 34091.575.6-97.291.575.6-97.2IIIA03100 100 113498.388.2-99.891.582.6-96.0 25092.277.2-97.590.375.7-96.3 3768.621.3-91.268.621.3-91.2IIIC00 13992.272.1-98.084.463.7-93.9 21680.851.4-93.480.851.4-93.4 31033.36.3-64.633.36.2-64.6 Conclusion: The current study demonstrates that incorporating the risk score with current AJCC staging significantly improves the ability to stratify breast cancer patients with respect to DSS and OS. We recommend that the risk score be incorporated into the forthcoming revision of the AJCC staging system. Citation Format: Mittendorf EA, Vila J, Yi M, Chavez-MacGregor M, Chen RL, Giordano SH, Hunt KK. Evaluation of a risk score based on biologic factors to enhance prognostic stratification by the American Joint Committee on Cancer (AJCC) Staging System [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-17.

Incorporation of serum carcinoembryonic antigen levels into the prognostic grouping system of colon cancer.

This study aimed to clarify the significance of preoperative serum carcinoembryonic antigen (CEA) on disease-free survival (DFS) in colon cancer and propose a new prognostic grouping system. A multiinstitutional retrospective cohort of 7296 colon cancer patients who underwent R0 surgery between 1997 and 2006 was analyzed. We stratified preoperative serum CEA values into three categories (C-stages): C0 (normal CEA), C1A (up to double the cutoff value), and C1B (more than double the cutoff value) and stratified each TNM stage by C-stage. Multivariate analyses using Cox regression models were used to analyze the significance of C-stage on 5-year DFS. CEA level was an independent factor affecting DFS; the 5-year DFS of patients with C0 and C1, as well as those with C1A and C1B, differed significantly (C0 84.6%, C1 69.8%, C1A 72.7%, and C1B 66.4%, P<0.0001). Additionally, the DFS of pStages IIC and C1B was significantly lower than of pStages IIIA and C0 (65.8 vs. 87.7%, respectively; hazard ratio 3.44, 95% confidence interval 1.97-5.88, P<0.0001). Moreover, the 5-year DFS of pStages IIIA and C0 or C1A did not differ significantly from pStages I and C1A (87.7 vs. 87.7%, P=0.90 and 86.4 vs. 87.7%, P=0.78, respectively). pStage IIC and C1B disease should be considered candidates for intensive adjuvant chemotherapy. Conversely, pStages IIIA and C0 or C1A could be exempted from adjuvant chemotherapy. Incorporating C-stage into the current TNM staging system may facilitate decision making regarding the use of adjuvant chemotherapy in colon cancer patients.

A proposal for a novel and simple TNM staging for gastric cancer.

21 Background: Current TNM staging system for gastric cancer has controversies regarding N classification. We aimed to develop a simple and novel TNM staging system for gastric cancer by re-grouping N classification. Methods: We retrospectively reviewed 14260 patients treated for gastric cancer. To develop simple combinations of TNM staging with similar weighted value between T and N classification, N classification was restructured with different cutoffs. The optimal cutoffs for the number of metastatic lymph node which maximize the x2 statistic of log-rank test for survival differences among patients were selected. C-statistic was used to compare the discriminating performance of the proposed N classification with the current N classification in the TNM staging system. We performed validation with 2 external datasets from a hospital in Korea (n = 1500) and SEER (n = 11324). Results: We identified the new cutoffs of N classification as 1~4, 5~10, 11~24, and 25 or more for N1, N2, N3a, and N3b, respectively. We found survival of the new N3b classification was similar to M1, regardless of T classification. Thus, we stratified these groups of N3b and M1 disease as stage IV, simultaneously. Our new TNM staging had similar weighted value between T and N classification resulting in simple combinations. (Table) Survival curves of subgroups in the new TNM staging had higher x2 value than current staging system (x2: 8239 vs. 7023, respectively) and homogeneity among subgroups in the same stage increased. However, C-statistics (0.801, 95%CI: 0.795, 0.807) of new model showed similar discrimination power than that (0.797, 95%CI: 0.791, 0.803) in 7th TNM staging system. C-statistics were also similar in other hospital in Korea (0.805 vs. 0.802, respectively) and SEER database (0.709 vs. 0.706, respectively). Conclusions: This novel staging system by recalculating cut-offs of N classification provides exceptionally simple and practical way to stratify substages in TNM staging for gastric cancer. [Table: see text]

Importance of maintaining body weight for prevention of distant metastasis of nasopharyngeal carcinoma: An alternative workflow for cancer-risk assessment.

Purpose: To design an alternative workflow for cancer-risk assessment to predict distant metastasis (DM) of nasopharyngeal carcinoma (NPC).Methods: We enrolled 234 patients with non-disseminated NPC and a family history of cancer who underwent intensity-modulated radiotherapy and concurrent chemo-radiotherapy with/without induction chemotherapy in our primary cohort. We conducted univariate and multivariate analyses of the associated prognostic factors, built a nomogram model for distant-metastasis-free survival (DMFS), and confirmed the prognostic value of weight-loss ratio (WTratio). The secondary cohort included 97 patients with available pre-DNA levels who were treated at our cancer center. We performed internal validation with the primary cohort and external validation with the secondary cohort, and compared the new DMFS model with the current 7th TNM staging system.Results: In the primary cohort, 95.9% patients experienced weight loss. The N group (N2-3 vs. N0-1, P = 0.037) and pre-DNA level (P = 0.02) were independent prognostic factors for DMFS in NPC patients. Smoking (P = 0.051) and WTratio (P = 0.052) showed a significant trend for DMFS. WTratio was an independent prognostic factor for DMFS (P = 0.03). Smoking, WTratio, N group, and pre-DNA level were merged to build a risk-score model for DMFS using a nomogram, which could predict survival after internal and external validation.Conclusions: Maintaining body weight during treatment is essential to prevent DM of NPC. Compared with the current 7th TNM staging system, the new DMFS model might better predict DM of NPC. The alternative workflow designed could be applied for prognostic analysis of other cancers.

The Prognostic Values of Preoperative Tumor Volume and Tumor Diameter in T1N0 Papillary Thyroid Cancer

Purpose The current TNM staging system for papillary thyroid cancer (PTC), which is based on tumor diameter, may not precisely reflect the true tumor burden. Therefore, we investigated whether preoperative tumor volume might more accurately reflect tumor burden and predict prognosis in patients with T1N0 PTC than preoperative tumor diameter. Materials and Methods We retrospectively reviewed data from 1,659 patients with T1N0 PTC, and after exclusion, a total of 1,081 patients were ultimately included. Tumor volume (V) was calculated for all patients using preoperative ultrasonography, and patients were grouped according to tumor diameter (T1a vs. T1b) and tumor volume (V1a vs. V1b). The recurrence-free survival (RFS) rates were then compared for these groups.ResultsThe mean follow-up time was 66.12±28.75 months, and 97.2% of the cohort experienced RFS. The optimal volume cut-off was defined as 0.545 cm3. There were no differences in RFS rates between T1a/T1b groups (all ages) and V1a/V1b groups (< 45 years of age). However, ≥ 45-year-old patients in the V1b group had a significantly poorer RFS rate than those in the V1a group. These results were confirmed by multivariate analysis.Conclusion Our results indicate that preoperative tumor volume may be more useful for predicting prognosis than tumor diameter in ≥ 45-year-old patients with T1N0 PTC.

CXC chemokine receptor 1 predicts postoperative prognosis and chemotherapeutic benefits for TNM II and III resectable gastric cancer patients.

BackroundAbnormal expression of CXC chemokine receptor 1 (CXCR1) has shown the ability to promote tumor angiogensis, invasion and metastasis in several cancers. The purpose of our curret study is to discover the clinical prognostic significance of CXCR1 in resectable gastric cancer.Methods330 gastric cancer patients who underwent R0 gastrectomy with standard D2 lymphadenectomy at Zhongshan Hospital, Fudan University between 2007 and 2008 were enrolled. CXCR1 expression was evaluated with use of immunohistochemical staining. The relation between CXCR1 expression and clinicopathological features and postoperative prognosis was respectively inspected.ResultsIn both discovery and validation data sets, CXCR1 high expression indicated poorer overall survival (OS) in TNM II and III patients. Furthermore, multivariate analysis identified CXCR1 expression and TNM stage as two independent prognostic factors for OS. Incorporating CXCR1 expression into current TNM staging system could generate a novel clinical predictive model for gastric cancer, showing better prognostic accuracy with respect to patients’ OS. More importantly, TNM II patients with higher CXCR1 expression were shown to significantly benefit from postoperative 5-fluorouracil (5-FU) based adjuvant chemotherapy (ACT).ConclusionCXCR1 in gastric cancer was identified as an independent adverse prognostic factor. Combining CXCR1 expression with current TNM staging system could lead to better risk stratification and more accurate prognosis for gastric cancer patients. High expression of CXCR1 identified a subgroup of TNM stage II gastric cancer patients who appeared to benefit from 5-FU based ACT.

Tumor Staging and HPV-Related Oropharyngeal Cancer.

The current TNM staging for oropharyngeal cancer (OSCC) was designed empirically for non-HPV-related disease. Emerging evidence suggests it is unsuited for Human papillomavirus (HPV)-related OSCC. Patients with HPV-positive tumors have improved prognosis, despite presenting at advanced stages. These shortcomings of the current staging system have been identified in single- and multi-institutional trials. Patients with HPV related OSCC typically present with advanced N-stages leading to higher stage groupings. A rarity of stages I and II therefore represents the nature of HPV-related OSCC. Concerning prognosis of the patients, N-category and extracapsular spread seem to be of minor importance, whereas advanced T-stages result in unfavourable outcome. Anatomical staging therefore has been implied into different proposals to prognostic risk classifications in HPV-related disease as an additive compound. Prognostic risk groupings are further enhanced by incorporating non-anatomical factors. To summarize, it can be suggested that the current TNM system alone has little prognostic value in HPV-related OSCC.

Are disseminated tumor cells in bone marrow and tumor-stroma ratio clinically applicable for patients undergoing surgical resection of primary colorectal cancer? The Leiden MRD study.

PurposeCurrent TNM staging does not appropriately identify high-risk colorectal cancer (CRC) patients. The aim of this study was to evaluate whether the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) and the presence of stroma in the primary tumor, i.e., the tumor-stroma ratio (TSR), in patients undergoing surgical resection of primary CRC provides information relevant for disease outcome.MethodsPatients with primary CRC (n = 125), consecutively admitted for curative resection between 2001 and 2007, were included in the study. All patients underwent BM aspiration before surgery. Detection of tumor cells was performed using immunocytochemical staining for cytokeratin (CK-ICC). The TSR was determined on diagnostic H&E stained sections of primary tumors.ResultsDTCs were detected in the BM of 23/125 patients (18 %). No association was found between BM status and overall survival (HR 0.97 (95 % CI 0.45–2.09), p = 0.93). Also, no significant difference was found in their 5-year survival rate (resp. 72 % and 68 % for BM-positive versus BM-negative patients). The TSR was found to be associated with a worse overall survival (HR 2.16, 95 % CI 1.02–4.57, p = 0.04) with 5-year survival rates of 84 % versus 62 % for stroma-low and stroma-high patients, respectively. No relation was found between the presence of DTCs and TSR.ConclusionsOur data indicate that the presence of DTCs in the BM of CRC patients is not associated with disease outcome. The TSR was, however, found to be associated with a worse overall survival, which indicates that for CRC the tumor microenvironment plays an important role in its behavior and prognosis.

Esophageal cancer: Anatomic particularities, staging, and imaging techniques

Cancer of the esophagus is a tumor with aggressive behavior that is usually diagnosed in advanced stages. The absence of serosa allows it to spread quickly to neighboring mediastinal structures, and an extensive lymphatic drainage network facilitates tumor spread even in early stages. The current TNM classification, harmonized with the classification for gastric cancer, provides new definitions for the anatomic classification, adds non-anatomic characteristics of the tumor, and includes tumors of the gastroesophageal junction. Combining endoscopic ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging provides greater accuracy in determining the initial clinical stage, and these imaging techniques play an essential role in the selection, planning, and evaluation of treatment. In this article, we review some particularities that explain the behavior of this tumor and we describe the current TNM staging system; furthermore, we discuss the different imaging tests available for its evaluation and include a diagnostic algorithm.

Prognostic significance and the role in TNM stage of extranodal metastasis within regional lymph nodes station in gastric carcinoma.

The role of extranodal metastasis (ENM) in TNM stage in gastric carcinoma (GC) is controversial. This study was aimed to make a detailed investigation of the prognostic significance and the role in TNM stage of ENM in GC. The patients with primary GC, who underwent gastrectomy with curative intention in West China Hospital from January 2005 to December 2011, were retrospectively enrolled. The prognosis and clinicopathological traits were compared between ENM positive (ENMP) and negative (ENMN) groups in all patients, TNM I-II, III and IV stages, respectively. The significance of the number and the role in TNM stage of ENM were also assessed. In our study, 1457 patients were enrolled, with 1324 (90.9%) in ENMN group and 133 (9.1%) in ENMP group. ENMP group had significantly more advanced GC and worse prognosis (all p<0.05) than ENMN group in all patients, TNM I-II stages and TNM III stage. ENM>2 subgroup had remarkably larger tumor size (p=0.002) and more advanced N stage (p=0.016) than ENM=1-2 subgroup. The number of ENM was an independent prognostic factor in ENMP group (p=0.029). The prognosis of ENM>2 in TNM I-III stages was significantly worse than ENMN patients in TNM III stage. The C-index of TNM stage plus the number of ENM was significantly higher than that of current TNM stage alone (p=0.005). In conclusion, the patients in ENMP subgroup had more advanced GC and worse prognosis than those in ENMN subgroup. It might be more reasonable to categorize ENM>2 into TNM IV stage.

Does tumor size improve the accuracy of prognostic prediction in patients with esophageal squamous cell carcinoma after surgical resection?

This study aimed to investigate whether the inclusion of tumor size could improve the prognostic accuracy in patients with esophageal squamous cell cancer (ESCC). A total of 387 patients with ESCC who underwent curative resection were enrolled in this analysis. The patients were categorized into small-sized tumors (SSTs) and large-sized tumors (LSTs) using an appropriate cut-off point for tumor size. Kaplan–Meier survival curve and log–rank test were used to evaluate the prognostic value of tumor size. A Cox regression model was adopted for multivariate analysis. Their accuracy was compared based on the presence or absence of tumor size. Using 3.5 cm as the optimal cut-off point, 228 and 159 patients presented with LSTs (≥ 3.5 cm) and SSTs (< 3.5 cm), respectively. The patients with LSTs had significantly worse prognoses than patients with SSTs (23.9% vs. 43.2%, P < 0.001). Multivariate analysis revealed that tumor size, histological type, invasion depth, and lymph node metastasis were independent predictors of overall survival. The addition of tumor size to the AJCC TNM staging improved the predictive accuracy of the 5-year survival rate by 3.9%. Further study showed that tumor size and T stage were independent predictors of the prognosis of node-negative patients, and the combination of tumor size and T stage improved the predictive accuracy by 3.7%. In conclusion, tumor size is indeed a simple and practical prognostic factor in patients with ESCC. It can be used to improve the prognostic accuracy of the current TNM staging, especially for patients with node-negative disease.

Lymph node ratio-based staging system as an alternative to the current TNM staging system to assess outcome in adenocarcinoma of the esophagogastric junction after surgical resection.

This study aimed to assess the prognostic value of the hypothetical tumor-N-ratio (rN)-metastasis (TrNM) staging system in adenocarcinoma of the esophagogastric junction (AEG). The clinical data of 387 AEG patients who received surgical resection were retrospectively reviewed. The optimal cut-off point of rN was calculated by the best cut-off approach using log-rank test. Kaplan-Meier plots and Cox regressions model were applied for univariate and multivariate survival analyses. A TrNM staging system based on rN was proposed. The discriminating ability of each staging was evaluated by using an adjusted hazard ratio (HR) and a −2log likelihood. The prediction accuracy of the model was assessed by using the area under the curve (AUC) and the Harrell's C-index. The number of examined lymph nodes (LNs) was correlated with metastatic LNs (r = 0.322, P < 0.001) but not with rN (r = 0.098, P > 0.05). The optimal cut-points of rN were calculated as 0, 0~0.3, 0.3~0.6, and 0.6~1.0. Univariate analysis revealed that pN and rN classifications significantly influenced patients’ RFS and OS (P < 0.001). Multivariate analysis adjusted for significant factors revealed that rN was recognized as an independent risk factor. A larger HR, a smaller −2log likelihood and a larger prediction accuracy were obtained for rN and the modified TrNM staging system. Taken together, our study demonstrates that the proposed N-ratio-based TrNM staging system is more reliable than the TNM staging system in evaluating prognosis of AEG patients after curative resection.

Cáncer de esófago: particularidades anatómicas, estadificación y técnicas de imagen

Cancer of the esophagus is a tumor with aggressive behavior that is usually diagnosed in advanced stages. The absence of serosa allows it to spread quickly to neighboring mediastinal structures, and an extensive lymphatic drainage network facilitates tumor spread even in early stages. The current TNM classification, harmonized with the classification for gastric cancer, provides new definitions for the anatomic classification, adds non-anatomic characteristics of the tumor, and includes tumors of the gastroesophageal junction. Combining endoscopic ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging provides greater accuracy in determining the initial clinical stage, and these imaging techniques play an essential role in the selection, planning, and evaluation of treatment. In this article, we review some particularities that explain the behavior of this tumor and we describe the current TNM staging system; furthermore, we discuss the different imaging tests available for its evaluation and include a diagnostic algorithm.