Tumor, Node And Metastasis Stage Research Articles

The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groups in the Forthcoming (Ninth) Edition of the TNM Classification for Lung Cancer

IntroductionThe TNM classification of lung cancer is periodically revised. The International Association for the Study of Lung Cancer collected and analyzed a new database to inform the forthcoming ninth edition of the TNM classification. The results are herewith presented. MethodsAfter exclusions, 76,518 patients from a total of 124,581 registered patients were available for analyses: 58,193 with clinical stage, 39,192 with pathologic stage, and 62,611 with best stage NSCLC. The proposed new N2 subcategories (N2a, involvement of single ipsilateral mediastinal or subcarinal nodal station, and N2b, involvement of multiple ipsilateral mediastinal nodal stations with or without involvement of the subcarinal nodal station) and the new M1c subcategories (M1c1, multiple extrathoracic metastases in one organ system, and M1c2, multiple extrathoracic metastases in multiple organ systems) were considered in the survival analyses. Several potential stage groupings were evaluated, using multiple analyses, including recursive partitioning, assessment of homogeneity within and discrimination between potential groups, clinical and statistical significance of survival differences, multivariable regression, and broad assessment of generalizability. ResultsT1N1, T1N2a, and T3N2a subgroups are assigned to IIA, IIB, and IIIA stage groups, respectively. T2aN2b and T2bN2b subgroups are assigned to IIIB. M1c1 and M1c2 remain in stage group IVB. Analyses reveal consistent ordering, discrimination of prognosis, and broad generalizability of the proposed ninth edition stage classification of lung cancer. ConclusionsThe proposed stages for the ninth edition TNM improve the granularity of nomenclature about anatomic extent that has benefits as treatment approaches become increasingly differentiated and complex.

Lung Cancer Staging—A Clinical Practice Review

Lung cancer is the leading cause of cancer-associated death globally. Staging provides classification of the anatomic extent of cancer that is used consistently worldwide. Lung cancer staging is necessary for prognostication, to inform treatment options, and to allow accurate representation in clinical trials. Staging also separates operable from inoperable disease. Since its introduction in the 1970s, the Tumor, Node and Metastasis (TNM) Staging System has undergone significant revisions, with the latest version, the eighth edition, being effective internationally since 2017. Advances in bronchoscopic and thoracoscopic technologies have expanded procedures to diagnose lung cancer and accurately define the anatomic stage. Understanding the advantages and disadvantages of available methods for staging lung cancer is critical to clinician decision making. In patients with lung cancer without distant metastases, the staging of mediastinal lymph nodes determines treatment options. To minimize the risk and cost, the most appropriate method of staging should identify the highest disease stage while carrying acceptable risk. Minimally invasive endoscopic needle techniques to stage the mediastinum are the first choice to assess for metastases in accessible lymph node stations. Surgical techniques are generally reserved for specific clinical situations, including following negative endoscopic needle techniques when suspicion for nodal involvement is high and to assess endoscopically inaccessible lymph nodes. This review provides a concise account of TNM staging of non-small cell lung cancer (NSCLC) and overview of procedures available for the staging of lung cancer.

Up Regulation of Ezrin and Radixin with respect to Grade of Tumors in Breast Cancer Patients

Background: Breast cancer (BC) is one of the main causes of death among women in Iran. Biomarkers involved in promotion and progression of disease is very important in management and control of BC outcomes. In this research, we aim to estimate the expression levels of Ezrin and Radixin, as two important factors in morphogenesis, endocytosis, exocytosis, adherence, and migration of cells, in BC patients and their relationship with pathological factors.
 Methods: One hundred and thirteen BC patients were involved in this research. Relative expression of Ezrin and Radixin genes were estimated with quantitative real-time PCR. Pathological data include the histology, tumor size, grade, lymphovascular invasion and clinical TNM (Tumor, Node, and Metastasis) staging of patients were recorded based on the pathology report and their relationship with relative expression of Ezrin and Radixin were estimated.
 Result: According to result Ezrin were over expressed in tumor samples in comparison to adjacent normal tissue. There is a significant relationship between over expression of Ezrin and Radixin and grade of tumor and necrosis. Also there is a direct relationship between relative expression of Ezrin and Radixin expression.
 Conclusions: These data support the role of Ezrin and Radixin in the biology of breast cancer and additional studies needed that determine the Ezrin and Radixin associated with phenotype and may validate them as markers of cancer progression and as a potential target for cancer therapy.

Construction a new nomogram prognostic model for predicting overall survival after radical resection of esophageal squamous cancer.

Esophageal cancer is one of the deadliest malignancies in the world, and 5-year overall survival (OS) of esophageal cancer ranges from 12% to 20%. Surgical resection remains the principal treatment. The American Joint Commission on Cancer (AJCC) TNM (tumor, node, and metastasis) staging system is a key guideline for prognosis and treatment decisions, but it cannot fully predict outcomes. Therefore, targeting the molecular and biological features of each patient's tumor, and identifying key prognostic biomarkers as effective survival predictors and therapeutic targets are highly important to clinicians and patients. In this study, three different methods, including Univariate Cox regression, Lasso regression, and Randomforest regression were used to screen the independent factors affecting the prognosis of esophageal squamous cell carcinoma and construct a nomogram prognostic model. The accuracy of the model was verified by comparing with TNM staging system and the reliability of the model was verified by internal cross validation. Preoperative neutrophil lymphocyte ratio(preNLR), N-stage, p53 level and tumor diameter were selected to construct the new prognostic model. Patients with higher preNLR level, higher N-stage, lower p53 level and larger tumor diameter had worse OS. The results of C-index, Decision Curve Analysis (DCA), and integrated discrimination improvement (IDI) showed that the new prognostic model has a better prediction than the TNM staging system. The accuracy and reliability of the nomogram prognostic model were higher than that of TNM staging system. It can effectively predict individual OS and provide theoretical basis for clinical decision making.

Tumeurs de la cavité orale et classification TNM (8e édition) : problématiques et recommandations

Stage of cancer at the time of the diagnosis is a key factor for the prognosis and the determination of appropriate treatment. Several cancer staging systems are used worldwide. The most useful staging system is the tumor, node and metastasis (TNM) staging system develop by the American Joint Committee on Cancer (AJCC) in collaboration with the Union for International Cancer Control (UICC) referred to as the AJCC TNM staging system. The AJCC TNM system classifies cancers by the size and extend of the primary tumor (T), involvement of regional lymph nodes (N) and the presence of distant metastases (M). AJCC and UICC periodically modify the AJCC TNM staging system according to newly acquired clinical, pathological and biological data improving understanding of cancer physiopathology. The 8th edition of AJCC TNM system is effective for cancer patients diagnosed on or after January 1, 2018. Here, we report the issues of the staging cancers of the oral cavity according to the 8th edition of AJCC TNM system. We focus on 2 new concepts defined in the 8th edition of AJCC TNM system: depth of invasion (DOI) and extranodal extension (ENE).

LCSCNet: A multi-level approach for lung cancer stage classification using 3D dense convolutional neural networks with concurrent squeeze-and-excitation module

Lung cancer, the deadliest disease worldwide, poses a massive threat to humankind. Various researchers have designed Computer-Aided-Diagnosis systems for the early-stage detection of lung cancer. However, patients are primarily diagnosed in advanced stages when treatment becomes complicated and dependent on multiple factors like size, nature, location of the tumor, and proper cancer staging. TNM (Tumor, Node, and Metastasis) staging provides all this information. This study aims to develop a novel and efficient approach to classify lung cancer stages based on TNM standards. We propose a multi-level 3D deep convolutional neural network, LCSCNet (Lung Cancer Stage Classification Network). The proposed network architecture consists of three similar classifier networks to classify three labels, T, N, and M-labels. First, we pre-process the data, in which the CT images are augmented, and the label files are processed to get the corresponding TNM labels. For the classification network, we implement a dense convolutional neural network with a concurrent squeeze & excitation module and asymmetric convolutions for classifying each label separately. The overall stage is determined by combining all three labels. The concurrent squeeze & excitation module helps the network focus on the essential information of the image, due to which the classification performance is enhanced. The asymmetric convolutions are introduced to reduce the computation complexity of the network. Two publicly available datasets are used for this study. We achieved average accuracies of 96.23% for T-Stage, 97.63% for N-Stage, and 96.92% for M-Stage classification. Furthermore, an overall stage classification accuracy of 97% is achieved.

Survival rates and prognostic factors of thyroid cancer: A retrospective cohort study

Introduction: The most prevalent endocrine malignancy is thyroid carcinoma. Thyroid cancer is much more common than it was previously. The prognosis of people with this condition can be impacted by a number of factors. Objectives: The purpose of this study was to assess the prognosis and survival rates of thyroid cancer patients in western Iran. Patients and Methods: This retrospective cohort study was performed on all patients (n = 312) with diagnosing thyroid cancer based on pathology results between 2011 and 2021. Demographic and clinical information and disease staging of patients based on TNM (tumor, node, and metastasis) system were extracted from patients’ medical records. Kaplan-Meier method, log-rank test, and Cox regression were used for the analysis of the data. The obtained data were analyzed in SPSS version 22. Results: Our findings showed that the mean survival time for all participants in the study was 39.9 months. Additional analysis revealed that the mean survival time is significantly lower in people who residence in urban areas. Furthermore, men, people aged 50-80 years old, and those who were in the TNM stage I had the highest mean survival time. Based on the univariate analysis age, TNM stage are associated with risk of death in patient with thyroid cancer. Conclusion: Death from thyroid cancer is correlated with patients’ age, gender, and disease stage. Age is important risk of death. Additionally, overall survival of the patients decreases with increasing time.

Prognostic and clinicopathological value of Twist expression in esophageal cancer: A meta-analysis.

BACKGROUNDTwist is a repressor of E-cadherin transcription that induces epithelial-mesenchymal transition and cancer metastasis. However, the prognostic value of Twist expression in patients with esophageal cancer remains controversial.AIMTo investigate the prognostic and clinicopathological value of Twist expression in esophageal cancer.METHODSPublished literature in databases such as EMBASE, Web of Science, PubMed, China National Knowledge Infrastructure, Wanfang, and VIP databases was searched for eligible articles. Participants with esophageal cancer whose tumor tissues underwent immunohistochemistry to detect the expression of Twist were considered. Our meta-analysis was conducted using Stata version 12.0. The hazard ratio (HR) and relative ratio (RR) with their 95%CI were pooled. Heterogeneity was estimated by I2 statistics.RESULTSEleven articles published between 2009 and 2021 fulfilled the selection criteria. The pooled HR for overall survival was 1.88 (95%CI: 1.32-2.69, I2 = 68.6%), and the pooled HR for disease-free survival/relapse-free survival/progression-free survival was 1.84 (95%CI: 1.12-3.02, I2 = 67.1%), suggesting that high Twist expression is associated with poor prognosis in esophageal cancer patients. In addition, overexpression of Twist was correlated with T stage (T3 + T4 vs T1 + T2, RR = 1.38, 95%CI: 1.14-1.67), lymph node metastasis (yes vs no, RR = 1.34, 95%CI: 1.11-1.60), distant metastasis (yes vs no, RR = 1.18, 95%CI: 1.02-1.35), tumor, node and metastasis (TNM) stage (III + IV vs I + II, RR = 1.35, 95%CI: 1.14-1.60), and clinical stage (III + IV vs I + II, RR = 1.58, 95%CI: 1.34-1.87). However, no correlation between Twist expression and age, gender, tumor location, differentiation, or venous invasion was observed.CONCLUSIONHigh expression of Twist is associated with poor esophageal cancer prognosis. Moreover, Twist overexpression is correlated with T stage, lymph node metastasis, distant metastasis, TNM stage, and clinical stage, which indicates that Twist might accelerate esophageal cancer progression and metastasis.

Comparative Study of Hypo-Fractionated Radiotherapy Versus Conventional Radiotherapy in Breast Cancer.

Background: Breast cancer is the most commonly diagnosed cancer causing death among females worldwide. Radiotherapy after lumpectomy/mastectomy in breast cancer cases is a successful treatment modality taking five weeks to complete. The aim of the present study is to compare the effectiveness of hypo-fractionated radiotherapy in breast cancer patients with conventional radiotherapy with respect to outcome and toxicity.Methods: Sixty patients were randomly divided equally into a conventional group, Group A (dose: 50 Gy in 25 fractions), and a hypo-fractionated short-course radiotherapy group, Group B (dose: 40 Gy in 16 fractions). After thorough clinical and laboratory examination of all patients, the disease status was assessed prior to radiotherapy and three and six months after completion of radiotherapy. The cardiopulmonary function was assessed using echocardiography and pulmonary function tests prior to the procedure. The assessment of the development of toxicity (dysphagia, skin, lung, and lymphedema) was done during every clinical visit.Results: The mean age of patients was 53.28 ± 9.73 years in Group A, and 55.67 ± 10.41 years in Group B (p=0.82). The right breast was involved in 13 (43.4%) patients in Group A and 14 (46.6%) in Group B, and the left breast was involved n 17 (56.6%) patients in Group A and 16 (53.4%) in Group B (p=0.81). Most of the patients were post-menopausal; 24 (80%) in Group A and 25 (83.4%) in Group B (p=0.91). Eleven (36.6%) patients were of stage T2N1M0 in both groups. However, no statistical difference was observed between the groups in the TNM (tumor, node, and metastasis) staging using the AJCC (American Joint Committee on Cancer) criteria (p=0.26). On comparing the responses in Group A and Group B, no significant difference was observed in either of the groups from immediate post-treatment to the 12-month follow-up period (p=0.53 and p=0.64, respectively).Conclusion: Hypo-fractionated radiotherapy is as effective as conventional radiotherapy and can be used as an alternative method for treatment following breast cancer surgery.

Identification of a Novel Five-Gene Signature as a Prognostic and Diagnostic Biomarker in Colorectal Cancers.

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. The current TNM (Tumor, Node, and Metastasis) classification approach is suboptimal in determining the prognosis of CRC patients. The prognosis for CRC is affected by a variety of features that are present at the initial diagnosis. Herein, we performed a systematic exploration and established a novel five-panel gene signature as a prognostic and early diagnosis biomarker after performing differential gene expression analyses in five independent in silico CRCs cohort and independently validating it in one clinical cohort, using immunohistochemistry. Four genes (BDNF, PTGS2, GSK3B, and CTNNB1) were significantly upregulated and one gene (HPGD) was significantly downregulated in primary tumor tissues compared with adjacent normal tissues throughout all the five in silico datasets. The univariate CoxPH analysis yielded a five-gene signature that accurately predicted overall survival (OS) and recurrence-free survival (RFS) in the in silico training (AUC = 0.73 and 0.69, respectively) and one independent in silico validation cohort (AUC = 0.69 and 0.74, respectively). This five-gene signature demonstrated significant associations with poor OS in independent clinical validation cohorts of colon cancer (CC) patients (AUC = 0.82). Intriguingly, a risk stratification model comprising of the five-gene signature together with TNM stage and gender status achieved an even superior AUC of 0.89 in the clinical cohorts. On the other hand, the circulating mRNA expression of the upregulated four-gene signature achieved a robust AUC = 0.83 with high sensitivity and specificity as a diagnosis marker in plasma from CRC patients. We have identified a novel, five-gene signature as an independent predictor of OS, which in combination with TNM stage and gender offers an easy-to-translate and facile assay for the personalized risk-assessment in CRC patients.

Deep Learning-Based Magnetic Resonance Imaging in the Evaluation of Tumor, Node, and Metastasis Staging of Renal Cancer

This study was aimed to investigate the diagnostic accuracy of magnetic resonance imaging (MRI) based on deep dictionary learning in TNM (tumor, node, and metastasis) staging of renal cell carcinoma. In this study, 82 patients with renal cancer were selected as the research object. The results were diagnosed by deep dictionary learning MRI, and TNM staging was performed by professional imaging personnel. MRI image will be reconstructed after deep dictionary learning to improve its image recognition ability. The pathological diagnosis will be handed over to the physiological pathology laboratory of the hospital for diagnosis. The staging results were compared with the pathological diagnostic staging results, and the results were analyzed by consistency statistics to evaluate the diagnostic value. The results showed that T staging was significantly consistent with the pathological diagnosis. 2 cases were misdiagnosed, and the accuracy rate was 97.56%. Compared with the pathological diagnosis, N staging had less obvious consistency. 10 cases were misdiagnosed, and the accuracy rate was 87.80%. M staging was significantly consistent with the pathological diagnosis. 4 cases were misdiagnosed. The accuracy rate was 95.12%. After laparotomy, it was found that 37 patients had emboli and 45 patients had no emboli, while 40 patients had emboli and 42 patients had no emboli by MRI. The accuracy rate was 96.34%. The results showed that in the evaluation of TNM staging by MRI imaging based on deep dictionary learning in patients with renal cell carcinoma, the diagnostic results of N staging and M staging were highly consistent with the pathological diagnosis, while the diagnostic results of T staging were slightly less accurate, and the diagnostic consistency was good. The results can provide effective support for the clinical application of MRI imaging based on deep dictionary learning as the clinical diagnosis of TNM staging of renal cell carcinoma.

Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling

The role of matrix metalloproteinase-2 (MMP-2) in tumor cell migration has been widely studied, however, the characteristics and effects of MMP-2 in clinical sample of metastatic colorectal cancer (CRC) remain poorly understood. Here, in order to unveil the perturbed proteomic signal during MMP-2 induced cancer progression, we analyzed plasma proteome of CRC patients according to disease progression, HCT116 cancer secretome upon MMP-2 knockdown, and publicly available CRC tissue proteome data. Collectively, the integrative analysis of multi-layered proteomes revealed that a protein cluster containing EMT (Epithelial-to-Mesenchymal Transition)-associated proteins such as CD9-integrin as well as MMP-2. The proteins of the cluster were regulated by MMP-2 perturbation and exhibited significantly increased expressions in tissue and plasma as disease progressed from TNM (Tumor, Node, and Metastasis) stage I to II. Furthermore, we also identified a plausible association between MMP-2 up-regulation and activation of focal adhesion kinase signaling in the proteogenomic analysis of CRC patient tissues. Based on these comparative and integrative analyses, we suggest that the high invasiveness in the metastatic CRC resulted from increased secretion of MMP-2 and CD9-integrin complex mediated by FAK signaling activation.

Correlation of Computed Tomography Parameters with Histology, Stage and Prognosis in Surgically Treated Thymomas.

Background and objectives: The histological classification and staging of thymic tumors remains a matter of debate. The correlation of computed tomography (CT) parameters with tumor histology and stage also still has to be completely assessed. The aim of this study was therefore to analyze the correlation of radiological parameters with histological and staging classifications of thymomas evaluating their prognostic role. Materials and Methods: Data of 50 patients with thymoma submitted to a complete surgical treatment between 2005 and 2015 were retrospectively analyzed. Tumors were classified according to the WHO and Suster and Moran (S&M) histological classifications and to the Masaoka–Koga and tumor, node and metastases (TNM) staging systems. The correlation of CT features with histology and stage and the prognostic role of histopathological and radiological features were assessed. Results: Five-year overall (OS) and disease-free survival (DFS) were 90.3% and 81.1%, respectively. A significant correlation of DFS with the Masaoka–Koga (p = 0.001) and TNM staging systems (p = 0.002) and with the S&M (p = 0.02) and WHO histological classifications (p = 0.04) was observed. CT scan features correlated with tumor stage, histology and prognosis. Moderately differentiated tumors (WHO B3) had a significantly higher incidence of irregular shape and contours (p = 0.002 and p = 0.001, respectively) and pericardial contact (p = 0.036). A larger tumor volume (p = 0.03) and a greater length of pleural contact (p = 0.04) adversely influenced DFS. The presence of pleural (p < 0.001) or lung invasion (p = 0.02) and of pleural effusion (p = 0.004) was associated with a significantly worse OS. Conclusions: Pre-operative CT scan parameters correlate with stage and histology, and have a prognostic role in surgically treated thymomas.

The malignant phenotype of calcineurin B homologous protein 2 in gastric cancer and its clinical significance

Objective: To study the expression and clinical significance of calcineurin B homologous protein 2 (CHP2) in gastric cancer (GC) and its effect on malignant phenotype of GC cells. Methods: The protein expression of CHP2 in 297 GC tissue and 198 normal gastric tissue samples were detected by immunohistochemistry. The relationship between the expression of CHP2 and clinicopathologic parameters of GC were analyzed. CHP2-overexpression plasmids and CHP2-interference plasmids were transfected into GC cell lines respectively. Wound healing assay and Transwell experiment was used to detect the invasion and migration ability of GC cells, and cell counting kit-8 (CCK-8) method was used to detect the proliferation ability of GC cells. Results: The positive expression rate of CHP2 in GC was 68.7% (204/297), which was higher in benign margin (34.1%) (31/91), chronic gastritis (59.1%) (13/22), intestinal metaplasia (34.2%) (13/38), low-grade intraepithelial neoplasia (40.0%) (12/30) and high-grade intraepithelial neoplasia (41.2%)(7/17). The positive expression of CHP2 was correlated with tumor, node and metastasis (TNM) stage, lymph node metastasis and distant metastasis (all P<0.05), but not with gender, age, Laurén classification, human epidermal growth factor receptor 2 (HER2) levels, depth of invasion, carcinoembryonic antigen (CEA) level and CEA 19-9 level (all P>0.05). The results of multivariate analysis showed that high expression of CHP2 and TNM stage were both independent parameters for predicting GC patient prognosis (both P<0.05). Interference of CHP2 expression in HGC-27 cells suppressed proliferation and migration significantly (P<0.05). However, over-expression CHP2 in AGS cells promoted proliferation, and migration significantly (P<0.05). Conclusion: CHP2 plays an important role in the development of GC, which is expected to be a molecular marker for patient prognosis and a potential target of targeted therapy for GC patients.

PTPN11 hypomethylation is associated with gastric cancer progression.

Protein tyrosine phosphatase non-receptor type 11 (PTPN11) encodes the tyrosine phosphatase SHP-2 that is overexpressed in gastric cancer (GC). In the present study, the association of PTPN11 methylation levels with the incidence of GC and its correlation with SHP-2 overexpression were investigated. The methylation levels of PTPN11 in tumor and adjacent normal tissues of 112 GC patients were assessed by quantitative methylation specific PCR (qMSP). The Cancer Genome Atlas (TCGA) public database was used to analyze the association between PTPN11 methylation and PTPN11 expression. Survival analyses were conducted in order to evaluate the prognostic value of PTPN11 methylation for GC. The results of the qMSP analysis indicated that the methylation levels of PTPN11 in GC tumor tissues were significantly decreased compared with those noted in the normal adjacent tissues (mean with standard deviation: 40.91±26.33 vs. 51.99±37.37, P=0.007). An inverse correlation between PTPN11 methylation levels and PTPN11 mRNA expression levels (P=4×10−6, r=−0.237) was noted. Subgroup analyses indicated that the association of PTPN11 hypomethylation with the incidence of GC was specific to male subjects (P=0.015), heavy drinking patients (P=0.019), patients with poor tumor differentiation (P=0.010) and patients with tumor node and metastasis (TNM) stage III+IV (P=0.008). Kaplan-Meier analyses and log-rank test suggested that PTPN11 hypomethylation was not associated with GC patient overall survival (P=0.605) and recurrence (P=0.485), although it could predict the recurrence of GC patients up to and including 60 years (≤60, P=0.049). The results indicated that PTPN11 levels were hypomethylated in GC patients. TCGA data analysis suggested that PTPN11 hypomethylation could cause an upregulation in the transcription levels of PTPN11. Although, this may explain the pattern of SHP-2 overexpression in GC, additional studies are required to verify this hypothesis. The association of PTPN11 hypomethylation with GC incidence may be specific to male patients, heavy drinking patients, patients with poor tumor differentiation and patients with TNM stage of III+IV. PTPN11 hypomethylation can be considered a biomarker for the recurrence of GC patients with an age of 60 years or lower.

Survival outcomes in surgically treated patients with advanced laryngeal cancer in Serbia

Background/Aim. Laryngeal carcinomas make 1%?3% of all head and neck malignancies.Treatment outcome and survival rates depend greatly on established stage of the disease. The purpose of this study was to examine the survival of the patients with advanced laryngeal carcinoma depending on gender, age, common risk factors (tobacco and alcohol use), primary tumor localization, histopathological tumor grade, clinical TNM (tumor, node and metastasis) stage and surgical treatment of the disease. Methods. Retrospective study included 252 patients treated surgically for advanced squamocellular carcinoma of the larynx in a threeyear period with five-year follow-up. Patients included in the study were treated primary with surgery, with postoperative radiotherapy and chemotherapy depending on the stage of the disease, intraoperative findings and tumor resection borders. Overall survival and disease-specific five-year survival of patients was calculated for demographical and clinical characteristics of the patients. Results. Overall 5-year survival of patients with operable advanced laryngeal cancer included in the study was 86.14% and disease-specific survival 86.51%. Lower overall and the disease-specific survival was associated with age, higher histological tumor grade and more extensive neck dissections. Conclusion. Primary total laryngectomy results in higher survival outcomes in cases of transglottic T3 and T4a laryngeal tumors. Patients should be informed of the likely increased mortality risks tied to the choice of surgical resection and treatment modality before their decision.

Patterns and Prognostic Value of Lymph Node Metastasis on Distant Metastasis and Survival in Nasopharyngeal Carcinoma: A Surveillance, Epidemiology, and End Results Study, 2006-2015.

This study was conducted to identify factors associated with lymph node (LN) metastasis in nasopharyngeal carcinoma (NPC) patients, analyze node distribution patterns, and explore the prognostic value of the LN metastasis level for survival. We included 2994 patients with primary NPC diagnosed between 2006 and 2015 with information in the Surveillance, Epidemiology, and End Results (SEER) database. Patients' demographic and clinicopathologic features were compared according to LN status using chi-squared tests. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates were calculated by the Kaplan–Meier method, and the differences were estimated by log-rank tests. Multivariate Cox proportional hazard models were used to evaluate independent risk factors for OS and CSS. Logistic regression was used to evaluate the risk of each LN metastasis category for distant metastasis. There were 695 patients in the N0 stage and 2299 with LN metastasis (classified as stage N1, N2, or N3). The overall incidence of LN metastasis was 76.8%. Sex and T stage were not associated with LN metastasis. Older patients had a significantly worse 5-year OS and CSS than younger patients. In terms of histologic type, keratinizing squamous cell carcinoma had the lowest 5-year OS and CSS at 48.2% and 53.8%, respectively. The most common nodal involvement level was II (65.9%), followed by III (29.1%), V (25.6%), I (17.6%), IV (15.7%), and retropharynx (13.5%). The skip metastasis rate was 5.7% (130/2299). Patients with only level II metastasis (classified as level 2) was the most common category, accounting for 30%. Compared to level 2, patients with only level I (classified as level 1) had an OR of 2.101 (95% CI: 1.090–4.047, P=0.027) for distant metastasis, patients with simultaneous levels II, III, IV, and V (classified as levels 2345) had the highest OR of 4.064 (95% CI: 2.155–7.666, P < 0.001) for distant metastasis, and level 24 had an OR of 3.003 (95% CI: 1.074–8.395, P=0.036) for distant metastasis. In survival analysis, levels 235 had a significant HR of 1.708 (95% CI: 1.089–2.678, P=0.020) for CSS compared to level 2 after adjustment for age, sex, race, histology, TNM (tumor, node, and metastasis) stage, and treatment.

Major depression but not minor to intermediate depression correlates with unfavorable prognosis in surgical colorectal cancer patients underwent adjuvant chemotherapy

ABSTRACTThis study aimed to investigate the correlation of anxiety/depression with clinicopathological features, and the association of anxiety/depression degrees with overall survival (OS) in surgical colorectal cancer (CRC) patients. Three hundred and eighty-one surgical CRC patients were consecutively enrolled and underwent adjuvant chemotherapy accordingly. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). Patients with no, minor, intermediate and major anxiety were 249 (65.4%), 79 (20.7%), 37 (9.7%) and 16 (4.2%), respectively, and patients with no, minor, intermediate and major depression were 231 (60.6%), 73 (19.2%), 44 (11.5%) and 33 (8.7%), respectively. Younger age, increased the pathological grade, elevated tumor, node and metastasis (TNM) stage, as well as higher education correlated with raised HADS-A score, while younger age, drinking history, increased pathological grade, elevated TNM stage and higher education associated with raised HADS-D score. There was no difference in OS among CRC patients with no anxiety, minor anxiety, intermediate anxiety and major anxiety. And CRC patients with major depression were of worse OS compared to those with no depression, minor depression or intermediate depression. Younger age, higher pathological grade, TNM stage and education associates with anxiety and depression, and major depression is negatively correlated with OS in surgical CRC patients underwent adjuvant chemotherapy.

Abstract 4907: Transcriptomic profiling identifies a novel mitochondrial gene expression signature that predicts recurrence in microsatellite stable stage II and III colorectal cancer

Abstract Purpose: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States. Current TNM (Tumor, Node, and Metastasis) classification approach is suboptimal in determining the prognosis of CRC patients. While there is a general consensus that stage II and III CRC patients with microsatellite instability (MSI) exhibit better outcomes, there is a lack of availability of biomarkers that can predict prognosis in microsatellite stable (MSS) patients. Given the emerging evidence that mitochondrial (mt) genomic instability is one of the hallmark features of cancer progression, herein, we systematically explored and established a novel mt-gene panel as a prognostic signature in CRC. Experimental design: Three genome wide mRNA expression profiling datasets were analyzed for the biomarker discovery (GSE33113, n=65) and validation (GSE14333, n=196; TCGA, n=62) of a mt-gene expression signature that predicts recurrence in stage II/III MSS CRC patients. Subsequently, a 14-gene signature was established, and independently tested (n=257) and validated (n=212) in two clinical cohorts, using qRT-PCR assays. The uni- and multi-variate Cox proportional hazard (CoxPH) regression analyses were performed to evaluate the performance of the mt-gene signature individually, and in combination with various clinicopathological factors (e.g. TNM staging, lymphatic invasion, and tumor infiltration) for predicting recurrence free survival (RFS). Results: The expression analysis of 568 mt-genes in CRC patients with and without recurrence, resulted in the identification of 32 significantly dysregulated genes (p&amp;lt;0.05). The univariate CoxPH analysis yielded a 14-gene signature that accurately predicted recurrence in the discovery (AUC = 0.89), and two independent validation cohorts (AUC = 0.75 and 0.79, respectively). This 14-gene signature demonstrated significant associations with poor RFS in independent testing and clinical validation cohorts of CRC patients (AUC = 0.87 and 0.73, respectively). Univariate analysis revealed that in addition to the mt-gene signature, TNM-stage (p = 0.007) and lymphatic invasion (p = 0.0004) were significant predictors of RFS; while multivariate analyses demonstrated that our mt-gene signature was an independent predictor (HR = 2.71; P&amp;lt;0.001) of tumor recurrence in stage II/III CRC patients. Intriguingly, a risk-stratification model comprising of the 14-gene signature together with TNM-stage and lymphatic invasion status achieved an even superior AUC of 0.89 and 0.78 in both clinical cohorts. Conclusions: We have identified a novel, 14-gene signature as an independent predictor of tumor recurrence; which in combination with TNM-stage and lymphatic invasion, offers an easy-to-translate and facile assay for the personalized risk-assessment in stage II/III MSS-CRC patients. Citation Format: SOUVIK GHATAK, Raju Kandimalla, Jasjit K. Banwait, Hiroyuki Uetake, Francesc Balaguer, Luis Bujanda, Ajay Goel. Transcriptomic profiling identifies a novel mitochondrial gene expression signature that predicts recurrence in microsatellite stable stage II and III colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4907.

AQP1 and AQP3 Expression are Associated With Severe Symptoms and Poor-prognosis of the Pancreatic Ductal Adenocarcinoma

Approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC) have metastatic disease with poor prognosis, but clinically available biomarkers for the diagnosis, prediction of prognosis, and target therapy have not yet been identified. To investigate the expression of aquaporin-1 (AQP1) and AQP3 protein and their clinicopathological significances in PDACs. AQP1 and AQP3 protein expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and 13 normal pancreatic tissues was measured by immunohistochemistry. Western blot showed that AQP1 and AQP3 protein expression was significantly higher in PDAC tissues than that in benign pancreatic tissues (P<0.01). Immunohistochemistry showed that the percentages of positive AQP1 and AQP3 expressions were significantly higher in PDAC tumors than that in peritumoral tissues, benign, and normal pancreatic tissues (P<0.01). Benign pancreatic lesions with positive AQP1 and AQP3 expression exhibited a dysplasia or intraepithelial neoplasia. The percentage of cases with positive AQP1 and AQP3 expression was significantly lower in PDAC patients without lymph node metastasis and invasion, and having low Tumor, Node and Metastasis (TNM) stage disease than in patients with lymph node metastasis, invasion, and high TNM stage disease (P<0.05 or <0.01). Kaplan-Meier survival analysis showed that positive AQP1 and AQP3 expression were significantly associated with survival in PDAC patients (P<0.001). Cox multivariate analysis revealed that positive AQP1 and AQP3 expression was independent poor prognosis factors in PDAC patients. The area under the curve of receiver operating characteristic curve was 0.669 for AQP1 and 0.707 for AQP3, respectively. Positive AQP1 and AQP3 expressions are associated with the tumorigenesis and progression of PDAC. Both AQP1 and AQP3 are a diagnostic marker of PDAC and a predictive marker of poor prognosis in PDAC patients.