• Chemoradiation
• Chemotherapy
• Radiotherapy
• Rectal cancer
• Total neoadjuvant therapy

• COPD
• Diabetes
• Immunotherapy
• Pneumonia
• Radiation therapy

• Elderly
• comorbidities
• mortality
• rectal cancer
• surgery

• Bevacizumab
• Colorectal cancer
• Combination
• Odds ratio

• Humans
• Middle Aged
• Aged
• Bevacizumab/therapeutic use
• Cetuximab/therapeutic use
• Panitumumab/therapeutic use
• Colorectal Neoplasms/pathology
• Colonic Neoplasms
• Rectal Neoplasms
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use

• Meta-analysis
• Metastatic colorectal cancer
• Overall survival
• Prognosis
• Progression-free survival
• Vitamin D

• Humans
• Vitamin D/therapeutic use
• Colorectal Neoplasms/pathology
• Colonic Neoplasms
• Rectal Neoplasms
• Proportional Hazards Models

• colorectal cancer
• disease-free survival
• prognosis
• survival
• vitamin D

• Extramural cancer deposits without lymph node structure (EX)
• Lymph node metastasis
• Tumor deposits (TDs)
• Tumor‐node‐metastasis (TNM) system
• tumor stage

• colorectal cancer
• inflammation
• oxaliplatin
• signature profile
• tumourspheres

• Surveillance, Epidemiology, and End Results (SEER)
• Survival paradox
• chemotherapy
• colon cancer
• propensity score matching (PSM)

• Biological therapies
• Left-sided tumors survival
• Metastatic colorectal cancer (mCRC)
• Right-sided tumors
• Systemic chemotherapy

• Male
• Humans
• Middle Aged
• Female
• Retrospective Studies
• Colorectal Neoplasms
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Colonic Neoplasms
• Rectal Neoplasms
• Biological Therapy

The purpose of this study is to comprehensively evaluate the prognostic role of tumor deposits (TD) in stage III colon cancer.

24,600 CC patients with III stage colon cancer were collected from the Surveillance, Epidemiology, and End Result (SEER) database and 618 CC patients from the Second Affiliated Hospital of Harbin Medical University. All patients were divided into development, internal, and external validation cohorts. The combination of positive lymph nodes (PLN) and the status or number of TD was defined as modified pN (mpN) and novel pN (npN). The Cox proportional hazard regression model was used to analyze the relationship between cancer-specific survival (CSS) and mpN or npN. CSS stratified by pN, mpN, and npN was analyzed by the Kaplan–Meier curves. The area under the receiver operating characteristic curve (AUC) was used to demonstrate the predictive abilities of the pN, mpN, and npN stages. The validation cohorts were used to validate the results.

The Cox proportional hazard regression model showed that mpN and npN were an independent prognostic factor for CSS. AUC showed that the predictive accuracy of mpN was better than that of the pN stage for 5-year CSS in the development (0.621 vs. 0.609, p < 0.001) and internal validation cohorts (0.618 vs. 0.612, p = 0.016) and the npN was also better than the pN stage for 5-year CSS in the development (0.623 vs. 0.609, p < 0.001) and internal validation cohorts (0.620 vs. 0.612, p = 0.001). However, there was no significant difference between the AUCs of mpN and npN. Moreover, the pN stage for 5-year CSS in the external validation cohort is 0.606 vs. 0.563, p = 0.045.

In stage III CC, mpN and npN may be superior to the pN stage in assessing prognosis, suggesting that the TD information should be included in the pN stage.

Tumor deposits (TDs) are acknowledged negative prognostic factors in colorectal cancer (CRC), and their pathogenesis remains a puzzle. This study aimed to construct and validate a nomogram available for preoperative TDs prediction in CRC patients.

Patients from the Surveillance, Epidemiology, and End Results (SEER) and the cancer genome atlas (TCGA) databases were randomly divided into training and validation sets according to the sample size ratio of 7:3. Univariate logistic regression was performed for identifying differentially expressed microRNAs between TDs and non-TDs. Nomograms for TDs prediction were developed from the multivariate logistic regression model with least absolute shrinkage and selection operator and were validated internally in terms of accuracy, calibration, and clinical utility. Based on the target genes, pathways tightly associated with TDs were selected using enrichment analysis.

Six clinicopathologic factors and expressions of six microRNAs (miR-614, miR-1197, miR-4770, miR-3136, miR-3173, and miR-4636) differed significantly between TDs and non-TDs CRC patients from the SEER and TCGA training sets. We compared potential prediction discrimination between two nomograms: a clinicopathologic nomogram and a six-microRNA signature nomogram. The six-microRNA signature nomogram revealed better accuracy than the clinicopathologic one for TDs prediction (AUC values of 0.96 and 0.93 in the validation cohort). The calibration plots and decision curve analysis demonstrated that the six-microRNA signature nomogram had better validity and a greater prognostic benefit versus the clinicopathologic one for TDs prediction. Calcium signaling pathways were closely associated with roles of the six microRNAs in TDs of CRC patients.

The six-microRNA signature nomogram can be used as an efficient tool for preoperative TDs prediction in CRC patients.

• National Natural Science Foundation of Chin

Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer (LARC). However, individual responses to preoperative CRT vary from patient to patient. The aim of this study is to develop a scoring system for the response of preoperative CRT in LARC using blood features derived from machine learning.

Patients who underwent total mesorectal excision after preoperative CRT were included in this study. The performance of machine learning models using blood features before CRT (pre-CRT) and from 1 to 2 weeks after CRT (early-CRT) was evaluated. Based on the best model, important features were selected. The scoring system was developed from the selected model and features. The performance of the new scoring system was compared with those of systemic inflammatory indicators: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and the prognostic nutritional index.

The models using early-CRT blood features had better performances than those using pre-CRT blood features. Based on the ridge regression model, which showed the best performance among the machine learning models (AUROC 0.6322 and AUPRC 0.5965), a novel scoring system for the response of preoperative CRT, named Response Prediction Score (RPS), was developed. The RPS system showed higher predictive power (AUROC 0.6747) than single blood features and systemic inflammatory indicators and stratified the tumor regression grade and overall downstaging clearly.

We discovered that we can more accurately predict CRT response by using early-treatment blood data. With larger data, we can develop a more accurate and reliable indicator that can be used in real daily practices. In the future, we urge the collection of early-treatment blood data and pre-treatment blood data.

• early-treatment blood features
• machine learning
• pathologic response
• prediction
• preoperative chemoradiotherapy
• rectal cancer

Prognostic factors have important utility in various aspects of cancer surveillance, including research, patient care, and cancer control programmes. Nevertheless, there is heterogeneity in the collection of prognostic factors and outcomes data globally. This study aimed to investigate perspectives on the utility and application of prognostic factors and clinical outcomes in cancer control programmes. A qualitative phenomenology approach using expert interviews was taken to derive a rich description of the current state and future outlook of cancer prognostic factors and clinical outcomes. Individuals with expertise in this work and from various regions and institutions were invited to take part in one-on-one semi-structured interviews. Four areas related to infrastructure and funding challenges were identified by participants, including (1) data collection and access; (2) variability in data reporting, coding, and definitions; (3) limited coordination among databases; and (4) conceptualization and prioritization of meaningful prognostic factors and outcomes. Two areas were identified regarding important future priorities for cancer control: (1) global investment and intention in cancer surveillance and (2) data governance and exchange globally. Participants emphasized the need for better global collection of prognostic factors and clinical outcomes data and support for standardized data collection and data exchange practices by cancer registries.

• cancer control
• clinical outcomes
• prognostic factors

• Data Collection
• Humans
• Prognosis
• Registries
• Research Design

Colorectal cancer (CRC) is the most diagnosed cancer among males and third among females in Saudi Arabia, with up to two-third diagnosed at advanced stage. The objective of our study was to estimate CRC survival and determine prognostic factors.

Ministry of National Guard- Health Affairs (MNG-HA) registry data was utilized to identify patients diagnosed with CRC between 2009 and 2017. Cases were followed until December 30th, 2017 to assess their one-, three-, and five-year CRC-specific survivals. Kaplan-Meier method and Cox proportional hazard models were used to assess survival from CRC.

A total of 1012 CRC patients were diagnosed during 2009–2017. Nearly, one-fourth of the patients presented with rectal tumor, 42.89% with left colon and 33.41% of the cases were diagnosed at distant metastasis stage. The overall one-, three-, and five-year survival were 83, 65 and 52.0%, respectively. The five-year survival was 79.85% for localized stage, 63.25% for regional stage and 20.31% for distant metastasis. Multivariate analyses showed that age, diagnosis period, stage, nationality, basis of diagnosis, morphology and location of tumor were associated with survival.

Findings reveal poor survival compared to Surveillance, Epidemiology, and End Results (SEER) population. Diagnoses at late stage and no surgical and/or perioperative chemotherapy were associated with increased risk of death. Population-based screening in this population should be considered.

• Colorectal cancer (CRC)
• Registry
• SEER
• Saudi Arabia
• Survival

• Colorectal cancer
• TNM classification
• Tumor deposits

• CKD-516
• Colorectal cancer
• Irinotecan
• Vascular-disrupting agent

The American Joint Committee on Cancer 8th classification states that colorectal cancer (CRC) is classified as N1c stage when regional lymph nodes (LNs) are negative and tumor deposits (TDs) are positive. However, how to classify TDs when regional LNs are positive remains unclear. The current study aimed to investigate the possibility of combining positive LNs and positive TDs to develop a modified pathological N (mpN) stage for CRC.

We retrospectively analyzed 9,198 patients with stage III CRC from the Surveillance, Epidemiology, and End Results program who underwent surgery (6,440 in the training cohort and 2,758 the validation cohort). The combination of positive LNs and TD status was defined as mpN stage. Overall survival (OS) according to mpN and pathological N (pN) stages was analyzed by the Kaplan–Meier method. The area under the curves (AUCs) and Akaike’s information criterion (AIC) were applied to assess the predictive discrimination abilities and goodness-of-fit of the model. The clinical benefits were measured using decision curve analyses. The validation cohort was used to validate the results.

AUC analysis showed that the prognostic discrimination of mpN stage (AUC = 0.628, 95% confidence interval (CI), 0.616–0.640) was better than that of pN stage (AUC = 0.618, 95% CI, 0.606–0.630, p = 0.006) for OS. The AIC demonstrated that mpN stage (AIC = 30,217) also showed superior model-fitting compared with pN stage (AIC = 30,257) and decision curve analyses revealed that mpN stage had better clinical benefits than pN stage. Similar results were found in the validation cohort.

Among patients with CRC and LN metastasis, mpN stage might be superior to pN stage for assessing prognosis and survival, suggesting that TD status should be included in the pN stage.

• colorectal cancer
• lymph node
• overall survival
• prognosis
• tumor deposit

• Saudi Arabia
• colorectal cancer
• registry
• survival

• Aged
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Bevacizumab/therapeutic use
• Capecitabine/therapeutic use
• Chemotherapy, Adjuvant
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/mortality
• Disease-Free Survival
• Female
• Fluorouracil/therapeutic use
• Humans
• Leucovorin/therapeutic use
• Male
• Middle Aged
• Neoplasm Staging
• Organoplatinum Compounds/therapeutic use
• Oxaloacetates/therapeutic use
• Proportional Hazards Models
• Treatment Outcome

• N1c
• nodal staging
• rectal cancer
• tumor deposits

National Comprehensive Cancer Network (NCCN) guidelines for stage III colon cancer define low-risk versus high-risk patients based on T (1 to 3 vs. 4) and N (1 vs. 2) status, with some variations in treatment. This study analyzes the impact of tumor deposits (TDs), T and N status, poor differentiation (PD), perineural invasion (PNI), and lymphovascular invasion (LVI) on survival.

A retrospective analysis (2010-2015) of the National Cancer Database of stage III colon cancer patients treated with both surgery and chemotherapy was conducted. Data was extracted on sex, race, age at diagnosis, Charlson-Deyo Score, histopathologic variables, and survival rates. Statistical analysis used the test of proportions, log-rank test for Kaplan-Meier curves, and Cox proportional hazard models.

For the 42,901 patients analyzed, 5-year survival rates were similar for LN⁺TD⁻ (59.8%) and LN⁻TD⁺ (58.2%), but significantly worse for LN⁺TD⁺ (41.5%) (P<0.001). The presence of LN⁺TD⁺ was more often associated with T4 (36.9%), N2 (55.1%), PD⁺ (37.4%), PNI⁺ (34.5%), and LVI⁺ (69.1%), than LN⁺TD⁻ or LN⁻TD⁺ (P<0.001). The hazard ratios for each variable were: TD: 1.34; T4: 1.71; N2: 1.44; PD⁺: 1.37; PNI: 1.11; LVI⁺: 1.18. LN⁻ patients with ≥3 TD⁺ (N1c) had worse overall survival than those with 1 to 2 TD⁺ (P<0.01), but similar to ≥4 LN⁺TD⁻ (N2) and 1 to 3 LN⁺TD⁺ (N1a-b). In our model, 5-year survival ranged from 23.4% for high-risk to 78.1% for low-risk patients (P<0.001).

This National Cancer Database (NCDB) analysis offers greater risk stratification and may prompt consideration of changes in American Joint Committee on Cancer (AJCC) classification (N2c, in addition to N1c) to reflect the different prognosis and guide management, as well as survivorship strategies, for TD⁺ stage III colon cancer patients.

• mucinous adenocarcinoma
• prognosis
• signet ring cell carcinoma
• survival analysis
• synchronous metastasis

• Adenocarcinoma/epidemiology
• Adenocarcinoma/secondary
• Adenocarcinoma/therapy
• Age Factors
• Aged
• Bone Neoplasms/epidemiology
• Bone Neoplasms/secondary
• Bone Neoplasms/therapy
• Brain Neoplasms/epidemiology
• Brain Neoplasms/secondary
• Brain Neoplasms/therapy
• Chemotherapy, Adjuvant/statistics & numerical data
• Colectomy/statistics & numerical data
• Colonic Neoplasms/mortality
• Colonic Neoplasms/pathology
• Colonic Neoplasms/therapy
• Female
• Follow-Up Studies
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms/epidemiology
• Liver Neoplasms/secondary
• Liver Neoplasms/therapy
• Lung Neoplasms/epidemiology
• Lung Neoplasms/secondary
• Lung Neoplasms/therapy
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Prognosis
• Risk Factors
• SEER Program/statistics & numerical data
• United States/epidemiology

• FOLFOX
• XELOX
• adjuvant
• bevacizumab
• colon cancer

• Extranodal tumor extension
• colorectal cancer
• perforation
• recurrence
• vascular invasion

• malignant pericardial effusion
• malignant pleural effusion
• non-small cell lung cancer
• prognosis

• ELFN1-AS1
• colon adenocarcinoma
• extracellular vesicles
• human umbilical cord mesenchymal stem cells

• colon adenocarcinoma
• mortality
• survival
• tumor deposits

• Adenocarcinoma/mortality
• Adenocarcinoma/pathology
• Adenocarcinoma/therapy
• Adult
• Aged
• Colonic Neoplasms/mortality
• Colonic Neoplasms/pathology
• Colonic Neoplasms/therapy
• Cross-Sectional Studies
• Female
• Humans
• Male
• Margins of Excision
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local/epidemiology
• Neoplasm Staging
• Survival Analysis
• Survival Rate

Carbohydrate antigen 19-9 (CA19-9) is one of the most widely used tumor markers in gastrointestinal cancer. However, serum CA19-9 is not a recommended routine measurement in colon cancer. In this study, we evaluated the value of the preoperative serum CA19-9 level for the prediction of postoperative prognosis in stage III colon cancer. The medical records of 367 consecutive patients with stage III colon cancer who underwent curative resection followed by adjuvant chemotherapy with oxaliplatin and capecitabine between December 2007 and April 2015 were retrospectively reviewed. We determined the optimal cutoff value of CA19-9 for 3-year recurrence using the receiver operating characteristic (ROC) method. Differences in disease-free survival (DFS) and overall survival (OS) rates stratified by CA19-9 level were compared by using Kaplan-Meier and log-rank tests. A Cox proportional hazards model was used to identify prognostic variables for DFS and OS. The statistically determined best cutoff value for CA19-9 was 24 U/ml. High CA19-9 levels (> 24 U/ml) were significantly associated with poorly differentiated tumors, abnormal carcinoembryonic antigen (CEA) levels, and a high cumulative incidence of lung metastasis. Additionally, compared with low CA19-9 levels, high preoperative CA19-9 levels were associated with inferior 3-year DFS and OS rates, especially for high-risk patients (T4Nany or TanyN2). Multivariate analyses revealed that CA19-9 was an independent factor associated with both DFS (hazard ratio [HR], 2.248; 95% confidence interval [CI], 1.393-3.628; P = 0.001) and OS (HR: 2.081; 95% CI: 1.137-3.808; P = 0.017). The results of this study showed that high levels of preoperative serum CA19-9 indicated a worse prognostic outcome for stage III colon cancer patients. An early follow-up protocol to assess lung metastasis and a full course of adjuvant chemotherapy should be used for these patients.

• CA19-9
• colon cancer
• prognosis
• stage III

• Carcinoembryonic antigen
• Colon cancer
• Propensity score–matched
• Stage I

• Anal Carcinoma
• Appendiceal
• Japanese Classification of Colorectal
• TNM eighth edition
• TNM seventh edition
• colorectal cancer

• Assessment of medical quality
• Clinical research
• The site-specific cancer registry

• Colon cancer
• calculators
• overall survival

• carcinoembryonic antigen
• colorectal carcinoma
• prognosis

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Carcinoembryonic Antigen/blood
• Carcinoembryonic Antigen/metabolism
• Colorectal Neoplasms/blood
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Retrospective Studies
• Young Adult

• Colorectal cancer
• FBXO2
• Ki67
• N-cadherin
• immunohistochemistry

• colorectal carcinoma
• mRNA-decapping enzyme 1a
• prognostic indicator
• survival rate

Smoking frequently leads to epigenetic alterations, including DNA methylation and histone modifications. The effect that smoking has on the DNA methylation levels at CCGG sites, the expression of trimethylation of histone H3 at lysine 27 (H3K27me3) and enhancer of zeste homolog 2 (EZH2), and their interactions in patients with non-small cell lung cancer (NSCLC) were analyzed. There were a total of 42 patients with NSCLC, 22 with adenocarcinomas and 20 with squamous cell carcinomas enrolled in the present study. Expression of H3K27me3, EZH2 and proliferating cellular nuclear antigen (PCNA) were immunohistochemically detected. DNA methylation at CCGG sites was evaluated via histoendonuclease-linked detection of DNA methylation sites. The apoptotic index of cancerous tissues obtained from patients of different smoking statuses was evaluated via the terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling method. The association with clinicopathological data was calculated relative to different smoking statuses. Compared with the non-smokers, smokers with NSCLC exhibited a significantly lower apoptotic index (P<0.05), and frequently had a lower level of DNA methylation at CCGG sites, lower H3K27me3 expression and a higher EZH2 expression (P<0.05). DNA methylation levels at CCGG sites were negatively correlated to the Brinkman index (P=0.017). Furthermore, there was a parallel association between the H3K27me3 and EZH2 expression levels in the majority of smokers, whereas in the majority of non-smokers, there was a diverging association (P=0.015). There was a diverging association between the PCNA and EZH2 expression levels in the majority of smokers; however, in the majority of non-smokers, there was a parallel association (P=0.048). In addition, the association between the CCGG methylation ratio and immunohistochemical expression of H3K27me3 was a parallel association in the majority of smokers, while in the majority of non-smokers there was a diverging association (P=0.049). Conclusively, patients with NSCLC and different smoking statuses exhibit different epigenetic characteristics. Additionally, DNA methylation levels at the CCGG sites may have the ability to determine associations between the expression levels of H3K27me3, EZH2 and PCNA.

• DNA methylation
• EZH2
• non-small cell lung cancer
• smoking
• trimethylation of histone H3 at lysine 27