• CEA
• ascites
• cancer
• peritoneal fluid
• serum

• Hematology index
• Locally advanced rectal cancer
• Neoadjuvant chemoradiotherapy
• Nomogram
• Pathological response

• Humans
• Nomograms
• Retrospective Studies
• Neoadjuvant Therapy
• Rectum/pathology
• Rectal Neoplasms/pathology
• Neoplasms, Second Primary/pathology
• Chemoradiotherapy

• biomarkers
• colorectal
• genomic
• multidisciplinary
• screening

• not available Sociedad Española de Oncología Médica (SEOM)
• not available Merck (Spain)

• CEA
• TRG
• cfDNA
• chemoradiotherapy
• ctDNA
• liquid biopsy
• miRNA
• pCR
• rectal cancer
• tumor response

• Humans
• Neoadjuvant Therapy
• Biomarkers, Tumor/genetics
• Rectal Neoplasms/pathology
• Treatment Outcome
• MicroRNAs/genetics
• Cell-Free Nucleic Acids

• pCR
• predictive model
• preoperative chemo-radiotherapy
• rectal cancer
• ultra-low rectal cancer

• Humans
• Carcinoembryonic Antigen
• Treatment Outcome
• Retrospective Studies
• Rectal Neoplasms/therapy
• Rectal Neoplasms/pathology
• Biomarkers, Tumor
• Chemoradiotherapy, Adjuvant
• Chemoradiotherapy
• Neoadjuvant Therapy
• Neoplasms, Second Primary
• Adenocarcinoma/therapy
• Adenocarcinoma/pathology

• Changhai Hospital Clinical Investigation Program
• Shenkang Center Innovation Research Program
• Youth Starup Fund

• carcinoembryonic antigen
• locally advanced rectal cancer
• risk factors
• total neoadjuvant therapy
• tumor regression response

• Complete response
• Machine learning
• Neoadjuvant therapy
• Rectal cancer

• biomarkers
• colorectal cancer
• gastric cancer
• neoadjuvant chemotherapy
• pancreatic cancer

• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Chemotherapy, Adjuvant/mortality
• Female
• Follow-Up Studies
• Gastrointestinal Neoplasms/drug therapy
• Gastrointestinal Neoplasms/pathology
• Humans
• Male
• Middle Aged
• Neoadjuvant Therapy/mortality
• Neoplasm Recurrence, Local/drug therapy
• Neoplasm Recurrence, Local/pathology
• Prognosis
• Retrospective Studies
• Survival Rate

• P30 CA196521 NCI NIH HHS
• Biostatistics Shared Resource Facility, Icahn School of Medicine at Mount Sinai

• Biomarker
• Chemoradiotherapy
• Locally advanced
• Short course
• Surgery

• Aged
• Antigens, Neoplasm/blood
• Antineoplastic Combined Chemotherapy Protocols
• Biomarkers, Tumor/blood
• Carcinoembryonic Antigen/blood
• Carcinoma, Non-Small-Cell Lung/blood
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Computational Biology
• Female
• GPI-Linked Proteins/blood
• Humans
• Keratin-19/blood
• Linear Models
• Lung Neoplasms/blood
• Lung Neoplasms/drug therapy
• Male
• Middle Aged
• Prognosis
• ROC Curve
• Retrospective Studies
• Treatment Outcome

Serum lipids have been reported as prognosticators for malignancies, including rectal cancer (RC). Yet, their value in predicting the response of RC to neoadjuvant chemoradiotherapy (NACRT) remains unknown. This study aimed to assess the predictive abilities of serum lipids for a bad response, and to build a serum lipid-based prediction model.

In total, 751 patients diagnosed with stage cII–III RC and treated with NACRT plus surgery from January 2007 to August 2018 were retrospectively reviewed and randomly divided into two data sets, in a ratio of 1:1. Receiver operating characteristics (ROC) analysis was conducted in the development set to select possible predictors of bad NACRT response from pathoclinical factors, including serum lipids. Multivariate logistic regression was conducted to further determine independent predictors, which were then used to develop a prediction index (PI). Finally, the PI was verified in the validation set, through ROC analysis and chi-squared test.

Five independent predictors were identified: tumor length ≥4 cm, cT4 stage, carcinoembryonic antigen ≥5.0 ng/mL, irradiation with three-dimensional conformal radiotherapy technique, and apolipoprotein A-I ≤1.20 g/L. Each of them was assigned a number of points. In the validation set, the area under the curve of PI appeared as 0.642 (95% confidence interval 0.586–0.697). The sensitivity, specificity, positive and negative predictive values, and concordance were 72.3%, 52.3%, 63.8%, 61.9%, and 63.0%, respectively.

Serum apolipoprotein A-I was found to correlate negatively with the RC response to NACRT. It could serve as a biomarker for guiding individualized treatment and a potential target for improving sensitivity to chemoradiation.

• apolipoprotein A-I
• prediction model
• radiotherapy
• rectal cancer
• tumor response

Preoperative neoadjuvant therapy is standard before surgery for locally advanced rectal cancer in current clinical treatment. However, patients with the same clinical TNM stage before treatment vary in clinical outcomes. More and more studies noted that pathological findings after preoperative neoadjuvant therapy are better prognostic factors to determine prognosis than clinical TNM stage in patients with locally advanced rectal cancer. The purpose of this study is to develop and validate models based on pathological findings to predict overall survival (OS) and disease-free survival (DFS).

A total of 3026 patients from two hospitals were included. The endpoint was OS and DFS. Significant predictors of OS on multivariate analysis were used to establish the nomogram.

The Harrell’s C index for OS prediction was 0.72 (95% confidence interval [CI], 0.68 to 0.77) in the training cohort, 0.66 (95% CI, 0.60 to 0.72) and 0.68 (95% CI, 0.64 to 0.73) in the internal and external validation cohorts. Using this nomogram, high- and low-risk groups for OS were defined in the training cohort. The 3-year OS was 78.1% (95% CI: 72.4–84.2%) for the high-risk group and 95% (95% CI: 93.6–96.5%) in the low-risk group (HR: 4.42, 95% CI: 3.22–6.05; P<0.001). This finding was also applied in the two external cohorts. Similarly, a nomogram that contained the same indices was developed and validated to predict for DFS.

Nomograms based on pathological findings are a reliable tool to predict 3-year OS and DFS rate in patients with locally advanced rectal cancer.

• disease-free survival
• locally advanced rectal cancer
• nomogram
• overall survival
• pathological findings

Preoperative chemoradiotherapy (CRT) is a standard treatment modality for locally advanced rectal cancer. However, CRT alone cannot improve overall survival. Approximately 20% of patients with CRT-resistant tumors show disease progression. Therefore, predictive factors for treatment response are needed to identify patients who will benefit from CRT. We theorized that the prognosis may vary if patients are classified according to pre- to post-CRT changes in carcinoembryonic antigen (CEA) levels.

To identify patients with locally advanced rectal cancer for preoperative chemoradiotherapy based on carcinoembryonic antigen levels.

We retrospectively included locally advanced rectal cancer patients who underwent preoperative CRT and curative resection between 2011 and 2017. Patients were assigned to groups A, B, and C based on pre- and post-CRT serum CEA levels: Both > 5; pre > 5 and post ≤ 5; and both ≤ 5 ng/mL, respectively. We compared the response to CRT based on changes in serum CEA levels. Receiver operating characteristic curve analysis was performed to determine optimal cutoff for neutrophil–lymphocyte ratio and platelet–lymphocyte ratio. Multivariate logistic regression analysis was used to evaluate the prognostic factors for pathologic complete response (pCR)/good response.

The cohort comprised 145 patients; of them, 27, 43, and 65 belonged to groups A, B, and C, respectively, according to changes in serum CEA levels before and after CRT. Pre- (P < 0.001) and post-CRT (P < 0.001) CEA levels and the ratio of down-staging (P = 0.013) were higher in Groups B and C than in Group A. The ratio of pathologic tumor regression grade 0/1 significantly differed among the groups (P = 0.003). Group C had the highest number of patients showing pCR (P < 0.001). Most patients with pCR showed pre- and post-CRT CEA levels < 5 ng/mL (P < 0.001, P = 0.008). Pre- and post-CRT CEA levels were important risk factors for pCR (OR = 18.71; 95%CI: 4.62–129.51, P < 0.001) and good response (OR = 5.07; 95%CI: 1.92–14.83, P = 0.002), respectively. Pre-CRT neutrophil–lymphocyte ratio and post-CRT T ≥ 3 stage were also prognostic factors for pCR or good response.

Pre- and post-CRT CEA levels, as well as change in CEA levels, were prognostic markers for treatment response to CRT and may facilitate treatment individualization for rectal cancer.

• Rectal cancer
• Neoadjuvant chemoradiation therapy
• Carcinoembryonic antigen levels
• Prognostic factor
• Change in serum carcinoembryonic antigen
• Response of chemoradiotherapy

• Carcinoembryonic Antigen
• Chemoradiotherapy
• Humans
• Neoadjuvant Therapy
• Neoplasm Staging
• Prognosis
• Rectal Neoplasms/pathology
• Rectal Neoplasms/therapy
• Retrospective Studies
• Treatment Outcome

•

Summarise the established knowledge on this subject.1

Middle-aged and older patients are at high risk of rectal adenocarcinoma; however, studies comprehensively analysing its predictors and the construction of visual nomogram models are limited.

To develop a new nomogram tool for predicting survival in middle-aged and elderly patients with rectal adenocarcinoma.

A total of 6,116 patients were randomly assigned in a 7:3 ratio to training and validation cohorts. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS) in the training set, and two nomogram prognostic models were constructed. The validity, accuracy, discrimination, predictive ability, and clinical utility of the models were assessed based on the concordance index (C-index), area under the receiver operating characteristics (ROC) curve, time-dependent area under the ROC curve (AUC), Kaplan-Meier survival curve, and decision curve analyses.

Predictors of OS and CSS were identified, and nomograms were successfully constructed. The calibration discrimination for both the OS and CSS nomogram prediction models was good (C-index: 0.763 and 0.787, respectively). The AUC showed excellent predictive performance, and the calibration curve exhibited significant predictive power for both nomograms. The time-dependent AUC showed that the predictive ability of the predictor-based nomogram was better than that of the TNM stage. The nomograms successfully discriminated high-, medium-, and low-risk patients for all-cause and cancer-specific mortality. The decision curve demonstrated that the nomograms are useful with respect to good decision power.

Our nomogram survival prediction models may aid in evaluating the prognosis of middle-aged and older patients with rectal adenocarcinoma and guiding the selection of the clinical treatment measures.

• Nomogram
• Prognostic model
• Rectum adenocarcinoma

Purpose: To investigate the value of carcinoembryonic antigen (CEA) decline in predicting pathological tumor regression and outcome for locally advanced rectal cancer (LARC) patients who received neoadjuvant therapy with elevated baseline CEA.

Methods: LARC patients with elevated pre-treatment CEA who received neoadjuvant therapy and radical tumor resection were retrospectively collected. Serum CEA level during treatment were recorded and the predictive value of pre-treatment CEA, post-treatment CEA and CEA ratio (CEA^{post-treatment} /CEA^{pre-treatment}) for tumor regression grade (TRG), overall survival and diseases free survival were estimated by logistic regression or cox proportional hazard regression.

Results: Two hundred and eighty-four LARC patients with elevated pre-treatment CEA were enrolled and the baseline, post-treatment CEA level and CEA ratio were 11.87 (5.02-731.31) ng/ml, 4.23 (0.50-173.80) ng/ml and 0.31(0.01-2.55) respectively. CEA level in 59.2% of the patients declined to normal after neoadjuvant therapy. Multivariate analysis showed that CEA ratio was an independent predictor for TRG (OR=3.463, 95% CI: 1.269-9.446, P=0.015) and tumor downstage (OR=0.393, 95% CI: 0.187-0.829, P=0.014). Patients with normalized post-treatment CEA level had better overall survival (P=0.010) and disease free survival (P=0.003) than those with elevated CEA level. Higher post-treatment CEA was an independent unfavored predictor for overall survival in LARC patients with elevated pre-treatment CEA (OR=1.042, 95% CI: 1.017-1.067, P=0.001).

Conclusion: Post/pre-treatment CEA ratio predicted tumor regression in term of TRG and tumor downstage for LARC patients with elevated pre-treatment CEA and higher post-treatment CEA predicted poor overall survival.

• Non-small cell lung cancer (NSCLC)
• carcinoembryonic antigen (CEA)
• lactate dehydrogenase (LDH)
• noninvasive quantification of tumor biomarkers
• small cell lung cancer (SCLC)

• Magnetic resonance imaging
• Neoadjuvant chemoradiotherapy
• Nomogram
• Rectal neoplasms
• Structured report template
• Tumour regression grade

• CXCR4
• Complete response
• NAT
• Neoadjuvant treatment
• Rectal adenocarcinoma
• TILs
• Treatment response
• Tumor infiltrating lymphocytes

• Adenocarcinoma/drug therapy
• Adenocarcinoma/surgery
• Aged
• Chemoradiotherapy/methods
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry/methods
• Lymphocytes, Tumor-Infiltrating/pathology
• Male
• Middle Aged
• Neoadjuvant Therapy/methods
• Neoplasm Staging/methods
• Neoplasm, Residual/pathology
• Receptors, CXCR4/metabolism
• Rectal Neoplasms/pathology
• Retrospective Studies

• P30 CA091842 NCI NIH HHS
• T32 CA009621 NCI NIH HHS
• UL1 TR000448 NCATS NIH HHS
• UL1 TR002345 NCATS NIH HHS