A Novel Nomogram to Predict the Postoperative Overall Survival in Gastrointestinal Cancer Patients
Condition: Gastrointestinal Cancers - Stomach; Gastrointestinal Cancers - Colorectal; Prognosis; Survival Analysis; Nutrition Assessment
MeSH terms: Gastrointestinal Neoplasms
Study type: Observational

Summary: 
      This multicenter retrospectively observational cohort study was conducted on participants
      with histologically confirmed gastric and colorectal cancer who underwent radical surgery in
      11 medical centers in China from August 1, 2015, to June 31, 2018. Baseline clinicopathologic
      data and nutritional status assessments including Nutrition Risk Screening 2002 (NRS 2002)
      score and Patient-generated Subjective Global Assessment (PG-SGA) rating were collected.
      Variables will be screened using the least absolute shrinkage and selection operator (LASSO)
      regression model and Cox regression analysis. Internal and external validations will be
      performed via the receiver operating curve (ROC), the area under the curve (AUC), the
      concordance index (C-index), calibration plots, decision curve analysis (DCA), and Five folds
      cross-validation by 200 times.
    

Detailed description: 
      1. Study design and patients This study is a multicenter retrospectively observational
           cohort study, which collected and followed up the patients with gastric cancer and
           colorectal cancer in 11 Chinese hospitals from August 1, 2015, to June 31, 2018. The
           eight sites of these were recruited as a training cohort, and the other three sites were
           recruited as an external validation cohort (Supplement Table 1). The inclusion criteria
           for both cohorts were complied with: 1) 18-80 years old; 2) postoperative pathological
           diagnosis of gastric or colorectal adenocarcinoma; 3) underwent radical surgery; 4) TNM
           stage ranged from stage I to stage III. The exclusion criteria included: 1) NRS 2002 or
           PG-SGA data was missing; 2) pathological diagnosis of gastric stump cancer, cancer in
           situ, or pin-point cancer; 3) in-hospital death or death within 30 days after surgery;
           4) preoperative neoadjuvant therapy; 5) preoperative endoscopic surgery; 6) the previous
           history of other malignant tumors; 7) pregnancy. This study was approved by the Ethics
           Committee of each hospital.

        2. Data collection The following clinical data were collected in this study: demographic
           characteristics (age, sex, height, weight, and BMI), age-adjusted Charlson Comorbidity
           Index (aCCI), NRS 2002 score, PG-SGA rating, pathological characteristics (tumor stage,
           type, differentiation, tumor size, and tumor vol-ume), surgical characteristics
           (operation type and intraoperative blood loss), hematological indicators
           [carcinoembryonic antigen (CEA), cancer antigen19-9 (CA19-9), albumin, pre-albumin,
           blood glucose, triglycerides (TG), alanine aminotransferase (ALT), aspartate
           aminotransferase (AST), total bilirubin, blood urea nitrogen (BUN), serum creatinine,
           hemoglobin, and white blood cell], and other clinical characteristics (postoperative
           complication and postoperative infection). These candidate variables were derived from
           previous studies and clinical experience. We obtained tumor staging from electronic
           medical records and pathological reports using the American Joint Committee on Cancer
           (AJCC) 8th edition. Tumor volume was derived from tumor length, width, and height using
           the following formulas: V = 1/2 × a × b2 or V = π/6 × a × b × c.

        3. Nutritional status assessments All the centers routinely perform nutritional status
           assessments on admission by the NRS 2002 and PG-SGA. We collected the NRS 2002 score and
           PG-SGA rating from the electronic medical record system.

           3.1 NRS 2002 NRS 2002 was used to estimate nutritional risk, accounting for inadequate
           nutritional status (low, moderate, or severe) and illness severity (low, moderate, or
           severe), with a 70-year age adjustment. The NRS 2002 score ranges from 0 to 7. For the
           NRS 2002, we employed three categories: no nutritional risk (<3), nutritional risk
           (3-4), and severe nutritional risk (≥5).

           3.2 PG-SGA The PG-SGA, a nutritional status assessment tool based on the SGA, was
           developed exclusively for cancer patients. This includes self-evaluation by patients as
           well as evaluation by medical professionals. The seven components that make up the core
           content are weight, food intake, symptoms, functional ability, illness and its
           relationship to nutritional needs, metabolic demand (stress), and physical examination.
           The first four components were assessed by patients, while the final three were assessed
           by medical professionals. Physical examination was used to determine muscular
           exhaustion, subcutaneous fat thickness, and edema. Decreased mass and tone in temporal
           regions, deltoids, and quads indicated muscular exhaustion. The triceps and midaxillary
           lines at the level of the lower ribs were studied for subcutaneous fat depletion. Edema
           was checked on the ankles. Patients were categorized as well-nourished (A), moderately
           malnourished (B), or severely malnourished (C) based on the foregoing assessments.

        4. Study Outcome The primary outcome of this study was OS, defined as the time from the
           date of surgery to the end of follow-up or death. Follow-up information was mainly
           collected through the follow-up database of gastric and colorectal cancer of each center
           combined with telephone, outpatient, or inpatient follow-ups.

        5. Statistical methods Measurement data will be expressed as means and standard deviations
           (SD), while enumeration data will be expressed as frequencies and respective
           percentages. Hematological indicators will be converted to categorical variables while
           analyzed. Variables will be initially screened using the least absolute shrinkage and
           selection operator (LASSO) regression. The variables with minimum λ will be further
           screened using univariate and multivariate Cox regression analysis to identify
           independent predictors. Then we will build a prediction model by multivariate Cox
           regression model and plot the nomogram. For user convenience, we will also create a
           dynamic nomogram webpage. Discrimination of the model will be assessed using the
           receiver operating curve (ROC), the area under the curve (AUC), and the concordance
           index (C-index). Calibration plots will be used to assess the calibration of the model.
           Decision curve analysis (DCA) will be used to evaluate the clinical utility of the
           model. The same assessments will be performed with an external validation cohort.
           Internal validation of the model will be performed using Five folds cross-validation by
           200 times. The cut-off values of the nomogram score which categorize patients into three
           categories (low-risk, middle-risk, and high-risk) will be calculated by X-tile 3.6.1
           version (https://medicine.yale.edu/lab/rimm/research/software/). Kaplan-Meier analysis
           will be used to do survival analyses. R 4.2.0 version (http://www.r-project.org) will be
           used for statistical analyses of this study. A two-tailed p <0.05 will be considered
           statistically significant.
    

Intervention name(s): observation
Intervention type(s): Other
Intervention description(s): There are no interventions.
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        The participants are who with histologically confirmed gastric and colorectal cancer who
        underwent radical surgery in 11 medical centers in China from August 1, 2015, to June 31,
        2018.
      
Keywords: Gastrointestinal Cancer; NRS 2002; Postoperative survival; Nomogram; multicenter study