Patients
We retrospectively retrieved the 563 cases of GIST ranging from the lowest to high risk according to the modified NIH risk classification, in Nanjing Drum Tower Hospital from January 2010 to December 2018. Among them, 349 cases were not treated with TKIs, and the other 214 cases received TKIs therapy. In this study, we selected patients classified as the intermediate and high risk, and divided them into two groups: TKIs-using group and TKIs-unused group. We intended to investigate whether OPNI can be a prognostic marker to these two groups. The inclusion criteria was set as follows: (1)Classified as intermediate and high risk according to modified NIH risk classification; (2) primary localized GISTs with R0 resection; (3) no other synchronous primary tumors; (4) complete medical records; (5) patients whose follow-up was done. Eventually, 280 GISTs were enrolled in this investigation. Among them, 102 patients received no therapies of imatinib, while 178 patients were treated by imatinib after operation. This study was approved by the Ethics Committee of Nanjing Drum Tower Hospital. And written informed consent was acquired from all the patients in this program.
Preoperative peripheral blood routine tests and OPNI evaluation
All the results of preoperative peripheral blood routine and blood biochemistry were obtained within 5 days before surgery. The NLR value was calculated as neutrophil count (109/L) divided by the lymphocyte count (109/L). The value of platelet-to-lymphocyte ratio (PLR) was calculated same as NLR. The OPNI was calculated as serum albumin (g/L) + 5×total lymphocyte count (109/L).
Clinicopathological features
All GISTs were initially diagnosed as gastrointestinal mesenchymal tumors by pathological ways based on a combination of histopathological evaluation and immunohistochemistry for CD117 or Discovered On GIST 1 (DOG1). They are further confirmed by CD34, desmin, SMA, S-100 expression. DNA mutation analysis of PDGFRA gene exons 12 and 18 or c-kit gene exons 9, 11, 13 and 17 were also made to determine the application of TKIs. In this study, clinical data and histopathological parameters are all collected from medical records. Clinical data includes age, gender, initial complaint, primary tumor site, tumor size, surgery options, tumor rupture (preoperative or intraoperative) , whether the TKIs were used and hospitalization time. Tumor size was accurately measured by pathologists after surgery. Histopathological factors include predominant cell type (spindle, epithelioid, or mixed), mitotic index (per 50 randomly selected high power fields [HPFs]), tumor necrosis and Ki-67 index. Risk stratification of each case was determined by modified NIH consensus criteria covering tumor size, mitotic index, tumor site, and rupture.
Follow-up
The patients after surgery were followed up through routine peripheral blood tests, abdominal ultrasonography, endoscopy and computed tomography (CT) every 6 months in the first 5 years, and then annually after 5 years to evaluate tumor recurrence or distant metastasis. Follow-up information was obtained by outpatient or hospitalized records , or direct contact with patients or their family. Relapse-free survival (RFS) is more suitable to evaluate patients’ survival than overall survival (OS). RFS was calculated from the date of surgery to the date of GIST relapse, metastasize or to the last follow-up date,.
Statistical analysis
All statistical analyses were calculated by using IBM SPSS Statistics, version 22.0 (IBM, New York, USA). The ranked and unordered categorical variables were respectively assessed by Mann–Whitney U and Chi-square test. The correlation of continuous variables was calculated by Pearson correlation coefficient, while discrete variables by Spearman’s correlation coefficient. Cox’s regression model was used to perform multivariate survival analyses. The log-rank test and Kaplan–Meier method were utilized to calculate univariate survival. The PLR, NLR, OPNI cut-off value was determined according to the receiver operating characteristic (ROC) curve analysis, which was performed based on the recurrence state at 9-year follow-up. The Youden indexwas estimated to determine the optimal cutoff value for PLR, NLR and OPNI, calculated as sensitivity - (1 – specificity). A P-value <0.05 was indicated to be statistical significant, and confidence intervals (CI) were calculated at the 95 % level.
In this study, we applied 1:1 propensity score matching to adjust patients for gender, age, primary tumor site, tumor size, mitotic index and risk stratification in order to reduce the effect of potential confounding factors and selection bias, such as patients’ baseline clinicopathologic factors or unequal patients distribution between the TKIs-used and TKIs-unused groups. A 0.05-width caliper of the standard deviation of the logit was set to match the two groups.