Is monocyte‐to‐lymphocyte ratio the best systematic inflammatory biomarker for the prognosis of gastrointestinal stromal tumors?

Surgery is the standard therapy for gastrointestinal stromal tumor (GIST) in a localized stadium and should be carried out whenever feasible. However, tumor recurrence is the main problem after resection of GIST. Therefore, the accurate determination of the risk for tumor recurrence is increasingly important to select the appropriate patients for adjuvant imatinib treatment. In recent decades, the role of inflammatory blood biomarkers, which may improve recurrence risk stratification and inform long‐term overall survival for patients with GIST, has been reported. In a recent issue of Journal of Surgical Oncology, Cananzi et al performed an interesting study in which authors aimed to determine whether neutrophil‐lymphocyte ratio (NLR), monocyte‐lymphocyte ratio (MLR), platelet‐lymphocyte ratio (PLR), neutrophil‐white blood cell ratio, lymphocyte white cell ratio, monocyte‐white cell ratio, and platelet‐ white cell ratio are prognostic risk factors after resection of primary GIST. Cox's regression multivariate analysis found that mitosis, NLR, MLR, and PLR were risk factors for disease‐free survival (DFS), with MLR showing the highest statistical significance and hazard ratio value. Moreover, MLR, NLR, and PLR were the only prognostic factors in the subgroup of patients with moderate to high Miettinenʼs risk class. A high value of MLR was associated with reduced DFS. We applaud Cananzi et al for first demonstrating the role of MLR as a predictor of recurrence in GIST. At the same time, their conclusions should be interpreted with caution in light of some concerns. First, their findings that MLR showing the highest statistical significance were only based on Cox's regression multivariate analysis. And the optimal threshold value was obtained using the logrank test by decile based on DFS data. The cut‐off value for dividing patients into high and low inflammatory blood biomarker groups using the receiver operating characteristic curves may be better than the logrank test by decile. If so, it will be more convenient to compare the seven areas under the curve of these inflammatory blood biomarkers. Second, (neoadjuvant/adjuvant) imatinib in the treatment of GIST has revolutionized GIST patients’ outcome by reducing the risk of local and distant recurrence and improving overall survival. And this may be one of the reasons that the authors use DFS, but not overall survival, as the primary outcome. All included patients underwent curative resection except two metastatic patients who received palliative resection. In addition, nine patients received neoadjuvant imatinib, and seven of them continued postoperatively. Overall, adjuvant imatinib was administered to 20 patients. All these patients with palliative resection or neoadjuvant/adjuvant imatinib therapy were included in DFS analysis. Just as the results from Table 2 in their study, neoadjuvant and adjuvant imatinib therapy showed the highest statistical significance. Furthermore, the number of such patients may not be comparable between patients with high and low inflammatory blood biomarkers groups. Therefore, all these patients who received palliative resection or neoadjuvant/adjuvant imatinib therapy should be excluded into the analysis. Third, the present study is the first demonstrating the role of MLR as a predictor of recurrence in GIST, while all others found PLR as a risk predictor. The authors should discuss the reasons. Fourth, the sentence “No significant correlations were found between DFS and age.and MWR” in the first paragraph of the Disease‐Free Survival Analysis section may misrepresent the findings in Table 2. In conclusion, these limitations may lead to improper interpretations regarding the presence of inflammation in these patients.