1 INTRODUCTION
Gastrointestinal stromal tumors (GIST) are the most common type of sarcoma derived from the digestive tract and are characterized by the common presence of oncogenic mutations in genes encoding the KIT or PDGFRA receptor tyrosine kinases.1 The advent of imatinib, a tyrosine kinase inhibitor (TKI), has greatly improved the oncological outcomes of GISTs. 1,2 It has been widely validated that the patients with resected GIST at intermediate-, high-risk could benefit from the imatinib adjuvant setting, especially recurrence-free survival (RFS).3-13 A randomized clinical trial (SSG XVIII/AIO) reported that RFS was significantly better in 3 years of imatinib when compared with 1-year arm, indicating that prolonged the duration of imatinib adjuvant therapy leading to improving the prognosis of these patients.10 Furthermore, it has been reported that about 50% of deaths may be avoided during the first 10 years of follow-up following surgical resection with longer adjuvant imatinib treatment.13
However, it is noted that approximately 50% of the patients discontinued imatinib treatment early. Of these, quite a proportion of patients are intolerant to imatinib-related adverse reactions.10 In real clinical practice, physician usually consider dose reduction for the above patients with GISTs to alleviate drug toxic effects and the maintenance of imatinib treatment.14-18So far, the feasibility of low-dose imatinib adjuvant therapy remains unknown. Generally, imatinib is initiated at a fixed dose of 400mg/d in the patients regardless of body, which is thought to be a potential contributor to variability in imatinib systemic exposure.
On the other hand, numerous studies have shown that imatinib plasma trough concentration (Cmin) is significantly associated with the prognosis of GISTs and chronic myelogenous leukemia (CML).19-21Furthermore, the patients with a threshold of Cmin ≥ 1100ng/mL have a favorable prognosis when compared to those with Cmin less than 1100ng/mL.19 Another real-world study demonstrated that the correlation of threshold of Cmin 760 ng/mL in patients with prolonged progression-free survival (PFS).20 Thus, it is necessary to underscore the significance of close clinical monitoring to continue imatinib treatment for patients at intermediate and high risk.
In this case, we conducted a retrospectively cross-sectional study, and collected and analyzed data on patients with resected GIST treated in our institute with imatinib at either 200 mg daily, 300 mg daily, 400 mg daily, or 600 mg daily, to elucidate the impact of different dosages of imatinib on these patients. In addition, the distribution of the imatinib Cmin at different levels of doses in patients was evaluated in this study. Collectively, the main objective of this study was to explore that imatinib Cmin, as a biomarker, is used to evaluate the feasibility, safety, and efficacy of the different levels of imatinib doses in the adjuvant treatment setting.