Preoperative imatinib treatment in patients with advanced gastrointestinal stromal tumors: patient experiences and systematic review of 563 patients

Abstract

Preoperative IM therapy for GIST is now a research focus. Due to the low incidence of the disease, there are few RCTs on the preoperative treatment for advanced GIST, let alone relevant meta-analysis. Efficacy of this therapy and targeting population are still undetermined. Therefore, the first part of this article is composed of a controlled retrospective study and demonstrates that preoperative therapy with IM can significantly improve the outcome of advanced GIST. In the second part of the paper, we further investigated what portion of advanced GIST patients benefit more from the therapy, based on a meta-analysis. As the disease is relatively rare, we involved 563 cases in the meta-analysis, much higher than in the controlled clinical studies (51 cases). The objective of this paper is to investigate effects of surgical resection on imatinib-treated advanced GIST. Twenty-two consecutive advanced GIST patients (Group A) with preoperative IM treatment were compared to 29 patients (Group B) who underwent initial tumor resection during the same period. Subsequently, a systematic review of 563 patients was applied to identify the benefit of the advanced GIST patients receiving imatinib before surgery. Compared with Group B, less patients in Group A underwent multivisceral resection (18.2% versus 48.3%, P = 0.026) or suffered tumor rupture at time of surgery (0% versus 17.2%, P = 0.04). The 3-year estimated progression-free survival of Group A (94.4%) was also superior to that of Group B (61.4%; P = 0.045). Subsequent meta-analysis indicated that primarily unresectable patients had higher complete resection and 2-year PFS rates than recurrent/metastasis patients (P = 0.005 and 0.20, respectively); (b) stable disease (SD) patients had better outcome in resection including resectability rate (P < 0.0001), PFS (P < 0.00001) and OS (P = 0.0008) than progressive disease (PD) patients; (c) in recurrent/metastatic PD patients, surgery played a minor role, because they had a higher bulky residual disease rate (P = 0.0005) and higher progression risk (P < 0.00001) within 2 years after surgery. Preoperative IM treatment improves prognosis of advanced GISTs. Among recurrent/metastatic patients, postimatinib surgery may benefit those who have SD after IM treatment but not those resistant to IM.

Keywords: Gastrointestinal stromal tumors; Imatinib; Surgical resection; Targeted therapy.

Fig. 1

Kaplan-Meier curves for the PFS and the OS according to the groups (Group A, patients received preoperative IM treatment; Group B, patients underwent surgery initially).

Fig. 2

Comparison of prognosis between unresectable and recurrent/metastasis GIST. (Top) Incomplete resection (R1/R2 resection) after preoperative IM treatment; (bottom) recurrence within 2 years after the surgery.

Fig. 3

Prognosis comparison between the advanced GIST patients with stable disease and progressive disease after the preoperative IM treatment. (Top) Incomplete resection (R1/R2) following the IM therapy; (middle) recurrence within 2 years after the surgery; (bottom) death within 2 years after the surgery.

Fig. 4

Prognosis comparison between the recurrent/metastatic GIST patients with stable disease and progressive disease after the preoperative IM treatment. (Top) Incomplete resection (R1/R2) following the IM therapy; (bottom) recurrence within 2 years after the surgery.