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Hepatic resection for metastatic gastrointestinal stromal tumors in the tyrosine kinase

Why this is important: It provides evidence that complete resection (R0 or R1) of liver metastases in combination with TKI therapy (e.g. Gleevec, Sutent, etc.) may improve survival of patients with GIST.

Purpose: Before TKIs, such as Gleevec, became available, the only option for GIST patients was surgery. Although TKIs have improved survival for people with metastatic GIST, it was unknown whether TKIs and complete surgical resection (R0 or R1) of liver metastases had an improved survival rate over TKIs or surgery alone.

Basic method of research: A review of demographics, tumor characteristics, treatments and outcomes of 39 patients who have received complete resection(R0 or R1) of liver metastases at the Liver Cancer Center at the University of Pittsburgh Medical Center, Johns Hopkins Hospital and Duke University Medical Center during 1995 -2010 was conducted. The median followup after metastectomy was about 40 months. The analysis of the data of the 39 patients was performed to 1) define predictors of survival after liver resection and 2) determine the optimal timing of TKI therapy for liver resection. 23 of 39 patients had taken TKIs prior to liver surgery (for a median of 18 months, range 9-52 months) and 4 had also taken sunitinib. It is not entirely clear from the paper, but it appears that the patients who took TKIs prior to liver surgery had actually developed liver mets while taking imatinib; therefore, these patients apparently had already become resistant to TKIs before the liver metastectomy. The patients who did not take TKIs prior to liver surgery had been operated on for their primary tumors before adjuvant imatinib was offered.

Results: The analysis showed thatpost-operative, but not pre-operative, TKI therapy predicted improved survival. However, if at least some of these patients were already resistant to imatinib or sunitinib, then this is not surprising. In this retrospective descriptive study the post-op-only group and the pre-op plus post-op groups were not comparable. Other potential predictors of improved survival included single liver metastases, smaller size of liver metastases, and absence of metastases to other parts of the body in addition to the liver. Some of the limitations of this study include the retrospective nature of the study, very small sample size, lack of information on the duration of post-operative TKI therapy, lack of information on important prognostic indicators such as mitotic rate and primary tumor size. However despite these limitations, the study recommends all patients with liver GIST metastases be treated with both surgery and post operative TKI therapy before signs of resistance become apparent.

Link to the abstract