Surgical management in metastatic gastrointestinal stromal tumor (GIST) patients after imatinib mesylate treatment.
OBJECTIVE
Imatinib mesylate (IM) demonstrates substantial efficacy in most patients with metastatic gastrointestinal stromal tumors (GISTs). However, progression of GIST eventually develops and emerges as a challenge. To assess the role of surgery in the multidisciplinary management of GISTs, we studied the surgical outcomes in GIST patients receiving IM.


METHODS
Between 2001 and May 2009, 161 metastatic GIST patients received IM. Among them, 35 patients undergoing 38 surgeries were investigated. Patients were categorized based on extent of disease before surgery (responsive or stable disease (PR, SD), local progression (LP), and generalized progression (GP)). Each tumor was investigated for genetic alteration before and after surgery.


RESULTS
Disease status before surgery was significantly associated with surgical result. Gross tumor clearance was achieved in 42.9% of patients with responsive disease, but only 4.8% of those with focal resistance and 0% of those with disease progression (P = 0.022). GIST patients with PR, SD, and LP had significant better 2-year progression-free survival and overall survival than those with GP. Secondary mutations tended to be found more frequently in GIST patients with LP after surgery than those with response (10/21 (47.6%) vs. 2/14 (14.3%); P = 0.07), indicating that surgery may prevent potential development of secondary mutation in GIST patients with response. Secondary kit mutations were also found more frequently with primary exon 11 mutation than those with exon 9 mutation (38.7% vs. 16.7%; P = 0.394).


CONCLUSIONS
Surgery may benefit selected GIST patients with PR, SD, and LP, especially for patients with LP because patients with LP had comparable survival to that of patients with responsive lesion. Surgery may prevent potential development of secondary mutations in selected patients with response after IM treatment. Secondary kit mutation was found more frequently in GIST patients with a primary kit exon 11 mutation than those with a primary kit exon 9 mutation.
Yeh
Chun-Nan
CN
GIST team, Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan. ycn@adm.cgmh.org.tw
Chen
Tsung-Wen
TW
Tseng
Jeng-Hwei
JH
Liu
Yu-Yin
YY
Wang
Shang-Yu
SY
Tsai
Chun-Yi
CY
Chiang
Kun-Chun
KC
Hwang
Tsann-Long
TL
Jan
Yi-Yin
YY
Chen
Miin-Fu
MF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D001549:Benzamides; D018450:Disease Progression; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha