Focal progression in patients with gastrointestinal stromal tumors after initial response to imatinib mesylate: a three-center-based study of 38 patients.
BACKGROUND
This study aimed to investigate the outcome of patients with advanced gastrointestinal stromal tumors (GISTs) exhibiting focal disease progression during imatinib therapy, treated by surgical resection and imatinib continuation.


METHODS
A consecutive series of 38 patients with metastatic GISTs who underwent treatment with imatinib at our centers during a defined period of time was evaluated. Patients were evaluated for demographics including tumor-related features, initial response, disease recurrence, and salvage treatment modalities, and were classified as having either focal or generalized progression upon presentation prior to salvage therapy.


RESULTS
After a median follow-up of 31.8 months, 25 of the 38 (65.8%) patients had progressed. Nine (36%) patients were classified as having focal and 16 (64%) as having generalized progression. Salvage therapies were: surgical resection and imatinib dose escalation in patients exhibiting focal progression and imatinib dose escalation alone in the majority of patients exhibiting generalized progression. Focal progression was associated with prolonged progression-free survival (PFS) and overall survival (OS) after salvage therapy as compared with generalized progression (median PFS and OS, 11.3 months and not attained, versus 2.5 and 22.8 months, respectively). Six-month PFS was 89% and 39% in patients exhibiting focal and generalized progression, respectively. KIT mutation analysis of controlled and progressive lesions was performed in 4 patients with focal progression. Secondary KIT mutations affected progressive lesions, whereas nonprogressive lesions harbored the original mutations only.


CONCLUSIONS
Patients with advanced GIST exhibiting focal disease progression during imatinib therapy may benefit from surgical resection and imatinib continuation. Imatinib resistance seems to be partial in these patients.
Al-Batran
Salah-Eddin
SE
Department of Hematology and Oncology, Krankenhaus Nordwest, Steinbacher Hohl 2-26, 60488 Frankfurt am Main, Germany.
Hartmann
Joerg Thomas
JT
Heidel
Florian
F
Stoehlmacher
Jan
J
Wardelmann
Eva
E
Dechow
Claudius
C
Düx
Markus
M
Izbicki
Jacob Robert
JR
Kraus
Thomas
T
Fischer
Thomas
T
Jäger
Elke
E
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit