Open AccessDownsizing Treatment with Tyrosine Kinase Inhibitors in Patients with Advanced Gastrointestinal Stromal Tumors Improved Resectability
Author(s) -
Sjölund Katarina,
Andersson Anna,
Nilsson Erik,
Nilsson Ola,
Ahlman Håkan,
Nilsson Bengt
Publication year - 2010
Publication title -
world journal of surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.115
H-Index - 148
eISSN - 1432-2323
pISSN - 0364-2313
DOI - 10.1007/s00268-010-0639-5
Subject(s) - sunitinib , imatinib , medicine , gist , tyrosine kinase inhibitor , pdgfra , imatinib mesylate , tyrosine kinase , stromal tumor , oncology , gastroenterology , surgery , cancer , stromal cell , receptor , myeloid leukemia
Background Gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase KIT. Most GISTs have mutations in the KIT or PDGFRA gene, causing activation of tyrosine kinase. Imatinib, a tyrosine kinase inhibitor (TKI), is the first‐line palliative treatment for advanced GISTs. Sunitinib was introduced for patients with mutations not responsive to imatinib. The aim was to compare the survival of patients with high‐risk resected GISTs treated with TKI prior to surgery with historical controls and to determine if organ‐preserving surgery was facilitated. Methods Ten high‐risk GIST‐patients had downsizing/adjuvant TKI treatment: nine with imatinib and one with sunitinib. The patients were matched with historical controls ( n = 89) treated with surgery alone, from our population‐based series ( n = 259). Mutational analysis of KIT and PDGFRA was performed in all cases. The progression‐free survival was calculated. Results The primary tumors decreased in mean diameter from 20.4 cm to 10.5 cm on downsizing imatinib. Four patients with R0 resection and a period of adjuvant imatinib had no recurrences versus 67% in the historical control group. Four patients with residual liver metastases have stable disease on continuous imatinib treatment after surgery. One patient has undergone reoperation with liver resection. The downsizing treatment led to organ‐preserving surgery in nine patients and improved preoperative nutritional status in one patient. Conclusions Downsizing TKI is recommended for patients with bulky tumors with invasion of adjacent organs. Sunitinib can be used for patients in case of imatinib resistance (e.g., wild‐type GISTs), underlining the importance of mutational analysis for optimal surgical planning.