Al-Batran Salah-Eddin, Hartmann Joerg Thomas, Heidel Florian, Stoehlmacher Jan, Wardelmann Eva, Dechow Claudius, Düx Markus, Izbicki Jacob Robert, Kraus Thomas, Fischer Thomas, Jäger Elke
Department of Hematology and Oncology, Krankenhaus Nordwest, Steinbacher Hohl 2-26, 60488 Frankfurt am Main, Germany.
Gastric Cancer. 2007;10(3):145-52. doi: 10.1007/s10120-007-0425-8. Epub 2007 Sep 26.
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.
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.
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.
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.
本研究旨在调查在伊马替尼治疗期间出现局限性疾病进展的晚期胃肠道间质瘤（GIST）患者，经手术切除并继续使用伊马替尼治疗后的结果。
对在我们中心特定时间段内接受伊马替尼治疗的38例转移性GIST患者进行了连续评估。评估患者的人口统计学特征，包括肿瘤相关特征、初始反应、疾病复发和挽救治疗方式，并在挽救治疗前就诊时将其分类为局限性或广泛性进展。
中位随访31.8个月后，38例患者中有25例（65.8%）出现进展。9例（36%）患者被分类为局限性进展，16例（64%）为广泛性进展。挽救治疗方法为：局限性进展患者采用手术切除并增加伊马替尼剂量，大多数广泛性进展患者仅增加伊马替尼剂量。与广泛性进展相比，局限性进展与挽救治疗后的无进展生存期（PFS）延长和总生存期（OS）延长相关（中位PFS和OS分别为11.3个月和未达到，而广泛性进展分别为2.5个月和22.8个月）。局限性和广泛性进展患者的6个月PFS分别为89%和39%。对4例局限性进展患者的对照病变和进展性病变进行了KIT突变分析。继发性KIT突变影响进展性病变，而非进展性病变仅含有原始突变。
在伊马替尼治疗期间出现局限性疾病进展的晚期GIST患者可能从手术切除并继续使用伊马替尼中获益。这些患者的伊马替尼耐药似乎是部分性的。
