title: Surgical resection of recurrent gastrointestinal stromal tumor after interruption of long-term nilotinib therapy.
abstract: BACKGROUND
  Nilotinib inhibits the tyrosine kinase activities of ABL1/BCR-ABL1, KIT, and platelet-derived growth factor receptors (PDGFRs). The results of a phase III clinical trial indicated that nilotinib could not be recommended for broad use as first-line therapy for gastrointestinal stromal tumor (GIST). However, some clinical studies have reported the effectiveness of nilotinib. We report here the cases of two patients who underwent surgical resections of nilotinib-resistant lesions after long-term nilotinib administration.
  
  
  METHODS
  Two Japanese female patients, aged 66 and 70 years, experienced peritoneal recurrence of intestinal GIST several years after surgery. Both were registered in the ENESTg1 trial and received nilotinib therapy. Although they continued nilotinib administration with a partial response according to the protocol, nilotinib-resistant lesions, which were diagnosed as focally progressive disease, developed and complete surgical resection was performed. Pathological examination revealed that the tumors were composed of viable KIT-positive spindle cells, and the recurrent tumors were diagnosed as nilotinib-resistant GIST. In gene mutation analysis, a secondary KIT gene mutation was detected in one case. Both patients have survived more than 5 years after the first surgery.
  
  
  CONCLUSIONS
  Of patients who were registered in this trial, we have encountered two patients with long-term effects after nilotinib administration. Moreover, secondary mutations in the KIT gene, similar to those involved in resistance to imatinib, might be involved in resistance to nilotinib.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Sugase
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. ttakahashi2@gesurg.med.osaka-u.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Division of Digestive and General Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Division of Digestive and General Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.affiliation: Department of Surgery, Sanjo General Hospital, Niigata, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hirota
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Makino
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Kurokawa
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Takiguchi
authors.affiliation: Division of Digestive and General Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
keywords: Nilotinib; Resistant GIST; Secondary mutation