Phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumours of the stomach

Kurokawa, Yukinori; Yang, Han Kwang; Cho, Haruhiko; Ryu, Min Hee; Masuzawa, Toru; Park, Sook Ryun; Matsumoto, Sohei; Lee, Hyuk Joon; Honda, Hiroshi; Kwon, Oh Kyoung; Ishikawa, Takashi; Lee, Kyung Hee; Nabeshima, Kazuhito; Kong, Seong Ho; Shimokawa, Toshio; Yook, Jeong Hwan; Doki, Yuichiro; Im, Seock Ah; Hirota, Seiichi; Hahn, Seokyung; Nishida, Toshirou; Kang, Yoon Koo

doi:10.1038/bjc.2017.144

Cited by 84 publications

(82 citation statements)

References 30 publications

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“…Studies indicate that the optimum duration of imatinib treatment ranges from 4 to 12 months [39, 40]. While 2 studies show that the duration of neoadjuvant therapy beyond 10 and 12 months will have bad outcomes considering the chances of tumor progression during long treatments [41, 42], a phase II study proved that promising duration is 6–9 months for large gastric GIST with high R0 resection rate and acceptable toxicity [35]. Consequently, extensive studies on GIST must thus shed further light on doses and duration of neoadjuvant therapy.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological and Prognostic Features of Surgical Management in Duodenal Gastrointestinal Stromal Tumors

Shi¹,

Huang²,

Wang³

et al. 2017

Dig Surg

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Background and Objectives: The rarity of duodenal gastrointestinal stromal tumors (DGIST) led to only limited data being available on their management and prognosis. We retrospectively analyzed the clinicopathological features, surgical treatments, adjuvant therapy, and prognosis of DGIST. Methods: Sixty-one patients were identified at diagnosis of primary DGIST from February 2005 to December 2015. One hundred twenty six patients with small intestinal gastrointestinal stromal tutors (GIST) were selected as control groups. Survival analyses were calculated using the Kaplan-Meier method. Results: Three- and five-year recurrence/metastasis-free survival rates of patients with DGIST were similar to those of patients with small intestinal GIST (p > 0.05 for all). Out of 61 cases with DGIST, 45 patients were treated with Limited Resection (LR). Sixteen patients were treated with Pancreaticoduodenectomy (PD). The 3- and 5-year recurrence/metastasis-free survival rates of the PD group and LR group were of no significant difference (p > 0.05 for all). Univariate analysis indicated that factors including surgical approaches, mitotic count, size, and risk grades were significantly associated with recurrence/metastasis-free survival (log-rank test, p < 0.05). Multivariate analysis demonstrated that the mitotic count was independently correlated with a worse recurrence/metastasis-free survival. Conclusions: Patients with radical resected DGIST had a favourable prognosis, which is similar to that of small intestinal GIST. Both LR and PD were optimal choices for treating DGIST.

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Section: Discussionmentioning

confidence: 99%

Clinicopathological and Prognostic Features of Surgical Management in Duodenal Gastrointestinal Stromal Tumors

Shi¹,

Huang²,

Wang³

et al. 2017

Dig Surg

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“…Primary endpoint of the Japanese-Korean UMIN00000003114 study was the R0 resection rate of gastric GIST larger than 10 cm [39]. GIST of other localizations were not included in this trial.…”

Section: Review Of the Literaturementioning

confidence: 99%

Neoadjuvant Therapy to Downstage the Extent of Resection of Gastrointestinal Stromal Tumors

Jakob¹,

Hohenberger²

2018

Visc Med

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Introduction: Gastrointestinal stromal tumors (GIST) are rare malignant tumors in terms of incidence, and they are not linked to specific symptoms. Often, primary tumors, particularly of the stomach, rectum, or rectovaginal space, are quite large when detected, and multivisceral resection seems to be the treatment of choice as the mainstay of therapy is complete tumor removal. If a gain-of-function mutation in the KIT gene is present, drug therapy with receptor tyrosine kinase inhibitors (RTKIs) might significantly downstage primary GIST tumors. Methods: A review of the literature was performed to identify the current evidence for preoperative treatment of GIST regarding toxicity, efficacy, and oncological outcome, including mutational data from our own database. Results: Four phase II as well as several cohort studies showed acceptable toxicity and no increased perioperative morbidity of preoperative imatinib. Progressive disease during preoperative treatment was a rare event, and partial response was achieved in 40-80% of all patients. For methodological reasons, the trials cannot prove an oncological long-term superiority of preoperative treatment. Conclusion: Preoperative therapy with imatinib is safe and recommended for patients with locally advanced GIST. Neoadjuvant imatinib therapy may enable less invasive and organ-sparing surgery, avoid tumor rupture during extensive resectional procedures, and improve the quality of perioperative RTKI treatment.

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“…Between 2010 and 2014, a phase II study of neoadjuvant imatinib for large gastric GIST was conducted in Japan and South Korea. Its short-term results were recently reported (12). The 53 patients registered in this study had no previous treatment and primary gastric GIST ≥10 cm.…”

Section: Asian Multinational Phase II Studymentioning

confidence: 65%

“…To avoid postoperative pancreatitis or pancreatic fistula, neoadjuvant imatinib for patients with large duodenal GIST may be considered. In the case of gastric GIST, neoadjuvant imatinib has been reported to be helpful for avoiding total gastrectomy (12,33). There is also the merit of making laparoscopic radical surgery possible by reducing the size of the tumor (34).…”

Section: Prevention Of Extended Surgerymentioning

confidence: 99%

Neoadjuvant therapy for gastrointestinal stromal tumor

Ishikawa

Kanda²,

Kameyama

et al. 2018

Transl. Gastroenterol. Hepatol.

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Molecular-targeting therapy using tyrosine kinase inhibitor imatinib mesylate is effective for metastasis/recurrent gastrointestinal stromal tumors (GISTs). Likewise, imatinib would be effective in the neoadjuvant therapy for high-risk GIST. Neoadjuvant therapy may have the potential to increase the complete resection rate and to avoid the surgical rupture by decreasing the tumor size. Thereby, it is expected that improvement of recurrence rate and survival rate can be obtained by neoadjuvant therapy. Neoadjuvant therapy is also expected to be favored from the viewpoint of organ/function preservation by tumor shrinkage. The existing results of clinical trials established the feasibility of neoadjuvant imatinib therapy. However, proof of the survival effectiveness of neoadjuvant imatinib therapy has not been sufficiently demonstrated. The aim of this article is to introduce previous evidence and strategies regarding neoadjuvant therapy for GIST.

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Phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumours of the stomach

Cited by 84 publications

References 30 publications

Clinicopathological and Prognostic Features of Surgical Management in Duodenal Gastrointestinal Stromal Tumors

Clinicopathological and Prognostic Features of Surgical Management in Duodenal Gastrointestinal Stromal Tumors

Neoadjuvant Therapy to Downstage the Extent of Resection of Gastrointestinal Stromal Tumors

Neoadjuvant therapy for gastrointestinal stromal tumor

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