Adjuvant therapy with imatinib mesylate after resection of primary high-risk gastrointestinal stromal tumors in Japanese patients

Gastrointestinal stromal tumors (GISTs) are malignant and rare form of soft tissue sarcoma of the digestive tract. The incidence of gastrointestinal stromal tumors is very low Kramer et al. 2005 Jejunal GISTs are extremely rare. Here we present a rare case of jejunal GIST with unusually large size at presentation. The patient presented with severe abdomen pain, exophytic growth, and dimorphic anemia. Surgical resection of the tumor was carried out, and operative findings revealed a 15 × 10 cm growth, arising from serosal surface of jejunum, at the antimesenteric surface. Diagnosis in this case was made by subjecting the resected specimen to immunohistochemical analysis. In view of large size of the resected tumor, and high-risk histopathological features, imatinib mesylate 400 mg once daily was given as adjuvant chemotherapy. Patient is asymptomatic without any evidence of tumor recurrence after six months of postoperative followup. Imatinib as such is recommended in metastatic, residual or recurrent cases of GISTs or which are surgically not removable; however, recent recommendations suggests the use of imatinib mesylate after radical surgery in high-risk cases, because it has shown a significant decrease in the recurrence rate, and the Food and Drug Administration (FDA) has also approved the use of imatinib as adjuvant therapy after complete resection of localized, primary GIST.

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Efficacy of Long-Term Adjuvant Therapy With Imatinib Mesylate After Extensive Surgical Treatment for Ruptured Gastrointestinal Stromal Tumors of the Small Intestine With Peritoneal Metastases: A Case Report

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709620970736 ◽

2020 ◽

Vol 8 ◽

pp. 232470962097073 ◽

Cited By ~ 1

Author(s):

Toshihisa Kimura ◽

Tamotsu Togawa ◽

Kenji Onishi ◽

Atsushi Iida ◽

Yasunori Sato ◽

...

Keyword(s):

Small Intestine ◽

Adjuvant Therapy ◽

Imatinib Mesylate ◽

Surgical Resection ◽

Gastrointestinal Stromal Tumors ◽

Peritoneal Metastases ◽

Metastatic Recurrence ◽

Stromal Tumors ◽

Dose Change

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Although most patients with advanced GISTs benefit from imatinib mesylate (IM) as standard targeted therapy, the optimal duration of adjuvant IM for GIST patients with high risk of recurrence who underwent surgical resection remains unknown. In this article, we present a case of a ruptured GIST of the small intestine accompanied by peritoneal metastases, which was effectively treated by surgical procedure followed by long-term adjuvant therapy with IM. Surgical resection was performed for the ruptured small intestinal GIST, and multitude of peritoneal metastases were cauterized. The patient received adjuvant therapy with IM (400 mg/day) for 12 years without an interruption or a dose change. Peritoneal metastatic recurrence was observed by the follow-up computed tomography scan obtained 12 years after surgery, and surgical resection of the recurrent GIST was performed. The molecular examination indicated a KIT exon 11 deletion mutation in both the primary GIST and recurrent GIST. An additional point mutation was observed in the recurrent GIST in exon 17 that caused resistance to IM. The present case might indicate that extensive removal of the tumor cells through surgery and long-term administration of IM without an interruption or a dose change were important for achieving improved recurrence-free survival in patients with ruptured GISTs of the small intestine with peritoneal metastases.

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The real world outcomes of 3-year adjuvant therapy with imatinib in patients with high-risk molecular profiled gastrointestinal stromal tumors (GIST).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e23524 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e23524-e23524

Author(s):

Piotr Rutkowski ◽

Marcin Zietek ◽

Bozena Cybulska-Stopa ◽

Joanna Streb ◽

Stanislaw Gluszek ◽

...

Keyword(s):

Clinical Trials ◽

High Risk ◽

Adjuvant Therapy ◽

Real World ◽

Gastrointestinal Stromal Tumors ◽

Disease Relapse ◽

Adjuvant Imatinib ◽

Stromal Tumors ◽

Exon 9 ◽

Exon 11

e23524 Background: The real-world data on outcomes of adjuvant therapy in high-risk gastrointestinal stromal tumors (GIST) are very limited. Methods: We have analyzed the data of 107 consecutive patients (52 male, 56 female) with GIST after resection treated with adjuvant imatinib (for planned 3 years with initial dose 400 mg daily, started not later than 4 months after operation) in 6 oncological centers in 2013-2018. All patients were required to have high risk of recurrence (at least 50% according to NCCN/AFIP criteria), known mutational status to exclude PDGFRA D842V mutants and KIT/PDGFRA-wild type cases from therapy. Median follow-up time was 24 months. Results: The most common primary localization of GIST was small bowel (63 patients; 59%), followed by the stomach (40 patients; 37%). The majority of GIST cases harbored exon 11 KIT mutations (88 cases, 82%), 11 cases had exon 9 KIT mutations (10%), 8 had other KIT/PDGFRA mutations potentially sensitive to imatinib. Thirty three patients (31%) finished 3-year adjuvant imatinib therapy as planned, 59 (55%) still continue therapy, 4 (4%) patients had finished adjuvant therapy prematurely due to toxicity, 6 (6%) due to disease progression on treatment and 5 (4%) due to other reasons. The disease relapse was detected in 16 patients, of them in 4 cases in exon 9 KIT mutants (36%), and 10 cases in patients with exon 11 KIT mutations (11%) [p < 0.05]. Estimated 4-year relapse-free survival (RFS) rate is 78%. Conclusions: The early results of adjuvant therapy with imatinib in routine practice outside clinical trials in high-risk mutation-drive GIST patients only confirm high efficacy of this therapy with better tolerability than in clinical trials. Moreover, overrepresentation of exon 9 KIT mutants in a group of patients with disease relapse may indicate that standard 400 mg dose in adjuvant treatment is not sufficient for prevention of disease relapse.

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