Pathological complete response in advanced gastric stromal tumor after imatinib mesylate therapy: a case report

A gastrointestinal stromal tumor (GIST) is a neoplasm exhibiting, in most cases, mutations of c-kit. Imatinib mesylate (IM) is the standard treatment for patients who have advanced GISTs, and has recently become the standard treatment in the adjuvant setting as well, but not all patients benefit equally. Although the response rate in patients treated with IM in prospective clinical studies is above 50% [1], complete response is rare. We report a case of a patient with a GIST who had a pathological complete response after neoadjuvant treatment with IM.

The management of GIST is carried out using a multidisciplinary approach. Standard treatment of localized GIST is complete surgical excision associated (or not) with adjuvant imatinib therapy. If R0 resection is not feasible, or if it can be achieved through less mutilating surgery in the case of cytoreduction, imatinib pretreatment is recommended [2, 3]. The benefit of adjuvant imatinib therapy after neoadjuvant therapy is still in exploration. To the best of our knowledge, no studies evaluating this strategy have been reported in the literature. Therefore, our case illustrates complete remission after adjuvant therapy in a patient who received IM as a neoadjuvant treatment. Complete pathological response in resection specimen is rarely reported. After a wide study of the literature, only nine clinical cases have been published of reports of complete pathologic response after imatinib therapy in locally advanced or metastatic GIST [4, 5]. Mutational analysis (KIT/platelet-derived growth factor receptor α (PDGFRA) receptor mutations) has predictive value for sensitivity to molecular targeted therapy as well as prognostic value, so that its inclusion in the diagnostic work-up of all GISTs is recommended [2]. Patients with exon 11 mutations of KIT have been found to have the best response to IM, better than those patients with exon 9 mutations of KIT [6]. We suppose that our patient had a mutation which confers a high sensitivity to IM. The mutational analysis in our patient will be done later in our institution's molecular laboratory. The clinical benefit of IM can also be correlated to IM plasma levels in patients with unresectable or metastatic GISTs, as well as a previous study [7] that suggests that a low steady-state plasma level of IM at day 29 after the initiation of IM treatment (<1100 ng/mL) might contribute to drug failure in patients with advanced GISTs. Mutational analysis may help to exclude patients with a less sensitive mutational status (for example, PDGFRA D842V mutations) from IM therapy or to tailor a therapy [2] so that it may also help clinicians to make a decision regarding whether to perform surgery or administer neoadjuvant therapy for resectable GISTs.

The pathological examination of our patient documented a complete response after IM therapy. Recently, it has been confirmed that the kinase genotypes of KIT and PDGFRA α can accurately predict a good response to IM therapy. We propose that this patient had a mutation conferring high sensitivity to IM.

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.