Dataset Information

Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors.

ABSTRACT: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and present predominantly in middle-aged and older individuals. Historically, the outlook for patients with GISTs was very poor because of the general lack of efficacy of conventional chemotherapy and the often limited surgical options. However, the recognition of the role of mutations of the v-kit Hardy/Zuckerman 4 feline sarcoma viral oncogene homolog KIT and the platelet derived growth factor receptor alpha gene PDGFR? in the development of GISTs led to the evaluation of potential antitumor effects of the tyrosine kinase inhibitors imatinib and, more recently, sunitinib. Consequently, these molecularly targeted therapies were introduced into clinical practice, and the outcome for patients with GISTs improved considerably. In the last few years, the European Society of Medical Oncology, the National Comprehensive Cancer Network, and the Canadian Advisory Committee on GIST each published a major set of guidelines or practice recommendations for the management of patients with GIST. In the current review, the latest recommendations from each organization are summarized in terms of diagnosis and risk assessment, tumor staging, surgical and/or drug treatment of primary resectable and recurrent metastatic disease, and patient follow-up and assessment. In addition, areas of consensus and points of divergence among the guidelines are highlighted along with any unresolved issues.

SUBMITTER: Blay JY

PROVIDER: S-EPMC4167025 | biostudies-other | 2010 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors.

Blay Jean-Yves JY von Mehren Margaret M Blackstein Martin E ME

Cancer 20101101 22

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and present predominantly in middle-aged and older individuals. Historically, the outlook for patients with GISTs was very poor because of the general lack of efficacy of conventional chemotherapy and the often limited surgical options. However, the recognition of the role of mutations of the v-kit Hardy/Zuckerman 4 feline sarcoma viral oncogene homolog KIT and the platelet derived growth ...[more]

PMID: 20661913

Similar Datasets

Project description:Gastrointestinal stromal tumors (GIST) are rare mesenchymal smooth muscle sarcomas that can arise anywhere within the gastrointestinal tract. Sporadic mutations within the tyrosine kinase receptors of the interstitial cells of Cajal have been identified as the key molecular step in GIST carcinogenesis. Although many patients are asymptomatic, the most common associated symptoms include: abdominal pain, dyspepsia, gastric outlet obstruction, and anorexia. Rarely, GIST can perforate causing life-threatening hemoperitoneum. Most are ultimately diagnosed on cross-sectional imaging studies (i.e., computed tomography and/or magnetic resonance imaging in combination with upper endoscopy. Endoscopic ultrasonographic localization of these tumors within the smooth muscle layer and acquisition of neoplastic spindle cells harboring mutations in the c-KIT gene is pathognomonic. Curative treatment requires a complete gross resection of the tumor. Both open and minimally invasive operations have been shown to reduce recurrence rates and improve long-term survival. While there is considerable debate over whether GIST can be benign neoplasms, we believe that all GIST have malignant potential, but vary in their propensity to recur after resection and metastasize to distant organ sites. Prognostic factors include location, size (i.e., > 5 cm), grade (> 5-10 mitoses per 50 high power fields and specific mutational events that are still being defined. Adjuvant therapy with tyrosine kinase inhibitors, such as imatinib mesylate, has been shown to reduce the risk of recurrence after one year of therapy. Treatment of locally-advanced or borderline resectable gastric GIST with neoadjuvant imatinib has been shown to induce regression in a minority of patients and stabilization in the majority of cases. This treatment strategy potentially reduces the need for more extensive surgical resections and increases the number of patients eligible for curative therapy. The modern surgical treatment of gastric GIST combines the novel use of targeted therapy and aggressive minimally invasive surgical procedures to provide effective treatment for this lethal, but rare gastrointestinal malignancy.

Project description:BackgroundAvapritinib, a novel inhibitor of KIT/PDGFRA, is approved in the U.S. for the treatment of adults with PDGFRA exon 18-mutant unresectable or metastatic gastrointestinal stromal tumors (U/M GISTs). We assessed the safety of avapritinib and provide evidence-based guidance on management of avapritinib-associated adverse events (AEs), including cognitive effects and intracranial bleeding.Materials and methodsWe performed a post hoc analysis of data from a two-part, single-arm dose escalation/expansion phase I study (NAVIGATOR; NCT02508532) in patients with U/M GISTs treated with oral avapritinib 30-600 mg once daily. The primary endpoints were safety and tolerability; the impact of dose modification (interruption and/or reduction) on progression-free survival (PFS) was a secondary endpoint. Efficacy analyses were limited to patients who started avapritinib at 300 mg (approved dose).ResultsOf 250 patients enrolled in the study, 74.0% presented with KIT mutation and 24.8% presented with PDGFRA exon 18-mutation; 66.8% started avapritinib at 300 mg. The most common treatment-related AEs (any grade) were nausea (59.2%), fatigue (50.0%), periorbital edema (42.0%), anemia (39.2%), diarrhea (36.0%), vomiting (36.0%), and increased lacrimation (30.8%). No treatment-related deaths occurred. Among 167 patients starting on 300 mg avapritinib, all-cause cognitive effects rate (grade 1-2) was 37.0% in all patients and 52.0% in patients ≥65 years. Cognitive effects improved to a lower grade more quickly with dose modification (1.3-3.1 weeks) than without (4.9-7.6 weeks). Median PFS was 11.4 months with dose modification and 7.2 months without.ConclusionTolerability-guided dose modification of avapritinib is an effective strategy for managing AEs in patients with GISTs.Implications for practiceEarly recognition of adverse events and tailored dose modification appear to be effective approaches for managing treatment-related adverse events and maintaining patients on avapritinib. Dose reduction does not appear to result in reduced efficacy. Patients' cognitive function should be assessed at baseline and monitored carefully throughout treatment with avapritinib for the onset of cognitive adverse events. Dose interruption is recommended at the first sign of any cognitive effect, including grade 1 events.

Dataset Information

Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors.

Publications

Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets