Current research and treatment for gastrointestinal stromal tumors

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest, especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene, BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential, and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure, targeted therapy in the form of tyrosine kinase inhibitors (TKIs) has revolutionized the management options. As the first-line TKI, imatinib offers treatment for advanced and metastatic GISTs, adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options, including prolonging the first-line TKI from 1 to 3 years, increasing the dose of TKI or switching to second-line TKI. Other newer TKIs, such as sunitinib and regorafenib, may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated, such as inhibitors of BRAF, heat shock protein 90, glutamine and mitogen-activated protein kinase signaling, as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe, North America and Asia are highlighted.

Surgical treatment of gastric GIST with acute bleeding using laparoscopic sleeve gastrectomy: A report of two cases

“…Pathology reports showed in both cases complete surgical resection (R0); the tumors were diagnosed as gastric GISTs in the very low-risk/low-risk category, and adjuvant chemotherapy was not necessary. 15 At one-month postoperative follow-up, no symptoms were referred by the patients. In the Case 1, the patient, who suffered also for morbid obesity, had lost 15 kg from the day of the operation (BMI 29.41 kg/m 2 ).…”

“…The patients’ postoperative recovery was uneventful for major complications. Pathology reports showed in both cases complete surgical resection (R0); the tumors were diagnosed as gastric GISTs in the very low‐risk/low‐risk category, and adjuvant chemotherapy was not necessary . At one‐month postoperative follow‐up, no symptoms were referred by the patients.…”

Les tumeurs stromales gastro-intestinales : expérience de vie réelle d’un centre marocain

“…Dans notre série, la fibroscopie gastrique réalisée pour les 16 cas de tumeurs gastriques a retrouvé un aspect de masse sous-muqueuse dans 5 cas. Les GIST apparaissent à la tomodensitométrie (TDM) sous forme d'une masse arrondie ou ovalaire à limites nettes, ayant un développement plutôt extraluminal avec des zones nécrotiques au centre pour les tumeurs volumineuses [1,10,15]. La TDM spiralé thoraco-abdomino-pelvienne est la référence dans le bilan d'extension des GIST [16].…”

“…Comparativement aux données de la littérature [1,31], ce faible taux de rémission complète est expliqué par le fait que les GIST dans notre série étaient diagnostiquées à un stade très avancé, 56,5 % étaient révélées par une masse abdominale palpable et 52,2 % étaient localement avancées ou métastatiques au moment du diagnostic.…”

“…Elles y touchent tous les segments : de l'oesophage à l'anus, et exceptionnellement le mésentère et le péritoine [1][2][3]. Historiquement, ces tumeurs ont été diagnostiquées à tort comme des léiomyomes, des léiomyosarcomes ou des léiomyoblastomes jusqu'à l'identification des mutations c-Kit et du récepteur du facteur de croissance dérivé des plaquettes (PDGFR) [4].…”