Outcome of Metastatic GIST in the Era before Tyrosine Kinase Inhibitors

Gold, Jason S.; Zwan, Sanne M. van der; Gönen, Mithat; Maki, Robert G.; Singer, Samuel; Brennan, Murray F.; Antonescu, Cristina R.; Matteo, Ronald P. De

doi:10.1245/s10434-006-9177-7

Cited by 105 publications

(47 citation statements)

References 29 publications

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“…Although we found no statistically significant difference between the different organs involved (p=0.08), some studies 11,19,20 have shown that the GIST location directly influences the prognosis and those located in the stomach had more favorable course than those found in other topographies. Statistically, we found that the colonic topography directly influenced prognosis, since five out ofthe six tumors had unfavorable follow-up (metastasis/death), which was also found in another study 3 . The importance of tumor size in GIST prognosis has undergone major changes since the publication of Miettinen et al…”

Section: Discussion Discussion Discussion Discussionsupporting

confidence: 82%

“…G astrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract 1 , their incidence being estimated at 14 to 20 cases per million population 2 ; they are more frequent in male patients older than 50 years old 3 . The pathogenesis is related to mutational changes in two tyrosine kinase receptors: KIT and PDGFR-alpha (plateletderived growth factor receptor alpha) on the surface of the interstitial cells of Cajal, the former being the most common (85% of cases) 4,5 .…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

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Comparative study of the different degrees of risk of gastrointestinal stromal tumor

Oliveira

Filho

Iglesias

et al. 2015

Rev. Col. Bras. Cir.

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ABSTRACT ABSTRACT ABSTRACTObjective Objective Objective Objective Objective: To evaluate the applicability of the main categories of risk and morphological factors in the prognosis of gastrointestinal stromal tumors. MethodsMethods Methods Methods Methods: we retrospectively studied fifty-four cases of GIST, assessing the main prognostic factors of this neoplasis: risk levels, topography, size, mitotic index, necrosis, histological subtype and immunophenotype. We also verified their association and the reduction of overall survival. Results Results ResultsResults Results: Univariate analysis showed that tumors with mitoses number greater than 5 per 50CGA (high-power fields), the presence of necrosis and a high risk for both the systems proposed by Fletcher and Miettinen had a significant association with reduced survival (p = 0.00001, 0.0056, 0.03 and 0.009, respectively). The remaining analyzed factors (size, histological subtype, topography and immunophenotype) had no such association. Multivariate analysis (Jacard index) showed that the Miettinen degree of risk was the one that best correlated with prognosis. Conclusion Conclusion Conclusion Conclusion Conclusion: the risk criteria of Fletcher and Miettinen are important in assessing the prognosis of patients with gastrointestinal stromal tumors, especially the latter, which adds to the mitotic index and the presence of tumor necrosis. G astrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract 1 , their incidence being estimated at 14 to 20 cases per million population 2 ; they are more frequent in male patients older than 50 years old 3 . The pathogenesis is related to mutational changes in two tyrosine kinase receptors: KIT and PDGFR-alpha (plateletderived growth factor receptor alpha) on the surface of the interstitial cells of Cajal, the former being the most common (85% of cases) 4,5 . Gastrointestinal stromal tumors can develop in any topography, from the esophagus to the rectum. However, they are more common in the stomach (50% to 60%), followed by small intestine (20% to 30%), colon (10%), rectum or esophagus (5%) 6 . Macroscopically, the tumor lesions often have a nodular form, transmural involvement and submucosal growth, with ulceration of the mucosa or not. In light microscopy, histology reveals three types: the most common spindle (70%), epidermoid (20%) and the mixed type (10%), when there is combination of epithelioid and spindle ones 7 . Key wordsThe diagnosis of stromal neoplasms is based on immunohistochemical study with CD117 marker, expressed in most such neoplasias 1 . Noteworthy are also other markers: DOG 1, nestin, theta protein kinase C and carbonic anhydrase II 8 . The differential diagnosis includes: desmoid tumor, inflammatory myofibroblastomas, leiomyoma, inflammatory fibroid polyp, neuroma, neurossarcoma, sarcomatoid mesothelioma and metastatic melanoma 7,9,10 GIST prognosis is still matter of discussion. Currently there are different classifications 7,[11][12...

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Section: Discussion Discussion Discussion Discussionsupporting

confidence: 82%

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

Comparative study of the different degrees of risk of gastrointestinal stromal tumor

Oliveira

Filho

Iglesias

et al. 2015

Rev. Col. Bras. Cir.

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“…genetic predisposition | sarcoma | pediatric G astrointestinal stromal tumor (GIST), the most common mesenchymal neoplasm of the gastrointestinal tract, is resistant to conventional cytotoxic chemotherapy (1). Oncogenic mutations in KIT or PDGFRA have been identified as central tumor-initiating events in many GISTs (2,3).…”

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confidence: 99%

Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations

Janeway

Kim

Lodish

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Carney-Stratakis syndrome, an inherited condition predisposing affected individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused by germline mutations in succinate dehydrogenase (SDH) subunits B, C, or D, leading to dysfunction of complex II of the electron transport chain. We evaluated the role of defective cellular respiration in sporadic GIST lacking mutations in KIT or PDGFRA (WT). Thirty-four patients with WT GIST without a personal or family history of paraganglioma were tested for SDH germline mutations. WT GISTs lacking demonstrable SDH genetic inactivation were evaluated for SDHB expression by immunohistochemistry and Western blotting and for complex II activity. For comparison, SDHB expression was also determined in KIT mutant and neurofibromatosis-1-associated GIST, and complex II activity was also measured in SDH-deficient paraganglioma and KIT mutant GIST; 4 of 34 patients (12%) with WT GIST without a personal or family history of paraganglioma had germline mutations in SDHB or SDHC. WT GISTs lacking somatic mutations or deletions in SDH subunits had either complete loss of or substantial reduction in SDHB protein expression, whereas most KIT mutant GISTs had strong SDHB expression. Complex II activity was substantially decreased in WT GISTs. WT GISTs, particularly those in younger patients, have defects in SDH mitochondrial complex II, and in a subset of these patients, GIST seems to arise from germline-inactivating SDH mutations. Testing for germline mutations in SDH is recommended in patients with WT GIST. These findings highlight a potential central role of SDH dysregulation in WT GIST oncogenesis.genetic predisposition | sarcoma | pediatric

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“…Its exact incidence remains unknown, but is estimated at 14.5 cases per million in Sweden [3]. They commonly occur in people above the age of 50, with almost a similar distribution across the male and female gender [3,4]. GISTs are most commonly found in the stomach and small bowel, but they can occur in all other parts of the gastrointestinal tract as well as the abdominal and pelvic cavity.…”

Section: Introductionmentioning

confidence: 99%

“…It represents a revolution in the treatment of this notoriously chemotherapy-resistant tumour. Historically, the response rate to chemotherapy was very low, and the median survival for advanced disease was between 12 and 24 months [4,5,15]. Several phase 1 and 2 trials established the high efficacy and good tolerability of imatinib in treatment of GISTs [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Imatinib in gastrointestinal stromal tumour: Northern Cancer Network Experience

Azribi¹,

Razak²,

Dildey³

et al. 2009

ecancer

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Imatinib treatment in metastatic or inoperable gastrointestinal stromal tumours (GIST) has shifted the paradigm of treatment of this disease. Successful clinical trials of imatinib led to rapid regulatory approval and, in England and Wales, National Institute for Health and Clinical Excellence (NICE) guidance on use of this technology. NICE recommend detailed audit of their guidelines in clinical practice. This audit reflects that guidance and was designed to document the use of imatinib in routine clinical practice. Methods:We conducted a retrospective audit of patients with GIST treated with imatinib from 1 February 2002 to 31 March 2007. Information gathered included patient demographics, disease characteristics and details of treatment administered, treatment response, toxicities and follow-up data. The primary objective was to record disease control rate (DCR), defined as a lack of progression on computed tomography at three months. Secondary end points of this audit were progression-free and overall survival. These were compared with published clinical trial results.Results: Thirty-six consecutive patients with a diagnosis of GIST treated with imatinib were identified. Median age of patients was 70.1 years. At the time of analysis, patients have been followed up for a median of 41.6 months. In total, patients were treated for a median of 15.8 months. Treatment was generally well tolerated with a small percentage of patients experiencing grade 3/4 toxicities. Disease control was observed in 30 patients (DCR, 83.3%, 95% CI 67.2-93.6, intention to treat analysis). The median progression free survival (PFS) in this cohort was 23.7 months (95% CI 12.9-34.4); while the median overall survival was 39.7 months (95% CI 22.8-56.5). Conclusion:Our data demonstrated that the treatment of unselected GIST patients within the NICE guidance compares favourably to previously published data of randomized registration studies of imatinib. Of note, the median age of this cohort is some ten years older than that reported in the trials. Imatinib was well tolerated with acceptable treatment-related adverse events.

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Outcome of Metastatic GIST in the Era before Tyrosine Kinase Inhibitors

Abstract: Treatment with imatinib appears to improve 2-year survival of metastatic GIST by approximately 20% when compared to surgery alone. The combination of imatinib and surgery for the treatment of metastatic GIST therefore warrants investigation.

Cited by 105 publications

References 29 publications

Comparative study of the different degrees of risk of gastrointestinal stromal tumor

Comparative study of the different degrees of risk of gastrointestinal stromal tumor

Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations

Imatinib in gastrointestinal stromal tumour: Northern Cancer Network Experience

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