Pathologic and Molecular Features Correlate With Long-Term Outcome After Adjuvant Therapy of Resected Primary GI Stromal Tumor: The ACOSOG Z9001 Trial

Corless, Christopher L.; Ballman, Karla V.; Antonescu, Cristina R.; Kolesnikova, Violetta; Maki, Robert G.; Pisters, Peter W.T.; Blackstein, Martin E.; Blanke, Charles D.; Demetri, George D.; Heinrich, Michael C.; Mehren, Margaret von; Patel, Shreyaskumar; McCarter, Martin D.; Owzar, Kouros; DeMatteo, Ronald P.

doi:10.1200/jco.2013.51.2046

Cited by 263 publications

(207 citation statements)

References 34 publications

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“…This is markedly better than the 18-24 months seen with advanced GIST as a whole cohort in various studies, but in line with what has been seen in the BRF 14 study (PFS: 39.4 months) (17,22). The operable cancers (including locally advanced) had a median EFS of 58 months ( 5 year EFS: 50%), which is lower than published data (14,21) for operated and locally advanced cancers. The differences can be attributed to the small sample size, short follow-up and real world nature of the data compared to trial data.…”

Section: Discussioncontrasting

confidence: 47%

“…A larger study, comprising 11 population based series (n=3,067; mutation analysis-1505), but untreated with IM, concluded that patients with PDGFRA mutations and those with KIT exon 11 duplication/single codon deletion mutations have a favorable recurrence free survival (RFS) with surgery alone (20). Conversely, in the adjuvant setting in operated tumors, mutation status has not replaced standard criteria with regard to the need for adjuvant IM, although data from long term follow up of the ACOSOG Z9001 Trial has suggested that KIT exon 11 deletions had maximal benefit from 1 year of adjuvant IM compared to other molecular subsets (21).…”

Section: Discussionmentioning

confidence: 99%

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Early outcomes of exon 11 mutants in GIST treated with standard dose Imatinib

et al. 2017

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Background: The exon 11 KIT mutant gastrointestinal stromal tumors (GIST) is a heterogeneous cohort with variable biological behavior based on different mutational subtypes. Methods:Patients with histologically proven GIST with KIT exon 11 mutations were selected from a prospectively maintained database, and evaluated for clinical characteristics and event free survival (EFS). Patients were divided into mutations upstream to codon 557 (G1), mutations involving codon 557-558 (G2) and mutation downstream to codon 558 (G3).Results: A total of 90 patients satisfied the inclusion criteria for study. Substitutions, indels and duplications were seen in 23 patients. Deletions were seen in 67 patients, of which 44 patients had large deletions (>6 base pairs), while 23 has small deletions (<6 base pairs). Complex mutations were seen in 15 patients. G2 mutations were noted in 33 patients, while G1 and G3 mutations were seen 32 and 25 patients respectively. With a median follow-up of 26 months, estimated median EFS for the entire cohort was 55 months. The G2 cohort had an inferior EFS compared to the G1 and G3 cohorts (46 vs. 55 months), but this did not achieve statistical significance (univariate analysis: P=0.075). On multivariate analysis, patients undergoing radical intent surgery vs. no surgery (58 vs. 55 months; P=0.005) and G1 or G3 vs. G2 cohort (P=0.058) showed trend towards improved EFS. Conclusions:In patients with GIST exon 11 codon 557-558 mutation subset there is a trend towards an inferior survival even when treated with imatinib mesylate (IM).

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Section: Discussioncontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Early outcomes of exon 11 mutants in GIST treated with standard dose Imatinib

et al. 2017

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“…Likewise, pazopanib demonstrated a potential response in heavily pretreated patients, though only five wild-type GIST patients were recruited in this phase II study . In the adjuvant setting, subanalyses of wild-type GISTs in both the ACOSOG Z9001 trial (Corless et al 2014) (32 patients) and the SSGXVIII (19 patients) did not detect any benefit. A recent report from the NIH pediatric and wild-type GIST clinics further supports the contention that disease progression was largely dependent on tumor biology, regardless of location and resection margins.…”

Section: Carney-stratakis Syndromementioning

confidence: 99%

Classification of gastrointestinal stromal tumor syndromes

Gopie

Faber

et al. 2018

Endocrine-Related Cancer

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, thought to derive from neoplastic outgrowth of the interstitial cells of Cajal. Building on recent advances in recognition, classification and diagnosis, the past two decades have seen a changing paradigm with molecular diagnostics and targeted therapies. KIT and PDGFRA mutations account for 85-90% of GIST carcinogenesis. However, the remaining 10-15% of GISTs, which until recently were called KIT/PDGFRA wild-type GISTs, have been found to have one of the several mutations, including in the SDHA, B, C, D, BRAF and NF1 genes. Though most of such GISTs are sporadic, a number of families with high incidence rates of GISTs and other associated clinical manifestations have been reported and found to harbor germline mutations in KIT, PDGFRA, SDH subunits and NF1. The goal of this review is to describe the mutations, clinical manifestations and therapeutic implications of syndromic and inherited GISTs in light of recent studies of their clinicopathologic range and pathogenesis.

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“…This addition was supported by DeMatteo et al (2000), who also added tumour size and mitotic rate (DeMatteo et al, 2000) as independent risk factors. The more recent phase III adjuvant imatinib trial, ACOSOG Z9001, also reported poorer long term outcomes in those patients with tumours arising from the small bowel (Corless et al, 2014). Tumour features associated with higher risk of metastasis include size >5cm, lobulated appearance, heterogeneously enhance on imaging, with mesenteric fat infiltration, ulceration, regional lymphadenopathy or an exophytic growth pattern on CT (Choi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal Stromal Tumours: A 10 Year Multicenter Audit

Watson¹,

Kelly²,

Malone³

et al. 2016

CCO

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Background: Gastrointestinal stromal tumours (GISTs) are unique neoplasms of the gastrointestinal (GI) tract. The development of targeted therapeutic agents such as imatinib mesylate (Glivec) has altered the way on how we now manage these rare malignancies. The aim of this study was to evaluate the management of GISTs in three Irish tertiary hospitals. Methods: We performed a retrospective, multicenter audit of patients diagnosed with gastrointestinal stromal tumours over a ten year period (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015). Results: 110 patients were included in the study. Abdominal pain was the most common presenting symptom, reported in 30% of patients, while 31% were incidental findings. The stomach was the most common primary site of disease, observed in 77% of cases. 15 patients had metastatic disease at the time of diagnosis (14%), and 10 of these patients had liver involvement. More than half of patients (61%) were managed with surgical excision alone (61%), while 24 were managed with surveillance and 28 patients treated with adjuvant Glivec, which was generally well tolerated. 18 patients (20%) demonstrated recurrent or progressive disease after first line treatment. 102 patients (93%) are alive today. Conclusion: While surgery is widely regarded as the primary treatment modality for GISTs the addition of imatinib mesylate has enabled physicians to deliver more personalised treatment while optimising patient outcomes.

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Pathologic and Molecular Features Correlate With Long-Term Outcome After Adjuvant Therapy of Resected Primary GI Stromal Tumor: The ACOSOG Z9001 Trial

Cited by 263 publications

References 34 publications

Early outcomes of exon 11 mutants in GIST treated with standard dose Imatinib

Early outcomes of exon 11 mutants in GIST treated with standard dose Imatinib

Classification of gastrointestinal stromal tumor syndromes

Gastrointestinal Stromal Tumours: A 10 Year Multicenter Audit

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