Gastrointestinal stromal tumors in Iceland, 1990–2003: The Icelandic GIST study, a population‐based incidence and pathologic risk stratification study

Tryggvason, Geir; Gíslason, Hjörtur; Magnússon, Magnús K.; Jónasson, Jón Gunnlaugur

doi:10.1002/ijc.21167

Cited by 329 publications

(280 citation statements)

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“…[1][2][3][4] This corresponds to between 3300 and 6000 new cases per year in the United States. Following surgical resection, GISTs often recur locally, spread diffusely throughout the serosal surfaces of the abdomen, and/or metastasize to the liver.…”

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confidence: 99%

Gastrointestinal stromal tumors: what do we know now?

2014

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract, arising from the interstitial cells of Cajal, primarily in the stomach and small intestine. They manifest a wide range of morphologies, from spindle cell to epithelioid, but are immunopositive for KIT (CD117) and/or DOG1 in essentially all cases. Although most tumors are localized at presentation, up to half will recur in the abdomen or spread to the liver. The growth of most GISTs is driven by oncogenic mutations in either of two receptor tyrosine kinases: KIT (75% of cases) or PDGFRA (10%). Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib, sunitinib, and regorafenib is effective in controlling unresectable disease; however, drug resistance caused by secondary KIT or PDGFRA mutations eventually develops in 90% of cases. Adjuvant therapy with imatinib is commonly used to reduce the likelihood of disease recurrence after primary surgery, and for this reason assessing the prognosis of newly resected tumors is one of the most important roles for pathologists. Approximately 15% of GISTs are negative for mutations in KIT and PDGFRA. Recent studies of these so-called wild-type GISTs have uncovered a number of other oncogenic drivers, including mutations in neurofibromatosis type I, RAS genes, BRAF, and subunits of the succinate dehydrogenase complex. Routine genotyping is strongly recommended for optimal management of GISTs, as the type and dose of TKI used for treatment is dependent on the mutation identified.

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confidence: 99%

Gastrointestinal stromal tumors: what do we know now?

2014

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“…5 The incidence of GIST is estimated at 11-14.5 cases per million per year. 6,7 The most frequent primary sites are gastric (50%) and small bowel (25%). Colorectal, oesophageal and peritoneal GISTs are less frequent.…”

Section: Description Of the Underlying Health Problemmentioning

confidence: 99%

Sunitinib for the treatment of gastrointestinal stromal tumours: a critique of the submission from Pfizer

Bond

Hoyle²,

Moxham³

et al. 2009

Health Technol Assess

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The submission's evidence for the clinical effectiveness and cost-effectiveness of sunitinib for the treatment of gastrointestinal stromal tumours (GISTs) is based on a randomised controlled trial (RCT) comparing sunitinib with placebo for people with unresectable and/or metastatic GIST after failure of imatinib and with Eastern Cooperative Oncology Group (ECOG) progression status 0-1, and an ongoing, non-comparative cohort study of a similar population but with ECOG progression status 0-4. The searches are appropriate and include all relevant studies and the RCT is of high quality. In the RCT sunitinib arm overall survival was 73 median weeks [95% confidence interval (CI) 61 to 83] versus 75 median weeks (95% CI 68 to 84) for the cohort study. However, time to tumour progression in the cohort study was different from that in the RCT sunitinib arm [41 (95% CI 36 to 47) versus 29 (95% CI 22 to 41) median weeks respectively]. Median progressionfree survival with sunitinib was 24.6 weeks (95% CI 12.1 to 28.4) versus 6.4 weeks (95% CI 4.4 to 10.0) on placebo (hazard ratio 0.333, 95% CI 0.238 to 0.467, p < 0.001). The manufacturer used a threestate Markov model to model the cost-effectiveness of sunitinib compared with best supportive care for GIST patients; the modelling approach and sources and justification of estimates are reasonable. The base-case incremental cost-effectiveness ratio (ICER) was £27,365 per quality-adjusted life-year (QALY) with the first cycle of sunitinib treatment not costed; when we included the cost of the first treatment cycle we estimated a base-case Discussion of ERG reports is invited. Visit the HTA website correspondence forum (www.hta.ac.uk/ correspond). DOI: 10.3310/hta13suppl2/10 Sunitinib for the treatment of gastrointestinal stromal tumours: a critique of the submission from Pfizer 70ICER of £32,636 per QALY. Pfizer's sensitivity analysis produced a range of ICERs from £15,536 per QALY to £59,002 per QALY. Weaknesses of the manufacturer's submission include that the evidence is based on only one published RCT; that 84% of the RCT control population crossed over to the intervention group, giving rise to the use of unusual rank preserved structural failure time (RPSFT) analysis to correct for possible bias; and that a number of errors and omissions were made in the probabilistic sensitivity analysis, meaning that it is not possible to come to firm conclusions about the cost-effectiveness of sunitinib for GIST in this patient population. In conclusion, during the blinded phase of the RCT, overall survival was significantly longer in the sunitinib arm than in the placebo arm (hazard ratio 0.491, 95% CI 0.290 to 0.831, p <0.007). However, intention-to-treat analysis of the entire study showed no statistically significant difference in overall survival for those who received sunitinib (73 weeks) versus those who received placebo (65 weeks) (hazard ratio 0.876, 95% CI 0.679 to 1.129, p = 0.306).

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“…Recent epidemiologic data from Sweden and Iceland report an incidence of 14.5 and 11 per million population, respectively, with a median age of diagnosis 66-69 years (Nilsson et al, 2005;Tryggvason et al, 2005).…”

Section: Introductionmentioning

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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Gastrointestinal stromal tumors in Iceland, 1990–2003: The Icelandic GIST study, a population‐based incidence and pathologic risk stratification study

Cited by 329 publications

References 20 publications

Gastrointestinal stromal tumors: what do we know now?

Gastrointestinal stromal tumors: what do we know now?

Sunitinib for the treatment of gastrointestinal stromal tumours: a critique of the submission from Pfizer

Gastrointestinal Stromal Tumours: A 10 Year Multicenter Audit

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