A literature review and database of how the primary KIT/PDGFRA variant of a gastrointestinal stromal tumour predicts for sensitivity to imatinib

Wong, Newton A C S; Garcia-Petit, Christel; Dangoor, Adam; Andrew, Nicola

doi:10.1016/j.cancergen.2022.09.002

Cited by 2 publications

(6 citation statements)

References 99 publications

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“…KIT exon 11 deletion/indel variants are the most common type of KIT mutations, occurring in about 40% of unselected GISTs [8] and adjuvant trial participants with data available (Table 3). KIT exon 11 deletion and indel variants are sensitive to imatinib in vitro [17,44], and patients with KIT exon 11 deletion mutation treated with imatinib in the metastatic setting benefit more from imatinib than patients with other types of KIT mutation [17,18,44].…”

Section: Kit Exon 11 Deletion and Indel Variantsmentioning

confidence: 99%

“…KIT exon 11 substitution variants occur in 20-25% of unselected GISTs [7,8], and they also occurred at a similar frequency in the adjuvant trials (Table 3). Most KIT exon 11 substitution variants are imatinib-sensitive in vitro, and most patients with advanced GISTs with KIT exon 11 substitution variants respond to imatinib [44].…”

Section: Kit Exon 11 Substitution Variantsmentioning

confidence: 99%

“…[7,8], and 6-9% of the patients who participated in registered adjuvant trials had the KIT exon 11 insertion variant (Table 3). Few data are available about their sensitivity to imatinib either in vitro or in silico, but they appear to be sensitive to imatinib in vivo [44].…”

Section: Kit Exon 11 Substitution Variantsmentioning

confidence: 99%

“…Patients with the KIT exon 9 variant have less favorable RFS and OS when treated with adjuvant imatinib than patients with other types of mutations [33,45]. KITexon-9-mutated GISTs are imatinib-sensitive in vitro/in silico, but higher drug doses may be needed [44]. A subgroup analysis from merged data from two large randomized trials that compared an imatinib dose of 400 mg once daily with 400 mg b.i.d.…”

Section: Kit Exon 9 Variantsmentioning

confidence: 99%

“…About 10-15% of GISTs harbor a mutation in PDGFRA, of which more than half are exon 18 D842V substitution mutations [7,8]. The PDGFRA D842V variant is insensitive to imatinib in vitro and in vivo [19,44] but sensitive to avapritinib [21,48]. Most of the other mutations that occur in PDGFRA exon 18 or PDGFRA exons 5, 12, and 14 are imatinibsensitive [44].…”

Section: Pdgfra Mutationsmentioning

confidence: 99%

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KIT and PDGFRA Variants and the Survival of Patients with Gastrointestinal Stromal Tumor Treated with Adjuvant Imatinib

Joensuu

2023

Cancers

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Adjuvant imatinib improves the recurrence-free survival and overall survival (OS) of patients with gastrointestinal stromal tumors (GISTs) who have a high risk of recurrence after surgery and is now considered standard treatment. Yet, OS benefit has been demonstrated in only one randomized study, the Scandinavian Sarcoma Group XVIII/AIO trial, where patients with high-risk GISTs were allocated to either 1 year or 3 years of adjuvant imatinib. SSGXVIII/AIO is also the only randomized trial in which adjuvant imatinib duration exceeding 2 years was evaluated. In this trial, the 3-year treatment led to a 45% reduction in the risk of death during the first 10 years that followed random allocation even though some of the patients did not have GISTs at tumor histology review, had mutations now known to be imatinib-resistant or had non-localized disease at study entry. In the subgroup of patients who had KIT exon 11 deletion/indel mutation, the reduction in the risk of death was 66% in favor of the longer treatment. Proper patient selection is of crucial importance since many patients are cured with surgery. Little evidence for OS benefit is available from randomized trials for patients whose GIST harbors KIT exon 9 mutation, KIT insertion mutation, PDGFRA D842V mutation, or lacks KIT and PDGFRA mutations. Adjuvant imatinib improves OS substantially if high-risk GISTs can be identified, treatment duration is long enough, and GISTs harbor an imatinib-sensitive mutation.

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Section: Kit Exon 11 Deletion and Indel Variantsmentioning

confidence: 99%

Section: Kit Exon 11 Substitution Variantsmentioning

confidence: 99%

Section: Kit Exon 11 Substitution Variantsmentioning

confidence: 99%

Section: Kit Exon 9 Variantsmentioning

confidence: 99%

Section: Pdgfra Mutationsmentioning

confidence: 99%

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KIT and PDGFRA Variants and the Survival of Patients with Gastrointestinal Stromal Tumor Treated with Adjuvant Imatinib

Joensuu

2023

Cancers

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Inflammatory Biomarker Correlations and Prognosis in High-risk Gastrointestinal Stromal Tumor Patients: A Multicenter Retrospective Analysis

Wang,

Qi,

Zhao

et al. 2024

Preprint

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Background The intricate prognosis of gastrointestinal stromal tumors (GISTs) has garnered significant attention, yet a gap persists in understanding the influence of inflammatory markers on the prognosis of high-risk GIST patients. This study investigated the relationship between various factors and the prognosis of high-risk GIST patients, with a specific focus on first recurrence-free survival (RFS) and overall survival (OS) as crucial prognostic indicators. Methods A comprehensive collection of clinical data was conducted on 145 high-risk GIST patients meeting specific inclusion and exclusion criteria at 17 medical centers in Ningxia, China, covering the period from January 2013 to December 2019. Single-factor analysis and survival curves were used to analyze the variables, while the Cox regression model evaluated independent prognostic factors. Results Within the cohort, a balanced male-to-female ratio of 1:1.1 was observed. Single-factor analysis revealed compelling associations between RFS and age, preoperative neutrophil-to-lymphocyte ratio (NLR), preoperative platelet-to-lymphocyte ratio (PLR), preoperative systemic immune-inflammatory index (SII), preoperative prognostic nutritional index (PNI), mitotic index, and imatinib (IM) with RFS in high-risk GIST patients. These variables also exhibited statistically significant associations with OS (all with p values < 0.05). Cox regression analysis revealed that age, preoperative NLR, mitotic index, IM, and adjuvant therapy independently impacted RFS. Additionally, the preoperative NLR and mitotic index emerged as independent factors influencing OS, all of which demonstrated statistical significance (p values < 0.05). Age exhibited a negative correlation with RFS, and early regular IM treatment following surgery significantly decreased the recurrence risk. An elevated NLR and higher mitotic indices were strongly linked to poorer RFS and OS. Conclusion The data revealed a significant correlation between age, preoperative NLR, and mitotic index and an unfavorable prognosis in high-risk GIST patients. Notably, the NLR was identified as a potential additional prognostic factor, enhancing the accuracy of predicting treatment efficacy and patient outcomes in high-risk patients with GISTs. Therefore, we advocate for the serious consideration of the NLR as a valuable addition to standard clinical practice for managing high-risk GIST patients.

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A literature review and database of how the primary KIT/PDGFRA variant of a gastrointestinal stromal tumour predicts for sensitivity to imatinib

Cited by 2 publications

References 99 publications

KIT and PDGFRA Variants and the Survival of Patients with Gastrointestinal Stromal Tumor Treated with Adjuvant Imatinib

KIT and PDGFRA Variants and the Survival of Patients with Gastrointestinal Stromal Tumor Treated with Adjuvant Imatinib

Inflammatory Biomarker Correlations and Prognosis in High-risk Gastrointestinal Stromal Tumor Patients: A Multicenter Retrospective Analysis

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