Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib

Serrano, César; García‐del‐Muro, Xavier; Valverde, Claudia; Sebio, Ana; Durán, José; Manzano, Aránzazu; Pajares, Isabel; Hindi, Nadia; Landolfi, Stefania; Jiménez, Laura; Rubió‐Casadevall, Jordi; Estival, Anna; Safont, María José; Pericay, Carles; Díaz‐Beveridge, Roberto; Martínez‐Marín, Virginia; Vicente-Baz, D.; Vivancos, Ana; Hernández‐Losa, Javier; Arribas, Joaquı́n; Carles, Joan

doi:10.1634/theoncologist.2018-0032

Cited by 9 publications

(9 citation statements)

References 24 publications

(54 reference statements)

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“…Amplicon sequencing was performed as previously described [31][32][33]. Specifically for this study, indexed libraries were pooled and sequenced in a HiSeq 2500 instrument (2X100) at an average coverage of 1000x for tissues samples and 5000x for plasmas.…”

Section: Tumor and Plasma Mutational Analysis By Amplicon Sequencingmentioning

confidence: 99%

Clinical value of next generation sequencing of plasma cell-free DNA in gastrointestinal stromal tumors

et al. 2020

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Background: Gastrointestinal stromal tumor (GIST) initiation and evolution is commonly framed by KIT/PDGFRA oncogenic activation, and in later stages by the polyclonal expansion of resistant subpopulations harboring KIT secondary mutations after the onset of imatinib resistance. Thus, circulating tumor (ct)DNA determination is expected to be an informative non-invasive dynamic biomarker in GIST patients. Methods: We performed amplicon-based next-generation sequencing (NGS) across 60 clinically relevant genes in 37 plasma samples from 18 GIST patients collected prospectively. ctDNA alterations were compared with NGS of matched tumor tissue samples (obtained either simultaneously or at the time of diagnosis) and cross-validated with droplet digital PCR (ddPCR). Results: We were able to identify cfDNA mutations in five out of 18 patients had detectable in at least one timepoint. Overall, NGS sensitivity for detection of cell-free (cf)DNA mutations in plasma was 28.6%, showing high concordance with ddPCR confirmation. We found that GIST had relatively low ctDNA shedding, and mutations were at low allele frequencies. ctDNA was detected only in GIST patients with advanced disease after imatinib failure, predicting tumor dynamics in serial monitoring. KIT secondary mutations were the only mechanism of resistance found across 10 imatinib-resistant GIST patients progressing to sunitinib or regorafenib. Conclusions: ctDNA evaluation with amplicon-based NGS detects KIT primary and secondary mutations in metastatic GIST patients, particularly after imatinib progression. GIST exhibits low ctDNA shedding, but ctDNA monitoring, when positive, reflects tumor dynamics.

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Section: Tumor and Plasma Mutational Analysis By Amplicon Sequencingmentioning

confidence: 99%

Clinical value of next generation sequencing of plasma cell-free DNA in gastrointestinal stromal tumors

et al. 2020

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“…Out of the 151 patients, 148 patients experienced adverse events, mostly diarrhea, asthenia, and eyelid or periorbital edema. A retrospective multicenter study [ 92 ] aimed to gain insight into GIST patients with unresectable or metastatic disease responding long-term to imatinib. Of these 58 long-term responders treated with imatinib for 5.5 to 10.4 years, 15 patients experienced new emerging adverse events after ≥ 5 years of treatment, including anemia, fatigue, renal failure, diarrhea, edema, and muscle cramps.…”

Section: Resultsmentioning

confidence: 99%

“…The following supporting information can be downloaded at: , Supplementary File S1: Search string; Supplementary File S2: Quality Assessment. References [ 21 , 22 , 23 , 26 , 27 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97...…”

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confidence: 99%

Health-Related Quality of Life and Side Effects in Gastrointestinal Stromal Tumor (GIST) Patients Treated with Tyrosine Kinase Inhibitors: A Systematic Review of the Literature

Wal

Elie

Cesne

et al. 2022

Cancers

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Background: The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of gastrointestinal stromal tumors (GISTs), resulting in a substantial gain in median overall survival. Subsequently, health-related quality of life (HRQoL) has become more relevant. Here, we systematically review the available literature on HRQoL issues and side effects of different TKIs registered for the treatment of GIST. Methods: A search through five databases was performed. Full reports in English describing HRQoL outcomes and/or side effects in GIST patients on TKI therapy were included. Results: A total of 104 papers were included; 13 studies addressed HRQoL, and 96 studies investigated adverse events. HRQoL in patients treated with imatinib, regorafenib, and ripretinib remained stable, whereas most sunitinib-treated patients reported a decrease in HRQoL. Severe fatigue and fear of recurrence or progression were specifically assessed as HRQoL issues and had a negative impact on overall HRQoL as well as psychological and physical well-being. The majority of studies focused on physician-reported side effects. Nearly all GIST patients treated with a TKI experienced at least one adverse event, mostly mild to moderate. Conclusions: Despite the fact that almost all patients treated with a TKI experienced side effects, this did not seem to affect overall HRQoL during TKI therapy. In daily practice, it are the side effects that hamper a patient’s HRQoL resulting in treatment adjustments, suggesting that the reported side effects were underestimated by physicians, or the measures used to assess HRQoL do not capture all relevant issues that determine a GIST patient’s HRQoL.

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“…PDGFRA act on the ATP binding site thereby inhibit the imatinib action. So, tumor having these mutations are resistance to the imatinib therapy (18). Mutation involving the exon 14 is the next common which shows substitution mutation and are better than other exon mutations in term of prognosis.…”

Section: Pdgfr Alphamentioning

confidence: 99%

“…The one which have deficiency of SDH gene are having mutation in SDH subunit SDHA, SDHB, SDHC, SDHD are common in stomach (18)(19).…”

Section: Wild Typementioning

confidence: 99%

Gastrointestinal Stromal Tumor: Review

Singh

Tiwary

Puneet

2022

Gal Int J Health Sci Res

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Gastrointestinal stromal tumours (GISTs) are one of the most common mesenchymal tumors affecting the gastrointestinal (GI) tract. GIST has undergone outstanding development in how they are presented, classified, assessed, diagnosed and treated over the last decade. Gastrointestinal stromal tumours (GIST) account for nearly less than 3% of all malignant GI tumours. The clinical presentation can differ depending on its location, tumour size and aggressiveness of the tumour. In this comprehensive review, we talk regarding the epidemiology, clinical features and diagnostic modalities for GIST. We also discuss our view regarding the treatment options for early stage, locally advanced and metastatic GIST. Indications for neoadjuvant and adjuvant therapy along with time of therapy are also explained. A concise discussion of most recent biomarkers is also provided. Keywords: GIST, Leiomyoma, Leiomyosarcoma, Leiomyoblastoma, Stromal tumours, Mesenchymal neoplasm.

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Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib

Cited by 9 publications

References 24 publications

Clinical value of next generation sequencing of plasma cell-free DNA in gastrointestinal stromal tumors

Clinical value of next generation sequencing of plasma cell-free DNA in gastrointestinal stromal tumors

Health-Related Quality of Life and Side Effects in Gastrointestinal Stromal Tumor (GIST) Patients Treated with Tyrosine Kinase Inhibitors: A Systematic Review of the Literature

Gastrointestinal Stromal Tumor: Review

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