Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib: an exploratory analysis of a randomized clinical triala
<h3>Importance</h3><p>Little is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (<i>KIT</i>) and platelet-derived growth factor receptor α (<i>PDGFRA</i>) mutations.&...
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
March 23, 2017
|
| In: |
JAMA oncology
Year: 2017, Jahrgang: 3, Heft: 5, Pages: 602-609 |
| ISSN: | 2374-2445 |
| DOI: | 10.1001/jamaoncol.2016.5751 |
| Online-Zugang: | Verlag, Volltext: https://jamanetwork.com/journals/jamaoncology/fullarticle/2612802 Verlag, Volltext: http://dx.doi.org/10.1001/jamaoncol.2016.5751 
|
| Verfasserangaben: | Heikki Joensuu, MD; Eva Wardelmann, MD; Harri Sihto, PhD; Mikael Eriksson, MD; Kirsten Sundby Hall, MD; Annette Reichardt, MD; Jörg T. Hartmann, MD; Daniel Pink, MD; Silke Cameron, MD; Peter Hohenberger, MD; Salah-Eddin Al-Batran, MD; Marcus Schlemmer, MD; Sebastian Bauer, MD; Bengt Nilsson, MD; Raija Kallio, MD; Jouni Junnila, MSc; Aki Vehtari, PhD; Peter Reichardt, MD |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1580534317 | ||
| 003 | DE-627 | ||
| 005 | 20220814235624.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180830s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1001/jamaoncol.2016.5751 |2 doi | |
| 035 | |a (DE-627)1580534317 | ||
| 035 | |a (DE-576)510534317 | ||
| 035 | |a (DE-599)BSZ510534317 | ||
| 035 | |a (OCoLC)1341017687 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Joensuu, Heikki |e VerfasserIn |0 (DE-588)1121118747 |0 (DE-627)873981472 |0 (DE-576)480718318 |4 aut | |
| 245 | 1 | 0 | |a Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib |b an exploratory analysis of a randomized clinical triala |c Heikki Joensuu, MD; Eva Wardelmann, MD; Harri Sihto, PhD; Mikael Eriksson, MD; Kirsten Sundby Hall, MD; Annette Reichardt, MD; Jörg T. Hartmann, MD; Daniel Pink, MD; Silke Cameron, MD; Peter Hohenberger, MD; Salah-Eddin Al-Batran, MD; Marcus Schlemmer, MD; Sebastian Bauer, MD; Bengt Nilsson, MD; Raija Kallio, MD; Jouni Junnila, MSc; Aki Vehtari, PhD; Peter Reichardt, MD |
| 264 | 1 | |c March 23, 2017 | |
| 300 | |a 8 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Published online March 23, 2017 | ||
| 500 | |a Gesehen am 30.08.2018 | ||
| 520 | |a <h3>Importance</h3><p>Little is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (<i>KIT</i>) and platelet-derived growth factor receptor α (<i>PDGFRA</i>) mutations.</p><h3>Objective</h3><p>To investigate the effect of<i>KIT</i>and<i>PDGFRA</i>mutations on recurrence-free survival (RFS) in patients with gastrointestinal stromal tumors (GISTs) treated with surgery and adjuvant imatinib.</p><h3>Design, Setting, and Participants</h3><p>This exploratory study is based on the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial. Between February 4, 2004, and September 29, 2008, 400 patients who had undergone surgery for GISTs with a high risk of recurrence were randomized to receive adjuvant imatinib for 1 or 3 years. Of the 397 patients who provided consent, 341 (85.9%) had centrally confirmed, localized GISTs with mutation analysis for<i>KIT</i>and<i>PDGFRA</i>performed centrally using conventional sequencing. During a median follow-up of 88 months (completed December 31, 2013), 142 patients had GIST recurrence. Data of the evaluable population were analyzed February 4, 2004, through December 31, 2013.</p><h3>Main Outcomes and Measures</h3><p>The main outcome was RFS. Mutations were grouped by the gene and exon.<i>KIT</i>exon 11 mutations were further grouped as deletion or insertion-deletion mutations, substitution mutations, insertion or duplication mutations, and mutations that involved codons 557 and/or 558.</p><h3>Results</h3><p>Of the 341 patients (175 men and 166 women; median age at study entry, 62 years) in the 1-year group and 60 years in the 3-year group), 274 (80.4%) had GISTs with a<i>KIT</i>mutation, 43 (12.6%) had GISTs that harbored a<i>PDGFRA</i>mutation, and 24 (7.0%) had GISTs that were wild type for these genes.<i>PDGFRA</i>mutations and<i>KIT</i>exon 11 insertion or duplication mutations were associated with favorable RFS, whereas<i>KIT</i>exon 9 mutations were associated with unfavorable outcome. Patients with<i>KIT</i>exon 11 deletion or insertion-deletion mutation had better RFS when allocated to the 3-year group compared with the 1-year group (5-year RFS, 71.0% vs 41.3%;<i>P</i> < .001), whereas no significant benefit from the 3-year treatment was found in the other mutational subgroups examined.<i>KIT</i>exon 11 deletion mutations, deletions that involved codons 557 and/or 558, and deletions that led to pTrp557_Lys558del were associated with poor RFS in the 1-year group but not in the 3-year group. Similarly, in the subset with<i>KIT</i>exon 11 deletion mutations, higher-than-the-median mitotic counts were associated with unfavorable RFS in the 1-year group but not in the 3-year group.</p><h3>Conclusions and Relevance</h3><p>Patients with<i>KIT</i>exon 11 deletion mutations benefit most from the longer duration of adjuvant imatinib. The duration of adjuvant imatinib modifies the risk of GIST recurrence associated with some<i>KIT</i>mutations, including deletions that affect exon 11 codons 557 and/or 558.</p><h3>Trial Registration</h3><p>clinicaltrials.gov Identifier:NCT00116935</p> | ||
| 700 | 1 | |a Hohenberger, Peter |d 1953- |e VerfasserIn |0 (DE-588)1025311469 |0 (DE-627)72202875X |0 (DE-576)370195574 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t JAMA oncology |d Chicago, Ill. : American Medical Association, 2015 |g 3(2017), 5, Seite 602-609 |h Online-Ressource |w (DE-627)818494301 |w (DE-600)2810928-4 |w (DE-576)426501284 |x 2374-2445 |7 nnas |a Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib an exploratory analysis of a randomized clinical triala |
| 773 | 1 | 8 | |g volume:3 |g year:2017 |g number:5 |g pages:602-609 |g extent:8 |a Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib an exploratory analysis of a randomized clinical triala |
| 856 | 4 | 0 | |u https://jamanetwork.com/journals/jamaoncology/fullarticle/2612802 |x Verlag |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1001/jamaoncol.2016.5751 |x Verlag |x Resolving-System |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20180830 | ||
| 993 | |a Article | ||
| 994 | |a 2017 | ||
| 998 | |g 1025311469 |a Hohenberger, Peter |m 1025311469:Hohenberger, Peter |d 60000 |d 61800 |e 60000PH1025311469 |e 61800PH1025311469 |k 0/60000/ |k 1/60000/61800/ |p 10 | ||
| 999 | |a KXP-PPN1580534317 |e 3024184597 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"relHost":[{"type":{"media":"Online-Ressource","bibl":"periodical"},"disp":"Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib an exploratory analysis of a randomized clinical trialaJAMA oncology","physDesc":[{"extent":"Online-Ressource"}],"recId":"818494301","corporate":[{"display":"American Medical Association","role":"isb","roleDisplay":"Herausgebendes Organ"}],"language":["eng"],"note":["Gesehen am 12.10.2017"],"pubHistory":["1.2015 -"],"title":[{"title_sort":"JAMA oncology","title":"JAMA oncology"}],"id":{"issn":["2374-2445"],"eki":["818494301"],"zdb":["2810928-4"]},"origin":[{"publisher":"American Medical Association","publisherPlace":"Chicago, Ill.","dateIssuedKey":"2015","dateIssuedDisp":"2015-"}],"part":{"extent":"8","year":"2017","pages":"602-609","volume":"3","issue":"5","text":"3(2017), 5, Seite 602-609"}}],"origin":[{"dateIssuedKey":"2017","dateIssuedDisp":"March 23, 2017"}],"id":{"eki":["1580534317"],"doi":["10.1001/jamaoncol.2016.5751"]},"person":[{"given":"Heikki","family":"Joensuu","role":"aut","roleDisplay":"VerfasserIn","display":"Joensuu, Heikki"},{"display":"Hohenberger, Peter","roleDisplay":"VerfasserIn","role":"aut","given":"Peter","family":"Hohenberger"}],"note":["Published online March 23, 2017","Gesehen am 30.08.2018"],"language":["eng"],"recId":"1580534317","physDesc":[{"extent":"8 S."}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"name":{"displayForm":["Heikki Joensuu, MD; Eva Wardelmann, MD; Harri Sihto, PhD; Mikael Eriksson, MD; Kirsten Sundby Hall, MD; Annette Reichardt, MD; Jörg T. Hartmann, MD; Daniel Pink, MD; Silke Cameron, MD; Peter Hohenberger, MD; Salah-Eddin Al-Batran, MD; Marcus Schlemmer, MD; Sebastian Bauer, MD; Bengt Nilsson, MD; Raija Kallio, MD; Jouni Junnila, MSc; Aki Vehtari, PhD; Peter Reichardt, MD"]},"title":[{"title_sort":"Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib","title":"Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib","subtitle":"an exploratory analysis of a randomized clinical triala"}]} | ||
| SRT | |a JOENSUUHEIEFFECTOFKI2320 | ||