Results of long-term follow-up for patients with advanced gastrointestinal stromal tumor underwent palliative surgery after tyrosine kinase inhibitors therapy.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e22515-e22515
Author(s):  
Haibo Qiu ◽  
Zhongguo Zhou ◽  
Xingyu Feng ◽  
Xiaowei Sun ◽  
Yingbo Chen ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumor ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Palliative Surgery ◽  
Stromal Tumor ◽  
Long Term Follow Up

scholarly journals A Report on 114 Patients Who Experienced Treatment Free Remission in a Single Institution during a 15 Years Period: Long Term Follow-up, Late Molecular Relapses and Second Attempts

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 27-27 ◽  
Author(s):  
Philippe Rousselot ◽  
Clémence Loiseau ◽  
Marc Delord ◽  
Caroline Besson ◽  
Jean-Michel Cayuela ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Median Duration ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Molecular Response ◽  
Single Institution ◽  
Long Term Follow Up

Background. The A-STIM (According to Stop IMatinib, NCT1038732) observational study established the loss of major molecular response (loss of MMR, BCR-ABL1 IS >0.1%) as a practical and safe criterion for restarting therapy in patients with CML who had stopped tyrosine kinase inhibitors after a prolonged (≥2 years) and sustained deep molecular response (J Clin Oncol. 2014;32(5):424-30). We focus now on the long-term prospective follow-up of a cohort of 114 patients from a single institution included in the A-STIM observatory in order to describe late events (late molecular relapses after 2 years or more in TFR and second TFR attempts). Methods: Adult chronic phase CML patients treated with tyrosine kinase inhibitors and in sustained (≥2 years) MR4.5 (BCR-ABL1 IS ≤0.0032%) were eligible. Patients with a previous history of resistance or mutations of the BCR-ABL tyrosine kinase domain were excluded. Molecular relapses were defined by loss of MMR. After TKI discontinuation, BCR-ABL transcripts were monitored monthly during the first 12 months, every 2-3 months during the 2nd year and every 3-6 months thereafter. Median follow-up from diagnosis of CML was 15.9 years. Results. Over a 15 years period, 114 patients followed at the Centre Hospitalier de Versailles were registered. Median age at diagnosis was 48.2 years, sex ratio was 0.5 and Sokal score distribution was 54%, 26% and 20% for the Low, intermediate and high-risk categories respectively. Median duration of TKIs before the first TFR attempt was 7.4 years. Thirty-six patients (31%) were previously treated with interferon, 62 (54%) received imatinib only and 52 (46%) were on 2G-TKIs at the time of discontinuation (13 as first line therapy and 39 after a switch for sub-optimal response or intolerance). Median follow-up in TFR1 was 5.4 years. TFR1 rates were 57.6% at 1 year, 53.8% at 3 years, 51.6% at 5 years and 44.5% after 7 years. The longest duration of ongoing TFR1 is 14.9 years. The duration of TKIs and the duration of MR4.5 were associated with a higher TFR1 rate; a trend was observed for previous exposure to interferon. Patients on 2G-TKIs (first or second line) had similar TFR1 rates as compared to patients on imatinib. Fifty-seven patients relapsed including 8 patients (14%) experiencing late molecular relapses. Of those, 4 patients relapsed after 5 years. The latest molecular relapse was observed after 6.4 years. In late relapsing patients, MR4.5 was lost after 10 months in median and MR4 after 22 months with a long-lasting period of fluctuations of the BCR-ABL1 ratio in-between MR4 and MR3 (a focus on patients with fluctuations of the BCR-ABL1 ratio will be presented at the congress). Out of the 57 patients who restarted a TKI, 31 patients (54%) experienced a second attempt. Median duration of TKIs between TFR1 and TFR2 was 2.9 years and total exposure to TKIs before TFR2 was 9 years. Fifteen patients (48%) were on imatinib before TFR2 whereas 16 where on 2G-TKI (52%). Median follow-up in TFR2 was 3.4 years. TFR2 rates were 53.9% at 1 year, 45.6% at 3 years and 39.9% after 5 years. The longest TFR2 is 9 years. No factor was associated with TFR2 duration, a switch to 2G-TKIs did not provide any advantage. Seventeen patients relapsed including 3 patient (17%) experiencing late molecular relapses. Anecdotally, 5 patients went to a third TFR attempt and 1 is in TFR3 for 5.2 years. Conclusion. Based on a 15 years' experience we were able to report on long term follow-up in TFR1 and in TFR2. Among patients experiencing molecular relapses, we observed 14% and 17% late relapses after more than 2 years after TFR1 and TFR2 respectively, suggesting that a long-term molecular follow-up is mandatory for CML patients in TFR. Figure Disclosures Rousselot: Incyte: Research Funding; Pfizer: Research Funding. Cayuela:Incyte: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau.

scholarly journals Advanced gastrointestinal stromal tumor patients benefit from palliative surgery after tyrosine kinase inhibitors therapy

Medicine ◽  
2018 ◽  
Vol 97 (2) ◽  
pp. e9097 ◽  
Author(s):  
Hai-Bo Qiu ◽  
Zhong-Guo Zhou ◽  
Xing-Yu Feng ◽  
Xue-Chao Liu ◽  
Jing Guo ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumor ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Palliative Surgery ◽  
Stromal Tumor ◽  
Tumor Patients

scholarly journals The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up

Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4361-4368 ◽  
Author(s):  
Ravin J. Garg ◽  
Hagop Kantarjian ◽  
Susan O'Brien ◽  
Alfonso Quintás-Cardama ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Chronic Phase ◽  
Best Response ◽  
Long Term Follow Up ◽  
New Treatment

Abstract Responses can be achieved with dasatinib or nilotinib after failure of 2 prior tyrosine kinase inhibitors (TKIs). We report on 48 chronic myeloid leukemia patients sequentially treated with 3 TKIs: 34 with dasatinib after imatinib/nilotinib failure and 14 with nilotinib after imatinib/dasatinib failure. Before the third TKI, 25 patients were in chronic phase (CP), 10 in accelerated phase (AP), and 13 in blast phase (BP). Best response to third TKI in CP was 5 major molecular responses (MMR), 3 complete cytogenetic (CCyR), 2 partial cytogenetic (PCyR), 3 minor cytogenetic (mCyR), 6 complete hematologic responses (CHR), and 6 with no response (NR). In AP, 1 patient achieved MMR, 1 CCyR, 2 PCyR, 1 mCyR, 4 CHR, and 1 NR. In BP, 1 achieved MMR, 2 CCyR, 1 PCyR, 1 mCyR, 2 returned to CP, and 6 NR. Median CCyR duration was 16.3 months; 3 CP patients achieving CCyR had a response more than 12 months. Median failure-free survival was 20 months for patients in CP, 5 months in AP, and 3 months in BP. Use of second-generation TKI after failure to 2 TKIs may induce responses, but these are usually not durable except in some CP patients. New treatment options are needed.

scholarly journals Long term term follow-up of tyrosine kinase inhibitors treatments in inoperable or relapsing diffuse type tenosynovial giant cell tumors (dTGCT)

PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0233046 ◽  
Author(s):  
Mehdi Brahmi ◽  
Philippe Cassier ◽  
Armelle Dufresne ◽  
Sylvie Chabaud ◽  
Marie Karanian ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Giant Cell ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Diffuse Type ◽  
Giant Cell Tumors

Sa1543 Long Term Follow-Up Result of Endoscopic Resection of Gastric Gastrointestinal Stromal Tumor

2015 ◽  
Vol 81 (5) ◽  
pp. AB254-AB255
Author(s):  
Min Jae Yang ◽  
Sun Gyo Lim ◽  
Sung Jae Shin ◽  
Kee Myung Lee
Keyword(s):  
Gastrointestinal Stromal Tumor ◽  
Endoscopic Resection ◽  
Stromal Tumor ◽  
Long Term Follow Up

scholarly journals The mechanisms of sensitization of gastrointestinal stromal tumor cells to DNA topoisomerase II inhibitors

2019 ◽  
Vol 100 (2) ◽  
pp. 245-251
Author(s):  
P D Dunaev ◽  
A R Galembikova ◽  
S V Boichuk
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumor ◽  
Tumor Cells ◽  
Tyrosine Kinase Inhibitors ◽  
Receptor Tyrosine Kinase ◽  
Topoisomerase Ii ◽  
Kinase Inhibitors ◽  
Stromal Tumor ◽  
Topoisomerase Ii Inhibitors ◽  
Receptor Tyrosine Kinase Inhibitors

Aim. To examine the ability of receptor tyrosine kinase inhibitors to modulate gastrointestinal stromal tumor cells sensitivity to DNA topoisomerase II inhibitors. Methods. The following receptor tyrosine kinase inhibitors were used in the present study - imatinib, crizotinib, cabozantinib and sunitinib. An ability of the named medications to sensitize gastrointestinal stromal tumor cells to DNA topoisomerase II inhibitor (doxorubicin) was examined by using an MTS-based colorimetric assay. The expression of apoptotic, DNA damage and repair markers was assessed with western blotting by using the corresponding monoclonal antibodies. Proliferative activity was examined in a real-time by utilizing an iCELLigence system (ACEA Biosciences Inc., USA). Results. We found that all above-mentioned receptor tyrosine kinase inhibitors were able to sensitize gastrointestinal stromal tumor cells to topoisomerase II inhibitors. This leads to the decrease of proliferative activity of tumors cells and enhancement of apoptotic cell death. Importantly, this effect was observed in imatinib-resistant gastrointestinal stromal tumor cells. One of the possible molecular mechanisms responsible for sensitization of these cells to topoisomerase II inhibitors was the ability of the target medications to inhibit the homologous recombination. This is evidenced by substantial decrease of Rad51 recombinase expression as a result of receptor tyrosine kinase inhibitor effect on the cells with DNA damage caused by topoisomerase II inhibitors. Conclusion. Receptor tyrosine kinase inhibitors are able to sensitize imatinib-resistant gastrointestinal stromal tumor cells to topoisomerase II inhibitors by inhibiting DNA homologous recombination.

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