scholarly journals 616 Rare KIT gene mutation in a recurrent GIST: Case Report

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
N O'Neill ◽  
D McManus ◽  
A Kennedy ◽  
M Eatock ◽  
E Napier
Keyword(s):  
Recurrent Disease ◽  
Locally Advanced ◽  
Complete Response ◽  
Maximal Response ◽  
Molecular Testing ◽  
Gastric Gist ◽  
Adjuvant Imatinib ◽  
Residual Stomach ◽  
Exon 11 ◽  
Viable Tumour

Abstract Introduction The diagnosis and treatment of Gastro-intestinal stromal tumours (GISTs) has been revolutionized by molecular pathology and targeted therapy. Description This patient was diagnosed with locally advanced gastric GIST in 2009. He was initially treated neoadjuvantly with imatinib from 2009- 2010. He underwent laparoscopic resection in 2010. Pathology showed almost complete response with only 1.5mm focus of viable tumour. He did not receive adjuvant imatinib as this was not established practice in 2010. Recurrent disease was resected in 2011. Mitotic count was 200/50hpf. Adjuvant imatinib was given for 5 years then discontinued in 2016. Imaging showed no recurrence over this time period. Molecular testing showed Kit Exon 11 mutation- this is common in GISTs and associated with response to imatinib. Recurrent disease was diagnosed 2018 with a 10x9cm mass between residual stomach and liver– he recommenced imatinib with partial response (maximal response was reached in 2020, but a new 3cm lesion was noted) He underwent further resection of the residual stomach and liver segmentectomy in 2020. Histology showed acellular areas of myxoid degeneration, indicating treatment response however viable tumour remained. Sequencing was performed. This showed the expected mutation in exon 11 but also a mutation in exon 13 of KIT- this has been shown recently to confer resistance to imatinib. Discussion Over 90% of GISTs harbour mutations in c-KIT. Recent work has demonstrated that some tumours acquire secondary mutations conferring resistance, following prolonged TKI therapy. Radiological and histopathological features correlate with such events and assist in deciding surgical management.

The role of neoadjuvant imatinib therapy of patients with primary locally advanced GIST.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11037-11037
Author(s):  
Peter Arkhiri ◽  
Irina Poddubnaya ◽  
Sergey N. Nered ◽  
Ivan N. Peregorodiev ◽  
Maxim P. Nikulin ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Surgical Resection ◽  
Combined Treatment ◽  
Locally Advanced ◽  
Percutaneous Biopsy ◽  
Imatinib Therapy ◽  
Maximal Response ◽  
Optimal Timing ◽  
Adjuvant Imatinib ◽  
Advanced Gist

11037 Background: percutaneous biopsy of gastrointestinal tumors is contraindicated, that is why prospective randomized trials of efficiency of preoperative imatinib therapy weren't conducted. According to the results of theRTOG S-0132/ACRIN 6665, CST1571-BDE43 and other studies, neoadjuvant imatinib therapy increase tumor resectability and improve progression-free and disease-specific survival. The optimal timing of surgical intervention is likely during the maximal response on treatment (6 to 12 months as a rule). Methods: We have analyzed the treatment results of 86 patients with locally advanced GIST which were treated since January 1st 2002 till 20 January 2016 at N.N. Blokhin Russian Cancer Centre. The primary tumor was located in the stomach - 32 pts (37,2%), duodenum and small bowel - 37 (43,1%), other (colon, rectum and extraorgan) – 17 pts ( 19,7%). The median follow-up time was 4.9 years. There are 4 groups in the trail: group 1 - 29 patients received only surgical treatment, group 2 - 12 pts– surgical resection with adjuvant imatinib therapy for 1 year; group 3 - 25 pts – adjuvant imatinib therapy for 3 years and group 4 - 17 pts– surgical resection with neoadjuvant and adjuvant imatinib therapy (1 - 3 years). The remained 3 patients received surgical resection with adjuvant imatinib therapy for 5 years. Results: Survival analyses showed a significant improvement of RFS and OS in patients who received combined treatment with neoadjuvant and adjuvant imatinib therapy. The five-year RFS in first group of patients was 10,8%, in 2 group - 16,7%, in 3 group - 68,4%, and 4 group - 79,8% (p = 0.0001). The 5-year overall survival in these groups was 42,6%, 66,7%, 76,1% and 91.6% ( p = 0,0072) respectively. In the patients with 5-years adjuvant therapy, diseases progression was not noted. During neoadjuvant therapy disease progression has been registered in two patients. The median time of preoperative imatinib therapy was 11 month (from 3 to 24 month). Neoadjuvant imatinib therapy increased the rate of R0 (14 pts – 82,4%) and organ-sparing (12 pts – 70,6%) resections. Conclusions: The optimal approach in patients with locally advanced GIST is combined surgical treatment with neoadjuvant and adjuvant (at least for 3 years) imatinib therapy.

scholarly journals Pathologic Complete Response in a Large Gastric GIST: Using Molecular Markers to Achieve Maximal Response to Neoadjuvant Imatinib

2018 ◽  
Vol 16 (12) ◽  
pp. 1424-1428 ◽  
Author(s):  
Joshua B. Brown ◽  
Reetesh K. Pai ◽  
Melissa A. Burgess ◽  
Jennifer Chennat ◽  
Amer H. Zureikat
Keyword(s):  
Molecular Markers ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Maximal Response ◽  
Gastric Gist

scholarly journals Gastrointestinalni tumor zeluca (GIST) kao uzrok masivnog krvarenja iz gornjih partija digestivnog trakta

2007 ◽  
Vol 54 (1) ◽  
pp. 169-171 ◽  
Author(s):  
V.R. Djukic ◽  
A.R. Karamarkovic ◽  
S. Mijatovic ◽  
M. Micev ◽  
V.M. Bumbasirevic ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Imatinib Mesylate ◽  
Kinase Inhibitor ◽  
Complete Response ◽  
Response To Treatment ◽  
Gastric Gist ◽  
Adjuvant Imatinib ◽  
Mesenchymal Tumors ◽  
Promising Treatment ◽  
Histopathology Examination

Gastrointestinal stromal tumors GIST are rare mesenchymal tumors of the gastrointestinal tract characterized by expression of a receptor that activates tyrosine kinase called C- kit. Since malignant GIST has an extremely poor prognosis even after surgical resection. The development of a tyrosine kinase inhibitor, STI571/imatinib mesylate/Gleevec, Glivec which inhibits the BCR-ABL, PDGF-R alpha, and C-Kit receptors, has changed the management of unrespectable malignant GIST and has improved the survival of patients with metastaic disease. We report a 32 year old male patient with subcardiale gastric GIST and massive gastrointestinale bleeding. The patient underwent total gastrectomy, D2 lymphadenestomy, distal pancreatectomy and splenectomy on 02.02. 2004. Histopathology examination of the primary tumor revealed a strong C-Kit expression and CD 34 +++, Ki67 20 and so called "Pure GIST" was approved Liver metastasis was detected on ultrasound and CT 12 months later and segmentectomy S7 was performed on 23.03.2005. Postoperative course was uneventful. HP examination - malignant 35 x 30 mm sarcoma like tumor of mesenchymal origin. The patient received adjuvant imatinib -mesylate Gleevec Novartis Pharma Basel 400 mg a day. The initial complete response to treatment continued to 24 months postoperatively Imatinib is a recent and very promising treatment extirpation remains the only curative treatment of malignant GIST as evidenced by our patient.

scholarly journals Complete Response With Immunotherapy: A Case of Metastatic Bladder Cancer

2021 ◽  
Vol 9 ◽  
pp. 232470962110356
Author(s):  
Balraj Singh ◽  
Parminder Kaur ◽  
Sachin Gupta ◽  
Nirmal Guragai ◽  
Michael Maroules
Keyword(s):  
Bladder Cancer ◽  
Cancer Immunotherapy ◽  
Locally Advanced ◽  
Complete Response ◽  
First Line ◽  
Novel Therapy ◽  
Metastatic Bladder Cancer ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Broad Variety

Bladder cancer is the most common urinary tract malignancy. Platinum-based chemotherapy is the first line of treatment in locally advanced or metastatic bladder cancer. Immunotherapy has become a novel therapy option in a broad variety of malignancies including bladder cancer. Immunotherapy is approved as first line of treatment in patients who are ineligible for platinum-based chemotherapy and second-line treatment for metastatic urothelial cancer who progressed after platinum-based treatments. We present the case of an 83-year-old female with metastatic bladder cancer who was chemotherapy ineligible and had complete response with immune checkpoint inhibitor pembrolizumab.

Neoadjuvant chemotherapy followed by radical surgery in locally advanced vulvar carcinoma: a single-institution experience

2021 ◽  
pp. 030089162110276
Author(s):  
Adorni Marco ◽  
Bazzurini Luca ◽  
Lissoni Andrea Alberto ◽  
Vecchione Francesca ◽  
Negri Serena ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Partial Response ◽  
Vulvar Cancer ◽  
Elderly Women ◽  
Radical Surgery ◽  
Locally Advanced ◽  
Complete Response ◽  
Tumor Burden ◽  
Clinical Response Rate

Background: Squamous cell carcinoma of the vulva is a rare malignancy that affects elderly women. About one-third of vulvar cancers are diagnosed in an advanced stage, requiring extensive surgery. Neoadjuvant chemotherapy (NACT) has been introduced to reduce local tumor burden. In this retrospective study, we analyze the efficacy and toxicity of NACT followed by radical surgery. Methods: Patients with locally advanced vulvar cancer (LAVC) treated at our institution with neoadjuvant platinum and paclitaxel-based chemotherapy ± ifosfamide followed by surgery at our institution were retrospectively identified. Results: Fourteen patients (93%) completed NACT with tolerable toxicities (G3–G4 toxicity: 30%). Thirteen patients (87%) underwent surgery. The overall clinical response rate on vulvar disease was 66% (20% complete response, 46% partial response), confirmed by histopathologic analysis, while on inguinal lymph nodes it was 69% (23% complete response, 46% partial response). At the pathologic examination, all patients had negative surgical margins. Three out of 9 patients (33%) with lesions infiltrating the urethral meatus and 4 patients out of 7 (57%) with anal involvement did not require urethral amputation or colostomy, respectively, after NACT. No severe postoperative complications were described. Overall survival at 5 years was 60%, and median overall survival was 76 months. Conclusion: NACT followed by surgery in locally advanced vulvar cancer is well tolerated and allows surgical modulation.

scholarly journals Alternative chemoradiotherapy in anal carcinoma patients with mutations in thymidylate synthase and dihydropyrimidine dehydrogenase genes

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Muhammad Wasif M. Saif ◽  
Ruchi Hamal ◽  
Nauman Siddiqui ◽  
Antonia Maloney ◽  
Melissa Smith
Keyword(s):  
Dihydropyrimidine Dehydrogenase ◽  
Anal Carcinoma ◽  
Complete Response ◽  
Genetic Mutations ◽  
Molecular Testing ◽  
Severe Toxicity ◽  
Metabolizing Enzymes ◽  
Radiological Response ◽  
A Prospective Study ◽  
To Receive

Background: 5-fluorouracil (5-FU) and mitomycin-C (MMC) with radiotherapy (RT) remain an established treatment for patients with anal cancer (AC). Genetic mutations in two major metabolizing enzymes for 5-FU; dihydropyrimidine dehydrogenase ( DPYD and thymidylate synthetase ( TYMS), have been associated with clinical response and toxicity. However, their place in the treatment of AC remains undetermined. Methods: We retrospectively reviewed 21 patients with AC, including T2-4, N0-1, M0 or T1-4, N2-3, and M0 treated between 2012 and 2018. All patients were treated with 5-FU 1,000 mg/m2/day via continuous intravenous (IV) infusion 1–4 and 29–32, MMC 10 mg/m2 IV bolus days 1 and 29 plus RT. Patients who developed ⩾3 grade toxicities were tested for the DPYD and TYMS genes. Treatment was either modified with reduced doses or changed to MMC 10 mg/m2 day 1 and 29 with cisplatin 25 mg/m2/week plus RT. Toxicities and responses were collected. Results: Six out of 21 patients who developed ⩾3 grade toxicities including pancytopenia, neutropenia, thrombocytopenia, mucositis, nausea, rash, and nephritis were found to have genetic mutations: TYMS 2RG/3RC ( n = 2), 3RG/3RC ( n = 1), 2R/2R ( n = 2), T YMS 3′UTR del/Ins ( n = 2), and DPYD c.2864A > T heterozygous ( n = 1). Two patients received 5-FU at a 50% reduced dose on days 29–32; one patient refused to receive 5-FU (continued with MMC and RT); one patient received only radiation therapy due to persistent pancytopenia despite the use of growth factors; two patients received an alternative regimen consisting of MMC 10 mg/m2 on day 29 with cisplatin (CDDP) 25 mg/m2/week plus RT; and two patients received cisplatin/MMC with RT from the beginning as they were prospectively detected to have TYMS abnormalities prior to dosing the chemotherapy. These patients tolerated treatment very well with only grade 2 toxicities. All the patients (4/4) on cisplatin/MMC achieved clinical complete response (cCR), while four patients (4/15) on 5-FU/MMC reached cCR at the first assessment. Radiological response showed complete response at the end of 24 weeks assessment. Conclusions: Molecular testing for DPYD and TYMS genes can allow us to identify patients who are most likely to respond or face severe toxicity to 5-FU in a potentially curable cancer. Combining radiation with CDDP with MMC in patients with AC is feasible. A prospective study based on pharmacogenetic testing comparing MMC/cisplatin with MMC/5-FU is indicated in patients with AC.

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