|Year : 2019 | Volume
| Issue : 1 | Page : 37-40
Complete radiographic response of a rectal gastrointestinal stromal tumor to imatinib mesylate
Hsing-Yu Yang1, Ming-Hung Lee2
1 Division of General Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwain
2 Division of Colorectal Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwain
|Date of Submission||27-Jun-2018|
|Date of Decision||26-Sep-2018|
|Date of Acceptance||01-Oct-2018|
|Date of Web Publication||1-Mar-2019|
Dr. Ming-Hung Lee
Division of Colorectal Surgery, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung City 813
Source of Support: None, Conflict of Interest: None
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. These tumors occur rarely in the rectal region, with an incidence of <3%. In this case report, an 80-year-old man complained of abdominal fullness and difficulty in defecating during a visit to our outpatient department. A radiographic image survey showed an extraluminal lesion over the rectum, and the pathological diagnosis was GIST. Imatinib mesylate, a neoadjuvant agent, was administered. The patient then refused further surgical intervention and continued imatinib mesylate treatment. Subsequent magnetic resonance images revealed no obvious lesion occupying the pelvic cavity. In addition to this case, we also performed a literature review of rectal GIST treatment strategies.
Keywords: Gastrointestinal stromal tumor, imatinib mesylate, radiographic response, rectal
|How to cite this article:|
Yang HY, Lee MH. Complete radiographic response of a rectal gastrointestinal stromal tumor to imatinib mesylate. J Cancer Res Pract 2019;6:37-40
|How to cite this URL:|
Yang HY, Lee MH. Complete radiographic response of a rectal gastrointestinal stromal tumor to imatinib mesylate. J Cancer Res Pract [serial online] 2019 [cited 2019 Jul 16];6:37-40. Available from: http://www.ejcrp.org/text.asp?2019/6/1/37/253247
| Introduction|| |
Gastrointestinal stromal tumors (GISTs) are rare tumors that express the CD117 oncogene, which can be detected by immunohistochemistry. The most common sites of GISTs are the stomach (70%) and small intestine (20%), and only 3% of cases localize to the rectum. Tyrosine kinase inhibitors, such as imatinib or sunitinib, are the mainstay treatment in the management of patients with advanced or metastatic GISTs. Locally advanced tumors may cause the disruption of adjacent organs under surgical resection without neoadjuvant target therapies. A case report on the complete pathological response to imatinib mesylate in a patient with extraintestinal GIST was published in 2014. In our case, the radiographic response was remarkable. Because the patient refused local resection of the advanced GIST, we had the opportunity to observe the resolution of the rectal GIST under treatment with only imatinib mesylate.
| Case Report|| |
An 80-year-old man with type II diabetes mellitus and chronic pancreatitis underwent a medical evaluation due to difficulty defecating and abdominal fullness for one month. Complete colonoscopy revealed a bulging mass in the anterior upper rectal wall, with intact mucosa [Figure 1], approximately 10 cm above the dentate line. Routine laboratory tests and tumor markers were normal (carcinoembryonic antigen <0.1). Abdominal and pelvic magnetic resonance imaging (MRI) revealed a well-demarcated solid mass with central necrosis (6.5 cm × 6.3 cm × 4.5 cm; 96 cc) [Figure 2] compressing the bladder, prostate, and rectum. While the tumor appeared to have infiltrated the muscular wall of the rectum, no other unusual findings were observed. A chest X-ray was normal, and a transperineal computed tomography (CT)-guided biopsy that was positive for GIST revealed a high risk of progressive disease [Figure 3]. After a multidisciplinary discussion regarding the risk of incomplete surgical resection and surgical risk, the patient was treated with 400 mg/day imatinib mesylate for 12 months to reduce the tumor size and increase the likelihood of curative surgery. Another MRI scan performed after 1 year of imatinib mesylate treatment revealed a marked reduction in tumor size (2.3 cm × 1.6 cm × 0.9 cm; 1.7 cc) [Figure 4]. The patient continued imatinib mesylate treatment for another 3 years because he refused a surgical intervention due to the high risk of anesthesia and because the symptoms had been relieved. The second and third MRI scans revealed no obvious lesion [Figure 5] and [Figure 6], and he is currently still receiving imatinib mesylate treatment (August 2018). We will continue to observe this patient for changes in rectal GIST status.
|Figure 1: Colonoscopy examination revealed an extraluminal-compressing mass lesion with intact mucosa (May 2014)|
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|Figure 2: A 96-cc well-demarcated solid mass with central necrosis occupied the pelvic cavity and compressed the rectal tube (May 2014)|
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|Figure 3: Pathological immunohistochemistry image: CD 117 showed positive and >5/50 number of mitoses per high-power field revealed high risk of gastrointestinal stromal tumor|
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|Figure 4: Follow-up magnetic resonance imaging revealed extreme shrinkage of the tumor (August 2015)|
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|Figure 5: Follow-up magnetic resonance imaging showed no obvious tumor lesion (August 2017)|
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|Figure 6: Follow-up magnetic resonance imaging was revealed no interval change (August 2018)|
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| Discussion|| |
GIST was first described in 1983 by Mazur and Clock as “a nonepithelial tumor group consisting of spindle cells and epithelioid cells." Rectal GISTs account for 3% of all new GIST cases in the European Union each year. Rectal GISTs are also rare in eastern countries and account for approximately 0.1% of all rectal neoplasms in South Korea. Owing to the low incidence of rectal GISTs, few review studies exist in PubMed and the English literature., We summarize the clinical manifestations of rectal GIST in [Table 1].
|Table 1: Clinical manifestation of rectal gastrointestinal stromal tumors|
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GISTs are diagnosed in biopsy tissue and can be dominantly CD117 (KIT) positive in immunohistochemical analysis. Complete surgical resection with negative tumor margins is the principal curative procedure for localized GISTs in all organs but is difficult to perform for rectal GISTs because of anatomical features that include the deep, narrow pelvis and proximity to the sphincter muscle. Imatinib mesylate is a selective inhibitor of the transmembrane KIT receptor, a protein tyrosine kinase. Imatinib inhibits the proliferation of GIST cells that are stimulated by activated KIT receptors. Imatinib has shown high response rates (and the potential for a complete pathologic response) in advanced disease settings, and many studies have reported the effect of neoadjuvant imatinib mesylate therapy to decrease tumor burden. In 2004, one randomized trial demonstrated that imatinib mesylate is a useful adjuvant treatment to achieve progression-free survival in patients with GIST, and one phase II trial has been completed. The most common therapeutic regimen involves a course of imatinib, commonly administered for 3–12 months, with frequent imaging studies and a re-evaluation to determine the optimal time for surgery. To date, the optimal duration of neoadjuvant imatinib treatment has not been established. The aim of imatinib treatment is to reduce the size of the tumor to facilitate complete surgical resection and/or increase the likelihood of organ preservation.
GISTs are usually seen as extraluminal tumors with heterogeneous enhancement, and intravenous contrast due to high vascularization, and contrast-enhanced CT is the standard imaging method for GIST. However, MRI can detect invasion of adjacent organs in greater detail than CT. In our case, we observed the response of the rectal GIST under imatinib mesylate without resistance. We used the standardized Response Evaluation Criteria in Solid Tumors (RECIST) to determine the response to neoadjuvant therapy. RECIST has allowed for notable improvements in increasing reproducibility and confidence in results. The response criteria include four degrees: complete response, partial response, stable disease, and progressive disease. A near-total complete radiographic response was found in this case without drug resistance after 4 years. In the EORTC phase III trial, the response to imatinib mesylate varied according to the site of exon mutations. The presence of exon 9-activating mutations in KIT was the strongest adverse prognostic factor for a response to imatinib, increasing the relative risk of progression by 171% (P < 0.0001) and the relative risk of death by 190% (P < 0.0001) compared with KIT exon 11 mutants. Analysis of KIT gene mutations is not a routine diagnostic study in our hospital. Owing to the excellent response to imatinib mesylate without drug resistance, we will consider mutation analysis in this patient in the future. However, we cannot conclude that the GIST was cured by imatinib mesylate because the patient refused a surgical intervention after the symptoms had been relieved, and he is currently still receiving imatinib mesylate. Our treatment plan was similar to that for chronic controllable diseases (e.g., hypertension or diabetes mellitus). In this report, we present a record of the observations of a patient with a rectal GIST who was treated with imatinib mesylate only.
| Conclusion|| |
Patients with rectal GIST can achieve a complete radiographic response after imatinib therapy. Our patient with a rectal GIST was treated with neoadjuvant imatinib without surgery, and future investigations with a longer follow-up duration are warranted to confirm our findings.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
This report is based in part on data from the Cancer Registry Database provided by the Cancer Center of Kaohsiung Veterans General Hospital.
| References|| |
Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, et al.
Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol 2002;33:459-65.
Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: An analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol 2005;100:162-8.
Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, et al.
Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003;21:4342-9.
Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al.
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N
Engl J Med 2002;347:472-80.
Quezada N, Acevedo F, Marambio A, León F, Galindo H, Roa JC, et al.
Complete pathological response to imatinib mesylate in an extraintestinal gastrointestinal stromal tumor. Int J Surg Case Rep 2014;5:681-5.
Mazur MT, Clark HB. Gastric stromal tumors. Reappraisal of histogenesis. Am J Surg Pathol 1983;7:507-19.
Nilsson B, Bümming P, Meis-Kindblom JM, Odén A, Dortok A, Gustavsson B, et al.
Gastrointestinal stromal tumors: The incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era – A population-based study in Western Sweden. Cancer 2005;103:821-9.
Baik SH, Kim NK, Lee CH, Lee KY, Sohn SK, Cho CH, et al.
Gastrointestinal stromal tumor of the rectum: An analysis of seven cases. Surg Today 2007;37:455-9.
Kameyama H, Kanda T, Tajima Y, Shimada Y, Ichikawa H, Hanyu T, et al.
Management of rectal gastrointestinal stromal tumor. Transl Gastroenterol Hepatol 2018;3:8.
Fujimoto Y, Akiyoshi T, Konishi T, Nagayama S, Fukunaga Y, Ueno M. Laparoscopic sphincter-preserving surgery (intersphincteric resection) after neoadjuvant imatinib treatment for gastrointestinal stromal tumor (GIST) of the rectum. Int J Colorectal Dis 2014;29:111-6.
Blay JY, Bonvalot S, Casali P, Choi H, Debiec-Richter M, Dei Tos AP, et al.
Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST consensus conference of 20-21 March 2004, under the auspices of ESMO. Ann Oncol 2005;16:566-78.
Chacón M, Roca E, Huertas E, Loria FS, Domenechini E. CASE 3. Pathologic complete remission of metastatic gastrointestinal stromal tumor after imatinib mesylate. J Clin Oncol 2005;23:1580-2.
Jones RL. Practical aspects of risk assessment in gastrointestinal stromal tumors. J Gastrointest Cancer 2014;45:262-7.
Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, et al.
Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: Randomised trial. Lancet 2004;364:1127-34.
DeMatteo RP, Ballman KV, Antonescu CR, Corless C, Kolesnikova V, von Mehren M, et al.
Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor: ACOSOG Z9000 (Alliance) intergroup phase 2 trial. Ann Surg 2013;258:422-9.
Choi H, Charnsangavej C, de Castro Faria S, Tamm EP, Benjamin RS, Johnson MM, et al.
CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: A quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol 2004;183:1619-28.
Kalkmann J, Zeile M, Antoch G, Berger F, Diederich S, Dinter D, et al.
Consensus report on the radiological management of patients with gastrointestinal stromal tumours (GIST): Recommendations of the German GIST Imaging Working Group. Cancer Imaging 2012;12:126-35.
Jiang ZX, Zhang SJ, Peng WJ, Yu BH. Rectal gastrointestinal stromal tumors: Imaging features with clinical and pathological correlation. World J Gastroenterol 2013;19:3108-16.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al.
New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.
Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, et al.
KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 2006;42:1093-103.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]