Erlandson RA, Klimstra DS, Woodruff JM.
Subclassification of gastrointestinal stromal tumors based on evaluation by electron microscopy and immunohistochemistry.
Ultrastruct Pathol. 1996 Jul-Aug;20(4):373-93. doi: 10.3109/01913129609016340.
Abstract/Text
Fifty-six gastrointestinal stromal tumors (GIST) were subclassified by ultrastructural examination and by immunophenotypic analysis using a panel of 13 antibodies. Eighty percent of the tumors originated in the stomach and small intestines. The neoplasms were classified as follows: 42.9% smooth muscle tumors (4 leiomyomas, 9 spindle cell and 8 epithelioid leiomyosarcomas, and 3 mixed spindle cell and epithelioid leiomyosarcomas); 37.5% gastrointestinal autonomic nerve tumors (GANT), 47.6% of which arose in the small intestines; 8.9% mixed leiomyosarcoma/neurogenic tumors; and 10.7% undifferentiated GIST, not otherwise specified. The muscle common actin antibody HHF-35, variably reactive with tumor cells composing 23 of 24 smooth muscle tumors, was found to be the most sensitive marker of leiomyocyte differentiation. One immunophenotypically questionable spindle cell leiomyosarcoma was diagnosed by electron microscopy. Since neuron specific enolase positive cells were found in 1/3 of the leiomyosarcoma cases, the ultrastructural demonstration of synapse-like structures and neurosecretory granules was required for diagnosing GANTs. The immunophenotype of the ultrastructurally undifferentiated GIST was vimentin and CD34+. Variable numbers of ultrastructurally undifferentiated cells also we found in all of the tumors except 2 leiomyomas. CD34 was also expressed in smooth muscle (54%) and GAN (62%) tumors. Despite their similar light microscopic appearance, GIST are phenotypically heterogeneous, requiring both ultrastructural and immunohistochemical studies for accurate characterization.
Mutrie CJ, Donahue DM, Wain JC, Wright CD, Gaissert HA, Grillo HC, Mathisen DJ, Allan JS.
Esophageal leiomyoma: a 40-year experience.
Ann Thorac Surg. 2005 Apr;79(4):1122-5. doi: 10.1016/j.athoracsur.2004.08.029.
Abstract/Text
BACKGROUND: Esophageal leiomyomas, although infrequent, are the most common benign intramural tumors of the esophagus. They represent 10% of all gastrointestinal leiomyomas and frequently cause symptoms, necessitating resection.
METHODS: The Massachusetts General Hospital Pathologic Database was reviewed over a 40-year period for patients who underwent surgical resection of esophageal leiomyomas. Data analyzed included demographic information, presenting symptoms, tumor location, tumor characteristics and histology, diagnostic procedures, and treatment modalities/outcomes. Fifty-three patients were identified; 31 patients were symptomatic from their leiomyomas.
RESULTS: Symptomatic patients presented at a mean age of 44 years old and exhibited a twofold male predominance. Mean tumor diameter among symptomatic patients was 5.3 cm, as compared to 1.5 cm in asymptomatic patients (p < 0.0001). Thirty of the symptomatic patients had solitary leiomyomas, and 1 patient had five separate leiomyomas. Eighty-four percent of the lesions in symptomatic patients occurred in the lower two-thirds of the esophagus, with epigastric discomfort being the most common presenting symptom. Among patients operated on solely for leiomyoma, 97% were enucleated without an esophageal resection. None of the leiomyomas showed malignant transformation or recurrence. All symptomatic patients had relief of symptoms, with no perioperative morbidity or mortality.
CONCLUSIONS: In a large pathologic series, over half of all patients with esophageal leiomyomas were symptomatic. Larger tumors were significantly more likely to be symptomatic. Local enucleation by a variety of surgical approaches was accomplished in most patients. All symptomatic patients had relief of symptoms, with no perioperative morbidity or mortality. There was no observed tendency for malignant transformation or recurrence.
Emory TS, Sobin LH, Lukes L, Lee DH, O'Leary TJ.
Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site.
Am J Surg Pathol. 1999 Jan;23(1):82-7. doi: 10.1097/00000478-199901000-00009.
Abstract/Text
Although the significance of various prognostic factors, such as tumor size and mitotic index (MI), has been well established for smooth-muscle tumors of the stomach, the significance of these factors in other sites is less well defined. We studied 1004 patients with gastrointestinal smooth-muscle tumors for whom vital status could be determined. The average MI and tumor size varied significantly among the five major sites examined: esophagus (53 cases), stomach (524 cases), small bowel 252 cases), colon/rectum (108 cases), and omentum/mesentery/peritoneum (67 cases). There was a significant difference in site-specific survival (p = 0.001), with 10-year survival varying between 50% and 70%. Multivariate analysis demonstrated tumor location (p = 0.0320), size (p = 0.0003), MI (p < 0.0001), and patient age (p < 0.0001) to each carry independent prognostic value. The significance of MI was highly site dependent. Separation of survival curves for the stomach, using a threshold for analysis of either 5 or 10 mitotic figures/50 high-power fields, was very good. In contrast, small-bowel tumors showed little separation between survival curves, regardless of whether a threshold of 1, 5, or 10 mitotic figures MF/50 high-power fields was used to distinguish groups. In no site were tumor size and MI alone sufficient to provide an accurate long-term prediction of prognosis. Although tumor location, size, MI, and age have independent value in predicting the prognosis of patients with gastrointestinal smooth-muscle tumors, better methods are still required to accurately predict clinical course.
Jiang W, Rice TW, Goldblum JR.
Esophageal leiomyoma: experience from a single institution.
Dis Esophagus. 2013 Feb-Mar;26(2):167-74. doi: 10.1111/j.1442-2050.2012.01345.x. Epub 2012 Mar 27.
Abstract/Text
Esophageal leiomyomas are rare. We report the clinicopathologic features of one of the largest series of esophageal leiomyomas from a single institution. We retrospectively reviewed the Cleveland Clinic pathology database (1985-2010) for patients with a diagnosis of esophageal leiomyoma(s). Clinicopathologic features of 30 cases from 28 patients were analyzed. The group included 15 females and 13 males with a mean age at diagnosis of 56 years. These include 9 excisions, 9 esophagectomies, and 12 endoscopic biopsies. Only one partial esophagectomy was performed solely for a symptomatic 14-cm leiomyoma; the remainder of the resections (n= 8) were for other indications, including esophageal cancer (Barrett's esophagus-related adenocarcinoma and squamous cell carcinoma) and emergent esophageal perforation, with leiomyoma being an incidental finding. One patient (2.5%) had two synchronous leiomyomas (14 cm and 0.3 cm). Tumor size ranged from 0.1 to 14 cm (mean = 2.0 cm). Mean tumor size among symptomatic patients was 5.2 cm, as compared with 0.4 cm in asymptomatic patients. Dysphagia was the most common complaint in symptomatic patients (71.4%). Sixty-nine percent of the tumors were located in the distal and middle thirds of the esophagus, with most (69.6%) arising from muscularis propria. Histologically, these tumors were composed of bland spindle cells with low cellularity, no nuclear atypia, or mitotic activity. Only one case (14 cm) showed focal moderate cellularity and nuclear atypia, with low mitotic activity (<1/10 high power field). Immunohistochemical studies showed tumor cells were positive for smooth muscle actin, and negative for CD34 and CD117. Follow-up information was available for 22 patients (78.6%), and none had adverse events related to leiomyoma. In summary, esophageal leiomyoma is a rare benign tumor of the esophagus. Patients with larger tumors were more likely to have symptoms. The majority of the tumors were in the lower and mid-esophagus, and arose from muscularis propria. These tumors behave in a clinically benign fashion.
© 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.
Hatch GF 3rd, Wertheimer-Hatch L, Hatch KF, Davis GB, Blanchard DK, Foster RS Jr, Skandalakis JE.
Tumors of the esophagus.
World J Surg. 2000 Apr;24(4):401-11. doi: 10.1007/s002689910065.
Abstract/Text
This collective review includes all available case reports of smooth muscle (stromal) tumors of the esophagus in the world literature. Compiling this review, we endeavored to examine cumulative and recently collected data of both benign and malignant esophageal smooth muscle tumors found in the literature spanning the period from 1875 to 1996, which totaled 1679 leiomyomas (LMs) and 165 leiomyosarcomas (LMSs). The peak age of occurrence of benign smooth muscle tumors in the esophagus was found to be between the ages of 30 and 59, whereas the highest frequency of malignant tumors was seen later in life, during the decade from age 60 to 69. The most common location of both LMs and LMSs was the lower third of the esophagus. Their patterns of growth differed; LMs were more likely to grow intramurally, and LMSs were predominantly intraluminal. Most patients with LMs presented with dysphagia and pain or discomfort; patients with LMSs additionally commonly complained of weight loss. As with smooth muscle tumors of other areas of the gastrointestinal tract, the duration of symptoms averaged 1 month to 1 year, and malignant tumors grew to larger sizes than benign neoplasms. Approximately one-third of LMSs had metastasized at diagnosis, and there was a 5-year survival rate of approximately 20%.
島津久明ら: 食道平滑筋腫と平滑筋肉腫—自験9例の報告と本邦文献上報告例の分析. 日外会誌1983;84: 355-368.
Koga H, Iida M, Suekane H, Aoyagi K, Yao T, Kimura Y, Masuda N, Fujishima M.
Rapidly growing esophageal leiomyosarcoma: case report and review of the literature.
Abdom Imaging. 1995 Jan-Feb;20(1):15-9. doi: 10.1007/BF00199635.
Abstract/Text
We evaluated a 72-year-old woman who was experiencing dysphagia. Esophageal leiomyosarcoma was diagnosed by barium meal study, upper gastrointestinal endoscopy, endoscopic ultrasonography (EUS), by computed tomography (CT). A barium meal study and esophagoscopy performed 3 months before the diagnosis of esophageal leiomyosarcoma showed no abnormalities. Therefore, the tumor appeared to have grown rapidly during the 3-month period.
Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J.
Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas.
Am J Surg Pathol. 2000 Feb;24(2):211-22. doi: 10.1097/00000478-200002000-00007.
Abstract/Text
Although rare elsewhere in the gastrointestinal tract, leiomyomas (LMs) are the most common esophageal mesenchymal neoplasms. In contrast, gastrointestinal stromal tumors (GISTs) predominate in the stomach and intestines but have not been documented in the esophagus. This study was undertaken to determine the clinicopathologic features and frequency of esophageal GISTs compared with LMs and leiomyosarcomas (LMSs) of the esophagus. A total of 68 stromal/smooth muscle tumors from the Armed Forces Institute of Pathology and the Haartman Institute of University of Helsinki were reclassified by current histologic and immunohistochemical criteria. There were 17 GISTs, 48 LMs, and three LMSs. The esophageal GISTs occurred in 12 men and five women with a median age of 63 years (range, 49-75 years). All tumors were from the lowest third of the esophagus, and the most common complaint was dysphagia, whereas two tumors were detected incidentally. Histologically the tumors had an overall basophilic appearance and showed combinations of solid, myxoid, and perivascular collarlike patterns with a spindle cell histology in 13 patients and epithelioid histology in four patients. All tumors were positive for CD117 and for CD34, whereas two patients were also positive for alpha-smooth muscle actin (SMA) and three patients were positive for desmin. One patient showed a unique immunophenotype with coexpression of CD117, CD34, SMA, and desmin. Nine patients died of disease, including all who had a tumor larger than 10 cm, and also one patient whose tumor showed five mitoses per 50 high-power fields. In comparison, esophageal LMs (n = 48) occurred in a younger population (median age, 35 years) but, similar to the GIST group, men predominated (67%). All LMs were clinically indolent tumors with no tumor-related mortality. The LMs showed eosinophilic cytoplasm, and were positive for desmin and SMA, and negative for CD117 and CD34. All three LMSs were large high-grade tumors that showed muscle cell markers but no CD117. All patients died of disease. Esophageal GISTs showed mutations in exon 11 of c-kit as described previously in gastric and intestinal GISTs. The separation of GISTs from esophageal LMs is important diagnostically because the former group has a high risk of malignant behavior.
Rosai J. Stromal tumors. In Ackerman’s Surgical Pathology, 8 th ed. Pp617-648, 691-693, Mosby-year Book, St Louis, Chicago, 1996.
Miettinen M, Virolainen M, Maarit-Sarlomo-Rikala.
Gastrointestinal stromal tumors--value of CD34 antigen in their identification and separation from true leiomyomas and schwannomas.
Am J Surg Pathol. 1995 Feb;19(2):207-16. doi: 10.1097/00000478-199502000-00009.
Abstract/Text
The term "gastrointestinal stromal tumor" (GIST) has been applied to mesenchymal tumors that represent neither typical leiomyomas nor schwannomas. In this study we analyzed immunohistochemically 67 histologically benign [< 2 mitoses/10 high-power field (HPF)], six borderline (3-5 mitoses/10 HPF), and 23 malignant GIST (> 5 mitoses/10 HPF) and compared them with 10 typical leiomyomas and 5 schwannomas of the gastrointestinal tract. The benign GISTs with spindle cell pattern (67 cases) were typically negative for muscle cell markers (only 3% positive for desmin and 25% for alpha-smooth muscle actin) and S100 protein, but 70% of the cases were positive for CD34, the myeloid progenitor cell antigen also present in endothelial cells and some fibroblasts. However, none of the cases was positive for CD31 (PECAM-1), a more endothelial cell-specific antigen. The absence of CD31 in GIST separates it from Kaposi's sarcoma, a tumor known to be positive for both CD34 and CD31. Fourteen cases of benign GIST of epithelioid cell type showed an immunophenotypic profile similar to the spindle cell tumors. The small intestinal tumors were more commonly actin positive and less commonly CD34 positive than were the gastric tumors. The malignant spindle and epithelioid GIST showed features essentially similar to those in corresponding benign tumors. In contrast, all typical leiomyomas were positive for muscle cell markers and were negative for CD34 and S100 protein. Gastrointestinal schwannomas were S100-protein positive, and negative for muscle markers and CD34. Our results show that gastrointestinal mesenchymal tumors can be immunophenotypically divided in categories that correlate with light microscopically defined diagnostic entities, namely typical leiomyomas, schwannomas, and GIST, most cases of the latter representing tumors of primitive mesenchymal cells that are CD34 positive.
Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y.
Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.
Science. 1998 Jan 23;279(5350):577-80. doi: 10.1126/science.279.5350.577.
Abstract/Text
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c-kit complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutively activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c-kit complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34.
日本癌治療学会：GIST診療ガイドライン第4版、金原出版、2023.
Demetri GD, Benjamin RS, Blanke CD, Blay JY, Casali P, Choi H, Corless CL, Debiec-Rychter M, DeMatteo RP, Ettinger DS, Fisher GA, Fletcher CD, Gronchi A, Hohenberger P, Hughes M, Joensuu H, Judson I, Le Cesne A, Maki RG, Morse M, Pappo AS, Pisters PW, Raut CP, Reichardt P, Tyler DS, Van den Abbeele AD, von Mehren M, Wayne JD, Zalcberg J; NCCN Task Force.
NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)--update of the NCCN clinical practice guidelines.
J Natl Compr Canc Netw. 2007 Jul;5 Suppl 2:S1-29; quiz S30.
Abstract/Text
The NCCN Soft Tissue Sarcoma Guidelines include a subsection about treatment recommendations for gastrointestinal stromal tumors (GISTs). The standard of practice rapidly changed after the introduction of effective molecularly targeted therapy (such as imatinib and sunitinib) for GIST. Because of these changes, NCCN organized a multidisciplinary panel composed of experts in the fields of medical oncology, molecular diagnostics, pathology, radiation oncology, and surgery to discuss the optimal approach for the care of patients with GIST at all stages of the disease. The GIST Task Force is composed of NCCN faculty and other key experts from the United States, Europe, and Australia. The Task Force met for the first time in October 2003 and again in December 2006 with the purpose of expanding on the existing NCCN guidelines for gastrointestinal sarcomas and identifying areas of future research to optimize our understanding and treatment of GIST.
Blay JY, Bonvalot S, Casali P, Choi H, Debiec-Richter M, Dei Tos AP, Emile JF, Gronchi A, Hogendoorn PC, Joensuu H, Le Cesne A, McClure J, Maurel J, Nupponen N, Ray-Coquard I, Reichardt P, Sciot R, Stroobants S, van Glabbeke M, van Oosterom A, Demetri GD; GIST consensus meeting panelists.
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 Apr;16(4):566-78. doi: 10.1093/annonc/mdi127.
Abstract/Text
BACKGROUND: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last 4 years. The objectives of this international consensus meeting were to describe the optimal management procedures for patients with GIST in localized and advanced stages, as well as research issues for the future.
MATERIALS AND METHODS: A panel of experts from six specialties, including pathology, molecular biology, imaging, surgery, medical oncology and methodologists for clinical practice guidelines from different European and extra European sarcoma societies were invited to a 2-day workshop. Several questions were selected by the organizing committee prior to the conference. Selected panelists reviewed the current levels of evidence for each point, and presented their conclusions during the meeting. These proposals were discussed, and consensus points were identified and categorized according to the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers and National Comprehensive Cancer Network (NCCN).
RESULTS: Thirty-two consensus points were identified, most from categories 2A of the NCCN and B2 of the SOR. Among these, the standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is an optional diagnostic procedure for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. The optimal criteria for tumor response to imatinib remain to be delineated, and should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield Units) on computed tomography and metabolic activity (i.e. reduction of FDG uptake on positron emission tomography). In a substantial proportion of patients, stable disease and even increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. Metastasis resection is an experimental procedure.
CONCLUSIONS: Consensus points in clinical management of GIST as well as questions for future clinical trials were identified during this consensus conference on GIST management.
DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF.
Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival.
Ann Surg. 2000 Jan;231(1):51-8. doi: 10.1097/00000658-200001000-00008.
Abstract/Text
OBJECTIVE: To analyze the outcome of 200 patients with gastrointestinal stromal tumor (GIST) who were treated at a single institution and followed up prospectively.
SUMMARY BACKGROUND DATA: A GIST is a visceral sarcoma that arises from the gastrointestinal tract. Surgical resection is the mainstay of treatment because adjuvant therapy is unproven.
METHODS: Two hundred patients with malignant GIST were admitted and treated at Memorial Hospital during the past 16 years. Patient, tumor, and treatment variables were analyzed to identify patterns of tumor recurrence and factors that predict survival.
RESULTS: Of the 200 patients, 46% had primary disease without metastasis, 47% had metastasis, and 7% had isolated local recurrence. In patients with primary disease who underwent complete resection of gross disease (n = 80), the 5-year actuarial survival rate was 54%, and survival was predicted by tumor size but not microscopic margins of resection. Recurrence of disease after resection was predominantly intraabdominal and involved the original tumor site, peritoneum, and liver.
CONCLUSIONS: GISTs are uncommon sarcomas. Tumor size predicts disease-specific survival in patients with primary disease who undergo complete gross resection. Tumor recurrence tends to be intraabdominal. Investigational protocols are indicated to reduce the rate of recurrence after resection and to improve the outcome for patients with GIST.
Fong Y, Coit DG, Woodruff JM, Brennan MF.
Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients.
Ann Surg. 1993 Jan;217(1):72-7. doi: 10.1097/00000658-199301000-00012.
Abstract/Text
To examine the natural history of lymph node metastasis from sarcomas and the utility of therapeutic lymphadenectomy, clinical histories of all adult patients identified by a prospective sarcoma database for the 10-year period July 1982 to July 1991 were examined. Of the 1772 sarcoma patients, 46 (2.6%) were identified with lymph node metastasis. Median follow-up of all patients from diagnosis of lymph node metastasis was 12.9 months (range, 0 to 100 months). Median survival for nonsurvivors was 12.7 months (range, 0 to 40.7). The tumor types with the highest incidence of lymph node metastasis are angiosarcoma (5/37 total cases; 13.5%), embryonal rhabdomyosarcoma (ERMS) (12/88 total cases; 13.6%), and epithelioid sarcoma (2/12 total cases; 16.7%). Lymph node metastasis from visceral primary (p = 0.004) and malignant fibrous histiocytomas (p = 0.006) were associated with particularly poor prognosis. Thirty-one patients underwent radical, therapeutic lymphadenectomy with curative intent, whereas 15 patients had less than curative procedures, in most cases biopsy only. Patients not treated with radical lymphadenectomy had a median survival of 4.3 months (range, 1 to 32) whereas radical lymphadenectomy was associated with a 16.3 month median survival and the only long-term survivors (46% 5-year survival by Kaplan-Meier). The authors conclude that lymph node metastases from sarcoma are rare in adults, but vigilance is warranted, especially in angiosarcoma, ERMS, and epithelioid subtypes. Radical lymphadenectomy is appropriate treatment for isolated metastasis to regional lymph nodes and may provide long-term survival.
Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H.
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.
N Engl J Med. 2002 Aug 15;347(7):472-80. doi: 10.1056/NEJMoa020461.
Abstract/Text
BACKGROUND: Constitutive activation of KIT receptor tyrosine kinase is critical in the pathogenesis of gastrointestinal stromal tumors. Imatinib mesylate, a selective tyrosine kinase inhibitor, has been shown in preclinical models and preliminary clinical studies to have activity against such tumors.
METHODS: We conducted an open-label, randomized, multicenter trial to evaluate the activity of imatinib in patients with advanced gastrointestinal stromal tumor. We assessed antitumor response and the safety and tolerability of the drug. Pharmacokinetics were assessed in a subgroup of patients.
RESULTS: A total of 147 patients were randomly assigned to receive 400 mg or 600 mg of imatinib daily. Overall, 79 patients (53.7 percent) had a partial response, 41 patients (27.9 percent) had stable disease, and for technical reasons, response could not be evaluated in 7 patients (4.8 percent). No patient had a complete response to the treatment. The median duration of response had not been reached after a median follow-up of 24 weeks after the onset of response. Early resistance to imatinib was noted in 20 patients (13.6 percent). Therapy was well tolerated, although mild-to-moderate edema, diarrhea, and fatigue were common. Gastrointestinal or intraabdominal hemorrhage occurred in approximately 5 percent of patients. There were no significant differences in toxic effects or response between the two doses. Imatinib was well absorbed, with pharmacokinetics similar to those reported in patients with chronic myeloid leukemia.
CONCLUSIONS: Imatinib induced a sustained objective response in more than half of patients with an advanced unresectable or metastatic gastrointestinal stromal tumor. Inhibition of the KIT signal-transduction pathway is a promising treatment for advanced gastrointestinal stromal tumors, which resist conventional chemotherapy.
Copyright 2002 Massachusetts Medical Society
