GIST: Current knowledge and treatment modalities
Authors:
J. Páral 1,2; P. Lochman 1,2; H. Kalábová 3; D. Hadži-Nikolov 4
Authors‘ workplace:
Katedra válečné chirurgie, Fakulta vojenského zdravotnictví Hradec Králové, Univerzita obrany Brno, vedoucí katedry: Doc. MUDr. Leo Klein, CSc.
1; Chirurgická klinika, Fakultní nemocnice a Lékařská fakulta Univerzity Karlovy v Hradci Králové, přednosta: Prof. MUDr. Alexander Ferko, CSc.
2; Klinika onkologie a radioterapie, Fakultní nemocnice a Lékařská fakulta Univerzity Karlovy, v Hradci Králové, přednosta: Prof. MUDr. Jiří Petera, Ph. D.
3; Fingerlandův ústav patologie, Fakultní nemocnice a Lékařská fakulta Univerzity Karlovy, v Hradci Králové, přednosta: Prof. MUDr. Aleš Ryška, Ph. D.
4
Published in:
Rozhl. Chir., 2012, roč. 91, č. 4, s. 189-198.
Category:
Review
Overview
GISTs represent a specific group of mesenchymal tumors with unpredictable biological features. Approximately 30% of newly diagnosed GIST tumors are malignant or have a high potential for malignancy. Currently, GISTs are routinely identified using histological, immunohistochemical, and molecular genetic assays. However, clinical diagnosis, particularly of small or intramural GISTs, might be difficult. Endoscopic examinations and fused PET/CT imaging are the most useful techniques for imaging and monitoring the disease progression.
Surgical treatment is the first-line treatment and the only method that might lead to full remission in patients with primary GISTs. At the present time, there is no consensus on the issues whether to perform resections in patients with positive margins and resections of metastases. Biological therapy with imatinib mesylate is recommended in patients with newly diagnosed, locally advanced, inoperable, or metastasizing gastrointestinal GISTs that express the c-KIT protein. Treatment may reduce a primary tumor to a size small enough for surgical excision. Current research is focused on the development of new therapies for the treatment of advanced disease and/or disease prophylaxis.
Key words:
stromal – tumor – morphology – diagnostics – treatment
Sources
1. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 2005;29:52–68.
2. Goettsch WG, Bos SD, Breekveldt-Postma N, Casparie M, Herings RM, Hogendoorn PC. Incidence of gastrointestinal stromal tumors is underestimated: Results of a nation-wide study. Eur J Cancer 2005;41:2868–2872.
3. Nilsson B, Bümming P, Meis-Kindblom JM, Odén A, Dortok A, Gustavsson, Sablinska K, Kindblom LG. Gastrointestinal stromal tumors: The incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era. Cancer 2005;103:821–829.
4. Prakash S, Sarran L, Socci N, DeMatteo RP, Eisenstat J, Greco AM, Maki RG, Wexler LH, LaQuaglia MP, Besmer P, Antonescu CR. Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature. J Pediatr Hematol Oncol 2005;27:179–187.
5. Stout AP. Bizarre smooth muscle tumors of the stomach. Cancer 1962;15:400–409.
6. Mazur MT, Clark HB. Gastric stromal tumors. Reappraisal of histogenesis. Am J Surg Pathol 1983;7:507–519.
7. Sircar K, Hewlett BR, Huizinga JD, Chorneyko K, Berezin I, Riddell RH. Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors. Am J Surg Pathol 1999;23:377–389.
8. Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 1998;152:1259–1269.
9. 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;279:577–580.
10. Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, Miettinen M. CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol 1998;11:728–34.
11. Besmer P, Murphy JE, George PC, Qiu FH, Bergold PJ, Lederman L, Snyder HW Jr, Brodeur D, Zuckerman EE, Hardy WD. A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. Nature 1986;320:415–421.
12. Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J 1987;6:3341–3351.
13. Hirota S, Ohashi A, Nishida T, Isozaki K, Kinoshita K, Shinomura Y, Kitamura Y. Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology 2003;125:660–667.
14. Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA. PDGFR – activating mutations in gastrointestinal stromal tumors. Science 2003;299:708–710.
15. Pauls K, Merkelbauch-Bruse S, Thal D, Buttner R, Wardelmann E. PDGFRalpha- and c-kit-mutated gastrointestinal stromal tumors (GISTs) are characterized by distinctive histological and immunohistochemical features. Histopathology 2005;46:166–175.
16. 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;347:472–480.
17. Hemmi A, Inaniwa Y, Ohnop S, Fujii Y, Terada N, Mitsumata M, Nemoto N. Relationship between skeinoid fibers and stromal matrix in gastrointestinal stromal tumors: morphometric analysis with quick-freezing and deep-etching method. Pathol Int 2001;51:338–48.
18. Debiec-Rychter M, Pauwels P, Lasota J, Franke S, De Vos R, De Wever, Hagemeijer A, Sciot R. Complex genetic alterations in gastrointestinal stromal tumors with autonomic nerve differentiation. Mod Pathol 2002;15:692–698.
19. Vandenbark GR, Decastro CM, Taylor H, Dew-Knight S, Kaufman RE. Cloning and structural analysis of the human c-kit gene. Oncogene 1992;7:1259–1266.
20. Miettinen M, Lasota J. Gastrointestinal stromal tumors-definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 2001;438:1–12.
21. Heinrich MC, Rubin BP, Longley BJ, Fletcher JA. Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol 2002;33:484–495.
22. Rubin BP, Heinrich MC, Corles CL, Gastrointestinal stromal tumour. Lancet 2007;369:1731–1741.
23. Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003;21:4342–4349.
24. Casali PG, Jost L, Reichardt P, Schlemmer M, Blay JY. ESMO Guidelines Working Group. Gastrointestinal stromal tumours: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2009;20,(4 Suppl):64–67.
25. Genome sequencing, Humane genome project information, 2009 http://www.ornl.gov/sci/techresources/Human_Genome/faq/seqfacts.shtml. Accessed January 7, 2009.
26. Espinosa I, Lee CH, Kim MK, Rouse BT, Subramanian S, Montgomery K, Varma S, Corless CL, Heinrich MC, Smith KS, Wang Z, Rubin B, Nielsen TO, Setz RS, Ross DT, West RB, Cleary ML, Van De Rijn M. A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors. Am J Surg Pathol 2008;32:210–218.
27. West RB, Corless CL, Chen X, Rubin BP, Subramanian S, Montgomery K, Zhu S, Ball CA, Nielsen TO, Patel R, Goldblum JR, Brown PO, Heinrich MC, Van De Rijn M. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 2004;165:107–113.
28. Li FP, Fletcher JA, Heinrich MC, Garber JE, Sallan SE, Curiel-Lewandrowski C, Duensing A, van de Rijn M, Schnipper LE, Demetri GD. Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred. J Clin Oncol 2005;23:2735–2743.
29. Chompret A, Kannengiesser C, Barrois M, Terrier P, Dahan P, Tursz T, Lenoir GM, Bressac-De Paillerets B. PDGFRA germline mutation in a family with multiple cases of gastrointestinal stromal tumor. Gastroenterology 2004;126:318–321.
30. Hirota S, Nishida T, Isozaki K, Taniguchi M, Nishikawa K, Ohashi A, Takabayashi A, Obayashi T, Okuno T, Kinoshita K, Chen H, Shinomura Y, Kitamura Y. Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene. Gastroenterology 2002;122:1493–1499.
31. Carney JA. Gastric stromal sarcoma, pulmonary chondroma, and extra-adrenal paraganglioma (Carney Triad): natural history, adrenocortical component, and possible familial occurrence. Mayo Clin Proc 1999;74:543–552.
32. Knop S, Schupp M, Wardelmann E, Stueker D, Horger MS, Kanz L, Einsele H, Kroeber SM. A new case of Carney triad: gastrointestinal stromal tumors and leiomyoma of the oesophagus do not show activating mutations of KIT and platelet-derived growth factor receptor alpha. J Clin Pathol 2006;59:1097–1099.
33. McWhinney SR, Pasini B, Stratakis CA. Familial gastrointestinal stromal tumors and germ-line mutations. N Engl J Med 2007;357:1054–1056.
34. Takazawa Y, Sakurai S, Sakuma Y, Ikeda T, Yamaguchi J, Hashizume Y, Yokoyama S, Motegi A, Fukayama M. Gastrointestinal stromal tumors of neurofibromatosis type I (von Recklinghausen’s disease). Am J Surg Pathol 2005;29:755–763.
35. Miettinen M, Lasota J, Sobin LH. Gastrointestinal stromal tumors of the stomach in children and young adults: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases with long-term follow-up and review of the literature. Am J Surg Pathol 2005;29:1373–1381.
36. Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1458 cases from 1992 to 2000. Am J Gastroenterol 2005;100:162–168.
37. 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;231:51–58.
38. Matsui N, Akahoshi K, Motomura Y, Kubokawa M, Kimura M, Ohuchi J, Honda K, Murata A, Endoh S, Miyazaki M, Oya M, Nakano S, Nakamura K. Endosonographic detection of dumbbell-shaped jejunal GIST using double balloon enteroscopy. Endoscopy 2008;40(2 Suppl):38–39.
39. Lok KH, Lai L, Yiu HL, Szeto ML, Leung SK. Endosonographic surveillance of small gastrointestinal tumors originating from muscularis propria. J Gastrointestin Liver Dis 2009;18:177–180.
40. Da Ronch T, Modesto A, Bazzocchi M. Gastrointestinal stromal tumor: spiral computed tomography features and pathologic correlation. Radiol Med 2006,111:661–673.
41. Van den Abbeele AD. The lessons of GIST-PET and PET/CT: a new paradigm for imaging. Oncologist 2008;13(2 Suppl):8–13.
42. Otani Y, Furukawa T, Yoshida M, Saikawa Y, Wada N, Ueda M, Kubota T, Mukai M, Kameyama K, Sugino Y, Kumai K, Kitajima M. Operative indications for relatively small (2-5 cm) gastrointestinal stromal tumor of the stomach based on analysis of 60 operated cases. Surgery 2006;139:484–492.
43. Hassan I, You YN, Shyyan R, Dozois EJ, Smyrk TC, Okuno SH, Schleck CD, Hodge DO, Donohue JH. Surgically managed gastrointestinal stromal tumors: a comparative and prognostic analysis. Ann Surg Oncol 2008;15:52–59.
44. 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 report: management of patients with gastrointestinal stromal tumor (GIST)-update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw 2007; 5(2 Suppl):1–29.
45. Ng EH, Pollock RE, Munsell MF, Atkinson EN, Romsdahl MM. Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg 1992;215:68–77.
46. Sexton JA, Pierce RA, Halpin VJ, Eagon JC, Hawkins WG, Linehan DC, Brunt LM, Frisella MM, Matthews BD. Laparoscopic gastric resection for gastrointestinal stromal tumors. Surg Endosc 2008;22:258–267.
47. 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;217:72–77.
48. Chen H, Pruitt A, Nicol TL, Gorgulu S, Choti MA. Complete hepatic resection of metastases from leiomyosarcoma prolongs survival. J Gastrointest Surg 1998;2:151–155.
49. Choi WH, Kim S, Hyung WJ, Yu JS, Park CI, Choi SH, Noh SH. Long-surviving patients with recurrent GIST after receiving cytoreductive surgery with imatinib therapy. Yonsei Med J 2009;50:437–440.
50. Ledo-Rodríguez A, Ulla-Rocha JL, Baltar-Arias R, Vázquez-Rodríguez S, Díaz-Saa W, González-Carrera V, Ledo-Barro L, Vázquez-Astray E. Endoscopic resection of rectal gastrointestinal stromal tumor (GIST) using band ligation. Rev Esp Enferm Dig 2009;101:870–871.
51. Kakushima N, Fujishiro M. Endoscopic submucosal dissection for gastrointestinal neoplasms. World J Gastroenterol 2008;14:2962– –2967.
52. Duffaud F, Le Cesne A. Imatinib in the treatment of solid tumors. Target Oncol 2009;4:45–56.
53. DeMatteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumor: a randomised, double-blind, placebo-controlled trial. Lancet 2009;373:1097–1104.
54. Gold JS, DeMatteo RP. Combined surgical and molecular therapy: the gastrointestinal stromal tumor model. Ann Surg 2006; 244:176–184.
55. Blay JY, Le Cesne A, Bui B, Duffaud F, Delbaldo C, Adenis A, Viens P, Rios M, Bompas E, Cupissol D, Guillemet C, Kerbrat P, Fayette J, Chabaud S, Berthaud P, Perol D. Prospective multicenter randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: The French Sarmoma Group. J Clin Oncol 2007;25:1107–1113.
56. Van Glabbeke M, Verweij J, Casali PG, Le Cesne A, Hohenberger P, Ray-Coquard I, Schlemmer M, van Oosterom AT, Goldstein D, Sciot R, Hogendoorn PC, Brown M, Bertulli R, Judson IR. Initial and late resistances to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group study. J Clin Oncol 2005;23:5795–5804.
57. Demetri GD, Heinrich MC, Fletcher JA, Fletcher CD, Van den Abbeele AD, Corless CL, Antonescu CR, George S, Morgan JA, Chen MH, Bello CL, Huang X, Cohen DP, Baum CM, Maki RG. Molecular target modulation, imaging, and clinical evaluation of gastrointestinal stromal tumor patients treated with sunitinib malate after imatinib failure. Clin Cancer Res 2009;15:5902–5909.
58. Chow LQ, Eckhardt SG. Sunitinib: from rational design to clinical efficacy. J Clin Oncol 2007;25:884–896.
59. George S, Blay JY, Casali PG, Le Cesne A, Srephenson P, Deprimo SE, Harmon CS, Law CN, Morgan JA, Raycoquard I, Tassell V, Cohen DP, Demetri GD. Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur J Cancer 2009;45:1959–1968.
60. Demetri GD, Casali PG, Blay JY, von Mehren M, Morgan JA, Bertulli R, Ray-Coquard I, Cassier P, Davey M, Borghaei H, Pink D, Debiec-Rychter M, Cheung W, Bailey SM, Veronese ML, Reichardt A, Fumagalli E, Reichardt P. A phase I study of single-agent nilotinib or in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res 2009;15:5910–5916.
61. Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumor after failure of imatinib: a randomised controlled trial. Lancet 2006;368:1329–1338.
62. Miettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med 2006;130:1466–1478.
63. Yokoi K, Tanaka N, Shoji K, Ishikawa N, Seya T, Horiba K, Kanazawa Y, Yamashita K, Ohaki Y, Tajiri T. A study of histopathological assessment criteria for assessing malignancy of gastrointestinal stromal tumor, from a clinical standpoint. J Gastroenterol 2005;40:467–473.
64. Longley BJ, Reguera MJ, Ma Y. Classes of c-kit activating mutations: proposed mechanisms of action and implications for disease classification and therapy. Leuk Res 2001;25:571–576.
65. Debiec-Rychter M, Dumez H, Judson I, Wasag B, Verweij J, Brown M, Dimitrijevic S, Sciot R, Stul M, Vranck H, Scurr M, Hagemeijer A, Van Glabbeke M, van Oosterom AT. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumors entered on phase I and II studies of the EORTC soft tissue and bone sarcoma group. Eur J Cancer 2004;40:689–695.
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