The online version of this article (doi:10.1186/1477-7819-10-111) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
Study concepts and design: RT, JW. Data acquisition: RT. Data analysis and interpration: All authors. Statistical analysis: RT, JW. Manuscript preparation: RT, CV, JW. Manuscript review: All authors. All authors read and approved the final manuscript.
Standard treatment for metastatic gastrointestinal stromal tumors (GISTs) is systemic therapy with imatinib. Surgery is performed to remove metastatic lesions to induce long-term remission or even curation. In other patients, surgery is performed to remove (focal) progressive or symptomatic lesions. The impact and long-term results of surgery after systemic therapy have not been clearly defined.
Between September 2001 and May 2010, all patients with metastatic GIST who underwent surgery for metastatic GIST after systemic therapy (that is, imatinib and sunitinib) at four Dutch specialized institutions were included. Primary end-points were progression-free survival (PFS) and overall survival (OS).
All 55 patients underwent surgery after treatment with systemic therapy. At the last follow-up, tumor recurrence or progression was noted after surgery in 48% of the patients who responded on systemic therapy, and in 85% of the patients who were treated while having progressive disease. Median PFS and OS were not reached in the group of responders. In the non-responders group PFS and OS were median 4 and 25 months, respectively. Response on systemic therapy and a surgical complete resection were significantly correlated to PFS and OS.
Surgery may play a role in responding patients. In patients with progressive disease, the role of surgery is more difficult to distinguish in this retrospective analysis since PFS is short. Which patients benefit and whether this improves long-term outcome should be established in a multicentric randomized trial.
Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, Bertulli R, Judson I: Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004, 364: 1127-1134. 10.1016/S0140-6736(04)17098-0. CrossRefPubMed
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. 10.1126/science.279.5350.577. CrossRefPubMed
van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, Martens M, Webb A, Sciot R, Van Glabbeke M, Silberman S, Nielsen OS, European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group: Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet. 2001, 358: 1421-1423. 10.1016/S0140-6736(01)06535-7. CrossRefPubMed
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. 10.1056/NEJMoa020461. CrossRefPubMed
Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, Raymond AK, Bramwell VH, Baker LH, Maki RG, Tanaka M, Hecht JR, Heinrich MC, Fletcher CD, Crowley JJ, Borden EC: Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008, 26: 626-632. 10.1200/JCO.2007.13.4452. CrossRefPubMed
Wardelmann E, Merkelbach-Bruse S, Pauls K, Thomas N, Schildhaus HU, Heinicke T, Speidel N, Pietsch T, Buettner R, Pink D, Reichardt P, Hohenberger P: Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res. 2006, 12: 1743-1749. 10.1158/1078-0432.CCR-05-1211. CrossRefPubMed
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 tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006, 368: 1329-1338. 10.1016/S0140-6736(06)69446-4. CrossRefPubMed
Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, Corless CL, Fletcher CD, Roberts PJ, Heinz D, Wehre E, Nikolova Z, Joensuu H: Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol. 2008, 26: 620-625. 10.1200/JCO.2007.13.4403. CrossRefPubMed
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 resistance 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. 10.1200/JCO.2005.11.601. CrossRefPubMed
Raut CP, Posner M, Desai J, Morgan JA, George S, Zahrieh D, Fletcher CD, Demetri GD, Bertagnolli MM: Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 2006, 24: 2325-2331. 10.1200/JCO.2005.05.3439. CrossRefPubMed
Rutkowski P, Nowecki Z, Nyckowski P, Dziewirski W, Grzesiakowska U, Nasierowska-Guttmejer A, Krawczyk M, Ruka W: Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. J Surg Oncol. 2006, 93: 304-311. 10.1002/jso.20466. CrossRefPubMed
Duffaud F, Therasse P: New guidelines to evaluate the response to treatment in solid tumors. Bull Cancer. 2000, 87: 881-886. PubMed
Blay JY, Le Cesne A, Ray-Coquard I, 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 multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol. 2007, 25: 1107-1113. 10.1200/JCO.2006.09.0183. CrossRefPubMed
Le Cesne A, Perol D, Ray-Coquard I, Bui B, Duffaud F, Rios M, Coindre JM, Emile JF, Berthaud P, Blay JY: Interruption of imatinib (IM) in GIST patients with advanced disease: Updated results of the prospective French Sarcoma Group randomized phase III trial on survival and quality of life. J Clin Oncol (Meeting Abstracts). 2005, 23: 9031- CrossRef
Le Cesne A, Van Glabbeke M, Verweij J, Casali PG, Findlay M, Reichardt P, Issels R, Judson I, Schoffski P, Leyvraz S, Bui B, Hogendoorn PC, Sciot R, Blay JY: Absence of progression as assessed by response evaluation criteria in solid tumors predicts survival in advanced GI stromal tumors treated with imatinib mesylate: the intergroup EORTC-ISG-AGITG phase III trial. J Clin Oncol. 2009, 27: 3969-3974. 10.1200/JCO.2008.21.3330. PubMedCentralCrossRefPubMed
Choi H, Charnsangavej C, de Castro Faria S, Tamm EP, Benjamin RS, Johnson MM, Macapinlac HA, Podoloff DA: 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: 1619-1628. CrossRefPubMed
Mearadji A, den Bakker MA, van Geel AN, Eggermont AM, Sleijfer S, Verweij J, de Wilt JH, Verhoef C: Decrease of CD117 expression as possible prognostic marker for recurrence in the resected specimen after imatinib treatment in patients with initially unresectable gastrointestinal stromal tumors: a clinicopathological analysis. Anticancer Drugs. 2008, 19: 607-612. 10.1097/CAD.0b013e32830138f9. CrossRefPubMed
Raut CP, Wang Q, Manola J, Morgan JA, George S, Wagner AJ, Butrynski JE, Fletcher CD, Demetri GD, Bertagnolli MM: Cytoreductive surgery in patients with metastatic gastrointestinal stromal tumor treated with sunitinib malate. Ann Surg Oncol. 2010, 17: 407-415. 10.1245/s10434-009-0784-y. CrossRefPubMed
- Surgery after treatment with imatinib and/or sunitinib in patients with metastasized gastrointestinal stromal tumors: is it worthwhile?
Frits van Coevorden
Henk H Hartgrink
Johannes J Bonenkamp
Winette T van der Graaf
Johannes H W de Wilt
- BioMed Central
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