Surgical debulking of gastrointestinal stromal tumors: Is it a reasonable option after second-line treatment with sunitinib?
- 132 Downloads
After imatinib treatment, the surgical management of patients affected by gastrointestinal stromal tumor (GIST) has been widely reported and often considered by many oncologists in clinical practice. Surgical results are correlated with disease responsiveness to tyrosine kinase inhibitors and with complete extirpation of all tumor sites. By now, no report specifically addressing surgical management after second-line treatment with sunitinib is still available. Most patients have an unresectable disease and do not have any other therapeutical options except for clinical trials.
Materials and methods
We report two clinical cases of patients with metastatic GISTs, who underwent surgery after sunitinib, and discuss the surgical management option in this clinical setting.
Both our patients had a long, durable stable disease on sunitinib, but one developed a chronic mild bleeding that does not call for emergency surgical interventions and the other one developed chronic heart toxicity. They were proposed to undergo surgery despite the unresectable diseases and received an incomplete resection because of residual metastatic lesions. They restarted sunitinib after surgery.
The poor prognosis after sunitinib treatment and the absence of alternative validated options open the debate on the assessment of surgical management of metastatic GISTs in this setting. The role of surgery should be investigated in clinical trials; however, the enrollment may be difficult. In clinical practice and after a multidisciplinary case patient discussion, surgery could represent a reasonable choice for advanced GISTs especially if the risk of surgery-related death is not too high.
KeywordsGastrointestinal stromal tumors Sunitinib Imatinib TK inhibitors Surgery
We thank CARISBO (Fondazione Cassa di Risparmio Bologna) for supporting the research programs on gastrointestinal stromal tumors (GISTs)
- Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, Leversha MA, Jeffrey PD, Desantis D, Singer S, Brennan MF, Maki RG, DeMatteo RP (2005) Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 11:4182–4190PubMedCrossRefGoogle Scholar
- Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janiceck M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347:472–480PubMedCrossRefGoogle Scholar
- 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 (2006) Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368:1329–1338PubMedCrossRefGoogle Scholar
- Haller F, Dekten S, Schulten H-J, Happel N, Gunawan B, Kuhlgatz J, Fuzesi L (2007) Surgical management after neoadjuvant imatinib therapy in gastrointestinal stromal tumors (GIST) with respect to imatinib resistance caused by secondary KIT mutations. Ann Surg Oncol 14:526–532PubMedCrossRefGoogle Scholar
- Heinrich MC, Corless CL, Demetri GD, Balnke 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, Silkerman S, Dimitrijevic S, Fletcher JA (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21:4342–4349PubMedCrossRefGoogle Scholar
- Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B, Sablinska K, Kindblom LG (2005) Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era—a population-based study in western Sweden. Cancer 103:821–829PubMedCrossRefGoogle Scholar
- Rutkowski P, Nowecki Z, Nyckowski P, Dziewirski W, Grzesiakowska U, Naisierowska-Guttmejer A, Krawczyck M, Ruka W (2006) Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. J Surg Oncol 93:304–311PubMedCrossRefGoogle Scholar
- Scaife CL, Hunt KK, Patel SR, Benjamin RS, Benjamin RS, Burgess MA, Chen LL, Trent J, Raymond AK, Cormier JN, Pisters PW, Pollock RE, Feig BW (2003) Is there a role for surgery in patients with unresectable cKIT+ gastrointestinal stromal tumors treated with imatinib mesylate? Am J Surg 186:665–669PubMedCrossRefGoogle Scholar
- Tamborini E, Bonadiman L, Greco A, Albertini V, Neri T, Gronchi A, Bertulli R, Colecchia M, Casali PG, Pierotti MA, Pilotti S (2004) A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology 127:294–299PubMedCrossRefGoogle Scholar
- Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay YJ, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, Bertulli R, Judson I (2004) Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 364:1127–1134PubMedCrossRefGoogle Scholar