Surgical debulking of gastrointestinal stromal tumors: Is it a reasonable option after second-line treatment with sunitinib?

  • M. A. Pantaleo
  • M. Di Battista
  • F. Catena
  • M. Astorino
  • M. Saponara
  • V. Di Scioscio
  • D. Santini
  • G. Piazzi
  • P. Castellucci
  • G. Brandi
  • G. Biasco
Rapid Communication

Abstract

Introduction

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.

Results

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.

Conclusions

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.

Keywords

Gastrointestinal stromal tumors Sunitinib Imatinib TK inhibitors Surgery 

Notes

Acknowledgments

We thank CARISBO (Fondazione Cassa di Risparmio Bologna) for supporting the research programs on gastrointestinal stromal tumors (GISTs)

References

  1. Andersson J, Bümming P, Meis-Kindblom JM, Sihto H, Nupponen N, Joensuu H, Odén A, Gustavsson B, Kindblom LG, Nilsson B (2006) Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis. Gastroenterology 130:1573–1581PubMedCrossRefGoogle Scholar
  2. Andtbacka RH, Ng CS, Scaife CL, Cormier JN, Hunt KK, Pisters PW, Pollock RE, Benjamin RS, Burgess MA, Chen LL, Trent J, Patel SR, Raymond K, Feig BW (2007) Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol 14:14–24PubMedCrossRefGoogle Scholar
  3. 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
  4. Benjamin RS, Blanke CD, Blay JY, Bonvalot S, Eisenberg B (2006) Management of gastrointestinal stromal tumors in the imatinib era: selected case studies. Oncologist 11:9–20PubMedCrossRefGoogle Scholar
  5. Bonvalot S, Eldweny H, Pechoux CL, Vanel D, Terrier P, Cavalcanti A, Robert C, Lassau N, Cesne AL (2006) Impact of surgery on advanced gastrointestinal stromal tumors (GIST) in the imatinib era. Ann Surg Oncol 13:1596–1603PubMedCrossRefGoogle Scholar
  6. DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF (2000) Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 231:51–58PubMedCrossRefGoogle Scholar
  7. DeMatteo RP, Maki RG, Singer S, Gonene M, Brennan MF, Antonescu CR (2007) Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor. Ann Surg 245:347–352PubMedCrossRefGoogle Scholar
  8. 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
  9. 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
  10. Gronchi A, Fiore M, Miselli F, Lagonigro MS, Coco P, Messina A, Pillotti S, Casali PG (2007) Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg 245:341–346PubMedCrossRefGoogle Scholar
  11. 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
  12. 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
  13. Jamali FK, Drawiche SS, El-Kinge N, Tawil A, Soweid AM (2007) Disease progression following imatinib failure in gastrointestinal stromal tumors: role of surgical therapy. Oncologist 12:438–442PubMedCrossRefGoogle Scholar
  14. Lux ML, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri G, Xiao S, Singer S, Fletcher CD, Fletcher JA (2000) KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol 156:791–795PubMedGoogle Scholar
  15. 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
  16. Ozguc H, Yilmazlar T, Yerci O, Soylu R, Tumay V, Filiz G, Zorluoglu A (2005) Analysis of prognostic and immunohistochemical factors in gastrointestinal stromal tumors with malignant potential. J Gastrointest Surg 9:418–429PubMedCrossRefGoogle Scholar
  17. Pierie JP, Choudry U, Muzikansky A, Yeap BY, Souba WW, Ott MJ (2001) The effect of surgery and grade on outcome of gastrointestinal stromal tumors. Arch Surg 136:383–389PubMedCrossRefGoogle Scholar
  18. Raut CP, Posner M, Desai J, Morgan JA, George S, Zahrieh G, Fletcher CD, Demetri GD, Bertagnolli MM (2006) Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol 24:2325–2331PubMedCrossRefGoogle Scholar
  19. 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
  20. 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
  21. 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
  22. 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
  23. Wu PC, Langerman A, Ryan CW, Hart J, Swiger S, Posner MC (2003) Surgical treatment of gastrointestinal stromal tumors in the imatinib era. Surgery 134:665–666CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • M. A. Pantaleo
    • 1
  • M. Di Battista
    • 1
  • F. Catena
    • 2
  • M. Astorino
    • 1
  • M. Saponara
    • 1
  • V. Di Scioscio
    • 3
  • D. Santini
    • 4
  • G. Piazzi
    • 5
  • P. Castellucci
    • 6
  • G. Brandi
    • 1
  • G. Biasco
    • 1
  1. 1.Institute of Hematology and Medical Oncology “L. A. Seragnoli”, Sant’ Orsola-Malpighi HospitalUniversity of BolognaBolognaItaly
  2. 2.Emergency Surgery and Transplant Department, Sant’Orsola-Malpighi HospitalUniversity of BolognaBolognaItaly
  3. 3.Department of Radiology, Sant’ Orsola-Malpighi HospitalUniversity of BolognaBolognaItaly
  4. 4.Department of Pathology, Sant’ Orsola-Malpighi HospitalUniversity of BolognaBolognaItaly
  5. 5.Centre of Applied Biomedical Research (CRBA), Sant’Orsola-Malpighi HospitalUniversity of BolognaBolognaItaly
  6. 6.Nuclear Medicine Service, Sant’Orsola-Malpighi HospitalUniversity of BolognaBolognaItaly

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