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Journal of Gastrointestinal Cancer

, Volume 50, Issue 4, pp 750–758 | Cite as

Outcomes After Surgical Resection Differ by Primary Tumor Location for Metastatic Gastrointestinal Stromal Tumors (GISTs): a Propensity Score Matching Population Study

  • Apostolos GaitanidisEmail author
  • Michail Alevizakos
  • Alexandra Tsaroucha
  • Michail Pitiakoudis
Original Research
  • 100 Downloads

Abstract

Purpose

Primary tumor location has been identified as an important prognostic factor among patients with gastrointestinal stromal tumors (GISTs). The purpose of this study is to identify how primary tumor location may affect outcomes after resection for patients with metastatic GISTs.

Methods

Patients with GISTs and distant metastases at diagnosis were identified in the Surveillance Epidemiology and End Results (SEER) database. Patients that underwent surgery were matched to patients that did not undergo surgery using propensity score matching (PSM) analysis.

Results

After PSM, 570 patients were identified (males 334 [58.6%], females 236 [41.4%], age 62 ± 13.9 years). Gastric tumors constituted the majority (325 [57%]), followed by small intestinal (136 [23.9%]), colorectal (19 [3.3%]), and retroperitoneal/peritoneal tumors (23 [4%]). Median follow-up was 25.5 months (95% CI 23–29 months). Undergoing surgery was associated with improved disease-specific survival (DSS) on both univariate (median not reached vs. 51 months, p < 0.001) and multivariate analyses (HR 4.98, 95% CI 2.23–11.12, p < 0.001). A sub-analysis of patients with gastric GISTs showed that undergoing surgery was the only significant factor associated with improved DSS (median not reached vs. 39 months, p < 0.001, HR 2.95, 95% CI 1.92–4.53). In contrast, undergoing surgery was not associated with improved survival for small intestinal, colorectal, or retroperitoneal/peritoneal tumors.

Conclusions

Surgery for gastric metastatic GISTs is associated with improved survival. No discernible benefit after surgical resection was identified for patients with small intestinal, colorectal, retroperitoneal, or peritoneal metastatic GISTs.

Keywords

Gastrointestinal stromal tumors GIST Sarcoma Metastases 

Notes

Acknowledgments

All the authors that contributed in the preparation of this manuscript have been mentioned.

Compliance with Ethical Standards

Conflict of Interest

The authors have nothing to disclose.

References

  1. 1.
    Ma GL, Murphy JD, Martinez ME, Sicklick JK. Epidemiology of gastrointestinal stromal tumors in the era of histology codes: results of a population-based study. Cancer Epidemiol Biomark Prev. 2015;24:298–302.CrossRefGoogle Scholar
  2. 2.
    Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol. 2005;100:162–8.CrossRefGoogle Scholar
  3. 3.
    Nilsson B, Bümming P, Meis-Kindblom JM, Odén A, Dortok A, Gustavsson B, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era. Cancer. Wiley Subscription Services, Inc., A Wiley Company. 2005;103:821–9.CrossRefGoogle Scholar
  4. 4.
    Roberts PJ, Eisenberg B. Clinical presentation of gastrointestinal stromal tumors and treatment of operable disease. Eur J Cancer. 2002;38:S37–8.CrossRefGoogle Scholar
  5. 5.
    Ford SJ, Gronchi A. Indications for surgery in advanced/metastatic GIST. Eur J Cancer. 2016;63:154–67.CrossRefGoogle Scholar
  6. 6.
    Fletcher CDM, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Int J Surg Pathol.Sage Publications Sage CA: Thousand Oaks. 2002;10:81–9.CrossRefGoogle Scholar
  7. 7.
    Lasota J, Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diagn Pathol. 2006;23:91–102.CrossRefGoogle Scholar
  8. 8.
    Demetri GD, von Mehren M, Antonescu CR, DeMatteo RP, Ganjoo KN, Maki RG, et al. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Cancer Netw. NIH Public Access. 2010;Suppl 2:S1–41.Google Scholar
  9. 9.
    Frankel TL, Chang AE, Wong SL. Surgical options for localized and advanced gastrointestinal stromal tumors. J Surg Oncol. 2011;104:882–7.CrossRefGoogle Scholar
  10. 10.
    Dagher R, Cohen M, Williams G, Rothmann M, Gobburu J, Robbie G, et al. Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin Cancer Res. 2002;8:3034–8.PubMedGoogle Scholar
  11. 11.
    DeMatteo RP, Ballman KV, Antonescu CR, Corless C, Kolesnikova V, von Mehren M, et al. Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor. Ann Surg. 2013;258:422–9.CrossRefGoogle Scholar
  12. 12.
    Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schütte J, et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor. JAMA. 2012;307:1265–72.CrossRefGoogle Scholar
  13. 13.
    Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hartmann JT, Pink D, et al. Adjuvant imatinib for high-risk GI stromal tumor: analysis of a randomized trial. J Clin Oncol. American Society of Clinical Oncology. 2016;34:244–50.CrossRefGoogle Scholar
  14. 14.
    Raut CP, Posner M, Desai J, Morgan JA, George S, Zahrieh D, et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. American Society of Clinical Oncology. 2006;24:2325–31.CrossRefGoogle Scholar
  15. 15.
    Andtbacka RHI, Ng CS, Scaife CL, Cormier JN, Hunt KK, Pisters PWT, et al. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol. 2006;14:14–24.CrossRefGoogle Scholar
  16. 16.
    Rutkowski P, Nowecki Z, Nyckowski P, Dziewirski W, Grzesiakowska U, Nasierowska-Guttmejer A, et al. Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. J Surg Oncol. Wiley Subscription Services, Inc., A Wiley Company. 2006;93:304–11.CrossRefGoogle Scholar
  17. 17.
    DeMatteo RP, Maki RG, Singer S, Gonen M, Brennan MF, Antonescu CR. Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor. Ann Surg. 2007;245:347–52.CrossRefGoogle Scholar
  18. 18.
    Colombo C, Ronellenfitsch U, Yuxin Z, Rutkowski P, Miceli R, Bylina E, et al. Clinical, pathological and surgical characteristics of duodenal gastrointestinal stromal tumor and their influence on survival: a multi-center study. Ann Surg Oncol. Springer-Verlag. 2012;19:3361–7.CrossRefGoogle Scholar
  19. 19.
    Gronchi A, Fiore M, Miselli F, Lagonigro MS, Coco P, Messina A, et al. Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg. 2007;245:341–6.CrossRefGoogle Scholar
  20. 20.
    Mussi C, Ronellenfitsch U, Jakob J, Tamborini E, Reichardt P, Casali PG, et al. Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients? Ann Oncol. Oxford University Press. 2010;21:403–8.CrossRefGoogle Scholar
  21. 21.
    Sym SJ, Ryu M, Lee J, Chang HM, Kim T, Kim HC, et al. Surgical intervention following imatinib treatment in patients with advanced gastrointestinal stromal tumors (GISTs). J Surg Oncol. Wiley Subscription Services, Inc., A Wiley Company. 2008;98:27–33.CrossRefGoogle Scholar
  22. 22.
    Rubió-Casadevall J, Martinez-Trufero J, Garcia-Albeniz X, Calabuig S, Lopez-Pousa A, del Muro JG, et al. Role of surgery in patients with recurrent, metastatic, or unresectable locally advanced gastrointestinal stromal tumors sensitive to Imatinib: a retrospective analysis of the Spanish Group for Research on Sarcoma (GEIS). Ann Surg Oncol. 2015;22:2948–57.CrossRefGoogle Scholar
  23. 23.
    von Mehren M, Randall RL, Benjamin RS, Boles S, Bui MM, Conrad EU, et al. Soft tissue sarcoma, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2017;14:758.CrossRefGoogle Scholar
  24. 24.
    ESMO/European Sarcoma Network Working Group. Gastrointestinal stromal tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25:iii21–6.CrossRefGoogle Scholar
  25. 25.
    Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol. 2008;39:1411–9.CrossRefGoogle Scholar
  26. 26.
    Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23:70–83.CrossRefGoogle Scholar
  27. 27.
    Mrowiec S, Jabłońska B, Liszka Ł, Pająk J, Leidgens M, Szydło R, et al. Prognostic factors for survival post surgery for patients with gastrointestinal stromal tumors. Eur Surg Res. 2012;48:3–9.CrossRefGoogle Scholar
  28. 28.
    Joensuu H, Vehtari A, Riihimäki J, Nishida T, Steigen SE, Brabec P, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13:265–74.CrossRefGoogle Scholar
  29. 29.
    DeMatteo RP, Gold JS, Saran L, Gönen M, Liau KH, Maki RG, et al. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer. 2008;112:608–15.CrossRefGoogle Scholar
  30. 30.
    National Cancer Institute. Overview of the SEER Program. 2013Google Scholar
  31. 31.
    Blay J-Y, Bonvalot S, Casali P, Choi H, Debiec-Richter M, Dei Tos AP, et al. 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;16:566–78.CrossRefGoogle Scholar
  32. 32.
    Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay J-Y, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004;364:1127–34.CrossRefGoogle Scholar
  33. 33.
    Maki RG, Blay J-Y, Demetri GD, Fletcher JA, Joensuu H, Martin-Broto J, et al. Key issues in the clinical management of gastrointestinal stromal tumors: an expert discussion. Oncologist. 2015;20:823–30.CrossRefGoogle Scholar
  34. 34.
    Kang Y-K, Ryu M-H, Yoo C, Ryoo B-Y, Kim HJ, Lee JJ, et al. Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2013;14:1175–82.CrossRefGoogle Scholar
  35. 35.
    Joensuu H, Eriksson M, Hall KS, Hartmann JT, Pink D, Schütte J, et al. Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib. Cancer. 2014;120:2325–33.CrossRefGoogle Scholar
  36. 36.
    Lasota J, Wozniak A, Sarlomo-Rikala M, Rys J, Kordek R, Nassar A, et al. Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors. Am J Pathol. 2000;157:1091–5.CrossRefGoogle Scholar
  37. 37.
    Antonescu CR, Sommer G, Sarran L, Tschernyavsky SJ, Riedel E, Woodruff JM, et al. Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors. Clin Cancer Res. American Association for Cancer Research. 2003;9:3329–37.PubMedGoogle Scholar
  38. 38.
    Lasota J, Corless CL, Heinrich MC, Debiec-Rychter M, Sciot R, Wardelmann E, et al. Clinicopathologic profile of gastrointestinal stromal tumors (GISTs) with primary KIT exon 13 or exon 17 mutations: a multicenter study on 54 cases. Mod Pathol. 2008;21:476–84.CrossRefGoogle Scholar
  39. 39.
    Bischof DA, Kim Y, Behman R, Karanicolas PJ, Quereshy FA, Blazer DG, et al. A nomogram to predict disease-free survival after surgical resection of GIST. J Gastrointest Surg. 2014;18:2123–9.CrossRefGoogle Scholar
  40. 40.
    Xia L, Zhang M-M, Ji L, Li X, Wu X-T. Resection combined with imatinib therapy for liver metastases of gastrointestinal stromal tumors. Surg Today. 2010;40:936–42.CrossRefGoogle Scholar
  41. 41.
    Bauer S, Rutkowski P, Hohenberger P, Miceli R, Fumagalli E, Siedlecki JA, et al. Long-term follow-up of patients with GIST undergoing metastasectomy in the era of imatinib? Analysis of prognostic factors (EORTC-STBSG collaborative study). Eur J Surg Oncol. 2014;40:412–9.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Second Department of Surgery, University General Hospital of AlexandroupoliDemocritus University of Thrace Medical SchoolAlexandroupoliGreece
  2. 2.Department of MedicineUniversity of Pittsburgh Medical CenterPittsburghUSA

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