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Published in: Annals of Surgical Oncology 9/2015

01-09-2015 | Gastrointestinal Oncology

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)

Authors: Jordi Rubió-Casadevall, MD, Javier Martinez-Trufero, MD, Xabier Garcia-Albeniz, MD, Silvia Calabuig, MD, Antonio Lopez-Pousa, MD, Javier Garcia del Muro, MD, Joaquin Fra, MD, Andrés Redondo, MD, Nuria Lainez, MD, Andrés Poveda, MD, Claudia Valverde, MD, Ana De Juan, MD, Isabel Sevilla, MD, Antonio Casado, MD, Raquel Andres, MD, Josefina Cruz, MD, Javier Martin-Broto, MD, Joan Maurel, MD, the Spanish Group for Research on Sarcoma (GEIS)

Published in: Annals of Surgical Oncology | Issue 9/2015

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Abstract

Background

Recurrent, metastatic, and locally advanced gastrointestinal stromal tumors (GISTs) can be treated successfully with imatinib mesylate. Surgery for residual disease has been suggested for nonrefractory metastatic GISTs to reduce the probability of resistant recurrent clones, although no randomized Phase III trial has been performed to answer the question about its benefit. We carried out an analysis of the outcome of patients with recurrent unresectable locally advanced or metastatic imatinib-sensitive priamary GIST in 14 institutions in Spain. We compared two cohorts: treated or not treated with surgery after partial response or stabilization by imatinib.

Patients and Methods

Data were obtained from the online GIST registry of the Spanish Group for Research in Sarcomas. Selected patients were then divided into two groups: group A, treated initially only with imatinib, and group B, treated additionally with metastasectomy. Baseline characteristics between groups were compared, and univariate and multivariate analysis for progression-free survival and overall survival (OS) were performed.

Results

Analysis was undertaken in 171 patients considered nonrefractory to imatinib. The median follow-up time was 56.6 months. Focusing on OS, the Eastern Cooperative Oncology Group performance status different than 0, extent of disease limited to one metastatic organ, and comparison between groups A or B achieved statistical difference in the multivariate analysis. Median survival was 59.9 months in group A and 87.6 months in group B.

Conclusions

Based in its benefit in OS, our study supports surgery of metastatic disease in GIST patients who respond to imatinib therapy.
Literature
1.
go back to reference Nilsson B, Bümming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course and prognostication in the pre-imatinib mesylate era: a population based study in western Sweden. Cancer. 2005;103(4):821–9.PubMedCrossRef Nilsson B, Bümming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course and prognostication in the pre-imatinib mesylate era: a population based study in western Sweden. Cancer. 2005;103(4):821–9.PubMedCrossRef
2.
go back to reference Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–80.PubMedCrossRef Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–80.PubMedCrossRef
3.
go back to reference Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708–10PubMedCrossRef Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708–10PubMedCrossRef
4.
go back to reference Blanke CD, Demetri GD, von Mehren M, et al. 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;26:620–5.PubMedCrossRef Blanke CD, Demetri GD, von Mehren M, et al. 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;26:620–5.PubMedCrossRef
5.
go back to reference Green S, Weiss GR. Southwest Oncology Group standard response criteria, end point definitions, and toxicity criteria. Invest New Drugs. 1992;10:239–53PubMedCrossRef Green S, Weiss GR. Southwest Oncology Group standard response criteria, end point definitions, and toxicity criteria. Invest New Drugs. 1992;10:239–53PubMedCrossRef
6.
go back to reference Blanke CD, Rankin C, Demetri GD, et al. 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;26:626–32.PubMedCrossRef Blanke CD, Rankin C, Demetri GD, et al. 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;26:626–32.PubMedCrossRef
7.
go back to reference Blay JY, Le CA, Ray-Coquard I, et al. 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;25:1107–13.PubMedCrossRef Blay JY, Le CA, Ray-Coquard I, et al. 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;25:1107–13.PubMedCrossRef
8.
9.
go back to reference Heinrich MC, Owzar K, Corles CL, et al. Correlation of kinase genotype and clinical outcome in the North American intergroup phase III trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol. 2008;26:5360–7.PubMedCentralPubMedCrossRef Heinrich MC, Owzar K, Corles CL, et al. Correlation of kinase genotype and clinical outcome in the North American intergroup phase III trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol. 2008;26:5360–7.PubMedCentralPubMedCrossRef
10.
go back to reference Wardelmann E, Merkelbach-Bruse S, Pauls K, et al. Polyclonal evolution of multiple secondary kit mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res. 2006;12(6):1743–9.PubMedCrossRef Wardelmann E, Merkelbach-Bruse S, Pauls K, et al. Polyclonal evolution of multiple secondary kit mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res. 2006;12(6):1743–9.PubMedCrossRef
11.
go back to reference Debiec- Rychter M, Cools J, Dumez H, et al. Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology. 2005;128(2):270–9.PubMedCrossRef Debiec- Rychter M, Cools J, Dumez H, et al. Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology. 2005;128(2):270–9.PubMedCrossRef
12.
go back to reference Van Glabbeke M, Verweij J, Casali PG, et al. 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;23:5795–804.PubMedCrossRef Van Glabbeke M, Verweij J, Casali PG, et al. 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;23:5795–804.PubMedCrossRef
13.
go back to reference Gronchi A, Fiore M, Miselli F, et al. Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg. 2007;245:341–6.PubMedCentralPubMedCrossRef Gronchi A, Fiore M, Miselli F, et al. Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg. 2007;245:341–6.PubMedCentralPubMedCrossRef
14.
go back to reference DeMatteo RP, Maki RG, Singer S, et al. Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor. Ann Surg. 2007;245:347–52.PubMedCentralPubMedCrossRef DeMatteo RP, Maki RG, Singer S, et al. Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor. Ann Surg. 2007;245:347–52.PubMedCentralPubMedCrossRef
15.
go back to reference Bauer S, Hartmann JT, de Wit M, et al. Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib. Int J Cancer. 2005;117:316–25PubMedCrossRef Bauer S, Hartmann JT, de Wit M, et al. Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib. Int J Cancer. 2005;117:316–25PubMedCrossRef
16.
go back to reference Andtbacka RH, Ng CS, Scaife CL, et al. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol. 2007;14:14–24.PubMedCrossRef Andtbacka RH, Ng CS, Scaife CL, et al. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol. 2007;14:14–24.PubMedCrossRef
17.
go back to reference Bonvalot S, Eldweny H, Péchoux CL, et al. Impact of surgery on advanced gastrointestinal stromal tumors (GIST) in the imatinib era. Ann Surg Oncol. 2006;13(12):1596–603.PubMedCrossRef Bonvalot S, Eldweny H, Péchoux CL, et al. Impact of surgery on advanced gastrointestinal stromal tumors (GIST) in the imatinib era. Ann Surg Oncol. 2006;13(12):1596–603.PubMedCrossRef
18.
go back to reference Raut CP, Posner M, Desai J, et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 2006;24:2325–31PubMedCrossRef Raut CP, Posner M, Desai J, et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 2006;24:2325–31PubMedCrossRef
19.
go back to reference Mussi C, Ronellenfitsch U, Jakib J, et al Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients? Ann Oncol. 2010;21:403–8PubMedCrossRef Mussi C, Ronellenfitsch U, Jakib J, et al Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients? Ann Oncol. 2010;21:403–8PubMedCrossRef
20.
go back to reference Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.PubMedCrossRef Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.PubMedCrossRef
21.
go back to reference Choi H, Charnsangavej C, Faria SC, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol. 2007;25:1753–9.PubMedCrossRef Choi H, Charnsangavej C, Faria SC, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol. 2007;25:1753–9.PubMedCrossRef
22.
go back to reference Bauer S, Rutkowski P, Hohenberger P, 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(4):412–9.PubMedCrossRef Bauer S, Rutkowski P, Hohenberger P, 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(4):412–9.PubMedCrossRef
Metadata
Title
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)
Authors
Jordi Rubió-Casadevall, MD
Javier Martinez-Trufero, MD
Xabier Garcia-Albeniz, MD
Silvia Calabuig, MD
Antonio Lopez-Pousa, MD
Javier Garcia del Muro, MD
Joaquin Fra, MD
Andrés Redondo, MD
Nuria Lainez, MD
Andrés Poveda, MD
Claudia Valverde, MD
Ana De Juan, MD
Isabel Sevilla, MD
Antonio Casado, MD
Raquel Andres, MD
Josefina Cruz, MD
Javier Martin-Broto, MD
Joan Maurel, MD
the Spanish Group for Research on Sarcoma (GEIS)
Publication date
01-09-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 9/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-4360-8

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