Metastatic gastrointestinal stromal tumor: A regional cancer center experience of 44 cases

M. C. Suresh Babu; Tamojit Chaudhuri; K. Govind Babu; K. C. Lakshmaiah; D. Lokanatha; Linu Abraham Jacob; A. H. Rudresha; K. N. Lokesh; L. K. Rajeev

doi:10.4103/sajc.sajc_290_16

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ORIGINAL ARTICLE : GI Cancer

06 (

); 118-121

doi:

10.4103/sajc.sajc_290_16

Metastatic gastrointestinal stromal tumor: A regional cancer center experience of 44 cases

M. C. Suresh Babu¹, Tamojit Chaudhuri^1,, K. Govind Babu¹, K. C. Lakshmaiah¹, D. Lokanatha¹, Linu Abraham Jacob¹, A. H. Rudresha¹, K. N. Lokesh¹, L. K. Rajeev¹

1 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka

*Corresponding author: Dr. Tamojit Chaudhuri. tamojit.cnmc@gmail.com

Published: 2020-12-22

MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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Abstract

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Historically, a poor prognosis for metastatic disease has been reported with systemic chemotherapy. Significant advances have been made in the last decade, since the introduction of different tyrosine kinase inhibitors (TKIs). Unfortunately, even though the TKIs have been used for a long time, there are very few published data of the experience of TKI therapy in metastatic GIST from India. Materials and Methods: Patients diagnosed with metastatic GIST from January 2005 to October 2016 at our center, who received first-line therapy with imatinib 400 mg/day, were reviewed retrospectively. Patients' profile, response to treatment, toxicity of TKI therapy, time to progression, and survival were evaluated. Results: Of the 44 metastatic GIST patients, 23 (52.2%) were males. Median age at diagnosis was 48 years. The most common presenting symptom was an abdominal pain (52%), followed by weight loss (23%). Most frequently affected metastatic site was liver (57%), followed by peritoneum (16%), and lungs (4.5%). Metastases to both liver and peritoneum were found in 10 patients (22.5%). All patients were initially treated with imatinib at a dose of 400 mg/day. Disease stabilization was documented in 21 cases (48%), and 13 patients (29%) achieved a partial response. TKI therapy was well-tolerated in most cases. Median progression-free survival (PFS) was 26 months, and estimated median survival was 48 months. Patients with lung metastases have a significantly inferior median PFS and overall survival, in comparison to patients with other metastatic sites (P < 0.05). Conclusions: Imatinib therapy was well tolerated and induced a sustained clinical benefit in more than half of the patients with metastatic GIST. Lung metastases seemed to be a poor prognostic factor in this patient population.

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References

Joensuu H, Fletcher C, Dimitrijevic S, Silberman S, Roberts P, Demetri G. Management of malignant gastrointestinal stromal tumours. Lancet Oncol 2002;3:655-64.
Sanders KM, Koh SD, Ward SM. Interstitial cells of Cajal as pacemakers in the gastrointestinal tract. Annu Rev Physiol 2006;68:307-43.
Zhao X, Yue C. Gastrointestinal stromal tumor. J Gastrointest Oncol 2012;3:189-208.
Miettinen M, Wang ZF, Lasota J. DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: A study of 1840 cases. Am J Surg Pathol 2009;33:1401-8.
Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol 2004;22:3813-25.
Søreide K, Sandvik OM, Søreide JA, Gudlaugsson E, Mangseth K, Haugland HK. Tyrosine-kinase mutations in c-KIT and PDGFR-alpha genes of imatinib naïve adult patients with gastrointestinal stromal tumours (GISTs) of the stomach and small intestine: Relation to tumour-biological risk-profile and long-term outcome. Clin Transl Oncol 2012;14:619-29.
Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347:472-80.
Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: A randomised controlled trial. Lancet 2006;368:1329-38.
Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381:295-302.
Pidhorecky I, Cheney RT, Kraybill WG, Gibbs JF. Gastrointestinal stromal tumors: Current diagnosis, biologic behavior, and management. Ann Surg Oncol 2000;7:705-12.
van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: A phase I study. Lancet 2001;358:1421-3.
Casali PG, Jost L, Reichardt P, Schlemmer M, Blay JY; ESMO Guidelines Working Group. Gastrointestinal stromal tumors: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008;19 Suppl 2:ii35-8.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®). Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. [Last accessed on 2016 Aug 06].
Andtbacka RH, Ng CS, Scaife CL, Cormier JN, Hunt KK, Pisters PW, et al. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol 2007;14:14-24.
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.
Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: Randomised trial. Lancet 2004;364:1127-34.
Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, 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.
Available from: http://www.clinicaltrials.gov/ct2/show/study/NCT00372567?term=gist+imatinib+sunitinibandrank=4. [Last accessed on 2011 Jul 07].
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 – A population-based study in western Sweden. Cancer 2005;103:821-9.
Tryggvason G, Gíslason HG, Magnússon MK, Jónasson JG. Gastrointestinal stromal tumors in Iceland, 1990-2003: The Icelandic GIST study, a population-based incidence and pathologic risk stratification study. Int J Cancer 2005;117:289-93.
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.
Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 2001;344:1052-6.
Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, 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.
Ghadyalpatil NS, Supriya C, Prachi P, Ashwin D, Avanish S. Gastrointestinal cancers in India: Treatment perspective. South Asian J Cancer 2016;5:126-36.
Shrikhande SV, Marda SS, Suradkar K, Arya S, Shetty GS, Bal M, et al. Gastrointestinal stromal tumors: Case series of 29 patients defining the role of imatinib prior to surgery. World J Surg 2012;36:864-71.
Das D, Ganguly S, Deb AR, Aich RK. Neoodjuvant imatinib mesylate for advanced primary and metastactic/recurrent gastro-intestinal stromal tumour (GIST). J Indian Med Assoc 2013;111:21-3.
Rajappa S, Muppavarapu KM, Uppin S, Digumarti R. Gastrointestinal stromal tumors: A single institution experience of 50 cases. Indian J Gastroenterol 2007;26:225-9.
Kapoor R, Khosla D, Kumar P, Kumar N, Bera A. Five-year follow up of patients with gastrointestinal stromal tumor: Recurrence-free survival by risk group. Asia Pac J Clin Oncol 2013;9:40-6.
Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003;21:4342-9.

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[1] Joensuu H, Fletcher C, Dimitrijevic S, Silberman S, Roberts P, Demetri G. Management of malignant gastrointestinal stromal tumours. Lancet Oncol 2002;3:655-64.

[2] Sanders KM, Koh SD, Ward SM. Interstitial cells of Cajal as pacemakers in the gastrointestinal tract. Annu Rev Physiol 2006;68:307-43.

[3] Zhao X, Yue C. Gastrointestinal stromal tumor. J Gastrointest Oncol 2012;3:189-208.

[4] Miettinen M, Wang ZF, Lasota J. DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: A study of 1840 cases. Am J Surg Pathol 2009;33:1401-8.

[5] Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol 2004;22:3813-25.

[6] Søreide K, Sandvik OM, Søreide JA, Gudlaugsson E, Mangseth K, Haugland HK. Tyrosine-kinase mutations in c-KIT and PDGFR-alpha genes of imatinib naïve adult patients with gastrointestinal stromal tumours (GISTs) of the stomach and small intestine: Relation to tumour-biological risk-profile and long-term outcome. Clin Transl Oncol 2012;14:619-29.

[7] Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347:472-80.

[8] Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: A randomised controlled trial. Lancet 2006;368:1329-38.

[9] Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381:295-302.

[10] Pidhorecky I, Cheney RT, Kraybill WG, Gibbs JF. Gastrointestinal stromal tumors: Current diagnosis, biologic behavior, and management. Ann Surg Oncol 2000;7:705-12.

[11] van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: A phase I study. Lancet 2001;358:1421-3.

[12] Casali PG, Jost L, Reichardt P, Schlemmer M, Blay JY; ESMO Guidelines Working Group. Gastrointestinal stromal tumors: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008;19 Suppl 2:ii35-8.

[13] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®). Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. [Last accessed on 2016 Aug 06].

[14] Andtbacka RH, Ng CS, Scaife CL, Cormier JN, Hunt KK, Pisters PW, et al. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol 2007;14:14-24.

[15] 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.

[16] Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: Randomised trial. Lancet 2004;364:1127-34.

[17] Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, 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.

[18] Available from: http://www.clinicaltrials.gov/ct2/show/study/NCT00372567?term=gist+imatinib+sunitinibandrank=4. [Last accessed on 2011 Jul 07].

[19] 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 – A population-based study in western Sweden. Cancer 2005;103:821-9.

[20] Tryggvason G, Gíslason HG, Magnússon MK, Jónasson JG. Gastrointestinal stromal tumors in Iceland, 1990-2003: The Icelandic GIST study, a population-based incidence and pathologic risk stratification study. Int J Cancer 2005;117:289-93.

[21] 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.

[22] Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 2001;344:1052-6.

[23] Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, 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.

[24] Ghadyalpatil NS, Supriya C, Prachi P, Ashwin D, Avanish S. Gastrointestinal cancers in India: Treatment perspective. South Asian J Cancer 2016;5:126-36.

[25] Shrikhande SV, Marda SS, Suradkar K, Arya S, Shetty GS, Bal M, et al. Gastrointestinal stromal tumors: Case series of 29 patients defining the role of imatinib prior to surgery. World J Surg 2012;36:864-71.

[26] Das D, Ganguly S, Deb AR, Aich RK. Neoodjuvant imatinib mesylate for advanced primary and metastactic/recurrent gastro-intestinal stromal tumour (GIST). J Indian Med Assoc 2013;111:21-3.

[27] Rajappa S, Muppavarapu KM, Uppin S, Digumarti R. Gastrointestinal stromal tumors: A single institution experience of 50 cases. Indian J Gastroenterol 2007;26:225-9.

[28] Kapoor R, Khosla D, Kumar P, Kumar N, Bera A. Five-year follow up of patients with gastrointestinal stromal tumor: Recurrence-free survival by risk group. Asia Pac J Clin Oncol 2013;9:40-6.

[29] Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003;21:4342-9.

Metastatic gastrointestinal stromal tumor: A regional cancer center experience of 44 cases

Abstract

Abstract

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References

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