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Published in: Journal of Gastrointestinal Surgery 12/2014

01-12-2014 | Original Article

A Nomogram to Predict Disease-Free Survival After Surgical Resection of GIST

Authors: Danielle A. Bischof, Yuhree Kim, Ramy Behman, Paul J. Karanicolas, Fayez A. Quereshy, Dan G. Blazer III, Shishir K. Maithel, T. Clark Gamblin, Todd W. Bauer, Timothy M. Pawlik

Published in: Journal of Gastrointestinal Surgery | Issue 12/2014

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Abstract

Background

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Adjuvant imatinib therapy has resulted in improved disease-free survival (DFS) following resection of primary GIST. The aim of our study was to create a nomogram to predict DFS following resection of GIST.

Method

Using a multi-institutional cohort of patients who underwent surgery for primary GIST at 7 academic hospitals in the USA and Canada between January 1998 and December 2012, a multivariable Cox proportional hazards model predicting DFS was created using backward stepwise selection. A nomogram to predict DFS following surgical resection of GIST was constructed with the variables selected in the multivariable model. We tested nomogram discrimination by calculating the C-statistic and compared the nomogram to four existing GIST prognostic stratification systems.

Results

A total of 365 patients who underwent surgery for primary GIST was included in the study. Using backward stepwise selection, sex, tumor size, tumor site, and mitotic rate were selected for incorporation into the nomogram. The nomogram demonstrated superior discrimination compared to the NIH criteria, modified NIH criteria, and Memorial Sloan-Kettering Nomogram and had similar discrimination to the Miettinen criteria (C-statistic 0.77 vs 0.73, 0.71, 0.71, and 0.78, respectively).

Conclusion

Four independent predictors of recurrence following surgery for primary GIST were used to create a nomogram to predict DFS. The nomogram stratified patients into prognostic groups and performed well on internal validation.
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Literature
1.
go back to reference Miettinen M, Lasota J. Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Archiv : an international journal of pathology 2001;438(1): 1–12.CrossRef Miettinen M, Lasota J. Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Archiv : an international journal of pathology 2001;438(1): 1–12.CrossRef
2.
go back to reference Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B, Sablinska K, Kindblom LG. 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(4): 821–829.PubMedCrossRef Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B, Sablinska K, Kindblom LG. 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(4): 821–829.PubMedCrossRef
3.
go back to reference Tryggvason G, Gislason HG, Magnusson MK, Jonasson JG. Gastrointestinal stromal tumors in Iceland, 1990–2003: the icelandic GIST study, a population-based incidence and pathologic risk stratification study. International journal of cancer Journal international du cancer 2005;117(2): 289–293.PubMedCrossRef Tryggvason G, Gislason HG, Magnusson MK, Jonasson JG. Gastrointestinal stromal tumors in Iceland, 1990–2003: the icelandic GIST study, a population-based incidence and pathologic risk stratification study. International journal of cancer Journal international du cancer 2005;117(2): 289–293.PubMedCrossRef
4.
go back to reference Woodall CE, 3rd, Brock GN, Fan J, Byam JA, Scoggins CR, McMasters KM, Martin RC, 2nd. An evaluation of 2537 gastrointestinal stromal tumors for a proposed clinical staging system. Archives of surgery 2009;144(7): 670–678.PubMedCrossRef Woodall CE, 3rd, Brock GN, Fan J, Byam JA, Scoggins CR, McMasters KM, Martin RC, 2nd. An evaluation of 2537 gastrointestinal stromal tumors for a proposed clinical staging system. Archives of surgery 2009;144(7): 670–678.PubMedCrossRef
5.
go back to reference von Mehren MG, S.; Meyer, C.; Riedel, R.; Van Tine, B. Soft Tissue Sarcoma. In: NCCN Clinical Practice Guidelines in Oncology; 2013. von Mehren MG, S.; Meyer, C.; Riedel, R.; Van Tine, B. Soft Tissue Sarcoma. In: NCCN Clinical Practice Guidelines in Oncology; 2013.
6.
go back to reference Hohenberger P, Ronellenfitsch U, Oladeji O, Pink D, Strobel P, Wardelmann E, Reichardt P. Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumour. The British journal of surgery 2010;97(12): 1854–1859.PubMedCrossRef Hohenberger P, Ronellenfitsch U, Oladeji O, Pink D, Strobel P, Wardelmann E, Reichardt P. Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumour. The British journal of surgery 2010;97(12): 1854–1859.PubMedCrossRef
7.
go back to reference Joensuu H, Vehtari A, Riihimaki J, Nishida T, Steigen SE, Brabec P, Plank L, Nilsson B, Cirilli C, Braconi C, Bordoni A, Magnusson MK, Linke Z, Sufliarsky J, Federico M, Jonasson JG, Dei Tos AP, Rutkowski P. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. The lancet oncology 2012;13(3): 265–274.PubMedCrossRef Joensuu H, Vehtari A, Riihimaki J, Nishida T, Steigen SE, Brabec P, Plank L, Nilsson B, Cirilli C, Braconi C, Bordoni A, Magnusson MK, Linke Z, Sufliarsky J, Federico M, Jonasson JG, Dei Tos AP, Rutkowski P. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. The lancet oncology 2012;13(3): 265–274.PubMedCrossRef
8.
go back to reference Dematteo RP, Gold JS, Saran L, Gonen M, Liau KH, Maki RG, Singer S, Besmer P, Brennan MF, Antonescu CR. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer 2008;112(3): 608–615.PubMedCrossRef Dematteo RP, Gold JS, Saran L, Gonen M, Liau KH, Maki RG, Singer S, Besmer P, Brennan MF, Antonescu CR. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer 2008;112(3): 608–615.PubMedCrossRef
9.
go back to reference Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Human pathology 2008;39(10): 1411–1419.PubMedCrossRef Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Human pathology 2008;39(10): 1411–1419.PubMedCrossRef
10.
go back to reference Miettinen M, Makhlouf H, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. The American journal of surgical pathology 2006;30(4): 477–489.PubMedCrossRef Miettinen M, Makhlouf H, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. The American journal of surgical pathology 2006;30(4): 477–489.PubMedCrossRef
11.
go back to reference Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. The American journal of surgical pathology 2005;29(1): 52–68.PubMedCrossRef Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. The American journal of surgical pathology 2005;29(1): 52–68.PubMedCrossRef
12.
go back to reference Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nature reviews Cancer 2011;11(12): 865–878.PubMed Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nature reviews Cancer 2011;11(12): 865–878.PubMed
13.
go back to reference Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K, American College of Surgeons Oncology Group Intergroup Adjuvant GST. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 2009;373(9669): 1097–1104.PubMedCentralPubMedCrossRef Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K, American College of Surgeons Oncology Group Intergroup Adjuvant GST. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 2009;373(9669): 1097–1104.PubMedCentralPubMedCrossRef
14.
go back to reference Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schutte J, Ramadori G, Hohenberger P, Duyster J, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Sarlomo-Rikala M, Nilsson B, Sihto H, Monge OR, Bono P, Kallio R, Vehtari A, Leinonen M, Alvegard T, Reichardt P. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA : the journal of the American Medical Association 2012;307(12): 1265–1272.CrossRef Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schutte J, Ramadori G, Hohenberger P, Duyster J, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Sarlomo-Rikala M, Nilsson B, Sihto H, Monge OR, Bono P, Kallio R, Vehtari A, Leinonen M, Alvegard T, Reichardt P. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA : the journal of the American Medical Association 2012;307(12): 1265–1272.CrossRef
15.
go back to reference Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O'Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Human pathology 2002;33(5): 459–465.PubMedCrossRef Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O'Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Human pathology 2002;33(5): 459–465.PubMedCrossRef
16.
go back to reference Gold JS, Gonen M, Gutierrez A, Broto JM, Garcia-del-Muro X, Smyrk TC, Maki RG, Singer S, Brennan MF, Antonescu CR, Donohue JH, DeMatteo RP. Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis. The lancet oncology 2009;10(11): 1045–1052.PubMedCentralPubMedCrossRef Gold JS, Gonen M, Gutierrez A, Broto JM, Garcia-del-Muro X, Smyrk TC, Maki RG, Singer S, Brennan MF, Antonescu CR, Donohue JH, DeMatteo RP. Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis. The lancet oncology 2009;10(11): 1045–1052.PubMedCentralPubMedCrossRef
17.
go back to reference Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Seminars in diagnostic pathology 2006;23(2): 70–83.PubMedCrossRef Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Seminars in diagnostic pathology 2006;23(2): 70–83.PubMedCrossRef
18.
go back to reference Kaplan EL, Meier P. Nonparametric-Estimation from Incomplete Observations. J Am Stat Assoc 1958;53(282): 457–481.CrossRef Kaplan EL, Meier P. Nonparametric-Estimation from Incomplete Observations. J Am Stat Assoc 1958;53(282): 457–481.CrossRef
19.
go back to reference Cox DR. Regression Models and Life-Tables. J Roy Stat Soc B 1972;34(2): 187–220. Cox DR. Regression Models and Life-Tables. J Roy Stat Soc B 1972;34(2): 187–220.
20.
go back to reference EW S. Case study on survival analysis: prediction of secondary cardiovascular events. Springer: New York, NY, 2008. EW S. Case study on survival analysis: prediction of secondary cardiovascular events. Springer: New York, NY, 2008.
21.
go back to reference Harrell FE, Jr., Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Statistics in medicine 1996;15(4): 361–387.PubMedCrossRef Harrell FE, Jr., Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Statistics in medicine 1996;15(4): 361–387.PubMedCrossRef
22.
go back to reference 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. Annals of surgery 2007;245(3): 347–352.PubMedCentralPubMedCrossRef 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. Annals of surgery 2007;245(3): 347–352.PubMedCentralPubMedCrossRef
23.
go back to reference Gold JS. Risk of Recurrence After Resection of Primary GIST: Available Tools Compared and Contrasted. The GIST Cancer Journal 2014;1(1): 20–23. Gold JS. Risk of Recurrence After Resection of Primary GIST: Available Tools Compared and Contrasted. The GIST Cancer Journal 2014;1(1): 20–23.
24.
go back to reference Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, Blay JY, Leyvraz S, Stul M, Casali PG, Zalcberg J, Verweij J, Van Glabbeke M, Hagemeijer A, Judson I, Tissue ES, Bone Sarcoma G, Italian Sarcoma G, Australasian GastroIntestinal Trials G. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. European journal of cancer 2006;42(8): 1093–1103.PubMedCrossRef Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, Blay JY, Leyvraz S, Stul M, Casali PG, Zalcberg J, Verweij J, Van Glabbeke M, Hagemeijer A, Judson I, Tissue ES, Bone Sarcoma G, Italian Sarcoma G, Australasian GastroIntestinal Trials G. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. European journal of cancer 2006;42(8): 1093–1103.PubMedCrossRef
25.
go back to reference Heinrich MC, Owzar K, Corless CL, Hollis D, Borden EC, Fletcher CD, Ryan CW, von Mehren M, Blanke CD, Rankin C, Benjamin RS, Bramwell VH, Demetri GD, Bertagnolli MM, Fletcher JA. 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2008;26(33): 5360–5367.CrossRef Heinrich MC, Owzar K, Corless CL, Hollis D, Borden EC, Fletcher CD, Ryan CW, von Mehren M, Blanke CD, Rankin C, Benjamin RS, Bramwell VH, Demetri GD, Bertagnolli MM, Fletcher JA. 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2008;26(33): 5360–5367.CrossRef
26.
go back to reference Martin J, Poveda A, Llombart-Bosch A, Ramos R, Lopez-Guerrero JA, Garcia del Muro J, Maurel J, Calabuig S, Gutierrez A, Gonzalez de Sande JL, Martinez J, De Juan A, Lainez N, Losa F, Alija V, Escudero P, Casado A, Garcia P, Blanco R, Buesa JM, Spanish Group for Sarcoma R. Deletions affecting codons 557–558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS). Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2005;23(25): 6190–6198.CrossRef Martin J, Poveda A, Llombart-Bosch A, Ramos R, Lopez-Guerrero JA, Garcia del Muro J, Maurel J, Calabuig S, Gutierrez A, Gonzalez de Sande JL, Martinez J, De Juan A, Lainez N, Losa F, Alija V, Escudero P, Casado A, Garcia P, Blanco R, Buesa JM, Spanish Group for Sarcoma R. Deletions affecting codons 557–558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS). Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2005;23(25): 6190–6198.CrossRef
Metadata
Title
A Nomogram to Predict Disease-Free Survival After Surgical Resection of GIST
Authors
Danielle A. Bischof
Yuhree Kim
Ramy Behman
Paul J. Karanicolas
Fayez A. Quereshy
Dan G. Blazer III
Shishir K. Maithel
T. Clark Gamblin
Todd W. Bauer
Timothy M. Pawlik
Publication date
01-12-2014
Publisher
Springer US
Published in
Journal of Gastrointestinal Surgery / Issue 12/2014
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-014-2658-2

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