Defining the Epidemiology of a Novel GIST Multiple Tumor Syndrome: Results of a Population-Based Analysis Jason K. Sicklick, MD, Grace L. Ma, Joel M. Baumgartner, MD, Lisa Madlensky, PhD, CGC, Chih-Min Tang, PhD, Adam M. Burgoyne, MD, PhD, Jonathan C. Trent, MD, PhD, Maria E. Martinez, PhD, and James D. Murphy, MD, MS
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Defining the Epidemiology of a Novel GIST Multiple Tumor Syndrome: Results of a Population-Based Analysis Jason K. Sicklick, MD, Grace L. Ma, Joel M. Baumgartner,
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Defining the Epidemiology of a Novel GIST Multiple Tumor Syndrome:Results of a Population-Based Analysis
Jason K. Sicklick, MD, Grace L. Ma, Joel M. Baumgartner, MD, Lisa Madlensky, PhD, CGC, Chih-Min Tang, PhD, Adam M. Burgoyne, MD, PhD, Jonathan C. Trent, MD, PhD, Maria E. Martinez, PhD,
and James D. Murphy, MD, MS
Relevant Disclosures
Consultant/Speaker for Novartis Pharmaceuticals (JKS, 2013).
Consultant for Novartis Pharmaceuticals (JCT, 2013)
Gastrointestinal Stromal Tumor• Approximately 95% of GISTs are considered non-hereditary
or sporadic.1-5
• Results of several descriptive, single institution case series suggest that patients with sporadic GIST develop synchronous or metachronous malignancies with frequencies far exceeding the often-cited 1-in-9 lifetime chance of developing 2 primary cancers.6
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1. Agaimy, A. and Hartmann, A. Pathologe 2010; 31(6): 430-7.2. Neuhann, T.M., Mansmann, V., Merkelbach-Bruse, S., et al. Am J Surg Pathol 2013; 37(6): 898-905.3. Kuroda, N., Tanida, N., Hirota, S., et al. Ann Diagn Pathol 2011; 15(5): 358-61.4. Ponti, G., Luppi, G., Martorana, D., et al. Oncol Rep 2010; 23(2): 437-44.5. Stratakis, C.A. and Carney, J.A. J Intern Med 2009; 266(1): 43-52.6. Kosary, C., LAG, R., and Miller, B., SEER Cancer statistics review 1973–1992: tables and graphs, National
Cancer Institute, N., Editor. 1995: Bethesda, MD.
Increased Frequency of Other Cancers
• 2006: Literature review of studies compromising 4,813 GIST patients, reported the frequency of additional malignancies was 4.5% to 33%.1
• 2010: Largest single institution study of 783 confirmed these findings, with 20.3% GIST patients developing ≥1 additional malignancies. 2
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1. Agaimy, A., Wunsch, P.H., Sobin, L.H., Lasota, J., and Miettinen, M. Semin Diagn Pathol 2006; 23(2): 120-9.
2. Pandurengan RK, Dumont AG, Araujo DM, Ludwig JA, Ravi V, Patel S, Garber J, Benjamin RS, Strom SS, and Trent JC. Ann Oncol 2010; 21(10): 2107-11.
Increased Frequency of Other Cancers
• Associations reported include:– Desmoids1
– Myeloid leukemias2
– Other GI malignancies discovered incidentally during resections for GIST
– GIST discovered incidentally during resections for other GI malignancies
• Limitations of published studies:– Based on single/multiple institutional series– Reported in a qualitative nature
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1. Dumont, A.G., Rink, L., Godwin, A.K., et al. Ann Oncol 2012; 23(5): 1335-40.2. Miettinen, M., Kraszewska, E., Sobin, L.H., and Lasota, J. Cancer 2008; 112(3): 645-9.
Purpose of Study
• To utilize a national cancer registry in the United States to investigate the rates and types of additional cancers in patients with GIST.
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Methods• We identified 6,112 patients diagnosed with GIST
between 2001 and 2011 in the Surveillance, Epidemiology, and End Results (SEER) database*– GI tumor site codes (C150-C189, C199, C209-C212, C218, C220-
Race White / Unknown 4,320 70.7%Black 1,079 17.7%Other 713 11.7%
* 30 patients exlcluded form prior epidemiologic analyses
Rates of Additional Cancers
38 x 25 x 12 cmTime of Additional Cancers Percent Cancer Before GIST (N=645) 60.7% Cancer During Same Month or After GIST (N=485) 45.7% Cancers Before and After GIST (N=68) 6.4%
Number of Additional Cancers Percent 1 Additional Cancer (N=913) 86.0% >1 Additional Cancer (N=149) 14.0% >2 Additional Cancers (N=16) 1.5%
* Other female genitourinary (GU) includes vulvar cancer (N=4), vaginal cancer (N=1), fallopian tube (N=2), and NOS (N=1).** Hepatobiliary adenocarcinoma includes liver adenocarcinoma (N=2), intrahepatic cholangiocarcinoma (N=1), extrahepatic cholangiocarcinoma (N=1), and ampullary adenocarcinoma (N=4).
NOTE: While multiple GISTs were characteristic of hereditary GIST syndromes, only 16 additional GIST cases were noted in the SEER cohort, accounting for only 1.3% of second cancers.
Timeline for Occurrence95% CI* P<0.05.
>
> 5 yr 1 yr before to 1 after
Limitations• Cancers were identified using histology and site-specific codes;
as such, misdiagnosis or miscoding remain potential sources of error.
• We likely underestimated the actual number of patients with GIST in the database, and the diagnoses of second GISTs might be indicative of the miscoding of metastatic disease.
• While we attempted to eliminate patients with hereditary syndromes from our analysis by excluding those diagnosed <20 yo, we had no way of directly identifying these patients.
• As with all studies on 2nd cancers, the elevated incidence and prevalence rates might be partially attributed to detection bias during work-up and treatment, rather than a truly meaningful link.
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Summary-1• 17.5% of GIST patients (or 1-in-5.7) developed an
additional cancer– 60.7% Before GIST– 45.7% After GIST– 1-in-16 patients develop cancers Before and After GIST
• Additional cancers were most often diagnosed within 1 year of GIST diagnosis
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Summary-2• Before and After– Sarcomas, NET-carcinoid tumors, colorectal
adenocarcinoma, and NHL
• Before Only– Melanomas – Adenocarcinomas of the esophagus, bladder, and
prostate
• After Only– Papillary thyroid cancer, NSCLC, bladder TCC– Adenocarcinomas of the stomach, small intestine,
kidneys, hepatopancreatobiliary system, and female GU tract
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Conclusion-1• These data point to the possibility of a new GIST multiple
tumor syndrome, which we believe to be distinct from known disorders such as:– Familial GIST syndromes
• Only 16 additional GIST cases were noted in the SEER cohort, accounting for only 1.3% of second cancers
– Neurofibromatosis type 1 (e.g., GIST, sarcomas, periampullary/PNETs, and pheochromocytoma)• Sarcomas and PNETS comprised only 7.1% (6.9% and 0.2%, respectively) of
the 1,224 additional cancers
– Carney's triad (gastric GIST, pulmonary chondroma, extra-adrenal paraganglioma, adrenal adenomas)• Benign tumors are not coded in SEER
– Carney-Stratakis syndrome (e.g., GIST and paragangliomas)
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Conclusion-2• To our knowledge, this is the first population-based study
to quantify the occurrence of specific malignancies before and after GIST.
• We confirmed many previous institutional studies and identified several novel cancer associations, providing a comprehensive description and statistical examination to support the existence of a new GIST multiple tumor syndrome.
• Further investigations are necessary to link these epidemiological findings with relevant clinical decision-making, including screening and prevention.