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A proposed risk assessment score for gastrointestinal stromal tumors based on evaluation of 19,030 cases from the National Cancer Database

Abstract

Background

Standard risk assessment algorithms for gastrointestinal stromal tumor (GIST) are based on anatomic and histopathological variables with arbitrarily defined subcategories. Our goal was to improve risk assessment for GIST through retrospective analysis of patient data.

Methods

The National Cancer Database (NCDB) was queried for patients with GIST; the final cohort consisted of 19,030 cases. Main outcomes were metastasis at presentation and overall survival. A test dataset was used to reevaluate risk stratification parameters in multivariate regression models. A novel risk assessment system was applied to the validation dataset and compared to other currently used risk assessment schemes.

Results

Analysis of observed prevalence of metastases at presentation suggested 7 cm and mitotic rates > 10 per 5 mm2 as optimal threshold values. A proposed risk stratification score showed statistical superiority compared to the National Comprehensive Cancer Network, American Joint Committee on Cancer, and modified National Institute of Health classifications in predicting probability of presentation with metastasis at diagnosis and 4-year overall survival after accounting for important covariables including patient age and comorbidities, year of diagnosis, and surgical/systemic therapeutic regimen.

Conclusions

Reexamination of prognostic factors for GIST demonstrated that current threshold values for tumor size and mitotic rate are suboptimal. A risk stratification score based on revised categorization of these factors outperformed currently used risk assessment algorithms.

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References

  1. 1.

    Miettinen M, El-Rifai W, Sobin L, et al. Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. Hum Pathol. 2002;33:478–83.

    Article  Google Scholar 

  2. 2.

    Miettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med. 2006;130:1466–78.

    CAS  Article  Google Scholar 

  3. 3.

    von Mehren M, Joensuu H. Gastrointestinal stromal tumors. J Clin Oncol. 2013;36:136–43.

    Article  Google Scholar 

  4. 4.

    Vehtari A, Riihimäki J, Joensuu H, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13:265–74.

    Article  Google Scholar 

  5. 5.

    Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol. 2008;39:1411–9.

    Article  Google Scholar 

  6. 6.

    Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23:70–83.

    Article  Google Scholar 

  7. 7.

    Miettinen M, Sobin L, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol. 2005;29:52–68.

    Article  Google Scholar 

  8. 8.

    Miettinen M, Makhlouf H, Sobin LH, et al. 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. Am J Surg Pathol. 2006;30:477–89.

    Article  Google Scholar 

  9. 9.

    Fletcher CDM, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002;33:459–65.

    Article  Google Scholar 

  10. 10.

    Goh BKP, Chow PKH, Yap WM, et al. Which is the optimal risk stratification system for surgically treated localized primary GIST? Comparison of three contemporary prognostic criteria in 171 tumors and a proposal for a modified Armed Forces Institute of Pathology risk criteria. Ann Surg Oncol. 2008;15:2153–63.

    Article  Google Scholar 

  11. 11.

    Gold JS, Gönen M, Gutiérrez A, et al. Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis. Lancet Oncology. 2009;10:1045–52.

    Article  Google Scholar 

  12. 12.

    Woodall CE, Brock GN, Fan J, et al. An evaluation of 2537 gastrointestinal stromal tumors for a proposed clinical staging system. Arch Surg. 2009;144:670–8.

    Article  Google Scholar 

  13. 13.

    Bischof D, Kim Y, Behman R, et al. A nomogram to predict disease-free survival after surgical resection of GIST. J Gastrointest Surg. 2014;18:2123–9.

    Article  Google Scholar 

  14. 14.

    von Mehren M, Joensuu H. Gastrointestinal stromal tumors. J Clin Oncol. 2018;36:136–43.

    Article  Google Scholar 

  15. 15.

    Bilimoria KY, Stewart AK, Winchester DP, et al. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008;15:683–90.

    Article  Google Scholar 

  16. 16.

    Fisher SB, Chiang YJ, Feig BW, et al. Comparative performance of the 7th and 8th editions of the American Joint Committee on Cancer staging systems for soft tissue sarcoma of the trunk and extremities. Ann Surg Oncol. 2018;25:1126–32.

    Article  Google Scholar 

  17. 17.

    Cates JMM. Modeling continuous prognostic factors in survival analysis: implications for tumor staging and assessing chemotherapy effect in osteosarcoma. Am J Surg Pathol. 2018;42:485–91.

    Article  Google Scholar 

  18. 18.

    Huggett BD, Cates JMM. The Vanderbilt staging system for retroperitoneal sarcoma: a validation study of 6,857 patients from the National Cancer Database. Mod Pathol. 2019;32:539–45.

    Article  Google Scholar 

  19. 19.

    Ashamalla M, Kodiyan J, Yanagihara TK, et al. Challenging AJCC 8 staging for soft tissue sarcoma using the NCDB. Int J Radiat Oncol Biol Phys. 2019;105:338–45.

    Article  Google Scholar 

  20. 20.

    Compton ML, Cates JMM. Evidence-based tumor staging of skeletal chondrosarcoma. Am J Surg Pathol. 2020;44:111–9.

    Article  Google Scholar 

  21. 21.

    Boffa DJ, Rosen JE, Mallin K, et al. Using the National Cancer Database for outcomes research: a review. JAMA Oncol. 2017;3:1722–8.

    Article  Google Scholar 

  22. 22.

    Human Mortality Database [Internet]. Available from: https://mortality.org/ [Accessed 2020 Nov 9].

  23. 23.

    Royston P, Parmar MKB. Flexible parametric proportional-hazards and proportional-odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects. Stat Med. 2002;21:2175–97.

    Article  Google Scholar 

  24. 24.

    Fluss R, Faraggi D, Reiser B. Estimation of the Youden Index and its associated cutoff point. Biom J. 2005;47:458–72.

    Article  Google Scholar 

  25. 25.

    Lui X. Classification accuracy and cut point selection. Stat Med. 2012;15:2676–86.

    Google Scholar 

  26. 26.

    Youden W. Index for rating diagnostic tests. Cancer. 1950;3:32–5.

    CAS  Article  Google Scholar 

  27. 27.

    SEER Cancer Statistics Review, 1975–2016. https://seer.cancer.gov/csr/1975_2016/ [Accessed 2020 Apr 13].

  28. 28.

    SEER*Stat Database: Incidence—SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2018 Sub (2000–2016), National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2019, based on the November 2018 submission. https://seer.cancer.gov/canques/survival.html. [Accessed 2020 Apr 08].

  29. 29.

    von Mehren M, Randall RL, Benjamin RS, et al. NCCN clinical practice guidelines in oncology. Soft tissue sarcoma. Version 1.2021. Available from: https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf. [Accessed 2021 Aug 26].

  30. 30.

    Güller U, Tarantino I, Cerny T, et al. Population-based SEER trend analysis of overall and cancer-specific survival in 5138 patients with gastrointestinal stromal tumor. BMC Cancer. 2015;15:557.

    Article  Google Scholar 

  31. 31.

    Güller U, Tarantino I, Cerny T, et al. Revisiting a dogma: similar survival of patients with small bowel and gastric GIST: a population-based propensity score SEER analysis. Gastric Cancer. 2017;20:49–60.

    Article  Google Scholar 

  32. 32.

    Ge XY, Lei LW, Ge F, et al. Analysis of risk factors of gastrointestinal stromal tumors in different age groups based on SEER database. Scand J Gastroenterol. 2019;54:480–4.

    Article  Google Scholar 

  33. 33.

    Collaborative Stage Data Collection System [Internet]. Available from: https://staging.seer.cancer.gov/cs/home/02.05.50/ [Accessed 2021 Aug 26].

  34. 34.

    Corless CL, Ballman KV, Antonescu CR, et al. Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: the ACOSOG Z9001 trial. J Clin Oncol. 2014;32:1563–70.

    CAS  Article  Google Scholar 

  35. 35.

    Ye H, Xin H, Zheng Q, et al. Prognostic role of the primary tumour site in patients with operable small intestine and gastrointestinal stromal tumours: a large population-based analysis. Oncotarget. 2018;9:8147–54.

    Article  Google Scholar 

  36. 36.

    Rutkowski P, Wozniak A, Dȩbiec-Rychter M, et al. Clinical utility of the new American Joint Committee on Cancer staging system for gastrointestinal stromal tumors: current overall survival after primary tumor resection. Cancer. 2011;117:4916–24.

    Article  Google Scholar 

  37. 37.

    Miettinen M, Wang ZF, Sarlomo-Rikala M, et al. Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age. Am J Surg Pathol. 2011;35:1712–21.

    Article  Google Scholar 

  38. 38.

    Ibrahim A, Chopra S. Succinate dehydrogenase-deficient gastrointestinal stromal tumors. Arch Pathol Lab Med. 2020;144:655–60.

    CAS  Article  Google Scholar 

  39. 39.

    Miettinen M, Lasota J. Succinate dehydrogenase deficient gastrointestinal stromal tumors (GISTs)—a review. Int J Biochem Cell Biol. 2014;53:514–9.

    CAS  Article  Google Scholar 

  40. 40.

    Janeway KA, Kim SY, Lodish M, et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Nat Acad Sci USA. 2011;108:314–8.

    CAS  Article  Google Scholar 

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Authors

Corresponding author

Correspondence to Justin Merrill Marken Cates.

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Conflicts of interest

Dr. Justin Cates serves on the Scientific Advisory Board for Eluciderm, Inc. Dr. Vincent Trinh was supported by the McLaughlin Fellow Scholarship granted by the Université de Montréal. Dr. Nooshin Dashti declares no conflict of interest.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. The data used herein was derived from a deidentified NCDB file.

Informed consent

The Institutional Research Board at Vanderbilt University Medical Center approved the study protocol; a waiver of informed consent was granted because no HIPAA identifiers were downloaded from the NCDB or used in the analytic protocol (IRB #210259).

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Trinh, V.QH., Dashti, N.K. & Cates, J.M.M. A proposed risk assessment score for gastrointestinal stromal tumors based on evaluation of 19,030 cases from the National Cancer Database. J Gastroenterol 56, 964–975 (2021). https://doi.org/10.1007/s00535-021-01831-x

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Keywords

  • Gastrointestinal stromal tumor
  • National Cancer Database
  • Modified NIH criteria
  • Nashville Risk Score