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GIST Recurrence Risk Calculator

1. Select model:

Tumor size:


Mitotic rate: Number of mitoses per 50 high powered fields (HPFs)


Location:


Tumor size:


Mitotic rate: Number of mitoses per 50 high powered fields (HPFs)


Tumour location:


Tumour rupture:


gold
Risk of recurrence:

GIST (Gastrointestinal tumor) recurrence risk calculator


The risk of recurrence in resected gastrointestinal stromal tumors is impacted by a number of variables: tumour size, mitotic index, primary location and tumor rupture. Gastric GISTs are noted to have a more favourable prognosis than intestinal GISTs with a similar profile.

Various model systems have been developed to predict recurrence risk in resected GISTs. Two popular tools, the Miettinen and the modified NIH classification are provided in this tool.

Risk of recurrence estimation is important in deciding on use of adjuvant therapy.

ESMO(1) and NCCN(2) guidelines recommend 3 years of adjuvant imatinib in patients with a high (>50%) risk of recurrence. This is based on a randomised trial showing relapse free survival (RFS) and overall survival benefit compared to 1 year of therapy in high risk patients (3). A previous placebo controlled trial also found that 1 year of imatinib improved RFS compared to placebo in patients with a tumor diameter >3cm (4).

Adjuvant imatinib is not recommended in patients with a low (<10%) risk of recurrence.

There is a lack of consensus on whether patients with an intermediate risk of recurrence (10-50%) should receive adjuvant imatinib, and the guidelines suggest a shared decision approach in such cases.

Approximately 80% of GISTs have an activating KIT mutation and 5-10% have PDGFRA mutations.

Adjuvant imatinib is indicated KIT and PDGFRA mutated tumors. The exception is PDGFRA exon 18 D824V mutations, which should not receive imatinib due to the lack of sensitivity with this genotype.

In tumors with KIT exon 9 mutation, there is data from the advanced disease setting to support the use of a higher dose of imatinib of 800mg/daily (as opposed to 400mg/daily) but prospective data in the adjuvant setting to support this are not currently available.

SDH deficient and NF1 related GISTs should not receive adjuvant imatinib due to lack of sensitivity.

Miettinen classification


This classification was developed by the Armed Forces Institute of Pathology and uses the variables tumor size, mitotic count and primary location(5). The model was developed based on long term follow up of more than 1800 patients (1055 gastric, 629 small intestinal, 144 duodenal, and 111 rectal GISTs)(6-9). Each primary tumor type was divided into 8 prognostic groups based on mitotic index and size and analysis of disease free survival performed on each prognostic group.

Modified NIH classification


This classfication system added tumor site and presence of tumor rupture to the original NIH classification system which was based on size and mitotic count (10-11). It accounts for non-gastric GISTs having a higher risk of recurrence than gastric GISTs. The model uses data from prior studies of outcomes in non-gastric GISTs(6) and studies showing tumor rupture as an independent predictor of high recurrence risk (12).

In this classification, tumors classified as high risk have a greater than 15-20% risk of recurrence within 10 to 15 years of diagnosis.
References:

  1. Casali PG, Blay JY, Abecassis N, et al. Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol. 2022;33(1):20-33. doi:10.1016/j.annonc.2021.09.005
  2. NCCN GIST guidelines. https://www.nccn.org/professionals/physician_gls/pdf/gist.pdf
  3. Joensuu H, Eriksson M, Sundby Hall K, et al. Adjuvant Imatinib for High-Risk GI Stromal Tumor: Analysis of a Randomized Trial. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(3):244-250. doi:10.1200/JCO.2015.62.9170
  4. Dematteo RP, Ballman K V, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet (London, England). 2009;373(9669):1097-1104. doi:10.1016/S0140-6736(09)60500-6
  5. 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. Am J Surg Pathol. 2006;30(4):477-489. doi:10.1097/00000478-200604000-00008
  6. 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. Am J Surg Pathol. 2005;29(1):52-68. doi:10.1097/01.pas.0000146010.92933.de
  7. Miettinen M, Kopczynski J, Makhlouf HR, et al. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. Am J Surg Pathol. 2003;27(5):625-641. doi:10.1097/00000478-200305000-00006
  8. Miettinen M, Furlong M, Sarlomo-Rikala M, Burke A, Sobin LH, Lasota J. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus: a clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases. Am J Surg Pathol. 2001;25(9):1121-1133. doi:10.1097/00000478-200109000-00002
  9. Fletcher CDM, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol. 2002;33(5):459-465. doi:https://doi.org/10.1053/hupa.2002.123545
  10. Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol. 2008;39(10):1411-1419. doi:https://doi.org/10.1016/j.humpath.2008.06.025
  11. Takahashi T, Nakajima K, Nishitani A, et al. An enhanced risk-group stratification system for more practical prognostication of clinically malignant gastrointestinal stromal tumors. Int J Clin Oncol. 2007;12(5):369-374. doi:10.1007/s10147-007-0705-7