Gastrointestinal Stromal Tumors (GISTs) Guidelines

Updated: Sep 28, 2016
  • Author: Michael A Choti, MD, MBA, FACS; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Guidelines

Guidelines Summary

Genetic Testing

The National Comprehensive Cancer Network (NCCN) Soft Tissue Sarcoma Panel specifically identifies Carney-Stratakis syndrome as associated with gastrointestinal stromal tumors (GISTs). NCCN recommends that in patients with GIST lacking KIT or PDGFRA mutations, SDH gene mutational analysis should be considered; loss of SDHB protein expression by immunohistochemistry is a useful screen to identify patients who would be candidates for germline mutation testing, but it is not diagnostic of a germline mutation. [36]

WHO Classification of Tumors

In 2013 the World Health Organization released an update of its 2002 classification system for tumors of the soft tissue and bone.  The update incorporated more detailed cytogenetic and molecular data into the classifications. Gastrointestinal stromal tumors (GISTs) have been added in the update, with three subtypes [70] :

  • Benign
  • Uncertain malignant potential
  • Malignant

Tumor Grading Systems

The French Federation of Cancer Centers Sarcoma Group (FNCLCC) system  [71] and the National Cancer Institute system are most commonly used for grading soft tissue sarcomas.6 Both are three-grade systems. [72] The FNCLCC is based on tumor differentiation, tumor necrosis and mitotic activity, while the NCI system bases the evaluation on histology, location and tumor necrosis. In comparison studies, the FNCLCC has shown slightly better ability to predict metastasis development and mortality.

Tumor Staging

Both NCCN and the European Society for Medical Oncology (ESMO) guidelines follow the tumor-node-metastasis (TNM) classification of the American Joint Cancer Committee/Union for International Cancer Control/ (AJCC/UICC) for staging of GISTs. Gastrointestinal stromal tumors (GIST) are staged separately from other sarcomas, with tumors graded as low or high. Anatomic stage/prognostic groupings for GIST are detailed in Table 1, below. [73]

Table 1. Staging of Gastrointestinal Stromal Tumors (Open Table in a new window)

Stage T N M Grade
IA T1 or T2 N0 M0 Low
IB T3 N0 M0 Low
II T1 N0 M0 High
T2 N0 M0 High
T4 N0 M0 Low
IIIA T3 N0 M0 High
IIIB T4 N0 M0 High
IV Any T N1 M0 Any grade
Any T Any N M1 Any grade

For description of GIST TNM designations, see Gastrointestinal Stromal Tumors Staging.

Diagnosis

The NCCN guidelines for gastrointestinal stromal tumors (GISTs) recommend evaluation and management, prior to initiation of therapy, by a multidisciplinary team with expertise and experience in sarcoma. Abdominal/pelvic CT scan with contrast, with or without MRI, is also indicated and chest imaging should be considered. Very small GISTS (<2 cm) may be evaluated with endoscopic ultrasound-guided fine-needle aspiration; for GISTS 2 cm or larger, endoscopy with or without ultrasound may also be indicated in select patients. [36]

Genetic testing for KIT and PDGFRA is a strong recommendation, and in the absence of KIT or PDGFRA mutations, testing for loss of SDHB protein expression by immunohistochemistry should be considered.  If SDHB expression is lost, then genetic counseling and germline mutation testing in SDH genes should be considered. In patients with advanced GISTs, identification of certain specific KIT and PDGFRA mutations helps predict responsiveness to imatinib and the possible benefit of a higher imatinib dose. [36]

ESMO guidelines recommend that patients with small esophagogastric or duodenal nodules <2 cm undergo endoscopic ultrasound assessment and then annual follow-up, reserving excision for patients whose tumor increases in size or becomes symptomatic. For small rectal nodules, however, the ESMO guidelines recommend biopsy/excision after ultrasound assessment, regardless of tumor size. In addition, all nodules 2 cm or larger require biopsy. [29]

Treatment

NCCN treatment recommendations for localized resectable disease include the following [36] :

  • Surgical resection is the primary treatment; for tumors <2 cm with no high-risk features, consider endoscopic surveillance at 6-12 month intervals
  • Preoperative treatment with imatinib may prevent accurate assessment of recurrence risk; consider preoperative imatinib only if surgical morbidity could be reduced by downstaging the tumor preoperatively
  • Testing the tumor to ensure it has a genotype that is likely to respond to imatinib (especially  KIT exon 11) is recommended prior to starting preoperative imatinib
  • Consider postoperative imatinib for at least 36 months  for high-risk tumors

ESMO guidelines discourage a laparoscopic approach for resection of large tumors. [29]

NCCN treatment recommendations for unresectable or metastatic disease include the following [36] :

  • Imatinib (category 1)
  • After assessment of therapeutic effect, resection may be considered or imatinib may be continued if resection is not feasible
  • Continuous daily dosing of sunitinib for patients with imatinib-resistant GIST
  • Regorafenib (category 1) for patients with disease progression on imatinib and sunitinib
  • Tyrosine kinase inhibitor (TKI) therapy should be continued as long as patients are receiving clinical benefit (response or stable disease)
  • Continuation of TKI therapy lifelong for palliation of symptoms is an essential component of best supportive care