Much scientific research in recent years has centered on uncovering prognostic indicators for malignant diseases. The main goal of treatment is always curative, but in cases in which that is currently impossible, the physician’s attention then turns toward extending and improving the quality of life of patients. 

Gastrointestinal stromal tumors (GIST) are cancers that can occur anywhere along the digestive tract. GISTs are most commonly known to occur in the stomach region (60%), with the second being the small intestine (30%). Currently, 0.70 per 100,000 people in the US are diagnosed with GISTs annually, with that number rising each year. 

At present, there is a lot of data on prognostic indicators for GISTs that can be useful to the treating physician. A study published in Translational Oncology reviewed “the clinicopathological characteristics of GISTs, the special molecular subtypes and other factors that may affect prognosis.”


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Commonly Recognized Prognostic Indicators 

The latest clinical guidelines (including the NCCN, ESMO/EURACAN, and French Intergroup Clinical Practice guidelines) recognize the following factors as significant in predicting prognosis: 

  • Mitotic rate 
  • Tumor size 
  • Tumor site 
  • Tumor rupture.

Researchers have studied the 4 prognostic indicators in great detail over the last few years, thus allowing physicians to better understand the extent to which these factors influence prognosis. For example, researchers have since discovered that with regards to tumor site, GISTs have a higher risk of recurrence in extra-gastric sites compared to those located in the gastric region. 

Beyond these 4 widely recognized prognostic indicators, researchers have also been able to look into the impact of GIST genotypes on prognosis. For example, 80% of GISTs have a functional mutation of KIT, with platelet-derived growth factor receptor alpha (PDGFRA) mutations accounting for 5% to 10% of cases. 

Read more about GIST patient education

GISTs tumors that are not associated with KIT or PDGFRA mutations are known as KIT/PDGFRA wild-type GISTs. Knowing the type of mutation associated with the GIST tumor is important because it is integral to clinical decision-making. Further research into the mutations of GISTs has shown they are associated with imatinib sensitivity and resistance. This is important because imatinib forms the first-line treatment of GISTs. Fortunately, research tells us that most mutation types respond well to the therapy. 

However, imatinib resistance can occur, and when it does, it is usually within a treatment period of less than 2 years. Secondary imatinib resistance is more commonly observed in patients with advanced or metastatic GISTs. Secondary imatinib resistance is most commonly caused by secondary mutations in KIT. Research has found that secondary KIT mutations occur in 40% of GIST patients with imatinib resistance. Secondary PDGFRA mutations are less common. 

This indicates that the time and type of secondary mutations are important factors in determining prognosis in patients with secondary imatinib resistance. Scientists have developed new tyrosine kinase inhibitors (TKIs) to deal with this problem, with mixed results. 

Other Prognostic Indicators 

Currently, surgical resection remains the first choice of treatment for GISTs, and R0 resection can be used for 45% to 60% of GISTs. This percentage increases when preoperative adjuvant therapy is used to shrink large GIST tumors to resectable sizes. This usually takes 6 to 12 months. 

However, tumor rupture can occur during surgery (or spontaneously). During surgery, any incision into, or disruption of, the tumor capsule can cause potential dissemination of tumor cells into the peritoneal cavity.

Tumor rupture is defined according to the Oslo sarcoma standard as below: 

  • Tumor fracture or spillage 
  • Blood-stained ascites
  • Gastrointestinal perforation at the tumor site 
  • Microscopic infiltration of an adjacent organ 
  • Intralesional dissection or piecemeal resection
  • Incisional biopsy. 

Tumor rupture carries a poor prognosis, with severe tumor rupture more likely to cause implant metastasis than a slight tumor rupture. 

The study authors also uncovered a list of other prognostic indicators: 

  • Gastrointestinal hemorrhage: poor recurrence-free survival (RFS) and overall survival (OS)
  • High Ki67 index: high risk of recurrence
  • High prognostic nutritional index (PNI): Longer RFS and OS
  • Tumor necrosis: Low disease-free survival (DFS) and poor OS
  • Aged more than 50 years: Lower disease-specific survival (DSS) and OS than in young people. 

Clinical Application

This study concludes that “in recent years, many prognostic factors have been found”, but the “lack of prospective, large sample, multicenter studies” means that “the level of evidence is not particularly high.” However, with “continuous study, there will be some factors added to the risk classifications to guide the treatment of GIST patients and improve their prognosis.”

In this article, a long list of prognostic indicators has been identified, but the question remains: how does this information translate to better patient care? When it comes to prognostic indicators, physicians should be wary of falling into the trap of wanting to know more just for the sake of knowing more. We can and must contemplate ways to use this information to improve patient care. 

For example, the widely recognized risk of tumor rupture on prognosis means that surgeons should avoid accidental iatrogenic tumor rupture as much as possible during surgery. In addition, the impact of advanced age on prognosis should encourage early surveillance among at-risk groups. It is these proactive measures that will make a real difference in the patients that we treat. 

References

Zhang H, Liu Q. Prognostic indicators for gastrointestinal stromal tumors: a review. Translational Oncology. 2020;13(10):100812. doi:10.1016/j.tranon.2020.100812

Nishida T, Hølmebakk T, Raut CP, Rutkowski P. Defining tumor rupture in gastrointestinal stromal tumor. Annals of Surgical Oncology. 2019;26(6):1669-1675. doi:10.1245/s10434-019-07297-9