All About Gastrointestinal Stromal Tumors (GIST)

Autor: OncoLink Team
Última Vez Revisión: 24 de mayo de 2018

What is a gastrointestinal stromal tumor (GIST)?

GIST is a soft tissue sarcoma that can arise anywhere in the gastro-intestinal (GI) tract. It is most commonly found in the stomach (60%) and the small intestine (30%). It can also be found in the colon, rectum, esophagus and appendix. Sarcoma is a cancer of the soft tissue or bone. GIST starts in an interstitial cell of Cajal (ICC’s), a special cell found only in the wall of the GI tract. These cells are part of the autonomic nervous system and play a role in how we digest food. GIST tumors can be benign (not cancerous) or malignant (cancer).

Soft tissues include muscles, tendons, fibrous tissues, fat, blood vessels, nerves, and synovial tissues (found in joints). Sarcomas are more specifically named by the tissues they affect. For example, sarcoma that arises from the bone is called osteosarcoma (although there are other types that form in the bone), and a sarcoma of the fat cells is called liposarcoma. (See list below for types of soft tissue sarcomas). Soft tissue sarcomas encompass a group of 50 different types of tumors, with most types considered extremely rare. Sarcomas account for 0.7% of all adult cancer diagnoses, with close to 12,000 new cases annually in the soft tissues and 2,900 new cases annually in the bone. Soft tissue sarcomas can develop from any site in the body, but the majority form in the extremities (about 50%), most commonly in the thigh. The remaining cases are evenly distributed throughout the rest of the body (10-15% in the trunk, <10% in the head & neck and 15% in the retroperitoneum).

What causes GIST and am I at risk?

GIST is a rare type of cancer. The latest statistics estimate there are about between 4000-5000 cases of GIST diagnosed in the United State each year. Older age (over 50) may increase risk of developing a GIST tumor. Men are diagnosed more often than women. Some have a genetic predisposition to GIST. This is called familial gastrointestinal stromal tumor syndrome. This syndrome is often associated with a mutation in the c-kit or PDGFRA gene. Other genetic syndromes that may be associated with an increased risk of GIST are neurofibromatosis type 1 (von Reclinkhausen disease) and Carney-Stratakis syndrome.

Because GIST is such a rare tumor, early screening tests do not exist and there is little one can do to actively reduce the risk of developing GIST.

What are the signs and symptoms of GIST?

How the GIST presents is often influenced by where in the GI tract it is located as well as its size. Most commonly, an individual will experience GI bleeding as the first symptom of GIST. However, GI bleeding can be caused by many medical issues. This bleeding can sometimes result in anemia. Other possible symptoms include abdominal pain, swelling or palpable mass in the abdomen, GI obstruction, fatigue, dysphagia (trouble swallowing), nausea/vomiting, decreased appetite and satiety (feeling full).

In some cases, the tumor can cause a stomach or intestinal obstruction (blockage) or perforation (tear). This is a medical emergency requiring immediate treatment.

How is GIST diagnosed?

In order to confirm a diagnosis of GIST, biopsy of the tumor is essential. The biopsy can also assist in deciding treatment course. GIST tumors can be very soft and fragile. It is essential that your treatment team have experience performing biopsies on presumed GIST tumors. A special kind of biopsy, called an EUS-FNA (endoscopic ultrasound fine needle aspiration) of the suspected tumor is the preferred type of biopsy as it carries a lower risk of bleeding, tumor rupture, and intra-abdominal tumor spread.

GIST tumors often express gene mutations called KIT (CD117) or PDGFRA. GIST tumors will have molecular testing to determine any mutations as this greatly impacts treatment decisions.

Your care team may also utilize various imaging tests to assist in initial diagnosis, staging and monitoring response to therapy. These tests may include CT and PET scans.

How is GIST staged?

Most tumor types are staged using a system developed by experts. The most widely used system has been developed by the American Joint Committee on Cancer (AJCC) (7th edition). It incorporates tumor size, histologic grade (how different the cells look under the microscope when compared to normal cells), and spread to lymph nodes or other body sites in determining the stage. The "T stage" represents the extent of the primary tumor itself. The "N stage" represents the degree of involvement of the lymph nodes. The "M stage" represents whether or not there is spread of the cancer to distant parts of the body. In GIST, a further classification, the "G," or histologic grade is also taken into account in staging. This include a measurement of the mitotic rate, or how fast the cancer cells are growing and dividing. A lower mitotic rate can be a predictor of a better outcome. The T, N, G, and M are combined to assign a stage, from I (one) denoting more limited disease, to IV (four) denoting more advanced disease.

The staging system is very complex, and the entire staging system is outlined at the end of this article. Though complicated, the staging system helps healthcare providers determine the extent of the cancer, and in turn, make treatment decisions for a patient's cancer. The stage of cancer, or extent of disease, is based on information gathered through the various tests done as the diagnosis and work-up of the cancer is being performed.

Staging provides the treatment team with important information to base treatment planning. However, another key factor in the treatment of GIST tumors is if they can be removed surgically (resected). The goal of resection is to remove all of the tumor.

What are the treatments for GIST?

Surgery

For tumors that are localized or have the potential to be resected (removed), surgery is often the first course of treatment. Again, because these tumors are fragile and carry a large risk of rupture, it is important that the surgeon have experience with removal of GIST tumors.

Surgical removal of GIST tumors can be done through incision (cutting the skin) or through laparoscopic procedures, however this depends on the size and location of the GIST tumor.

Targeted Therapy

Because of genetic mutations associated with GIST, many tumors are highly responsive to targeted therapy, which are medications that target an abnormality found specifically on the cancer cells. The targeted therapies used for GIST are called tyrosine kinase inhibitors or multikinase inhibitors. Tyrosine kinase inhibitors are designed to block the action of a specific enzyme called tyrosine kinase. This enzyme plays a major role in the function of cells, and is active in cancer cells, promoting tumor growth and progression. The primary medication used in the treatment of GIST is imatinib. This medication is used after surgery, for 1-3 years depending on tumor size and location, to keep the tumor from coming back. This may be referred to as maintenance therapy. This medication can also be used before surgery (called neo-adjuvant therapy) to shrink the tumor and increase the possibility of complete removal of the tumor.

Other medications, including sunitinib, sorefenib, nilotinib, dasatanib, pazopanib, everolimus and regorafenib can also be used in the treatment of GIST when the disease progresses after first line treatment with imatinib.

Interventional Procedures

Radiofrequency embolization, embolization or chemoembolization may also be used in the treatment of progressive GIST. Chemoembolization delivers chemotherapy directly to the tumor through the artery that supplies blood to the tumor. The artery is then blocked (embolized) to cut off the flow of blood to the tumor. Radiofrequency embolization utilizes high energy radio waves which heat the tumor and destroy cancer cells. These procedures are typically performed by interventional radiologists.

Radiation Therapy

There is little role for radiation therapy in the treatment of GIST. However, it may be used on a case by case basis to palliate symptoms caused by metastatic disease to other organs.

Clinical Trials

There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow Up Care and Survivorship

After surgery and when on maintenance therapy with medication, you will be likely be evaluated by your healthcare provider for physical exam and lab tests every 3-6 months for five years, then annually. Your provider will also order imaging (CT scan) yearly or more often if indicated.

Fear of recurrence, relationship challenges, the financial impact of cancer treatment, employment issues and coping strategies are common emotional and practical issues experienced by GIST survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With some 15 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

Resources for More Information

Patient Services Incorporated (PSI)
Provides co-pay assistance for patients with GIST and public insurance (Medicare/Medicaid/VA).  Funds are dependent on availability.
http://www.patientservicesinc.org/For-Patients/Supported-Illnesses

Sarcoma Foundation of America
The SFA raises money for sarcoma research and aims to raise awareness of sarcoma. The site has information for patients as well.
http://www.curesarcoma.org/

Appendix: Complete GIST Staging

American Joint Committee on Cancer, 8th Edition, 2016

Primary Tumor (T)

Description

TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

T1

Tumor 2 cm or less

T2

Tumor more than 2 cm but not more than 5 cm

T3

Tumor more than 5 cm but not more than 10 cm

T4

Tumor more than 10 cm in greatest dimension

Regional Lymph Nodes (N)

Regional Lymph Nodes (N)

Description

N0

No regional lymph node metastasis or unknown lymph node status

N1

Regional lymph node metastasis

Distant Metastasis (M)

Distant

Metastasis

Description

M0

No distant metastasis

M1

Distant metastasis

Histologic Grade (G)

Histologic

Grade G)

Description

Low

5 or fewer mitoses per 5 mm2, or per 50 HPF

High

Over 5 mitoses per 5 mm2, or per 50 HPF

Anatomic Stage/Prognostic Groups-Gastric GIST

Group

T

N

M

Mitotic rate

Stage IA

T1 or T2

N0

M0

Low

Stage IB

T3

N0

M0

Low

Stage II

T1

T2

T4

N0

N0

N0

M0

M0

M0

High

High

Low

Stage IIIA

T3

N0

M0

High

Stage IIIB

T4

N0

M0

High

Stage IV

Any T

Any T

N1

Any N

M0

M1

Any rate

Any rate

Note: Also to be used for omentum.

Anatomic Stage/Prognostic Groups- Small Intestine GIST

Group

T

N

M

Mitotic rate

Stage I

T1 or T2

N0

M0

Low

Stage II

T3

N0

M0

Low

Stage IIIA

T1

T4

N0

N0

M0

M0

High

Low

Stage IIIB

T2

T3

T4

N0

N0

N0

M0

M0

M0

High

High

High

Stage IV

Any T

Any T

N1

Any N

M0

M1

Any rate

Any rate

Note: Also to be used for esophagus, colorectal, mesentery, and peritoneum

Referencias

ACS Gastrointestinal Stromal Tumors http://www.cancer.org/cancer/gastrointestinalstromaltumorgist/index

NCCN Guidelines http://www.nccn.org/ (soft tissue sarcomas) login required

Benjamin, R. S., & Casali, P. G. (2016). Adjuvant Imatinib for GI Stromal Tumors: When and For How Long? Journal of Clinical Oncology34(3), 215-218.

Demetri, G. D., Reichardt, P., Kang, Y. K., Blay, J. Y., Rutkowski, P., Gelderblom, H., ... & Badalamenti, G. (2013). Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. The Lancet381(9863), 295-302.

De Vogelaere, K., Van Loo, I., Peters, O., Hoorens, A., Haentjens, P., & Delvaux, G. (2012). Laparoscopic resection of gastric gastrointestinal stromal tumors (GIST) is safe and effective, irrespective of tumor size. Surgical Endoscopy26(8), 2339-2345.

ESMO/European Sarcoma Network Working Group. (2012). Gastrointestinal stromal tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology23(suppl 7), vii49-vii55.

Hsu, J. T., Le, P. H., Kuo, C. F., Chiou, M. J., Kuo, C. J., Chen, T. H., ... & Jan, Y. Y. (2017). Imatinib dose escalation versus sunitinib as a second-line treatment against advanced gastrointestinal stromal tumors: A nationwide population-based cohort study. Oncotarget8(41), 71128.

Jakob, J., Mussi, C., Ronellenfitsch, U., Wardelmann, E., Negri, T., Gronchi, A., & Hohenberger, P. (2013). Gastrointestinal stromal tumor of the rectum: results of surgical and multimodality therapy in the era of imatinib. Annals of surgical oncology20(2), 586-592.

Joensuu, H., & DeMatteo, R. P. (2012). The management of gastrointestinal stromal tumors: a model for targeted and multidisciplinary therapy of malignancy. Annual review of medicine63, 247.

Joensuu, H., Eriksson, M., Hall, K. S., Hartmann, J. T., Pink, D., Schütte, J., ... & Schlemmer, M. (2014). Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib. Cancer120(15), 2325-2333.

Joensuu, H., Eriksson, M., Hall, K. S., Hartmann, J. T., Pink, D., Schütte, J., ... & Schlemmer, M. (2012). One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. Jama307(12), 1265-1272.

Lim, K. T., & Tan, K. Y. (2017). Current research and treatment for gastrointestinal stromal tumors. World journal of gastroenterology23(27), 4856.

Miettinen, M., & Lasota, J. (2013). Gastrointestinal stromal tumors. Gastroenterology Clinics of North America42(2), 399-415.

Morris, A. D., Maithel, S. K., & Kooby, D. A. (2017). Management of Liver Metastases of Gastrointestinal Stromal Tumors. In Gastrointestinal Stromal Tumors (pp. 209-223). Springer, Cham.

O’Regan, K. N., Shinagare, A. B., Saboo, S. S., Ramaiya, N. H., Jagannathan, J. P., & Tirumani, S. H. (2013). Gastrointestinal stromal tumors (GIST): lesser known facts. Clinical Imaging37(5), 821-829.

Peparini, N., & Chirletti, P. (2013). Tumor rupture during surgery for gastrointestinal stromal tumors: pay attention. World J Gastroenterol19(12), 2009-2010.

Plumb, A. A., Kochhar, R., Leahy, M., & Taylor, M. B. (2013). Patterns of recurrence of gastrointestinal stromal tumour (GIST) following complete resection: implications for follow-up. Clinical Radiology68(8), 770-775.

Postow, M. A., & Robson, M. E. (2012). Inherited gastrointestinal stromal tumor syndromes: mutations, clinical features, and therapeutic implications. Clinical Sarcoma Research2(1), 1.

Tap, W. D., & Schwartz, G. K. (2014). That's the "GIST" of it: use of adjuvant imatinib after resection of a primary GI stromal tumor. Journal of Clinical Oncology32(15), 1543-1546.

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