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Treatment for gastrointestinal stromal tumors (GISTs) depends mainly on factors such as:

• If the tumor can be resected (removed) with surgery, which is based on the size of the tumor, where it is, and how far it has spread
• How quickly the tumor is growing (its mitotic rate)
• If the tumor cells have certain gene mutations
• The risk of the tumor coming back after treatment

Other factors, such as a person’s age and overall health, can be important as well.

Localized, smaller (resectable) tumors

Most small GISTs need to be treated. But some very small tumors (less than 2 centimeters across) that are not causing any symptoms might never grow enough to cause any problems. One option for such a tumor might be to just watch it carefully, checking it with endoscopy at regular intervals, such as once or twice a year. As long as it is not growing, you might not need further treatment.

Surgery is the main treatment for most other small tumors. The need for further treatment after surgery depends on the risk of the GIST coming back.

Tumors that are small and are not growing quickly typically have a low risk of coming back, so often no further treatment is needed.

The risk of a GIST coming back after surgery is higher if:

• The tumor is larger
• It did not start in the stomach
• The cancer cells are dividing quickly (have a high mitotic rate)

If the doctor thinks that the cancer has an intermediate or high risk of coming back based on these factors, adjuvant treatment with the targeted drug imatinib (Gleevec) is typically recommended for at least a year after surgery. For tumors that are highly likely to come back, many doctors now recommend at least 3 years of imatinib.

The doctor will likely test the tumor cells for certain changes in the KIT and PDGFRA genes before prescribing imatinib. This is because imatinib isn’t likely to be helpful for tumors that don’t have one of these gene changes?.

Localized, larger (marginally resectable) tumors

Tumors that are larger or in places that make them harder to remove (resect) completely might require more extensive surgery, which could cause health problems both in the short term and later on. Because of this, surgery is not typically the first treatment.

Treatment with the targeted drug imatinib (Gleevec) is usually done first to try to shrink the tumor. But before starting treatment, it’s important to be sure that the tumor is in fact a GIST, so a biopsy is needed. As part of the testing of the biopsy sample, the tumor cells are typically checked for certain changes in the KIT and PDGFRA genes. This is because imatinib isn’t likely to be helpful for tumors that don’t have one of these gene changes. If imatinib is given, it is continued at least until the tumor stops shrinking.

If the tumor shrinks enough, surgery might be done if the doctor thinks it can be removed safely. Imatinib will likely be continued after surgery to help lower the chance that the cancer will come back.

If the tumor doesn’t shrink enough to make surgery possible, imatinib is often continued for as long as it seems to help. If it's no longer working, sometimes upping the dose can be helpful. If not, or if the side effects are too severe, another targeted drug, sunitinib (Sutent), may be tried instead. If sunitinib is no longer working, regorafenib (Stivarga) may help some people. If this drug is no longer working, ripretinib (Qinlock) may be helpful.

Tumors that are not removable or have spread to distant sites (unresectable tumors)

Treatment options for unresectable GISTs depend on why they are unresectable and, if they have spread, how extensive the spread is.

Surgery is not typically the first treatment for these tumors, so before starting treatment, it’s important to confirm that the tumor is in fact a GIST with a biopsy. 

The targeted drug imatinib (Gleevec) is typically the preferred first treatment for most advanced GISTs. (The targeted drug avapritinib (Ayvakit) might be used instead if the cancer cells have certain changes in the PDGFRA gene.) As part of the testing of the biopsy sample, the tumor cells might be checked for certain changes in the KIT and PDGFRA genes. This can give an idea of how likely it is that imatinib (or avapritinib) will be helpful.

If imatinib is used, it is continued for as long as the tumor doesn’t grow (and the side effects are tolerable). If the tumor starts to grow again, it may respond to increasing the dose of imatinib. If not, or if the side effects from imatinib are too severe, a switch to sunitinib (Sutent) may be helpful. If sunitinib is no longer working, regorafenib (Stivarga) may help some people. If regorafenib is no longer helpful, ripretinib (Qinlock) may be an option.

If the tumor shrinks enough with targeted therapy, surgery may then be an option for some people. This might be followed by more targeted therapy if it is still effective.

If the cancer has spread to only 1 or 2 sites in the abdomen (such as the liver), the doctor may advise removing the main tumor and trying to remove these other tumors as well. If this is the case, be sure to talk with your doctor about what the goals of treatment are (whether it is to try to cure the cancer, to help you live longer, or to prevent or reduce symptoms), as well as its possible benefits and risks.

Other options to treat cancers that have spread to the liver include ablation and embolization to try to destroy these tumors.

Cancers that are no longer responding to the targeted drugs discussed above can be hard to treat. Some doctors may recommend trying other targeted drugs, such as sorafenib (Nexavar), dasatinib (Sprycel), nilotinib (Tasigna), or pazopanib (Votrient), although it’s not yet clear how helpful these drugs are.

Standard chemotherapy drugs are usually not very effective. Taking part in a clinical trial of a newer treatment may be a good option for some people.

Recurrent tumors

When a cancer comes back after treatment, it is called a recurrence. If the cancer comes back (recurs) in or near the place it started, it is called a local recurrence. If it recurs at other sites (like the lungs or liver), it is called a distant recurrence. Treatment options for recurrent GISTs depend on the location and extent of the recurrence.

For most recurrences, treatment with the targeted drug imatinib (Gleevec) is often the first option to try to shrink any tumors, as long as it is still effective and the patient can tolerate taking it. If the starting dose of imatinib doesn't work, the dose can be increased. Another option is to try other targeted drugs, such as sunitinib (Sutent), regorafenib (Stivarga), or ripretinib (Qinlock).

If the cancer comes back as one or more well-defined tumors, removing or destroying the tumor may be an option. Doctors are still not certain if removing GISTs that come back after treatment helps people live longer, so it's important to discuss the risks and benefits of this treatment with your doctor and family.

Radiation therapy might also be an option to help treat symptoms such as pain, especially in tumors in the bones.

If the targeted drugs mentioned above are no longer helpful, some doctors may recommend trying other targeted drugs, such as sorafenib (Nexavar), dasatinib (Sprycel), nilotinib (Tasigna), or pazopanib (Votrient), although it’s not yet clear how helpful these drugs are.

Because these cancers are often hard to treat, you may want to consider taking part in clinical trials of newer treatments as well.