Treatment Update: Tenosynovial Giant Cell Tumor (TGCT)

Although TGCT is not cancerous, it is most often treated by an oncologist, as they understand how tumors grow and can guide treatment decisions. Treatment for

TGCT is individualized depending on the type of TGCT, its location, its risk of recurring and the symptoms being experienced. Active surveillance (close monitoring) may be an approach if there are no symptoms, the tumor is slow-growing or if surgery poses a significant risk.

Surgery

Surgery is the main treatment for TGCT. The tumor (or tumors) is excised (removed) along with any inflamed joint tissue. The surgery may be “open” (cutting the skin and tissues) or arthroscopic, a less invasive procedure in which a few cuts are made around the joint and a small camera is inserted to guide the surgery. Additional surgery may be needed if the tumor (or tumors) returns.

Total joint replacement (arthroplasty) may be needed in advanced cases where chronic inflammation has caused severe joint degeneration. Arthroplasty improves function and reduces pain by replacing the damaged joint with plastic, metal or ceramic parts.

Radiation

Radiation therapy is primarily used after surgery for diffuse or recurrent TGCT.

• External beam radiation uses a machine, called a linear accelerator, to direct multiple beams of radiation to the tumor. The use of CT (computerized tomography) and PET (positron emission tomography) scans allows radiation oncologists to accurately target tumors, shaping the radiation beams to the size and dimensions of the tumor to help spare healthy tissue.

• Image-Guided Intensity-Modulated Radiotherapy (IG-IMRT) is a newer, more precise technique that further minimizes damage to surrounding healthy tissue.

Targeted Therapy

Targeted therapies are designed to target the specific cell mechanisms that are important for the growth and survival of tumor cells.

If surgery is not possible or effective, there are two oral therapies approved by the U.S. Food and Drug Administration (FDA) designed to inhibit the Colony-Stimulating Factor 1 Receptor (CSF1R): pexidartinib (Turalio), approved in 2019, and vimseltinib (Romvimza), approved in 2025. The overexpression of CSF1R drives the tumor formation in TGCT.

All treatments can cause side effects. It’s important that you report any side effects that you experience to your health care team so they can help you manage them. Report them right away—don’t wait for your next appointment. Doing so will improve your quality of life and allow you to maintain your treatment plan. It’s important to remember that not all patients experience all side effects, and patients may experience side effects not listed here.

Radiation

The side effects of radiation therapy can include dryness, swelling, peeling, redness and (rarely) blistering. If a reaction occurs, contact your health care team so the appropriate treatment can be prescribed. It’s especially important to contact your health care team if there is any open skin or painful area, as this could indicate an infection. Infections can be treated with an oral antibiotic or topical antibiotic cream.

Side Effects of Targeted Therapy

Pexidartinib is associated with serious liver-related side effects, and the medication is only available through the FDA-mandated Turalio REMS (Risk Evaluation and Mitigation Strategy) program. There is no evidence of liver injury with vimseltinib; the most common side effects include swelling, rash, headaches and fatigue.

Treatment Side Effects

All cancer treatments can cause side effects. It’s important that you report any side effects that you experience to your health care team so they can help you manage them. Report them right away—don’t wait for your next appointment. Doing so will improve your quality of life and allow you to stick with your treatment plan. It’s important to remember that not all patients experience all side effects, and patients may experience side effects not listed here.

Side Effects of Chemotherapy

The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are used, and can include:

• Fatigue
• Headaches
• Reduction in blood cell counts, with need for transfusions of red blood cells or platelets
• Fatigue
• Bruising or bleeding
• Abnormal taste of food; loss of appetite
• Nausea
• Rashes
• Hair loss
• Hearing loss
• Diarrhea
• Mouth sores or painful swallowing
• Changes in the skin (dryness, rashes, darkening, or lines on the fingernails)
• Pain, tingling, and numbness, especially in hands and feet (neuropathy)

Side Effects of Targeted Treatments and Hormone Therapy

Targeted treatment drugs and hormone therapy don’t have the same effect on the body as do chemotherapy drugs, but they can still cause side effects.

Side effects of certain targeted therapies can include diarrhea, liver problems (such as hepatitis and elevated liver enzymes), nerve damage, problems with blood clotting and wound healing, and high blood pressure.

The side effects of hormone therapy are dependent on the type of therapy and include hot flashes (seen more with tamoxifen) and joint pain (seen more with aromatase inhibitors).

Side Effects of Radiation Therapy

Changes to the skin are the most common side effects of radiation therapy; those changes can include dryness, swelling, peeling, redness, and blistering. It’s especially important to contact your health care team if there is any open skin or painful areas, as this could indicate an infection.

You may want to add that radiation can also produce systemic symptoms such as fatigue. In the setting of metastatic breast cancer, radiation is used to palliate symptoms and is often given to treat bone pain. Side-effects depend on the radiation site (also known as field). For example, if a patient is getting radiation to the pelvis or low back, she may also have diarrhea because there is bowel in or near the field being treated.

General Side Effects

Some side effects may occur across treatment approaches. This section provides tips and guidance on how to manage these side effects should they occur.

Digestive Tract Symptoms

Nausea and vomiting

• Avoid food with strong odors, as well as overly sweet, greasy, fried, or highly seasoned food.
• Nibble on dry crackers or toast. These bland foods are easy on the stomach.
• Having something in your stomach when you take medication may help ease nausea.
• Many effective medications for nausea and vomiting have been developed in recent years; talk to your doctor about whether any may be right for you.

Diarrhea

• Drink plenty of water. Ask your doctor about using drinks such as Gatorade which provide electrolytes as well as liquid. Electrolytes are body salts that must stay in balance for cells to work properly.
• Over-the-counter medicines such as loperamide (Imodium A-D and others) and prescription drugs are available for diarrhea but should be used only if necessary. If the diarrhea is bad enough that you need medicine, discuss it with your doctor or nurse.
• The BRAT diet (bananas, rice, applesauce, toast) and soluble fiber such as oats, bran and barley can help with diarrhea. Foods high in insoluble fiber, such as leafy greens and most fruits should be avoided as they can worsen diarrhea. Oily foods should also be avoided.
• Low fat food choices are less likely to cause diarrhea than fatty, greasy, or fried foods. The fats you eat should come from healthy sources, such as olive oil, canola oil, avocado, olives, nuts, and seeds.

Fatigue

Fatigue (extreme tiredness not helped by sleep) is one of the most common side effects of many cancer treatments. If you are taking a medication, your doctor may lower the dose of the drug, as long as it does not make the treatment less effective. If you are experiencing fatigue, talk to your doctor about whether taking a smaller dose is right for you.

There are a number of other tips for reducing fatigue:

• Take several short naps or breaks.
• Take short walks or do some light exercise, if possible.
• Try easier or shorter versions of the activities you enjoy.
• Ask your family or friends to help you with tasks you find difficult or tiring.

Fatigue can be a symptom of other illnesses, such as anemia, diabetes, thyroid problems, heart disease, rheumatoid arthritis, and depression. So be sure to ask your doctor if he or she thinks any of these conditions may be contributing to your fatigue.

Pain

There are a number of options for pain relief, including prescription and over-the-counter medications. It’s important to talk to a member of your health care team before taking any over-the counter medication, to determine if they are safe and will not interfere with your treatments. Many pain medications can lead to constipation, which may make your pain worse. Your doctor can prescribe medications that help to avoid constipation.

Physical therapy, acupuncture, and massage may also be of help in managing your pain. Other techniques, such as mindfulness meditation, deep breathing exercises, and yoga may also be helpful. Consult with a member of your health care team before beginning any of these activities.

Q: How rare is TGCT?

A: TGCT is extremely rare, with only 11-50 cases per million people each year. Although it can affect people of any age, it is most commonly diagnosed between the ages of 30 and 50, and is slightly more common in women than in men.

Q: What is the recurrence risk of TGCT? Are there any dietary or lifestyle changes that help reduce recurrence?

A: The lifetime recurrence risk in localized TGCT is as high as 15%; in diffuse TGCT it can be as high or higher than 70%. No specific diet or lifestyle modifications have been identified as reducing the risk of TGCT or its recurrence.

Q: Is TGCT ever treated with chemotherapy or immunotherapy?

A: TGCT is not treated with chemotherapy or immunotherapy. The only medicines approved by the FDA to treat TGCT are targeted therapies that inhibit (block) the Colony-Stimulating Factor 1 Receptor (CSF1R); the overexpression of which leads to tumor growth.

Q: Are there any clinical trials in progress for TGCT?

A: The phase lll MANEUVER trial is evaluating the investigational therapy pimicotinib for the treatment of TGCT. Like the