Diagnosis and Treatment

Welcome.

My name is Dr. Mrinal Gounder, M.D., and I am a medical oncologist practicing at Memorial Sloan Kettering Cancer Center in New York City. For more than a decade, I have devoted my efforts to building a clinical practice where I take care of a large number of people diagnosed with desmoid tumors. I am also the Scientific Director of DTRF. As a cancer researcher, I am passionate about finding a cure and discovering new drugs to treat desmoid tumors.

If you are reading this page, it is likely that you, your child or your loved ones may have been diagnosed with a desmoid tumor. It is normal to feel frightened, anxious, frustrated, confused or isolated. This is a very rare condition, but the good news is that you are no longer alone. We are here to help and support you. We hope that this web page provides you with information that will empower you and your doctor to make an informed medical decision together. We hope that the broader patient community of DTRF will be a safe space for you to meet other patients and their families – to connect and exchange your stories and experiences.

The good news is that this is often a treatable (and sometimes even curable) condition. I am happy to share that in the last decade – thanks to the Desmoid Tumor Research Foundation – we have been able to build a community of patients, their caregivers, doctors and researchers. This has helped gather a tremendous amount of knowledge about how best to treat desmoid tumors. Thanks in part to DTRF’s support for cutting-edge research, we are now seeing an exciting number of new drugs and modalities to treat this condition.

We are here to help and support you.

Dr. Mrinal Gounder

Mrinal Gounder, M.D. Melanoma and Sarcoma Service,Memorial Sloan-Kettering Cancer Center Scientific Director, The Desmoid Tumor Research Foundation

Read Dr. Gounder’s paper , “Locally Aggressive Connective Tissue Tumors” in the Journal of Clinical Oncology.

Please remember that desmoid tumors are very complex and the below information is a general overview and not intended as medical advice for any individual problem, or as a diagnosis, treatment plan, or recommendation for a particular course of action, and should not be used as a substitute for professional medical advice and services. Please do not delay in seeking professional medical advice regarding your individual circumstances.

What is a desmoid tumor or aggressive fibromatosis?

Desmoid tumors arise from a cell called a “fibroblast” or “myofibroblast” that has proliferated excessively. A fibroblast is a type of cell that is found throughout our body in connective and soft tissues. They are the structural support for our vital organs (e.g. lung, liver, blood vessels, heart, kidneys, skin, intestines etc) and are also involved in wound healing. Because of the prevalence of connective and soft tissues, desmoid tumors can occur at most sites of the body and are commonly found in the extremities, abdominal wall and intra-abdominally.

The desmoid tumor clinical course is unpredictable, and some desmoid tumors will spontaneously regress (~20%), others will remain stable (40-50%) and some will increase in size (30-40%). They can be locally invasive and have a high incidence of local recurrence, but they do not metastasize from one body part to another. For many patients, desmoid tumors are not life-threatening. However, their clinical course is unpredictable, and research is ongoing to determine what prognostic factors might help discern which desmoid tumors will need treatment and which will not. In some cases, desmoid tumors can become life-threatening when they compress important organs such as intestines, kidneys, lungs, blood vessels, nerves, etc.

Desmoid tumors are rare.

In the United States, approximately 1,500 people are diagnosed with desmoid tumors every year. This means that out of a million people approximately 5-6 people are diagnosed with desmoid tumors each year. Because of inconsistent and inaccurate reporting procedures, accurate statistics about the number of desmoid tumor cases are difficult to calculate. Individuals between the ages of 15 and 60 are most often affected, but this disease can occur in anyone including very young children. They occur more commonly in women than in men (2:1), and there are no racial or ethnic differences in predisposition to disease.

Causes of desmoid tumors

The exact cause of most desmoid tumors is unknown, and thus they are called “sporadic” or random. Up to 90% of desmoid tumors arise sporadically and have a mutation in a gene called beta-catenin (CTNNB1). Common point mutations within the CTNNB1 gene are known, such as T41A, S45F, S45P, but are still an active topic of research as to their relevance to the disease. These point mutations are not, at this time, clinically actionable.

A minority of desmoid tumors are caused by a heritable cancer predisposition syndrome called Familial Adenomatous Polyposis or FAP. These desmoid tumors are the result of mutations in the adenomatous polyposis coli gene (APC). Patients with FAP are predisposed to forming numerous polyps in the intestines and – if untreated – go on to develop colorectal cancer. Patients with FAP are often recommended to undergo surgical removal of their colon and/or rectum. Approximately 10-30% of FAP patients will develop a desmoid tumor in their lifetime. FAP-associated desmoid tumors are most commonly found intra-abdominally and may be larger and multifocal. A specific subtype of FAP is called Gardner Syndrome.

Studies have associated desmoid tumors with prior trauma, high estrogenic states, and pregnancy. These associations are not fully understood, and research is ongoing to better understand them.

Diagnosis

The diagnosis of a desmoid tumor is made after the tumor is biopsied and examined under the microscope by a trained pathologist, ideally a soft tissue pathologist. The pathologist examines the tumor cells under the microscope looking for special features that define desmoid tumors. Microscopically, desmoid tumor cells appear as moderately cellular, infiltrative spindle cell proliferations that are set in a collagenous stroma. A key diagnostic feature is the nuclear staining of beta-catenin found in the majority of sporadic desmoid tumors. A lower percentage of FAP-associated desmoid tumors reportedly express nuclear beta-catenin.

A mutational analysis is recommended to confirm the diagnosis and if the tumor is likely sporadic (CTNNB1 mutation) or arises from syndromic condition such as FAP (APC mutation).

Desmoid tumors may also be evaluated by non-invasive methods such as ultrasound, CT and/or MRI scans.

Treatments

There is not one standard of care treatment protocol for desmoid tumors. Efforts have been pursued to standardized care, and evidence-based, consensus guidelines for treatment were published in 2020 by an international team of desmoid tumor experts. Read The Global Consensus Paper on the Management of Desmoid Tumors to learn more about consensus treatment guidelines.

It is important that patients be evaluated and ideally treated by a desmoid tumor expert. These experts are often specialists in sarcoma care. Sarcoma specialists are found at major academic medical centers and can help support patient care through a multidisciplinary team that includes medical oncology, surgical oncology, radiology, interventional radiology, pathology who have significant expertise in desmoid tumor care. These hospitals may have designations as a National Comprehensive Cancer Network (NCCN) or as a SARC Center.

Treatment Options

After diagnosis, the first line of treatment is often a period of active surveillance because many desmoid tumors will regress or remain stable. Active surveillance involves the patient’s medical team carefully monitoring the tumor via MRI or CT scans. A move toward treatment from active surveillance may be recommended after subsequent progression or increase of symptom burden. When the desmoid tumor is located near critical structures, such as mesenteric or head and neck locations, treatment may begin earlier due to the higher risk of morbidity. The decision to proceed with active surveillance is on a case-by-case basis and should be discussed with your medical team.

There is no single accepted medical treatment for desmoid tumors. Based on the patient’s medical health and nature of their desmoid tumor, their medical oncologist will discuss the best options currently available. Research has shown shrinkage or stabilization of tumor size and/or improvement in symptoms after a wide variety of treatments. Chemotherapy is a drug that is usually injected/infused into the veins. A few chemotherapies that are commonly used include: doxorubicin, Doxil (liposomal doxorubicin), dacarbazine, methotrexate, vinorelbine and vinblastine. These chemotherapies can have a wide range of short and long-term side effects. A new class of agents called tyrosine kinase inhibitors (e.g. sorafenib, pazopanib) have shown benefit in desmoid tumors by shrinking the tumors or slowing down the growth. These are pills taken by mouth at home.

Historically, surgery was recommended as the first line of treatment. However, research has shown that desmoid tumors have a high risk of local recurrence even with good surgical margins. While statistics vary, about 25 to 60 percent of patients who undergo surgery can have a local recurrence (returning at or near the original site). Surgery also can cause significant morbidity due to the wide margins needed to remove the whole tumor.

Scientific research has shown that some types of desmoid tumors have much higher risk of recurrence after surgery than others. This can be estimated using an online calculator:

All nomograms are estimations and are not always accurate. When making a decision to undergo surgery, you should have an open conversation with your surgeon and medical oncologist about the risk of recurrence, time to recurrence and the short-term and long-term side-effects of the surgery. Increasingly, surgery is falling out of favor for desmoid tumors given their high risk of recurrence and other side effects. In some circumstances, surgery may be the best option and can result in great outcomes including a cure. In conclusion, the decision to undergo surgery is a complex one and should be carefully considered.

In general, many sarcoma experts do not recommend radiation for desmoid tumors. This is out of the concern for developing a new, aggressive sarcoma due to the radiation. However, radiation therapy may be an effective option for certain patients in specific circumstances. The dose and duration of radiation is highly variable, and your radiation oncologist will discuss that with you. Both the short-term and long-term side effects from radiation should be carefully considered. In conclusion, the decision to undergo radiation is a complex one and needs to be discussed with your entire team.

Ablation does not use radiation but rather heat or cold (“cryo”) to kill the desmoid tumor Cryoablation is a locoregional therapy designed to be a less invasive option to treat desmoid tumors. Cryoablation involves placing probes into the tumor to directly injure tumor cells through ice formation and thawing.High-intensity Focused Ultrasound (HIFU) is a minimally invasive method to treat desmoid tumors. HIFU focuses ultrasound waves directly to the tumor cells, to preferentially kill tumor cells without damaging the surrounding normal tissue. Learn more about high intensity focused ultrasound.

These are emerging techniques, and the experience to date is limited to a few, specialized medical centers, and the long-term results are not yet known. In conclusion, the decision to undergo ablation (hot, cold or ultrasound) is a very technical and complex one and needs to be discussed carefully with the interventional radiologist and your medical and surgical oncologist.

Clinical Trials

While a great amount of progress has been made in our understanding of desmoid tumors, there is still a long road ahead. While many therapies are available to treat desmoid tumors, there are new drugs being evaluated in clinical trials. Clinical trials are often a way to get access to a new modality or treatment but the decision to participate in a particular clinical trial should be carefully weighted. Not all clinical trials may be appropriate for you. Before you participate in a clinical trial talk to your team of doctors.