The Challenges and Complexities of Sarcoma

Researchers from Sylvester’s sarcoma program, which leads the Southeast in patient treatment and clinical phase 1 trials, share their thoughts during Sarcoma Awareness Month.

July is Sarcoma Awareness Month. Awareness of sarcoma — a cancer of the bone or soft tissues including cartilage, fat, muscle or blood vessels — can be trickier than awareness of, say, breast cancer or colorectal cancer. Not only are sarcomas rare, comprising around 1% of all cancers, but there is no way to screen for them and a diagnosis can take months. Sarcoma awareness, it turns out, is for physicians as well as patients.

Every year, approximately 1.7 million Americans receive a cancer diagnosis. While breast cancer accounts for around 280,000 of those cases, sarcomas will number about 17,000 — 14,000 in the soft tissue and 3,000 in the bone.

Breast cancer starts in the breast, and colon cancer in the colon. But sarcoma can start anywhere, “because it starts in the connective tissue which is all over your body,” said Gina D’Amato, M.D., assistant director of clinical research at Sylvester Comprehensive Cancer Center, part of UHealth – University of Miami Health System. “There are over 170 different types of sarcoma.”

Awareness Is Key

The first sign of sarcoma may be a non-painful lump or a bump on the arm or leg. A patient may have it for a while without becoming alarmed. Even if the lump hurts, it’s common for patients to think they only pulled a muscle and not seek medical attention right away. After the patient sees a physician, it could still take six months or longer to make the diagnosis. According to Dr. D’Amato, “If we could get the word out to citizens and doctors” that anything greater than a two-centimeter lump — about the diameter of a penny — could be a sarcoma, it could make an enormous difference.

Often, physicians will think they are looking at an infection or an injury, so they’ll send the patient to a non-sarcoma specialist. In neither circumstance is the patient sent to an orthopedic/musculoskeletal oncologist or surgical oncologist with expertise in sarcoma. But because sarcoma experts see so many sarcomas, they are more likely to spot one.

“What we see is rare, but that’s what we focus on daily,” said Francis John Hornicek Jr., M.D., director of orthopedic oncology at Sylvester and chair of the department of orthopedics at the Miller School of Medicine.

Diagnosis Pathway

“Lack of awareness leads to a delay in diagnosis,” said Jonathan Trent, M.D., Ph.D., associate director for clinical research at Sylvester Comprehensive Cancer Center. In some cases, he said, the diagnosis can take years, during which time the tumor spreads. Another reason for delayed diagnoses is that not all patients come to sarcoma centers.

“We work with 20 experts,” said Dr. Trent. “We discuss every patient together, we come up with a plan for every patient.” The team focuses exclusively on sarcomas. According to a number of studies, said Dr. Trent, survival rates are better for patients who go to a sarcoma center.

Physicians, said Dr. Trent, should “have a lower threshold to do an ultrasound and a lower threshold for a biopsy if the ultrasound is concerning.” Then the biopsy should be reviewed by a sarcoma pathologist.

“When they look at it under the microscope there is rarely 100% certainty,” cautioned Dr. Trent. “There will be a list of other possibilities” — a differential diagnosis — “so the biopsy should be reviewed by a sarcoma specialist.”

A sarcoma pathologist changes the diagnosis around 25% of the time, said Dr. Trent. “Everything we do afterward in terms of surgery, chemotherapy and radiation is dependent on the expert pathologist.”

Screening Strategies

Another reason why sarcomas are often diagnosed at a later stage: There are no screening strategies. With nothing corresponding to a mammography or coloscopy, physicians must be trained to recognize what could be a sarcoma. And patients should be aware, too.

“If something is going on with your body that is not normal, you should tell your doctor,” said Dr. D’Amato. Sarcoma is generally thought to be non-hereditary, she said. “But as we see more patients, we are testing tumors and seeing that there is more of a genetic component than we thought.”

Sarcoma may be associated with a mutation in several hereditary genes such as NF-1, Rb or p53 according to Dr. D’Amato. “We are recommending that cancer patients who have family members with cancer, especially sarcoma, be referred to genetic counseling,” she said.

At present, Sylvester is running 17 phase 1, 2 and 3 clinical trials on sarcoma, including the only phase 1 trials in the southeastern U.S. “We have some exciting new drugs,” said Dr. Trent. Sylvester researchers are testing immunotherapy and KIT inhibitors; there is a clinical trial for liposarcoma, one type of which is caused by NDM2 and CDK4 genes. “We have brand new first-in-human inhibitors called checkpoint inhibitors,” said Dr. Trent. “We have a number of first-in-human trials.”

Diverse Patients

Miami is a good place for clinical trials because of its ethnic diversity. “If you are doing clinical trials and only white males or white females are in the study, other ethnic groups may have different enzymes, respond to treatments differently,” said Dr. D’Amato. “We need to have clinical trials that reflect diverse patient populations.”

The cure for sarcoma is surgery, said Dr. D’Amato, but sometimes patients aren’t diagnosed in time, or surgeons can’t remove the tumor, or there is a high risk of spread. To prevent it from coming back or at least to control it, Sylvester uses a targeted therapy to interrupt the molecular abnormalities that drive cancer.

“Instead of killing cancer cells while it’s growing and dividing, we stop the signal,” said Dr. D’Amato. “There are oral and IV medications, and by doing molecular profiling on the tumor we can potentially tailor treatments not approved for sarcoma in a clinical trial at Sylvester.” Sometimes radiation is used to shrink the tumor, but usually not when it’s reached an advanced stage. Also, some sarcomas have a limited response to radiation.

Sarcoma is one of the more common types of children’s cancer. Adults get other kinds of cancer that children don’t. While children are no more susceptible than adults to sarcoma, according to Dr. D’Amato, “if you are a child with cancer, the chance of it being a sarcoma is higher, but as an adult, the chance that it’s a sarcoma is low.”

Sylvester treats approximately 900 new sarcoma patients a year, a large number for a relatively rare cancer. “We have all this expertise,” said Dr. D’Amato. “Patients are coming from all over — from Florida, from other states and other countries — because we have such a good program.”

Tags: Dr. Francis Hornicek, Dr. Gina D'Amato, Dr. Jonathan Trent, Phase 1 clinical trials, phase 2 clinical trial, phase 3 clinical trials, sarcoma