Proton therapy, immunotherapy, clinical trials among the newest treatments for sarcomas

South Florida cancer specialists are finding new ways to treat people who have sarcoma, a cancer that occurs in the bones and soft tissues and which often affects children.

Dr. Maggie Eidson Fader, a pediatric hematologist-oncologist who is the director of the pediatric sarcoma and solid tumor program at Nicklaus Children’s Hospital in Miami, says that each year in the United States, approximately 1,500 to 1,700 children will be diagnosed with sarcoma.

“These cancers comprise 15% of childhood cancers,” she says, “yet are considered rare tumors.” (In adults, sarcomas are estimated to be about 1 percent of all cancers.)

“Because they are rare, the discovery of new and effective therapies has been quite slow,” she adds.

Eidson Fader says that funding for research is lacking compared with funding for more common types of cancers. Treatments are often expensive, she adds, due complex medical care, hospitalizations and sophisticated surgeries to remove the cancer while preserving function.

“One big roadblock to funding cures is that no two of these tumors are exactly alike, and so the “one treatment fits all” approach has met with limited success,” she says.

The Pediatric Sarcoma and Solid Tumor Program at Nicklaus has the largest pediatric limb salvage program in the state. Eidson Fader says the hospital’s orthopedic oncologists customize each child’s procedure to remove the tumors while preserving the function of the leg, arm, or other limbs affected – with the aim of preventing amputation.

“The pediatric surgeons use techniques like HIPEC (Hyperthermic Intraperitoneal Chemoperfusion) surgery to remove complex abdominal cancers,” she says. “Our radiation oncologists treat patients with proton therapy, offered for children in only a few centers in Florida.”

Eidson Fader says members of Pediatric Sarcoma Program focus on developing research trials, which she says are potential pathways for personalized medicine. Trials currently open include the multi-center Phase III Vigil trial for relapsed Ewing Sarcoma, a cancer that most often occurs in and around the bones, as well as investigating a vaccine therapy using the patient’s own tumor cells.

children’s unique tumors,” says Eidson Fader.

The American Cancer Society estimates about 13,130 new soft tissue sarcomas will be diagnosed (7,470 in males and 5,660 in females) in the United States in 2020, and about 5,350 people (2,870 males and 2,480 females) are expected to die of soft tissue sarcomas nationwide in 2020. These statistics include both adults and children.

Jonathan Trent, M.D., Ph.D., an oncologist, is the director of the sarcoma program at Sylvester Comprehensive Cancer Center at the University of Miami, where he is also the associate director for clinical research.

“We have had two major discoveries revolving around the use of immunotherapy for patients with sarcoma,” he said.

In one type of cancer, alveolar soft part sarcoma (ASPS), he and his team found that targeted therapy plus immunotherapy — to remove the camouflage that cancer cells use to hide from the immune system — resulted in shrinkage of the sarcoma by more than 30% of its original size. The shrinkages occurred in just over 50% of the 33 patients who participated in the clinical trial. The findings were published in The Lancet Oncology medical journal.

“We believe that the targeted therapy (an inhibitor of tumor blood vessels) choked off the blood supply to the cancer resulting in cancer-cell death,” he said, “and the immunotherapy activated the patients’ own immune system.”

Trent said that the other major breakthrough was when a patient who was enrolled in the above-mentioned trial, who had a highly malignant vascular tumor called cutaneous angiosarcoma, showed “massive tumor shrinkage” following the trial.

“This led us to enroll other angiosarcoma patients on several of our various immunotherapy clinical trials and treat some outside of FDA approval,” he said.

“When we analyzed the data, we found that 71% of patients with angiosarcoma had substantial reduction in tumor size — more than 30% of the tumor diameter,” said Trent. “Several patients had complete response and are still in remission today.”

Those patients had been resistant to chemotherapy.

He and his team are developing a prospective registration study that they hope will lead to FDA approval of immunotherapy for angiosarcoma.

“Many physicians and investigators have thought there is no role for immunotherapy for patients with sarcoma,” Trent said. “Our clinical research and patient-care at Sylvester has proven otherwise.”

Isabel Rodriguez, 66, of Hialeah, was diagnosed with angiosarcoma in July 2013. Prior to her diagnosis, she noticed a strange growth on her nose.

“At first I thought it was something like a blackhead, but it started turning ugly and growing,” she said.

She went to a dermatologist who then referred her to an oncologist at Sylvester, where she underwent several months of chemotherapy and radiation, but results were unsuccessful.

In 2014, her nose was amputated.

“It was devastating,” she said. “It was horrible to see myself like that.”

In total, her treatment lasted for three years.

Rodriguez said that her cancer was so aggressive that it grew past the area they were treating.

“I really thought I was going to die,” she said.

In 2017, her oncologist at Sylvester, Dr. Breelyn A. Wilky, informed her of a new clinical trial that was opening at Sylvester – the one that Trent headed; he was the senior author of the study. (Wilky was the first author of the study; she wrote the protocol and the findings for the study under Trent’s guidance.)

Rodriguez said Wilky recommended it because she had run out of treatment options.

If the trial didn’t work out, I would die, but if I didn’t try it, I would die anyway,” she reasoned. “To me it was worth doing the treatments.”

Now, almost two years later, she is cancer-free. She has regular MRIs and biopsies, which have all returned negative. She wears a prosthetic nose because she doesn’t want to go through any more surgeries, not even one to rebuild her nose. She regularly volunteers at her church, something she enjoyed doing before her diagnosis.

“If somebody is considering a clinical trial, I would tell them: Don’t think about it twice. Do it. You’re helping yourself and you’re helping science,” she said.

Dr. Jorge Manrique-Succar leads the sarcoma program at Cleveland Clinic Florida in Weston.

The program is comprised of fellowship-trained orthopedic surgeons, medical oncologists, radiation oncologists, plastic surgeons, and musculoskeletal radiologists.

“As part of the sarcoma group of the Cleveland Clinic Foundation, specialists from both Cleveland Clinic in Ohio and Florida meet in a virtual, multidisciplinary tumor board every Monday morning,” says Manrique-Succar.

“Here, all cases with their respective pathology slides, radiology images, and medical diagnoses, are discussed,” he says. “This allows for a thorough academic discussion and formulation of treatment plans based on scientific evidence and the experience of many team members.

“Today, more than 90 percent of patients with sarcomas can avoid amputation and see a minimal chance of recurrence,” says Manrique-Succar.