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Anthony Elias, MD

The University of Colorado Cancer Center has taken important steps toward joining a small number of institutions nationwide with dedicated programs for treating and conducting research into sarcomas.

Sarcomas, which are tumors that form in the bones and connective tissues, are exceedingly rare and complex. They account for only 1 to 2 percent of all cancers, but there are some 55 malignant tumor subtypes, said Anthony Elias, MD, medical director for the Cancer Center’s breast and sarcoma programs. The tumors are often aggressive, heightening the importance of a multidisciplinary care team that includes surgical, medical, and radiation oncologists, as well as specialized nursing.

Yet the relatively small volume of cases means that most institutions don’t have a clinic that focuses solely on sarcomas. One that does is the Dana Farber Cancer Institute in Boston, where Elias completed his oncology fellowship. He trained with Karen Antman, MD, now provost of the Boston University Medical Campus and dean of the Boston University School of Medicine.

Antman developed and established protocols for treating sarcomas and mesotheliomas, knowledge that Elias brought to the Cancer Center in 2001. He initially worked on sarcoma cases with Andrew Kraft, MD, who was then chief of the Medical Oncology Division with the CU School of Medicine. After Kraft left for the Medical University of South Carolina in 2004, Elias took over managing sarcoma patients.

The number of sarcoma cases Elias saw steadily increased, from perhaps one new case every two weeks to four new patients a week today, he said. Until four months ago, however, Elias remained a self-described “one-man show,” fitting sarcoma cases around his heavy clinic schedule with breast cancer patients.

Hands on deck.

But with the arrival last September of Victor Villalobos, MD, PhD, from Stanford University Medical Center, the Cancer Center is scheduling more sarcoma patients and reviewing selected cases in twice-monthly multidisciplinary sarcoma tumor board meetings.

Villalobos sees new sarcoma patients, reducing Elias’s clinical load. The two see patients in the Breast Center five days a week, but plans have been approved for a dedicated sarcoma clinic, to be housed in a remodeled third-floor section of the Anschutz Cancer Pavilion.

Villalobos is also working with Elias to build the Cancer Center’s participation in clinical trials for sarcoma treatments – an area of growing interest for drug companies.

The Cancer Center is currently participating in seven clinical trials of drugs treating a variety of sarcomas, including those arising in the fat cells, bones, cartilage, and joints, Villalobos said. Another five are in the works. The trials reflect a broad range of therapeutic approaches.

There are neoadjuvant and adjuvant therapies (those given before and after primary treatment, respectively); oral medications and chemotherapy infusions; drugs that target specific cell mutations; and immunotherapies designed to thwart tumors from recurring.

“We’re trying to capture patients where they are in their disease,” said Villalobos, “and give them a broad range of options.”

Under the microscope.

Genetics is the key to the pharmaceutical industry’s heightened interest in sarcomas, Elias said. About 50 percent of sarcomas have “known driver mutations,” he said, compared with only about 15 percent of lung cancer tumors.

“That’s what has saved sarcoma research,” Elias said. From a rare disease group drug companies viewed as a poor investment risk, sarcomas became a “proof of principle” that the future lies in developing targeted therapies tailored to the genetic signature of a patient’s disease, he said.

The nature of sarcomas also makes them an intriguing subject for research, Villalobos said. Unlike lung and skin cancers, which generally develop from massively complex cellular mutations, sarcomas are often the result of a single “catastrophic” genetic change, he said. That makes learning how the tumors work and developing therapies that target them a still formidable but less daunting task.

Sarcomas have also become an attractive therapeutic target for drug companies in an increasingly crowded cancer market that makes Food and Drug Administration approval more difficult, Villalobos said. “They’re looking more closely at ‘orphan diseases’ like sarcomas,” he said.

Many battle fronts.

It’s especially important for the Cancer Center to build capacity for sarcoma patients because the odds of survival and recovery increase dramatically with early detection, before tumors have metastasized, Villalobos said.

“Our focus is on getting patients to no measurable cancer,” he said, “and treatment works better when there is only a small amount of disease.”

If surgeons are able to remove tumors and treat the cancer locally, a patient’s chances of becoming disease-free increase to as much as 30 or 40 percent, he said. A further goal is to develop therapies that harness the immune system and act as a vaccine to prevent tumors from recurring after surgical excision, Villalobos said.

The importance of an experienced team is heightened because of the consequences of a mistake in the biopsy, diagnosis, and treatment of sarcomas, Elias added. For example, if a tumor biopsy inadvertently cuts across connective tissue compartments, the error opens the door to the sarcoma spreading, potentially increasing the number of surgeries needed to remove tumors, and widening the radiation field needed to kill the cancer cells.

In one case, Elias said, a physician – not at the Cancer Center – attempting to biopsy a mass on the patient’s pelvic wall cut through the belly, possibly contaminating the abdominal cavity with lethal tumors and decreasing the patient’s chances of survival.

A multidisciplinary team is also essential for sarcoma patients because of the complexity of the treatment regimen, Elias noted. The tumors may appear in many areas of the body, requiring gastrointestinal, orthopedic, head and neck, or hand surgery. A single patient may need several surgeries as part of a treatment plan that also includes chemo and radiation therapy and drug treatment in various combinations, Elias said.

“The goal is to keep the tumor burden down and even give patients a treatment holiday,” he said. “But it takes a lot of multidisciplinary action.”

Expanding the fight.

The Cancer Center’s expertise in sarcomas extends beyond the walls of the Cancer Center and University of Colorado Hospital. Adult providers also collaborate with pediatric sarcoma experts Lia Gore, MD, and Carrye Cost, MD, at Children’s Hospital Colorado. The connection is a key to broadening understanding of sarcomas because pediatric patients tend to respond much better to treatment than do adults, Elias said.

“Adults generally don’t tolerate the intensity of treatment as well,” he said. “We’re making an effort to understand why age matters.”

Meanwhile, Elias and Villalobos forge ahead with plans to take the sarcoma program to the next stage. With work commencing on a dedicated clinic space, they are recruiting a nurse practitioner and looking to develop home-grown clinical research trials to supplement company-sponsored studies. Villalobos sees it as a ground-floor opportunity to join the small group of national programs with expertise in a small but important corner of the cancer universe.

“I’m here to help build the program and add to what Anthony has already done,” Villalobos said. “We have a tight group that can serve the Denver area and possibly expand to the Rocky Mountain region.”