A new clinical trial at MUSC Hollings Cancer Center is testing the feasibility of offering a shorter course of preoperative radiation therapy for sarcoma patients to ease the logistical burden of accessing treatment.
That burden can be significant. Sarcoma, a cancer of soft tissues, is best treated at a high-volume sarcoma center like Hollings that can provide multidisciplinary care that's coordinated across orthopedic/surgical oncology, radiation oncology and medical oncology, said radiation oncologist Jennifer Harper, M.D., who developed the trial.
But under the standard course of treatment, sarcoma patients would need to be at the center for five weeks of preoperative radiation therapy, five days a week.
For Janet Grubb, who lives in North Myrtle Beach, that would have meant racking up $7,000 to $8,000 in expenses to remain in Charleston during treatment of the myxofibrosarcoma in her left thigh, she said. Instead, she jumped at the chance to enroll in the trial and get her radiation done within a week.
"The lodging was insurmountable," she said. "Plus, because this was growing so fast, I wanted it to be removed as quickly as possible, hoping to save my leg."
Grubb will have her surgery Oct. 17. The preoperative radiation therapy can decrease the chance that the cancer returns after surgery and gives her the best chance of avoiding amputation, for which she is grateful.
Harper said that she was motivated to develop this trial in order to be able to offer patients more options.
"Whatever we do, we need to think about how can we make this less hard for the patient? Whether it's time commitment or whether it's financial burdens, what can we do to make it a bit easier on the patient and more doable? Because we could think of the most magical drugs in the world, the most complex treatment algorithms, but if the patients cannot do it, then you're not going to help them."Jennifer Harper, M.D.
Radiation therapy for the treatment of sarcoma is trending toward this shorter regimen. Termed "hypofractionated," patients receive a lower overall dosage of radiation, but each individual treatment consists of a larger dose than would be given during a longer regimen. Hypofractionated treatments have been shown to be equivalent to longer courses of radiation in breast cancer, prostate cancer and in some phase II clinical trials for sarcoma of the limbs, she said.
Usually, a new treatment would undergo large randomized trials before it could be called the new "gold standard." But that's harder to accomplish when the cancer is rare.
"We don't have enough patients in one center – or even probably in one country – to do a randomized trial large enough with enough statistical power to compare local control rates for standard versus hypofractionated courses of preoperative radiotherapy," Harper said. "There are few randomized trials in sarcoma, and all of them have been challenged by the small number of eligible patients with this diagnosis."
However, there have been promising phase II trials, and other centers are developing their own trials. Because the hypofractionated therapy isn't standard, a clinical trial was the way to make it available to Hollings patients.
"I believe the goals of cancer investigation should focus on removing the barriers to care," Harper explained. "Whatever we do, we need to think about how can we make this less hard for the patient? Whether it's time commitment or whether it's financial burdens, what can we do to make it a bit easier on the patient and more doable? Because we could think of the most magical drugs in the world, the most complex treatment algorithms, but if the patients cannot do it, then you're not going to help them."
Developing the clinical trial
Harper knew that she wanted to offer the hypofractionated therapy as a clinical trial option, but she wasn't sure how to go about doing that. She turned to sarcoma researcher Nancy Klauber-DeMore, M.D., for advice.
Klauber-Demore is a co-leader of the Developmental Cancer Therapeutics research program, one of three research programs at Hollings, and has been heavily involved in a new initiative called the Hollings Advisory for Rapid Translation, or HART.
As the only National Cancer Institute-designated cancer center in the state, Hollings has a mission not only to treat patients with the latest therapies but also to develop new therapies and treatments. HART helps faculty members to flesh out their concepts, work out the protocols and gain approvals from the boards and committees charged with protecting human research subjects.
As Harper worked with HART, Klauber-DeMore saw an opportunity to add a basic science research component to the trial. Klauber-DeMore has been studying secreted frizzled-related protein 2 (SFRP2) in different types of sarcomas. If the levels of this protein change after radiation treatment, it could be a candidate to become a biomarker – something that tells doctors whether an individual's cancer is likely to respond to treatment or that measures how well treatment is working.
"We're looking at SFRP2 before treatment and after treatment to see if the levels change and, if they change, if they correlate with response," Klauber-DeMore said.
Harper also worked with Marvella Ford, Ph.D., associate director of Population Science and Community Outreach and Engagement at Hollings, and Hollings behavioral scientist Katherine Sterba, Ph.D., to develop a survey to understand what led patients to participate in the trial.
Their answers could help Hollings to develop clinical trials that respond to what is important to patients beyond first-rate care.
Harper has been pleased with the response to the trial so far. The trial opened Aug. 15, and already two patients have enrolled.
Trial participant Grubb said she had no hesitation about signing up. The staff at Hollings clearly cared about her outcome, she said.
"The staff is fabulous. Very caring and concerned. They just treat you with the utmost respect, and I really, really do appreciate that."
