New study demonstrates high rates of tumor death in patients receiving regimen

A new pilot study suggests that treating soft-tissue sarcoma with a new regimen of intense chemotherapy and a short course of radiation before surgery may be beneficial. About 41 percent of study participants were found to have complete tumor death at the time of surgery. This is important because preoperative tumor death may be a predictor of survival for people with soft tissue sarcoma, an uncommon group of malignant tumors affecting about 8,000 people in the United States annually.

"Our early results suggest good short-term outcome with this aggressive approach," said Christopher Ryan, M.D., lead study investigator and member of the Oregon Health & Science University Cancer Institute. Not much data is available about preoperative tumor death, or necrosis, without chemotherapy, however an older series with a less-aggressive pre-surgery regimen resulted in a 13 percent rate of necrosis.

High-grade soft tissue sarcomas are a group of malignancies that often affect otherwise healthy young people. Tumors often appear as masses on the legs or arms, but also include gastrointestinal stromal tumors, pediatric sarcomas, and sarcomas of the uterus.

"Soft-tissue sarcoma tumors are varied and often complicated, so multidisciplinary care by an experienced sarcoma team is important to successful treatment," said Ryan, also an assistant professor of medicine (hematology and medical oncology) in the OHSU School of Medicine. "Surgical, orthopaedic, and medical oncologists; radiation oncologists; and pathologists all have important roles in treating soft-tissue sarcoma."

Sarcoma teams around the country provide preoperative chemotherapy. However, while some recent data suggest chemotherapy may help keep sarcoma from spreading, it is considered a controversial treatment because it never has clearly been shown to improve survival. Well-designed large, randomized studies have not been performed for a number of reasons, including the rarity of this disease.

Radiation is less controversial than chemotherapy and can be necessary treatment in order to avoid amputation. Depending on the preference of the treatment team, radiation can be given either before or after surgery. "Giving radiation treatments before surgery has a greater risk of wound healing complications, but probably a lower risk of long-term complications because a lower dose is used before surgery than would be used after surgery," Ryan said.

Ryan and colleagues presented data from their study of the new high-dose chemotherapy regimen combined with a shorter-course of radiation on May 16 at the 41st annual meeting of the American Society for Clinical Oncologists in Orlando, Fla.

"About half of high-risk sarcoma patients die despite surgery and radiation," Ryan said. "We wanted to see if the addition of this intense regimen could improve response to treatment."

For the study, researchers completed enrollment of 27 research subjects in the multi-site, phase II clinical trial. Eligible subjects had localized soft-tissue sarcoma featuring an intermediate or high-grade tumor larger than 5 centimeters located in an extremity or body wall site. They were newly diagnosed with no metastases and had not received chemotherapy, radiation or biotherapy prior to participating in the clinical trial.

Twenty-two patients have completed treatment through surgery. With a median follow-up of 10 months, one patient had a local recurrence, three patients had developed metastatic disease and two patients subsequently died from metastatic disease.

"We found this aggressive therapy to be associated with significant, but manageable toxicity, and the wound complication rate has been modest," said Ryan. "Further follow-up is needed to correlate outcome with preoperative tumor death."

Arthur Hung, M.D., assistant professor of radiation oncology in the OHSU School of Medicine and member of the OHSU Cancer Institute, and James Hayden, M.D., assistant professor of medicine orthopaedics and rehabilitation in the OHSU School of Medicine, are study co-authors. Hung, Hayden and Ryan, along with several other specialists, comprise OHSU's multidisciplinary sarcoma care team. OHSU is one of only two sites in the Northwest to have assembled such a team.

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