"Soft tissue sarcomas are extraordinarily heterogeneous, so experience is particularly important when deciding among treatment options," says medical oncologist Thierry M. Jahan, M.D.
Jahan notes that because earlier sarcoma research was limited by the relative scarcity of cases, initial studies tended to treat sarcomas as a homogeneous group. Consequently, treatment was often limited to a combination of surgery and radiation. Yet, as sarcoma programs have accumulated experience, they have found that for certain sarcomas, using chemotherapy in conjunction with surgery and radiation can actually be quite effective.
At UCSF Medical Center, referring physicians typically send orthopaedic surgeon Richard J. O'Donnell, M.D., and general surgeon Eric K. Nakakura, M.D., Ph.D, patients with painful, growing soft tissue masses. If their initial examination convinces them that there is a sarcoma concern, they move on to a staging workup that includes various imaging modalities and, eventually, either a needle or incisional biopsy.
Once a tumor has been subtyped by Andrew E. Horvai, M.D., Ph.D, the team discusses the case at the sarcoma program tumor board that meets twice a month at UCSF Medical Center — and, of course, with the patient. In some cases, the team recommends chemotherapy in addition to surgery and radiation.
"For tumors that are high-grade, deep and larger than five centimeters (which have a high likelihood of relapse), we believe that the evidence over the last 10 or 15 years indicates that chemo can have a positive effect," says O'Donnell. Jahan often oversees two to three chemotherapy cycles prior to surgery. O'Donnell and Nakakura then remove the primary tumor. If necessary, thoracic surgeon Michael J. Mann, M.D., resects lung lesions, often with a minimally invasive procedure called video-assisted thoracoscopic surgery.
When appropriate, the team also offers patients the option of intraoperative radiation therapy (IORT). The potential benefits of IORT include its ability to reduce or prevent complications associated with pre- and postoperative radiation, to ensure a clear field with optimized margins, and to reduce the field for postoperative dosing. "We also use IORT when Dr. O'Donnell believes there will be microscopic disease remaining after resection due to the close proximity of the tumor to nerves or vessels," says radiation oncologist Alexander R. Gottschalk, M.D., Ph.D.
The procedure, which requires that a hospital have a mobile linear accelerator available for the operating room, is associated with very little toxicity.
After surgery, most patients require another five to six weeks of radiation or several cycles of chemotherapy or both. For technical reasons, some remain at UCSF for these treatments. But, says O'Donnell, "We always leave the decision to the patient and their physician."
When patients do opt for postoperative treatment in their home community, the team works closely with referring physicians to convey treatment recommendations.
For radiation, some postoperative treatment is very straightforward. But in other cases, it can be difficult to replicate Gottschalk's direct observation of the surgery, his experience with sarcomas and his access to equipment that enables such procedures as image-guided radiation therapy. "But we do our best to convey all of the necessary information," he says.
For chemo, Jahan typically faxes a sample order to the referring physicians to ensure that they and their nurses are comfortable with the procedures. "The devil is in the details," says Jahan. "Watching fluids, side effects and the loss of electrolytes can all be tricky for clinical teams that don't regularly use chemo in these cases." In the future, he hopes to open a chemo infusion unit at Mount Zion that would facilitate an aggressive research program.
To contact Dr. Richard O'Donnell, call (415) 885-3800.
Stem Cells and Tissue Regeneration
With a major stem cell research grant, Ophir Klein, M.D., Ph.D, is exploring the molecular processes that regulate the behavior of dental stem cells in mice, with the goal of promoting tooth regeneration and treating craniofacial abnormalities in humans.