Benefits and Risks of New Radiotherapies in Children

By Jeffrey Norris, UCSF Today | May 30, 2007

Thanks to rarely talked-about recent advances in radiation treatments, young children are surviving cancers that would have been incurable a decade ago. One strategy that is helping to boost survival is radiation treatment provided at the time of surgery. UCSF and fewer than a dozen other medical centers nationwide are at the forefront in advancing this mode of treatment, called intraoperative radiation therapy (IORT).

With IORT, patients do not have to return for successive rounds of therapy after surgery. Those who receive the most common standard alternative, external beam radiation therapy (EBRT), typically receive treatment five days a week for several weeks. Another advantage of IORT over EBRT is that the surgical team is better able to position normal tissue out of the path of beamed radiation. This lessens the risk that healthy tissue will be damaged, and allows oncologists to deliver higher doses of radiation to tumors.

Survival and Side Effects
Like chemotherapy, radiation treatments can have side effects. IORT involves giving a high radiation dose over a short period of time -- typically 10 to 15 units, called grays, compared with an average cumulative dose of 20 to 60 grays for EBRT. IORT has very limited short-term side effects.

But aggressive treatments also have long-term side effects. With growing numbers of patients outliving cancer, physicians are learning more about long-term risks, such as scarring and fibrosis. Clinical researchers now are on the lookout for harbingers of future complications of treatment even as they aim to deliver more powerful, better targeted blows to tumors.

IORT May Be Lifesaving in Neuroblastoma
UCSF is a leading referral center for the treatment of pediatric cancers. UCSF radiation oncologists are pioneering the use of IORT in the treatment of the nation's most difficult cases of neuroblastoma, a leading childhood cancer. Neuroblastoma is a cancer that arises in nerve tissue that resembles residual embryonic tissue. It is the most common solid tumor that develops outside the brain in children. Neuroblastoma rarely arises in children past age 10. It most often occurs in the adrenal gland atop the kidneys, or in nerve fibers of the chest or abdomen.

For two decades, oncologists have treated the most aggressive cases of neuroblastoma with surgery, high doses of chemotherapy and some form of radiation. These high-dose treatments kill tumor cells more effectively. But the treatments also result in toxicities in many normal tissues, such as the death of bone marrow cells that make blood and immune cells. Thanks to these high-dose combinations of radiotherapy and chemotherapy, survival among neuroblastoma patients has improved greatly over the past two decades. Even so, among the 45 percent with high-risk tumors, the worst prognosis, only about one in three lives free of cancer regrowth for three years or more.

Since the mid-1980s, oncologists at UCSF have been pioneering the use of IORT, with or without EBRT, as the radiation component of therapy. To generate high-energy radiation for treatment, UCSF surgeons use a mobile linear accelerator called a Mobetron right in the operating room. Patients don't have to be moved during surgery to receive treatment.

Amy Gillis, a fourth-year UCSF resident in radiation oncology, recently worked with UCSF radiation oncologist Daphne Haas-Kogan and pediatric oncologist Katherine Matthay to review 31 consecutive cases of high-risk abdominal neuroblastoma treated with IORT at UCSF. Gillis, who presented findings at the annual meeting of the American Society for Therapeutic Radiation and Oncology, estimated that nearly one-half of patients survived, or were on track to survive, three years or more without cancer regrowth. The best results occurred when tumor location permitted surgeons to remove all visible cancer.

Read more at Jeffrey Norris, UCSF Today