April 2010

Helical IMRT — New Treatments Taking Shape
for Multiple Myeloma

By Thomas Rockwell ‘Rock’ Mackie, PhD
Radiology Today
Vol. 11 No. 4 P. 8

Myeloma (also known as multiple myeloma) is the second most prevalent blood cancer after lymphoma. More than 750,000 people worldwide suffer from the bone marrow disorder that affects plasma cells, according to the International Myeloma Foundation. Myeloma diagnoses are on the rise in industrialized countries, with more than 20,000 new cases identified annually in the United States.

While the five-year survival rate ranges from 10% to 50%, new treatments are enabling some myeloma patients to live 20 years or more after their diagnosis. One of the most common methods of treating myeloma combines chemotherapy and total body irradiation (TBI) as a preconditioning treatment prior to bone marrow transplantation. TBI involves exposing the entire body to radiation to destroy a patient’s bone marrow. Doing this suppresses the immune response the body would mount against the subsequent transplant. The radiation also helps kill residual cancer cells. After the TBI treatment, the patient then receives a bone marrow transplant.

With TBI, the same radiation dose is delivered to the rest of the body as to the bone marrow, often using a single, large beam directed from one to four angles. Throughout a typical one-week course of radiation for TBI treatment, a patient receives a cumulative dose of 10 to 12 Gy to the whole body, including healthy tissues and organs. Also, the radiation delivery is not uniform, with narrower regions of the body such as the neck receiving a higher dose than broader regions such as the hips.

Studies in the 1990s suggested that a higher radiation dose of 16 Gy was more effective in achieving the goals of TBI, but with traditional techniques, even doses of 10 to 12 Gy can result in significant side effects. For example, in the short term, patients may experience hair loss, skin irritation, nausea, vomiting, diarrhea, and mouth sores. Long-term problems can include damage to the lungs or other organs, infertility, cataracts, and even a risk of leukemia or other cancers several years after the initial TBI treatment.
Focus on the Marrow
Several cancer centers and radiation oncologists around the world are exploring a way to enhance the effectiveness of radiation in stem cell transplantation by increasing the dosage while limiting the exposure of a patient’s healthy tissues and organs. Called total marrow irradiation (TMI), this treatment utilizes the TomoTherapy radiation therapy system to deliver targeted doses of radiation to only the skeleton where it is needed.

The therapy system combines modern 3D imaging with helical intensity-modulated radiation therapy (IMRT) delivery to help clinicians avoid sensitive tissue, such as the lungs, kidneys, liver, and reproductive organs, while delivering the optimal dose directly to the bone marrow. Different than the wider beams typically used in TBI, helical IMRT treatments rely on thousands of tiny beamlets directed in a continuous spiral pattern from all 360 degrees around a patient. The system’s integrated imaging helps clinicians position the patient so the radiation dose delivered on each treatment day accurately encompasses the skeleton as planned. By approaching radiation delivery in this manner, the system can reduce the dosage received by healthy tissue and organs and theoretically reduce radiation-related side effects.
The Patient Experience
In 2005, Carol Ramnarine was diagnosed with myeloma and became the first patient to be treated with TMI using TomoTherapy technology during a clinical trial led by Jeffrey Wong, MD, chair of radiation oncology at City of Hope, a National Cancer Institute-designated Comprehensive Cancer Center in Duarte, Calif., and his colleague George Somlo, MD, FACP.

“Standard total-body irradiation is often a life-saving procedure. We knew TomoTherapy could deliver radiation in ways not possible with previous technology,” Wong wrote in a profile article about Ramnarine’s treatment, noting that one question he was hoping to address in his trial was whether the reduction of radiation doses to healthy organs using targeted TMI also would reduce side effects.

The initial experience treating Ramnarine with helical IMRT did show fewer and less-severe side effects.

“I didn’t have the side effects you hear about,” Ramnarine says. “No mouth sores, almost no nausea. A little itchy, dry skin.”

“We expected the usual side effects of standard total-body irradiation,” Wong says. “The day her treatment was completed, we were aware of her side effects—or lack of. One of the doctors asked, ‘Are you sure you’ve given her enough?’”

The treatment was effective. Within a few days of her TomoTherapy treatment, Ramnarine’s blood count dropped as expected, and she was able to undergo a bone marrow transplant. She has now been in remission for nearly five years.

Clinical Research
In addition to City of Hope, a number of other cancer centers are using the system to deliver TMI treatments.  These facilities, including Far Eastern Memorial Hospital in Taiwan and the University of Minnesota in Minneapolis, are contributing to clinical research on the short- and long-term viability of TomoTherapy helical IMRT treatments that target bone marrow in myeloma patients. Clinicians and researchers from these facilities have published early studies on TMI showing the treatment to be feasible for achieving similar results as TBI while providing dosimetric advantages and reducing the toxicity of the treatment. Wong says that with helical IMRT, “We’re seeing normal organs receiving less than 65% of the total radiation [and] sometimes that’s as low as 15%.”

Researchers think additional clinical trials will show that using helical IMRT will enable clinicians to increase dosage up to 16 Gy without compromising patient safety and with fewer side effects than standard TBI delivering 10 to 12 Gy. In addition, researchers believe long-term studies of the system may improve survival rates by 10% to 20% compared with TBI.

— Thomas Rockwell ‘Rock’ Mackie, PhD, cofounded TomoTherapy Inc in 1997 and has served as chairman of its board of directors since 1999. He has been a professor in the departments of medical physics and human oncology at the University of Wisconsin, where he established the TomoTherapy research program.