Greg Frieherr

Research from Japan documenting remarkable survival rates among patients with inoperable lung cancer may only hint at the potential of proton-beam radiation therapy. The study out of the Proton Medical Research Center in Tennoudai, Japan, documented high survival rates for 55 patients suffering from stage I inoperable non-small-cell lung cancer.

Thirty-five patients with stage II-IIIb NSCLC were treated from November 2001 to July 2008 with different doses. Peripherally and centrally located tumors were irradiated with a median proton dose of 78.3 Gy.

The two-year progression-free survival (PFS) rate among the stage I patients was 88.7% and the local control rate was 97%, the authors, led by 

Local (PFS) for stage II-III patients was 93.3% at one year and 65.9% at two years during a median observation period of 16.9 months. Local recurrence took place in 11.4% of patients with 37.1% developing regional recurrence, and 20% developing distant metastases. The PFS for stage II-III patients was 59.6% at one year and 29.2% at two years. The overall survival rate of stage II-III patients was 81.8% at one year and 58.9% at two years. A total of 42.9% developed grade 1 toxicities and 17.1% developed grade 2 toxicities. There were no cases of grade 3 or greater toxicities, the authors said (Int J Radiat Oncol Biol Phys online, September 30, 2010).

These rates contrast starkly with reported overall survival rates at five years for NSCLC patients treated with conventional radiotherapy, ranging from 6% to 31.4%. The difference may be due in part to the follow-up time differences in the available data: Two years for proton-beam radiation therapy and five for conventional therapy. But even for those treated with stereotactic radiosurgery, a highly precise form of radiation therapy, the survival rate is just is 54.7% after two years.
Reports of success with proton-beam therapy have seemed almost anecdotal because of the relatively few sites that offer this type of therapy. Much of the work has focused on cancers of the prostate and brain. But lately, with the rising number of proton-beam centers in the U.S. and around the world, other applications are being tried.

More research is needed to compare the relative effectiveness of proton-beam and stereotactic radiosurgery, the Japanese investigators said, just in regard to patients with stage I inoperable NSCLC. They urged a randomized clinical trial to clarify the survival benefit that might be achieved from using proton-beam radiation therapy.

Study results reflect inherent advantages of proton particles

The next five to 10 years will be an exciting time as proton-beam radiation therapy protocols come online for lung cancer, cancers of the esophagus and pancreas, liver tumors, and gynecological cancers, said Dr. Williams, chair of the ASTRO board of directors.

Dr. Williams explained that high-energy protons penetrate to a certain depth in the body, which is calculable and controllable, and then they stop. "For this reason, there’s always been interest in using them for localized tumors," said Dr. Williams, medical director of radiation oncology at Boca Raton Community Hospital in Florida.

Advances in computers have made proton targeting more precise. So has technology that controls the proton beam, turning it on and off to match the rhythm of a patient’s respiration.

"[Using it on] small lung tumors is a perfect application because you can exactly target the tumor and control for respiratory motion, eliminating the tumors without the need for surgery," he said. "So the results (obtained in Japan) are very exciting. They are a natural reflection of the inherent potential advantages of the particles themselves."

Proton-beam radiation therapy typically focuses on localized tumors because protons are best applied when the tumors are highly defined. "If you have regional spread, then local control obviously is not as relevant," Dr. Williams said. "This increasing number of proton-beam therapy facilities allows us to explore new levels of dose intensity and capitalize on increased local control using particle therapy."

Greg Frieherr

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Future of Proton-Beam Radiation Therapy Shines Among Inoperable Lung Cancers