For Inoperable Early Lung Cancer, "First Significant Change in 50 Years"

November 4, 2009 (Chicago, Illinois) — Stereotactic body radiation therapy provided an extremely high rate of local control (98%) at 3 years in a small trial of patients with inoperable early-stage lung cancer, according to the results of a new study presented here at the American Society for Radiation Oncology (ASTRO) 51st Annual Meeting.

Dr. Robert Timmerman (Courtesy of ASTRO)

This control rate — indicative of the stopped growth of the cancer — with stereotactic body radiation therapy is "strikingly better than conventional radiotherapy," said lead author Robert D. Timmerman, MD, from the University of Texas Southwestern Medical Center in Dallas, at a meeting press conference.

Conventional radiotherapy provides a local control rate of 30% to 50%, he explained.

Among the 55 patients treated with stereotactic body radiation therapy, the rate of overall survival at 3 years was 56%, which compares favorably with historic results with conventional radiation, which are in the neighborhood of 30% to 50%, Dr. Timmerman added. The median follow-up was 48.1 months and the median patient age was 72 years.

We don't need to do a phase 3 trial.

The results of this phase 2 trial should signal a change in practice, suggested Stephen Hahn, MD, from the University of Pennsylvania School of Medicine in Philadelphia, who moderated the press conference. "We don't need to do a phase 3 trial, because it would be an ethical dilemma to treat these patients with conventional radiation and not offer them stereotactic radiation," he said.

Lead author Dr. Timmerman was more emphatic in his assessment of the results: "This is the first significant change in these patients in 50 years."

Patients with inoperable lung cancer do "relatively poorly" because of their inability to undergo surgery, said Dr. Hahn. Thus, any improvement in outcome is "highly significant," he explained.

About 25% of all lung cancer in the United States is early stage, and about 20% of that patient group will have inoperable disease, Dr. Timmerman noted.

In addition to being more effective than conventional radiation, stereotactic radiation is administered much more quickly. Conventional radiation in these patients takes 6 to 7 weeks, said Dr. Timmerman, whereas stereotactic radiation takes place in 3 outpatient sessions in only 1 week.

The current trial was a single-group study. However, Dr. Timmerman noted, a trial comparing this new approach and conventional radiation is underway in Europe and another is planned in Australia.

The success of the trial creates other possibilities for this radiotherapy, said Dr. Timmerman. "It also begs the question of whether stereotactic body radiation therapy should be considered in healthier patients with lung cancer who are treated with surgery," he said.

Stereotactic body radiation therapy is often referred to by the brand names of the manufacturers, including Axesse, CyberKnife, Gamma Knife, Novalis, Primatom, Synergy, X-Knife, TomoTherapy, and Trilogy, according the ASTRO.

For Smaller Peripheral Lung Cancers

The trial was run by the Radiation Therapy Oncology Group (0236), which is the first North American cooperative group trial to use stereotactic body radiation therapy.

It is for medically frail patients.

Dr. Timmerman noted that stereotactic radiation will not "unseat surgery" as the primary choice of treatment for lung cancer. "It is for medically frail patients," he said.

The incoming president of ASTRO placed a slightly different emphasis on the trial. "This will not replace regular radiation in the treatment of lung cancer. Most lung tumors are not suited for this treatment, which is best for smaller peripheral lung cancers," Anthony Zietman, MD, from Harvard Medical School in Boston, Massachusetts, told Medscape Oncology.

Indeed, in the trial, eligible patients had T1 and T2 tumors of 5 cm or less or had T3 tumors in the chest wall (also 5 cm or less).

Eligible patients also had to have had biopsy-proven, nonsmall-cell lung cancer and comorbidities, such as emphysema, heart disease, and diabetes, that disallow surgery as a treatment option, said Dr. Timmerman.

The prescription dose was 20 Gy per fraction for 3 fractions, for a total dose of 60 Gy.

At 36 months, among the 55 evaluable patients, there was only 1 failure in local control, meaning that the therapy provided a 98% rate of local control. Also, 11 patients (20%) had disseminated failure and 10 patients (18%) died at 36 months, said Dr. Timmerman.

Protocol-related grade 3 and 4 adverse events were reported in 7 (13%) and 2 (4%) patients, respectively. The most common severe adverse event categories were pulmonary/upper respiratory and musculoskeletal. No patients died from treatment. Overall, the events were described as "moderate" by Dr. Timmerman.

"The evidence suggests it is safe," said Dr. Zietman. "When you blast tumors with high doses of radiation, there are safety concerns."

The study was supported by grants from the National Cancer Institute and Advanced Technology Consortium. Dr. Timmerman reports receiving research grants from Elekta Oncology and Varian Medical Systems, and is a consultant to D3 Corporation. Dr. Hahn and Dr. Zietman have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 51st Annual Meeting: Abstract 5. Presented November 2, 2009.