New RT Methods Promising in Early Lung Ca

WASHINGTON-After many decades with few advances in radiotherapy, important new methods of delivering radiotherapy have emerged in the past 10 years, a number of which show the promise of increasing local control-and thus, survival-in lung cancer, said Robert D. Timmerman, MD, vice-chair, Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas. Speaking at the Geriatric Oncology Consortium 2005 meeting, "Advancing Cancer Care in the Elderly," Dr. Timmerman discussed new radiotherapy techniques of potential benefit to elderly patients with early lung cancer.

Unfortunately, Dr. Timmerman explained, older patients with early-stage lung cancer often cannot have surgery because they are frail and have comorbidities. They typically are treated only with conventional radiotherapy, yet without surgery, he said, their chance of survival plummets: In stage I lung cancer, for example, 3- to 5-year survival rates range from 60% to 70% in patients who undergo surgery, but are only 30% to 45% with conventional radiation therapy. Similar differences are seen in stage II patients. Patients who have surgery "do profoundly better," he said.

Better survival outcomes for patients receiving radiotherapy alone are on the horizon, however, with the advent of several new approaches.

Promising new treatment strategies include techniques to increase the total dose of radiation, as well as hypofractionation, which delivers the total dose in fewer sessions, or fractions, over a shorter time period.

Many of these new approaches show evidence of raising local control rates, Dr. Timmerman said. Because surgery has been shown to improve local control by the same percentages that it improves survival, he said, it seems reasonable "to hypothesize that if we could increase local control using radiotherapy, we could increase survival as well."

The most dramatic data on local control, he added, have been reported from early high-dose trials. In phase I dose-escalation trials, investigators have used 3D conformal radiation to deliver doses up to 100 Gy, nearly twice the conventional 60-Gy dose. Data from a study at the University of Michigan (Int J Radiat Oncol Biol Phys 63:324-333, 2005) showed a 2-year local control rate of 61% at a dose of 92 Gy, which is "dramatically better" than what would be expected from conventional doses, he said.

One disadvantage of dose-escalation approaches is the length of time it takes to deliver the total dose-9 to 10 weeks, vs 6 weeks with conventional radiotherapy. Not only is this inconvenient for the patient, Dr. Timmerman said, but there are also data suggesting that tumor cells can develop resistance to radiotherapy over that period of time.

One potential solution to this problem is hypofractionation, which delivers radiation over a shorter time period-15 to 21 treatments over 3 or 4 weeks-by giving patients higher doses in fewer sessions. Aggressive hypofractionation goes a step further, delivering very few treatments (typically 3 to 5) via unconventionally large doses.

Stereotactic Body RT

An important evolving approach that has shown benefit in the treatment of primary and metastatic tumors in a variety of cancer types is stereotactic body radiation therapy (SBRT). This newly emerging treatment method delivers a single fraction or multiple fractions of high-dose ionizing radiation with high targeting accuracy and rapid dose falloff. Radiation delivery must be highly targeted and carefully monitored to address substantial organ motion.

In October 2004, the American College of Radiology and the American Society for Therapeutic Radiology and Oncology released a jointly developed guideline for performing SBRT, including suggested techniques for limiting movement of the target volume during treatment planning and delivery.

Dr. Timmerman reported on an SBRT dose-escalation study in early lung cancer in which he was a co-investigator (Chest 124:1946-1955, 2003). "To our great surprise and astonishment, we kept going up and up in dose without getting prohibitive toxicity, until we had delivered massive doses of radiation," he said. Patients were able to receive 20 Gy or 22 Gy per fraction; only three fractions were needed, and they were delivered over a period of 1 week, he added.

In a follow-up phase II trial, patients will receive three fractions at 20 Gy or 22 Gy per fraction. The researchers have set the target rate for local control at 80% after 2 years. SBRT, Dr. Timmerman concluded, seems likely to be an important new treatment paradigm for the future of radiation oncology.