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
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
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
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