ST. LOUISThree-dimensional (3D) conformal radiation therapy is being
widely used for treatment of prostate cancer and has been successful at
reducing rectal toxicities. "Conformal radiotherapy has allowed dose
escalation with acceptable or even reduced rates of severe morbidity,"
Jeff M. Michalski, MD, reported. He added, however, that "we have to
start paying attention to the low-grade morbidity. Grade 1 and grade 2
toxicity may predict development of severe late complications." Dr.
Michalski is assistant professor of radiology, Mallinckrodt Institute of
Radiology, Washington University, St. Louis.
"The Radiation Therapy Oncology Group (RTOG) began a clinical trial
of dose escalation using conformal radiation therapy in the early
1990s," he noted. "This was a classic dose-escalation study. We
expected by the time we got to 79.2 Gy that we would have reached our limit
of toxicity. Treatments were given at 1.8 Gy per day to a minimum planning
target volume dose, which really means giving the center part of the
prostate gland a dose of 71 or 77 Gy at this dose level. At 79.2 Gy, the
center part of the gland is getting close to 82 Gy."
Patients were stratified into three groups: those who had little risk of
seminal vesicle invasion; patients whose risk of seminal vesicle invasion
exceeded 15%; and patients with T-3 disease. Institutions created 3D
treatment plans and used a data exchange format to transmit it by the
Internet to St. Louis, where it was reviewed and put into a searchable
"We had anticipated finishing our dose escalation trial at 79.2 Gy,
but we did not see any toxicity early on and then opened it up to two
additional dose levels. This time we lowered the total dose but increased
the dose per fraction. Biologically these two doses are a little bit higher
than in the 79.2 Gy arm. Data are still maturing, but to date we haven’t
seen any toxicities to suggest that even these dose levels are
intolerable," Dr. Michalski said.
Moving to Phase III
The RTOG investigators are proceeding to a Phase III randomized trial at
the 79.2 Gy dose. "We feel that this represents a high enough dose
escalation to show a difference compared to a standard dose arm of roughly
70 Gy in 39 fractions," Dr. Michalski said.
"With conformal radiation therapy we are able to reduce the rate of
rectal toxicity compared to standard or older techniques of radiation
therapy," Dr. Michalski said. Researchers from the Fox Chase Cancer
Center had shown that as the central axis dose to the prostate gland
increased, the probability of injury to the rectum rose steeply. This
prompted them to add a block of the rectum at the final 10 Gy, which reduced
the dose to the rectum and the risk of rectal toxicity.