Nick Mulcahy

September 27, 2011

September 27, 2011 — Intensity-modulated radiation therapy (IMRT) resulted in 26% fewer late bowel and rectal adverse effects (grade 2+) than 3-dimensional conformal radiation therapy (3D-CRT) in a toxicity study of 748 men with localized prostate cancer treated with high-dose radiation.

This result from a multivariate analysis, which was not statistically significant but represented a trend toward a clinically meaningful reduction, were presented at a press briefing held in advance of the American Society for Radiation Oncology (ASTRO) 53rd Annual Meeting.

IMRT was also associated with a statistically significant reduction in acute grade 2+ gastrointestinal (GI) and genitourinary (GU) toxicity, according to investigators from Radiation Therapy Oncology Group (RTOG) 0126, a phase 3 dose-escalation trial.

"I believe the study supports the use of IMRT in the management of localized prostate cancer," summarized study chair Jeff Michalski, MD, from Washington University Medical Center in St. Louis, Missouri, at the briefing.

In RTOG 0126, Dr. Michalski and colleagues are comparing the toxicity rates of high-dose radiation therapy and standard-dose radiation treatment. The primary purpose of RTOG 0126 is to "prove that the higher doses achievable with 3D-CRT are justified by an improvement in local tumor control, freedom from PSA [prostate-specific antigen] failure, and overall survival," according to a trial group document.

The study initially evaluated only 3D-CRT at different doses but, a year after its start in 2004, included IMRT as well, said Dr. Michalski.

The study scheme calls for men to be stratified by Gleason score and PSA, and then randomized into 1 of 2 treatment groups. In the first group, patients receive either 3D-CRT or IMRT at a standard dose (70.2 Gy in 39 fractions). In the second group, patients receive either 3D-CRT or IMRT at a high dose (79.2 Gy in 44 fractions).

The RTOG 0126 results are from a preliminary analysis of acute and late toxicity in 748 men in the second group — those receiving high-dose radiation therapy.

The study is the first "contemporary" cohort of patients in a multicenter trial comparing IMRT and 3D-CRT showing a benefit with IMRT, said Dr. Michalski. A dose-escalation trial conducted at Memorial Sloan-Kettering Cancer Center in New York City has demonstrated the ability to administer high-dose IMRT with acceptable toxicity, he added.

The study also shows that IMRT allows for less radiation to the bladder and bowel, said Dr. Michalski.

Health-policy experts will be interested in the results, given the reductions in toxicity, said ASTRO president elect Michael Steinberg, MD, who moderated the press briefing. The results are "more than interesting — even impressive," said Dr. Steinberg, who is from the University of California at Los Angeles Health System.

White Men More Vulnerable to Rectal Toxicity?

Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and proximal seminal vesicles (P+pSV), followed by a 23.4 Gy to the prostate only. IMRT patients were treated with 79.2 Gy to the P+pSV. The CTC and RTOG/EORTC late-morbidity scoring systems were used to evaluate acute and late effects. Univariate and multivariate comparisons for effects were undertaken.

Of the 748 patients in the high-dose group, 491 were treated with 3D-CRT and 257 were treated with IMRT. Because of the late inclusion of IMRT, median follow-up was 4.6 years for patients in the 3D-CRT group and 3.5 years for those in the IMRT group.

In terms of acute toxicity (both GI and GU adverse effects), in the 3D-CRT group, there were 16.9% grade 2 events, 2.5% grade 3 events, and no grade 4 or 5 events. In the IMRT group, there were 13.9% grade 2 events, 2.4% grade 3 events, 0.4% grade 4 events, and no grade 5 events.

In terms of late toxicity (both GI and GU), in the 3D-CRT group, there were 23.6% grade 2 events, 8.9% grade 3 events, 0.4% grade 4 events, and 0.2% grade 5 events (1 death). In the IMRT group, there were 19.9% grade 2 events, 4.7% grade 3 events, 0.4% grade 4 events, and no grade 5 events.

Both univariate and multivariate analyses showed a statistically significant decrease in grade 2+ acute collective GI/GU toxicity for IMRT, report the authors in their abstract.

There were no significant differences with 3D-CRT or IMRT for acute or late grade 2+ or 3+ GU toxicities. On multivariate analysis, IMRT showed a trend toward a 26% reduction in grade 2+ late GI toxicity (P = .099), as noted above.

The study also showed that there was a significant increase (15%) in rectal adverse effects associated with white men, compared with men of other races, regardless of the radiation treatment.

"The racial differences were definitely surprising and we are still unsure why they exist," said Dr. Michalski in a press statement. "While it could be a real difference in the tolerance to treatment, it could also represent cultural differences in reporting side effects and physician interpretation of patient descriptions. This will be the topic of further investigation."

The study was supported by the ASTRO Radiation Oncology Institute and the National Cancer Institute. The authors have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 53rd Annual Meeting: Abstract 2. To be presented October 3, 2011.


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