Dose-escalated IMRT appears safe in prostate cancer patients

Dose-escalated intensity-modulated radiation therapy (IMRT) with use of a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can safely treat patients with localized prostate cancer with limited grade 2 or 3 late toxicity, according to a recently published study.

While previous research has shown that dose-escalated radiation therapy provides better prostate cancer control than lower-dose therapy in a shorter time period, data on the late toxicity of moderate hypofractionated regimens are limited. This randomized trial from the University of Texas MD Anderson Cancer Center compares the late toxicity outcomes of men with localized prostate cancer treated with either conventionally fractionated IMRT (CIMRT) or dose-escalated hypofractionated IMRT (HIMRT).

Results were published in the International Journal of Radiation Oncology • Biology • Physics (2014; 88:1074-84).

Men with organ-confined prostate cancer (median age, 68 years) were enrolled in the study from January 2001 to January 2010 and were randomized to receive either CIMRT (75.6 Gy in 1.8-Gy fractions over 8.5 weeks) or dose-escalated HIMRT (72 Gy in 2.4-Gy fractions over 6 weeks). One hundred and one men received CIMRT and 102 received HIMRT.

Physician-reported toxicity was evaluated for all patients during treatment and at each follow-up visit. After completion of radiation therapy, follow-up was conducted at least every 6 months for the first 2 years following treatment, and annually thereafter. Median follow-up was 6 years.

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Late gastrointestinal (GI) and genitourinary (GU) toxicity were analyzed, starting 90 days after treatment, using modified Radiation Therapy Oncology Group toxicity grading. In the CIMRT arm, 17% experienced grade 1 GI toxicity, 4% experienced grade 2 GI toxicity, and 1% experienced grade 3 GI toxicity. In the HIMRT arm, 26% experienced grade 1 GI toxicity, 9% experienced grade 2 GI toxicity, and 2% experienced grade 3 GI toxicity. There was a numeric increase in the absolute frequency of late GI toxicity for men treated with HIMRT, but the difference was not statistically significant.

The 5-year actuarial grade 2 or 3 late GI toxicity was 5.1% (95% confidence interval) for patients treated with CIMRT and 10% for patients treated with HIMRT. The increase in late GI toxicity for men receiving HIMRT was the result of moderate and high radiation dose to a larger proportion of the rectum, which suggests that more stringent dose constraints for the rectum may result in lower late GI toxicity for those patients.

Additionally, there was not a statistically significant difference in the absolute frequency of late GU toxicity in men treated with CIMRT or HIMRT. In the CIMRT arm, 15% experienced grade 1 GU toxicity, 14% experienced grade 2 GU toxicity, and 1% experienced grade 3 GU toxicity. In the HIMRT arm, 10% experienced grade 1 GU toxicity and 15% experienced grade 2 GU toxicity; no patients reported grade 3 GU toxicity. The 5-year actuarial grade 2 or 3 late GU toxicity was 16.5% (95% CI) among patients treated with CIMRT and 15.8% among those treated with HIMRT.

“These results demonstrate that the length of radiation treatment for prostate cancer can be safely decreased to 6 weeks (from 8.5 weeks) by delivering larger daily doses of radiation without increasing the urinary and bowel effects. Decreasing the length of treatment decreases the cost and is more convenient for patients,” said co-author Karen E. Hoffman, MD, of the University of Texas MD Anderson Cancer Center, Houston.

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