Dose-Escalated Hypofractionated IMRT for Localized Prostate Cancer Has Similar Side Effects Compared to Conventional IMRT
Dose-escalated intensity-modulated radiotherapy 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 study by Hoffman et al published in the International Journal of Radiation Oncology • Biology • Physics.
Previous randomized clinical trials have shown that dose-escalated radiotherapy improves prostate cancer control compared to lower-dose conventional radiotherapy. Conventional fractionation of dose-escalated radiotherapy (1.8- or 2-Gy fractions) can take up to 9 weeks to complete, while hypofractionated radiation therapy can deliver a higher biologically effective dose over a shorter period of time (6 weeks) and has the potential to increase prostate cancer control without increasing toxicity. However, there are limited data on the late toxicity of moderate hypofractionated regimens for prostate cancer.
This randomized trial from The University of Texas MD Anderson Cancer Center compared the late toxicity outcomes of men with localized prostate cancer treated with either conventionally fractionated or dose-escalated hypofractionated intensity-modulated radiotherapy.
Study Design
The trial enrolled men with localized prostate cancer from January 2001 to January 2010. Patients were randomly assigned to receive either conventionally fractionated intensity-modulated radiotherapy (75.6 Gy in 1.8-Gy fractions over 8.5 weeks) or dose-escalated hypofractionated intensity-modulated radiotherapy (72 Gy in 2.4 Gy fractions over 6 weeks).
Eligible patients had biopsy-proven prostate adenocarcinoma; good performance status; stage T1b-T3b disease; prostate-specific antigen (PSA) ≤ 20 ng/ml; Gleason score < 10; and no clinical, radiographic, or pathologic evidence of nodal or bone metastasis. Patients with stage cT3c or cT4 disease, a history of prior pelvic radiation therapy, or who received more than 4 months of hormone ablation therapy with prior or planned radical prostate surgery, and with concurrent active malignancy other than nonmetastatic skin cancer or early-stage chronic lymphocytic leukemia were not eligible for the trial.
The median age of the patient cohort was 68. Of the 203 patients analyzed in the study, 72% (146) had stage T1 disease and 89% (181) had a PSA < 10 ng/ml. Thirty-four percent (70) had Gleason 6 disease, 65% (131) had Gleason 7 disease, and 1% (2) had Gleason 8 disease. Patients were classified into low-risk (28%), intermediate risk (71%) and high-risk (1%) disease using current National Comprehensive Cancer Network risk-group definitions.
All patients were treated with static-field intensity-modulated radiotherapy. One hundred and one men received conventionally fractionated intensity-modulated radiotherapy, and 102 men received dose-escalated hypofractionated intensity-modulated radiotherapy. 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 post-treatment, and annually thereafter. Median follow-up was 6 years.
Late gastrointestinal (GI) and genitourinary (GU) toxicity were analyzed in this study, starting 90 days post-treatment, using modified Radiation Therapy Oncology Group toxicity grading.
Gastrointestinal Toxicity
In the conventionally fractionated arm, 17% of patients experienced grade 1 GI toxicity, 4% experienced grade 2 GI toxicity, and 1% experienced grade 3 GI toxicity. In the dose-escalated hypofractionated 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 hypofractionated intensity-modulated radiotherapy, but the difference was not statistically significant. The 5-year actuarial grade 2 or 3 late GI toxicity was 5.1% (95% confidence interval [CI]) for patients treated with conventionally fractionated intensity-modulated radiotherapy and 10% for patients treated with dose-escalated hypofractionated therapy.
The increase in late GI toxicity for men receiving dose-escalated hypofractionated radiotherapy 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.
Genitourinary Toxicity
Additionally, there was not a statistically significant difference in the absolute frequency of late GU toxicity in men treated with conventionally fractionated or dose-escalated hypofractionated intensity-modulated radiotherapy. In the conventionally fractionated arm, 15% experienced grade 1 GU toxicity, 14% experienced grade 2 GU toxicity, and 1% experienced grade 3 GU toxicity. In the dose-escalated hypofractionated 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) for patients treated with conventionally fractionated intensity-modulated radiotherapy and 15.8% for patients treated with dose-escalated hypofractionated intensity-modulated radiotherapy.
“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,” said Karen E. Hoffman, MD, a coauthor of the study and Assistant Professor in the Division of Radiation Oncology at The University of Texas MD Anderson Cancer Center in Houston. “Decreasing the length of treatment decreases the cost and is more convenient for patients.”
Dr. Hoffman is the corresponding author of the International Journal of Radiation Oncology • Biology • Physics article.
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