International Journal of Radiation Oncology*Biology*Physics
Clinical investigation: prostateHigh-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients
Introduction
High-dose three-dimensional conformal radiotherapy (3D-CRT) has been shown to improve local control and disease-free survival in patients with localized prostate cancer 1, 2, 3, 4. Dose levels of 75.6 Gy and higher have been associated with improved outcomes for patients with favorable, intermediate, and unfavorable prognostic risk features (5). Although the rate of severe (≥ Grade 3) late toxicities was low for patients treated at these dose levels, a higher incidence of Grade 2 rectal and urinary toxicities was observed when the dose was escalated from 64.8 to 81 Gy with conventional 3D-CRT techniques. The incidence of late Grade 2 rectal bleeding among patients who received 75.6–81 Gy was 17% compared to 6% for those treated to lower dose levels 1, 6.
Several investigators have shown that the volume of normal tissue exposed to higher radiation dose levels may represent the most significant factor affecting the development of late Grade 2 toxicity. Jackson et al. (7) found that in patients treated to 70.2 and 75.6 Gy with 3D-CRT, the mean rectal dose-volume histogram was significantly increased in patients who had rectal bleeding as compared to nonbleeders. Storey et al. (8) reported that rectal toxicity was observed more often among those patients treated to ≥70 Gy who had 30% or more of the rectum exposed to higher doses. Together, these data have corroborated the importance of the volume effect and its impact on late toxicity development in the setting of dose escalation strategies.
Recognizing that dose escalation was associated with greater risk of toxicity if a greater volume of normal tissue was treated to high dose levels, we implemented intensity-modulated radiotherapy (IMRT) to further improve the conformality of the dose distribution and thereby facilitate dose escalation for patients with localized prostate cancer. We reported previously that this enhancement in technology was associated with a significantly lower incidence of acute and late rectal toxicities (9). Subsequently, more than 700 patients have been treated with IMRT at our institution. In this report, we present the preliminary tolerance outcome of these patients who were treated to dose levels of 81 and 86.4 Gy. The data indicate that to date, the acute and late toxicity profiles are excellent, and despite the enhanced conformality associated with IMRT, the biochemical outcome is apparently not compromised.
Section snippets
Methods and materials
Between April 1996 and January 2001, 772 patients with clinically localized prostate cancer were treated with IMRT. These patients include the initial 85 patients treated to 81 and 86.4 Gy dose levels enrolled on an institutional review board Phase I dose escalation study, as described previously. Their median age was 69 years (range: 46–86 years). Pretreatment diagnostic evaluations were performed, as previously described (10). The American Joint Committee on Cancer 1997 clinical stage (11)
Toxicity
High-dose IMRT was well tolerated acutely. As shown in Table 1, 35 patients (4.5%) developed acute Grade 2 rectal toxicity, and no patient experienced acute Grade 3 or higher rectal symptoms. Two hundred seventeen patients (28%) developed acute Grade 2 urinary symptoms, and one experienced urinary retention (Grade 3) toward the end of his treatment course.
The rates of late complications are shown in Table 2. Eleven patients (1.5%) developed Grade 2 rectal bleeding at a median of 9 months
Discussion
To our knowledge, these data represent the largest compilation of IMRT-treated patients and demonstrate the feasibility of high-dose radiation delivery with IMRT for patients with localized prostate cancer. IMRT was used throughout the entire treatment course, and as reported previously, the average time spent by the patient in the treatment room (including port-film verification) for this five-field approach was approximately 15 minutes, similar to our previous six-field 3D-CRT technique (9).
References (25)
- et al.
Dose escalation with three dimensional conformal radiation therapy affects the outcome in prostate cancer
Int J Radiat Oncol Biol Phys
(1998) - et al.
Dose selection for prostate cancer based on dose comparison and dose response studies
Int J Radiat Oncol Biol Phys
(2000) - et al.
Importance of high radiation doses (72 Gy or greater) in the treatment of stage T1-T3 adenocarcinoma of the prostate
Urology
(2000) - et al.
High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer
J Urol
(2001) - et al.
Late rectal bleeding after conformal radiotherapy of prostate cancer. II. Volume effects and dose-volume histograms
Int J Radiat Oncol Biol Phys
(2001) - et al.
Complications from radiotherapy dose escalation in prostate cancerPreliminary results of a randomized trial
Int J Radiat Oncol Biol Phys
(2000) - et al.
Clinical experience with intensity modulated radiation therapy (IMRT) in prostate cancer
Radiother Oncol
(2000) - et al.
Conformal radiation treatment of prostate cancer using inversely planned intensity-modulated photon beams produced with dynamic multileaf collimation
Int J Radiat Oncol Biol Phys
(1996) - et al.
Planning, delivery, and quality assurance of intensity-modulated radiotherapy using dynamic multileaf collimatorA strategy for large-scale implementation for the treatment of carcinoma of the prostate
Int J Radiat Oncol Biol Phys
(1997) - et al.
The potential and limitations of the inverse radiotherapy technique
Radiother Oncol
(1994)