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      Risk factors for rectal bleeding associated with I-125 brachytherapy for prostate cancer

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          The purpose of this study was to determine the risk factors for rectal bleeding after prostate brachytherapy. Between April 2005 and September 2009, 89 patients with T1c-2cN0M0 prostate cancer were treated with permanent I-125 seed implantation alone. The prostate prescription dose was 145 Gy, and the grade of rectal bleeding was scored according to the Common Terminology Criteria for Adverse Events version 4.0. Post-treatment planning was performed with fusion images of computerized tomography and magnetic resonance imaging 4–5 weeks after brachytherapy. Patient characteristics and dosimetric parameters were evaluated to determine risk factors for bleeding. The calculated parameters included the rectal volume in cubic centimeters that received >50–200% of the prescribed dose (RV50–200) and the minimal doses received by 1–30% of the rectal volume (RD1–30). The median follow-up time was 42 months (ranging 18–73 months). Grade 1 rectal bleeding occurred in 24 (27.0%) patients, but no Grade 2 or severe bleeding was observed. Usage of anticoagulants had a significant correlation with the occurrence of bleeding ( P = 0.007). The RV100–150 and RD1–10 were significantly higher in patients with rectal bleeding than in those without bleeding. The RV100 was identified as a possible threshold value; the 3-year rectal bleeding rate in patients with an RV100 > 1.0 cm 3 was 36%, whereas that with an RV100 ≤ 1.0 cm 3 was 14% ( P < 0.05). Although no Grade 2 morbidity developed in this study, the RV100 should be kept below 1.0 cm 3, especially in additional dose-escalated brachytherapy.

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          Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer.

          To report the long-term results of a randomized radiotherapy dose escalation trial for prostate cancer. From 1993 to 1998, a total of 301 patients with stage T1b to T3 prostate cancer were accrued to a randomized external beam dose escalation trial using 70 Gy versus 78 Gy. The median follow-up is now 8.7 years. Kaplan-Meier analysis was used to compute rates of prostate-specific antigen (PSA) failure (nadir + 2), clinical failure, distant metastasis, disease-specific, and overall survival as well as complication rates at 8 years post-treatment. For all patients, freedom from biochemical or clinical failure (FFF) was superior for the 78-Gy arm, 78%, as compared with 59% for the 70-Gy arm (p = 0.004, and an even greater benefit was seen in patients with initial PSA >10 ng/ml (78% vs. 39%, p = 0.001). The clinical failure rate was significantly reduced in the 78-Gy arm as well (7% vs. 15%, p = 0.014). Twice as many patients either died of prostate cancer or are currently alive with cancer in the 70-Gy arm. Gastrointestinal toxicity of grade 2 or greater occurred twice as often in the high dose patients (26% vs. 13%), although genitourinary toxicity of grade 2 or greater was less (13% vs. 8%) and not statistically significantly different. Dose-volume histogram analysis showed that the complication rate could be significantly decreased by reducing the amount of treated rectum. Modest escalation in radiotherapy dose improved freedom from biochemical and clinical progression with the largest benefit in prostate cancer patients with PSA >10 ng/ml.
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            Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial.

            Clinically localized prostate cancer is very prevalent among US men, but recurrence after treatment with conventional radiation therapy is common. To evaluate the hypothesis that increasing the radiation dose delivered to men with clinically localized prostate cancer improves disease outcome. Randomized controlled trial of 393 patients with stage T1b through T2b prostate cancer and prostate-specific antigen (PSA) levels less than 15 ng/mL randomized between January 1996 and December 1999 and treated at 2 US academic institutions. Median age was 67 years and median PSA level was 6.3 ng/mL. Median follow-up was 5.5 (range, 1.2-8.2) years. Patients were randomized to receive external beam radiation to a total dose of either 70.2 Gy (conventional dose) or 79.2 Gy (high dose). This was delivered using a combination of conformal photon and proton beams. Increasing PSA level (ie, biochemical failure) 5 years after treatment. The proportions of men free from biochemical failure at 5 years were 78.8% [corrected] (95% confidence interval, 73.1%-84.6%) [corrected] for conventional-dose and 91.3% [corrected] (95% confidence interval, 87.2%-95.4%) [corrected] for high-dose therapy (P<.001), a 59% [corrected] reduction in the risk of failure. The advantage to high-dose therapy was statistically significant [corrected] in both the low-risk subgroup [corrected] (risk reduction, 84% [P<.001]) [corrected] There has been no significant difference in overall survival rates between the treatment groups. Only 1% of patients receiving conventional-dose and 2% receiving high-dose radiation experienced acute urinary or rectal morbidity of Radiation Therapy Oncology Group (RTOG) grade 3 or greater. So far, only 2% and 1%, respectively, have experienced late morbidity of RTOG grade 3 or greater. Men with clinically localized prostate cancer have a lower risk of biochemical failure if they receive high-dose rather than conventional-dose conformal radiation. This advantage was achieved without any associated increase in RTOG grade 3 acute or late urinary or rectal morbidity.
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              Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy.

              To determine whether a dose of 78 Gy improves outcome compared with a conventional dose of 68 Gy for prostate cancer patients treated with three-dimensional conformal radiotherapy. Between June 1997 and February 2003, stage T1b-4 prostate cancer patients were enrolled onto a multicenter randomized trial comparing 68 Gy with 78 Gy. Patients were stratified by institution, age, (neo)adjuvant hormonal therapy (HT), and treatment group. Four treatment groups (with specific radiation volumes) were defined based on the probability of seminal vesicle involvement. The primary end point was freedom from failure (FFF). Failure was defined as clinical failure or biochemical failure, according to the American Society of Therapeutic Radiation Oncology definition. Other end points were freedom from clinical failure (FFCF), overall survival (OS), and toxicity. Median follow-up time was 51 months. Of the 669 enrolled patients, 664 were included in the analysis. HT was prescribed for 143 patients. FFF was significantly better in the 78-Gy arm compared with the 68-Gy arm (5-year FFF rate, 64% v 54%, respectively), with an adjusted hazard ratio of 0.74 (P = .02). No significant differences in FFCF or OS were seen between the treatment arms. There was no difference in late genitourinary toxicity of Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer grade 2 or more and a slightly higher nonsignificant incidence of late gastrointestinal toxicity of grade 2 or more. This multicenter randomized trial shows a significantly improved FFF in prostate cancer patients treated with a higher dose of radiotherapy.

                Author and article information

                J Radiat Res
                J. Radiat. Res
                Journal of Radiation Research
                Oxford University Press
                November 2012
                1 August 2012
                1 August 2012
                : 53
                : 6
                : 923-929
                [1 ]Department of Radiation Oncology, Isesaki Municipal Hospital, 12-1, Tsunatorimoto-machi, Isesaki-shi, Gunma 372-0802, Japan
                [2 ]Department of Urology, Isesaki Municipal Hospital, 12-1, Tsunatorimoto-machi, Isesaki-shi, Gunma 372-0802, Japan
                [3 ]Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
                Author notes
                [* ]Corresponding author. Department of Radiation Oncology, Isesaki Municipal Hospital, 12-1, Tsunatorimoto-machi, Isesaki-shi, Gunma 372-0802, Japan. Tel: +81-270-25-5022; Fax: +81-270-25-5023; Email: kusauko@
                © The Author 2012. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Therapeutic Radiology and Oncology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.



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