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Six-Dimensional Correction of Intra-Fractional Prostate Motion with CyberKnife Stereotactic Body Radiation Therapy

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      Abstract

      Large fraction radiation therapy offers a shorter course of treatment and radiobiological advantages for prostate cancer treatment. The CyberKnife is an attractive technology for delivering large fraction doses based on the ability to deliver highly conformal radiation therapy to moving targets. In addition to intra-fractional translational motion (left–right, superior–inferior, and anterior–posterior), prostate rotation (pitch, roll, and yaw) can increase geographical miss risk. We describe our experience with six-dimensional (6D) intra-fraction prostate motion correction using CyberKnife stereotactic body radiation therapy (SBRT). Eighty-eight patients were treated by SBRT alone or with supplemental external radiation therapy. Trans-perineal placement of four gold fiducials within the prostate accommodated X-ray guided prostate localization and beam adjustment. Fiducial separation and non-overlapping positioning permitted the orthogonal imaging required for 6D tracking. Fiducial placement accuracy was assessed using the CyberKnife fiducial extraction algorithm. Acute toxicities were assessed using Common Toxicity Criteria v3. There were no Grade 3, or higher, complications and acute morbidity was minimal. Ninety-eight percent of patients completed treatment employing 6D prostate motion tracking with intra-fractional beam correction. Suboptimal fiducial placement limited treatment to 3D tracking in two patients. Our experience may guide others in performing 6D correction of prostate motion with CyberKnife SBRT.

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      Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial.

      In men with localised prostate cancer, conformal radiotherapy (CFRT) could deliver higher doses of radiation than does standard-dose conventional radical external-beam radiotherapy, and could improve long-term efficacy, potentially at the cost of increased toxicity. We aimed to present the first analyses of effectiveness from the MRC RT01 randomised controlled trial. The MRC RT01 trial included 843 men with localised prostate cancer who were randomly assigned to standard-dose CFRT or escalated-dose CFRT, both administered with neoadjuvant androgen suppression. Primary endpoints were biochemical-progression-free survival (bPFS), freedom from local progression, metastases-free survival, overall survival, and late toxicity scores. The toxicity scores were measured with questionnaires for physicians and patients that included the Radiation Therapy Oncology Group (RTOG), the Late Effects on Normal Tissue: Subjective/Objective/Management (LENT/SOM) scales, and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI) scales. Analysis was done by intention to treat. This trial is registered at the Current Controlled Trials website http://www.controlled-trials.com/ISRCTN47772397. Between January, 1998, and December, 2002, 843 men were randomly assigned to escalated-dose CFRT (n=422) or standard-dose CFRT (n=421). In the escalated group, the hazard ratio (HR) for bPFS was 0.67 (95% CI 0.53-0.85, p=0.0007). We noted 71% bPFS (108 cumulative events) and 60% bPFS (149 cumulative events) by 5 years in the escalated and standard groups, respectively. HR for clinical progression-free survival was 0.69 (0.47-1.02; p=0.064); local control was 0.65 (0.36-1.18; p=0.16); freedom from salvage androgen suppression was 0.78 (0.57-1.07; p=0.12); and metastases-free survival was 0.74 (0.47-1.18; p=0.21). HR for late bowel toxicity in the escalated group was 1.47 (1.12-1.92) according to the RTOG (grade >/=2) scale; 1.44 (1.16-1.80) according to the LENT/SOM (grade >/=2) scales; and 1.28 (1.03-1.60) according to the UCLA PCI (score >/=30) scale. 33% of the escalated and 24% of the standard group reported late bowel toxicity within 5 years of starting treatment. HR for late bladder toxicity according to the RTOG (grade >/=2) scale was 1.36 (0.90-2.06), but this finding was not supported by the LENT/SOM (grade >/=2) scales (HR 1.07 [0.90-1.29]), nor the UCLA PCI (score >/=30) scale (HR 1.05 [0.81-1.36]). Escalated-dose CFRT with neoadjuvant androgen suppression seems clinically worthwhile in terms of bPFS, progression-free survival, and decreased use of salvage androgen suppression. This additional efficacy is offset by an increased incidence of longer term adverse events.
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        Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial.

        A randomized radiotherapy dose escalation trial was undertaken between 1993 and 1998 to compare the efficacy of 70 vs. 78 Gy in controlling prostate cancer. A total of 305 Stage T1-T3 patients were entered into the trial and, of these, 301 with a median follow-up of 60 months, were assessable. Of the 301 patients, 150 were in the 70 Gy arm and 151 were in the 78 Gy arm. The primary end point was freedom from failure (FFF), including biochemical failure, which was defined as 3 rises in the prostate-specific antigen (PSA) level. Kaplan-Meier survival analyses were calculated from the completion of radiotherapy. The log-rank test was used to compare the groups. Cox proportional hazard regression analysis was used to examine the independence of study randomization in multivariate analysis. There was an even distribution of patients by randomization arm and stage, Gleason score, and pretreatment PSA level. The FFF rates for the 70- and 78 Gy arms at 6 years were 64% and 70%, respectively (p = 0.03). Dose escalation to 78 Gy preferentially benefited those with a pretreatment PSA >10 ng/mL; the FFF rate was 62% for the 78 Gy arm vs. 43% for those who received 70 Gy (p = 0.01). For patients with a pretreatment PSA 10 ng/mL who were treated to 78 Gy (98% vs. 88% at 6 years, p = 0.056). Rectal side effects were also significantly greater in the 78 Gy group. Grade 2 or higher toxicity rates at 6 years were 12% and 26% for the 70 Gy and 78 Gy arms, respectively (p = 0.001). Grade 2 or higher bladder complications were similar at 10%. For patients in the 78 Gy arm, Grade 2 or higher rectal toxicity correlated highly with the proportion of the rectum treated to >70 Gy. An increase of 8 Gy resulted in a highly significant improvement in FFF for patients at intermediate-to-high risk, although the rectal reactions were also increased. Dose escalation techniques that limit the rectal volume that receives >or=70 Gy to <25% should be used.
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          Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes

          Purpose Hypofractionated, stereotactic body radiotherapy (SBRT) is an emerging treatment approach for prostate cancer. We present the outcomes for low-risk prostate cancer patients with a median follow-up of 5 years after SBRT. Method and Materials Between Dec. 2003 and Dec. 2005, a pooled cohort of 41 consecutive patients from Stanford, CA and Naples, FL received SBRT with CyberKnife for clinically localized, low-risk prostate cancer. Prescribed dose was 35-36.25 Gy in five fractions. No patient received hormone therapy. Kaplan-Meier biochemical progression-free survival (defined using the Phoenix method) and RTOG toxicity outcomes were assessed. Results At a median follow-up of 5 years, the biochemical progression-free survival was 93% (95% CI = 84.7% to 100%). Acute side effects resolved within 1-3 months of treatment completion. There were no grade 4 toxicities. No late grade 3 rectal toxicity occurred, and only one late grade 3 genitourinary toxicity occurred following repeated urologic instrumentation. Conclusion Five-year results of SBRT for localized prostate cancer demonstrate the efficacy and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are underway to further explore this treatment approach.
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            Author and article information

            Affiliations
            1simpleDepartment of Radiation Medicine, Georgetown University Hospital Washington, DC, USA
            2simpleDepartment of Radiology, Georgetown University Hospital Washington, DC, USA
            Author notes

            Edited by: Joe O’Sullivan, Queen’s University Belfast, UK

            Reviewed by: Alan Hounsell, Belfast Health and Social Care Trust, UK; Nicholas Van As, Royal Marsden Hospital, UK

            *Correspondence: Sean P. Collins, Department of Radiation Medicine, Georgetown University Medical Center, 3800 Reservoir Road, Northwest, Washington, DC 20007, USA. e-mail: spc9@ 123456georgetown.edu

            This article was submitted to Frontiers in Radiation Oncology, a specialty of Frontiers in Oncology.

            Journal
            Front Oncol
            Front Oncol
            Front. Oncol.
            Frontiers in Oncology
            Frontiers Research Foundation
            2234-943X
            14 October 2011
            08 December 2011
            2011
            : 1
            3356099
            22655248
            10.3389/fonc.2011.00048
            Copyright © 2011 Lei, Piel, Oermann, Chen, Ju, Dahal, Hanscom, Kim, Yu, Zhang, Collins, Jha, Dritschilo, Suy and Collins.

            This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

            Counts
            Figures: 4, Tables: 2, Equations: 0, References: 56, Pages: 7, Words: 6175
            Categories
            Oncology
            Original Research

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