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

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      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 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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          Volumetric modulated arc therapy (VMAT) vs. serial tomotherapy, step-and-shoot IMRT and 3D-conformal RT for treatment of prostate cancer.

          Volumetric modulated arc therapy (VMAT), a complex treatment strategy for intensity-modulated radiation therapy, may increase treatment efficiency and has recently been established clinically. This analysis compares VMAT against established IMRT and 3D-conformal radiation therapy (3D-CRT) delivery techniques. Based on CT datasets of 9 patients treated for prostate cancer step-and-shoot IMRT, serial tomotherapy (MIMiC), 3D-CRT and VMAT were compared with regard to plan quality and treatment efficiency. Two VMAT approaches (one rotation (VMAT1x) and one rotation plus a second 200 degrees rotation (VMAT2x)) were calculated for the plan comparison. Plan quality was assessed by calculating homogeneity and conformity index (HI and CI), dose to normal tissue (non-target) and D(95%) (dose encompassing 95% of the target volume). For plan efficiency evaluation, treatment time and number of monitor units (MU) were considered. For MIMiC/IMRT(MLC)/VMAT2x/VMAT1x/3D-CRT, mean CI was 1.5/1.23/1.45/1.51/1.46 and HI was 1.19/1.1/1.09/1.11/1.04. For a prescribed dose of 76 Gy, mean doses to organs-at-risk (OAR) were 50.69 Gy/53.99 Gy/60.29 Gy/61.59 Gy/66.33 Gy for the anterior half of the rectum and 31.85 Gy/34.89 Gy/38.75 Gy/38.57 Gy/55.43 Gy for the posterior rectum. Volumes of non-target normal tissue receiving > or =70% of prescribed dose (53 Gy) were 337 ml/284 ml/482 ml/505 ml/414 ml, for > or =50% (38 Gy) 869 ml/933 ml/1155 ml/1231 ml/1993 ml and for > or =30% (23 Gy) 2819 ml/3414 ml/3340 ml/3438 ml /3061 ml. D(95%) was 69.79 Gy/70.51 Gy/71,7 Gy/71.59 Gy/73.42 Gy. Mean treatment time was 12 min/6 min/3.7 min/1.8 min/2.5 min. All approaches yield treatment plans of improved quality when compared to 3D-conformal treatments, with serial tomotherapy providing best OAR sparing and VMAT being the most efficient treatment option in our comparison. Plans which were calculated with 3D-CRT provided good target coverage but resulted in higher dose to the rectum.

            Author and article information

            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@

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

            Front Oncol
            Front Oncol
            Front. Oncol.
            Frontiers in Oncology
            Frontiers Research Foundation
            14 October 2011
            08 December 2011
            : 1
            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.

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


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