the prostate is in front of the rectum and is separated by just a fascia . as a result , the location of the prostate is significantly affected by rectal volume . in particular , the location of the peripheral zone can be easily affected by a change in rectal volume because the peripheral zone abuts the anterior wall of the rectum . therefore , it is necessary to include the peripheral zone in a radiotherapy ( rt ) field . when the rectum is distended , it can push the prostate anteriorly , especially the peripheral zone , and give rise to inadequate irradiation in some portion of the prostate . increased risk of biochemical and local failures was reported in patients whose rectums were distended on rt planning ( rtp ) computed tomography ( ct ) for prostate cancers . hence , it is recommended that a patient undergo rtp ct again after rectal emptying if the patient had a distended rectum at the time of a rtp ct scan . rectal emptying can reduce the degree of prostate motion   and additionally intrafractional motion . in one study , a 10% probability of prostate movement of more than 3 mm occurred in 1 and 20 minutes in full and empty rectum groups , respectively . accordingly , we decided to apply a rectal enema before each rt fraction to limit the inter- and intrafraction prostate movements resulting from changes in rectal volume . setup uncertainty could be reduced markedly with the use of image - guided rt ( igrt ) , which uses the prostate itself for the rt setup , compared with conventional rt , which uses skin markers or pelvic bones for the rt setup . among the methods for igrt , prostate alignment with implanted fiducial markers results in the least interuser disagreement compared with that with anatomy or contours . in as much as the implanted fiducial markers can be used as a surrogate for a prostate igrt with implanted fiducial markers can improve prostate alignment further over that with bony pelvis or soft tissues . although the implanted fiducial markers can increase the accuracy of the prostate setup for rt , they are not used routinely in korea because of their invasive nature . some radiation oncologists implement igrt with pelvic bones or soft tissues instead . there may be a larger discrepancy in prostate locations between rt setup with pelvic bones or soft tissues and that with implanted fiducial markers . despite the effect of rectal volume on a prostate position , studies about the spatial difference of prostates after rt setup we were intrigued about the discrepancy of prostate locations after rectal emptying . in the present study , to limit the change in rectal volume , a rectal enema was administered before every rt fraction . to investigate the difference in prostate locations at pelvic bone alignment after rectal emptying , we retrospectively analyzed the data of patients who received igrt after a rectal enema . from october 2010 to september 2012 , 15 consecutive patients with localized prostate adenocarcinoma who received curative igrt at dong - a university hospital , busan , south korea , were enrolled in this retrospective analysis . prior to igrt , three gold fiducial markers ( civco , kalona , ia , usa ) were implanted under transrectal ultrasound guidance . the markers were 0.8 mm in diameter and 3 mm in length , and their surface was knurled to prevent migration . rectal enemas with 50 ml of 50% glycerin were administered to all patients before rtp ct and each rt fraction to make rectal volumes less variable . rtp ct was taken more than 1 week after marker implantation to avoid the temporary distortion of the prostate shape due to inflammation or edema . patients lay supine with an ankle immobilization device and underwent rtp ct from the fourth lumbar vertebra to about 3 cm below the ischial tuberosities with a slice interval of 2 - 3 mm . the clinical target volume ( ctv ) the planning target volume ( ptv ) was built with the ctv plus a 5-mm margin except for the posterior expansion of 4 mm . all patients received a ptv dose of 70.0 gy in 28 fractions with intensity - modulated rt plans by use of iplan 3.0 ( brainlab , feldkirchen , germany ) . two oblique kv x - rays were taken before each rt fraction passing through the isocenter of the patient in directions from floor to ceiling . the radio - opaque implanted fiducial markers were used as the surrogate of the prostate . the implanted fiducial markers on the two oblique kv x - ray images were fused with those on the digitally reconstructed radiographs of rtp ct by use of the exaxtrac / novalis - body system ( brainlab ) for the igrt setup . patient setups were approved when the difference between them was less than 1 mm in each right - left ( rl ) , supero - inferior ( si ) , and antero - posterior ( ap ) direction ( fig . we proceeded to off - line bone alignment virtually at the position of approved fiducial marker alignment . coordinates of a virtual prostate at bone alignment and those of an actual prostate at implanted fiducial marker alignment were calculated automatically with the exaxtrac / novalisbody system . the spatial difference between them the result was as follows :   where x , y , and z represented the rl , si , and ap directions , respectively ( fig . 2 ) . interfraction prostate displacement was drawn from all the spatial differences after bone alignments in all rt fractions , and the directional analysis ( rl , si , and ap directions ) was performed . the mean and standard deviation ( sd ) of the interfraction prostate displacements were analyzed . then systematic and random errors were produced from the sd (  ) of the means and root mean square (  ) of the sds , respectively . we calculated required margins around the ctv for the interfraction prostate displacement after bone alignment according to the recipe of van herk et al . : 2.5 times  plus 0.7 times  , which was devised to deliver a minimum cumulative ctv dose of at least 95% of the prescribed dose for 90% of the patients . the directional vectors of the interfraction prostate displacement were compared with a paired t - test . from october 2010 to september 2012 , 15 consecutive patients with localized prostate adenocarcinoma who received curative igrt at dong - a university hospital , busan , south korea , were enrolled in this retrospective analysis . prior to igrt , three gold fiducial markers ( civco , kalona , ia , usa ) were implanted under transrectal ultrasound guidance . the markers were 0.8 mm in diameter and 3 mm in length , and their surface was knurled to prevent migration . rectal enemas with 50 ml of 50% glycerin were administered to all patients before rtp ct and each rt fraction to make rectal volumes less variable . rtp ct was taken more than 1 week after marker implantation to avoid the temporary distortion of the prostate shape due to inflammation or edema . patients lay supine with an ankle immobilization device and underwent rtp ct from the fourth lumbar vertebra to about 3 cm below the ischial tuberosities with a slice interval of 2 - 3 mm . the clinical target volume ( ctv ) was defined as the prostate plus seminal vesicles according to patient characteristics . the planning target volume ( ptv ) was built with the ctv plus a 5-mm margin except for the posterior expansion of 4 mm . all patients received a ptv dose of 70.0 gy in 28 fractions with intensity - modulated rt plans by use of iplan 3.0 ( brainlab , feldkirchen , germany ) . two oblique kv x - rays were taken before each rt fraction passing through the isocenter of the patient in directions from floor to ceiling . the radio - opaque implanted fiducial markers were used as the surrogate of the prostate . the implanted fiducial markers on the two oblique kv x - ray images were fused with those on the digitally reconstructed radiographs of rtp ct by use of the exaxtrac / novalis - body system ( brainlab ) for the igrt setup . patient setups were approved when the difference between them was less than 1 mm in each right - left ( rl ) , supero - inferior ( si ) , and antero - posterior ( ap ) direction ( fig . we proceeded to off - line bone alignment virtually at the position of approved fiducial marker alignment . coordinates of a virtual prostate at bone alignment and those of an actual prostate at implanted fiducial marker alignment were calculated automatically with the exaxtrac / novalisbody system . the spatial difference between them the result was as follows :   where x , y , and z represented the rl , si , and ap directions , respectively ( fig . 2 ) . interfraction prostate displacement was drawn from all the spatial differences after bone alignments in all rt fractions , and the directional analysis ( rl , si , and ap directions ) was performed . the mean and standard deviation ( sd ) of the interfraction prostate displacements were analyzed . then systematic and random errors were produced from the sd (  ) of the means and root mean square (  ) of the sds , respectively . we calculated required margins around the ctv for the interfraction prostate displacement after bone alignment according to the recipe of van herk et al . : 2.5 times  plus 0.7 times  , which was devised to deliver a minimum cumulative ctv dose of at least 95% of the prescribed dose for 90% of the patients . the directional vectors of the interfraction prostate displacement were compared with a paired t - test . 3 ) . more than 3 mm and 5 mm of prostate displacements were found in 44.0% and 15.7% of all rt fractions , respectively . the directional analysis showed that the displacements in the ap and si directions were greater than those in the rl direction ( p<0.05 ) ( table 1 ) . the required margin for ctv - to - ptv expansion with the formula of van herk et al was 4.97 mm after a bone matched setup in the prostate cancer patients who received a rectal enema before each rt fraction . from the directional analysis , the required ctv - to - ptv margins in the rl , ap , and si directions were 0.41 mm , 4.35 mm , and 3.50 mm , respectively . 3 ) . more than 3 mm and 5 mm of prostate displacements were found in 44.0% and 15.7% of all rt fractions , respectively . the directional analysis showed that the displacements in the ap and si directions were greater than those in the rl direction ( p<0.05 ) ( table 1 ) . the required margin for ctv - to - ptv expansion with the formula of van herk et al was 4.97 mm after a bone matched setup in the prostate cancer patients who received a rectal enema before each rt fraction . from the directional analysis , the required ctv - to - ptv margins in the rl , ap , and si directions were 0.41 mm , 4.35 mm , and 3.50 mm , respectively . rectal filling has a greater correlation with the extent of prostate motion than does bladder filling . therefore , it was reasonable to assume that reducing rectal volume could decrease the interfraction prostate movement . accordingly , we administered a rectal enema before every igrt fraction in localized prostate cancer patients in this study . the interfraction prostate displacement after bone matching ranged from 3.92.3 mm to 5.83.1 mm in some studies ( table 2 ) . although implanted fiducial markers are known to make the least interobserver difference compared with contours or anatomies for prostate identification , various methods were used in previous studies . to reduce the risk of prostate misidentification as much as possible , implanted fiducial markers were utilized in this study . despite the well known effect of rectal filling on prostate motion , the effect of rectal emptying was suggested by ogino et al . , who evaluated the effect of rectal gas on interfraction prostate displacement . those authors found that the interfraction prostate movement was reduced in the patients who evacuated rectal gas compared with those who did not . we thought that a rectal enema could evacuate feces as well as gas out of the rectum . therefore , we expected that a rectal enema before every rt fraction would reduce the interfraction prostate displacement . the interfraction prostate motion after bone alignment was smaller in this study , which used a rectal enema before each rt fraction , 3.182.03 mm , than in other studies that did not use rectal emptying , with values of more than 4.6 mm . peng et al .   also used rectal emptying prior to each rt fraction , but the interfraction prostate displacement seemed a little larger than in other studies that did not used rectal emptying . thus , we suspect that the unexpectedly larger interfraction prostate motion may be attributed to some degree to inadequate rectal emptying . in clinical practice , defining a target volume is complicated . a larger expansion around a tumor results in fewer misses in irradiating the tumor but greater potential for damaging normal tissues . therefore , the margin on the tumor should be determined after full consideration of the probability of normal tissue damage . in terms of the necessary margin that would account for interfraction prostate movement after bone alignment , the required margins in the rl direction have been reported to be significantly smaller than those in the si and ap directions , with values ranging from 1.6 to 3.1 mm in the rl direction , from 8.9 to 8.92 mm in the si direction , and from 10.2 to 10.7 mm in the ap direction . the required margin in the rl direction was less than in other directions in the present study also , but the magnitudes were smaller than in other studies . the interfraction prostate motion without rectal enema was borrowed from other studies and was compared with the results of this study . the absence of results of rectal volume alteration and prostate shape before and after rectal enema was another limitation . reported that the lateral dimension of the distended rectum was reduced after rectal evacuation with a rectal enema . they also found that the posterior border of the prostate became flat over most of the length of the prostate gland . from those findings , we considered that a rectal enema could reduce the rectal volume and make the prostate shape unaffected by the rectal distension . therefore , we conceived that a rectal enema could be useful for prostate rt setup . compared with other bone alignment studies , the interfraction prostate displacement and resultant required ptv margins were less in this study , which seems to be the effect of the rectal enema before each rt fraction . in future studies on the effectiveness of a rectal enema on the interfraction prostate movement , we can confidently reduce the ptv margin with the use of a rectal enema in prostate cancer patients . in the current study , interfraction prostate displacement was less frequently observed when a rectal enema was performed prior to the procedure . a rectal enema can be used to reduce interfraction prostate displacement and the resulting ctv - to - ptv margin .
purposeto assess the effect of a rectal enema on interfraction prostate movement in bone alignment ( ba ) for prostate radiotherapy ( rt ) , we analyzed the spatial difference in prostates in a bone - matched setup.materials and methodswe performed ba retrospectively with data from prostate cancer patients who underwent image - guided rt ( igrt ) . 
 the prostate was identified with implanted fiducial markers . 
 the setup for the igrt was conducted with the matching of three fiducial markers on rt planning computed tomography images and those on two oblique kv x - ray images . 
 offline ba was performed at the same position . 
 the coordinates of a virtual prostate in ba and a real prostate were obtained by use of the exaxtrac / novalisbody system , and the distance between them was calculated as the spatial difference . 
 interfraction prostate displacement was drawn from the comparison of the spatial differences.resultsa total of 15 patients with localized prostate cancer treated with curative hypofractionated igrt were enrolled . 
 a total of 420 fractions were analyzed . 
 the mean of the interfraction prostate displacements after ba was 3.122.00 mm ( range , 0.20 - 10.53 mm ) . 
 the directional difference was profound in the anterior - posterior and supero - inferior directions ( 2.141.73 mm and 1.971.44 mm , respectively ) compared with the right - left direction ( 0.260.22 mm , p<0.05 ) . 
 the required margin around the clinical target volume was 4.97 mm with the formula of van herk et al.conclusionsthe interfraction prostate displacement was less frequent when a rectal enema was performed before the procedure . 
 a rectal enema can be used to reduce interfraction prostate displacement and resulting clinical target volume - to - planning target volume margin .