aside from non - melanoma skin cancer , prostate cancer ( pc ) is the most common cancer in men in the united states and europe , with a rapid increasing incidence in the last two decades .
radiotherapy is one of the most important curative options in treating localized pc . for high - risk pc , standard dose ( 70 gy ) plus long - term anti -
androgen therapy became the gold standard after the publication of eortc 22863   and rtog 92 - 02   trial results .
furthermore , pollack et al .   shown that dose escalation ( 78 gy ) was a key point for biochemical control .
many studies have confirmed positive effect of dose escalation on disease local control using radiation therapy [ 58 ] .
however , dose escalation delivered through 3d external beam radiation therapy ( ebrt ) was associated with a higher rate of gastro - intestinal ( gi ) and genito - urinary ( gu ) toxicities . using intensity modulated radiation therapy ( imrt ) , zelefsky et al .   shown that a total dose of 81 gy could be delivered to the prostate increasing the rate of biochemical control without increasing the rate of gu and gi toxicities . intensity - modulated radiation therapy for pc
is generally performed through 8 to 9 consecutive weeks ; nevertheless , due to the low / ratio of the prostatic tissue , clinical research was directed toward hypofractionation concept .
randomized trials comparing standard radiation dose ( 2 gy / f , 1.8 gy / f ) versus  soft  hypofractionated regimen ( 2.5 gy / f to 3 gy / f ) using ebrt confirmed that the two regimens were equivalent in terms of acute and late toxicity [ 11 , 12 ] . high - dose rate ( hdr ) brachytherapy boost following ebrt delivering a total dose of 46 gy to the pelvis or prostatic fossa , represents a smart technique to not only increase the dose to the prostate , but also significantly reduce the number of round trips to the radiation facility . in february 2009 , we integrated the hdr brachytherapy boost program in pc treatment .
we report the results in terms of acute gu and gi toxicity observed between these three different regimens .
between february 2009 and july 2013 , 216 consecutive patients underwent a hdr brachytherapy boost for pc . over the study period , two different treatment planning systems ( tps )
were used : plato ( nucletron bv , veenendaal , the netherlands ) from february 2009 to may 2012 , and oncentra brachy ( nucletron , an elekta company , elekta ab , stockholm , sweden ) from june 2012 until now . in order to avoid any comparative bias , we analysed the first 124 patients treated with the same tps ( plato ) . from 02/2009 to 01/2010 , 30 patients ( group 1 = g1 ; 24% ) were treated with 3  6 gy over 2 days . in order to make this procedure more comfortable for the patient and
less time - consuming for the medical staff , from 01/2010 to 01/2011 , 52 patients ( group 2 = g2 ; 42% ) received 2 fractions of 9 gy over 2 days , while from 01/2011 to 05/2012 , 42 patients ( group 3 = g3 ; 34% ) were treated with a single fraction of 14 gy .
this observational study retrospectively analysed the acute gu and gi toxicities occurred during the first 6 months after the implant in the 3 treatment groups .
all the patients underwent imaging studies , including magnetic resonance , computed tomography , and bone scan .
appropriate patient selection was performed according to the american brachytherapy society ( abs ) consensus guidelines for hdr prostate brachytherapy .
patients were treated with a first course of ebrt , delivering 46 gy in 23 fractions .
the dose was delivered to the icru point using high - energy x - photons ( > 10 mv ) . according to the calculated risk of lymph node involvement , the clinical target volume ( ctv ) was the whole pelvis or the prostatic fossa ( prostate and seminal vesicles ) for high- (  15% ) and low - risk ( < 15% ) of lymph node involvement , respectively .
the planning target volume ( ptv ) was defined as a 1 cm margin around the ctv in all directions , and reduced to 5 mm at the prostate rectal interface .
short and long - term androgen deprivation therapy ( adt ) was proposed to intermediate and high - risk patients , respectively .
this procedure was performed under general anaesthesia . using transrectal ultrasound ( trus ) guidance , 15 to 17 catheters ( sharp needles ; nucletron , an elekta company , elekta
ab , stockholm , sweden ) were implanted transperineally and periurethrally through a dedicated template .
after recovery , post - implant planning ct - scan was directly performed in the radiation oncology department for treatment planning purposes .
ctv ( prostate ) and organs at risk ( oar  urethra and rectum ) were outlined .
the prostatic portion of the urethra was outlined plus a 10 mm additional margin above the base and below the apex , while the rectum was outlined from the anorectal junction to the rectosigmoid junction .
brachytherapy boost delivered 3  6 gy , 2  9 gy , and 1  14 gy for g1 , g2 , and g3 , respectively .
considering / 1.5 gy for prostatic tissue , eqd2 ( equivalent dose at 2 gy / fraction ) were 39 gy , 54 gy , and 62 gy for g1 , g2 , and g3 , respectively .
dose constraints for prostate were v100 ( ctv receiving 100% of the prescribed dose ) > 95% , v150 < 35% , and v200 < 15% , d90 ( dose delivered to 90% of ctv ) > 105% , and d100% > 80% .
dose constraints used for oars relied on the brachytherapy regimen groups . because of the slight dose escalation between g1/g2 ( eqd21.5 39 gy , 54 gy ) and g3 ( eqd21.5 62 gy ) , more restrictive dose constraints were considered for g3 patients .
consequently , for g1/g2 , vu125 ( percentage of the urethra volume receiving 125% of the prescribed dose ) and vr100 ( percentage of the rectum volume receiving 100% of the prescribed dose ) should be less than 1% , while for g3 patients , vu115 ( percentage of the urethra volume receiving 115% of the prescribed dose ) and vr90 ( percentage of the rectum volume receiving 90% of the prescribed dose ) should be less than 1% ( fig .
dose - volume adaptation was manually achieved using graphical optimization ( plato , nucletron bv , veenendaal , the netherlands ) by dwell location and time variation .
patients treated with multiple fractions after a single insertion were re - scanned before each fraction , followed by re - optimization with regard to the risk of catheter migration .
the first fraction was given post - operatively ( at day 0 ) , while the following fractions were given at day 1 ( with at least 6 hours interval between the 2 and 3 fraction for g1 ) .
dose distribution obtained after planning using plato ( nucletron bv , veenendaal , the netherlands ) on sagittal ( a ) and transversal ( b ) view 
  patients were followed at 1 month after the implant , then every 6 months with an assessment of serum prostate specific antigen level ( psa ) , physical examination , patient symptom assessment , and digital rectal examination in case of rising psa .
acute gu and gi toxicities were scored according to the common terminology criteria for adverse event ( ctcae v3.0 ) . for gu complications ,
we analysed stricture / stenosis , frequency / urgency , retention , incontinence , cystitis and bladder spasms while for gi complications we analysed haemorrhoids , anal incontinence , and proctitis . because a longer follow - up is needed to assess sexual toxicity , and due to the high number of patients who received adt , this complication was not assessed .
biochemical failure was defined as psa nadir plus 2 ng / ml . data were entered and stored on an access file , and then transferred into r.2.14.1 software for statistical analysis .
 test or fisher 's exact test was used for category comparison . student test or
anova or non - parametric kruskal - wallis was performed to test variables expressed as categories versus continuous variables .
if this test was significant , we used the test of tukey or nemenyi test to compare these categories .
we also showed the median survival and confidence intervals at 95% of the studied population ( kaplan - meier method ) .
tests of significance were two - sided , and considered significant when the p value was 0.05 or less .
between february 2009 and july 2013 , 216 consecutive patients underwent a hdr brachytherapy boost for pc . over the study period , two different treatment planning systems ( tps )
were used : plato ( nucletron bv , veenendaal , the netherlands ) from february 2009 to may 2012 , and oncentra brachy ( nucletron , an elekta company , elekta ab , stockholm , sweden ) from june 2012 until now . in order to avoid any comparative bias , we analysed the first 124 patients treated with the same tps ( plato ) . from 02/2009 to 01/2010 , 30 patients ( group 1 = g1 ; 24% ) were treated with 3  6 gy over 2 days . in order to make this procedure more comfortable for the patient and
less time - consuming for the medical staff , from 01/2010 to 01/2011 , 52 patients ( group 2 = g2 ; 42% ) received 2 fractions of 9 gy over 2 days , while from 01/2011 to 05/2012 , 42 patients ( group 3 = g3 ; 34% ) were treated with a single fraction of 14 gy .
this observational study retrospectively analysed the acute gu and gi toxicities occurred during the first 6 months after the implant in the 3 treatment groups .
all the patients underwent imaging studies , including magnetic resonance , computed tomography , and bone scan .
appropriate patient selection was performed according to the american brachytherapy society ( abs ) consensus guidelines for hdr prostate brachytherapy .
patients were treated with a first course of ebrt , delivering 46 gy in 23 fractions .
the dose was delivered to the icru point using high - energy x - photons ( > 10 mv ) . according to the calculated risk of lymph node involvement , the clinical target volume ( ctv ) was the whole pelvis or the prostatic fossa ( prostate and seminal vesicles ) for high- (  15% ) and low - risk ( < 15% ) of lymph node involvement , respectively .
the planning target volume ( ptv ) was defined as a 1 cm margin around the ctv in all directions , and reduced to 5 mm at the prostate rectal interface .
short and long - term androgen deprivation therapy ( adt ) was proposed to intermediate and high - risk patients , respectively .
this procedure was performed under general anaesthesia . using transrectal ultrasound ( trus ) guidance , 15 to 17 catheters ( sharp needles ; nucletron , an elekta company , elekta
ab , stockholm , sweden ) were implanted transperineally and periurethrally through a dedicated template .
after recovery , post - implant planning ct - scan was directly performed in the radiation oncology department for treatment planning purposes .
ctv ( prostate ) and organs at risk ( oar  urethra and rectum ) were outlined .
the prostatic portion of the urethra was outlined plus a 10 mm additional margin above the base and below the apex , while the rectum was outlined from the anorectal junction to the rectosigmoid junction .
brachytherapy boost delivered 3  6 gy , 2  9 gy , and 1  14 gy for g1 , g2 , and g3 , respectively .
considering / 1.5 gy for prostatic tissue , eqd2 ( equivalent dose at 2 gy / fraction ) were 39 gy , 54 gy , and 62 gy for g1 , g2 , and g3 , respectively .
dose constraints for prostate were v100 ( ctv receiving 100% of the prescribed dose ) > 95% , v150 < 35% , and v200 < 15% , d90 ( dose delivered to 90% of ctv ) > 105% , and d100% > 80% .
dose constraints used for oars relied on the brachytherapy regimen groups . because of the slight dose escalation between g1/g2 ( eqd21.5 39 gy , 54 gy ) and g3 ( eqd21.5 62 gy ) , more restrictive dose constraints were considered for g3 patients .
consequently , for g1/g2 , vu125 ( percentage of the urethra volume receiving 125% of the prescribed dose ) and vr100 ( percentage of the rectum volume receiving 100% of the prescribed dose ) should be less than 1% , while for g3 patients , vu115 ( percentage of the urethra volume receiving 115% of the prescribed dose ) and vr90 ( percentage of the rectum volume receiving 90% of the prescribed dose ) should be less than 1% ( fig .
dose - volume adaptation was manually achieved using graphical optimization ( plato , nucletron bv , veenendaal , the netherlands ) by dwell location and time variation .
patients treated with multiple fractions after a single insertion were re - scanned before each fraction , followed by re - optimization with regard to the risk of catheter migration .
the first fraction was given post - operatively ( at day 0 ) , while the following fractions were given at day 1 ( with at least 6 hours interval between the 2 and 3 fraction for g1 ) .
dose distribution obtained after planning using plato ( nucletron bv , veenendaal , the netherlands ) on sagittal ( a ) and transversal ( b ) view 

patients were followed at 1 month after the implant , then every 6 months with an assessment of serum prostate specific antigen level ( psa ) , physical examination , patient symptom assessment , and digital rectal examination in case of rising psa .
acute gu and gi toxicities were scored according to the common terminology criteria for adverse event ( ctcae v3.0 ) . for gu complications ,
we analysed stricture / stenosis , frequency / urgency , retention , incontinence , cystitis and bladder spasms while for gi complications we analysed haemorrhoids , anal incontinence , and proctitis . because a longer follow - up is needed to assess sexual toxicity , and due to the high number of patients who received adt , this complication was not assessed .
data were entered and stored on an access file , and then transferred into r.2.14.1 software for statistical analysis .
 test or fisher 's exact test was used for category comparison . student test or
anova or non - parametric kruskal - wallis was performed to test variables expressed as categories versus continuous variables .
if this test was significant , we used the test of tukey or nemenyi test to compare these categories .
we also showed the median survival and confidence intervals at 95% of the studied population ( kaplan - meier method ) .
tests of significance were two - sided , and considered significant when the p value was 0.05 or less .
patient and treatment characteristics are reported in table 1 . regarding patient ( age , risk group factors ) and treatment ( ebrt , adt ) data ,
the majority of the patients were classified as high ( 73.4% ) or intermediate ( 19.3% ) risk regarding to d'amico classification
. sixty - five percent of the patients ( 81 patients ) received whole pelvic ebrt while 80% ( 99 cases ) underwent adt .
the median time interval between ebrt and hdr brachytherapy boost was 14 days ( ranged 0 - 43 ) . 
 
patient characteristics according to the treatment group n  number of patients , ebrt  external beam radiation therapy , adt  androgen deprivation therapy , int rt / brachy  time interval between the end of ebrt and high - dose rate brachytherapy expressed in days dosimetric data are reported in table 2 . because no significant dosimetric differences were noticed between g1/g2 patients regarding 1 , 2 and 3 post - implant ct - scan ( data not shown ) , the 1 ct - scan was used for dosimetric comparisons between the 3 treatment groups .
median ctv were equivalent in 3 groups ( 36 , 33 , and 32 cc for g1 , g2 , and g3 , respectively , p = 0.088 ) .
d90 for g3 ( 105% ) was significantly decreased compared to the d90 calculated for g1 ( 114% ) , and g2 ( 111% ) ( p < 0.001 ) as well as v100 ( 97 , 96 , and 95% for g1 , g2 , and g3 , respectively ; p = 0.013 ) , while v150 and v200 significantly decreased from g1 to g3 ( v150 : 45 , 36 , and 27% for g1 , g2 , and g3 , respectively ; p < 0.001 and v200 : 16 , 12 , and 9 for g1 , g2 , and g3 , respectively p < 0.001 ) .
dose homogeneity index ( dhi ) for g3 ( 69% ) was significantly better compared to dhi noticed for g1 ( 54% ) and g2 ( 61% ) ( p < 0.001 ) . for oars ( urethra and rectum ) ,
dosimetric results were significantly improved in g3 compare to g1 and g2 ( p < 0.001 ) ( table 2 ) .
assuming  3 gy for urethra and rectum , eqd2 of the dose delivered by the boost to oars significantly decreased from g1 to g3 for both urethra ( d10u : 52 , 47 , and 46 gy for g1 , g2 , and g3 , respectively ; p < 0.001 ) and rectum ( d2r : 28 , 27 , and 26 gy for g1 , g2 , and g3 , respectively ; p < 0.001 ) ( table 2 ) . 
 
dosimetric data and equivalent doses at 2 gy for ctv ( eqd2 / 1.5 gy ) and organs at risk ( eqd2 / 3 gy ) according to the treatment group ctv  clinical target volume ( prostate ) , d90  dose delivered to 90% of ctv expressed in percentage and in eqd2 with /1.5 gy , d100  dose delivered to 100% of ctv expressed in percentage and in equivalence of the dose at 2 gy per fraction ( eqd2 ) with / 1.5 gy , v100  ctv receiving 100% of the prescribed dose expressed in percentage and in cubic centimetres , v150  ctv receiving 150% of the prescribed dose expressed in percentage and in cubic centimetres , v200  ctv receiving 200% of the prescribed dose expressed in percentage and in cubic centimetres , dhi  dose homogeneity index , d0.1u  dose delivered to 0.1 cc of the urethral volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d1u  dose delivered to 1 cc of the urethral volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d10u  dose delivered to 10% of urethral volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d30u  dose delivered to 30% of urethral volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d01r  dose delivered to 0.1 cc of the rectal volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d1r  dose delivered to 1 cc of the rectal volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d2r  dose delivered to 2 cc of the rectal volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy the median follow - up was 25 months ( ranged 8 - 46.9 ) .
genito - urinary and gi complication grades for each treatment group were summarized in table 3 .
the rates of acute gi and gu toxicities observed at 1 and 6 months after hdr brachytherapy boost were mainly grade 1 with few grade 2 ( gu : 5% at 1 month ; gi : 1% at 6 months ) .
no grade 3 toxicity was observed in the whole population , while one patient in group 1 developed grade 4 gu toxicity consisting in a post - operative septic syndrome treated in intensive - care unit during 14 days .
analysis of genito - urinary ( gu ) and gastro - intestinal ( gi ) complications observed at 1 and 6 months after hdrb boost regarding to the complication grade ( ctcv3.0 ) and the different fractionation schemes percentages of complication among patients who developed gu and/or gi complications gu  genito - urinary complications , gi  gastro - intestinal complications , fract . schemes 
fractionation schemes regarding the acute gu and gi toxicities occurred in the 3 treatment groups , no significant differences were observed at 1 and 6 months after the hdr brachytherapy boost between g1 , g2 , and g3 treatment groups ( table 3 ) .
patient and treatment characteristics are reported in table 1 . regarding patient ( age , risk group factors ) and treatment ( ebrt , adt ) data ,
the majority of the patients were classified as high ( 73.4% ) or intermediate ( 19.3% ) risk regarding to d'amico classification
. sixty - five percent of the patients ( 81 patients ) received whole pelvic ebrt while 80% ( 99 cases ) underwent adt .
the median time interval between ebrt and hdr brachytherapy boost was 14 days ( ranged 0 - 43 ) . 
 
patient characteristics according to the treatment group n  number of patients , ebrt  external beam radiation therapy , adt  androgen deprivation therapy , int rt / brachy  time interval between the end of ebrt and high - dose rate brachytherapy expressed in days dosimetric data are reported in table 2 . because no significant dosimetric differences were noticed between g1/g2 patients regarding 1 , 2 and 3 post - implant ct - scan ( data not shown ) , the 1 ct - scan was used for dosimetric comparisons between the 3 treatment groups .
median ctv were equivalent in 3 groups ( 36 , 33 , and 32 cc for g1 , g2 , and g3 , respectively , p = 0.088 ) .
d90 for g3 ( 105% ) was significantly decreased compared to the d90 calculated for g1 ( 114% ) , and g2 ( 111% ) ( p < 0.001 ) as well as v100 ( 97 , 96 , and 95% for g1 , g2 , and g3 , respectively ; p = 0.013 ) , while v150 and v200 significantly decreased from g1 to g3 ( v150 : 45 , 36 , and 27% for g1 , g2 , and g3 , respectively ; p < 0.001 and v200 : 16 , 12 , and 9 for g1 , g2 , and g3 , respectively p < 0.001 ) .
dose homogeneity index ( dhi ) for g3 ( 69% ) was significantly better compared to dhi noticed for g1 ( 54% ) and g2 ( 61% ) ( p < 0.001 ) . for oars ( urethra and rectum ) ,
dosimetric results were significantly improved in g3 compare to g1 and g2 ( p < 0.001 ) ( table 2 ) .
assuming  3 gy for urethra and rectum , eqd2 of the dose delivered by the boost to oars significantly decreased from g1 to g3 for both urethra ( d10u : 52 , 47 , and 46 gy for g1 , g2 , and g3 , respectively ; p < 0.001 ) and rectum ( d2r : 28 , 27 , and 26 gy for g1 , g2 , and g3 , respectively ; p < 0.001 ) ( table 2 ) . 
 
dosimetric data and equivalent doses at 2 gy for ctv ( eqd2 / 1.5 gy ) and organs at risk ( eqd2 / 3 gy ) according to the treatment group ctv  clinical target volume ( prostate ) , d90  dose delivered to 90% of ctv expressed in percentage and in eqd2 with /1.5 gy , d100  dose delivered to 100% of ctv expressed in percentage and in equivalence of the dose at 2 gy per fraction ( eqd2 ) with / 1.5 gy , v100  ctv receiving 100% of the prescribed dose expressed in percentage and in cubic centimetres , v150  ctv receiving 150% of the prescribed dose expressed in percentage and in cubic centimetres , v200  ctv receiving 200% of the prescribed dose expressed in percentage and in cubic centimetres , dhi  dose homogeneity index , d0.1u  dose delivered to 0.1 cc of the urethral volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d1u  dose delivered to 1 cc of the urethral volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d10u  dose delivered to 10% of urethral volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d30u  dose delivered to 30% of urethral volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d01r  dose delivered to 0.1 cc of the rectal volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d1r  dose delivered to 1 cc of the rectal volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy , d2r  dose delivered to 2 cc of the rectal volume expressed in percentage of the prescribed dose and in eqd2 with / 3 gy
genito - urinary and gi complication grades for each treatment group were summarized in table 3 .
the rates of acute gi and gu toxicities observed at 1 and 6 months after hdr brachytherapy boost were mainly grade 1 with few grade 2 ( gu : 5% at 1 month ; gi : 1% at 6 months ) .
no grade 3 toxicity was observed in the whole population , while one patient in group 1 developed grade 4 gu toxicity consisting in a post - operative septic syndrome treated in intensive - care unit during 14 days .
analysis of genito - urinary ( gu ) and gastro - intestinal ( gi ) complications observed at 1 and 6 months after hdrb boost regarding to the complication grade ( ctcv3.0 ) and the different fractionation schemes percentages of complication among patients who developed gu and/or gi complications gu  genito - urinary complications , gi  gastro - intestinal complications , fract .
the acute gu and gi toxicities occurred in the 3 treatment groups , no significant differences were observed at 1 and 6 months after the hdr brachytherapy boost between g1 , g2 , and g3 treatment groups ( table 3 ) .
dose escalation for prostate cancer radiation treatment represents a key point in order to improve biochemical control . according to the meta - analysis published by viani et al . , high - dose radiotherapy was superior to conventional dose radiotherapy in preventing biochemical failure in all risk groups , suggesting that high - dose radiotherapy should be offered to all patients regardless of their risk status .
the low / ratio indicates that prostate tumours are more sensitive to high radiation doses per fraction than most other malignancies .
therefore , many investigators have directed their efforts to deliver hypofractionated ebrt . in this field ,
the use of brachytherapy boost in addition to pelvic ebrt up to 46 gy represents a smart and attractive option [ 22 , 23 ] .
indeed , brachytherapy allows an  intrinsic  dose escalation due to the overdose volumes generated by the interstitial position of the radioactive source within the prostatic tissues , and lead to a biological advantage over external beam radiation boost technique .
brachytherapy boost has not only a potential advantage on clinical outcome , but also allows to make the treatment more acceptable for the patient due to less transportations to the medical insurance for reimbursement , and for the medical staff dealing with a less time consuming procedure . in this field
, hdrb appears to give at least equivalent clinical outcomes compared to low - dose rate brachytherapy .
a matched - pair analysis comparing prostate cancer ebrt + hdr vs. ebrt alone demonstrated a significant advantage in 5-year biochemical control in favour to the combination modality .
two randomized trials have confirmed the superiority of the combination therapy using either low   or high - dose rate   iridium sources in terms of biochemical control with at least similar late gu and gi toxicity with a potential advantage for acute rectal complications .
however , these studies used as  conventional  ebrt arm a total dose around 70 gy which is now considered as a low dose regarding biochemical control probability . nevertheless , even in case of very high - dose delivered to the prostate ( 86.4 gy ) using a imrt technique , deutsch et al
.   showed in a retrospective comparative analysis between ebrt vs. brachytherapy boost that the biochemical control remained significantly better in the brachytherapy group ( 3  7 gy ) .
whatever , it remains difficult to compare ebrt with brachytherapy boost techniques , because the dose delivered by brachytherapy will be always higher compare to the same prescribed dose delivered by ebrt ( overdose volumes ) .
this fact introduces an initial bias , which complicates the comparison between the two boost techniques . taking all together ,
currently , there is no standard fractionation scheme , and numerous protocols have been tested with various numbers of fractions ( ranged from 1 to 5 ) and dose per fraction ( ranged from 4.75 to 15 gy ) .
it appears more comfortable for both patient and medical staff to reduce as far as possible the number of brachytherapy fractions respecting a similar biological effect , and clinical outcome in terms of toxicity and efficacy . in this filed
, we started our brachytherapy boost program using 3 fractions in 2 days ( 3  6 gy ) , while one fraction of 14 gy became our standard protocol allowing to implant the needles , treat the patient and remove all the materials in the same day ( one day procedure ) . according to acute gi and gu toxicities , hoskin et al .  
reported in a phase iii randomised trial that hdrb boost technique could significantly reduce gi toxicity with equivalent gu complication rates compared to those observed with ebrt . regarding acute gi and gu toxicities , we reported mainly grade 1 complications and especially no significant differences between the 3 fractionations schemes . furthermore , the dose distribution improved according to the learning curve , although the dose constraints for oars were more restrictive . our results in terms of eqd2 for urethra and rectum ( boost eqd2 + ebrt 46 gy ) respect the recently published gec - estro recommendations , which propose for urethra d0.1cc and d10  120 gy eqd2 with d30  105 gy eqd2 , and for rectum d2cc  75 gy eqd2 .
currently , the right fractionation remains under debate , but following strict implantation rules , there is a strong rational to propose a prostate cancer hdrb boost using a single fraction , providing similar results in terms of acute toxicity , and more comfortable procedure for patient and less time consuming for medical staff .
however , longer follow - up is needed to confirm that single fraction of hdrb used as boost will give consistent results in terms of clinical outcome .
the right fractionation remains under discussion , but prostate cancer hdrb boost using a single fraction ( providing similar results in terms of acute toxicity ) is more comfortable for the patient , less time consuming for the medical staff .
 purposeto analyse early toxicity of high - dose - rate brachytherapy ( hdrb ) boost for prostate cancer using 3 fractionation schemes.material and methodsfrom february 2009 to may 2012 , after the first course of external beam radiation therapy ( ebrt 46 gy/23 f ) , 124 patients underwent hdrb boost for low ( 7% ) , intermediate ( 19% ) , and high - risk ( 73% ) prostate cancers . from february to december 2009 , group 1 ( g1 ) = 18 gy/3 f/2 d ( 24% ) ; from january 2010 to april 2011 , group 2 ( g2 ) = 18 gy/2 f/2 d ( 42% ) , and from may to september 2011 , group 3 ( g3 ) = 14 gy/1 f/1 d ( 34% ) . 
 planning and ct - scan was performed before each fraction . 
 dose constraints for g1/g2 were v100 rectum = 0 and v125 urethra = 0 , while for g3 v90 rectum = 0 and v115 urethra = 0 . 
 genito - urinary ( gu ) and gastro - intestinal ( gi ) acute toxicities were assessed at 1 month ( for the 3 fractionation schemes ) and 6 months ( for 18 gy/3 f and 18 gy/2 f ) after the boost ( ctcv3.0).resultsmedian follow - up was 25 months ( 8 - 46.9 ) , median age was 71 years ( 50 - 82 ) , and median ctv was 31 cc ( 16 - 71 ) . 
 the grades of acute gi and gu toxicities at 1 and 6 months after hdrb were mainly grade 1 with few grade 2 ( gu : 5% at 1 month ; gi : 1% at 6 months ) . 
 one patient developed g4 sepsis toxicity 2 days after hdrb and recovered without after - effects . 
 no significant differences were observed at 1 and 6 months after the hdrb between treatment groups.conclusionsthe right fractionation remains under discussion , but prostate cancer hdrb boost using a single fraction ( providing similar results in terms of acute toxicity ) is more comfortable for the patient , and less time consuming for the medical staff . 