post - operative radiotherapy is an established adjuvant treatment after radical hysterectomy with intermediate- and high - risk early - stage cervical cancer patients [ 1 , 2 ] .
a conventional radiation technique for post - operative cervical cancer patients is whole - pelvic radiation therapy ( wprt ) requiring four static photon fields .
this technique exposes most of the contents of the true pelvis , including the small bowel as well as the target volume .
the highly conformal technique of intensity - modulated radiation therapy ( imrt ) has the potential for delivering the required radiation dose to the target volume , while avoiding surrounding normal tissues , and its effectiveness has been validated in several anatomical sites such as head - and - neck [ 3 , 4 ] or prostate cancer treatment [ 5 , 6 ] .
however , the advantage of using the complex imrt technique in the field of gynecologic cancer has not yet been determined [ 79 ] and demands a prospective clinical trial for its validation .
the radiation therapy oncology group ( rtog ) launched a multi - institutional prospective phase ii trial ( rtog 0418 ) using imrt for post - operative endometrial and cervical patients in order to determine whether imrt could reduce short - term bowel toxicity .
recently , a positive preliminary result was presented . in japan , because of the concern about possible severe late bowel complications related to the combination of surgery and radiotherapy , and because of a positive result from adjuvant chemotherapy alone for intermediate- and high - risk post - operative cervical cancer patients , several institutions dare not use adjuvant radiation therapy for early - stage intermediate- or high - risk post - operative cervical cancer patients . since the rtog 0418 trial included not only cervical cancer but also endometrial cancer patients , it was decided that the effectiveness and safety of imrt should be validated including only post - operative cervical cancer patients in a japanese multicenter prospective clinical trial . as a preparation for this clinical trial
, it was regarded as important to ascertain the current status of imrt for post - operative cervical cancer in japan .
the object of this study was to perform a surveillance study of imrt for post - operative cervical cancer in a working group within the radiation therapy study group ( rtsg ) of the japan clinical oncology group ( jcog ) .
in 2013 , the working group conducted a surveillance using a questionnaire asking about the precise methods of conducting imrt .
six leading academic institutions in the field of gynecologic oncology , who have already commenced applying imrt for post - operative cervical cancer patients in clinical practice , were selected for the current survey .
data collection included : ( i ) the technical environment for imrt ; ( ii ) patient preparation before taking planning computed tomography ( ct ) ; ( iii ) the technique for determining the target volume and the normal structure ; ( iv ) the prescription dose , the dose constraint for organs at risk ( oars ) , how to define the prescription dose ; and ( v ) how patients were set up in daily treatment .
half of the institutions used conventional static imrt , while the others used volumetric - modulated arc therapy ( vmat ) .
one institution used a 15-mv photon beam , which could deliver radiation to deep - seated organs . 

all except one institution used either a vacuum cushion or a shell for patient body fixation , which was important for highly precise radiation therapy as imrt .
, vosveld 9a , 2110 wijnegem , belgium ) , which was capable of fixing a patient 's hips , legs and feet . according to the rtog 0418 protocol ,
in contrast to the rtog protocol , most of the institutions did not visualize the vaginal cuff before taking planning ct . 

2.a bar graph showing the way of patient preparation before taking planning ct . a bar graph showing the way of patient preparation before taking planning ct .
figure  3 shows how physicians define the clinical target volume ( ctv ) . for the elective lymph node region ,
all institutions used the guideline for pelvic nodal ctv created by the japan clinical oncology group gynecologic cancer study group ( jcog  gcsg ) . for contouring the vaginal cuff , the paracolpium and the parametrium , which may contain microscopic cancer cells after radical hysterectomy , four institutions used the rtog guideline   for reference , while two institutions used the jcog 
gcsg guideline for the intact uterus   with modification , because the uterus no longer existed after surgery .
two institutions used the fusion ct images taken with the bladder full and empty according to the rtog protocol to account for the internal motion of the ctv vaginal cuff , while others contoured the ctv vaginal cuff based on one ct series , adding a 510 mm internal margin . 

3.a bar graph showing which guidelines physicians used as a reference when contouring the target volumes . a bar graph showing which guidelines physicians used as a reference when contouring the target volumes .
the organs which were commonly selected as oars were the rectum , the bladder , the femoral head , and the small bowel / peritoneal cavity .
one institution contoured the bowel loop , four the peritoneal cavity , and one did not contour either the bowel loop or the peritoneal cavity . 

4.a bar graph showing which normal structures were selected as organs as risk ( oars ) . a bar graph showing which normal structures
the total prescription dose was either 50 gy/25 fr in 2 gy per fraction or 50.4 gy/28 fr in 1.8 gy per fraction .
five institutions used the planning target volume ( ptv ) dmean ( mean dose of the ptv ) as a prescription point , while one institution used ptv d95 ( lowest dose encompassing 95% of the ptv ) .
as for the dose constraint for oars , one institution did not set any specific dose constraint . in this institution
the attending physician checked the dose distribution and paid careful attention to hot spots in oar .
the other five institutions used the individual dose constraint definition , and this is summarized in table  1 .
preliminary compliance rates of dose constraints for oars for five to eleven patients treated during the study period are also summarized in table  1 . 

table  1.dose constraint for oarinstitution a ( adherence rate , n = 10)institution b ( adherence rate , n = 10)institution c ( adherence rate , n = 11)institution d ( adherence rate , n = 5)institution e ( adherence rate , n = 5)rectumv50 gy < 40% , dmax < 55 gy ( 100%)v50 gy < 35% ( 80%)v40 gy < 60% ( 18.2%)v50 gy < 35% ( 100%)v40 gy < 80% ( 40%)bladderv45 gy <
50% , dmax < 55 gy ( 80%)v45 gy < 70% , v50 gy < 35% ( 80%)v45 gy < 35% ( 36.4%)v50 gy < 35% ( 100%)v45 gy < 35% ( 60%)small bowel / peritoneumv40 gy < 40% , v55 gy
30% ( 45.5%)v40 gy < 30% ( 80%)v40 gy < 30% ( 80%)femoral headv30 gy < 20% ( 80%)v30 gy < 15% ( 20%)v30 gy < 15% ( 36.4%)dmean < 30 gy ( 80%)pelvic bonev20 gy < 80% ( 80%)v10 gy < 90% , v40 gy <
37% ( 20%)cauda equinadmax < 50 gy ( 40%)oar = organ at risk . 
 fig .  5.a bar graph showing the prescription dose and the definition of prescription dose .
dose constraint for oar a bar graph showing the prescription dose and the definition of prescription dose . with regard to the daily set - up of image - guided radiation therapy ( igrt )
, three institutions took cone - beam ct ( cbct ) every day , one three times a week and two once a week .
three institutions encouraged patients to empty the rectum every day before treatment , whereas no instruction concerning rectum emptying was given to patients in the other three institutions ; however , in two out of these three institutions , cbct was taken every day and if large amounts of gas or stools were found , patients were asked to empty the rectum before irradiation .
figure  6 shows a typical dose distribution of imrt for post - operative cervical cancer patients from the six institutions participating in this study . 

6.a typical dose distribution of imrt for postoperative cervical cancer patients from six institutions participating in this study : institutions a 
f ( a  f ) . a typical dose distribution of imrt for postoperative cervical cancer patients from six institutions participating in this study : institutions a 
planning and delivery of radiation therapy have changed dramatically over the past several decades , and imrt is one of the most complicated and error - prone techniques , and thus requires thorough quality assurance programs , not only for multicenter clinical trials but for daily practical use . as a preparation for a future clinical trial using adjuvant imrt for post - operative cervical cancer patients , it was considered to be important to know the current status of imrt in terms of post - operative radiotherapy for cervical cancer in japan ; therefore , the current surveillance study was performed .
half of the institutions used vmat , for which it was shown that the treatment time will be shortened compared with conventional static imrt for pelvic irradiation , but a dosimetric benefit would not be expected .
the high - energy photon beam has an advantage of delivering photons to deep - seated organs with less attenuation ; however , it brings with it a concern about creating neutrons along with photons . in the latest patterns of care study ( pcs ) for cervical cancer in japan ,
the most appropriate machine energy should be discussed for developing the protocol of a future clinical trial .
although visualization of the vaginal cuff was recommended in the rtog protocol , most institutions did not visualize them .
it was supposed that inserting markers into the vaginal cuff would require manpower , time and patient endurance of pain .
one institution inserted a small piece of gauze soaked with a contrast agent into the vaginal cuff , whereas it was not permitted to insert gauze into the vagina in the rtog protocol because it would potentially cause anatomical changes relative to the surrounding structures .
it was considered to be feasible if only a small piece of gauze was manipulated ; however , the impact from volume changes of the bladder and the rectum is considered to be more significant .
therefore , inserting a small piece of gauze with a contrast agent will be included in the protocol of a future clinical trial .
it was supposed that when the bladder was filled with urine , the bowel would be pushed away from the small pelvis and it would protect the small bowel from radiation exposure .
however , reproducibility of bladder filling is problematic because the pelvic nerve plexus has already been damaged to varying degrees by radical hysterectomy ; therefore , monitoring daily bladder filling by some means needs to be considered to ensure the accuracy of the treatment .
the reason why the rtog guideline   was not used as a reference to contour the ctv lymph node was that the definition of the ctv lymph node according to the jcog 
first , in the jcog  gcsg guideline , the cranial margin was set at the bifurcation of the aorta , not based on the bony structure as in the rtog guideline .
it would be difficult to categorize the recurrence as a regional ( pelvic recurrence ) or a distant ( para - aortic nodal ) failure when the previous pelvic field was constructed based on the bony anatomy .
second , the japanese guideline involved the adipose connective tissue between the iliopsoas muscles and the lateral surface of the vertebral body , which was not included in the rtog guideline .
this area was also included in the atlas of taylor et al . [ 18 , 19 ] .
therefore , the current rtog definition may be insufficient in terms of lateral expansion of the ctv for the internal iliac node .
as for the ctv vaginal cuff , while four institutions used the rtog guideline , two institutions used the jcog  gcsg guideline for the intact uterus .
not all institutions used the rtog guideline , because the rtog guideline did not describe the paracolpium and the parametrium in detail .
although , theoretically , the jcog  gcsg guideline for the intact uterus was not appropriate for contouring the post - operative female pelvis , the jcog
therefore , this guideline can be used as a reference in contouring the paracolpium and the parametrium after making some modification .
we are now creating a consensus - based guideline for ctv vaginal cuff as well as the paracolpium and the parametrium ( which may contain microscopic cancer cells , even after r0 radical hysterectomy ) , because there exists no such consensus guideline other than the rtog guideline . with regard to the internal organ motion of the ctv vaginal cuff , two institutions used the fusion ct with the bladder full and empty according to the rtog protocol , while others contoured the ctv vaginal cuff based on one ct series , adding 510 mm internal margin to ctv vaginal cuff .
the vagina is sandwiched by the rectum and the bladder , whose volume will potentially vary from time to time ; therefore , it was considered to be important to make a consensus on the internal margin for the ctv vaginal cuff .
whereas all but one institution selected the small bowel or the peritoneal cavity as an oar , with four institutions contouring the peritoneal cavity and one the bowel loop , it was not standardized as to whether to contour only the bowel loop itself or the peritoneal cavity as well . in the current study , four institutions contoured the peritoneal cavity and one the bowel loop . the dose
 volume relationship will not be reliable if it is not consistent whether the bowel loop or the peritoneal cavity is contoured .
volume relationship was found between chronic gastrointestinal ( gi ) complications and dose to the small bowel loops , whereas no parameter for the peritoneal cavity was significantly associated with gi complications . on the other hand
, some modification of the definition will be required if the peritoneal cavity is to be used as an oar , because part of the bowels are embedded in the retroperitoneal space , such as the ascending or the descending colon .
therefore , we will also develop a consensus - based definition of what constitutes normal structures for the post - operative cervical cancer patient .
most institutions did not employ ptv d95 as the prescription point for concern about possible dose escalation compared with the conventional dose prescription according to icru report 50 .
consequently , the rtog 0418 protocol , in which ptv d97 was used as a prescription dose , was considered to be a more aggressive prescription dose in our working group .
the dose constraint for oars and preliminary compliance rates of dose constraints for oars are summarized in table  1 . because every institution used individual dose constraints , and contouring of the small bowel / peritoneum was not uniform , a large variation in the actual compliance rate was found .
rtog 0418   reported that 6676% of patients did not meet the dose criteria for the bladder and the rectum , and the dose constraint was loosened in the next rtog 1203 protocol because it was considered to be too strict .
it is , therefore , important to set achievable and clinically relevant dose constraints as well as to develop a consensus of contours for oars , especially the small bowel / peritoneum , for a future clinical trial using imrt for post - operative cervical cancer patients .
the six institutions that contributed to this study were equipped with modern linear accelerators capable of doing cbct for daily set - up .
it is very important to ensure accurate daily patient set - up when using imrt , which can generate a very steep and complicated dose distribution , especially when applied in such a large field as the pelvic region .
if imrt is to become a standard therapy for post - operative cervical cancer , which is unfortunately still a relatively common cancer in our country , many institutions will need to update their accelerators with modern machines ; this will contribute to improving the quality of radiation therapy in our country .
the valuable information reported here was derived from six leading institutions in the field of gynecological oncology .
this study was partially supported by the cancer research development fund ( 23-a-13 , 26-a-4 and 26-a-28 ) .
funding to pay the open access publication charges for this article was provided by the cancer research development fund ( 23-a-13 , 26-a-4 and 26-a-28 ) .
 intensity - modulated radiation therapy ( imrt ) was recently introduced to the field of gynecologic malignancies ; however , its value is not yet validated . 
 a clinical trial is in preparation to investigate the efficacy and feasibility of imrt for postoperative cervical cancer . 
 the object of this study was to perform a surveillance study of imrt for post - operative cervical cancer . 
 a questionnaire regarding the precise methods of conducting imrt was sent to six institutions that had already introduced imrt for post - operative cervical cancer , and the data were analyzed . 
 half of the institutions used static imrt and the others used volumetric - modulated arc therapy ( vmat ) . 
 most institutions used body - immobilizing devices for patient fixation . 
 most institutions instructed patients to fill their bladder before undergoing planning ct or daily treatment . 
 while one institution inserted metallic markers and another one used radio - contrast  soaked gauze to visualize the vaginal cuff , the other institutions used nothing for vaginal cuff visualization . 
 most institutions defined the clinical target volumes according to the japan clinical oncology group or the radiation therapy oncology group guidelines . 
 only one institution used a prescribed dose based on 95% of the ptv ( d95 ) , while the rest used the mean dose ( dmean ) . 
 this valuable information from six leading institutions will be utilized in a future prospective clinical trial . 