cervical cancer is mainly treated by radiotherapy which consists of external beam radiation therapy ( ebrt ) and intracavitary radiation therapy ( icrt ) . due to technological advances
intensity modulated radiation therapy ( imrt ) , a form of conformal radiation therapy , is increasingly being used nowadays in cervical cancer since several studies have reported dosimetric and clinical benefit over conventional whole pelvis ebrt [ 17 ] .
though icrt is an integral part of treatment , imrt is posing a challenge to it .
interstitial brachytherapy ( ibt ) is used as an alternative to icrt in patients with extensive disease in the cervix , obliteration of the cervical os , narrow vagina , extension of disease into the lower vagina and parametrical disease beyond the high dose range of the intracavitary applicators . even though ibt is a better option in such patients ,
the associated morbidity due to physical injury and radiation dose to organs at risk ( oar ) still remains a concern [ 8 , 9 ] .
imrt , which has been suggested to replace icrt , can potentially further reduce the oar doses .
concomitant use of ibt and imrt will synergize the potential benefits , physical and biological , of both . for this
, we have devised a new technique called interstitial brachytherapy guided intensity modulated radiotherapy ( ibgimrt ) which can be highly conformal .
this technique utilizes the imrt planning on the tumor volume defined by implantation of ibt needles . before its clinical application
, we conducted a dosimetric study for comparing the treatment plans of ibt and ibgimrt .
ct scan images of 18 patients with primary cervical carcinoma stage iiib , who have been already treated by high dose rate ( hdr ) ibt following whole pelvis ebrt , were used for this study . the ebrt dose schedule consisted of 40 gy in 22 fractions over 5.5 weeks to whole pelvis with four field box technique followed by 10 gy in 5 fractions over 5 days with midline shield ( split field ) .
following ebrt , they were assessed for standard icrt application ( hdr 7 gy  3 , weekly ) and were found unsuitable due to various geometrical and dosimetric reasons .
we decided to treat them by ibt ( 2 sessions of hdr 10 gy each , one week apart ) instead of standard icrt .
the implant was performed under spinal / epidural anesthesia using martinez universal perineal interstitial template ( mupit ) with the assistance of trans - rectal ultrasonography ( trus ) .
foley s tri - lumen urinary catheter was inserted and the bulb was inflated with 7 cm of contrast material ( 2 cm hypaque and 5 cm of normal saline ) . thorough clinical examination and trus imaging of the pelvis was done before inserting the stainless steel needles with blind ends .
number of needles to be inserted was determined by the target volume decided by pretreatment clinical and radiological ( ct / mri ) findings as well as operative clinical & trus findings .
needle injury to various pelvic organs like urinary bladder , rectum and small bowel was avoided as they were well visualized on trus .
thus the target area was adequately covered by the needles , maintaining adequate distance from the normal structures .
after the completion of the needle implantation , template was fixed to the perineal skin with the help of stitches .
a dose of 10 gy was delivered and the template was removed immediately after completing the treatment . after a gap of 1 week another implant was repeated for delivering 10 gy .
a planning ct scan of the whole pelvis was done with slice thickness of 2.5 mm .
brachytherapy planning was performed in plato planning system , version 14.1 ( nucletron , netherlands ) where target and oar were delineated .
the contour drawn by the line joining the outermost needles on the each ct slice constituted the boundary of the target ( fig .
the cranio - caudal extent of the target was decided by selecting the length of needles keeping in mind the clinical findings . due to overlapping of the target and oar volumes ,
once the target volume and oar volumes were finalized , the same were transferred to external beam imrt eclipse planning system ( version 7.35 , varian medical system , usa ) through dicom - rt .
for ibt planning , implant needles were also marked on each slice in order to reconstruct the needle length .
simultaneously two comparative plans were generated , one each on plato ( ibt ) and eclipse ( ibgimrt ) for a prescription dose 10 gy to the target . for ibt plan , step size of 2.5 mm was selected . only dwell positions within the target volume were activated .
if needed , optimization was done to achieve the best plan . for imrt plan , 7 - 9 co - planar 6 mv photon beams ( mlc width 10 mm , dynamic imrt ) were chosen .
dose constraints were set to minimize the volume of normal tissue receiving the prescription dose without compromising target coverage .
ct scan image showing the interstitial brachytherapy needles , contouring of target volume , bladder and rectum dose conformality and normal tissue avoidance were used to compare the two rival plans .
following dosimetric indices were used for comparison : volume receiving 95% of prescription dose ( v95 ) , conformal index ( coin ) and external volume index ( ei ) for target .
coin is a unique index that accounts for the entire dose inside the treated volume , not just inside the target volume , but also outside of any contoured structures .
we calculated the coin by using the following formula : tvref was defined as the volume within target volume ( tv ) that was also within the referenced isodose , and vref was defined as the volume ( inside and outside of tv ) within the reference isodose .
ei was defined as the ratio of the volume of normal tissue that received a dose equal to or greater than the reference dose to the target volume . for oar , dose received by volume of 1 cm ( d1cc ) ,
2 cm ( d2cc ) , 5 cm ( d5cc ) and also volume received by 50% ( v50 ) and 75% ( v75 ) of prescription dose were evaluated for both bladder and rectum .
the statistical analysis was done using paired t - test and a p - value of < 0.05 was considered significant .
the implant was performed under spinal / epidural anesthesia using martinez universal perineal interstitial template ( mupit ) with the assistance of trans - rectal ultrasonography ( trus ) .
foley s tri - lumen urinary catheter was inserted and the bulb was inflated with 7 cm of contrast material ( 2 cm hypaque and 5 cm of normal saline ) . thorough clinical examination and trus imaging of the pelvis was done before inserting the stainless steel needles with blind ends .
number of needles to be inserted was determined by the target volume decided by pretreatment clinical and radiological ( ct / mri ) findings as well as operative clinical & trus findings .
needle injury to various pelvic organs like urinary bladder , rectum and small bowel was avoided as they were well visualized on trus .
thus the target area was adequately covered by the needles , maintaining adequate distance from the normal structures .
after the completion of the needle implantation , template was fixed to the perineal skin with the help of stitches .
a dose of 10 gy was delivered and the template was removed immediately after completing the treatment . after a gap of 1 week another implant was repeated for delivering 10 gy .
a planning ct scan of the whole pelvis was done with slice thickness of 2.5 mm .
brachytherapy planning was performed in plato planning system , version 14.1 ( nucletron , netherlands ) where target and oar were delineated . the contour drawn by the line joining the outermost needles on
the cranio - caudal extent of the target was decided by selecting the length of needles keeping in mind the clinical findings . due to overlapping of the target and oar volumes ,
once the target volume and oar volumes were finalized , the same were transferred to external beam imrt eclipse planning system ( version 7.35 , varian medical system , usa ) through dicom - rt . for ibt planning , implant needles were also marked on each slice in order to reconstruct the needle length .
simultaneously two comparative plans were generated , one each on plato ( ibt ) and eclipse ( ibgimrt ) for a prescription dose 10 gy to the target . for ibt plan , step size of 2.5 mm was selected . only dwell positions within the target volume were activated .
if needed , optimization was done to achieve the best plan . for imrt plan , 7 - 9 co - planar 6 mv photon beams ( mlc width 10 mm , dynamic imrt ) were chosen .
dose constraints were set to minimize the volume of normal tissue receiving the prescription dose without compromising target coverage .
ct scan image showing the interstitial brachytherapy needles , contouring of target volume , bladder and rectum
dose conformality and normal tissue avoidance were used to compare the two rival plans . following dosimetric indices
were used for comparison : volume receiving 95% of prescription dose ( v95 ) , conformal index ( coin ) and external volume index ( ei ) for target .
coin is a unique index that accounts for the entire dose inside the treated volume , not just inside the target volume , but also outside of any contoured structures .
we calculated the coin by using the following formula : tvref was defined as the volume within target volume ( tv ) that was also within the referenced isodose , and vref was defined as the volume ( inside and outside of tv ) within the reference isodose .
ei was defined as the ratio of the volume of normal tissue that received a dose equal to or greater than the reference dose to the target volume . for oar , dose received by volume of 1 cm ( d1cc ) , 2 cm ( d2cc ) , 5 cm ( d5cc ) and also volume received by 50% ( v50 ) and
the statistical analysis was done using paired t - test and a p - value of < 0.05 was considered significant .

 figure 2 demonstrates the example of a patient planned by both ibt and our new technique ibgimrt .
the mean value with standard deviation for all target conformality indices ( coin , ei and v95 ) are shown in table 1 .
though the v95 was better with ibt , coin and ei were better with ibgimrt .
the maximum difference in v95 between ibt and ibgimrt plans was 20.1% which was statistically significant ( p < 0.0047 ) .
the maximum difference in ei between ibt and ibgimrt plan was 36.4% ( p < 0.0028 ) .
comparison between ibt and ibgimrt planning ibt  interstitial brachytherapy , ibgimrt  interstitial brachytherapy guided intensity modulated radiotherapy example of a patient showing the comparison of two plans .
target volume is shown by thick red color line while prescription isodose line is shown by thin red line outer to target .
( d ) imrt dose distribution of the same patient comparison of the dose volume histograms for oar ( bladder and rectum ) by two rival plans resulted in overall better avoidance of oar with ibgimrt .
as shown in table 1 , mean d1cc , d2cc and d5cc values for bladder were 8.3 gy , 7.6 gy and 6.4 gy ; and 7.8 gy , 7.3 gy and 5.8 gy with ibt and ibgimrt , respectively ; however the difference was not statistically significant ( p > 0.05 ) .
similar observations for rectum with ibt vs. ibgimrt were 11.2 gy vs. 7 gy , 10.5 gy vs. 6.4 gy and 9.1 gy vs. 4.8 gy respectively and the difference was statistically significant for all the values ( p < 0.01 ) .
the v50 and v75 values for bladder were slightly better with ibgimrt as compared to ibt but statistically no significant .
there is an emerging feeling among the radiation oncologists worldwide that imrt has a potential of replacing the most brachytherapy ( bt ) treatments whether it is icrt for cervix or ibt for prostate cancer .
though studies relating cervical cancer have already shown the benefit of imrt over conventional ebrt in terms of dosimetry and toxicity , there are very few studies comparing icrt and imrt [ 1315 ] , and none comparing the ibt and imrt . a study by roeske et al .   evaluated the use of imrt as a replacement for bt in cervical cancer by generating boost plans in 10 patients .
though the study did not compare directly the icrt and imrt dosimetry , authors found that a total dose of 79 gy was possible ( 45 gy pelvic rt plus a 34 gy imrt boost ) .
subsequently , a study by low et al .   compared the dosimetry of icrt with imrt .
they observed that imrt dose distributions covered point a isodose surfaces while reducing the dose to the bladder and rectum . in a patient with unfavorable anatomy , significantly better dose coverage of the target tissues
kavanagh et al .   used imrt instead of icrt , adopting simultaneous integrated boost imrt ( sibimrt ) technique and reported that bladder and rectum doses were significantly better with the use of imrt .
based on these 3 reports , the issue of imrt replacing bt in cervical cancer is being debated with arguments in favor and against [ 16 , 17 ] .
so far , there is no study in the literature comparing ibt and imrt in cervix .
it delivers a concentrated dose of radiation to the target area ; and minimal dose to oar as compared to icrt .
though , in use for last 30 years or so , it had not gained wide popularity neither among patients or radiation oncologists due to various reasons : invasive & cumbersome procedure , lack of expertise , associated morbidity and lack of convincing data .
various series [ 8 , 9 ] on ibt in gynecological malignancies , primary as well as recurrent , have reported 4 - 18% risk of severe late toxicity like recto - vaginal fistulas . on the contrary
considering the increasing popularity of imrt and emerging data on bt - imrt comparison in various sites like breast [ 18 , 19 ] and prostate , ibt in cervix is likely to face , sooner or later , a stiff challenge .
both techniques have good potentials and we believe in their complementary use rather than substitute of each other . with this aim ,
we have conducted the present study for testing its dosimetric superiority by comparing with ibt .
ours is a unique study since no study in the literature , so far , has compared , directly or indirectly , ibt with imrt ( ibgimrt ) in cervical cancer . for a strict and head to head comparison ,
we have kept the target volume same for both plans even though , a certain margin outside the ctv , for creating ptv , is mandatory in imrt planning for countering the day to day setup errors . in brachytherapy planning ,
we have chosen 10 gy as the prescription dose since our treatment protocol uses ibt of hdr 10 gy each in 2 sessions , one week apart .
the results of our dosimetric study in 18 patients have shown that ibgimrt in comparison to ibt provided significantly better overall conformality and reduced doses to oar , proving its dosimetric superiority .
since rectum is more susceptible to radiation injury , this dose reduction can be of good help in clinical practice .
some of the indices are better with ibt ( v95 ) and hence our hypothesis of combining the two techniques seems justifiable .
the visualization of the tumor , especially the parametrial disease , on the ct / mri scan is not very good . with our technique , while the ibt needles are being inserted under anesthesia , there is a better clinical appreciation of the pelvic disease .
simultaneously the real time use of trus provides additional information of the tumor and pelvic structures .
correlation of this clinical disease assessment during anesthesia with imaging findings helps in better definition of the target volume .
secondly , the ibt treatment is usually fractionated spread over 2 - 3 days . during the course of ibt
the 50% of the treatment is carried out with ibt and rest with ibgimrt with similar dose per fraction and number of fractions .
for example in a given patient , if ibt dosimetry is equally good or better , then higher dose may be given by ibt and rest by imrt .
thus , various biological and physical advantages of both are exploited in order to improve the clinical outcome .
thirdly , various pelvic structures especially uterus , cervix and hence the tumor are mobile structures since they are suspended by the ligaments .
the ibt needles in situ fix the target region and hence minimize the risk of target movement which is key to any radiation treatment especially ebrt and more so , treatment like imrt . for the same reason , we have kept the target volume same for both ibt and ibgimrt planning in this present study . as it happens with every new technique
, we expect readers to question some of the points in our new technique , ibgimrt .
for example , all forms of conformal ebrt treatments ( like imrt ) ; require application of strict immobilization devices which might be problematic in a patient having implant needles in situ . during the imrt treatment ,
but these shortcomings can be slowly overcome in the subsequent study involving its clinical use .
to conclude , the novel technique ibgimrt devised by us has shown it s dosimetric superiority over ibt in cervical cancer .
 purposeinterstitial brachytherapy ( ibt ) is used as an alternative to intracavitary radiotherapy in the management of cervical carcinoma . 
 we have devised a new technique called interstitial brachytherapy guided intensity modulated radiotherapy ( ibgimrt ) which can potentially reduce doses to organs at risk ( oars ) . 
 it utilizes imrt planning on the target volume ( tv ) defined by implantation of ibt needles . 
 this study compares the dosimetry of ibt and ibgimrt.material and methodsct scan images of 18 patients with cervical cancer , who have been already treated by hdr - bt , were used to generate two rival plans , ibt and ibgimrt , for a prescription dose of 10 gy . following dosimetric factors were used for comparison : volume receiving 95% of prescription dose ( v95 ) , conformity index ( coin ) and external volume index ( ei ) for target and for oar , dose received by volume of 1 cm3 ( d1cc ) , 2 cm3 ( d2cc ) , 5 cm3 ( d5cc ) and also volume receiving 50% and 75% of prescription dose ( v50 and v75).resultsthe two plans resulted in coin difference of 49.8% ( p < 0.0001 ) and ei difference of 36.4% ( p < 0.0028 ) in favor of ibgimrt . 
 mean d1cc , d2cc and d5cc values for bladder were 8.3 gy , 7.6 gy and 6.4 gy ; and 7.8 gy , 7.3 gy and 5.8 gy with ibt and ibgimrt , respectively ( p > 0.05 ) . 
 similar figures for rectum with ibt vs. ibgimrt were 11.2 gy vs. 7.02 gy , 10.5 gy vs. 6.4 gy and 9.1 gy vs. 4.8 gy respectively ( p < 0.01).conclusionsour novel technique , ibgimrt , has shown its dosimetric superiority and therefore needs to be studied in clinical set up . 
Purpose
Material and methods
Brachytherapy procedure
Treatment planning
Dosimetric comparison
Statistical analysis
Results
Discussion