nearly 12 200 new cases of cervical cancer are diagnosed annually in the u.s . .
cervical cancer is a leading health problem worldwide , causing approximately 40 000 deaths per year in developed nations and 234 000 in developing counties annually .
the standard of care for cervical cancer requires concomitant chemotherapy with external - beam radiotherapy ( ebrt ) and brachytherapy ( bt ) .
the bt treatment planning technique , even for high - dose - rate treatments ( hdr ) , has remained unchanged for decades . utilizing 2-dimensional ( 2-d ) orthogonal radiographs ,
a plan is created using the manchester system in which the radiation dose is prescribed to point a : an estimate of where the uterine artery intersects with the ureter [ 2 , 3 ] irrespective of an individual patient 's tumor characteristics .
. 1 of reference ) often occurs in a high - gradient region of the isodose distribution .
however , studies of on the impact of different definitions of point a are limited to conference abstracts [ 69 ] . definitions and potential errors of manchester point a and new point a. a ) manchester point a. b ) new point a the use of 2-d imaging in hdr bt is shifting towards the use of magnetic resonance imaging ( mri ) to acquire volumetric data of the macroscopic tumor region [ 10 , 11 ] .
mri guidance allows treatments to be optimized to tumor volumes while sparing organs - at - risk ( oars ) .
computed tomography ( ct ) , though effective for other treatment sites , is inferior to mri in accurately distinguishing the tumor and tissues of the cervix . with the advent of 3-dimensional ( 3-d ) imaging the prescription dose shifts away from point
where previously point a would be treated to the prescription dose , the new target for 3-d image guided conformal treatments is for 90% of the high - risk clinical target volume ( hr - ctv d90 ) to receive at least the prescribed dose .
the international mri - guided , conformal bt protocol ( embrace : an international study on mri - guided brachytherapy in locally advanced cervical cancer ) recommends that hr - ctv d90 receives the conventional point a dose .
recent studies have reported significant correlation between dose - volume - histogram ( dvh ) parameters ( d90 and d100 ) and local tumor control .
however , the gynaecological european group of curietherapie and the european society for therapeutic radiology and oncology ( gec - estro ) still recommend the recording of conventional point a doses during 3d - image based planning , at least for a transition period .
also recommended is the investigation of correlation back to conventional dose measurements : point a dose and the volumetric - dose in ctv . both gec - estro recommendations and the embrace protocol
recommend mri - guided , conformal bt plans report point a doses even when dose is prescribed to hr - ctv d90 .
however , the effect of point a definition on these correlations has not been reported until this present study .
the original point a concept of the manchester system reported in 1938   has never changed : 2 cm lateral to the central canal of the uterus and 2 cm up from the mucous membrane of the lateral fornix , in the axis of the uterus .
the superior aspects of the vaginal ovoids were originally used as a landmark for the vaginal fornix . in 1953
, a cervical flange was proposed due to the difficulty recognizing the ovoids superior edge on radiographs , this was referred to as revised point a , although it creates a wider variation of point a locations due to the tandem placement being independent of the ovoid position . to minimize these variations , many institutions developed their own definition of point a , including the use of the superior tip of the ovoids in a sagittal radiograph as a landmark for the vaginal fornix [ 8 , 9 ] .
in an effort to standardize point a definitions , the american brachytherapy society ( abs ) introduced a new point a definition .
1):manchester point a : 2 cm superior to the tandem flange and 2 cm lateral from the center of tandem .
this was the revised point a from 1953 .new point a : the new point definition as recommended by the abs . draw a line through the center of each ovoid .
( r + 2 ) cm superiorly along the tandem from the intersection of this line , where r is the radius of the ovoid and 2 cm lateral from the center of the tandem . 
 
manchester point a : 2 cm superior to the tandem flange and 2 cm lateral from the center of tandem .
new point a : the new point definition as recommended by the abs . draw a line through the center of each ovoid .
( r + 2 ) cm superiorly along the tandem from the intersection of this line , where r is the radius of the ovoid and 2 cm lateral from the center of the tandem .
it should be noted that all point a definitions will be co - located when the applicator is correctly implanted . for clarity , this work will use the form 
manchester point a  or  new point a  to refer to the specific definitions and  point a  to refer to the general treatment concept
. a total of 55 hdr plans from patients with biopsy - proven cervical cancer who received radiotherapy ( rt ) were retrospectively studied after approval from the local institutional review board .
2d - f ) from a high resolution ( 3.0 tesla ) siemens magnetom trio 3 t mr scanner ( siemens medical solutions , erlangen , germany ) . only the 25 plans using mri were analyzed using dvh parameters .
in addition , the 25 plans were retrospectively re - planned using conformal planning techniques . in the authors institutional protocol , the majority of patients with figo ( international federation of gynecology and obstetrics ) stage ib2 and above cervical cancer received ebrt , hdr bt and weekly concomitant cisplatin infusion .
bt fractionation schemes consisted of either 3 fractions of 7.5 gy or 5 fractions of 5.5 gy , with occasional minor variations .
a titanium fletcher - suit - declos style tandem - and - ovoids ( t&o ) applicator ( varian medical systems , palo alto , ca ) was used for all plans , along with the brachyvision treatment planning system ( version 8.9 , varian medical systems , palo alto , ca ) .
part ( a ) shows coronal and sagittal radiograph images and example locations of the two points , ( b ) shows the full isodose set for a normalized to new point a , and ( c ) shows the 100% isodose lines for both point a definitions
. parts ( d ) through ( f ) show high resolution ( 3.0 tesla ) mr images with hr - ctv and oar contours and conformal plan isodose lines all conventional , clinical plans had been optimized to generate standard pear - shaped isodose distributions using reference lines that were located 2 cm lateral from the tandem and 0.5 cm lateral from each ovoid 's surface ( fig .
2 ) . the locations of manchester point a and new point a were retrospectively defined by a single person to avoid inter - physicist variation . for both point definitions , the stand pear - shaped isodose lines were re - normalized such that the point received the prescribed dose .
the 25 plans using mri were also retrospectively re - planned with the intention of generating mri - guided , conformal plans ( fig .
2d - f ) in accordance with gec - estro recommendations [ 10 , 11 ] and embrace protocol .
the details of the mri scan protocols for the t&o hdr bt procedure were summarized in the previous study .
an experienced physician contoured the intermediate risk ctv ( ir - ctv ) , the high risk ctv ( hr - ctv ) and organs - at - risk ( oar ) according to gec - estro recommendations [ 10 , 11 ] and embrace protocol .
a conformal plan was optimized to achieve the following : hr - ctv d90 was to receive the prescription dose and d2cc ( the minimum dose within the 2 cc of tissue receiving the greatest dose ) of each oar was to receive less than the limits of the gec - estro recommendations [ 10 , 11 ] and embrace protocol .
the recommended limits of d2cc for the rectum , bladder and sigmoid colon are 75 gy , 90 gy , and 75 gy , respectively .
these limits are the combined ebrt and hdr doses in terms of eqd2 ( equivalent dose in 2 gy fractions of ebrt , using an / value of 3 ) .
ebrt plan data were used during conformal hdr plan optimization procedures to apply the recommended oar limits .
the hybrid - inverse optimization described in our previous work   was utilized for all conformal plans ( fig .
2 ) : starting with a conventional point a plan , dose - volume objectives were set and inverse planning performed .
the isodose lines and dvh measurements of the optimized plan were then checked and further inverse planning or graphical dose shaping used where necessary . among total 55 conventional plans ,
the 30 plans guided by 2-d radiographs were analyzed by measuring the volume receiving 100% or more of the prescription dose ( v100% ) , the total reference air kerma ( trak ) , and the dose to the rectum and bladder points of icru report # 38 ( international commission on radiation units and measurement ) . the other 25 conventional plans using mri were further analyzed using dvh parameters , including the minimum dose received by 90% of the hr - ctv ( d90 ) and the minimum dose to the hottest 2cc of each oar ( d2cc ) .
all dvh parameters were analyzed only for hdr plans no ebrt plan data were analyzed .
for each measurement of a plan re - normalized using manchester point a ( manchester point a plan ) , for example , a corresponding measurement was taken using the new point a normalized plan ( new point h plan ) . as the focus was on systematic differences between these plans
, we took the percent difference of each pair as the first step of our analysis .
this was done with respect to the new point a plans such that negative results indicated a lower value in the point a plan ( see fig .
average percent differences of manchester point a plans when normalized to new point a plans .
negative values indicate lower results for the manchester point a plans . the 95% confidence interval is marked the 25 conformal plans using mri were also analyzed by dvh parameters , along with the 2-d parameters v100% , trak , and rectal and bladder point doses . in conformal plans , the correlation between tumor coverage values such as hr - ctv d90 , d100 or ir - ctv d90 and point a doses are of interest , since the majority of clinical outcomes are linked with these point measurements
it is noted that conformal plans do not use point a to generate plans , but use hr - ctv and oar to perform volume optimization .
therefore , we quantified how the correlation is affected by different point a definitions for a given conformal plan .
specifically percent differences between manchester point a or new point a dose and tumor coverage values ( d90 or d100 ) were taken with respect to the dose volume measurement values , with negative results indicating a lower value in the point dose ( cf .
4 ) . for all dose - volume parameter analysis ( i.e. d90 , d100 , and d2cc )
, physical doses were converted to eqd2 values using / = 3 for healthy tissue and / = 10 for target volumes [ 10 , 11 ] .
percent differences between manchester point a ( point h ) doses and prescription doses & tumor coverage metric from mri - guided , conformal plans .
the original point a concept of the manchester system reported in 1938   has never changed : 2 cm lateral to the central canal of the uterus and 2 cm up from the mucous membrane of the lateral fornix , in the axis of the uterus .
the superior aspects of the vaginal ovoids were originally used as a landmark for the vaginal fornix . in 1953
, a cervical flange was proposed due to the difficulty recognizing the ovoids superior edge on radiographs , this was referred to as revised point a , although it creates a wider variation of point a locations due to the tandem placement being independent of the ovoid position . to minimize these variations , many institutions developed their own definition of point a , including the use of the superior tip of the ovoids in a sagittal radiograph as a landmark for the vaginal fornix [ 8 , 9 ] .
in an effort to standardize point a definitions , the american brachytherapy society ( abs ) introduced a new point a definition .
1):manchester point a : 2 cm superior to the tandem flange and 2 cm lateral from the center of tandem .
this was the revised point a from 1953 .new point a : the new point definition as recommended by the abs . draw a line through the center of each ovoid .
( r + 2 ) cm superiorly along the tandem from the intersection of this line , where r is the radius of the ovoid and 2 cm lateral from the center of the tandem . 
 
manchester point a : 2 cm superior to the tandem flange and 2 cm lateral from the center of tandem .
new point a : the new point definition as recommended by the abs . draw a line through the center of each ovoid .
( r + 2 ) cm superiorly along the tandem from the intersection of this line , where r is the radius of the ovoid and 2 cm lateral from the center of the tandem .
it should be noted that all point a definitions will be co - located when the applicator is correctly implanted . for clarity , this work will use the form 
manchester point a  or  new point a  to refer to the specific definitions and  point a  to refer to the general treatment concept .
a total of 55 hdr plans from patients with biopsy - proven cervical cancer who received radiotherapy ( rt ) were retrospectively studied after approval from the local institutional review board .
2d - f ) from a high resolution ( 3.0 tesla ) siemens magnetom trio 3 t mr scanner ( siemens medical solutions , erlangen , germany ) .
in addition , the 25 plans were retrospectively re - planned using conformal planning techniques . in the authors institutional protocol , the majority of patients with figo ( international federation of gynecology and obstetrics ) stage ib2 and above cervical cancer received ebrt , hdr bt and weekly concomitant cisplatin infusion .
bt fractionation schemes consisted of either 3 fractions of 7.5 gy or 5 fractions of 5.5 gy , with occasional minor variations . a titanium fletcher - suit - declos style tandem - and - ovoids ( t&o ) applicator ( varian medical systems , palo alto , ca )
was used for all plans , along with the brachyvision treatment planning system ( version 8.9 , varian medical systems , palo alto , ca ) .
part ( a ) shows coronal and sagittal radiograph images and example locations of the two points , ( b ) shows the full isodose set for a normalized to new point a , and ( c ) shows the 100% isodose lines for both point a definitions .
parts ( d ) through ( f ) show high resolution ( 3.0 tesla ) mr images with hr - ctv and oar contours and conformal plan isodose lines all conventional , clinical plans had been optimized to generate standard pear - shaped isodose distributions using reference lines that were located 2 cm lateral from the tandem and 0.5 cm lateral from each ovoid 's surface ( fig .
2 ) . the locations of manchester point a and new point a were retrospectively defined by a single person to avoid inter - physicist variation . for both point definitions , the stand pear - shaped isodose lines were re - normalized such that the point received the prescribed dose .
the 25 plans using mri were also retrospectively re - planned with the intention of generating mri - guided , conformal plans ( fig .
2d - f ) in accordance with gec - estro recommendations [ 10 , 11 ] and embrace protocol .
the details of the mri scan protocols for the t&o hdr bt procedure were summarized in the previous study .
an experienced physician contoured the intermediate risk ctv ( ir - ctv ) , the high risk ctv ( hr - ctv ) and organs - at - risk ( oar ) according to gec - estro recommendations [ 10 , 11 ] and embrace protocol .
a conformal plan was optimized to achieve the following : hr - ctv d90 was to receive the prescription dose and d2cc ( the minimum dose within the 2 cc of tissue receiving the greatest dose ) of each oar was to receive less than the limits of the gec - estro recommendations [ 10 , 11 ] and embrace protocol .
the recommended limits of d2cc for the rectum , bladder and sigmoid colon are 75 gy , 90 gy , and 75 gy , respectively .
these limits are the combined ebrt and hdr doses in terms of eqd2 ( equivalent dose in 2 gy fractions of ebrt , using an / value of 3 ) .
ebrt plan data were used during conformal hdr plan optimization procedures to apply the recommended oar limits .
the hybrid - inverse optimization described in our previous work   was utilized for all conformal plans ( fig .
2 ) : starting with a conventional point a plan , dose - volume objectives were set and inverse planning performed . the isodose lines and dvh measurements of the optimized plan
among total 55 conventional plans , the 30 plans guided by 2-d radiographs were analyzed by measuring the volume receiving 100% or more of the prescription dose ( v100% ) , the total reference air kerma ( trak ) , and the dose to the rectum and bladder points of icru report # 38 ( international commission on radiation units and measurement ) . the other 25 conventional plans using mri were further analyzed using dvh parameters , including the minimum dose received by 90% of the hr - ctv ( d90 ) and the minimum dose to the hottest 2cc of each oar ( d2cc ) .
all dvh parameters were analyzed only for hdr plans no ebrt plan data were analyzed . for each measurement of a plan re - normalized using manchester point a ( manchester point a plan ) , for example , a corresponding measurement was taken using the new point a normalized plan ( new point h plan ) . as the focus was on systematic differences between these plans , we took the percent difference of each pair as the first step of our analysis .
this was done with respect to the new point a plans such that negative results indicated a lower value in the point a plan ( see fig .
average percent differences of manchester point a plans when normalized to new point a plans .
the 95% confidence interval is marked the 25 conformal plans using mri were also analyzed by dvh parameters , along with the 2-d parameters v100% , trak , and rectal and bladder point doses . in conformal plans , the correlation between tumor coverage values such as hr - ctv d90 , d100 or ir - ctv d90 and point a doses are of interest , since the majority of clinical outcomes are linked with these point measurements .
it is noted that conformal plans do not use point a to generate plans , but use hr - ctv and oar to perform volume optimization .
therefore , we quantified how the correlation is affected by different point a definitions for a given conformal plan .
specifically percent differences between manchester point a or new point a dose and tumor coverage values ( d90 or d100 ) were taken with respect to the dose volume measurement values , with negative results indicating a lower value in the point dose ( cf .
4 ) . for all dose - volume parameter analysis ( i.e. d90 , d100 , and d2cc )
, physical doses were converted to eqd2 values using / = 3 for healthy tissue and / = 10 for target volumes [ 10 , 11 ] .
percent differences between manchester point a ( point h ) doses and prescription doses & tumor coverage metric from mri - guided , conformal plans .
we found that a conventional , point a based plan is minimally affected by variations caused by implant procedure and/or patient anatomy when new point a definition was used .
for any plan , there is both a left and right side point a and the normalization ensures that their average dose values equal the prescribed dose .
we observed that the percent deviations of the higher single point a values with respect to the prescription doses were up to 9.5% ( mean 1.7% , ci95  0.5% , p
< 0.001 ) and for new point a up to 6.7% ( mean 1.5% , ci95  0.3% , p < 0.001 ) . across the 55 plans , manchester point a
was found to be mean distance of 0.6 cm from new point a ( ci95 0.1 cm , max 2.1 cm , p < 0.001 ) . in other words ,
figure 2a shows a sample radiograph of a case with a distance of over 2 cm between different point a definitions , which caused the plotted separation in 100% isodose lines .
3 : we plotted the average percent difference of measurements from plans normalized to point a with respect to corresponding measurements from those normalized to new point a. a significant ( p < 0.005 ) difference was seen between different point a definitions when v100% , trak and icru rectal and bladder point doses were considered .
the biggest dosimetric impact due to point a definitions were in the v100% and trak values , both of which represent the overall amount of radiation delivered .
the maximum differences between manchester point a and new point a were 20% and 12% for v100% and trak , respectively .
we found that plans normalized to point a had lower dosimetric values , on average , than those normalized to new point a ( fig .
3 ) . this is because new point a was generally located superiorly to manchester point a , resulting in a larger area enclosed by the 100% isodose line for new point a plans ( fig .
3 shows the mean percent differences for each ctv and oar in which all variations were less than 2% .
we next considered mri - guided , conformal plans . in each of these plans ,
the point dose values at manchester point a and new point a were recorded and compared to the prescription dose and volumetric tumor coverage values ( hr - ctv d90 , d100 and ir - ctv d90 ) ( see fig .
all point a doses and prescription doses were converted to eqd2 values using / = 10 [ 10 , 11 ] .
figure 4 shows the percent differences of point a doses , the prescription dose and tumor coverage values .
the relationship between point a doses and volumetric tumor coverage values were not considerably changed due to point a definition .
the mean changes of no more than 2% were observed on the prescription dose , hr - ctv d90 and ir - ctv d90 due the point a definition .
the relationship between point a dose and hr - ctv d100 was maximally changed ( i.e. mean 9% ) due to the point a definition . new point a still showed smaller variations from the prescribed dose than those of manchester point a.
the variance seen between point a definitions comes from two main sources : i ) imprecise implantation of the applicator and/or ii ) inter - planner differences while defining either point a on 2-d radiographs or 3-d imaging datasets .
the latter should be limited if all planners are well trained and has been removed from this study entirely as the same investigator performed the task in all cases .
there was no such restriction , however , on the applicator implantation : this process is inherently imprecise due to visualization difficulties and patient anatomy and is the source of the deviation between point a definitions .
the most recent abs guideline 2012   updated the new point a definition to first move to the midpoint between the two ovoids , then superiorly r + 2 cm along the tandem ( see fig . 1 in ref .
is expected to result in a yet more robust point definition . in this study ,
mean deviations were found to have a minimal effect on conventional plans , as only small differences were found between plans normalized to different point definitions .
this finding matches the study of eng et al .   showing less than 3% variation between manchester point a and new point a plans when considering doses to point b , icru rectum point or icru bladder point .
point b was reported as a poor surrogate for pelvic lymph node dose , so it was excluded as a dosimetric measurement in this study .
we found the plans normalized to new point a had on average 2 - 3% higher trak or v100% values over those normalized to manchester point a. these findings match the results of howell et al . , showing that a plan normalized to new point a generated slightly higher doses .
there is no literature describing the impact on clinical outcomes due to a 2 - 3% increase in overall dose .
the variation in tumor coverage for conventional point a plans was summarized in our previous study . here ,
the mean variations due to the use of different point a definition were found to be relatively small .
however , we found maximal trak changes of 11 - 12% and volumetric metrics such as hr - ctv d90 .
thus , the correlation between point a doses and volumetric tumor coverage ( e.g. hr - ctv d90 ) can be changed up to 11 - 12% due to different point a definitions .
it is recommended that the use of a new point a definition for those studies is adopted . with the development of
mri - guided , conformal bt , the correlation between conventional point a doses and dose - volume parameters of hr - ctv / ir - ctv have been reported , although no phase iii clinical outcome studies between mri - guided , conformal bt and conventional point a based bt are presently available . using the more stable new point a definition
is expected to enable better clinical outcome analysis , including deeper understanding of the correlations between point a dose and dose - volume parameters of the hr - ctv .
 purposeto investigate the dosimetric impact of point a definitions on both conventional point a plans and mri - guided conformal high - dose - rate ( hdr ) brachytherapy plans.material and methodsfifty - five hdr plans of 36 patients with figo stage i to iv cervical cancer were retrospectively studied ; these included 30 conventional treatments and 25 conformal plans . 
 two different point a definitions were explored : the revised manchester point a and the new point a as recommended by the american brachytherapy society . 
 conventional plans were produced by varying only the point a definition and the normalized isodose lines . 
 conformal plans were retrospectively generated per gec - estro recommendations based upon 3.0 tesla mri data.resultssmall yet significant variations were found in point a locations ( mean : 0.5 cm , maximum : 2.1 cm , p < 0.001 ) . 
 the use of a new point a caused minimal dose variation for both conventional and conformal plans . 
 conventional plans normalized to the new point a generated up to 12% ( avg . 
 1 - 3% ) higher overall dose in terms of higher total reference air kerma than plans normalized to other points . 
 dosimetric changes due to point a definitions were up to 11 - 12% ( avg . 
 less than 2% ) on target volumes or organs-at-risk.conclusionsfor both conventional and conformal plans , the new point a definition leads to smaller variations caused during implant and/or differences in patient anatomy . using the new point 
 a is expected to produce more consistent brachytherapy plans and improve outcome analysis . 