

ORIGINAL ARTICLE 

Ahead of print publication 


Effect of different definitions of prescription point “A” in high dose rate brachytherapy for cervical cancer
Shraddha Srivastava^{1}, Nirmal Kumar Painuly^{1}, Surendra Prasad Mishra^{2}, Kirti Srivastava^{1}, Navin Singh^{1}, Madan Lal Brahma Bhatt^{1}
^{1} Department of Radiotherapy, King George's Medical University, Lucknow, Uttar Pradesh, India ^{2} Department of Radiation Oncology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Correspondence Address: Shraddha Srivastava, Asst. Professor, Department of Radiotherapy, King George's Medical University, Lucknow  226 003, Uttar Pradesh India
Source of Support: None, Conflict of Interest: None DOI: 10.4103/jcrt.JCRT_480_18
Aim: This study intended to compare the dosimetric parameters using different definitions of prescription point A in high dose rate (HDR) brachytherapy of cervical cancer patients. Background: Manchester point A has been widely used for prescribing dose in brachytherapy. However, due to certain limitations of this point, a new definition of point A has been recommended by the American Brachytherapy Society (ABS). Materials and Methods: We retrospectively investigated 55 computed tomographybased plans of 20 cervical cancer patients treated with Ir192based intracavitary HDR brachytherapy. The dose of 7 Gy in 3 fractions each was prescribed to point A using revised Manchester definition of point A (A_{MAN}) and ABS guideline definition (A_{ABS}). The effect of both definitions on various parameters including dose to point A and 90% of tumor volume (D_{90}), dose received by 2cc volume of bladder, rectum and small bowel and treatment volume receiving 100% of prescription dose (V_{100}) was analyzed. Results: Mean percentage difference of point A_{MAN} dose and A_{ABS} dose with respect to prescription dose was 1.25% ± 1.43% and 1.21% ± 1.01%, respectively. Mean V_{100} was 80.4 ± 20.45cc and 88.47 ± 16.78cc for A_{MAN} and A_{ABS} plans, respectively, while mean percentage difference between prescribed dose and D_{90} was found to be –37.90% ± 25.06% and –30.47% ± 25.50% respectively for both the definitions. Conclusion: Doses to both Manchester point A and ABS point A may be recorded during the transition period. However, ABS point A can be preferred over the Manchester point A as it conforms better with the desired dosimetric outcome and is found to be more static.
Keywords: Brachytherapy, cervical cancer, high dose rate, point A
How to cite this URL: Srivastava S, Painuly NK, Mishra SP, Srivastava K, Singh N, Bhatt ML. Effect of different definitions of prescription point “A” in high dose rate brachytherapy for cervical cancer. J Can Res Ther [Epub ahead of print] [cited 2019 Aug 18]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=260132 
> Introduction   
The role of intracavitary brachytherapy (ICBT) in the treatment of cervical cancer is well established. Conventional treatment planning based on twodimensional (2D) orthogonal radiographs where dose is prescribed to point A has been widely used across the globe. However, with recent advancement in threedimensional (3D) imaging, computed tomography (CT), and magnetic resonance imaging (MRI)based treatment planning has gained popularity over 2Dplanning technique as they can help in volumetric dose assessment of target and organs at risk (OARs).^{[1],[2]} Targetbased prescription can be used if 3D imaging is available. Better softtissue visualization on MRI image makes it a modality of choice. However, its limited availability makes CT, a less sensitive tool though, an alternate choice for target assessment.^{[3],[4]} Dosevolume parameters such as D_{90} and D_{100} (minimum dose delivered to 90% and 100% of the target volume) that are used in 3Dimagebased brachytherapy although give volumetric dose assessment of target, GECESTRO still recommends to report dose to point A.^{[2]} Therefore, Manchester point A still remains a popular choice for dose recording.
Since the geometry of application can get disturbed with patient movement, the position of point A can change relative to change in tandem position. As point A lies in highdose gradient region, any positional change leads to variation in dose received by point A.^{[5]} Therefore, it becomes necessary to acknowledge and minimize these variations. One such initiative was taken by the American Brachytherapy Society (ABS) which gave its recommendation in 2012 on new definition of point A.^{[6],[7]} This new point A was defined to remove the practice of defining point A relative to flange as the dose values observed with this concept were not found consistent^{[5]} owing to applicator displacement or anatomical reasons.
In the present study, we have compared the effect of using two different point A definitions, Manchester point A (A_{MAN}) and ABS point A (A_{ABS}), on volumetric and dosimetric parameters of target and critical structures. We have also tried to observe the relation between point A and 3Ddosevolume parameters.^{[8]}
> Materials and Methods   
Fiftyfive CTbased high dose rateICRT applications of 20 retrospectively treated cervical carcinoma patients between 2016 and 2017 with FIGO staging from IIB to IIIB using Fletcher Williamson stainless steel applicators consisting of two ovoids (diameter 20 mm, 25 mm, and 30 mm) and a uterine tandem (angles 15°, 30°, and 45°) were studied. Highrisk clinical target volume (HRCTV) and OARs such as bladder and rectum were contoured using GYN GECGESTRO guidelines^{[1],[2],[3]} in Oncentra Brachy Treatment planning system (version 4.5.2), Elekta, The Netherlands. In these previously treated plans, point A (A_{MAN}) was defined using revised Manchester definition, i.e., 2 cm superior to the flange of the tandem and 2 cm lateral to uterine tandem.^{[9]} The dose of 7 Gy per fraction delivered in three fractions was prescribed to point A_{MAN}. Plans were optimized in patients where rectum and bladder doses exceeded their tolerance values in accordance to institutional protocol.
New point A (A_{ABS}) was introduced in same CTbased plans in accordance with 2012 ABS recommendations. To determine A_{ABS} in treatmentplanning computer a line passing through center of two ovoids was drawn. At the intersection point of this line with tandem, a distance equal to radius plus 2 cm superiorly was marked along the tandem and from this point 2 cm laterally to tandem, point A_{ABS} was marked. [Figure 1] represents the different isodose levels when the two definitions, Manchester and ABS, are used for prescription point.  Figure 1: Manchester and American Brachytherapy Society definition of point A. (a) Manchester point A and (b) ABS point A
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Source positions in new point A_{ABS}based plans were kept same as in A_{MAN}based plans however normalization was done at this new point A_{ABS}. Dose received by both point A_{MAN} and A_{ABS}, 2cc volume of OARs (D_{2cc}) and minimum dose received by 90% and 100% of HRCTV, i.e., D_{90} and D_{100} were recorded in both plans. Treatment volumes enclosed by 100% isodose line (V_{100}), total reference air kerma (TRAK), and geometric shifts between point A_{MAN} and A_{ABS} were also reported.
Statistical analysis using Paired ttest was performed to compare mean point A dose, D_{90}, D_{2cc}, and V_{100} values between Manchester and ABS plans.
> Results   
On comparing ABS and Manchester point Abased plans, it was found that mean percentage dose difference between higher single point A_{MAN} values (of the twopoint As, left and right to the tandem) with respect to prescription dose was 1.25% ± 1.43% while for A_{ABS} values with respect to prescription dose was 1.21% ±1.01%. On statistical analysis, no significant difference (P = 0.42) was found between the mean point A doses of A_{MAN} and A_{ABS}. [Figure 2] compares the point A dose in A_{MAN} and A_{ABS} plans with respect to number of applications.  Figure 2: Point A dose for Manchester and American Brachytherapy Society plans versus number of applications
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Dose to 2cc, 1cc, and 0.1 cc volumes of bladder, rectum, and small bowel were obtained and listed in [Table 1]. The ratio of D_{2cc} dose and prescription dose was found to be 86.76% ± 30.90%, 62% ± 18%, and 54% ± 23% for bladder, rectum, and bowel for A_{MAN} based plans while 101% ± 32%, 71% ± 16%, and 62 ± 26% for A_{ABS} based plans [Table 2]. These values were significantly different (P < 0.05) in both plans.  Table 1: Comparison of D_{2cc}, D_{1cc} and D_{0.1cc} volume of bladder, rectum and bowel between Manchester and American Brachytherapy Society plans
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 Table 2: Comparison of different dosimetric parameters between Manchester and American Brachytherapy Society plans
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Mean percentage difference between prescribed dose and D_{90} for A_{MAN} plans was found to be −37.90% ± 25.06% and −30.47% ± 25.50% for A_{ABS} plans. Mean percentage difference between prescribed dose and D_{100} was −62.85% ± 13.12% and −58.31% ± 15.65% for and A_{MAN} and A_{ABS} plans, respectively [Table 2]. A significant difference (P = 0.002) was observed between ABS and Manchester plans in terms of mean percentage change between D_{90} and prescribed dose and D_{100} and prescribed dose, respectively.
Plans based on point A_{ABS}, normalization exhibited 8.73% ± 18.10% higher TRAK values. Average volumes of HRCTV receiving the 100% of prescription dose in A_{MAN} and A_{ABS} plans were 44.09 ± 17.29cc and 50.65 ± 16.98cc, respectively. Mean treatment volumes enclosed by 100% isodose line (V_{100}) were 80.4 ± 20.45cc and 88.47 ± 16.78cc for A_{MAN} and A_{ABS} plans, respectively. V_{100} differed by a mean percentage difference of 15.18% ± 29.34% and significant difference (P = 0.003) was observed between the two definitions. The comparison of these dosimetric parameters has been shown in [Table 2]. The average shift between A_{ABS} and A_{MAN} location was found to be 9.6 ± 1.3 mm. ABS point A was thus found to be situated superiorly to Manchester point A. [Figure 3] demonstrates the relation between the ratio V100_{ABS}/V100_{MAN} and ratio D_{ABS}/D_{MAN} with shift in point A where V100_{ABS}/V100_{MAN} represents the ratio of treatment volume enclosed by 100% isodose line in A_{ABS} and A_{MAN} plans respectively and D_{ABS}/D_{MAN} represents the ratio of mean doses received by point A_{ABS} and A_{MAN}, respectively. It is visible from the figure that there is no correlation between the shift and the ratios V100_{ABS}/V100_{MAN} and D_{ABS}/D_{MAN}.  Figure 3: Ratio of V100_{ABS}/V100_{MAN} and D_{ABS}/D_{MAN} versus shift in point A
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> Discussion   
Manchester point A has been used for decades as prescription point in ICBT of cervix cancer. However, since the location of this point A varies with the geometry of application, there arises a need for a more stable prescription point. In this study, we have compared plans based on Manchester point A and on point A introduced by ABS 2012 guidelines. Our findings suggest that the mean point A doses of Manchester and ABS plans did not differ significantly. The mean difference of point A with respect to prescription dose was 1.25% ± 1.43% for Manchester and 1.21% ± 1.01% for ABS plans which was similar to findings of Anderson et al.^{[10]} whose values were 1.7% and 1.5% for Manchester and ABS definitions, respectively. Kim et al.^{[11]} also reported similar results (mean 2.2% ± 3.0% for Manchester point and mean 1.8% ± 1.3% for ABS point). Howell et al.^{[12]} also concluded that the average percentage dose to Manchester point was greater than the average percentage dose to ABS point as Manchester point lies more close to ovoids thus receiving more dose. These results were in congruence with our findings.
As shown in [Table 2], the average ratio of D_{2cc} dose to prescription dose was found to be higher for ABS plans which resembled results of Zhang et al.^{[8]} who found average D_{2cc} doses for rectum and bladder to be 51% and 89% of prescribed dose respectively for Manchester point A and 60% and 106% of prescribed dose respectively for ABS point A. Similar results were derived from the study done by Howell et al.^{[12]} who showed that prescribing dose to ABS point A leads to higher bladder and rectum dose over prescribing dose to Manchester point A. The reason for higher OAR doses in ABS plans could be due to the fact that ABS point A lies superiorly above the Manchester point A. Significant difference in OAR doses observed in our study was similar to the results of Chennupati et al.^{[13]}
V_{100} was higher for ABS plans which matches with the observation of Anderson et al.^{[10]} and Zhang et al.^{[8]} who concluded that treatment volume enclosed by 100% isodose level was higher for plans normalized to ABS point A at this point was situated superiorly to Manchester point A. Kim et al.^{[11]} also demonstrated percentage difference of −3% between V_{100} values of ABS and Manchester plans and established that using ABS point A as prescription point increased the total delivered dose. However, the mean percentage difference in our study was 15.18% which was higher than the findings of Anderson et al. who calculated mean percentage change of 3%. The most probable reason for the large variation may be due to anatomical constraints, small pelvis and smaller separation between rectovaginal septum.
For HRCTV, we found that mean percentage difference between D_{90} and prescribed dose was lower in ABS plans, and thus dose received by 90% volume of tumor volume was higher in plans using ABS point A definition for prescribing dose. There was a significant difference in D_{90} values of A_{ABS} and A_{MAN} plans. This differed from Anderson et al.^{[10]} findings who found mean percentage difference between D_{90} parameter of two definitions to be not more than 2%. This variation is again due to anatomical constraints and small pelvic diameters. In another study done by Chennupati et al.^{[13]} it was reported that placement errors in point A with respect to various point A definitions have different effects on tumor doses. This could be a possible reason for the variation in D_{90} values of our results.
A_{ABS} plans in our study had on average 8.73% higher TRAK as compared to A_{MAN} plans. This was somewhere close to the results of Anderson et al.^{[10]} who had found this value to be around 2%–3% and Kim et al.^{[11]} who showed that plans normalized to ABS point A had higher TRAK and thus prescribing to this point increased the total dose up to 2%. Zhang et al.^{[8]} had reported TRAK to be 14% higher for ABS point Abased plans which is different from our result. This difference could be due to the use of LDR brachytherapy machine in their methodology.
The mean distance of A_{ABS} point from A_{MAN} point was found to be 9.6 ± 1.3 mm in our study. Zhang et al.^{[8]} and Anderson et al.^{[10]} calculated this shift to be 8.9 ± 5.4 mm and 6 mm, respectively. Chennupati et al.^{[13]} results were also close to our value.
> Conclusion   
Point A has remained a consistent choice for dose prescription so far. However, due to variation in point A location, several definitions of point A have been explored. In this study, we compared the traditionally used Manchester point A definition and recently introduced point A definition by ABS and found that each of them had an impact on the dosimetric parameters. The study revealed that doses to both the points may be recorded during the transition period. However, ABS point A can be preferred over the Manchester point A as it conforms better with the desired outcome, is less susceptible to dose variations with geometrical changes and found to be more static.
Financial support and sponsorship
This work was funded by Intramural faculty research seed grant from King George's Medical University.
Conflicts of interest
There are no conflicts of interest.
> References   
1.  HaieMeder C, Pötter R, Van Limbergen E, Briot E, De Brabandere M, Dimopoulos J, et al. Recommendations from gynaecological (GYN) GECESTRO working group (I): Concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:23545. 
2.  Pötter R, HaieMeder C, Van Limbergen E, Barillot I, De Brabandere M, Dimopoulos J, et al. Recommendations from gynaecological (GYN) GEC ESTRO working group (II): Concepts and terms in 3D imagebased treatment planning in cervix cancer brachytherapy3D dose volume parameters and aspects of 3D imagebased anatomy, radiation physics, radiobiology. Radiother Oncol 2006;78:6777. 
3.  Viswanathan AN, Dimopoulos J, Kirisits C, Berger D, Pötter R. Computed tomography versus magnetic resonance imagingbased contouring in cervical cancer brachytherapy: Results of a prospective trial and preliminary guidelines for standardized contours. Int J Radiat Oncol Biol Phys 2007;68:4918. 
4.  Krishnatry R, Patel FD, Singh P, Sharma SC, Oinam AS, Shukla AK, et al. CT or MRI for imagebased brachytherapy in cervical cancer. Jpn J Clin Oncol 2012;42:30913. 
5.  Potish R, Gerbi B, Engler GP. Dose Prescription, dose Specification, and Applicator Geometry in Intracavitary Therapy. Madison, WI: Medical Physics Publishing; 1995. 
6.  Eng TY, Cummins S, Baake D. Point A or point H in prescribing highdoserate (HDR) intracavitary brachytherapy for cervical carcinoma? Int J Radiat Oncol Biol Phys 2007;69:S3967. 
7.  Demandante C, Eng T, Yam M, Baacke D, Kim G. Comparison of high dose rate (HDR) brachytherapy doseprescription to point a versus to point h in the treatment of cervical carcinoma. Int J Radiat Oncol Biol Phys 2008;72:S3645. 
8.  Zhang M, Chen T, Kim LH, Nelson C, Gabel M, Narra V, et al. Threedimensional dosimetric considerations from different point A definitions in cervical cancer lowdoserate brachytherapy. J Contemp Brachytherapy 2013;5:2226. 
9.  Tod M, Meredith WJ. Treatment of cancer of the cervix uteri, a revised Manchester method. Br J Radiol 1953;26:2527. 
10.  Anderson J, Huang Y, Kim Y. Dosimetric impact of point A definition on highdoserate brachytherapy for cervical cancer: Evaluations on conventional point A and MRIguided, conformal plans. J Contemp Brachytherapy 2012;4:2416. 
11.  Kim Y, Huang Y, Bayouth J, Flynn R, Bhatia S, Jacobson G, et al. Dosimetric consequences of the prescription point H of ABS recommendation in the era of MRI guided brachytherapy for cervical cancer: Based on GYN GECESTRO recommendations of MRI guided brachytherapy. Int J Radiat Oncol Biol Phys 2008;72:S5867. 
12.  Howell R, Prete J, Wiatrowski W, Beat M, Blough M. Calculation/comparison of dose to point “H” according to the ABS recommendations for HDR brachytherapy for carcinoma of the cervix to the dose to point “A” based on the revised Manchester system. Int J Radiat Oncol Biol Phys 2001;51:3301. 
13.  Chennupati S, Merz B, KalpathyCramer J, Wissel A, Wang S. Variations in point dose specification in 3dimensional planning for intracavitary cervical brachytherapy. Int J Radiat Oncol Biol Phys 2011;81:S46970. 
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
