|Ahead of print publication
Estimation and comparison of integral dose to target and organs at risk in three-dimensional computed tomography image-based treatment planning of carcinoma uterine cervix with two high-dose-rate brachytherapy sources:60Co and192Ir
Suresh Yadav1, OP Singh2, S Choudhary3, Dinesh Kumar Saroj4, Veenita Yogi2, Brijesh Goswami5
1 Department of Radiotherapy, Gandhi Medical College, Bhopal; Department of Physics, Rabindranath Tagore University, Raisen, Madhya Pradesh, India
2 Department of Radiotherapy, Gandhi Medical College, Bhopal, Madhya Pradesh, India
3 Department of Physics, Rabindranath Tagore University, Raisen, Madhya Pradesh, India
4 Department of Radiotherapy, Chirayu Medical College and Hospital, Bhopal, India
5 Department of Radiotherapy, Indraprastha Apollo Hospital, New Delhi, India
|Date of Submission||22-Mar-2019|
|Date of Decision||16-May-2019|
|Date of Acceptance||10-Jun-2019|
|Date of Web Publication||28-Jan-2020|
Department of Radiotherapy, Gandhi Medical College, Bhopal - 462 001, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
Background: Iridium-192 (192 Ir) has been a widely accepted radioisotope for high-dose-rate (HDR) brachytherapy. Recently, Cobalt-60 (60 Co) radioisotope with a longer half-life (5.26 years) has been gaining popularity due to economic and logistical reasons as compared with the traditional192 Ir.
Aim:This study aimed to evaluate and compare the integral dose (ID) to the target and organs at risk (OARs) with two HDR brachytherapy sources in brachytherapy treatment of carcinoma uterine cervix to find appropriate HDR radioisotopes for clinical benefit.
Materials and Methods: This is a retrospective analysis of 52 computed tomography image-based brachytherapy plans of 52 patients who have received intracavitary treatment with192 Ir HDR source. For each patient plan, one additional set of plan was created using60 Co source in place of192 Ir source keeping the same dwell position, and again dose was optimized. The volume and mean dose for target, OARs, and volume structures of 400%, 200%, 150%, 100%, and 50% were recorded for the estimation and comparison of ID.
Results: The mean ID to high-risk clinical target volume was significantly higher by 5.84% in60 Co plan than that in192 Ir plan. For OARs, the mean ID to the rectum was significantly higher by 2.60% in60 Co plan as compared to192 Ir plan, whereas for bladder and sigmoid colon, it was lower in60 Co plan than that in192 Ir plan. The mean ID of central dose volume structures of 400%, 200%, 150%, 100%, and 50% was higher by 12.97%, 9.77%, 8.16%, 6.10%, and 3.22%, respectively, in60 Co plan than that of192 Ir plan.
Conclusion: The results of our study concluded that192 Ir HDR radioisotope should be preferred for intracavitary brachytherapy due to its ideal physical characteristics for better clinical outcomes.
Keywords: 192Ir,60Co, carcinoma uterine cervix, high-dose-rate brachytherapy, integral dose
|How to cite this URL:|
Yadav S, Singh O P, Choudhary S, Saroj DK, Yogi V, Goswami B. Estimation and comparison of integral dose to target and organs at risk in three-dimensional computed tomography image-based treatment planning of carcinoma uterine cervix with two high-dose-rate brachytherapy sources:60Co and192Ir. J Can Res Ther [Epub ahead of print] [cited 2020 Oct 20]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=277100
| > Introduction|| |
Cancer of the uterine cervix is the most common malignancy of female genital organ in the developing world. In India, 96,922 new cases and 60,078 deaths of cancer cervix had been registered in 2018 according to a population-based registry program. In developing countries, most cancers are diagnosed in advanced stages, which make them difficult to treat, and carcinoma of the uterine cervix (Ca Cx) is no exception. Intracavitary high-dose-rate (HDR) brachytherapy has become an established and definitive treatment for Ca Cx either alone or along with external beam radiotherapy (EBRT). By the 1980s, Iridium-192 (192 Ir) had become the most popular radionuclide for HDR brachytherapy due to its smaller physical size. While the availability of miniaturized high-specific-activity Cobalt-60 (60 Co) sources for HDR brachytherapy is a recent development, the use of physically larger60 Co sources in low-dose-rate applications has a long history dating back to the 1960s and 1970s with Cathetron, Ralstron, and Selectron treatment units reported in 1964 by Henschke et al.
In the recent 10 years, the adoption and use of60 Co sources in modern HDR brachytherapy units is gaining popularity worldwide in radiotherapy centers. These new systems utilize miniaturized60 Co sources, rather than the traditional192 Ir sources, and are gaining popularity due to longer source replacement intervals, which leads to lower operating costs and a reduced frequency of movement of radioactive sources between countries, compared to192 Ir. Typical remote afterloading HDR brachytherapy units use192 Ir source with a nominal source activity of around 10 Ci (370 GBq) or60 Co source with an initial nominal activity of 2 Ci (74 GBq). The longer half-life (5.26 years) of60 Co radioisotope is the major advantage in comparison to the shorter half-life (73.8 days) of192 Ir radioisotope. The use of60 Co radioisotopes in HDR brachytherapy applications will, therefore, cut down the number of frequent source exchanges significantly and thus seems to be a more economical alternative to192 Ir HDR radioisotope. Recently,60 Co radioisotopes have become available with identical geometrical sizes as miniaturized192 Ir radioisotopes [Table 1].,,, The different physical characteristics of192 Ir and60 Co HDR radioisotopes are listed in [Table 1]. Strohmaier and Zwierzchowski have reviewed the dose deposition differences around single60 Co and192 Ir source (anisotropy, radial dose function, and isodose curves) and found no advantage and disadvantage. This review was based on the available work done by Venselaar et al., Richter et al., and Park et al., who confined their analysis to point dose and qualitative isodose comparisons only.
|Table 1: Physical characteristic of Iridium-192 and Cobalt-60 radioisotopes|
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The main advantage of brachytherapy technique is that it delivers high localized radiation dose to tumor volume with dose falls very rapidly outside; hence, less integral dose (ID) to normal tissues is received. The inverse square law is the most dominant physical effect in brachytherapy. The higher photon mean energy of60 Co (1.25 MeV) as compared with192 Ir (0.38 MeV) leads higher dose to tissues at larger distances from the sources. ID is the measure of total energy absorbed in treated volume. The ID attempts to describe energy deposition within the whole body, and it is historically considered a physical quantity capable of representing the “physical aggression” and risk of complications due to radiation therapy. Albeit it is generally accepted that the probability of damage to normal tissue and risk of secondary malignancy increases with the increase in ID, this quantity is rarely utilized to predict clinical outcome. Over the last two decades, advancement in technology, fabrication of newer radioisotopes, progress in imaging (computed tomography [CT] and magnetic resonance imaging [MRI]), and computer-controlled afterloading machine have opened the gate of a new era of brachytherapy. With three-dimensional (3D) image-based planning, it may be feasible to assess the relationship of dose–volume response by evaluating the combined dose from EBRT and brachytherapy.
This study aimed to evaluate and compare the ID to the target and organs at risk (OARs) by two HDR brachytherapy sources in brachytherapy treatment of Ca Cx to find appropriate HDR radioisotopes for clinical benefit.
| > Materials and Methods|| |
In this retrospective study, 52 3D CT image-based plans of 52 patients (only the first fraction plan of each patient) who have received intracavitary treatment for Ca Cx with HDR brachytherapy were selected. The mean age of the patients was 49.56 ± 7.34 years, and their The International Federation of Gynecology and Obstetrics (FIGO) stage range was IIB–IVA. All the patients selected for this study were previously treated with192 Ir HDR source. All the patients had received a dose of 46–50 Gy (2 Gy/fraction for 23–25 fraction over a period of 5 weeks) by EBRT either on a 6 MV medical linear accelerator or on a tele-cobalt unit using either four-field box technique or two parallel opposed Anterior-posterior/posterior-anterior (AP-PA) fields before brachytherapy treatments. Followed by EBRT, all the patients were planned to receive a dose of 21 Gy (7 Gy per fraction for three fractions over a period of 3 weeks) by means of intracavitary brachytherapy using a Fletcher-style tandem and ovoid (T and O) applicator set with a fixed geometry. All patients were explained about the CT image-based intracavitary brachytherapy procedure prior to applicator insertion, and informed consents were taken. Applicator reconstruction and contouring of critical organs (bladder, rectum, and sigmoid colon) and tumor (high-risk clinical target volume [HR-CTV]) were performed by a radiation oncologist following the American Brachytherapy Society (ABS)/ The Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) guidelines. The CT scan had a slice thickness of 2.5 mm. The dose was prescribed at 7 Gy/fraction on point “A” as per the ABS guidelines. The treatment plans were optimized in such a way that the total EQD2 dose including EBRT and brachytherapy was kept at ≤75 Gy for rectum and sigmoid colon and ≤90 Gy for bladder. To mitigate interpersonal variations, reconstruction and contouring were done by a single radiation oncologist, and planning was done by a single medical physicist.
In this retrospective study, re-plans were created on CT image-based plans of patients who were already planned and treated with192 Ir HDR source using a fixed-geometry T and O applicator on Varian Gamma Med Plus (Varian Medical Systems, Palo Alto, CA, USA) HDR machine. For each plan generated with192 Ir, one additional set of plan was created using60 Co in place of192 Ir source keeping the same dwell positions, and again, the dose was optimized. Dose optimization and planning objective in60 Co plans were kept similar to192 Ir plans. For each patient, a total of two plans were generated. Thus, a total of 104 3D CT image-based plans were evaluated in this study. Varian Brachy Vision treatment planning system (TPS) version 8.9 (Varian Medical System, Palo Alto, CA, USA) was used for treatment planning. 192 Ir Gamma Med Plus HDR source was formerly commissioned in TPS and routinely used for HDR treatment planning. Bebig60 Co (Co0.A86) HDR source manufactured by Eckert and Ziegler BEBIG GmbH, Germany was modeled into Brachy vision TPS using dosimetric data as input from Granero et al. The validations of TPS calculations for60 Co were done by performing manual calculations using AAPM TG-43 formalism,, and results were in good agreement.
ID is the total energy absorbed by the organ and estimated based on mean organ dose and mean organ density and volume as defined in Equation 1 below:
ID = D− × ρ− × V (Gy × kg),(1)
where D− is mean organ dose, ρ− is mean organ density, and V is organ volume., In the present study, organ was considered uniform density, and ID was estimated by Equation 2 given below:
ID = Mean dose × volume (Gy × L)(2)
For estimation and comparison of ID of two HDR brachytherapy sources, the volume and mean dose were recorded. As per the GEC-ESTRO, ABS, and ICRU 89 guidelines, the dose–volume parameters such as V400%, V200%, V150%, V100%, and V50% (volume covering 400%, 200%, 150%, 100%, and 50% isodose lines of prescribed dose, respectively) were considered and converted into volume structures using tandem length of 6.0 cm for all plans. For estimation of ID, the volume and mean dose of tumor (HR-CTV), OARs (bladder, rectum, and sigmoid colon), and dose volume structures of 400%, 200%, 150%, 100%, and 50% were recorded and evaluated.
Statistical Software Package for the Social Sciences (SPSS) version 20 (IBM Corporation, USA) software was used for statistical analysis. Descriptive analysis was performed to determine the mean and standard deviation (SD) of IDs of target and OARs. A paired two-tailed t-test was performed to compare the ID from two radioisotopes (192 Ir and60 Co) at a confidence level of 95%. P < 0.05 was considered for the significance of statistical inferences.
| > Results|| |
The dosimetric values (volume and mean dose) of target (HR-CTV) and OARs (bladder, rectum, and sigmoid colon) for treatment plans generated with192 Ir and60 Co radioisotopes are summarized in [Table 2]. These dosimetric values of target and OARs were evaluated using cumulative dose–volume histograms as shown in [Figure 1]. The volume of target and OARs were expressed as mean ± SD in liter (L). The mean dose for target and OAR were expressed as mean ± SD in Gy. The ID for target and OARs was estimated using Equation 2. The comparison of ID for target and OARs between treatment plans generated with192 Ir and60 Co is compiled in [Table 3]. The ID for target and OARs was also expressed as mean ± SD in Gy.L.
|Table 2: Dosimetric values of target (high-risk clinical target volume) and organs at risk (bladder, rectum, and sigmoid colon) for plans generated with Iridium-192 and Cobalt-60 high-dose-rate radioisotopes|
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|Figure 1: Cumulative dose–volume histograms for high-risk clinical target volume and rectum, bladder, and sigmoid colon (s. colon) in Iridium-192 and Cobalt-60 plans|
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|Table 3: Comparison of integral dose for target (high-risk clinical target volume) and organs at risk (bladder, rectum, and sigmoid colon) between Iridium-192 and Cobalt-60 plans|
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The results demonstrated that the ID for HR-CTV was 0.788 ± 0.090 Gy.L and 0.834 ± 0.095 Gy.L in192 Ir and60 Co plans, respectively. For HR-CTV, the mean ID was 5.84% higher in60 Co plan than192 Ir plan. There was a significant difference between192 Ir plan and60 Co plan (P < 0.05). The ID for bladder was 0.126 ± 0.049 Gy.L and 0.125 ± 0.048 Gy.L in192 Ir and60 Co plans, respectively. For bladder, the mean ID was 0.79% lower in60 Co plan than192 Ir plan. There was a significant difference between192 Ir plan and60 Co plan (P = 0.001 < 0.05). The ID for rectum was 0.077 ± 0.019 Gy.L and 0.079 ± 0.019 Gy.L in192 Ir and60 Co plans, respectively. For rectum, the mean ID was 2.60% higher in60 Co than192 Ir plan. There was a significant difference between192 Ir and60 Co plans (P < 0.05). The ID for sigmoid colon was 0.115 ± 0.035 Gy.L and 0.114 ± 0.035 Gy.L in192 Ir and60 Co plans, respectively. For sigmoid colon, the mean ID was 0.87% lower in60 Co plan than192 Ir plan. There was a significant difference between192 Ir and60 Co plans (P< 0.05).
[Figure 2] and [Figure 3] illustrate the volumetric structures covering 400%, 200%, 150%, 100%, and 50% isodose line of prescribed dose for192 Ir and60 Co plans, respectively. The dosimetric values (volume and mean dose) of structures covering 400%, 200%, 150%, 100%, and 50% isodose line of prescribed dose are summarized in [Table 4] for treatment plans generated with192 Ir and60 Co HDR radioisotopes. The volume of these structures was expressed as mean ± SD in L. The mean dose to these structures was expressed as mean ± SD in Gy. The volumes of these structures include the applicator volume. The ID for structures covering 400%, 200%, 150%, 100%, and 50% isodose lines was estimated by multiplying volume and mean dose using Equation 2. The comparison of ID for structures covering 400%, 200%, 150%, 100%, and 50% isodose lines between treatment plans generated with192 Ir and60 Co HDR radioisotopes is presented in [Table 5]. The ID of these structures was expressed as mean ± SD in Gy.L.
|Figure 2: Illustration of volumetric structures covering 400%, 200%, 150%, 100%, and 50% isodose line of prescribed dose around target for Iridium-192 plan in (a) transversal view, (b) frontal view, (c) sagittal view, and (d) model view|
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|Figure 3: Illustration of volumetric structures covering 400%, 200%, 150%, 100%, and 50% isodose line of prescribed dose around target for Cobalt-60 plan in (a) transversal view, (b) frontal view, (c) sagittal view, and (d) model view|
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|Table 4: Dosimetric values of structures covering 400%, 200%, 150%, 100%, and 50% isodose line for plans generated with Iridium-192 and Cobalt-60 high-dose-rate radioisotopes|
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|Table 5: Comparison of integral dose for 400%, 200%, 150%, 100%, and 50% isodose line structures between Iridium-192 and Cobalt-60 plans|
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The results demonstrated that the ID for 400% isodose line structures was 0.455 ± 0.024 Gy.L and 0.514 ± 0.068 Gy.L in192 Ir and60 Co plans, respectively. For structures covering 400% isodose line, the mean ID was significantly higher by 12.97% in60 Co plan than192 Ir plan (P< 0.05). For 200% isodose line structure, the ID was 0.983 ± 0.041 Gy.L and 1.079 ± 0.043 Gy.L in192 Ir and60 Co plans, respectively. For structures covering 200% isodose line, the mean ID was significantly higher by 9.77% in60 Co plan than192 Ir plan (P< 0.05). For 150% isodose line structure, the ID was 1.262 ± 0.049 Gy.L and 1.365 ± 0.052 Gy.L in192 Ir and60 Co plans, respectively. For structures covering 150% isodose line, the mean ID was significantly higher by 8.16% in60 Co plan than1292 Ir plan (P< 0.05). The ID for 100% isodose line structure was 1.720 ± 0.067 Gy.L and 1.825 ± 0.070 Gy.L in192 Ir and60 Co plans, respectively. For structures covering 100% isodose line, the mean ID was significantly higher (6.10%) in60 Co plan than that in1292 Ir plan (P< 0.05). The ID for 50% isodose line structure was 2.706 ± 0.108 Gy.L and 2.793 ± 0.108 Gy.L in192 Ir and60 Co plans, respectively. For structures covering 50% isodose line, the mean ID was also significantly higher (3.22%) in60 Co plan than that in1292 Ir plan (P< 0.05). Thus, for structures covering 400%, 200%, 150%, 100%, and 50% isodose line of the prescribed dose, there was significantly higher mean ID in60 Co plan than that in192 Ir plan.
| > Discussion|| |
The physical characteristics for an ideal HDR brachytherapy source should have (i) optimum gamma energy to provide maximum dose deposition and simultaneously low enough to avoid radiation protection problem. The ideal gamma energy range is 0.2-0.4 MeV; (ii) longer half-life to avoid frequent source change interval; and (iii) higher specific activity for fabrication of miniaturized source which results in greater flexibility. The optimum gamma energy (mean 0.38 Mev) and higher specific activity of192 Ir radioisotopes are advantageous over60 Co radioisotopes. The only one disadvantage is shorter half-life (73.8 days) of192 Ir which necessitates source replacement at an interval of 4 months. The longer half-life (5.26 years) of60 Co offers longer source replacement interval, and the higher gamma energy (mean 1.25 MeV) requires thicker shielding for radiation protection.
The results of our study show that mean ID for HR-CTV was significantly higher in60 Co plan than that in192 Ir plan. Palmer et al. demonstrated that60 Co source delivers higher doses along the continuation of applicator axis than192 Ir source, as a result of less self-absorption inside the line source of60 Co (higher gamma energy) than192 Ir. These differences were due to variations in inherent physical characteristics of60 Co and Ir192 sources. Palmer et al.'s study demonstrated that there was small but statistically significant hike in the volume of HR-CTV covered by prescription dose in60 Co plan than192 Ir plan. These observations were for the treatment plans created under identical loading and point “A-” based dose prescription method. The dose distribution differences can be eliminated by opting dose prescription to HR-CTV and dwell time optimization technique. Whereas the dose prescription to point “A” in intracavitary HDR brachytherapy is still common, especially in low- and middle-income countries. The results of 2014 survey by the ABS showed that the use of point “A-” and HR-CTV-based dose prescription was 42% and 52%, in comparison of 76% and 14% in 2007 ABS survey. The updated ABS 2014 survey by Grover et al. reported that in the UK, the use of CT, MRI, and X-ray in image-based brachytherapy planning was at 95%, 34%, and 15%, respectively.
The results of our study show that the rectum mean doses were higher in60 Co plan than that in192 Ir plan. Thus, mean ID for rectum was significantly higher in60 Co plan than that in192 Ir plan. Whereas for bladder and sigmoid colon, the mean doses were lower in60 Co plan than that in192 Ir plan. Hence, in the current study, the mean ID for bladder and sigmoid colon was significantly lower in60 Co plan than that in192 Ir plan. Venselaar et al. study investigated the dose values at large distances from two brachytherapy sources60 Co and192 Ir, for the evaluation of integral dose to organs far distant from target volume. They concluded that for distances up to 20 cm, the dose values from192 Ir source were slightly higher (proportion of 1.14 at 10 cm and 1.05 at 20 cm), but for distances larger than 25 cm, the dose values from60 Co sources were higher (proportion 1.16 at 30 cm, 1.68 at 45 cm, and 2.57 at 60 cm). These results suggested higher IDs for60 Co brachytherapy source than192 Ir source. Another study by Richter et al. concluded that for the same dose in target, the ID was lower in60 Co plan compared to192 Ir plan within a radius of 20 cm, but outside this limit, the relationship was reversed due to higher photon mean energy of60 Co source.
Park et al. compared the dose distributions of HDR brachytherapy planning based on two-dimensional image using60 Co (BEBIG) and192 Ir (microselectron) sources under identical loading patterns. The results of Park et al. study reported an average increase of 0.83±1.48 % to the ICRU rectum reference point and an average decrease of 1.14±0.61 % to the ICRU bladder reference point, when using60 Co source instead of192 Ir source.
In our current research, the results show that the volumes and mean doses of structures covering 400%, 200%, 150%, 100%, and 50% isodose lines were higher in60 Co plan than that in192 Ir plan. Thus, mean ID of these structures was significantly higher in60 Co plan than that in192 Ir plan. This indicates that a higher central volume around the targets bearing applicators is probably gaining a higher ID in60 Co plan than192 Ir plan. In few deliberations on the clinical implications of overdose region, Prabhakar has reviewed various studies in his research and concluded that hike in high-dose region may be disadvantageous.
Ntekim et al. in their study on acute gastrointestinal and genitourinary toxicity associated with60 Co source in brachytherapy treatment of Ca Cx reported that 3% of patients had Grade 3 gastrointestinal toxicity, while all others had ≤ Grade 2 toxicity, and this is comparable with previous results. Mosalaei et al. in their study concluded that the overall survival and disease-free survival rate was 62.4% for 10 years, with local recurrences in 12.2% of patients, and less than 6% of patients experienced severe gastrointestinal and genitourinary toxicity in HDR brachytherapy treatment of Ca Cx with60 Co source. Ntekim et al. and Mosalaei et al. demonstrated60 Co to be a tolerable isotope with some extent of toxicity and to be economical in low-resource settings for HDR brachytherapy treatments of Ca Cx. Ordinarily, higher ID increases the possibility of secondary cancers and also increases the acute toxicities of normal tissues. Nguyen et al. concluded that deposited radiation dose is related to absorbed energy into the tissue which might be the outcome of cytotoxic injuries of cells distant from the field. The higher ID to normal tissue or organ might not cause prompt concern, but it may have late consequences.
| > Conclusion|| |
The results of our study demonstrated that the use of60 Co HDR radioisotopes in brachytherapy treatment for Ca Cx would produce higher ID to target, rectum, and central dose volume structures around applicator as compared to192 Ir radioisotopes, whereas theoretically,60 Co radioisotopes due to their higher mean gamma energy produce less absorption, attenuation, and scattering effects in comparison to192 Ir radioisotopes. The reduction in these effects will result in lower dose to nearest tissues (target) and higher dose to distant tissues (OARs) with60 Co radioisotopes than with192 Ir radioisotopes. The overestimations of these effects are based on TG-43 formalism for dose calculation in brachytherapy planning. Our study emphasized that192 Ir HDR radioisotope should be preferred in intracavitary brachytherapy due to its ideal physical characteristics and biological beneficial effect on tumor. It also delivers less ID to OARs due to higher attenuation. This study would be helpful to choose appropriate HDR radioisotopes for better clinical outcomes.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]