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Study of the effects of dwell time deviation constraints on inverse planning simulated annealing optimized plans of intracavitary brachytherapy of cancer cervix


1 Department of Radiotherapy, Lok Nayak Hospital, New Delhi; Research and Development Centre, Bharathiar University, Coimbatore, Tamil Nadu, India
2 Department of Radiotherapy, Dr. B.R.A. IRCH, AIIMS, New Delhi, India
3 Department of Radiotherapy, Lok Nayak Hospital, New Delhi, India

Correspondence Address:
Saurabh Roy,
Department of Radiotherapy, Lok Nayak Hospital, Room No. 123, Gate No. 2, Jawaharlal Nehru Marg, New Delhi - 110 002
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_246_18

 > Abstract 


Purpose: High Dose Rate (HDR) remote afterloading brachytherapy machine and advanced treatment planning system have made it possible to make variations in individual dwell times across a catheter according to tumour density and for sparing normal structures. New inverse planning technique such as Inverse Planning Simulated Annealing (IPSA) has also been introduced. But very few institutions are venturing towards volume based IPSA optimised intracavitary brachytherapy. This study focuses on dwell time deviation constraint (DTDC) feature of IPSA based optimization which restricts the large variation of dwell time across the catheter.
Methods and Material: For this retrospective study we have generated IPSA optimised intracavitary brachytherapy plans for 20 cancer cervix applications. The initial DTDC value of each IPSA plan was kept 0.0. Later on gradual increment was made in DTDC values in step of 0.2. Plan modulation index (M) defined by Ryan L. Smith et al was used for characterising the variation of dwell time modulation with respect to gradual increase in DTDC parameter.
Results: Plan modulation index gradually decreases with increasing value of DTDC from 0.0 to 1.0. There was the 83% decrease in M value from IPSA of DTDC 0.0 to fully constrained IPSA of DTDC1.0. There is reduction of 8.26% and 6.95% for D2cc values of rectum and bladder respectively for DTDC 1.0 compared to DTDC 0.0.
Conclusions: One of the benefits of applying DTDC constrained in IPSA plan is that, it removes local hot spots. It's another advantage is the reduction in rectum and bladder dose.

Keywords: Dwell time deviation constraint, intracavitary brachytherapy, inverse planning in brachytherapy, inverse planning simulated annealing



How to cite this URL:
Roy S, Subramani V, Singh K, Rathi AK, Savita A, Aditi A. Study of the effects of dwell time deviation constraints on inverse planning simulated annealing optimized plans of intracavitary brachytherapy of cancer cervix. J Can Res Ther [Epub ahead of print] [cited 2019 Dec 13]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=251621




 > Introduction Top


Cervical cancer is one of the most common types of cancer among women globally. It is the second most common cancer in women in India, and nearly 85% of the burden is in developing countries.[1] Point A based Manchester system is the most common method for treatment prescription for intracavitary brachytherapy (ICBT) of cervical cancer. The popularity of Manchester system-based ICBT approach is due to its wider acceptability. However, some investigators have questioned the effectiveness of this method with regard to dose to normal structures and target.[2],[3],[4],[5] Especially, the ICRU Report No. 38 dictates dose distributions based on the visualization of the applicator and bony landmarks instead of dose coverage of a tumor and critical structures.[2] However, with the advent of three-dimensional (3D) imaging modality and sophisticated treatment planning system (TPS), it has now become possible to do volume-based high-dose-rate (HDR) ICBT which focuses on dose to tumour and critical structures.

In point A based Manchester system, treatment dwell position and dwell times are adjusted with trial and error method to obtain the desired dose distribution. There are options for adjusting dwell time using manual optimization, for which good clinical experience is required. The satisfactory clinical results achieved due to this optimization depend on particular operator. Other optimization methods such as dose-point and geometric optimization do not use anatomical information but are based on the location of the active dwells.

For overcoming these problems associated with manual, dose-point, and graphical optimization, inverse planning simulated annealing (IPSA) has been developed at the University of California, San Francisco, USA.[6],[7] IPSA has made it possible to optimize dwell time and dwell position configuration according to already defined anatomy-based dose constraints. In this optimization method, optimal solution is achieved by minimizing the objective function through an iterative process. IPSA has been found to be superior with respect to target coverage and normal-tissue sparing compared with traditional optimization methods for prostate[8],[9],[10],[11],[12],[13] and gynecological malignancies.[6],[14],[15]

IPSA solutions for the treatment of cervical cancer have found to be with large variation in dwell times.[16] These high values of dwell time compared to nearby dwell positions may lead to isolated high-dose volumes in the vaginal wall.[17],[18],[19],[20]

To overcome this problem in the treatment of cervical cancer ICBT, Chajon et al. suggested to draw a 5-mm delineation around each catheter and to apply a minimal volume dose constraint to these dummy structures.[16] The effect of implementation of help structure in tandem and ovoid applicator set has already been investigated.[21]

Another solution to the problem of occurrence of large dwell times is provided in Oncentra TPS (Oncentra Brachy version 4.5.1, Nucletron an Elekta company, Elekta AB, Stockholm, Sweden), which has the availability of dwell time deviation constraint (DTDC) parameter which restricts variation in dwell time deviation.[22] The DTDC parameter can have any value between 0.0 and 1.0, with an increment of 0.1. Here, DTDC values of 0.0 and 1.0 indicate unconstrained and fully constrained IPSA plans for dwell time deviation, respectively. DTDC pushes the system to avoid single positions with very high dwell times and also averts dwell time reduction to zero when the dwell position is not at all required to cover the contoured target.

The purpose of this work is to study the variation in high-dose volumes characterized by V150% and V200% in target volume, along with other dosimetric parameters against the gradual increment in DTDC values from 0.0 to 1.0. This is one of the first studies in which DTDC feature has been used for restricting the large segregated dwell times in IPSA-based ICBT plans. Volumetric dose prescription in ICBT is still done with caution and strict compliance with point A-based dose distribution is also followed. This study addresses the very important issue of formation of large segregated dwell times in IPSA-based ICBT plans which may help other institutions to venture into the new possibility of volumetric dose prescription to ICBT with IPSA approach.


 > Materials and Methods Top


This is a retrospective study of 20 consecutive ICBT applications for primary cervical cancers. The patients chosen for this research underwent conventional external radiation therapy and HDR brachytherapy (BT) between May 2016 and January 2017. All patients were Stage IIB–IIIB as per the International Federation of Gynecology and Obstetrics 2009 Staging System. Patients were treated with external radiation therapy using Cobalt-60 teletherapy machine in a conventional fractionation by either AP-PA or four fields depending on the patients AP separation; the whole pelvis was irradiated to 50 Gy in 25 fractions in 5 weeks, concurrent with weekly intravenous cisplatin of 40 mg/m2.

Following completion of external beam radiotherapy, ICBT was performed. After preanesthetic checkup, and overnight fasting with adequate bowel preparation, ICRT applicator insertion was done under spinal anesthesia in operation theater (OT). An examination under anesthesia was done and Foley catheter was placed. After uterine sounding and assessment of uterocervical length, central tandem was placed with the maximum fitting ovoids as per anatomy of a patient. Adequate packing was used to keep the treatment device in the same position for the whole treatment period and to push the bladder anteriorly and rectum posteriorly. Planning computed tomographic (CT) scan was done with 5-mm slices for the pelvis, used for reconstruction of catheters. Clinical target volume (CTV) as assessed in the OT (including the whole uterus, cervix, and upper one-third of vagina with visible/palpable disease and parametrial extension of disease) and seen on planning CT was delineated along with the bladder and rectum.

The delineation of CTV was primarily based on the assessment done in the OT along with the baseline disease as seen on radiological (CT/magnetic resonance imaging) imaging of the patient. Delineation was done by adjusting the center and width feature so as to minimize the artifacts due to the metal applicator. CTV volume data are provided in [Table 1].
Table 1: Clinical target volumes for 20 applications

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Inverse treatment planning using IPSA was implemented in Oncentra TPS. Treatment was received by all patients as per the standard prescription to point A of 3 fractions of 7 Gy each as an institutional protocol. However, as this was a retrospective study with IPSA plan, dose to CTV was prescribed for carrying out this study. [Table 2] shows the dose objectives and weighting factors used for the IPSA plans.
Table 2: Dose objectives and weighting factors used for the inverse planning simulated annealing plans

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In IPSA, an optimal plan is obtained which meets the dose objective parameters of both CTV and the organ at risk (OAR). The relative importance of any parameter is represented by weights. The optimized plan consists of optimal dwell positions and dwell times. To restrict the occurrence of large variation in dwell times in IPSA plans, additional help structures around the tandem and ovoid were contoured and combined into the inverse optimization. In case of unacceptable dose distribution, the optimization parameters were modified and the calculation was repeated again until our desired objective was obtained.

Once the optimized IPSA solution was obtained, the DTDC value was increased from 0.0 to 1.0 in step of 0.2 without changing the IPSA solution. Dose–volume histograms (DVHs) for CTV and OARs were evaluated for each value of DTDC. For dosimetric evaluation regarding the CTV, minimum percentage dose relative to prescribed dose received by 90% of the target volume, D90% along with the target volume receiving the prescribed dose, V100%, was studied. V150% and V200% of CTV were also evaluated for the high-dose volumes. For rectum and bladder, the maximum dose to the most exposed 2 cubic centimeter volume, D2cc, was determined. Total reference air kerma (TRAK) was also determined. All these data were compared with varying values of DTDC using Student's t-test. A level of significance of 0.05 was considered to determine the statistically significant differences. To interpret the difference in dwell time distribution, as the DTDC parameter was increased, plan modulation index (M) was used, as defined by Smith et al.[23] It is described as the maximum deviation of dwell time from the average dwell time for each catheter, normalized to the maximum dwell time for the treatment plan, averaged over all catheters in the plan. The equation for plan modulation index (M) is given in Equation 1.



Where Tmax, i is the maximum dwell time in each catheter, i; Tavg, i is the average dwell time for catheter i; Tmax is the maximum dwell time for the plan; and n is the total number of catheters. The M parameter was then used as a measure of the dwell time deviation for each IPSA optimized plan as the DTDC parameter was increased. The HDR BT was delivered with a Fletcher Williamson Asia Pacific applicator set (part number 085.260), connected to a remote after-loader MicroSelectron HDR V3 (18 Channel) machine, with Ir-192 source (Nucletron B.V., Veenendaal, The Netherlands)


 > Results Top


Proper IPSA solution was obtained by putting dose constrains to CTV and OARs and help structures. After achieving satisfactory dose distribution, the IPSA solution was kept constant and DTDC value was varied from 0.0 to 1.0 in step of 0.2. The initial IPSA solution without DTDC constraint was giving more heterogeneous dwell time distribution across the three applicators as expected. Gradual increment in DTDC value gave successive decrease in the occurrence of these heterogeneous dwell time distributions.

Plan modulation index gradually decreased with increasing value of DTDC from 0.0 to 1.0, giving rise to a more homogeneous dwell time distribution within each catheter. [Figure 1] shows the average plan modulation index for all 20 applications as the DTDC parameter is increased. There was 83% decrease in M value from IPSA of DTDC 0.0 to fully constrained IPSA of DTDC 1.0. DTDC also affects the amount of active dwell positions.
Figure 1: Effect of increased dwell time deviation constraint on plan modulation index (m)

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It was found that the number of activated dwell positions decreases for DTDC value of 0.0–0.2 but then gradually increases for increasing DTDC values as shown in [Figure 2].
Figure 2: Effect of increasing dwell time deviation constraint on average activated dwell position (%) and treatment dwell time (%)

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Unconstrained IPSA plan has isolated large dwell positions with large patches of increased dwell times. Its another characteristic is the large quantity of vacant dwell positions. With increasing value of DTDC, the vacant dwell positions were filled to make the dose distribution more homogeneous; this eventually caused increase in the number of activated dwell positions.

Total treatment time of IPSA plan decreases with an increase in DTDC value [Figure 2]. The constrained IPSA plans generally had a reduced total treatment time than unconstrained IPSA plans. For unconstrained IPSA plans, isolated dwell position had very large dwell times. Dwell times for constrained IPSA plans had total treatment time combining all dwell time lesser than the unconstrained scenario.

CTV D90% was found to be decreasing with increment in DTDC value [Figure 3]. There were 6.89% and 18.13% decrease in average CTV D90% value for DTDC 0.4 and 1.0, respectively, compared to average D90% for IPSA plan of DTDC 0.0. V100% was also reducing with increasing DTDC and rate of its reduction declined from DTDC value 0.0–0.6 and then increased till 1.0 [Figure 4].
Figure 3: Effect of increasing dwell time deviation constraint on average clinical target volume D90 (%)

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Figure 4: Effect of increasing dwell time deviation constraint on average clinical target volume V100 (%), V150 (%), and V200 (%)

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CTV V150% and CTV V200% were used for assessing the high-dose volumes in the treatment plans. [Figure 4] shows the variation of these indicators as the DTDC is increased from 0.0 to 1.0.

There were 4.37% and 11.23% decrease in average CTV V150% values for DTDC 0.4 and DTDC 1.0, respectively, compared to DTDC 0.0. There were 5.74% and 11.44% decrease in average CTV V200% values for DTDC 0.4 and DTDC 1.0, respectively, compared to DTDC 0.0. Average D2cc values for rectum and bladder [Figure 5] decrease with increasing DTDC values. There was reduction of 8.26% and 6.95% for D2cc values of rectum and bladder, respectively, for DTDC 1.0 compared to DTDC 0.0.
Figure 5: Effect of increasing dwell time deviation constraint on average D2cc rectum and bladder (%)

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 > Discussion Top


The traditional Manchester system is designed to prescribe dose to point A for various combinations of intravaginal and intrauterine source combinations, whereas the aim of inverse and manual plans is to give dose to CTV, while minimizing the dose to OAR. There have been several studies for examining the implementation of IPSA plan for carrying out cervix ICBT and interstitial BT.[16],[17],[21],[24],[25],[26],[27] This is probably the first study for investigating the effects of DTDC on IPSA plans of ICBT of cervical cancer.

One of the reasons that IPSA plan in ICBT is not implemented in most of the centers is, it creates high-dose volumes in CTV due to the formation of segregated large dwell times in catheters. A large variation of dwell times was observed with IPSA for tandem and ovoid application;[16] to overcome this problem, the use of help structures was suggested.

Nucletron Oncentra TPS has added a feature of DTDC parameter to the IPSA optimization process. This parameter controls the allowable dwell times in the optimization process and can be set to a value between 0 and 1 in increments of 0.1. A DTDC value of 0.0 corresponds to completely unrestricted dwell times and DTDC value of 1.0 results in homogeneous dwell times.[23] The DTDC parameter lessens the occurrence of large dwell times within each catheter.

The plan modulation index determined for each DTDC increment shows a reduction in the deviation observed as shown in [Figure 1]. This shows the decrease of dwell time deviation as the DTDC parameter was increased. Similar results were obtained in the study regarding the implementation of IPSA with varying DTDC values for prostate cases.[23] The plan modulation index highly depends on DTDC as seen in [Figure 1] (P = 000) and can be utilized to compare different plans for the same or different patients.

It was observed that number of dwell positions was increasing with increasing DTDC value. Increase in number of dwell positions for inverse optimization-based plans was recorded in other studies[16],[18],[19] which are in accordance with this study. DTDC forces IPSA optimization system to avoid single positions with very high dwell times and also avoids dwell time reduction to zero even if the position is not needed to cover the contoured target which eventually leads to increase in dwell positions. Increasing the DTDC value was also causing homogeneity in dwell time values; this uniformity led to reduction in localized high-dose volumes and more homogeneous dose distribution. This was evident from decrease in V150% and V200% values for DTDC value 1 compared to DTDC value 0 [P = 0.63 and 0.66, respectively, [Table 3]. Increase in high-dose volume indicated by V200% was seen in a study related to IPSA implementation in tandem and ovoid-based ICBT,[21] but it was without DTDC considerations.
Table 3: Dose-volume parameters for the clinical target volume and organ at risks

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The spatial distribution of high-dose volumes has to be taken into account by inverse optimization algorithms to avoid unexpected high doses in the parametrium or vaginal wall.[28] High doses are not undesirable, but they should be confined inside the cervix and uterus where the tumor is located. The implementation of DTDC in IPSA planning achieves this important goal.

There was decrease in D90% with increasing value of DTDC, though not significant (P = 0.28), indicating the compromise with target coverage while increasing DTDC value. D90% value for IPSA plan was compared with manual optimized plans,[16],[19],[27] with no significant change. Further inclusion of increasing DTDC decreases D90% but not significantly for ICBT cases as can be seen from this study. The ineffectiveness of DTDC on D90% was also seen in prostate cases.[29]

Rectum and bladder D2cc values were decreasing with increasing DTDC from 0 to 1, but the difference was not significant with P value of 0.49 and 0.48, respectively. IPSA with unconstrained dwell time deviation resulted in abrupt variation in the dwell time in the catheters. For these unconstrained IPSA plans, the dwell time near to a critical structure was turned off completely, while long dwell times were noticed just next to the critical structures and near to the CTV, where optimum dose was required. This leads to higher dose to rectum and bladder. In case of increasing DTDC values, which were causing lesser deviation in dwell time across the dwell positions, lower values of dwell times were allotted near to critical structures for making dwell times across the dwell positions more homogeneous. This leads to lower dose to bladder and rectum with increasing DTDC values. There are other studies indicating observed reduction of rectum and bladder D2cc doses in IPSA-based plans compared to standard Manchester-based ICBT plans.[18],[25] This study indicates that the inclusion of DTDC parameters helps in reducing D2cc dose to bladder and rectum in IPSA-based ICBT cases.

TRAK value was decreasing with increasing DTDC parameters [Figure 6]. The significant decrease in TRAK for inverse plan compared to standard Manchester-based plan is already documented.[18] Inclusion of increasing value of DTDC parameter does not stop the decrease in TRAK value as can be seen from this study. The observed decrease in TRAK implicates toward the dose sculpting characteristic of IPSA. Application of DTDC constraint for IPSA plan causes reduction of high-dose volumes in CTV and OARs but at the cost of decreased target coverage. In this regard, implementation of DTDC should be used with caution.
Figure 6: Effect of increasing dwell time deviation constraint on total reference air kerma

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 > Conclusion Top


Formation of large segregated dwell times in IPSA plan is a major reason, which restricts implementation of IPSA for ICBT of cervical cancer. Two solutions for this problem are (1) drawing help structures around the tandem and ovoid and to include them in ISPA solution and (2) implementing DTDC parameter in IPSA solution.

In this study, both the options were combined and used for reducing large dwell times in ICBT of cervical cancer. The resulting plan was with reduction in high-dose volumes in CTV and lowered doses to OARs but with decreased CTV coverage. The method used in this study gives a feasible solution for controlling high-dose volumes in general and more specifically for avoiding high-dose volumes in normal tissue. Although contouring the target volume and OARs on CT images with metal applicator is a concern, owing to the artifacts because of metal applicator, this error was minimized by adjusting the center and width feature to aid in better visualization. Furthermore, contouring was based primarily on the assessment of disease in OT and primary imaging at baseline rather than completely based on visualization on the scan with applicators. Therefore, CTV was drawn as an overcontour for all applications.

There is a further need of research for finding out optimum value of DTDC for IPSA plan of ICBT. Proper use of the DTDC parameter requires the planner to select a balance between limiting the dwell time variations while still achieving clinical dosimetric objectives.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Kolkman-Deurloo IK, Deleye XG, Jansen PP, Koper PC. Anatomy based inverse planning in HDR prostate brachytherapy. Radiother Oncol 2004;73:73-7.  Back to cited text no. 11
    
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Dewitt KD, Hsu IC, Speight J, Weinberg VK, Lessard E, Pouliot J, et al. 3D inverse treatment planning for the tandem and ovoid applicator in cervical cancer. Int J Radiat Oncol Biol Phys 2005;63:1270-4.  Back to cited text no. 14
    
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Jamema SV, Sharma S, Mahantshetty U, Engineer R, Shrivastava SK, Deshpande DD, et al. Comparison of IPSA with dose-point optimization and manual optimization for interstitial template brachytherapy for gynecologic cancers. Brachytherapy 2011;10:306-12.  Back to cited text no. 15
    
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Chajon E, Dumas I, Touleimat M, Magné N, Coulot J, Verstraet R, et al. Inverse planning approach for 3-D MRI-based pulse-dose rate intracavitary brachytherapy in cervix cancer. Int J Radiat Oncol Biol Phys 2007;69:955-61.  Back to cited text no. 16
    
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