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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 55-61

Can a low-energy photon beam be suitable for the treatment of cervical malignancies? A dosimetric analysis


1 Medical Physics Division, Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
2 Amity Institute of Applied Sciences, Amity University, Noida, Uttar Pradesh, India
3 Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India

Date of Submission09-Sep-2020
Date of Acceptance22-Oct-2020
Date of Web Publication31-Dec-2020

Correspondence Address:
Mr. Manindra Bhushan
Medical Physics Division, Radiation Oncology Department, Rajiv Gandhi Cancer Institute & Research Centre, Sector-5, Rohini, Delhi 110085.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jco.jco_30_20

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  Abstract 

Background: Radiotherapy to a patient with cervical cancer can be delivered by four-field “box technique” with a benefit of much less dose to intervening tissues along with a better and homogenous dose distribution at the target location. An important ingredient for a good radiotherapy planning is the choice of beam energy. The present study aims to investigate the feasibility of a 4 MV photon beam for the treatment of cervical cancers. Materials and Methods: A population of 20 patients, with carcinoma cervix, was included in the study. All the patients were planned for a prescribed dose of 45 Gy in 25 fractions. Results: Plans were evaluated for planning target volume and found better in terms of coverage and hot spots using 6 MV. The homogeneity index (HI) was 1.1 for both the energies. Similarly, conformity index (CI) was 2.0 depending on the method used for 4 MV and 6 MV photons. Although the HI and CI were comparable for both the plans, yet it seems significantly better for 6 MV. This indicates that spillage in 6 MV plans is lesser as compare to 4 MV. The present study reveals that there is a significant reduction in total monitor units in the plans with 6 MV photon beams, leading to fewer chances of secondary malignancies. Conclusion: A 6 MV photon beam has some proven mileage over 4 MV in terms of target coverage, dose homogeneity, and conformity and remains the best suitable photon energy for the treatment of cervical malignancies.

Keywords: Box-field, cervical malignancies, intensity-modulated radiotherapy, photon, radiation


How to cite this article:
Bhushan M, Tripathi D, Kumar L, Chowdhary RL, Kakria A, Kumar P, Mitra S, Gairola M. Can a low-energy photon beam be suitable for the treatment of cervical malignancies? A dosimetric analysis. J Curr Oncol 2020;3:55-61

How to cite this URL:
Bhushan M, Tripathi D, Kumar L, Chowdhary RL, Kakria A, Kumar P, Mitra S, Gairola M. Can a low-energy photon beam be suitable for the treatment of cervical malignancies? A dosimetric analysis. J Curr Oncol [serial online] 2020 [cited 2021 Jan 19];3:55-61. Available from: https://www.journalofcurrentoncology.org/text.asp?2020/3/2/55/305851




  Background Top


Carcinoma of the cervix is the second[1],[2] most common cancer in India and third[3],[4] most common malignancy worldwide. Owing to increased health awareness, the mortality rates of cervical cancer have come down significantly but a lot needs to be done as it still remains a threat in developing countries.

External beam radiotherapy forms the backbone of curative treatment in locally advanced tumors. The traditional approach for treating carcinoma cervix remains a two-field technique using antero-posterior and posteroanterior portals in case of less obese patients.[5] But this technique not only delivers unnecessary dose to all the critical structures coming in the beam path such as bladder, rectum, and subcutaneous tissue, but inferior dose distribution in the region of the parametrium. Alternately, a technique which overcomes the shortcoming of two field technique is “box technique.” In this technique, a total of four fields are used, two lateral plus anterior and posterior fields, due to which the intervening tissues get a much less dose with homogenous dose at the tumor location.[6]

An important ingredient for a good radiotherapy planning is the choice of beam energy. The common choice of beam energy is 6 MV for most of the treatment sites. This choice in beam energy is backed up by a plethora of published literature pertaining specifically to gynecological malignancies in their studies. Tyagi et al.,[7] Yadav et al.,[8] and Kumar et al.[9] have also found that 6 MV is the most suitable photon energy for the treatment of carcinoma cervix.

The use of higher photon energy has some drawbacks of neutron production. Besides having a drawback of neutron production, it has been shown that the use of higher beam energy can result in up to 40% rise in collimator leaf leakage when compared with 6 MV beam energy. Huq et al.[10] measured average leakage ~2.5% and 3.5% for 6 MV and 25 MV, respectively. Increased leakage results in higher radiotherapy doses delivered to normal tissues; consequently, increase the chances of secondary malignancies. An increase in secondary malignancies due to radiation leakage has made the selection of beam energy in radiotherapy planning all the more imperative. However, it is a matter of discussion among the different practitioners to use lower photon energy and its impact on tumor targets and normal healthy tissues.

The choice of an accurate treatment calculation algorithm is another crucial aspect of radiotherapy planning which can have a large effect on dose distribution. Convolution-superposition, pencil-beam-convolution, collapsed-cone, analytical-anisotropic-algorithm, Acuros-XB, and Monte Carlo are different commercially available algorithms in the treatment planning systems (TPSs). Monte Carlo algorithm is considered as gold-standard among all the algorithms due to increased accuracy. Plans were optimized and calculated using the “Monte Carlo” algorithm. The TPS is designed in such a way that it optimized the plan in the first phase using pencil-beam convolution (PBC) algorithm and then the output is “segmented” and “calculated” in the second phase using the “Monte Carlo” algorithm.

The present study aims to investigate whether 4 MV photon energy offers a better target coverage and healthy tissue sparing as compared to 6 MV. 4 MV photon energy is commercially available in Elekta Synergy Platform, Varian Clinac 600CD/6EX, and Varian Clinac 600C/CD linear accelerators. We have evaluated the impact of photon beam energy on the treatment plan quality in carcinoma cervix using the box technique.


  Materials and Methods Top


Ethical approval

The study has been approved by the Institutional Review Board and Ethics Committee of Rajiv Gandhi Cancer Institute and Research Centre (Ref: Res/SCM/43/2020/116) and it confirms with provisions of the Declaration of Helsinki.

Patient selection

A population of 20 patients, with carcinoma cervix, was included in the study. These patients had received the treatment with 6 MV photon energy. These plans were recalculated for 4 MV photon energy and evaluated for the present study.

Simulation and target delineation

Tomographic scans were done for all the patients on our computed tomographic unit (Siemens Somatom sensation open) to avoid any geographical miss in contour delineation.[11] All the patients were immobilized using a thermoplastic mask (POCL orfit). The scans were obtained in the supine position with a slice thickness of 2.5mm. The acquired images were transferred to contouring workstations in DICOM (Digital Image Communication) format. A study by Russel et al.,[12] highlighted the importance of pelvic magnetic resonance imaging (MRI) in the placement of pelvic portals of the box technique. MRI scans were used as inputs in the contouring process by fusing them with planning CT scans for better delineation of the target and other volumes at risk.

MONACO SIM (Elekta medical systems Inc., Version 5.0) contouring station was used to contour planning target volume (PTV) and other organs at risk (OARs). The scans were taken from the L2 vertebral body to 5 cm below the ischial tuberosities [Figure 1]. Fiducial markers were placed on the patient on orfit cast before CT scan acquisition. As per the institutional policy of “bladder protocol,” the patient was asked to drink 500mL of water and wait for ~40min prior to CT scan and daily routine treatment.
Figure 1: Delineation of PTV and OARs

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The tumor targets and critical structures were marked by a radiation oncologist as per International Commission on Radiation Units and Measurements (ICRU) and Radiotherapy Oncology Group (RTOG) recommendations.[13],[14] Gross tumor volume (GTV) and clinical target volume (CTV) were delineated and an isotropic margin of 1 cm was given to generate the PTV.[15],[16],[17] Margin to PTV can be reduced with the help of effective immobilization and an on-table imaging facility.[18] The margin was not reduced due to the on-board “Mega-Voltage (MV) imaging” facility, used for patient setup.

Treatment planning parameters

All the patients were planned for a prescribed dose of 45 Gy in 25 fractions with a daily session dose limit of 1.8 Gy. Our treatment planning goal was to cover 98% prescription dose to 98% of PTV volume, i.e. 98% PTV volume should be covered by at least 98% of dose prescribed. The dose to bladder, rectum, and bowel was restricted in such a manner that there should not be any hot spot (dose more than 107% of prescription dose) lying on them. Dose to femoral heads was kept as low as possible.

All the treatment plans were generated on MONACO (Elekta medical systems, Version 5.0) TPS using gantry angles 0°, 180° , 90°, and 270° with collimator 0° and couch 0°. Beam arrangements were kept the same to analyze the effect of different energies. Our linear accelerator (Linac) (synergy platform; Elekta medical systems) is capable of generating photon beams of 4 and 6 MV energies. None of the patients was treated using 4 MV photon energy due to the retrospective nature of our study. The multi-leaf-collimator (MLC) facilitates the treatment planner to shape the target accurately as per beam-eye-view (BEV). Our Linac is equipped with 80 MLC leaves (maximum field size: 40 cm × 40 cm and leaf thickness: 1 cm).

To achieve an optimized output, the planner may play with the beam weights but we have not changed any parameter to maintain comparability with 6 MV photon energy plans.

Plan evaluation parameters

PTV was evaluated for D98 (dose to 98% volume of PTV), D2 (dose to 2% volume of PTV), D50 (dose to 50% volume of PTV), Dmax (maximum dose to PTV), Dmean (average dose received by PTV), V107% (percentage volume of PTV receiving 107% of dose prescribed), and V110% (percentage volume of PTV receiving 110% of dose prescribed).

Conformity index (CI) is a criterion which quantifies the relation between isodoses and delineated structures by geometric intersection methods. The evaluation of different conformity indices provides information about the homogeneous distribution of dose with the target. Following formulae were used to calculate the CI and homogeneity index (HI).

Conformity indices

Conformity number (CN)[19]:



where TVRI is target volume covered by the reference isodose (98%), TV is volume of tumor target, VRI is volume of reference isodose, i.e. 98%.

CI_RTOG (CIRTOG)[20]: {VRI/TV} and CI_ healthy tissue (CIHT)[21]: {TVRI/VRI}

CN includes the fraction of target coverage and the fraction of volume of nontumorous tissues obtaining a dose more or equal to the dose prescribed. It varies from 0 to 1 (from “no spatial concordance” to “perfect conformation”). Lomax and Scheib[21] highlighted that the CI should be at least 0.6 for conformal plans.

Homogeneity indices



where Imax is maximum isodose in the target and RI is reference isodose.

As per literature published by Semenenko et al.,[24] the ideal value of HI is 1 and it increases as the plan becomes less homogeneous. As per recommendations of RTOG, the value of HI has certain interpretations like HI ≤ 2.0, treatment plan stands with protocol but the value, 2.0 ≤ HI ≤ 2.5 shows minor violation, and HI ≥ 2.5 shows major violation from the standards.

Bladder and rectum were evaluated for Dmax (maximum dose received by respective organ), Dmean (mean dose received by respective organ), D2cc (dose received by 2 cc volume of a respective organ), V45Gy (percentage volume of respective organ receiving 45 Gy), and V50Gy (percentage volume of respective organ receiving 50 Gy).

Parameters evaluated for bowel were V5Gy (percentage volume of particular organ receiving 5 Gy), V30Gy (percentage volume of particular organ receiving 30 Gy), Dmean (mean dose received by particular organ), and V15Gy (percentage volume of particular organ receiving 15 Gy). Mean dose to femoral heads and total monitor units (TMUs) were also evaluated.

Statistical analysis

SPSS (Statistical Package for the Social Sciences; version 20.0) software, designed in Chicago (USA), was used to analyze the data. For comparing means, a paired t-test was used for normally distributed data and Wilcoxon signed rank test was used for data that were not normally distributed. The normal distribution of the data was checked using the “Shapiro–Wilk” test (numerical method) and the quantile–quantile (Q–Q) plot (graphical method). P-value of <0.05 was considered significant and <0.05 on the Shapiro–Wilk test was considered to be not normally distributed.


  Results Top


Dosimetric analysis was carried out for all the isocentric plans made for selected 20 patients using 4 MV and 6 MV photon energies, respectively. Dose–volume histograms (DVHs) were compared and results were tabulated.

DVH analysis of PTV and OARs

Plans were evaluated for PTV and different OARs based on pre-selected parameters [Figure 2]. Plans were better in terms of coverage and hot spots for the PTV using 6 MV. D98% was 44.22 ± 0.20 Gy and 44.51 ± 0.13 Gy for 4 and 6 MV, respectively. D2% was 50.26 ± 1.11 Gy and 49.05 ± 0.76 Gy for 4 and 6 MV, respectively. The value of D50% was 47.77 ± 0.71 Gy and 46.85 ± 0.55 Gy for 4 and 6 MV, respectively. 6 MV has shown significantly better results in terms of all the parameters chosen as compare to the 4 MV beam [Table 1].
Figure 2: Dose–volume histogram (DVH)

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Table 1: Evaluation of PTV parameters using 4 and 6 MV photon beam

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D50Gy for the bladder and rectum for 4 and 6 MV treatment plans were significantly superior for 6 MV (P = 0.003 and P = 0.033) and tabulated as 8.47 ± 19.71, 2.17 ± 7.09, 11.38 ± 22.16, and 4.35 ± 11.32%, respectively. Similarly, low-dose parameter D5Gy for the bowel was 89.08 ± 14.71 and 88.01 ± 15.09% for 4 and 6 MV, respectively, and was significantly better for 6 MV (P = 0.001) [Figure 3]. The mean dose to femoral heads was comparable in both the plans [Table 2].
Figure 3: Dose coverage of 100% and 95% of the prescription dose

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Table 2: Dosimetric analysis of OARs

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HI, CI, and TMU

HI was either 0.1 or 1.1 for both the energies. Similarly, CI varied from 0.5 to 2.0 depending on the method used for 4 and 6 MV photons. In all the cases, the 6 MV photon beam has shown significantly better results as compare to the 4 MV beam. Monitor units required to deliver the plan were 273.67 ± 20.24 and 243.13 ± 14.68 MU for 4 and 6 MV, respectively, and were ~11% lesser for 6 MV treatment plans (P = 0.001) [Table 3].
Table 3: CI, HI, and TMU

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  Discussion Top


Intensity-modulated radiotherapy is an advanced technique in radiotherapy practice to deliver the conformal dose to the patients undergoing pelvic radiation. Mutrikah et al.[5] also recommended 3D RTP, for pelvic irradiation, to decrease uncertainties in radiation planning and treatment delivery. The advancement of technology has some benefits but not without its share of disadvantages. In these techniques, treatment planners have the freedom to place the beams from different gantry directions and modulated optimized plans are delivered with the help of MLC motions (either step-and-shoot or dynamic movement) for the treatment of patients with a different diagnosis. But the biggest drawback with these techniques is the geographic or anatomic miss during the treatment. One can rely on the setup verification procedure which helps in reducing the PTV margins but even minor errors in target delineation can lead to persistence or recurrence of a disease. Even the very recent volumetric modulated arc-therapy has the similar drawbacks of geographic miss and has more chances of secondary malignancies due to low-dose contribution as integral dose.

Deposition of unwanted doses to healthy tissues might enhance the chances of secondary cancers. Available literature also describes a possible correlation between integral dose and secondary malignancies.[25],[26]

D’Souza et al.[27] reported that beam portal and beam energy are the most important factors in reducing normal tissue integral dose (NTID). As per the study conducted by Slosarek et al.,[28] the lowest integral dose was recorded when the VMAT technique with beams of 20 MV photon energy was used. He suggested that the integral dose to normal structures increases with advanced techniques like cyber-knife and tomotherapy.

Four-field “box technique” has the advantage of proper coverage of tumor target at cost of some more doses to nearby critical organs. This reduces the probability of recurrence of in-field disease. Thakur et al.[29] also highlighted that box technique for cervical carcinoma can be utilized to improve dose homogeneity with the help of accurate portals and proper margins.

As per recommendations of ICRU 50, variation within 95% to 107% of the prescription dose is permissible for the tumor target volume.[13] However, a variation of ±10% is widely accepted for most of the clinical practices.[30] Due to the inherent limitations of box technique, treatment plans were finalized with spots of more than 110% prescription dose. Researchers[31],[32] have recommended that 110% and 115% of prescribed dose should not exceed 20% and 2%, respectively, in IMRT. The V110% and V115% criteria used for IMRT plans were extrapolated to the conformal radiation therapy (CRT) plans as there is no literature available on conventional planning for the same plan parameters to the best of our knowledge. Furthermore, in the plans finalized in the CRT group, the high-dose regions (V110% or higher) were confined within the CTV volumes delineated by the radiation oncologist to minimize the damage to surrounding OARs. V110% inside the PTV was kept below 20% as cited across various previous publications.[33] The latter criterion of 115% was not evaluated in our study. We have evaluated 107% and 110% of the prescribed dose and were resulted as 34.39 ± 17.52%, 12.73 ± 14.35%, 9.35 ± 14.86%, and 2.53 ± 6.58% for 4 and 6 MV, respectively. 6 MV photon beam was significantly superior in terms of both the parameters. Although the HI and CI were comparable for both the plans, yet it seems significantly better for 6 MV. This indicates that spillage in 6 MV plans is lesser as compare to 4 MV.

The use of higher photon beam energy might be a point for discussion for the patients undergoing treatment of carcinoma cervix, but the existing literature suggests that in the backdrop of increased neutron production leading to higher chances of secondary malignancies using beam energies beyond 10 MV may not be a prudent idea.[34],[35]

Sternick et al.[36] noted that there is no significance of using different photon energies ranging from 4 to 18 MV with the use of intensity modulation technique which is similar to our findings. Similarly, the use of tele-cobalt beam gives a more peripheral dose to the patient which is also not suitable for this purpose.

Total numbers of monitor units (MUs) are also very important factors in patient treatment. More monitor units prolong the treatment and increase the intra-fraction errors[37] which finally led to inaccuracies in treatment delivery. The present study reveals that there is a significant reduction in TMUs in the plans with 6 MV photon beams.

Limitation

The limitation of the present study is that it is a dosimetric study and correlation with clinical evidence needs to be assessed.


  Conclusion Top


The four-field “box-technique” is a time-tested standard planning technique for the treatment of carcinoma cervix. 6 MV photon beam has some proven mileage in terms of target coverage, dose homogeneity, and plan conformity over 4 MV and remains the best suitable photon energy for the treatment of cervical cancers.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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