Evaluating the influence of 6MV and 10MV photon beams on cervical cancer volumetric-modulated arc therapy plans

Abstract

BACKGROUND:

Cervical cancer is a common gynecological cancer among women worldwide.

OBJECTIVE:

To determine the effects of 6 MV and 10 MV volumetric-modulated arc therapy (VMAT) photon beams on the target volume (TV) planning and critical organs in cases of cervical cancer.

METHODS:

Fifty patients with carcinoma of the cervix who underwent radiotherapy were selected. The transverse diameter (T) of the cross section of the upper edge of the sacroiliac joint on computerized tomography (CT) images of the patients was measured, and the mean value was calculated as 34 cm. All patients were divided into two groups: Group A (T $<$ 34 cm) and Group B (T $>$ 34 cm). The VMAT plans were generated using 6 MV and 10 MV plans separately. The prescription dose was 47.5 Gy, and the daily dose was 1.9 Gy.

RESULTS:

In Group A, the planning target volume (PTV) dose assessment parameters of 6 MV and 10 MV plans and their homogeneity and conformity indices were not statistically significantly different. A significant difference was observed between the 6 MV and 10 MV plans for the PTV dose assessment parameters and the homogeneity index of the plans for Group B. The monitor units (MUs) of the 10 MV plans were lower than in the 6 MV plans in both Groups A and B, and the difference was statistically significant. The assessment parameter V ${}_{\textit{40 Gy}}$ of both the rectum and bladder in the 6 MV plans was smaller than the corresponding parameter in the 10 MV plans in Group A; in Group B, the assessment parameter $V_{\textit{50 Gy}}$ of the rectum in the 10 MV plans was smaller than in the 6 MV plans.

CONCLUSION:

When T $<$ 34 cm, 6 MV energy is more suitable for the external irradiation of cervical cancer. When T $>$ 34 cm, 10 MV energy is more suitable for cervical cancer radiotherapy. Therefore, 10 MV should be considered for patients with a large abdominal size.

Keywords

Volumetric-modulated arc therapy cervical cancer transverse diameter 6 MV 10 MV

1. Introduction

Cervical cancer is a common gynecological cancer among women worldwide [1]. Women in developing countries are mostly affected by this type of cancer, and it is the primary cause of cancer-related deaths in women [2]. External beam radiotherapy (EBRT) is accepted as a standard of care for the management of cervical cancer worldwide [3]. The purpose of external radiotherapy for cervical cancer is to achieve an optimal balance between maximizing the doses to the tumor and minimizing the risk of side effects and long-term complications to organs at risk (OARs). One of the fundamental challenges in radiation therapy is the selection of appropriate energy for implementing an effective therapeutic plan and delivering high-quality treatment. In addition, selecting the appropriate energy for dose calculations depends on several factors, including the depth of the tumor, the homogeneity or heterogeneity of the tissue, the density of the tumor, and the presence of normal tissue located on the radiation beam’s path [4, 5].

Several prospective and observational studies have shown that middle-aged women (40–60 years) tend to gain weight, especially abdominal fat, with a shift toward visceral fat distribution [6, 7, 8].

The plan evaluation of volumetric-modulated arc therapy (VMAT) is similar to that of intensity-modulated radiation therapy (IMRT), as described by Karl Otto [9]. A multi-leaf collimator (MLC) alters the shape of the treatment field as the gantry rotates around the patient dynamically. The VMAT reported by many authors was a superior delivery method for an equivalent dosimetric quality using fewer monitor units (MUs) compared with IMRT and three-dimensional conformal radiation therapy technologies [10, 11, 12]. Compared with IMRT, VMAT has shown superiority in protecting OARs, and its target volume (TV) coverage has equaled or bettered that of IMRT in EBRT for cervical cancer [13, 14].

This study was designed to compare the dosimetric effects of different photon beam energies in the treatment of carcinoma of the cervix with an increase in female weight, mainly in terms of the accumulation of abdominal fat.

2. Material and methods

The abdominal posture of a patient can be observed intuitively using positioning computerized tomography (CT) images. In this study, the length of the transverse diameter (T) at the upper sacroiliac joint cross section in the CT images of patients with cervical cancer was used as a reference to study the relationship between the length of the transverse diameter and the selection of radiotherapy energy.

2.1 Population of patients

This retrospective analysis was reviewed and approved by the institutional review board of Huai’an First Hospital. This retrospective planning study included 50 patients who were treated for cervical cancer at the Department of Radiation Oncology of the Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University from January 2017 to March 2020. All patients underwent a CT simulation (PHILIPS Brilliance Big Bore CT) in a supine position. The CT images were acquired with a slice thickness of 3 mm. Subsequently, the CT images were transmitted to a Monaco workstation (Elekta, Atlanta, GA, USA). The average measurement of the T of the cross section of the upper edge of the sacroiliac joint on the patients’ CT images was 34 cm.

2.2 Target and organs at risk delineation

The Monaco workstation was used to delineate the TV and OARs for all patients. The clinical TV (CTV) included the lymph node regions (common iliac, external iliac, internal iliac, presacral, and obturator), uterus, adnexa, and vagina. A margin of 0.7 cm was given to the CTV to generate the planning target volume (PTV). The bladder, rectum, small intestine, and femoral head were outlined. The contour of the bladder from the apex to the dome was drawn, while the rectum was contoured from the anus (at the inferior level of the ischial tuberosity) to the rectosigmoid junction. The contours of the bilateral femoral heads were drawn up to the level of the ischial tuberosity [15].

2.3 Treatment planning

The 6 MV and 10 MV beam energy treatments were delivered on a Versa HD linear accelerator (Elekta, Atlanta, GA, USA) with a 160 MLC. The MU calibration was performed according to the International Atomic Energy Agency’s report no. 398. The VMAT plans were generated retrospectively using the Monaco 5.1.1 treatment planning system (Elekta, Atlanta, GA, USA). All VMAT plans consisted of two arcs with a 360 ${}^{\circ}$ gantry rotation. Each plan was designed by the Monte Carlo algorithm using a calculation grid size of 3 mm. The statistical uncertainty per calculation was 1%. The prescription dose was 47.5 Gy, with a daily dose of 1.9 Gy. It was stipulated that not less than 98% volume of the PTV should receive a dose less than the prescribed dose, and not more than 2% volume of the PTV should receive a dose of more than 110% of the prescription dose. For the OAR, critical structure constraints followed the Radiation Therapy Oncology Group’s 1203 guidelines [16]. The optimized parameters used for the OARs are shown in Table 1.

Table 1
The optimized parameters used for OARs

OARs	Parameters
Bladder	V ${}_{\textit{45 Gy}}<$ 50%
Rectum	V ${}_{\textit{45 Gy}}<$ 50%
Intestine	$D_{2\%}<$ 50 Gy
Femoral heads and necks	V ${}_{\textit{50 Gy}}<$ 10%

OARs: Organs at risk.

Both the 6 MV and the 10 MV beam energy plans, which we retrospectively created, were used for research purposes only. To ensure that the similarity or difference between the studied plans was only due to the level of energy, the same optimization constraints were applied to all energy plans, while all the other parameters remained constant.

3. Dose-volumetric analysis

Plan quality assessments were conducted based on different dosimetric parameters of the PTV and OARs. A cumulative dose – volume histogram (DVH) was generated by the Monaco Treatment Planning System to evaluate different dosimetric parameters of the PTV and OARs.

According to the International Commission on Radiological Units and measurement’s report no. 83 [17], the PTV dose assessment compares the maximum dose D ${}_{2\%}$ (which represents the dose received by $\leqslant$ 2% of the PTV volume), the average dose D ${}_{\textit{mean}}$ , and the minimum dose D ${}_{98\%}$ (which represents the minimum dose received by 98% of the PTV volume).

The DVH parameters were also analyzed for the normal structures of the bladder, rectum, and intestine. The 6 MV and 10 MV plans were compared for the bladder and rectum in terms of D ${}_{\textit{mean}}$ and V ${}_{\textit{30 Gy}}$ , V ${}_{\textit{40 Gy}}$ and V ${}_{\textit{50 Gy}}$ , where V ${}_{\textit{30∼{}Gy}}$ , V ${}_{\textit{40∼{}Gy}}$ , and V ${}_{\textit{50∼{}Gy}}$ were the dose volumes of 30 Gy, 40 Gy, and 50 Gy, respectively, for the OARs. The 6 MV and 10 MV plans were compared for the intestine in terms of $D_{2\%}$ and $D_{\textit{mean}}$ .

3.1 Conformity index

The conformity index (CI) evaluates the degree of conformity of resulting dose distributions for both groups. The CI was calculated, as follows [18, 19]:

$\displaystyle\textit{CI}=\left({\textit{TV}_{\textit{PI}}^{2}}\right)/\left(% \textit{TV}\times V_{\textit{PI}}\right),$ (1)

where $\textit{TV}_{\textit{PI}}$ represents the TV receiving the prescription dose, TV represents the total TV, and $V_{\textit{PI}}$ represents the total volume receiving the prescription dose (47.5 Gy). The closer the CI is to 1, the more conformal the target dose distribution.

3.2 Homogeneity index

The homogeneity index (HI) was evaluated to find the homogeneity of dose distribution within the PTV. The HI was calculated, as follows [20]:

$\displaystyle\textit{HI}=(D_{2\%}-D_{98\%})/D_{50\%},$ (2)

where $D_{50\%}$ represents the dose covering 50% of the PTV. An ideal value of 0 represents complete homogeneity within the PTV.

3.3 Normal tissue integral dose

The normal tissue integral dose (NTID) was calculated to determine the dose to normal tissues outside the PTV (Body-PTV). Integral doses were calculated to analyze the plan quality based on the following formula considering uniform tissue density [21, 22]. These were compared in terms of doses to the volumes of $D_{2\%}$ , $D_{5\%}$ (which represents the dose received by 5% of the PTV), and volumes of 2 Gy ( $V_{\textit{2 Gy}}$ ), and 5 Gy ( $V_{\textit{5 Gy}}$ ) for normal tissues.

$\displaystyle\text{NTID}=D_{\textit{mean}}\times\text{volume of normal tissue % outside the PTV}.$ (3)

The 50 patients were divided into two groups: T $<$ 34 cm for Group A ( $n=$ 27) and T $>$ 34 cm for Group B ( $n=$ 23).

The data in this paper were expressed as mean $\pm$ SD, and a data analysis was performed using nonparametric tests (the Wilcoxon signed-rank test) to determine the dose-volumetric differences for the 6 MV vs. 10 MV plans of Groups A and B. All analyses were performed using the SPSS Statistics package (version 21, IBM Corp., USA).

4. Results

4.1 General patient information

All 50 patients (26–76 years of age) who were treated for cervical cancer from January 2017 to March 2020 were included. The T of the cross section of the upper edge of the sacroiliac joint on the patients’ CT images was measured. It ranged from 27.39 to 42.2 cm, with an average of 34 cm. The distribution of T is shown in Fig. 1.

4.2 Planning target volume

The plan evaluations showed a similar dose coverage to the PTV for both the 6 MV and 10 MV energies. The average PTV in the present study was 1,222 $\pm$ 243 cm ${}^{3}$ and 1,491 $\pm$ 363 cm ${}^{3}$ for Groups A and B, respectively. In Group B, a significant difference ( $p<$ 0.05) was observed between the 6 MV and 10 MV plans for $D_{2\%}$ and $D_{\textit{mean}}$ . The $D_{2\%}$ and $D_{\textit{mean}}$ of the PTV for the 10 MV plans were less than in all the 6 MV plans for Group B (Table 2). Similarly, the HI was significantly different ( $p<$ 0.05) between the 6 MV and 10 MV plans for Group B. The MUs results also followed a similar pattern ( $p<$ 0.05) for the 6 MV and 10 MV plans. The MUs and NTID results showed a significant difference ( $p<$ 0.05) for the 6 MV and 10 MV plans for Groups A and B. The CI values of the two groups were not statistically significantly different.

Table 2
PTV dose distribution of VMAT plan for group A and group B with different photon energies ( $\bar{x}\pm s$ )

	Group A ( $n=$ 27)				$P$	Group B ( $n=$ 23)				$P$
	6 MV		10 MV			6 MV		10 MV
PTV/D ${}_{2\%}$ (Gy)	50.77	$\pm$ 0.3	50.69	$\pm$ 0.34	0.337	50.87	$\pm$ 0.35	50.63	$\pm$ 0.36	0.001
PTV/D ${}_{98\%}$ (Gy)	46.98	$\pm$ 0.09	46.97	$\pm$ 0.09	0.325	46.9	$\pm$ 0.34	46.99	$\pm$ 0.1	0.083
PTV/mean(Gy)	49.02	$\pm$ 0.17	49.01	$\pm$ 0.2	0.885	49.09	$\pm$ 0.21	48.99	$\pm$ 0.21	0.007
HI	0.077	$\pm$ 0.007	0.076	$\pm$ 0.008	0.581	0.081	$\pm$ 0.012	0.074	$\pm$ 0.009	0.001
CI	0.93	$\pm$ 0.014	0.93	$\pm$ 0.017	0.946	0.92	$\pm$ 0.026	0.92	$\pm$ 0.024	0.904
MUs	1116.5	$\pm$ 112.17	1064.06	$\pm$ 109.52	0.004	1198.74	$\pm$ 153.86	1136.9	$\pm$ 126.19	0.018
NTID(10 ${}^{5}$ ccGy)	2.32	$\pm$ 0.4	2.29	$\pm$ 0.4	0.003	3.23	$\pm$ 0.77	3.18	$\pm$ 0.74	0.001

PTV: Planning target volume; VMAT: Volumetric-modulated arc therapy; HI: Homogeneity index; CI: Conformity index; MUs: Monitor Units; NTID: Normal tissue integral dose.

Figure 1.

The transverse diameter (T) distributionof the cross-section of the upper edge of the sacroiliac joint on CT images of the patients.

4.3 Organs at risk

4.3.1 Rectum

The $V_{\textit{40 Gy}}$ of the rectum was significantly less ( $p<$ 0.05) in the case of the 6 MV plans compared with the 10 MV plans in Group A, while the V ${}_{\textit{50 Gy}}$ of the rectum in the case of the 10 MV plans was smaller than in the 6 MV plans in Groups A and B, although this was not statistically significant (Table 3).

Table 3
OARs dose distribution of VMAT plan for group A and Group B with different photon energies ( $\bar{x}\pm s$ )

	Group A ( $n=$ 27)				$P$	Group B ( $n=$ 23)				$P$
	6 MV		10 MV			6 MV		10 MV
Rectum
Mean(Gy)	41.57	$\pm$ 2.82	40.12	$\pm$ 8.31	0.381	38.73	$\pm$ 8.91	38.77	$\pm$ 8.89	0.685
$D_{5\%}$ (Gy)	49.75	$\pm$ 0.58	49.69	$\pm$ 0.44	0.313	49.55	$\pm$ 0.67	49.35	$\pm$ 0.52	0.073
V ${}_{\textit{30 Gy}}$ (%)	86.25	$\pm$ 8.8	87.34	$\pm$ 7.85	0.290	82.51	$\pm$ 12.16	83.16	$\pm$ 11.47	0.078
V ${}_{\textit{40 Gy}}$ (%)	66.44	$\pm$ 12.16	67.67	$\pm$ 12.11	0.004	61.51	$\pm$ 14.37	61.52	$\pm$ 14.27	0.964
V ${}_{\textit{50 Gy}}$ (%)	4.4	$\pm$ 3.72	3.59	$\pm$ 3.75	0.316	3.41	$\pm$ 4.12	1.89	$\pm$ 2.47	0.050
Bladder
Mean(Gy)	38.71	$\pm$ 2.67	37.47	$\pm$ 7.31	0.737	39.2	$\pm$ 4.8	39.25	$\pm$ 4.78	0.715
$D_{5\%}$ (Gy)	49.88	$\pm$ 0.4	49.83	$\pm$ 0.43	0.597	49.62	$\pm$ 0.84	49.66	$\pm$ 0.6	0.181
V ${}_{\textit{30 Gy}}$ (%)	73.48	$\pm$ 10.28	74.12	$\pm$ 10.97	0.059	75.52	$\pm$ 16.98	75.94	$\pm$ 16.23	0.308
V ${}_{\textit{40 Gy}}$ (%)	55.14	$\pm$ 11.45	55.73	$\pm$ 11.47	0.006	58.49	$\pm$ 18.52	58.79	$\pm$ 18.49	0.080
V ${}_{\textit{50 Gy}}$ (%)	5.05	$\pm$ 3.57	4.46	$\pm$ 3.78	0.407	4.55	$\pm$ 3.49	4.16	$\pm$ 4.67	0.224
Intestine
$D_{2\%}$ (Gy)	48.68	$\pm$ 2.03	48.75	$\pm$ 1.73	0.773	48.66	$\pm$ 2.17	48.65	$\pm$ 1.69	0.236
Mean(Gy)	25.37	$\pm$ 4.96	25.58	$\pm$ 5	0.068	24.64	$\pm$ 4.59	24.69	$\pm$ 4.61	0.648
Body-PTV
$D_{2\%}$ (Gy)	41.82	$\pm$ 2.02	42.17	$\pm$ 2.11	0.002	41.66	$\pm$ 2.05	42.05	$\pm$ 1.84	0.004
$D_{5\%}$ (Gy)	35.11	$\pm$ 2.1	35.54	$\pm$ 2.4	0.007	34.71	$\pm$ 2.7	34.87	$\pm$ 2.7	0.236
V ${}_{\textit{2 Gy}}$ (%)	59.99	$\pm$ 14.05	59.66	$\pm$ 12.81	0.013	61.79	$\pm$ 12.48	61.4	$\pm$ 12.4	0.000
V ${}_{\textit{5 Gy}}$ (%)	51.71	$\pm$ 12.28	51.03	$\pm$ 12.26	0.001	52.57	$\pm$ 11.13	52.26	$\pm$ 11.16	0.012

OARs: Organs at risk; VMAT: Volumetric-modulated arc therapy; PTV: Planning target volume.

4.3.2 Bladder

The doses evaluated for the bladder in each plan were within tolerance. The percentage volumes of the bladder receiving V ${}_{\textit{40 Gy}}$ were significantly less ( $p<$ 0.05) in the case of the 6 MV plans compared with the 10 MV plans in Group A. Compared with the 6 MV plans, the V ${}_{\textit{50 Gy}}$ and the D ${}_{5\%}$ of the bladder for the 10 MV plans in Groups A and B were reduced, but the reduction was not statistically significant (Table 3).

4.3.3 Small intestine

The parameters of the small intestine showed no significant difference between the 6 and 10 MV plans in the two groups (Table 3).

4.3.4 Integral dose and low-dose evaluation for normal tissues

The 10 MV plans delivered a lower NTID compared with the 6 MV plans in Groups A and B (Table 2), and the difference was statistically significant. For low-dose volumes of normal tissue, the $D_{2\%}$ , $D_{5\%}$ , V ${}_{\textit{2 Gy}}$ , and V ${}_{\textit{5 Gy}}$ of normal tissues were calculated from the DVH and are summarized in Table 3. The $D_{2\%}$ and $D_{5\%}$ were significantly lower ( $p<$ 0.05) for the 6 MV plans compared with the 10 MV plans in Group A, and the $D_{2\%}$ was significantly lower ( $p<$ 0.05) for the 6 MV plans compared with the 10 MV plans in Group B. Apart from this, the V ${}_{\textit{2 Gy}}$ and V ${}_{\textit{5 Gy}}$ were significantly lower ( $p<$ 0.05) for the 10 MV plans in comparison with the 6 MV plans in Groups A and B.

5. Discussion

Treatment decisions for every patient are based on an analysis of the benefits versus the risks. Clearly, the choice of energy is important when designing a radiotherapy plan. Pirzkall et al. [23] researched the number of beams and the effect of the energy on normal tissues outside the target for the treatment of deep tumors using IMRT. They concluded that the energy selection had a significant influence on the dose distribution in the 1-cm outer edge area around the target. Even when using 9-field IMRT, higher energies should be used to reduce the dose to normal tissues and the risk of subsequent effects. Followill et al. [24] found that higher energy is preferred to reduce subsequent low-dose effects in normal tissues in the IMRT of pelvic and thoracic tumors.

In this study, the MUs of the 10 MV plans were lower than in the 6 MV plans in both Groups A and B, which was statistically significant. Additionally, the NTID and the low-dose volume (V ${}_{\textit{2 Gy}}$ , V ${}_{\textit{5 Gy}}$ ) of normal tissues in the 10 MV plans were both lower than in the 6 MV plans. It has been reported that the increase in the NTID is a potential risk factor for the development of secondary malignancies [25, 26]. The NTID can be reduced by increasing the beam energy [21], and our findings agree with the conclusions of the abovementioned studies. In addition, the D ${}_{2\%}$ of the Body-PTV of the 6 MV plans was significantly lower than in the 10 MV plans.

The dosimetric data did not show any statistically significant difference ( $p>$ 0.05) for target coverage for the 6 MV plans and the 10 MV plans in Group A (Table 2). In Group B, the $D_{2\%}$ and the $D_{\textit{mean}}$ of the PTV in the 10 MV plans were significantly lower than in the 6 MV plans. Kim et al. [27] reported similar findings and concluded that an increased mean target dose indicated homogeneity decreases. The present study also observed that the 10 MV plans had a lower HI than the 6 MV plans for Group B ( $p<$ 0.05), which means that the 10 MV plans had better homogeneity.

In this paper, data from the OARs (the bladder, rectum, and intestine) in Group A showed that the rectum V ${}_{\textit{40 Gy}}$ and bladder V ${}_{\textit{40 Gy}}$ in the 6 MV plans were both smaller than in the 10 MV plans, and the differences were statistically significant. In Group B, the rectum $D_{5\%}$ and V ${}_{\textit{50 Gy}}$ in the 10 MV plans were both smaller than those in the 6 MV plans, and the differences were statistically significant. Other assessment parameters had no statistical significance in either Group A or B.

Our study is not without limitations. It used a small sample size and was a single-institute investigation, which likely limited our statistical power to detect significant differences in some of the body composition measurements and outcomes. Furthermore, the length of the longitudinal diameter at the upper sacroiliac joint cross section (L) in the CT images of patients has also been observed, and the relationship between L and radiation energy has not been determined. In addition, the relationship between a larger margin and energy has not been identified, so it is necessary to expand the sample size for further study.

6. Conclusion

This study carefully investigated the dosimetric difference between 6 MV and 10 MV plans for cervical cancer with different abdominal widths and presented an overview to better understand the difference between 6 MV and 10 MV energy for their future clinical use in the EBRT of cervical cancer plans. Under the equipment conditions of our radiotherapy research center, the 10 MV plans were more beneficial for cervical cancer with a wider abdomen compared with the 6 MV plans, while 6 MV energy is more suitable for the EBRT treatment of cervical cancer with a smaller abdominal size.

Funding

None to report.

Ethical approval and consent to participate

The study was conducted with approval from the Ethics Committee of The Affiliated Huaian No.1 People’s Hospital (approval no. YX-2020-164-01). The study was conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent prior to enrollment in the study.

Footnotes

Acknowledgments

The authors would like to acknowledge the hard and dedicated work of all the staff that implemented the intervention and evaluation components of the study.

Conflict of interest

The authors declare that they have no competing interests.

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