Introduction

The rate of Rectal Cancer (RC), the tenth most lethal cancer, has dramatically increased worldwide. The number of new rectal cancer cases was estimated at 732,210 in 2020 [ 1 ]. In recent years, the use of preoperative chemoradiotherapy for localized rectal cancer has widely become accepted due to some advantages, such as tumor down-staging, reduction of local recurrence risk, and improved overall survival [ 2 ]. However, radiotherapy as a therapeutic option has significant clinical benefits, and some significant risks are associated with treatment-related adverse events [ 3 ].

Modern Radiotherapy (RT) techniques can help to reduce the side effects of radiation, such as modern radiotherapy technique (Helical Tomotherapy (HT)), yielding highly conformal distributions of radiation dose to the target and minimizing the level of radiation exposure to the Organs at Risk (OARs) [ 4 ]. The treatment of rectal tumors primarily aimed to achieve adequate radiation dose to the rectum and sparing of OARs, such as bladder, small bowel, and femoral heads, and accurate delineation of Gross Tumor Volume (GTV), and Clinical Target Volume (CTV) [ 5 ].

Tumor delineation and treatment planning in rectal tumors are based on Computed Tomography (CT) images. However, there are some limitations of CT images in the delineation of treatment volumes in pelvic structures, including poor contrast between soft tissues, artifacts from large bony structures or metal prostheses, and partial volume effects [ 6 ]. Recently, Magnetic Resonance Imaging (MRI) can complement CT imaging by improving soft tissue contrast, reducing large bony structure artifacts, and enhancing better contrast resolution .

Moreover, MR images provide better visualization of tumor extent and nodal involvement in some sites. For these reasons, co-registered MRI and CT images (MRI/CT) can be used for a better definition of treatment goals. The effect of co-registered MRI/CT images is investigated on tumor volume delineation , showing that delineated volumes based on CT images were not always the same as delineated volumes based on MRI/CT images. Some studies have reported that smaller GTV and CTV based on MRI/CT images and differences between treatment volumes can impress delivered radiation dose to the OARs [ 11 , 12 ]. Bird et al. [ 11 ] demonstrated that smaller delineated GTV-based MRI/CT images in anorectal tumors cause a reduction of delivered doses to the OARs, such as the bladder and small bowel.

Using MR images based on CT simulation instead of CT images alone is challenging in radiation therapy departments. Therefore, assessment of the role of co-registered MRI/CT images in HT treatment planning for rectal cancer is important for dose delivery of the target and reduction dose of OARs.

To the best of our knowledge, there is no published work on the evaluation of MRI/CT images in rectal cancer patients for HT treatment planning. For this reason, HT treatment plans were analyzed for comparison of both planning methods in the present study. This study aimed to compare volumetric and dosimetric parameters between MRI/CT and CT images alone for treatment planning of rectal cancer tomotherapy, and also to assess the influence of co-registered MRI/CT-based target delineation on the dose to the target and OARs, such as small bowel, bladder, and femoral heads during tomotherapy.

Material and Methods

Patients

In this cross-sectional prospective study, 12 patients with rectal cancer including 7 males and 5 females with a mean age of 60 years (range of 30-81 years) were selected after approval by the Isfahan University of Medical Sciences ethics committee. All patients were referred to the Department of Radiation Oncology, Seyed Al-Shohada Hospital, Isfahan for pre-operative chemo-radiation therapy between February 2022 and December 2022. All tumors were staged by echo endoscopy, diagnostic MRI, and CT.

Scanning methods

All patients underwent simulation CT and diagnostic MR images. Simulation CT scans were obtained using Siemens SOMATOM (Confidence® RT, Pro) with and without contrast enhancement. Patients were scanned with bladder filling protocol in the prone position, and all scans were obtained at 3 mm slice thickness. The MR images were obtained on a 1.5 T (Siemens MAGNETOM, Symphony) scanner with T₂W 2D turbo spin echo and T₁W 2D turbo spin echo sequences.

Image Fusion and Contouring

All images were imported into Radixact-X9® tomotherapy machine TPS (accuracy precision treatment planning system V2.0.1.1) for image fusion, contouring, and treatment planning. Both imaging methods were matched using a deformable fusion algorithm [ 13 ]. Then, all fused images were visually reviewed by a Radiation Oncologist and a Medical Physicist. An expert radiation oncologist delineated GTV, CTV, and OARs according to the Radiation Therapy Oncology Group (RTOG) protocols [ 14 ]. Based on the CT and MRI/CT images, two different GTVs were delineated for each patient: GTV_CT and GTV_MRI/CT, respectively. At first, GTV_CT was manually delineated in all slices, in which the tumor was visible, and GTV_MRI/CT was then delineated at a week interval by the same radiation oncologist. In the same way, CTV_CT and CTV_MRI/CT were defined. Clinical target volume included the GTV mesorectal, presacral, common, and internal iliac lymph nodes [ 14 ]. In addition, some OARs were contoured, including the bladder, small bowel, and femoral heads. In the end, the PTV was generated with a 3-mm margin around the CTV.

Treatment planning

Following the contouring process, tomotherapy plans were performed for all cases. The prescription dose for PTV was 45 Gy in 25 fractions of 1.8 Gy. Also, dose constraints are defined as covering ≥98% of the PTV with ≥93% of the prescribed dose, V35<180 cc for small bowel, V40<40% for femoral heads, and V40<40% for bladder. All plans were generated using a 5-cm field width, a pitch ranging from 0.28 to 0.43, and a modulation factor of 2 to 3. For each patient, planning was defined for two PTVs (CT and MRI/CT) under the same condition. All plans were reviewed by the Physicist and Oncologist. Treatment plans were compared after analyzing the Dose Volume Histogram (DVH) and target volumes.

Plan evaluation

For volumetric comparison, GTV_CT and GTV_MRI/CT were calculated by the treatment planning software, and CTV and PTV volumes were compared. To evaluate the plans, dosimetric parameters were calculated using DVH data. For PTV, the Conformity Index (CI) and Homogeneity Index (HI) were calculated according to the following equations [ 15 , 16 ]:

$\begin{array}{cc}\mathrm{CI}=\frac{V_{\mathrm{45}}\mathrm{Gy}}{V_{\mathrm{PTV}}}& \mathrm{(1)}\end{array}$

$\begin{array}{cc}\mathrm{HI}=\frac{I_{\max }}{\mathrm{RI}}& \mathrm{(2)}\end{array}$

where V₄₅ Gy is the volume of PTV that receives 45 Gy radiation dose, V_PTV is the volume of PTV, I_max is the maximum isodose in the target, and RI is the reference isodose. For OARs, such as bladder, both femoral heads and small bowel, D_mean (mean dose) and D_max (maximum dose) were analyzed; Also, V_n% (percent volume of the organ that receives at least dose of n Gy) and Dn% (a dose received by n% of the volume of organ) were reported in various levels.

Statistical analysis

For all volumetric and dosimetric parameters of MRI/CT and CT-based plans, normality tests were performed. Paired Wilcoxon tests were used to compare the variables since none of the parameters showed normal distribution. The data analysis was carried out using SPSS version 22.0 statistical software and a P-value<0.05 was considered statistically significant.

Results

As stated in methods section, the tumors were staged and their outputs are shown in Table 1.

Volume comparisons

The results of the volumetric analysis are shown in Figure 1. According to both volume delineation methods, Table 2 presents GTV, CTV, and PTV mean volumes. In GTV_CT, the mean value was significantly higher than in GTV_MRI/CT (243.00±145.00 vs. 219.02±131.00, P<0.001). CTV_CT showed a significantly higher mean value than CTV_MRI/CT (504.00±241.00 vs. 461.00±249.00, P<0.001). In addition, the mean value of the PTV_CT was significantly higher in the CT-based planning method compared to MRI/CT-based planning method (675.00±263.00 vs. 602.00±266.03, P=0.019). The PTV_CT was larger than the PTV_MRI/CT in 9 cases (75%) and smaller in only 3 cases (25%).

Figure 1. Volumetric comparison between CT-based and MRI/CT-based treatment volume delineation. (CT: Computed Tomography, MRI: Magnetic Resonance Imaging, GTV: Gross Tumor Volume, CTV: Clinical Target Volume, PTV: Planning Target Volume)

Dosimetric comparisons

1. Planning target volume (PTV)

Table 3 shows the results of D_mean, CI, and HI parameters for CT- and MRI/CT-based plans. The mean HI value in CT-based plans was significantly higher than that in MRI/CT-based plans (1.08±0.03 vs. 1.06±0.02, P=0.005). Additionally, the mean value for the D_mean parameter was significantly lower in PTV_CT than in PTV_MRI/CT (4613.00±79.00 vs. 4620.00±99.00). Also, Figure 2 shows the radiation dose distribution in PTV_CT and PTV_MRI/CT.

Figure 2. (A) Image fusion with deformable registration algorithm. (B and C) Dose distribution comparison between MRI/CT-based contour (B) and CT-based contour (C) in the same patient and same slice. (CT: Computed Tomography, MRI: Magnetic Resonance Imaging)

2. Bladder

D_max, D_mean, D_50%, and D_98% for bladders in CT-based plans were significantly higher than in MRI/CT-based plans (P-value =0.004, P-value=0.005, P-value=0.015, and P-value=0.019, respectively) (Table 3). For both V_40% and V_45% parameters, CT-based plans had significantly higher mean values than those of MRI/CT-based plans (P-value=0.010 and P-value=0.026, respectively). However, no significant difference was found between the two planning methods in V_30% (P-value =0.099).

3. Small bowel

D_max, D_mean, D_50%, V_40%, and V_45% mean values for both planning methods are mentioned in Table 3. All mean values were significantly higher in CT-based plans (P-value=0.028, P-value<0.001, P-value<0.001, P-value<0.001, P-value<0.001, respectively). However, the opposite results were obtained for the V_20% and V_30% parameters.

4. Femoral heads

In Table 3, the mean values of D_max, D_mean, D_50%, V_20%, and V_30% were presented for femoral heads. For the left femoral head, the mean values of D_max, D_50%, and V_20% parameters were significantly higher in the CT-based planning method compared to MRI/CT-based planning method (P-value=0.034, P-value<0.001, P-value=0.004, respectively). On the other hand, there was no significant difference in D_mean and V_30%.

In the right femoral head, the mean value of D_max and V_30% was significantly lower in the MRI/CT-based planning method than in the CT-based planning method (P-value=0.034 and P-value<0.001, respectively). In addition, no significant difference was observed in other parameters.

Discussion

Accurate target volume delineation is a critical issue in rectal radiotherapy, with the use of the HT technique. This study aimed to compare volumetric and dosimetric parameters between MRI/CT- and CT-based treatment plans for rectal cancer tomotherapy.

Due to CT limitations, it has recently become more common to use MR imaging for treatment planning. Better soft tissue contrast, lower large bony structure artifacts, and better contrast resolution are some of the advantages of MRI over CT [ 17 ]. The MRI scan can be acquired in the treatment position or the diagnostic position. For using MRI/CT for treatment planning, it is recommended that the MRI scan be acquired in the treatment position. However, some clinical centers do not have access to MRI scanners that can scan the patient in the treatment position [ 18 ].

In this study, a deformable image registration algorithm was used to register diagnostic MRI images with CT simulation images (Figure 2A). The target volumes derived from MRI/CT and CT images were compared and their delivered dose of target and OARs in both planning methods were analyzed.

B. O’Neill et al. [ 19 ] showed tumor volumes on MRI were smaller, shorter, and more distal from the anal sphincter than those defined on CT. Tan et al. [ 10 ] showed that rectal treatment volumes are lower in co-registered MRI and CT images than only CT images. In addition, Bird et al. [ 11 ] released that MRI data in rectal radiotherapy, either in MRI-only planning or MRI/CT planning can lead to a decrease in target volume and delivered doses to OARs. However, research results may be affected by new radiotherapy techniques. According to the results, the GTVs, CTVs, and PTVs delineated with simulation CT were significantly larger than those delineated with MRI/CT. In the present study, CT significantly overestimates target volumes in rectal cancer (Table 2), due to poor soft tissue contrast in CT, leading to defining larger volumes in an attempt to minimize regional misses [ 10 , 11 ].

The correct target volumes delineating is essential for achieving a better target volume dose distribution and reducing doses to the OARs. Consequently, it is expected that the dose delivered to the OARs decreases due to the smaller PTV in MRI/CT-based planning. The present study also compared CT- and MRI/CT-based planning methods based on dosimetric parameters. The findings of the present work showed that HI and CI parameters were significantly improved in PTV_MRI/CT compared to PTV_CT. Additionally, D_mean was significantly higher in PTV_MRI/CT than in PTV_CT.

Results of this study showed the MRI/CT-based planning method achieves better results than CT-based planning in terms of dose conformity and dose homogeneity in the PTV. In rectal cancer radiotherapy, the small bowel is the most important organ, which is dose-limited and causes toxicity in patients [ 20 ].

This study also showed most of the dosimetric parameters (D_max, D_mean, D_50%, D_50%, V_40%, and V_45%) were significantly higher in the CT-based plans than in the MRI/CT-based plans in the small bowel. Also, in the bladder, all dosimetric parameters except V_30% (P-value=0.099) were statistically higher in CT-based plans than in MRI/CT-based plans. In femoral heads, several of the dosimetric parameters showed higher mean values in CT-based plans compared to MRI/CT-based plans, reducing the probability of avascular necrosis occurring [ 21 ]. However, the difference between the two methods was not as great as in other organs at risk. In the present study, the smaller MRI/CT-based target volumes delivered less dose to the OARs, especially the small bowel. The MRI/CT-based planning method also improved dose distribution in the PTV, which confirms the results of previously studies [ 10 , 11 ]. Findings of this work showed it is possible to define safer treatment planning by using deformable registration of MRI/CT-based plans than only CT-based plans.

The present study has some limitations as follows: 1) the small number of patients, 2) a change in tumor volume due to the one-day interval between the CT and MRI scans, and 3) contouring by two or more radiation Oncologists, separately, instead of one radiation Oncologist.

Conclusion

In this work, mean values of GTV, CTV, and PTV are lower in CT-based plans in comparison with MRI/CT-based plans. In addition, MRI/CT-based plans may lead to better dose coverage and dose homogeneity for the target and also reduce the delivered dose to the bladder, small bowel, and femoral heads in comparison with CT-based plans. Accordingly, co-registration of diagnostic MRI images with CT simulation images can improve the efficiency of tomotherapy treatment plans for rectal cancer patients.

Authors’ Contribution

B. Rahmani contributed to idea formation, proposal writing, data collection, and drafting of the manuscript. D. Shahbazi-Gahrouei contributed to idea formation and development, data interpretation and analysis, editing of the manuscript, and supervised the research project as the principal person. M. Roayaei contributed to idea development and data collection. All the authors read, modified, and approved the final version of the manuscript.

Ethical Approval

This work was approved by the Isfahan University of Medical Sciences Ethics Committee (IR.MUI.MED.REC.1401.052).

Informed Consent

Before entering the study, each participant signed a consent form.

Funding

This work was financially supported (grant No: 340129) by Isfahan University of Medical Sciences, Isfahan, Iran.

Conflict of Interest

None

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