Research on Using IMRT Plan for Preoperative Rectal Cancer Patients

Aims: Research the possibility of using IMRT for rectal cancer patients in preoperative radiotherapy. Methods and Material: The research object is the preoperative radiotherapy plan for rectal cancer patients. The research group made two plans (IMRT, 3DCRT) for each image series of 34 rectal cancer patients who have received preoperative radiotherapy in Hanoi Oncology Hos-pital; and then compared the dose distribution on PTV, bladder, intestine, femoral bones, the average MU, and QA results of two types of plan. Results: The 95% isodose line and 50% isodose of IMRT plan are closer than those of 3DCRT plan. The average dose of PTV in IMRT plan and 3DCRT plan are 5006 ± 23 cGy and 5036 ± 42 cGy, respectively. The HTCI and HI values of IMRT and 3D plan are 0.97 ± 0.026 and 5.37 ± 1.32; 1.00 ± 0.003 and 7.08 ± 0.88. About the dose of organ at risk: The maximum dose, average dose on the right, left femoral head in the IMRT plan are less than those values in the 3DCRT plan (6.2 Gy, 6 Gy, 7.4 Gy, 9 Gy, respectively). The maximum dose and average dose on the bladder of the IMRT plan are smaller than those values of the


Abstract
Aims: Research the possibility of using IMRT for rectal cancer patients in preoperative radiotherapy. Methods and Material: The research object is the preoperative radiotherapy plan for rectal cancer patients. The research group made two plans (IMRT, 3DCRT) for each image series of 34 rectal cancer patients who have received preoperative radiotherapy in Hanoi Oncology Hospital; and then compared the dose distribution on PTV, bladder, intestine, femoral bones, the average MU, and QA results of two types of plan. Results: The 95% isodose line and 50% isodose of IMRT plan are closer than those of 3DCRT plan. The average dose of PTV in IMRT plan and 3DCRT plan are 5006 ± 23 cGy and 5036 ± 42 cGy, respectively. The HTCI and HI values of IMRT and 3D plan are 0.97 ± 0.026 and 5.37 ± 1.32; 1.00 ± 0.003 and 7.08 ± 0.88. About the dose of organ at risk: The maximum dose, average dose on the right, left femoral head in the IMRT plan are less than those values in the 3DCRT plan (6.2 Gy, 6 Gy, 7.4 Gy, 9 Gy, respectively). The maximum dose and average dose on the bladder of the IMRT plan are smaller than those values of the 3DCRT plan (5.3 Gy, 1.5 times, respectively). The maximum dose and average dose of intestine in the IMRT plan was less than those values in the 3DCRT plan (4.3 Gy, 1.54 times, respectively). The MU number of IMRT plan is 1.5 times bigger than that of 3DCRT plan. Gamma index of IMRT plan is better than that of 3DCRT plan (99% compared with 97%). Conclusions: Using IMRT plan in preoperative radiotherapy for rectal cancer patients can still ensure covered PTV as well as the 3D PLAN. Furthermore, the dose of PTV in the IMRT plan is more uniform than those in the 3D plan, and the dose effect on the OAR surrounding PTV is much lower than when using the 3D plan. When IMRT plan were used to treat the preoperative rectal cancer patients, the LINAC took more time than when using 3DCRT plan.

Introduction
According IMRT significantly reduces dose to nearby organs, such as femoral heads, gonads, bladder, and colon, thereby yielding lower effective doses compared to the conventional radiotherapy [9]. Among the IMRT plans, plan with the 6 MV beam energy results in the lowest effective dose. Salma K. Jabbour et al. also compared the acute toxicities of IMRT to 3D-conformal radiation therapy (3DCRT) in the treatment of rectal cancer, the research showed that IMRT reduces doses of the irradiated small bowel and IMRT can reduce median charges to small bowel by 5.1 Gy for rectal cancer [6].

Materials and Methods
Patients and simulation Thirty four patients with rectal cancer, subjected to radical preoperative radiotherapy were selected for this study. The research protocol was reviewed and approved by the Ethics Committee of Hanoi Oncology Hospital. All patients were simulated supine position with a full bladder. Computer tomography (CT) scans were acquired with 5 mm slice thickness through the L1 vertebral body to 5 cm below the perineum. The patients had urinated, drank a liter of water, and then waited for 30 minutes before being taken CT simulation [13] [14] [16] [17] [18].
Target volume definition Target volumes were outlined on the planning CT scan by the treating radiation oncologist. The clinical target volume (CTV) was delineated according to published consensus guidelines [21]. The planning target volume (PTV) was defined with margins around the CTV of 0.5 cm. The bladder, small bowel and femur heads were contoured as an organ at risk (OAR). The small bowel, bladder were outlined 0.5 cm outside of PTV, and femur heads were fully outlined.
In addition, the healthy tissue was defined as the patient's volume included in the CT dataset minus 1.5 cm margin of the PTV volume.
Dose constraints for PTV and OAR.
Plan evaluation and comparison Both of 3D CRT and IMRT plans were created verification plan. Then these plans were controlled quality by Delta 4 system, which is a product of Scandidos Company. The parameters of this system were set Dose Deviation (DD) 3%; Distance to Agreement (DTA) 3 mm; Gamma Index (GI) 95% [21].
Dosimetric parameters to analyze target coverage and dose distribution in the PTV are: 1) 3D max dose of plan (D max ); 2) max dose for PTV (D maxPTV ); 3) minimum dose of PTV (D mimPTV ), 4) mean dose of PTV (D meanPTV ); the dose value cover 5% of PTV volume on Dose Volume Histogram (D 5% ), the volume of PTV is covered with 95% of dose prescription (V 95% ); the volume of PTV (V PTV ). Homogeneity Index (HI) and HTCI Healthy Tissues Conformity Index (HTCI) were calculated with following formulas [ The mean dose, maximum dose of bladder, small bowel, femoral heads, number of MU in both types of plan were selected, plotted on the graph. Probability density function was used to calculate the probability of the selected value.

1) Comparison of dose distribution on the transverse CT slice
In Figure 1, observing the 95% isodose line, that is the green line, in pairs of the sections (transversal, horizontal, vertical) of CT images of both IMRT and 3DCRT plans, the results showed that the isodose line of the IMRT plan bends and circles around the PTV line (the red line), and avoids the intestines (yellow line in the picture). In contrast, those of 3DCRT plan cover the PTV, and entire the intestine. Observing the lower isodose line, the 50% isodose line (the blue line) in the IMRT plan bends in PTV shape, and evades the intestine. However, the 3D CRT plan's dose is distributed in the entirebody in the direction of the beams, and it covers almost all the pelvis region.

2) Plan evaluation using Dose Volume Histogram (DVH)
According to the Figure 2, the PTV dose in IMRT plan is similar to the PTV dose in 3DCRT plan. Meanwhile the Figure 3 and the Figure 4 show that the dose of OAR in IMRT plan is lower than that in 3DCRT plan.    Figure 5 shows that the max dose and mean dose of PTV in IMRT plan are similar to these in 3DCRT plan. However, the minimum dose of PTV in IMRT is lower than it in 3DCRT plan. Figure 6 shows that the HTCI value of 3DCRT plan is equal one, and HTCI value of IMRT plan is almost equal one. Meanwhile, HI value of IMRT plan   . It shows that the maximum dose on the femoral head in both type of plan are smaller than 50 Gy. The average dose is not more than 10% of the volume that femoral head receives, which is equal to and greater than 40 Gy. The maximum dose on the bladder in the IMRT plan is smaller than 50 Gy. The average dose on the bladder of the IMRT plan is smaller than 40 Gy; those results meet the dose constraints. But the maximum and average doses of the bladder in the 3DCRT plan are bigger than 50 Gy and 40 Gy, respectively, which do not meet the dose constraints. The intestinal dose of both types of plan do not meet the dose constraint for intestine in the above section. Figure 8 shows that the intestinal volume receiving dose more than or equal  to 15 Gy in IMRT plan is smaller than in 3DCRT plan (238 c 3 compared with 287 c 3 ).

5)
Result of a quality control plan, MU number of plan Figure 9 illustrates that gamma index of IMRT plan is better than that of 3DCRT plan (99% versus 97%). It means that 99% of measured points of IMRT plan passed. However, the passed measured points of 3DCRT are 97% of measured points. Figure 10 shows that the number MU of IMRT was over five times higher than that of 3DCRT plan (1332 MU versus 258 MU). Discussion of DVH results: The results on the top right corner of Figure 2 show that the minimum dose of PTV in the IMRT plan is lower than in the 3DCRT plan. The reason for this result is that the process of optimizing the IMRT plan that the authors have optimized the 95% isodose line was closely covered PTV, so there were some PTV points had not been completely covered. However, as mentioned above, it is confirmed that 95% isodose line of the prescribed  dose surrounding PTV can be changed dynamically in the IMRT plan. At the bottom right corner of Figure 2, it shows that the volume of PTV having dose more than prescribed dose was less than that of 3D CRT plan. The results in Figure 3 and Figure 4 confirmed again that IMRT plan conserved OAR better than 3DCRT plan, which is the same with the results in the research of Jun Shang et a and also other research [12]. In the research about comparing IMRT with 3DCRT in prostate treatment, Gary Luxton et al showed that the dose of bladder, bowel, femur in DVH of IMRT plan is better than those in 3DCRT plan [13].

Discussion
The dose result on PTV: Quantitatively, Figure 5 shows that the max dose on both PTV in IMRT and 3DCRT plans were matched with the dose constraint for PTV (that must be less than 53.9 Gy); and the average dose of PVT in both types of plan were similar with prescribed dose (50 Gy).
The HTCI value of the 3DCRT plan was 1; it means 100% of the PTV is covered by the 95% of prescribed dose. The HTCI of the IMRT plan was 0.97, meaning that 97% of the PTV is covered by the 95% of prescribed dose. The IMRT plan should be re-optimized to increase to 100% of the PTV volume covered by 95% of prescribed dose.
The HI value of the IMRT plan was closer to zero than that value of the 3DCRT plan was. It means the difference between D 95% and D 5% of IMRT plan is smaller than that of 3DCRT plan. So the dose distribution in the PTV of the IMRT plan was more uniform than that of the 3DCRT plan. The reason is that the number of fields in the IMRT plan is over two time higher than that of 3DCRT plan, moreover the IMRT has intensity modulation during the bean on but 3DCRT did not have that. These reasons permit the IMRT plan avoid OAR better than 3DCRT plandoes.
The dose result on OAR: The maximum dose, average dose on the right, left femoral head in the IMRT plan were less than those values of the 3DCRT plan (6.2 Gy, 6 Gy, 7.4 Gy, 9 Gy, respectively). The maximum dose and average dose on the bladder of the IMRT plan were smaller than those values of the 3DCRT plan (5.3 Gy, 1.5 times, respectively). In the research "dosimetry and radiobiologic model comparison for IMRT and 3D conformal radiotherapy in treatment of carcinoma of the prostate" of Gary Luxton et al., IMRT plans have the mean dose that is smaller by 2.4 Gy (6.7%) for bladder and 1.7 Gy (4.4%) for the rectum [13]. The maximum dose and average dose of the intestine in the IMRT plan were less than those values (4.3 Gy, 1.54 times, respectively). Moreover, the volume of intestine receiving dose equal to and greater than 15 Gy in the IMRT plan was smaller than that value of the 3D plan (238 c 3 versus 287 c 3 ).
The quality assurance result indicated that the difference between calculated dose and measured dose of the IMRT plan is smaller that that value of the 3DCRT plan. The MU number result showed that the MU number of the IMRT plan was 5.1 times higher than this number of the 3DCRT plan. It means that beam on time of the IMRT plan would be about 5 times larger than that of  [7].
The number MU of IMRT plan in this research is smaller than that of IMRT in David Followill's research (1332 MU comparing with 23,800 MU), both research used Varian MLC modulated. Therefore, ensuring the accuracy and safety for patients, when IMRT plan is used for preoperative radiotherapy, is extremely important. It confirms that using immobilization equipment during CT simulation and treatment, and quality assurance IMRT plan before using are essential.

Conclusion
The collected results and above data analysis prove that using IMRT plan in preoperative radiotherapy for rectal cancer patients can still ensure that PTV is covered as well as when using 3DCRT plan. Moreover, the dose distribution on PTV in the IMRT plan is more uniform than that in the 3DCRT plan, and the affection dose on OAR in the IMRT plan is lower than that in the 3DCRT plan. When using the IMRT plan in preoperative radiotherapy to treat rectal cancer, the LINAC takes five times longer to beam on than when using 3DCRT plan. It recommends that clinical centers should be equipped with immobilization and QA plan equipment.