Intensity Modulated Radiation Therapy vs. Volumetric Modulated Arc Therapy in Locally Advanced Unresectable Pancreatic Cancer: Dosimetric Study

Pancreatic carcinoma is considered one of the most complicated cancers in treatment. VMAT technique is a novel IMRT form. Pancreatic motion is an essential problem in its radiotherapy planning, VMAT can lessen this risk of motion by shortening the time of treatment therefore it can minimize radiotherapy toxicity. Our study aim was to define if VMAT achieves a high dose distribution and more dose homogeneity with shorter overall treatment time in comparison to IMRT. Patients and methods: The medical records of five patients of locally advanced unresectable pancreatic cancer treated by conventional fractionation using VMAT were reviewed and re-planned by IMRT techniques at International Medical Center, Cairo, Egypt. Results: Both techniques have comparable PTV54 target coverage. PTV50.4 is statistically significant and better in VMAT than IMRT. Both techniques have comparable sparing in case of liver, RT kidney and bowel. Sparing of left kidney and stomach is more significant and better in VMAT than IMRT. However, the spinal cord is relatively better spared in IMRT than VMAT. Lower Integral dose is attained in IMRT than VMAT so IMRT can achieve further reduction of complication rates in pancreatic cancer. VMAT has shorter treatment time beam on than IMRT and more conformity and homogeneity index.


Introduction
Pancreatic carcinoma is one of the most complicated cancers in treatment.There are 2 approaches in its treatment such as "chemoradiotherapy followed by chemotherapy" and "chemotherapy alone" [1].This difference is due to pancreas site since it is placed in the middle of many critical structures [2].
IMRT is a superior mode of high-precision radiotherapy [3].VMAT technique is a novel IMRT form [4,5].As in pancreatic radiotherapy planning, its motion is an essential problem, VMAT can lessen this risk of motion by shortening the time of treatment therefore it Patients and methods: The medical records of five patients of locally advanced unresectable pancreatic cancer treated by conventional fractionation using VMAT were reviewed and re-planned by IMRT techniques at International Medical Center, Cairo, Egypt.
Results: Both techniques have comparable PTV54 target coverage.PTV50.4 is statistically significant and better in VMAT than IMRT.
Both techniques have comparable sparing in case of liver, RT kidney and bowel.Sparing of left kidney and stomach is more significant and better in VMAT than IMRT.However, the spinal cord is relatively better spared in IMRT than VMAT.
Lower Integral dose is attained in IMRT than VMAT so IMRT can achieve further reduction of complication rates in pancreatic cancer.
VMAT has shorter treatment time beam on than IMRT and more conformity and homogeneity index.

Conclusions:
VMAT provided a higher dose distribution regarding to organs at risk as all OAR have statistically significant better sparing in case of VMAT than IMRT except the spinal cord without compromising CTV coverage.Moreover VMAT can achieve more dose homogeneity in shorter treatment time.has a hopeful effect on minimizing radiotherapy toxicity [6][7][8].

Aim of Our Study
Our study aim was to define if VMAT achieves a high dose distribution and more dose homogeneity with shorter overall treatment time in comparison to IMRT depended on 4D-CT target volume coverage and organs at risk doses in definitive treatment by concurrant chemoradiotherapy in locally advanced unresectable pancreatic cancer.

Study design
The medical records of five patients of locally advanced unresectable pancreatic cancer treated by conventional fractionation using VMAT were reviewed and re-planned by IMRT techniques at International Medical Center, Cairo, Egypt.PTV50.4 is contoured and covering 5 mm around CTV that encompasses all relevant nodal regions including the porta hepatis, celiac/SMA and PA/RP lymph nodes in all techniques delivering 28 fractions with 1.8 Gy per fraction.PTV54 is contoured and covering 5 mm margin around GTV that consists of hypodense area "a biopsy proven disease in the pancreas and any positive lymph nodes visualized on diagnostic pancreatic protocol CT".The same objectives were determined for both IMRT and VMAT plans.Contouring of OAR was done according to RTOG guidelines [9].Adapted from RTOG 1102(IMRT, 2.2-54Gy).

Planning system
IMRT technique: Six to eight fields were calculated using the dynamic IMRT technique, 10 Mv energy and Monte Carlo Algorithm at different angles.
VMAT technique: Plans were generated using dynamic VMAT and Monte Carlo Algorithm and 2-3 arcs of 6-10 Mv in clockwise and counterclockwise.

Plan evaluation:
We compared target volumes coverage, critical organs sparing, integral dose, Homogeneity index, Conformity index and beam on treatment time between two plans.

Statistical analysis
Using Microsoft Office Excel 2010 for windows for data collection, tabulation and statistically analysis and SPSS 22.0 for windows.Expression of Continuous Quantitative variables were done as the mean ± SD & median (range).Check of continuous data for normality was done by using Shapiro Walk test.Using of Wilcoxon singed ranks test was done for two dependent groups of non-normally distributed data.All tests were two sided.P-value < 0.05 was considered statistically significant.

Results
Table 1 and Table 2.

Target volumes
Both IMRT and VMAT techniques have comparable PTV54 target coverage.PTV50.4 is statistically significant and better in VMAT than IMRT so it is in favor of VMAT than IMRT.

Organ at risk sparing
IMRT & VMAT techniques have comparable sparing in case of liver, RT kidney and bowel.Sparing of left kidney and stomach is more significant and better in VMAT than IMRT so it is more in favor of VMAT than IMRT.However, the spinal cord is relatively better spared in IMRT than VMAT.

Integral dose (Normal tissue outside PTV)
The integral dose represents the total energy deposited by ionizing radiation within a body.Lower Integral dose is attained in IMRT than VMAT so IMRT can achieve further reduction of complication rates in pancreatic cancer and this is in favor of IMRT than VMAT technique.(P value 0.038).

Beam on treatment time and dose homogeneity
VMAT has shorter treatment time beam on (median 0.7600) than IMRT (median 1.6700) (P value 0.042) and more conformity (P value 0.025) and homogeneity index (P value 0.042) so it can achieve more dose homogeneity.
IMRT & VMAT techniques have comparable sparing in case of liver, RT kidney and bowel.Sparing of left kidney and stomach is more significant and better in VMAT than IMRT so it is more in favor of VMAT than IMRT.However, the spinal cord is relatively better spared in IMRT than VMAT.

Discussion
Pancreatic cancer radiotherapy is a complex area due to its site and movement factor due to organ In our study spinal cord max dose is less in IMRT (p value 0.039) than VMAT in contrast to Jethwa, et al. study 2018 [16].
In pancreatic cancer radiotherapy planning, to overcome the motion factor, using new radiotherapy technologies for reduction normal organ doses [17].Sangalli, et al., studied 4DCT planning impact for unresectable pancreatic cancer patients.Via using this planning system, target volumes lessened by 37% in comparison to standard target delineation [14].In our study, 4DCT simulation was done as a standard approach for radiotherapy planning of pancreas cancer patients.
Lower Integral dose is attained in IMRT than VMAT so IMRT can achieve further reduction of complication rates in pancreatic cancer and this is in favor of IMRT than VMAT technique.This finding is in agree with many previous dosimetric studies as Chen, et al., [18].
VMAT has shorter treatment time beam on than IMRT and more conformity and homogeneity index so it can achieve more dose homogeneity as reported in previous dosimetric studies [19].motion and respiration.IMRT has been proved to improve dosimetric parameters and minimize the doses delivered to normal critical tissues.The first significant problem of radiotherapy is the high recurrence rate of acute adverse of gastrointestinal tract via concurrent chemo radiotherapy.The second problem was intrafraction motion in pancreas cancer.Using VMAT could achieve more effective dose distribution and more target coverage and more dose homogeneity.In our study IMRT & VMAT techniques have comparable sparing in case of liver, RT kidney and bowel.Sparing of left kidney and stomach is more significant and better in VMAT than IMRT so it is more in favor of VMAT than IMRT in accordance with SEZEN, et al. study at 2017 [11].
As our study, Ali, et al., analyzed the dosimetric data of 10 patients and the conclusion of this study that using VMAT in patients with pancreatic cancer either for curative or adjuvant radiotherapy intent, achieved lower mean doses of both kidney in comparison to IMRT, however similar other organ doses of both techniques were detected [12].
One of the essential acute adverse effects was caused by the dose that delivered to the small bowel during therapy.It is revealed that radiotherapy toxicity can be achieved with even large volume of low dose areas (5-15 Gy) [13].This is a great care for using of recent

Conclusions
In the dosimetric comparison of ssIMRT and VMAT techniques based on 4D CT scans in the cases of locally advanced irresectable pancreatic cancer patients, both plans achieve dosimetric organ goals, however VMAT provided a higher dose distribution regarding to organs at risk as all OAR have statistically significant better sparing in case of VMAT than IMRT except the spinal cord without compromising CTV coverage.Moreover VMAT can achieve more dose homogeneity in shorter treatment time.This study is restricted by a quite small number of patients but these results could be hopeful for more and more usage of VMAT for pancreatic cancer as routine as the other sites for example cancers of head and neck.

Table 1 :
All patients' characteristics and statistics are showed.

Table 2 :
Comparison between VMAT plan and IMRT plan regarding dosimetric parameters.
Continuous variables were expressed as mean ± SD & median (range); a: Wilcoxon singed ranks test; p-value < 0.05 is significant