IMRT Planning Using 5, 7 and 9 Radiation Field Directions for Nasopharyngeal Cancer Cases

Nasopharyngeal carcinoma (NPC) is one of the deadliest cancers in the world. In treating NPC, Intensity Modulated Radiation Therapy (IMRT) uses radiation fields from several directions to kill cancer cells and shrink tumours. IMRT requires accurate planning using the Treatment Planning System (TPS) to avoid organs at risk (OARs) around the nasopharyngeal cavity. The purpose of this study is to analyse the results of different number of radiation field directions in treatment planning for nasopharyngeal cancer using IMRT. The study focuses on the distribution of dose in the target tumour and organs at risk around the target. The treatment planning parameters are Dose Volume Histogram (DVH), Conformity Index (CI), Homogeneity Index (HI), dose at organs at risk (OARs) and beam on time (BOT). This study used TPS Monaco with the Monte Carlo algorithm and the inverse planning method. Based on DVH, CI, HI and BOT parameters, the results of this study indicate that the most optimal number of radiation field directions to give prescribed doses was 9 radiation field directions. There was no significant difference in the average dose received by OARs in planning with 7 and 9 radiation field directions. In the planning using 5 field directions, some of the OARs received doses above the tolerance limit. While in the planning using 7 and 9 field directions, most of the OARs received doses below the tolerated doses which met the permitted treatment requirements.


Introduction
Cancer is one of the deadliest diseases in the world.Nasopharyngeal Carcinoma (NPC) or commonly called nasopharyngeal cancer is an example of a malignant cancer.In Indonesia, NPC is the 4th most common type of cancer after cervical cancer, breast cancer and lung cancer [1].Based on the 2020 Global Cancer Observatory (GLOBOCAN) data, every year there are 133,354 new cases of NPC and 88,008 deaths from NPC [2].
Radiotherapy is a cancer treatment that uses high-energy ionizing radiation to kill cancer cells.Intensity Modulated Radiation Therapy (IMRT) is a high-precision radiotherapy that uses a computercontrolled linear accelerator to deliver precise radiation doses to tumor areas.IMRT uses multiple radiation fields of varying sizes and intensities to irradiate tumors with precision and accuracy.The goal of IMRT is to shape the radiation dose to avoid or reduce exposure to healthy tissue and limit treatment side effects when administering therapeutic doses to cancer [3].
In the study of Su et al [4], the IMRT technique provides a good 5-year survival rate for NPC.To implement the IMRT technique, a TPS computer performs calculations for several radiation fields that are not uniform in intensity according to what the TPS computer has planned in an inverse manner.The quality of the planning produced by the IMRT technique depends on the amount and direction of the radiation field used by considering the condition of the target tumor against the number and position of the at-risk organs around it.However, the number of radiation fields used must also be compromised by the processing time at TPS, the duration of therapy, and the distribution of the resulting doses.For this reason, it is necessary to determine the optimal number of radiation field directions to be used.With 5 to 9 beams at different angles, Zope et al [5] have carried out dose analysis in IMRT plans for prostate cancer, in terms of conformity index, homogeneity index and monitor units.They found that both 5 beam and 7 beam IMRT plans show non-significant difference, and the IMRT plans with 5 field use a lesser number of monitor units, leads to the lesser beam on time.Ibrahim et al [6] have compared 9-field IMRT to 7-field IMRT in the treatment of NPC.They found that 9F-IMRT provides better homogenous dose to planning target volume and more sparing of organs at risk over 7F-IMRT for NPC patients.Elvira et al [7] have compared 4 treatment plans using IMRT 5 field beam angle optimization (O5), IMRT 5 field manually (M5), IMRT 7 field beam angle optimization (O7) and IMRT 7 field manually (M7) for stage III NPC patients using Eclipse Treatment Planning System.Analysis of conformity index, homogeneity index, and dose at organs at risk extracted from their dose volume histograms, shows that the planning results of M7 are superior to those of M5, O5, and O7.
The purpose of this study is to analyze the results of 5, 7 and 9 field directions in treatment planning for nasopharyngeal cancer using IMRT.The parameters of the treatment planning results are the Dose Volume Histogram (DVH), Conformity Index (CI), Homogeneity Index (HI), dose at organs at risk (OARs) and beam on time (BOT).DVH represents the statistical data of given doses in volumes of interest, such as tumor and OARs surrounding the tumor.The prescribed dose must be given to the tumor to kill it, whereas the doses given at OARs must not be more than their limited values to prevent the damage.CI represents the agreement of the dose distribution on target tumor, HI represents the uniformity of dose distribution in the target volume, whereas BOT represents the irradiation time.

Materials and Methods
IMRT planning in this study was made using the Monaco Treatment Planning System (TPS) unit with the inverse planning method.Variations in the number of radiation fields used were 5, 7, and 9 for each case.The parameters of TPS results such as DVH, CI, HI, dose at OAR, total monitor unit (MU), and irradiation time will be compared to obtain the optimal treatment condition for each case of nasopharyngeal cancer with the IMRT technique.This research was conducted at Hasan Sadikin Hospital in Bandung from June to August 2022.
The samples are 8 nasopharyngeal cancer cases, mostly have tumor with extension of the intracranial, hypopharyngeal, orbital, or infratemporal fossa, unilateral/bilateral metastases in lymph nodes, with no distant metastases.
For each case, the computed tomography (CT) scan image data are transferred to a virtual simulator, and the target tumor and surrounding risky organs are determined by a radiation oncologist.The data are then transferred to the TPS for planning.In the planning, the DVH of planned target volume (PTV) and OARs are analyzed to determine CI and HI values and their doses, as well as the total MU and the irradiation time.From the results, the optimal number of radiation fields was determined for cases of nasopharyngeal cancer.

Results
Figure 1 shows a sample of DVH in nasopharyngeal cancer case using 5 field directions.It contains of DVH of PTV and OARs (brain stem, spinal cord, parotid, eye and lens) for nasopharyngeal cancer cases.The DVH curves of other cases are not presented since the pictures are similar.However, the important information from the DVH curves has been extracted and presented in Table 1 and 2  In the treatment planning using 5, 7 and 9 field directions for 8 nasopharyngeal cancer cases, the volume of planned tumor target (VPTV) can be determined, and therefore the volume that cover 95% PTV dose (V95%), also the dose covered in 98% PTV (D98%), the dose covered in 2% PTV(D2%) and the dose covered in 50% PTV (D50%) can be obtained from the DVH curves of PTV (Table 1).From the data, Conformity Index, defined by CI=V95%/TV based on ICRU Report 62, and Homogeneity Index, defined by HI=(D2%-D98%)/D50% based on ICRU Report 83, can be calculated [7].The data of the Segment Number (SN), the Total Monitor Unit (TMU), and the Beam on Time (BOT) obtained in the treatment planning using 5, 7 and 9 field directions for 8 nasopharyngeal cancer cases are also given in Table 1.In the treatment planning using 5, 7 and 9 field directions for 8 nasopharyngeal cancer cases, from the DVH curves of OARs, it can be obtained the dose in brain stem (OAR1), the dose in spinal cord (OAR2), percent volume of right parotid that has dose less than 3000 cGy (OAR3), percent volume of left parotid that has dose less than 3000 cGy (OAR4), the dose in right eye(OAR5), the dose in left eye (OAR6), the dose in right lens (OAR7), and the doses in left lens (OAR8).These data are represented in Table 2.The dose to at-risk organs (OARs) around the target must be evaluated to determined which organs are potentially exposed to radiation and have a risk effect on radiation.The limits of Organ at Risk (OAR) doses in nasopharyngeal cancer according to Keputusan MenKes RI [1] are as follows: Brain Stem Maximum dose of 54 Gy, Spinal cord Maximum dose 45 Gy, Eye Maximum dose 50 Gy, Lens Maximum Dose 20 Gy, and Parotid gland 50% volume < 3000 cGy.

Discussion
The Conformity Index (CI) value determines the agreement of the dose distribution on target tumor.The closest index to one implies high target volume coverage (PTV) and minimal unnecessary irradiation of the surrounding tissue [8].The ideal conformity index value is 1, which means that the isodose curve for the prescribed dose fits the PTV.In this study, the conformity index (CI) obtained for the 8 cases ranged from 0.82 -1.00 (Table 1).The lowest CI values were obtained in planning using 5 field directions, then followed by higher CI values in planning using 7 and 9 field directions.Both planning using 7 and 9 field directions meets the criteria for the treatment of nasopharyngeal cancer.However, planning using 9 field directions gives better results.
Homogeneity Index (HI) is an objective tool to analyze the uniformity of dose distribution in the target volume.The uniformity index is influenced by the minimum, maximum, and average target doses according to its definition.In the ICRU 83 report on IMRT, the maximum dose is represented by a dose of 2% of the target volume, the minimum dose is represented by a dose of 98% of the target volume, and the average dose is represented by 50% of the target volume.The ideal value for uniformity index is 0 which means that all PTV doses are uniform.The expected values of the standard ICRU are 98% of target volume is covered by 95% of the planned dose, 2% of target volume is covered by 107% of the planned dose, and 50% of target volume is covered by 50% of the planned dose, which leading up to HI=0,24.If the maximum dose is 95%, then the HI value is getting closer to 0. HI values acceptable in the ICRU criteria are 0 -0.3 [9].In this study, the homogeneity index (HI) values obtained for the 8 cases ranged from 0.20 -0.07 for all field directions (Table 1).These values are less than 0.3, means the homogeneity index obtained meets the criteria of ICRU.The order of the highest to lowest homogeneity index values is obtained from planning using 5 field directions, 7 field directions, and 9 field directions.These results indicate that in planning with using 9 field directions, the dose at PTV is more homogeneous compared to 5 and 7 field directions.
For brainstem, the maximum dose must be less than 54 Gy or 5400 cGy.In this study, for the 8 cases in planning using all field directions, Table 2 shows all the brainstem doses (OAR1) were at the safe limit.There is no clear trend in brainstem dose values between planning using 5, 7, and 9 field directions and the brainstem dose values have no significant difference.
For spinal cord, the maximum dose must be less than 45 Gy or 4500 cGy.Table 2 also indicates all the spinal cord doses (OAR2) were at the safe limit for all 8 cases in planning using all field directions, except for 5 field direction in case 2. There is no clear trend in spinal cord dose values between planning using 5, 7, and 9 field directions and the spinal cord dose values have no significant difference.
For parotid gland, the allowable limit of volume with a dose of 3000cGy is less than 50%.In Table 2, the volumes of the right parotid (OAR3) for all field directions in most cases are within the allowed limits, except case 4.This happens because the right parotid organ in case 4 is very close to the target volume.Meanwhile, the volumes of the left parotid (OAR4) using 7 and 9 field directions in most cases are within the allowed limits, except case 6.This happens because the right parotid organ in case 6 is very to the target volume.Using 5 field direction planning for right and left parotids, there are 6 cases which exceed the allowed limits.There is no clear trend of the parotid volume with a dose of 3000cGy for 5, 7 and 9 field directions.
The maximum dose allowed in the eye must be less than 5000 cGy.In this study, the right eye doses (OAR5) in most cases were at the safe limit for all field directions, except for 5 field direction in case 6.Meanwhile, the left eye doses (OAR6) in most cases were at the safe limit for all field directions, except for 9 field direction in case 2. There is no clear trend of the eye doses for 5, 7 and 9 field directions.
The maximum dose used on lenses is less than 20 Gy or 2000 cGy.In this study, the right lens doses (OAR7) and the left lens doses (OAR8) in most cases were at the safe limit for all field directions, except for 5 field direction in case 2 and 8.There is no clear trend of the lens doses for 5, 7 and 9 field directions.
Table 1 indicates that the more the number of field directions used, the higher the segment number (SN), total MU (TMU), and beam on time (BOT).The higher the segment number (SN) and total MU (TMU) will result in better uniformity of dose distribution on target volume and increase the doses received by the target tumor.These agree with the observed homogeneity index (HI) and conformity index (CI).However, higher beam on time (BOT) leads to increase irradiation time with higher number of field directions.From 5 to 7 field directions, the BOT increases between 115-212 seconds, and from 7 to 9 field directions, the BOT increases between 115-212 seconds for the 8 studied cases.In this case, the patient must be cooperative to prevent movement during treatment.
Using the OARs criteria for the treatment of nasopharyngeal cancer, most cases were at the safe limit for all field directions and there is no clear trend for 5, 7 and 9 field directions.This agrees with the planning purpose to protect the OARs.In few cases, when the OARs were very closed to the target, result in OARs dose exceed the limit, which hard to be avoided.The doses at OARs are attempted not to exceed their limits while the tumor is given dose as maximum as possible simultaneously during the planning.It seems that this mechanism affects no clear trend in OAR doses for 5, 7, and 9 field directions.
Regarding the obtained data of PTV and OARs doses, conformity index, homogeneity index, planning using 7 and 9 field directions meets the criteria for the treatment of nasopharyngeal cancer.Although planning using 9 field directions gives better results, the irradiation time takes longer than planning using 5 and 7 field directions.In the process of radiation treatment, the longer irradiation time needs to immobilize patient longer.However, preventing patient movement during treatment is one of problems during radiation treatment.Therefore, planning using 7 field directions seems to be better than planning using 5 and 9 field directions.

Conclusions
In IMRT planning for 8 nasopharyngeal cases using TPS Monaco, it is obtained that planning using 9 field directions can give dose on the target approximate to the prescription dose better than planning using 5 and 7 field directions.Their conformity index (CI) values are closer to 1, meaning better coverage than planning using 7 and 5 field directions.Their homogeneity index (HI) values are the smallest in planning 5, 7, and 9 field directions.Therefore, planning using 9 irradiation fields has the best dose uniformity.
As the planning purpose is to protect the OARs, in most cases with planning using 5, 7 and 9 field directions, most OARs received doses at safe limit and met the permitted treatment requirements.It cannot be avoided that few OARs received exceed doses because of its close position to the target.
Compare to planning using 5 and 7 field directions, planning using 9 field directions has the highest number of segments, total MU, and beam on time.Since planning using 9 field directions has the longest time of irradiation, preventing patient movement during treatment is crucial. .

Table 1 .
Conformity Index, Homogeneity Index, total MU and Beam on Time nasopharyngeal cancer patients.

Table 2 .
OARs of nasopharyngeal cancer patients.