A Comparative Study of Dosimetric Analysis of Three Different Sets of Five Fields and Seven Fields IMRT Plans for Prostate Cancer ()
1. Introduction
Intensity-Modulated Radiation Therapy (IMRT) is significant Radiation delivery technique for prostate cancer. However, the anatomical location of the prostate, which is in close proximity to the rectum, bladder, penile bulb, and femoral heads exposes these organs at risk of receiving radiation dose and subsequent toxicity during prostate cancer treatment by radiation. Historically, radiation was delivered using 4 field box techniques, which limited the total dose that could be delivered to the prostate without exceeding the tolerance dose limit of surrounding critical normal structures. Multiple studies have shown an improved tumor control rate with dose-escalated radiation therapy to prostate [1] [2] [3] [4] several single institution series has reported a reduction in late toxicity with the introduction of IMRT compared to 3DCRT, even with dose escalation [4] [5] .
The use of IMRT in the treatment of localized prostate cancer is associated with significantly lower doses of radiation delivered to the rectum and bladder. The ability of IMRT to reduce dose to nearby normal structures without sacrificing dose coverage of the target makes it an ideal treatment modality for prostate cancer.
The beam orientations used for the IMRT treatment of prostate cancer are still selected empirically, without any guideline. In the past several groups have investigated the number and orientations of beams in IMRT of prostate cancer [6] [7] . Practically in the treatment of prostate cancer by IMRT technique five to seven beams of different gantry angle are used.
The aim of this study is to compare the dose to normal tissues and dose-limiting structures such as rectum and urinary bladder, conformity index, homogeneity index, number of monitor units required for the treatment of prostate cancer when using the same prescription doses, same planning system and PTV margins with 3 sets of five and seven beam IMRT plans.
2. Methods & Material
A thermoplastic pelvic mask was used to immobilize the patients and CT reference isocenter were marked on the mask with the help of fidiucial lead balls. Planning CT scan with 3 mm thickness was acquired in the treatment position from level L2-3 to the ischial tuberosity. They were placed in supine position with special instruction to keep their rectum empty and bladder comfortably full at the time of simulation and during each treatment fraction. CT slices of patient were transferred to Elekta focal-SIM contouring workstation via DICOM for contouring.
For this study, 6 different IMRT plans were created for each of the 10 patients undergoing radical radiation treatment for prostate cancer. The IMRT plans generated included 3 different set of 5 beam gantry angles 5B1 (0˚, 50˚, 100˚, 260˚, 310˚) as shown in Figure 1, 5B2 (45˚, 105˚, 180˚, 225˚, 315˚) as shown in Figure 2, 5B3 (0˚, 75˚, 135˚, 225˚, 285˚) as shown in Figure 3 and 3 different sets of 7 beam gantry angle 7B1 (0˚, 51˚, 102˚, 153˚, 204˚, 255˚, 306˚) as shown in Figure 4, 7B2 (0˚, 37˚, 75˚, 135˚, 225˚, 285˚, 327˚) as shown in Figure 5, 7B3 (25˚, 75˚, 130˚, 180˚, 230˚, 280˚, 335˚) as shown in Figure 6. Thus, a total of 60 plans were generated using step & shoot treatment delivery technique with 80 leaf Multileaf collimator and leaf width of 1cm at the isocenter. The IMRT plans were created using Xio TPS with 6 MV photon and superposition algorithms. A hypo fractionated prescription dose of 70 Gy/28# at 2.5 Gy per fraction was used. The plans were evaluated with the help of Dose Volume Histogram.
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Figure 1. 5B1 (0˚, 50˚, 100˚, 260˚, 310˚).
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Figure 2. 5B2 (45˚, 105˚, 180˚, 225˚, 315˚).
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Figure 3. 5B3 (0˚, 75˚, 135˚, 225˚, 285˚).
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Figure 4. 7B1 (0˚, 51˚, 102˚, 153˚, 204˚, 255˚, 306˚).
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Figure 5. 7B2 (0˚, 37˚, 75˚ 135˚, 225˚, 285˚, 327˚).
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Figure 6. 7B3 (25˚, 75˚, 130˚, 180˚, 230˚, 280˚, 335˚).
The dose coverage for each patient’s six different IMRT plans for the PTV are designated to an international Commission Radiation Units and Measurements report 62 reference point in the PTV, Medium coverage of the planned target volume to be 95% of the prescribed dose while the maximum dose in the target volume to be not greater than 107% of the prescribed dose and number of MUs were evaluated. Normal tissue like rectum and urinary bladder receiving maximum, Minimum and V65 Gy < 35% & V70 Gy < 25% volume in different IMRT plans are calculated. Femoral head maximum dose is below 54 Gy and Penile bulb Dmean less than or equal to 52.5 Gy (optional in the protocol) for all plans.
Analysis of Physical Parameter in Intensity Modulated Radiotherapy Plans:
The plans were evaluated for approval with following Plan evaluation parameters:
· HI—Homogeneity Index = D5%/D95%, where D5% and D95% are minimum dose to 5% & 95% of the target volume respectively [8] .
· CI formula as suggested by ICRU Report 62 which was originally reported in RTOG 90-05 protocol [9] .
CI—Conformity Index (for 95% of PD) = Volume receiving 95% of PD/PTV
Homogeneity index indicates the dose homogeneity in the target volume and Conformity index indicates the dose confinement near to target volume and level of dose spillage in normal tissue volume around the target volume. Value of HI and CI = 1 is best; although it is not possible practically and the value of both indices always remain higher than 1 lower than near about 1.
Statistical Analysis
Data was entered on excel sheet and ANOVA with turkey multiple comparison test and Kruskal-Wallis test with Dunn’s Multiple Comparison Test was applied for parametric and non-parametric data respectively using Graph pad (version 5) software. A P-value ≤ 0.05 was considered statistically significant.
3. Result
Ø The doses which are delivered to the V65 & V70 Urinary Bladder dose in different IMRT plans are as shown in Tables 1-4 and we observed non-significant (P > 0.05) difference between the groups using ANOVA test with turkey multiple comparison test.
The doses which are delivered to the V65 & V70 rectum dose in different IMRT plans are as shown in Tables 5-8 and we observed non-significant (P > 0.05) difference between the groups using Kruskal-Wallis test with Dunn’s Multiple Comparison Test.
Mean of Maximum doses deliver to bladder in all 6 IMRT plans 5B1, 5B2, 5B3, 7B1, 7B2, 7B3 to all 10 patients are 75.29 Gy, 74.99 Gy, 74.60 Gy, 74.98 Gy, 75.25 Gy and 75.22 Gy (P = 0.0.00023, 0.787912/NS, = 0.000995, 0.000113 and 0.000342). But there is non-significant difference between all IMRT accept 5B3
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Table 1. V65 Urinary bladder dose in different IMRT plans.
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Table 2. Tukey’s multiple comparison test for V65 of urinary bladder in different IMRT plans.
Significant (s), Non-Significant (ns).
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Table 3. V70 urinary bladder dose in different IMRT plans.
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Table 4. Tukey’s multiple comparison test for V70 urinary bladder dose in different IMRT plans.
Significant (s), Non-Significant (ns).
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Table 5. V65 rectum dose in different IMRT plans.
as shown in Figure 7 & Figure 8.
Mean of Maximum doses deliver to rectum in all 6 IMRT plans 5B1, 5B2, 5B3, 7B1, 7B2, and 7B3 to all 10 patients are 73.78 Gy, 73.36 Gy, 74.21 Gy, 74.50 Gy, 74.34 Gy and 74.21 Gy, (P = 0.35951/NS, 0.560054/NS, 0.026766/S, P = 0.018904/S, 0.027704/S and 0 respectively). But there is significant difference between all IMRT accept 5B3 as shown in Figure 9 & Figure 10.
For conformity index of various IMRT plans there is non-significant (P > 0.05) difference between the various groups using ANOVA test with turkey
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Table 6. Tukey’s multiple comparison test for V65 rectum dose in different IMRT plans.
Significant (s), Non-Significant (ns).
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Table 7. V70 rectum dose in different IMRT plans.
multiple comparison test as shown in Figure 11 and Table 9 and Table 10.
For Homogeneity index of various IMRT plans there are non-significant (P > 0.05) difference between the various groups using ANOVA test with turkey multiple comparison test as shown in Figure 12 and as shown in Table 11 and Table 12.
For Monitor Unit of various IMRT plans there are non-significant (P > 0.05) difference between the groups using Kruskal-Wallis test with Dunn’s Multiple Comparison Test as shown in Table 13 & Table 14.
5 field IMRT plans achieved a 14.9% relative decrease in the mean number of monitor units for radiation delivery as compared to 7 field IMRT plans (mean
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Table 8. Tukey’s multiple comparison test for V70 rectum dose in different IMRT plans.
Significant (s), Non-Significant (ns).
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Figure 7. V65 urinary bladder dose in different IMRT plans.
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Figure 8. V70 urinary bladder dose in different IMRT plans.
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Figure 9. Rectum V65 dose for different IMRT plans.
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Figure 10. Rectum V70 dose for different IMRT plans.
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Figure 11. Conformity index of various IMRT plans.
MU of all 3 sets 668.288 Vs 817.387) as shown in Figure 13 and Table 15.
Ø All IMRT plans, 3 different set of 7 beam gantry angles and 3 different set of 5 beam gantry angles, differed slightly in the measured parameters, however none of them was statistically significant.
Ø Conformity index, Homogeneity index and monitor units all showed non-significant (P > 0.05) difference between the various groups of different IMRT plans.
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Figure 12. Homogeneity index of various IMRT plans.
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Figure 13. Monitor unit of various IMRT plans.
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Table 9. Conformity index of various IMRT plans.
Ø However, 5 field IMRT plans achieved a 14.9% relative decrease in the mean number of monitor units for radiation delivery as compared to 7 field IMRT plans.
4. Discussion
Prostate cancer is the most frequently diagnosed cancer among men in over
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Table 10. Tukey’s multiple comparison test for conformity index of various IMRT plans.
Significant (s), Non-Significant (ns).
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Table 11. Homogeneity index of various IMRT plans.
one-half of the countries of the world [10] . Several treatment alternatives exist for localized prostate cancer, including observation, prostatectomy, brachytherapy and external beam radiation therapy (EBRT). The outcome of the treatment of early prostate cancer has improved in recent years mainly due to the radiation dose escalation [11] .
The major advantage of IMRT is the ability to decrease the dose to critical structures, which in turn lowers the radiation toxicity effects [12] . In recent years, dose escalation has been shown to improve the probability of local tumour
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Table 12. Tukey’s multiple comparison test for homogeneity index of various IMRT plans.
Significant (s), Non-Significant (ns).
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Table 13. Monitor units of various IMRT plans.
control in prostate cancer [11] [13] . The increase of normal tissue integral dose with multiple beam radiation therapy during IMRT is also a major concern due to the potential risk of the secondary malignancies especially in younger patients [14] .
IMRT uses beam modulation with the help of multileaf collimators and complicated inverse planning software and calculation algorithms. Beam configuration may have significant influence on the quality of an IMRT treatment. The planning process is time taking as it compares different beam configurations
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Table 14. Dunn’s multiple comparison test of various IMRT plans.
Significant (s), Non-Significant (ns).
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Table 15. Comparison of the mean dosimetric parameters.
from different angles to get the best optimization possible. This often becomes a tedious process, especially in centers with limited resources and large number of patients. Empirically, 5 to 7 field IMRT plans with various beam angles are used in treating prostate cancer. The use of an optimal starting gantry angle for 5 equiangular-spaced beams facilitate rectal sparing and can produce plans that are equivalent to those employing 7 equiangular-spaced beams [15] . Mahdavi et al. also concluded that in comparison to the 7 field technique, the 5 field IMRT technique has resulted in improved IMRT dose conformity, homogeneity, and lesser MUs used for radiation therapy [16] .
In this study we have used 3 different sets of 5 beam gantry angle and 3 different sets of 7 beam gantry angle and tried to find the best combination which can be applied in general to our patients. The results show that though there are slight differences in various measured parameters, none of them are statistically significant. Both conformity index and Homogeneity index showed non-significant (P > 0.05) difference between the various groups of different IMRT plans. Monitor units also showed non-significance difference between various groups. However, 5 field IMRT plans achieved a 14.9% relative decrease in the mean number of monitor units for radiation delivery as compared to 7 field IMRT plans. Due to the lesser number of monitor units in 5 beam gantry angles, treatment was completed in lesser time and also resulted in lesser integral dose to normal tissue and lesser chance of secondary malignancy.
5. Conclusion
Radiation therapy for prostate cancer has evolved drastically over the past few years. The Intensity Modulated Radiation Therapy (IMRT) is a novel form of radiation delivery technique for prostate cancer which allows dose escalation and therefore improved tumour control. Various techniques in terms of number of beams and angles can be used to get the desired dose distribution, but the process is time-consuming. After trying 6 different combinations of beams in our patients we found that in terms of conformity index, homogeneity index and monitor units both 5 beam and 7 beam IMRT technique show non-significant difference. However, 5 field IMRT plans use a lesser number of monitor units per treatment than 7 field IMRT plans. A decrease in monitor units also leads to the lesser linear accelerator beam-on time and consequently lesser treatment time and running cost. Thus, in a high-volume centre with 5 field technique we can treat more patients in lesser time.
Limitation of This Study
1) Small sample size.
2) The clinical correlation of doses received by OARs in this of acute & late toxicities was not done.
3) Require prospective, randomized study with large sample size and long term follow up for assessing significant clinical outcome.
Ethical Clearance
The study is a comparison of different treatment plans in the same data set. However, there was no change in the patient’s treatment plan for the proposed study. So ethical committee clearance was not required.
The study has been approved and allowed by the Head of the Institute.
Acknowledgements
Dr. Richa Chauhan, MCS, Patna.
Finical Support
None.