BioMed Research International

BioMed Research International / 2020 / Article

Research Article | Open Access

Volume 2020 |Article ID 9097352 | https://doi.org/10.1155/2020/9097352

Du Tang, Zhan Liang, Fada Guan, Zhen Yang, "Dosimetric and Radiobiological Comparison of Five Techniques for Postmastectomy Radiotherapy with Simultaneous Integrated Boost", BioMed Research International, vol. 2020, Article ID 9097352, 9 pages, 2020. https://doi.org/10.1155/2020/9097352

Dosimetric and Radiobiological Comparison of Five Techniques for Postmastectomy Radiotherapy with Simultaneous Integrated Boost

Academic Editor: Xin-yuan Guan
Received02 Feb 2020
Revised08 Jun 2020
Accepted10 Jun 2020
Published21 Jul 2020

Abstract

Purpose. To compare five techniques for the postmastectomy radiotherapy (PMRT) with simultaneous integrated boost (SIB). Materials and Methods. Twenty patients with left-sided breast cancer were retrospectively selected. Five treatment plans were created for each patient: TomoDirect (TD), unblocked helical TomoTherapy (unb-HT), blocked HT (b-HT), hybrid intensity-modulated radiotherapy (hy-IMRT), and fixed-field IMRT (ff-IMRT). A dose of 50.4 Gy in 28 fractions to PTVtotal and 60.2 Gy in 28 fractions to PTVboost were prescribed. The dosimetric parameters for targets and organs at risk (OARs), the normal tissue complication probability (NTCP), the second cancer complication probability (SCCP) for OARs, and the treatment efficiency were assessed and compared. Results. TD plans and hy-IMRT plans had similar good dose coverage and homogeneity for both PTVboost and PTVtotal and superior dose sparing for the lungs and heart. The ff-IMRT plans had similar dosimetric results for the target volumes compared with the TD and hy-IMRT plans, but gave a relatively higher NTCP and SCCP for the lungs. The unb-HT plans exhibited the highest OAR mean dose, highest NTCP for the lungs () and heart (), and highest SCCP for the lungs () and contralateral breast () among all techniques. The b-HT plans significantly outperformed unb-HT plans with respect to the sparing of the lungs and heart. This technique also showed the best conformity index () for PTVboost and the optimal NTCP for the lungs () and heart (). Concerning the delivery efficiency, the hy-IMRT and ff-IMRT achieved much higher delivery efficiency compared with TomoTherapy plans. Conclusion. Of the five techniques studied, TD and hy-IMRT are considered the preferable options for PMRT with SIB for left-sided breast cancer treatment and can be routinely applied in clinical practice.

1. Introduction

Postmastectomy radiotherapy (PMRT) plays a critical role in breast cancer treatment. Previous studies have demonstrated a significant improvement in overall and local survival after PMRT in breast cancer patients [1, 2]. The use of a tumor-bed boost scheme has shown the further improvement in the local-regional control for patients with high-risk features [3]. Although there is lack of randomized data to guide the boost dose setting, the boost technique is accepted as a routine practice in many centers [35]. According to our local protocol, the simultaneous integrated boost (SIB) scheme is administrated for high-risk cases. The delivery of PMRT with SIB for patients is challenging due to the large target volume size, high prescription dose, and proximity to critical organs, especially for patients who suffer from left-sided breast cancer. Therefore, it is of great importance to find the optimal technique for PMRT with SIB.

Advanced RT techniques, such as fixed-field IMRT (ff-IMRT), or further developments, such as TomoTherapy, now allow treating multiple target volumes with different prescribed doses in a single plan. Previous studies have demonstrated that IMRT and TomoTherapy outperformed conventional three-dimensional conformal radiotherapy (3DCRT) for the whole breast irradiation [68]. Several studies have already been published comparing various treatment modalities for PMRT treatment without the boost scheme [911] and the whole breast irradiation [8, 12, 13]. Very few publications, however, have focused on such comparison in PMRT with SIB. Since the dose prescription scheme and the definition of the target volumes in previous studies were different from those for PMRT with SIB, the results in previous studies cannot simply be transferred to the treatment for this group of patients. Dedicated planning studies for PMRT with SIB are therefore necessary to identify the appropriate techniques. Moreover, the feasibility of TomoDirect (TD) [14], a nonrotational treatment option in the new version of TomoTherapy, is yet to be studied for PMRT with SIB. In this study, the comparison of dosimetric parameters, radiobiology indices, and delivery efficiency among the TD, helical TomoTherapy (HT), ff-IMRT, and hy-IMRT plans was performed for PMRT with SIB.

2. Materials and Methods

2.1. Patient Selection, CT Simulation, and Contouring

Twenty patients who underwent PMRT with SIB in Xiangya Hospital of Central South University between December 2016 and July 2019 were retrospectively selected in this study. The inclusion criteria were as follows: (1) female patients older than 18 years with left-sided breast carcinoma, who had undergone radical mastectomy; (2) diagnosis of invasive cancer was pathologically confirmed; (3) surgical margin was negative; (4) had received chemotherapy in accordance with standards and guidelines before radiotherapy. Table 1 outlines the patient characteristics.


CharacteristicValue

Age (y)
 Median49.5
 Range30-65
Menopausal status ()
 Pre12
 Post8
Histologic grading
 Grade 214
 Grade 36
Tumor size (cm)
 Median3.25
 Range1.5-10
ER/PR status ()
 Negative9
 Positive11
Her-2 status ()
 Negative14
 Positive6
Chemotherapy ()
 Preoperative13
 Postoperative7

The free-breathing CT scans were obtained from the level of the mandible to the lower abdomen on a SOMATOM Definition AS CT scanner (Siemens Medical Solutions, Erlangen, Germany) with a slice thickness of 3 mm. Patients were immobilized on a customized evacuated vacuum bag, in the supine position with the use of a wing board for arm positioning above the head. The clinical target volume (CTV) and OARs for each patient were contoured by the attending physician. The CTV was defined as chest wall (CW), internal mammary nodes (IMNs), and axillary and supraclavicular lymph nodes. A margin of 5 mm was added to the CTV, given the PTVtotal, to consider for daily setup and organ motion. The boost volume was drawn to include the site of surgically removed tumor, according to pre- and postoperative CT images and surgical reports. A setup safety margin of 5 mm was added, given the PTVboost. Both PTVtotal and PTVboost were constrained to be inside the body surface. A 5 mm bolus was applied to the skin of the left CW to ensure adequate skin dose [1]. The following OARs were considered: contralateral breast, lungs (including ipsilateral lung and contralateral lung), heart, and spinal cord.

2.2. Treatment Planning

6 MV photons were used in all the plans. The prescription doses () were 50.4 Gy in 28 fractions and 60.2 Gy in 28 fractions for PTVtotal and PTVboost, respectively. The optimization goal was to achieve ≥95% of PTVtotal and PTVboost receives 100% of . Meanwhile, the following dose constraints were used for OARs in the optimization: (1) , , , for the ipsilateral lung; (2) , for the contralateral lung; (3) , , , for the heart; (4) , for the contralateral breast.

The TD and HT plans were created and optimized on the TomoHD™ planning station (version 5.1.1.6, Accuray Inc., Sunnyvale, CA). For TD plans, the paired tangential beam angles were used. Moreover, two additional fields with modified gantry angles of ±10° from the tangential beam set and an anterior supraclavicular field were employed. Two HT plans were created with and without a complete blocking structure. For HT plans with the blocking structure (b-HT), the primary radiation beams were limited to pass through part of the lungs and heart to improve the dose sparing. For HT plans without the blocking structure (unb-HT), the primary beams can pass through the lungs and heart. A jaw size of 2.5 cm, a pitch of 0.25, a modulation factor (MF) of 2.0, and a fine calculation grid of were set for all TomoTherapy plans. The dose calculation was performed using the convolution/superposition algorithm. During planning, once the dose objectives of PTVtotal and PTVboost were achieved, the optimization was sustained to reduce the OAR dose until the plan could no longer be improved.

The ff-IMRT and hy-IMRT plans were created on the Eclipse Treatment Planning System (TPS version 13.6, Varian Medical Systems, Palo Alto, CA) for a Varian 23EX Linac. For ff-IMRT plans, the dose was contributed by five IMRT beams with the same gantry angle settings with the TD plans. In hy-IMRT plans, the same five IMRT beams and a pair of tangential CRT fields were used. The CRT fields delivered 70% of the to the PTVtotal, and the other five IMRT fields were optimized based on the CRT beams, providing the remaining dose to PTVtotal and PTVboost. Anisotropic analytical algorithm (AAA) and a grid of were used for dose calculations.

2.3. Plan Evaluation

Multiple DVH metrics were extracted to compare the dose coverage of the target volumes and the dose sparing of OARs. For PTVboost, the conformity index (CI) was calculated using the formula [15], where TVPIV is the target encompassed within the volume covered by the prescription isodose surface (PIV) and TV is the total volume of the target. The homogeneity index was calculated using . For PTVtotal, the quality of dose coverage () [13] and the heterogeneity index (hI) [13] were calculated using and , respectively.

The NTCP for the lungs and heart and the SCCP for the lungs and contralateral breast were evaluated to quantify the risk of late injury of OARs. Prior to the calculation of radiobiological metrics, the physical dose was corrected for the fractionation effect using the linear-quadratic (LQ) model [16] (). The differential dose-volume histograms (dDVH) were then imported into an in-house MATLAB-based program (MathWorks, Natick, MA) to calculate the NTCP and SCCP values.

The NTCP for the lungs to developing pneumonitis was estimated using the Lyman-Kutcher-Burman (LKB) model [17, 18]. The NTCP for the lungs was calculated with the following parameters: , , and [19, 20].

The NTCP for cardiac mortality endpoint was calculated using the widely accepted relative seriality (RS) model [21]. The parameters used in the RS model were , , and [22].

The SCCP was calculated for the lungs and contralateral breast with the Schneider model [23, 24] using where is the cell radio sensitivity (Gy-1) and Inorg is the absolute cancer incidence rate in percent per gray for the specific organ. The parameters used to calculate SCCP were and [23] for the lungs and and [24] for the contralateral breast, respectively.

To compare the delivery efficiency, the number of monitor units (MUs) and the delivery beam-on time were also analyzed.

2.4. Statistical Analysis

Statistics of the data were presented as (SD). The differences of the dosimetric parameters and the radiobiological metrics between the five plans were analyzed using ANOVA and post hoc Tukey test with SPSS statistical software (version 23.0, Chicago, IL). The difference was considered statistically significant if .

3. Results

3.1. Planning Target Volumes

The mean volume of PTVboost and PTVtotal of the twenty patients was (ranging from 22.7 to 113.1 cm3) and (ranging from 393.2 to 917.7 cm3), respectively. The dosimetric parameters, radiobiological metrics, and delivery efficiency results were summarized in Table 2. The values for multiple comparisons using post hoc Tukey test are presented in Table 3. The isodose distributions and DVHs for one typical patient were shown in Figures 1 and 2, respectively.


ParameterTDunb-HTb-HTff-IMRThy-IMRT

PTVboost
(Gy)
(Gy)
(Gy)
(%)
 CI
 HI
PTVtotal
(Gy)
(Gy)
(Gy)
 hI
Lungs
(%)
(%)
 NTCP (‰)
 SCCP (%)
IL lung
(%)
(%)
(Gy)
CL lung
(%)
(Gy)
Heart
(%)
(%)
(%)
(%)
(Gy)
 NTCP (%)
CL breast
(Gy)
 SCCP (%)
Spinal cord
(Gy)
Delivery efficiency
 MU
 Time (s)

TD: TomoDirect; unb-HT: helical TomoTherapy without blocking structure; b-HT: helical TomoTherapy with blocking structure; ff-IMRT: fixed-field IMRT; hy-IMRT: hybrid IMRT. (Gy): dose absorbed by certain percentage (%) of the structure; (%): fractional volume exposed to certain radiation dose; IL lung: ipsilateral lung; CL lung: contralateral lung; CL breast: contralateral breast; similarly hereinafter.

ParameterTD vs. unb-HTTD vs. b-HTTD vs. ff-IMRTTD vs. hy-IMRTunb-HT vs. b-HTunb-HT vs. ff-IMRTunb-HT vs. hy-IMRTb-HT vs. ff-IMRTb-HT vs. hy-MRTff-IMRT vs. hy-IMRT

PTVboost
0.9971.0000.0390.7710.9890.0150.5620.0560.8430.435
0.7730.9990.9850.9850.6160.9680.9680.93600.9361.000
0.0120.0680.2010.0300.9720.801<0.0010.988<0.001<0.001
1.0000.4521.0001.0001.0000.3610.2700.4420.3401.000
 CI0.019<0.0010.9890.9760.0480.0690.090<0.001<0.0011.000
 HI<0.0010.0050.0400.8980.7200.288<0.0010.952<0.0010.003
PTVtotal
0.050<0.0010.0120.0940.0030.9851.0000.0180.0011.000
0.4680.3440.6430.6981.0000.9990.997.0.9880.9811.000
<0.0010.7331.0000.952<0.001<0.001<0.0010.6430.2990.979
0.061<0.0010.0210.1190.0050.9950.9990.0180.0020.961
 hI0.016<0.0010.0160.8460.0241.0000.2010.024<0.0010.201
Lungs
<0.0010.3640.1830.989<0.001<0.001<0.0010.9950.6640.418
<0.0010.9990.9910.295<0.001<0.001<0.0010.9590.1920.562
 NTCP<0.0011.0001.0001.000<0.001<0.001<0.0011.0001.0001.000
 SCCP<0.0010.1300.4851.000<0.001<0.001<0.0010.9420.1940.610
IL lung
<0.0010.0080.0020.241<0.001<0.001<0.0010.9870.6730.361
<0.0010.9800.9980.327<0.001<0.001<0.0010.9000.1090.520
<0.0010.9771.0000.956<0.001<0.001<0.0010.9791.0000.959
CL lung
<0.0010.9980.9840.977<0.001<0.001<0.0011.0000.8910.796
<0.0010.9971.0000.860<0.001<0.001<0.0010.9860.6780.927
Heart
<0.0010.8430.1610.965<0.001<0.001<0.0010.0120.4490.489
<0.0010.6740.5560.471<0.001<0.001<0.0010.0430.9980.018
<0.0010.9561.0000.992<0.001<0.001<0.0010.9070.9990.973
<0.0010.9081.0001.000<0.001<0.001<0.0010.9030.9201.000
<0.0010.9010.9861.000<0.001<0.001<0.0010.6300.9540.958
 NTCP0.0080.3030.9991.000<0.004<0.001<0.0090.4300.2970.999
CL breast
<0.001<0.0010.9830.682<0.001<0.001<0.0010.001<0.0010.936
 SCCP<0.001<0.0010.9310.152<0.001<0.001<0.0010.001<0.0010.559
Spinal cord
0.2250.9950.9750.9800.4230.0600.0660.8620.8791.000
Delivery efficiency
 MU<0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.0011.000
 Time0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.001<0.0011.000

The difference is statistically significant.

All techniques meet the clinical requirements of PTVboost and PTVtotal dose coverage. For PTVboost, we found no significant difference in , , and () among the five techniques, except that in unb-HT () and in TD () plans was slightly higher than that in ff-IMRT (). The hy-IMRT plans exhibited the lowest mean dose () followed by TD plans (), while there was no significant difference between the other three techniques. The b-HT technique provides the optimal conformity () followed by unb-HT (, ), hy-IMRT (, ), ff-IMRT (, ), and TD (, ). The best HI was achieved in hy-IMRT with , followed by TD plans with . Relatively lower HI values were provided by ff-IMRT (), unb-HT (), and b-HT () plans, but there was no significant difference between them.

For PTVtotal, b-HT exhibited a lower () than the other four techniques. There was no significant difference in of the five techniques. The unb-HT plans exhibited higher mean dose () than the b-HT plans (, ), the TD plans (, ), the ff-IMRT plans (, ), and the hy-IMRT plans (, ). TD plans exhibited the best quality of dose coverage and homogeneity by showing the highest and lowest , respectively. On the contrary, b-HT plans gave the lowest (, ) and the highest hI (