Differences in superficial dose distribution in patients receiving intensity modulated radiotherapy (IMRT) after radical mastectomy

Introduction

Breast cancer has emerged as a significant health concern among women worldwide with continuously increasing incidence (1). Following radical surgery, breast cancer has a local recurrence rate of 10–30%, primarily affecting the chest wall (2). The accuracy of the dose on the chest wall in postoperative radiotherapy is crucial to treatment success. The superficial region of the chest wall, where residual tumor cells may remain after surgery, is particularly critical. Additionally, the skin in this region may exhibit redness, dryness, or even skin breakdown if exposed to excessive radiation when not fully healed. Conversely, insufficient radiation doses may lead to tumor recurrence. Therefore, the accuracy of the dose delivery in this region directly affects the efficacy of radiotherapy for breast cancer (3). Research has demonstrated that postoperative chest wall radiation therapy can reduce the local recurrence rate by 67% (4). Fixed-beam intensity modulated radiotherapy (IMRT) involves planning and dose evaluation based on static computed tomography (CT) images. However, respiratory motion causes continuous spatial and shape changes in the target area and surrounding normal tissues during actual treatment. This can result in disparities between the actual and calculated dose distributions by the treatment planning system (TPS), leading to inadequate coverage of superficial targets or the presence of high-dose regions. Consequently, this may compromise the effectiveness of post-radical mastectomy radiotherapy or result in excessive skin exposure. Furthermore, respiratory movements notably affect the target region of thoracic tumors and the organs at risk, resulting in discrepancies between the actual absorbed dose in radiation therapy and the dose calculated by the planning system, thereby affecting therapeutic efficacy (5). In this study, a detector capable of monitoring superficial doses was employed to examine variations in target dose for patients receiving radiotherapy after radical mastectomy. Additionally, a phantom was used to investigate dose distribution patterns. High-energy X-rays have a dose build-up effect, leading to inadequate tumor dose on the chest wall during postoperative breast cancer radiotherapy. To eliminate this effect, a compensatory film of specific thickness is applied to a patient’s skin surface during radiotherapy to augment the tumor dose (6). Because the patient’s respiratory movements affect the skin surface dose on the chest wall, radiotherapy accuracy should be improved and respiratory movement should be managed to mitigate its influence. Patients can effectively control their respiratory amplitudes when radiotherapy was delivered through the deep inspiration breath-hold (DIBH) technique. Furthermore, real-time in vivo dosimetry (IVD) serves as a direct and effective quality control measure, facilitating the monitoring of chest wall dose during radiotherapy in patients with breast cancer. Tracking the deviation between the actual treatment dose received by patients and the planned dose offers reliable data for clinicians to promptly identify and address any issues. The results were compared with the calculated values of TPS markers and analyzed. Moreover, the study evaluated the effects of different respiratory amplitudes of patients after breast cancer surgeries under IMRT on chest wall dose, utilizing a respiratory-movement driving platform. We present this article in accordance with the TREND reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-64/rc).

Methods

Research methods

Two sets of experiments were conducted for this study. The first involved in vivo dose monitoring of patients, while the second involved dose monitoring using a phantom at various motion amplitudes.

Patient eligibility

Simulation localization

Thirty patients with left breast cancer, scheduled to undergo IMRT after radical surgery, were selected for this study. The patients were treated in a TrueBeam linac (Varian Medical Systems, Inc., 3100 Hansen Way Palo Aito, CA, USA) at the Proton Center of Shandong Cancer Hospital between August 2022 and October 2022. The age range of the patients was 30 to 50 years, with an average age of 41 years. All 30 patients were fitted with breast brackets. Among the patients, 15 were assigned to Group A and underwent scanning in the free breathing (FB) state. The remaining 15 patients were assigned to Group B and received training in the DIBH (Catalyst C-rad system) technique. These patients could hold their breath for more than 35 s and repeatedly hold their breath at least six times. Before assuming the standard treatment posture, probes were positioned to correspond to the center of the healthy nipple. Three probes were placed in a row 2 cm above the affected chest wall’s original nipple position, while two probes were positioned 2 cm to the left and right, and three other probes were placed 2 cm below. Positioning markers were affixed at these eight designated locations to facilitate dose identification at these points in the TPS. The thickness of the slow acquisition CT image reconstruction layers for the two groups was 3 mm. The scanning range extended from the lower jaw to cover the entire chest.

Treatment planning

The acquired images were imported into the Eclipse TPS. Clinical doctors delineated the regions of the affected chest wall, supraclavicular, and infraclavicular lymph nodes as the clinical target volume (CTV). A 5–10 mm expansion around the CTV was defined as the planning target volume (PTV). All patients were prescribed 50 Gy in 25 fractions of 2 Gy fixed beam intensity modulated radiotherapy, which was applied to the chest target of radical mastectomy and covered with a 5 mm bolus. Each plan was contoured by one radiation oncologist which avoid any variations in the planning process. Figure 1 illustrates the measurement of TPS marker doses in the patients’ target volume. Once the plan was finalized, it was transferred to a Varian linear accelerator, TrueBeam, for treatment.

Figure 1 Dose measurement of TPS markers. TPS, treatment planning system.

Ethical statement

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of Cancer Hospital of Shandong First Medical University (No. 202212003). Informed consent was taken from all patients.

Dosimetry

The linear accelerator employed in this study was the TrueBeam model manufactured by Varian. The IVD system utilized eight quantum effect devices (QED) probes (manufactured by SunNuclear^TM, USA) (6–12 MV), with an active size of 0.8 mm × 0.8 mm. There is not internal buildup in the diode dosimetry. Because this type of diode dosimetry is made for IVD for patients. Accepted a custom-made moving platform and the Model 036S-CVXX-xx anthropomorphic chest phantom were used to simulate respiratory motion. The respiratory motion was simulated using a home-made moving platform driving the phantom in anterior-posterior direction movement at four different amplitudes: 5, 10, 15, and 20 mm.

QED scaling and calibration

The QED probe used for the IVD system in this study consists of a silicon diode semiconductor crystal. This probe is a convenient tool for surface dosimetry because of it’s a small size, real-time readings, and simple operation, and it can be easily placed on the surface of the patient’s skin and phantom. Semiconductor detectors are widely used for patient dosimetry for photon and electron beams. They have high sensitivity 18,000 times more sensitive and high spatial resolution compared to the air-filled ionization chamber with the same volume.

• Stability testing: the stability of the probes was verified by positioning eight QED probes on the surface of solid water and covering it with a blouse. The square field of the accelerator was 10 cm × 10 cm, with a source-to-surface distance (SSD) of 100 cm and X-ray quality of 6 MV. The accelerator was set to deliver 100 MU, and the entire process was repeated five times.
• Calibration: the QED probes were calibrated under standard conditions (SSD =100 cm and field size =10 cm × 10 cm). A square field with dimensions of 10 cm × 10 cm, an SSD of 100 cm, and 6 MV X-ray energy was used. Calibration was performed at the Dmax with a dose of 100 MU. The probe reading was calibrated to 100 cGy. Under the same conditions, a solid water phantom was used to simulate the measurement in the planning system. The dose obtained at a depth of 5 mm in the subcutaneous tissue was 86.7 cGy. The calibration factor of QED probe is 0.867. At 5 mm underwater, the dose of the QED detector relative to the maximum point is 0.867. Finally, the detector reading is multiplied by a factor of 0.867 to obtain the final actual measured dose. Then, the final actual dose is analyzed and compared with the labeled measuring point in TPS.

Dose measurement in post-radical mastectomy radiotherapy

During radiotherapy, eight probes are mounted sequentially to the surface of the skin. Patients using the DIBH technique utilized the Catalyst HD surface monitoring system for respiratory management. The Catalyst HD surface monitoring system is made for the setup for IMRT, in order to improve the dose accuracy. Gated treatment involves setting a predefined threshold within a range of 3 mm, which halts the beam if the translation error exceeds 3 mm. The patients were instructed to perform DIBH after breathing normally. The treatment tables and patient positions were adjusted to align the marked lines on the patient’s body surface with the laser, as depicted in Figure 2. The dose readings from the first three fractions were recorded for each patient, and the average of these three values was calculated.

Figure 2 Real-time monitoring of patients and C-rad gated treatment. The image is published with the patient’s consent.

Respiratory movement simulation

Chest displacement during respiration patients after radical mastectomy was simulated using a driving platform. Eight positions were designated on the phantom, and positioning markers were affixed to these predetermined locations. The resulting images were imported into the Eclipse planning system for physicists to perform plans and design tasks. A single prescribed dose of 2 Gy was planned for each motion amplitude. Once the plan was confirmed, it was sent to the Varian linear accelerator TrueBeam for beam output. The dose variation pattern corresponding to different respiratory amplitudes was observed.

Dose measurement on anthropomorphic chest phantom

The surface dose of the chest wall following radical mastectomy was simulated and measured using an anthropomorphic chest phantom. The phantom and the driving platform were positioned on the treatment table. A treatment plan utilizing IMRT was designed for four different motion amplitudes: 5, 10, 15, and 20 mm. The positioning process was carried out according to the plan, and the previously calibrated QED probes were placed at the predetermined eight positions on the phantom, as depicted in Figure 3. The probes were securely fixed and covered with tissue compensation film. The plan was implemented, and the plan was delivered three times for each motion amplitude. The dosimeter was used to measure the values after each treatment, and the average of the three measurements was calculated.

Figure 3 Platform driving the phantom to execute planned irradiation.

Statistical analysis

The measured values of patients were statistically evaluated using SPSS 25.0 software. The measurement data were presented as mean ± standard deviation (x¯±s). When the paired data did not follow a normal distribution, the Wilcoxon rank sum test was employed to assess the difference between the measured and planned values of the surface dose. Statistical significance was achieved for P values lower than 0.05.

The measured values obtained under different motion amplitudes of the driving platform were analyzed using R4.2.1 statistical software. The measurement data were described as mean ± standard deviation (x¯±s). When the paired data did not exhibit a normal distribution, the Wilcoxon rank sum test was utilized to determine the difference between the measured and planned values of the surface dose, with P<0.05 as statistically significant.

Results

Probe stability analysis

Eight probes of the two base stations were selected for repetitive experiments. The experimental results indicated that all eight probes tended to be stable. The probe positions are depicted in Figure 4. The repeatability error was less than 3%, satisfying the requirements for clinical use. The results are presented in Figures 5,6.

Figure 4 Probe* position setting. *, the two groups of probe points A and B are connected to two base stations.

Figure 5 Base station A. The two groups of probe points A and B are connected to two base stations.

Figure 6 Base station B. The two groups of probe points A and B are connected to two base stations.

Analysis of in vivo measurement

The comparison between patients in the DIBH and FB groups and TPS is presented in Figure 7. The vertical axis represents the absolute dose. The DIBH treatment approach is more consistent with the computer-planned value compared with the FB treatment.

Figure 7 Data distribution map of DIBH and FB. DIBH, deep inspiration breath-hold; FB, free breathing; MV, measure values; TPS, treatment planning system.

Effects of different motion amplitudes on dose distribution

The impact of different motion amplitudes on the dose of the mammary chest wall is presented in Figure 8. It showcases the measurement results of the phantom’s dose at various amplitudes driven by the motion platform. The horizontal axis represents the amplitude, while the vertical axis represents the absolute dose. Figure 8 reveals that when the amplitude of chest wall motion falls within a specific range, the hybrid IMRT has a negligible effect on the surface dose distribution of the chest wall. However, as the motion amplitude increases and surpasses 15 mm, the surface of the chest wall may deviate from the target during irradiation, leading to a lower dose than planned on the body surface.

Figure 8 Differences in dose measurements with different motion amplitudes. The values shown in the figure are the mean ± standard deviation. TPS, treatment planning system; MV, measurement values.

Discussion

A series of necessary quality assurance measures are adopted to ensure that all aspects of the treatment adhere to international standards. In this study, IVD was used to obtain real-time, highly accurate, and reliable measurement data. The silicon diode semiconductor detector, used herein, has distinct advantages in terms of real-time reading and is a widely adopted tool for IVD measurement worldwide.

The effects of respiratory movement on the surface dose of the chest wall in IMRT treatment after radical mastectomy were investigated. Respiratory movement induces thoracic undulation, and in the case of radical mastectomy, the target area for radiotherapy is located on the superficial thorax. Variations in respiratory amplitude can lead to an underestimation or overestimation of the expansion of the tumor target area, resulting in missed target coverage or excessive radiation doses to normal organs. A dose build-up region forms during X-ray irradiation, resulting in a low-dose volume on the skin surface, approximately 3 mm below the subcutaneous tissue. Equivalent compensation films are commonly used to mitigate the dose build-up effect and increase the surface dose in clinical settings (7). The chest wall of patients after radical mastectomy is curved, with uneven skin surface thickness. Postoperative adjuvant chest wall radiotherapy has attracted increasing attention. Many studies have confirmed its positive impact on local control rates and long-term survival rates. Appropriate chest wall irradiation can enhance local control rates and overall survival rates (8). Soong et al. utilized a thermoluminescent dosimeter to measure the average skin dose without filling, with 0.5 cm of filling, and with 1.0 cm of filling when irradiating the tangential chest wall field with 6 MV X-rays (9). The measured doses were 65%, 97%, and 103% of the prescribed dose, respectively. In our study, the average skin doses measured for FB and DIBH were 202±8.22 and 204.42±8.67 cGy, respectively, corresponding to 97% and 99% of the prescribed dose. This discrepancy can be attributed to the uncertainty of the TPS in modeling subcutaneous dose build-up regions. The current use of fillers presents challenges in ensuring optimal adherence to the skin. Moreover, patients may experience shortness of breath and increased chest wall undulation due to nervousness during radiotherapy. Therefore, the measured skin dose is lower than the planned dose, consistent with the findings of other relevant studies. Lateral electron disequilibrium may also contribute to these discrepancies (10).

This study demonstrated that minor fluctuations in the respiratory amplitude curve do not substantially affect the surface dose of the chest wall. As long as the respiratory amplitude remains within a specific range, the chest wall movement remains within the modeling area defined by the planning system and aligns with the plateau region of the dose gradient rather than the dose-decreasing region. Consequently, the dose delivered to the chest wall does not change substantially. Additionally, dynamic IMRT technology introduces changes in the shape of the radiation field as the chest wall moves. The simultaneous movements of the chest wall and the multi-leaf collimator interact with the dose distribution within the target area (11). Therefore, minor variations in respiratory amplitude do not lead to noticeable dose variations. However, when the respiratory amplitude exceeds 15 mm, the measured dose decreases substantially, and the chest wall surface deviates from the intended target, resulting in insufficient radiation dosage reaching the skin surface. In clinical practice, most radiotherapy plans are based on static imaging. However, motion artifacts arising from respiratory movement can lead to up to an 89% discrepancy in three-dimensional volume reconstruction of the target area (12). To address this issue, 4D-CT scanning technology can be used to accurately capture the target volumes, allowing for personalized safety margins based on patients’ motion amplitudes and reducing damage to normal tissues. Furthermore, the forward-looking respiratory gating technique, the DIBH method, and real-time tracking radiation therapy can be employed to mitigate errors due to organ motion resulting from respiratory movement.

Conclusions

For postoperative IMRT in radical mastectomy cases, the use of the IVD system allows for verification of the surface dose on the chest wall. It has been observed that when the respiratory amplitude exceeds 15 mm, the target area on the chest wall’s surface deviates from its intended location, resulting in the prescribed dose not being achieved. Additionally, in DIBH radiotherapy following radical mastectomy, the C-rad Catalyst HD system enables auxiliary positioning correction before treatment and real-time monitoring during treatment. Therefore, this method is expected to find widespread application in the clinical field of radiotherapy. During fix-beam IMRT radiotherapy following radical mastectomy, minor respiratory movements do not substantially affect the superficial dose on the bolus-covered chest wall target. However, high-amplitude respiratory movements can lead to target dose variations of up to 10%, potentially compromising the effectiveness of the treatment. Therefore, implementing respiratory management protocols is crucial for specific cases of patients receiving radiotherapy after radical mastectomy.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the TREND reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-64/rc

Funding: This work was supported by the National Natural Science Foundation of China (No. 82172072, to J.Z.) and the Foundation of Taishan Scholars, China (No. tsqn201909140, to J.Z.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-64/coif). J.Z. reports that this work was supported by the National Natural Science Foundation of China (No. 82172072) and the Foundation of Taishan Scholars, China (No. tsqn201909140). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of Cancer Hospital of Shandong First Medical University (No. 202212003). Informed consent was taken from all patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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