Dosimetric Study and Robustness Analysis of Base Note Intensive Locked Field Radiotherapy for Left Breast Cancer

Introduction

Breast cancer is one of the most common malignant tumours in women, and radiotherapy is an important part of the comprehensive treatment of breast cancer.¹ Postoperative radiotherapy can effectively reduce the likelihood of local and regional lymph node recurrence. For patients with intermediate and advanced stage disease, adjuvant radiotherapy is usually needed to the lymphatic drainage area above and below the clavicle and to the breast area in the chest wall.² The number of fields and field angles used for treatment and fixed-field intensity tuning vary between investigators and extensive dosimetric comparisons have been made.³ The prognosis of breast cancer is favorable, and the radiation carcinogenic effect after radiotherapy has attracted increasing attention. Michael H conducted an in-depth and systematic analysis of the articles published between 2006 and 2017, and concluded that low-dose radiation increases the risk of related tumors.⁴ Pericarditis, valvular dysfunction, cardiomyopathy and coronary artery disease are some of the most severe advanced cardiotoxic effects that make the incidence of radiation-induced heart disease between 5% and 10% with in 10–30 years after irradiation.⁵ Fixed tungsten door, which is the lead door, relies on the movement of the MLC to meet the optimal design. Fixed tungsten grating technology is an intensity modulation technique that can reduce leakage rays by locking multiple gratings, and the technique of intensity-modulated radiotherapy can limit the range of the field of view.⁶ It is estimated that by following classic fractionated radiotherapy, the risk of cardiac mortality is <1% for 15 years when one-tenth of the whole heart volume receives less than 25 Gray (Gy),⁷ and it could reduce the dose to the normal organs such as lung and heart in the radiotherapy of patients with breast cancer. Moreover, cardiac damage was found to be correlated with the heart-absorbed dose with 7.4% rate increase of ischemic heart disease per one Gy (95% confidence interval, 2.9–14.5; P<0.001), with no minimum threshold for risk.⁸ Afifi et al⁹ revealed that BC remains the main cause of death, and that heart disease may be an important cause of cancer-unrelated deaths. Due to the fact that the large coronary arteries are located deep in the heart, they increase linearly with the average dose to the heart.¹⁰ Optimizing the dose distribution in the heart by fixing the tungsten gate, known as field-locking, can reduce radiation damage.^11–13

There are many uncertainties in the planning and delivery of radiotherapy.^14,15 The intensity modulation technique is mainly based on the movement of the multileaf collimator (MLC) to achieve intensity modulation in the field, and the change in MLC position will have different effects on the target area and organs at risk. In the present study, a specific shot-field fixation tungsten gate intensity-modulated radiation therapy (IMRT) plan was designed separately from the split-field plan for patients after radical surgery for breast cancer with supraclavicular lymph node metastases.

The use of dose robustness and correlation of dose distributions in photon radiotherapy has been relatively little studied, with motion and uncertainty in radiotherapy leading to the onset of robustness. As the complexity of radiotherapy planning increases, the same applies to the need for plan robustness.¹⁶ In the present study, focus was addressed on the effect of field-locking and field-splitting plans on the dose distribution to the target area and critical organs after radical left breast cancer surgery, as well as the introduction of offsets of 3, 5 and 7 mm in six directions and the recalculation of perturbed dose distributions. To compare the dose difference (∆D) between the original and perturbed plans according to the robustness of the plan and to understand how the difference varies between the dose distribution to the target area and the dose distributions to the heart, lung, contralateral breast and other critical organs, they were irradiated with different dose volumes. In the present study, the advantages and disadvantages of the two plans and the sensitivity of these two modalities to positional shifts were investigated with the aim of providing a reference for clinical preference.

Materials and Methods

Case selection

These data are purely theoretical studies and have obtained informed consent from the study participants. The present study was approved (approval no. XJZ-LL-2019-001) by the Ethics Committee of The Affiliated Cancer Hospital of Xinjiang Medical University (Urumqi, China). A total of 30 patients who received adjuvant radiotherapy after radical mastectomy for breast cancer treated at The Affiliated Cancer Hospital of Xinjiang Medical University between January 2019 and May 2021 were retrospectively analyzed. The irradiation target area includes the chest wall and regional lymph nodes (RNI). Written informed consent was obtained from all patients. Patient characteristics are listed in Table 1.

Table 1 Clinical and Statistical Characteristics of the Patient Cohort

Position fixation and CT scanning

The position was fixed with a body membrane. Siemens Somatom Sensation 16-row spiral CT was performed in supine position. The scanning range is from chest Lower sternum to the level of tracheal protrusion (Figure 1). The irradiation technology adopts tangential IMRT.

Figure 1 Example of CT scan of left breast cancer. Abbreviation: CT, computed tomography.

Prescribing dose requirements

Post-scan CT images were transferred from the network to the Varian Eclipse 11.0 workstation, and all target areas and organs at risk were outlined by an experienced oncologist and reviewed and approved by a senior physician. Dosimetric evaluation for planning target volume (PTV) was D_95% ≥50 Gy, and the remaining observations were 95% dose coverage for PTV (D_95%) and 98% dose coverage (D_98%). V_{30 Gy}, V_{20 Gy}, V_{5 Gy}, D_mean for the ipsilateral lung (Lung L) and V_{5 Gy}, D_mean for the heart, V_{5 Gy}, D_mean for the contralateral lung (Lung R) and V_{10 Gy}, D_mean for the contralateral breast (Breast R), as well as maximum dose (D_max) and mean dose (D_mean) for the left anterior descending coronary artery (LAD). Dx% denotes the dose received in Gy for x% of the volume, and VyGy denotes y Gy of the volume.

Plan design

All breast cancer plans were designed on a Varian Eclipse workstation. IMRT was delivered using six MV X-rays with a total of seven fields and fixed rack angles of 315, 330, 350, 10, 80, 105 and 120° (Figure 2). The plan design was performed on a VarianEclipse workstation. Appropriate optimization parameters were selected according to the physician’s prescription dose requirements, lock-field means fixed tungsten door, which is the lead door, relies on the movement of the MLC to meet the optimal design, and the optimization parameters were guaranteed to remain constant throughout the design of the lock-field and split-field plans, with only the state of the MLC varying. Optimization objectives, convolutional optimization and iterative optimization were used, with the MLC angle set to zero for the sub-field plan. The field locking plan aims to avoid the affected lungs as much as possible, while ensuring that the target area on the direction of incidence of the field falls as much as possible within the irradiation field (boundary X ≤13.9 cm). The specific irradiation mode is shown in Figure 3.

Figure 2 Intensity-modulated radiation therapy was delivered using 6 MV X-rays with a total of seven fields.

Figure 3 Lock field shooting mode and Div field plan shooting mode.

Robustness quantification methods

In order to simulate the dose changes due to pendulum or systematic errors, 18 perturbed dose distributions were calculated for the 7-field locking plan and the 7-field splitting plan, respectively: the dose changes that should be induced by shifting the centre of the centre by ±3, ±5 and ±7 mm, respectively, from its reference point in the up-down (S-I), left-right (L-R), and anterior-posterior (A-P) directions. In the present study, dose-volume histogram (DVH) was used as a robust quantification method and the dosimetric parameters in both plans are shown in the DVH curves. Differences in dosimetric parameters (∆Dx% and ∆Vy-Gy) were used for calculations, and values with smaller differences indicated improved robustness.

Statistical analyses

SPSS (version 20.0; IBM Corp) was used for statistical analysis. Non-parametric Wilcoxon signed rank test was used for data that did not fit the normal distribution, and paired sample t-test was used for data that fit the normal distribution. T-tests were used for those that conform to normal distribution, and paired sample non-parametric tests were used for those that do not conform to normal distribution.

Results

Dose distribution in target areas and organs at risk

The dose distribution in each target area for both the field-locking and field-splitting plans meets the clinical requirements. The D_98%, D_95% and D_mean of each PTV differed little (P≥0.05), as shown in Table 2.

Table 2 Dosimetric Parameters of D98%, D95% and Dmean of 30 Patients with Normal PTV in 7F-Locked Field Plan and 7F-Dividing Field Plan

For left lung V₅, V₂₀ and D_mean, the field-locking plan was lower than the field-splitting plan, and the difference was statistically significant; for right lung V₅ and D_mean, heart V₅ and D_mean, right breast D_mean and LAD the field-locking plan was lower than the field-splitting plan, and the difference was statistically significant (all P<0.05), as shown in Table 3.

Table 3 Dosimetric Parameters of Lung L, Lung R, Heart, Breast R and LAD in 30 Patients

Plan robustness evaluation

A plan robustness quantification method is used where ∆D is calculated, and corresponds to the plan robustness of the structure. The dose volume changes for PTV∆D_98%, PTV∆D_95% and PTV∆D_mean when introducing positional offsets in the six directions are demonstrated in Figures 4–6. PTV∆D_98%, ∆D_95% and ∆D_mean are shown in Table 4.

Table 4 Dosimetric Differences Between the Two Plans After Moving the PTV in All Directions

Figure 4 Dose difference of PTV ∆D98% between the reference and perturbed 7F- Lock IMRT and 7F-Div-IMRT plans for different isocenter shifts. Black dots indicate 7F Lock Field plans; square boxes indicate 7F-Div-IMRT plans. Abbreviations: IMRT, intensity-modulated radiation therapy; PTV, planning target volume.

Figure 5 Dose difference of PTV ∆D95% between the reference and perturbed 7F- Lock IMRT and 7F-Div-IMRT plans for different isocenter shifts. Black dots indicate 7F Lock Field plans; square boxes indicate 7F-Div-IMRT plans. Abbreviations: IMRT, intensity-modulated radiation therapy; PTV, planning target volume.

Figure 6 Dose difference of PTV ∆Dmean between the reference and perturbed 7F- Lock IMRT and 7F-Div-IMRT plans for different isocenter shifts. Black dots indicate 7F Lock Field plans; square diamond boxes indicate 7F-Div-IMRT plans. Abbreviations: IMRT, intensity-modulated radiation therapy; PTV, planning target volume.

PTV∆D_98% (L3, P3, S3, I3, L5, P5, I5, S7, I7), the ∆D of the lock-field plan was markedly larger, the robustness needs to be improved and the difference was statistically significant (P<0.05). PTV∆D_95% (L3 mm, R3, A3, P3, S3, I3, L5, A5, P5, I5, L7, R7, P7, S7) variations in the dose of the lock-field program were more variable, with greater robustness to be improved and a statistically significant difference (P<0.05). In the PTVD_mean (L3, P3, S3, I3, L5, R5, A5, P5, S5, L7, R7, A7, S7), the variation in the change in the dose of the lock-field plan was greater, the robustness needs to be improved, and the difference was statistically significant (P<0.05).

In Lung L ∆5 (L3, R3, P3, I3, L5, P5, S5, I5, L7, P7), Lung L ∆20 (L3, P3, L5, P5, L7, P7) and Heart∆_mean (I3, L5, P5, S5, L7) were smaller than the split-field plan, the robustness of the locked-field plan was improved, and the difference was statistically significant (P<0.05), as revealed in Figures 7–9 and Table 5.

Table 5 Dosimetric Difference Statistics Between the 7F-Locked Field Plan and the 7F-Dividing Field Plan of OARS After Moving in All Directions

Figure 7 Dose difference of Lung L ∆V5 between the reference and perturbed 7F- Lock IMRT and 7F-Div-IMRT plans for different isocenter shifts. Black dots indicate 7F Lock Field plans; square boxes indicate 7F-Div-IMRT plans. IMRT, intensity-modulated radiation therapy; PTV, planning target volume.

Figure 8 Dose difference of Lung L ∆V20 between the reference and perturbed 7F- Lock IMRT and 7F-Div-IMRT plans for different isocenter shifts. Black dots indicate 7F Lock Field plans; square boxes indicate 7F-Div-IMRT plans.

Figure 9 Dose difference of Heart ∆Dmean between the reference and perturbed 7F- Lock IMRT and 7F-Div-IMRT plans for different isocenter shifts. Black dots indicate 7F Lock Field plans; square boxes indicate 7F-Div-IMRT plans. Abbreviations: IMRT, intensity-modulated radiation therapy.

Discussion

Although the focus is on the survival of patients with breast cancer, the potentially harmful effects of radiation caused by medical imaging need to be investigated further.

In order to reduce the image caused by low doses, a locking field calculation method was used, where the fixed locking technique refers to locking the lead gate; the lock field plan has been widely used in radiotherapy for nasopharyngeal, rectal, cervical and gastric cancer. If the size of the lead gate is not set properly in the intensity tuning plan, it may cause a certain loss of the irradiated dose to the target area as well as to the critical organs.^17–19 In the present study, the field-locking method was mainly used to investigate the effects of field-locking and field-splitting breast cancer IMRT plans on the dose to the target area and critical organs, and it was found that the D_98%, D_95% and D_mean values of the target area (PTV) of the two plans had little difference and were not statistically different, which indicated that there was not marked variability between the two techniques in fulfilling the dose distribution to the target area. Adjuvant radiotherapy for patients with left breast cancer is associated with an increased risk of cardiac injury.^20,21 The magnitude of this risk is directly proportional to the average dose to the heart.^22,23 In addition, the design of the field-locking intensity adjustment technique for breast cancer patients in the present study yielded lower V₅, V₂₀ and D_mean for the left lung; V₅, D_mean for the right lung; V₅, D_mean for the heart; and D_mean for the right breast in the field-locking plan than in the field-splitting plan, and the difference was statistically significant, which suggested that the field-locking plan can reduce the low-dose region of the left lung to reduce the leakage of the radiation, while fulfilling the clinically required target-area coverage. The LAD dose, on the other hand, did not change significantly, probably due to the relatively small volume, which could not benefit from the Lock fields.

The study contrasts intensity-modulated radiotherapy plans for left-sided breast cancer, finding minimal differences in D98%, D95% and Dmean values of the planning target volume (PTV) between field-locked and field-split plans。The field-locking plan excels in safeguarding critical organs-left lung, right lung, heart, right breast, and left anterior descending coronary artery. Notably, it reduces the low-dose region in the left lung, mitigating radiation leakage.

Despite organ protection benefits, the field-locked plan displays heightened sensitivity to positional deviation for the target PTV. Robustness analyses reveal larger variations in PTV dose metrics, highlighting potential stability challenges during dose execution. However, whether there is a difference in the robustness of the field-locking plan compared with the original plan was also the focus of the current study; robustness considers the uncertainty during treatment and posing, and robustness is investigated to minimize instability during dose execution.^24,25 For the variation of PTV ∆D_98%, ∆D_95% and ∆D_mean, the field-locking plan was larger than the field-splitting plan, and the difference was statistically significant, with larger values indicating poorer robustness. The field-locked plan was smaller than the field-split plan for changes in Lung L ∆₅, Lung L ∆₂₀ and Heart ∆_mean, and the difference was statistically significant, indicating that the advantages of the field-locked tuning plan are more evident in terms of protecting the organs at risk. Implementing the field-locking intensity adjustment technique yields significant reductions in V5, V20, and D_mean for the left lung; V5 and D_mean for the right lung; V5 and D_mean for the heart; and D_mean for the right breast. This indicates an effective reduction in low-dose regions while maintaining target-area coverage. Although the current sample size is limited, please propose a strategy to gradually scale up the sample size according to our plan, and emphasize how to improve the prediction accuracy and optimize the service through data collection, data processing, model optimization and tuning before the sample size reaches a certain size. At the same time, please note that in the process of sample size expansion, please maintain the protection of sample privacy and comply with relevant laws and regulations on data security.

Lock field intensity modulation technology is used to better protect important organs such as the lungs and heart while ensuring normal irradiation of the target area, reducing the occurrence of complications. In the future, we will analyze the remaining organs other than PTV, left lung and heart, laying a more comprehensive theoretical foundation for clinical treatment.

Conclusion

The field locking intensity adjustment scheme can not only reduce the low dose to key organs but also has more obvious advantages in the robustness of key organs. However, the robustness of the target area needs to be improved, and the accuracy of the position needs to be improved in future treatments. In terms of dosage, current research has identified the advantages of locked in field plans in cancer.