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Department of Physics & Astronomy, University of Calgary, Calgary, AB, CanadaDepartment of Oncology, University of Calgary, Calgary, AB, CanadaTom Baker Cancer Centre, Calgary, AB, Canada
Department of Physics & Astronomy, University of Calgary, Calgary, AB, CanadaDepartment of Oncology, University of Calgary, Calgary, AB, CanadaTom Baker Cancer Centre, Calgary, AB, Canada
To inform clinical practice for women receiving post-mastectomy radiotherapy (PMRT), this study demonstrates the dosimetric impact of removing daily bolus on skin and subcutaneous tissue. Two planning strategies were used: clinical field-based (n = 30) and volume-based planning (n = 10). The clinical field-based plans were created with bolus and recalculated without bolus for comparison. The volume-based plans were created with bolus to ensure a minimum target coverage of the chest wall PTV and recalculated without bolus. In each scenario, the dose to superficial structures, including skin (3 mm and 5 mm) and subcutaneous tissue (a 2 mm layer, 3 mm deep from surface) were reported. Additionally, the difference in the clinically evaluated dosimetry to skin and subcutaneous tissue in volume-based plans were recalculated using Acuros (AXB) and compared to the Anisotropic Analytical Algorithm (AAA) algorithm. For all treatment planning strategies, chest wall coverage (V90%) was maintained. As expected, superficial structures demonstrate significant loss in coverage. The largest difference observed in the most superficial 3 mm where V90% coverage is reduced from a mean (± standard deviation) of 95.1% (± 2.8) to 18.9% (± 5.6) for clinical field-based treatments with and without bolus, respectively. For volume-based planning, the subcutaneous tissue maintains a V90% of 90.5% (± 7.0) compared to the clinical field-based planning coverage of 84.4% (± 8.0). In all skin and subcutaneous tissue, the AAA algorithm underestimates the volume of the 90% isodose. Removing bolus results in minimal dosimetric differences in the chest wall and significantly lower skin dose while dose to the subcutaneous tissue is maintained. Unless the skin has disease involvement, the most superficial 3 mm is not considered part of the target volume. The continued use of the AAA algorithm is supported for the PMRT setting.
Local failure and acute radiodermatological toxicity in patients undergoing radiation therapy with and without postmastectomy chest wall bolus: Is bolus ever necessary?.
Local failure and acute radiodermatological toxicity in patients undergoing radiation therapy with and without postmastectomy chest wall bolus: Is bolus ever necessary?.
Consequently, the use of bolus has been a heavily debated topic in recent years and recent evidence supports transitioning away from its routine use for appropriately selected patients.
A 2007 international survey of 1035 Oncologists found that clinical practice varies widely amongst physicians and institutions, reporting bolus use as the following: 68% always, 26% in specific indications, and 6% never.
These results varied geographically, with respondents from the Americas being more likely to use bolus. More recently, a 2021 analysis of 13 studies (including a total sample size of 3756) reported that the rates of local recurrence are similar for patients undergoing post-mastectomy radiation therapy when treated with and without bolus, with a pooled local recurrence rate of 3.5% with bolus and 3.6% without bolus.
However, significantly higher rates of grade 3 dermatitis were observed in the patients treated with bolus. These studies ultimately conclude that treating without bolus does not worsen the probability of local recurrence but does improve toxicity rates.
Recently, a multidisciplinary, international breast cancer expert group reviewed the current evidence and published consensus recommendations regarding bolus use. These consensus recommendations have been published by a multidisciplinary, international breast cancer expert group.
A Delphi study and international consensus recommendations: The use of bolus in the setting of postmastectomy radiation therapy for early breast cancer.
The recommendations aim to address the lack of randomized trial evidence and provide the radiation medicine community with guidelines for the appropriate use of bolus. The expert panel advises against the use of bolus as there is insufficient evidence to support an increase in local control. Our current study provides clinicians a quantitative reference of the dosimetric differences that will be observed if transitioning practice to reduce the use of daily bolus in selected patient groups. This study provides the results oriented to anatomical landmarks of the skin and subcutaneous tissue, which are expected to experience the most significant dosimetric changes, and have been studied for post-mastectomy local recurrence patterns.
In the context of the skin and subcutaneous tissues, three investigations were performed to report the dosimetric differences that would be observed without using bolus for PMRT. Figure 1 shows the schematic for the study design.
I.
Clinical field-based planning: To determine the effect of removing bolus for practitioners that clinically define field borders. Plans with bolus were generated with this approach and used to treat patients in the clinic. For the study, the bolus was digitally removed, and dose was recalculated. This subset of treatment plans was deliberately not re-optimized because field-based planning does not use a target volume for optimization and dose evaluation.
II.
Volume-based planning: To determine the effect of removing bolus for practitioners that define breast target volumes to be used in treatment planning with optimization to meet dose constraints. The chest wall was contoured by a radiation oncologist and new treatment plans were generated both with and without bolus, where target coverage was deliberately planned for and assessed using dose-volume histogram metrics.
III.
Variability in clinically reported dose: To report the difference in the treatment planning calculated dosimetry to skin and subcutaneous tissue, volume-based plans were recalculated using two commercially available calculation algorithms: Acuros XB (AXB) algorithm (Varian Medical Systems, Palo Alto, CA) and the Anisotropic Analytical Algorithm (AAA) algorithm (Varian Medical Systems, Palo Alto, CA). In 2010, the AXB algorithm was developed to address the limitations of AAA algorithm in superficial regions and areas of inhomogeneities.
Dose distributions in SBRT of lung tumors: Comparison between two different treatment planning algorithms and Monte-Carlo simulation including breathing motions.
Therefore, the AXB algorithm provides a more accurate estimate of dose deposited in superficial tissue and may be used to inform clinicians of the superficial dose changes with the removal of daily bolus for treatment.
Fig. 1Study layout. The workflow describes the allocation of the patients to both clinical field-based planning and volume-based planning. The subset of patients assigned to each planning strategy are further grouped to quantify the dosimetric changes to anatomical structures for dose calculation and planning with and without daily bolus (5 mm).
The following methodologies are common to all three investigations described above.
Patient demographics
The study was conducted on 30 sequential patients who received post-mastectomy radiotherapy with bolus to the chest wall and regional lymphatic nodes at a single institution between November 2018 and April 2019. None of the patients included in this study had breast reconstruction surgery.
Treatment planning techniques
All 30 patients were treated with 4256 cGy in 16 daily fractions to the chest wall and regional nodes using a conventional 4-field approach with modulation being achieved by field-in-field optimization. For all patients, a 5 mm bolus was applied for treatment of the chest wall field. Tangential fields were used to irradiate the chest wall and an anterior-posterior parallel-opposed-pair was used to irradiate the supraclavicular nodes. Field weighting and energy (6MV, 15 MV, or mixed) were selected based on plan quality.
For all volume-based planning, target coverage the volume receiving 90% of the prescription dose was required to be at least 90%.
In all cases where dose metrics are reported and compared, a two-sided t-test with alpha = 0.05 is used to measure significant differences.
In all sub studies, bolus is digitally applied during treatment planning covering only the chest wall volume (not the supraclavicular fields). A 5 mm daily bolus made of superflab (Radiation Products Design Inc., MN) is applied during treatment.
Volume definitions
For all clinical treatments, the chest wall volume is defined by field borders and not contoured. For a 10-patient subset, the chest wall was contoured according to Radiation Therapy Oncology Group (RTOG) guidelines,
with the cranial extent at the caudal border of the clavicle head, the caudal extent apparent loss of breast tissue (based on contralateral breast or wiring), anteriorly to skin, posteriorly to the rib-pleural interface including pectoralis muscles, chest wall muscles, and ribs, laterally to mid-axillary clinical reference, and medially to the sternal-rib junction. The volume includes all tissue within these borders that overlay the lung. An evaluation chest wall volume is defined by cropping anteriorly by 5 mm from skin.
All 30 patients had two volumes created to evaluate superficial dose:
I.
Skin (3 mm): a 3 mm rind, and
II.
Subcutaneous tissue: a 2 mm layer beyond the 3 mm to represent the subcutaneous tissue.
Local failure and acute radiodermatological toxicity in patients undergoing radiation therapy with and without postmastectomy chest wall bolus: Is bolus ever necessary?.
These volumes are shown on an axial CT slice in Fig. 2, with inset to represent the skin and subcutaneous volumes. Dose metrics are reported with the assumption that the complete target coverage in the post-mastectomy setting was considered part of the intended volume to be covered by the prescription dose (i.e., skin is not explicitly an organ at risk).
Fig. 2Anatomical contours. The two anatomical structures are illustrated directly on CT, with inset (orange box) to increase interpretability. Within the inset, the skin (3 mm) is shown in in light blue and the subcutaneous structure (2 mm) in dark blue.
Using the 30 patient image datasets, clinically delivered bolus treatment plans were duplicated and the bolus was digitally removed. The resultant dosimetry for the bolus and nonbolus plans were compared using the clinically standard algorithm, Anisotropic Analytical Algorithm (AAA) (version 15.6). The paired treatment plans were compared for V90% coverage of the chest wall dose evaluation volume as well as the V90% for skin and subcutaneous tissue contours. Energy was investigated as a variable for the clinically selected beam energies (6 MV only, 15 MV only, or a mix of these two energies).
Volume-based planning
For the 10-patient subset with chest wall contours, two new treatment plans were created with and without bolus. In both sets of plans, the chest wall contour was used to guide planning and ensure coverage to the target of 90% of the prescription dose. Once both plans met clinical constraints, the V90% was used to compare dosimetry for superficial structures.
Variability in clinically reported dose
The bolus and nonbolus plans for the 10-patient subset were compared using the AAA and ACUROS XB (AXB) algorithms. The difference between the AAA and AXB algorithms is calculated for each skin and subcutaneous structure V90% to demonstrate the variability between dose calculation algorithms.
The replanning methodology was only applied to the volume-based planning because field based is subjective. In field-based planning there is inherently nothing to hold constant to ensure a fair comparison. As such, field base planning demonstrates the effect of removing bolus and the volume-based planning the difference in purposefully planning to a volume with and without bolus.
Results
Patient demographics
For the 30 patients in the study, the patient characteristics are reported in-line text. Of the 30 patients, 12 were left breast and 18 were right breast patients. Median (range) age was 56 (36 to 85) years. A median (range) of 337 (297 to 364) MUs were delivered per fraction. Four patients were treated with 6 MV, six were treated with 15 MV and 20 were treated with mixed 6 MV and 15 MV. All plans were photon energies only.
Clinical field-based planning
The V90% coverage is compared for treatment plans created with and without bolus and is shown in Fig 3A.
Fig. 3Dosimetry for (A) clinical field-based planning and (B) volume-based planning. In each boxplot, each data point is displayed with bars indicating the range and the box encompassing the 25th to 75th percentile and median line. Plans with daily bolus and without bolus are displayed in blue and orange, respectively. The yellow shaded box highlights the results of the comparison between subcutaneous dosimetry for clinical field-based planning (investigation (i)) and volume-based planning (investigation (ii)).
For all three superficial structures, dosimetric differences are significant (p < 0.05). As expected, the largest change in coverage is found in the most superficial skin 3 mm, where the V90% is reduced from a mean (± standard deviation) of 95.1% (± 2.8) to 18.9% (± 5.6) for treatments with and without bolus, respectively. The chest wall evaluation volume does not report a significant difference (p = 0.82) in target coverage with and without bolus.
The impact of energy selection for this patient cohort is evaluated by comparing the 15 MV only (n = 6) and all 6 MV only patient plans. In the subcutaneous region (2 mm), nine out of the lowest 10 coverage without bolus had 100% 15 MV (n = 6) or at least 70% 15 MV (n = 3).
Volume-based planning
For the 10 patients with volume-based planning, dose metrics are displayed in Fig. 3B. This result matches the differences reported in Fig. 3A, where the dose to superficial structures is significantly different with and without bolus. Treatment plans with and without bolus resulted in no significant difference to the chest wall evaluation volume coverage.
More specifically, the purpose of this investigation was to determine if deliberate planning to target volumes preserved superficial prescription dose. Volume-based planning resulted in statistically significant improvement in the subcutaneous region compared to the clinical field-based planning (p = 0.04). The data used for this comparison is highlighted by the shaded yellow box in Figs. 3A and 3B. For this subcutaneous region, the volume-based planning maintained a V90% of 90.5% (± 7.0) compared to the clinical field-based planning coverage of 84.4% (± 8.0). This indicates deliberate optimization in volume-based planning does provide an advantage in maintaining the delivery of the prescription dose to the subcutaneous region.
Variability in clinically reported dose
For the 10-patient subset, dose was evaluated using the AXB dose calculation algorithm and is compared to the results from the previous section using the AAA algorithm. For each of the four structures, the dosimetry is reported in Fig. 4.
Fig. 4Reported V90% dosimetry for the AAA and AXB dose calculation algorithms for skin, subcutaneous structure, and chest wall. In each boxplot, each data point is displayed with bars indicating the range and the box encompassing the 25th to 75th percentile and median line.
For all structures in the bolus setting, no statistical difference is observed between the AAA and AXB algorithms reported dose (blue box plots compared to green box plots). In plans with no bolus, the three superficial structures reported a statistical difference (orange box plots compared to purple box plots). In all cases, the AAA algorithm under-reported the dose compared to the AXB algorithm. More specifically, in the subcutaneous tissue, dose calculated without bolus using the AXB algorithm reports that the V90% was greater than 90%, indicating that deep of 3 mm, prescription dose is maintained in this region. This contrasts with dose calculation without bolus using the AAA algorithm, which indicates the V90% was less than 90% for three of the 10 patients. This result reported by the AXB algorithm supports the clinical evidence in which no increase in local recurrence is reported with and without bolus.
Discussion
The benefits of using bolus in post mastectomy radiation therapy has been a subject of debate over the past two decades. When used for treatment, bolus ensures target coverage of the superficial and subcutaneous tissue while accepting an increase to acute radiation induced skin toxicity. The recent international consensus study concluded that bolus is likely not beneficial in many clinical treatments and supports the removal of daily bolus for most scenarios. From these recommendations, it is timely and important to better understand the dosimetric changes in the superficial anatomical structures should clinicians and institutions choose to adopt these guidelines.
Clinically acceptable treatment plans can be made without bolus for patients undergoing PMRT to ensure coverage to the chest wall target volume.
Local failure and acute radiodermatological toxicity in patients undergoing radiation therapy with and without postmastectomy chest wall bolus: Is bolus ever necessary?.
In both clinical field-based and volume-based planning strategies, the superficial structures demonstrated the largest coverage difference with and without bolus. This is the region most responsible for acute radiation dermatitis,
so it is consistent with these results that toxicity differences are observed. With the prescription dose maintained for chest wall and subcutaneous structures and reduced for skin structures, the transition in clinical practice to minimize the use of bolus for routine practice is supported.
Delineation of the chest wall varies across studies and clinical standard practice. Typically if skin is not involved, the volume can be cropped 3 to 5 mm from the skin.
The study results demonstrate that in this target definition range, sufficient prescription dose is maintained in chest wall and subcutaneous regions though small improvements in maintaining dose in the subcutaneous region for volume-based planning may be observed.
Use of bolus remains recommended in specific clinical scenarios. Those detailed in the international consensus recommendations include cases of mastectomy for ductal carcinoma in situ (DCIS) or invasive cancer with positive anterior margins without overlying skin removed; for any case of skin involvement; for any inflammatory tumour stage; or any other case where the skin is at high risk of recurrence. Additionally, bolus should be used for chest wall recurrence and inoperable or fungating cancer.
A Delphi study and international consensus recommendations: The use of bolus in the setting of postmastectomy radiation therapy for early breast cancer.
A Delphi study and international consensus recommendations: The use of bolus in the setting of postmastectomy radiation therapy for early breast cancer.
and in this context, the results of this study represent a conservative difference between bolus and no bolus dosimetry. Less frequent use or thinner bolus would result in a smaller difference.
The AAA algorithm is commonly utilized in clinical settings and has been previously validated in the whole breast setting.
However, in the PMRT context where the dosimetric consequences of bolus removal are an open question, this study provides additional clinical context for practitioners aiming to adapt their practice to the recent recommendations.
A Delphi study and international consensus recommendations: The use of bolus in the setting of postmastectomy radiation therapy for early breast cancer.
The commercially available AXB dose calculation algorithm was introduced to address the limitations of AAA, specifically in areas of inhomogeneity and tissue interfaces. A comparison the clinically relevant differences between AAA and AXB have previously been investigated for simple tangent geometry and intact regional nodal irradiation.
While both these studies found differences in reported dose, the clinical significance does not warrant the use of the AXB algorithm. In the current study, dose differences are observed between the two algorithms are observed in the superficial region (3 mm), the dose reported in the subcutaneous and chest wall region using both algorithms are sufficient for clinical decision-making.
Conclusion
Removing bolus results in small dosimetric differences in the chest wall and significantly lower skin doses. For the chest wall coverage, no statistical or clinical difference between AAA and AXB algorithms is observed. For the subcutaneous region, the prescription dose is well-maintained, however, clinicians should expect a decreased V90% in the most superficial 3 mm. Unless the skin has disease involvement, the most superficial 3 mm is not considered part of the target volume. The continued use of the AAA algorithm is supported for the PMRT setting for treatment plans without bolus.
Author Responsible for Statistical Analysis
Sarah Quirk and Michael Roumeliotis.
Declaration of Competing Interest
None.
Funding
None.
Acknowledgment
None.
Data Availability Statement
Research data are stored in an institutional repository and will be shared upon request to the corresponding author.
References
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Evaluation of skin dose associated with different frequencies of bolus applications in post-mastectomy three-dimensional conformal radiotherapy.
Local failure and acute radiodermatological toxicity in patients undergoing radiation therapy with and without postmastectomy chest wall bolus: Is bolus ever necessary?.
A Delphi study and international consensus recommendations: The use of bolus in the setting of postmastectomy radiation therapy for early breast cancer.
Dose distributions in SBRT of lung tumors: Comparison between two different treatment planning algorithms and Monte-Carlo simulation including breathing motions.
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