Abstract
Introduction
Radiation therapy is a treatment option for primary, additional, or palliative treatment of skin cancer. 1 Research indicates a control rate of 87% to 100% for skin tumors 2 to 5 years following radiation therapy 1 which is the preferred approach for large, surgically complex, or inoperable tumors, and a valuable alternative for elderly patients. 1 It can also be used postsurgery to eliminate the residual lesion and prevent recurrence. Approximately 50% of patients with cancer undergo radiation therapy, yet in low-income countries, late diagnoses and limited resources reduce this to 25% to 40%.2,3 Radiation therapy is an essential component of cancer treatment for all types of tumors, high-energy linacs made by Varian (Varian Medical Systems) and Elekta (Elekta AB) are most common linear accelerators used for electron and photon therapy at multiple energy levels. It should be noted that Siemens stopped manufacturing its Artiste, Oncor, and Primus linear accelerators since January 2012.
Radiotherapy options for skin cancer treatment include brachytherapy, electronic brachytherapy (intra-operative radiotherapy), kV X-ray therapy, and electron beam therapy. 1 The choice of treatment option for each patient depends on the extent of the disease, its location, availability of equipment, and the radiotherapy team practices. 4
Since the early 1950s, high-energy electron treatments have played a crucial role in radiation therapy as they have high linear energy transfer (LET) and cause more DNA chemical changes than photons, which can lead to damage in superficial cancerous cells, 5 specifically those up to 5 cm deep, so, this method is notable for its marked reduction in dosage beyond the tumor's boundaries. 6 In terms of biological effectiveness, radiation's biological efficacy, influenced by factors like LET, dose, and cell radiosensitivity, varies; high LET radiation (ie, electron) deposits more energy than its low LET (ie, photons) counterpart.5,7 The aim in radiation therapy is to maximize tumor control probability (TCP) while minimizing normal tissue complication probability (NTCP). It means effective tumor control while reduces side effects and harm to healthy tissues. Electron beam irradiation is a safe and highly effective treatment with a cure rate over 95%, making it a valuable option for skin cancer and an excellent treatment modality for epithelial skin cancer, especially in cosmetically sensitive areas, where surgery is less favorable. Additionally, it proves beneficial for postoperative treatment in case of residual or recurrent disease. 8 The electron clinical markup remains the main approach to treating small skin cancers especially in centers that do not have a kilovoltage superficial unit or even more rarely a brachytherapy suite. The VMAT approach for treating a small 1 cm skin cancer such as a basal cell carcinoma (BCC) (which makes up more that 85% of all skin cancers) would be considered inappropriate use of resources and even acceptable dosimetry whereas the electron beam is an integral component of a linac and is readily available and deliverable. 8 In electron beam therapy, an applicator constructed from an alloy material often utilized alongside Cerrobend cutouts to mold the electron beam, conforming it to the shape of the targeted area (ie, tumor). 9 The cones are usually positioned 5 cm from the patient's skin surface when delivering treatment at a source-to-surface distance (SSD) of 100 cm. 10 Cones provide collimation and ensure relatively sharp field edges and a flat radiation beam. 11 However, specific irradiation techniques for example total skin electron irradiation 12 stand as exceptions to this approach. The purpose of utilizing cones or applicators is to restrict the electron beam, reducing its lateral dispersion from the accelerator head to the patient's skin. 9 In the process of electron beam therapy, as the electron beam passes through the scattering foil, the electrons scatter sufficiently when interacting with various components within the accelerator head, applicator, cutouts (inserts), and the air between the exit window and the patient. This scattering results in the emission of X-rays and production of low-energy electrons which causes the formation of clinically unacceptable penumbra. This leads to additional dose outside the treatment area, which is known as peripheral doses, as well as increased the absorbed dose. 12 Furthermore, the electron component contributes to peripheral dose through 3 primary mechanisms: (1) scattering out of the applicator, (2) penetration of collimating structures within the applicator, and (3) direct exit into the surrounding air without interacting with applicator components. 13 Notably, the latter 2 mechanisms—penetration and direct escape—are more common with higher-energy beams, while scattering is characteristic of lower-energy beams. Furthermore, as the energy surpasses 12 MeV, neutron contamination becomes prevalent. 14 The neutron fluence escalates with the electron beam energy. 14 These neutrons interact with nuclei in the LINAC head, bunker walls, and patient, triggering nuclear reactions. Resultant neutron capture can lead to prompt gamma-ray and nuclei activation, some decaying by β− emission.15-17 Given neutrons’ high radiobiological effectiveness, their presence around LINACs in radiotherapy can contribute to nontrivial patient doses, potentially correlating with cancer relapse and new tumor initiation. 14 Furthermore, such contamination poses an occupational hazard for facility staff, underscoring the importance of assessing risks associated with neutron exposure in these environments. 14 However, studies by various groups, including Nath et al, 18 Lin et al, 19 Biltekin et al, 20 and Cardenas et al, 21 have corroborated that neutron contamination is less pronounced in electron beams compared to photon beams since the cross-section of electronuclear (e,n) reactions is smaller, by about 2 orders of magnitude, compared to photo-nuclear (γ,n) reactions. 22 This difference is attributed to the lower bremsstrahlung efficiency, which means that a higher number of electrons is required to produce a certain number of photons. 22 Additionally, photon beams penetrate tissues more deeply, requiring higher electron gun currents for electron irradiation. Consequently, by even only considering the differences in neutron generation cross-sections, the electron mode is expected to produce at least 2 orders of magnitude fewer neutrons compared to the photon mode. 22
A comprehensive comparison of linear accelerators from Varian, Elekta, and Siemen vendors has been conducted. 23 Each manufacturers create applicator designs and materials based on their unique linear accelerator gantry head configurations.13,24,25 Moreover, each vendor supplies a range of applicator sizes to accommodate different treatment fields sizes. In addition to this, for a more customized field shape, a lead or metal alloy cutout may be constructed and placed on the applicator as close to the patient as possible. Once an applicator is attached to the gantry head, the jaw settings are automatically locked through an integrated interlock system, ensuring consistent electron radiotherapy for that specific applicator and energy setting.
Recent advancements in external radiotherapy enable precise dose administration to target areas, reducing harm to adjacent healthy tissues. 26 As a result, there has been an increase in overall survival rates for various cancer types. 27 Long-term cancer survivors face a higher risk of subsequent malignancies. 28 The incidence of secondary cancers has significantly increased due to a growing population of cancer survivors and an aging demographics, rising from 9% of all cancer diagnoses in 1975–1979 to 19% in 2005–2009. 29 There is well-documented evidence indicating that secondary cancer risks are linked to radiotherapy and a study by Berrington et al 30 has estimated that about 10% of secondary cancers in adults can be attributed to radiotherapy. However, the relationship between radiotherapy dose and possibility of secondary cancer induction is not straightforward. Existing models are based on the atomic bomb survivor data and are mainly applicable to photon treatments with large uncertainties. 31 The out-of-field dose is usually considered insignificant in electron treatments; however, radiation carcinogenesis has no threshold and could even occur at doses below 0.1 Sv (ICRP 103). 32 Measuring the electron out-of-field dose may enable the evaluation of possible damage to surrounding tissues in clinical cases such as: electron patch for breast and internal mammary chain (IMC) treatments, neck node treatments at extended SSD, testicular boost for total body treatment. Dose to pacemakers could also be affected. 9 Hence, understanding peripheral doses is pivotal, especially when critical organs or the patient's skin are proximal to the applicator's side, as this knowledge enhances patient safety and optimizes treatment efficacy.
The aim of this review is to provide a comprehensive understanding of peripheral doses outside the applicator in electron beam therapy. This overview is provided by analyzing research on linear accelerators supplied by Varian, Elekta, and Siemens. Furthermore, significant findings pertaining to peripheral dose patterns beyond the applicator will be the central focus of present work. This examination will encompass variations resulting from factors such as beam energy, applicator design, field size, gantry angles, and depth. Additionally, mitigation strategies will be identified and characterized, including the utilization of bolus material, custom cutouts, and treatment method optimization. These strategies aim to elevate patient safety in the context of electron beam therapy.
This overview will benefit radiation oncologists, medical physicists, radiation therapists, and researchers. The findings are expected to instructions for treatment planning enhancement, optimization of dose delivery techniques, and the elevation of patient safety.
A systematic search of electronic databases such as PubMed and Web of Science was undertaken to identify recent and relevant publications. Key search terms included “electron beam therapy”, “linear accelerators”, and “peripheral dose”. The inclusion criteria encompassed dose assessments, distribution data, and potential mitigation techniques for peripheral exposure.
Methods
In this review, a comprehensive literature exploration was undertaken, with a specific focus on articles written in English spanning the period from 1978 to July 2023. The exploration was conducted in accordance with the PRISMA standards. The emphasis of this exploration was placed on the identification of studies that delved into the analysis of peripheral doses concerning various electron beam energies and applicator pairings. Furthermore, the reference lists of all eligible papers were meticulously screened to uncover studies that might have been omitted through the initial search terms. Studies were excluded based on the following criteria: (1) peripheral or out-of-field doses not being central to the research; (2) absence of electron beam utilization; or (3) lack of involvement of applicators.
Through a targeted search conducted across 3 prominent databases—PubMed, Web of Science, and Scopus—using predefined search parameters illustrated in Figure 1, a total of 132 relevant articles were identified. Initial screenings focused on titles and abstracts, resulting in the removal of unrelated or redundant studies. Subsequent to this initial selection, a comprehensive evaluation of the content within the remaining papers was carried out, ultimately resulting in a final selection of 7 articles that were deemed pertinent for inclusion in this review (as detailed in Table 1).
PRISMA flow diagram illustrating the systematic literature search and selection process.
Literature Review: Peripheral Doses Outside Applicator for Electron Therapy.
Abbreviations: MC, Monte Carlo; TPS, treatment planning systems.
Results
Number of papers has been published on radiation (leakage) outside the applicator.7-9,15,16,21-32,34,38-41 Measurements conducted through the utilization of ionization chambers,9,21,24,25,33-35,38-43 films,13,34,37-40,44 and thermoluminescent dosimeters36,45,46 to evaluate out-of-field radiation collimated by electron applicators. Van der Larese examines the scatter contribution of individual walls of MEL SL75-20 linear accelerator's applicator and proposed that the shape of the beam profile is determined by the 2 walls defining the dimension. 33 Andrew et al, 45 Richard A Keys et al, 34 Edward et al, 39 and Perec and Kubo et al 44 investigated the radiation leakage at the surface of the applicator of Varian Clinac-18, Clinac-20, Clinac-2500 and Clinac-1800, respectively. Perec and Kubo, along with their collaborators, mitigated the leakage by adding a 1 mm thick layer of lead onto the applicator's surface. Edward et al found that in Clinac-18 and Clinac-20 Varian machine photon jaws were too wide allowing electron to escape through unshielded region of the electron applicator. Ebert et al investigated the transmitted and scattered radiation outside the radiation field of the Siemens KD2 linac using a Monte Carlo (MC) simulation method. 47
Battum et al studied the scattered radiation from Varian 2300 C/D, Siemens Primus, and Elekta SLi electron applicators. 25 In this study, it was discovered that scattered radiation at the surface of a water phantoms can be as high as 12%, which inversely depends on depth. While, with Varian applicators, it showed a dependency on beam energy. Moreover, Battum et al observed that applicators with a larger field size of 25 × 25 cm2 exhibit a reduced contribution of scattered radiation at the central axis (CAX) compared to those with a smaller field size of 10 × 10 cm2.
Chow and Grigorov 13 reported the highest peak value of peripheral dose for Varian 21 EX, approximately 1% of central-axis dmax, at a distance of about 12 cm from the CAX on a film placed on the surface of a solid water phantom (SWP). This measurement was obtained using a 10 × 10 cm² applicator and a cutout for the 4 MeV electron beam along both the cross-plane and in-plane axes. Furthermore, this study revealed that the peripheral peak dose at a depth of 1 cm in the SWP increased proportionally with the angle of obliquity. Specifically, the local peak dose escalated by approximately 3% for each degree of increase in angle, causing a displacement of about 7 mm toward the CAX as the angle increased from 0 to 15°. The peak surface dose was positioned approximately 12 cm away from the CAX. At a depth of 1 cm and at the location of the peak dose spot, the peripheral dose was measured to be approximately 1% of the prescribed dose when using the 10 × 10 cm² applicator and cutout.
Peripheral dose value for Oncor Linear accelerator was measured by Iktueren et al. 35 Author observed 1.4% dose peak (profiles were normalized to the CAX of the treatment field), located 6 cm away from the field edge, with a 10 × 10 cm², where the CAX received 100% dose. This phenomenon occurred at a gantry angle of 0° for both 6 and 9 MeV electron beams. In the case of the 15 MeV electron beam, a 2.3% dose peak was observed under similar conditions. Further investigations revealed that the peak dose reduced as the depth increased, reaching values between 2.5% to 4% of central axis dmax depending on the size of the treatment field. At gantry angles of 10° and 20°, 6 and 9 MeV electron beams exhibited small peaks, with maximum doses observed at depths of 0.2 and 1 cm. In contrast, the 15 MeV electron beam did not exhibit peaks at depths of 0.2 and 1 cm when the gantry angles were set at 10° and 20°. In addition to this, comparisons were made between the measured peripheral doses outside the applicators and the data generated by a treatment planning system (TPS) using the pencil beam algorithm. These comparisons indicated that dose calculations could be reliably performed up to a distance of 3 cm outside the treatment field.
Alabdoaburas et al 36 investigated the out-of-field doses in water phantom for Siemen Oncor, Simen Primus, and Varian 2300 C/D. Notably, when Siemens applicators were used, a distinct peak dose was identified at approximately 12 to 15 cm beyond the field edge, specifically at a depth of 1 cm. This phenomenon was consistent across various field sizes and electron beam energies. For the Siemens Primus linac equipped with a 10 × 10 cm² applicator, the peak dose reached 2.3%, 1%, 0.9%, and 1.3% of the maximum central axis dose (dmax) for 6, 9, 12, and 18 MeV electron beams, respectively. As for the Siemens Oncor linac with the same 10 × 10 cm² applicator, the peak dose values were 0.8%, 1%, 1.4%, and 1.6% of dmax for 6, 9, 12, and 14 MeV electron beams, respectively, and these values increased with larger applicator sizes. On the other hand, when considering the Varian 2300C/D linac, the doses measured at 12.5 cm beyond the field edge were 0.3%, 0.6%, 0.5%, and 1.1% of dmax for 6, 9, 12, and 18 MeV electron beams, respectively, and these values also showed an increase with larger applicator sizes. Notably, no distinct peak dose was observed for the Varian applicator across these energy levels. These findings provide valuable insights into the out-of-field dose characteristics associated with these linacs and applicators, which can contribute significantly to our understanding of radiation therapy delivery.
Haghparast et al 37 measured the peripheral does for Elekta Synergy linac. For this study, the author normalized the peripheral dose profiles to a distance of 2 cm from the edge of each treatment field. Notably, the highest peak in the peripheral dose was observed when using an 18 MeV electron beam, located 3 cm from the outer edge of the applicator. This peak dose increased as the energy level of the electron beam increased. Specifically, when a 20 × 20 cm² applicator was employed, the peak dose for an 18 MeV electron beam reached 1.6% at the surface of the phantom and at a distance of 2 cm from the outer edge of the applicator. In comparison, for a 6 MeV electron beam within the same applicator size, the peak dose at the same distance was measured at 1.15%. It was observed that the peak dose diminished as the depth increased and increased with an increase in the size of the treatment field. Additionally, the peak dose shifted closer to the central beam axis with an increase in the gantry angle, similar result was also observed by Chow and Grigorov 13 with Varian 21 EX linac.
Discussion
Electron beam radiation therapy continues to serve as an effective method for treatment of skin cancer, prioritizing precise targeting and minimal impact on adjacent healthy tissues.
During the course of electron beam treatment, radiation leakage from the accelerator head and scattering originating from both the accelerator components and the patient contribute to the deposition of radiation dose in the tissues beyond the intended treatment area. 30 For instance, accurate knowledge of out-of-field radiation doses in radiation therapy is essential for assessing the effect on healthy tissues. In patients with potentially adjacent organs at risk peripheral dose could lead to adverse effects such as cataracts, or secondary malignancies when using photon beam. 31 To develop a risk model to estimate the effects of out-of-field dose on inducing secondary cancers, further epidemiologic studies and detailed out-of-field dose information are required, presenting a significant challenge 31 especially as patients are not usually monitored for the out of field doses.
Although electron applicators primarily absorb electrons, their interactions with gantry components (eg, ion chambers), applicator, cutout, and the air gap between the patient and the applicator's end result in X-ray photons. These photons subsequently produce secondary electrons. Both these scattered electrons and photons can either deviate outside the treatment region or intensify the absorbed dose. 12
In Battum et al found that Elekta SLi applicator yield lower scatter compared to Varian 2300/CD and Siemens Primus but have a pronounced effective angular discrepancy. In a previous study by Van Battum et al, 48 it was observed that Elekta applicators displayed broader penumbras due to increased initial angular variance. While modifications in applicator design can reduce scattered radiation, they may also enhance this angular variance. Furthermore, in comparison to previous measurements conducted on a CGR Sagittaire accelerator equipped with a scanning beam and a trimmer system25,49 the scattered radiation from the applicators was notably higher for all 3 accelerators.
Meanwhile, Chow and Grigorov’s 13 investigated the dependence of peripheral dose on the angle of obliquity, cutout and applicators sizes of Varian 21 EX linac. Their findings showed that peripheral doses increase with angular changes (0.81, 0.95, 1.09, and 1.27 cGy for 0, 5, 10, and 15 gantry angles, respectively), highlighting the need for extra care during treatments, especially when using low-energy electron beams. Furthermore, Chow et al. mentioned that electron beams are not likely to escape or penetrate the applicator. However, the major source of peripheral dose could be the electron scattering. To verify this, the authors recommended using MC simulation. 13
Studies conducted by Iktueren et al, 35 Alabdoaburas et al, 36 and Haghparast et al 37 sheds light on the factors affecting the peripheral doses, such as depth, field size, applicator size, gantry angle, and beam energy. A significant observation made by Iktueren et al was the limitation of TPS in accurately estimating peripheral doses, which introduces a clinical risk concerning the irradiation of sensitive organs like the eyes.
This concern is particularly significant for low-energy electron beams, such as 6 MeV, which are often used for treating surface lesions. Alabdoaburas et al 36 also emphasized the necessity for TPS to account for these out-of-field doses, ensuring the safety of peripheral organs, particularly when a peak dose occurs.
The contribution of radiation scattered and transmitted by the applicator to the dose outside the radiation field has been investigated using MC simulation. For instance, Ebert et al 47 analyzed the scattered and transmitted radiation outside the radiation field of the Siemens KD2 linear accelerator using the EGS4 MC method. They found that the major perturbation in the incident beam characteristics caused by an applicator is from scattered electrons, and the fluence and energy characteristics of scattered electrons were dependent on the primary beam energy and the applicator and aperture configuration. In another study, Tomohiro et al 12 investigated the peripheral dose outside the radiation field of a Varian Clinac 2100CD applicator for a range of energies (4, 6, 9, 12, and 16 MeV) using a detailed MC simulation in EGSnrc at 5 mm depth in a water phantom for the 10 × 10 cm2 applicator. They found approximately 3% to 2% of dose was received from the field edge up to 2 cm, and about 1% of the dose was received beyond the 2 up to 12 cm from the field edge. These results were in agreement with an independent experimental study conducted by Chow et al, confirming that the peripheral dose outside the field is significantly affected by radiation scattered or transmitted from the applicator, and the effect increases with electron beam energy.
The breadth of existing research on electron beam radiation therapy underscores its important role in treating various cancers while emphasizing the complex considerations around peripheral doses, accessories selection, and energy variability. Literatures demonstrate the criticality of precise treatment planning to mitigate the risks associated with unintentional irradiation of tissues adjacent to the targeted malignancy. Key factors influencing peripheral doses include the type of linear accelerator, applicator size, beam energy, and even the depth at which the tumor is located. These considerations are pivotal for developing robust TPS that can accurately capture both in-field and out-of-field doses.
The mitigation of peripheral doses in electron beam radiotherapy has gained considerable scholarly attention.9,13,21,46 Chow and Grigorov 13 have proposed the utilization of lead foil either to wrap the lower section of the applicator or to position additional shielding directly on the patient. They discussed that awareness of the dose properties outside the applicator is crucial, especially when employing low-energy electron beams in treatments.
Similarly, Yeboah et al 9 investigated the modification of the Siemens Primus applicator's sidewalls by adding a 1 mm thick lead sheet. Their findings indicated considerable reductions in peak peripheral doses, amounting to 80% and 74% for incident electron beams of 9 and 18 MeV, respectively. The study underlines that their choice of a 1 mm lead thickness not only prioritizes weight considerations but also minimizes interference with clinical electron beams. Cardenas et al 21 take a different approach, suggesting that applying a water-equivalent bolus with a thickness determined by E(MeV)/4 could significantly reduce out-of-field doses. Their study indicates that such a bolus reduces out-of-field doses to <0.5% up to a depth equal to the central-axis dmax for a given electron energy. Huifang et al 46 explored the use of lead aprons (LAs) for shielding and noted that increasing the number of LA layers and the distance from the central beam axis significantly diminished out-of-field doses. In particular, for 4 MeV the use of LAs reduced the doses by up to approximately 98% at 30 cm from the central beam axis in comparison to scenarios without shielding.
Conclusion
The literature supports the need for accuracy in electron beam radiation therapy. Although each electron applicator is specifically designed to provide a flat field for a specified depth at a specific SSD, it is important to verify the out-of-field doses for each applicator. Advanced tools, equipment, and protocols are essential for maintaining a delicate balance between effective treatment and patient safety. With the advancement of technology, continuous research, and careful treatment planning are essential. For accurate radiation therapy, it is important to conduct a comprehensive analysis on each linear accelerator due to differences in internal structure of the linac head and applicator geometries, for each linac model and manufacturer. Employing advanced computational methods, such as the GEANT4 MC simulation, facilitates a nuanced understanding of beam particle interactions. MC simulations can elucidate the complex scattering mechanisms inherent in radiation therapy, thereby enabling the development of strategies to limit the undesired scattered radiation. Effective management of peripheral doses is intricate, requiring precise tools and techniques to balance the treatment efficacy with potential risks. The overarching goal is to target the disease effectively while safeguarding the surrounding healthy tissues.
Footnotes
Abbreviations
Author's Contributions
KDM and PR were involved in conception and design of the study, and library searches.
KDM, PR, JD, MI, and TM were involved in writing the manuscript. PR and JD were involved in critical review and supervision.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethics Approval Statement
Not applicable, because this article does not contain any studies with human or animal subjects.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Informed Consent
Not applicable, because this article does not contain any studies with human or animal subjects.
Trial Registration
Not applicable, because this article does not contain any clinical trials.
