3D-Printing Advances in Radiotherapy

*Reza Shamsabadi*

## **Abstract**

As radiotherapy techniques have been becoming more applied in medicine, the success of radiotherapy treatment lies in an optimal radiation dosage distribution in tumor as well as dose limitation to the normal tissues. Accordingly, the application of three-dimensional (3D) printing technology, as an additive manufacturing (AM) process in radiotherapy technique, is proliferating rapidly due to the reduced manufacturing costs, improved printing precision, and the speed of 3D printers. The advent of 3D printers in medical fields, especially in radiotherapy, allows to produce any given specific design for patients from novel 3D printable materials. Generally, the applications of this modern industry in radiotherapy can be counted as the creation of traditional patient-specific bolus, brachytherapy applicators, personalized medical devices, physical phantoms for quality assurance (QA), compensator blocks, and patient-specific immobilization devices. Despite the technological advancements of 3D printing in radiotherapy practices, due to the high manufacturing cost, the printing speed, time-consuming workflows, poor conformability, and poor repeatability of applied materials, it is not currently well supported by most radiotherapy techniques. The applications of the 3D printing technology as well as its limitations in radiotherapy are discussed in following.

**Keywords:** radiotherapy, patient-specific bolus, brachytherapy applicators, personalized medical devices, physical phantoms

## **1. Introduction**

### **1.1 Radiotherapy overview**

Radiotherapy has been introduced as one of the most effective modalities for patients with various types of tumors, which can be given in several ways [1]. Totally, about 50% of all patients with cancer require radiotherapy during the course of their treatment process [2]. The success of a complex radiotherapy technique lies in an optimal radiation dosage distribution in tumor as well as dose limitation to the normal tissues [3]. Delivering an optimal radiation dosage highly depends on the precision in patient setup and immobilization [4]. Despite good therapeutic results, due to the damaging of the surrounding healthy tissues, radiotherapy can have negative side effects [5]. In this regard, combined modalities with radiotherapy have increasingly performed to improve local tumor control and negative effects reduction.

## **1.2 The 3D printing technology in radiotherapy field**

Nowadays, the prospects of the medical technology have changed drastically due to the increasing rate of accessibility and versatility of 3D printing technology, especially when combined with medical imaging. Recently, owing to the advantages of 3D printing method such as versatility and commercial availability, it has been increasingly incorporated into medical practices. Totally, the 3D printing can be regarded as an ideal technology to optimize individual treatments [6], which provides practical and affordable ways for radiotherapy treatments. Due to the reduced manufacturing costs, improved printing precision, and the speed of the 3D printers, 3D printing technology has been exponentially becoming more commercial and accessible over the five decades.

The advent of commercially available 3D printers has been widely adopted in a diverse type of applications, ranging from training to therapeutic usages [7, 8]. Recently, due to the ease of creation and testing the novel designs, as well as the comparative affordability of 3D printers, 3D printing technology has been employed in radiotherapy for the construction of treatment accessories [9–13], and patient geometry or material reproduction [14–19]. Due to the personalization requirement, 3D printers can be used to create objects to accommodate a specific patient's treatment.

3D printing technology has been introduced as an efficient stage for production of custom-made devices to be applied in external beam radiotherapy. Preparation of organ models and rapid manufacturing of personalized medical devices can be obtained by 3D printing technology [20]. Successful printing of a 3D object highly depends on accurately segmentation of achieved patient's imaging data through the computed tomography (CT) or magnetic resonance imaging (MRI) [21].

The 3D printer's utilization in medical fields, especially in radiotherapy, allows to rapidly produce any given specific design for patients from anatomic images using a variety of stock materials [22]. Hence, 3D printing technology can truly enhance the patient care, especially in radiotherapy field [23]. Patient-specific models, which may not be readily obtainable with the traditional techniques, can be produced by 3D printing alternative method and ultimately increase the accuracy of the treatment [22].

The applications of the 3D printed objects in radiotherapy have been discussed in following.

## **2. The 3D printing applications in radiotherapy**

In the last few years, 3D printing technology is being used in radiotherapy technique for a wide variety of applications, including creation of traditional patient-specific bolus and brachytherapy applicators, personalized medical devices, and reproducible and sophisticated physical phantoms production of various anatomical models for quality assurance. Further applications include compensator blocks, patient-specific immobilization devices, and beam modulators, which commonly have been less described [22]. The current applications of AM industry (3D printing technology) in radiotherapy are shown in **Figure 1**.

## **2.1 Traditional patient-specific bolus**

To improve the radiation dose delivery during the high-energy radiotherapy treatment, patient-specific boluses are often applied, which on the one hand reduce

#### **Figure 1.**

*The current applications of AM in radiotherapy as of 2018 [24].*

the irradiation to healthy tissues and on the other hand increase the dose homogeneity for patients with complex surface contours [25]. Hence, more homogeneous dose can be delivered to the target by boluses through providing additional absorption and scattering of ionizing radiation. Besides, radiotherapy bolus is used to eliminate the skin-sparing effect [26].

In electron radiotherapy, customized bolus particularly acts as a layer of skin tissues, which provides a desired dose at superficial lesions as well as favorable curative radiotherapy outcomes [27]. The performance of the boluses in irradiation with photons is shifting the build-up region to ensure about the maximum absorbed dose at the tumor region [28].

The main problem of commercially available boluses is the poor accommodation with the irregular surfaces of patients such as the ear, nose, and scalp. This issue can lead to an air gap between the bolus and the irregular surfaces [29], and finally affect the prescribed dose. The 3D printing technology can afford these issues by creating anatomically matching boluses to achieve the individualized various complex structures [30].

Presently, 3D printed boluses are being increasingly applied in modern radiotherapy. Each 3D printed bolus must exhibit three attributes including uniformity and reproducible bulk density as well as closely match to the surface especially while using the rigid material [31]. Compared to the commercial flat bolus, the 3D printed bolus allows an appropriate fit to the patient's skin surface. The applications of the 3D printed boluses are shown in **Figure 2**.

Applied blouses are usually made of various water-equivalent materials (to control the radiation absorption and scattering in the bolus) such as wet gauze, paraffin, beeswax, and vaseline. Because of the unique physical properties (i.e., toughness, flexibility, and viscoelasticity) of soft polymers including plastics (resins), hydrogels, silicone elastomers, TangoPlus, and polyurethane soft polymers-made modern radiotherapy, bolus has begun to appear [27]. In spite of several advantages over the commercially available boluses, the ingredient materials of 3D printed boluses are often rigid thermo-plastics material, particularly acrylonitrile butadiene styrene (ABS). Besides, various tissue-equivalent printing materials such as polylactic acid (PLA), thermoplastic polyurethane (TPU), and polyvinyl acetate have been reported

**Figure 2.**

*Varying tissue-equivalent bolus materials for (A) ear [32], (B) mycosis fungoides of the face [13], (C) breast [32], (D) hand [32], (E) nose of the RANDO phantom [33].*

and validated for radiotherapy applications [34]. Rigid-made boluses are uncomfortable for the patient that limits the proper contact with surface as well as anatomical changes over a treatment period [32].

The CT imaging data are a common way to design 3D patient-specific boluses, which can be obtained by two CT scans. The first scan acquires image data for reconstructing the shape designing. The second is conducted with the 3D bolus for dose calculation in the treatment planning. Hence, patient may receive an extra irradiation dosage. Moreover, some other designs can be produced by optical scanning, which are expensive and sometimes require complicated processing [31]. To achieve the similar characteristics such as irradiated biological tissues, 3D printed boluses are usually filled with water or paraffin wax [35].

Small gaps between the printed bolus and the head phantom surface are a problem, which are caused by the immobilization with the thermoplastic mask. This issue could be improved by directly putting the printed bolus onto the patient skin and under the thermoplastic mask [23].

Besides the method and the applied material for boluses, there is still a growing concern that radiations can affect physical properties of 3D blouses and even cause them to change or contract. The effect of ionizing radiations on the physical features of the printing materials in radiotherapy was investigated by Jezierska et al. [35]. The reported results demonstrated that owing to the radiotherapy process, the applications of therapeutic X-ray dosage do not significantly affect physical characteristics including hardness and dimensions of ABS-printed boluses [35].

## **2.2 Compensators**

Compensator devices are manufactured with the molding and casting process for the radiotherapy of megavoltage X-ray [34]. During the total body irradiation, *3D-Printing Advances in Radiotherapy DOI: http://dx.doi.org/10.5772/intechopen.109153*

**Figure 3.**

*The workflow of compensator devices. The four steps of the algorithm including (A) initial plan, (B) modulation and smoothing, (C) dose evaluation and recalculation, and (D) export and preparation for print [38].*

patient-specific compensators are attached near the primary beam to attenuate the radiation dose and deliver a uniform dose distribution to the whole body [36].

During fabrication of the patient-specific compensators, the treatment field size, beam energy, and depth of the interested point should be considered. Due to the fabrication process and involved materials, patient-specific compensators are often expensive [34]. Hence, additive manufacturing of 3D printed patient-specific compensators not only reduces the costs and manufacturing time, but also has the ability for developing the complex geometries as the beam attenuation [37]. The workflow of compensator devices is shown in **Figure 3**.

### **2.3 Brachytherapy molds**

Besides the radiotherapy boluses, further novel applications of the 3D printing technology in radiotherapy have primarily been performed to produce brachytherapy applicators to improve radiation dose delivery. Due to the well-unconformity to the uneven surfaces (such as the eyes, lips, and nose), it seems essential to use the surface applicators directly to the patient's thermoplastic mask or develop patient-specific molds in accordance with various anatomic sites.

Owing to the 3D printer advances, it can be a proper solution to create the patient-specific molds [39]. 3D printed applicators eliminate the need for a mask, which generally provide more convenient approach for the patient. The uniform dose distribution to the irregular curved surfaces by performing the 3D printed applicator results in decreasing the radiation toxicity and normal tissue complications [40].

Brachytherapy (as the short distance radiotherapy) is a form of radiotherapy technique, which provides a fast dose fall-off by using small radioisotopes, which are connected to applicators or catheters placed to treat small superficial lesions [41]. Due to the steep dose fall-off around the source, performance of the brachytherapy applicator is crucial, where inappropriate placement of the source results in inexpedient dose distribution [12]. To obtain a safe and effective brachytherapy treatment, the applied applicators should have a proper accordance with the treatment surface in the stable position, the source of which uniformly covers the treatment volume [12]. 3D printers may offer a more convenient and affordable method to produce surface mold applicators for a wide variety of irregular sites including the hands, breasts, and the face [42].

It has been affirmed that brachytherapy is an efficient and well-tolerated modality for skin cancer, low toxicity of which can be achieved. Due to the irregular surface of the skin lesions in the radiotherapy of melanoma cancer, brachytherapy mold is often used to fit along the surface [43].

Water equivalent-made surface brachytherapy applicators may be used to accurately guide the position of radioactive sources and fit closely to surface of patient's skin. This type of brachytherapy applicator is typically manufactured by a wax layer, built upon a thermoplastic shell. Some small hollows guide the radioactive seed implantation as well as helping the flexible drive cable [12].

Currently, different types of commercial standard applicators such as vaginal brachytherapy applicators and flap-style flexible silicon rubber applicators such as Harrison-Anderson-Mick (HAM) or Freiburg Flap applicators (for extended superficial malignancies) have been used [12].

3D printing offers cost-effective and more convenient method to produce surface applicators for various sites including the hands, breasts, and the face. Typically, for non-melanoma skin cancer brachytherapy, reductions about 34% in time and 49.5% in financial cost have been reported. Furthermore, 3D printing technology has been proposed to produce the desired applicator shapes for gynecological tumors (especially with narrow vaginal vaults) and surface molds for skin applicators. Besides, the application of 3D-printed templates has been reported for the treatment of recurrent head and neck malignancies [29].

Due to the requirement of biocompatible material for printing brachytherapy applicator, selected materials for such a purpose depend on the type of tissue and the length of the contact [44]. It should be noted that employed materials for rapid prototyping of customized brachytherapy applicators must be biocompatible, sterilizable, and free of CT scanning artifacts with the similar dose attenuation properties such as water [45]. The dosimetric properties of employed materials for brachytherapy applicators have been assessed previously. For example, the dosimetric properties of PC-ISO material as the water-equivalency material were evaluated by Cunha et al. [44], in 2015 for gynecological brachytherapy applicators. In 2016, a personalized 3D printed vaginal template was developed by Lindegaard et al. [9], to guide commercially available applicators.

### **2.4 Anthropomorphic phantoms production**

Since the radiation dose cannot be directly measured in patients during the radiotherapy, to ensure about the accuracy of the dose delivery and conformal dose distributions, the treatment planning system algorithms, and the quality assurance, it is common to build phantoms, which mimic radiation attributes of humans. To achieve ideal or optimal radiotherapy outcomes, the results of patient-specific

**Figure 4.** *The number of publications for AM dosimetry radiotherapy phantoms until 2018 [24].*

phantoms should be combined with treatment planning systems. Using 3D printed phantoms, all parts of preclinical radiation examinations including planning, image guidance, and treatment delivery can be assessed by clinicians to verify the treatment planning and the calibration of the applied treatment techniques. An observed linear ascending trend for dosimetry applications of manufactured radiotherapy phantoms through the 3D printing technology is indicated in **Figure 4**.

To assess the QA of new modalities or validate the patient treatment plans using the calculated absorbed dose by means of thermoluminescent dosimeters (TLD), film dosimetry, and ionization chambers, commercially available phantoms are often utilized [46]. The QA process can be affected by the phantom limitations including not fully pretending the patient-specific anatomical and pathological characteristics, which eventually lead to errors in absorbed dose measurement. Owing to the advances of 3D printed radiotherapy phantoms including fast and high-resolution workflows as well as multi-material printing, the need for QA procedure is becoming more achievable [47].

The four main steps of 3D printed phantoms fabrication can be observed in **Figure 5**. These steps include 1) imaging, 2) segmentation for region of interests (ROI), 3) slicing the segmented 3D models, numerically controlled process of desktop 3D printers (called gcode), as well as printing parameter modifications, and finally, 4) printing models and final implementation for imaging or dosimetry applications.

To create the 3D printed phantoms, utilized printing technologies include fused deposition modeling (FDM) and polymer material jetting (PJT/MJT) [48].

The applications of the 3D printed phantoms have been demonstrated in various literatures [34, 49, 50]. The simulation of realistic lung movements has been

#### **Figure 5.**

*The patient-specific phantoms workflow through the 3D printing technology [24].*

demonstrated by Yoon et al. [51], through the 3D-printed lung phantom with printed lung lesions. Furthermore, Jahnke et al. [52] have evaluated the feasibility of manufacturing the realistic head phantom through i) paper-based 3D printing method and ii) customized laser object manufacturing printer. However, a promising result has been achieved in this study, and the CT tissue-equivalence and dosimetry assessments need further quantifiable assessments.

However, the performance of traditionally available phantoms may be limited by the geometry and physical properties, and 3D printed phantoms enable to develop a viable, low-cost alternative. Recently, 3D printed phantoms with inhomogeneous materials have been increasingly taken into consideration. Ehler et al. [16] employed the 3D printing of a head phantom using ABS material, which was filled with a modified M3 mix (with the density of about 1.05 g/cc).

## **2.5 3D printed organs**

With the developments of 3D printing technology, production of organ models has also experienced massive progress [20]. 3D printed organ models still have some difficulties such as high cost, time-consuming, low production accuracy, and limited simulation characteristic, which limit their further applications [53]. Sometimes, complicated image segmentation and 3D model creating processes may require several days of labor, expensive materials and software as well as a long-learning period. There is still limitation for currently employed materials to perfectly mimic the characteristics of soft tissues [53]. Furthermore, errors would be inevitable while dividing large models into several small parts for printing and assembly process.

## **2.6 Immobilization devices**

Before the radiotherapy treatment, immobilizing devices are utilized to accurately set the position and rigidly immobilize patients. Beaded bags, polyurethane foam castings, orthopedic plastics, and head masks are commonly used as the immobilization

#### **Figure 6.**

*The workflow of 3D printed immobilization devices.*

devices [54, 55]. To minimize patient movements during the radiotherapy process, external immobilization of the equipment (such as headrests, vac-bags, thermoplastic masks, or shells) is frequently applied, which can result in localized dose distribution on the tumor site [56]. Besides, healthy tissues can be protected from the radiation exposure and the effectiveness of radiotherapy treatments can be improved.

Besides the head and neck, 3D printed immobilization devices can be applied for immobilization of the abdominal area, mouth, and breasts [57]. The workflow of 3D printed immobilization devices is shown in **Figure 6**.

Besides the CT data, surface laser scanner (generation of a reference model for immobilizing shell construction) is the other procedure to develop printable models. 3D printed immobilizers can be created with a range of printing techniques including FDM, stereolithography (SLA), selective laser sintering (SLS), and PJT/MJT. Laycock et al. [58] have assessed the feasibility of VisiJet SL Clear, for immobilization of devices through the FDM printing technology. To achieve an accurate position in radiation therapy, thermoplastic material is routinely performed. For example, the head immobilization during the radiotherapy is most practically accomplished by thermoplastic masks. Since the skill of the human fabricator for manufacturing the immobilizers is crucial, these mentioned devices have a variable quality [59].

Today, immobilization masks are commonly utilized for head and abdominal fixation. Thermoplastic and PLA materials are commonly accomplished for head and abdominal immobilization mask generation, respectively [34]. However, 3D printed fixation masks improve patient comfort and eliminate the thermoforming process for mask manufacturing, and immobilization masks modeling may be a time-consuming process, which strongly depends on the healthcare professional and potentially results in inconvenience for the patient [60].

### **2.7 Other applications**

For more applications of 3D printed objects in radiotherapy, the fabrication of Cerrobend® grids for spatially modulated therapy can be mentioned. Grid therapy is part of a novel treatment method, which provides passive-scattering proton beams with a fixed range for stereotactic radiosurgery as well as the manufacturing of oral stents from CT images used during radiotherapy of head and neck [29].

## **3. Applied material for 3D objects in radiotherapy**

The most commonly applied materials for manufacturing the 3D objects are ABS and PLA, which may differ from metallic alloys with other thermoplastics [61]. PLA as the most widely used biodegradable polyester has the strong potential to be applied in industrial applications or in medicine as a biomaterial. PLA production has numerous advantages as well as ecology, biocompatibility, and better thermal resistance than other biopolymers. Since PLA products are nontoxic, they are potentially able to be applied in biomedical applications [62].

#### **Figure 7.**

*The timeline of discovered important materials for 3D printing applications [66].*

Due to the bolusing effect of thermoplastic materials on the patient surface, the dose buildup can be affected [60]. To reduce this bolusing effect, it has been reported that multi jet fusion (MJF) method, which is uncommonly flexible in various additives, may be an opportunity to develop low physical/electron density materials [60].

The dosimetric, biological, and physical characteristics of applied materials for 3D printed objects have been investigated in several literatures [63–65]. Suitable materials for 3D printing models in radiotherapy applications should have similar characteristics to water such as radiation attenuation, scatter properties, and biocompatibility [27]. For example, ABS and PLA have the advantages of electron density similar to water and low failure rate, respectively. The ABS is prone to layer separation. Besides, the PLA has the potential of high electron density and easy wrapping [12].

The timeline of discovered materials for 3D printing applications is summarized in **Figure 7**.

## **4. The 3D printing barriers in radiotherapy**

In spite of the advantages of 3D printing technology in current radiotherapy practices, for the clinical implementations, this modern technology appears to be low. Despite the recent significant developments, the size, capability, and print speed are still considered as the limitation factors for affordable 3D printers [63]. Hence, for successful clinical implementation of 3D printing in radiotherapy, besides the mentioned factors, QA of 3D-printed objects as well as the material characteristics and efficient workflow should be considered [29].

In radiotherapy technique, the manufacturing cost of printed objects is probably the major determining factor for 3D printing technology in radiotherapy clinical practice, especially for creation of the small targets [59]. Despite the manufacturing cost decrements in recent years, high resolution of commercial printers is still expensive. Sometimes, the workflows of 3D printing objects may require several days, precise information about the target, and expensive materials. Besides, some applied materials have disadvantage such as rough craftsmanship, poor conformability, and poor repeatability [64]. Utilized raw materials to perfectly mimic the characteristics of soft tissues may be the other limitation and determined factor for 3D model

creation in radiotherapy. Low resolution, the necessity of post-processing stage, and poor mechanical properties are the other disadvantages of 3D printing technology in radiotherapy. Hence, there are still some limitations to be overcome to achieve the requirements for such clinical practices [65, 67].

## **5. Conclusion**

The 3D printing technology is rapidly evolving, where at present the AM-radiotherapy field can be regarded as an exciting phase of exploration and innovation. This technology, like any new technology, has introduced many advantages and possibilities in medical field. It holds the potential to be applied in radiotherapy for a wide variety of objects including patient-specific bolus, brachytherapy applicators, personalized medical devices, physical phantoms for radiotherapy QA, compensator blocks, and patient-specific immobilization devices. Low-cost 3D printed objects can result in the accurate and comfortable custom-made devices, which will ultimately improve the treatment outcomes. Due to the rapid developments and increased clinical applications, the additional use of 3D printing within radiotherapy will likely emerge.

Due to the importance of personalized radiotherapy devices, 3D printing technology can be applied to improve the quality of life, reduce the setup times, improve patient comfort, and enhance reproducibility and reliability. The modern 3D printers have facilitated the design and fabrication of patient-specific radiotherapy phantoms and ultimately result in precise, cost-effective, high-resolution phantoms with the multi-material printing workflows.

In spite of the impressive growth of 3D printing technology in medicine, the advantages in radiotherapy field are not still fully realized. However, it requires an updated and current legislation to guarantee its correct performance in radiotherapy.

## **Author details**

Reza Shamsabadi Hakim Sabzevari University, Sabzavar, Iran

\*Address all correspondence to: rshams220@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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## **Chapter 15**
