3D Printing (3DP), also known as Additive Manufacturing (AM) enables the low-cost and customization of anthropomorphic radiotherapy phantoms. Phantoms are utilized, in-vitro, for the treatment planning of cancer patients and the quality assurance of new radiotherapy techniques, to validate target doses and minimize the effects of ionizing radiation on surrounding healthy tissues.
Modern radiotherapy involves the use of Computed Tomography (CT) imaging, 3D-treatment planning, and the implementation of quality assurance (QA) processes to produce highly conformal dose distributions and ensure the safe and accurate delivery of the planned treatment. It is common to manufacture phantoms using the molding and casting process, that emulates the radiation properties of the average human tissue as radiation dose cannot be directly measured from patients.
As part of the QA of patient treatment plans, patient-specific dose measurements are often performed using phantoms combined with various dose measurement tools such as thermoluminescent dosimeters (TLD), radiochromic films, or ion chambers. Unfortunately, commercial phantoms are associated with expensive tissue-substitute materials, high fabrication costs, and long manufacturing lead times. In addition, these phantoms only emulate the average human proportion, consist of standardized tissue heterogeneity, and do not accommodate pathological features, which limits personalized treatments for patients. For example, the current radiotherapy phantom market is yet to provide phantoms that emulate obese patients and have limited ranges for emulating pediatric patients .
This article discusses some of the basic concepts surrounding the manufacture of 3DP phantoms, their clinical significance and requirements, their associated manufacturing techniques and materials, and the future of 3DP phantoms for radiotherapy use.
Anthropomorphic radiotherapy phantoms for treatment planning.
The treatment planning procedure is a significant part of radiotherapy, which determines the optimal treatment parameters to be used for the management of a patient’s disease via radiotherapy means. These treatment parameters include target volume, dose-limiting structures, treatment volume, dose prescription, dose fractionation, dose distribution, the positioning of the patient, treatment machine settings, and adjuvant therapies (e.g. chemotherapy, hormone therapy, targeted therapy, or biological therapy) 
The role of a phantom is to act as a human proxy to experimentally visualize and evaluate treatment options tailored for the patient(s). This importance signifies the current limitations of anthropomorphic phantoms as they only follow the average body proportion and radiation attenuations of a ‘healthy’ person, and lack patient-specific pathological features, particularly for the emulation of lesion shape, density, and positioning . Therefore, these limitations provide a significant opportunity for the 3D printing technology in highlighting low manufacturing costs and phantom customization.
Customization of phantoms enabled by 3DP.
3D printing provides opportunities for the inexpensive manufacture of customizable devices as observed from the current literature not only for radiotherapy phantoms but also for other radiotherapy devices including bolus and compensators to achieve personalized dose distributions for irregular surfaces; electron beam shielding devices to block ionizing beams and scattered rays; immobilizers to secure patients during treatment to avoid unnecessary movements during treatment and; brachytherapy moulds to allow targeted radiation treatment using catheters to allow the insertion of radioactive seeds close to the lesion [3,4].
Novel 3D printing workflows have been developed to accommodate imaging tissue-like heterogeneity utilising 3D printing materials, via modification of infill parameters, and the in-house development of materials to modify their radiation attenuation properties.
Types of 3DP phantoms.
Early versions of additively manufactured radiotherapy phantoms were manufactured as-shell phantoms, which are hollowed phantoms filled with various tissue-equivalent materials (sawdust, silicone gels, cork).
The emergence of better AM technologies has attracted interest in exploring the simulation of human tissue heterogeneity, classified as as-printed phantoms. Heterogeneity in printed phantoms can be achieved using modified material extrusion (MEX) printing parameters such as infilling patterns and percentage, printing nozzle size, temperature, and more recently, the modification of material extrusion rate.
Furthermore, contrast variations can also be achieved by constructing phantoms with two or more different AM materials (multiple material printing); doping filaments with high-density materials such as bismuth and barium sulfate to increase the observed HU range; and the use of controlled voided structures within the manufactured phantoms to precisely controlled HU values.
Recent studies have illustrated the combination of these manufactured phantoms with commercially available motion platforms and in-house motion devices to further stimulate body movements, especially the thorax’s respiratory movements (classified as 4D-AM phantoms) (see Figure 3). See more recent reviews of 3D printing phantoms in the literature from [3, 4, 5, 7].
Figure 3 below illustrates more in detail that 3DP phantoms are divided into two manufacturing processes, (1) direct manufacturing process utilizing only commercial or in-house 3DP materials for manufacture phantoms, and (2) indirect manufacturing process utilizing 3DP materials (commercial or in-house) and are assembled with tissue-substitutes (non-3DP materials) to manufacture phantoms). These 3DP phantoms are categorized into a solid phantom, a deformable phantom utilizing deformable 3DP materials, or a 4D phantom, which are either solid or deformable phantom attached to a motion platform to simulate patient movements.
Video 1. Comparison of 3DP bone phantom with the associated patient CT dataset .
Clinical requirements and implications.
More recently, printing guidelines and recommendations for 3DP in medicine have been developed by the SIG (Special Interest Group on 3D printing), a group representing the Radiological Society of North America . The guidelines and recommendations are divided into four main processes including:
- Medical image acquisition – commonly used imaging modality involves CT or MRI. Associated patient data should have sufficient spatial resolution to accurately represent anatomy to be modelled.
- Image data preparation and manipulation – includes image segmentation, 3D CAD design, and file documentation.
- Generation of the 3D-printed model –involves the printing process, post-processing, and model inspection.
- Quality Control program – involves the delivery and discussion with referring physicians, pre-operative planning, material biocompatibility, cleaning, and sterilisation, and clinical appropriateness.
Regarding printing materials, it is essential to consider the photoelectric and Compton effects when comparing result outputs with human tissues. Photoelectric effect serves as the dominant phenomena at low x-ray energies ranging below 200 KeV, hence for imaging modalities (CT, MRI, PET). At higher x-ray energies up to 10 MeV, Compton effects can be considered as the dominant phenomena, where material attenuation differs depending on their elemental composition, signifying how radiation doses are distributed . Ideally, 3DP phantoms aim to simulate not only the patient’s proportion and pathological features but also both the imaging attenuation of human tissues, the photoelectric effect, and the dose attenuation of tissues, the Compton effect.
Also, for any given 3D printing material to be tissue or water equivalent, it must have the same effective atomic number, number of electrons per gram, and mass density. However, since the Compton effect is the predominant mode of interaction for MV photon beams in the clinical range, the necessary condition for water equivalence for such beams is the same electron density (number of electrons per cubic centimetre) as that of water.
The future of 3DP phantoms.
Despite lower manufacturing costs and complex geometrical capabilities of 3D printing in developing anthropomorphic radiotherapy phantoms, there exists numerous uncertainties with regards to their reproducibility and sustainability.
At present, the commonly utilized 3DP technology for developing phantoms, modified material extrusion (MEX), is still yet to be fully exploited to its full potential for manufacturing clinically viable phantoms for routine use. MEX comes with inherent limitations in comparison with other printing techniques such as Material jetting technologies (MJT) and Stereolithography (SLA) where significant void defects are observed, which in turn produces structurally weak and non-uniform dense objects affecting the phantoms reproducibility and sustainability.
Although being still a new area of research compared to the 3DP of surgical guides and implants, 3DP phantoms will soon be able to compete clinically and be more accepted globally as clinicians and engineers work towards quantifying the associated manufacturing uncertainties, explore innovative 3DP methods, and tissue-equivalent materials for the customization of 3DP phantoms, and its implementation for complex case studies comparing 3DP phantoms and commercial phantoms. Furthermore, it is also recommended that proper documentation of these 3DP phantoms (i.e. printing parameters, printing machine description, the body of the application, imaging modality used, material and printing costs, printing and time, printing workflow, post-processing procedures be implemented as it will play a significant role in providing guidance for developing clinical regulations and cost reimbursements for such devices in the future.
Some references in this work are a collection of collaborative efforts conducted by myself and researchers at RMIT’s Centre for Additive Manufacturing (RCAM) involving Professor Martin Leary and Distinguished Professor. Milan Brandt and Sir Peter MacCallum Cancer Centre physical sciences department involving Distinguished Professor Tomas Kron and Senior medical physicist, Dr. Adam Yeo.
 Khan, F.M., Gibbons, J.P. and Sperduto, P.W., 2016. Khan’s treatment planning in radiation oncology. Lippincott Williams & Wilkins.
 Kron, T., Ungureanu, E., Antony, R., Hardcastle, N., Clements, N., Ukath, J., Fox, C., Lonski, P., Wanigaratne, D. and Haworth, A., 2017. Patient specific quality control for Stereotactic Ablative Body Radiotherapy (SABR): it takes more than one phantom. In Journal of Physics: Conference Series (Vol. 777, No. 1, p. 012017). IOP Publishing.
 Tino, R., Yeo, A., Leary, M., Brandt, M. and Kron, T., 2019. A systematic review on 3D-printed imaging and dosimetry phantoms in radiation therapy. Technology in cancer research & treatment, 18, p.1533033819870208.
 Tino, R., Leary, M., Yeo, A., Kyriakou, E., Kron, T. and Brandt, M., 2020. Additive manufacturing in radiation oncology: a review of clinical practice, emerging trends and research opportunities. International Journal of Extreme Manufacturing, 2(1), p.012003.
 Leary, M., Kron, T., Keller, C., Franich, R., Lonski, P., Subic, A. and Brandt, M., 2015. Additive manufacture of custom radiation dosimetry phantoms: An automated method compatible with commercial polymer 3D printers. Materials & Design, 86, pp.487-499.
 Leary, M., Tino, R., Keller, C., Franich, R., Yeo, A., Lonski, P., Kyriakou, E., Kron, T. and Brandt, M., 2020. Additive manufacture of lung equivalent anthropomorphic phantoms: a method to control hounsfield number utilizing partial volume effect. Journal of Engineering and Science in Medical Diagnostics and Therapy, 3(1).
 Filippou, V. and Tsoumpas, C., 2018. Recent advances on the development of phantoms using 3D printing for imaging with CT, MRI, PET, SPECT, and ultrasound. Medical physics, 45(9), pp.e740-e760.
 Tino, R., Yeo, A., Brandt, M., Leary, M. and Kron, T., 2021. The interlace deposition method of bone equivalent material extrusion 3D printing for imaging in radiotherapy. Materials & Design, 199, p.109439.
 Chepelev, L., Wake, N., Ryan, J., Althobaity, W., Gupta, A., Arribas, E., Santiago, L., Ballard, D.H., Wang, K.C., Weadock, W. and Ionita, C.N., 2018. Radiological Society of North America (RSNA) 3D printing Special Interest Group (SIG): guidelines for medical 3D printing and appropriateness for clinical scenarios. 3D printing in medicine, 4(1), pp.1-38.
About the Author:
Other than being the editorial assistant of 3DHeals, Rance Tino has a B.S in Biomedical Engineering at the Royal Melbourne Institute of Technology (RMIT), Australia. Rance continued the academic pathway at RMIT as a Ph.D. candidate and is currently in his last year of candidacy. His current research is in collaboration with the Victoria Comprehensive Cancer Centre (VCCC), in particular with the Sir Peter MacCallum Physical Sciences department in developing novel Radiotherapy Phantoms using 3D printing for lung cancer treatment planning. His research is currently funded by the ARC Industrial Training Centre in Additive Biomanufacturing, which is a team effort in developing the next generation of Additive Biomanufacturing technologies and future leaders in Australia.