Challenges and solutions in 3D printing for oncology: a narrative review

Introduction

Background

The rapid development of oncology requires innovative approaches for improved diagnosis, treatment, and research. Recently, the field of oncology has shown increasing interest in the application of three-dimensional (3D) printing technology (1). The process of creating three-dimensional objects through additive manufacturing involves the utilization of various methods, equipment, and materials. 3D printing, also recognized as additive manufacturing, derives its name from the prevailing additive nature of most 3D printing processes (2). The techniques and materials used vary from one 3D printing technology to another. 3D printing methods can be classified according to the physical state of the main material, namely solid, liquid or powder. Different methods are used for different types of materials; details are beyond the scope of this review, but are widely available in the literature (3). Several distinct physical transformations play a role in 3D printing, such as melt extrusion, light polymerization, continuous liquid interface production, and sintering.

In medicine, 3D printing can be divided into two categories: conventional 3D printing, where non-biological materials (such as thermoplastic filaments or liquids) are used to build predefined structures, and bioprinting, which prints liquid and gel-based materials containing living cells and tissues (4). Both are used in oncology. Conventional 3D printing has been around for more than 50 years (5). Nevertheless, its full potential has not yet been fully released.

The first applications of conventional 3D printing in oncology were focused on creating anatomical models of organs and tumors made from plastic filaments for surgical planning and educational purposes. Such models are typically based on images obtained from data reconstructed from imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). The implementation of such models has enabled more precise and effective surgeries, as well as a reduction in total procedure time (6,7). More advanced applications in cancer surgery include visualizations for reconstructive surgery. Moreover, 3D printing has been utilized to create dedicated implants for cancer patients, especially in situations where tissue removal or reconstruction is required (8). Customized implants produced through additive manufacturing from titanium powder have been used for over 15 years in orthopedic oncology or maxillofacial surgery (9).

Radiation oncology is another large subdiscipline where 3D printing finds wide application. The field requires highly individualized treatment, necessitating the fabrication of custom-made boluses, brachytherapy applicators, immobilization systems, and quality assurance devices (10).

Rationale and knowledge gap

Despite very encouraging promises and reports from preclinical and clinical applications of conventional 3D printing, the technology has not been widely adopted into clinical practice yet. There are still several unresolved issues that limit its use. One of the main issues is the low quality of evidence and the lack of guidelines on this topic. It is difficult to introduce 3D printing into routine clinical practice based only on case reports or case series. This is mainly due to the absence of detailed data regarding costs, scalability, legal issues, and standardization. Therefore, a review of available data may help categorize the available knowledge and serve as a guideline for clinicians who wish to start utilizing 3D printing in their oncological practice.

Objective

This study aims to examine the current extent of 3D printing applications in oncology. The goal is to identify solutions that can be routinely used in clinical practice and distinguish them from those that are strictly experimental or conceptual. We present this article in accordance with the Narrative Review reporting checklist (available at https://cco.amegroups.com/article/view/10.21037/cco-24-4/rc).

Methods

A literature search to identify comments, reviews, and preclinical and clinical studies discussing the utilization of 3D printing in oncology published before December 1, 2023 (Table 1) was conducted. PubMed and Google Scholar Review were searched for relevant studies. We allowed analysis of cross-suggestions. A strategy employing two keywords to search the databases included “3D printing” and/or “oncology” as necessary phrases. This narrative review excludes the issues related to bioprinting and technical aspects of 3D printing. In total, we found 1,584 articles. The selection of discussed articles was performed by consensus among all authors. We have summarized all the articles discussed in the main text in Table S1.

Radiation oncology

Rooney et al. conducted a systematic review of 103 publications on the applications of 3D printing in radiation oncology (11). The authors analyzed 3D printing applications in medical settings, identifying the most common uses as quality assurance phantoms (26%), brachytherapy applicators (20%), and bolus (17%). Most of these studies (63%) were pre-clinical feasibility studies, with a smaller proportion being clinical investigations such as case reports or cohort studies predominantly focusing on brachytherapy applicators and bolus. Clinical studies generally had small sample sizes (median of 10 participants). There was a notable increase in the number of articles published annually from 2012 to 2018, highlighting growing interest in this field. Most studies reported successful implementation of 3D printing, citing accuracy and cost-effectiveness, though a minority focused on basic or translational research and workflow or cost evaluations.

3D-printed phantoms can reflect the anatomy of a specific patient whereas mass-produced phantoms use average conditions (12). Thus, 3D printed phantoms mimic anatomical situations more accurately and enable higher quality assurance in radiation oncology. This capability allows medical physicists to assess dose distribution with greater accuracy and refine treatment plans before the actual patient treatment, minimizing the risk of over- or underdosing. The group of scientists reported methods of production and validation of 3D-printed anthropomorphic phantoms (13). The study focused on creating an individualized, anthropomorphic lung phantom using cost-effective 3D printing, based on anonymized human chest CT images. This phantom, designed to mimic human chest anatomy and radiation attenuation properties, was made using a 3D-printed skin shell filled with materials like CaCO₃, MgO, and agarose, which have similar radiation attenuation characteristics to human tissues. The phantom’s effectiveness was validated by comparing ion chamber measurements with treatment planning system calculations based on three independent calculation algorithms. The obtained results showed a high compliance, indicating that 3D printing can effectively create personalized phantoms for accurate radiation dose verification, enhancing personalized medical treatment and efficiency while reducing costs. Another potentially interesting application could be the fabrication of a pregnant female phantom for accurate assessment of out-of-field and fetal doses or pediatric phantoms to assess integral radiation dose, critical for avoiding late side effects (14-16).

3D printing may offer more tailored treatment in brachytherapy, a procedure where radioactive sources are placed directly within or near tumors allowing delivery of higher radiation doses precisely to the irradiated area while minimizing its influence on surrounding tissues. 3D printing has simplified the creation of patient-specific brachytherapy applicators, ensuring optimal placement and dose distribution. These applicators can be customized to match the shape and size of the tumor cavity, offering improved flexibility and reducing radiation exposure to organs at risk (17). The most promising indications for 3D-printed brachytherapy applications seem to be cervical and skin cancers (18,19). Several small studies have examined the production and clinical use of 3D-printed brachytherapy applicators (18-22). While these studies have yielded positive results, the technology has not yet been validated in larger clinical trials.

Another investigated utilization of 3D printing in radiotherapy is the customization of boluses and immobilization devices (23). In radiotherapy, a bolus is a tissue-equivalent material placed on a patient’s skin to overcome the skin-sparing effect of higher-energy radiation. They play a special role in the treatment of superficial lesions by improving the uniformity of dose distribution and adequate coverage of the entire treated area (24). 3D printing enables the creation of bolus that can be tailored to the unique anatomy of a patient, enhancing both adherence and patient comfort (25-27). One study compared the use of 3D printed bolus with conventional bolus to reduce cardiac and pulmonary toxicity in postmastectomy patients who underwent volumetric modulated arc therapy (28). The authors concluded that the use of 3D-printed bolus helped achieve the aim. Similarly, immobilization devices such as head and neck masks, headrests, or bite blocks can be individually customized for each patient, improving immobilization and positioning reproducibility during treatment (29).

A less popular but still viable option is to use 3D printing to create radiation shielding devices and electron cutouts (30). These devices help to modify the shape of a beam to protect organs at risk of excessive radiation exposure during treatment. Customization of shielding and collimation components based on clinical situation, may result in improvement of treatment plan conformity, and facilitate the work of medical physicists.

Additionally, 3D-printed anatomical models can help medical residents gain a better understanding of anatomy, which is crucial in the training process of radiation oncologists (31).

Cancer surgery

Surgical oncology

In surgical oncology, 3D printing enables the visualization of patient imaging data in a tangible, spatial form by converting and printing models based on CT or MRI images. This enables physicians to better plan surgeries and understand tumor spread in a particular situation which may result in improved outcomes and reduced procedure time and cost (32). Cancer surgeons practice surgeries on patient-specific models, refining their skills and reducing surgery time.

Obtaining micro- and macroscopically clear and adequate margins is a critical factor in cancer surgery. Microscopically radical surgery significantly increases the rate of local control (33). 3D printing may help assess tumor margins by making 3D-printed models of tumor specimens and surrounding tissues, allowing real-time assessment (34). This helps surgeons make decisions about the proper extent of tissue resection required, reducing the likelihood of leaving residual cancer cells.

3D printing enables the production of personalized surgical instruments that are customized to the type of planned surgery (35). Tailored instruments can be created to match the specific features of the tumor, making minimally invasive or complex surgeries more manageable while minimizing harm to healthy tissues. Advantages of 3D printed surgical instruments compared to traditional tools can be also customization and ease of modification according to a clinician’s preferences (36). In addition, it is possible to print so-called “surgical guides” to better plan complex procedures (37). These guides help surgeons accurately position incisions, and implants, or remove tumors.

Moreover, an important and widely adopted application of 3D printing is creating custom replacement implants after extensive cancer surgeries (38). This method allows for the fabrication of implants meeting the patient-specific anatomical requirements. It uses data derived from medical imaging. The implants can be made of different materials, including those releasing antibiotics (39,40). This personalized approach enhances implant integration and contributes to patient comfort and functional recovery, leading to an improved quality of life for cancer survivors undergoing post-surgical implantation procedures (41). Moreover, 3D-printed implants enable better osseointegration than conventional implants (42).

For example, 3D-printed implants can be used in maxillofacial surgery. One technical report highlights the burgeoning role of 3D printing in the medical field, particularly in enhancing personalized patient treatment while reducing manufacturing costs (43). Focusing on mandibular reconstruction with fibula free flaps, the authors address the issue of prohibitively expensive CT-guided molding cutting guides, traditionally costing between €2,000 to €6,000. Through a collaborative effort involving the CNRS, engineering students, and a biomedical company, the team has developed more affordable cutting guides and 3D-printed mandible templates, which can be delivered in just 7 days. The project’s innovation lies in its ability to rapidly produce these items at a significantly lower cost. The authors detail the production logistics and the successful results obtained, aiming to make this technology accessible to all patients. 3D printing may also contribute to thoracic surgery by making custom-made prosthesis for reconstructions after tumor resections and printing training models for invasive procedures like video-assisted thoracic surgery (44).

Orthopedic oncology

3D printing technology revolutionized modern orthopedic oncology. In some case it may even enable limb-sparing surgery instead of amputation (45). Manufacturing of implants using titanium alloy (Ti6Al4V) through electron beam melting technology opened new horizons for bone tumor surgeons. Before that, patients who underwent surgical resections for bone sarcomas that could not be reconstructed with off-the-shelf implants were often left heavily crippled due to limited options for reconstructing the removed segments or entire bones. Pelvic resections of innominate bone for primary or secondary bone tumors that are most difficult to reconstruct with standard implants, reconstructions of bones in the foot or hand, vertebrae, dedicated stems, or modifications to standard implants are all possible with the use of 3D additive manufacturing (46). This technology allows the replacement of virtually any bone or a bony fragment with an implant that reflects the patient’s exact anatomy or includes modifications introduced by the surgeon (see Figure 1).

Figure 1 The use of a custom-made prosthesis in treating a bone tumor of the second metacarpal bone.

The process of modeling the implants based on thin-slice reconstructions of nonenhanced CT, preferably with slice thickness of 0.6 mm, which allows for accurate reconstruction. However, this may vary depending on the recommendations of the implant manufacturer. Not only implants but also cutting jigs can be manufactured to aid surgeons during operation, allowing for exact cuts with safety margins. During the planning and designing of the implant, close cooperation of the surgeon with the manufacturing company’s engineer is a must to obtain the most satisfactory results (47).

In a small retrospective cohort analysis, Xu et al. analyzed selected surgery-related parameters in two groups of patients with pelvic tumors who underwent tumor removal followed by reconstruction (48). In the first group patients were treated with a nail rod system or a steel plate while in the second group, patients were implanted with individualized 3D-printed prostheses. The authors reported improved outcomes in patients treated with printed implants, explaining the difference by a reduction in surgical trauma, shorter surgical time, and improved functional recovery of patients postoperatively. Another interesting report presented a case of 36-year-old male with the left calf chondrosarcoma, confirmed by biopsy (49). Despite the initial recommendation of amputation, a novel limb-salvage procedure was chosen instead. This involved removing the tumor, reconstructing the blood supply, and implanting a customized, 3D-printed prosthesis with a porous interface to connect the knee prosthesis to the remaining small bone segment. Over a 16-month follow-up, the patient experienced no soft tissue or prosthesis complications, showed no signs of recurrence or metastasis, and retained walking ability with full range of motion in the tibiotalar joint.

Other applications

Medical oncology

In medical oncology 3D printing technology is being explored for developing drug delivery systems that can be tailored to release chemotherapy drugs at a controlled rate. This can potentially reduce side effects and improve treatment efficacy. For example, some researchers have developed a novel approach to reduce the systemic toxicity of chemotherapy (50). They designed porous absorbers that capture cytostatics from the bloodstream after their effect on tumors, thereby preventing the drugs from causing side effects to the healthy tissues. These absorbers are created using 3D printing technology for their support structure, which is then coated with a nanostructured block copolymer. This polymer has a specific section, polystyrene sulfonate, that binds to doxorubicin, a commonly used chemotherapy drug known for its effectiveness in multiple cancers and significant side effects. The absorbers are intended to be used during chemotherapy via minimally invasive image-guided endovascular surgeries. Tests in swine models showed that these absorbers could capture about 64% of the administered doxorubicin without causing immediate adverse effects or complications like blood clots or vein wall dissection.

Hyperthermia

Recent advancements in soft magnetic nanocomposites have paved the way for the development of programmable magnetic robots with shape-shifting capabilities, offering promising prospects in various biomedical applications. Overcoming challenges posed by the low magnetization and simple geometry of magnetic hydrogels, these studies present an innovative solution using 3D printing to create composite structures consisting of magnetic hydrogels and elastomers (51-53). By subjecting magneto-thermo-sensitive hydrogels containing Fe₃O₄ nanoparticles, such as poly(N-isopropylacrylamide) (PNIPAm), to an alternating magnetic field, they undergo rapid volume reduction due to the magnetothermal effect. The difference in responsiveness between magnetic hydrogels and elastomers enables complex shape transformations in the composite structures. Through magnetic hyperthermia, these shape-transforming structures can encapsulate and eradicate cancer cells, specifically human malignant melanoma cells. The study reports a remarkable 50% reduction in cancer cell survival during the deformation process. Other papers also present encouraging results of the integration of 3D printing, magnetic fields or waves, and hyperthermia (54-56). However, all methods mentioned in this section are strictly experimental and are not yet integrated into clinical practice or clinical trials.

Patients’ education

3D-printed models help patients visualize their condition, improving understanding of their diagnosis and treatment plan (57,58). The printing technology is similar to the models that are used in the surgery, but the application and the target group are different. Nevertheless, only few reports on this topic are available in the literature (59). One study reported a preliminary evaluation of personalized 3D-printed models to enhance patient comprehension during the informed consent process for surgical resection of stage I lung cancer (60). Over three months in 2018, 20 adult patients with suspected stage I lung cancer were enrolled and randomly assigned to two groups: one receiving a half-life-size patient-specific 3D-printed model as part of the informed consent process and the other serving as the control group without such models. Patients in the 3D-printing group demonstrated significantly higher knowledge scores related to their surgery compared to the control group. While total scores and scores related to benefit, risk, alternative treatments, and satisfaction did not significantly differ between the groups, personalized 3D printing showed promise in improving patient comprehension during the informed consent process for surgical resection in stage I lung cancer cases. Another relatively large study investigated the impact of using patient-specific 3D models, including 3D printed and augmented reality models, for patient education in the context of renal and prostate cancer (61). A total of 200 patients with MRI-visible prostate cancer or renal masses were enrolled and randomly assigned to receive pre-operative planning with standard imaging alone or in combination with a patient-specific 3D model based on their medical imaging data. Patients completed surveys to assess their understanding of the disease and treatment plan. The results showed that 3D printed models significantly improved patient comprehension compared to standard imaging alone, including a better understanding of disease, cancer size, cancer location, treatment plan, and comfort level with the treatment plan. The study concluded that patient-specific 3D models, particularly 3D printed ones, are valuable tools for enhancing patient education in the context of renal and prostate cancer.

Chances and limitations

Although 3D printing holds great promise, it faces several challenges that need to be addressed, including cost, scalability, regulatory considerations, and standardization. The most significant concerns in all analyzed aspects were summarized in Table 2.

Cost

On the one hand, the introduction of 3D printing may significantly reduce the cost of some expensive equipment necessary for advanced oncological procedures (62). One example of quality assurance and medical dosimetry in radiation oncology is the use of anthropomorphic phantoms (63). These phantoms allow for accurate and reliable measurements of complex dose delivery to tumors and organs at risk, as they are made of materials that mimic human tissue. However, the high cost of these phantoms makes them unavailable to many radiotherapy departments. Fabrication of cheaper, 3D-printed phantoms may be a chance to improve radiotherapy quality in middle and low-income countries or smaller radiotherapy departments (64). What is more, custom-made printed prostheses in particular circumstances may be much cheaper than their commercially available equivalent (43).

On the other hand, the cost of 3D printing could change due to technical issues in a particular clinical situation. For example, the cost of anatomical models made before surgery can make up a significant portion of the total procedure cost. According to an analysis by Ravi et al., the average cost of an anatomical model was $2,737, while the cost of surgery was $213,450 (65). The authors emphasized the financial benefits of 3D printing, specifically the reduction in procedure time achieved by using the model, which amounted to an impressive $2,900 per patient saved with the model. However, it is important to note that the cost savings associated with surgical procedures may not be as significant in less developed countries where medical costs are generally much lower. In addition, filaments approved for medical purposes are more expensive than those used in pre-clinical assessments (66). Therefore, the actual clinical cost of application could be significantly higher than assumed in preliminary research. Another example of an important but expensive application of 3D printing is the improvement of communication between physicians and patients using 3D models. While the cost of $1,000 per model may limit their widespread introduction into routine practice, research has shown that such models can significantly improve a patient’s understanding of surgical resection of lung cancer (60). Moreover, 3D printing is time-consuming, especially in the case of complicated, custom-made metal prostheses. Finally, it should be noted that there is currently a lack of validated pharmacoeconomic models or reliable economic simulations for the implementation of 3D printing in clinical practice. It is important to acknowledge that any available data is based on numerous reports and general assumptions about the growth of the 3D printing market, which may not necessarily reflect the full picture.

Scalability

Scalability refers to a business’s capacity to adapt to increased workload or market demands, allowing it to switch into a ‘mass production’ mode. While scalability may seem contradictory to the main assumption of 3D printing, personalization, it is important for any business to avoid collapse (67). Many good ideas will never see their routine application. Achieving scalability in 3D printing, especially in sectors such as medicine can be a complex process that requires interdisciplinary cooperation (30). Several strategies can be considered to effectively scale 3D printing technologies. First, continuous development and investment include faster printers, better software, more durable and versatile materials, and more precise printing techniques. One possible strategy is to introduce high-precision 3D printing (68). This method, which uses a multiphoton process, has become a tool for efficiently prototyping miniaturized designs for products in photonics and medical packaging. It overcomes limitations in size, shape, and material class. This advanced method significantly increases fabrication speed, allowing to produce high-quality microlenses in seconds per lens. This paves the way for high throughput and industrial scalability. Simultaneously, it is necessary to constantly reduce costs for the widespread adoption of 3D printers and materials. To achieve scalability of 3D printing in oncology, one can increase printer production, develop cost-effective materials, and improve printing process efficiency. Other strategies to consider include maintaining quality control, integrating 3D printing into existing supply chains, expanding educational programs for a skilled workforce, fostering collaborations and partnerships across sectors, and ensuring regulatory compliance. In addition, while 3D-printing custom-made complex systems or implants should only be done by specialized manufacturers, 3D printing of simple thermoplastic or gel models, such as boluses for radiotherapy, can be done in hospitals.

Regulatory issues

Angela Daly’s detailed study shows that 3D printing is regulated, although it might seem otherwise (69). This regulation includes a mix of legal rules and standards that vary from country to country. These include technical standards, rules for medical products, and laws about intellectual property (IP)—things like copyright, patents, and protecting business secrets. Apart from these specific rules, general legal ideas, like being responsible for causing harm (tort) or breaking the law (criminal liability), also apply in certain cases. The regulatory setup for 3D printing includes both clear legal rules and other forms of control like technology standards. In medical uses of 3D printing, ethical issues are also important (70). The main legal areas focused on 3D printing in medicine are IP laws and special rules for medical products. But, broader legal concepts, such as regulations regarding unauthorized creation of items or being legally responsible for accidents or harm, are relevant too. One of the big challenges with 3D printing is that it changes how things are usually made (71). People can make things at home or in small workshops, which can bypass the usual ways of manufacturing. This leads to questions and uncertainties about how well current IP laws and medical rules fit with 3D printing. Even with these challenges, it’s clear that the existing legal systems can be applied to 3D printing, just like they are to other new technologies. This review doesn’t go into all the details of these rules and challenges, but it’s important to know that these issues could make using 3D printing more complicated, especially in oncology.

Standardization

Standardization is directly related to the two other factors, scalability, and regulations. It is also necessary for ensuring safety, efficacy, and quality in the production of medical devices and implants using 3D printing (72). It becomes increasingly important to establish uniform definitions, protocols and materials (73,74). Material standards require biocompatible, safe, and mechanically suitable materials for patient use. Equally important is the standardized manufacturing processes that ensure consistent quality (75). This includes everything from design to the actual printing and post-processing of medical items. It involves rigorous measures to ensure that each product meets the required specifications, including sterility, mechanical strength, and durability tests. Design standards also play a role, particularly for custom implants or devices, ensuring anatomical correctness and functional integrity. The next important issue is quality control (76). Meeting regulatory requirements with standards set by bodies such as the Food and Drug Administration or the European Medicines Agency is obligatory for the approval of 3D-printed medical items. Clinical validation of 3D-printed medical products through testing and clinical trials is also a part of standardization, confirming the safety and effectiveness of these products for patient use (77). Probably, it is currently the weakest point in spreading the 3D printing technique in the oncology field. Finally, ethical considerations should not be forgotten, especially when printing with biological materials or creating custom implants are involved. This includes managing patient consent and data privacy issues (78).

Comments

In this narrative review, we have provided a broad overview related to the utilization of conventional 3D printing technology in modern oncology, shown wide areas of application and novel fields, and summarized the chances and limitations of the most important aspects of 3D printing. The information presented in this review relies primarily on a combination of literature exploration and the authors’ research expertise. 3D printing has great potential in oncology as it makes this field highly personalized and opens new possibilities. However, it is essential to acknowledge certain limitations associated with this narrative review. Firstly, it may be susceptible to publication bias, particularly within the research and development domain, where negative findings are often underreported, leading to an overrepresentation of positive outcomes. Furthermore, the level of generated evidence from most published studies concerning 3D printing in oncology remains low. Third, except for custom-made prostheses, none of the described solutions have been widely introduced into clinical practice. Lastly, given the narrative nature of this review, there is a potential for the authors to introduce selection biases both during their literature search and their interpretation of the findings from the studies included. Further research on this topic is warranted, particularly regarding the dissemination of findings that may have produced unfavorable results.

Conclusions

In conclusion, 3D printing has become a valuable tool in oncology by improving diagnostics, treatment strategies, therapeutic development, and patient engagement. However, this technology is still considered experimental and is primarily used in case-based scenarios rather than as a routine approach. Although there has been a steady increase in the volume of literature on 3D printing, the focus has mainly been on pre-clinical exploration or case reports. Clinical studies, which are limited in sample size, are available but scarce. Therefore, there is a pressing need for more extensive investigations that delineate the clinical utilization and assessment of developed 3D printing technologies within larger cohorts to comprehensively ascertain their efficacy and application in real-world clinical scenarios.

Acknowledgments

Funding: This work was supported by The National Centre for Research and Development “LIDER” program, project number (LIDER/22/0111/L-12/20/NCBR/2021).

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://cco.amegroups.com/article/view/10.21037/cco-24-4/rc

Peer Review File: Available at https://cco.amegroups.com/article/view/10.21037/cco-24-4/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-24-4/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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