1. Introduction
Cancer patients frequently present for radiotherapy with titanium implants, with head and neck cases being particularly challenging to plan. The patient computer tomography (CT) and cone beam computer tomography (CBCT) images were created using kV x-rays which show image artefacts and may obscure critical information at the bone-implant interface. The patient treatment dose is perturbed by the titanium, creating low and high dose regions, which are known to be poorly predicted by treatment planning systems [
1- Nevelsky A.
- Borzov E.
- Daniel S.
- Bar-Deroma R.
Perturbation effects of the carbon fiber-PEEK screws on radiotherapy dose distribution.
,
2- Akyol O.
- Dirican B.
- Toklu T.
- Eren H.
- Olgar T.
Investigating the effect of dental implant materials with different densities on radiotherapy dose distribution using Monte-Carlo simulation and pencil beam convolution algorithm.
]. The practical implication of a high dose region in the vicinity of the implant could compromise healing and regeneration of bone, with the ultimate risk of infection and implant failure, requiring major surgical revision, especially in the case of the spinal cord should re-irradiation be required. Conversely, any cancer cells in a low dose region will be under-treated, potentially leading to a recurrence [
3Eaton DJ, Byrne JP, Cosgrove VP, Thomas SJ. Unintended doses in radiotherapy-over, under and outside? Br J Radiol 2018;91:20170863-. https://doi.org/10.1259/bjr.20170863.
,
4Lessons Learnt from Past Incidents and Accidents in Radiation Oncology.
].
Bone prosthetic implants have typically been constructed as solid metal objects. In an attempt to reduce the effective stiffness of the implant, reduce stress shielding and to allow for increased osseointegration, customised 3D printed porous structures have become available [
5- Simon U.
- Augat P.
- Ignatius A.
- Claes L.
Influence of the stiffness of bone defect implants on the mechanical conditions at the interface—a finite element analysis with contact.
,
6- Li J.
- Jansen J.A.
- Walboomers X.F.
- van den Beucken J.J.J.P.
Mechanical aspects of dental implants and osseointegration: A narrative review.
]. Conversely, in a radiation field, it is not immediately obvious how the titanium scaffold might perturb the dose inside the scaffold, affecting the regenerating tissue inside the pores, which will in turn affect the success of the implant.
For simple beam arrangements and implant designs, the dose distribution has been reported. Nevelsky, Akyol and Müller provided evidence for significant dose enhancements (∼20%) on the entrance interface of a titanium object and a large dose reduction (∼20%) on the exit interface [
1- Nevelsky A.
- Borzov E.
- Daniel S.
- Bar-Deroma R.
Perturbation effects of the carbon fiber-PEEK screws on radiotherapy dose distribution.
,
2- Akyol O.
- Dirican B.
- Toklu T.
- Eren H.
- Olgar T.
Investigating the effect of dental implant materials with different densities on radiotherapy dose distribution using Monte-Carlo simulation and pencil beam convolution algorithm.
,
7- Müller B.S.
- Ryang Y.-M.
- Oechsner M.
- Düsberg M.
- Meyer B.
- Combs S.E.
- et al.
The dosimetric impact of stabilizing spinal implants in radiotherapy treatment planning with protons and photons: standard titanium alloy vs. radiolucent carbon-fiber-reinforced PEEK systems.
]. For a cylindrical meshed metallic stent, with a lower effective density than the shell stent of identical volume, Li et al., found that the lower effective density reduced the expected perturbation of both a 6MV and a 15MV photon beam [
[8]- Li X.A.
- Chibani O.
- Greenwald B.
- Suntharalingam M.
Radiotherapy dose perturbation of metallic esophageal stents.
], indicating that the porosity of the metal object is a significant factor affecting the dose distribution. While studies using Monte Carlo (MC) simulation and experimental measurement have determined the dose perturbation caused by metal structures [
[9]- Reft C.
- Alecu R.
- Das I.J.
- Gerbi B.J.
- Keall P.
- Lief E.
- et al.
Dosimetric considerations for patients with HIP prostheses undergoing pelvic irradiation. Report of the AAPM Radiation Therapy Committee Task Group 63.
], they have not reported on the dose within the pores of a bone implant scaffold and along the interfaces of the material.
MC simulation is ideally suited to this task, because of the difficulty in taking measurements with sufficient spatial resolution within the fine pores of a scaffold implant. While film dosimetry provides high spatial resolution, the porous implant designs typically have complex geometries with pore diameters in the order of 0.5 mm or less, which makes it difficult if not impossible to position the film. However, film dosimetry has been successfully used to measure the dose distribution at the implant tissue interface [
2- Akyol O.
- Dirican B.
- Toklu T.
- Eren H.
- Olgar T.
Investigating the effect of dental implant materials with different densities on radiotherapy dose distribution using Monte-Carlo simulation and pencil beam convolution algorithm.
,
9- Reft C.
- Alecu R.
- Das I.J.
- Gerbi B.J.
- Keall P.
- Lief E.
- et al.
Dosimetric considerations for patients with HIP prostheses undergoing pelvic irradiation. Report of the AAPM Radiation Therapy Committee Task Group 63.
]. MC also gives the option to understand the fundamental physics explaining the dose distribution by differentiating between particles of different origins and trajectories.
Here a simulation study was presented for three implant designs. The traditional titanium and an emerging implant material, poly-ether-ether-ketone, (PEEK) were used as implant materials. Thermoplastics of the poly-aryl-ether-ketone (PAEK) family, including PEEK, are emerging as an alternative, because they provide a better material property match to bone and are reported to cause minimal dose perturbation [
[10]- Ramakrishna S.
- Mayer J.
- Wintermantel E.
- Leong K.W.
Biomedical applications of polymer-composite materials: a review.
]. Due to their lower effective atomic number and density, these carbon based plastics exhibit almost tissue-equivalent radiation scattering properties between the 10 keV and 10 MeV range of energies (with
and
and reduced dose perturbation relative to titanium [
11- Wu S.
- Liu X.
- Hu T.
- Chu P.K.
- Ho J.P.Y.
- Chan Y.L.
- et al.
A Biomimetic Hierarchical Scaffold: Natural Growth of Nanotitanates on Three-Dimensional Microporous Ti-Based Metals.
,
12- Mavrogenis A.
- Dimitriou R.
- Parvizi J.
- Babis G.
Biology of implant osseointegration.
]. A reference to the attenuation coefficients as a function of photon energy are shown in the
Supplementary material A (Figure A). PEEK is of particular interest, as it is biocompatible, has a higher elastic modulus than most polymers (3–4 GPa), lying between the modulus for cancellous (1 GPa) and trabecular (14 GPa) bone [
13- Najeeb S.
- Zafar M.S.
- Khurshid Z.
- Siddiqui F.
Applications of polyetheretherketone (PEEK) in oral implantology and prosthodontics.
,
14- Panayotov I.V.
- Orti V.
- Cuisinier F.
- Yachouh J.
Polyetheretherketone (PEEK) for medical applications.
,
15- Schwitalla A.
- Müller W.-D.
PEEK Dental Implants: A Review of the Literature.
,
16- Trindade R.
- Albrektsson T.
- Galli S.
- Prgomet Z.
- Tengvall P.
- Wennerberg A.
Bone Immune Response to Materials, Part I: Titanium, PEEK and Copper in Comparison to Sham at 10 Days in Rabbit Tibia.
,
17- Sandler J.
- Werner P.
- Shaffer M.S.P.
- Demchuk V.
- Altstädt V.
- Windle A.H.
Carbon-nanofibre-reinforced poly(ether ether ketone) composites.
,
18- Han X.
- Yang D.
- Yang C.
- Spintzyk S.
- Scheideler L.
- Li P.
- et al.
Carbon Fiber Reinforced PEEK Composites Based on 3D-Printing Technology for Orthopedic and Dental Applications.
]. PEEK can also be 3D printed, enabling implants to be quickly customised for individual patients and manufactured with porosity to facilitate osseointegration.
Our aim is to describe the dose distribution for these structures, two of which are currently used in head and neck orthopaedic surgery. The novelty of this study was that it enabled us to determine the dose distribution within the micro-structures of complex geometries rather than just on the external interfaces and provides insight on specific features of the implant which can reduce the perturbations to osseointegrating cells. The second aspect of this study provided a measure of risk to the osseointegrating cells in and around implants constructed from titanium and PEEK.
3. Results
Fig. 2c shows that on the proximal tissue-implant interface, there was a 15% increase in dose when the implant material is titanium and <5% when it was PEEK. At the exit interface, the reduction in dose was of the order of 10% for titanium and an enhancement of 5% for the PEEK implant. In
Fig. 2d, where only the dose to the pores of the implant was shown, a dose maximum was observed for the pore of the titanium ring, however, it was not a sharp gradient as seen at the entrance and exit interface, but a broader peak with a significant, albeit reduced enhancement of 12%. The maxima also occurred at a slightly deeper position within the pore, rather than at the implant tissue interface. For the PEEK pores, there was a slight reduction in dose before the proximal interface of 2%, however within the pore, the perturbations were minimal. The dose profile in
Fig. 2e shows that there were sudden changes in dose depending on the relative location of the pores in the titanium/PEEK rings. For the titanium rings, there was a sharp increase in dose between 16 and 18% at the implant-pore boundary of the ring. This was generally followed by a reduction in dose to a local minimum within the pore, ranging from 8 to 12% and subsequently other maxima towards the pore to implant edge. The dose in the actual titanium implant remained close to that of water at the proximal interface. In comparison, the dose profile corresponding to the PEEK implant had a similar shape to the titanium but was shifted down by 10%. Within the pores of the PEEK rings, the dose remained within 2–5 % of the dose to water. The local minima in dose that was observed in the pore of the titanium implant were not present within the PEEK. The dose within the bulk of the PEEK implant was between 5 and 10% lower than the dose to water.
The characteristic dose enhancements and reductions from titanium are shown in
Fig. 3,
Fig. 4 at the entrance and exit interfaces (c) and as previously shown in
Fig. 2, demonstrate sharp changes in dose at most cavity-implant boundaries.
Fig. 3c, shows that the dose distribution behaves somewhat like a sawtooth function and varied between sharp maxima and broad minima. For the titanium implant, the dose reached a maximum at 18% at the proximal interface, unlike for PEEK where the dose remained unperturbed compared to water. The reduction in dose compared to water shown in
Fig. 3c refers to the dose within the PEEK implant and was a small reduction (<5%).
Fig. 3d shows the sawtooth behaviour seen in
Fig. 3c. The maximum dose occurs at the point where the layers alternate in orientation.
The perturbations of dose within the pores of the PEEK implant were small (<2%), whereas for titanium the dose distribution exhibited a sawtooth behaviour. For each set of alternating layers in titanium, the dose can increase or decrease by 2–7% and was also depth dependent.
Fig. 3e depicts the dose profile for the “woodpile” structure and shows a large increase in dose within the first layer for the titanium structure of 18% and a minimum corresponding to a reduction of −7% towards the scaffold boundaries and −2% within the structure. The dose profile for PEEK shows similar behaviour with the dose maxima were observed to remain within 1% of the dose to water and the dose minima correspond to reductions of −7%.
Fig. 4 shows dose distributions for the facial mesh structure. The dose enhancement and reduction arising from the titanium were similar in magnitude to those calculated previously, with similarly shaped dose distributions, most notably for the depth dose curves in
Fig. 4c and d. A significant enhancement of dose (>15%) was observed within the implants, despite the very small thickness (<0.5 mm).
4. Discussion
In this study, it was found that the geometry of the implant can significantly impact the dose distributions within the micro-structures. While these effects were more prominent for titanium, they were still present for PEEK implants. The dose profiles of
Fig. 2,
Fig. 3,
Fig. 4,
Fig. 5,
Fig. 6 further demonstrate the sudden dose gradients which occurred in the titanium implant, located at the pore-titanium interface. Previous studies, which have predominantly focused on the dose to the exterior interfaces as measured by Akyol, Nevelsky and Müller [
1- Nevelsky A.
- Borzov E.
- Daniel S.
- Bar-Deroma R.
Perturbation effects of the carbon fiber-PEEK screws on radiotherapy dose distribution.
,
2- Akyol O.
- Dirican B.
- Toklu T.
- Eren H.
- Olgar T.
Investigating the effect of dental implant materials with different densities on radiotherapy dose distribution using Monte-Carlo simulation and pencil beam convolution algorithm.
,
7- Müller B.S.
- Ryang Y.-M.
- Oechsner M.
- Düsberg M.
- Meyer B.
- Combs S.E.
- et al.
The dosimetric impact of stabilizing spinal implants in radiotherapy treatment planning with protons and photons: standard titanium alloy vs. radiolucent carbon-fiber-reinforced PEEK systems.
], show agreement with the results of this paper. The dose perturbations at the proximal and exit interface that arose from titanium were found to vary between 15 and 20% with discrepancies arising from geometric and irradiation factors. However, the limitation of these studies was that they only focused on the proximal and exit interfaces of the implant and used simple geometric arrangements. By concentrating on the internal geometries of the implant, the steep dose gradients arising between the interfaces of tissue and titanium were identified. The increase in dose at the titanium-tissue interface arises from an increase in secondary electrons which deposit more of their energy close to the boundary of the implant. This was especially pronounced for the ringed implant in
Fig. 2, where the higher dose is present as a red region along the exterior boundary, along the inner circumference of the ring and as sharp dose gradients in the profile in
Fig. 2e. When these implants were constructed from PEEK, there was still a dose gradient with the maximum dose remaining close to water. For greater visibility, the high and low dose regions within the pores of the ringed scaffold are shown in supplementary E. However, the significant dose reduction is only observed within the physical implant of PEEK and not in the tissue. These doses should be of no concern to the regenerating tissue.
For the woodpile structure, the unique feature lies in the sawtooth behaviour in the depth dose curves as shown in
Fig. 3c-d, for both PEEK and titanium implants. In both instances, the sawtooth arises from the alternating forward and backwards scatter of secondaries as the primary photon beam alternates between layers. This region of increased dose was also shown in
Fig. 3a where the increased dose from the back scatter can be seen as a set of horizontal lines, partially covered from the solid titanium layer above. For the woodpile implant constructed from titanium, such a microstructure possesses high dose gradients from both backscattered and laterally scattered electrons enveloping the internal surfaces resulting in high doses administered to regenerating cells. For the PEEK woodpile implant, while the sawtooth behaviour was present, the maximum doses were within a safe margin of that to water.
The dose within the meshed implant displayed similar behaviour to the other implants with the characteristic increase and decrease in dose at the proximal and exit interfaces. Within the structure of the implant, the pores were still subjected to high doses (10% increase) even with the small thickness of the implant. Given the small size of the pores, the laterally scattered secondaries from the titanium contribute greatly to the marked dose enhancement. Compared to the other implants, there is a greater degree of statistical variance due to the reduced sample size, by the application of the binary mask. The close proximity and spacing of the pores result in regions of sharp dose gradients, which are masked when computing the surface integral over the whole surface.
For all cases the radiation dose was observed to be highest in the tissue directly above the implant entrance interface for titanium and within the pores for the first half of the scaffold implant, closer to the entrance interface as shown in
Fig. 2d. The regenerating bone on these surfaces are therefore at the highest risk of adverse radiation effects. In contrast, when the same scaffold was made from PEEK, the dose to the pores throughout the scaffold implant was closer to that expected in water and in the absence of an implant. Furthermore, due to the water-equivalent attenuation properties of PEEK and relatively homogenous dose distribution, imaging will not incur artifacts and commercial treatment planning is likely to be more accurate than for titanium implants [
[2]- Akyol O.
- Dirican B.
- Toklu T.
- Eren H.
- Olgar T.
Investigating the effect of dental implant materials with different densities on radiotherapy dose distribution using Monte-Carlo simulation and pencil beam convolution algorithm.
]. For patients who require radiotherapy and implant as a result of surgery, it is critical that radiotherapy is started as soon as the bone has sufficiently healed [
[9]- Reft C.
- Alecu R.
- Das I.J.
- Gerbi B.J.
- Keall P.
- Lief E.
- et al.
Dosimetric considerations for patients with HIP prostheses undergoing pelvic irradiation. Report of the AAPM Radiation Therapy Committee Task Group 63.
].
The survival fraction for the SAOS-2 cell line, calculated using the linear quadratic model as illustrated in the method and the curves plotted in
Fig. 6. For an administered dose of 2 Gy to the implant surface, the equivalent dose to the cells within a PEEK scaffold was approximately 2 Gy, however for the titanium implant, the equivalent dose was 2.34 Gy, which translates to a reduction in survival of 7.2%. Alternatively, for the weakly perturbing PEEK implant, the survival fraction is unchanged. An error of 5% in dose delivery is considered an incident in radiotherapy. For a given dose enhancement of approximately 15%, the survival is reduced by a further 7.2%, which can impact outcomes such as tumor control probability (TCP) and normal tissue toxicity. Given the inhomogenous dose distributions within the volume of the titanium implant, there will be regions where tissue toxicity is high and tumor control is low. For implants which are osseointegrating, it is important to consider the change in survival fraction in order to avoid subsequent potential implant failure, osseonecrosis and even reversal surgery [
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Accuracy of secondary maxillofacial reconstruction with prefabricated fibula grafts using 3D planning and guided reconstruction.
].
These findings are important since there are claims that radiotherapy patients are overrepresented in the group of patients requiring surgical reversal of implants, although it is difficult to find conclusive data in the literature since patients requiring substantial implants are also likely to have more advanced cancers and do less well. The results presented here are evidence of increased dose to the regenerating cells about a titanium implant and within the pores of a scaffold implant design, of a magnitude likely to have a significant biological effect. Furthermore, any cancer cells populating shielded surfaces within the titanium implant are at a risk of being underdosed, potentially compromising the radiotherapy treatment. The same implant constructed from PEEK will not exhibit this dose perturbation, avoiding all the additional steps that have been incorporated into radiotherapy to correct for a titanium object in the beam.
Data availability statement for this work
All data is available upon request from the corresponding author. Email at gkat2146@uni.sydney.edu.au.
Article info
Publication history
Published online: May 21, 2022
Accepted:
April 27,
2022
Received in revised form:
April 26,
2022
Received:
September 29,
2021
Copyright
© 2022 The Authors. Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.