A multiwell applicator for conformal brachytherapy of superficial skin tumors: A simulation study

Brachytherapy of thin skin tumors using beta particles can protect underlying sensitive structures such as the bone because of the rapid dose falloff of this type of radiation in tissue. The current work describes a skin brachytherapy applicator, based on beta radiation, that can provide the needed cell‐killing radiation dose matched to the shape of individual skin tumors.


| INTRODUC TI ON
Nonmelanoma skin cancer (NMSC) is the most commonly diagnosed malignancy in humans. In the United States alone, more than 3 million NMSCs are diagnosed annually. 1 The primary treatment for skin cancer is surgery, which is the physical removal of the lesion from the skin tissue, including safety margins. It can be done either by a standard excision or by the Mohs surgery whereby the skin tumor is removed in a layer-by-layer fashion. 2 Since surgery exhibits an excellent control rate of the skin tumor, it is considered as the standard of care for skin cancer patients. 3 However, this procedure cannot be indicated for all patients, primarily because of post-surgery complications.
In such cases where surgery is not recommended to the skin cancer patients, radiation therapy techniques are used as an efficient alternative. 4 One of the commonly used radiation therapy techniques in dermatology practices is brachytherapy, in which a source of activity is placed in close contact with the target to deposit the prescribed dose in its volume. Brachytherapy of skin tumors was first reported in 1899 after the discovery of radium. 5  with a half-value layer of 3 mm in the lead. 6 Since these applicators have fixed geometries, it is not possible to shape the dose distribution based on the tumor shape on the skin surface.
To address this need, we describe in this paper a new surface applicator for superficial skin tumors that allows a radiation dose delivery based on the tumor shape on the skin surface. We suggest a 3D-printed multiwell brachytherapy applicator subsequently filled with a radioactive gel to create the source of radiation based on the 2D shape of the skin tumor. The radioisotope of choice for creating a radioactive gel is a beta-emitting isotope. Because of their shortrange in tissue (typically <10 mm), beta particles can suitably be used for treating thin skin lesions of around 3-4 mm thickness. It can be specifically advantageous when the thin lesion is located right on top of bony structures or very close to the eye.
In the current work, the proposed applicator and the workflow of its application to a skin tumor have been illustrated. The capability of the applicator to conform the dose distribution was also studied using Monte Carlo Simulation methods.

| Applicator design and fabrication
The applicator was designed using a Computer-Aided Design (CAD) program (SolidWorks 2018, Dassault Systèmes) with a body dimension of (25 × 35 × 10) mm 3 . Then, a number of 63 wells of 2 × 2 × 1 mm 3 were cut-extruded in a 7 × 9 array in one face of it. The wells were separated by 1-mm thick walls. The CAD models were then imported into the Slic3r G-code generator to convert it to the printing instruction files. Then, the applicator and its template were fabricated using a 3D printer (Form 2, Formlabs).
The printed models of the applicator and its template are given in

| Implementation of the applicator
The current applicator can produce a planar source of beta radiation with an effective area of about (20 × 25) mm 2 . However, for larger tumors, the size of the applicator and its template can be enlarged accordingly. The treatment workflow for skin brachytherapy using the multiwell applicator is given in Figure 2. The process starts with the delineation of the skin tumor and its safety margin. Then, a grid is drawn on the treatment area to determine the pattern based on which wells of the applicator will contain the beta-emitting gel. The grid also provides a reference for accurately fixing the template on the skin. To prepare the applicator to apply to the patient, the desired wells of the applicator are filled with beta-emitting gel and allowed to harden. A detailed description of the radioactive gel can be found in our previous work. 7 In the end, the applicator is placed into the template, which was previously fixed on the site of the grid.

| Monte Carlo simulation
For dosimetric studies, the 2D dose profile and the percent depth dose (PDD) from the applicator were determined using Monte Carlo methods. We simulated the applicator and the skin phantom, then filled the wells of the applicator with beta-emitting gel and calculated the absorbed dose in skin issue. First, the capability of the applicator for conforming the dose to a skin tumor of irregular shape was evaluated. To this end, a random shape of radiation source was created by filling specific wells of the applicator with beta-emitting gel. Then, the corresponding 2D dose profile was simulated at the shallow depth of 0.06 mm. After that, all wells of the applicator were filled with a radioactive source to create a uniform distribution of radiation source with a rectangular shape.
Then, the dose profiles on the transverse plane perpendicular to the applicator were calculated. It was calculated for five depths

| RE SULTS
The digital model of the applicator with an arbitrary shape of the Y-90 source distribution and the corresponding dose profile at the shallow depth is presented in Figure 3. As shown, the 2D dose profile F I G U R E 2 The workflow of implementation of the multiwell skin brachytherapy applicator; delineation of the treatment area (1), grid-based multiwell array of treatment area (2), mirror image of the array (3), filling the wells of the applicator with beta-emitting gel and based on the pattern of the grid (4), fixation of the template on the tumor site (5), and placement of the applicator into its template (6)  In Figure 4, the calculated transverse dose profile (TDP) at different depths from this applicator, as well as the PDD, is presented.
Comparing the dose profile at different depths shows that the effect of the walls between wells on the dose nonhomogeneity decreases as we go deeper into the skin layers. In the PDD curve, the pattern of dose deposition clearly shows how the significant part of beta radiation is absorbed within the first layers of the skin tissue. Based on this curve, the beta radiation dose from the applicator beyond the 4 mm depth drops to less than 10% of the shallow dose. The PPD becomes almost zero beyond the depth of 7 mm.

| D ISCUSS I ON
In the current study, a new multiwell skin brachytherapy applicator with beta-emitting sources has been introduced. Results of the simulation study showed the dose distribution from this applicator can be conformed to the shape of a tumor in the skin entry by adjusting the pattern of the source distribution in the applicator. Because of the rapid dose falloff of beta radiation in tissue, the use of this applicator can be advantageous when a skin lesion is located right on top of a sensitive structure such as bone or very close to the eye.
Beta-emitting isotopes have successfully been used in several nuclear medicine and brachytherapy practices. A traditional and well-established procedure using a beta-emitting isotope is the treating of hyperthyroidism using Iodine-131 (I-131) radioisotope. 10 Another promising application of beta radiation has been the treatment of inoperable liver tumors using Y-90 microspheres. 11 Intracoronary radiation therapy using Phosphorus-32 (P-32) stent for the prevention of restenosis is another therapeutic use of beta-emitting isotopes. 12 Radiation therapy of eye tumors using a hand-held Strontium-90 (Sr-90) applicator or eye brachytherapy plaques containing Ruthenium-106 (Ru-106) is another successful use of beta-emitting isotopes to manage disease. 13 The use of beta-emitting isotopes for brachytherapy of skin tumors is not an established method. However, there are several studies that assessed and showed its effectiveness in treating thin skin malignancies. [14][15][16][17] There are also some works aiming at developing methods for creating therapeutic models based on beta-emitting isotopes for skin cancer. [18][19][20][21][22][23] They are mainly focused on creating planar sources of beta radiation applicable to skin tumors, with very few studies focusing on conforming the dose to the skin tumor shape. 7,24 The current multiwell brachytherapy applicator presents a simple method to conform the dose of beta radiation to the superficial skin tumors. As the applicator is fabricated using 3D printing technology and with plastic materials, the manufacturing process of the applicator body is quick and inexpensive. In addition to that, once the radioactive source is provided, the radioactive gel can be prepared, added, and hardened in the applicator in <1 hour. The applicator body, with a wall thickness of about 5 mm, can absorb a significant part of the beta radiation in unwanted directions and provide shielding for that.
Unlike the conventional skin brachytherapy applicators, the proposed applicator and its template can be fixed on the patient's skin without a supporting arm. A direct result of the in-situ fixation of the applicator will be the reduced setup error during the treatment delivery. A comfortable situation for the patient, where they do not have to be immobilized, is another feature of this light-weight applicator.
Besides the features that this applicator may offer for skin cancer patients, its limitations should not be ignored. Firstly, this applicator is only suitable for thin skin tumors of around 3-4 mm in thickness. In addition, as the radiation source of this applicator is unsealed, special radiation safety considerations are needed to be satisfied when handling the applicator.

| CON CLUS ION
In the current work, a multiwell skin brachytherapy applicator that can be loaded with a beta-emitting isotope, such as Y-90, was described. A dosimetry study using Monte Carlo simulation methods showed the capability of this skin brachytherapy applicator in conforming the beta radiation dose to the tumor shape on the skin surface. The beta-emitting source used in this applicator not only can lead to sparing sensitive structures beneath the tumor but makes the shielding of the source easier, compared with the gamma-emitting sources.

ACK N OWLED G M ENT
This research was financially supported by the Federal Ministry of Education and Research (BMBF) in the context of the "INKA" project (Grand Number 03IPT7100X).

CO N FLI C T O F I NTE R E S T
The authors report no conflict of interest.