Brachytherapy is a type of internal radiation therapy that is used to treat cervical cancer. It involves the application of a radioactive source in close proximity to the tumour. This can be done either by directly inserting the source into (or close to) the tumour using interstitial hollow needles, or by loading the source into an intracavitary applicator that is placed in the vaginal cavity. Standard applicator types may lead to suboptimal radioactive source placement, possibly resulting in underexposure of target volumes and overexposure of organs at risk, especially in advanced cancers. Customised applicators and optimised needle channels based on the patient's MRI/CT data could enhance conformity between target volumes and prescribed isodose. Hence, the goal of this project was to develop and validate a design for a 3D-printed brachytherapy applicator which geometry is based on the patient's vaginal cavity and which features optimised interstitial needle channels based on the patient's anatomy and tumour location. Various analyses have been conducted which have led to the establishment of a list of requirements for the applicator design. Based on this list of requirements, two conceptual designs have been presented: one fully 3D-printed design and one design that is clicked on the Geneva ovoid tubes. Through the creation of prototypes, these conceptual designs have been refined into two final designs which were manufactured in PA12 using selective laser sintering. The dose attenuation properties of PA12 were evaluated and compared to that of water. Furthermore, the potential needle positions within the proximal end of both designs have been analysed. For both designs, a final prototype based on a phantom's vaginal cavity geometry has been created. The usability of these prototypes has been tested by three radiotherapist-oncologists, who also provided feedback on the designs. Upon analysing their feedback and the outcomes of the other evaluations, recommendations for future designs have been formulated. The conducted dosimetry experiment yielded a maximum difference of 0.8% between the average percent dose depth curves of water and PA12, which can be considered a water-equivalent response. This allows PA12 to be used as the material for the applicator. The result of the potential needle position analysis suggest that the first design provides more space for personalised needle channels in the top of the applicator compared to the second design. The three radiotherapist-oncologists validated the usability of both final prototypes. Two designs of a patient-tailored 3D-printed brachytherapy applicator containing optimised interstitial needle channels based on the patient's anatomy and tumour location have been presented, produced and validated. Based on the outcomes of the conducted evaluations, there can be concluded that the first concept shows the most promise to be used as a design for a patient-tailored 3D printed brachytherapy applicator. However, to ensure the proper functioning of the working principles, further development is required. If the recommended improvements are implemented, the design has the potential to be used as applicator in the treatment of cervical cancer.

Brachytherapy (BT) is an essential component in the curative treatment of cervical cancer. With commercial BT implant devices, called applicators, the radioactive sources can only be positioned in fixed intracavitary channels or in a fixed array of interstitial needles. Patient-tailored BT applicators containing individualised needle channels have the potential to enhance the delivered dose to the tumour while minimising tissue damage of the organs-at-risk (OARs). During the optimisation process of the needle channels, several constraints must be considered. The needle paths in the applicator are curvature-constrained, and the needles should not collide with each other or potentially perforate OARs. Furthermore, clinicians can impose additional constraints based on their preferences. Existing approaches in literature for optimising needle placement in patient-tailored BT applicators for cervical cancer treatment have employed various algorithms. However, these approaches often rely on significant approximations. For instance, some assume that all needles are inserted in parallel or focus solely on optimising geometric coverage as opposed to optimising the dose distribution. Moreover, the few methods in literature incorporating needle path planning in the optimisation process require manually pre-specified dwell positions. To improve dose conformity and minimise the dependence on the clinician’s expertise and time, there is a need for the development of software that optimises the needle placement and paths without resorting to these severe assumptions. This work proposes and validates a novel three-stage approach to generate a patient-tailored applicator configuration without resorting to fully geometric optimisation. First, a high-potential set of dwell positions is obtained by running a modified version of the dwell time optimisation software BiCycle (Erasmus Medical Centre, Rotterdam, the Netherlands) on a grid of possible dwell positions. This results in a resolution optimal treatment plan when not considering geometry and applicator constraints. The positions with the highest dwell times according to the resolution optimal treatment plan are selected in the high-potential set. Next, a weighted set cover problem is used iteratively to find a combination of feasible needle segments to cover all dwell points in the high-potential set at a minimum distance. Lastly, needle channels to steer the needle to these segments are simultaneously optimised to be of minimum curvature and mutually collision-free. To evaluate our approach, a virtual configuration and planning study was performed in a cohort of 22 locally advanced cervical cancer patients previously treated with the Venezia (Elekta AB, Stockholm, Sweden). The resulting treatment plans of the clinically used configuration were compared with the resulting treatment plans of the proposed patient-tailored and grid configurations on clinically relevant dose-volume histogram parameters, dwell times, conformity index and number of interstitial needles. Statistical significance is assessed with Wilcoxon signed-rank tests. The proposed workflow was demonstrated to be feasible, and for every patient, a configuration could be generated in clinically acceptable time. All treatment plans generated for the grid configuration, the patient-tailored configuration and the clinical configuration were acceptable following the EMBRACE ll aims. Planning aims, however, were met more frequently with both the grid configurations (145/151 instances) and the patient-tailored configurations (137/151 instances) in comparison with the clinically used configurations (119/151 instances). The treatment plans generated with the grid configurations obtained significantly better (p < 0.01) median normalised CTVIR D98 dose with respect to the clinical configurations. Moreover, with the grid configurations, there was a significant improvement in median normalised D2cm3 dose for the bladder (p < 0.001), rectum (p < 0.001), sigmoid (p < 0.01) and bowel (p < 0.001) compared to treatment plans obtained with the clinical configurations. The treatment plans generated with the patient-tailored configurations obtained comparable target doses, but median normalised D2cm3 doses for the bladder (p < 0.001), rectum (p < 0.01) and bowel (p < 0.01) were significantly better for the patient-tailored configurations compared to the clinical configurations. The proposed automated patient-tailored BT source channel configuration planning method was demonstrated to be clinically feasible. The resulting treatment plans have dosimetric advantages over the treatment plans generated with the clinical applicator configuration. Improvements to the intracavitary dwell position placement are expected to further increase dose conformity.