With an estimated 570.000 new cases and 311.000 cancer related deaths in 2018, cervical cancer is the fourth most common cause of cancer and cancer related deaths worldwide [1]. Brachytherapy (BT) is a key component in the curative treatment of cervical cancer [2]. In addition, gynaecological BT is used for the treatment of recurrent cancer in the vagina and as adjuvant therapy to reduce post-hysterectomy vaginal recurrences. Brachytherapy delivers radiotherapy locally, inside or near the tumour. This is achieved by guiding radioactive sources through channels in an applicator in the vaginal or uterine cavity (intracavitary applicators) or directly into tumour containing tissue (interstitial needles). Treatment planning of source dwell times and positions determines the dose distribution. An optimal BT treatment plan has high conformity, indicating an exact overlap of the target volume and prescribed isodose [3]. High conformity results in optimal target coverage and local tumour control, while minimising dose absorbed by surrounding healthy tissues, i.e. organs at risk (OAR). Personal and societal impact of treatment optimisation is crucial, as 5-year survival rates are at 65% and the majority of women are in their early decades of life [4].
Recently, substantial steps were made to improve radiation conformity, including the introduction of 3D imaging (CT/MRI) and the subsequent adaptation of BT treatment planning to the individual patients’ anatomy, i.e. Image Guided Adaptive Brachytherapy (IGABT). Yet, target coverage and local control remain suboptimal for larger tumours with extensive paravaginal or parametrial involvement (stage IIIA: 71%; IIIB: 75%) [4, 5]. Moreover, 12.5% of women reported substantial urinary toxicity, 25% experienced substantial bowel symptoms, and vaginal morbidity was frequently observed (53% mild, 19% moderate), impacting on (sexual) quality of life [6,7,8,9]. This underlines the importance of BT conformity to reduce toxicity and impact on quality of life.
Currently, commercially available intracavitary applicators are one-size-fits-all products with fixed, rigid shapes and interstitial needle channels have fixed positions and angles. Most used intravaginal applicator shapes include ovoids, ring and cylinder. These shapes have been designed to obtain a historic standard pear formed dose distribution, while the thickness of these applicator parts kept high dose areas within the applicator. The main disadvantages are that these shapes do not align with individual anatomy, especially when this has been altered due to changes by cancer growth. Although the newest applicators have both parallel and oblique running needle channels, their positions and angels are fixed, hampering the ability to optimise the BT dose distribution remains insufficient (Fig. 1). Although target coverage is good in smaller tumours, considerable volumes of healthy tissue often receive an unnecessary dose. For larger tumours, especially those with substantial extensions in the distal parametria or lower (para)vagina, available standard applicators are particularly ill-adapted [10]. Supplementary free-hand or template based interstitial needles are required to improve target coverage. However, image guidance for accurate placement is often limited and conformity is subjected to the available techniques and skills of the Radiation Oncologist.
Recent developments in 3D printing have enabled a novel approach to BT in which applicators are patient-tailored by considering the individual target and healthy tissue volumes. During adjuvant, recurrent and primary BT, this approach can offer advantages for reliable applicator positioning within and between fractionated BT treatments [11], targeting lesions near or behind tissue folds [12], introducing curved needle channels and minimising the number of needles required [13], and enabling proficient treatment for patients with lesions in low-incidence locations, e.g. involving the lower (para)vagina or distal parametrium.
Several groups have developed personalised applicators, but have focussed either on intracavitary applicators, or on guided interstitial needle angles. The best known example of customised applicators is the vaginal mould technique, as described by Magné et al. Applicators were produced in a casting process with cervicovaginal impressions on the basis of alginate liquid pastes [11]. The intracavitary applicators were considered low-cost alternatives with a good patient tolerance. Huang et al. used 3D printed individual templates for needle guidance in head and neck BT, which resulted in an accurate transition from pre-planned to placed needle locations [14]. In various studies, 3D printing techniques have been used to improve the diametrical fit of intracavitary vaginal cylinder applicators [15,16,17]. Sethi et al. evaluated custom-fit cylinders for three patients that could not be treated adequately with commercial applicators [16]. The 3-D printing material used, PC-ISO, was biocompatible (ISO-10993 and USP Class VI) and gamma and EtO sterilisable. Interstitial needles were placed under transrectal ultrasound (TRUS) guidance. Lindegaard et al. developed 3D printed tandem-ring implants with customised needle channel locations [18]. Pre-planning, data processing and production were performed in-house within 3 days. Two studies have reported intracavitary vaginal topography-based prints using computed tomography (CT) data [13, 19]. The applicator developed by Wiebe et al. included curved intracavitary needle channels and consisted of two dove-tail connected parts to facilitate device insertion and removal [19].
To the authors knowledge, this is the first study to produce 3D printed vaginal topography-based applicators from MRI data. The applicators include multi-curved needle channels for both intracavitary and guided interstitial use. The article covers workflow-related aspects on data acquisition, segmented volume post-processing and instrument design, including an analysis of needle channel radius constraints.