ARCHITECT

Background

High dose rate (HDR) brachytherapy (BT) is a key component in the curative treatment of locally advanced cervical cancer. Unlike external beam radiation therapy, which delivers radiation from outside the body, in HDR-BT a small radioactive source is placed directly inside or next to the tumour. This source travels through channels in a device called an applicator, which is inserted into the vagina and uterus, or through needles placed directly into the tumour. HDR-BT is used alongside external radiation to deliver a highly targeted dose to the tumour, while minimizing side effects in nearby organs such as the bladder, rectum, sigmoid colon, and bowel. Realising a high conformity requires dose planning, i.e., determining the dwell locations and times of the radioactive source. Within conventional one-size-fits-all applicators, the source positioning freedom is limited by a fixed set of channels and needle insertion positions. In current clinical practice, avoiding local recurrence remains difficult in patients with larger tumours and (para)vaginal or parametrial involvement (FIGO stage IIIA: 71%; IIIB: 75%). In addition, substantial urinary and bowel symptoms have been reported in 12.5% and 25% of women, respectively. Vaginal morbidity is also often observed (53% mild, 19% moderate), impacting (sexual) quality of life. This underlines that BT treatments need to improve for larger and complex tumours, and that treatment toxicity needs to decrease for all treated women.

Objectives

By basing needle locations on the patient’s anatomy through custom applicators, we may improve achievable dose distributions. In the ARCHITECT project we develop 3D printed patient-tailored cervical cancer BT applicators that guide needles to optimal locations. Our aim is to create an automated pipeline for applicator development in compliance with medical device regulations, and evaluate its feasibility in a clinical study.

Study population

The intended study population consists of patients with locally advanced cervical cancer (FIGO stages IB-IV), including patients with parametrium, vaginal or nodal involvement. For anatomy and dosimetric planning studies, data of 90 locally advanced cervical cancer patients treated at the Erasmus MC were prospectively acquired. The clinical study will be a prospective experimental study and aims to demonstrate feasibility and effectiveness of the patient-tailored applicator.

Patient experience and time-action analysis

• Prospective study to determine patient experience (perceived pain, anxiety, and duration) as well as timing each treatment step of cervical cancer BT;
• This study highlights the complexity, duration and impact on patient experience of the current workflow. It marks areas for improvement, particularly in enhancing patient comfort/pain and reducing the overall procedure duration. This work was critical for our risk analysis and risk mitigation to adapt the workflow by introducing of patient-tailored applicators.

Patient anatomy characterisation

• Prospective study to characterise the anatomy of the vaginal cavity and high-risk clinical target volume (CTVHR) during pre-BT MR and the first BT application;
• This study quantifies patient variability and geometric parameters to be used for the development of patient-tailored applicators. It shows the need for modular applicators, with custom or class-based needle configurations.

Automated patient-tailored applicator generation

• Virtual planning study to develop and evaluate software for patient-tailored BT applicator generation. Software automatically establishes optimal needle configurations that are compared with clinically used configurations;
• This study illustrates feasibility of our automated planning approach. Patient-tailored configurations could be generated in clinically feasible time, and yielded high-quality treatment plans.

Patient selection for tailored applicators

• Virtual planning study to determine which patients would benefit most from patient-tailored BT applicators. Machine learning models are trained to predict organ doses based on input geometry;
• This study shows the potential of anatomy-based patient selection for patient-tailored applicators. In addition, the models could be used for quality assurance of treatment plans.

Dosimetric evaluation of patient-tailored applicators

• Virtual planning study to compare plan quality between patient-tailored needle configurations and clinically used configurations. Evaluation includes both dosimetric parameters and qualitative assessments of the dose distributions.
• This study aims to demonstrate the geometric and dosimetric benefits of patient-tailored needle configurations, and to further identify patients subgroups that benefit most from this approach.

Clinical evaluation of the patient-tailored applicators

• Clinical evaluation study to assess the feasibility of the patient-tailored applicator during brachytherapy for locally advanced cervical cancer.
• Furthermore, the plan quality, user experience, workflow, pain and cost of the patient-tailored applicator are assessed.

This project was supported by a grant from the Dutch Research Council (NWO), Dutch Cancer Society (KWF) and Top Sector Life Sciences & Health (LSH) (Project No. 17921).

• Delft University of Technology, Delft, The Netherlands;
• Elekta AB, Stockholm, Sweden;
• Oceanz, Ede, The Netherlands;
• Stichting Olijf, Utrecht, The Netherlands;
• University Medical Centre Utrecht, Utrecht, The Netherlands.

MRI-driven design of customised 3D printed gynaecological brachytherapy applicators with curved needle channels. Laan, R. C., Nout, R. A., Dankelman, J., & van de Berg, N. J. (2019). 3D printing in medicine, 5, 1-8.  

An anthropomorphic deformable phantom of the vaginal wall and cavity. Somerwil, P. C., Nout, R. A., Mens, J. W. M., Kolkman-Deurloo, I. K. K., Van Beekhuizen, H. J., Dankelman, J., & Van De Berg, N. J. (2021). Biomedical Physics & Engineering Express, 7(5), 055019.  

Multibody dynamic modeling of the behavior of flexible instruments used in cervical cancer brachytherapy. Straathof, R., Meijaard, J. P., van Vliet‐Pérez, S. M., Kolkman‐Deurloo, I. K. K., Nout, R. A., Heijmen, B. J., Wauben, Linda S. G. L., Dankelman, J., van de Berg, N. J. (2024). Medical Physics, 51(5), 3698-3710.  

Time-action and patient experience analyses of locally advanced cervical cancer brachytherapy. van Vliet–Pérez, S. M., van Paassen, R., Wauben, L. S., Straathof, R., van de Berg, N. J., Dankelman, J., Heijmen, B., Kolkman-Deurloo, I. K. K., Nout, R. A. (2024). Brachytherapy, 23(3), 274-281. 

Automated planning of curved needle channels in 3D printed patient-tailored applicators for cervical cancer brachytherapy. Straathof, R., van Vliet-Pérez, S. M., Kolkman-Deurloo, I. K. K., Wauben, L. S., Nout, R. A., Heijmen, B. J., ... & van de Berg, N. J. (2024). Physics in Medicine & Biology, 69(23), 235007. 

Remi Nout (principal investigator)
Nick van de Berg (principal investigator)
Inger-Karine Kolkman-Deurloo (principal investigator)
Jenny Dankelman (principal investigator)
Henrike Westerveld (researcher)
Ben Heijmen (researcher)
Linda Wauben (researcher)
Robin Straathof (researcher)
Sharline van Vliet-Perez (researcher)