Factors associated with participation in a proton therapy clinical trial: a cross-sectional survey of Danish patients with head and neck cancer.

Background and purpose: Participation in proton therapy (PT) trials may be affected by structural, clinical, and individual factors, potentially excluding certain patient groups. Such disparities can lead to unequal access to potential research benefits and may limit the generalisability of trial findings. This study aimed to identify factors associated with participation in a Danish randomised controlled trial (RCT) comparing proton versus photon radiotherapy for head and neck cancer.

Patients and methods: This national cross-sectional study invited patients with pharyngeal and laryngeal cancer, referred for curative-intent radiotherapy at seven Danish radiotherapy clinics between 2022 and 2025, to complete a survey. Respondents were categorised based on enrollment status in a national RCT comparing proton versus photon radiotherapy. Clinical, demographic, psychosocial, and lifestyle data were collected and linked to clinical registry data. Multiple logistic regression was used to assess exposure variables associated with trial participation.

Results: Of 304 respondents, 120 (39%) were enrolled in the RCT. Female gender, older age, greater geographical distance to the PT centre, mobility limitations, lower self-rated health status, and lower ability to actively engage with healthcare providers (Health Literacy Questionnaire scale 6) were significantly associated with lower odds of participation. No significant associations were observed for income, education, marital status, or anxiety.

Interpretation: The findings indicate that demographic, geographical, functional, and communication--related factors may limit participation in PT trials. This highlights the need for interventions that enhance the delivery of trial information, strengthen communication between patients and healthcare professionals, and support informed clinical trial decision-making.