Danish Breast Cancer Group Skagen Trial 1: A report on annual trial participation

ABSTRACT

Purpose or Objective Clinical trials are essential to improve cancer treatment. Trials rely on wide-ranging patient (pt) participation to gain adequate sample sizes and externally applicable results. The Danish Breast Cancer Group (DBCG) develops national guidelines for breast cancer therapy, and this is preferably through clinical trials. During 2015-2021 moderately hypofractionated adjuvant loco-regional breast cancer (BC) radiation therapy (RT) was tested in an international trial, the DBCG SKAGEN Trial 1, testing 50Gy/25 fr (standard) versus 40Gy/15fr (experimental). The trial inclusion criteria were broad, thus any pt with indication for loco-regional RT (LR-RT) for unilateral early high-risk BC with no prior cancer and willing/able to participate in the 10-year follow up was a candidate.Recently, the inclusion of pts in trials may have been particularly challenged due to difficulties imposed by the COVID 19 pandemic. Hitherto, the DBCG has had no evidencebased knowledge about trial participation rates (TPR). These are important for evaluating the applicability of the trial results and planning of future RT trials. We present annual trial participation rates during the inclusion period. Materials and Methods The international DBCG SKAGEN Trial 1 randomized patients from 2015 to July 1st 2021, and the 17 participating institutions from 7 countries accrued 2,963 patients. Eight of these institutions accruing 2,184 pts in all delivered data on the total number of pts treated with LR-RT during the inclusion period. We calculated annual TPRs per institution and overall as TPR (number pts enrolled per year/ number pts treated with LR-RT per year). Results From 6,929 pts receiving LR-RT, 2,184 pts were enrolled, corresponding to an overall TPR of 31.5% (figure 1). In all eight institutions, accrual was running from 2016 (figure 2). From 2016, the average single institution TPR per year ranged from 14.4% to 50.4%. Annual TPRs varied with time most institutions experienced a modest decline in TPR during 2019-2020, while in 2021 TPR seemed to stabilize. In one institution, accrual was terminated during 2020 due to COVID 19 related restrictions.(Figure Presented)(Figure Presented)Conclusion TPRs displayed considerable variation across institutions and time and were vulnerable to COVID 19 related restrictions. Even with a straight-forward trial design and the prospect of a shortened LR-RT course, only one institution succeeded in accruing more than half of the patients likely to be trial candidates. The results indicate, that a TPR around 50% was feasible for the best performing department, thus implying a large potential for better trial accrual in most centres. In future trials, systematic monitoring of TPRs and reasons for not participating should be undertaken to optimize trial designs and accrual procedures