Evidence from large patient cohorts has the potential to provide further support of new therapies developed in randomised trials, but also demonstrate gains and risks from radiation therapy (RT) which may not be reported from other trials and studies. In particular, relatively seldom events may be documented only in large patient cohorts.
The Danish Breast Cancer Group (DBCG) was established in 1977 to provide nationwide clinical guidelines for therapy of early breast cancer patients, and also develop new guidelines through evidence generating clinical studies. Denmark has 5.5 mio inhabitants, and currently around 4700 newly diagnosed breast cancer patients yearly. All Danish departments treating breast cancer patients report data on diagnosis, pathology, surgery, systemic therapy, RT and cancer events to the database. Every department follows the DBCG guidelines ensuring a homogeneous treatment strategy across the country.
This strategy holds great potential for practice-changing clinical studies, and four examples are demonstrated here. The first example is the prospective cohort DBCG IMN (internal mammary node) study, where the DBCG RT Committee in 2003 decided not to irradiate the IMN in left-sided node-positive breast cancer patients, whilst IMN would be irradiated in right-sided breast cancer (1). The first results from >3.000 patients treated 2003-2007 according to this guideline were shown in 2014, whereafter the DBCG RT Committee immediately and unanimously modified the DBCG guidelines in favor of IMN RT for all node-positive breast cancer patients. The DBCG is currently investigating the cohort treated 2008-2014 according to the ±IMN guideline (N>5000 patients).
The second example is the retrospective DBCG Heart study investigating the risk of RT associated heart disease in >22.000 irradiated breast cancer patients. A total of 204 cases were identified, and a case-control study demonstrated that using CT-based breast cancer RT leads to relatively low radiation doses to the heart. No association between RT and risk of ischemic heart disease could be identified at median 7.4 yr follow up (2).
A third example is the DBCG RT Nation study collecting all RT plans used for loco-regional RT of 9.000 high-risk breast cancer patients during 2008-2016. The planning CT scan, delineations of target volumes and organs at risk (OAR), treatment plans and dose distributions are stored in the national dose plan bank, the DcmCollab (3). Using these data, several studies are investigating e.g. adherence to DBCG RT guidelines, quality assurance of RT across departments, and dose distributions in selected targets and OAR (4,5).
The last example is the prospective DBCG Center and Clinic for Late Effects (DCCL), which includes nationwide prospective collection of PRO from diagnosis to end of follow up in all Danish breast cancer patients, and the PRO results are collected into the DBCG database. The PRO collection is carried out through an app using internationally validated in addition to DBCG developed questionnaires at relevant time points according to the treatment provided. Importantly, the patient receives direct feedback through the app depending on the responses.
The above initiatives are only feasible because every department in Denmark follows the DBCG guidelines with a high ambition and willingness for collaboration inside DBCG. Treating according to nationwide guidelines improves the quality of therapy for every patient, ensures that patients are treated as equal as possible, provides comfort to the doctor knowing that high-level therapy is used, and opens the possibility for documenting the outcome of modern therapy in large patient cohorts.
(1) Thorsen LBJ, Offersen BV, Danø H, et al. DBCG-IMN: A Population-Based Cohort Study on the Effect of Internal Mammary Node Irradiation in Early Node-Positive Breast Cancer. Journal of Clinical Oncology 2015
(2) Milo MLH, Møller DS, Nyeng TB, Hoffmann L et al. No correlation between radiation dose to cardiac substructures and coronary artery disease in early breast cancer patients: A DBCG case-control study, ESTRO 2021 abstract
(3) Krogh SL, Lorenzen E, Hansen CR et al. Collecting Complete Radiotherapy Plan Data of 11,000+ Patients in a National Database, ESTRO 2022 abstract
(4) Refsgaard LR, Skarsø ER, Ravkilde T et al. Dose and volume of the heart and internal mammary lymph nodes in Denmark 2008-2016 (DBCG RT Nation study), ESTRO 2022 abstract
(5) Skarsø ER, Refsgaard LR, Ravkilde T et al. Parametrization of artery delineation and nationwide implementation in the DBCG RT Nation cohort, ESTRO 2022 abstract