A nested case-control study on radiation dose-response for cardiac events in breast cancer patients in Germany
Dan Baaken,
Hiltrud Merzenich,
Marcus Schmidt,
Inga Bekes,
Lukas Schwentner,
Wolfgang Janni,
Achim Wöckel,
Manfred Mayr,
Stephan Mose,
Thomas Merz,
Voica Ghilescu,
Jona Renner,
Detlef Bartkowiak,
Thomas Wiegel,
Maria Blettner,
Heinz Schmidberger,
Daniel Wollschläger
Affiliations
Dan Baaken
University Medical Center of the Johannes Gutenberg-University Mainz, Institute of Medical Biostatistics, Epidemiology and Informatics, 55101, Mainz, Germany; Corresponding author. University Medical Center of the Johannes Gutenberg-University Mainz, Institute of Medical Biostatistics, Epidemiology and Informatics, Obere Zahlbacher Straße 69, 55131, Mainz, Germany.
Hiltrud Merzenich
University Medical Center of the Johannes Gutenberg-University Mainz, Institute of Medical Biostatistics, Epidemiology and Informatics, 55101, Mainz, Germany
Marcus Schmidt
University Medical Center of the Johannes Gutenberg-University Mainz, Department of Obstetrics and Gynecology, 55101, Mainz, Germany
Inga Bekes
University Hospital Ulm, Department of Gynecology and Obstetrics, 89075, Ulm, Germany
Lukas Schwentner
University Hospital Ulm, Department of Gynecology and Obstetrics, 89075, Ulm, Germany
Wolfgang Janni
University Hospital Ulm, Department of Gynecology and Obstetrics, 89075, Ulm, Germany
Achim Wöckel
University Hospital Ulm, Department of Gynecology and Obstetrics, 89075, Ulm, Germany; University Hospital Würzburg, 97080, Würzburg, Germany
Manfred Mayr
Strahlentherapie Süd am Klinikum Kaufbeuren, 87600, Kaufbeuren, Germany
Stephan Mose
Schwarzwald-Baar Klinikum, Klinik für Strahlentherapie und Radioonkologie, 78052, Villingen-Schwenningen, Germany
Thomas Merz
Kliniken Landkreis Heidenheim gGmbH, Department of Radiation Oncology and Radiotherapy, 89522, Heidenheim, Germany
Voica Ghilescu
Kliniken Landkreis Heidenheim gGmbH, Department of Radiation Oncology and Radiotherapy, 89522, Heidenheim, Germany
Jona Renner
University Hospital Ulm, Department of Radiation Oncology, 89081, Ulm, Germany
Detlef Bartkowiak
University Hospital Ulm, Department of Radiation Oncology, 89081, Ulm, Germany
Thomas Wiegel
University Hospital Ulm, Department of Radiation Oncology, 89081, Ulm, Germany
Maria Blettner
University Medical Center of the Johannes Gutenberg-University Mainz, Institute of Medical Biostatistics, Epidemiology and Informatics, 55101, Mainz, Germany
Heinz Schmidberger
University Medical Center of the Johannes Gutenberg-University Mainz, Department of Radiation Oncology and Radiation Therapy, 55101, Mainz, Germany
Daniel Wollschläger
University Medical Center of the Johannes Gutenberg-University Mainz, Institute of Medical Biostatistics, Epidemiology and Informatics, 55101, Mainz, Germany
Background: Previous studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT. Methods: In a cohort of 11,982 BC patients diagnosed in 1998–2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events. Results: Mean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94–1.05, P = .72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98–1.01, P = .68). Conclusions: Contrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events.
