Late cardiac events from lymphoma treatment -a meta-regression analysis of dose/response
MO-0641
Abstract
Late cardiac events from lymphoma treatment -a meta-regression analysis of dose/response
Authors: Lotte Nygård1, Ivan Richter Vogelius1, Søren M Bentzen2, Lena Specht1
1Copenhagen University Hospital, Rigshospitalet, Department of Oncology, Copenhagen, Denmark; 2University of Maryland, School of Medicine, Department of Epidemiology and Public Health, Baltimore, MD, USA
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Purpose or Objective
Treatment of lymphoma is highly curable but there can be long-term cardiotoxicity associated with both radiation and chemotherapy. We performed a meta-regression analysis of long-term cardiac events from lymphoma treatment. The objective was to identify dose-response relationships for both anthracycline and radiotherapy on the risk of cardiotoxic events subdivided in congestive heart failure (CHF), ischemic heart disease (IHD), and valvular heart disease (VHD).
Material and Methods
Data on lymphoma patients was sought in PubMed with inclusion of papers published between January 2000 until December 2021. Patient numbers should be above 100. Data should contain cardiac outcomes in lymphoma patients, radiation doses to the heart and anthracycline doses. Cardiac outcomes should be reported for CHF, IHD and/or VHD for a study to be included.
Results
We found eleven eligible papers. All three cardiac outcomes had relevant cumulative incidence twenty-five years post treatment (CHF around 5%, IHD 5-10% and VHD 10-15 %).
The excess relative risk (ERR) of CHF for anthracyclines per 100mg/m2 was 74% (CI: 55% to 94%). For radiotherapy, ERR of CHF per Gy of mean heart dose was 6.1%/Gy (CI: 4.3% to 7.8%). Corresponding numbers for the other endpoints were: IHD: No significant effect of anthracycline dose, ERR=5.5%/Gy (CI: 3.1% to 7.9%). VHD: ERR=25%/100mg/m2 (CI: 13% to 36%) and ERR=10%/Gy (CI: 6% to 15%). There were no signs of a “safe” lower dose level for neither anthracyclines nor radiotherapy dose on the affected endpoints. No interaction between the two cardiotoxic agents could be identified. Figure 1 shows the fit for CHF and Figure 2 shows all models of ERR versus dose.
Conclusion
The risk of heart morbidity in the decades following lymphoma treatment remains a challenge. Radiotherapy dose to the heart and anthracycline containing chemotherapy regimens show independent toxicity profiles specific to the endpoints CHF, IHD and VHD. Knowledge of the expected dose to the heart is essential in minimizing the risk of cardiotoxicity when evaluating alternative treatment approaches for lymphoma patients.