Page 409 - 2014 Printable Abstract Book
P. 409
(PS7-56) Cardiovascular diseases after Hodgkin lymphoma treatment: 35-years risk and sequence of
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events. Flora E. van Leeuwen, PhD ; Frederika A. Van Nimwegen ; M. Schaapveld, PhD ; Cecile P.M. Janus ;
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Augustinus D.G. Krol ; John M.M. Raemaekers, PhD ; Eefke J. Petersen, PhD ; and Berthe M.P. Aleman ,
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Netherlands Cancer Institute, Amsterdam, Netherlands ; Daniel den Hoed Cancer Center/ErasmusMC,
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Rotterdam, Netherlands ; Leiden University Medical Center, Leiden, Netherlands ; Radboud University
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Medical Center, Nijmegen, Netherlands ; and Utrecht University Medical Center, Utrecht, Netherlands 5
Background: Hodgkin lymphoma (HL) survivors treated with radiotherapy (RT), often in
combination with chemotherapy (CT), are known to be at increased risk of cardiovascular disease (CVD),
causing excess morbidity and mortality. It is unclear, however, whether the increased risk persists after
35 years and which factors influence this risk. Methods: A cohort study was performed including 2,525 5-
year HL survivors, diagnosed before age 51 and treated between the years 1965 - 1995. We assessed CVD
endpoints (ischemic heart disease [IHD], congestive heart failure and cardiomyopathy [HF] and valvular
heart disease [VHD]) up to October 2013 through questionnaires to general practitioners and
cardiologists. Cumulative incidences of CVDs were estimated accounting for death as a competing risk.
Risk factors were evaluated using Cox regression. Standardized Incidence Ratios (SIRs) were estimated to
compare CVD risk with the general population. Results: We identified 1732 CVDs in 798 patients, after a
median follow-up of 20 years. Following mediastinal radiotherapy (medRT), the 35-year cumulative
incidence of CVD was 47.6% (95%CI: 44.8%-50.4%), compared to 19.5% in patients not treated with
medRT (15.1%-24.3%). At ≥35 years after HL diagnosis, our patients still had a 2.4-fold increased SIR of
primary IHD or HF (95%CI: 1.4-3.9), compared to the general population, corresponding to 265 excess
cases per 10,000 person years. Of all first cardiac events, the most frequently diagnosed cardiac event
was IHD (50%), followed by VHD (35%). Fifty-two % of CVD patients developed multiple CVDs; 92% of
these patients had received medRT; among patients with one CVD and patients without any CVDs, these
proportions were 90% and 77%, respectively (p<0.001). After adjustment for CT, mediastinal RT increased
the risks of different CVDs independently, with Hazard Ratios (HRs): 2.3, (95%CI: 1.7-3.2), HR: 5.5 (95%CI:
3.4-9.0) and HR: 2.4 (95%CI: 1.3-3.9) for IHD, VHD and CHF (as a first event), respectively). Furthermore,
we observed radiation dose-response relationships for IHD, VHD and CHF (p<0.001). High prescribed
radiation doses of ≥36 Gy to the mediastinum increased the risk of developing any CVD 3.9-fold (95%CI:
3.1-4.9) compared to patients not treated with medRT. Lower radiation doses of 30-35 Gy and 10-29 Gy
also significantly increased CVD risk (HR: 3.1 and 1.7, respectively). Median survival time after a first CVD
was 5.3 years. Conclusions: The risk of CVD is strongly increased for at least 35 years following HL
treatment, especially after mediastinal RT. For IHD, VHD and CHF risk increases with higher prescribed
radiation doses. Multiple CVDs are frequently observed. Physicians should be aware of the persistently
increased risk of CVDs and the increased risk of developing subsequent CVDs.
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2
1
1
events. Flora E. van Leeuwen, PhD ; Frederika A. Van Nimwegen ; M. Schaapveld, PhD ; Cecile P.M. Janus ;
1
5
4
3
Augustinus D.G. Krol ; John M.M. Raemaekers, PhD ; Eefke J. Petersen, PhD ; and Berthe M.P. Aleman ,
1
Netherlands Cancer Institute, Amsterdam, Netherlands ; Daniel den Hoed Cancer Center/ErasmusMC,
3
2
Rotterdam, Netherlands ; Leiden University Medical Center, Leiden, Netherlands ; Radboud University
4
Medical Center, Nijmegen, Netherlands ; and Utrecht University Medical Center, Utrecht, Netherlands 5
Background: Hodgkin lymphoma (HL) survivors treated with radiotherapy (RT), often in
combination with chemotherapy (CT), are known to be at increased risk of cardiovascular disease (CVD),
causing excess morbidity and mortality. It is unclear, however, whether the increased risk persists after
35 years and which factors influence this risk. Methods: A cohort study was performed including 2,525 5-
year HL survivors, diagnosed before age 51 and treated between the years 1965 - 1995. We assessed CVD
endpoints (ischemic heart disease [IHD], congestive heart failure and cardiomyopathy [HF] and valvular
heart disease [VHD]) up to October 2013 through questionnaires to general practitioners and
cardiologists. Cumulative incidences of CVDs were estimated accounting for death as a competing risk.
Risk factors were evaluated using Cox regression. Standardized Incidence Ratios (SIRs) were estimated to
compare CVD risk with the general population. Results: We identified 1732 CVDs in 798 patients, after a
median follow-up of 20 years. Following mediastinal radiotherapy (medRT), the 35-year cumulative
incidence of CVD was 47.6% (95%CI: 44.8%-50.4%), compared to 19.5% in patients not treated with
medRT (15.1%-24.3%). At ≥35 years after HL diagnosis, our patients still had a 2.4-fold increased SIR of
primary IHD or HF (95%CI: 1.4-3.9), compared to the general population, corresponding to 265 excess
cases per 10,000 person years. Of all first cardiac events, the most frequently diagnosed cardiac event
was IHD (50%), followed by VHD (35%). Fifty-two % of CVD patients developed multiple CVDs; 92% of
these patients had received medRT; among patients with one CVD and patients without any CVDs, these
proportions were 90% and 77%, respectively (p<0.001). After adjustment for CT, mediastinal RT increased
the risks of different CVDs independently, with Hazard Ratios (HRs): 2.3, (95%CI: 1.7-3.2), HR: 5.5 (95%CI:
3.4-9.0) and HR: 2.4 (95%CI: 1.3-3.9) for IHD, VHD and CHF (as a first event), respectively). Furthermore,
we observed radiation dose-response relationships for IHD, VHD and CHF (p<0.001). High prescribed
radiation doses of ≥36 Gy to the mediastinum increased the risk of developing any CVD 3.9-fold (95%CI:
3.1-4.9) compared to patients not treated with medRT. Lower radiation doses of 30-35 Gy and 10-29 Gy
also significantly increased CVD risk (HR: 3.1 and 1.7, respectively). Median survival time after a first CVD
was 5.3 years. Conclusions: The risk of CVD is strongly increased for at least 35 years following HL
treatment, especially after mediastinal RT. For IHD, VHD and CHF risk increases with higher prescribed
radiation doses. Multiple CVDs are frequently observed. Physicians should be aware of the persistently
increased risk of CVDs and the increased risk of developing subsequent CVDs.
