Comparing causes of death of Hodgkin lymphoma and breast cancer patients between medical records and cause-of-death statistics

Simone de Vries,1 Michael Schaapveld,1 Jan WPF Kardaun,2,3 Kim H de Bruin,2 Augustinus DG Krol,4 Pieternella J Lugtenburg,5 Judy N Jacobse,1 Berthe MP Aleman,6 Flora E van Leeuwen1 1Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; 2Department of Health and Care, Statistics Netherlands, The Hague, the Netherlands; 3Department of Public Health, Academic Medical Center, Amsterdam, the Netherlands; 4Department of Radiotherapy, Leiden University Medical Center, Leiden, the Netherlands; 5Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 6Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands Objective: Obtaining accurate data about causes of death may be difficult in patients with a complicated disease history, including cancer survivors. This study compared causes of death derived from medical records (CODMR) with causes of death derived from death certificates (CODDC) as processed by Statistics Netherlands of patients primarily treated for Hodgkin lymphoma (HL) or breast cancer (BC).Methods: Two hospital-based cohorts comprising 1,215 HL patients who died in the period 1980–2013 and 714 BC patients who died in the period 2000–2013 were linked with cause-of-death statistics files. The level of agreement was assessed for common underlying causes of death using Cohen’s kappa, and original death certificates were reviewed when CODDC and CODMR showed discrepancies. We examined the influence of using CODDC or CODMR on standardized mortality ratio (SMR) estimates.Results: Agreement for the most common causes of death, including selected malignant neoplasms and circulatory and respiratory diseases, was 81% for HL patients and 97% for BC patients. HL was more often reported as CODDC (CODDC=33.1% vs. CODMR=23.2%), whereas circulatory disease (CODDC=15.6% vs. CODMR=20.9%) or other diseases potentially related to HL treatment were more often reported as CODMR. Compared to SMRs based on CODDC, SMRs based on CODMR complemented with CODDC were lower for HL and higher for circulatory disease.Conclusion: Overall, we observed high levels of agreement between CODMR and CODDC for common causes of death in HL and BC patients. Observed discrepancies between CODMR and CODDC frequently occurred in the presence of late effects of treatment for HL. Keywords: cause of death, Hodgkin lymphoma, breast cancer, mortality statistic

Exposure of the heart and cardiac valves in women irradiated for breast cancer 1970-2009

Purpose To describe cardiac exposure from breast cancer radiotherapy regimens used during 1970-2009 for the development of dose-response relationships and to consider the associated radiation-risks using existing dose-response relationships. Material and Methods Radiotherapy charts for 771 women in the Netherlands selected for case control studies of heart disease after breast cancer radiotherapy were used to reconstruct 44 regimens on a typical CT-dataset. Doses were estimated for the whole heart (WH), left ventricle (LV) and cardiac valves. Results For breast/chest wall radiotherapy average WH doses decreased during 1970-2009. For internal mammary chain (IMC) radiotherapy WH doses were highest during the 1980s and 1990s when direct anterior fields were used and reduced in the 2000s when oblique fields were introduced. Average doses varied substantially for IMC regimens (WH 2-33 Gy, LV 30 Gy from most regimens. Conclusions Radiation-risks of IHD from breast/chest wall regimens likely reduced during 1970-2009. Direct anterior IMC regimens likely increased the risks of IHD and VHD over this time period but the use of oblique IMC fields from 2003 may have lowered these risks. These data provide a unique opportunity to develop dose-response relationships

Radiation Dose-Response for Risk of Myocardial Infarction in Breast Cancer Survivors

Purpose: Previous reports suggest that radiation therapy for breast cancer (BC) can cause ischemic heart disease, with the radiation-related risk increasing linearly with mean whole heart dose (MWHD). This study aimed to validate these findings in younger BC patients and to investigate additional risk factors for radiation-related myocardial infarction (MI). Methods and Materials: A nested case-control study was conducted within a cohort of BC survivors treated during 1970 to 2009. Cases were 183 patients with MI as their first heart disease after BC. One control per case was selected and matched on age and BC diagnosis date. Information on treatment and cardiovascular risk factors was abstracted from medical and radiation charts. Cardiac doses were estimated for each woman by reconstructing her regimen using modern 3-dimensional computed tomography planning on a typical patient computed tomography scan. Results: Median age at BC of cases and controls was 50.2 years (interquartile range, 45.7-54.7). Median time to MI was 13.6 years (interquartile range, 9.9-18.1). Median MWHD was 8.9 Gy (range, 0.3-35.2 Gy). MI rate increased linearly with increasing MWHD (excess rate ratio [ERR] per Gy, 6.4%; 95% confidence interval, 1.3%-16.0%). Patients receiving ≥20 Gy MWHD had a 3.4-fold (95% confidence interval, 1.5-7.6) higher MI rate than unirradiated patients. ERRs were higher for younger women, with borderline significance (ERR&lt;45years, 24.2%/Gy; ERR≥50years, 2.5%/Gy; Pinteraction = .054). Whole heart dose-volume parameters did not modify the dose-response relationship significantly. Conclusions: MI rate after radiation for BC increases linearly with MWHD. Reductions in MWHD are expected to contribute to better cardiovascular health of BC survivors.</p

Risk of heart failure after systemic treatment for early breast cancer: results of a cohort study

Purpose: Anthracyclines and trastuzumab can increase the risk of heart failure (HF), but long-term cardiotoxicity data in breast cancer (BC) patients treated at younger ages are limited. Furthermore, it is unknown whether aromatase inhibitors are associated with HF risk. Methods: HF risk was studied in a multicenter cohort of BC survivors treated during 2000–2009, at age < 61 years. Information on treatment and cardiovascular disease incidence was collected through medical records, general practitioners and cardiologists. Analyses included multivariable Cox regression and cumulative incidence curves. Results: In total, 10,209 women with a median age at BC diagnosis of 50.3 years and a median follow-up of 8.9 years were enrolled in the study. Anthracycline-based chemotherapy was associated with HF (hazard ratio [HR] 2.18, 95% confidence interval [CI] 1.41–3.39) and risk increased with increasing cumulative anthracycline dose. For trastuzumab, HF risk was highest within the first 2 years after treatment (HR0–2 years: 13.06, 95% CI 5.70–29.92) and decreased thereafter (HR2–4 years: 4.84, 95% CI 1.99–11.75 and HR≥4 years: 0.64, 95% CI 0.23–1.81). The 10-year cumulative incidence of HF was 4.8% (95% CI 3.2–6.8) among patients treated with anthracyclines and trastuzumab. One-third of patients who developed HF after trastuzumab had long-term impaired cardiac function. Patients treated with aromatase inhibitors alone also had higher HF risk (HR 2.18, 95% CI 1.24–3.82) compared to patients not receiving endocrine therapy. Conclusions: Our results stress the importance of considering anthracycline-free regimens in BC patients who need trastuzumab-containing treatment. The association between aromatase inhibitors and HF needs confirmation

Radiation Dose-Response for Risk of Myocardial Infarction in Breast Cancer Survivors

Purpose: Previous reports suggest that radiation therapy for breast cancer (BC) can cause ischemic heart disease, with the radiation-related risk increasing linearly with mean whole heart dose (MWHD). This study aimed to validate these findings in younger BC patients and to investigate additional risk factors for radiation-related myocardial infarction (MI). Methods and Materials: A nested case-control study was conducted within a cohort of BC survivors treated during 1970 to 2009. Cases were 183 patients with MI as their first heart disease after BC. One control per case was selected and matched on age and BC diagnosis date. Information on treatment and cardiovascular risk factors was abstracted from medical and radiation charts. Cardiac doses were estimated for each woman by reconstructing her regimen using modern 3-dimensional computed tomography planning on a typical patient computed tomography scan. Results: Median age at BC of cases and controls was 50.2 years (interquartile range, 45.7-54.7). Median time to MI was 13.6 years (interquartile range, 9.9-18.1). Median MWHD was 8.9 Gy (range, 0.3-35.2 Gy). MI rate increased linearly with increasing MWHD (excess rate ratio [ERR] per Gy, 6.4%; 95% confidence interval, 1.3%-16.0%). Patients receiving ≥20 Gy MWHD had a 3.4-fold (95% confidence interval, 1.5-7.6) higher MI rate than unirradiated patients. ERRs were higher for younger women, with borderline significance (ERRand#60;45years, 24.2%/Gy; ERRand#8805;50years, 2.5%/Gy; Pinteraction = .054). Whole heart dose-volume parameters did not modify the dose-response relationship significantly. Conclusions: MI rate after radiation for BC increases linearly with MWHD. Reductions in MWHD are expected to contribute to better cardiovascular health of BC survivors.</p

Cardiovascular disease incidence after internal mammary chain irradiation and anthracycline-based chemotherapy for breast cancer

Background Improved breast cancer (BC) survival and evidence showing beneficial effects of internal mammary chain (IMC) irradiation underscore the importance of studying late cardiovascular effects of BC treatment. Methods We assessed cardiovascular disease (CVD) incidence in 14,645 Dutch BC patients aged &lt;62 years, treated during 1970–2009. Analyses included proportional hazards models and general population comparisons. Results CVD rate-ratio for left-versus-right breast irradiation without IMC was 1.11 (95% CI 0.93–1.32). Compared to right-sided breast irradiation only, IMC irradiation (interquartile range mean heart doses 9–17 Gy) was associated with increases in CVD rate overall, ischaemic heart disease (IHD), heart failure (HF) and valvular heart disease (hazard ratios (HRs): 1.6–2.4). IHD risk remained increased until at least 20 years after treatment. Anthracycline-based chemotherapy was associated with an increased HF rate (HR = 4.18, 95% CI 3.07–5.69), emerging &lt;5 years and remaining increased at least 10–15 years after treatment. IMC irradiation combined with anthracycline-based chemotherapy was associated with substantially increased HF rate (HR = 9.23 95% CI 6.01–14.18), compared to neither IMC irradiation nor anthracycline-based chemotherapy. Conclusions Women treated with anthracycline-based chemotherapy and IMC irradiation (in an older era) with considerable mean heart dose exposure have substantially increased incidence of several CVDs. Screening may be appropriate for some BC patient groups

Cardiovascular disease incidence after internal mammary chain irradiation and anthracycline-based chemotherapy for breast cancer

Background Improved breast cancer (BC) survival and evidence showing beneficial effects of internal mammary chain (IMC) irradiation underscore the importance of studying late cardiovascular effects of BC treatment. Methods We assessed cardiovascular disease (CVD) incidence in 14,645 Dutch BC patients aged <62 years, treated during 1970–2009. Analyses included proportional hazards models and general population comparisons. Results CVD rate-ratio for left-versus-right breast irradiation without IMC was 1.11 (95% CI 0.93–1.32). Compared to right-sided breast irradiation only, IMC irradiation (interquartile range mean heart doses 9–17 Gy) was associated with increases in CVD rate overall, ischaemic heart disease (IHD), heart failure (HF) and valvular heart disease (hazard ratios (HRs): 1.6–2.4). IHD risk remained increased until at least 20 years after treatment. Anthracycline-based chemotherapy was associated with an increased HF rate (HR = 4.18, 95% CI 3.07–5.69), emerging <5 years and remaining increased at least 10–15 years after treatment. IMC irradiation combined with anthracycline-based chemotherapy was associated with substantially increased HF rate (HR = 9.23 95% CI 6.01–14.18), compared to neither IMC irradiation nor anthracycline-based chemotherapy. Conclusions Women treated with anthracycline-based chemotherapy and IMC irradiation (in an older era) with considerable mean heart dose exposure have substantially increased incidence of several CVDs. Screening may be appropriate for some BC patient groups