Background While malignant bone sarcoma is rare in the general population, it is the second most common malignancy among children and young adults. (Neo)adjuvant systemic treatment carries a significant risk of cardiotoxicity (CTx) in the form of late-onset left ventricular dysfunction and heart failure. There are several long-term follow up protocols in place for survivors of childhood and adolescent cancers, but when sarcoma is diagnosed at higher age the best follow up practice is less clear and there is little known about the long-term risk and mode of onset of CTx. Purpose To evaluate the effect of age at sarcoma diagnosis on incidence of cardiotoxicity (CTx) and time-to-CTx. Methods This single-center retrospective analysis of CTx of sarcoma treatment was performed at a tertiary sarcoma center in the Netherlands (Leiden University Medical Center, LUMC) among patients with a high-grade osteosarcoma (OS) and Ewing sarcoma (ES). All patients were diagnosed and treated over a 36-year period (1982 and 2018) at LUMC, and followed up until August 2021. The main inclusion criterium was exposure to doxorubicin-containing chemotherapy regimens. The exposure of interest was age at cancer diagnosis with a cut-off for older age at ≥30 years (age30+) The primary study endpoint was incident clinically relevant CTx at follow up, defined as composite of pharmacological heart failure (HF) treatment initiation, HF admissions and ICD implantation. Cause-specific Cox modeling was performed to calculate the hazard ratio (HR) of age group and incidence of both the primary study endpoint and competing risk of all cause death. Results The study population consisted of 556 patients (69.0% OS, 31.0% ES) with a median age at sarcoma diagnosis of 19 [p25-p75: 15–30] years and the majority of patients were male (60.4%). 146 patients were in the age30+ group (26.3%). In a median follow up time of 5.5 [2.0–13.2] years, 27 patients reached the primary endpoint (4.9%). In 7/27 cases an urgent HF hospitalization was the first manifestation of HF and the remaining cases met the primary endpoint due to pharmacological HF treatment imitation. At the end of follow up mortality was 49.3% of patients. The vast majority of patients died of malignancy-related causes (95.6%). When correcting for female sex and sarcoma type, age30+ at sarcoma diagnosis was associated with a near 3.5 fold increased risk of HF compared to when sarcoma was diagnosed below 30: HR 3.39 (95% CI: 1.57–7.31), p=0.019. For the age30+ group whom experienced CTx the time-to-event was shorter compared to those diagnosed below 30 years at: respectively 5.5 years vs. 12.6 years (see Figure 1; Wilcoxon rank-sum test: p=0.012). Conclusions Sarcoma patients above 30 years at diagnosis have an increased risk of CTx and time to development of CTx was significantly shorter. Funding Acknowledgement Type of funding sources: None.
Purpose To assess survival trends after ST-elevation myocardial infarction (STEMI) in patients with a prior cancer diagnosis and to evaluate the drivers of prognosis over a follow-up period of five years. Methods Patients with a known cancer diagnosis, admitted with STEMI between 2004–2014 and treated with primary PCI were recruited from the STEMI-clinical registry of our institution. Detailed information on cancer diagnosis, -stage, and treatment regimen were collected from the institutional and national cancer registry system and all patients were followed prospectively. Results In the 215 included patients the cumulative incidence of all-cause death after 5 years of follow-up was 38.2% (N=61). The cause of death was predominantly malignancy-related (N=29, 47.4% of deaths) and only 9 patients (14.8% of deaths) died of a cardiovascular cause. After correcting for age and sex – a recent cancer diagnosis (<1yr relative to >10 yr, HR 3.405 [95% CI: 1.552–7.470], p=0.002), distant metastasis at presentation (HR 2.603 [1.236–5.481], p=0.012), ongoing cancer treatment at presentation (HR 1.878 [1.015–3.475], p=0.045) and natural logarithm of maximum creatinine kinase level (HR 1.345 [1.044–1.733], p=0.022) were significant predictors of long-term mortality. While prevalent renal insufficiency showed significant association with all-cause mortality (HR 2.302 [1.289–4.111], p=0.005), other known determinants of long-term prognosis after STEMI – a history of diabetes mellitus (HR 1.250 [0.566–2.761], p=0.581), hypertension (HR 0.623 [0.393–1.085], p=0.150), and culprit vessel left anterior descending artery or left main artery (HR 1.066 [0.641–1.771], p=0.806) were not significantly associated with survival at 5-years follow-up. Conclusion Cancer patients admitted with STEMI have a poor survival with one third of patients died at 5 year follow up. Cancer was the most common cause of death and malignancy-related factors made a significant impact on prognosis, while most of the established cardiovascular determinants of prognosis were not significantly associated with long-term survival. FUNDunding Acknowledgement Type of funding sources: None. Cumulative incidence curve
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