Cardiac and vascular late sequelae in long-term survivors of childhood and adolescent cancer
Hematology, Oncology
Cardiology, Angiology
Pediatric and Adolescent Medicine
Final Report Abstract
In the CVSS-study 1,002 childhood cancer survivors diagnosed with neoplasia prior to 15 years of age between 1980 and 1990 prospectively underwent a systematic, standardized clinical and laboratory cardiovascular screening, identical to the population-based cohort of the Gutenberg Health Study (GHS). According to the bias analysis study results can be transferred to the majority of the living source population. Prevalences of cardiovascular risk factors and cardiovascular disease of childhood cancer survivors (CCS) were compared to the general population. An increased risk for occurrence of arterial hypertension and dyslipidaemia was found for CCS. Moreover, results indicate a premature occurrence of theses risk factors of approximately six and eight years, respectively. Overt cardiovascular disease was present in 4.5% of CCS; the most frequent entities were congestive heart failure and venous thromboembolism. Survivors were nearly at a two-fold elevated risk for cardiovascular disease. Cardiovascular risk factors and cardiovascular disease increased with age without reaching a plateau over time. Heart failure (defined by echocardiography, including the symptomatic and asymptomatic state) was prevalent in 12% of childhood cancer survivors, the majority being asymptomatic. CCS were at significantly higher risk for developing heart failure independently of their higher prevalence of CVRF. The prevalence of heart failure with preserved ejection fraction (i.e. diastolic dysfunction) was relatively higher than heart failure with reduced ejection fraction (i.e. systolic dysfunction) compared to the general population. Systolic dysfunction was primarily associated with history of tumor entities, with individuals with former bone tumors and soft tissue sarcoma having the highest prevalence of heart failure in the sample. Diastolic dysfunction was associated with the higher burden of cardiovascular risk factors, but not with the tumor entity in childhood cancer survivors only. Vascular stiffness as measured by photo plethysmography was increased and the frequency of stiffness exceeding the age-related reference limit was 5.2-fold was considerably higher in childhood cancer survivors than in the general population. The increase of vascular stiffness occurred independently of the presence of arterial hypertension. In the subgroup of leukemia survivors, younger age at cancer diagnosis was found to be a beneficial effect on the increase o stiffness. In general, higher vascular stiffness was found among all tumor entities. Unexpectedly, not only the subgroup of CCS with a history of previous chemo- or radiotherapy demonstrated stiffer vessels, but also former patients who did not receive any chemo- or radiotherapy revealed stiffer vessels compared to the population. This suggests an effect of cancer per se, probably through its potent proinflammatory and procoagulatory properties that can trigger structural changes within the arterial wall resulting in the stiffer vessels. Most importantly, the finding of increased arterial stiffness independent from arterial hypertension supports the idea of other than traditional mechanisms to be involved in the cancer-dependent promotion of arterial stiffness. The analysis of platelet function in CCS demonstrates an important correlation between traditional CVRFs and TG potential in presence of platelets only. Sex specific differences in TG were found with females presenting with higher TG in obesity and systolic hypertension. These results highlight the potential of platelet coagulant function as tool for identifying cancer survivors at higher risk for adverse cardiovascular events. Thirty-two percent of survivors reported clinically relevant distress, with women being more burdend then men. Compared to the general population, all forms of mental distress were more prevalent among long-term survivors. Somatic symptom burden was most strongly increased, followed by generalized anxiety, depression and panic. CVSS-study participants especially reported feeling tired/low energy, trouble sleeping, headaches, and back pain. Survivors of childhood cancer experienced 6.4 times the number of cardiac deaths expected in the general population. These findings on cardiac causes of death among five-year survivors of childhood cancer are in good agreement with results from larger cohort studies. The findings in these young adult childhood cancer survivors indicate a considerably increased risk for premature cardiovascular disease and a high burden of cardiovascular morbidity and mortality in the long term. The CVSS-study provides evidence-based knowledge of the cardiovascular health status in childhood cancer survivors to improve follow-up care. The results highlight the need for medical as well as psycho-social support among survivors of childhood cancer. The medical support should not end with the termination of cancer treatment but instead be a long-term effort.
Publications
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(2018) Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: data from the German CVSS-study. European heart journal 39 (17) 1555–1562
Faber, J.; Wingerter, A.; Neu, M. A.; Henninger, N.; Eckerle, S.; Münzel, T.; Lackner, K. J.; Beutel, M. E.; Blettner, M.; Rathmann, W.; Peters, A.; Meisinger, C.; Linkohr, B.; Neuhauser, H.; Kaatsch, P.; Spix, C.; Schneider, A.; Merzenich, H.; Panova-Noe
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Kardiale und vaskuläre Spätfolgen von Langzeitüberlebenden nach Krebs im Kindes- und Jugendalter: ein multidisziplinärer klinischer, epidemiologischer und genetischer Ansatz. Monatsschr Kinderheilkd 2013; 161:1065–1079
S. Eckerle, A. Wingerter, J. Faber, P. Wild, C. Spix
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Kardiale und vaskuläre Spätfolgen bei Langzeitüberlebenden nach Krebserkrankungen im Kindesalter (CVSS). GMDS Meeting Göttingen 07.- 10. 09.2014
Spix C, Hennewig U, Eckerle S, Henninger N, Faber J, Wild PS
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Kardiale und vaskuläre Spätfolgen von Langzeit-Überlebenden nach Krebs im Kindes- und Jugendalter. Monatsschr Kinderheilkd 2014 [Suppl 2] 162:116–203
Faber J., Spix C., Eckerle S., Henninger N., Hennewig U., Wild P.S.
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Kardiale und vaskuläre Spätfolgen von Langzeit-Überlebenden nach Krebs im Kindes- und Jugendalter: ein multidisziplinärer klinischer, epidemiologischer und genetischer Ansatz (Cardiac and vascular late sequelae in long-term survivors of childhood and adolescent cancer, CVSS) – ein Zwischenstand nach dem ersten Studienjahr. Monatsschr Kinderheilkd 2014 [Suppl 2] 162:265–273
Claudia Spix, Susan Eckerle, Nicole Henninger, Peter Scholz-Kreisel, Philipp S. Wild, Jörg Faber
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Cardiac and vascular late sequelae in long-term survivors of childhood cancer” study (CVSS): Preliminary analysis of participants and non-responders. PanCare Meeting, Dublin 27.-29.5.2015
Eckerle S, Schneider A, Henninger N, Neu MA, Wingerter A, Wild PS, Spix C, Faber J
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Cardiovascular sequelae in long-term survivors of childhood cancer study (CVSS). Strahlenther Onkol (2015) 191:687–692
S. Eckerle, N. Henninger, A. Schneider, M.A. Neu, A. Wingerter, P. Wild, C. Spix, J. Faber
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Cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS-) study - first results. PanCare meeting, Lübeck, 03.-04.10.2017
Arthur Wingerter, Jörg Faber, Astrid Schneider, Susan Eckerle, Hiltrud Merzenich, Philipp Wild
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CVSS Studie: Kardiale und vaskuläre Spätfolgen bei Langzeit-Überlebenden nach Krebs im Kindesalter. DGEPI Lübeck, 05.-08.09.2017
Astrid Schneider, Hiltrud Merzenich, Susan Eckerle, Philipp Wild, Jörg Faber, Arthur Wingerter
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Platelet-related thrombin generation in adult survivors of childhood cancer. Res Pract Thromb Haemost, 2017, (suppl. abstract PB637)
Marina Panova-Noeva, Frederic Haydl, Markus Nagler, Susan Eckerle, Miriam Michler-Abo Mustafa, Maren Paul, Dagmar-Laubert-Reh, Henri M. Spronk, Hiltrud Merzenich, Jörg Faber, Karl J. Lackner, Hugo ten Cate, Philipp S. Wild
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Prevalence of cardiovascular late sequelae in long-term survivors of childhood cancer: A systematic review and meta-analysis. Pediatr Blood Cancer. 2017 Jul;64(7)
Scholz-Kreisel P, Spix C, Blettner M, Eckerle S, Faber J, Wild P, Merzenich H, Hennewig U
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2021): Development of heart failure in long-term survivors of childhood cancer: results from the cvss study. In: European Heart Journal 42 (Supplement_1)
Göbel S, Wingerter A, Prochaska JH, Schulz A, Schneider A, Neu MA, Henninger N, Eckerle S, Spix C, Kaatsch P, Panova-Noeva M, Arnold N, Beutel M, Lackner K, Münzel T, Lam CS, Merzenich H, Faber J, Wild PS
