Role of Cancer Treatment in Long-Term Overall and Cardiovascular Mortality After Childhood Cancer

Tukenova, Markhaba; Guibout, Catherine; Oberlin, Odile; Doyon, F; Mousannif, Abdeddahir; Haddy, Nadia; Guérin, Sylvie; Pacquement, Hélène; Aouba, A.; Hawkins, Mike; Winter, Dave; Bourhis, Jean; Lefkopoulos, Dimitri; Diallo, Ibrahima; Vathaire, Florent de

doi:10.1200/jco.2008.20.2267

Cited by 403 publications

(284 citation statements)

References 38 publications

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“…23,24 Mediastinal irradiation and higher dose of anthracycline administration have been described as critical risk factors for the development of numerous cardiac complications. [25][26][27] In line with these observations, especially early onset HL survivors stood out with the highest SMRs due to cardiovascular death causes (SMR 9.2, 95% CI 3.8-14.5 and SMR 5.0, 95% CI 3.8-6.3 for childhood and YA survivors, respectively). Furthermore, the concomitant therapy with herceptin, cyclophosphamide, bleomycin, vincristine, amsacrine, mitoxantrone may contribute to an elevated risk for cardiotoxicity.…”

Section: Epidemiologysupporting

confidence: 71%

“…6,7 However, the cancer survivors as well as siblings were more likely to die from other death causes compared to the general population (SMR 2.7, 95% CI 2.3-3.1 among all cancer survivors and SMR 1.7, 95% CI 1.5-1.8 among siblings, respectively) like in earlier studies. 4,7,11,25 We chose a sibling cohort as another reference group to reduce the influence of genetic and environmental confounders when analyzing the effects of cancer and its therapy on late mortality. The markedly higher SMR due to other death causes among cancer survivors compared to siblings supports the selection of the sibling cohort to lower the impact of confounders in our analysis.…”

Section: Epidemiologymentioning

confidence: 99%

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Late mortality among 5‐year survivors of early onset cancer: A population‐based register study

Kero

Järvelä

Arola

et al. 2014

Intl Journal of Cancer

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To date, only few studies have been published documenting late mortality among early onset cancer survivors, especially regarding young adulthood (YA) malignancies. Our nation-wide population-based registry study provides information concerning cause-specific long-term mortality among 16,769 5-year survivors of early onset cancer (aged 0-34 years at diagnosis), with follow-up for death extending from 1971 through 2012. A sibling cohort and population data were used as reference. The overall standardized mortality ratio (SMR) of cancer patients was 4.6-fold, (95% CI 4.4-4.8). Highest SMRs were found for malignancies (12.8,3), infectious (4.8, 95%CI 2.9-6.7) and cardiovascular diseases (1.9, 95% CI 1.7-2.1). Malignancies and cardiovascular diseases accounted for the largest number of deaths. Childhood and YA cancer survivors with the same primary cancer site had a similarly elevated overall SMR with the exception of markedly higher SMRs after childhood Hodgkin lymphoma. The highest cumulative non-malignancy-related mortality was due to cardiovascular disease with a steady rise throughout the follow-up, but strongly dependent on the primary cancer site and age at diagnosis. In childhood cancer survivors, the cumulative cardiovascular mortality did not reduce over time. However, overall and malignancyrelated mortality showed a declining tendency towards the most recent periods after both, childhood and YA cancer. Our findings on non-malignancy-related mortality stress the need to set up long-term individual follow-up with a focus on cardiovascular late effects for early onset cancer survivors, especially for YA cancer survivors still lacking those.Advances in therapies for early onset cancer have lead to a substantial increase in 5-year survival rates. 1-3 Thus far the main focus of late effect research has been on the morbidity and mortality of childhood cancer survivors aged up to 21 years at cancer diagnosis. [4][5][6][7][8][9] Only few studies have investigated those topics for the survivors of young adult (YA) cancer patients aged from 20 to 34 years at cancer diagnosis. [10][11][12] Previous studies have found elevated risks for chronic health conditions which contribute to higher mortality among survivors of childhood cancer patients compared to the general population. 5,9,13,14 Patterns of increased excess mortality after childhood cancer have been shown to be dependent on time from cancer diagnosis and cause of death. 4,7,11 The success of improved cancer survival is overshadowed by the life-threatening chronic health outcomes that cancer survivors are more likely to suffer from. Thus, the growing population of early onset cancer survivors has a strong need for adequate individualized follow-up to detect and possibly reduce treatment-related morbidities and mortality. 15 After the survival of childhood cancer, the adoption of a healthy lifestyle including physical activity may lower especially the risk of developing late cardiovascular sequelae. 16 Thus, promoting the control of known cardiovascular risk fa...

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Section: Epidemiologysupporting

confidence: 71%

Section: Epidemiologymentioning

confidence: 99%

Late mortality among 5‐year survivors of early onset cancer: A population‐based register study

Kero

Järvelä

Arola

et al. 2014

Intl Journal of Cancer

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“…The mechanisms relevant for lower doses are likely to differ from those relevant at higher (e.g., radiotherapeutic) doses. However, risks in studies of medically-exposed groups, with relevant organ doses usually well above 0.5 Gy, are generally consistent with those in populations exposed at the much lower doses and dose rates discussed above [3][4][5][6]44], suggesting that mechanisms operating at high doses and high dose rates may be similar to those at low doses and dose rates. The fact that the IHD risks using mean heart dose in these high-dose/partial-body exposed groups are similar to the risks in the generally uniformly whole-body-exposed groups using whole-body dose discussed above ( Table 7) also suggests that mean dose to the heart is the most relevant metric for predicting radiation-associated IHD [44].…”

Section: Discussionmentioning

confidence: 55%

“…Therapeutic doses of ionizing radiation to the heart and large arteries are associated with various types of circulatory disease [3][4][5][6]. More recently, and controversially, studies on several groups exposed to low-to-moderate doses of radiation have reported excess mortality and morbidity from circulatory diseases, in particular the Life Span Study (LSS) of Japanese atomic bomb survivors [7] and several occupationally exposed cohorts [8].…”

Section: Introductionmentioning

confidence: 99%

Circulatory disease mortality in the Massachusetts tuberculosis fluoroscopy cohort study

et al. 2015

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High-dose ionizing radiation is associated with circulatory disease. Risks from lower-dose fractionated exposures, such as from diagnostic radiation procedures, remain unclear. In this study we aimed to ascertain the relationship between fractionated low-to-medium dose radiation exposure and circulatory disease mortality in a cohort of 13,568 tuberculosis patients in Massachusetts, some with fluoroscopy screenings, between 1916 and 1961 and follow-up until the end of 2002. Analysis of mortality was in relation to cumulative thyroid (cerebrovascular) or lung (all other circulatory disease) radiation dose via Poisson regression. Over the full dose range, there was no overall radiation-related excess risk of death from circulatory disease (n = 3221; excess relative risk/Gy -0.023; 95 % CI -0.067, 0.028; p = 0.3574). Risk was somewhat elevated in hypertensive heart disease (n = 89; excess relative risk/Gy 0.357; 95 % CI -0.043, 1.030, p = 0.0907) and slightly decreased in ischemic heart dis-ease (n = 1950; excess relative risk/Gy -0.077; 95 % CI -0.130, -0.012; p = 0.0211). However, under 0.5 Gy, there was a borderline significant increasing trend for all circulatory disease (excess relative risk/Gy 0.345; 95 % CI -0.032, 0.764; p = 0.0743) and for ischemic heart disease (excess relative risk/Gy 0.465; 95 % CI, -0.032, 1.034, p = 0.0682). Pneumolobectomy increased radiation-associated risk (excess relative risk/Gy 0.252; 95 % CI 0.024, 0.579). Fractionation of dose did not modify excess risk. In summary, we found no evidence of radiation-associated excess circulatory death risk overall, but there are indications of excess circulatory death risk at lower doses (<0.5 Gy). Although consistent with other radiation-exposed groups, the indications of higher risk at lower doses are unusual and should be confirmed against other data.

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“…Such studies have the merit of following up large cohorts of patients treated for different tumors with different therapies in different periods of time. They usually rely on information through national health registries [11,16]. Causes of death are consequently grouped according to general classifications, that is, diseases of the cardiovascular or respiratory system, making it impossible to go into more detail.…”

Section: Discussionmentioning

confidence: 99%

Long‐term results in childhood rhabdomyosarcoma: A report from the Italian cooperative study RMS 79

Bisogno

Pastore

Perilongo

et al. 2011

Pediatric Blood & Cancer

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BackgroundThe results obtained by protocols for children with rhabdomyosarcoma (RMS) have improved in recent decades. Survival curves usually reach a plateau 3 years after the diagnosis, suggesting that long‐term survival can be expected, but late events are known to occur. We analyzed the long‐term results of the RMS 79 protocol to investigate the type and impact of such events.ProcedureFrom 1979 to 1987, 163 children with RMS diagnosed at 21 Italian institutions were registered. Each institution was contacted every year to record patients' status after the end of treatment. When patients were lost to follow‐up, their status was checked by inquiring at the Registry Offices of the towns of residence and the cause of death or occurrence of second cancers was investigated by contacting the patients or their family by phone.ResultsOverall, 16 patients had late events, that is, 7 tumor recurrences, 6 second tumors, and 3 deaths due to treatment‐related complications. The overall survival rates dropped from 62.6 at 3 years to 52.8 at 20 years. By multivariate analysis, the characteristics influencing long‐term survival were histology, tumor site and size, and IRS group. Factors predictive of any kind of late event were tumor site and IRS group.ConclusionsMajor late events can significantly affect the long‐term survival of children with RMS. Modern protocols should provide for a much longer follow‐up than is usually considered to confirm the results achieved and enable possible correlations between primary treatment and late events to be investigated. Pediatr Blood Cancer 2012; 58: 872–876. © 2011 Wiley Periodicals, Inc.

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Role of Cancer Treatment in Long-Term Overall and Cardiovascular Mortality After Childhood Cancer

Cited by 403 publications

References 38 publications

Late mortality among 5‐year survivors of early onset cancer: A population‐based register study

Late mortality among 5‐year survivors of early onset cancer: A population‐based register study

Circulatory disease mortality in the Massachusetts tuberculosis fluoroscopy cohort study

Long‐term results in childhood rhabdomyosarcoma: A report from the Italian cooperative study RMS 79

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