Age at exposure and attained age variations of cancer risk in the Japanese A‐bomb and radiotherapy cohorts

Schneider, Uwe; Walsh, Linda

doi:10.1118/1.4927062

Cited by 6 publications

(3 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the LSS alone, the preferred ERR model was dependent on attained age, but essentially independent on age at exposure after correcting for attained age (Preston et al 2007 ; Brenner et al 2018 ). Comparing different RT studies, Schneider and Walsh ( 2015 ) found a decreasing risk with increasing age at exposure; however, no data were available for persons with age at exposure of 50 years or older. A more detailed discussion on these points can be found in Eidemüller et al ( 2021 ) and the corresponding supplement.…”

Section: Discussionmentioning

confidence: 99%

Estimating long-term health risks after breast cancer radiotherapy: merging evidence from low and high doses

Simonetto

Wollschläger

Kundrát

et al. 2021

Radiat Environ Biophys

View full text Add to dashboard Cite

In breast cancer radiotherapy, substantial radiation exposure of organs other than the treated breast cannot be avoided, potentially inducing second primary cancer or heart disease. While distant organs and large parts of nearby ones receive doses in the mGy–Gy range, small parts of the heart, lung and bone marrow often receive doses as high as 50 Gy. Contemporary treatment planning allows for considerable flexibility in the distribution of this exposure. To optimise treatment with regards to long-term health risks, evidence-based risk estimates are required for the entire broad range of exposures. Here, we thus propose an approach that combines data from medical and epidemiological studies with different exposure conditions. Approximating cancer induction as a local process, we estimate organ cancer risks by integrating organ-specific dose–response relationships over the organ dose distributions. For highly exposed organ parts, specific high-dose risk models based on studies with medical exposure are applied. For organs or their parts receiving relatively low doses, established dose–response models based on radiation-epidemiological data are used. Joining the models in the intermediate dose range leads to a combined, in general non-linear, dose response supported by data over the whole relevant dose range. For heart diseases, a linear model consistent with high- and low-dose studies is presented. The resulting estimates of long-term health risks are largely compatible with rate ratios observed in randomised breast cancer radiotherapy trials. The risk models have been implemented in a software tool PASSOS that estimates long-term risks for individual breast cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Estimating long-term health risks after breast cancer radiotherapy: merging evidence from low and high doses

Simonetto

Wollschläger

Kundrát

et al. 2021

Radiat Environ Biophys

View full text Add to dashboard Cite

show abstract

“…For the definition of the risk profiles and baseline risk calculation (Table 1), we followed Brenner et al [24] for major coronary events and the risk prediction formula from Bach et al [25] for baseline risks of lung cancer. Regarding secondary contralateral BC, radiation-induced secondary BC is assumed to be mainly relevant for exposure at younger ages [26-28]. Therefore, an intermediate 10-year baseline risk was estimated for a woman aged 40 years using the Tyrer-Cuzick model [29].…”

Section: Methodsmentioning

confidence: 99%

Mammary Chain Irradiation in Left-Sided Breast Cancer: Can We Reduce the Risk of Secondary Cancer and Ischaemic Heart Disease with Modern Intensity-Modulated Radiotherapy Techniques?

et al. 2020

View full text Add to dashboard Cite

Introduction: The aim of the present study was to estimate the impact of the addition of internal mammary chain (IMC) irradiation in node-positive left-sided breast cancer (BC) patients undergoing regional nodal irradiation (RNI) and comparatively evaluate excess relative and absolute risks of radiation-induced lung cancer/BC and ischaemic heart disease for intensity-modulated radiotherapy (IMRT) versus 3D conformal radiotherapy (3D-CRT). Methods: Four treatment plans were created (3D-CRT and IMRT –/+ IMC) for each of the 10 evaluated patients, and estimates of excess relative risk (ERR) and 10-year excess absolute risk (EAR) were calculated for radiation-induced lung cancer/BC and coronary events using linear, linear-exponential and plateau models. Results: The addition of IMC irradiation to RNI signiﬁcantly increased the dose exposure of the heart, lung and contralateral breast using both techniques, increasing ERR for secondary lung cancer (58 vs. 44%, p = 0.002), contralateral BC (49 vs. 31%, p = 0.002) and ischaemic heart disease (41 vs. 27%, p = 0.002, IMRT plans). IMRT signiﬁcantly reduced the mean cardiac dose and mean lung dose as compared to 3D-CRT, decreasing ERR for major coronary events (64% 3D-CRT vs. 41% IMRT, p = 0.002) and ERR for secondary lung cancer (75 vs. 58%, p = 0.004) in IMC irradiation, without a significant impact on secondary contralateral BC risks. Conclusion: Although IMC irradiation has been shown to increase survival rates in node-positive BC patients, it increased dose exposure of organs at risk in left-sided BC, resulting in significantly increased risks for secondary lung cancer/contralateral BC and ischaemic heart disease. In this setting, the adoption of IMRT seems advantageous when compared to 3D-CRT.

show abstract

“…However, how complexity of the initial lesion impacts down-stream events that inform cancer susceptibility in old vs. young individuals has not been defined. Breast cancer risk appears to decrease with increasing age of radiation exposure not only for A bomb survivors but also for radiotherapy cohorts [7]. The mechanistic underpinnings of these age-related differences in radiation-induced breast cancer susceptibility are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Lesion complexity drives age related cancer susceptibility in human mammary epithelial cells

Sridharan

Enerio

LaBarge

et al. 2017

Aging

View full text Add to dashboard Cite

Exposures to various DNA damaging agents can deregulate a wide array of critical mechanisms that maintain genome integrity. It is unclear how these processes are impacted by one's age at the time of exposure and the complexity of the DNA lesion. To clarify this, we employed radiation as a tool to generate simple and complex lesions in normal primary human mammary epithelial cells derived from women of various ages. We hypothesized that genomic instability in the progeny of older cells exposed to complex damages will be exacerbated by age-associated deterioration in function and accentuate age-related cancer predisposition. Centrosome aberrations and changes in stem cell numbers were examined to assess cancer susceptibility. Our data show that the frequency of centrosome aberrations proportionately increases with age following complex damage causing exposures. However, a dose-dependent increase in stem cell numbers was independent of both age and the nature of the insult. Phospho-protein signatures provide mechanistic clues to signaling networks implicated in these effects. Together these studies suggest that complex damage can threaten the genome stability of the stem cell population in older people. Propagation of this instability is subject to influence by the microenvironment and will ultimately define cancer risk in the older population.

show abstract

Age at exposure and attained age variations of cancer risk in the Japanese A‐bomb and radiotherapy cohorts

Cited by 6 publications

References 45 publications

Estimating long-term health risks after breast cancer radiotherapy: merging evidence from low and high doses

Estimating long-term health risks after breast cancer radiotherapy: merging evidence from low and high doses

Mammary Chain Irradiation in Left-Sided Breast Cancer: Can We Reduce the Risk of Secondary Cancer and Ischaemic Heart Disease with Modern Intensity-Modulated Radiotherapy Techniques?

Lesion complexity drives age related cancer susceptibility in human mammary epithelial cells

Contact Info

Product

Resources

About