New insights into the risk of breast cancer in childhood cancer survivors treated with chest radiation: A report from the Childhood Cancer Survivor Study (CCSS) and the Women's Environmental Cancer and Radiation Epidemiology(WECARE) Study.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. CRA9513-CRA9513 ◽  
Author(s):  
Chaya S. Moskowitz ◽  
Joanne F. Chou ◽  
Suzanne L. Wolden ◽  
Jonine L. Bernstein ◽  
Jyoti Malhotra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cumulative Incidence ◽  
Childhood Cancer Survivors ◽  
Population Based ◽  
Cancer Surveillance ◽  
Brca1 And Brca2 ◽  
First Degree Relatives ◽  
Mutation Carriers

CRA9513 Background: The risk of breast cancer (BC) by age 50 among women treated for childhood cancer with chest radiation therapy (RT) and how this risk compares with that of BRCA1 and BRCA2 (BRCA1/2) mutation carriers is unknown. Methods: We evaluated the risk of BC in a cohort of 1268 female 5-yr childhood cancer survivors treated with chest RT and estimated the cumulative incidence of BC non-parametrically treating death as a competing risk. The cumulative incidence of BC in BRCA1/2 mutation carriers was estimated with the kin-cohort method using data from 4570 female first-degree relatives of women diagnosed with unilateral BC (probands) participating in the WECARE Study. Absolute Excess Risks (AERs) were estimated using population-based data from the SEER program. Results: With a median follow-up of 26 yrs (range 5-39) for the CCSS cohort, 175 women were diagnosed with BC at a median age of 38 yrs (range 24-53) and a median latency of 23 yrs (range 7-38); the overall cumulative incidence of BC by age 50 was 24% (95% confidence interval [CI] 20-28%) and among Hodgkin lymphoma survivors was 30% (95% CI 25-35%). In comparison, among first-degree relatives of WECARE Study probands 324 were diagnosed with BC (median age at diagnosis, 55 yrs (range 26-90)). The estimated cumulative incidence by age 50 was 31% (95% CI 16-47%) and 10% (95% CI 2-23%) in carriers of BRCA1 and BRCA2 mutations, respectively. The population cumulative incidence of BC is 4% by age 50. Among the childhood cancer survivors, AERs for BCs diagnosed per 10,000 person-years of observation were respectively 34 (95% CI 18-52), 27 (95% CI 11-45), and 95 (95% CI 78-112) among women treated with 10-19 Gy (23%), 20-29 Gy (17%), and 30+ Gy (56%) of chest RT. Conclusions: Women treated for childhood cancer with chest RT have a substantial risk of BC comparable to BRCA1/2 mutation carriers and considerably greater than that of the general population. Women treated with 10-19 Gy RT had an increased excess risk warranting consideration of breast cancer surveillance strategies similar to the current recommendations for women treated with > 20 Gy.

Incidence and predictors of significant hearing loss requiring hearing assistive devices among childhood cancer survivors: A population-based study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10055-10055
Author(s):  
Sumit Gupta ◽  
Cindy Lau ◽  
Bonnie Cooke ◽  
Stephen Hall ◽  
Paul C. Nathan ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cumulative Incidence ◽  
Childhood Cancer Survivors ◽  
Population Based ◽  
Assistive Devices ◽  
Healthcare Data ◽  
High Risk Populations ◽  
Treatment Predictors

10055 Background: Though hearing loss is a significant late effect among childhood cancer survivors, recent guidelines note insufficient evidence to quantify natural history or risk associated with specific exposures. We examined the long-term incidence and predictors of hearing loss requiring hearing amplification devices (HAD) using population-based healthcare data. Methods: In Ontario, Canada, HAD costs are subsidized by the provincial Assistive Devices Program (ADP). Ontario children age <18 years at cancer diagnosis between 1987-2016 were identified using a pediatric cancer registry and linked to ADP claims. The cumulative incidence of HAD use was compared between cases and matched controls. Patient, disease, and treatment predictors of HAD were examined. Results: We identified 11,842 cases and 59,210 matched controls. Cases were at higher risk of HAD [hazard ratio (HR) 12.8, 95% confidence interval (95CI) 9.8-16.7; p<0.001]. The cumulative incidence of HAD among survivors was 2.1% (95CI 1.7-2.5%) at 20-years and 6.4% (95CI 2.8-12.1%) at 30-years. 30-year incidence was highest in survivors of neuroblastoma (10.7%, 95CI 3.8-21.7%) and hepatoblastoma (16.2%, 95CI 8.6-26.0%). Predictors of HAD in multivariable analyses included age 0-4 years at diagnosis (vs. 5-9 years, HR 2.2, 95CI 1.4-3.3; p<0.001). Relative to no cisplatin exposure, patients receiving 1-200mg/m2 were not at greater risk, unlike those receiving higher cumulative doses (Table). Relative to no radiation, those receiving ≤32Gy were at no higher risk, unlike while those receiving >32Gy. Carboplatin exposure was not associated with HAD. Conclusions: Childhood cancer survivors are at elevated risk of requiring HAD which continues to rise between 20 and 30 years from diagnosis. Thresholds of cisplatin and radiation exposure exist above which risk substantially increases. Prolonged monitoring and trials of otoprotective agents are warranted in high-risk populations. [Table: see text]

scholarly journals Second primary breast cancer in BRCA1 and BRCA2 mutation carriers: 10-year cumulative incidence in the Breast Cancer Family Registry

2015 ◽  
Vol 151 (3) ◽  
pp. 653-660 ◽  
Author(s):  
Tehillah S. Menes ◽  
Mary Beth Terry ◽  
David Goldgar ◽  
Irene L. Andrulis ◽  
Julia A. Knight ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cumulative Incidence ◽  
Primary Breast Cancer ◽  
Brca2 Mutation ◽  
Second Primary ◽  
Brca1 And Brca2 ◽  
Breast Cancer Family ◽  
Cancer Family ◽  
Mutation Carriers

Genetic and treatment risks for diabetes mellitus (DM) in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS) and St. Jude Lifetime (SJLIFE) cohorts.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10014-10014
Author(s):  
Melissa A. Richard ◽  
Sogol Mostoufi-Moab ◽  
Nisha Rathore ◽  
Austin L. Brown ◽  
Stephen J. Chanock ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Cancer Treatment ◽  
Childhood Cancer ◽  
Regulatory Region ◽  
Childhood Cancer Survivors ◽  
Population Based ◽  
European Ancestry ◽  
Radiation Group ◽  
Increased Risk

10014 Background: Childhood cancer survivors face increased risk for DM, a polygenic trait also attributable to cancer treatment exposures, particularly abdominal radiation. We aimed to characterize the role of genetic and treatment risk factors for DM among two large cohorts of childhood cancer survivors. Methods: We performed a nested case-control genome-wide association study for DM managed with oral medications in the original CCSS cohort (diagnosed 1970-1986). Logistic regression was conducted in the total sample (N = 5083) and stratified by 1) European ancestry (EA) and 2) abdominal radiation. Replication of suggestive variants (P < 1×10-7) using Fisher’s exact test was performed in independent cohorts: i) CCSS expansion diagnosed 1987-1999 (N = 2588) and ii) SJLIFE diagnosed 1962-2012 (N = 2182). To evaluate the effect of cancer treatment on the background genetic predisposition to DM, we estimated standardized effect sizes (Z’) among EA survivors in each abdominal radiation group for 398 index variants from the largest population-based EA DM study. Radiation group Z’ estimates were compared using linear regression. Results: In the original CCSS cohort we identified nine variants associated with DM and provide further support for four linked variants in the ERCC6L2 locus. Among all survivors, the rs55849673-A allele was associated with increased odds for DM among survivors in the original CCSS cohort (minor allele frequency [MAF]-cases = 0.055; MAF-controls = 0.024; adjusted odds ratio [aOR] = 2.9, 95% CI: 2.0-4.2, P = 3.7×10-8). Allele frequencies were consistent in the CCSS expansion (MAF-cases = 0.075; MAF-controls = 0.028; P = 0.07) and SJLIFE (MAF-cases = 0.036; MAF-controls = 0.027; P = 0.5). Additionally, rs55849673-A estimates were consistent among EA survivors and stronger among survivors not treated with abdominal radiation (MAF-cases = 0.052; MAF-controls = 0.021; aOR = 3.6, P = 1.6×10-6). Notably, in the CCSS expansion all rs55849673-A EA carriers who developed DM did not receive abdominal radiation (MAF-cases = 0.1; MAF-controls = 0.026; P = 0.04). More broadly, the Z’ of population-based DM index variants were 78% lower in survivors treated with abdominal radiation than survivors not treated with abdominal radiation (beta = 0.22; P = 0.01), indicating the background genetic risk for DM may be altered by treatment. Conclusions: We provide evidence for a novel locus of DM in childhood cancer survivors. This locus is a regulatory region associated with expression of ERCC6L2, a gene implicated in an East Asian population-based DM study. Taken together, our findings support the overwhelming effect of abdominal radiation on DM risk in childhood cancer survivors, relative to other risk factors, and provide insight on a genetic locus that may be useful for DM risk prediction in the context of cancer treatment.

scholarly journals Mortality After Breast Cancer Among Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

2019 ◽  
Vol 37 (24) ◽  
pp. 2120-2130 ◽  
Author(s):  
Chaya S. Moskowitz ◽  
Joanne F. Chou ◽  
Joseph P. Neglia ◽  
Ann H. Partridge ◽  
Rebecca M. Howell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cancer Survivor ◽  
De Novo ◽  
Childhood Cancer Survivors ◽  
Childhood Cancer Survivor ◽  
Malignant Neoplasms ◽  
Childhood Cancer Survivor Study ◽  
Survivors Of Childhood Cancer

PURPOSE Female survivors of childhood cancer have a high risk of subsequent breast cancer. We describe the ensuing risk for mortality and additional breast cancers. PATIENTS AND METHODS Female participants in the Childhood Cancer Survivor Study, a cohort of 5-year survivors of cancer diagnosed between 1970 and 1986 before age 21 years, and subsequently diagnosed with breast cancer (n = 274; median age at breast cancer diagnosis, 38 years; range, 20 to 58 years) were matched to a control group (n = 1,095) with de novo breast cancer. Hazard ratios (HRs) and 95% CIs were estimated from cause-specific proportional hazards models. RESULTS Ninety-two childhood cancer survivors died, 49 as a result of breast cancer. Overall survival after breast cancer was 73% by 10 years. Subsequent risk of death as a result of any cause was higher among childhood cancer survivors than among controls (HR, 2.2; 95% CI, 1.7 to 3.0) and remained elevated after adjusting for breast cancer treatment (HR, 2.4; 95% CI, 1.7 to 3.2). Although breast cancer–specific mortality was modestly elevated among childhood cancer survivors (HR, 1.3; 95% CI, 0.9 to 2.0), survivors were five times more likely to die as a result of other health-related causes, including other subsequent malignant neoplasms and cardiovascular or pulmonary disease (HR, 5.5; 95% CI, 3.4 to 9.0). The cumulative incidence of a second asynchronous breast cancer also was elevated significantly compared with controls ( P < .001). CONCLUSION Mortality after breast cancer was higher in childhood cancer survivors than in women with de novo breast cancer. This increased mortality reflects the burden of comorbidity and highlights the need for risk-reducing interventions.

scholarly journals Incidence of Influenza Among Childhood Cancer Survivors in South Korea: A Population-based Retrospective Analysis

In Vivo ◽  
2020 ◽  
Vol 34 (2) ◽  
pp. 929-933 ◽  
Author(s):  
JAESUNG HEO ◽  
HYUN JOO JUNG ◽  
O KYU NOH ◽  
LOGYOUNG KIM ◽  
JUN EUN PARK
Keyword(s):  
South Korea ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Retrospective Analysis ◽  
Childhood Cancer Survivors ◽  
Population Based

Neuromuscular dysfunction and associated health/socioeconomic outcomes: A report from the Childhood Cancer Survivor Study (CCSS).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10546-10546
Author(s):  
Rozalyn L Rodwin ◽  
Yan Chen ◽  
Yutaka Yasui ◽  
Wendy M. Leisenring ◽  
Todd M. Gibson ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cumulative Incidence ◽  
Childhood Cancer Survivors ◽  
Soft Tissue Tumors ◽  
Motor Dysfunction ◽  
Vinca Alkaloids ◽  
Socioeconomic Outcomes ◽  
Neuromuscular Dysfunction

10546 Background: Childhood cancer survivors are at risk for neuromuscular dysfunction. We estimated the prevalence and cumulative incidence of neuromuscular dysfunction in a cohort of childhood cancer survivors and examined associations with treatment exposures and health/socioeconomic outcomes. Methods: CCSS participants ≥5 years from cancer diagnosed between 1970-1999 (n = 25,583, 46.5% female, median [range] age 54.4 [15.1-57.6] years) and siblings (n = 5,044, 52.3% female, median [range] age 54.1 [32.5-57.0] years) were included. Neuromuscular dysfunction was identified by self-report of 1) motor dysfunction: impaired balance, tremor, or extremity weakness; 2) sensory dysfunction: impaired touch sensation. Multivariable analyses examined predictors of dysfunction by diagnosis. Results: Cumulative incidence of neuromuscular dysfunction was elevated at 20 years from diagnosis in survivors (24.3%, 95% CI 23.8-24.8; motor 18.2%, sensory 13.5%) versus siblings (8.9%, 95% CI 8.1-9.7). In survivors five years from diagnosis, motor dysfunction was associated with exposure to cytarabine (OR = 1.39, 95% CI 1.10-1.77) and spinal radiation (OR = 2.11, 95% CI 1.31-3.41) in acute lymphoblastic leukemia/non-hodgkin lymphoma (ALL/NHL), vinca alkaloids (OR 1.29, 95% CI 1.03-1.60) and brain radiation (OR = 1.58, 95% CI 1.35-1.85) in central nervous system tumors, and cytarabine (OR = 3.73, 95% CI 1.62-8.57) and non-brain/spine radiation (OR = 1.84, 95% CI 1.42-2.40) in bone/soft tissue tumors. Sensory dysfunction was associated with exposure to vinca alkaloids (OR = 3.45, 95% CI 1.06-11.22) in ALL/NHL, and platinum agents (OR = 1.31, 95% CI 1.03-1.67) and spinal radiation (OR = 3.71, 95% CI 1.24-11.11) in bone/soft tissue tumors. Survivors with neuromuscular dysfunction were at increased risk for adverse health/socioeconomic outcomes (Table). Conclusions: Neuromuscular dysfunction is a prevalent morbidity in childhood cancer survivors, associated with specific therapies within a particular diagnosis. Interventions are needed to identify and improve neuromuscular dysfunction given its association with adverse health/socioeconomic outcomes. [Table: see text]

Diabetes Risk in Childhood Cancer Survivors: A Population-Based Study

2018 ◽  
Vol 42 (5) ◽  
pp. 533-539 ◽  
Author(s):  
Iliana C. Lega ◽  
Jason D. Pole ◽  
Peter C. Austin ◽  
Cindy Lau ◽  
Paul C. Nathan ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Childhood Cancer Survivors ◽  
Population Based ◽  
Diabetes Risk ◽  
Population Based Study

scholarly journals Increased risk of cardiac ischaemia in a pan-European cohort of 36 205 childhood cancer survivors: a PanCareSurFup study

Heart ◽  
2020 ◽  
Vol 107 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Elizabeth Arnoldina Maria Feijen ◽  
Elvira C van Dalen ◽  
Heleen J H van der Pal ◽  
Raoul C Reulen ◽  
David L Winter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Childhood Cancer Survivors ◽  
Cardiac Ischaemia ◽  
Number Of Patients ◽  
Increased Risk

ObjectiveIn this report, we determine the cumulative incidence of symptomatic cardiac ischaemia and its risk factors among European 5-year childhood cancer survivors (CCS) participating in the PanCareSurFup study.MethodsEight data providers (France, Hungary, Italy (two cohorts), the Netherlands, Slovenia, Switzerland and the UK) participating in PanCareSurFup ascertained and validated symptomatic cardiac events among their 36 205 eligible CCS. Data on symptomatic cardiac ischaemia were graded according to the Criteria for Adverse Events V.3.0 (grade 3–5). We calculated cumulative incidences, both overall and for different subgroups based on treatment and malignancy, and used multivariable Cox regression to analyse risk factors.ResultsOverall, 302 out of the 36 205 CCS developed symptomatic cardiac ischaemia during follow-up (median follow-up time after primary cancer diagnosis: 23.0 years). The cumulative incidence by age 60 was 5.4% (95% CI 4.6% to 6.2%). Men (7.1% (95% CI 5.8 to 8.4)) had higher rates than women (3.4% (95% CI 2.4 to 4.4)) (p<0.0001). Of importance is that a significant number of patients (41/302) were affected as teens or young adults (14–30 years). Treatment with radiotherapy/chemotherapy conferred twofold risk (95% CI 1.5 to 3.0) and cases in these patients appeared earlier than in CCS without treatment/surgery only (15% vs 3% prior to age 30 years, respectively (p=0.04)).ConclusionsIn this very large European childhood cancer cohort, we found that by age 60 years, 1 in 18 CCS will develop a severe, life-threatening or fatal cardiac ischaemia, especially in lymphoma survivors and CCS treated with radiotherapy and chemotherapy increases the risk significantly.

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