Neurocognitive outcomes in survivors of early adolescent and young adult (eAYA) hematologic cancers from the Childhood Cancer Survivor Study (CCSS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10029-10029
Author(s):  
Amy Yuan Wang ◽  
Yan Chen ◽  
Yutaka Yasui ◽  
Wendy Stock ◽  
Wendy M. Leisenring ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
General Health ◽  
Neurocognitive Impairment ◽  
Childhood All ◽  
Poor General Health ◽  
Hematologic Cancer ◽  
Diagnosis Group ◽  
Childhood Survivors

10029 Background: Neurocognitive impairment in eAYA hematologic cancer survivors has not been well described, despite intensive neurotoxic therapies. We examined prevalence and risk for such impairment in hematologic cancer survivors diagnosed during eAYA compared to a younger age. Methods: We identified 1,213 eAYA (diagnosed at 15-21 years; median [range] follow-up age 40 [30-54]) and 4,538 childhood (diagnosed at <15 years; median age 30 [17-48]) survivors of ALL (n= 301 vs 3274), AML (n= 77 vs 424), and Hodgkin lymphoma (HL; n= 835 vs 840) from the CCSS (diagnosed 1970-1999) who completed the Neurocognitive Questionnaire. Impairment was defined as a score >90% of normative data in task efficiency (TE), organization (Org), memory (Mem), and emotional regulation (ER) domains. 1,014 age-matched siblings were controls. Treatment by diagnosis group, chronic health conditions, health status and health behaviors were examined as risk factors for neurocognitive impairment using multivariable logistic regression. Adjusted odds ratios (ORs) and corresponding 95% CI are reported. Results: Prevalence of neurocognitive impairment (≥1 impaired domain) was similar for eAYAs and childhood survivors of HL (31.0% vs 29.6%, p=0.54) and AML (36.4% vs 40.3%, p=0.51), although eAYA AML survivors were more likely to have impaired Mem (OR=2.3, 95% CI 1.0-5.4). eAYA ALL survivors were less likely to have neurocognitive impairment than childhood ALL survivors (28.2% vs 38.5%, p<.001) due to lower risk for impaired TE (OR=0.7, 95% CI 0.4-1.0) and Org (OR=0.5, 95% CI 0.4-0.9). No factors, including cranial radiation (RT), explained the rate differences. Treatment by diagnosis group (including cranial RT in ALL, chest RT in HL, and salvage therapy use) was not consistently associated with neurocognitive impairment in eAYA survivors. However, anthracycline dose ≥120mg/m2 was a risk factor for impaired ER (OR=6.0, 95% CI 2.0-17.9) only in eAYA ALL survivors. Presence of a neurologic health condition was associated with impairment in all 4 domains in eAYA (ORs ranged 1.7-2.9) and childhood cancer survivors (ORs ranged 1.9-5.3). eAYA survivors with a respiratory condition were more likely to have impaired TE (OR=2.1, 95% CI 1.2-3.8). Being in good general health was associated with less impairment across all 4 domains for eAYA (ORs ranged 0.2-0.4) and childhood survivors (ORs ranged 0.3-0.5). eAYA survivors who never smoked were less likely to have impaired ER (OR=0.4, 95% CI 0.2-0.6) than those who smoke. Conclusions: Survivors of hematologic cancers diagnosed during eAYA are susceptible to neurocognitive impairment at rates similar to those diagnosed at younger ages. Having comorbidities and being in fair/poor general health are risk factors for impairment. Higher anthracycline exposure in ALL survivors diagnosed during eAYA was the only therapy associated with impairment rates.

scholarly journals Validation of questionnaire-reported chest wall abnormalities with a telephone interview in Swiss childhood cancer survivors

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rahel Kasteler ◽  
Christa Lichtensteiger ◽  
Christina Schindera ◽  
Marc Ansari ◽  
Claudia E. Kuehni ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Chest Wall ◽  
Daily Life ◽  
Well Being ◽  
Childhood Cancer Survivors ◽  
Thoracic Wall ◽  
Medical Attention ◽  
The Impact

Abstract Background Chest wall abnormalities are a poorly studied complication after treatment for childhood cancer. Chest wall abnormalities are not well-described in the literature, and little is known on the impact on daily life of survivors. Methods We investigated prevalence and risk factors of chest wall abnormalities in childhood cancer survivors in a nationwide, population-based cohort study (Swiss Childhood Cancer Survivor Study) with a questionnaire survey. We then interviewed a nested sample of survivors to validate types of chest wall abnormalities and understand their impact on the daily life of survivors. Results Forty-eight of 2382 (95%CI 2–3%) survivors reported a chest wall abnormality. Risk factors were older age at cancer diagnosis (16–20 years; OR 2.5, 95%CI 1.0–6.1), lymphoma (OR 3.8, 95%CI 1.2–11.4), and central nervous system tumors (OR 9.5, 95%CI 3.0–30.1) as underlying disease, and treatment with thoracic radiotherapy (OR 2.0, 95%CI 1.0–4.2), surgery to the chest (OR 4.5, 95%CI 1.8–11.5), or chemotherapy (OR 2.9, 95%CI 1.0–8.1). The nature of the chest wall abnormalities varied and included thoracic wall deformities (30%), deformations of the spine (5%) or both (55%), and scars (10%). Chest wall abnormalities affected daily life in two thirds (13/20) of those who reported these problems and necessitated medical attention for 15 (75%) survivors. Conclusion It is important that, during follow-up care, physicians pay attention to chest wall abnormalities, which are rare late effects of cancer treatment, but can considerably affect the well-being of cancer survivors.

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.

New insights in cisplatin and radiation-induced ototoxicity: A French Childhood Cancer Survivors Study (FCCSS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10061-10061 ◽  
Author(s):  
Brice Fresneau ◽  
Felicia Santos ◽  
Rodrigue Allodji ◽  
Chiraz Fayech ◽  
Stephanie Bolle ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Inner Ear ◽  
Hearing Aids ◽  
Social Deprivation ◽  
Childhood Cancer Survivors ◽  
Solid Cancer ◽  
Cranial Radiotherapy

10061 Background: Platinum chemotherapy (CT) and cranial radiotherapy (RT) are risk factors of ototoxicity. Effects of RT dose at inner ear and of other CT were investigated. Methods: Of 7670 5-year childhood cancer survivors from the FCCSS treated before 20 years of age in 1942-2000 for solid cancer or lymphoma, 5243 with ototoxicity long-term follow-up data were included. Severe ototoxicity, defined as the need of hearing aids or Brock grade 3-4 hearing loss, was identified from self-administrated questionnaires, clinical visits and cohort linkage with the French Hospital Database and health insurance information system (SNIIRAM). The mean RT dose at inner ear was estimated using home-made software. Multivariable Cox models adjusted for gender, age at diagnosis, time period and social deprivation index was used to identify risk factors for severe ototoxicity. Results: After a mean follow-up of 30 years, 199 cases of severe ototoxicity were identified. Cumulative incidences at 30 and 50 years of age (30,50y-CumInc) were, 2.8% (95%CI = 2.4-3.3) and 5.5% (4.6-6.5), respectively. Mean RT dose at inner ear (Hazard Ratio HR = 1.6 (95%CI = 1.0-2.5), 4.5 (2.7-7.2), 5.7 (3.0-10.8) and 14.0 (9.2-21.2) for 0- < 5, 5- < 30, 30- < 40 and ≥40 Gy), as well as cisplatin (HR = 2.8, 95%CI = 1.9-4.0), melphalan (HR = 3.3, 95%CI = 1.9-5.7) and busulfan exposure (HR = 2.6, 95%CI = 1.6-4.4) were significantly associated with severe ototoxicity. Concerning melphalan (n = 199/5243 exposed), almost all cases were identified in neuroblostma patients (NBL), who also received cisplatin 200mg/m²/cycle (26/92 NBL, 30y-CumInc = 36.4% (95%CI = 25.9-48.4), vs. 3/107 non-NBL, 30y-CumInc = 1.6% (0.4-5.6)). Concerning busulfan (n = 131/5243 exposed), all cases were identified in NBL (n = 16/63, all treated with melphalan and cisplatin) and brain tumors (n = 13/28, all with RT at inner ear ≥5Gy). The 30y-CumInc in patients with RT at inner ear ≥5Gy was 7.4% (95%CI = 5.7-9.6) and 39.8% (22.5-60.0) respectively with and without busulfan. Conclusions: RT at inner ear has significant deleterious impact on audition, with cumulative incidence still worsening > 30years after RT, and with likely potentiation by busulfan. The deleterious effect of melphalan was related to previous treatment with cisplatin, either by interaction between these drugs, or by the high cisplatin dose by cycle used in NBL.

Health and cancer concerns among siblings of childhood cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12117-12117
Author(s):  
Sonia Morales ◽  
Sedigheh Mirzaei Salehabadi ◽  
Deokumar Srivastava ◽  
Todd M. Gibson ◽  
Wendy M. Leisenring ◽  
...  
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
Health Status ◽  
Cancer Risk ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Psychosocial Problems ◽  
Matched Pair ◽  
Future Health ◽  
Grade 3

12117 Background: Siblings of long-term survivors of childhood cancer can be at risk for persistent concerns regarding their future health and risk for cancer. We examined self-perceived future health and cancer risk concerns among such siblings. Methods: 3,969 siblings (median age 29 [range 18–56] years) of 5+ year matched pair cancer survivors (n= 3,969; age 25 [6–48] years; time since diagnosis 19.6 [9.6-33.8] years) in the CCSS self-reported physical/psychosocial problems, including concerns regarding future health and cancer risk (dichotomized as concerned vs not concerned). Chronic health conditions (CHC) were graded using the Common Terminology Criteria for Adverse Events system: mild (grade 1), moderate (grade 2), severe/disabling (grade 3),or life-threatening (grade 4). Sibling demographics, their matched survivor’s diagnosis, era and treatment components, complications (death, relapse, disfigurement) as well as self-reported health status and CHCs for siblings and survivors were examined as potential risk factors for concern using multivariable logistic regression. Adjusted odds ratios (OR) and 95% confidence intervals (CI) are reported. Results: The prevalence of siblings reporting concerns regarding health and cancer risk decreased based on decades of matched survivor diagnosis: 1970-79 (73.3%; 63.9%), 1980-89 (67.2%; 62.6%), 1990-99 (45.7%; 52.3%). Risk factors for concerns included sibling poor/fair current health (future health OR 3.65, 95% CI 2.37-5.62; cancer risk OR 1.54, 1.12-2.13) compared to good/very good/excellent health. Sibling grade 2 (future health OR 1.46, 1.23-1.74; cancer risk OR 1.20, 1.01-1.42) or grade 3-4 CHCs (future health OR 1.37, 1.09-1.71; cancer risk OR 1.28, 1.03-1.58) were associated with greater concerns compared to those with less than grade 2 CHCs. Survivor treatment with chemotherapy/radiation was associated with elevated cancer risk concerns (OR 1.51, 1.13-2.02) compared to surgery/no therapy. Siblings of survivors with grade 3-4 CHCs (OR 1.35, 1.12-1.63) had greater future health concerns compared to those with less than grade 2 CHCs. Sibling bereavement was a risk factor for future health (OR 1.45, 1.04-2.03) and cancer risk (OR 1.44, 1.05-1.99) concerns. Conclusions: The prevalence of sibling concerns regarding future health and cancer have diminished in more recent decades. Subgroups of siblings are at-risk for concerns over future health and cancer risk, partially determined by medical characteristics of their survivor and their own health status.

scholarly journals Physical activity and cardiovascular risk factors in childhood cancer survivors

2014 ◽  
Vol 62 (2) ◽  
pp. 305-310 ◽  
Author(s):  
Megan E. Slater ◽  
Julie A. Ross ◽  
Aaron S. Kelly ◽  
Donald R. Dengel ◽  
James S. Hodges ◽  
...  
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cardiovascular Risk Factors ◽  
Childhood Cancer Survivors

scholarly journals Racial/Ethnic Differences in Adverse Outcomes Among Childhood Cancer Survivors: The Childhood Cancer Survivor Study

2016 ◽  
Vol 34 (14) ◽  
pp. 1634-1643 ◽  
Author(s):  
Qi Liu ◽  
Wendy M. Leisenring ◽  
Kirsten K. Ness ◽  
Leslie L. Robison ◽  
Gregory T. Armstrong ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Ethnic Differences ◽  
Childhood Cancer Survivors ◽  
Adverse Outcomes ◽  
Chronic Health Conditions ◽  
Health Conditions ◽  
Childhood Cancer Survivor Study ◽  
Racial Ethnic

Purpose Childhood cancer survivors carry a high burden of treatment-related morbidity; however, race/ethnicity–specific risks of adverse outcomes are not well understood. Methods Data from the Childhood Cancer Survivor Study, a cohort of survivors of at least 5 years, were used to compare Hispanic (n = 750, 5.4%) and non-Hispanic black (NHB: n = 694, 5.0%) survivors to non-Hispanic white patients (NHW: n = 12,397, 89.6%) for late mortality, subsequent neoplasms, and chronic health conditions. Results NHBs and Hispanics reported lower socioeconomic status (SES) and higher prevalence of obesity, and NHBs reported higher prevalence of hypertension. NHBs had higher rate of all-cause mortality (relative rate [RR], 1.4; 95% CI, 1.1 to 1.9; P = .008), which was abrogated (RR, 1.0; 95% CI, 0.8 to 1.4; P = .9) after adjusting for SES. Nonmelanoma skin cancer was not observed among irradiated NHBs, and the risk was lower among Hispanic survivors (RR, 0.3; 95% CI, 0.1 to 0.7) compared with NHWs. Both NHBs and Hispanics demonstrated elevated risks for diabetes; these risks persisted after adjusting for SES and obesity (NHBs: RR, 2.8; 95% CI, 1.1 to 6.7; Hispanics: RR, 3.1; 95% CI, 1.5 to 6.4). NHBs were more likely to report cardiac conditions (RR, 1.8; 95% CI, 1.1 to 2.7), but the risk was attenuated after adjusting for cardiovascular risk factors. Therapeutic exposures did not affect racial/ethnic differences in mortality (all cause or cause specific), chronic health conditions, or subsequent neoplasms. Conclusion By and large, NHB and Hispanic childhood cancer survivors experience a comparable burden of morbidity and mortality to their NHW counterparts. The few differences in risk were explained by the racial/ethnic differences in socioeconomic status and/or cardiovascular risk factors.

scholarly journals METABOLIC SYNDROME PARAMETERS, DETERMINANTS, AND BIOMARKERS IN ADULT SURVIVORS OF CHILDHOOD CANCER: PROTOCOL OF THE DUTCH CHILDHOOD CANCER SURVIVOR STUDY METABOLIC SYNDROME (DUTCH LATER METS STUDY) (Preprint)

2020 ◽  
Author(s):  
Vincent Pluimakers ◽  
Marta Fiocco ◽  
Jenneke van Atteveld ◽  
Monique Hobbelink ◽  
Dorine Bresters ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Previous Treatment ◽  
Adult Survivors ◽  
Childhood Cancer Survivors ◽  
Snp Analysis ◽  
Cross Sectional ◽  
Survivors Of Childhood Cancer

BACKGROUND Potential late effects of treatment for childhood cancer include adiposity, insulin resistance, dyslipidemia and hypertension. These risk factors cluster together as metabolic syndrome (MetS) and increase the risk for development of diabetes mellitus and cardio- and cerebrovascular disease. Knowledge on risk factors, timely diagnosis and preventive strategies is of importance to prevent cardio- and cerebrovascular complications and improve quality of life. Currently, no studies in national cohorts on prevalence and determinants of MetS in childhood cancer survivors including biomarkers and genetic predisposition are available. OBJECTIVE The objectives of the Dutch LATER METS study are to assess 1) the prevalence and risk factors of MetS and its separate components, and 2) the potential value of additional biomarkers, in the national cohort of adult long-term survivors of childhood cancer. METHODS This is a cross-sectional study, based on recruitment of all survivors treated in the Netherlands between 1963 and 2002. MetS will be classified according to the definitions of the National Cholesterol Education Program (NCEP-ATP III) as well as the Joint Interim Statement (JIS), and compared to reference data. Dual-energy X-ray absorptiometry (DXA) scans were performed to assess body composition in more detail. The effect of patient characteristics, previous treatment, and genetic variation on the risk of MetS will be assessed. The diagnostic and predictive value of novel biomarkers will be tested. RESULTS Patient accrual started in 2016 and lasted until April 2020. A total of 2380 survivors has participated, in seven pediatric oncology hospitals. From July 2020, biomarker testing, SNP analysis and data analysis will be performed. CONCLUSIONS The Dutch LATER METS study will provide knowledge on clinical and genetic determinants of MetS, and the diagnostic value of biomarkers, in childhood cancer survivors. The results of this study will be used to optimize surveillance guidelines for MetS in survivors, based on enhanced risk stratification and screening strategies. This will improve diagnosis of MetS, and prevent complications. CLINICALTRIAL Registered at toetsingonline.nl, NL32117.018.10

Improving paediatric cardiologists’ awareness about the needs of childhood cancer survivors: results of a single-centre directed educational initiative

2019 ◽  
Vol 29 (06) ◽  
pp. 808-812 ◽  
Author(s):  
Kirsten Rose-Felker ◽  
Karen Effinger ◽  
Michael S Kelleman ◽  
Ritu Sachdeva ◽  
Lillian R. Meacham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Cancer Treatment ◽  
Childhood Cancer ◽  
Educational Intervention ◽  
Childhood Cancer Survivors ◽  
Baseline Survey ◽  
Post Intervention ◽  
Web Based ◽  
Related Risk

AbstractBackground:Cardiovascular disease is a leading cause of morbidity and mortality in childhood cancer survivors. Cardiologists must be aware of risk factors and long-term follow-up guidelines, which have historically been the purview of oncologists. Little is known about paediatric cardiologists’ knowledge regarding the cardiotoxicity of cancer treatment and how to improve this knowledge.Methods:A total of 58 paediatric cardiologists anonymously completed a 21-question, web-based survey focused on four cardio-oncology themes: cancer treatment-related risk factors (n = 6), patient-related risk factors (n = 6), recommended surveillance (n = 3), and cardiac-specific considerations (n = 6). Following the baseline survey, a multi-disciplinary team of paediatric cardiologists and cancer survivor providers developed an in-person and web-based educational intervention. A post-intervention survey was conducted 5 months later.Results:The response rate was 41/58 (70.7%) pre-intervention and 30/58 (51.7%) post-intervention. On the baseline survey, the percentage of correct answers was 68.8 ± 10.3%, which improved to 79.2 ± 16.2% after the intervention (p = 0.009). The theme with the most profound knowledge deficit was surveillance; however, it also had the greatest improvement after the intervention (49.6 ± 26.7 versus 66.7 ± 27.7% correct, p = 0.025). Individual questions with the largest per cent improvement pertained to risk of cardiac dysfunction with time since treatment (52.4 versus 93.1%, p = 0.002) and the role of dexrazoxane (48.8 versus 82.8%, p = 0.020).Conclusion:Specific knowledge deficits about the care of paediatric cancer survivors were identified amongst cardiologists using a web-based survey. Knowledge of surveillance was initially lowest but improved the most after an educational intervention. This highlights the need for cardio-oncology-based educational initiatives among paediatric cardiologists.

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