scholarly journals Hypogonadism in Children with a Previous History of Cancer: Endocrine Management and Follow-Up

2019 ◽  
Vol 91 (2) ◽  
pp. 93-103 ◽  
Author(s):  
Hanneke M. van Santen ◽  
Marry M. van den Heuvel-Eibrink ◽  
Marianne D. van de Wetering ◽  
W. Hamish Wallace
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Previous History ◽  
Childhood Cancer Survivors ◽  
History Of ◽  
Primary Gonadal Failure ◽  
History Of Cancer ◽  
Gonadal Failure

Hypogonadism after treatment for childhood cancer is a recognized complication and its cause may be subdivided into primary gonadal failure and central hypogonadism. Here, we provide an overview of the risk factors for the development of hypogonadism, assessment and potential interventions and give a summary of the current recommendations for management and follow-up of hypogonadism in childhood cancer survivors.

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.

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.

scholarly journals Asymptomatic systolic dysfunction on contemporary echocardiography in anthracycline-treated long-term childhood cancer survivors: a systematic review

2021 ◽  
Author(s):  
Remy Merkx ◽  
Jan M. Leerink ◽  
Esmée C. de Baat ◽  
Elizabeth A. M. Feijen ◽  
Wouter E. M. Kok ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Systolic Dysfunction ◽  
Global Longitudinal Strain ◽  
Childhood Cancer Survivors ◽  
Left Ventricular ◽  
Heart Region ◽  
Echocardiographic Parameters

Abstract Purpose Echocardiographic surveillance for asymptomatic left ventricular systolic dysfunction (ALVSD) is advised in childhood cancer survivors (CCS), because of their risk of heart failure after anthracycline treatment. ALVSD can be assessed with different echocardiographic parameters. We systematically reviewed the prevalence and risk factors of late ALVSD, as defined by contemporary and more traditional echocardiographic parameters. Methods We searched databases from 2001 to 2020 for studies on ≥ 100 asymptomatic 5-year CCS treated with anthracyclines, with or without radiotherapy involving the heart region. Outcomes of interest were prevalence of ALVSD—measured with volumetric methods (ejection fraction; LVEF), myocardial strain, or linear methods (fractional shortening; FS)—and its risk factors from multivariable analyses. Results Eleven included studies represented 3840 CCS. All studies had methodological limitations. An LVEF < 50% was observed in three studies in 1–6% of CCS, and reduced global longitudinal strain (GLS) was reported in three studies in 9–30% of CCS, both after a median follow-up of 9 to 23 years. GLS was abnormal in 20–28% of subjects with normal LVEF. Abnormal FS was reported in six studies in 0.3–30% of CCS, defined with various cut-off values (< 25 to < 30%), at a median follow-up of 10 to 18 years. Across echocardiographic parameters, reported risk factors were cumulative anthracycline dose and radiotherapy involving the heart region, with no ‘safe’ dose for ALVSD. Conclusions GLS identifies higher prevalence of ALVSD in anthracycline-treated CCS, than LVEF. Implications for Cancer Survivors The diagnostic and prognostic value of GLS should be evaluated within large cohorts. Protocol registration PROSPERO CRD42019126588

Health Outcomes in Childhood Cancer Survivors: Screening for Anthracycline-Induced Cardiac Toxicity.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 70-70
Author(s):  
Jeffrey R. Andolina ◽  
Kimberley Dilley
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cardiac Toxicity ◽  
Childhood Cancer Survivors ◽  
Oncology Group ◽  
History Of ◽  
Underweight Patients ◽  
Anthracycline Dose

Abstract Abstract 70 Background: Cardiac toxicity secondary to anthracyclines is a significant problem in childhood cancer survivors, and the Children's Oncology Group (COG) has developed a recommended screening protocol for echocardiograms based on age at diagnosis, cumulative anthracycline dose, and chest radiation. The objective of this study was to assess the yield of screening and risk factors for cardiac toxicity in long-term survivors. Methods: A retrospective medical record review was performed for all patients seen in a single institution long-term survivor clinic from 2000 through 2007. Patients eligible for analysis included any patient previously treated with anthracyclines and/or chest radiation; patients with prior cardiac disease were excluded. Results: 370 patients were eligible for analysis; 206 (56%) patients were male, 236 (64%) were white, and 197 (53%) were ≤5 years of age at diagnosis. The most common diagnoses included acute lymphoblastic anemia in 152 (41%) patients and Wilms' tumor in 44 (12%). 360 (97%) patients received anthracyclines, and the median dose received was 190 mg/m2. Fifty (14%) patients received radiation to the chest only while an additional 64 (17%) patients received total body irradiation. Overall, 308/370 (83%) patients had received at least one screening echocardiogram with a mean time from diagnosis to latest follow-up of 9.3 years. Younger patients at diagnosis were more likely to be screened during follow-up (p=0.007). All other measured factors were similar between those screened and not screened, including diagnosis, sex, BMI, anthracycline dose, and having received radiation. Of all patients receiving a screening echocardiogram, 24/308 (8%) patients had an abnormal echocardiogram defined as shortening fraction (SF) <28%. By the end of the study period, 9 patients had been placed on cardiac medications for the treatment of cardiac dysfunction identified through screening. Anthracycline dose was associated with a future abnormal echocardiogram; odds ratio (OR) of ever having SF<28% was 9.2 (95% CI: 3.1–27.6) for anthracycline dose ≥250 mg/m2. For all patients who had received an echocardiogram and received an anthracycline dose ≥250 mg/m2, 20/122 (16%) had a SF<28%; for patients who received an anthracycline dose <250 mg/m2, only 4/185 (2%) had a SF<28% (p<0.001). Further, only 1 patient who received a dose <175 mg/m2 had a SF<28%. Age, sex, chest radiation, type of anthracycline, history of relapse, and history of stem cell transplant were not associated with an abnormal echocardiogram in univariate analyses. Body mass index (BMI) was calculated from available weight and height data at latest follow-up visit. BMI category was significantly associated with having an abnormal echocardiogram, as currently underweight patients (BMI <5th%) were more likely to have a SF<28% than their heavier counterparts (p=0.001). For currently underweight patients, 4/12 (33%) had an abnormal echocardiogram with a SF<28%; for all patients in a non-underweight category, only 15/216 (7%) had a SF<28%. This result was significant with an OR of 6.7 (95% CI: 1.8–24.8). Conclusions: We found anthracycline toxicity to be dependent on dose although not on age, with a significantly increased risk with doses ≥250 mg/m2. We also describe a novel association between underweight status and anthracycline-induced cardiac toxicity. Eighty-three percent of patients at our institution are being screened by echocardiography. Our data support the current screening recommendations of the Children's Oncology Group (COG), as 24 patients were identified with decreased cardiac function. Echocardiography is a relatively inexpensive tool to identify patients with late-onset cardiac toxicity and may positively impact the medical care for the growing population of childhood cancer survivors. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Childhood Cancer and the Risk of ESKD

2020 ◽  
pp. ASN.2020071002
Author(s):  
Ronit Calderon-Margalit ◽  
Oren Pleniceanu ◽  
Dorit Tzur ◽  
Michal Stern-Zimmer ◽  
Arnon Afek ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Military Service ◽  
Benign Tumor ◽  
Childhood Cancer Survivors ◽  
Cox Proportional Hazards ◽  
Benign Tumors ◽  
Increased Risk ◽  
History Of

BackgroundIncreasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors’ exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease.MethodsTo assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997. After obtaining detailed histories, we divided the cohort into three groups: participants without a history of tumors, those with a history of a benign tumor (nonmalignant tumor with functional impairment), and those with a history of malignancy (excluding kidney cancer). This database was linked to the Israeli ESKD registry to identify incident ESKD cases. We used Cox proportional hazards models to estimate the hazard ratio (HR) of ESKD.ResultsOf the 1,468,600 participants in the cohort, 1,444,345 had no history of tumors, 23,282 had a history of a benign tumor, and 973 had a history of malignancy. During a mean follow-up of 30.3 years, 2416 (0.2%) participants without a history of tumors developed ESKD. Although a history of benign tumors was not associated with an increased ESKD risk, participants with a history of malignancy exhibited a substantially elevated risk for ESKD compared with participants lacking a history of tumors, after controlling for age, sex, enrollment period, and paternal origin (adjusted HR, 3.2; 95% confidence interval, 1.3 to 7.7).ConclusionsChildhood cancer is associated with an increased risk for ESKD, suggesting the need for tighter and longer nephrological follow-up.

Long-Term Risk of Venous Thromboembolism in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

2018 ◽  
Vol 36 (31) ◽  
pp. 3144-3151 ◽  
Author(s):  
Arin L. Madenci ◽  
Brent R. Weil ◽  
Qi Liu ◽  
Andrew J. Murphy ◽  
Todd M. Gibson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cancer Survivor ◽  
Childhood Cancer Survivors ◽  
Increased Risk ◽  
Childhood Cancer Survivor Study ◽  
Survivors Of Childhood Cancer

Purpose To estimate the incidence of late-occurring venous thromboembolism (VTE) among survivors of childhood cancer and to identify risk factors for VTE to facilitate diagnosis and prevention. Methods The Childhood Cancer Survivor Study is a multi-institutional cohort of 24,355 5-year childhood cancer survivors (diagnosed between 1970 and 1999; median age at last follow-up, 28.7 years [range, 5.6 to 58.9 years]; median follow-up since diagnosis, 21.3 years [range, 5.0 to 39.2 years]) and 5,051 sibling participants. The primary end point was self-reported late (≥ 5 years after cancer diagnosis) VTE. Rate ratios (RRs) were estimated with multivariable piecewise exponential models. Results Late VTE incidence among survivors and siblings was 1.1 and 0.5 events per 1,000 person-years, respectively (RR, 2.2; 95% CI, 1.7 to 2.8), with 2.5 excess events per 100 survivors over 35 years. Among survivors, risk factors for VTE were female sex (RR, 1.3; 95% CI, 1.1 to 1.6), cisplatin (reference none; 1 to 199 mg/m2: RR, 3.0 [95% CI, 1.4 to 6.5]; 200 to 399 mg/m2: RR, 1.9 [95% CI, 1.0 to 3.6]; ≥ 400 mg/m2: RR, 2.0 [95% CI, 1.2 to 3.3]), l-asparaginase (RR, 1.3; 95% CI, 1.0 to 1.7), obesity or underweight (reference body mass index [BMI] 18.5 to 24.9 kg/m2; BMI ≥ 30.0 kg/m2: RR, 1.6 [95% CI, 1.2 to 2.0]; BMI < 18.5 kg/m2: RR, 2.4 [95% CI, 1.7 to 3.4]), and late cancer recurrence or subsequent malignant neoplasm (RR, 4.6; 95% CI, 3.6 to 5.8). Among lower-extremity osteosarcoma survivors, limb salvage (reference amputation; RR, 3.1; 95% CI, 1.2 to 7.5) and cisplatin 200 to 399 or ≥ 400 mg/m2 (reference none; RR, 4.0 [95% CI, 1.1 to 14.6] and 2.9 [95% CI, 1.1 to 8.0], respectively) were independently associated with late VTE. VTE was associated with increased risk for nonexternal cause late mortality (RR, 1.9; 95% CI, 1.6 to 2.3). Conclusion Childhood cancer survivors are at increased risk for VTE across their lifespan and a diagnosis of VTE increases mortality risk. Interventions that target potentially modifiable comorbidities, such as obesity, warrant consideration, with prophylaxis for high-risk survivors, including those treated with cisplatin and limb-sparing approaches.

Increased late mortality in underweight survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

2017 ◽  
Vol 35 (5_suppl) ◽  
pp. 110-110
Author(s):  
Emily S. Tonorezos ◽  
Lillian R. Meacham ◽  
Joanne F. Chou ◽  
Chaya S. Moskowitz ◽  
Wendy M. Leisenring ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cancer Survivor ◽  
Childhood Cancer Survivors ◽  
Normal Weight ◽  
Late Mortality ◽  
History Of ◽  
Childhood Cancer Survivor Study ◽  
Survivors Of Childhood Cancer

110 Background: Approximately one-in-ten adult survivors of childhood cancer are underweight. While the consequences of being overweight or obese have been well-described, outcomes among underweight childhood cancer survivors are unknown. Methods: Underweight was defined as a body mass index (BMI)< 18.5 kg/m2, calculated from self-reported height and weight on either the baseline or the first follow-up questionnaire from the Childhood Cancer Survivor Study (CCSS). National Death Index provided death data and self-reported subsequent malignant neoplasm were validated by pathology report. Chi-square test was used to examine the association between underweight status (< 8.5 kg/m2 vs ≥ 18.5 kg/m2) and baseline demographic characteristics. Marginal models with generalized estimating equations were used to evaluate the associations between BMI and outcomes. Results: Of 9454 survivors (median age 35 years old, range 17-58, with an average of 17.5 years from diagnosis), 627 (6.6%) participants were underweight at baseline and had at least two years of additional follow-up. 29 of 184 deaths were among underweight survivors. In univariate analysis, underweight status was more common among females (9.1% vs 4.5 %, p<0.01) and participants with younger age (8.2% for <5 yrs vs. 6.1% for >=5yr, p<.01), lower household income (8.9% for <$20,000 vs. 6.0% for >=$20,000, p<0.01), and a history of a grade 3 to 4 chronic condition (p = 0.05). After adjustment for these factors, in addition to race/ethnicity, prior smoking, and a history of radiation therapy, the odds of all-cause mortality within two years of BMI report was 2.82 (95% CI: 1.64-2.2; p<0.01) for underweight survivors, compared to normal weight survivors. The risk of subsequent malignant neoplasms within two years of BMI report among underweight survivors compared to normal weight survivors was not significantly increased (OR 1.31; 95% CI: 0.60-2.85; p = 0.49). Conclusions: Childhood cancer survivors who are underweight are at significant risk for late mortality that is unrelated to smoking status, chronic illness, or second malignancy. Whether targeted nutritional interventions would ameliorate this risk is unknown.

scholarly journals Longitudinal lung function in childhood cancer survivors after hematopoietic stem cell transplantation

2021 ◽  
Author(s):  
Maria Otth ◽  
Sophie Yammine ◽  
Jakob Usemann ◽  
Philipp Latzin ◽  
Luzius Mader ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Pulmonary Function ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Childhood Cancer Survivors ◽  
Pulmonary Dysfunction ◽  
Hematopoietic Stem ◽  
Z Scores

AbstractLongitudinal data on pulmonary function after pediatric allogeneic or autologous hematopoietic stem cell transplantation (HSCT) are rare. We examined pulmonary function and associated risk factors in 5-year childhood cancer survivors (CCSs) longitudinally. We included 74 CCSs diagnosed between 1976 and 2010, treated with HSCT, and with at least two pulmonary function tests performed during follow-up. Median follow-up was 9 years (range 6–13). We described pulmonary function as z-scores for lung volumes (forced vital capacity [FVC], residual volume [RV], total lung capacity [TLC]), flows (forced expiratory volume in 1 s [FEV1], maximal mid-expiratory flow [MMEF]), and diffusion capacity for carbon monoxide (DLCO) and assessed associations with potential risk factors using multivariable regression analysis. The median z-scores for FEV1, FVC, and TLC were below the expected throughout the follow-up period. This was not the case for RV, MMEF and DLCO. Female gender, radiotherapy to the chest, and relapse were associated with lower z-scores of FEV1, FVC, MMEF, RV or DLCO. Childhood cancer survivors after HSCT are at risk of pulmonary dysfunction. The complex and multifactorial etiology of pulmonary dysfunction emphasizes the need for longitudinal prospective studies to better characterize the course and causes of pulmonary function impairment in CCSs.

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