Dataset Information

Pregnancy, time to pregnancy and obstetric outcomes among female childhood cancer survivors: results of the DCOG LATER-VEVO study.

ABSTRACT:

Purpose

To evaluate pregnancy rates, time to pregnancy (TTP) and obstetric outcomes in female childhood cancer survivors (CCSs) and to identify specific diagnosis- and treatment-related factors associated with these outcomes.

Methods

The study is part of the DCOG LATER-VEVO study, a nationwide multicenter cohort study evaluating fertility among long-term Dutch female CCSs. Data were collected by questionnaire. The current study included 1095 CCSs and 812 controls, consisting of sisters of CCSs and a random sample of women from the general population.

Results

Among the subgroup of women who ever had the desire to become pregnant, the chance of becoming pregnant was significantly lower for CCSs than controls (OR 0.5, 95%CI 0.4-0.8). Moreover, TTP was 1.1 times longer for CCSs compared to controls (p?=?0.09) and was significantly longer in survivors of CNS and renal tumours. Overall, no differences were found between CCSs and controls regarding the probability of ever having had a miscarriage, still birth, or induced abortion. However, CCSs had a significantly increased risk of delivering preterm (OR 2.2, 95%CI 1.3-3.7) and delivering via caesarean section (OR 1.8, 95%CI 1.2-2.6). Treatment with lower abdominal/pelvic radiotherapy was strongly associated with several adverse obstetric outcomes.

Conclusion

CCSs are less likely to have ever been pregnant. Among those who do become pregnant, certain subgroups of CCSs are at increased risk of longer TTP. Moreover, as pregnant CCSs, especially those treated with lower abdominal/pelvic radiotherapy, are more likely to develop various adverse obstetric outcomes, appropriate obstetric care is highly advocated.

SUBMITTER: van Dijk M

PROVIDER: S-EPMC7230041 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Pregnancy, time to pregnancy and obstetric outcomes among female childhood cancer survivors: results of the DCOG LATER-VEVO study.

van Dijk M M van Leeuwen F E FE Overbeek A A Lambalk C B CB van den Heuvel-Eibrink M M MM van Dorp W W Tissing W J WJ Kremer L C LC Loonen J J JJ Versluys B B Bresters D D Ronckers C M CM van der Pal H J HJ Beerendonk C C M CCM Kaspers G J L GJL van Dulmen-den Broeder E E van den Berg M H MH

Journal of cancer research and clinical oncology 20200327 6

<h4>Purpose</h4>To evaluate pregnancy rates, time to pregnancy (TTP) and obstetric outcomes in female childhood cancer survivors (CCSs) and to identify specific diagnosis- and treatment-related factors associated with these outcomes.<h4>Methods</h4>The study is part of the DCOG LATER-VEVO study, a nationwide multicenter cohort study evaluating fertility among long-term Dutch female CCSs. Data were collected by questionnaire. The current study included 1095 CCSs and 812 controls, consisting of si ...[more]

PMID: 32221745

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Project description:IntroductionApproximately 80% of children, adolescents and young adults (CAYA) cancer patients are expected to fully recover and survive for five years or more. The reproductive health is a particular area of their concern. Evidence demonstrates that previous therapeutic treatments for cancer and comorbidities may have harmful effects on female fertility and delivery outcomes, which will significantly affect patient quality of life. However, these reports are heterogeneous. Therefore, the purpose of this study is to provide the up-to-date evidence on the risk of adverse obstetric and perinatal outcomes in female survivors of childhood or adolescent cancer.Methods and analysisThis meta-analysis will be carried out and reported with adherence to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Cochrane Handbook. We will search online databases including PubMed, Cochrane Library, and Embase from inception to August, 2022 to identify all relevant cohort studies examining the relationship between cancer and subsequent obstetric and perinatal outcomes. Data extraction from eligible studies will be conducted and crosschecked separately by two investigators using pre-tested standardized data extraction forms. Discrepancies will be resolved via a third investigator. Methodological quality assessment for each study will be conducted using the Newcastle-Ottawa scale (NOS) tool. We will apply the DerSimonian-Laird random-effects model to calculate the pooled estimates. Further sources of heterogeneity will be explored by performing subgroup analysis based on multiple study characteristics. Potential publication bias will be assessed by inspection of a funnel plot, Begg's and Egger's regression tests of funnel plot asymmetry.Ethics and disseminationEthical approval will not be required as all data used for this pooled analysis will be obtained from published cohort studies. The results of this study will be disseminated in a peer-reviewed journal and conference presentation.Osf registration numberDOI 10.17605/OSF.IO/K6QBG.

Project description:PurposeCurrent information regarding pregnancy-associated cardiomyopathy among women treated for childhood cancer is insufficient to appropriately guide counseling and patient management. This study aims to characterize its prevalence within a large cohort of females exposed to cardiotoxic therapy.MethodsThis is a retrospective cohort study of female cancer survivors treated at St. Jude Children's Research Hospital between 1963 and 2006, at least 5 years from diagnosis, ≥13 years old at last follow-up, and with at least one successful pregnancy. Pregnancy-associated cardiomyopathy was defined as shortening fraction <28 % or ejection fraction <50 % or treatment for cardiomyopathy during or up to 5 months after completion of pregnancy.ResultsAmong the 847 female cancer survivors with 1554 completed pregnancies, only 3 (0.3 %) developed pregnancy-associated cardiomyopathy and 40 developed non-pregnancy-associated cardiomyopathy either 5 months postpartum (n = 14) or prior to pregnancy (n = 26). Among those with cardiomyopathy prior to pregnancy (n = 26), cardiac function deteriorated during pregnancy in eight patients (three patients with normalization of cardiac function prior to pregnancy, three with persistently abnormal cardiac function, and two for whom resolution of cardiomyopathy was unknown prior to pregnancy). Patients that developed cardiomyopathy received a higher median dose of anthracyclines compared to those that did not (321 versus 164 mg/m(2); p < 0.01).ConclusionsPregnancy-associated cardiomyopathy in childhood cancer survivors is rare.Implications for cancer survivorsMost female childhood cancer survivors will have no cardiac complications during or after childbirth; however, those with a history of cardiotoxic therapies should be followed carefully during pregnancy, particularly those with a history of anthracycline exposures and if they had documented previous or current subclinical or symptomatic cardiomyopathy.

Project description:BackgroundThe objective of this study was to compare the health-related quality of life (HRQOL) of Dutch adult male and female childhood cancer survivors (CCSs) to general population references and to study medical determinants.MethodsCCSs from the Dutch Childhood Cancer Survivor Study LATER cohort (1963-2001) part 2, who were 18 years old or older (time since diagnosis ≥ 5 years), were invited to complete the TNO-AZL Questionnaire for Adult Health-Related Quality of Life. Domain scores and proportions of CCSs with impaired HRQOL (score < 25th percentile of the reference scores) were compared with references via Mann-Whitney U tests and logistic regression analyses corrected for age and sex (P < .004). Interactions of group with sex were included if they were significant (P < .05). Moreover, medical determinants were analyzed with multivariable logistic regression analyses.ResultsHRQOL scores for 1766 CCSs (mean age, 35.9 years [standard deviation, 9.4 years]; male, 51%; response rate, 71%) differed from references on most domains with small effect sizes. Both male and female CCSs were more often impaired in gross and fine motor functioning, cognitive functioning, sleep, and vitality with odds ratios (ORs) > 1.4. In addition, female CCSs were more often impaired in daily activities, pain, and sexuality (ORs, 1.4-1.9) and were less often aggressive (OR, 0.6). CCCs of central nervous system (CNS) tumors, bone tumors, and retinoblastoma and those with cranial, abdominopelvic, or lower extremity radiotherapy were at increased risk of impairment in 1 or more domains.ConclusionsDutch adult CCSs, especially females, have impaired HRQOL in several domains; this is most pronounced in cognitive functioning. The vulnerabilities of subgroups at risk, such as CCSs of CNS tumors, were confirmed. Surveillance of HRQOL and multidisciplinary survivor care are recommended.Lay summaryThe health-related quality of life in a Dutch nationwide cohort of 1766 survivors of childhood cancer was studied. Survivors of childhood cancer were found to have lower health-related quality of life in several domains (eg, motor functioning and vitality) in comparison with the general population. They most often reported low cognitive functioning (eg, memory and attention). Females had low health-related quality of life in more domains than males. Survivors of brain tumors had low health-related quality of life in most domains. Monitoring health-related quality of life regularly and collaborating between disciplines in survivor care is recommended.

Project description:BackgroundThe effect of many contemporary chemotherapeutic drugs on pregnancy and livebirth is not well established. We aimed to establish the effects of these drugs on pregnancy in male and female survivors of childhood cancer not exposed to pelvic or cranial radiotherapy.MethodsWe used data from a subset of the Childhood Cancer Survivor Study cohort, which followed 5-year survivors of the most common types of childhood cancer who were diagnosed before age 21 years and treated at 27 institutions in the USA and Canada between 1970 and 1999. We extracted doses of 14 alkylating and similar DNA interstrand crosslinking drugs from medical records. We used sex-specific Cox models to establish the independent effects of each drug and the cumulative cyclophosphamide equivalent dose of all drugs in relation to pregnancies and livebirths occurring between ages 15 years and 44 years. We included siblings of survivors as a comparison group.FindingsWe included 10 938 survivors and 3949 siblings. After a median follow-up of 8 years (IQR 4-12) from cohort entry or at age 15 years, whichever was later, 4149 (38%) survivors reported having or siring a pregnancy, of whom 3453 (83%) individuals reported at least one livebirth. After a median follow-up of 10 years (IQR 6-15), 2445 (62%) siblings reported having or siring a pregnancy, of whom 2201 (90%) individuals reported at least one livebirth. In multivariable analysis, survivors had a decreased likelihood of siring or having a pregnancy versus siblings (male survivors: hazard ratio [HR] 0·63, 95% CI 0·58-0·68; p<0·0001; female survivors: 0·87, 0·81-0·94; p<0·0001) or of having a livebirth (male survivors: 0·63, 0·58-0·69; p<0·0001; female survivors: 0·82, 0·76-0·89; p<0·0001). In male survivors, reduced likelihood of pregnancy was associated with upper tertile doses of cyclophosphamide (HR 0·60, 95% CI 0·51-0·71; p<0·0001), ifosfamide (0·42, 0·23-0·79; p=0·0069), procarbazine (0·30, 0·20-0·46; p<0·0001) and cisplatin (0·56, 0·39-0·82; p=0·0023). Cyclophosphamide equivalent dose in male survivors was significantly associated with a decreased likelihood of siring a pregnancy (per 5000 mg/m(2) increments: HR 0·82, 95% CI 0·79-0·86; p<0·0001). However, in female survivors, only busulfan (<450 mg/m(2) HR 0·22, 95% CI 0·06-0·79; p=0·020; ≥450 mg/m(2) 0·14, 0·03-0·55; p=0·0051) and doses of lomustine equal to or greater than 411 mg/m(2) (0·41, 0·17-0·98; p=0·046) were significantly associated with reduced pregnancy; cyclophosphamide equivalent dose was associated with risk only at the highest doses in analyses categorised by quartile (upper quartile vs no exposure: HR 0·85, 95% CI 0·74-0·98; p=0·023). Results for livebirth were similar to those for pregnancy.InterpretationGreater doses of contemporary alkylating drugs and cisplatin were associated with a decreased likelihood of siring a pregnancy in male survivors of childhood cancer. However, our findings should provide reassurance to most female survivors treated with chemotherapy without radiotherapy to the pelvis or brain, given that chemotherapy-specific effects on pregnancy were generally few. Nevertheless, consideration of fertility preservation before cancer treatment remains important to maximise the reproductive potential of all adolescents newly diagnosed with cancer.FundingNational Cancer Institute, National Institutes of Health, and the American Lebanese-Syrian Associated Charities.

Dataset Information

Pregnancy, time to pregnancy and obstetric outcomes among female childhood cancer survivors: results of the DCOG LATER-VEVO study.

Purpose

Methods

Results

Conclusion

Publications

Pregnancy, time to pregnancy and obstetric outcomes among female childhood cancer survivors: results of the DCOG LATER-VEVO study.

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