A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges

<p>Abstract</p> <p>Background</p> <p>Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered methodological challenges of a nationwide study in the Netherlands investigating the effects of treatment on reproductive function, ovarian reserve, premature menopause and pregnancy outcomes in female childhood cancer survivors (CCS), the DCOG LATER-VEVO study.</p> <p>Methods</p> <p>The study is a retrospective cohort study consisting of two parts: a questionnaire assessing medical, menstrual, and obstetric history, and a clinical assessment evaluating ovarian and uterine function by hormonal analyses and transvaginal ultrasound measurements. The eligible study population consists of adult female 5-year survivors of childhood cancer treated in the Netherlands, whereas the control group consists of age-matched sisters of the participating CCS. To date, study invitations have been sent to 1611 CCS and 429 sister controls, of which 1215 (75%) and 333 (78%) have responded so far. Of these responders, the majority consented to participate in both parts of the study (53% vs. 65% for CCS and sister controls respectively). Several challenges were encountered involving the study population: dealing with bias due to the differences in characteristics of several types of (non-) participants and finding an adequately sized and well-matched control group. Moreover, the challenges related to the data collection process included: differences in response rates between web-based and paper-based questionnaires, validity of self-reported outcomes, interpretation of clinical measurements of women using hormonal contraceptives, and inter- and intra-observer variation of the ultrasound measurements.</p> <p>Discussion</p> <p>The DCOG LATER-VEVO study will provide valuable information about the reproductive potential of paediatric cancer patients as well as long-term survivors of childhood cancer. Other investigators planning to conduct large cohort studies on late effects may encounter similar challenges as those encountered during this study. The solutions to these challenges described in this paper may be useful to these investigators.</p> <p>Trial registration</p> <p>NTR2922; <url>http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922</url></p

Reciprocal Prospective Relationships Between Loneliness and Weight Status in Late Childhood and Early Adolescence

Adolescents who do not conform to weight ideals are vulnerable to disapproval and victimization from peers in school. But, missing from the literature is a prospective examination of weight status and feelings of loneliness that might come from those experiences. Using data from the Québec Longitudinal Study of Child Development, we filled that gap by examining the prospective associations between loneliness and weight status when the sample was aged 10 to 13 years. At ages 10, 12, and 13 years, 1042 youth (572 females; 92% from French speaking homes) reported on their loneliness and were weighed and measured. Family income sufficiency was included in our analyses given its relationship with weight status, but also its possible link with loneliness during early adolescence. The findings showed that (1) weight status and loneliness were not associated concurrently; (2) weight status predicted increases in loneliness from ages 12 to 13 years; and (3) loneliness predicted increases in weight from ages 12 to 13 years among female adolescents, but weight loss among male adolescents. The fact that loneliness was involved in weight gain for females suggests that interventions focused on reducing loneliness and increasing connection with peers during early adolescence could help in reducing obesity

Initial psychometric properties of the experiences questionnaire: validation of a self-report measure of decentering.

Decentering is defined as the ability to observe one's thoughts and feelings as temporary, objective events in the mind, as opposed to reflections of the self that are necessarily true. The Experiences Questionnaire (EQ) was designed to measure both decentering and rumination but has not been empirically validated. The current study investigated the factor structure of the EQ in both undergraduate and clinical populations. A single, unifactorial decentering construct emerged using 2 undergraduate samples. The convergent and discriminant validity of this decentering factor was demonstrated in negative relationships with measures of depression symptoms, depressive rumination, experiential avoidance, and emotion regulation. Finally, the factor structure of the EQ was replicated in a clinical sample of individuals in remission from depression, and the decentering factor evidenced a negative relationship to concurrent levels of depression symptoms. Findings from this series of studies offer initial support for the EQ as a measure of decentering

Risk and temporal changes of heart failure among 5-year childhood cancer survivors: a DCOG-LATER study

Background Heart failure is one of the most important late effects after treatment for cancer in childhood. The goals of this study were to evaluate the risk of heart failure, temporal changes by treatment periods, and the risk factors for heart failure in childhood cancer survivors (CCS). Methods and Results The DCOG‐LATER (Dutch Childhood Oncology Group–Long‐Term Effects After Childhood Cancer) cohort includes 6,165 5‐year CCS diagnosed between 1963 and 2002. Details on prior cancer diagnosis and treatment were collected for this nationwide cohort. Cause‐specific cumulative incidences and risk factors of heart failure were obtained. Cardiac follow‐up was complete for 5,845 CCS (94.8%). After a median follow‐up of 19.8 years and at a median attained age of 27.3 years, 116 survivors developed symptomatic heart failure. The cumulative incidence of developing heart failure 40 years after childhood cancer diagnosis was 4.4% (3.4%–5.5%) among all CCS. The cumulative incidence of heart failure grade ≥3 among survivors treated in the more recent treatment periods was higher compared with survivors treated earlier (Gray test, P=0.05). Mortality due to heart failure decreased in the more recent treatment periods (Gray test, P=0.02). In multivariable analysis, survivors treated with a higher dose of mitoxantrone or cyclophosphamide had a higher risk of heart failure than survivors who were exposed to lower doses. Conclusions CCS treated with mitoxantrone, cyclophosphamide, anthracyclines, or radiotherapy involving the heart are at a high risk for severe, life‐threatening or fatal heart failure at a young age. Although mortality decreased, the incidence of severe or life‐threatening heart failure increased with more recent treatment periods

Risk and temporal changes of heart failure among 5-year childhood cancer survivors: a DCOG-LATER study

Background Heart failure is one of the most important late effects after treatment for cancer in childhood. The goals of this study were to evaluate the risk of heart failure, temporal changes by treatment periods, and the risk factors for heart failure in childhood cancer survivors (CCS). Methods and Results The DCOG‐LATER (Dutch Childhood Oncology Group–Long‐Term Effects After Childhood Cancer) cohort includes 6,165 5‐year CCS diagnosed between 1963 and 2002. Details on prior cancer diagnosis and treatment were collected for this nationwide cohort. Cause‐specific cumulative incidences and risk factors of heart failure were obtained. Cardiac follow‐up was complete for 5,845 CCS (94.8%). After a median follow‐up of 19.8 years and at a median attained age of 27.3 years, 116 survivors developed symptomatic heart failure. The cumulative incidence of developing heart failure 40 years after childhood cancer diagnosis was 4.4% (3.4%–5.5%) among all CCS. The cumulative incidence of heart failure grade ≥3 among survivors treated in the more recent treatment periods was higher compared with survivors treated earlier (Gray test, P=0.05). Mortality due to heart failure decreased in the more recent treatment periods (Gray test, P=0.02). In multivariable analysis, survivors treated with a higher dose of mitoxantrone or cyclophosphamide had a higher risk of heart failure than survivors who were exposed to lower doses. Conclusions CCS treated with mitoxantrone, cyclophosphamide, anthracyclines, or radiotherapy involving the heart are at a high risk for severe, life‐threatening or fatal heart failure at a young age. Although mortality decreased, the incidence of severe or life‐threatening heart failure increased with more recent treatment periods

Colorectal Adenomas and Cancers After Childhood Cancer Treatment: A DCOG-LATER Record Linkage Study

Background: Although colorectal adenomas serve as prime target for colorectal cancer (CRC) surveillance in other high-risk groups, data on adenoma risk after childhood cancer are lacking. We evaluated the risk of histologically confirmed colorectal adenomas among childhood cancer survivors. A secondary aim was to assess CRC risk. Methods: The DCOG-LATER cohort study includes five-year Dutch childhood cancer survivors and a sibling comparison group (n ¼ 883). Colorectal tumors were identified from the population-based Dutch Pathology Registry (PALGA). We calculated cumulative incidences of adenomas/CRCs for survivors and siblings. For adenomas, multivariable Cox regression models were used to evaluate potential risk factors. All statistical tests were two-sided. Results: Among 5843 five-year survivors (median follow-up ¼ 24.9 years), 78 individuals developed an adenoma. Cumulative incidence by age 45 years was 3.6% (95% confidence interval [CI] ¼ 2.2% to 5.6%) after abdominopelvic radiotherapy (AP-RT; 49 cases) vs 2.0% (95% CI ¼ 1.3% to 2.8%) among survivors without AP-RT (28 cases; Pdifference ¼ .07) and vs 1.0% (95% CI ¼ 0.3% to 2.6%) among siblings (6 cases) (Pdifference ¼ .03). Factors associated with adenoma risk were AP-RT (hazard ratio [HR] ¼ 2.12, 95% CI ¼ 1.24 to 3.60), total body irradiation (TBI; HR ¼ 10.55, 95% CI ¼ 5.20 to 21.42), cisplatin (HR ¼ 2.13; 95% CI ¼ 0.74 to 6.07 for ; HR ¼ 3.85, 95% CI ¼ 1.45 to 10.26 for 480 mg/m2 ; Ptrend ¼ .62), a hepatoblastoma diagnosis (HR ¼ 27.12, 95% CI ¼ 8.80 to 83.58), and family history of early-onset CRC (HR ¼ 20.46, 95% CI ¼ 8.10 to 51.70). Procarbazine was statistically significantly associated among survivors without AP-RT/TBI (HR ¼ 2.71, 95% CI ¼ 1.28 to 5.74). Thirteen CRCs occurred. Conclusion: We provide evidence for excess risk of colorectal adenomas and CRCs among childhood cancer survivors. Adenoma risk factors include AP-RT, TBI, cisplatin, and procarbazine. Hepatoblastoma (familial adenomatous polyposisassociated) and family history of early-onset CRC were confirmed as strong risk factors. A full benefit-vs-harm evaluation of CRC screening among high-risk childhood cancer survivors warrants consideration