Background and Aims

Survivors of childhood or AYA cancers are at risk for adverse reproductive outcomes.

Methods

Using provincial health databases, we assembled a cohort of female cancer survivors diagnosed at < 21 years from 1985-2012 in Ontario. Survivors were matched by age and geographic region to females without prior cancer (controls). Outcomes included recognized pregnancies, perinatal and obstetrical complications (including a composite severe maternal morbidity [SMM] outcome). Multivariable Cox proportional hazard and modified Poisson models compared survivors to controls and evaluated risk factors in survivors.

Results

3,486 survivors were matched to 17,428 controls. Median age at cancer diagnosis was 12 years (IQR 5-16); median follow-up was 26 years (IQR 21-32). At age 25 years, the cumulative incidence was 11.2% (95%CI 10.0-12.4%) among survivors and 13.9% (95%CI 13.3-14.4%) among controls (hazard ratio [HR] 0.79, 95%CI 0.73-0.86). Among women with a recognized pregnancy, 581 (97.0%) survivors carried a pregnancy >20 weeks vs 3,791 (97.6%) controls (relative risk [RR] 1.01, 95%CI 0.98-1.04). Factors associated with a decreased likelihood of achieving a pregnancy among survivors included cranial radiation (HR 0.56, 95%CI 0.39-81) and hematopoietic stem cell transplantation (HSCT) (HR 0.43, 95%CI 0.25-0.75). Among women who carried a pregnancy >20 weeks, survivors were at elevated risk for SMM (RR 2.31, 95%CI 1.49-3.59) and cardiac morbidity (RR 3.23, 95%CI 1.58-6.60). Factors associated with SMM included brain tumour (RR 7.37, 95%CI 1.58-34.20) and pre-existing kidney disease (RR 3.87, 95%CI 1.13-13.20). Among livebirth pregnancies, survivors were at higher risk of preterm birth (RR 1.56, 95%CI 1.23-1.98), especially those who received HSCT (RR 7.11, 95%CI 0.65-2.12).

Conclusions

Survivors are less likely to achieve a recognized pregnancy compared to women without prior cancer. They are at elevated risk for SMM, cardiac morbidity and preterm birth. High-risk obstetrical care is recommended for those at elevated risk of an adverse outcome.

Background and Aims

Female childhood cancer survivors (CCS) show large inter-individual variability in the impact of alkylating chemotherapy, given as childhood cancer treatment, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability. Alkylating agents induce apoptosis of cancer cells by damaging DNA and inhibiting cellular metabolisms, DNA replication and transcription. Girls with less efficient DNA damage response systems may be more vulnerable to the adverse effects of alkylating agents leading to ovarian dysfunction later in life, compared to women with a fully efficient DNA damage repair system.

Methods

To evaluate ovarian function, Anti-Müllerian hormone (AMH) levels were assessed in a discovery cohort of female CCS from the Dutch DCOG LATER-VEVO (N=285), and results were validated in the pan-European PanCareLIFE (N=465), and the USA-based St. Jude Lifetime Cohort (N=391). Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analyzed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using meta-analysis.

Results

Meta-analysis across the three independent cohorts showed a significant interaction effect (p = 3.0 × 10^-4) between rs11668344 of BRSK1 (allele frequency = 0.34) among CCS treated with high dose alkylating agents (CED score ≥8,000 mg/m²), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (OR genotype AA: 2.01 vs AG: 5.00).

Conclusions

Female CCS carrying a common BRSK1 gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy. Further research, validating our findings and identifying additional risk-contributing genetic variants, may enable individualized counseling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer.

Background and Aims

Adolescent and young adult survivors of childhood cancer (AYA) are at risk for physical and psychological late-effects from their treatment. However, they struggle with survivor self-management (e.g., knowledge, health behaviors, follow-up care). This study assessed the incremental benefit [compared to survivorship care plans (SCP) alone] and acceptability of the AYA STEPS mobile app intervention for survivors of childhood cancer.

Methods

AYA (N=226; Mage=20.3, 46% female, 72% Non-Hispanic, White) received an individualized SCP and were randomized to receive the app or not. The app delivered 1-2 tailored health messages per day for 16 weeks, and contained features for disease self-management. Primary outcomes, measured at baseline, 4 months, and 8 months, were health knowledge and health goal progress. ANCOVA assessed changes in primary outcomes over time, controlling for baseline. Primary analyses focused on group differences. Secondary analysis considered objective app engagement (or dosage) as a continuous predictor. App acceptability was measured at 4 months.

Results

The intervention group did not demonstrate significantly greater improvement in health knowledge or health goal progress at 4 or 8 month follow-up compared to the SCP only group. In secondary analyses, greater percentage of messages read was associated with improved health knowledge (p=.01), and greater progress towards health goals (p=.002) at 4 months; the latter was sustained at 8 months (p=.02). Greater number of days in app was associated with greater goal progress at 4 (p=.006) and 8 months (p=.004). More than 75% of patients endorsed that the app was easy to use, improved their health knowledge and would continue using it if given the choice.

Conclusions

Results support the promise of digital health interventions to improve AYA self-management. Not surprisingly, there is incremental benefit with greater engagement. Such interventions must be designed to maximize dosage and motivation to engage, which may differ by individuals.

Background and Aims

With over 400,000 childhood cancer survivors in the US, structured follow-up care is essential. Survivorship care plans (SCP) are provided to childhood cancer survivors to help them navigate complex survivorship cancer care. Confidence in knowledge about SCP by caregivers may impact utilization and health outcomes. We aimed to compare confidence in SCP knowledge in caregivers of childhood cancer survivors by socio-demographics, language, health literacy (HL) and acculturation (if Hispanic).

Methods

English or Spanish-speaking caregivers of childhood cancer survivors (>2 years from end-of-therapy) aged 2-24 years from our survivorship clinic were recruited to participate in the study. Caregivers completed surveys to assess the variables of interest. Outcomes were analyzed using t-tests, Chi-Square tests, or Mann-Whitney U tests.

Results

Two hundred-sixty caregivers (56% female, 56.4% Hispanic) of pediatric cancer survivors were enrolled. Hispanic caregivers were younger, with less education and lower socioeconomic status. Compared to non-Hispanic caregivers, a higher proportion of Hispanic caregivers reported high confidence in SCP knowledge (p=0.022). Caregivers with lower education (p=0.015), and limited English proficiency (LEP) [p=0.010] also reported higher confidence. Patients in the higher confidence group had lower objective HL: TOFHLA (p=0.003) and NVS (p<0.001) yet higher subjective HL: CRI (p=0.002).

Conclusions

Unexpectedly, high confidence in SCP knowledge was associated with Hispanic ethnicity, higher subjective HL (although lower objective HL), lower education, and LEP. Consistent with our findings, low disease knowledge may correlate with overconfidence in one’s perception of medical information, as reported in some underserved populations. Therefore, high confidence alone is unlikely to predict utilization of SCP. It is important to identify caregivers with objectively low HL, LEP, and low education as appropriate individualization of the SCP and tailored education to the individual’s language and HL may improve SCP utilization. Future research should evaluate which factors predict SCP utilization and design interventions to improve health outcomes.

Background and Aims

The development and progress of late effects of cancer treatment in childhood cancer survivors (CCS) can be positively modified by CCS adopting healthy behaviours. Healthcare professionals (HCPs) have a key role in supporting CCS engagement with healthier behaviours. However, HCPs may experience obstacles which may impede doing so in consultations. To understand these issues across HCPs in Europe, we aimed at exploring facilitators and barriers of health behaviour support in CCS as perceived by HCPs.

Methods

We conducted 4 focus groups with representative HCPs of academic follow-up care clinics across Europe (Czech Republic, Sweden, Belgium, and the Netherlands). Discussions were recorded and transcribed verbatim. The Theoretical Domains Framework (TDF), covering domains of influences on behaviour, was used to inform the semi-structured interview guide.

Results

We recruited 25 HCPs, comprising (paediatric) oncologists (44%), nurses (28%), and other supporting HCPs (28%). Two themes emerged from inductive analyses as barriers for behaviour change support based on their high frequency; lack of time and lack of knowledge. Firstly, lack of dedicated time during consultations to discuss health behaviours in a proper way was perceived as an important barrier for HCPs. Having an appropriate organisational structure of consultations to provide time for behavioural change support was commonly viewed as a facilitating factor. Secondly, a frequently expressed concern regarding lack of knowledge was the insufficient education of HCPs on health behaviours and its relationship with late effects. Having an established network in which CCS can be referred to for health behaviour change, e.g. diet or physical, was found to be a main facilitator.

Conclusions

This study has identified HCP’s lack of time and knowledge as key barriers in supporting health behaviour change in CCS. This further understanding of barriers and facilitators will support the PanCareFollowUp project in ensuring high quality standardized survivorship care in follow-up care clinics across Europe.

Background and Aims

Breast cancer (BC) is the most common invasive subsequent malignant neoplasm in childhood cancer survivors though limited data exist on BC rates over time.

Methods

We examined treatment exposures and BC incidence rates in ≥5-year female survivors in CCSS diagnosed between 1970 and 1999, using piecewise exponential modeling for rate ratio (RR) estimation with 95% confidence intervals (CI), adjusting for age at childhood cancer diagnosis and attained age.

Results

Among 11,550 females (median age 30.5y, range 5.6-65.9), 361 females developed 428 BCs (319 invasive; 109 in-situ; median age 39.5y, range 19.9-58.8). The 15-yr cumulative incidence decreased from 0.6% in the 1970s to 0.2% in the 1990s (p_trend=0.004). Survivors’ treatment exposures changed greatly from 1970-74 to 1995-99: overall percentage exposed to chest-directed radiation (ChestRT) decreased from 37% to 17%; ChestRT without anthracyclines decreased from 37% to 5%; low-dose anthracyclines (1-249 mg/m²) without ChestRT increased from 3% to 43%; pelvic-RT decreased from 28% to 12%; and overall alkylator exposure stayed relatively constant, increasing from 39% to 54%. Multivariable analysis revealed anthracyclines were associated with higher BC rates: relative to neither ChestRT or anthracyclines, no ChestRT+anthracyclines 1-249 mg/m² (RR=2.12, CI:0.97-4.65); no ChestRT+anthracyclines ≥250 mg/m² (RR=3.45,CI:1.92-6.21); ChestRT+no anthracyclines (RR=7.84, CI:4.53-13.59); ChestRT+anthracyclines 1-249 mg/m² (RR=8.81, CI:4.52-17.18); and ChestRT+anthracyclines ≥250 mg/m² (RR=10.18, CI:4.95-20.95).

BC rate time trend was 21% reduction every 5 years without accounting for treatment changes (RR=0.79, CI:0.70-0.90); when the decrease in ChestRT use was accounted for this declined to 12% (RR=0.88, CI:0.77-1.00); and when the increase in anthracyclines use was additionally accounted for, it increased to 16% (RR=0.84, CI:0.73-0.97)].

Conclusions

BC rates in more recently treated survivors are lower, due largely to the decrease in ChestRT slightly tempered by the concurrent increase in anthracycline use. Future work should focus on the BC rate decline unexplained by these changes in treatment exposures.