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

Goal adjustment strategies operationalised and empirically examined in adolescents with cancer

Adolescents facing cancer may need to adjust their personal life goals. Theories identified several goal adjustment strategies, but their use has not been tested. Therefore, this study operationalises goal adjustment strategies and examines their use. Adolescent cancer patients listed their goals 3 and 12 months post-diagnosis. Goals received scores on five goal characteristics: life domain, level of abstraction, importance, attainability and effort. Results showed that adolescents with cancer (N = 30, mean age: 14.2 years, 60% female) used four of five strategies described in theory, while one additional strategy was found. These findings suggest that adolescents with cancer use goal adjustment strategies as measured by goal characteristics over tim

Does Chemotherapy-Induced Gastrointestinal Mucositis Affect the Bioavailability and Efficacy of Anti-Infective Drugs?

Antimicrobial prophylaxis is increasingly being used in patients with hematological malignancies receiving high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT). However, few studies have focused on the potential impact of gastrointestinal mucositis (GI-M), a frequently observed side effect of chemotherapy in patients with cancer that affects the gastrointestinal microenvironment, on drug absorption. In this review, we discuss how chemotherapy leads to an overall loss of mucosal surface area and consequently to uncontrolled transport across the barrier. The barrier function is depending on intestinal luminal pH, intestinal motility, and diet. Another factor contributing to drug absorption is the gut microbiota, as it modulates the bioavailability of orally administrated drugs by altering the gastrointestinal properties. To better understand the complex interplay of factors in GI-M and drug absorption we suggest: (i) the longitudinal characterization of the impact of GI-M severity on drug exposure in patients, (ii) the development of tools to predict drug absorption, and (iii) strategies that allow the support of the gut microbiota. These studies will provide relevant data to better design strategies to reduce the severity and impact of GI-M in patients with cancer

Risk stratification in febrile neutropenic episodes in adolescent/young adult patients with cancer.

BACKGROUND: Risk-stratified management of febrile neutropenia (FN) allows intensive management of high-risk cases and early discharge of low-risk cases. Most risk stratification systems predicting severe infection from admission variables have been derived from childhood or adult populations and consequently their value in adolescents/young adults (AYA) may vary. Our objective was to determine their value in this population. METHODS: Data from the 'predicting infectious complications in children with cancer' (PICNICC) individual participant data collaboration were used to evaluate six previously described risk stratification schema in the AYA population. Complete case analyses were undertaken for five 'paediatric' rules, with imputation for specific missing variables of the 'adult' rule. The predictive performance of the rules or the outcome microbiologically defined infection (sensitivity, specificity and predictive values) were compared. RESULTS: Among the 5,127 episodes of FN in 3,504 patients in the PICNICC collaboration data set, 603 episodes of FN from 478 patients in 20 studies were of patients 16-25 years old. The six rules demonstrated variable sensitivity (33-96%) and specificity (13-83%). Their overall discriminatory ability was poor (area under the receiver operator curve estimates 0.514-0.593). CONCLUSIONS: Both paediatric and adult FN risk stratification schema perform poorly in AYA with cancer. An alternative rule or clinical recognition of their limitations is required

Thyroid dysfunction during treatment with systemic antineoplastic therapy for childhood cancer: A systematic review

Thyroid dysfunction is known to occur following radiotherapy or chemotherapy for childhood cancer. Thyroid dysfunction during treatment for childhood cancer has, however, not been studied extensively, although thyroid hormones are of utmost importance during childhood. This information is needed to develop adequate screening protocols and may be of special importance with upcoming drugs, such as checkpoint inhibitors, which are highly associated with thyroid dysfunction in adults. In this systematic review we have evaluated the occurrence and risk factors for thyroid dysfunction in children during treatment with systemic antineoplastic drugs, up to three months after the end of therapy. Two review authors independently performed the study selection, data extraction and risk of bias assessment of included studies. After an extensive search (January 2021), in total six heterogeneous articles were included, reporting on 91 childhood cancer patients with a thyroid function test during treatment with systemic antineoplastic therapy for childhood cancer. All studies had risk of bias issues. Primary hypothyroidism was found in 18% of children treated with high dose interferon-α (HDI-α) and in 0–10% after tyrosine kinase inhibitors (TKIs). Transient euthyroid sick syndrome (ESS) was common (in 42–100%) during treatment with systematic multi-agent chemotherapy. Only one study addressed possible risk factors, showing different types of treatment to increase the risk. However, the exact prevalence, risk factors and clinical consequences of thyroid dysfunction remain unclear. Prospective high-quality studies including large study samples are needed to longitudinally assess the prevalence, risk factors and possible consequences of thyroid dysfunction during childhood cancer treatment

Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study

Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54-64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome