Late mortality among 5-year survivors of childhood cancer: A systematic review and meta-analysis.

BACKGROUND: Childhood cancer survivors are at increased risk of late mortality (death ≥5 years after diagnosis) from cancer recurrence and treatment-related late effects. The authors conducted a systematic review and meta-analysis to provide comprehensive estimates of late mortality risk among survivors internationally and to investigate differences in risk across world regions. METHODS: Health sciences databases were searched for cohort studies comprised of 5-year childhood cancer survivors in which the risk of mortality was evaluated across multiple cancer types. Eligible studies assessed all-cause mortality risk in survivors relative to the general population using the standardized mortality ratio (SMR). The absolute excess risk (AER) was assessed as a secondary measure to examine excess deaths. Cause-specific mortality risk was also assessed, if reported. SMRs from nonoverlapping cohorts were combined in subgroup meta-analysis, and the effect of world region was tested in univariate meta-regression. RESULTS: Nineteen studies were included, and cohort sizes ranged from 314 to 77,423 survivors. Throughout survivorship, SMRs for all-cause mortality generally declined, whereas AERs increased after 15-20 years from diagnosis in several cohorts. All-cause SMRs were significantly lower overall in North American studies than in European studies (relative SMR, 0.63; 95% confidence interval, 0.49-0.80). SMRs for subsequent malignant neoplasms and for cardiovascular, respiratory, and external causes did not vary significantly between world regions. CONCLUSIONS: The current findings suggest that late mortality risk may differ significantly between world regions, but these conclusions are based on a limited number of studies with considerable heterogeneity. Reasons for regional differences remain unclear but may be better elucidated through future analyses of individual-level data.

Physical late effects of treatment among survivors of childhood cancer in low- and middle-income countries: a systematic review.

PURPOSE: Physical late effects of treatment are well-documented among childhood cancer survivors in high-income countries, but whether prevalence and risk factors are comparable in low- and middle-income countries (LMICs) is unclear. We conducted a systematic review to assess physical late effect outcomes among childhood cancer survivors in LMICs. METHODS: Five health sciences databases were searched from inception to November 2022 in all languages. We included observational studies conducted in LMICs that evaluated physical late effects of treatment in childhood cancer survivors. Mean or median cohort follow-up must have been ≥ 5 years from original cancer diagnosis. RESULTS: Sixteen full articles and five conference abstracts were included. Studies were conducted in lower-middle (n = 12, 57%) or upper-middle income (n = 9, 43%) countries; nearly half (n = 9, 43%) were conducted in India. Five cohorts (24%) were comprised entirely of 5-year survivors. Subsequent malignant neoplasms were reported in 0-11% of survivors (n = 10 studies). Hypothyroidism and metabolic syndrome prevalence ranged from 2-49% (n = 4 studies) and 4-17% (n = 5 studies), respectively. Gonadal dysfunction ranged from 3-47% (n = 4 studies). Cardiac dysfunction ranged from 1-16% (n = 3 studies). Late effects of the musculoskeletal and urinary systems were least investigated. CONCLUSIONS: Substantial knowledge gaps exist in LMIC childhood cancer survivorship. No low-income country data were found. In middle-income countries, late effects were defined and assessed variably and limited by selection bias and small sample sizes. IMPLICATIONS FOR CANCER SURVIVORS: Survivors in LMICs can experience physical late effects of treatment, though additionally systematically collected data from survivor cohorts are needed to fill knowledge gaps.

Cost-Effectiveness of a Quality Improvement Initiative for the Clinical Management of Children with Newly Diagnosed Immune Thrombocytopenia.

OBJECTIVE: To assess the cost-effectiveness of an evidence-informed institutional protocol for physicians that encouraged management of children with newly diagnosed immune thrombocytopenia (ITP) with observation over active therapy, where appropriate. STUDY DESIGN: We conducted a probabilistic cost-effectiveness analysis from an institutional perspective using a decision tree with a 1 year time horizon. Patient-level data were retrospectively ascertained for children diagnosed in pre-protocol (2007-2009) and post-protocol (2013-2018) time periods. ITP resolution was defined as achieving a sustained platelet count of >100 × 103/µL at 9-12 months after diagnosis. Outpatient care and inpatient costs were obtained from the institution and provincial sources. Intervention costs accounted for quality improvement initiative preparation and staff physician training. Incremental costs, incremental effects, and CIs were calculated from 10 000 model iterations. RESULTS: Forty-eight patients were followed for 1 year in the pre-protocol period and 84 in the post-protocol period. After protocol implementation, an average cost savings per child managed of $2055 (95% CI: $656, $3890) Canadian Dollars was observed, as was a higher proportion of resolved ITP cases. The implementation strategy remained less costly and more effective in 99.7% of model iterations. CONCLUSIONS: Implementation of an evidence-informed institutional protocol to guide physicians toward increased uptake of observation over active therapy when managing children with newly diagnosed ITP resulted in significant cost savings on a per case basis, even after accounting for training-related costs. Though the long-term cost implications regarding the sustainability of the intervention are not yet known, it is anticipated that continued institutional savings could occur.

Gynecologic Symptoms among Hormone Receptor-Positive Breast Cancer Patients on Oral Endocrine Therapy: A Cross-Sectional Study.

Endocrine therapy (ET) for hormone receptor-positive (HR+) breast cancer can contribute to gynecologic symptoms (GS) that impact vaginal health, sexual function, and quality of life (QoL). A cross-sectional study was conducted at St. Michael's Hospital in Toronto, Canada between July 2017 and June 2018 to examine the occurrence and frequency of GS among HR+ breast cancer patients on ET, patient-provider communication, female sexual dysfunction (FSD), and QoL. A Treatment Experience questionnaire was developed for this study and the Female Sexual Function Index (FSFI) and Menopause-Specific Quality of Life questionnaire (MENQOL) were also administered. Of 151 patients surveyed, 77 (51.0%) were on tamoxifen and 74 (49.0%) on an aromatase inhibitor. Most patients (84.1%, 95% confidence interval [CI] 77.3% to 89.5%) experienced at least one GS "all the time" or "often", or one or more infections, in the past year. Only 44 (31.9%) patients reported that their oncologist had ever previously asked them about experiencing GS. The prevalence of FSD was 61.2% (95% CI 46.2% to 74.8%) among 49 sexually active patients that completed the FSFI. Symptoms captured in the MENQOL's vasomotor domain were deemed most bothersome. Side effect management and patient-provider communication should be prioritized to optimize GS, vaginal health, and sexual function of ET users.

No clear choice between Newcastle-Ottawa Scale and Appraisal Tool for Cross-Sectional Studies to assess methodological quality in cross-sectional studies of health-related quality of life and breast cancer.

OBJECTIVES: The aim of the study was to compare the inter-rater reliability, concurrent validity, completion time, and ease of use of two methodological quality (MQ) assessment tools for cross-sectional studies: an adapted Newcastle-Ottawa Scale (NOS) and the Appraisal Tool for Cross-Sectional Studies (AXIS). STUDY DESIGN AND SETTING: Two raters applied the NOS and AXIS to 63 cross-sectional studies of health-related quality of life and breast cancer. RESULTS: AXIS demonstrated poor inter-rater reliability (intraclass correlation coefficient [ICC] = 0.49) and required more than double the amount of time to complete compared with the NOS, which demonstrated moderate reliability (ICC = 0.73). For concurrent validity, weak and moderate positive relationships existed between NOS and AXIS (rater 1: r = 0.26; rater 2: r = 0.45). Ease of using the tools was affected by the indirectness of MQ assessments, perceived thoroughness of the tools' content, and user experience. CONCLUSION: This study was the first to assess the psychometric properties of a cross-sectional NOS and AXIS. The results did not support a clear choice between selecting either tool for evaluating MQ in cross-sectional studies.