Stroke impact on mortality and psychologic morbidity within the Childhood Cancer Survivor Study.

BackgroundPoor socioeconomic and health-related quality of life (HRQOL) outcomes in survivors of childhood cancer can lead to distress and overall negatively impact the lives of these individuals. The current report has highlighted the impact of stroke and stroke recurrence on mortality, psychological HRQOL, and socioeconomic outcomes within the Childhood Cancer Survivor Study (CCSS).MethodsThe CCSS is a retrospective cohort study with longitudinal follow-up concerning survivors of pediatric cancer who were diagnosed between 1970 and 1986. Mortality rates per 100 person-years were calculated across 3 periods: 1) prior to stroke; 2) after first stroke and before recurrent stroke; and 3) after recurrent stroke. Socioeconomic outcomes, the standardized Brief Symptoms Inventory-18, the Medical Outcomes Study 36-Item Short Form Health Survey, and the CCSS-Neurocognitive Questionnaire also were assessed.ResultsAmong 14,358 participants (median age, 39.7 years), 224 had a stroke after their cancer diagnosis (single stroke in 161 patients and recurrent stroke in 63 patients). Based on 2636 deaths, all-cause late mortality rates were 0.70 (95% CI, 0.68-0.73) prior to stroke, 1.03 (95% CI, 0.73-1.46) after the first stroke, and 2.42 (95% CI, 1.48-3.94) after the recurrent stroke. Among 7304 survivors, those with stroke were more likely to live with a caregiver (single stroke odds ratio [OR], 2.3 [95% CI, 1.4-3.8]; and recurrent stroke OR, 5.3 [95% CI, 1.7-16.8]) compared with stroke-free survivors. Stroke negatively impacted task efficiency (single stroke OR, 2.4 [95% CI, 1.4-4.1] and recurrent stroke OR, 3.3 [95% CI, 1.1-10.3]) and memory (single stroke OR, 2.1 [95% CI, 1.2-3.7]; and recurrent stroke OR, 3.5 [95% CI, 1.1-10.5]).ConclusionsStroke and stroke recurrence are associated with increased mortality and negatively impact HRQOL measures in survivors of pediatric cancer

Follow-Up Care for Breast and Colorectal Cancer Across the Globe: Survey Findings From 27 Countries

Purpose: The purpose of this study was to describe follow-up care for breast and colorectal cancer survivors in countries with varying levels of resources and highlight challenges regarding posttreatment survivorship care. Methods: We surveyed one key stakeholder from each of 27 countries with expertise in survivorship care on questions including the components/structure of follow-up care, delivery of treatment summaries and survivorship care plans, and involvement of primary care in survivorship. Descriptive analyses were performed to characterize results across countries and variations between the WHO income categories (low, middle, high). We also performed a qualitative content analysis of narratives related to survivorship care challenges to identify major themes. Results: Seven low- or /lower-middle-income countries (LIC/LMIC), seven upper-middle-income countries (UMIC), and 13 high-income countries (HICs) were included in this study. Results indicate that 44.4% of countries with a National Cancer Control Plan currently address survivorship care. Additional findings indicate that HICs use guidelines more often than those in LICs/LMICs and UMICs. There was great variation among countries regardless of income level. Common challenges include issues with workforce, communication and care coordination, distance/transportation issues, psychosocial support, and lack of focus on follow-up care. Conclusion: This information can guide researchers, providers, and policy makers in efforts to improve the quality of survivorship care on a national and global basis. As the number of cancer survivors increases globally, countries will need to prioritize their long-term needs. Future efforts should focus on efforts to bridge oncology and primary care, building international partnerships, and implementation of guidelines

Risk factors for overweight and obesity after childhood acute lymphoblastic leukemia in North America and Switzerland: A comparison of two cohort studies.

BACKGROUND After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors. METHODS We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in North America and Switzerland (678) siblings. We assessed risk factors for overweight (BMI 25-29.9 kg/m2 ) and obesity (≥30 kg/m2 ) using multinomial regression. RESULTS We found overweight and obesity significantly more common among survivors in North America when compared with survivors in Switzerland [overweight: 30%, 95% confidence interval (CI): 27-32 vs. 24%, 21-29; obesity: 29%, 27-32 vs. 7%, 5-10] and siblings (overweight: 30%, 27-32 vs. 25%, 22-29; obesity: 24%, 22-26 vs. 6%, 4-8). Survivors in North America [odds ratio (OR) = 1.24, 1.01-1.53] and Switzerland (1.27, 0.74-2.21) were slightly more often obese than siblings. Among survivors, risk factors for obesity included residency in North America (5.8, 3.7-9.0); male (1.7, 1.3-2.3); attained age (≥45 years: 5.1, 2.4-10.8); Non-Hispanic Black (3.4, 1.6-7.0); low household income (2.3, 1.4-3.5); young age at diagnosis (1.6, 1.1-2.2). Cranial radiotherapy ≥18 Gray was only a risk factor for overweight (1.4, 1.0-1.8); steroids were not associated with overweight or obesity. Interaction tests found no evidence of difference in risk factors between cohorts. CONCLUSIONS Although treatment-related risk for overweight and obesity were similar between regions, higher prevalence among survivors in North America identifies important sociodemographic drivers for informing health policy and targeted intervention trials

Predicting acute ovarian failure in female survivors of childhood cancer: a cohort study in the Childhood Cancer Survivor Study (CCSS) and the St Jude Lifetime Cohort (SJLIFE).

BACKGROUND: Cancer treatment can cause gonadal impairment. Acute ovarian failure is defined as the permanent loss of ovarian function within 5 years of cancer diagnosis. We aimed to develop and validate risk prediction tools to provide accurate clinical guidance for paediatric patients with cancer. METHODS: In this cohort study, prediction models of acute ovarian failure risk were developed using eligible female US and Canadian participants in the Childhood Cancer Survivor Study (CCSS) cohort and validated in the St Jude Lifetime Cohort (SJLIFE) Study. 5-year survivors from the CCSS cohort were included if they were at least 18 years old at their most recent follow-up and had complete treatment exposure and adequate menstrual history (including age at menarche, current menstrual status, age at last menstruation, and menopausal aetiology) information available. Participants in the SJLIFE cohort were at least 10-year survivors. Participants were excluded from the prediction analysis if they had an ovarian hormone deficiency, had missing exposure information, or had indeterminate ovarian status. The outcome of acute ovarian failure was defined as permanent loss of ovarian function within 5 years of cancer diagnosis or no menarche after cancer treatment by the age of 18 years. Logistic regression, random forest, and support vector machines were used as candidate methods to develop the risk prediction models in the CCSS cohort. Prediction performance was evaluated internally (in the CCSS cohort) and externally (in the SJLIFE cohort) using the areas under the receiver operating characteristic curve (AUC) and the precision-recall curve (average precision [AP; average positive predictive value]). FINDINGS: Data from the CCSS cohort were collected for participants followed up between Nov 3, 1992, and Nov 25, 2016, and from the SJLIFE cohort for participants followed up between Oct 17, 2007, and April 16, 2012. Of 11 336 female CCSS participants, 5886 (51·9%) met all inclusion criteria for analysis. 1644 participants were identified from the SJLIFE cohort, of whom 875 (53·2%) were eligible for analysis. 353 (6·0%) of analysed CCSS participants and 50 (5·7%) of analysed SJLIFE participants had acute ovarian failure. The overall median follow-up for the CCSS cohort was 23·9 years (IQR 20·4-27·9), and for SJLIFE it was 23·9 years (19·0-30·0). The three candidate methods (logistic regression, random forest, and support vector machines) yielded similar results, and a prescribed dose model with abdominal and pelvic radiation doses and an ovarian dose model with ovarian radiation dosimetry using logistic regression were selected. Common predictors in both models were history of haematopoietic stem-cell transplantation, cumulative alkylating drug dose, and an interaction between age at cancer diagnosis and haematopoietic stem-cell transplant. External validation of the model in the SJLIFE cohort produced an estimated AUC of 0·94 (95% CI 0·90-0·98) and AP of 0·68 (95% CI 0·53-0·81) for the ovarian dose model, and AUC of 0·96 (0·94-0·97) and AP of 0·46 (0·34-0·61) for the prescribed dose model. Based on these models, an online risk calculator has been developed for clinical use. INTERPRETATION: Both acute ovarian failure risk prediction models performed well. The ovarian dose model is preferred if ovarian radiation dosimetry is available. The models, along with the online risk calculator, could help clinical discussions regarding the need for fertility preservation interventions in girls and young women newly diagnosed with cancer

Risk, risk factors and surveillance of subsequent malignant neoplasms in childhood cancer survivors: a review

Subsequent malignant neoplasms (SMNs) in childhood cancer survivors cause substantial morbidity and mortality. This review summarizes recent literature on SMN epidemiology, risk factors, surveillance, and interventions. Survivors of childhood cancer experience long-term increased SMN risk compared with the general population, with a greater than twofold increased solid tumor risk extending beyond age 40 years. There is a dose-dependent increased risk for solid tumors after radiotherapy, with the highest risks for tumors occurring in or near the treatment field (eg, greater than fivefold increased risk for breast, brain, thyroid, skin, bone, and soft tissue malignancies). Alkylating and anthracycline chemotherapies increase the risk for development of several solid malignancies in addition to acute leukemia/myelodysplasia, and these risks may be modified by other patient characteristics, such as age at exposure and, potentially, inherited genetic susceptibility. Strategies for identifying survivors at risk and initiating long-term surveillance have improved and interventions are underway to improve knowledge about late-treatment effects among survivors and caregivers. Better understanding of treatment-related risk factors and genetic susceptibility holds promise for refining surveillance strategies and, ultimately, upfront cancer therapies

Risk stratification of childhood cancer survivors necessary for evidence-based clinical long-term follow-up

Background: Reorganisation of clinical follow-up care in England was proposed by the National Cancer Survivorship Initiative (NCSI), based on cancer type and treatment, ranging from Level 1 (supported self-management) to Level 3 (consultant-led care). The objective of this study was to provide an investigation of the risks of serious adverse health-outcomes associated with NCSI Levels of clinical care using a large population-based cohort of childhood cancer survivors. Methods: The British Childhood Cancer Survivor Study (BCCSS) was used to investigate risks of specific causes of death, subsequent primary neoplasms (SPNs) and non-fatal non-neoplastic outcomes by NCSI Level. Results: Cumulative (excess) risks of specified adverse outcomes by 45 years from diagnosis among non-leukaemic survivors assigned to NCSI Levels 1, 2 and 3 were for: SPNs—5% (two-fold expected), 14% (four-fold expected) and 21% (eight-fold expected); non-neoplastic death—2% (two-fold expected), 4% (three-fold expected) and 8% (seven-fold expected); non-fatal non-neoplastic condition—14%, 27% and 40%, respectively. Consequently overall cumulative risks of any adverse health outcome were 21%, 45% and 69%, respectively. Conclusions: Despite its simplicity the risk stratification tool provides clear and strong discrimination between survivors assigned to different NCSI Levels in terms of long-term cumulative and excess risks of serious adverse outcomes

Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer.

Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m-2: 1.24, 95% confidence interval (CI): 1.18-1.31), with more than twofold increased risk for survivors treated with ≥200 mg m-2 cumulative doxorubicin dose versus no doxorubicin (HR: 2.50 for 200-299 mg m-2, HR: 2.33 for 300-399 mg m-2 and HR: 2.78 for ≥400 mg m-2). For daunorubicin, the associations were not statistically significant. Epirubicin was associated with increased SBC risk (yes/no, HR: 3.25, 95% CI: 1.59-6.63). For patients treated with or without chest irradiation, HRs per 100 mg m-2 of doxorubicin were 1.11 (95% CI: 1.02-1.21) and 1.26 (95% CI: 1.17-1.36), respectively. Our findings support that early initiation of SBC surveillance may be reasonable for survivors who received ≥200 mg m-2 cumulative doxorubicin dose and should be considered in SBC surveillance guidelines for survivors and future treatment protocols

Relative Burden of Cancer and Noncancer Mortality Among Long-Term Survivors of Breast, Prostate, and Colorectal Cancer in the US

IMPORTANCE: Improvements in cancer outcomes have led to a need to better understand long-term oncologic and nononcologic outcomes and quantify cancer-specific vs noncancer-specific mortality risks among long-term survivors. OBJECTIVE: To assess absolute and relative cancer-specific vs noncancer-specific mortality rates among long-term survivors of cancer, as well as associated risk factors. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 627 702 patients in the Surveillance, Epidemiology, and End Results cancer registry with breast, prostate, or colorectal cancer who received a diagnosis between January 1, 2003, and December 31, 2014, who received definitive treatment for localized disease and who were alive 5 years after their initial diagnosis (ie, long-term survivors of cancer). Statistical analysis was conducted from November 2022 to January 2023. MAIN OUTCOMES AND MEASURES: Survival time ratios (TRs) were calculated using accelerated failure time models, and the primary outcome of interest examined was death from index cancer vs alternative (nonindex cancer) mortality across breast, prostate, colon, and rectal cancer cohorts. Secondary outcomes included subgroup mortality in cancer-specific risk groups, categorized based on prognostic factors, and proportion of deaths due to cancer-specific vs noncancer-specific causes. Independent variables included age, sex, race and ethnicity, income, residence, stage, grade, estrogen receptor status, progesterone receptor status, prostate-specific antigen level, and Gleason score. Follow-up ended in 2019. RESULTS: The study included 627 702 patients (mean [SD] age, 61.1 [12.3] years; 434 848 women [69.3%]): 364 230 with breast cancer, 118 839 with prostate cancer, and 144 633 with colorectal cancer who survived 5 years or more from an initial diagnosis of early-stage cancer. Factors associated with shorter median cancer-specific survival included stage III disease for breast cancer (TR, 0.54; 95% CI, 0.53-0.55) and colorectal cancer (colon: TR, 0.60; 95% CI, 0.58-0.62; rectal: TR, 0.71; 95% CI, 0.69-0.74), as well as a Gleason score of 8 or higher for prostate cancer (TR, 0.61; 95% CI, 0.58-0.63). For all cancer cohorts, patients at low risk had at least a 3-fold higher noncancer-specific mortality compared with cancer-specific mortality at 10 years of diagnosis. Patients at high risk had a higher cumulative incidence of cancer-specific mortality than noncancer-specific mortality in all cancer cohorts except prostate. CONCLUSIONS AND RELEVANCE: This study is the first to date to examine competing oncologic and nononcologic risks focusing on long-term adult survivors of cancer. Knowledge of the relative risks facing long-term survivors may help provide pragmatic guidance to patients and clinicians regarding the importance of ongoing primary and oncologic-focused care