Difficulties with negotiating and achieving desired social outcomes in life may be exacerbated by the experience of childhood cancer, including adverse effects from therapies used to achieve a cure. ...This review of previous publications from the Childhood Cancer Survivor Study (CCSS) and other relevant literature provides insight into the prevalence of, and risk factors for, poor educational attainment, less than optimal employment status, and interpersonal relationship issues among long-term survivors of childhood cancer. The impacts of emotional health and physical disability on social outcomes are also examined. Study results suggest that childhood cancer survivors generally have similar high school graduation rates, but are more likely to require special education services than sibling comparison groups. Survivors are slightly less likely than expected to attend college, and are more likely to be unemployed and not married as young adults. Cancers and treatments that result in impairment to the CNS, particularly brain tumors, or that impact sensory functioning, such as hearing loss, are associated with greater risk for undesirable social outcomes, as are emotional health problems and physical disability. This review of relevant data from CCSS and other studies provides information on risk factors for social problems into adulthood. A greater understanding of the long-term social impacts from the diagnosis and treatment of childhood cancer is critically important for developing targeted interventions to prevent or ameliorate adverse psychosocial effects.
Risk-stratified therapy, which modifies treatment on the basis of clinical and biologic features, has improved 5-year overall survival of childhood acute lymphoblastic leukemia (ALL) to 90%, but its ...impact on long-term toxicity remains unknown.
We assessed all-cause and health-related late mortality (including late effects of cancer therapy), subsequent malignant neoplasms (SMNs), chronic health conditions, and neurocognitive outcomes among 6,148 survivors of childhood ALL (median age, 27.9 years; range, 5.9-61.9 years) diagnosed between 1970 and 1999. Therapy combinations and treatment intensity defined 6 groups: 1970s-like (70s), standard- or high-risk 1980s-like (80sSR, 80sHR) and 1990s-like (90sSR, 90sHR), and relapse/transplantation (R/BMT). Cumulative incidence, standardized mortality ratios, and standardized incidence ratios were compared between treatment groups and with the US population.
Overall, 20-year all-cause late mortality was 6.6% (95% CI, 6.0 to 7.1). Compared with 70s, 90sSR and 90sHR experienced lower health-related late mortality (rate ratio 95% CI: 90sSR, 0.2 0.1 to 0.4; 90sHR, 0.3 0.1 to 0.7), comparable to the US population (standardized mortality ratio 95% CI: 90sSR, 1.3 0.8 to 2.0; 90sHR, 1.7 0.7 to 3.5). Compared with 70s, 90sSR had a lower rate of SMN (rate ratio 95% CI, 0.3 0.1 to 0.6) that was not different from that of the US population (standardized incidence ratio 95% CI, 1.0 0.6 to 1.6). The 90sSR group had fewer severe chronic health conditions than the 70s (20-year cumulative incidence 95% CI, 11.0% 9.7% to 12.3%
22.5% 19.4% to 25.5%) and a lower prevalence of impaired memory (prevalence ratio 95% CI, 0.7 0.6 to 0.9) and task efficiency (0.5 0.4 to 0.7).
Risk-stratified therapy has reduced late morbidity and mortality among contemporary survivors of standard-risk ALL, represented by 90sSR. Health-related late mortality and SMN risks among 5-year survivors of contemporary, standard-risk childhood ALL are comparable to the general population.
Immune-checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape for multiple malignancies and the health of the gut microbiome (GM) is strongly linked with therapeutic responses to ...ICI. This review explores the implications of diet and medication on the GM for patients receiving ICI. Clinical trials are underway to explore the impact of factors such as faecal microbiota transfer, probiotics, prebiotics, bacteria consortia and a number of dietary interventions on patients receiving ICI. Randomised controlled trials are lacking, and inferences are currently based on short-term clinical and observational studies. Antibiotics should be avoided before ICI initiation, and depending on prospective data, future consideration may be given to temporary delay of initiation of non-urgent ICI if patient has had broad spectrum antibiotics within 1 month of planned treatment initiation. Proton pump inhibitor use should be discontinued when not clearly indicated and potential switch to a histamine H2-receptor antagonist considered. Patients should be advised to minimise animal meat intake and maximise plants, aiming to consume ≥30 plant types weekly. A high fibre intake (>30 g/day) has been seen to be beneficial in increasing the chance of ICI response. Fermented foods may have a beneficial effect on the GM and should be introduced where possible. Ideally, all patients should be referred to a nutritionist or dietician with knowledge of GM before commencing ICI.
•Therapeutic response to immune-checkpoint inhibitor (ICI) is linked to the gut microbiome.•Care needs to be given to protecting the microbiome, both by clinicians and patients.•Patients' diets should focus on diversity, variety, plentiful plants, protein and dietary fibres.•Antibiotics and many other common medications can adversely affect responses to ICI.•Before and during ICI patients should have access to nutritional support.
Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of ...therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment.
We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk.
Among 23 601 survivors with a median follow-up of 21 years (IQR 15–25), the 20-year cumulative incidence of at least one grade 3–5 chronic condition decreased significantly from 33·2% (95% CI 32·0–34·3) in those diagnosed 1970–79 to 29·3% (28·4–30·2; p<0·0001) in 1980–89, and 27·5% (26·4–28·6; p=0·012 vs 1980–89) in 1990–99. By comparison, the 20-year cumulative incidence of at least one grade 3–5 condition in 5051 siblings was 4·6% (95% CI 3·9–5·2). The 15-year cumulative incidence of at least one grade 3–5 condition was lower for survivors diagnosed 1990–99 compared with those diagnosed 1970–79 for Hodgkin lymphoma (17·7% 95% CI 15·0–20·5 vs 26·4% 23·8–29·1; p<0·0001), non-Hodgkin lymphoma (16·9% 14·0–19·7 vs 23·8% 19·9–27·7; p=0.0053), astrocytoma (30·5% 27·8–33·2 vs 47·3% 42·9–51·7; p<0·0001), Wilms tumour (11·9% 9·5–14·3 vs 17·6% 14·3–20·8; p=0·034), soft tissue sarcoma (28·3% 23·5–33·1 vs 36·5% 31·5–41·4; p=0·021), and osteosarcoma (65·6% 60·6–70·6 vs 87·5% 84·1–91·0; p<0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3–5 condition was higher (1990–99 vs 1970–79) for medulloblastoma or primitive neuroectodermal tumour (58·9% 54·4–63·3 vs 42·9% 34·9–50·9; p=0·00060), and neuroblastoma (25·0% 21·8–28·2 vs 18·0% 14·5–21·6; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3–5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64–0·92; HR with treatment in the model=0·89, 95% CI 0·72–1·11; pmediation=0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95% CI 0·65–0·85; HR with treatment=0·91, 95% CI 0·73–1·12; pmediation=0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970–79 to survivors diagnosed 1990–99 were noted for endocrinopathies (5·9% 5·3–6·4 vs 2·8% 2·5–3·2; p<0·0001), subsequent malignant neoplasms (2·7% 2·3–3·1 vs 1·9% 1·6–2·2; p=0·0033), musculoskeletal conditions (5·8% 5·2–6·4 vs 3·3% 2·9–3·6; p<0·0001), and gastrointestinal conditions (2·3% 2·0–2·7 vs 1·5% 1·3–1·8; p=0·00037), while hearing loss increased (3·0% 2·6–3·5 vs 5·7% 5·2–6·1; p<0·0001).
Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population.
National Cancer Institute and the American Lebanese-Syrian Associated Charities.
Hearing loss is a significant late effect among childhood cancer survivors. Recent guidelines note insufficient evidence to quantify its natural history or risk associated with specific exposures. We ...examined the long-term incidence and predictors of hearing loss requiring hearing amplification devices (HADs) using population-based health care data.
In Ontario, Canada, HAD costs are subsidized by the Assistive Devices Program (ADP). Ontario children < 18 years of age at cancer diagnosis between 1987 and 2016 were identified and linked to ADP claims. Cumulative HAD incidence was compared between cases and matched controls. Patient, disease, and treatment predictors of HAD were examined.
We identified 11,842 cases and 59,210 controls. Cases were at higher risk for HAD (hazard ratio HR, 12.8; 95% CI, 9.8 to 16.7;
< .001). The cumulative incidence of HAD among survivors was 2.1% (95% CI, 1.7% to 2.5%) at 20 years and 6.4% (95% CI, 2.8% to 12.1%) at 30 years post-diagnosis. The 30-year incidence was highest in neuroblastoma (10.7%; 95% CI, 3.8% to 21.7%) and hepatoblastoma (16.2%; 95% CI, 8.6% to 26.0%) survivors. Predictors of HAD in multivariable analyses included age 0-4 years at diagnosis (
5-9 years; HR, 2.2; 95% CI, 1.4-3.3;
< .001). Relative to no cisplatin exposure, patients receiving < 200 mg/m
were not at greater risk, unlike those receiving higher cumulative doses. Relative to no cranial or facial radiation, those who had received ≤ 32.00 Gy were at no higher risk, unlike those who had received > 32.00 Gy. Carboplatin exposure was not associated with HAD.
Childhood cancer survivors are at elevated risk for requiring HAD, which continues to increase between 20 and 30 years after diagnosis. Thresholds of cisplatin and radiation exposure exist, above which risk substantially increases. Prolonged monitoring and trials of otoprotective agents are warranted in high-risk populations.
By the end of the twelfth century, the Byzantine genos was a politically effective social group based upon ties of consanguineous kinship, but, importantly, it was also a cultural construct, an idea ...that held very real power, yet defies easy categorization. This study explores the role and function of the Byzantine aristocratic family group, or genos , as a distinct social entity, particularly its political and cultural role, as it appears in a variety of sources in the tenth through twelfth centuries.
This
paper presents a timely and constructive critique of mainstream SIDS research. It is concerning that twenty-first century medical science has not provided an answer to the tragic enigma of SIDS. ...The paper helps explain why this is so and illustrates possible shortcomings in the investigation of Sudden Infant Death Syndrome/Sudden Unexplained Infant Death (SIDS/SUID) by mainstream researchers. Mainstream findings are often based on questionable and dogmatic assumptions that return to founding notions such as the Triple Risk Hypothesis and the contention that the mechanisms underlying SIDS/SUID are heterogeneous in nature. The paper illustrates how the pathological findings in SIDS have been under-investigated (or ignored) and that key epidemiological risk factors have slipped from memory. This apparent amnesia has resulted in failure to use these established SIDS facts to substantiate the significance of various neuropathological, neurochemical, or other research findings. These unsupported findings and their derivative hypotheses are therefore ill-founded and lack scientific rigor.
The deficits of SIDS "science" revealed in this paper explain why the SIDS enigma has not yet been solved. To make progress in understanding SIDS, it is important that researchers, as scientists, uphold standards of research. Encouragement for new directions of research is offered.
Childhood, adolescent, and young adult (CAYA) cancer survivors treated with platinum-based drugs, head or brain radiotherapy, or both have an increased risk of ototoxicity (hearing loss, tinnitus, or ...both). To ensure optimal care and reduce consequent problems—such as speech and language, social–emotional development, and learning difficulties—for these CAYA cancer survivors, clinical practice guidelines for monitoring ototoxicity are essential. The implementation of surveillance across clinical settings is hindered by differences in definitions of hearing loss, recommendations for surveillance modalities, and remediation. To address these deficiencies, the International Guideline Harmonization Group organised an international multidisciplinary panel, including 32 experts from ten countries, to evaluate the quality of evidence for ototoxicity following platinum-based chemotherapy and head or brain radiotherapy, and formulate and harmonise ototoxicity surveillance recommendations for CAYA cancer survivors.
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