Health care systems and providers have a responsibility to ensure that access to cancer clinical trials, opportunities to complete the trial, and access to lifelong survivor care are all thoughtfully ...examined with an equity lens. This will allow the greatest possible number of pediatric and adolescent and young adult cancer patients to receive the highest quality of care possible, in treatment and beyond.
Summary Survivors of childhood cancer treated with anthracycline chemotherapy or chest radiation are at an increased risk of developing congestive heart failure. In this population, congestive heart ...failure is well recognised as a progressive disorder, with a variable period of asymptomatic cardiomyopathy that precedes signs and symptoms. As a result, several clinical practice guidelines have been developed independently to help with detection and treatment of asymptomatic cardiomyopathy. These guidelines differ with regards to definitions of at-risk populations, surveillance modality and frequency, and recommendations for interventions. Differences between these guidelines could hinder the effective implementation of these recommendations. We report on the results of an international collaboration to harmonise existing cardiomyopathy surveillance recommendations using an evidence-based approach that relied on standardised definitions for outcomes of interest and transparent presentation of the quality of the evidence. The resultant recommendations were graded according to the quality of the evidence and the potential benefit gained from early detection and intervention.
Background
For parents, a diagnosis of cancer in their child is a traumatic experience. However, there is conflicting evidence about the risk of developing mental illness among parents following ...diagnosis. Our objective was to conduct a meta‐analysis to determine the prevalence of mental illness in parents of children with cancer.
Methods
Four databases were searched to identify articles describing the prevalence of anxiety, depression, or posttraumatic stress disorder (PTSD) in parents of pediatric cancer patients. Two reviewers independently screened and extracted data. Subgroup analyses by gender and phase of cancer experience were selected a priori. Studies were reviewed in accordance with PRISMA guidelines.
Results
Of 11 394 articles identified, 58 met inclusion criteria. Reported prevalence was highly heterogeneous, ranging from 5% to 65% for anxiety (pooled prevalence 21% 95% CI, 13%–35%), 7% to 91% for depression (pooled prevalence 28% 95% CI, 23%–35%), and 4% to 75% for PTSD (pooled prevalence 26% 95% CI, 22%–32%). Prevalence was consistently higher than noncancer parental controls. Heterogeneity was not explained by parental gender or child's cancer phase and was instead likely due to significant methodological differences in measurement tools and defined thresholds.
Conclusions
Parents of children with cancer have a higher prevalence of anxiety, depression, and PTSD compared with population controls. Yet, the reported prevalence of mental illness was highly variable, hampering any conclusive findings on absolute prevalence. To better understand the risk of long‐term mental illness in this population and target interventions, future studies must adhere to standardized reporting and methods.
Uveal melanoma represents ∼85% of all ocular melanomas and up to 50% of patients develop metastatic disease. Metastases are most frequently localised to the liver and, as few patients are candidates ...for potentially curative surgery, this is associated with a poor prognosis. There is currently little published evidence for the optimal management and treatment of metastatic uveal melanoma and the lack of effective therapies in this setting has led to the widespread use of systemic treatments for patients with cutaneous melanoma. Uveal and cutaneous melanomas are intrinsically different diseases and so dedicated management strategies and therapies for uveal melanoma are much needed. This review explores the biology of uveal melanoma and how this relates to ongoing trials of targeted therapies in the metastatic disease setting. In addition, we consider the options to optimise patient management and care.
Alterations in treatment intensity and decreased use of radiation therapy have reduced the risk of late treatment-related death in long-term survivors of childhood cancer.
In the 1960s, fewer than ...half the children in whom cancer was diagnosed were still alive 5 years later.
1
Now, more than 83% of patients with a childhood cancer in the United States become 5-year survivors of the disease.
2
As a result, in 2013 it was estimated that there were more than 420,000 survivors of childhood cancer in the United States and that by the year 2020 this number would surpass 500,000.
3
Increased success in the treatment of childhood cancers has been achieved through the systematic conduct of clinical trials to assess the efficacy of multimodal approaches involving combination chemotherapy, . . .
Although a diagnosis of childhood cancer can have a profound effect on the entire family unit, its impact on the long-term mental health of family members is not well characterized.
A provincial ...childhood cancer registry in Ontario, Canada, was linked to birth records to identify separate population-based cohorts of mothers and siblings of children diagnosed with cancer between 1998 and 2014. The mother and sibling cohorts were matched to corresponding population controls and linked to health services data. The rate of mental health-related outpatient visits (family physician, psychiatrist) and the incidence of severe psychiatric events (psychiatric emergency department visit, psychiatric hospitalization, suicide) were compared between mothers and siblings and their controls. Possible predictors of mental health outcomes were examined, including demographics, characteristics of the cancer-affected child, and cancer treatment.
We identified 4,773 mothers and 7,897 siblings of children diagnosed with cancer during the study period. Compared with controls, both groups experienced elevated rates of outpatient visits (mothers: rate ratio RR, 1.4;
< .0001; siblings: RR, 1.1;
< .0001). The risk of severe psychiatric events was not increased in either cohort. Mother and sibling demographic factors associated with increased risk of adverse mental health included younger maternal age at cancer diagnosis, low socioeconomic status, and rural residence among mothers and older sibling age among siblings. Treatment-related variables pertaining to the cancer-affected child were not associated with mental health outcomes. Mental health outcomes clustered within families.
Both mothers and siblings experience elevated and prolonged need for mental health-related health care as compared with the general population. Demographic risk factors predict subpopulations at highest risk. Increased psychosocial support for family members during and after cancer therapy is warranted.
Treatment outcomes among survivors of cancer diagnosed during adolescence and early young adulthood have not been characterised independently of survivors of cancers diagnosed during childhood. We ...aimed to describe chronic health conditions and all-cause and cause-specific mortality among survivors of early-adolescent and young adult cancer.
The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study with longitudinal follow-up of 5-year survivors diagnosed with cancer before the age of 21 years at 27 academic institutions in the USA and Canada between 1970 and 1999. We evaluated outcomes among survivors of early-adolescent and young adult cancer (aged 15–20 years at diagnosis) and survivors diagnosed at age younger than 15 years (matched on primary cancer diagnosis, including leukaemia, lymphoma, CNS tumours, neuroblastoma, Wilms tumour, soft-tissue sarcomas, and bone cancer) by comparing both groups to siblings of the same age. Mortality was ascertained with the National Death Index. Chronic health conditions were classified with the Common Terminology Criteria for Adverse Events. Standardised mortality ratios (SMRs) were estimated with age-specific, sex-specific, and calendar year-specific US rates. Cox proportional hazard models estimated hazard ratios (HRs) for chronic health conditions and 95% CIs.
Among 5804 early-adolescent and young adult survivors (median age 42 years, IQR 34–50) the SMR compared to the general population for all-cause mortality was 5·9 (95% CI 5·5–6·2) and among 5804 childhood cancer survivors (median age 34 years; 27–42), it was 6·2 (5·8–6·6). Early-adolescent and young adult survivors had lower SMRs for death from health-related causes (ie, conditions that exclude recurrence or progression of the primary cancer and external causes, but include the late effects of cancer therapy) than did childhood cancer survivors (SMR 4·8 95% CI 4·4–5·1 vs 6·8 6·2–7·4), which was primarily evident more than 20 years after cancer diagnosis. Early-adolescent and young adult cancer survivors and childhood cancer survivors were both at greater risk of developing severe and disabling, life-threatening, or fatal (grade 3–5) health conditions than siblings of the same age (HR 4·2 95% CI 3·7–4·8 for early adolescent and young adult cancer survivors and 5·6 4·9–6·3 for childhood cancer survivors), and at increased risk of developing grade 3–5 cardiac (4·3 3·5–5·4 and 5·6 4·5–7·1), endocrine (3·9 2·9–5·1 and 6·4 5·1–8·0), and musculoskeletal conditions (6·5 3·9–11·1 and 8·0 4·6–14·0) when compared with siblings of the same age, although all these risks were lower for early-adolescent and young adult survivors than for childhood cancer survivors.
Early-adolescent and young adult cancer survivors had higher risks of mortality and severe and life threatening chronic health conditions than the general population. However, early-adolescent and young adult cancer survivors had lower non-recurrent, health-related SMRs and relative risks of developing grade 3–5 chronic health conditions than childhood cancer survivors, by comparison with siblings of the same age, which were most notable more than 20 years after their original cancer. These results highlight the need for long-term screening of both childhood and early-adolescent and young adult cancer survivors.
National Cancer Institute and American Lebanese-Syrian Associated Charities.
In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase ...III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy.
Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine).
In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor.
This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.
In long-term follow-up of more than 500 patients with melanoma containing a
BRAF
V600E or V600K mutation, a combination of dabrafenib plus trametinib was associated with progression-free survival in ...19% of the patients and overall survival in 34% at 5 years. A complete response to dabrafenib plus trametinib was the strongest predictor of long-term survival.
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