Several randomized controlled trials (RCTs) have demonstrated that dexrazoxane reduces anthracycline cardiotoxicity in adults, but use in children has been hindered by lack of direct evidence of ...cardioprotection and concerns regarding second malignant neoplasms (SMNs). This study aimed to systematically review the evidence regarding dexrazoxane in children.
We searched Medline, Embase, the Cochrane Library, and abstracts for RCTs and nonrandomized studies (NRSs) that compared dexrazoxane to no cardioprotection among children. We combined findings using random-effects models. All statistical tests were two-sided.
Eleven eligible publications reported results from five RCTs (1254 patients), and 15 publications reported results from 12 NRSs (3385 patients). Dexrazoxane did not impact clinical cardiotoxicity in RCTs because of a low cardiotoxic event rate (three events among all patients) but was associated with a reduction in subclinical cardiotoxicity. Among NRSs, dexrazoxane was associated with a reduction in clinical cardiotoxicity (relative risk (RR) = 0.29, P = .001) and clinical+subclinical cardiotoxicity (RR = 0.43, P < .001). Among RCTs, 17 of 635 (2.7%) patients treated with dexrazoxane developed an SMN compared with seven of 619 (1.1%) who did not receive dexrazoxane (RR = 2.37, P = .06). Two RCTs that used concurrent etoposide reported an increased risk of acute myeloid leukemia, while one that used cranial radiation reported an increased risk of brain tumors. Event-free survival did not differ (P = .91).
Dexrazoxane is associated with a statistically significant risk reduction for most cardiotoxic outcomes. Dexrazoxane is associated with a statistically borderline increase in SMNs, possibly because of an interaction with concurrent cancer therapies. The decision to use dexrazoxane in children should balance the risks of cardiotoxicity and SMNs specific to each treatment protocol.
Adolescents and young adults (AYA) with cancer are an understudied group. Much of what is known about long‐term outcomes after AYA cancer has been derived from cohorts of childhood cancer survivors, ...which seldom include patients at the older end of the AYA age spectrum. In general, AYA cancer survivors have a lower risk for premature mortality, subsequent primary neoplasms and chronic health conditions than childhood cancer survivors. However, AYA cancer survivors are vulnerable to psychosocial challenges, concerns about fertility and relationships and financial toxicity. No single model is optimal for the care of these survivors, but it is generally agreed that all survivors require a survivor care plan that promotes their adherence to evidence‐based surveillance guidelines. There is a need to create survivor cohorts that include the full range of AYA ages and diagnoses to be able to address the many pressing questions that remain unanswered in this vulnerable population.
Abstract
Background
Cancer and its treatment can result in lifelong medical financial hardship, which we aimed to describe among adult survivors of adolescent and young adult (AYA) cancers in the ...United States.
Methods
We identified adult (aged ≥18 years) survivors of AYA cancers (diagnosed ages 15-39 years) and adults without a cancer history from the 2010-2018 National Health Interview Surveys. Proportions of respondents reporting measures in different hardship domains (material eg, problems paying bills, psychological eg, distress, and behavioral eg, forgoing care due to cost) were compared between groups using multivariable logistic regression models and hardship intensity (cooccurrence of hardship domains) using ordinal logistic regression. Cost-related changes in prescription medication use were assessed separately.
Results
A total of 2588 AYA cancer survivors (median = 31 interquartile range = 26-35 years at diagnosis; 75.0% more than 6 years and 50.0% more than 16 years since diagnosis) and 256 964 adults without a cancer history were identified. Survivors were more likely to report at least 1 hardship measure in material (36.7% vs 27.7%, P < .001) and behavioral (28.4% vs 21.2%, P < .001) domains, hardship in all 3 domains (13.1% vs 8.7%, P < .001), and at least 1 cost-related prescription medication nonadherence (13.7% vs 10.3%, P = .001) behavior.
Conclusions
Adult survivors of AYA cancers are more likely to experience medical financial hardship across multiple domains compared with adults without a cancer history. Health-care providers must recognize this inequity and its impact on survivors’ health, and multifaceted interventions are necessary to address underlying causes.
Preclinical data suggest the combination of an anti-programmed death receptor 1 antibody plus dabrafenib and trametinib to have superior antitumor activity compared with dabrafenib plus trametinib ...alone. These observations are supported by translational evidence suggesting that immune checkpoint inhibitors plus targeted therapy may improve treatment outcomes in patients with
V600-mutant metastatic melanoma. COMBI-i is a phase III trial evaluating spartalizumab, an anti-programmed death receptor 1 antibody, in combination with dabrafenib and trametinib (sparta-DabTram), versus placebo plus dabrafenib and trametinib (placebo-DabTram) in patients with
V600-mutant unresectable or metastatic melanoma.
Patients received spartalizumab 400 mg intravenously every 4 weeks plus dabrafenib 150 mg orally twice daily and trametinib 2 mg orally once daily or placebo-DabTram. Participants were age ≥ 18 years with unresectable or metastatic
V600-mutant melanoma. The primary end point was investigator-assessed progression-free survival. Overall survival was a key secondary end point (ClinicalTrials.gov identifier: NCT02967692).
At data cutoff (July 1, 2020), the median progression-free survival was 16.2 months (95% CI, 12.7 to 23.9 months) in the sparta-DabTram arm versus 12.0 months (95% CI, 10.2 to 15.4 months) in the placebo-DabTram arm (hazard ratio, 0.82 95% CI, 0.66 to 1.03;
= .042 one-sided; nonsignificant). The objective response rates were 69% (183 of 267 patients) versus 64% (170 of 265 patients), respectively. Grade ≥ 3 treatment-related adverse events occurred in 55% (146 of 267) of patients in the sparta-DabTram arm and 33% (88 of 264) in the placebo-DabTram arm.
The study did not meet its primary end point; broad first-line use of sparta-DabTram is not supported by these results. Further biomarker-driven investigation may identify patient subpopulations who could benefit from checkpoint inhibitor plus targeted therapy combinations.
Complementary Health Approaches (CHA) are commonly used by children with cancer; however, a few health care providers (HCPs) inquire about the use of CHA. A standardized questionnaire could ...facilitate such clinical discussions. We aimed to adapt and determine the face and content validity of the "Which Health Approaches and Treatments are you using?" (WHAT) child and parent-report questionnaires in pediatric oncology.
An electronic Delphi survey that included children with cancer (8-18 years), parents, and HCPs and CHA researchers was conducted to reach consensus on the content of the WHAT questionnaires in pediatric oncology. Children and parents from the Hospital for Sick Children (SickKids), and HCPs and researchers from the International Society of Pediatric Oncology and Pediatric Complementary and Alternative Medicine Research and Education Network completed the survey. To determine the face and content validity of the questionnaires, two iterative cycles of individual interviews were conducted with purposive samples of children (8-18 years), parents, and HCPs from SickKids.
Consensus was reached on all domains and items of the original WHAT questionnaires after one Delphi cycle (n = 61). For face and content validity testing, the first cycle of interviews (n = 19) revealed that the questionnaires were mostly comprehensive and relevant. However, the paper-based format of the original WHAT was not user-friendly, and generic items were vague and not aimed at facilitating clinical dialogues about CHA use. The WHAT questionnaires were then modified into electronic cancer-specific self- and proxy-report questionnaires including 13 and 15 items, respectively. The second cycle (n = 21) showed no need for further changes.
The modified electronic cancer-specific WHAT questionnaires showed adequate face and content validity. The next step is to determine inter-rater reliability, construct validity, and feasibility of administration of the modified WHAT questionnaires in pediatric oncology.
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.
This systematic review and meta‐analysis demonstrated that, across international settings, childhood cancer survivors remain at an increased risk of all‐cause and cause‐specific mortality for decades after their cancer diagnosis. These findings suggest that late mortality risk might differ significantly between world regions, but these conclusions are based on a limited number of studies with considerable heterogeneity.
A unique collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and ...Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on the systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to 2-cm safety margins. Sentinel lymph node dissection shall be performed as a staging procedure in patients with tumor thickness ≥1.0 mm or ≥0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions in stage III/IV patients should be primarily made by an interdisciplinary oncology team (“tumor board”). Adjuvant therapies can be proposed in stage III/completely resected stage IV patients and are primarily anti-PD-1, independent of mutational status, or alternatively dabrafenib plus trametinib for BRAF mutant patients. In distant metastases (stage IV), either resected or not, systemic treatment is always indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies shall be considered. In stage IV melanoma with a BRAF-V600 E/K mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy. In patients with primary resistance to immunotherapy and harboring a BRAF-V600 E/K mutation, this therapy shall be offered as second-line therapy. Systemic therapy in stage III/IV melanoma is a rapidly changing landscape, and it is likely that these recommendations may change in the near future.
Adult survivors of childhood cancer are at elevated risk of morbidity and mortality compared to the general population, but their adherence to lifelong periodic surveillance is suboptimal. We aimed ...to examine adherence to surveillance guidelines for high-yield tests and identify risk factors for nonadherence in adult survivors of childhood cancer.
In this retrospective, population-based cohort study, we used health care administrative data from Ontario, Canada, to identify adult survivors of childhood cancer diagnosed between 1986 and 2014 who were at elevated risk of therapy-related colorectal cancer, breast cancer, or cardiomyopathy. Using a Poisson regression framework, we assessed longitudinal adherence and predictors of adherence to the Children's Oncology Group surveillance guideline.
Among 3241 survivors, 327 (10%), 234 (7%), and 3205 (99%) were at elevated risk for colorectal cancer, breast cancer, and cardiomyopathy, respectively. Within these cohorts, only 13%, 6%, and 53% were adherent to recommended surveillance as of February 2020. During a median follow-up of 7.8 years, the proportion of time spent adherent was 14% among survivors at elevated risk for colorectal cancer, 10% for breast cancer, and 43% for cardiomyopathy. Significant predictors of adherence varied across the risk groups, but higher comorbidity was associated with adherence to recommended surveillance.
Survivors of childhood cancer in Ontario are rarely up to date for recommended surveillance tests. Tailored interventions beyond specialized clinics are needed to improve surveillance adherence.
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