BackgroundTreatment abandonment (TxA) is recognized as a leading cause of treatment failure for children with cancer in low-and-middle-income countries (LMC). However, its global frequency and burden have remained elusive due to lack of global data. This study aimed to obtain an estimate using survey and population data.MethodsChildhood cancer clinicians (medical oncologists, surgeons, and radiation therapists), nurses, social workers, and psychologists involved in care of children with cancer were approached through an online survey February-May 2012. Incidence and population data were obtained from public sources. Descriptive, univariable, and multivariable analyses were conducted.Results602 responses from 101 countries were obtained from physicians (84%), practicing pediatric hematology/oncology (83%) in general or children’s hospitals (79%). Results suggested, 23,854 (15%) of 155,088 children <15 years old newly diagnosed with cancer annually in the countries analyzed, abandon therapy. Importantly, 83% of new childhood cancer cases and 99% of TxA were attributable to LMC. The annual number of cases of TxA expected in LMC worldwide (26,166) was nearly equivalent to the annual number of cancer cases in children <15 years expected in HIC (26,368). Approximately two thirds of LMC had median TxA≥6%, but TxA ≥6% was reported in high- (9%), upper-middle- (41%), lower-middle- (80%), and low-income countries (90%, p<0.001). Most LMC centers reporting TxA>6% were outside the capital. Lower national income category, higher reliance on out-of-pocket payments, and high prevalence of economic hardship at the center were independent contextual predictors for TxA ≥6% (p<0.001). Global survival data available for more developed and less developed regions suggests TxA may account for at least a third of the survival gap between HIC and LMC.ConclusionResults show TxA is prevalent (compromising cancer survival for 1 in 7 children globally), confirm the suspected high burden of TxA in LMC, and illustrate the negative impact of poverty on its occurrence. The present estimates may appear small compared to the global burden of child death from malnutrition and infection (measured in millions). However, absolute numbers suggest the burden of TxA in LMC is nearly equivalent to annually losing all kids diagnosed with cancer in HIC just to TxA, without even considering deaths from disease progression, relapse or toxicity–the main causes of childhood cancer mortality in HIC. Results document the importance of monitoring and addressing TxA as part of childhood cancer outcomes in at-risk settings.

BackgroundUnderstanding and addressing treatment abandonment (TxA) is crucial for bridging the pediatric cancer survival gap between high-income (HIC) and low-and middle-income countries (LMC). In childhood cancer, TxA is defined as failure to start or complete curative cancer therapy and known to be a complex phenomenon. With rising interest on causes and consequences of TxA in LMC, this study aimed to establish the lay-of-the-land regarding determinants of TxA globally, perform and promote comparative research, and raise awareness on this subject.MethodsPhysicians (medical oncologists, surgeons, and radiation therapists), nurses, social workers, and psychologists involved in care of children with cancer were approached through an online survey February-May 2012. Queries addressed social, economic, and treatment-related determinants of TxA. Free-text comments were collected. Descriptive and qualitative analyses were performed. Appraisal of overall frequency, burden, and predictors of TxA has been reported separately.Results581 responses from 101 countries were obtained (contact rate = 26%, cooperation rate = 70%). Most respondents were physicians (86%), practicing pediatric hematology/oncology (86%) for >10 years (54%). Providers from LMC considered social/economic factors (families’ low socioeconomic status, low education, and long travel time), as most influential in increasing risk of TxA. Treatment-related considerations such as preference for complementary and alternative medicine and concerns about treatment adverse effects and toxicity, were perceived to play an important role in both LMC and HIC. Perceived prognosis seemed to mediate the role of other determinants such as diagnosis and treatment phase on TxA risk. For example, high-risk of TxA was most frequently reported when prognosis clearly worsened (i.e. lack of response to therapy, relapse), or conversely when the patient appeared improved (i.e. induction completed, mass removed), as well as before aggressive/mutilating surgery. Provider responses allowed development of an expanded conceptual model of determinants of TxA; one which illustrates established and emerging individual, family, center, and context specific factors to be considered in order to tackle this problem. Emerging factors included vulnerability, family dynamics, perceptions, center capacity, public awareness, and governmental healthcare financing, among others.ConclusionTxA is a complex and multifactorial phenomenon. With increased recognition of the role of TxA on global pediatric cancer outcomes, factors beyond social/economic status and beliefs have emerged. Our results provide insights regarding the role of established determinants of TxA in different geographical and economic contexts, allow probing of key determinants by deliberating their mechanisms, and allow building an expanded conceptual model of established and emerging determinants TxA.

Unique incidence patterns of childhood extracranial embryonal tumors exist by race and ethnicity in the United States. The interplay between race/ethnicity and genetics, epigenetics, and gene-environment interactions in the causation of these cancers deserves further investigation.

Bipolar disorder (BD) is a common, recurring psychiatric illness with unknown pathogenesis. Recent studies suggest that microRNA (miRNA) levels in brains of BD patients are significantly altered, and these changes may offer insight into BD pathology or etiology. Previously, we observed significant alterations of miR-29c levels in extracellular vesicles (EVs) extracted from prefrontal cortex (Brodmann area 9, BA9) of BD patients. In this study, we show that EVs extracted from the anterior cingulate cortex (BA24), a crucial area for modulating emotional expression and affect, have increased levels of miR-149 in BD patients compared to controls. Because miR-149 has been shown to inhibit glial proliferation, increased miR-149 expression in BA24-derived EVs is consistent with the previously reported reduced glial cell numbers in BA24 of patients diagnosed with either familial BD or familial major depressive disorder. qPCR analysis of laser-microdissected neuronal and glial cells from BA24 cortical samples of BD patients verified that the glial, but not neuronal, population exhibits significantly increased miR-149 expression. Finally, we report altered expression of both miR-149 and miR-29c in EVs extracted from brains of Flinders Sensitive Line rats, a well-validated animal model exhibiting depressive-like behaviors and glial (astrocytic) dysfunction. These findings warrant future investigations into the potential of using EV miRNA signatures as biomarkers to further enhance the biological definition of BD. © 2017 Wiley Periodicals, Inc.