Population Of Childhood Cancer Survivors Research Articles

Inter-individual variation in ovarian reserve after gonadotoxic treatment in female childhood cancer survivors – a genome-wide association study: results from PanCareLIFE

ObjectiveWe aimed to discover new variants associated with low ovarian reserve after gonadotoxic treatment among adult female childhood cancer survivors using a genome-wide association study approach. DesignGenome-wide association study. SubjectsA discovery cohort of adult female childhood cancer survivors, from the pan‐European PanCareLIFE cohort (n=743; median age: 25.8 years), excluding those who received bilateral ovarian irradiation, bilateral oophorectomy, central nerve system or total body irradiation, or stem cell transplantation. Replication was attempted in the USA‐based St. Jude Lifetime Cohort (n=391; median age: 31.3 years). ExposureFemale childhood cancer survivors are at risk of therapy‐related gonadal impairment. Alkylating agents are well‐established risk factors, and the inter‐individual variability in gonadotoxicity may be explained by genetic polymorphisms. Data were collected in real-life conditions and cyclophosphamide equivalent dose was used to quantify alkylation agent exposure. InterventionNo intervention was performed. Main Outcome MeasureAnti‐Müllerian hormone (AMH) levels served as a proxy for ovarian function and findings were combined in a meta‐analysis. ResultsThree genome-wide significant (<5.0x10-8) and 16 genome-wide suggestive (<5.0x10-6) loci were associated with log-transformed AMH levels, adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study in the PanCareLIFE cohort. Based on effect allele frequency (EAF) (>0.01 if not genome-wide significant), p-value (<5.0×10−6), and biological relevance, 15 SNPs were selected for replication. None of the SNPs were statistically significantly associated with AMH levels. A meta-analysis indicated that rs78861946 was associated at borderline genome-wide statistical significance (Reference/effect allele: C/T; EAF: 0.04, Beta (SE): −0.484 (0.091), p‐value= 9.39×10−8). ConclusionThis study found no genetic variants associated with a lower ovarian reserve after gonadotoxic treatment, as the findings of this GWAS were not statistically significant replicated in the replication cohort. Suggestive evidence for potential importance of one variant is briefly discussed, but the lack of statistical significance calls for larger cohort sizes. As the population of childhood cancer survivors is increasing, large-scale and systematic research is needed to identify genetic variants that could aid predictive risk models of gonadotoxicity and as well as fertility preservation options for childhood cancer survivors.

Detecting High-Dose Methotrexate-Induced Brain Changes in Pediatric and Young Adult Cancer Survivors Using [18F]FDG PET/MRI: A Pilot Study.

Significant improvements in treatments for children with cancer have resulted in a growing population of childhood cancer survivors who may face long-term adverse outcomes. Here, we aimed to diagnose high-dose methotrexate-induced brain injury on [18F]FDG PET/MRI and correlate the results with cognitive impairment identified by neurocognitive testing in pediatric cancer survivors. Methods: In this prospective, single-center pilot study, 10 children and young adults with sarcoma (n = 5), lymphoma (n = 4), or leukemia (n = 1) underwent dedicated brain [18F]FDG PET/MRI and a 2-h expert neuropsychologic evaluation on the same day, including the Wechsler Abbreviated Scale of Intelligence, second edition, for intellectual functioning; Delis-Kaplan Executive Function System (DKEFS) for executive functioning; and Wide Range Assessment of Memory and Learning, second edition (WRAML), for verbal and visual memory. Using PMOD software, we measured the SUVmean, cortical thickness, mean cerebral blood flow (CBFmean), and mean apparent diffusion coefficient of 3 different cortical regions (prefrontal cortex, cingulate gyrus, and hippocampus) that are routinely involved during the above-specified neurocognitive testing. Standardized scores of different measures were converted to z scores. Pairs of multivariable regression models (one for z scores < 0 and one for z scores > 0) were fitted for each brain region, imaging measure, and test score. Heteroscedasticity regression models were used to account for heterogeneity in variances between brain regions and to adjust for clustering within patients. Results: The regression analysis showed a significant correlation between the SUVmean of the prefrontal cortex and cingulum and DKEFS-sequential tracking (DKEFS-TM4) z scores (P = 0.003 and P = 0.012, respectively). The SUVmean of the hippocampus did not correlate with DKEFS-TM4 z scores (P = 0.111). The SUVmean for any evaluated brain regions did not correlate significantly with WRAML-visual memory (WRAML-VIS) z scores. CBFmean showed a positive correlation with SUVmean (r = 0.56, P = 0.01). The CBFmean of the cingulum, hippocampus, and prefrontal cortex correlated significantly with DKEFS-TM4 (all P < 0.001). In addition, the hippocampal CBFmean correlated significantly with negative WRAML-VIS z scores (P = 0.003). Conclusion: High-dose methotrexate-induced brain injury can manifest as a reduction in glucose metabolism and blood flow in specific brain areas, which can be detected with [18F]FDG PET/MRI. The SUVmean and CBFmean of the prefrontal cortex and cingulum can serve as quantitative measures for detecting executive functioning problems. Hippocampal CBFmean could also be useful for monitoring memory problems.

Registration, incidence patterns, and survival trends of central nervous system tumors among children in Germany 1980-2019: An analysis of 40years based on data from the German Childhood Cancer Registry.

Tumors of the central nervous system (CNS) are the second most common type of pediatric cancer in Germany. We aimed to describe registration practice, incidence, and survival patterns for childhood CNS tumors in Germany for the past 40years. Including all CNS tumor cases in children diagnosed at ages 0-14years registered at the German Childhood Cancer Registry (GCCR) in 1980-2019 (for survival analysis 1980-2016), we calculated age-specific and age-standardized incidence rates (ASIR) over time, average annual percentage changes (AAPC), and 1- and 5-year overall survival. While we observed a pronounced increase in ASIR after the establishment of the GCCR during the 1980s, ASIR for all pediatric CNS tumors combined continued to increase markedly from 28.6 per million in 1990-1999 to 43.3 in 2010-2019 (AAPC=2.7% in 1991-2010, AAPC=0.3% in 2010-2019). The 5-year overall survival from CNS tumors improved from 63% in the 1980s, 70% in the 1990s to 79% in 2010-2016. These improvements have occurred across all age groups. Children diagnosed with ependymomas and choroid plexus tumors experienced the strongest increase (from 54% to 81%). Observed increases in incidence rates for pediatric CNS tumors are likely only partially caused by actual increasing case numbers. The majority is a function of improved registration and, to a minor extent, improvements in diagnostics. Survival from pediatric CNS tumors has, by and large, improved consistently, leading to a growing population of childhood cancer survivors with diverse health biographies and risk of lifelong adverse impact on health and wellbeing.

Hypogonadism and neurocognitive outcomes among childhood cancer survivors.

Childhood cancer survivors are at risk for hypogonadism. The impact of hypogonadism on neurocognitive impairment and emotional distress in the non-cancer population has been shown; however, the relationship among the childhood cancer survivor population is unknown. We aimed to evaluate the contribution of hypogonadism to neurocognitive impairment and emotional distress among survivors. Cross-sectional study using retrospective cohort. In total, 3628 survivors who completed standard neurocognitive tests (six domains: processing speed, memory, executive function, attention, academics, and global cognition) and self-reported emotional distress were included in our study. Participants were stratified by sex and gonadal status. Outcomes were compared between hypogonadal and eugonadal groups by multivariable analysis, adjusting for established predictors, and mediation analyses to determine the direct/indirect effects of hypogonadism on outcomes. The hypogonadal group exhibited a higher prevalence of neurocognitive impairment across domains, but no difference in emotional distress. Hypogonadal females exhibited higher relative risk (1.7, 95% CI, 1.2-2.5) for impaired visual processing speed, compared to eugonadal females after adjusting for cancer-related variables. In mediation models, hypogonadism had a significant direct (P < .01) and indirect (from P < .01) impact on impairment in visual processing speed among females. Males demonstrated direct (P = .03) and indirect (P = .04) impact of hypogonadism on motor processing speed. Processing speed may be the most vulnerable neurocognitive domain associated with hypogonadism in survivors, while other domains were mainly impacted by cancer-related variables. Our findings support the need for further evaluation of the impact of sex hormone replacement therapy on neurocognitive function.

Diabetes in childhood cancer survivors: emerging concepts in pathophysiology and future directions.

With advancements in cancer treatment and supportive care, there is a growing population of childhood cancer survivors who experience a substantial burden of comorbidities related to having received cancer treatment at a young age. Despite an overall reduction in the incidence of most chronic health conditions in childhood cancer survivors over the past several decades, the cumulative incidence of certain late effects, in particular diabetes mellitus (DM), has increased. The implications are significant, because DM is a key risk factor for cardiovascular disease, a leading cause of premature death in childhood cancer survivors. The underlying pathophysiology of DM in cancer survivors is multifactorial. DM develops at younger ages in survivors compared to controls, which may reflect an "accelerated aging" phenotype in these individuals. The treatment-related exposures (i.e., chemotherapy, radiation) that increase risk for DM in childhood cancer survivors may be more than additive with established DM risk factors (e.g., older age, obesity, race, and ethnicity). Emerging research also points to parallels in cellular processes implicated in aging- and cancer treatment-related DM. Still, there remains marked inter-individual variability regarding risk of DM that is not explained by demographic and therapeutic risk factors alone. Recent studies have highlighted the role of germline genetic risk factors and epigenetic modifications that are associated with risk of DM in both the general and oncology populations. This review summarizes our current understanding of recognized risk factors for DM in childhood cancer survivors to help inform targeted approaches for disease screening, prevention, and treatment. Furthermore, it highlights the existing scientific gaps in understanding the relative contributions of individual therapeutic exposures and the mechanisms by which they exert their effects that uniquely predispose this population to DM following cancer treatment.

Quality of life of adolescent and adult survivors of childhood cancer in Europe-A systematic review.

Advances in diagnostics and treatment of childhood cancer during the past few decades have substantially increased survival, resulting in a growing population of survivors of childhood cancer. Somatic and mental late effects of the cancer and the treatment may impact the quality of life (QoL). Previous reviews of QoL in survivors of childhood cancer have shown contradictory findings across studies and the majority of studies included have been based on data from North America and may not be directly comparable to a European setting. The aim of our study was to critically evaluate and summarise the latest evidence on the QoL of childhood cancer survivors in Europe and to identify survivors at particular risk. The eligible studies were published between 2008 and 2022, conducted in Europe and included participants who had survived at least 5 years after diagnosis of a childhood cancer. The main outcome of interest was QoL of survivors which was measured with validated qualitative and quantitative QoL questionnaires. A systematic literature search conducted in PubMed, EMBASE, PsycINFO and CINALH resulted in inclusion of 36 articles with a total of 14 342 survivors of childhood cancer. The majority of included studies found that childhood cancer survivors reported poorer QoL than comparisons. Female gender, treatment with haematopoietic stem cell transplantation and a brain tumour diagnosis were associated with lower QoL. With a growing population of childhood cancer survivors with many years ahead of them, targeted interventions and optimal follow-up care are important to improve the QoL of survivors.

Children with Cancer: Shared Care and Transition of Care.

Survival of childhood cancer is increasing, resulting in a growing population of childhood cancer survivors who enter the health care system. There is widespread agreement on the need for effective transition programs for age-appropriate care for these individuals. However, the transition from pediatric to adult care can be a particularly confusing and overwhelming experience for the survivors of childhood cancer or children requiring long term treatment. The concept of transition implies more than just transfer of a cancer patient /more often a survivor to adult care; the preparation of which must begin well before the event of transfer. The transfer of a pediatric case to adult team could have many implications like a feeling of insecurity culminating in psychosocial issues. There is another concept in management of cancers: 'Shared care' which is essentially integration and coordination of care to develop an effective and collaborative relationship between primary and cancer care physicians. The care of patients from diagnosis to treatment is complex and requires the expertise of a wide range of care providers who are new to patients/survivors. This review article elaborates on both transition of care and shared care as applicable to India.

Congenital anomalies and health outcomes among survivors of childhood cancer: A report from the childhood cancer survivor study.

e22021 Background: Although congenital anomalies are established risk factors for developing childhood cancer, less is known about health outcomes among survivors of childhood cancer with known congenital anomalies. Therefore, we estimated the risk of chronic health conditions (CHCs) and subsequent malignant neoplasms (SMNs) among survivors of childhood cancer by congenital anomaly status in the Childhood Cancer Survivor Study (CCSS). Methods: Overall, 22,247 five-year survivors self-reported congenital anomalies. We included 16 conditions present at birth, excluding self-reported genetic conditions. Patient-reported CHCs were graded using the Common Terminology Criteria for Adverse Events (CTCAE v. 4.03). Self-reported SMNs were confirmed through pathology report review. Hazard ratios (HR) of CHCs comparing survivors with vs. without congenital anomalies and their 95% confidence intervals (CI) were estimated using Cox regression with age as the time scale, adjusted for race/ethnicity, education, household income, health insurance, and original cancer treatment. Results: Among survivors (median age at cancer diagnosis 6 years (range 3-12), age at follow-up 31 years (range 25-39)), 16.9% (n = 3880) reported a congenital anomaly. The most common anomalies included: large/multiple birth marks (n = 1540, 40.4%); congenital heart defects (n = 693, 18.4%); and kidney, bladder, or genital abnormalities (n = 607, 14.6%). Relative to survivors without anomalies, those with anomalies more commonly had astrocytoma, Wilms tumor, and neuroblastoma primary cancers (p &lt; 0.001), treated with radiation (p = 0.011), cyclophosphamide (p &lt; 0.001), anthracyclines (p &lt; 0.001), and epipodophyllotoxins (p = 0.044), and younger age at cancer diagnosis (11.3% vs. 5.7% diagnosed prior to one year of age, p &lt; 0.001). Survivors with anomalies were more likely to develop any CHC (CTCAE grades 1-5 HR: 1.31, 95% CI: 1.23, 1.39); severe, disabling, life-threatening or fatal CHCs (grades 3-5 HR: 1.42 (95% CI: 1.28, 1.58); and multiple CHCs (≥2 conditions HR: 1.36, 95% CI: 1.27, 1.46; ≥3 conditions HR: 1.49, 95% CI: 1.37, 1.63). Survivors with anomalies had increased risk for adverse outcomes across multiple systems (all p &lt; 0.001), including: hearing/vision/speech (HR: 1.37); urinary (HR: 1.42); hormonal/endocrine (HR: 1.24); heart/circulatory (HR: 1.35); digestive (HR: 1.49); and brain systems (HR: 1.42). We observed no differences in the risk of any SMN by congenital anomaly status (HR: 1.12, 95% CI: 0.90, 1.38). Conclusions: In our assessment, survivors of childhood cancer with self-reported congenital anomalies had an increased risk of developing CHCs compared to survivors without reported anomalies, but no increased risk of SMNs. Evaluating congenital anomalies allows identification of a population of childhood cancer survivors at high risk for poor long-term health outcomes.

How the long-term follow-up is organized in young adult survivors of childhood cancer

SummaryThe survival after childhood cancer has improved substantially, therefore the population of childhood cancer survivors is increasing. This growing population of childhood cancer survivors, however, is at risk of a spectrum of adverse health outcomes. Unfortunately, until now, there was a lack of comprehensive follow-up recommendations.The purpuse of this article is to provide information on recently developed harmonized evidence-based guidelines and the structure to provide complex long term follow up for childhood cancer survivors. We pointed out the need for a multidisciplinary pediatric and adult specialist team, who together develop multidisciplinary long-term follow-up clinics.

What it looks like to ‘mind the gaps’ in a Midwest survivorship clinic for childhood cancer survivors

BackgroundAs cancer prevalence increases and treatment improves, the population of childhood cancer survivors (CCS) will see remarkable growth. This population requires guideline-based survivorship care into adulthood; however, numerous gaps in care are common including record documentation, medical knowledge, and access to healthcare. Here we describe the patients seen in a US Midwest survivorship transition clinic (STC) and the aspects of the clinic designed to address the gaps in care this cohort faces. MethodsAfter IRB approval, a retrospective chart review was completed for patients established in the STC between 2014 and 2022. ResultsA total of 261 patients were identified. The patients had an average age of 12 years at the time of cancer diagnosis and an average age of 28 years at clinic establishment. Patients presented from 9 states and 139 zip codes. We identified 42 different primary cancers with acute lymphoblastic leukemia (24.5%) and Hodgkin’s Lymphoma (19.2%) most common. We found that 244 (93.5%) received chemotherapy, 138 (52.9%) received radiation, and 41 (15.7%) underwent bone marrow transplant. Secondary malignancies were diagnosed in 29 (11.1%) patients with breast (23.3%) and thyroid (23.3%) malignancies most common. DiscussionThe clinical diversity, complex treatment history, and prevalence of secondary malignancies in this CCS population emphasizes the importance close follow-up and adherence to survivorship guidelines. Through strong local partnerships and a specialized nursing navigator this STC addresses care gaps common in this population. Although limitations persist, STCs are a strong model of care to address the unique care needs of this growing population of complex patients.

Çocukluk Çağı Kanseri

Kanser fizyolojik bir bozukluk olan tümör oluşumuyla kendini gösteren kontrolsüz hücre çoğalması ile karakterize olan bir hastalıktır. Çocukluk çağı kanseri çocuklarda önde gelen ölüm nedenidir. Dünya Sağlık Örgütünün çocuk sağlığına yaptığı vurgunun ardından, dünya çapındaki çoğu hükümet çocukluk çağı kanser araştırmalarını kolaylaştırmak için önlemler almıştır. Multimodalite terapisinin ortaya çıkmasıyla birlikte son beş yılda kanserden ölüm oranının azaldığını ve bugün çoğu Avrupa ve Kuzey Amerika ülkesinde kanserde sağ kalımın %80’i aştığı görülmektedir. Hayatta kalmadaki önemli gelişmeler, çocukluk çağı kanserden kurtulanların sürekli artan bir popülasyonuna yol açmıştır. Çocukluk çağı kanserinden kurtulanlar, kanser ve tedavisinde atfedilebilecek çeşitli ağır bedensel, zihinsel sağlık durumlarının yanı sıra olumsuz sosyal, sosyoekonomik sonuçlara ve azalmış psikolojik refah ile yaşam kalitesi de risk altındadır. Çocuklarda erken tanı önemlidir çünkü yetişkinlerdeki gibi tarama testleri yoktur burada görev çocuğun takibini yapan hekimlere düşmektedir. Çalışmalar, günlük fiziksel aktivitedeki azalmanın kronik hastalıkların/durumların birincil nedeni olduğu ve fiziksel aktivitenin/egzersizin hareketsizliğin neden olduğu işlev bozukluklarının rehabilitasyon tedavisi (terapi) olduğu fikrini kanıtlıyor. Bu derlemenin amacı çocukluk çağı kanseri hakkında genel bilgileri ve fiziksel aktivitenin etkilerinin incelenmesidir.

Understanding adult survivors of childhood cancers: An analysis of a survivorship transitions clinic.

227 Background: As the prevalence of patients with cancer increases and improvements to treatment continue, the population of childhood cancer survivors (CCS) will see remarkable growth in coming years. Care for CCS requires collaboration between oncologists and primary care practitioners (PCPs). Long term follow up calls for unique attention to survivorship guidelines, the late effects of treatment, and the risk of secondary malignancies. To meet these needs, the cancer center at the University of Kansas Health System partnered with internal medicine to establish a primary care based STC. This study aimed to describe and analyze the population of cancer survivors in this clinic. Methods: After obtaining IRB approval, a retrospective chart review was completed for patients established in the STC between 2014 and 2022. Subjects were de-identified and analysis was performed using Microsoft Excel. Results: The 261 patients were 57% (150) female and had an average age of 12 (2 months - 41 years) at the time of cancer diagnosis and an average age of 28 (18 – 61 years) at the time of of clinic establishment. Patients were from 9 states, 47 counties, and 139 unique zipcodes. We identified 42 different cancers among the patients with ALL (24.5%) and Hodgkin’s Lymphoma (19.2%) most common. We found that 244 (93.5%) received chemotherapy, 138 (52.9%) received radiation, and 41 (15.7%) underwent bone marrow transplant. Secondary cancers were diagnosed in 30 (11.5%) of the patients with breast (23.3%) and thyroid (23.3%) malignancies most common. Three of these patients had two secondary malignancies. Conclusions: Our CCS population was clinically diverse in malignancy and treatment regimen. Nearly half of the patients received therapy in combination, adding to the complexity of late effects risks and care monitoring. This is emphasized by the prevalence of secondary malignancies which enforces the need for close follow up and adherence to survivorship guidelines. We found that despite the young age of cancer diagnosis, many of the patients established care in our clinic well into adulthood which is concerning for a gap in survivorship care as patients transition from treatment to follow up. Finally, the wide catchment area of this clinic is unique and shows the success of rural survivorship care at a tertiary medical center.

A Mobile Application for Childhood Cancer Survivorship Care: A Cross Sectional Survey Study

The population of childhood cancer survivors (CCS) is growing, along with the number of CCS who will experience physiological and psychosocial late effects from their prior cancer treatments. Educational interventions need.

021 Short term consequences of childhood cancer

The survival rates of all subtypes of childhood cancer have increased over the last decades thanks to improved treatment regimens. Nowadays, over 80% of children with cancer will survive the disease. Therefore, the childhood cancer survivor population is growing. Because of this increasing number, the consequences or effects of cancer treatment became more apparent. It has been shown that almost 75 percent of the survivors have one or more unwanted side effects of anticancer treatment. One of these effects is gonadal dysfunction.

Childhood cancer survivorship in China: An overview of the past two decades.

Across countries in the world, China has the largest population of childhood cancer survivors. Research and care for the childhood cancer survivor population in China is fragmented. We searched studies published in English or Chinese language between January 1, 2000 and June 30, 2021, which examined various aspects of childhood cancer survivorship in China. The existing China-focused studies were largely based on a single institution, convenient samplings with relatively small sample sizes, restricted geographic areas, cross-sectional design, and focused on young survivors in their childhood or adolescence. These studies primarily focused on the physical late effects of cancer and its treatment, as well as the inferior psychological wellbeing among childhood cancer survivors, with few studies examining financial hardship, health promotion, and disease prevention, or healthcare delivery in survivorship. Our findings highlight the urgent need for research and evidence-based survivorship care to serve the childhood cancer survivor population in China.

Cardiovascular Health Status And Genetic Risk In Survivors of Childhood Neuroblastoma and Nephroblastoma Treated With Doxorubicin: Protocol of the Pharmacogenetic Part of the LESS-Anthra Cross-Sectional Cohort Study.

BackgroundIn childhood cancer survivors (survival of 5 years or more after diagnosis), cardiac toxicity is the most common nonmalignant cause of death attributed to treatment-related consequences. Identifying patients at risk of developing late cardiac toxicity is therefore crucial to improving treatment outcomes. The use of genetic markers has been proposed, together with clinical risk factors, to predict individual risk of cardiac toxicity from cancer therapies, such as doxorubicin.ObjectiveThe primary aim of this study is to evaluate the value of multimarker genetic testing for RARG rs2229774, UGT1A6 rs17863783, and SLC28A3 rs7853758 for predicting doxorubicin-induced cardiotoxicity. The secondary aim is to replicate previously described associations of candidate genetic markers with doxorubicin-induced cardiotoxicity. Moreover, we will evaluate the prevalence of cardiovascular dysfunction in childhood cancer survivors after neuroblastoma or nephroblastoma.MethodsThis is the pharmacogenetic substudy of the research project Structural Optimization for Children With Cancer After Anthracycline Therapy (LESS-Anthra). We invited 2158 survivors of childhood neuroblastoma or nephroblastoma treated with doxorubicin according to the trial protocols of SIOP 9/GPOH, SIOP 93-01/GPOH, SIOP 2001/GPOH, NB 90, NB 97, or NB 2004 to participate in this prospective cross-sectional cohort study. The study participants underwent a cardiological examination and were asked to provide a blood or saliva sample for genotyping. The study participants' health statuses and cardiovascular diagnoses were recorded using a questionnaire completed by the cardiologist. Digital echocardiographic data were centrally evaluated to determine the contractile function parameters. Medical data on the tumor diagnosis and treatment protocol were taken from the study documentation. Survivors were screened for variants of several candidate genes by TaqMan genotyping.ResultsThis study includes 657 survivors treated with doxorubicin for childhood cancer, the largest German cohort assembled to date to investigate cardiovascular late effects. Data analyses are yet to be completed.ConclusionsThis study will define the genetic risk related to 3 marker genes proposed in a pharmacogenetic guideline for risk assessment. Moreover, the results of this study will show the prevalence of cardiovascular dysfunction in survivors of pediatric neuroblastoma or nephroblastoma who were treated with doxorubicin. The results will help to improve primary treatment and follow-up care, thus reducing cardiovascular late effects in the growing population of childhood cancer survivors.Trial RegistrationGerman Clinical Trials Register DRKS00015084; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015084International Registered Report Identifier (IRRID)DERR1-10.2196/27898

Immunosenescence in Childhood Cancer Survivors and in Elderly: A Comparison and Implication for Risk Stratification.

The population of childhood cancer survivors (CCS) has grown rapidly in recent decades. Although cured of their original malignancy, these individuals are at increased risk of serious late effects, including age-associated complications. An impaired immune system has been linked to the emergence of these conditions in the elderly and CCS, likely due to senescent immune cell phenotypes accompanied by low-grade inflammation, which in the elderly is known as “inflammaging.” Whether these observations in the elderly and CCS are underpinned by similar mechanisms is unclear. If so, existing knowledge on immunosenescent phenotypes and inflammaging might potentially serve to benefit CCS. We summarize recent findings on the immune changes in CCS and the elderly, and highlight the similarities and identify areas for future research. Improving our understanding of the underlying mechanisms and immunosenescent markers of accelerated immune aging might help us to identify individuals at increased risk of serious health complications.

Survivors of childhood cancer in Latin America: Role of foundations and peer groups in the lack of transition processes to adult long-term follow-up.

BackgroundOver the last decade, the population of childhood cancer survivors has rapidly increased in Latin America, opening a long chapter of challenges for healthcare providers in these countries to provide follow‐up and adult care.AimIn the process of exploring childhood cancer parent and patient engagement in resource‐limited settings, we highlight the challenges faced by Latin American survivors from El Salvador, Mexico, and Peru as they transitioned from receiving cancer treatment to life as a cancer survivors.Methods and ResultsFocus group discussions and interviews were performed as part of a larger qualitative study involving 10 low and middle‐income countries in four continents regarding patient and caregiver engagement in childhood cancer treatment. We present the results of the Latin‐American survivors and their experiences finishing treatment and life outside the pediatric oncology follow‐up system. Themes regarding a) losing eligibility for pediatric surveillance and care, b) the importance of peer survivors, and c) the need for giving back were part of their stories.ConclusionWe suggest that given the lack of organized support from healthcare systems and providers for survivors' proper transition into adult‐centered care, foundations and non‐governmental organizations can provide transitional support, offer space for guidance/information, and work towards collaboration among systems for future integrated programs.

Skeletal Muscle and Childhood Cancer: Where are we now and where we go from here.

Skeletal muscle (muscle) is essential for physical health and for metabolic integrity, with sarcopenia (progressive muscle mass loss and weakness), a pre-curser of aging and chronic disease. Loss of lean mass and muscle quality (force generation per unit of muscle) in the general population are associated with fatigue, weakness, and slowed walking speed, eventually interfering with the ability to maintain physical independence, and impacting participation in social roles and quality of life. Muscle mass and strength impairments are also documented during childhood cancer treatment, which often persist into adult survivorship, and contribute to an aging phenotype in this vulnerable population. Although several treatment exposures appear to confer increased risk for loss of mass and strength that persists after therapy, the pathophysiology responsible for poor muscle quantity and quality is not well understood in the childhood cancer survivor population. This is partly due to limited access to both pediatric and adult survivor muscle tissue samples, and to difficulties surrounding non-invasive investigative approaches for muscle assessment. Because muscle accounts for just under half of the body's mass, and is essential for movement, metabolism and metabolic health, understanding mechanisms of injury responsible for both initial and persistent dysfunction is important, and will provide a foundation for intervention. The purpose of this review is to provide an overview of the available evidence describing associations between childhood cancer, its treatment, and muscle outcomes, identifying gaps in current knowledge.

Profits, public health, and patient care: caring for childhood cancer survivors.

Advances in therapy over the last several decades have contributed to dramatic growth in the population of childhood cancer survivors [1]. Unfortunately, cancer treatments can harm developing organs, leaving some childhood survivors at high risk for subsequent chronic illness, including heart failure, lung disease, cognitive problems, reproductive health issues, and secondary cancers [2]. These long-term adverse effects can reduce the life expectancy of survivors compared to their age-matched noncancer peers and reduce their quality of life over the course of survivorship [3, 4]. The burden of chronic disease, psychosocial concerns together with the growing numbers of adult and young adult survivors of childhood cancer has led to a critical need for evidence-based models of care to improve clinical and behavioral outcomes for this population [5]. Benedict et al. (see this issue) [6] present the case for hospital-based specialty clinics as a care model for childhood cancer survivors. This work is very timely given shortages in institutional resources for survivorship care [7] and requirements for survivorship programs new accreditation standards by the American College of Surgeons Commission on Cancer, which include the delivery of a Survivorship Care Plan to cancer patients at the conclusion of their treatment [8]. The authors are to be lauded for their use of an interesting economic approach to provide data to motivate hospital administrators to invest in a survivorship clinic. The study presents a retrospective financial accounting analysis of procedures recommended by the “Children’s Oncology Group (COG) guidelines” at a single nonprofit institution in New York. The researchers report a potential “profit opportunity loss” of $348,700 (in 2019 dollars) over a period of 3 years from 2010 to 2012 due to nonuniversal use of recommended procedures and care. Further, they found that nonuniversal use of guideline care occurred among individuals who were uninsured and underinsured and racial minorities, arguably the most vulnerable groups. Motivating providers and patients to routinely undergo office visits and procedures to potentially detect disease that led to additional services (e.g., breast cancer screening with MRI generating biopsies and surgeries) was projected to increase hospital profits. The authors argue that the ability to capture this potential profit would lead to increased investment to support clinical operations, and this investment could then improve survivors’ outcomes.