Childhood cancer survival rates have risen dramatically over the past decades, with the majority of young patients now living well into adulthood. That success has exposed a new challenge: late effects of treatment, including cardiovascular complications, reduced bone mineral density, chronic fatigue, musculoskeletal problems, and psychological distress. Physical activity is widely regarded as one of the most powerful, modifiable tools to prevent, delay, or mitigate these late effects. Guidelines recommend that children and adolescents accumulate at least 60 minutes of moderate-to-vigorous physical activity (MVPA) per day, while adults should aim for 150 to 300 minutes of moderate activity per week. Yet most prior research has relied on weekly or daily averages — a blunt instrument that tells us nothing about how activity is actually distributed across the week, or on which days survivors might need the most support.

The new study, led by first author Mari Bratteteig of the Oslo Centre for Biostatistics and Epidemiology at Oslo University Hospital and the Norwegian School of Sport Sciences, set out to change that. Drawing on data from two large research programs — the Physical Activity in Childhood Cancer Survivors (PACCS) study, which included adolescents aged 9 to 18, and the Swiss SURfit randomized controlled trial, which included adult survivors aged 18 to 49 — the researchers analyzed hip-worn ActiGraph GT3X+ accelerometry from 434 adolescent and 156 adult survivors. Participants wore the devices for one to two weeks, capturing the vertical-axis acceleration used to classify time spent in MVPA and light physical activity (LPA). Controls came from the PACCS comparison group and the Norwegian National Physical Activity Survey 2, with the adult controls matched exactly to survivors on sex and age.

The methodological heart of the study lies in its use of multivariate latent class mixed models, a statistical framework capable of grouping individuals based on the shape of their repeated daily measurements over time. Rather than asking whether survivors move more or less on average than healthy peers, the model asks whether distinct patterns of day-to-day movement exist within the population — and whether individuals can be reliably assigned to one of those patterns. The team ran models with one through six classes, testing 50 different sets of initial parameter values to avoid convergence toward local maxima, and selected the optimal model using the Akaike information criterion, the Bayesian information criterion, entropy as a measure of class discrimination, and the minimum class size needed for stability. Both MVPA and LPA were entered simultaneously into the models, meaning the classes were defined by the interplay of two intensities rather than one — a methodological first in this population.

The results were revealing. Among adolescent survivors, four distinct weekly trajectories emerged. Twenty percent of the group fell into a “Low regular” pattern, averaging only about 30 minutes of MVPA and 140 minutes of LPA per day — never approaching the guideline of 60 minutes of MVPA on any day of the week. A further 32 percent followed a “Medium, drop weekend” trajectory, sustaining roughly 60 minutes of MVPA on weekdays before falling to around 30 minutes on Saturday and Sunday. Eight percent showed a curious “Medium, peak Friday” pattern, with activity climbing steadily from Monday to Friday and then collapsing over the weekend. The largest group — 41 percent — followed a stable “Medium regular” trajectory of about 60 minutes of MVPA and 200 minutes of LPA every day, closely in line with guidelines.

Adult survivors showed a different landscape. Forty percent followed a “Medium regular” trajectory at about 40 minutes of MVPA and 250 minutes of LPA daily. Thirty-one percent again showed the weekend drop, falling from roughly 50 minutes of MVPA on weekdays to about 20 minutes on weekends. Twenty-three percent maintained steady MVPA but accumulated a striking 350 minutes of LPA per day — a pattern the authors suggest may reflect manual labor, with its emphasis on walking and lifting, among those with lower educational attainment. Only 6 percent — nine individuals — achieved a “High, drop weekend” trajectory, exceeding 60 minutes of MVPA and 400 minutes of LPA on most weekdays. Notably, no “Low regular” MVPA trajectory was identified among adult survivors at all.

When the researchers compared survivors with healthy controls, the picture grew even more interesting. Among adolescents, the four trajectory shapes were broadly similar between survivors and controls, but survivors showed fewer fluctuations and narrower confidence intervals — a pattern the authors interpret cautiously, possibly as “energy economization” or more planned, structured behavior shaped by the demands of living with late effects. More striking was the allocation: only 20 percent of adolescent survivors, versus 31 percent of controls, occupied the Low regular class, and survivors were overrepresented in the two medium-activity classes. Among adults, three of four trajectories were comparable between groups, and survivors again showed a more favorable distribution, with no equivalent of the low-activity class found in 17 percent of controls.

Who ended up in which trajectory? Across both age groups, the dominant factors were sex, age, sleep duration, and educational level. The most vulnerable group — adolescent survivors in the Low regular class — was disproportionately female, older, slept fewer than eight hours on weeknights, and had survived central nervous system (CNS) tumors, a finding consistent with the motor and sensory impairments that can follow brain tumor treatment. Importantly, the authors note that physical activity has been shown to support neural recovery and enhance motor proficiency and cognitive function specifically among CNS tumor survivors, making this subgroup a clear priority for targeted intervention. Sleep, a modifiable behavior, emerged as a particularly intriguing thread: adolescent and adult survivors with low weekday sleep were concentrated in the least and most extreme classes, and the authors suggest that improving sleep hygiene may be an underexplored lever for increasing activity.

The weekend drop may prove to be the study’s most actionable finding. More than one-third of both adolescent and adult survivors showed a marked collapse in activity from weekdays to weekends — the precise opposite of the “weekend warrior” pattern debated in the general population, where people accumulate little weekday activity but catch up on weekends. The authors propose several plausible mechanisms: depleted energy after an intense week, the absence of active commuting to school or work, and the lack of organized sports or structured leisure on weekends. Because the drop is so common and so spatially and temporally predictable, interventions designed specifically to shore up weekend activity — community programs, family-based activities, telecoached weekend plans — could deliver disproportionate gains in total weekly activity volume.

The study is not without limitations, which the authors confront directly. Accelerometers under-register activities with little vertical movement, such as cycling, strength training, and swimming. One to two weeks of monitoring may not capture habitual behavior, although prior evidence suggests physical activity is reasonably stable over time. Sedentary time was not included in the models despite its known independent effects on health. The adult survivor sample came from the baseline of a randomized controlled trial testing an exercise intervention, raising the possibility of selection bias — survivors who volunteer for an activity-focused trial are likely unusually motivated — so the favorable adult survivor comparisons should be read with caution. Low inclusion rates in both the SURfit trial (19 percent) and the Norwegian survey (26 percent), and small numbers in certain diagnostic strata, meant that all reported group differences remain descriptive rather than formally adjusted.

Nevertheless, the implications for clinical practice are substantial. The findings demonstrate that the population of childhood cancer survivors is not uniformly inactive — most adolescent and adult survivors in this study followed patterns consistent with or close to public health guidelines — but also that a substantial and identifiable subgroup faces persistent, daily barriers to movement. Knowing that female adolescent survivors of CNS tumors who sleep poorly are concentrated in the least active class gives clinicians a concrete profile to screen for during follow-up care. Knowing that weekends are the weak link for a third of survivors gives intervention designers a specific target. The authors call for future research to determine which of these weekly trajectories are most beneficial — or most harmful — for long-term physical and mental health, and to investigate whether structuring activity differently across the week can translate into measurable reductions in late effects. In a population that continues to grow as survival rates climb, that knowledge could turn physical activity from a generic recommendation into a genuinely personalized tool of survivorship medicine.

Hematopoietic cell transplantation, commonly known as HCT, replaces damaged or diseased blood-forming cells with healthy stem cells. It can be lifesaving for children with leukemia, other cancers, inherited blood disorders and immune-system diseases. As survival rates have improved, however, physicians have increasingly recognized that the end of treatment does not necessarily mark the end of its consequences. Short stature and impaired growth are among the most common long-term effects observed in children who undergo transplantation.

A research team from the Japanese Children’s Cancer Group, led by investigators at Hiroshima University, examined how growth hormone therapy affects final adult height in childhood HCT survivors diagnosed with post-transplant short stature. The researchers conducted a nationwide, multicenter retrospective cohort study, collecting information on patients’ growth patterns, transplant histories, medical complications and treatment responses. Their results were published in Frontiers in Endocrinology on May 20, 2026.

The study included 268 patients, with final adult height data available for 171. Among those with documented final height measurements, 58 had received growth hormone, while 113 had not. The investigators compared final height using standard deviation scores, or SDS, a statistical measure that shows how a person’s height differs from the average for individuals of the same age and sex. They also analyzed factors including age at diagnosis, age at transplantation, sex, underlying disease, transplant type, radiation exposure and transplant-related complications.

Patients treated with growth hormone generally achieved better final height outcomes than those who did not receive the therapy. Growth hormone, or GH, is a protein produced by the pituitary gland that stimulates the liver and other tissues to release insulin-like growth factor 1, known as IGF-1. This hormone promotes the multiplication and maturation of growth-plate cells in long bones. When GH signaling is insufficient, or when the growth plates remain responsive but the body lacks adequate stimulation, medical GH replacement can accelerate linear growth.

The Japanese study suggests that GH therapy may work differently in HCT survivors than it does in children with classical growth hormone deficiency. In many conventional cases, the most rapid increase in height occurs relatively soon after treatment begins, followed by a gradual slowing as the child approaches skeletal maturity. In the transplant-survivor group, however, height gains sometimes continued to accumulate for five years or longer, with additional improvement still visible at final adult height. This prolonged response may reflect the complex, delayed effects of transplantation, prior chemotherapy, radiation and chronic illness on the growth plates and endocrine system.

The strongest negative predictor of final height was total body irradiation, or TBI. This conditioning treatment is used before some transplants to destroy residual cancer cells and suppress the recipient’s immune system, reducing the risk that the new stem cells will be rejected. However, radiation can directly damage the growth plates, which are regions of cartilage responsible for the lengthening of bones during childhood. It can also affect the hypothalamus and pituitary gland, disrupting the hormonal signals that regulate growth. These effects may help explain why patients exposed to TBI showed more limited height outcomes, even when treated with GH.

The investigators also identified differences associated with transplant type and chronic graft-versus-host disease, a complication in which donor immune cells attack the recipient’s tissues after an allogeneic transplant. Such inflammation can affect multiple organs, alter nutrition and physical development, and require prolonged treatment with corticosteroids or other immunosuppressive drugs. The contrast between allogeneic transplants, which use donor cells, and autologous transplants, which return the patient’s own previously collected cells, further suggests that more than one biological pathway contributes to post-transplant growth failure.

Because the study was retrospective and not a randomized clinical trial, it cannot prove that GH therapy alone caused the observed improvement. Patients who received treatment may have differed from untreated patients in ways that influenced their growth, and the availability of final height data was incomplete. Even so, the findings offer important evidence for long-term survivorship care. The authors emphasize that growth monitoring should continue for years after transplantation and that treatment decisions should account for radiation exposure, chronic GVHD, transplant type, pubertal development and other endocrine risks. The next challenge is to determine why some survivors respond strongly to GH while others gain little, allowing physicians to identify high-risk patients earlier and tailor therapy more precisely. For children who survive transplantation, the goal is increasingly extending beyond survival itself: it is helping them reach their biological growth potential and maintain health throughout adulthood.

Subject of Research: People

Article Title: Growth hormone therapy after hematopoietic cell transplantation in childhood: a nationwide survey and longitudinal cohort study

News Publication Date: 20-May-2026

Web References: https://doi.org/10.3389/fendo.2026.1831711

References: Shimomura, M. et al. “Growth hormone therapy after hematopoietic cell transplantation in childhood: a nationwide survey and longitudinal cohort study.” Frontiers in Endocrinology, published May 20, 2026. DOI: 10.3389/fendo.2026.1831711

Image Credits: Maiko Shimomura et al., Frontiers in Endocrinology, May 20, 2026

Keywords: growth hormone therapy, childhood stem cell transplantation, hematopoietic cell transplantation, short stature, final adult height, total body irradiation, chronic graft-versus-host disease, pediatric cancer survivorship, endocrinology, growth impairment

Childhood cancer survival has seen remarkable improvement over recent decades due to advances in therapy and early detection. However, survivors frequently face an increased risk of chronic health conditions typically associated with aging, including cognitive decline. The study led by Williams et al. offers a comprehensive analysis of how epigenetic factors and telomere biology could influence the neurocognitive trajectories of survivors years after treatment completion.

Central to this investigation is the concept of epigenetic age acceleration—a process whereby the biological age of cells, as measured by DNA methylation patterns, surpasses chronological age. This acceleration reflects an accumulation of molecular damage and altered gene regulation, akin to hastened cellular aging. The researchers employed cutting-edge methylation profiling to quantify epigenetic age in a cohort of long-term childhood cancer survivors, revealing significant associations with cognitive performance metrics.

Parallel to epigenetic modifications, telomere length serves as a well-established marker of cellular aging. Telomeres, the protective caps at chromosome ends, naturally shorten with each cell division, but this process may be expedited by genotoxic stress, including chemotherapy and radiation. By measuring leukocyte telomere length, the study examined whether telomere attrition correlates with neurocognitive dysfunction in cancer survivors, providing an integrative view of the molecular aging landscape.

The participant pool comprised individuals treated for childhood malignancies and subsequently followed for extensive periods, allowing unprecedented insight into long-term aging effects. Cognitive assessments encompassed domains such as memory, attention, and executive function, yielding a multidimensional understanding of neurological outcomes in this population. Finding robust links between epigenetic age and cognitive decline suggests that accelerated biological aging may be a critical mediator of adverse neurocognitive sequelae.

Intriguingly, while epigenetic age acceleration demonstrated strong correlations with neurocognitive impairments, telomere length showed more nuanced associations. This divergence implies that while both markers are indicative of biological aging, epigenetic changes may more directly reflect the functional consequences on brain health. The data underscore the necessity of considering multiple aging biomarkers to capture the complexity of survivorship biology fully.

Mechanistically, cancer treatments are known to induce oxidative stress and DNA damage, factors that can disrupt epigenetic regulation and telomere maintenance. This study’s findings suggest that therapeutic insults in early life could leave a lasting imprint on the epigenome and chromosomal integrity, setting survivors on an accelerated aging trajectory that manifests as cognitive decline decades later. The prospect of identifying such molecular signatures opens avenues for targeted interventions.

From a clinical standpoint, these insights hold promise for developing prognostic tools to identify survivors at heightened risk for early neurocognitive deterioration. Epigenetic age, captured through non-invasive blood-based assays, could serve as a valuable biomarker to monitor long-term health and tailor supportive care strategies. Early detection of accelerated aging might enable timely cognitive rehabilitation or pharmacological approaches to mitigate decline.

Furthermore, this research contributes to the growing paradigm that cancer survivorship is not merely about remission but involves managing the chronic, systemic effects of treatment across the lifespan. By elucidating biological aging mechanisms, the study challenges clinicians to adopt holistic models of care that integrate molecular diagnostics with neuropsychological support, aiming to preserve quality of life for survivors.

Future investigations will be crucial to dissect causal pathways and determine whether interventions that modulate epigenetic age or telomere dynamics can reverse or slow neurocognitive decline. Lifestyle modifications, pharmacotherapies targeting epigenetic enzymes, and telomerase activators represent promising domains for research. Longitudinal studies will also clarify how aging biomarkers fluctuate over time in survivors compared to non-cancer populations.

Moreover, the interplay of genetic predispositions, environmental exposures, and treatment modalities in shaping epigenetic aging warrants further exploration. Understanding heterogeneity within survivor cohorts may allow precision medicine approaches, customizing monitoring and treatment plans based on individual molecular profiles and risk factors.

This landmark inquiry by Williams and colleagues not only enhances fundamental knowledge of biological aging in cancer survivorship but also exemplifies the power of integrative molecular epidemiology. Combining epigenomics, telomere biology, and cognitive phenotyping establishes a new template for investigating the long-term consequences of childhood diseases and their therapies.

As the population of childhood cancer survivors continues to grow, the imperative to address their unique aging-related challenges intensifies. Through unraveling the molecular underpinnings of survivorship biology, research such as this lays the groundwork for transformative clinical innovations. The convergence of aging science and oncology heralds a future where the adverse effects of life-saving cancer treatments can be anticipated, monitored, and ultimately ameliorated.

In summary, this study reveals that epigenetic age acceleration and telomere length are intimately linked to the neurocognitive health of long-term childhood cancer survivors. The nuanced relationships between these molecular markers and cognitive outcomes highlight the complexity of survivorship biology and emphasize the need for continued multidisciplinary research. These findings propel the field towards a more comprehensive understanding of how early-life cancer and its treatment reverberate across the molecular and cognitive dimensions of aging.

With the growing adoption of epigenetic clocks and telomere assessment in clinical research, the potential to identify at-risk individuals and develop targeted therapies is becoming increasingly tangible. The transformative implications of such work extend beyond survivorship, offering insights into the broader landscape of aging-related cognitive decline and chronic disease.

Ultimately, by integrating molecular biomarkers with clinical phenotypes, Williams et al. have forged a path toward personalized survivorship care. Their contribution underscores the vital intersection of epigenetics, telomere biology, and neurocognitive function — a frontier that promises to redefine how science understands and manages the enduring effects of childhood cancer across the lifespan.

Subject of Research: Epigenetic age acceleration, telomere length, and neurocognitive function in long-term survivors of childhood cancer.

Article Title: Epigenetic age acceleration, telomere length, and neurocognitive function in long-term survivors of childhood cancer.

Article References:
Williams, A.M., Phillips, N.S., Dong, Q. et al. Epigenetic age acceleration, telomere length, and neurocognitive function in long-term survivors of childhood cancer. Nat Commun 16, 10655 (2025). https://doi.org/10.1038/s41467-025-65664-5

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41467-025-65664-5

Childhood cancer survivors represent a uniquely susceptible group whose medical challenges extend far beyond remission. As advances in oncology have improved survival rates dramatically, attention has shifted toward the long-term sequelae that these survivors face, including the development of subsequent neoplasms. The biological mechanisms underpinning this increased risk are multifactorial, involving genetic predispositions, treatment-related exposures, and increasingly, modifiable lifestyle factors such as body mass index (BMI) and physical activity levels.

The study meticulously analyzed data from a well-defined cohort of childhood cancer survivors, applying robust epidemiological methods to isolate the contributions of obesity and physical exercise to the risk profile for secondary tumor formation. Obesity emerged as a potent risk factor, correlating with heightened susceptibility to various neoplasm types beyond the initial malignancy. This finding is consistent with growing evidence linking adiposity to carcinogenesis through pathways involving chronic inflammation, hormonal imbalances, and metabolic dysregulation.

In contrast, higher levels of physical activity demonstrated a protective association, significantly reducing the incidence of subsequent neoplasms. Physical exercise is known to modulate immune function, reduce systemic inflammation, and favorably alter metabolic parameters, mechanisms that may collectively lower the risk of tumor development. These inverse relationships underscore the plasticity of cancer risk in response to lifestyle modifications and highlight physical activity as a critical component in survivorship care.

The study’s design incorporated detailed assessments of BMI and self-reported physical activity, adjusting for confounding variables such as age, sex, initial cancer type, and treatment modalities. This granularity allowed the researchers to control for potential biases and strengthen the causal inference between lifestyle factors and neoplasm risk. It underscores the importance of integrating comprehensive behavioral data into survivorship research to uncover actionable prevention strategies.

From a mechanistic perspective, obesity potentiates carcinogenesis through several interrelated biological processes. Enlarged adipose tissue acts as an endocrine organ producing pro-inflammatory cytokines and adipokines that promote cellular proliferation and inhibit apoptosis. Additionally, obesity-driven insulin resistance and hyperinsulinemia can stimulate insulin-like growth factor pathways, known for their oncogenic potential. These alterations create a permissive environment for malignant transformation and tumor progression.

Conversely, physical activity exerts a multifaceted protective effect. Regular exercise enhances DNA repair mechanisms, reduces oxidative stress, and improves immune surveillance, thereby countering the carcinogenic milieu fostered by obesity. Moreover, exercise-induced modulation of hormone levels, including reductions in circulating estrogens and androgens, further dampens tumor-promoting signals. Thus, the physiological benefits of physical activity extend far beyond metabolic health into the realm of cancer prevention.

Considering these findings, the study’s authors advocate for the incorporation of lifestyle interventions in clinical guidelines for childhood cancer survivors. Such interventions should prioritize weight management and promote regular, tailored physical activity regimens as integral components of survivorship care plans. This approach aligns with a precision medicine framework that addresses the unique risk profiles and needs of individual survivors.

Future research directions are poised to investigate the efficacy of specific behavioral programs targeting obesity reduction and exercise promotion within survivor populations. Randomized controlled trials evaluating these interventions could provide high-quality evidence to inform best practices and ultimately reduce the burden of subsequent neoplasms. Additionally, mechanistic studies exploring molecular signaling pathways influenced by adiposity and exercise will enhance our understanding of cancer biology in the context of survivorship.

Importantly, this research contributes to a paradigm shift recognizing survivorship not merely as a phase of life after cancer treatment but as an opportunity to implement preventive strategies that alter the trajectory of long-term health outcomes. The intersection of oncology, epidemiology, and behavioral science holds immense promise for improving quality of life and longevity among childhood cancer survivors.

The implications of these insights resonate beyond the research community, urging public health stakeholders and clinicians to foster environments that support healthy lifestyles from early life stages. Addressing obesity and physical inactivity at a population level may have substantial ripple effects in reducing cancer incidence and improving survivorship outcomes across diverse demographics.

In conclusion, this seminal study robustly establishes obesity as a modifiable risk factor associated with increased incidence of subsequent neoplasms after childhood cancer, while validating physical activity as a protective agent. The evidence compels a multidisciplinary response integrating oncological care, behavioral counseling, and public health initiatives to optimize survivorship trajectories and prevent cancer recurrence and secondary malignancies.

Subject of Research: Impact of obesity and physical activity on the risk of subsequent neoplasms among childhood cancer survivors.

Article Title: Not provided.

News Publication Date: Not provided.

Web References: Not provided.

References: DOI 10.1001/jamaoncol.2025.1340

Keywords: Neoplasms, Physical exercise, Body mass index, Cancer, Children, Risk factors, Disease prevention, Disease intervention, Oncology, Research on children, Obesity