Pediatric Cancer Survivors Research Articles

Cerebral blood flow and structural connectivity after working memory or physical training in paediatric cancer survivors – Exploratory findings

ABSTRACT Paediatric cancer survivors often suffer from cognitive long-term difficulties. Consequently, strengthening cognition is of major clinical relevance. This study investigated cerebral changes in relation to cognition in non-brain tumour paediatric cancer survivors after working memory or physical training compared to a control group. Thirty-four children (≥one-year post-treatment) either underwent eight weeks of working memory training (n = 10), physical training (n = 11), or a waiting period (n = 13). Cognition and MRI, including arterial spin labelling and diffusion tensor imaging, were assessed at three time points (baseline, post-training, and three-month follow-up). Results show lower cerebral blood flow immediately after working memory training (z = −2.073, p = .038) and higher structural connectivity at the three-month follow-up (z = −2.240, p = .025). No cerebral changes occurred after physical training. Short-term changes in cerebral blood flow correlated with short-term changes in cognitive flexibility (r = −.667, p = .049), while long-term changes in structural connectivity correlated with long-term changes in working memory (r = .786, p = .021). Despite the caution given when interpreting data from small samples, this study suggests a link between working memory training and neurophysiological changes. Further research is needed to validate these findings.

Risk of transfusion-related iron overload varies based on oncologic diagnosis and associated treatment: Retrospective analysis from a single pediatric cancer center.

Transfusion-related iron overload (TRIO) is a widely acknowledged late effect of antineoplastic therapy in pediatric cancer survivors, but firm guidelines as to screening protocols or at-risk populations are lacking in the literature. We performed retrospective analysis of all oncology patients diagnosed at our center from 2014 to 2019, who underwent TRIO screening as part of an internal quality improvement project. Correlations of MRI-confirmed TRIO with patient-, disease-, and treatment-specific features were evaluated. We show that a tiered screening algorithm for TRIO, when followed as intended, led to the identification of the highest proportion of patients with TRIO. We confirm that cardiac TRIO is quite rare in the oncology patient population. However, accepted surrogate markers including red blood cell transfused volume and ferritin only modestly correlated with TRIO in our patient cohort. Instead, we found that older age, leukemia diagnosis, anthracycline exposure, and receipt of stem cell transplant were most strongly associated with risk for TRIO. We describe associations between TRIO and patient, disease, and treatment characteristics in a multivariate risk model that could lead to an improved risk stratification of off-therapy patients, and which should be validated in a prospective manner.

Experiences of Exercise-Related Worry Among Chinese Childhood Cancer Survivors and Their Carers: A Qualitative Study.

The low levels of physical activity in childhood cancer survivors have increasingly garnered attention from nursing scholars. Exercise-related worry is a prominent barrier, yet the understanding of such experiences among childhood cancer survivors and their primary caregivers remains scarce. The aim of this study was to further understand the factors contributing to exercise-related worry from the perspective of childhood cancer survivors and their primary caregivers. In this qualitative study, we conducted face-to-face semistructured interviews with childhood cancer survivors (n = 20) and carers (n = 20) in 2 hospitals in China. The interviews were analyzed according to thematic analysis. Two main themes and 8 subthemes emerged: (1) internal factors: changes in the perception of physical activity (threat perception from the disease, active avoidance of stressful events, lack of safety due to past experiences), and (2) external factors: weak support system (limited peer support, family strength, feeling abandoned by the tumor team, reintegration into school, external environmental constraints). In summary, exercise-related worry is from internal factors and can be influenced by external factors. There are various factors contributing to the concerns of exercise in childhood cancer survivors, which may be a key factor for their significantly lower levels of physical activity compared to guideline recommendations. The findings of this study call for healthcare professionals to provide additional assistance for childhood cancer survivors with exercise-related worry and establish personalized mechanisms for supporting physical activity in pediatric cancer survivors within the Chinese healthcare system.

Adolescent and young adult (AYA) pediatric cancer survivors’ knowledge, behaviors, beliefs, and adjustment differences across weight ranges

ABSTRACT Obesity presents significant medical and psychosocial risks for adolescent and young adult (AYA) pediatric cancer survivors (AYACS). Using screening data collected for a new healthy lifestyle pilot RCT, this study evaluated differences in AYACS’ physical activity and nutrition-related knowledge, behaviors, beliefs, and adjustments across weight ranges. AYACS with elevated body mass index (BMI; i.e. overweight, obese) reported significantly lower self-esteem, body esteem, and weight-related self-efficacy, as well as greater depressive symptoms and anxiety symptoms compared to AYACS with average weight. AYACS with average weight also reported better interpersonal relationship quality and stress management compared to AYACS with elevated BMI. Our findings provide insight to better tailor our newly developed healthy lifestyle-focused interventions for AYACS.

Perceived vulnerability related to health in cancer post-treated adolescent in Iran: a content analysis

BackgroundThe prevalence of cancer is increasing, which significantly impacts the health and various aspects of the lives of cancer-post-treated adolescents. Adolescents with cancer have many negative consequences, including increased vulnerability. Therefore, this study aimed to explore the perceived vulnerability of cancer-post-treated adolescents using a deep examination of experiences and perceptions of participants.MethodsThis study was conducted on 18 participants, who were selected based on purposive sampling in 2023 using a qualitative method through a content analysis approach in Iran. A face-to-face and semi-structured individual interview was used to collect data. Inclusion criteria were children aged 11–19 years, with no history of diseases except cancer, at least one year passed since their last treatment and were aware of their disease. Inclusion criteria for other participants were Parents of childhood cancer survivors whose child is under 19 years old. Health care providers that had at least one year of experience working with and caring for pediatric cancer survivors. The research objective, participation principle, and interview recording were explained to the participants before the interview started. The criteria of credibility, dependability, confirmability and transferability were included to support the trustworthiness of data. The data was analyzed using the conventional qualitative content analysis method and MAXQDA10 software was used for data management.ResultsThe participants included 12 cancer-post-treated adolescents, two parents, two nurses, one doctor, and one cancer charity representative. The data analysis identified three categories: “Confusion in early adolescence”, “Psychological turmoil of disease”, and “Physical burden of the disease”. Finally, the latent content was formulated in to a “Perceived vulnerability” overarching theme.ConclusionIdentifying the patient’s perceptions and beliefs is one of the current health problems to improve the quality of life and facilitate the optimal transition from adolescence to adulthood and adult care. Health professionals have an opportunity to address factors that increase survivors’ sense of vulnerability to health problems by correcting knowledge gaps.

Exploring the interagency collaboration between a pediatric oncology health care setting and community schools.

Globally, approximately 400,000 youth are diagnosed with pediatric cancer each year. Treatment-related side effects, psychosocial challenges, and frequent school absences may adversely impact learning and the education experience among these youth. Efforts to enhance interagency collaboration between health care settings and community schools are imperative to facilitate school reintegration. The Standards for the Psychosocial Care of Children with Cancer and Their Families outline specific guidelines related to the continuity of education for students impacted by pediatric cancer. In particular, the Academic Continuity and School Reentry Support and Monitoring and Assessment of Neuropsychological Outcomes standards of care highlighted within this article align with extant programmatic efforts for transitioning hospitalized school-aged children back into community schools. This article aims to describe systematic programmatic efforts within hospital-based psychosocial programs that are consistent with the Standards for the Psychosocial Care of Children with Cancer and Their Families, as well as interagency collaboration with community schools to support student-centered education for youth impacted by pediatric cancer. Resources for school psychologists, teachers, hospital-based programs, and others involved in student-centered education for pediatric cancer patients and survivors are presented. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Telomere Length in Adolescent and Young Adult Survivors of Childhood Cancer.

We examined the leukocyte relative telomere length (RTL) in Korean adolescent and young adult (AYA) survivors of childhood cancer and evaluated the association of leukocyte RTL with multiple factors, including malignancy type, cancer treatment, age, and chronic health conditions (CHCs). Eighty-eight AYA survivors of childhood cancer with a median follow-up period of 73 months were recruited. RTL in pediatric cancer survivors was not significantly shorter than the predicted value for age-matched references. Neither age at diagnosis nor duration of therapy influenced the RTL. Among the 43 patients with hematologic malignancies, those who underwent allogeneic hematopoietic stem cell transplantation (HSCT) showed a significant shortening of the RTL compared with those who did not (p = 0.039). Among the 15 patients who underwent allogeneic HSCT, those who developed acute graft-versus-host disease (GVHD) of grade II or higher had significantly shorter RTL than those who did not (p = 0.012). Patients with grade II CHCs had significantly shorter RTL than those without CHCs or with grade I CHCs (p = 0.001). Survivors with ≥2 CHCs also exhibited shorter RTL (p = 0.027). Overall, pediatric cancer survivors had similar telomere lengths compared to age-matched references. HSCT recipients and patients with severe or multiple CHCs had shorter telomeres. GVHD augmented telomere attrition in HSCT recipients.

“I Didn't Know What I Didn't Know”: Assessment of Adolescent Oncology Patient Engagement in Decision-Making

IntroductionLittle is known about the best way to engage an adolescent oncology patient in decision-making. To integrate adolescent oncology patients most effectively in decision-making, it is important to understand their perceptions not only as adolescents but also as adult survivors who have had time to reflect upon their experience. The purpose of this study is to explore perceptions of survivors of pediatric cancer to better understand their attitudes toward participation in decision-making, decisional regret, and use of decision-support tools. MethodsAn electronic survey tool, containing open- and closed-ended responses, was distributed to adult cancer survivors diagnosed and treated for cancer between the ages of 9 and 18 at a Midwestern, Comprehensive Cancer Center within a tertiary care academic hospital. ResultsSeventy responses were received. Nearly all respondents (96%) reported that decisions made on their behalf were consistent with their desires most/all the time. Almost one-fifth felt that increased involvement would have intensified their anxiety. Eighty-five percent did not regret choices made about their cancer treatment, and 88% would have made the same choices again. Respondents desired more targeted information on the long-term impacts of treatment (i.e., infertility, memory difficulties, mental health concerns), and they highlighted the importance of communication in the decision-making process. ConclusionsAdolescents want to participate in the decision-making process in a way that accommodates their understanding of the pathology and potential impacts of treatment. Our results suggest that developing a simple intervention to help facilitate provision of such anticipatory guidance may be helpful.

Addressing gaps and enhancing experiences in support services for families of pediatric cancer survivors.

Childhood cancer's enduring challenges extend beyond primary therapy. Diverse medical and psychosocial services are available to assist families in follow-up care. This interview study sought to gain a thorough understanding of family motives, satisfaction levels, and barriers to utilization. The design of this cross-sectional study involves a qualitative content analysis of semi-structured interviews. We interviewed parents of minor cancer survivors within the first 5 years after primary treatment. Survivors readily accessed medical support services when necessary. While parents expressed overall satisfaction with the available services, there was a notable gap in their knowledge regarding appropriate psychosocial and family-orientated services. Barriers to access included geographical distances, time constraints, and the absence of childcare options. There are familial challenges and burdens that fall outside the scope of conventional care services. Tailoring services to family-centered needs, providing more information and easier access to interventions might help to reduce barriers. Existing need notwithstanding, families did not frequently utilize psychosocial services as they did medical ones. Identified barriers included lack of awareness, limited availability, long distances, and scheduling conflicts. While many studies primarily focus on adult patients or young adults, the present study examines the gaps and strengths in follow-up care for pediatric cancer survivors and their families. By acknowledging and addressing the unique challenges and strengths of families with pediatric cancer survivors, we can lead to a more tailored and effective follow-up approach that can enhance their overall well-being by minimizing barriers and providing targeted support.

A 12-year overview of fertility preservation practice in Nordic pediatric oncology centers.

Fertility preservation is the only option to safeguard fertility following gonadotoxic treatments. This study aimed to provide an updated status on fertility preservation for pediatric cancer patients in the Nordic countries. A questionnaire consisting of 14 questions was sent to directors of 18 main pediatric oncology centers in the Nordic countries in 2010 and 2022. We received information regarding indications, guidelines, counseling, and available fertility preservation options. The response rates were 89% in 2010 and 72% in 2022. The results reveal an increase in clinical practice guidelines on fertility preservation for cancer patients, from 25% in 2010 to 70% in 2022. Counseling on fertility preservation options in 2022 was more specific and offered to most patients who fulfilled indications for fertility preservation (from 19 to 77%). Sperm cryopreservation continues to be the predominant fertility preservation method for pubertal boys in the Nordic countries. However, there has been a notable increase in the availability of testicular tissue preservation for prepubertal boys (0 to 62%). A similar increase in the offer of ovarian tissue preservation for prepubertal girls (0 to 92%) was observed among pediatric cancer patients. The past decade has shown commendable advancements in fertility preservation for pediatric cancer patients in the Nordic countries. As fertility care evolves globally, continuous assessment of regional practices and challenges is imperative to enhance the quality of care and life for pediatric cancer survivors in the Nordic regions.

When Lightning Strikes Twice: Routes to Second Malignancies in Young Patients.

Given the rarity of cancer in childhood, it should be even more uncommon for pediatric cancer survivors to develop a second, independent malignancy, yet they incur a greatly elevated risk after initial remission. In this issue of Cancer Discovery, Sánchez-Guixé and colleagues unpick the origins of second tumours in four children, and the potential role platinum-based chemotherapy may play in subsequent tumorigenesis. See related article by Sánchez-Guixé et al., p. 953 (8).

Pharmacogenomic studies of fertility outcomes in pediatric cancer survivors - A systematic review.

For the same age, sex, and dosage, there can be significant variation in fertility outcomes in childhood cancer survivors. Genetics may explain this variation. This study aims to: (i) review the genetic contributions to infertility, (ii) search for pharmacogenomic studies looking at interactions of cancer treatment, genetic predisposition and fertility-related outcomes. Systematic searches in MEDLINE Ovid, Embase Classic+Embase, and PubMed were conducted using the following selection criteria: (i) pediatric, adolescent, and young adult cancer survivors, below 25 years old at the time of diagnosis, (ii) fertility outcome measures after cancer therapy, (iii) genetic considerations. Studies were excluded if they were (i) conducted in animal models, (ii) were not published in English, (iii) editorial letters, (iv) theses. Articles were screened in Covidence by at least two independent reviewers, followed by data extraction and a risk of bias assessment using the Quality in Prognostic Studies tool. Eight articles were reviewed with a total of 29 genes. Outcome measures included sperm concentration, azoospermia, AMH levels, assessment of premature menopause, ever being pregnant or siring a pregnancy. Three studies included replication cohorts, which attempted replication of SNP findings for NPY2R, BRSK1, FANCI, CYP2C19, CYP3A4, and CYP2B6. Six studies were rated with a high risk of bias. Differing methods may explain a lack of replication, and small cohorts may have contributed to few significant findings. Larger, prospective longitudinal studies with an unbiased genome-wide focus will be important to replicate significant results, which can be applied clinically.

Risk of low bone mineral density in young pediatric cancer survivors with sarcopenia.

10070 Background: Required treatments to cure pediatric cancer at such a young age increase the risk of later health-related complications. Early exposure to DNA damaging agents, during a vital period of active skeletal growth, interferes with accrual of bone mass. Treatments not only impair bone health, but also affect skeletal muscle function and mass. Long-term pediatric cancer survivors present these limitations due to myofibrillary atrophy caused by degradation of myosin heavy chain and decrease in myosin synthesis death. Muscle weakness (both muscle strength deficits and low lean mass hereafter referred to as sarcopenia) and low areal bone mineral density (aBMD) have been observed to coexist in adult survivors of paediatric cancer. However, in young pediatric cancers survivors, associations between sarcopenia and low aBMD are not well described. Therefore, this study aimed to examine the risk of low aBMD in young pediatric cancer survivors with sarcopenia confirmed/probable, compared to not having sarcopenia. Methods: This cross-sectional study included 116 pediatric cancer survivors (12.1±3.3 years old; 42% female) enrolled on a randomized controlled trial designed to improve bone health (iBoneFIT project). Handgrip strength was used to assessed muscle strength. Dual-energy X-ray absorptiometry estimated aBMD (g/cm2) at the total body (less head), lumbar spine, total hip and femoral neck, and appendicular lean mass index (ALMI, kg/m2). Sarcopenia status was determined using age and sex specific international reference data from a healthy population. “No sarcopenia” was defined when muscle strength was >decile 2. “Sarcopenia probable” was defined when muscle strength was ≤decile 2 and ALMI Z-score was > -1.5 standard deviation (SD). “Sarcopenia confirmed” was defined when muscle strength was ≤decile 2 and ALMI Z-score ≤-1.5 SD. Logistic regression, adjusted for time from treatment completion and radiation exposure, was used to evaluate the risk of low aBMD (age-, sex- and race-specific aBMD Z-score < -1.0) by sarcopenia status. Results: More than one-third of survivors met criteria for sarcopenia confirmed (37.9%); 19.0% met criteria for sarcopenia probable. Survivors with sarcopenia confirmed had higher risk of low aBMD at the total body (odd ratio [OR]: 6.91, 95% confidence interval [CI]: 2.31-24.15), total hip (OR: 2.98, 95% CI: 1.02-9.54) and femoral neck (OR: 4.72, 95% CI: 1.72-14.19) than those without sarcopenia. Survivors with sarcopenia probable had higher risk of having low aBMD only at the total body (OR: 4.13, 95% CI: 1.04-17.60) than those without sarcopenia. Conclusions: Over one-third of young paediatric cancer survivors presented sarcopenia confirmed with higher risk of low aBMD. These findings suggest that interventions to mitigate osteosarcopenia in this population should be implemented at early stages after treatment completion.

Patient-caregiver dyad concordance of transition readiness assessment for adolescent with cancer: A network analysis.

The concordance of adolescents with cancer and caregivers was examined, and the core elements of transition readiness were identified. In this cross-sectional study, 196 adolescent-caregiver dyads completed the Chinese version of Self-Management and Transition to Adulthood with Rx = Treatment Questionnaire and its parent version between March 2023 and August 2023. Intraclass correlation coefficients, paired t-tests and network analysis were used for data analysis. Caregivers reported slightly lower scores for transition readiness than adolescents (3.28 vs. 3.32). Healthcare engagement and provider communication were core elements in transition readiness networks. At the dyad level, agreement between adolescents' and caregivers' transition readiness ranged from poor to fair (intraclass correlation coefficients 0.103-0.486), and a significant difference in structure was found between the two networks. Caregivers tended to underestimate adolescents' transition readiness. Attaining better concordance between adolescents and family caregivers is critical to aligning roles and responsibilities in the transition process. This study extends the evidence on the variation in adolescents' transition readiness, clarifying the complex associative relationships among the elements of transition readiness, which can be potential pathways for improving transition readiness. Second, this study is the first to assess transition readiness from a dyad's perspective. The findings highlighted the patient-caregiver incongruence in rating patients' transition readiness, suggesting that targeted dyadic interventions should be developed and implemented to improve patient-caregiver transition readiness concordance, facilitate effective communication and mutuality between patients and caregivers, and contribute to their collaboration during the transition of adolescents and optimization of outcomes. WHAT PROBLEM DID THE STUDY ADDRESS?: Increased long-term survival rates of survivors of paediatric cancer highlighted the significant need for care continuity. Transitional readiness is an important predictor of adolescent survivor's ability to adapt to a long-term survival period. Assessments of adolescents' transition readiness are limited and overlook the synergies between family caregivers and adolescents in the transition period. WHAT WERE THE MAIN FINDINGS?: The levels of agreement on rating transition readiness varied from poor to fair among adolescent-caregiver dyads, and caregivers tended to underestimate adolescents' transition readiness. The findings highlighted the patient-caregiver incongruence in rating patients' transition readiness. Targeted dyadic interventions should be developed and implemented to improve patient-caregiver's transition readiness concordance, and facilitate effective communication and mutuality between patients and caregivers. Study methods and results reported in adherence to the STROBE checklist. No patients or members of the public were involved in the study. The main findings introduce pathways for improving transition readiness, which can enhance healthcare transition among other medical populations.

Bone age and dental late effects in childhood cancer survivors: Radiographic findings in a Brazilian sample.

Changes in bone age and tooth development are late side effects of cancer therapy and can be identified by imaging examination. To evaluate the late effects of antineoplastic treatment on bone age and dental development in childhood cancer survivors. This is a retrospective case-control study on paediatric cancer survivors of both sexes who underwent antineoplastic treatment with 5-15 years of survival. Carpal radiographs were assessed for bone age and growth curve, and panoramic radiographs were used to evaluate dental development and alterations. Carpal radiographs were analyzed using the Greulich and Pyle inspection method, and the Martins and Sakima method was used to analyze the growth curve. All tests were applied with a confidence level of 95%. The study and control groups comprised 28 and 56 patients, respectively. There was no significant difference in bone age and growth curve between the study and control groups. Nonetheless, when sex was compared to chronological and bone ages, there was a significant difference in bone age (p = 0.019) and an underestimation in both groups and sexes in the Greulich and Pyle method. As to late dental effects, dental agenesia, microdontia, gyroversion, and unerupted teeth were found. Dental shape alterations mainly involve the root region. Close multidisciplinary collaboration is necessary during the follow-up period of young patients who have survived cancer.

EDA2R reflects the acute brain response to cranial irradiation in liquid biopsies.

Cranial radiotherapy is standard of care for high-grade brain tumors and metastases; however, it induces debilitating neurocognitive impairments in cancer survivors, especially children. As the numbers of pediatric brain cancer survivors continue improving, the numbers of individuals developing life-long neurocognitive sequalae are consequently expected to rise. Yet, there are no established biomarkers estimating the degree of the irradiation-induced brain injury at completion of radiotherapy to predict the severity of the expected neurocognitive complications. We aimed to identify sensitive biomarkers associated with brain response to irradiation that can be measured in easily accessible clinical materials, such as liquid biopsies. Juvenile mice were subjected to cranial irradiation with 0.5, 1, 2, 4, and 8 Gy. Cerebrospinal fluid (CSF), plasma, and brains were collected at acute, subacute, and subchronic phases after irradiation, and processed for proteomic screens, and molecular and histological analyses. We found that the levels of ectodysplasin A2 receptor (EDA2R), member of tumor necrosis factor receptor superfamily, increased significantly in the CSF after cranial irradiation, even at lower irradiation doses. The levels of EDA2R were increased globally in the brain acutely after irradiation and decreased over time. EDA2R was predominantly expressed by neurons, and the temporal dynamics of EDA2R in the brain was reflected in the plasma samples. We propose EDA2R as a promising potential biomarker reflecting irradiation-induced brain injury in liquid biopsies. The levels of EDA2R upon completion of radiotherapy may aid in predicting the severity of IR-induced neurocognitive sequalae at a very early stage after treatment.

Factors impacting physical activity among post-treatment pediatric cancer survivors with overweight and obesity.

Pediatric cancer survivors (PCS) with overweight and obesity are at risk for various secondary chronic diseases. Although previous research has found physical activity (PA) as beneficial after treatment, the PA levels are low among PCS, highlighting the need for lifestyle interventions targeting PA. A secondary analysis of preliminary baseline data from a multi-site trial, NOURISH-T + , a healthy lifestyle intervention for PCS with overweight and obesity, and their caregivers, was conducted to assess factors related to PCS PA (i.e., moderate to vigorous intensity PA, MVPA). Kendall's Tau-b was used to assess correlations between PCS MVPA, health and treatment-related factors, and caregivers' sedentary behavior and MVPA. Wilcoxon Signed Ranks Test was used to assess the differences between PCS and caregiver sedentary behavior and MVPA. A multiple linear regression analysis was performed to determine predictors of PCS MVPA. Seventy-three PCS-caregiver dyads were included in this analysis (N = 146). Many of the PCS were female, diagnosed with Acute Lymphoblastic Leukemia, stage 1, with a mean body mass index (BMI) percentile of 94.4 ± 4.7. Caregivers were female and parents to the PCS. Significant correlations were found between PCS MVPA, time since treatment, PCS weight change since COVID, caregiver sedentary behavior and MVPA. Significant differences were observed between PCS and caregiver sedentary behavior and MVPA. Household income, radiation treatment, and caregiver MVPA were significant predictors of PCS MVPA. Conclusions: Demographics, cancer treatment type, and caregiver role modeling are important factors to consider when developing future lifestyle interventions for PCS. (NCT04656496, registered 12-07-2020). • Parents/caregivers are presumed to be a potential influence on their children's physical activity What is new: • Parents/caregivers' moderate-to-vigorous physical activity is the strongest predictor of their children's (pediatric cancer survivors') physical activity.

Impact of sociodemographic factors, stress, and communication on health-related quality of life in survivors of pediatric cancer.

While most research has largely focused on medical risks associated with reduced health-related quality of life (HRQOL) in survivors, sociodemographic and family factors may also play a role. Thus, we longitudinally examined sociodemographic factors and family factors associated with survivor HRQOL, including adolescent's cancer-specific stress, mother's general stress, and mother-adolescent communication. Mothers (N=80) and survivors (ages 10-23, N=50) were assessed 5years following initial diagnosis. Mothers completed measures regarding sociodemographic background adolescent's cancer-specific stress, mother's general stress, mother-adolescent communication, and adolescent HRQOL. Survivors also reported on their own HRQOL. Two hierarchical multiple regressions examined predictors of (a) mother's report of adolescent HRQOL, and (b) survivor's self-report of HRQOL. The final model predicting mother-reported adolescent HRQOL was significant, F(5,74)=21.18, p<.001, and explained 59% of the variance in HRQoL. Significant predictors included adolescent stress (β=-.37, p<.001), mothers' stress (β=-.42, p<.001), and communication (β=.19, p=.03). The final model predicting survivor-reported HRQOL was also significant, F(5,44)=5.16, p<.01 and explained 24% of the variance in HRQOL. Significant predictors included adolescent stress (β=-.37, p=.01) and communication (β=-.31, p=.04). Sociodemographic factors were not a significant predictor of HRQOL in any model. Family stress and communication offer potential points of intervention to improve HRQOL of pediatric cancer survivors from mother and survivor perspectives. While additional research is needed, healthcare professionals should encourage stress management and strong mother-child communication to enhance survivors' long-term HRQOL. Such interventions may be complimentary to efforts targeting the known sociodemographic factors that often affect health.

Tandem High-Dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors.

This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT). Patients (aged < 19 years) diagnosed with or treated for pediatric solid tumors between 1994 and 2014 were retrospectively analyzed. The cumulative incidence of SMN was estimated using competing risk methods by considering death as a competing risk. A total of 1,435 patients (413 with brain tumors and 1,022 with extracranial solid tumors) were enrolled. Seventy-one patients developed 74 SMNs, with a 10-year and 20-year cumulative incidence of 2.680±0.002% and 10.193±0.024%, respectively. The types of SMN included carcinoma in 28 (37.8%), sarcoma in 24 (32.4%), and hematologic malignancy in 15 (20.3%) cases. Osteosarcoma and thyroid carcinoma were the most frequently diagnosed tumors. Multivariate analysis showed that radiotherapy (RT) > 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively. The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric 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.