Adult Survivors Of Childhood Cancer Research Articles

Reduced Lower Body Muscular Strength and Endurance among Adult Survivors of Childhood Cancer

Reduced Lower Body Muscular Strength and Endurance among Adult Survivors of Childhood Cancer

Quality of Life of Adolescents and Young Adult Survivors of Childhood Cancer: A Qualitative Study.

To analyse how adolescents and young adults who survived childhood cancer experience their quality of life and to explore their meanings and conceptualisations of quality of life. Narrative design following Squire's method. In-person and virtual recruitment, due to the global COVID-19 pandemic, was carried out in Brazil between May and November 2021. Eighteen semi-structured virtual interviews were conducted with childhood cancer survivors. These data were analysed using reflexive thematic analysis and employing a triangulation of investigators. Four subthemes were identified, encompassing participants' perceptions and meanings of quality of life. Through the reflection and synthesis of these subthemes, a central theme emerged entitled 'New self', capturing the profound impact of the cancer and survival experience on every aspect of the self, along with participants' sense of having gained 'a new life' and a 'second chance'. The study provides a rich and nuanced understanding of quality of life for childhood cancer survivors. The results highlight that after all the changes in life due to cancer, integrating the new self becomes a central aspect of quality of life for survivors. Recognising the profound shifts in self-perception that survivors of childhood cancer undergo, nurses should engage early in empowering patients and families, offering education, space and support to help adolescents and young adults grow throughout their journey. The richness and depth inherent in qualitative data on quality of life can inform the development of care standards and health policies for survivors, guide the allocation of strategic resources and shape the development of plans and interventions focusing on childhood cancer survivors. The COREQ checklist was used. No patient or public contribution.

Social Reintegration and Stigma Among Childhood Cancer Survivors in West Kenya.

Purpose: The population of childhood cancer survivors in low- and middle-income countries is set to increase due to diagnosis and treatment advancements. However, cancer is still associated with stigma that may hinder societal re-entry. This study explores the social reintegration and stigmatization of Kenyan childhood cancer survivors to develop targeted interventions for follow-up care. Methods: Adult survivors of childhood cancers who completed treatment at the largest referral hospital in Western Kenya were interviewed using semi-structured questionnaires between 2021 and 2022. Stigma was assessed using the Social Impact Scale. Results: Twenty-six survivors (median age 20 years) were interviewed, with 16 (62%) being males. All survivors missed classes during treatment, and 16 (62%) had to repeat school grades after treatment completion. Many (13; 50%) reported negative feelings about the situation at school. Six (23%) were excluded from school activities and four were bullied (15%). Most 25 (96%) could not openly speak about cancer to all community members. Reasons for lacking social support, avoidance, and discrimination were cancer is a curse, contagious, or inheritable. Nine (35%) felt that their marital prospects were negatively affected by their cancer history. Stigma was higher for survivors who received a negative response after cancer disclosure (p = 0.001) and survivors with negative perspectives on their marital prospects (p = 0.002). Survivors recommended community and school education, peer support groups, and counseling. Conclusion: Childhood cancer survivors in Kenya face difficulties with social reintegration and stigmatization. Outreach campaigns focusing on education at schools and communities should be implemented. Counseling and support groups may facilitate re-entry into society.

The Triglycerides - Glucose Index: An independent predictor of late subclinical cardiotoxicity in adult survivors of childhood, adolescent and young adult cancer

Abstract Introduction The Triglycerides - Glucose index (TyG index) has been identified as a reliable alternative for estimating insulin resistance (IR). Numerous recent studies have provided strong statistical evidence suggesting that this index is associated with the development and prognosis of cardiovascular pathologies. Objectives The aim of this study was to investigate the predictive role of the TyG index on the decrease in left ventricular longitudinal global strain (GLS) assessed on two-dimensional echocardiography in asymptomatic adult survivors of childhood, adolescent and young adult cancer. Methods The study included patients aged 18 years and older, asymptomatic cardiovascular survivors of childhood, adolescent and young adult cancer treated with anthracyclines with or without mediastinal radiotherapy. Anthropometric characteristics, cardiovascular risk factors and cancer treatment-related characteristics were collected. The TyG index was calculated using the formula: ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. GLS was assessed and expressed as an absolute value. A GLS equal to 17.3% was retained as the threshold value after calculation in a referent group matched to patients according to age and gender. Cardiac biomarkers GDF 15, ultra-sensitive troponin I and NT-proBNP levels were measured in addition to fasting blood glucose and lipid profiles. Multivariate analysis using linear regression was performed to identify associations between these different parameters. Results A total of 105 cancer survivors from childhood, adolescence and young adulthood were included. The sex ratio was 1.3. The mean age of the patients was 25 years, the mean time since completion of cancer treatment was 10.6 years, the mean cumulative doses of anthracyclines and mediastinal radiotherapy were successively 245.75 ± 75.14 mg/m2 and 34.6 ± 6.19 Gy. Mean GLS was 18.5 ± 2.83%, mean LVEF 60.6 ± 5.69%. None of the patients had any known diabetes or treatment to lower blood glucose or triglyceride levels. No patient had a history of cardiovascular disease. In the univariate study, the factors associated with lower GLS were patient age at recruitment (p = 0.03), mean time since completion of cancer treatment when this was greater than ten years (p = 0.005), dyslipidemia (p = 0.012), obesity (p = 0.037) and TyG (p = 0.037). In multivariate analysis, lower GLS was related to mean time since completion of cancer treatment (p = 0.015) and TyG index (p = 0.002). Conclusion Our results suggest that the TyG index, as a simple and inexpensive marker of insulin resistance, could help identify cancer survivors from childhood, adolescence and young adulthood who would be at risk of subclinical cardiac dysfunction. Prospective studies with larger numbers are needed to confirm these findings.

Early life cisplatin exposure induces nerve growth factor mediated neuroinflammation and chemotherapy induced neuropathic pain.

Chemotherapy-induced neuropathic pain (CINP) is a common adverse health related comorbidity that manifests later in life in paediatric cancer patients. Current analgesia is ineffective, aligning closely with our lack of understanding of CINP. The aim of this study was to investigate how cisplatin induces nerve growth factor mediated neuroinflammation and nociceptor sensitisation. In a rodent model of cisplatin induced survivorship pain, cisplatin induced a neuroinflammatory environment in the dorsal root ganglia (DRG) demonstrated by nerve growth factor (NGF) positive macrophages infiltrating into the DRG. Cisplatin treated CD11b/F480 positive macrophages expressed more NGF compared to vehicle treated. Primary DRG sensory neuronal cultures demonstrated enhanced NGF-dependent TRPV1 mediated nociceptor activity after cisplatin treatment. Increased nociceptor activity was also observed when cultured DRG neurons were treated with conditioned media from cisplatin activated macrophages. Elevated nociceptor activity was dose-dependently inhibited by a neutralising NGF antibody. Intraperitoneal administration of a NGF neutralising antibody reduced cisplatin-induced mechanical hypersensitivity and aberrant nociceptor intraepidermal nerve fibre density. These findings identify that a monocyte/macrophage driven NGF/TrkA pathway is a novel analgesic target for adult survivors of childhood cancer.

Fear of Cancer Recurrence in Adult Survivors of Childhood Cancer

Fear of cancer recurrence is common among survivors of adult-onset cancer and associated with increased distress, functional impairment, and health care utilization. However, little is known about the prevalence and risk factors of fear of cancer recurrence among adult survivors of childhood cancer who are also at high risk for subsequent malignant neoplasms. To characterize the prevalence of and risk factors for clinically significant fear of cancer recurrence in adult survivors of childhood cancer. This cross-sectional investigation included participants recruited from the Childhood Cancer Survivor Study, a retrospective cohort study of long-term childhood cancer survivors treated at 31 institutions between 1970 and 1999 across North America. Participants were recruited and completed psychosocial measures via online survey between October 2018 and April 2019. Cancer and treatment-related variables were abstracted from medical records. Data were analyzed from May 2023 to July 2024. Clinically significant fear of cancer recurrence was assessed via the Fear of Cancer Recurrence Inventory-Short Form. Poisson regression models estimated prevalence ratios (PRs) with 95% CIs adjusted for age and sex to examine the associations of demographic, disease, treatment, and psychosocial variables with fear of cancer recurrence. The final sample included 229 adult survivors of childhood cancer (115 female [50.2%]; mean [SD] age, 39.6 [9.9] years; mean [SD] time since diagnosis, 31.7 [8.4] years). Among survivors, 38 (16.6%; 95% CI, 11.6%-21.6%) reported clinically significant fear of cancer recurrence, and an additional 36 (15.7%) reported high fear of cancer recurrence. Clinically significant fear of cancer recurrence was associated with unemployment (PR, 2.5; 95% CI, 1.3-4.8), presence of neurologic chronic health conditions (PR, 3.3; 95% CI, 1.8-6.1), treatment with pelvic radiation (PR, 2.9; 95% CI, 1.5-5.6), and amputation or limb sparing surgery (PR, 2.4; 95% CI, 1.2-4.9). Higher risk of clinically significant fear of cancer recurrence was also associated with having either elevated anxiety or depression (PR, 2.6; 95% CI, 1.2-5.9), having both elevated (PR, 3.2; 95% CI, 1.2-8.4), and perceived poor health status (PR, 3.0; 95% CI, 3.1-9.7). Decades following treatment, one-third of childhood cancer survivors in this study reported elevated fear their cancer will recur or a subsequent malignant neoplasm will develop. Findings suggest that fear of cancer recurrence should be routinely screened, and clinically significant symptoms intervened upon as a part of survivorship care.

Sugar and sugar-sweetened beverages in relation to premature aging in adult survivors of childhood cancer.

Premature aging is a significant concern in adult survivors of childhood cancer as they develop aging-related conditions at a younger age than their peers with no history of childhood cancer. Although modifiable lifestyle factors, such as diet, are postulated to affect aging process, supporting evidence is sparse. We examined if the consumption of sugar and sugar-sweetened beverages was related to premature aging in 3322 adult survivors of childhood cancer in the St. Jude Lifetime Cohort. Premature aging was assessed using the Deficit Accumulation Index (DAI) that was a ratio of the number of age-related chronic health conditions each survivor had out of 44 conditions total. Multinomial logistic regressions adjusting for confounders were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). There were 46% of childhood cancer survivors consumed SSBs once or more times per day. High intake of sugar, especially sugars added to foods during preparation or processing, and habitual consumption of sugar-sweetened beverage were associated with an increased risk of premature aging. Our findings support a need to include strategies to reduce sugar and sugar-sweetened beverages consumption in lifestyle interventions to promote healthy aging in adult survivors of childhood cancer.

Autonomic Dysfunction Among Adult Survivors of Childhood Cancer in the St. Jude Lifetime Cohort Study

BackgroundThe burden and functional significance of autonomic dysfunction among survivors of childhood cancer is unknown. ObjectivesWe evaluated the prevalence, risk factors, and functional relevance of autonomic dysfunction in survivors. MethodsWe conducted a cross-sectional prospective evaluation of 1,041 adult survivors of childhood cancer treated with anthracyclines (31.1%), chest-directed radiation (13.5%), both (19.5%), or neither (35.9%), and 286 community control subjects enrolled in the SJLIFE (St Jude Lifetime Cohort Study). Four measures of autonomic dysfunction were evaluated: elevated resting heart rate, decreased heart rate reserve, decreased systolic blood pressure response to exercise, and delayed heart rate recovery. Logistic regression tested associations with impaired cardiorespiratory fitness (peak Vo2 < 80% predicted). ResultsSurvivors (50.7% female) were 9.0 ± 5.8 years at cancer diagnosis and 35.5 ± 8.9 years at evaluation. Prevalence (survivors vs control subjects) of elevated resting heart rate (17.9% vs 7.0%), decreased heart rate reserve (21.7% vs 9.1%), decreased systolic blood pressure response to exercise (25.3% vs 12.6%), and delayed heart rate recovery (24.3% vs 10.6%) was more than 2-fold higher among survivors (P < 0.001 for all). Carboplatin (adjusted OR: 2.50; 95% CI: 1.42-4.40; P = 0.001), chest-directed radiation therapy (adjusted OR: 2.06; 95% CI: 1.52-2.75; P < 0.001), and cranial radiation (adjusted OR: 1.49; 95% CI: 1.08-2.05; P = 0.015) were associated with an increased likelihood of having ≥2 measures of autonomic dysfunction. Survivors with ≥2 measures of autonomic dysfunction were at increased risk for impaired cardiorespiratory fitness (adjusted OR: 2.71; 95% CI: 1.82-4.02; P < 0.001). ConclusionsSurvivors of childhood cancer manifest a higher prevalence of autonomic dysfunction associated with impaired cardiorespiratory fitness.

Radiotherapy-associated Sensorineural Hearing Loss in Pediatric Oncology Patients.

During the radiotherapeutic treatment of pediatric oncology patients, they would be at a latent risk of developing ionizing radiation-induced ototoxicity when the cochlea or auditory nerve is located within the radiation field. Sensorineural hearing loss (SNHL) is an irreversible late complication of radiotherapy, and its incidence depends on various factors such as the patient's hearing sensitivity, total radiation dose to the cochlea, radiotherapy fractionation regimen, age and chemoradiation. Importantly, this complication exhibits serious challenges to adult survivors of childhood cancer, as it has been linked to impairments in academic achievement, psychosocial development, independent living skills, and employment in the survivor population. Therefore, early detection and proper management can alleviate academic, speech, language, social, and psychological morbidity arising from hearing deficits. In the present review, we have addressed issues such as underlying mechanisms of radiation-induced SNHL, audiometric findings of pediatric cancer patients treated with radiotherapy, and management and protection measures against radiation-induced ototoxicity.

Building a community-academic partnership to expand services for childhood cancer survivors in a rural, low-income region in California.

360 Background: Community-engaged research is an effective approach to address health disparities that is well-established in the public health domain and has not been widely applied in childhood cancer survivorship. We present our multi-year experience building a community-academic partnership and community-engaged childhood cancer survivorship research portfolio. Methods: We have developed a partnership between Jacob’s Heart Children’s Cancer Support Services, a nonprofit community-based organization (CBO) and an academic pediatric cancer survivorship team, with the goal of improving health outcomes for childhood cancer survivors and their families in the Salinas Valley, a rural, low-income region in California with majority Hispanic/Latino/a/e residents. Our partnership process is guided by principles of community-based participatory research, prioritizing trust and involving community members as equal partners in all phases of research. Results: In year 1 (2021-2022), we held successive meetings which identified common goals and shared values, established the collaboration, and sought funding to advance our goals. In year 2 (2022-2023), with internal grant funding, we conducted a qualitative needs assessment interviewing childhood cancer survivors, parents, and CBO staff. Teamwork enriched the data analysis and allowed us to identify problems in communication as an area of need, which directly informed subsequent grant proposals. In year 3 (2023-2024), with external funding we began a multi-year study to understand and improve survivorship-related communication among Hispanic/Latino/a/e young adult childhood cancer survivors, their parents, and clinicians. Current and future projects include collaborative design and pilot testing of a novel communication intervention, formation of a dedicated community advisory board, and a CBO-driven program evaluation. Findings from our community-engaged studies have prompted new sets of research questions and illustrate opportunities for institutional change in the clinic setting. In parallel, the CBO has leveraged research findings in real-time to identify barriers to seeking support among childhood cancer survivors and families, and adapted and improved programming for families in response. Through our joint research portfolio, we have incorporated training and mentorship for staff at the CBO and medical trainees at the academic center. Conclusions: A community-academic partnership in a rural, low-income region has the potential to reduce health disparities and improve childhood cancer survivors’ health outcomes through collaborative program development and community-engaged research. Fueled by mutual investment and strong momentum, our partnership facilitates an interconnected cycle of research and practice change that is grounded in community needs.

Abstract B139: Redlining bias and progression of chronic health conditions in survivors of childhood cancer: A report from the St. Jude lifetime cohort study

Abstract Background/Aims: Racial health disparities have been linked to racial and residential segregation. Redlining bias is a special form of racial and residential segregation involving the systematic denial of mortgages, insurance, and other financial services to racial/ethnic minorities. This study examined associations between redlining bias and the progression of chronic health conditions (CHCs) in adult survivors of childhood cancer. Methods: We included 1,670 adult survivors of childhood cancer from the St. Jude Lifetime Cohort Study who had undergone two or more clinical assessments. Over 200 individual CHCs were graded using a modified CTCAE version and aggregated to determine the global CHC burden. CHC progression from baseline to follow-up evaluation was classified as either worsening over time (from Grade 2 to 3-5 or from Grade 3 to 4-5) or new-onset (from Grades 0-1 to 2-5). Survivors' home addresses at baseline (2007-2020) were linked to contemporary redlining bias data (2010-2017) created by Beyer et al. (J Clin Oncol, 2021). Redlining bias was defined as the odds ratio of a mortgage application denial for properties in a local area versus all metropolitan statistical areas and further classified as high (≥2.0), moderate (1.0-1.9), low (0.5-0.9), or least bias (&amp;lt;0.5). Multivariable logistic regression tested associations of risk for worsening/new-onset CHCs (vs. no progression) with redlining bias (high vs. moderate/low/least bias), adjusting for age, sex, treatment factors, personal socioeconomic status (SES; education and health insurance), and lifestyle factors. Joint effects of redlining bias and personal SES on CHC progression were also evaluated. Results: Survivors’ mean±SD age at baseline was 31.7±8.3 years; 17.5% lived in high and 19.5% in moderate redlining neighborhoods. The bivariate analysis found that living in a neighborhood classified as having high redlining bias (vs. moderate/low/least bias) increased the risk of progression of the global burden of CHCs (OR=1.32, 95% CI: 1.02-1.70). Multivariable analysis found significant associations of redlining bias with the risk of worsening/new-onset of individual CHCs such as cardiomyopathy (OR=1.63, 95% CI: 1.07-2.48), peripheral motor neuropathy (OR=1.56, 95% CI: 1.00-2.44), asthma (OR=1.85, 95% CI: 1.04-3.32), and restrictive pulmonary deficit (OR=1.79, 95% CI: 1.05-3.04). Considering joint effects, survivors enrolled in public insurance programs and living in a high redlining area had a higher risk of progression of the global burden of CHCs (OR=1.73, 95% CI: 1.05-2.87) and of worsening/new-onset in peripheral motor neuropathy (OR=3.18, 95% CI: 1.57-6.42) and restrictive pulmonary deficit (OR=5.29, 95% CI: 2.46-11.37) CHCs. Conclusions: The significant associations of redlining bias with the progression of CHCs among adult survivors of childhood cancer suggest an urgent need for interventions (typically social or healthcare policies) targeting neighborhoods with high discriminatory exposures to prevent CHC burden in this population. Citation Format: Jaesung Choi, Madeline R. Horan, Nickhill Bhakta, Deo Kumar Srivastava, Kirsten K. Ness, Gregory T. Armstrong, Melissa M. Hudson, I-Chan Huang. Redlining bias and progression of chronic health conditions in survivors of childhood cancer: A report from the St. Jude lifetime cohort study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B139.

Neighborhood vulnerability and associations with poor health-related quality of life among adult survivors of childhood cancer.

Few studies have investigated the relationship between neighborhood vulnerability and health-related quality of life (HRQOL) in the childhood cancer population. This study evaluated the impact of neighborhood vulnerability on HRQOL among adult survivors of childhood cancer. This cross-sectional study included 4393 adult survivors of childhood cancer from the St Jude Lifetime Cohort Study. At the baseline (2007-2020), HRQOL was assessed using the SF36v2's physical and mental components summaries (PCS and MCS). Neighborhood vulnerability was assessed using the overall, domain, and indicator-specific scores of the Social Vulnerability Index (SVI) and Minority Health SVI (MHSVI). Multivariable logistic regression was used to evaluate associations of neighborhood vulnerability (quartiles: Q1-Q4) with impaired HRQOL (1SD below the norm), adjusting for diagnosis, demographics, personal socioeconomic status (SES), lifestyle, and chronic health condition burden. Interactions of SVI and MHSVI with personal SES on impaired HRQOL were analyzed. Among survivors, 51.9% were male, averaging 30.3 years of age at evaluation and 21.5 years since diagnosis. Comparing neighborhoods with higher vs lower vulnerability (Q4 vs Q1), overall (odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.19 to 2.16) and domain-specific vulnerability (socioeconomic: OR = 1.59, 95% CI = 1.18 to 2.15; household composition: OR = 1.54, 95% CI = 1.16 to 2.06; housing and transportation: OR = 1.33, 95% CI = 1.00 to 1.76; medical vulnerability: OR = 1.60, 95% CI = 1.22 to 2.09) were significantly associated with impaired PCS, but not MCS. Residing in neighborhoods lacking urgent care clinics was significantly associated with impaired PCS (OR = 1.39, 95% CI = 1.08 to 1.78). Having lower vs higher personal education and living in higher vulnerability neighborhoods were associated with more impaired PCS (Pinteraction = .021). Specific aspects of neighborhood vulnerability increase the risk for impaired physical HRQOL. Addressing these neighborhood factors is essential to enhance the HRQOL of survivors.

Late effects surveillance adherence among young adult childhood cancer survivors: A population-based study.

Lifelong, guideline-based monitoring for late effects is recommended for childhood cancer survivors (CCS). We examined rates of receiving surveillance tests among at-risk young adult CCS in a population-based study (n=253; 50% Hispanic/Latino; mean post-treatment interval 14.5years, range: 5-22). Adherence rates were 36.1%, 31.9%, and 36.4% among those indicated for cardiac (n=119), thyroid (n=68), and breast (n=66) surveillance, respectively, indicating that poor surveillance among long-term CCS is widespread. Receipt of any of these surveillance tests was positively associated with being in follow-up care, having any health insurance (vs. none), and receiving education about need for follow-up with surveillance (all p-values less than.05).

Mental wellness and health-related quality of life of young adult survivors of childhood cancer in Singapore.

Childhood cancer survivors (CCS) are at risk of experiencing psychological distress years after completing cancer treatments. We aimed to assess the prevalence and associated risk factors affecting psychological distress and health-related quality of life (HRQOL) among CCS in Singapore, and compare with their siblings without a history of or existing cancer as control. We recruited 143 young adult CCS aged ≥18 years attending survivorship clinics at KK Women's and Children's Hospital in Singapore who were in remission for ≥5 years and treatment-free for ≥2 years, and 57 siblings. CCS and siblings were matched at a 1:1 ratio based on sociodemographic factors yielding 46 pairs for comparison. Among CCS participants, 79 (55.2%) were male, 86 (60.1%) had leukaemia, 29 (20.3%) had solid tumours, 15 (10.5%) had lymphoma and 13 (9.1%) had brain tumours. All participants completed the Brief Symptom Inventory-18 (BSI-18) and Medical Outcomes Short Form-36 (MOS SF-36) questionnaires from August 2021 to July 2022. There were 35 (24.5%) CCS who reported psychological distress in the BSI-18 Global Severity Index. Five (3.5%) and 31 (21.7%) CCS reported low HRQOL in the physical and mental composite scores, respectively. Mean scores between CCS and their siblings were not statistically significant across all domains of the BSI-18 and MOS SF-36. Associated risk factors for psychological distress and low HRQOL among CCS were history of psychiatric illness after cancer diagnosis and mood affected by the COVID-19 pandemic. CCS reported significant psychological distress and low HRQOL although they were not statistically different from their siblings. A holistic and risk factor-centric follow-up programme can aid early detection and mitigation of psychological late effects for CCS and their families.

Establishing a Standard Operating Procedure for Fertility Preservation in Adolescent and Young Adult Male Survivors of Childhood Cancers: Addressing a Gap in Care in the Republic of Ireland

Establishing a Standard Operating Procedure for Fertility Preservation in Adolescent and Young Adult Male Survivors of Childhood Cancers: Addressing a Gap in Care in the Republic of Ireland

Using mHealth Technology to Evaluate Daily Symptom Burden among Adult Survivors of Childhood Cancer: A Feasibility Study.

Cancer therapies predispose survivors to a high symptom burden. This study utilized mobile health (mHealth) technology to assess the feasibility of collecting daily symptoms from adult survivors of childhood cancer to evaluate symptom fluctuation and associations with future health-related quality-of-life (HRQOL). This prospective study used an mHealth platform to distribute a 20-item cancer-related symptom survey (5 consecutive days each month) and an HRQOL survey (the day after the symptom survey) over 3 consecutive months to participants from the Childhood Cancer Survivor Study. These surveys comprised a PROMIS-29 Profile and Neuro-QOL assessed HRQOL. Daily symptom burden was calculated by summing the severity (mild, moderate, or severe) of 20 symptoms. Univariate linear mixed-effects models were used to analyze total, person-to-person, day-to-day, and month-to-month variability for the burden of 20 individual symptoms. Multivariable linear regression was used to analyze the association between daily symptom burden in the first month and HRQOL in the third month, adjusted for covariates. Out of the 60 survivors invited, 41 participated in this study (68% enrollment rate); 83% reported their symptoms ≥3 times and 95% reported HRQOL in each study week across 3 months. Variability of daily symptom burden differed from person-to-person (74%), day-to-day (18%), and month-to-month (8%). Higher first-month symptom burden was associated with poorer HRQOL related to anxiety (regression coefficient: 6.56; 95% CI: 4.10-9.02), depression (6.32; 95% CI: 3.18-9.47), fatigue (7.93; 95% CI: 5.11-10.80), sleep (6.07; 95% CI: 3.43-8.70), pain (5.16; 95% CI: 2.11-8.22), and cognitive function (-6.89; 95% CI: -10.00 to -3.79) in the third month. Daily assessment revealed fluctuations in symptomology, and higher symptom burden was associated with poorer HRQOL in the future. Utilizing mHealth technology for daily symptom assessment improves our understanding of symptom dynamics and sources of variability.

Cisplatin induced alterations in nociceptor developmental trajectory elicits a TrkA dependent platinum-based chemotherapy induced neuropathic pain

Cisplatin-based chemotherapy is a common treatment for paediatric cancer. Unfortunately, cisplatin treatment causes neuropathic pain, a highly prevalent adverse health related complication in adult childhood cancer survivors. Due to minimal understanding of this condition, there are currently no condition tailored analgesics available. Here we investigated an alteration in nociceptor maturation that results in neuronal sensitisation and manifestation of cisplatin induced survivorship pain in a TrkA dependent manner. Cisplatin was administered (i.p. 0.1 mg/kg Postnatal day 14 and 16) to neonatal male and female Wistar rats and nociceptive behavioural assays were performed. In vitro studies utilised isolated neonatal dorsal root ganglia sensory neurons treated with cisplatin (5 μg/ml) to elucidate impact upon nociceptor activation and neurite growth, in combination with TrkA inhibition (GW441756 10 nM and 100 nM). Cisplatin treated male and female neonatal Wistar rats developed a delayed but lasting mechanical and heat hypersensitivity. Cisplatin administration led to increased TrkA expression in dorsal root ganglia sensory neurons. Nerve growth factor (NGF) induced TrkA activation led to sensory neuritogenesis and nociceptor sensitisation, which could be prevented through pharmacological TrkA inhibition (GW441756 either s.c. 100 nM or i.p. 2 mg/kg). Administration of TrkA antagonist suppressed cisplatin induced TRPV1 mediated nociceptor sensitisation and prevented cisplatin induced neuropathic pain. These studies provide greater understanding of the underlying mechanisms that cause cisplatin induced childhood cancer survivorship pain and allowing identification of potential therapeutic targets.

Unmet Reproductive Health Care Information Needs of Female Young Adult Survivors of Childhood Cancer: Oncology Providers' Perspectives.

This study aimed to characterize unmet reproductive health needs of female young adult survivors of childhood cancer (YASCC), as understood by oncology providers (N = 10) caring for this patient population. Providers completed brief online questionnaires and a one-time semi-structured interview. Descriptive statistics characterized quantitative data, and rapid qualitative analysis identified themes in interview data. In survey data, providers rated fertility as a top concern among YASCC. Qualitative data identified specific under-addressed reproductive and sexual health information needs for patients and also for their providers. The results provide preliminary knowledge to inform the development of behavioral interventions to address patients' unmet needs.

Associations between mitochondrial copy number, exercise capacity, physiologic cost of walking, and cardiac strain in young adult survivors of childhood cancer.

Childhood cancer survivors are at risk for cardiac dysfunction and impaired physical performance, though underlying cellular mechanisms are not well studied. In this cross-sectional study, we examined the association between peripheral blood mitochondrial DNA copy number (mtDNA-CN, a proxy for mitochondrial function) and markers of performance impairment and cardiac dysfunction. Whole-genome sequencing, validated by quantitative polymerase chain reaction, was used to estimate mtDNA-CN in 1720 adult survivors of childhood cancer (48.5% female; mean age = 30.7years, standard deviation (SD) = 9.0). Multivariable logistic regression was performed to evaluate the associations between mtDNA-CN and exercise intolerance, walking inefficiency, and abnormal global longitudinal strain (GLS), adjusting for treatment exposures, age, sex, and race and ethnicity. The prevalence of exercise intolerance, walking inefficiency, and abnormal GLS among survivors was 25.7%, 10.7%, and 31.7%, respectively. Each SD increase of mtDNA-CN was associated with decreased odds of abnormal GLS (adjusted odds ratio (OR) = 0.88, p = 0.04) but was not associated with exercise intolerance (OR = 1.02, p = 0.76) or walking inefficiency (OR = 1.06, p = 0.46). Alkylating agent exposure was associated with increased odds of exercise intolerance (OR = 2.25, p < 0.0001), walking inefficiency (OR = 2.37, p < 0.0001), and abnormal GLS (OR = 1.78, p = 0.0002). Increased mtDNA-CN is associated with decreased odds of abnormal cardiac function in childhood cancer survivors. These findings demonstrate a potential role for mtDNA-CN as a biomarker of early cardiac dysfunction in this population.

Feasibility, reproducibility, and accuracy of echocardiographic right ventricular systolic function assessments in childhood cancer survivors at risk for heart failure.

We sought to assess the feasibility, reproducibility, and accuracy of conventional and newer echocardiographic measures of right ventricular (RV) systolic function in adolescent and young adult childhood cancer survivors treated with anthracyclines. Echocardiography and cardiac magnetic resonance imaging (CMR) were acquired ≤60 days apart in prospectively recruited survivors and RV functional measures were quantitated by blinded observers. Repeat quantitation was performed in a subset to evaluate reproducibility. For each echocardiographic measure, Spearman correlations with CMR measures were calculated, and values in participants with CMR RV ejection fraction (RVEF) ≥48% and RVEF <48% were compared using two sample Wilcoxon rank-sum tests. Among 58 participants, mean age was 18.2 years (range 13.1-25.2) and five participants had CMR RVEF <48%. Intra- and inter-observer coefficients of variation were 8.2%-10.1% and 10.5%-12.0% for adjusted automated strain measures, and 5.2%-8.7% and 2.7% for 3D RVEF, respectively. No echocardiographic measures were significantly correlated with CMR RVEF; only tricuspid annular plane systolic excursion was correlated with CMR RV stroke volume (r=.392, p=.003). Participants with RV dysfunction had worse automated global longitudinal strain (-20.3% vs. -23.9%, p=.007) and free wall longitudinal strain (-23.7% vs. -26.7%, p=.09). Echocardiographic strain and 3D RV function measurements were feasible and reproducible in at-risk childhood cancer survivors. Although not associated with CMR RVEF in this population with predominantly normal RV function, automated strain measurements were more abnormal in participants with RV dysfunction, suggesting potential clinical utility of these measures.