The impact of CNS-directed treatment on quality of life in childhood cancer survivors.

PURPOSE: Pediatric cancer survivors may have lower quality of life (QoL), but most research has assessed outcomes either in treatment or long-term survivorship. We focused on early survivorship (i.e., 3 and 5 years post-diagnosis), examining the impact of CNS-directed treatment on child QoL, as well as sex and age at diagnosis as potential moderators. METHODS: Families of children with cancer (ages 5-17) were recruited at diagnosis or relapse (N = 336). Survivors completed the PedsQL at 3 (n = 96) and 5 years (n = 108), along with mothers (101 and 105, respectively) and fathers (45 and 53, respectively). The impact of CNS treatment, sex, and age at diagnosis on child QoL was examined over both time since diagnosis and time since last treatment using mixed model analyses. RESULTS: Parent-report of the child's total QoL was in the normative range and stable between 3 and 5 years when examining time since diagnosis, while child reported QoL improved over time (p = 0.04). In terms of time since last treatment, mother and child both reported the child's QoL improved over time (p = 0.0002 and p = 0.0006, respectively). Based on parent-report, males with CNS-directed treatment had lower total QoL than females and males who did not receive CNS-directed treatment. Age at diagnosis did not moderate the impact of treatment type on total QoL. CONCLUSIONS: Quality of life (QoL) in early survivorship may be low among males who received CNS-directed treatment. However, this was only evident on parent-report. Interventions to improve child QoL should focus on male survivors who received CNS-directed treatment, as well as females regardless of treatment type.

Impact of central nervous system-directed treatment on competence and adjustment among children in early cancer survivorship.

BACKGROUND: Central nervous system (CNS)-directed treatments can cause long-term academic, social, and emotional difficulties for children with cancer. However, limited research has examined the emergence of problems longitudinally and has often stratified risk by diagnosis alone. Therefore, this study compared competence and adjustment in children, who did and did not receive CNS-directed treatment, over the first 3 years following a cancer diagnosis. PROCEDURE: Mothers, fathers, and children (ages 5-18 years at diagnosis) from 217 families reported on the child's competence (academic, social) and adjustment (anxious/depressed, withdrawn/depressed) near a new cancer diagnosis or relapse and 3 years later. Children were categorized into CNS-directed treatment (n = 112; including cranial radiation, intrathecal chemotherapy, and/or neurosurgery) and non-CNS-directed treatment (n = 105) groups. RESULTS: At enrollment, there were few differences in competence and emotional adjustment among children based on treatment or diagnostic group. At 3 years, mothers and fathers reported poorer social competence for the CNS-directed treatment group, and fathers reported poorer school competence for the CNS-directed treatment group. Over time, father ratings of social competence increased for the non-CNS-directed treatment group, but not the CNS-directed treatment group. While father ratings of academic competence declined for the CNS-directed treatment group, mother ratings declined the most for children diagnosed with a brain tumor. All children demonstrated higher anxious/depressed scores over time. CONCLUSIONS: CNS-directed treatment may be a valuable indicator to identify childhood cancer survivors at risk for poor competence during early survivorship. Follow-up screening and supportive services are recommended, as well as additional longitudinal research.

Impact of a Best Practice Prevention Bundle on Central Line-associated Bloodstream Infection (CLABSI) Rates and Outcomes in Pediatric Hematology, Oncology, and Hematopoietic Cell Transplantation Patients in Inpatient and Ambulatory Settings.

BACKGROUND: Pediatric hematology, oncology, and hematopoietic cell transplantation (HCT) patients are at increased risk for bloodstream infections. The authors sought to evaluate the influence of a standardized best practice central venous catheter (CVC) maintenance bundle on the burden of and risk factors for mucosal barrier injury (MBI) and non-MBI central line-associated bloodstream infections (CLABSIs) across a common inpatient and ambulatory continuum in this high-risk population. METHODS: A retrospective cohort study of patients with underlying malignancy, hematologic disorders, and HCT recipients with a CVC in place at the time of CLABSI diagnosis in both inpatient and ambulatory settings from January 1, 2012 to December 31, 2016. Descriptive, nonparametric statistics were used to describe patient characteristics and outcomes. Logistic regression analyses were applied to identify potential risk factors for inpatient versus ambulatory and MBI versus non-MBI CLABSI. RESULTS: During the 5-year period, 118 of 808 (14.6%) patients had 159 laboratory-confirmed CLABSIs for ambulatory and inpatient CLABSI rates of 0.27 CLABSI/1000 and 2.2 CLABSI/1000 CVC days, respectively. CLABSI occurred more frequently in hospitalized patients after HCT and with underlying leukemia, most frequently caused by Gram-negative bacteria. MBI CLABSI accounted for 42% of all CLABSI with a 3-fold higher risk in hospitalized patients. Having multiple CVC or a CVC that was not a port independently associated with higher CLABSI risk. CONCLUSIONS: In our cohort, non-MBI CLABSI continued to account for the majority of CLABSI. CVC type is independently associated with higher overall CLABSI risk. Further studies are needed to reliably define additional prevention strategies when CLABSI maintenance bundles elements are optimized in this high-risk population.

Growing up after childhood cancer: maturity and life satisfaction in young adulthood.

PURPOSE: Young individuals face a variety of developmental tasks as they mature into adulthood. For survivors of childhood cancer, growing up may be more difficult due to their illness and late effects from treatment. This study is the first to quantitatively examine perceptions of maturity and how these perceptions contribute to satisfaction with life among young adult survivors of childhood cancer. METHODS: Ninety survivors of childhood cancer (Mage = 29.8; 7-37 years post-diagnosis) were recruited to complete online surveys on how mature they felt relative to peers, their perceived maturity on three domains (financial, personal, social), and life satisfaction. RESULTS: Most survivors (62%; n = 56) felt they grew up faster than their peers, and over half (56%; n = 50) felt more mature. Perceived maturity was high on all three domains, but brain tumor survivors reported significantly lower maturity than other survivors (d = 0.76-1.11). All maturity domains were positively associated with life satisfaction (r = .49-.56). Hierarchical linear regressions indicated that 44% of the variance in life satisfaction was explained by perceptions of growing up slower (ß = - 1.08, p = .004) and marginally by greater perceived personal maturity (ß = 0.45, p = .061). CONCLUSIONS: Childhood cancer can influence development, with most survivors feeling that they grew up faster and were more mature than peers. Personal maturity was related to life satisfaction, with survivors of brain tumors or those who felt they grew up slower at greatest risk for lower life satisfaction. Future research and clinical practice should consider survivors' development and maturation across the life span to promote overall well-being.

Trajectories of health behaviors across early childhood cancer survivorship.

OBJECTIVE: The majority of childhood cancer survivors develop at least one late effect subsequent to treatment (eg, cardiovascular disease and obesity). Consistent engagement in recommended health behaviors may mitigate some of these conditions. Researchers have identified early survivorship as a teachable moment, yet few studies have examined positive health behaviors during this period. METHODS: Families of children with cancer (ages 5-17) were initially recruited following a diagnosis or relapse of cancer. Three years post diagnosis, survivors (n = 82, Mage  = 13.3, SD = 3.7) and their mothers (n = 103, Mage  = 41.1, SD = 7.6) completed a questionnaire assessing exercise, dietary, and sleep patterns among survivors. A follow-up assessment was conducted 2 years later. Mixed models tested change in health behavior over time. RESULTS: At 3- and 5-year post diagnosis, mother and self-report indicated that few survivors engaged in appropriate levels of low-intensity exercise, fruit/vegetable intake, and dairy consumption. However, most survivors engaged in recommended levels of high intensity exercise, fast food restriction, and sleep. Health behaviors remained stable over time, except for mother report of sleep duration, which decreased (b = -0.6, P < 0.001). Brain tumor diagnosis predicted a larger decrease in self-report of sleep duration compared with other diagnoses (P = 0.04). Income predicted fast food intake such that higher income was associated with decreased intake over time, whereas lower income was associated with increased intake (P = 0.04). CONCLUSIONS: During early survivorship, several health behaviors fell short of expectations for exercise and diet and did not improve upon reaching 5-year post diagnosis. Providers should evaluate survivors' health behaviors, including sleep, early and often, intervening when necessary.

Psychosexual development and satisfaction with timing of developmental milestones among adult survivors of childhood cancer.

OBJECTIVE: To extend the limited research on psychosexual development among childhood cancer survivors, by not only focusing on the prevalence and age of milestone attainment, but also survivors' attitudes toward the timing of reaching such milestones. METHODS: Adult survivors of childhood cancer (N = 90; Mage  = 29.8, SD = 5.2), recruited from a US pediatric institution, completed online surveys indicating whether they had reached 5 milestones of psychosexual development (ie, first kiss, first boy-/girlfriend, first physical intimacy, sexual debut, first time in love), age at attainment, and perceptions about the timing (ie, right time, wished it had happened earlier, wished they had waited). RESULTS: Almost all survivors had reached each milestone (≥90%), except for sexual debut (83.3%). Survivors reported their first kiss as the earliest milestone at age 14.6 (N = 82, 92%) and falling in love as the latest milestone at age 18.8 (N = 80; 90%). This timing did not differ by sex/cancer-specific factors. Most survivors (~60%) felt they reached each milestone at the right time. Compared with US normative data, both male and female survivors were less likely to have experienced their sexual debut and were approximately 1.5 years older at sexual debut. Nevertheless, 59% of survivors felt that this timing was right and 31% wished they had waited longer. CONCLUSIONS: This is the first study to demonstrate that although childhood cancer survivors may delay some aspects of psychosexual development, most are satisfied with this timing. Research and clinical practice should emphasize survivors' perceptions/satisfaction toward psychosexual development rather than focusing only on normative milestone attainment.

A multiyear quality improvement project to increase influenza vaccination in a pediatric oncology population undergoing active therapy.

BACKGROUND: In an effort to reduce morbidity and mortality from vaccine preventable influenza infection, national consensus guidelines recommend vaccination of patients who are immunocompromised as a result of receiving cancer therapy. Quality improvement (QI) processes are a proven method used to improve vaccination rates. PROCEDURE: We conducted a QI initiative aimed at increasing influenza vaccination in oncology patients undergoing active treatment. Primary drivers for the project focused on patient education, staff and provider education, and communication regarding vaccine-eligible patients. We performed a retrospective analysis of influenza infection among the vaccine-eligible population. This approach has validity at our institution because of the consistent follow-up and hospital admission pattern of cancer patients on active therapy such that nearly all follow-up care is delivered at our institution. RESULTS: We successfully achieved greater than 87% vaccination of eligible patients each vaccine season (September to March). During the recommended timeframe for delivering influenza vaccine between September and December of each vaccine season, we offered the vaccine to 100% of patients on active therapy and vaccinated >90%. Barriers to success, including vaccine refusals, increased late in the vaccine season. Influenza infection was documented in 0.5-7.3% of the vaccine-eligible group. CONCLUSION: A robust influenza vaccination program implemented using a standardized QI approach can sustain a high vaccination rate in a pediatric oncology population receiving active treatment. The influenza infection rate was under 10% in the vaccinated group.

Psychosexual development and satisfaction in long-term survivors of childhood cancer: Neurotoxic treatment intensity as a risk indicator.

BACKGROUND: Risk factors for impairment in psychosexual development and satisfaction among adult survivors of childhood cancer are poorly understood. The authors compared psychosexual outcomes between survivors and healthy controls, and tested whether at-risk survivors can be identified by 1) treatment neurotoxicity or 2) diagnosis. METHODS: A total of 144 young adult survivors of childhood cancer and 144 matched controls completed questionnaires regarding psychosexual development, sexual satisfaction, and satisfaction with relationship status. Survivors were aged 20 to 40 years and were 5 to 34 years after diagnosis. Using medical chart data, survivors were divided into non-neurotoxic (48 survivors), low-dose (36 survivors), and high-dose (58 survivors) neurotoxic treatment groups. RESULTS: Apart from having fewer lifetime sex partners, survivors did not appear to differ from controls. However, survivors of brain tumors and any survivor who received high-dose neurotoxic treatment reported the lowest rates of achieving milestones of psychosexual development, whereas sexual and relationship status satisfaction were found to be related to relationship status. Neurotoxic treatment intensity further distinguished between survivors of brain tumors with and without psychosexual impairment. CONCLUSIONS: The intensity of neurotoxic treatment may be a valuable indicator of risk for psychosexual impairment relative to diagnosis alone. Health care providers should assess romantic/sexual problems among survivors at risk and make referrals if needed. Cancer 2017;123:1869-1876. © 2017 American Cancer Society.

Family estimates of risk for neurocognitive late effects following pediatric cancer: From diagnosis through the first three years of survivorship.

BACKGROUND: Families often express a need for additional information about neurocognitive late effects (NCLE) after a pediatric cancer diagnosis. Therefore, we examined: (i) differences in parent, child, and oncologist estimates of risk for NCLE; (ii) whether the estimates of parents and/or children change over time; and (iii) whether estimates are different for children treated with central nervous system (CNS) directed therapies. PROCEDURE: Mothers, fathers, and children (initial age: 5-17, self-report: >10) from 258 families reported their perceived likelihood of the child developing "thinking/learning problems" on a visual analog scale (0-100%) at 2 months (T1), 1 year (T2), and 3 years (T3) following cancer diagnosis/relapse. Oncologists estimated the likelihood of NCLE at T1. Children were separated into groups based on CNS-directed treatment (n = 137; neurosurgery, intrathecal chemotherapy, and/or craniospinal radiation) or no CNS treatment. RESULTS: Mother, father, and child estimates of risk for NCLE were similar to oncologists and to one another around diagnosis (T1). Although there were no significant mean differences, a considerable subset of family members either underestimated their child's risk for NCLE (>40%) or overestimated the risk for NCLE (20%) in comparison to oncologists. At T2 and T3, the estimates of mothers were significantly higher than children. Linear growth curves indicated that mothers' estimates for children with CNS-directed treatment significantly increased throughout the first 3 years of survivorship. CONCLUSIONS: Considering that accurate understanding of NCLE is essential to seeking appropriate assessment and intervention, healthcare providers should focus on implementing family-based education early in treatment and throughout survivorship care.

Body issues, sexual satisfaction, and relationship status satisfaction in long-term childhood cancer survivors and healthy controls.

OBJECTIVE: Research on body image and sexual satisfaction after adult onset cancer has shown significant and lasting impairments regarding survivors' sexuality and romantic relationships. However, knowledge about these topics and their associations in adult survivors of childhood cancer is largely lacking. METHODS: Participants completed web-based questionnaires concerning body image, body dissociation, sexual satisfaction, and relationship status satisfaction (i.e., satisfaction with either being in a relationship or being single). Survivors (n = 87) and controls (n = 87) were matched on age and gender, with a mean age of 27 years (range: 20-40). Survivors were most often diagnosed with leukemia (46%), at an average of 16 years prior to study participation (range: 6-33 years). RESULTS: Similar numbers of survivors and controls were single (n = 24/31), in a committed relationship (n = 33/23), or married (n = 30/33). Survivors and controls reported comparable levels of body image, body dissociation, sexual experiences, and sexual and status satisfaction (d = 0.15-0.28). Higher status satisfaction was associated with being in a relationship (compared with being single, ß = 0.439), more positive body image (ß = 0.196), and higher sexual satisfaction (ß = 0.200). CONCLUSIONS: Adult survivors of childhood cancer were comparable to healthy peers regarding views of their bodies and psychosexual development, which was unexpected. Independent of whether people experienced cancer or not, their status satisfaction was associated with their relationship status, body image, and sexual satisfaction. Future research should explore why sexual and body problems are identified after adult onset cancer, whereas this seems to be less of a problem in childhood cancer survivors.

Clinical outcomes and efficacy of stereotactic body radiation therapy in children, adolescents, and young adults with metastatic solid tumors.

OBJECTIVE: The objective of this study is to report disease outcomes and toxicity with the use of stereotactic body radiation therapy (SBRT) in the treatment of pediatric metastatic disease. METHODS: All pediatric and adolescent young adult (AYA) patients' who received SBRT were included between the years 2000 and 2020. Study endpoints included local control (LC), progression-free survival (PFS), overall survival (OS), cumulative incidence (CI) of death or local failure and toxicity. The end points with respect to survival and LC were calculated using the Kaplan-Meier estimate. The cumulative incidence of local failure was calculated using death as a competing risk. RESULTS: 16 patients with 36 lesions irradiated met inclusion criteria and formed the study cohort. The median OS and PFS for the entire cohort were 17 months and 15.7 months, respectively. The 1 year OS for the entire cohort was 75%. The 6- and 12 month local control was 85 and 78%, respectively. There were no local failures in irradiated lesions for patients who received a BED10≥100 Gy. Patients who were treated with SBRT who had ≤5 metastatic lesions at first recurrence had a superior 1 year OS of 100 vs 50% for those with >5 lesions. One patient (6.3%) experienced a Grade 3 central nervous system toxicity. CONCLUSION: LC was excellent with SBRT delivered to metastatic disease, particularly for lesions receiving a BED10≥100 Gy. High-grade toxicity was rare in our patient population. Patients with five or fewer metastatic sites have a significantly better OS compared to >5 sites. ADVANCES IN KNOWLEDGE: This study demonstrates that SBRT is safe and efficacious in the treatment of pediatric oligometastatic disease.

Romantic Relationships and Physical Intimacy Among Survivors of Childhood Cancer.

Purpose: Childhood cancer survivors are at risk for impaired psychosocial functioning, but limited research has focused on psychosexual outcomes in young adulthood. This qualitative study examined the perceived impact of childhood cancer on adult survivors' romantic relationships and sexual/physical intimacy. Methods: Phone interviews were completed with adult survivors of childhood cancer, exploring the impact of cancer on (1) romantic relationships and (2) sexual/physical intimacy. Verbatim transcripts were coded using thematic content analysis until saturation was confirmed (n = 40). Results: Survivors in this study (n = 40) were 23-42 years old (M = 29.8; 63% female) and 10-37 years postdiagnosis (M = 18.4). Regarding romantic relationships, 60% of participants reported a negative impact, while 55% of participants reported positive effects; ∼25% of participants reported no impact of childhood cancer on adult romantic relationships. Negative themes included fertility-related concerns, physical effects (e.g., self-consciousness), feeling emotionally guarded, and delayed dating. Positive themes were creating new perspectives, increased maturity, and stronger bonds with partners. Forty percent of survivors in this study perceived having fewer partners than peers. Regarding sexual/physical intimacy, 68% of participants reported a negative impact (themes: body image, fertility-related concerns, sexual/physical dysfunction), while 33% of participants reported no effects. Conclusions: This study demonstrates both positive and negative effects of childhood cancer on adult survivors' romantic relationships, whereas effects on physical intimacy were predominantly negative. Further research is needed to inform effective psychosexual interventions, and health care providers should routinely address these topics in survivorship care.

Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "Head Start" III: a multi-institutional, prospective clinical trial.

BACKGROUND: "Head Start" III, was a prospective clinical trial using intensive induction followed by myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) to either avoid or reduce the dose/volume of irradiation in young children with medulloblastoma. METHODS: Following surgery, patients received 5 cycles of induction followed by myeloablative chemotherapy using carboplatin, thiotepa, and etoposide with AuHCR. Irradiation was reserved for children >6 years old at diagnosis or with residual tumor post-induction. RESULTS: Between 2003 and 2009, 92 children <10 years old with medulloblastoma were enrolled. Five-year event-free survival (EFS) and overall survival (OS) rates (±SE) were 46 ±â€…5% and 62 ±â€…5% for all patients, 61 ±â€…8% and 77 ±â€…7% for localized medulloblastoma, and 35 ±â€…7% and 52 ±â€…7% for disseminated patients. Nodular/desmoplastic (ND) medulloblastoma patients had 5-year EFS and OS (±SE) rates of 89 ±â€…6% and 89 ±â€…6% compared with 26 ±â€…6% and 53 ±â€…7% for classic and 38 ±â€…13% and 46 ±â€…14% for large-cell/anaplastic (LCA) medulloblastoma, respectively. In multivariate Cox regression analysis, histology was the only significant independent predictor of EFS after adjusting for stage, extent of resection, regimen, age, and sex (P <0.0001). Five-year irradiation-free EFS was 78 ±â€…8% for ND and 21 ±â€…5% for classic/LCA medulloblastoma patients. Myelosuppression was the most common toxicity, with 2 toxic deaths. Twenty-four survivors completed neurocognitive evaluation at a mean of 4.9 years post-diagnosis. IQ and memory scores were within average range overall, whereas processing speed and adaptive functioning were low-average. CONCLUSION: We report excellent survival and preservation of mean IQ and memory for young children with ND medulloblastoma using high-dose chemotherapy, with most patients surviving without irradiation.

A multi-institutional experience in pediatric high-grade glioma.

INTRODUCTION: Pediatric high-grade gliomas are rare tumors with poor outcomes and incompletely defined management. We conducted a multi-institutional retrospective study to evaluate association of clinical, pathologic, and treatment characteristics with outcomes. MATERIALS AND METHODS: Fifty-one patients treated from 1984 to 2008 at the Ohio State University or University of Michigan were included. Histologic subgroups were compared. Log-rank and stepwise Cox proportional hazard modeling were used to analyze progression-free survival (PFS) and overall survival (OS) within the whole group, grade III subgroup, grade IV subgroup, and sub-total resection/biopsy subgroup. RESULTS: Median OS was 27.6 months. Grade III histology, complete tumor resection, and cerebral tumor location correlated with improved PFS and OS. Temozolomide use and chemotherapy after radiotherapy or chemoradiation (CRT) were associated with better PFS while seizure at presentation was associated with better OS. In multivariate analysis, complete resection and chemotherapy following radiotherapy or CRT were independent predictors for improved PFS and OS. For grade III and IV subgroups, complete resection was associated with improved OS (grade III) and seizure presentation was associated with improved OS (grade IV). In the incompletely resection subgroup, temozolomide use and concurrent CRT independently correlated with improved PFS, while higher radiation dose (≥59.4 Gy) and adjuvant chemotherapy were independently associated with improved OS. DISCUSSION: Total resection and receiving chemotherapy adjuvant to radiation or CRT are most closely associated with improved PFS and OS. For higher risk incompletely resected patients, temozolomide use and treatment intensification with concurrent CRT, adjuvant chemotherapy, and higher radiation dose were associated with improved outcomes.

Coincidence FDG-PET in the evaluation of Langerhans' cell histiocytosis: preliminary findings.

BACKGROUND: Bone involvement in Langerhans' cell histiocytosis (LCH) is common. Both bone scintigraphy and plain films are used to identify osseous lesions, but lack specificity for disease activity and response to therapy. FDG-PET is a sensitive technique for identifying bone lesions when histiocytes are present. OBJECTIVE. To describe the potential of coincidence FDG-PET (cFDG-PET) for identification of active bone lesions in LCH and to determine whether it can provide more specific information regarding lesional response to therapy than bone scintigraphy or radiography. MATERIALS AND METHODS: The clinical data and imaging findings of three patients with osseous lesions of LCH were retrospectively reviewed. RESULTS: cFDG-PET identified all active LCH osseous lesions in these patients, differentiated active from healed lesions, and demonstrated normalization of uptake in a treated lesion earlier than bone scintigraphy and radiography. CONCLUSION: cFDG-PET appears to have greater specificity than bone scintigraphy and radiography for the identification of active osseous lesions in LCH. It also may predict response to treatment earlier than conventional techniques. Its use in the evaluation of LCH warrants further study.