Long-term health-related quality of life in young childhood cancer survivors and their parents.

PURPOSE: Few studies have investigated the health-related quality of life (HRQoL) of young childhood cancer survivors and their parents. This study describes parent and child cancer survivor HRQoL compared to population norms and identifies factors influencing child and parent HRQoL. METHODS: We recruited parents of survivors who were currently <16 years, and >5 years postdiagnosis. Parents reported on their child's HRQoL (Kidscreen-10), and their own HRQoL (EQ-5D-5L). Parents rated their resilience and fear of cancer recurrence and listed their child's cancer-related late effects. RESULTS: One hundred eighty-two parents of survivors (mean age = 12.4 years old and 9.7 years postdiagnosis) participated. Parent-reported child HRQoL was significantly lower than population norms (48.4 vs. 50.7, p < .009). Parents most commonly reported that their child experienced sadness and loneliness (18.1%). Experiencing more late effects and receiving treatments other than surgery were associated with worse child HRQoL. Parents' average HRQoL was high (0.90) and no different to population norms. However 38.5% of parents reported HRQoL that was clinically meaningfully different from perfect health, and parents experienced more problems with anxiety/depression (43.4%) than population norms (24.7%, p < .0001). Worse child HRQoL, lower parent resilience, and higher fear of recurrence was associated with worse parent HRQoL. CONCLUSIONS: Parents report that young survivors experience small but significant ongoing reductions in HRQoL. While overall mean levels of HRQoL were no different to population norms, a subset of parents reported HRQoL that was clinically meaningfully different from perfect health. Managing young survivors' late effects and improving parents' resilience through survivorship may improve HRQoL in long-term survivorship.

Improving management of fever in neutropenic children with cancer across multiple sites.

OBJECTIVE: To evaluate the effectiveness of a clinical pathway in achieving antibiotic administration in less than 60 minutes for children with cancer, presenting with fever and neutropenia. Secondary objectives were to determine association between time to antibiotics (TTA) and other variables including fever duration, location of care and intravenous access types. METHODS: Following introduction of the clinical pathway, we collected prospective data about management of all cases that did and did not use the pathway across multiple sites over 16 months. A follow-up audit was conducted after 12 months. RESULTS: We evaluated a total of 453 presentations. Use of the clinical pathway was significantly associated with achieving TTA in less than 60 minutes (RR 0.69, 95% CI 0.56-0.85, p = <0.001). Despite varying use of the pathway over time, the median time to antibiotics was achieved in both the initial study period (57 minutes) and sustained at follow-up (60 minutes). TTA was also associated with types of intravenous access device and location of care and with length of stay. We did not find any association between TTA and any other variables. CONCLUSION: Clinical pathways improve fever management in this patient cohort. Ongoing education and auditing to identify factors which impact processes of care are necessary.

Persistent Symptoms, Quality of Life, and Correlates with Health Self-Efficacy in Adolescent and Young Adult Survivors of Childhood Cancer.

Purpose: The numbers of adolescent and young adult (AYA) survivors of childhood cancer are exponentially growing. To ensure suitable services are available to meet the needs of this growing population, understanding the experience of late effects, quality of life, and potentially modifiable factors, such as self-efficacy, is required. Methods: AYA survivors of childhood cancer recruited through an After Cancer Therapy Service at a Children's Hospital rated their symptoms experience, quality of life, and self-efficacy using the Patient Reported Outcome Common Terminology Criteria for Adverse Events, Functional Assessment of Cancer Therapy-General (FACT-G), and Patient-Reported Outcomes Measurement Information System (PROMIS®), respectively. Descriptive statistics were used to characterize the sample. Quality-of-life scores were compared with population norms. Regression analyses were used to explore the relationships between symptom experience, quality of life, and self-efficacy. Results: Thirty participants (mean age 22 ± 4.4 years) reported an average of nine symptoms as persistently experienced at moderate or higher rated intensity among participants (standard deviation ±8.7; range: 0-32; interquartile range: 2-16); over half (n = 17, 56.7%) had finished treatment 10 or more years ago. Participants scored lower on the FACT-G Physical Well-being and Emotional Well-being, and higher on Social Well-being subscales than the general population. Around two-thirds of participants were confident in their ability to self-manage their health based on their health self-efficacy score. Bivariate linear regression identified a statistically significant increase in the overall quality of life with increased self-efficacy, adjusted for age and sex (0.60, 95% confidence interval [CI] 0.30-0.90, p < 0.01). Higher symptom burden was associated with a lower overall quality of life after adjusting for age and sex (-0.95, 95% CI: -1.35 to -0.54, p < 0.001). Conclusion: Young cancer survivors experience a substantial number of persistent symptoms related to their cancer treatment that may negatively impact aspects of their quality of life. Health self-efficacy is a potential target for future interventions.

Coronary artery disease surveillance among childhood, adolescent and young adult cancer survivors: A systematic review and recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

BACKGROUND: Coronary artery disease (CAD) is a concerning late outcome for cancer survivors. However, uniform surveillance guidelines are lacking. AIM: To harmonise international recommendations for CAD surveillance for survivors of childhood, adolescent and young adult (CAYA) cancers. METHODS: A systematic literature review was performed and evidence graded using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Eligibility included English language studies, a minimum of 20 off-therapy cancer survivors assessed for CAD, and 75% diagnosed prior to age 35 years. All study designs were included, and a multidisciplinary guideline panel formulated and graded recommendations. RESULTS: 32 of 522 identified articles met eligibility criteria. The prevalence of CAD ranged from 0 to 72% and was significantly increased compared to control populations. The risk of CAD was increased among survivors who received radiotherapy exposing the heart, especially at doses ≥15 Gy (moderate-quality evidence). The guideline panel agreed that healthcare providers and CAYA cancer survivors treated with radiotherapy exposing the heart should be counselled about the increased risk for premature CAD. While the evidence is insufficient to support primary screening, monitoring and early management of modifiable cardiovascular risk factors are recommended. Initiation and frequency of surveillance should be based on the intensity of treatment exposures, family history, and presence of co-morbidities but at least by age 40 years and at a minimum of every 5 years. All were strong recommendations. CONCLUSION: These systematically assessed and harmonised recommendations for CAD surveillance will inform care and guide research concerning this critical outcome for CAYA cancer survivors.

Addressing the barriers to optimal management of febrile neutropenia in children with cancer.

PURPOSE: Fever and associated neutropenia presentations are frequent occurrences for children with cancer. Prompt treatment is required to prevent adverse outcomes; however, delays are common. In Australia's vast landscape, presentations occur in both tertiary metropolitan sites and smaller regional sites. Management and experiences differ between sites. Our primary aim was to identify the barriers to optimal management of febrile neutropenia in children with cancer from patient/parent and clinician perspectives. METHODS: A mixed methods approach was used where quantitative data was supplemented by qualitative data. Data were prospectively collected from parents (n=81) and clinicians (n=42) about all children who presented with fever across multiple diverse hospital locations. A subset of parents (n=9) and clinicians (n=19) completed semi-structured interviews. RESULTS: Delays in assessment and treatment were reported by 31% of parents and up to 36% of clinicians. Four distinct time points where delays occurred were identified: 1) pre-presentation; 2) initial assessment; 3) blood collection and establishing intravenous access, and 4) preparation and administration of antibiotics. Although reasons for delay were diverse, they were primarily related to clinician's knowledge and awareness of fever management, and intravenous access device factors. Interventions were formulated to target these barriers and streamline processes. CONCLUSION: We identified multifactorial reasons for delays at different time points in care. Regional centres and families have unique needs which require considerations and tailored interventions. Ongoing education, monitoring compliance with initiation of practice changes and identifying and overcoming barriers as they arise are strategies for improving management of the febrile child with cancer.

Body composition, dietary intake and physical activity of young survivors of childhood cancer.

AIM: To describe the body composition, dietary intake and physical activity and of paediatric, adolescent and young adult childhood cancer survivors (CCS) and examine the factors that impact body composition after treatment. METHODS: This prospective cross-sectional study involved 74 subjects who were at least three years post treatment. Measurements included anthropometry, whole body potassium counting, air displacement plethysmography, and three day physical activity and diet diaries. RESULTS: The CCS had significantly reduced body cell mass index Z-scores compared to controls (p = 0.0001), with 59% considered undernourished. The CCS had a significantly higher percent fat (p = 0.002) than the controls, with 27% classified as obese. The intake of 60% of CCS met estimated energy requirements, but the CCS consumed high amount of energy from fat and low amount of energy from carbohydrates. A high percentage of CCS did not meet their dietary requirements for calcium (61%), magnesium (46%), folate (38%) and iodine (38%). The CCS group had a light active lifestyle with 64% spending more than 2 h daily on screen time. Receiving a bone marrow transplant (r = -0.27; p = 0.02) and physical activity level (r = 0.49; p = 0.0001) were significantly correlated with body cell mass index. CONCLUSIONS: This study demonstrates that increased fat mass and decreased body cell mass is a concern for CCS and that CCS have poor health behaviours including light active lifestyles, excessive screentime, high fat intake, and poor intake of essential nutrients. This study has highlighted that CCS are at risk of both obesity and undernutrition and that increasing body cell mass as well as decreasing fat mass should be a focus of energy balance interventions in survivorship. There is a need for parents and children undergoing treatment for cancer to be educated about diet quality and importance of daily physical activity to ensure healthy habits are established and maintained into survivorship.

Videophone support for an eight-year-old boy undergoing paediatric bone marrow transplantation.

We report the use of an Internet-based videophone to support a child undergoing bone marrow transplantation (BMT). Over the Christmas period, an eight-year-old boy with an underlying diagnosis of attention-deficit/hyperactivity disorder (ADHD) and a history of absconding and aggressive non-compliant behaviour was treated by BMT. We installed an Internet-based videophone in the patient's hospital room two days post-transplant. A second videophone was installed in the patient's home and used the existing home telephone line. In all, 14 videophone calls were made over a nine-day period. The videophone improved interfamily social and emotional support, and appeared to reduce some of the inherent anxiety and distress resulting from paediatric bone marrow transplantation.

Late magnetic resonance imaging features of leukoencephalopathy in children with central nervous system tumours following high-dose methotrexate and neuraxis radiation therapy.

High-dose methotrexate (HDMTX) is used increasingly to treat children with central nervous system (CNS) tumours. Although the neuro-imaging features of leukoencephalopathy associated with systemic or intrathecal methotrexate administered after cranial radiation have been well described, the extent to which the sequencing of HDMTX prior to cranial radiation in infants and children predisposes to late neuroradiological features of leukoencephalopathy is unknown. This report describes the National Cancer Institute (NCI) toxicity grade of leukoencephalopathy based on magnetic resonance imaging (MRI) findings in all patients who survived 4 or more years after treatment on an earlier phase II study. These patients, with newly diagnosed CNS embryonal tumours, were in the age range 3.5-14.2 years (median 6.9 years) at diagnosis, and received four courses of pre-irradiation combination chemotherapy, including HDMTX 8 g/m(2). Following completion of the 'up-front' phase II study, all patients received conventionally fractionated whole brain doses of 36-50.4 Gy. The radiation dose and treatment volumes were determined individually according to the primary tumour location and results of extent of disease evaluations. The most recent MRI brain scans, obtained 4.0-10.5 years (median 6.5 years) after radiation therapy and comprising a minimum of T1, T1 following gadolinium and T2 sequences, were reviewed centrally to assess the neuroradiological grade of leukoencephalopathy, based on the NCI Common Terminology Criteria for Adverse Events, v3.0. Grade I changes (mild increase in subarachnoid space, and/or mild ventriculomegaly, and/or small/focal T2 hyperintensities) were evident in 8 of the 12 patients and grade II changes (moderate increase in subarachnoid space and/or moderate ventriculomegaly, and/or focal T2 hyperintensities extending to the centrum ovale) were found in the remaining 4. In conclusion, treatment with multiple courses of HDMTX prior to 36-50.4 Gy cranial radiation did not result in moderate to severe MRI features of leukoencephalopathy. Future studies in paediatric neuro-oncology patients, involving HDMTX combined with prospective neuropsychological evaluations appear justified.

Body composition of children with cancer during treatment and in survivorship.

BACKGROUND: Malnutrition as assessed with the use of body-composition measurements is a poorly understood short- and long-term complication of childhood cancer. OBJECTIVES: We aimed to evaluate the body composition of 2 childhood cancer cohorts as follows: 1) children currently undergoing cancer treatment and 2) childhood cancer survivors. We also aimed to compare the prevalence of obesity and undernutrition between the cancer groups and investigate the impact of cancer type on body composition. DESIGN: Eighty-two children during the treatment of cancer and 53 childhood cancer survivors were involved in the study. Height, weight, body cell mass, percentage of fat, fat mass index, and fat-free mass index were assessed. Subjects were compared with age- and sex-matched healthy controls. RESULTS: The on-treatment group had a higher percentage of fat (P = 0.0001) and fat mass index (P = 0.0001) and a significantly lower body cell mass index (P = 0.0001) and fat-free mass index (P = 0.003) than did matched controls. The survivor group had a significantly higher percentage of fat (P = 0.03) and fat mass index (P = 0.04) and significantly lower body cell mass index (P = 0.0001) than did matched controls. The prevalence of undernutrition was high in both groups with 48% (95% CI: 36%, 60%) of the on-treatment group and 53% (95% CI: 40%, 66%) of the survivors considered undernourished. According to the percentage of fat cutoffs, significantly more on-treatment patients were obese (55%; 95% CI: 40%, 60%) than were survivors (26%; 95% CI: 14%, 38%) (P = 0.005). There were no statistically significant differences in body composition between cancer types in either the on-treatment or the survivor group. CONCLUSIONS: Overnutrition and undernutrition are major concerns in the short and long term for children with cancer. Children treated for cancer have increased fat mass and decreased body cell mass, which are evident during treatment and in survivorship. This trial was registered at http://www.ANZCTR.org.au as ACTRN12614001279617 and ACTRN12614001269628.

Exposure to diagnostic radiological procedures and the risk of childhood acute lymphoblastic leukemia.

BACKGROUND: Diagnostic irradiation of the mother during pregnancy increases the risk of childhood acute lymphoblastic leukemia (ALL). There is inconsistent evidence on associations between ALL and other parental or childhood diagnostic irradiation. The aim of this analysis is to investigate whether diagnostic X-rays of the mother before birth, of the father before conception, or of the child increased the risk of childhood ALL. METHODS: Data from 389 cases and 876 frequency-matched controls were analyzed using unconditional logistic regression, adjusting for study matching factors and potential confounders. A meta-analysis of our findings in relation to paternal X-rays before conception with the published findings of previous studies was also conducted. RESULTS: There was no evidence of an increased risk with maternal abdominal X-rays before the birth of the index child or with the child having any X-rays more than 6 months before the censoring date. The odds ratio (OR) for any paternal abdominal X-ray before conception was 1.17 [95% confidence interval (95% CI), 0.88-1.55], and 1.47 (95% CI, 0.98-2.21) for more than one X-ray. The OR for any paternal intravenous pyelogram before conception was 3.56 (95% CI, 1.59-7.98). The pooled OR for this study with previous studies of any paternal abdominal X-rays before conception was 1.17 (95% CI, 0.92-1.48). CONCLUSIONS: There was some evidence of an increased risk of ALL in the offspring if the father had more than one abdominal X-ray before conception or had ever had an intravenous pyelogram. IMPACT: We plan to repeat this analysis by using pooled data to improve precision.

Activity of postoperative carboplatin, etoposide, and high-dose methotrexate in pediatric CNS embryonal tumors: results of a phase II study in newly diagnosed children.

BACKGROUND: Chemotherapy is used as an alternative to irradiation or to minimize the irradiation exposure among infants with medulloblastoma or other CNS embryonal tumors. Adjuvant chemotherapy is commonly used in older children with high-risk medulloblastoma to improve survival or to allow a reduction in the craniospinal irradiation dose in standard-risk patients. However, optimal multimodality therapy, including the precise role of chemotherapy, has not been defined for these groups of patients. The objective of the present study is to assess the efficacy and toxicity of four postoperative courses of carboplatin, etoposide, and high-dose methotrexate in newly diagnosed children with medulloblastoma or other CNS embryonal tumors. PROCEDURE: Twenty-eight children, aged from 0.3 to 15.9 years (median, 6.2 years) with post-operative measurable residual CNS embryonal tumors were enrolled, comprising medulloblastoma (n = 19), supratentorial PNET (n = 7), and pineoblastoma (n = 2). Post-operative chemotherapy comprised carboplatin 350 mg/m(2) and etoposide 100 mg/m(2) on Days 1 & 2, and methotrexate 8 g/m(2) on Day 3, repeated at 21-28-day intervals for a total of four courses. Therapy following completion of the initial Phase II study was influenced by patient age and investigator preference. RESULTS: The combined complete response rate (CR, 7/19) and partial response rate (PR, 7/19) was 74% in patients with medulloblastoma, 89% for patients with PNET/pineoblastoma (CR, 2/9 and PR, 6/9), and for all patients it was 79%. Patients aged < 3 years at diagnosis had a combined PR and CR rate of 71% compared to 81% in patients aged > 3 years. Treatment was well tolerated although myelosuppression and thrombocytopenia were common. CONCLUSIONS: The combination of carboplatin, etoposide, and high-dose methotrexate is highly active in pediatric patients with CNS embryonal tumors.

Results of consecutive trials for children newly diagnosed with acute myeloid leukemia from the Australian and New Zealand Children's Cancer Study Group.

Despite improvements in the treatment of acute myeloid leukemia (AML), approximately 50% of children die of the disease. Clinical trials in adult patients with AML indicate that idarubicin may have superior efficacy when compared to daunorubicin in the remission-induction phases of chemotherapy. We conducted consecutive clinical trials in children with newly diagnosed AML in which daunorubicin (group 1, n = 102) or idarubicin (group 2, n = 160) was used during the remission-induction (RI) and the early consolidation phases of chemotherapy. Idarubicin was given at a dose of either 10 mg/m(2) (group 2A, n = 106) or 12 mg/m(2) (group 2B, n = 53). A high rate of RI was achieved for all groups (95% group 1, 90% group 2A, 94% group 2B). There were no significant differences in 5-year event-free survival (EFS) or in overall survival (OS) when the 3 groups were compared (group 1: EFS 50%, OS 56%; group 2A: EFS 50%, OS 60%; group 2B: EFS 34%, OS 50%). RI deaths resulting from treatment toxicity were low-2% for group 1 and 5% for group 2. More gastrointestinal, pulmonary, and renal toxicity but fewer infections were observed in patients receiving idarubicin (P <.001, P =.04, P =.03, respectively). Following RI chemotherapy, all patients received 3 to 4 more courses of identical chemotherapy and then underwent either autologous (n = 156) or an allogeneic bone marrow transplantation (BMT) (n = 35). OS was higher in allogeneic BMT patients than in autologous BMT patients (79% vs 63%; P =.23). We conclude that daunorubicin is as effective as idarubicin for remission-induction therapy for childhood AML and has reduced toxicity.