Long-term Outcomes Following Active Surveillance of Low-grade Prostate Cancer: A Population-based Study Using a Landmark Approach.

PURPOSE: Active surveillance is widely used to manage low-risk prostate cancer, but population-level long-term outcomes are limited. Our objective was to determine long-term population-level oncological outcomes in active surveillance patients. A secondary objective examined the active surveillance discontinuation rate. MATERIALS AND METHODS: In this retrospective, population-based study using linked administrative databases from Ontario, Canada, we identified low-grade prostate cancer patients managed with active surveillance or initial treatment between 2002-2014. The 10- and 15-year metastasis-free survival, overall survival, and cancer-specific survival were compared between active surveillance and initial treatment. A landmark of 24 months was selected for the primary analysis. Long-term outcomes were examined using multivariable proportional hazards models and a propensity-based approach. RESULTS: The cohort consisted of 21,282 low-grade prostate cancer patients with a median follow-up of 9.8 years. At 10-year follow-up the survival rate of remaining on active surveillance was 39%, metastasis-free survival was 94.2%, overall survival 88.7%, and cancer-specific survival 98.1%. In adjusted models active surveillance was associated with higher risk of metastasis (HR 1.34, 95%CI 1.15-1.57), overall mortality (HR 1.12, 95%CI 1.01-1.24), and prostate cancer-specific mortality (HR 1.66, 95%CI 1.15-2.39) compared to initial treatment. Survival analysis using 7,525 propensity-matched pairs was consistent with the primary analysis for metastasis-free survival, overall survival and cancer-specific survival. CONCLUSIONS: In this large population-based study of long-term outcomes in men with low-grade prostate cancer, active surveillance is associated with excellent long-term metastasis-free survival and overall survival. However, long-term cancer-specific survival was slightly inferior (1% worse at 10 years with active surveillance), and this must be balanced against known harms of overtreatment.

Plantar flexion, dorsiflexion, range of movement and hindfoot deviation are important determinants of foot function in children.

PURPOSE: Paediatric foot surgery is often performed to restore anatomical shape or range of movement (ROM). The purpose of this study was to determine how foot morphology and ROM are associated with foot function in children aged five to 16 years of age. METHODS: Participants included 89 patients with foot disorders and 58 healthy controls. In addition to measuring children's foot alignment and ankle ROM, children and parents completed the Oxford Ankle and Foot Questionnaire (OxAFQ). RESULTS: Mean age was 10.3 years for patients and 10.6 years for controls; 53 of 89 patients had clubfoot. All foot measurements and scores on the OxAFQ significantly differed (p < 0.001) between patients and controls. Patients and their parents significantly differed on the physical (p = 0.03) and emotional (p = 0.02) domains of the OxAFQ, with parents' ratings being lower than their children. Moderate correlations (r = 0.54 to 0.059; p < 0.001) were found between physical domain (reported by parents on the OxAFQ) and dorsiflexion-knee flexed, and foot- arc-of-movement. Moderate correlations were found between physical domain (reported by children on OxAFQ) and foot-arc-of-movement (r = 0.56; p < 0.001). Patients in the surgical group showed moderate correlations (r = 0.57;, p < 0.001) between physical domain (reported by children on OxAFQ) and plantar flexion, and foot arc-of-movement. The control group and the patients in non-surgical subgroup showed no significant correlations. CONCLUSION: Plantar flexion, arc of ankle ROM and hindfoot alignment impact foot function in children with foot deformities. Parents report significantly lower scores on the OxAFQ when judging foot functioning. LEVEL OF EVIDENCE: Level II. Prognostic Studies.

Long-term recovery of quality of life and physical function over three years in adult survivors of acute myeloid leukemia after intensive chemotherapy.

We previously described impairments in quality of life (QOL) and physical function among acute myeloid leukemia (AML) survivors between diagnosis and 1 year. The aim of the current study is to describe and compare to normative data QOL and physical function recovery over 3 years from diagnosis and treatment with intensive chemotherapy (IC). At assessments done at baseline (pre-IC) and at 11 time points over 3 years, QOL, fatigue, and 3 physical performance measures (PPMs; grip strength, 6-min walk test (6MWT), and timed chair stands) were collected. Long-term recovery was defined by reaching scores within the minimum clinically important difference of normative data. Global QOL recovery was seen in 79% at 1 year, 75% at 2 years, and 86% at 3 years. At 3 years, the QLQ-C30 subscales with the greatest recovery were physical and emotional functioning. For FACT-fatigue, recovery was seen in 68% at 1 year and 77% at 3 years. Recovery on PPMs was poorer on average, with only 17% on the 6MWT and 42% in grip strength returning to normal at 3 years. The vast majority of AML survivors after IC achieve recovery in QOL and fatigue by three years. However, recovery in physical performance remained blunted.

Effects of the community-based Wellspring Cancer Exercise Program on functional and psychosocial outcomes in cancer survivors.

PURPOSE: In this study, we examined the effects of a 30-week community-based exercise program on cancer-related fatigue, quality of life, and other health-related outcomes in a sample of adults with mixed cancer diagnoses. METHODS: This prospective cohort study looked at outcomes for participants involved in the Wellspring Cancer Exercise Program in southern Ontario. The program consisted of an initial phase of two supervised sessions weekly for 10 weeks and a transition phase of one supervised session weekly for the subsequent 20 weeks. Outcomes were measured at baseline and every 10 weeks throughout the intervention, as well as at 16 weeks after program completion. RESULTS: During a period of 13 months, 229 of the 355 cancer survivors who enrolled in the exercise program consented to participate in the study. Participants attended 71% of the supervised exercise sessions in the initial phase and 49% in the transition phase. From baseline to the end of the initial phase, significant improvements in cancer-related fatigue, 6-minute walk test, social well-being, systolic blood pressure, balance, and physical activity volume were observed. During the transition phase, health-related quality of life and emotional well-being improved significantly. CONCLUSIONS: The Wellspring Cancer Exercise Program is associated with clinically meaningful improvements in cancer-related fatigue and functional aerobic capacity. Several other aspects of well-being in cancer survivors also improved for participants in the program. Community-based cancer exercise programs such as the Wellspring Cancer Exercise Program can improve well-being for cancer survivors and can provide an effective option that enhances sustainability and accessibility to exercise services for this population.

Interventions for preventing cardiomyopathy due to anthracyclines: a Bayesian network meta-analysis.

Background: The relative efficacy of interventions for primary prevention of anthracycline-associated cardiotoxicity is unknown. Methods: We conducted a systematic review of randomized controlled trials for primary prevention of anthracycline-associated cardiotoxicity in adult cancer patients. We used hierarchal outcome definitions in the following order of priority: (1) composite of heart failure or decline in left ventricular ejection fraction, (2) decline in ejection fraction, or (3) heart failure. Data were analyzed using a Bayesian network meta-analysis with random effects. Results: A total of 16 trials reported cardiotoxicity as a dichotomous outcome among 1918 patients, evaluating dexrazoxane, angiotensin antagonists, beta-blockers, combination angiotensin antagonists and beta-blockers, statins, Co-enzyme Q-10, prenylamine, and N-acetylcysteine. Compared with control, dexrazoxane reduced cardiotoxicity with a pooled odds ratio (OR) of 0.26 (95% credible interval [CrI] 0.11-0.74) and had the highest probability (33%) of being most effective. No other agent was demonstrably better than placebo. Angiotensin antagonists had an 84% probability of being most effective in a sensitivity analysis excluding one outlying study (OR 0.06 [95% CrI 0.01- 0.24]). When the outcome was restricted to heart failure, dexrazoxane was associated with an OR of 0.12 (95% CrI 0.06-0.23) relative to control and had 58% probability of being most effective, while angiotensin antagonists had an OR of 0.18 (95% CrI 0.05-0.55). Available data suggested that dexrazoxane and angiotensin antagonists did not affect malignancy response rate or risk of death. Conclusion: Moderate quality data suggest that dexrazoxane, and low quality data suggest angiotensin antagonists, are likely to be effective for cardiotoxicity prevention.

Long-term health care costs for prostate cancer patients on androgen deprivation therapy.

BACKGROUND: Comparing relative costs for androgen deprivation therapy (adt) protocols in prostate cancer (pca) requires an examination of all health care resources, not only those specific to pca. The objective of the present study was to use administrative data to estimate total health care costs in a population-based cohort of pca patients. METHODS: Patients in Ontario with pca who started 90 days or more of adt at age 66 years or older during 1995-2005 were selected from cancer registry and health care administrative databases. We classified patients (n = 21,818) by regimen (medical castration, orchiectomy, anti-androgen monotherapy, medical castration with anti-androgen, orchiectomy with anti-androgen) and indication (neoadjuvant, adjuvant, metastatic disease, biochemical recurrence, primary nonmetastatic). Using nonparametric regression methods, with inverse probability weighting to adjust for censoring, and bootstrapping, we computed mean 1-year, 5-year, and 10-year longitudinal total direct medical costs (2009 Canadian dollars). RESULTS: Mean first-year costs were highest for metastatic disease, ranging from $24,400 for orchiectomy to $32,120 for anti-androgen monotherapy. Mean first-year costs for all other indications were less than $20,000. Mean 5-year and 10-year costs were lowest for neoadjuvant treatment: approximately $43,000 and $81,000 respectively, with differences of less than $4,000 between regimens. Annual costs were highest in the first year of adt. Orchiectomy was the least costly regimen for most time periods, but was limited to primary and metastatic indications. Outpatient drugs, including pharmacologic adt, accounted for 17%-65% of total first-year costs. CONCLUSIONS: Compared with combined therapies, the adt monotherapies, particularly orchiectomy when clinically feasible, are more economical. Our methods exemplified the use of algorithms to elucidate clinical information from administrative data. Our approach can be adapted for other cancers to expand the range of studies using Canadian administrative data.

A phase II exercise randomized controlled trial for patients with acute myeloid leukemia undergoing induction chemotherapy.

Curative treatment for acute myeloid leukemia (AML) involves induction chemotherapy (IC) which is associated with bed rest and toxicities, leading to worsening quality of life (QOL), fatigue, and fitness. Exercise during IC may ameliorate declines but has not been rigorously tested. We examined the efficacy of supervised exercise during IC on QOL, fatigue, and fitness. Eighty-three inpatients age 18-80 scheduled to receive IC for newly diagnosed or relapsed AML were randomized 2:1 (exercise intervention:control group). Study measures were completed at baseline, post-IC, and following the first cycle of consolidation. The intervention consisted of a supervised mixed-modality, moderate-intensity exercise program (4-5 days per week, 30-60min per session) throughout admission. Recruitment was good (56%), retention excellent (96%), and adherence was 54%. Global QOL improved similarly in both groups from baseline to post-IC (between-group difference 3.0 points, p=0.62). Fatigue improved in the exercise group from baseline to post-IC (potentially clinically important between-group difference of 3.6 points, p=0.23). Aerobic fitness, lower body strength, and grip strength improved in the exercise group (between-group differences p=0.005, p<0.001, p=0.03, respectively). Supervised exercise for patients with AML undergoing IC is feasible, safe, and appears effective at improving fitness and possibly fatigue. A larger trial is warranted.

Fetal skeletal dysplasias in a tertiary care center: radiology, pathology, and molecular analysis of 112 cases.

Fetal skeletal dysplasias are a heterogeneous group of rare genetic disorders, affecting approximately 2.4-4.5 of 10,000 births. We performed a retrospective review of the perinatal autopsies conducted between the years 2002-2011 at our center. The study population consisted of fetuses diagnosed with skeletal dysplasia with subsequent termination, stillbirth and live-born who died shortly after birth. Of the 2002 autopsies performed, 112 (5.6%) were diagnosed with skeletal dysplasia. These 112 cases encompassed 17 of 40 groups of Nosology 2010. The two most common Nosology groups were osteogenesis imperfecta [OI, 27/112 (24%)] and the fibroblast growth factor receptor type 3 (FGFR3) chondrodysplasias [27/112 (24%)]. The most common specific diagnoses were thanatophoric dysplasia (TD) type 1 [20 (17.9%)], and OI type 2 [20 (17.9%)]. The combined radiology, pathology, and genetic investigations and grouping the cases using Nosology 2010 resulted in a specific diagnosis in 96 of 112 cases.

Refinement of the symptom screening in pediatrics tool (SSPedi).

BACKGROUND: Objective was to evaluate and refine a new instrument for paediatric cancer symptom screening named the Symptom Screening in Pediatrics Tool (SSPedi). METHODS: Respondents were children 8-18 years of age undergoing active cancer treatment and parents of eligible children. Respondents completed SSPedi once and then responded to semi-structured questions. They rated how easy or difficult SSPedi was to complete. For items containing two concepts, we asked respondents whether concepts should remain together or be separated into two questions. We also asked about each item's importance and whether items were missing. Cognitive probing was conducted in children to evaluate their understanding of items and the response scale. After each group of 10 children and 10 parents, responses were reviewed to determine whether modifications were required. Recruitment ceased with the first group of 10 children in which modifications were not required. RESULTS: Thirty children and 20 parents were required to achieve a final version of SSPedi. Fifteen items remain in the final version; the score ranges from 0 to 60. CONCLUSIONS: Using opinions of children with cancer and parents of paediatric cancer patients, we successfully developed a symptom screening tool that is easy to complete, is understandable and demonstrates content validity.

Temporal lobe dysplasia: a characteristic sonographic finding in thanatophoric dysplasia.

OBJECTIVE: To determine the incidence of temporal lobe dysplasia (TLD) detected on prenatal ultrasound in thanatophoric dysplasia (TD) over an 11-year period in a tertiary referral center. METHODS: An 11-year retrospective review of perinatal autopsies from 2002 to 2013 was performed to identify cases of TD. The ultrasound images and corresponding reports of all TD cases were examined for the presence of TLD. The same set of images subsequently underwent a retrospective review by a perinatal radiologist with knowledge of the features of TLD to determine whether they could be identified. RESULTS: Thirty-one cases of TD underwent perinatal autopsy, and prenatal ultrasound imaging was available for review in 24 (77%). Mean gestational age at diagnosis of TD was 21.3 (range, 18-36) weeks. TLD was identified and reported in 6/24 (25%) cases; all six cases occurred after 2007. Retrospective interpretation of the ultrasound images identified features of TLD in 10 additional cases. In total, 16/24 (67%) cases displayed sonographic evidence of TLD. Temporal trends showed that TLD features were present in 50% (5/10) of all TD cases between 2002 and 2006 and in 79% (11/14) of those detected between 2007 and 2013. CONCLUSIONS: At present, the detection rate of TLD by ultrasound is low but may be increased by modified brain images that enhance visualization of the temporal lobes. Prenatal identification of TLD may help in the prenatal diagnosis of TD and thus provide more accurate prenatal counseling and guide molecular investigations to confirm the specific diagnosis of TD.

Do quality of life or physical function at diagnosis predict short-term outcomes during intensive chemotherapy in AML?

BACKGROUND: Intensive chemotherapy (IC) used to treat acute myeloid leukemia (AML) is associated with toxicity, particularly in older adults. Emerging data suggest that baseline quality of life (QOL) and physical function may predict outcomes in oncology, although data in AML are limited. We investigated the association between baseline QOL and physical function with short-term treatment outcomes in adults and elderly AML patients. MATERIALS AND METHODS: We conducted a prospective, longitudinal study of adults (age 18+) AML patients undergoing IC. Before starting IC, patients completed the European Organisation for the Research and Treatment of Cancer (EORTC) 30-item questionnaire (QLQ-C30) and Functional Assessment of Cancer Therapy Fatigue subscale (FACT-Fatigue) in addition to physical function tests (grip strength, timed chair stands, 2-min walk test). Outcomes included 60-day mortality, intensive care unit (ICU) admission and achievement of complete remission (CR). Logistic regression was carried out to evaluate each outcome. RESULTS: Of the 239 patients (median age 57.5 years), 56.7% were male and median Charlson comorbidity score was 0. Sixty-day mortality, ICU admission and CR occurred in 9 (3.7%), 15 (6.3%) and 167 (69.9%) patients, respectively. Using univariate regression, neither QOL nor physical function at presentation was predictive of 60-day mortality (all P > 0.05), whereas ICU admission (P < 0.001) and remission status at 30 days (P = 0.007) were. Fatigue (P = 0.004) and role functioning (P = 0.003) were predictors of ICU admission; QOL and physical function were not. A higher Charlson score predicted ICU admission (P = 0.01) and remission status (P = 0.002). The cytogenetic risk group was associated with achievement of CR (P = 0.02); QOL and physical function were not (all P > 0.05). Findings were similar when patients age 60+ were examined. Relationships between fatigue and role functioning with ICU admission deserve further exploration. CONCLUSIONS: Baseline QOL and physical function tests in this prospective study were not associated with short-term mortality, ICU admission or achievement of CR after the first cycle of chemotherapy.

Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D.

SUMMARY: Androgen deprivation therapy in 80 men was associated with declines in bone mineral density (BMD), which were greatest in the first year, and in the lumbar spine compared to controls. Vitamin D use was associated with improved BMD in the lumbar spine and in the first year. INTRODUCTION: Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased risk of fractures. Although loss of BMD appears to be greatest within the first year of starting ADT, there are few long-term studies of change in BMD, and risk factors for bone loss are not well-characterized. METHODS: Men aged 50+ with nonmetastatic prostate cancer starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Matched controls were men with prostate cancer not receiving ADT. Multivariable regression analysis examined predictors of BMD loss. RESULTS: Eighty ADT users and 80 controls were enrolled (mean age 69 years); 52.5 % had osteopenia and 8.1 % had osteoporosis at baseline. After 1 year, in adjusted models, ADT was associated with significant losses in lumbar spine BMD compared to controls (-2.57 %, p = 0.006), with a trend towards greater declines at the total hip (p = 0.09). BMD changes in years 2 and 3 were much smaller and not statistically different from controls. Use of vitamin D but not calcium was associated with improved BMD in the lumbar spine in year 1 (+6.19 %, p < 0.001) with smaller nonsignificant increases at other sites (+0.86 % femoral neck, +0.86 % total hip, p > 0.10) primarily in the first year. CONCLUSIONS: Loss of BMD associated with ADT is greatest at the lumbar spine and in the first year. Vitamin D but not calcium may be protective particularly in the first year of ADT use.

Immigrant patients with chronic hepatitis C and advanced fibrosis have a higher risk of hepatocellular carcinoma.

To explore the impact of the differences in baseline characteristics between immigrants with chronic hepatitis C (CHC) and native-born patients on the prognosis of advanced fibrosis. A retrospective cohort study was conducted in 318 patients (including 128 immigrants) with CHC and advanced fibrosis attending a tertiary referral clinic. Patients' medical records were reviewed to collect data describing immigrant status, baseline characteristics, and liver-related clinical outcomes. Kaplan-Meier (KM) analyses and Cox proportional-hazards regression analyses were performed to explore the differences between the two groups with respect to clinical outcomes. Relative to native-born patients, immigrant patients were older, more likely to be female, and more likely to be Asian. Immigrants were less likely to be heavy drinkers, heavy smokers, injection drug users, and more likely to have type 2 diabetes. KM analyses indicated that immigrant patients had a significantly higher risk of hepatocellular carcinoma (HCC) than Canadian-born patients (P = 0.005). Univariate Cox proportional-hazards analyses indicated that immigrant status (hazard ratio (HR) 2.22; P = 0.006), age (HR 1.07; P < 0.001), heavy drinking (HR 2.69; P = 0.001), heavy smoking (HR 2.03; P = 0.019), and type 2 diabetes (HR 2.06; P = 0.011) were significantly associated with the risk of HCC. Multivariable Cox proportional-hazards analyses showed that immigrant status was not an independent risk factor for HCC (HR 1.37; P = 0.318) after adjusting for age and type 2 diabetes. Older age and higher prevalence of type 2 diabetes accounted for the increased risk of HCC among immigrant patients with CHC and advanced fibrosis.

Older age is associated with similar quality of life and physical function compared to younger age during intensive chemotherapy for acute myeloid leukemia.

We examined the quality of life (QOL) and physical function over the first three cycles of intensive chemotherapy in 103 newly diagnosed younger (18-59 years, n=64) and older adults (age 60 or older, n=39) with acute myeloid leukemia. Both QOL and physical function were worse than normative data. QOL was fairly stable over time and similar in both age groups, whereas physical function generally improved over time, although the improvement was somewhat greater in younger than older adults. Compared to younger adults, older adults tolerate intensive chemotherapy quite well from QOL and physical function perspectives.

Levels of sex hormones have limited effect on cognition in older men with or without prostate cancer.

Androgen deprivation therapy is commonly used to treat prostate cancer, but by lowering testosterone levels it may affect cognitive function. However, the relationship between testosterone and cognition remains unclear. We examined the relationship between sex hormones (total testosterone, bioavailable testosterone, and estradiol) and cognition in a cross-sectional study of 198 older men (mean age 69.2 years, median education 16 years) with and without prostate cancer, none of who had started androgen deprivation therapy. We found relationships between total testosterone and two of four measures of working memory. Similar relationships were found in regression analyses adjusted for age and education with both total testosterone and estradiol. Neither hormone was related to other cognitive domains, nor was bioavailable testosterone level. Although cognitive function was not generally related to sex hormone levels in older men, there may be a weak association with working memory. These results may help guide future studies.

Utility and health-related quality of life in prostate cancer patients 12 months after radical prostatectomy or radiation therapy.

This study aims to examine and compare changes in quality of life after two common treatments for prostate cancer (PC), radical prostatectomy (RP) and radiation therapy (RT). Patients newly diagnosed with localized PC, scheduled to receive RP (n=68) or RT (n=66), completed three cancer/PC-specific psychometric instruments and three PC-specific utility instruments before treatment, and 2 and 12 months after treatment. We assessed the magnitude and time course of changes in psychometric and utility measures, and differences between treatments. The results showed that RP was associated with significant urinary and sexual dysfunction; RT caused bowel problems. Fatigue and pain were common to both. RP patients reported more problems with physical, role and social function. Utilities decreased significantly after both treatments. Effects were most severe 2 months post treatment, and then showed some recovery, but many endured for 1 year. After 1 year, 30-60% of patients had utility scores that were clinically significantly worse than at baseline. Secondary androgen deprivation therapy also significantly decreased psychometric and utility measures of quality of life. Many adverse symptoms reported 2 months after RP and RT endure for 1 year. Despite different symptom profiles, RP and RT result in similar utility decrements.

Individual and contextual factors associated with follow-up use of diabetes self-management education programmes: a multisite prospective analysis.

AIMS: Although a considerable body of research supports the efficacy of diabetes self-management education (DSME), these programmes are often challenged by high attrition rates. Little is known about factors influencing follow-up use of DSME services, thus the aim of this study was to identify these factors. METHODS: In this multisite prospective analysis, adults with Type 2 diabetes (n = 268) who attended one of two diabetes management centres (DMCs) were followed over a 1-year period from their initial visit. The influence of individual and contextual factors on the number of contacts with DMC providers was examined. Data were analysed within the context of the Health Behavioral Model of Health Services Utilization. RESULTS: In a multivariable negative binomial regression model, the number of contacts over 1 year was greater for those who were female, non-smokers, unemployed, self-referred to the DMC, lived closer to the DMC, had a lower body mass index, or had a longer known duration of diabetes. Follow-up use of services differed significantly between the two sites. Provider contacts were greater at the centre that offered flexible hours of services and a variety of optional educational modules. CONCLUSIONS: Healthcare professionals need to encourage ongoing use of DSME, particularly for individuals prone to lower follow-up use of these services. Providing services that are accessible, convenient, and can easily fit into patients' schedules may increase follow-up use. Further exploration into how operations and delivery of these services influence utilization patterns is strongly recommended.

Serial controlled N-of-1 trials of topical vitamin E as prophylaxis for chemotherapy-induced oral mucositis in paediatric patients.

The objectives were (1) to determine whether in children undergoing doxorubicin-containing chemotherapy, topical vitamin E decreases an objective measurement of oral mucositis compared to placebo, and (2) to assess the feasibility of an innovative trial design in paediatric cancer, combining N-of-1 trials using Bayesian meta-analysis. We conducted a series of N-of-1, double-blinded, randomised controlled trials in children > or = 6 years of age receiving repeated cycles of identical doxorubicin-containing chemotherapy. Each study cycle was followed by topical vitamin E (800 mg) or placebo. We enroled 16 children and 45 post chemotherapy cycles were randomised to vitamin E (N=22) or placebo (N=23). There was no difference in objective mucositis scores with a mean score of 0.2 with vitamin E and 0.3 with placebo. Topical vitamin E does not reduce doxorubicin-induced oral mucositis in children. The use of N-of-1 studies and Bayesian meta-analysis may facilitate the study of some therapies in paediatric oncology.