This document proposes a study designed to investigate the association between executive function abilities and social anxiety in a group of adolescent survivors of Acute Lymphocytic Leukemia (ALL) who were treated with chemotherapy for central nervous system prophylaxis. The proposed study is also designed to evaluate a possible interaction effect between executive function abilities and social skills in their impact on social anxiety in this population. The report provides detailed background information describing ALL and available treatments for the disease. It also reviews the literature on both acute and late effects of chemotherapy, with particular attention placed on understanding both neurocognitive and psychosocial effects in the context of adolescent development. The proposed project involves collecting parent and teacher reports to measure the constructs of Executive Function and Social Skills. Parent measures may be completed in English or Spanish. Self-reports of Social Anxiety symptoms in the adolescent survivor sample will also be collected. Simultaneous regression analyses will be used to analyze the influence of executive function abilities on social anxiety. Sequential multiple regression analyses will then be conducted to check for differences in the magnitude of the relationship between executive function abilities and social anxiety with varying levels of social skills. Significant results would inform the development of targeted interventions. For example, if it is determined that executive function abilities are indeed associated with social anxiety symptoms, existing programs focused on neurocognitive remediation could begin to monitor participants for anxiety and provide preventative therapeutic intervention. Additionally, if social skills is confirmed as a moderator, evidence-based interventions targeting the development of social skills in the survivor population would be warranted as well. / text

Evidence from the pediatric traumatic brain injury and pediatric brain tumor populations suggests that positive family functioning serves as a protective factor for neurocognitive outcomes of children who survive these conditions. However, no research has been found that examines whether positive family functioning similarly moderates the effects of CNS-directed chemotherapy on the neurocognitive functioning of survivors of pediatric ALL. The purpose of this study is to examine the effect of family functioning upon neurocognitive outcome among survivors of pediatric ALL treated with chemotherapy. Based upon a multidimensional model of attention and Anderson’s model of executive function (EF), four subcomponents of attention (selective, divided, sustained, and shifting) and four subcomponents of EF (working memory, planning, inhibition, and processing speed) will be examined. Sequential, or hierarchical, multiple regression analyses will be conducted to examine the relationship between family functioning and neurocognitive functioning among survivors of pediatric ALL as well as a comparison group of healthy children. Data for the ALL group and the comparison group will be examined using separate analyses, with demographic and treatment-related variables entered first, followed by a family functioning variable. For the ALL group, family functioning is expected to explain a significant amount of variance in neurocognitive outcome, even after controlling for demographic and treatment-related variables. It is expected that this relationship will not be found for the comparison group. If so, this would have important implications for the survivors and their families. For example, survivors from families with lower levels of functioning could be identified early through screening measures and their families could receive targeted interventions aimed at improving family functioning and thus survivor outcomes. / text

Background: Growing numbers of patients with cancer are surviving following treatment with pelvic radiotherapy. Eighty per cent will experience acute gastrointestinal (GI) toxicity during treatment and 50% will subsequently have a change in their bowel habit which will affect their quality of life. The main project in this thesis aims to determine whether delivery of a gastrointestinal bundle of care will decrease GI acute toxicity and late effects of pelvic chemoradiotherapy. Additional work in the thesis evaluated the newer technique of Volumetric Modulated Arc Therapy (VMAT) which delivers decreased dose to the organs at risk on planning scans. We aimed to determine outcomes of this technique in terms of patient-reported acute toxicity and late effects. There is no internationally accepted patient reported outcome measure to capture this toxicity data and this issue was addressed using Rasch analysis in a third project. Methods: A randomised controlled trial was performed. Patients who were scheduled to undergo potentially curative chemoradiotherapy for cervix and bladder cancers were recruited and randomised. The treatment group received dietetic input and if they developed lower GI symptoms they underwent investigations and treatment for bile acid malabsorption, small bowel bacterial overgrowth and lactose intolerance. The control group received standard care. Patients who were to undergo VMAT to treat gynaecological malignancy completed patient-reported outcomes at baseline, end of treatment and one year. The rates of patient-reported toxicity were compared with those of a historical cohort and were correlated with the volume of small bowel which was irradiated. Thirdly the technique of Rasch analysis was used to evaluate the Common Terminology Criteria for Adverse Events derived patient reported outcome to measure pelvic toxicity of gynaecological cancer treatments. Results: It was feasible and acceptable to deliver a GI care bundle to patients undergoing chemotherapy and pelvic radiotherapy. All patients' data were available for analysis for the primary outcome and 29 patients' data were available at the 1 year time point. GI toxicity at 6 weeks was predicted by the trial group, suggesting that the intervention benefited the patients in terms of GI toxicity at 6 weeks. It is not yet clear whether this benefit is maintained at the 1 year time point. The frequencies of acute and late GI toxicity reported by patients undergoing VMAT were similar to that of a historical cohort who received conformal therapy. There was not a strong association between the volume of small bowel which was irradiated and the toxicity which was reported suggesting that other factors are involved in the development of toxicity. Rasch analysis of the pelvic symptom questionnaire demonstrated the main issue to be response dependency. When this was accounted for by grouping items into sub-tests the questionnaire could be made to be unidimensional and showed high reliability in a symptomatic population. Conclusion: GI intervention holds promise as a measure to reduce the acute toxicity and late effects of pelvic radiotherapy. Although newer radiotherapy techniques appear to decrease the dose delivered to the small bowel this does not translate to a reduction in patient-reported toxicity. The measurement of toxicity is complex and patient-reported outcome measures should be developed with techniques such as Rasch analysis to ensure meaningful data is available to guide further developments to reduce GI toxicity secondary to pelvic radiotherapy.

Objectives: To describe utilization of specialised prenatal care by high-risk survivors and evaluate echocardiogram use in echocardiogram-need survivors, as per survivorship guideline recommendations. Methods: Retrospective population-based matched survivor:control study utilizing Ontario health administrative data. Survivors were classified as high-risk/low-risk for obstetrical outcomes, and as echocardiogram-need (yes/no) for echocardiogram outcomes. Associations were tested using logistic regression. Results: 11% (n=363) of 3,204 pregnant survivors were classified as high-risk. Over 90% received specialized prenatal care. Living in a rural area was associated with lower use. (AOR 0.51; 95% CI 0.44-0.59). Since 2003, 32% (560/1,737) of survivors had an echocardiogram-need. Only 14% (77/560) had ≥1 echocardiogram, this was not associated with rurality nor neighbourhood income quintile. Conclusions: Although the majority of high-risk survivors receive specialized prenatal care, geographic inequality in care persists. Despite survivorship guidelines, >85% of echocardiogram-need pregnant survivors do not have an echocardiogram performed; future work should address this gap in care.

Objectives: To describe utilization of specialised prenatal care by high-risk survivors and evaluate echocardiogram use in echocardiogram-need survivors, as per survivorship guideline recommendations. Methods: Retrospective population-based matched survivor:control study utilizing Ontario health administrative data. Survivors were classified as high-risk/low-risk for obstetrical outcomes, and as echocardiogram-need (yes/no) for echocardiogram outcomes. Associations were tested using logistic regression. Results: 11% (n=363) of 3,204 pregnant survivors were classified as high-risk. Over 90% received specialized prenatal care. Living in a rural area was associated with lower use. (AOR 0.51; 95% CI 0.44-0.59). Since 2003, 32% (560/1,737) of survivors had an echocardiogram-need. Only 14% (77/560) had ≥1 echocardiogram, this was not associated with rurality nor neighbourhood income quintile. Conclusions: Although the majority of high-risk survivors receive specialized prenatal care, geographic inequality in care persists. Despite survivorship guidelines, >85% of echocardiogram-need pregnant survivors do not have an echocardiogram performed; future work should address this gap in care.

No description available.

Radiotherapy has been shown to increase the subsequent risk of heart disease among survivors of breast cancer, but little is known about factors, other than the dose of radiation delivered to the heart, which determine the magnitude of the risk. In addition, survivors of teenage and young adult cancer are internationally acknowledged as an understudied population, and limited information is available on their late health risks. This thesis sought to utilise the largest observational datasets available to date for these populations: the Collaborative Group on Observational Studies of Breast Cancer Survivors and the Teenage and Young Adult Cancer Survivor Study. These were used to firstly characterise the radiation-related risks of heart disease and lung cancer, and secondly to provide an overview of the long-term risk of heart disease for the entire spectrum of cancers diagnosed in teenagers and young adults aged 15 to 39. Initially, a methodology study and systematic review demonstrated that selection effects and other biases can be very problematic during analyses of observational cohorts, particularly when using a radiotherapy comparison. However, in the case of heart disease and lung cancer, one can take advantage of the breast being a paired organ and use a laterality comparison, particularly when laterality played little effect in treatment selection. This comparison was used throughout the analyses of breast cancer patients. This thesis demonstrated that adjuvant radiotherapy for breast cancer significantly increased the risk of heart disease among women with left-sided breast cancer and those patients with ipsilateral lung cancer. Interestingly, younger women were at the highest risk of heart disease, and a progressive proportional decrease in risk with increasing age at diagnosis was found, which has not been shown before. It also suggested that radiotherapy and chemotherapy combined may further increase the risk of heart disease among breast cancer patients. Survivors of teenage and young adult cancer, particularly Hodgkin lymphoma, were at a significantly raised cardiac mortality risk compared to the matched general population. The findings of this thesis provide evidence to support continued follow-up for cancer patients, as survivors were found to be at a substantial risk into the second or third decade after treatment. It has permitted the detection of groups of individuals at particularly increased risks, for example younger patients and survivors of Hodgkin lymphoma diagnosed in teenagers and young adults, for whom closer monitoring for late effects or measures to reduce the risk, such as adaptations to treatment, may be appropriate. Finally, evidence was also presented to support the development of clinical follow-up guidelines specifically for survivors of teenage and young adult cancer.

No description available.

Prostate cancer is the most common cancer among Canadian men. The standard treatment in high-risk category is radical radiation, with androgen suppression treatment (AST). Significant disease progression is reported despite this approach. Radiation dose escalation has been shown to improve disease-free survival; however, it results in higher toxicities. Hypofractionated radiation schedules (larger dose each fraction in shorter overall treatment time) are expected to deliver higher biological doses. A hypofractionated scheme was used in this study to escalate radiation doses with AST. Treatment was well tolerated acutely. Early results of self-administered quality of life reported by patients shows a decrease in QOL which is comparable to other treatment schedules. Significant positional variation of the prostate was observed during treatment. Therefore, we suggest daily target verification to avoid a target miss. Initial late effects are reasonable and early treatment outcomes are promising. Longer follow-up is required for full outcomes assessments.

In Australia, up to 80% of individuals diagnosed with childhood cancer are now expected to survive for more than five years after their initial diagnosis. However, survivors of childhood cancer are at risk of developing late sequelae as a consequence of therapies received during childhood. The aim of this study was to determine the incidence of selected late sequelae in a cohort of Australian childhood cancer survivors and identify treatment and genetic factors that may modify the risk of late sequelae in survivors. Our study included 1150 individuals treated for childhood cancer at the Sydney Children??s Hospital between 1962 and 1999, who had remained in remission >3 years and were confirmed to be alive. Rates of mortality and second cancers among survivors were compared against population rates to determine standardised mortality and incidence ratios. Survivors completed a questionnaire on the incidence of adverse health conditions and provided a buccal specimen. Real time PCR was used to detect polymorphisms in genes involved in drug detoxification and transport. Rates of mortality and secondary cancers were found to be 7.5-fold (95%CI 5.4-10.1) and 4.9-fold (95%CI 2.9-8.0) higher among survivors of childhood cancer relative to the general population, respectively, with the highest risks observed for those survivors previously treated for Hodgkin??s disease. Over 60% of survivors reported at least one cardiopulmonary, endocrine or sensory-motor condition following diagnosis of childhood cancer; the most frequently observed conditions included growth hormone deficiency, hypothyroidism, and hypertension. Late sequelae were most frequently reported by females and survivors of brain tumours. Genetic investigations showed that an increased risk of growth hormone deficiency was associated with homozygosity for the GSTM1 null polymorphism, while no gene associations were observed to influence the risk of second cancers among survivors. Our study demonstrates that survivors of childhood cancer are at risk of developing a variety of health conditions as a result of anti-cancer therapies received during childhood. Determining risk factors for late sequelae based on therapy type, lifestyle and genetic predisposition will enable the optimisation of treatment protocols and promote the future well-being of childhood cancer survivors.