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1.
J Adolesc Young Adult Oncol ; 10(2): 202-208, 2021 04.
Article in English | MEDLINE | ID: mdl-32856982

ABSTRACT

Purpose: While central nervous system (CNS) tumors account for only 10% of adolescent and young adult (AYA) cancers, they are the leading cause of cancer death in this age group. Using national data for Australia, we describe the presentation, treatment, and survival for AYAs diagnosed with CNS tumors. Methods: A population-based study of 15-24 year-olds diagnosed with CNS tumors (low- and high-grade glioma [LGG, HGG], medulloblastoma [MB], primitive neuroectodermal tumors [PNET], ependymoma [EP]) or other (e.g., low-grade neuronal tumor) between 2007 and 2012. Clinical details were extracted from hospital medical records for each patient. Treatment centers were classified as pediatric or adult services. Results: Two hundred seventy-five patients (129 LGG, 77 HGG, 23 MB, 10 PNET, 19 EP, 17 other) were identified, with 17% treated at pediatric hospitals. Symptoms (headache [53%], nausea [31%]) were present for a median of 3 weeks before consulting a health professional. Of LGG patients, 15% had radiotherapy (RT) and 12% chemotherapy (CT). Of HGG patients, 81% had RT and 75% CT. All MB and PNET were managed with surgery, and 74% of MB and 80% of PNET had both RT and CT. Treatment did not differ by treatment center type. Five-year survival for LGG and EP was over 80%, but was 42% for HGG and 20% for PNET. Conclusions: This national, population-based study indicates similar treatment for AYA patients with CNS tumors between pediatric and adult services. Poor outcomes for HGG and PNET patients highlight the need for clinical trials of novel approaches for these tumors.


Subject(s)
Central Nervous System Neoplasms , Adolescent , Australia/epidemiology , Brain Neoplasms/therapy , Central Nervous System Neoplasms/epidemiology , Central Nervous System Neoplasms/therapy , Cerebellar Neoplasms , Humans , Neuroectodermal Tumors, Primitive/therapy , Treatment Outcome , Young Adult
2.
Curr Oncol Rep ; 22(4): 34, 2020 03 13.
Article in English | MEDLINE | ID: mdl-32170510

ABSTRACT

PURPOSE OF REVIEW: Opioids are the only class of drug with the proven ability to control severe pain. The introduction of stringent opioid prescribing restrictions has inevitably impacted upon the ability of those prescribing opioids for advanced life-limited disease to practice as previously and could limit the supply of adequate pain relief to patients with cancer. This review considers the evidence that symptom management of patients with advanced cancer contributes to the "opioid problem" and whether there is adequate recognition of the risks involved. RECENT FINDINGS: The literature suggests that the risk of opioid abuse is low in the palliative care population as is the risk of legal consequences for doctors prescribing opioids at the end of life. However, as many patients with cancer are living longer or surviving with chronic pain, palliative care physicians must be cognisant not only of the risks of long term opioid use but also of the risk of opioid misuse. Adherence to evidence or consensus-based guidelines is necessary to avoid inappropriate prescribing. In palliative care, it is appropriate not only to exercise a reasonable degree of opioid control and surveillance, primarily for the good of society, but also to ensure that the ability to treat pain in patients with advanced malignant disease is not compromised.


Subject(s)
Analgesics, Opioid/therapeutic use , Drug Prescriptions/statistics & numerical data , Palliative Care/methods , Practice Patterns, Physicians'/statistics & numerical data , Public Health/methods , Chronic Pain/prevention & control , Humans , Opioid-Related Disorders/prevention & control , Pain Management/methods , Practice Guidelines as Topic/standards , Public Health/standards
3.
J Pain Symptom Manage ; 59(4): 856-863, 2020 04.
Article in English | MEDLINE | ID: mdl-31866486

ABSTRACT

CONTEXT: Medications commonly used for symptom control along with other known risk factors have the potential to prolong ventricular repolarization as measured by the QT interval (the time from the start of the Q wave to the end of the T wave) on a standard electrocardiogram (ECG). OBJECTIVES: To document the prevalence of a prolonged QT interval corrected for heart rate (QTc) interval in the palliative/oncology setting, compare automatic ECG QTc measurements with manual readings and identify any correlation between QTc prolongation and the use of drugs or other risk factors. METHODS: A convenience sample of consecutive patients with cancer, admitted under or known to the palliative/supportive care teams in two metropolitan hospitals, and willing to provide an ECG recording and basic demographic information including QTc risk factors were included. Both automated and manually calculated QTc intervals were recorded. Multivariable analysis was used to determine risk factors independently associated with prolonged QTc intervals. RESULTS: Of the 389 participants, there was a significant difference in mean QTc between sites using automated but not manual calculations. Manual readings were therefore used with predetermined cutoffs of 0.44 seconds (males) and 0.46 seconds (females). Seventy-two (18.5%) of the participants had a prolonged QTc with six (1.5%) having a prolongation of >0.50 seconds. At-risk drugs were being taken by 218 participants (56.0% of total cohort). Factors shown to be associated with QTc prolongation included age, gender, performance status, and hypocalcemia. No specific medication was associated with increased risk. CONCLUSION: Although almost 20% of patients receiving palliative care had prolongation of QTc, the possibility of serious consequences appeared to be low despite the frequent occurrence of risk factors.


Subject(s)
Long QT Syndrome , Neoplasms , Electrocardiography , Female , Humans , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Long QT Syndrome/epidemiology , Male , Neoplasms/drug therapy , Neoplasms/epidemiology , Palliative Care , Prevalence
4.
J Adolesc Young Adult Oncol ; 8(3): 272-280, 2019 06.
Article in English | MEDLINE | ID: mdl-30822262

ABSTRACT

Background: While overall survival (OS) for cancer in adolescents and young adults (AYA) has improved, there has been little change in AYA survival for several types of sarcomas. Using national data for Australia we describe (1) the treatment centers caring for AYA sarcoma, (2) treatments provided, and (3) survival outcomes. Procedure: National population-based study assessing treatment of 15-24 year-olds diagnosed with soft tissue sarcoma (STS), bone sarcoma (BS), and Ewing family tumors (ET) between 2007 and 2012. Treatment details were abstracted from hospital medical records. Treatment centers were classified as pediatric or adult specialist AYA/sarcoma center, or other adult. Cox proportional hazard regression analyses examined associations between type of treatment center and OS. Results: Sixty-one hospitals delivered treatment to 318 patients (135 STS; 91 BS, 92 ET), with 9%, 22%, and 17% of STS, BS, and ET, respectively, treated at pediatric and 62%, 59%, and 71% at adult specialist hospitals. Of 18-24 year-olds, 82% of BS, 90% of ET, and 73% of rhabdomyosarcomas at adult specialist centers were on a trial or standard protocol, compared with 42%, 89%, and 100%, respectively, at nonspecialist adult hospitals. After adjusting for disease and patient characteristics, survival was not associated with treatment center type for any disease type. However, ET survival was poorer for patients not receiving a standard chemotherapy protocol. Conclusions: Around 10% of AYA sarcoma patients attending adult hospitals were not on a standard protocol. Poorer survival for ET patients not on a standard protocol highlights the importance of ensuring all patients receive optimal care.


Subject(s)
Sarcoma/therapy , Adolescent , Adult , Australia , Female , Humans , Male , Young Adult
5.
Arch Dis Child ; 104(3): 237-245, 2019 03.
Article in English | MEDLINE | ID: mdl-30279157

ABSTRACT

BACKGROUND: Chronic conditions are the leading cause of mortality, morbidity and disability in children. However, children and caregivers are rarely involved in identifying research priorities, which may limit the value of research in supporting patient-centred practice and policy. OBJECTIVE: To identify priorities of patients, caregivers and health professionals for research in childhood chronic conditions and describe the reason for their choices. SETTING: An Australian paediatric hospital and health consumer organisations. METHODS: Recruited participants (n=73) included patients aged 8 to 14 years with a chronic condition (n=3), parents/caregivers of children aged 0 to 18 years with a chronic condition (n=19), representatives from consumer organisations (n=13) and health professionals including clinicians, researches (n=38) identified and discussed research priorities. Transcripts were thematically analysed. RESULTS: Seventy-eight research questions were identified. Five themes underpinned participants' priorities: maintaining a sense of normality (enabling participation in school, supporting social functioning, promoting understanding and acceptance), empowering self-management and partnership in care (overcoming communication barriers, gaining knowledge and skills, motivation for treatment adherence, making informed decisions, access and understanding of complementary and alternative therapies),strengthening ability to cope (learning to have a positive outlook, preparing for home care management, transitioning to adult services), broadening focus to family (supporting sibling well-being, parental resilience and financial loss, alleviating caregiver burden), and improving quality and scope of health and social care (readdressing variability and inequities, preventing disease complications and treatment side effects, identifying risk factors, improving long-term outcomes, harnessing technology, integrating multidisciplinary services). CONCLUSION: Research priorities identified by children, caregivers and health professionals emphasise a focus on life participation, psychosocial well-being, impact on family and quality of care. These priorities may be used by funding and policy organisations in establishing a paediatric research agenda.


Subject(s)
Chronic Disease/therapy , Health Priorities , Adolescent , Attitude to Health , Child , Child, Preschool , Consensus , Consumer Behavior , Hospitals, Pediatric , Humans , Infant , Infant, Newborn , New South Wales , Patient Participation
7.
Cancer J ; 24(6): 336-341, 2018.
Article in English | MEDLINE | ID: mdl-30480579

ABSTRACT

Meeting shortfalls in the provision of care to adolescents and young adults with cancer has focused largely on improving outcomes and psychosocial support. A significant percentage of adolescents and young adults with cancer will die of disease because of initial poor prognosis conditions or disease relapse. In adults, progress has been made in the concept of an integrated cancer/palliative care service. In pediatric oncology, the application of this philosophy of care has lagged behind somewhat. In the case of adolescents, particularly those with advanced cancer, the palliative care needs, in a broader sense than only end-of-life care, are often not adequately met, irrespective of whether treatment is delivered in a pediatric or adult cancer service. There are a number of age-specific aspects to palliative and supportive care for adolescents. Complex interactions between clinicians, parents, and patients potentially limit the young person's ability to influence care planning. The wide variation in real or perceived competency at this age, the developmental challenges in relation to behavior, communication, and coping strategy all require particular professional expertise that is not always available.


Subject(s)
Adaptation, Psychological , Adolescent Behavior/psychology , Neoplasms/therapy , Palliative Care/methods , Patient Participation , Adolescent , Adolescent Development , Age Factors , Attitude to Death , Decision Making , Hospice Care/methods , Hospice Care/organization & administration , Humans , Medical Oncology/methods , Medical Oncology/organization & administration , Neoplasms/mortality , Neoplasms/psychology , Palliative Care/organization & administration , Patient Care Planning , Patient Care Team/organization & administration
8.
Semin Oncol ; 45(5-6): 275-283, 2018 10.
Article in English | MEDLINE | ID: mdl-30327126

ABSTRACT

International data indicate that rates of clinical trial enrolment for Adolescents and Young Adults (AYAs) with cancer are markedly lower than for any other age group. This paper reviews the recent literature reporting international trends in clinical trial enrolment since 2010. Subsequently, we present the first population-based, national assessment of clinical trial enrolment for AYAs with cancer in Australia. Reported rates of trial enrolment from Australia, Canada, the United States, and the United Kingdom were variable, though consistently low, ranging between 2% and 29%. Trial enrolment was higher for younger AYAs (typically 15-19 years) and those attending pediatric hospitals, and this was replicated in the recent Australian data. The findings highlight a lack of substantial improvement in AYA clinical trial enrolment and in particular, a need for improved opportunities to access trials for patients treated at adult centers.


Subject(s)
Clinical Trials as Topic , Neoplasms/epidemiology , Adolescent , Adult , Age Factors , Age of Onset , Female , Humans , Male , Neoplasms/diagnosis , Neoplasms/etiology , Neoplasms/therapy , Patient Participation , Young Adult
9.
Br J Haematol ; 182(6): 859-869, 2018 09.
Article in English | MEDLINE | ID: mdl-29984828

ABSTRACT

We determined the risk factors associated with poor survival in children and adolescents with de novo mature B cell non-Hodgkin lymphoma (B-NHL) who had refractory or relapsed disease during or after the French-American-British mature lymphoma B (FAB/LMB) 96 multi-agent chemotherapy. Among the 1 111 registered on study, 104 patients (9·4%) had refractory disease or disease relapse after first complete remission. Among these 104 patients, 28 (27%) patients had refractory disease and 76 (73%) had relapsed disease. The estimated 1- and 2-year overall survival (OS) (95% confidence interval) was 31·5% (23·3-41·0%) and 22·3% (15·3-31·4%), respectively. Prognostic analysis of OS using a Cox multivariate model showed that factors independently associated with OS included lactate dehydrogenase ≥2 upper normal limit [hazard ratio (HR) = 2·86 (1·57-5·2), P = 0·0006]; time to failure (>6 months) [HR = 0·59 (0·36-0·97), P = 0·038]; and failure in bone marrow [HR = 2·78 (1·65-4·68), P = 0·0001]. New therapeutic strategies are required to significantly reduce refractory disease and disease relapse in patients with newly diagnosed mature B-NHL and, more importantly, there is a critical need to develop novel retrieval approaches in patients with chemotherapy-resistant disease.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, B-Cell/drug therapy , Adolescent , Bone Marrow Diseases , Carmustine/therapeutic use , Child , Doxorubicin/therapeutic use , Female , Fluorouracil/therapeutic use , Humans , Isoenzymes/blood , L-Lactate Dehydrogenase/blood , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/epidemiology , Lymphoma, B-Cell/mortality , Male , Prognosis , Proportional Hazards Models , Risk Factors , Salvage Therapy/methods , Salvage Therapy/mortality , Survival Analysis , Time Factors
10.
J Adolesc Young Adult Oncol ; 7(3): 339-348, 2018 06.
Article in English | MEDLINE | ID: mdl-29746187

ABSTRACT

Global recognition of the need to improve outcomes for adolescents and young adults (AYA) with cancer has led to the development of specific oncology programs and services. In Australia, Youth Cancer Services (YCS) are now established across the country. While each service has been shaped by nationally agreed principles, program development has been influenced by local policy and geographic differences. Queensland is a vast state with a widely dispersed population; coordination of cancer services for young people across this landscape presents unique challenges. The Queensland YCS (QYCS) work in a consultative partnership model with primary treating teams, across both pediatric and adult tertiary cancer services. Understanding how cancer services approach challenges and service development can provide guidance for other developing services. In this article, we describe the goals and development of QYCS and review the outcomes achieved in the service to date. We reviewed referral data and retrieved statewide clinical activity from the web-based data system. We compared these data with cancer registry data to identify disparities and areas for service development. While the service has achieved notable outcomes, challenges remain. These include recruitment of appropriately skilled and trained health professionals for this newly developing area of oncology. In addition, there is an ongoing need to advocate for this relatively small patient group, and to promote awareness and understanding of the need for AYA-specific services. With the dispersed population and concentration of services in metropolitan Brisbane, identifying and testing new innovative models, including telehealth, to reach all AYA diagnosed with cancer regardless of location of care are priorities.


Subject(s)
Health Services Accessibility/standards , Models, Statistical , Neoplasms/therapy , Quality of Health Care/standards , Referral and Consultation/standards , Adolescent , Adult , Australia , Female , Follow-Up Studies , Humans , Male , Prognosis , Telemedicine , Young Adult
11.
Arch Dis Child ; 103(10): 942-951, 2018 10.
Article in English | MEDLINE | ID: mdl-29643102

ABSTRACT

OBJECTIVE: To evaluate research priority setting approaches in childhood chronic diseases and to describe the priorities of stakeholders including patients, caregivers/families and health professionals. DESIGN: We conducted a systematic review of MEDLINE, Embase, PsycINFO and CINAHL from inception to 16 October 2016. Studies that elicited stakeholder priorities for paediatric chronic disease research were eligible for inclusion. Data on the prioritisation process were extracted using an appraisal checklist. Generated priorities were collated into common topic areas. RESULTS: We identified 83 studies (n=15 722). Twenty (24%) studies involved parents/caregivers and four (5%) children. The top three health areas were cancer (11%), neurology (8%) and endocrine/metabolism (8%). Priority topic areas were treatment (78%), disease trajectory (48%), quality of life/psychosocial impact (48%), disease onset/prevention (43%), knowledge/self-management (33%), prevalence (30%), diagnostic methods (28%), access to healthcare (25%) and transition to adulthood (12%). The methods included workshops, Delphi techniques, surveys and focus groups/interviews. Specific methods for collecting and prioritising research topics were described in only 60% of studies. Most reviewed studies were conducted in high-income nations. CONCLUSIONS: Research priority setting activities in paediatric chronic disease cover many discipline areas and have elicited a broad range of topics. However, child/caregiver involvement is uncommon, and the methods often lack clarity. A systematic and explicit process that involves patients and families in partnership may help to inform a more patient and family-relevant research agenda in paediatric chronic disease.


Subject(s)
Chronic Disease/psychology , Quality of Life , Caregivers , Child , Health Personnel , Humans , Outcome Assessment, Health Care , Stakeholder Participation
12.
J Adolesc Young Adult Oncol ; 7(3): 315-325, 2018 06.
Article in English | MEDLINE | ID: mdl-29356588

ABSTRACT

PURPOSE: To examine the care experiences of Australian Adolescents and Young Adults (AYAs) with cancer during a period when youth cancer services (YCS) were developing across the country. METHODS: A cross-sectional, self-report survey completed by 207 recently diagnosed AYAs with cancer, recruited from the population-based cancer registries of Australia's two most populous states. AYAs were 15 to 24 years old when diagnosed with any form of cancer (except melanoma <3 mm or stage I/II). Respondents indicated whether certain events/experiences occurred at various points along the cancer care pathway and the treatment centers attended. Treatment centers with YCS were identified. RESULTS: Participating AYAs were an average of 9 months post-diagnosis. AYAs were treated in over 60 centers, with only 31% attending YCS. While experiences relating to delivery of treatment were generally positive, supportive care experiences and emotional support were missing for many. Information provision at the end of treatment was low, with 60% not receiving a treatment summary and 50% not receiving a written follow-up care plan. In addition, 42% never/rarely received information relevant to their age, and only 54% reported that healthcare professionals definitely checked their understanding of the information provided. AYAs attending YCS were more likely to report age-appropriate treatment settings, information provision, and emotional support. CONCLUSION: While care experiences were generally positive for most AYAs, attending YCS was associated with better communication and supportive care experiences. As only a third of the AYAs surveyed attended these services, efforts are needed to increase AYA access to YCS.


Subject(s)
Attitude to Health , Cancer Survivors/psychology , Needs Assessment , Neoplasms/psychology , Palliative Care , Quality of Life , Adaptation, Psychological , Adolescent , Adult , Australia , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Patient Satisfaction , Prognosis , Retrospective Studies , Surveys and Questionnaires , Young Adult
13.
Psychooncology ; 27(3): 990-997, 2018 03.
Article in English | MEDLINE | ID: mdl-29278663

ABSTRACT

OBJECTIVE: To examine the relationship between the cancer care experiences of adolescents and young adults (AYAs) and their quality of life. METHODS: Two hundred and nine AYAs completed a cross-sectional, self-report survey distributed through the population-based cancer registries in 2 Australian states (New South Wales and Victoria). Eligible AYAs were 15 to 24 years old when diagnosed with any cancer (excluding early-stage melanoma) and were 3 to 24 months post-diagnosis. Questions examined whether particular care experiences occurred for the patient at different points in the cancer care pathway, including diagnosis, treatment, inpatient care, and at the end of treatment. Quality of life was assessed using the Functional Assessment of Cancer Therapy-General scale. RESULTS: Positive experiences of care at diagnosis, during treatment, during inpatient stays, and when finishing treatment were associated with higher functional, emotional, and social well-being. However, these associations generally became nonsignificant when communication and support experiences were included in the model. Inpatient experiences positively influenced emotional well-being over and above the effect of communication and support experiences. CONCLUSIONS: The results suggest that, for most AYAs' quality of life outcomes, positive experiences of age-appropriate communication and emotional support may underpin the effect of positive experiences of care throughout the cancer care pathway. The results support the need for communication and support tailored to an AYA audience, as recognised by recent Australian and international guidelines on the care of AYAs with cancer.


Subject(s)
Neoplasms/psychology , Neoplasms/therapy , Patient Satisfaction , Quality of Life/psychology , Adolescent , Adult , Australia , Cross-Sectional Studies , Female , Humans , Male , Young Adult
14.
J Pain Symptom Manage ; 55(3): 962-967, 2018 03.
Article in English | MEDLINE | ID: mdl-29208477

ABSTRACT

CONTEXT: In advanced cancer, abnormal sleep patterns may contribute to poor quality of life, but the impact of opioid-related sleep disorders has not been explored in detail in these patients. OBJECTIVE: To document sleep and respiratory patterns in patients with cancer, receiving a range of opioids, determine factors that contribute to severity of central or obstructive apnea, and to what extent these contribute to sleep disturbance. METHODS: Adults with advanced cancer admitted to a palliative care service underwent a sleep analysis by an unattended polysomnography. Total sleep time, apnea hypopnea index, central apnea index, obstructive apnea hypopnea index, arousal index, and oxygen desaturation were measured. Baseline assessment included body habitus, Mallampati score, comorbidity indices, concomitant medications, and the Berlin questionnaire. Epworth Sleepiness Scale, Stanford Sleepiness Scale, and Wu cancer fatigue scales were documented. RESULTS: Twenty-eight patients were studied, including 25 receiving opioids. In the latter group, the apnea hypopnea index was mildly abnormal in six patients and severely abnormal in 10 patients. Central apnea index and obstructive apnea hypopnea index were abnormal in nine and 17 patients, respectively. There was no significant correlation between opioid dose and polysomnographic results. CONCLUSION: In patients with advanced cancer receiving opioid analgesia, there was a high prevalence of respiratory disturbance, both central and obstructive, and deranged sleep patterns. Addressing sleep-disordered breathing in cancer patients has the potential to improve daytime drowsiness and quality of life.


Subject(s)
Analgesics, Opioid/therapeutic use , Neoplasms/therapy , Palliative Care , Respiration/drug effects , Sleep/drug effects , Adult , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/physiopathology , Polysomnography , Prevalence , Quality of Life , Sleep Apnea Syndromes/drug therapy , Sleep Apnea Syndromes/epidemiology , Sleep Apnea Syndromes/physiopathology
15.
Intern Med J ; 47(9): 1089-1090, 2017 09.
Article in English | MEDLINE | ID: mdl-28891188
17.
Intern Med J ; 47(6): 632-636, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28580748

ABSTRACT

In the context of a therapeutic opioid epidemic, particularly in the USA, where increasingly stringent screening for 'at risk' individuals and close monitoring of opioid prescription and use is strongly recommended, the issue of misuse within the cancer population must be addressed. Most patients with advanced cancer will have pain requiring opioid therapy at some stage during their disease course. In the majority, this will provide good pain relief with no short- or longer-term adverse sequelae. A subset will present with substance misuse issues that will influence management and prescribing practice. The potential ethical issues of limiting effective analgesia on the basis of addiction risk or history must be acknowledged. Both a judgemental or 'relaxed' approach to such patients is problematic. Ignoring the situation will not be in the patient's best interest, but an undue focus on this aspect may damage therapeutic relationships with clinicians and adversely affect a holistic approach to care. Clinical practitioners must be aware of the risk factors for opioid misuse and in patients who are not under palliative care consider screening prior to commencing opioids. Clinicians must be able to manage and monitor those identified as having an opioid misuse problem.


Subject(s)
Analgesics, Opioid/therapeutic use , Cancer Pain/drug therapy , Neoplasms/drug therapy , Opioid-Related Disorders/prevention & control , Pain Management/methods , Adolescent , Adult , Analgesics, Opioid/adverse effects , Cancer Pain/epidemiology , Cancer Pain/psychology , Chronic Pain/drug therapy , Chronic Pain/epidemiology , Chronic Pain/psychology , Humans , Neoplasms/epidemiology , Neoplasms/psychology , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/psychology , Pain Management/standards , Risk Factors
18.
Cancer Chemother Pharmacol ; 80(1): 15-25, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28444427

ABSTRACT

PURPOSE: Anthracyclines are a mainstay of the treatment of several childhood malignancies, but their utility is limited by dose-related cardiotoxicity. This study is aimed to explore the link between exposure of paediatric cancer patients to doxorubicin and its metabolite doxorubicinol, and cardiac troponin I (cTnI). METHODS: In a prospective pilot study plasma doxorubicin, doxorubicinol, and cTnI concentrations were measured in samples from children undergoing cancer chemotherapy. A mixed-effects population pharmacokinetic model for doxorubicin and doxorubicinol and in combination with a turn-over model for cTnI were developed. RESULTS: Seventeen patients, aged 3.4-14.7 year, treated for a variety of cancers had 99 doxorubicin and 119 doxorubicinol concentrations analysed from samples drawn between 0.5 and 336 h after the start of the infusion. Eleven patients had received previous doses of anthracyclines, with a median cumulative prior dose of 90 mg/m2 (range 0-225 mg/m2). The median administered doxorubicin dose was 30 mg/m2 (range 25-75 mg/m2). Doxorubicin disposition was described by a three-compartment model with first-order elimination and metabolism to doxorubicinol. Body surface area was related to all clearance and distribution parameters and age further influenced clearance (CL, 58.7 L/h/1.8 m2 for an average 8.4-year-old patient). Combined doxorubicin and metabolite exposure stimulated a temporary increase in cTnI in plasma, with a concentration of 11.8 µg/L required to achieve half-maximal effect. Prior cumulative anthracycline dosage received by patients was predictive of an increased cTnI baseline prior to a new doxorubicin dose. CONCLUSION: Prior anthracycline exposure increased baseline cTnI in a dose-dependent manner, consistent with the known cumulative risk of anthracycline exposure-induced cardiotoxicity.


Subject(s)
Doxorubicin/analogs & derivatives , Doxorubicin/pharmacokinetics , Models, Biological , Neoplasms/drug therapy , Troponin I/metabolism , Adolescent , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/pharmacokinetics , Cardiotoxicity/etiology , Child , Child, Preschool , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Female , Humans , Male , Pilot Projects , Prospective Studies
20.
Br J Haematol ; 173(4): 507-30, 2016 05.
Article in English | MEDLINE | ID: mdl-27133800

ABSTRACT

The 5th International Symposium on Childhood, Adolescent and Young Adult (CAYA) Non-Hodgkin Lymphoma (NHL) was held in Varese, Italy, from 21-25 October 2015. This review represents a summary of the scientific sessions of this international symposium including childhood, adolescent and young adult (AYA) NHL in countries with limited socio-economic resources, AYA NHL, anaplastic large cell lymphoma, post-transplant lymphoproliferative disease, B-cell NHL, lymphoblastic lymphoma, T/natural killer cell NHL and immunological therapies in NHL. Most importantly, the new International Paediatric NHL Staging System (IPNHLSS) and International Paediatric NHL Response Criteria (IPNHLRC) were introduced during the symposium. The symposium brought together a multinational and multidisciplinary group of clinicians and basic scientists focused in this field of haematological malignancies.


Subject(s)
Lymphoma, Non-Hodgkin , Adolescent , Child , Child, Preschool , Developing Countries , Female , Humans , Infant , Infant, Newborn , Internationality , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/mortality , Male , Survival Analysis , Treatment Outcome , Young Adult
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