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Symptom management during chemotherapy

Paediatrics and Child Health, 4, 24, pages 166 - 171

Abstract

Improvements in survival for children and young people with cancer have drawn increasing attention to the impact of symptoms on their experience of the disease and treatment. The symptom burden associated with chemotherapy treatment regimes continues throughout the illness trajectory, includes anticipatory symptoms and extends beyond the completion of treatment in some circumstances. This review explores assessment and management of common symptoms, in particular those identified as sources of distress by children, parents and professionals. Included are pain, mucositis, nausea and vomiting, weight loss and poor nutrition, fatigue, sleep and mood disturbances. Attention is drawn to developing a holistic approach which considers relevant biological, psychological and sociocultural factors in assessment and management and the interrelationship of multiple symptoms.

Keywords: chemotherapy, fatigue, mood disturbance, mucositis, nausea and vomiting, nutrition, pain, sleep disturbance, symptom assessment, symptom management, weight loss.

Introduction

Globally there are an estimated 263 000 new cases of cancer affecting people younger than 20 years, two thirds of these cases will occur in children under the age of 15 years. In high income countries 80% of these children will survive joining the cohort of one in 1000 adult survivors of childhood or adolescent cancer in high income countries. Multimodal chemotherapy has become the treatment that the majority of children and young people diagnosed with childhood cancer will receive. This approach to childhood cancer treatment and supportive care are credited with the significant improvements in survival over the last 40 years. Moreover improvements in supportive care have reduced the mortality and morbidity associated with intensive chemotherapeutic regimes.

Chemotherapeutic regimes result in significant symptom burden for children and young people in addition to those symptoms that arise as an indirect or direct result of the disease itself. Current trials in cancer therapies alongside a primary goal of increased survival are also directed towards the reduction of acute and long term side effects and the symptoms children and young people experience during chemotherapy.

This review will discuss the most common symptoms experienced by children and young people as a result of chemotherapy for childhood cancer, how these can be recognized, effectively assessed and managed as part of the child's holistic care. In this review we include as symptoms, both measurable and observable phenomena (sometimes described as signs) such as mucositis and vomiting alongside events and experiences only discernible to the child and family and potentially less amenable to measurement, such as fatigue and mood. We recognize that although it may be possible to predict symptoms associated with specific chemotherapeutic agents and regimes, the experience of symptoms is unique to the child and variable over the illness requiring on-going assessment on an individual basis. In addition symptoms are not experienced in isolation, therefore we advocate a holistic approach to management that addresses the relevant biological, psychological and sociocultural factors which should be considered by healthcare professionals.

Assessment of symptoms

Woodgate et al. (2003) advocated the reconceptualization of symptoms during treatment for childhood cancer as ‘feeling’ states rather than side effects. This perspective is validated in the accounts of children and young people (CYP) who speak of ‘days when I wake up and feel like I have been hit by a truck’ and ‘Gastric Armageddon’. CYP accounts also draw attention to the limitations of assessment tools that consider symptoms as single entities that can be evaluated and compared through assigned numeric values. Recent research on symptom clusters, where two or more symptoms occur together such as pain and fatigue, show that co-occurrence of symptoms increases symptom severity affecting functioning and quality of life.

Recognition of symptoms as a complex biopsychosocial process requires clinicians to synthesize these elements, collected through physical observation and examination, clinical investigation, self-reporting by the CYP and proxy reporting by parents to achieve a comprehensive, meaningful and timely assessment. A number of assessment tools have been developed to determine the incidence, severity and impact on the child of single and multiple symptoms. These tools have been primarily utilized to research symptoms in children with cancer and therefore their utility for clinical practice has yet to be fully tested. Never the less they bear consideration as part of an initial, objective and on-going assessment process to determine the occurrence, cause and effectiveness of symptom management interventions.

Assessment must recognize that the occurrence and severity of symptoms can change over the course of chemotherapy. Baggott et al. (2010) used the Memorial Symptom Assessment tool (MSAS) longitudinally with 66 children (10–18 years) and determined that although some symptoms decreased in occurrence, severity did not necessarily diminish, across a course of chemotherapy. This is important for effective symptom management particularly as increasingly short periods of hospitalization become the norm for many chemotherapeutic regimes. In addition to the provision of clear information about potential symptoms and the interventions to manage them, paediatric oncology services should be organized to facilitate timely reassessment outside the hospital setting, utilizing local health services (such as community nurses) and/or symptom review that can be initiated by the treatment centre, parents and CYP. Several centres have reported the benefits of web and phone based technology to support symptom assessment. On-going dialogue between healthcare professionals, parents and CYP is essential as under reporting of symptoms can relate to assessment tools that lack sensitivity and specificity and do not account for the developmental diversity in the paediatric oncology population. Furthermore both CYP and parents are reluctant to report symptoms which they anticipate cannot be alleviated and are seen as an inevitable part of the cancer experience.

Pain

Pain is common in children with cancer. It is one of the most prevalent, and also the most feared symptoms. Pain is an integral element of the cancer experience; often present at diagnosis, as a consequence of treatment therapies; as a feature in survivors; common in progressive disease and towards the end of life. Professionals working in the field need to be competent in the management of multiple pain states: acute pain, chronic pain, recurring pain, procedure related pain and pain at the end of life.

Pain is typically under reported and under treated in children with cancer. Patterns of opioid consumption in cancer patients show that children begin opioid treatment significantly later than comparable adult groups. Reasons for this are complex and include lack of acknowledgement, poor identification of pain, deficient assessment and management of pain. Concordance between nurse assessment/documentation and child reporting of pain is limited.

Agreement between child and parent pain assessment is also unclear. Parent–child agreement for nausea, pain and lethargy was only moderate in a review of symptoms aged 7–12 years. A recent study has found that many parents of children being treated for cancer reported concerns regarding analgesics used to treat their children's pain and misconceptions about how children express pain. It is essential that professionals provide adequate education and support to CYP and families to address these misconceptions to prevent under treatment of pain, particularly when care is home based.

Pain management approaches

Pain specialists advocate a mechanism based, multimodal approach to the management of cancer pain. As pain is multidimensional, involving the emotional and sensory experience of the child within their developmental level and social and cultural framework, optimal pain relief can only be achieved through holistic assessment. Without attention to the psychological and existential wellbeing of the child, pharmacological management in isolation will not achieve desired effect.

Understanding the science of pain in relation to the clinical setting enables an integration of psychological, physical, interventional and complementary therapies to optimize pain relief. For example, non pharmacological and integrative therapies can stimulate efferent inhibiting pathways descending from the periaqueductal grey, thereby decreasing nociception, and providing effective self-coping skills for the child. The use of non pharmacological therapies such as massage, acupuncture, hypnosis and guided imagery are recognized as essential elements to children's cancer pain management.

The latest initiative ‘WHO Guidelines on the Pharmacological Treatment of Persisting Pain in Children with Medical Illness’ 2012 has taken the best available current evidence and developed a new guideline to improve the management of pain in children.

Pain in cancer is often a combination of nociceptive (visceral and/or somatic) and neuropathic pain. The choice of analgesic drug is made on the basis of assessment of pain and its severity. Opioids are introduced once simple analgesia (paracetamol and ibuprofen) is no longer effective or if assessment indicates more than mild pain. Some analgesics do offer a genuine advantage over morphine, either because of the drugs pharmacokinetic profile such as other receptor activity or because of the formulations available. For example transdermal fentanyl may be advantageous in a child unable or refusing to take enteral medications.

Opioids can be used alone or in combination with many other medications. Patient-controlled analgesia (PCA) permits even very young children to self-administer small doses of parenteral opioid at frequent intervals and has the versatility to provide a continuous or background infusion at the same time. As children with malignancy have been found to have a high frequency of episodes of breakthrough pain (characterized by ‘sharp’ or ‘shooting pain’ lasting seconds to minutes) during treatment the most effective management is a patient-controlled analgesia opioid bolus dose. A variation of PCA is ‘parent/nurse controlled analgesia’ (PNCA), which has been successfully and safely adopted for use in children being treated for cancer.

Standard dosing of opioids adequately treats most cancer pain in children; however, a significant group requires more extensive management. These challenging pain states occur more commonly among patients with solid tumours involving bone, spine and major nerves and require a different prescribing strategy. There are many causes of neuropathic pain in this cohort. Chemotherapeutic agents, particularly the vinco-alkaloids, can cause persisting neuropathic pain; solid tumour infiltration into the somatosensory system or direct tissue invasion, and phantom limb pain can also be responsible. Bone pain is also common and is typically a focal, deep seated and intense pain that a child may describe as ‘boring’ or ‘like a drill’ and indicates to by pointing to a specific spot. Skills specific to the management of these unique pain syndromes are essential to support a child through cancer treatment. Failure to identify specific pain mechanism and use of targeted analgesia may be one reason for the considerable prevalence of pain in children with cancer.

Parents of children with advanced cancer with no chance of cure, report high levels of symptoms burden, particularly pain. Palliative chemotherapy, predominantly via the enteral route, is frequently given in the hope that it will improve symptoms and slow disease progression, however there seems no clear evidence that it improves analgesia. Existential suffering of parents must also be acknowledged when considering symptom burden.

Pain produces negative psychological effects and has been shown to be directly related to quality of life. Despite attempts at addressing pain management in the paediatric cancer population pain is still a common symptom, often unacknowledged and poorly managed. For this reason pain must be proactively managed by the clinical team.

Mucositis

Mucositis is a toxic inflammatory reaction that can affect the entire gastrointestinal tract from the mouth to the anus. The prevalence of chemotherapy-induced mucositis ranges between 30 and 75% dependent on the treatment schedule followed. Mucositis can appear as erythematous burn-like lesions or ulcerations that may be focal or diffuse. Symptoms include: pain, inflammation, dry mouth, ulceration, desquamation of oral mucosa, gums and palate; dry and cracked lips, and bleeding.

Chemotherapy damages and destroys the epithelial cells of the gastrointestinal tract and oral mucosa directly as it disrupts cell production, maturation and replacement; and indirectly due to increased risk of bleeding and infection caused by thrombocytopenia and neutropenia in the myelosuppressed CYP with cancer. It also affects the production and flow of saliva, and the microbial flora of the gastrointestinal tract.

Management is aimed at maintaining good oral hygiene. Regular oral assessment is an important measure to detect early signs of deteriorating oral status and reduce infection risk, and should involve a thorough and systematic approach, taught to the CYP and their parents/carers. An oral and dental assessment linked to a cancer centre should occur at diagnosis and throughout treatment to reduce the exacerbation of pre-existing dental caries. Use of prophylactic and treatment algorithms can help tailor mouthcare to the child's risk of developing mucositis (these are often based on chemotherapy regimens) and the clinical status of the oral mucosa. Minimal oral hygiene should involve cleaning of teeth twice daily using a soft toothbrush and fluoride toothpaste. The use of chlorhexidine routinely is no longer recommended, except when unable to brush the teeth, in which case the mouth can be cleaned with oral sponges moistened with water or diluted chlorhexidine.

Damage to the mucosa can also cause associated symptoms of dysphagia, altered nutritional status, weight loss, and diarrhoea. Infection with micro-organisms most commonly fungal (candida), viral infections (including herpes simplex) and bacterial infections may lead to a life-threatening systemic infection. There should be a low threshold for switching from oral to parenteral routes to manage complications of pain and poor nutritional intake. Early management with patient-controlled analgesia allows titration of analgesia, and can enable the child to tolerate mouthcare more readily and resume some enteral feeding.

Nausea and vomiting

Over 50% of children on treatment experience these symptoms which are associated with significant level of distress. Adolescents report poorer control of nausea and vomiting than younger children during chemotherapy.

Although the causes of nausea and vomiting may be multifactorial and require clarification during assessment to promote effective management chemotherapy-induced nausea and vomiting (CINV) remains one of the most reported symptoms despite advances in antiemetic therapies. A recent Cochrane review defined three clinical phases of CINV as illustrated in Table 1 .

Table 1 Phases of chemotherapy related nausea and vomiting

Type Definition Prevalence
Anticipatory nausea and vomiting Symptoms precede administration of chemotherapy, often following a previous experience of poorly controlled CINV 20–30%
Acute nausea and vomiting Symptoms following administration of chemotherapy, and within 24 hours Variable dependent on emetogenicity but can be upwards of 90%
Delayed nausea and vomiting Symptoms occur 24 hours after chemotherapy administration Up to 50% usually following platinum compounds or alkylating agents

Knowledge of the emetogenic potential of chemotherapy and biological therapies, and risk stratified antiemetic regimens provide the basis for managing CINV. Unfortunately clinical trials of antiemetic combinations tend to report vomiting rather than nausea which is often reported by CYP as the more distressing symptom. Intractable or inadequately controlled CINV can lead to anticipatory nausea and vomiting (ANV), weight loss and poor nutrition, and negatively impacts on compliance with treatment and quality of life.

CINV is generally mediated centrally via stimulation of the chemoreceptor trigger zone (CTZ) and peripherally via activation of vagal afferents stimulated by release of 5-HT (serotonin) from the gut mucosa of the gastrointestinal tract. These pathways in turn stimulate the vomiting centre. ANV is thought to occur due to stimulation of the cerebral cortex and limbic system by anxiety and sensory stimuli.

Phillips et al., 2011 reviewed 28 randomized trials examining 23 drug combinations of antiemetics for preventing and treating CINV suggests that 5-HT3 antagonists with the addition of dexamethasone are effective in patients receiving highly emetogenic chemotherapy although the risk-benefit profile of additional steroids remains uncertain. In clinical practice use of dexamethasone as an adjunct is omitted, if the child is receiving a chemotherapy regimen containing steroids.

Studies of children's coping strategies for CINV found that distraction and wishful thinking were the most frequently used coping strategies, with social support and distraction reported as the most effective.

Weight loss and poor nutrition

Weight loss in the child with cancer can be multifactorial and complex, occurring in over 60% of children. The child's condition and/or treatment can cause loss of appetite (reported in 84% of children) often further complicated by symptoms of pain, mucositis, nausea and vomiting, constipation and diarrhoea. Altered taste due to chemotherapy can stop a child enjoying food. Metabolic changes associated with anorexia can cause cachexia, which is thought to result from an imbalance between the body's energy needs versus energy availability. Prolonged and frequent hospital admissions coupled with dislike of hospital food, and mismatching food delivery to the child's hunger are sociocultural factors which can impact adversely a child's nutritional intake leading to weight loss. Psychological factors that may contribute to poor nutrition and weight loss include the emotional burden of diagnosis and treatment, coupled with fatigue, depression and anxiety.

Management involves regular and accurate recording of weight, input and output, and assessment of nutritional status. Studies indicate that well-nourished children are better able to tolerate treatment and resist infection. Good nutrition is necessary for children to achieve normal growth and development. Nutritional algorithms allow children at risk of poor nutrition and weight loss to be identified, and utilization of appropriate nutritional care pathways to reflect the child's individual needs. Care should be planned that addresses the biopsychosocial factors contributing towards weight loss and poor nutrition: for example maintaining the child's home mealtime regimes, protecting mealtimes (stopping interventions during mealtimes) ensuring snacks are available to match periods of hunger. A multidisciplinary team approach would include parents, dieticians, psychologists and play specialists to help improve nutrition.

Physiological management tends to focus on a stepped process that requires clear guidance from the MDT when to move from one step to the next, see Figure 1 . Treatment should also focus on managing any underlying cause and exacerbating factors such as nausea and vomiting, mucositis, diarrhoea and constipation.

gr1

Figure 1 Stepped process for nutrition management.

Fatigue

Fatigue is increasingly recognized as one of the most consistently occurring symptoms associated with cancer treatment. CYP, parents and health professionals all report it as a frequent and sometimes severe and distressing aspect of treatment, occurring in 80–90% of CYP on treatment. It has been variously defined as a ‘persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning and can be described in terms of perceived energy, mental capacity and psychological status’ (National Comprehensive Cancer Network); and ‘a profound sense of being tired or having difficulty with movement such as arms and legs, or opening eyes which is influenced by environmental factors particularly hospitalisation’. Fatigue can be conceptualized as a series of experiences for CYP that were physically and mentally exhausting, increasing their need to sleep and severe limiting all activities ‘I am wiped out …My body is just too tired for me to care’ (Woodgate et al., 2003).

There is some evidence that although fatigue is a symptom that is always present during treatment frequency of occurrence and intensity varies across the chemotherapy treatment trajectory, for example being most intense following several days of chemotherapy and reducing between treatments. Although intensity reduced, the majority of patents continue to report moderate to severe/very severe scores. Fatigue is associated with sleep wake disturbances, corticosteroids, depression and vomiting. Although physical activity can contribute to fatigue adolescents report boredom and inactivity as a causal factor and hospitalization as a location of care which increases its frequency and intensity. Younger children's descriptions of fatigue are more focused on the physical sensations of fatigue assessing intensity in relation to their pre illness activity levels.

Fatigue (tiredness, lethargy, lack of energy) is a specific symptom in several multiple symptom assessment instruments. In addition two fatigue specific instruments are identified in the literature (1) The fatigue scale – Child (7–12 years)/Adolescent (13–18 years)/Parent – assessing frequency and intensity (2) PedsQL Multidimensional Fatigue Scale – assessing general fatigue, cognitive fatigue and sleep/rest fatigue for three self report age groups of CYP and an additional parental proxy report 2–4 years. The use of single symptom assessment scales in clinical practice can be problematic for patient burden and they assume that symptoms are experienced in isolation, although they do provide the opportunity to assess in detail symptoms that require further attention.

Physical activity programmes and cognitive behaviour therapy have been demonstrated as feasible interventions for chemotherapy associated fatigue, however their impact on frequency and intensity in the practice setting have yet to be determined. CYP identify distractions such as visitors and activities during hospitalization as well as quiet and private time, rest, going outside, blood transfusions, eating and drinking as strategies to alleviate fatigue.

Sleep disturbance

This symptom is also frequently reported by CYP undergoing cancer treatment, with 35–40% experiencing disrupted sleep. Inadequate sleep in relation to time or quality can have a number of health and well-being implications for CYP, including sustaining normal physiological growth, disruption of natural killer cell and cytokine activity, endocrine regulation as well as behavioural and cognitive consequences. Assessment of sleep requires attention to both the amount of sleep (school age children require 9–10 hours per 24 hours) and the quality of sleep (sleep efficiency measures the ratio of actual sleep relative to the time in bed, with 90% regarded as acceptable for children). The majority of studies of sleep disturbances during chemotherapy have focused on children's experiences during hospitalization, however it is important to note that 42% of children undergoing maintenance therapy for Acute Lymphoblastic Leukaemia were reported by their parents as experiencing sleep disturbances and parents also report changes in sleep patterns for over 60% of children since their diagnosis with cancer.

Assessment of sleep disturbance requires attention to total sleep time over 24 hours, bedtime and sleep onset time, number and duration of nocturnal awakenings, daytime naps, child and family sleep hygiene patterns pre and post diagnosis in addition to variations across the illness trajectory and physical assessment to determine other contributors to sleep wake disturbances such as obstructive sleep apnoea.

During hospitalization for chemotherapy reported patterns of going to bed and waking up were delayed compared to home routines and average times for that age group, the majority of children studied did not achieve the recommended total sleep time. The most frequently reported aspect of sleep disturbance is an increase in the number and duration of night time awakenings. School age children typically awaken briefly for four to six times during the night between their 90 minute sleep cycles. Frequent wakening's as many as 40 per night reduce the total sleep time and suggest that more time spent in bed does not necessarily indicate better sleep quality. The failure to complete sleep cycles can have acute implications, increased fatigue, irritability and reduction in daytime functions and quality of life, as well as impacting negatively on physiological growth, cognitive abilities and creating adverse sleep patterns that persist beyond treatment completion.

The precise relationship of sleep disturbance to specific chemotherapeutic regimes remains unclear. During hospitalization attention should be given to interventions aimed at promoting sleep hygiene individualized to the child's personal preferences and home routine. For example reductions in night time noise levels, re-structuring medication schedules to reduce the doses planned for typical bedtime hours, reviewing vital sign monitoring practices and pre-empting symptoms such as pain and nausea to reduce their occurrence during sleep times. Similarly in the home setting attention to assessing sources of sleep disruption and the promotion of sleep hygiene measures should be an integral part of care management in this setting.

Mood disturbance

Children and young people report symptoms of feeling sad and depressed, anxiety, fear and worry throughout their treatment trajectories and beyond. The prevalence of these symptoms when assessed individually is variable from 30 to 70%. Individual studies that have focused on comparing rates of clinical significance of depression and anxiety for example with healthy peers suggest that the lower rates correspond with the upper ranges of normal and there is little evidence that this symptom persists beyond treatment. However reviews of multiple symptoms continue to identify mood disturbances, including fear and feeling sad as amongst the most common cancer related symptoms of concern to CYP and their families. Unravelling the casual relationships of these symptoms to chemotherapy is particularly challenging.

Adolescents in particular have identified the changes in appearance, bought about by chemotherapy such as hair loss, weight gain and loss as a particular source of emotional distress, alongside changes brought about by treatment delivery such as central venous access devices. Qualitative data from CYP about their treatment experiences show how feeling unlike their usual selves was distressing. They identified being ‘cranky’, ‘grumpy’ and irritable as a source of concern in particular when it led to behaviours with their family members they regretted. They anticipated that these mood changes, although unpleasant would resolve on completion of treatment.

Discussion

This review has demonstrated that symptoms are best viewed as multidimensional subjective feeling states in the childhood cancer population. They occur frequently during treatment, extending in some cases long after treatment is completed and are not always optimally managed. The assessment of symptoms can present a number of challenges, including the diversity of the paediatric cancer population, in terms of child development, underlying diagnosis, chemotherapeutic regimens, the organization and delivery of cancer treatment.

Children, including those as young as 5 years, have demonstrated their ability to self-report symptoms using a number of multidimensional symptom s scales, however CYP of all ages report these as inadequate representations of their symptom experiences. Although self-reporting by CYP should be considered gold standard for assessment, parents and healthcare professionals (HCP) have significant roles to play in symptom assessment and indeed management. Parent reports are essential in younger children whose more limited verbal reports and behaviours are likely to be less well understood by HCP. Whist for older children, although parent reports may not concur with the CYP, their assessment is also meaningful. HCP assessments are able to offer some anticipatory information based on their additional knowledge of the biological and psychosocial effects of chemotherapy. Therefore adequate assessment requires a synthesis of these perspectives, undertaken systematically to provide a foundation for productive and on-going dialogue between CYP, parents and HCP to achieve effective interventions for symptom relief.

Evidence based guidelines for the management of symptoms such as pain, mucositis and nausea are available and it is imperative that these are integrated into the everyday practice of paediatric oncology care. Greater knowledge and understanding is still required on disease and treatment specific symptom trajectories in order that more effective management strategies for assessment and interventions can be developed, tested and integrated into clinical practice.

Topical in the current literature is the focus on clusters of symptoms experienced together during illness. Pain is a very common feature of the symptom clusters identified in paediatric cancer. In a recent review pain and fatigue are the most common symptoms analyzed for correlations in symptom cluster research in children with cancer. Pain and fatigue are associated with sleep disturbance, anxiety, anorexia and nausea and vomiting. Finally the interrelationship between symptoms that CYP report as clusters requires further research to realize the goal of multidimensional symptom management for the individual child undergoing chemotherapy treatment for cancer.

Practice points

 

  • Comprehensive and consistent holistic assessment across the illness and treatment trajectory is the foundation of effective symptom management for CYP during chemotherapy.
  • Acknowledgement of multiple symptoms existing concurrently and awareness of their synergetic effect on the child's symptom burden.
  • Anticipatory information and education for parents, CYP and healthcare professionals to facilitate early intervention to manage cancer symptoms is advised.

Further reading

  • 1 C. Baggot, M. Dodd, C. Kennedy, N. Marina, C. Miaskowski. Multiple symptoms in paediatric oncology patients: a systematic review. J Pediat Oncol Nurs. 2009;26:325-339
  • 2 E. Beecham, R. Howard, R. McCulloch, et al. Pharmacological interventions for pain for life-limiting conditions in children and adolescents. Cochrane Database Syst Rev. 2013;10.1002/14651858.CD010750 Art No.: CD010750
  • 3 J.J. Collins, T.D. Devine, G.S. Dick, et al. The measurement of symptoms in young children with cancer: the validation of the memorial symptom assessment scale in children aged 7–12. J Pain Symptom Manage. 2002;23:10-16 Crossref
  • 4 L.L. Dupis, M. Ethier, D. Tomlinson, T. Hesser, L. Sung. A systematic review of symptom assessment scales in children with cancer. BMC Cancer. 2012;12:430-436
  • 5 J.M. Erickson, C.F. MacPherson, S. Ameringer, et al. Symptoms and symptom clusters in adolescents receiving cancer treatment: a review of the literature. Int J Nurs Stud. 2013;50:847-869 Crossref
  • 6 S.J. Friedrichsdorf, N. Andrea Postier. Management of neuropathic pain in children with cancer. Curr Opin Support Palliat Care. 2013;7:131-138 Crossref
  • 7 L. Hedén, U. Poder, L. von Essen, G. Ljungman. Parents' perceptions of their child's symptom burden during and after cancer treatment. J Pain Symptom Manage. 2013;46:366-375
  • 8 D. Kelly, F. Gibson (Eds.) Cancer care for adolescents and young adults (Blackwell Publishing, Oxford, 2008)
  • 9 S.A. Kestler, G. Lobiondo-Wood. Review of symptom experiences in children and adolescents with cancer. Cancer Nurs. 2012;35:E31-E49 Crossref
  • 10 R.S. Phillips, S. Gopaul, F. Gibson, et al. Antiemetic medication for prevention and treatment of chemotherapy induced nausea and vomiting in childhood. Cochrane Database Syst Rev. 2010;10.1002/14651858.CD007786.pub2 Art. No.:CD007786
  • 11 K. Prichard-Jones, R. Pieters, G.H. Reaman, et al. Improving cancer for children and young people (1) sustaining innovation and improvement in the treatment of childhood cancer: lessons from high income countries. Lancet Oncol. 2013; http://dx.Doi.org/10.1016/S1470-2045(13)70010-X
  • 12 C. Rodgers, R. Norville, O. Taylor, et al. Children's coping strategies for chemotherapy-induced nausea and vomiting. Oncol Nurs Forum. 2012;39:202-209 Crossref
  • 13 C.C. Rodgers, M.C. Hooke, M.J. Hockenberry. Symptom clusters in children. Curr Opin Support Palliat Care. 2013;7:67-72 Crossref
  • 14 WHO. WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses. (, 2012) http://www.who.int/medicines/areas/quality_safety/guide_perspainchild/en/
  • 15 R. Woodgate, L. Degner, R. Yanofsky. A different perspective to approaching cancer symptoms in children. J Pain Symptom Manage. 2003;26:800-817 Crossref

Footnotes

Renee McCulloch BM BS MRCP Dip Pal Med Consultant in Paediatric Palliative Medicine, The Louis Dundas Centre, Oncology Outreach and Palliative Care, Great Ormond Street Hospital NHS Foundation Trust, London, UK. Conflicts of interest: none declared

June Hemsley BSc Children's Nursing RN Child Clinical Nurse Specialist Lead Nurse, The Louis Dundas Centre, Oncology Outreach and Palliative Care, Great Ormond Street Hospital NHS Foundation Trust, London, UK. Conflicts of interest: none declared

Paula Kelly PhD Msc BA(Hons) PGCE RGN RSCN RNT P.ONC Cert Senior Research Associate, The Louis Dundas Centre for Children's Palliative Care, University College London – Institute of Child Health, London, UK. Conflicts of interest: none declared


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