Malignant disease
Cancer in children is not common.
• Around 1 child in 500 develops cancer by 15 years of age.
• Each year, in Western countries, there are 120–140 new cases per million children aged under 15 years, equivalent to about 1500 new cases each year in the UK.
The types of disease seen (Fig. 21.1) are very different from those in adults, where carcinomas of the lung, breast, gut and skin predominate. The age at presentation varies with the different types of disease:
• Leukaemia affects children at all ages (although there is an early childhood peak).
• Neuroblastoma and Wilms tumour are almost always seen in the first 6 years of life.
• Hodgkin lymphoma and bone tumours have their peak incidence in adolescence and early adult life.
Despite significant improvements in survival over the last four decades (Fig. 21.2), cancer is the commonest disease causing death in childhood (beyond the neonatal period). Overall, the 5-year survival of children with all forms of cancer is about 75%, most of whom can be considered cured, although cure rates vary considerably for different diagnoses. This improved life expectancy can be attributed mainly to the introduction of multi-agent chemotherapy, supportive care and specialist multidisciplinary management. However, for some children, the price of survival is long-term medical or psychosocial difficulties.
In children, leukaemia is the most common malignancy followed by brain tumours.Aetiology
In most cases, the precise aetiology of childhood cancer is unclear, but it is likely to involve an interaction between environmental factors (e.g. viral infection) and host genetic susceptibility. In fact, there are very few established environmental risk factors, and although cancer occurs as a result of mutations in cellular growth controlling genes, which are usually sporadic but may be inherited, in most cases a specific gene mutation is unknown. One example of an inherited cancer is bilateral retinoblastoma, which is associated with a mutation within the RB gene located on chromosome 13. There is a wide range of syndromes associated with an increased risk of cancer in childhood, e.g. associations exist between Down syndrome and leukaemia, and neurofibromatosis and glioma. In time, the further identification of biological characteristics of specific tumour cells may also help elucidate the basic pathogenetic mechanisms behind their origin.
Investigations
Initial symptoms can be very non-specific and this can often lead to significant delays in diagnosis. Once a diagnosis of malignancy is suspected, the child should be referred to a specialist centre for further investigation.
Radiology
The location of solid tumours and evidence of any metastases are identified and localised, using a combination of ultrasound, plain X-rays, CT and MRI scans. Nuclear medicine imaging (e.g. radiolabelled technetium bone scan) may be useful to identify bone or bone marrow disease or, using special markers (MIBG scan), localise tumours of neural crest origin, e.g. neuroblastoma.
Pathology
All diagnoses must be confirmed histologically, either by bone marrow aspiration for cases of leukaemia or by biopsy for most solid tumours, although this may not always be possible for brain tumours. Histological techniques such as immunohistochemistry are routinely used to differentiate tumour types. Molecular and genetic techniques are also used to confirm diagnosis (e.g. translocation of chromosomes 11 and 22 in Ewing sarcoma) and to predict prognosis (e.g. amplification of the ‘N-myc’ oncogene associated with a poor prognosis in neuroblastoma).
Management
Once malignancy has been diagnosed, the parents and child need to be seen and the diagnosis explained to them in a realistic, yet positive way. Detailed investigation to define the extent of the disease (staging) is paramount to planning treatment. Children are usually treated as part of national and international collaborative studies that offer consistency in care and have contributed to improvements in outcome.
In the UK, children with cancer are initially investigated and treated in specialist centres where experienced multidisciplinary teams can provide the intensive medical and psychosocial support required. Subsequent management is often shared between the specialist centre, referral hospital and local services within the community, to provide the optimum care with the least disruption to the family.
Teenagers and young adults (TYA)
Survival statistics suggest that teenagers and young adults have poorer outcomes than children and constitute a distinct population. This relates both to the specific types and biological behaviour of their tumours and to their particular social/psychological needs. This has prompted the development of age-appropriate treatment protocols, facilities and support networks.
Treatment
Treatment may involve chemotherapy, surgery or radiotherapy, alone or in combination.
Chemotherapy
• as primary curative treatment, e.g. in acute lymphoblastic leukaemia
• to control primary or metastatic disease before definitive local treatment with surgery and/or radiotherapy, e.g. in sarcoma or neuroblastoma
• as adjuvant treatment to deal with residual disease and to eliminate presumed micrometastases, e.g. after initial local treatment with surgery in Wilms tumour
The use of biologically targeted therapies and their role in combination with conventional treatment modalities is an area of active research that is likely to increase in importance in the near future.
Radiotherapy
This retains a role in the treatment of some tumours, but the risk of damage to growth and function of normal tissue is greater in a child than in an adult. The need for adequate protection of normal tissues and for careful positioning and immobilisation of the patient during treatment raises practical difficulties, particularly in young children.
Surgery
Initial surgery is frequently restricted to biopsy to establish the diagnosis, and more extensive operations are usually undertaken to remove residual tumour after chemotherapy and/or radiotherapy.
High-dose therapy with bone marrow rescue
The limitation of both chemotherapy and radiotherapy is the risk of irreversible damage to normal tissues, particularly bone marrow. Transplantation of bone marrow stem cells can be used as a strategy to intensify the treatment of patients with the administration of potentially lethal doses of chemotherapy and/or radiation. The source of the marrow stem cells may be allogeneic (from a compatible donor) or autologous (from the patient him/herself, harvested beforehand, while the marrow is uninvolved or in remission). Allogeneic transplantation is principally used in the management of high-risk or relapsed leukaemia and autologous stem cell support is used most commonly in the treatment of children with solid tumours whose prognosis is poor using conventional chemotherapy, e.g. advanced neuroblastoma.
Supportive care and side-effects of treatment
Cancer treatment produces frequent, predictable and often severe multisystem side-effects (Fig. 21.3). Supportive care is an important part of management and improvements in this aspect of cancer care have contributed to the increasing survival rates.
Infection from immunosuppression
Due to both treatment (chemotherapy or wide-field radiation) and underlying disease, children with cancer are immunocompromised and at risk of serious infection. Children with fever and neutropenia must be admitted promptly to hospital for cultures and treatment with broad-spectrum antibiotics. Some important opportunistic infections associated with therapy for cancer include Pneumocystis jiroveci (carinii) pneumonia (especially in children with leukaemia), disseminated fungal infection (e.g. aspergillosis and candidiasis) and coagulase-negative staphylococcal infections of central venous catheters.
Most common viral infections are no worse in children with cancer than in other children, but measles and varicella zoster (chickenpox) may have atypical presentation and can be life-threatening. If non-immune, immunocompromised children are at risk from contact with measles or varicella, some protection can be afforded by prompt administration of immunoglobulin or zoster immune globulin. Aciclovir is used to treat established varicella infection, but no treatment is available for measles. During chemotherapy and from 6 months to a year subsequently, the use of live vaccines is contraindicated due to depressed immunity. After this period, re-immunisation against common childhood infections is recommended.
Bone marrow suppression
Anaemia may require blood transfusions. Thrombocytopaenia presents the hazard of bleeding, and considerable blood product support may be required, particularly for children with leukaemia, those undergoing intensive therapy requiring bone marrow transplantation and in the more intensive solid tumour protocols.
Gastrointestinal damage, nausea and vomiting and nutritional compromise
Mouth ulcers are common, painful and, when severe, can prevent a child eating adequately. Many chemotherapy agents are nauseating and induce vomiting, which may be only partially prevented by the routine use of antiemetic drugs. These two complications can result in significant nutritional compromise. Chemotherapy-induced gut mucosal damage also causes diarrhoea and may predispose to Gram-negative infection.
Drug-specific side-effects
Many individual drugs have very specific side-effects: e.g. cardiotoxicity with doxorubicin; renal failure and deafness with cisplatin; haemorrhagic cystitis with cyclophosphamide; and neuropathy with vincristine. The extent of these side-effects is not always predictable and patients require careful monitoring during, and in some cases, after treatment is complete.
Other supportive care issues
Fertility preservation
Some patients may be at risk of infertility as a result of their cancer treatment. Appropriate fertility preservation techniques may involve surgically moving a testis or ovary out of the radiotherapy field; sperm banking (which should be offered to boys mature enough to achieve this); and consideration of newer techniques such as cryopreservation of ovarian cortical tissue, although the long-term efficacy of this is still uncertain.
Venous access
The discomfort of multiple venepunctures for blood sampling and intravenous infusions can be avoided with central venous catheters, although these do carry a risk of infection (Fig. 21.4).
Fever with neutropenia requires hospital admission, cultures and intravenous antibiotics.Psychosocial support
The diagnosis of a potentially fatal illness has an enormous and long-lasting impact on the whole family. They need the opportunity to discuss the implications of the diagnosis and its treatment and their anxiety, fear, guilt and sadness. Most will benefit from the counselling and practical support provided by health professionals. Help with practical issues, including transport, finances, accommodation and care of siblings, is an early priority. The provision of detailed written material for parents will help them understand their child’s disease and treatment. The children themselves, and their siblings, need an age-appropriate explanation of the disease. Once treatment is established and the disease appears to be under control, families should be encouraged to return to as normal a lifestyle as possible. Early return to school is important and children with cancer should not be allowed to under-achieve the expectations previously held for them. It is easy to underestimate the severe stress that persists within families in relation to the uncertainty of the long-term outcome. This often manifests itself as marital problems in parents and behavioural difficulties in both the child and siblings.
Leukaemia
Acute lymphoblastic leukaemia (ALL) accounts for 80% of leukaemia in children. Most of the remainder is acute myeloid/acute non-lymphocytic leukaemia (AML/ANLL). Chronic myeloid leukaemia and other myeloproliferative disorders are rare.
Clinical presentation
Presentation of acute lymphoblastic leukaemia peaks at 2–5 years. Clinical symptoms and signs result from disseminated disease and systemic ill-health from infiltration of the bone marrow or other organs with leukaemic blast cells (Fig. 21.5). In most children, leukaemia presents insidiously over several weeks (see Case History 21.1) but in some children the illness presents and progresses very rapidly.
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