Cancer Research UK : Childhood Cancer treatment and follow-up

Childhood Cancer treatment and follow-up

The treatment of childhood cancer in the UK and Eire is usually co-ordinated, if not carried out, by one of the 22 United Kingdom Children's Cancer Study Group centres.

Much of this treatment is based on the results of previous clinical trials or part of current national or international clinical trials.1

For several types of cancer, survival has been found to be higher among children treated in clinical trials or treated at specialist centres.2-3

Surgery, chemotherapy, radiotherapy and combinations of any or all of these form the mainstay of treatment for most childhood cancers. Stem cell transplantation is becoming more widely used for some conditions, and other new therapies are being tried.

Follow-up

Long-term clinical follow-up

There is currently some debate about which survivors of childhood cancer should continue to be followed up indefinitely.4 Individuals who have had surgery only, or a small amount of chemotherapy with drugs that have no known long-term effects, may need no follow-up.These include, for example, some Wilms' tumour patients treated with surgery alone, who need only to be made aware of the fact that one kidney has been removed and the reason.

Children who have had intensive, prolonged multi-agent chemotherapy or radiotherapy should be followed up by clinicians who have experience in diagnosing and treating problems which occur after such treatment.

Many of the individuals who are going to have ongoing problems are obvious by five years from the end of treatment - a time at which many clinicians choose to transfer patients to a long term follow-up clinic.

There are also groups of patients who are recognised as being at increased risk of running into specific problems. For example, high doses of anthracyclines can damage cardiac muscle, and either radiotherapy to certain sites or high-dose therapy combined with stem-cell treatment may lead to a reduction in fertility.5

Second malignancies

All children who have had one cancer are at slightly higher risk of having a second malignant neoplasm.

Overall, the risk of developing a second cancer within 25 years is about 4%.6-8 The risk will be higher if they are from a family with increased risk of cancer and there is a particularly high risk of developing a second cancer for survivors of the heritable form of retinoblastoma.9

The risk is also higher for survivors who have had radiotherapy or certain drugs as part of their treatment.10-11 Among survivors who have had radiotherapy the risk increases with radiation dose.10

Survivors of ALL treated after 1983 in the USA showed a cumulative incidence of any second neoplasm of 1.2% at 10 years (a 7.2-fold increase). The risk of second neoplasm increased with radiation dose.12

The commonest second tumours after ALL are in the central nervous system and the risk is greatest for those treated at younger ages. A study looking especially at the risk after total body irradiation (as used in bone arrow/stem cell transplantation) found rates of new solid cancers 8.3 times higher than expected among those who survived ten or more years.13

The evidence for chemotherapeutic agents as risk factors for the development of subsequent neoplasms is less clear-cut. Epipodophyllotoxins, alkylating agents and antimetabolites have all been implicated.

The risk of secondary AML or myelodysplasia in children treated with epipodophyllotoxins is 2- 4% at six years; in some studies the risk increased with cumulative dose14-15, while in others it was related to schedule and dose intensity.16-17

Epidemiological studies of late effects

Other, less serious late effects have until recently been less well documented, but large epidemiological studies of long-term survivors of childhood cancer in the UK and North America will in due course yield a comprehensive picture of the health and quality of life of the rapidly increasing number of adult survivors.4, 18

Future

Although great strides have been made in the treatment of many types of childhood malignancy, in others there is room for more improvement. For example there are currently international clinical trials of new drugs and new ways of giving radiotherapy in childhood brain tumours.

For diseases such as ALL, where the cure rate is as high as 80%, the relatively small proportion of children who do not respond adequately to treatment continue to be a challenge to the clinicians. The more recent trials aim to give those individuals at greater risk of relapse more intensive and prolonged therapy.

There are also continued efforts to improve the safe delivery of multi-agent chemotherapy and bone marrow transplantation.

For details on current clinical trials in childhood cancer see UKCCSG

The improvements in the treatment of childhood cancer since the 1960s have meant that for children diagnosed with cancer today the chance of cure is high. The challenges for the future are to minimise the long term effects, both physical and psychological, of these cures, while striving for further increases in survival.

References

Ablett, S., Recruiting children into cancer trials--role of the United Kingdom Children's Cancer Study Group (UKCCSG). Br J Cancer, 2003. 88(11): p. 1661-5
Stiller, C.A., Centralised treatment, entry to trials and survival. Br J Cancer, 1994. 70(2): p. 352-62
Stiller, C.A., Patterns of care and survival for children with acute lymphoblastic leukaemia diagnosed between 1980 and 1994. Arch Dis Child, 1999. 81(3): p. 202-8
Taylor, A., Long-term follow-up of survivors of childhood cancer in the UK. Pediatr Blood Cancer, 2004. 42(2): p. 161-8
Wallace, W.H., Developing strategies for long term follow up of survivors of childhood cancer. Bmj, 2001. 323(7307): p. 271-4
Neglia, J.P., Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study. J Natl Cancer Inst, 2001. 93(8): p. 618-29
Hawkins, M.M., G.J. Draper, and J.E. Kingston, Incidence of second primary tumours among childhood cancer survivors. Br J Cancer, 1987. 56(3): p. 339-47
Olsen, J., Second malignant neoplasms after cancer in childhood or adolescence. Nordic Society of Paediatric Haematology and Oncology Association of the Nordic Cancer Registries. Bmj, 1993. 307(6911): p. 1030-6
Fletcher, O., et al., Lifetime risks of common cancers among retinoblastoma survivors. J Natl Cancer Inst, 2004. 96(5): p. 357-63
Garwicz, S., Second malignant neoplasms after cancer in childhood and adolescence: a population-based case-control study in the 5 Nordic countries. The Nordic Society for Pediatric Hematology and Oncology. The Association of the Nordic Cancer Registries. Int J Cancer, 2000. 88(4): p. 672-8
De Vathaire, F., Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment. Br J Cancer, 1999. 79(11-12): p. 1884-93
Bhatia, S., Low incidence of second neoplasms among children diagnosed with acute lymphoblastic leukemia after 1983. Blood, 2002. 99(12): p. 4257-64
Curtis, R.E., Solid cancers after bone marrow transplantation. N Engl J Med, 1997. 336(13): p. 897-904
Hawkins, M.M., et al., Epipodophyllotoxins, alkylating agents, and radiation and risk of secondary leukaemia after childhood cancer. Bmj, 1992. 304(6832): p. 951-8
Le Deley, M.C., Risk of secondary leukemia after a solid tumor in childhood according to the dose of epipodophyllotoxins and anthracyclines: a case-control study by the Societe Francaise d'Oncologie Pediatrique. J Clin Oncol, 2003. 21(6): p. 1074-81
Smith, M.A., Secondary leukemia or myelodysplastic syndrome after treatment with epipodophyllotoxins. J Clin Oncol, 1999. 17(2): p. 569-77
Pui, C.H., Acute myeloid leukemia in children treated with epipodophyllotoxins for acute lymphoblastic leukemia. N Engl J Med, 1991. 325(24): p. 1682-7
Robison, L.L., Study design and cohort characteristics of the Childhood Cancer Survivor Study: a multi-institutional collaborative project. Med Pediatr Oncol, 2002. 38(4): p. 229-39

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