Guideline 76: Long term follow up care or survivors of childhood cancer

Long term follow up of survivors of childhood cancer
Section 1: Introduction

1.1 Population covered by the guideline

This guideline is applicable to all young people who have survived cancer, and who may experience expected and unexpected late effects that are related to the treatment received, rather than the specific cancer. The guideline is aimed at primary care staff who have cancer survivors as their patients, as well as secondary care and long term follow up (late effects) clinic staff who usually manage the long term care of this group.

1.2 Definitions

Childhood cancers exhibit greater diversity in terms of anatomical site and histological type than adult cancers, where carcinomas of the breast, lung and gut predominate.

Of all childhood cancers, approximately:

one third are leukaemias and 80% of these are acute lymphoblastic leukaemia (ALL)
25% are brain and spinal tumours
15% are embryonal tumours (neuroblastoma, retinoblastoma, Wilms’ tumour and hepatoblastoma)
11% are lymphomas (Hodgkin’s and non-Hodgkin’s lymphomas; NHL)

The remainder is comprised of bone (osteosarcoma and Ewing’s sarcoma) and soft tissue tumours (rhabdomyosarcoma), and a variety of more rare tumours.¹

1.3 Remit of the guideline

Childhood cancer may be treated with surgery, chemotherapy, radiotherapy and/or bone marrow transplantation. Long term morbidity risks in childhood cancer survivors largely relate to treatment modality and the challenge remains to further improve survival rates whilst reducing the incidence and severity of such treatment-induced late effects. A major challenge faced by paediatric oncologists is to sustain the excellent survival rates whilst striving to achieve optimal quality of life. With follow up and early detection and treatment, many potential problems may be ameliorated, allowing cancer survivors to enjoy full and active lives.

This guideline covers five key areas:

assessment and achievement of normal growth (see section 3)
achievement of normal progression through puberty and factors affecting fertility (see section 4)
early identification, assessment and treatment of cardiac abnormalities (see section 5)
assessment of thyroid function (see section 6)
assessment and achievement of optimum neurodevelopment and psychological health (see section 7).

The guideline does not systematically address other important areas, including second malignancy, or renal, respiratory and liver dysfunction. Late effects involving vision and hearing have also not been addressed.

1.4 The need for a guideline

Continuing therapeutic advances for the management of childhood malignancies mean that the majority of children can realistically expect long term survival.^{1,
2} Cancer in childhood is rare, with about 125 new cases per year in Scotland, and a cumulative risk of around one in 500 by the age of 15 years. With long term survival rates of around 70%, it has been estimated that by the year 2010, about one in 715 of the adult population will be a long term survivor of childhood cancer (NHSScotland Information and Statistics Division, unpublished data).

Table 1: 5-year survival rates (%) in childhood cancers from 1962-1996.
(Source - National Registry of Childhood Tumours)

	1962-66	1967-71	1972-76	1977-81	1982-86	1987-91	1992-96
ALL	4	17	44	56	70	75	81
Acute non-lymphoblastic leukaemia	2	2	7	17	30	47	54
CNS	37	37	43	48	54	57	68
Ewing's	25	23	40	34	45	68	61
Gonadal germ-cell	55	52	56	74	90	94	96
Hodgkin's	39	68	81	89	89	93	94
NHL	17	21	26	45	67	76	78
Neuroblastoma	18	17	19	31	43	41	53
Osteosarcoma	17	18	22	25	47	51	57
Retinoblastoma	88	86	86	88	90	95	96
Rhabdomyo-sarcoma	25	23	33	44	58	59	66
Wilms'	29	43	62	76	80	82	80
ALL CANCERS	24	29	42	51	62	67	73

Data up to 1999 show that these survival rates have been sustained (NHSScotland Information and Statistics Division, unpublished data). Large epidemiological studies have analysed the subsequent mortality and its causes in children and adolescents who survived five years from the diagnosis of cancer. Two studies^{3,
4} found that 5-year survivors of childhood cancer have a standardised mortality ratio of 11 (ie an 11 fold increased risk of death in subsequent years when compared with age and sex specific expected rates for the general population). A North American study ³ described a cohort of 20,227 5-year survivors of cancer diagnosed between 1970 and 1986 before the age of 21, which included 208,947 person years of follow up. The risk of death in this cohort was significantly higher in females (standardised mortality ratio, SMR=18.2), individuals diagnosed with cancer before the age of 5 years (SMR=14.0) and those with an initial diagnosis of leukaemia (SMR=15.5) or central nervous system tumour (SMR=15.7). The leading cause of death among 5-year survivors was recurrence of the original cancer with a statistically significant excess mortality rate seen due to subsequent malignancies (SMR=19.4) as well as cardiac (SMR=8.2), pulmonary (SMR=9.2) and other causes (SMR=3.3). Of the cohort, 90% were alive at the time of the study with death due to recurrent cancer accounting for 67% of all deaths. There was no excess mortality from external causes, for example, road traffic accidents. These studies may provide a resource for understanding how mortality may be reduced further, and how modifications of current therapy may reduce treatment related mortality in the future.

An important challenge for this guideline is to make evidence based recommendations for the long term follow up of survivors that address their needs. In areas where there is no evidence, the guideline highlights research opportunities to study and evaluate the long term effects of treatment so that promising interventions can be assessed through collaborative multicentre studies.⁵

1.5 Statement of intent

This guideline is not intended to be construed or to serve as a standard of medical care. Standards of care are determined on the basis of all clinical data available for an individual case and are subject to change as scientific knowledge and technology advance and patterns of care evolve. These parameters of practice should be considered guidelines only. Adherence to them will not ensure a successful outcome in every case, nor should they be construed as including all proper methods of care or excluding other acceptable methods of care aimed at the same results. The ultimate judgement regarding a particular clinical procedure or treatment plan must be made by the doctor, following discussion of the options with the patient, in light of the diagnostic and treatment choices available. However, it is advised that significant departures from the national guideline or any local guidelines derived from it should be fully documented in the patient’s case notes at the time the relevant decision is taken.

1.6 Review and updating

This guideline was issued in 2004 and will be considered for review as new evidence becomes available. Any updates to the guideline in the interim period will be noted on the SIGN website: www.sign.ac.uk