Table 1

Summary of SIGN recommendations on long-term follow-up of survivors of childhood cancer

Late effectHigh-risk factorsSpecific late effectsScreening methods/ managementEvidence level/grade
Subsequent primary cancers (SPCs)Genetic predisposition, eg, NF-1Dependent on syndromeAs per guidance for specific syndromes
RadiotherapyDelayed presentation >5 years from treatment, at edge of radiation field (eg, mediastinal radiotherapy and breast SPCs)No consensus
Promote healthy lifestyle behaviours
Chemotherapy* (alkylating agents, epipodophyllotoxins)Increased risk of all SPCsNo consensus
Promote healthy lifestyle behaviours
Sub-/infertilityBoth sexes
 Cranial radiotherapyHypogonadotropic hypogonadism (pubertal arrest/ delay)See individual sections for assessment depending on sex3
 Pelvic radiotherapySexual dysfunctionConsider psychological referral3–4/D
 Chemotherapy* (alkylating agents)AzoospermiaSemen analysis±cryopreservation, FSH, inhibin B3/D
 Gonadal radiotherapy/ total body irradiation (TBI)Azoospermia
Hypergonadotropic hypogonadism (less likely—pubertal arrest/ delay, sexual dysfunction)
Semen analysis±cryopreservation, FSH, inhibin B
Regular pubertal assessment, LH, testosterone
±pubertal induction/ testosterone supplementation
 Chemotherapy* (alkylating agents)Hypergonadotropic hypogonadism (pubertal arrest/ delay/ oligoamenorrhoea)Regular pubertal assessment, FSH, AMH
±pubertal induction/ female hormone replacement therapy
±oocyte cryopreservation if postpubertal
 Abdominopelvic radiotherapyHypergonadotropic hypogonadism
Uterine dysfunction (premature delivery, low birth weight)
Cardiac effectsChemotherapy (anthracyclines)Congestive heart failureEchocardiography: Fractional shortening (FS) and ejection fraction (EF) measurements
2–3 yearly if anthracycline dose >250 mg/m2
5 yearly if anthracycline dose <250 mg/m2
Treat as per regular heart failure/cardiovascular disease guidelines
Promote healthy lifestyle behaviours
Cardiac/mediastinal radiotherapy Cardiovascular (especially coronary artery) disease
Bone healthChemotherapy (glucocorticoids, high dose methotrexate, 6-mercaptopurine)
Cranial radiotherapy
Bone marrow transplantation
Endocrine dysfunction (GH deficiency, hypogonadism, hypothyroidism)
Osteoporosis (osteonecrosis with glucocorticoids)Dual energy X-ray absorptiometry (DXA)/ peripheral quantitative CT/ quantitative ultrasound: BMD or bone mineral content (BMC) Z-scores adjusted for age, sex and height 2 years post-end of treatment
Serial measurements not required unless abnormal or clinical change
Sex steroid replacement
Promote healthy lifestyle behaviours
Metabolic syndromeALL (especially after bone marrow transplantation)
Brain tumours (especially after cranial radiotherapy and growth hormone deficiency)
Insulin resistance
Cardiovascular disease
BP and BMI: Annually in all survivors
Fasting glucose, insulin, lipid profile:
2-yearly if obese/ overweight
5-yearly if normal weight
Treat as per regular obesity guidelines
Cognitive outcomesCranial radiotherapyCognitive decline
Psychosocial dysfunction
Neuropsychological assessment: Pretreatment and then annually3/D
GrowthCraniopharyngiomas (and other hypothalamopituitary tumours)Growth hormone deficiency
Pubertal delay/ arrest
Regular height monitoring
Pituitary function testing at diagnosis and regularly thereafter
Cranial radiotherapyGrowth hormone deficiency
Precocious puberty
Pubertal delay/ arrest
Other pituitary hormone deficiencies
Regular height monitoring and pubertal assessment
Paediatric endocrinology referral if reduced height velocity
(Cranio) spinal radiotherapySpinal growth retardationRegular height monitoring+sitting height2+/B
Thyroid dysfunctionNeck, (cranio) spinal and total body irradiation
MIBG therapy
Primary hypothyroidism
Thyroid nodules
Thyroid cancer
Thyroid function tests: At end of treatment and then annually
Thyroid hormone replacement
No consensus about thyroid nodules/ cancer—patient education
Cranial radiotherapySecondary/tertiary hypothyroidism
Chemotherapy?Unclear mechanism
  • *Clinicans should note that all chemotherapy may be associated with an increased risk of SPCs and sub-/infertility. ALL, acute lymphoblastic leukaemia; AMH, anti-Mullerian hormone; BMD, bone mineral density; BMI, body mass index; FSH, follicle-stimulating hormone; LH, luteinising hormone; MIBG, metaiodobenzylguanidine; NF-1, neurofibromatosis type 1; SIGN, Scottish Intercollegiate Guidelines Network.