Summary of SIGN recommendations on long-term follow-up of survivors of childhood cancer
| Late effect | High-risk factors | Specific late effects | Screening methods/ management | Evidence level/grade |
|---|---|---|---|---|
| Subsequent primary cancers (SPCs) | Genetic predisposition, eg, NF-1 | Dependent on syndrome | As per guidance for specific syndromes | |
| Radiotherapy | Delayed presentation >5 years from treatment, at edge of radiation field (eg, mediastinal radiotherapy and breast SPCs) | No consensus Promote healthy lifestyle behaviours | 3/C | |
| Chemotherapy* (alkylating agents, epipodophyllotoxins) | Increased risk of all SPCs | No consensus Promote healthy lifestyle behaviours | 3/C | |
| Sub-/infertility | Both sexes | |||
| Cranial radiotherapy | Hypogonadotropic hypogonadism (pubertal arrest/ delay) | See individual sections for assessment depending on sex | 3 | |
| Pelvic radiotherapy | Sexual dysfunction | Consider psychological referral | 3–4/D | |
| Boys | ||||
| Chemotherapy* (alkylating agents) | Azoospermia | Semen analysis±cryopreservation, FSH, inhibin B | 3/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 | 2±3/D | |
| Girls | ||||
| Chemotherapy* (alkylating agents) | Hypergonadotropic hypogonadism (pubertal arrest/ delay/ oligoamenorrhoea) | Regular pubertal assessment, FSH, AMH ±pubertal induction/ female hormone replacement therapy ±oocyte cryopreservation if postpubertal | 3/D | |
| Abdominopelvic radiotherapy | Hypergonadotropic hypogonadism Uterine dysfunction (premature delivery, low birth weight) | |||
| Cardiac effects | Chemotherapy (anthracyclines) | Congestive heart failure | Echocardiography: 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 | 3–4/D 3/D |
| Cardiac/mediastinal radiotherapy | Cardiovascular (especially coronary artery) disease | |||
| Bone health | Chemotherapy (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 | 3/D |
| Metabolic syndrome | ALL (especially after bone marrow transplantation) Brain tumours (especially after cranial radiotherapy and growth hormone deficiency) | Obesity Dyslipidaemia 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 | 3–4/D |
| Cognitive outcomes | Cranial radiotherapy | Cognitive decline Psychosocial dysfunction | Neuropsychological assessment: Pretreatment and then annually | 3/D |
| Growth | Craniopharyngiomas (and other hypothalamopituitary tumours) | Growth hormone deficiency Pubertal delay/ arrest | Regular height monitoring Pituitary function testing at diagnosis and regularly thereafter | 2+/B-C |
| Cranial radiotherapy | Growth hormone deficiency Precocious puberty Pubertal delay/ arrest Other pituitary hormone deficiencies | Regular height monitoring and pubertal assessment Paediatric endocrinology referral if reduced height velocity | 2+-2++/B-C | |
| (Cranio) spinal radiotherapy | Spinal growth retardation | Regular height monitoring+sitting height | 2+/B | |
| Thyroid dysfunction | Neck, (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 | 2±2++/D |
| Cranial radiotherapy | Secondary/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.