Table 3.

Common potential late effects, associated risk factors and health screening recommendations for pediatric CNS (central nervous system) tumsor survivors

Potential Late Effect	Risk Factor	Health Screening Recommendations **
Altered Bone Composition Osteonecrosis (avascular necrosis) Osteopenia Osteoporosis	Chemotherapy: antimetabolite (methotrexate Corticosteroids: (dexamethasone Radiation: Brain	History: joint pain, swelling, immobility, limited range of motion Physical: musculoskeletal exam Imaging: bone density evaluation
Cerebrovascular Complications Stroke Moyamoya Occlusive cerebral vasculopathy Cavernomas	Radiation: Brain (≥18cGy)	History: hemiparesis, hemiplegia, weakness, aphasia Physical: neurologic exam Measurements: blood pressure Imaging: MRI Brain, MRA Referral: Neurology, Physical and Occupational therapy
Dental Problems Enamel dysplasia Increased risk for dental caries Root thinning/shortening Tooth/root agenesis	Any chemotherapy Radiation: Brain	History: dry mouth Physical: oral exam Referral: Dental
Endocrine: Gonadal Dysfunction Female: Delayed/arrested puberty Premature menopause Infertility Male: Delayed/arrested puberty Testosterone deficiency/insufficiency Reduced fertility Oligospermia Azoospermia Infertility	Chemotherapy: alkylating agents (busulfan, cyclophosphamide, ifosfamide, lomustine, procarbazine, thiotepa) and heavy metals (carboplatin, cisplatin Radiation: Spine	History (All): pubertal onset, tempo of puberty, sexual function History (Females): menstruation, pregnancy Physical (All): tanner staging Physical (Male): testicular volume Screening Labs (Females): FSH/LH, Estradiol level Screening Labs (Males): FSH/LH, Morning Testosterone, Sperm analysis Referral (All): Reproductive endocrinology Referral (Females): Gynecology, Referral (Males): Urology
Endocrine: Hormonal Deficiency FSH/LH deficiency	Radiation: Brain	See above
Endocrine: Metabolic Syndrome Type II diabetes Insulin resistance Abnormal lipids	Radiation: Brain Neurosurgery: Brain (suprasellar region)	History: polyuria, polydipsia, polyphagia Measurements: Height, Weight, BMI Labs: Na, K, glucose, Cl, CO2, fasting lipid panel, insulin, HgA1C, Referral: Endocrinology
Endocrine: Hypothalamic Pituitary Dysfunction Growth hormone (GH) deficiency Precocious puberty FSH/LH deficiency Hx vag dryness, decreased libido	Radiation: Brain (≥ 18cGy Radiation: Brain (≥ 30cGy)	History: previous growth velocity, fatigue, onset of puberty, nutritional status Physical (All): tanner staging Physical (Male): testicular volume Measurements: height, weight, BMI (Note the corresponding percentile on growth chart Imaging: bone age Labs (All): CBC, Electrolytes, LFTs, FSH/LH, TSH, Free T4, Labs (Male): testosterone level Referral: Endocrinology
Endocrine: Hypothalamic Pituitary Dysfunction Adrenocorticotropic hormone (ACTH) deficiency (adrenal insufficiency)	Radiation: Brain (≥ 30cGy)	History: anorexia, dehydration, hypoglycemia, lethargy, unexplained HTN Labs: morning cortisol
Endocrine: Hypothalamic Pituitary Dysfunction TSH deficiency	Radiation: Brain (≥ 30cGy)	History: fatigue, wt gain cold intol, constipation, weight gain, dry skin, brittle hair, depressed mood PE: ht, wt, hair, skin, thyroid Labs: Free T4
Endocrine: Hypothalamic Pituitary Dysfunction Hyperprolactinemia	Radiation: Brain (≥ 40cGy)	History: galactorrhea or decreased libido Labs: prolactin if pt has galactorrhea, or decreased libido
Endocrine: Obesity Overweight Obesity	Radiation: Brain	History: diet and activity level Measurements: height, weight, BMI, blood pressure Referral: Nutritionist
Endocrine: Thyroid Problems Primary hypothyroidism Thyroid nodule	Radiation: Brain/Spine	History: fatigue, cold intolerance, constipation, weight gain, dry skin, brittle hair, depressed mood Physical: hair, skin, thyroid exam Measurements: height, weight (Note the corresponding percentile on growth chart Labs: TSH, Free T4 Referral: Endocrinology
ENT Problems chronic sinusitis	Radiation: Brain	History: rhinorrhea, nasal discharge Referral: ENT
Eye Problems Gaze paresis Nystagmus Ocular nerve palsy Optic atrophy Papilledema Vision deficits Cataracts	Corticosteroids: (dexamethasone Radiation: Brain Chemotherapy: busulfan	History: visual changes (decreased acuity, diplopia Physical: eye exam (visual acuity, fundoscopic exam for lens opacity Referral: Ophthalmologist
GI: Bowel Dysfunction Neurogenic bowel Fecal incontinence	Neurosurgery: Spinal Cord	History: Chronic constipation, Fecal soiling Physical: Rectal exam Referral: GI
GU: Bladder Dysfunction Neurogenic bladder Urinary incontinence	Radiation: Spine (lumbar, sacral, cauda equina Neurosurgery: Spinal Cord	History: urinary urgency/frequency, urinary incontinence/retention, dysuria, nocturia, abnormal urinary stream Measurements: blood pressure Labs: BUN, Creatinine, Na, K, Cl, CO,Ca, Mg, PO4; Urinalysis Referral: Urology
GU: Urinary Tract Dysfunction Dysfunctional voiding Hemorrhagic cystitis	Chemotherapy: alkylating agents (cyclophosphamide, ifosfamide Radiation: Spine (sacral, total spine)	History: Urinary urgency/frequency, urinary incontinence/retention, dysuria, nocturia, abnormal urinary stream Measurements: blood pressure Labs: BUN, Creatinine, Na, K, Cl, CO, Ca, Mg, PO4, Urinalysis Referral: Urology
GU: Renal Glomerular injury HTN Tubular/renal insufficiency	Chemotherapy:, carboplatin, cisplatin, cyclophosphamide	Measurement: blood pressure Labs: same as above Referral: Nephrology
Hearing Problems Hearing loss (sensorineural) Tinnitus Vertigo	Chemotherapy: heavy metals (carboplatin, cisplatin)	History: hearing difficulty, tinnitus, vertigo Physical: otoscopic exam Screening: audiogram Referral: Audiology; speech therapy for patients with hearing loss.
Ototoxicity Tympano sclerosis Conductive hear loss Sensorineural hearing loss	Radiation Brain >30	See above
Musculoskeletal Alteration: Growth Problems Decreased spinal growth Short stature	Radiation: Spine (all fields)	Measurements: limb lengths, sitting height, height, weight Referral: Orthopedic
Musculoskeletal Alteration: Spine Deformity Scoliosis/Kyphosis	Radiation: Spine Neurosurgery: Spinal Cord (laminectomy, laminoplasty)	Physical: spine exam for scoliosis and kyphosis Referral: Orthopedic
Neurocognitive Dysfunction Attention Behavioral change Diminished IQ Executive function (planning, organizing) Learning deficits (particularly in math and reading comprehension) Memory Processing speed Visual-motor integration	Chemotherapy: antimetabolite (methotrexate Radiation: Brain Neurosurgery: Brain	History: educational and/or vocational progress Physical: neurologic exam Screening: formal neuropsychological evaluation Referral: Neuropsychology
Neurological: Clinical leukoencephalopathy Ataxia Dysarthria Dysphagia Headaches Hemiparesis Seizures Spasticity	Chemotherapy: antimetabolite (methotrexate), cytarabine Radiation: Brain ≥24cGy Neurosurgery: Brain	History: cognitive, motor, sensory deficits, seizures, other neurologic symptoms Physical: neurologic exam Imaging: MRI Brain, MRA Referral: Neurology
Neurological: Impaired CSF Diversion Hydrocephalus Shunt malfunction	Neurosurgery: Brain	Imaging: X-ray shunt series (skull and abdominal images Referral: Neurosurgery
Neurological: Motor and/or sensory deficits Paralysis Movement disorders Ataxia Eye problems (ocular nerve palsy, gaze paresis, nystagmus, papilledema, optic atrophy)	Neurosurgery: Brain	Physical: neurologic exam Referral: Neurology, Physiatrist/rehabilitation medicine specialist, speech, physical, occupational therapies
Neurosensory Problems: Peripheral motor and/or sensory neuropathy Foot drop Paresthesias Sensory deficits Areflexia Weakness	Chemotherapy with plant alkaloids (vinblastine, vincristine)and heavy metals (carboplatin, cisplatin)	History: areflexia, weakness, foot drop, paresthesias, dysesthesias Physical: neurologic exam Referral: Neurologist and physical therapy for symptomatic neuropathy
Pulmonary Dysfunction Pulmonary fibrosis	Chemotherapy: alkylating agents (lomustine, busulfan)	History: Cough, SOB, DOE, wheezing, poor growth Measurements: height, weight Physical: Pulmonary exam Screening: PFTs (complete pulmonary function testing)
Psychosocial/Behavioral Anxiety Depression Educational problems Post traumatic stress disorder (PTSD) Risky behaviors Social withdrawal Unemployment	Any cancer experience	History: psychosocial assessment (educational and/or vocational progress, social withdrawal Referral: Psychiatry
Second Malignancy Acute myeloid leukemia (AML)	Chemotherapy: epipodophyllotoxins (etoposide Chemotherapy: high dose alkylating agents (cyclophosphamide, ifosfamide, lomustine)	History: fatigue, bleeding, easy bruising Physical: dermatological exam (pallor, petechiae, purpura Labs: CBC, bone marrow exam as indicated Referral: Oncology
Second Malignancy Bladder	Chemotherapy: high dose alkylating agents (cyclophosphamide, ifosfamide, lomustine)	History: hematuria, urinary urgency, urinary frequency, dysuria Labs: Urinalysis Referral: Urology
Second Malignancy Thyroid	Radiation: Brain/Spine	Physical: thyroid exam Referral: Endocrinology
Second Malignancy Recurrence of the primary brain tumor Secondary benign or malignant neoplasm occurring in or near radiation field (i.e. radiation induced meningioma or skin lesion)	Radiation: Brain	History: headaches, vomiting, cognitive, motor or sensory deficits, seizures and other neurologic symptoms; skin changes (i.e. moles Physical: Neurologic exam, Ophthalmology exam, Dermatological exam Imaging: MRI Brain Referral: Oncology, Neurology, Neurosurgery, Dermatology
Sexual Dysfunction Psychosexual Dysfunction	Neurosurgery: Spinal Cord	History (Males): erectile/ejaculatory dysfunction History (Females): altered, diminished or loss of sensation, dyspareunia Referral (Males): Urology Referral (Females): Gynecology Referral (All): counseling

Children’s Oncology Group. Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer version 4.0. http://www.survivorshipguidelines.org/pdf/LTFUGuidelines_40.pdf. October 2013. Accessed 12/01/14