TABLE 1

Potential Late Effects of Selected Therapeutic Interventions for Childhood Cancer According to Organ System

Organ SystemTherapeutic ExposuresPotential Late Effect
ChemotherapyRadiation Therapy FieldSurgery
SkinAll fieldsDysplastic nevi; skin cancer
OcularBusulfan; corticosteroidsCranial; orbital/eye; TBINeurosurgeryCataracts; retinopathy (XRT doses ≥ 30 Gy only); ocular nerve palsy (neurosurgery only)
AuditoryCisplatin; carboplatin (in myeloablative doses only)≥30 Gy to: cranial, ear/infratemporal, nasopharyngealSensorineural hearing loss; conductive hearing loss (XRT only); Eustachian tube dysfunction (XRT only)
DentalAny chemotherapy before development of secondary dentitionHead and neck fields that include the oral cavity or salivary glands (eg, cranial, oropharyngeal, mantle, TBI)Dental maldevelopment (tooth/root agenesis, microdontia, enamel dysplasia); periodontal disease; dental caries; osteoradionecrosis (XRT doses ≥ 40 Gy)
CardiovascularAnthracycline agents (eg, doxorubicin, daunorubicin)Chest (eg, mantle, mediastinal); upper abdominalCardiomyopathy; congestive heart failure; arrhythmia; subclinical left ventricular dysfunction; XRT only: valvular disease, atherosclerotic heart disease, myocardial infarction, and pericarditis, pericardial fibrosis
PulmonaryBleomycin; busulfan; carmustine; lomustineChest (mantle, mediastinal, whole lung); TBIPulmonary resection; lobectomyPulmonary fibrosis; interstitial pneumonitis; restrictive/obstructive lung disease; pulmonary dysfunction
BreastChest (mantle, mediastinal, axillary, whole lung, TBI)Breast tissue hypoplasia; breast cancer (XRT doses ≥ 20 Gy)
GastrointestinalAbdominal, pelvic (doses ≥ 30 Gy)Laparotomy; pelvic/spinal surgeryChronic enterocolitis; gastrointestinal tract strictures; adhesions/obstruction; fecal incontinence; colon cancer (XRT only; doses ≥ 30 Gy)
LiverAntimetabolites (mercaptopurine, thioguanine, methotrexate)Abdominal (doses ≥ 30 Gy)Hepatic dysfunction; veno-occlusive disease (VOD); hepatic fibrosis, cirrhosis; cholelithiasis
RenalCisplatin; carboplatin; ifosfamide; methotrexateAbdominal (including kidney)NephrectomyGlomerular toxicity; tubular dysfunction; renal insufficiency; hypertension
BladderCyclophosphamide; ifosfamidePelvic (including bladder); lumbar-sacral spineSpinal surgery; cystectomyHemorrhagic cystitis; bladder fibrosis; dysfunctional voiding; neurogenic bladder; bladder malignancy (cyclophosphamide, XRT)
Sexual/reproductive
    MalesAlkylating agents (eg, busulfan, carmustine, lomustine, cyclophosphamide, mechlorethamine, melphalan, procarbazine)Hypothalamic-pituitary; testicular; pelvic; TBIPelvic/spinal surgery; orchiectomyDelayed/arrested puberty; hypogonadism; infertility; erectile/ejaculatory dysfunction
    FemalesAlkylating agents (eg, busulfan, carmustine, lomustine, cyclophosphamide, mechlorethamine, melphalan, procarbazine)Hypothalamic-pituitary; pelvic; ovarian; lumbar-sacral spine; TBIOophorectomyDelayed/arrested puberty; premature menopause; infertility; uterine vascular insufficiency (XRT only); vaginal fibrosis/stenosis (XRT only)
Endocrine/metabolicHypothalamic-pituitary; neck (thyroid)ThyroidectomyGrowth hormone deficiency; precocious puberty; hypothyroidism; thyroid nodules/cancer; XRT doses ≥ 40 Gy: hyperprolactinemia, central adrenal insufficiency, gonadotropin deficiency, and hyperthyroidism
MusculoskeletalCorticosteroids; methotrexateOsteopenia/osteoporosis; osteonecrosis
All fieldsReduced/uneven growth; reduced function/mobility; hypoplasia, fibrosis; radiation-induced fracture (doses ≥ 40 Gy); scoliosis/kyphosis (trunk fields only); secondary benign or malignant neoplasm
Amputation; limb sparingReduced/uneven growth; reduced function/mobility
NeurocognitiveMethotrexate (intrathecal administration or IV doses ≥ 1000 mg/m2); cytarabine (IV doses ≥ 1000 mg/m2)Cranial; ear/infratemporal; total body irradiationNeurosurgeryNeurocognitive deficits (executive function, attention, memory, processing speed, visual motor integration); learning deficits; diminished IQ
Central nervous systemMethotrexate, cytarabine (intrathecal administration or IV doses ≥ 1000 mg/m2)Doses ≥ 18 Gy to: cranial, orbital/eye, ear/infratemporal, nasopharyngealNeurosurgeryLeukoencephalopathy (spasticity, ataxia, dysarthria, dysphagia, hemiparesis, seizures [chemotherapy and XRT]); motor and sensory deficits; cerebrovascular complications (stroke, Moya Moya, occlusive cerebral; vasculopathy [XRT and surgery]) Brain tumor (any XRT dose)
Peripheral nervous systemPlant alkaloids (vincristine, vinblastine); cisplatin, carboplatinSpinal surgeryPeripheral sensory or motor neuropathy
ImmunologicAbdomen, left upper quadrant, spleen (doses ≥ 40 Gy)SplenectomyLife-threatening infection related to functional or anatomic asplenia (note: functional asplenia can also occur as a consequence of active chronic graft-vs-host disease after hematopoietic stem cell transplant)
PsychosocialAnyAnyAnySocial withdrawal; educational problems; depression; anxiety; posttraumatic stress
  • This table briefly summarizes potential late effects for selected therapeutic exposures only; the complete set of long-term follow-up guidelines from the Children's Oncology Group, including screening recommendations, is available at www.survivorshipguidelines.org. XRT indicates radiation therapy; TBI, total body irradiation; IV, intravenous.