Grades of recommendations (1, 2A, 2B, 3) are defined at the end of the "Major Recommendations" field.
Note from the Children's Oncology Group and the National Guideline Clearinghouse (NGC): The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers (COG LTFU) are organized according to therapeutic exposures; this guideline has been divided into individual summaries. In addition to the current summary, the following are available:
In order to accurately derive individualized screening recommendations for a specific childhood cancer survivor using this guideline, see "Using the COG LTFU Guidelines to Develop Individualized Screening Recommendations" in the original guideline document. (Note: For ease of use, a Patient-Specific Guideline Identification Tool has been developed to streamline the process and is included in Appendix I of the original guideline document.)
Guideline Organization
The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers are organized according to therapeutic exposures, arranged by column as follows:
System |
Body system (e.g., auditory, musculoskeletal) most relevant to each guideline section. |
Score |
Score assigned by expert panel representing the strength of data from the literature linking a specific late effect with a therapeutic exposure coupled with an assessment of the appropriateness of the screening recommendation based on collective clinical experience. |
Section Number |
Unique identifier for each guideline section corresponding with listing in Index. |
Therapeutic Agent |
Therapeutic intervention for malignancy, including chemotherapy, radiation, surgery, blood/serum products, hematopoietic cell transplant, and other therapeutic modalities. |
Risk Factors |
Host factors (e.g., age, sex, race, genetic predisposition), treatment factors (e.g., cumulative dose of therapeutic agent, mode of administration, combinations of agents), medical conditions (e.g., pre-morbid or co-morbid conditions), and health behaviors (e.g., diet, smoking, alcohol use) that may increase risk of developing the complication. |
Highest Risk Factors |
Conditions (host factors, treatment factors, medical conditions and/or health behaviors) associated with the highest risk for developing the complication. |
Periodic Evaluations |
Recommended screening evaluations, including health history, physical examination, laboratory evaluation, imaging, and psychosocial assessment. Recommendation for minimum frequency of periodic evaluations is based on risk factors and magnitude of risk, as supported by the medical literature and/or the combined clinical experience of the reviewers and panel of experts. |
Health Counseling/ Further Considerations |
Health Links: Health education materials developed specifically to accompany these guidelines. Title(s) of Health Link(s) relevant to each guideline section are referenced in this column. Health Link documents are included in Appendix II of the original guideline document.
Counseling: Suggested patient counseling regarding measures to prevent/reduce risk or promote early detection of the potential treatment complication.
Resources: See the original guideline document for lists of books and web sites that may provide the clinician with additional relevant information.
Considerations for Further Testing and Intervention: Recommendations for further diagnostic evaluations beyond minimum screening for individuals with positive screening tests, recommendations for consultation and/or referral, and recommendations for management of exacerbating or predisposing conditions.
|
References |
References are listed immediately following each guideline section in the original guideline document. Included are medical citations that provide evidence for the association of the therapeutic intervention with the specific treatment complication and/or evaluation of predisposing risk factors. In addition, some general review articles have been included in the Reference section of the original guideline document for clinician convenience. |
Note: See the end of the "Major Recommendations" field for explanations of abbreviations included in the summary.
System = Dental
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
6 |
Any Chemotherapy |
Dental Abnormalities
Tooth/root agenesis
Root thinning/shortening
Enamel dysplasia
|
Host Factors
Any patient who had not developed permanent dentition at time of cancer therapy
Treatment Factors
Any radiation treatment involving the oral cavity or salivary glands
|
Host Factors
Younger age at treatment, especially <5 years old
|
Physical
Oral exam
(Yearly)
Screening
Dental exam and cleaning
(Every six months)
|
Health Links
See "Patient Resources" field
Dental Health
Considerations for Further Testing and Intervention
Regular dental care including fluoride applications. Baseline panorex prior to dental procedures to evaluate root development.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Male reproductive
Scores = Alkylating agents: 1
Heavy metals: 2A
Non-classical alkylators: 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
7a |
Alkylating Agents
Busulfan
Carmustine (BCNU)
Chlorambucil
Cyclophosphamide
Ifosfamide
Lomustine (CCNU)
Mechlorethamine
Melphalan
Procarbazine
Thiotepa
Heavy Metals
Carboplatin
Cisplatin
Non-Classical Alkylators
Dacarbazine (DTIC)
Temozolomide
|
Gonadal dysfunction (testicular)
Delayed/arrested puberty
Hypogonadism
Oligospermia
Azoospermia
Infertility
|
Treatment Factors
Higher cumulative doses of alkylators or combinations of alkylators
Combined with radiation to:
- Abdomen/pelvis
- Testes
- Brain, cranium (neuroendocrine axis)
Health Behaviors
Smoking
Info Link
Doses that cause gonadal dysfunction show individual variation. Germ cell function (spermatogenesis) is impaired at lower doses compared to Leydig cell (testosterone production) function. Prepubertal status does not protect from gonadal injury in males.
|
Host Factors
Male gender
Treatment Factors
MOPP >3 cycles
Busulfan >600 mg/m2
Cyclophosphamide cumulative dose >7.5 g/m2 or as conditioning for HCT
Any alkylators combined with:
- Testicular radiation
- Pelvic radiation
- TBI
|
History
Pubertal (onset, tempo)
Sexual function (erections, nocturnal emissions, libido)
Medication use impacting sexual function
(Yearly)
Physical
Tanner stage
Testicular volume by Prader orchidometry
(Yearly until sexually mature)
Screening
FSH
LH
Testosterone
(Baseline at age 14 and as clinically indicated in patients with delayed puberty and/or clinical signs and symptoms of testosterone deficiency)
Semen analysis
(As requested by patient and for evaluation of infertility. Periodic evaluation over time is recommended as resumption of spermatogenesis can occur up to 10 years post therapy)
|
Health Links
See "Patient Resources" field
Male Health Issues
Resources
Extensive information regarding infertility for patients and healthcare professionals is available on the following websites:
American Society for Reproductive Medicine (www.asrm.org)
Fertile Hope (www.fertilehope.org)
Counseling
Counsel regarding the need for contraception, since there is tremendous individual variability in gonadal toxicity after exposure to alkylating agents. Recovery of fertility may occur years after therapy.
Considerations for Further Testing and Intervention
Bone density evaluation for osteopenia/osteoporosis in hypogonadal patients. Refer to endocrinologist for delayed puberty or persistently abnormal hormone levels. Hormonal replacement therapy for hypogonadal patients. Reproductive endocrinology/urology referral for infertility evaluation and consultation regarding assisted reproductive technologies.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Female reproductive
Scores = Alkylating agents: 1
Heavy metals: 2A
Non-classical alkylators: 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
7b |
Alkylating Agents
Busulfan
Carmustine (BCNU)
Chlorambucil
Cyclophosphamide
Ifosfamide
Lomustine (CCNU)
Mechlorethamine
Melphalan
Procarbazine
Thiotepa
Heavy Metals
Carboplatin
Cisplatin
Non-Classical Alkylators
Dacarbazine (DTIC)
Temozolomide
|
Gonadal dysfunction (ovarian)
Delayed/arrested puberty
Premature menopause
Infertility
|
Treatment Factors
Higher cumulative doses of alkylators or combinations of alkylators
Combined with radiation to:
- Abdomen/pelvis
- Lumbar or sacral spine (from ovarian scatter)
- Brain, cranium (neuroendocrine axis)
Health Behaviors
Smoking
Info Link
Doses that cause gonadal dysfunction show individual variation. Females can typically maintain gonadal function at higher cumulative doses than males.
|
Treatment Factors
MOPP >3 cycles
Busulfan >600 mg/m2
Cyclophosphamide cumulative dose >7.5 g/m2 or as conditioning for HCT
Any alkylators combined with:
|
History
Pubertal (onset, tempo)
Menstrual/pregnancy history
Sexual function (vaginal dryness, libido)
Medication use impacting sexual function
(Yearly)
Physical
Tanner stage
(Yearly until sexually mature)
Screening
FSH
LH
Estradiol
(Baseline at age 13 and as clinically indicated in patients with delayed puberty, irregular menses, primary or secondary amenorrhea, and/or clinical signs and symptoms of estrogen deficiency)
|
Health Links
See "Patient Resources" field
Female Health Issues
Resources
Extensive information regarding infertility for patients and healthcare professionals is available on the following websites:
American Society for Reproductive Medicine (www.asrm.org)
Fertile Hope (www.fertilehope.org)
Counseling
Counsel currently menstruating women at increased risk of early menopause to be cautious about delaying childbearing.
Counsel regarding the need for contraception, since there is tremendous individual variability in gonadal toxicity after exposure to alkylating agents. Recovery of fertility may occur years after therapy.
Considerations for Further Testing and Intervention
Bone density evaluation for osteopenia/osteoporosis in hypogonadal patients. Refer to endocrinologist for delayed puberty or persistently abnormal hormone levels. Hormonal replacement therapy for hypogonadal patients. Reproductive endocrinology referral for infertility evaluation and consultation regarding assisted reproductive technologies. Consider 2 months off hormonal replacement in women with ovarian failure to assess ovarian recovery.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = SMN
Scores = Alkylating agents: 1
Heavy metals: 2A
Non-classical alkylators: 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
8 |
Alkylating Agents
Busulfan
Carmustine (BCNU)
Chlorambucil
Cyclophosphamide
Ifosfamide
Lomustine (CCNU)
Mechlorethamine
Melphalan
Procarbazine
Thiotepa
Heavy Metals
Carboplatin
Cisplatin
Non-Classical Alkylators
Dacarbazine (DTIC)
Temozolomide
|
Acute myeloid leukemia
Myelodysplasia
|
Treatment Factors
Less than 10 years since exposure to agent
Higher cumulative alkylator dose or combination of alkylators
Note: Melphalan and mechlorethamine are more potent leukemogens than cyclophosphamide
Medical Conditions
Splenectomy (conflicting evidence)
|
|
History
Fatigue
Bleeding
Easy bruising
(Yearly, up to 10 years after exposure to agent)
Physical
Dermatologic exam (pallor, petechiae, purpura)
(Yearly, up to 10 years after exposure to agent)
Screening
CBC/differential
(Yearly, up to 10 years after exposure to agent)
|
Health Links
See "Patient Resources" field
Reducing the Risk of Second Cancers
Counseling
Counsel to promptly report fatigue, pallor, petechiae, or bone pain.
Considerations for Further Testing and Intervention
Bone marrow exam as clinically indicated
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Pulmonary
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
9 |
Alkylating Agents
Busulfan
Carmustine (BCNU)
Lomustine (CCNU)
|
Pulmonary fibrosis |
Treatment factors
Higher cumulative doses
Combined with bleomycin
Medical Conditions
Atopic history
Health Behaviors
Smoking
|
Treatment Factors
BCNU >600 mg/m2
Busulfan >500 mg (transplant doses)
Combined with:
|
History
Cough
SOB
DOE
Wheezing
(Yearly)
Physical
Pulmonary exam
(Yearly)
Screening
Chest x-ray
PFTs (including DLCO and spirometry)
(Baseline at entry into long-term followup. Repeat as clinically indicated in patients with abnormal results or progressive pulmonary dysfunction.)
|
Health Links
See "Patient Resources" field
Pulmonary Health
Resources
Extensive information regarding smoking cessation is available for patients on the NCI's website: www.smokefree.gov.
Counseling
Counsel regarding tobacco avoidance/smoking cessation. Due to the potential pulmonary toxicity of this therapy, patients who desire to SCUBA dive should be advised to obtain medical clearance from a diving medicine specialist.
Considerations for Further Testing and Intervention
In patients with abnormal PFTs and/or CXR, consider repeat evaluation prior to general anesthesia. Pulmonary consultation for symptomatic pulmonary dysfunction. Influenza and pneumococcal vaccines.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Ocular
Score = 2B
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
10 |
Alkylating Agents
Busulfan
|
Cataracts |
Treatment factors
Combined with corticosteroids
|
Treatment Factors
Combined with cranial, orbital, or eye radiation
TBI
Longer interval since treatment
|
History
Visual difficulties
(Yearly)
Physical
Eye exam (visual acuity, funduscopic exam for lens opacity)
(Yearly)
|
Health Links
See "Patient Resources" field
Cataracts
Considerations for Further Testing and Intervention
Ophthalmology consultation if problem identified. Refer patients with visual deficits to school liaison in community or cancer center (psychologist, social worker, school counselor) to facilitate acquisition of educational resources.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Urinary
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
11 |
Alkylating Agents
Cyclophosphamide
Ifosfamide
|
Urinary tract toxicity
Hemorrhagic cystitis
Bladder fibrosis
Dysfunctional voiding
Vesicoureteral reflux
Hydronephrosis
|
Treatment Factors
Higher cumulative doses (decreased incidence with Mesna)
Combined with: pelvic radiation
Health Behaviors
Alcohol use
Smoking
|
Treatment Factors
Cyclophosphamide dose >3 g/m2
Pelvic radiation dose >30 Gy
|
History
Hematuria
Urinary urgency/frequency
Urinary incontinence/retention
Dysuria
Nocturia
Abnormal urinary stream
(Yearly)
Screening
Urinalysis
(Yearly)
|
Health Links
See "Patient Resources" field
Bladder Health
Counseling
Counsel to promptly report dysuria or gross hematuria
Considerations for Further Testing and Intervention
Urine culture, spot urine calcium/creatinine ratio, and ultrasound of kidneys and bladder for patients with microscopic hematuria (defined as >5 RBC/HPF on at least 2 occasions). Nephrology or urology referral for patients with culture-negative microscopic hematuria AND abnormal ultrasound and/or abnormal calcium/creatinine ratio. Urology referral for patients with culture negative macroscopic hematuria.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = SMN
Score = 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
12 |
Alkylating Agents
Cyclophosphamide
|
Bladder malignancy |
Treatment Factors
Combined with: pelvic radiation
Health Behaviors
Alcohol use
Smoking
|
|
History
Hematuria
Urinary urgency/frequency
Urinary incontinence/retention
Dysuria
Nocturia
Abnormal urinary stream
(Yearly)
Screening
Urinalysis
(Yearly)
|
Health Links
See "Patient Resources" field
Bladder Health
Counseling
Counsel to promptly report dysuria or gross hematuria
Considerations for Further Testing and Intervention
Urine culture, spot urine calcium/creatinine ratio, and ultrasound of kidneys and bladder for patients with microscopic hematuria (defined as >5 RBC/HPF on at least 2 occasions). Nephrology or urology referral for patients with culture-negative microscopic hematuria AND abnormal ultrasound and/or abnormal calcium/creatinine ratio. Urology referral for patients with culture negative macroscopic hematuria.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Urinary
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
13 |
Alkylating Agents
Ifosfamide
|
Renal toxicity
Glomerular toxicity
Tubular toxicity (renal tubular acidosis, Fanconi's syndrome, hypophosphatemic rickets)
|
Host Factors
Younger age at treatment
Mononephric
Treatment Factors
Higher cumulative dose
Combined with other nephrotoxic agents, such as:
- Cisplatin
- Carboplatin
- Aminoglycosides
- Amphotericin
- Immunosuppressants
- Methotrexate
- Radiation impacting the kidney
Medical Conditions
Tumor infiltration of kidney(s)
Pre-existing renal impairment
Nephrectomy
|
Host Factors
Age <5 years at time of treatment
Treatment Factors
Ifosfamide dose >60 g/m2
Renal radiation dose >15 Gy
|
Physical
Blood pressure
(Yearly)
Screening
BUN
Creatinine
Na, K, Cl, CO2
Ca, Mg, PO4
(Baseline at entry into long-term followup. If abnormal, repeat as clinically indicated.)
Urinalysis
(Yearly)
|
Health Links
See "Patient Resources" field
Kidney Health
See also: Single Kidney Health
Considerations for Further Testing and Intervention
Electrolyte supplements for patients with persistent electrolyte wasting. Nephrology consultation for patients with hypertension, proteinuria, or progressive renal insufficiency
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Auditory
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
14 |
Heavy Metals
Carboplatin
(in myeloablative doses only)
Cisplatin
Info Link: Patients who received carboplatin in non-myeloablative doses do not appear to be at risk for clinically significant ototoxicity based on results of currently available studies.
|
Ototoxicity
Sensorineural hearing loss
Tinnitus
Vertigo
|
Host Factors
Age <4 years at treatment
Treatment Factors
Combined with:
- Cranial/ear radiation
- Ototoxic drugs (e.g., aminoglycosides, loop diuretics)
Medical Conditions
Chronic otitis
Cerumen impaction
Renal dysfunction
|
Host Factors
CNS neoplasm
Treatment Factors
Cumulative cisplatin dose >360 mg/m2
High dose cisplatin (i.e., 40 mg/m2 per day x 5 days per course)
Cisplatin administered after cranial/ear radiation
Carboplatin conditioning for HCT
Radiation involving ear >30 Gy
|
History
Hearing difficulties (with/without background noise)
Tinnitus
Vertigo
(Yearly)
Physical
Otoscopic exam
(Yearly)
Screening
Complete pure tone audiogram or brainstem auditory evoked response [BAER, ABR]
(Baseline at entry into long-term followup. If hearing loss is detected, test at least yearly, or as recommended by audiologist. For patients who also received cranial/ear radiation, test yearly after completion of therapy for 5 years [for patients <10 years old, continue yearly until age 10], then every 5 years. If clinical suspicion of hearing loss at any time, test as clinically indicated. If audiogram is inconclusive or unevaluable, refer to audiologist for consideration of electrophysiologic testing e.g., OAEs.)
Info Link:
Complete pure tone audiogram should include testing of both ears:
- Air conduction from 250 to 8000 Hz
- Bone conduction if air conduction thresholds exceed bone by 15 dB at any frequency
- Speech discrimination evaluation
OAEs measure outer hair cell function only. Because carboplatin selectively damages inner hair cells, patients treated with carboplatin should not be evaluated with OAEs.
|
Health Links
See "Patient Resources" field
Hearing Loss
Educational Issues
Considerations for Further Testing and Intervention
Audiology consultation for amplification in patients with progressive hearing loss. Speech and language therapy for children with hearing loss. Otolaryngology consultation in patients with chronic infection, cerumen impaction, or other anatomical problems exacerbating or contributing to hearing loss. Refer patients with auditory deficits to school liaison in community or cancer center (psychologist, social worker, school counselor) to facilitate provision of educational resources. Consider specific needs and/or preferential classroom seating, FM amplification system, and other educational assistance as indicated.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = PNS
Scores = 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
15 |
Heavy Metals
Carboplatin
Cisplatin
|
Peripheral sensory neuropathy
Info Link: Neuropathy presents as persistent effect after therapy and is typically not late in onset
|
Treatment Factors
Combined with:
- Vincristine
- Taxanes
- Gemcitabine
|
Treatment Factors
Cumulative cisplatin dose >300 mg/m2
|
History
Peripheral neuropathy
(Yearly until 2 to 3 years after therapy. Monitor yearly if symptoms persist.)
Physical
Neurologic exam
(Yearly until 2 to 3 years after therapy. Monitor yearly if symptoms persist.)
|
Health Links
See "Patient Resources" field
Peripheral Neuropathy
Considerations for Further Testing and Intervention
Physical therapy referral for patients with symptomatic neuropathy. Physical and occupational therapy assessment of hand function. Consider treatment with agent effective for neuropathic pain (e.g., gabapentin or amitriptyline).
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Urinary
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
16 |
Heavy Metals
Carboplatin
Cisplatin
|
Renal toxicity
Glomerular injury
Tubular injury
Renal insufficiency
|
Host Factors
Mononephric
Treatment Factors
Combined with other nephrotoxic agents such as:
- Ifosfamide
- Aminoglycosides
- Amphotericin
- Immunosuppressants
- Methotrexate
- Radiation impacting the kidney
Medical Conditions
Diabetes mellitus
Hypertension
Nephrectomy
|
Treatment Factors
Cisplatin dose >200 mg/m2
Renal radiation dose >15 Gy
|
Physical
Blood pressure
(Yearly)
Screening
BUN
Creatinine
Na, K, Cl, CO2
Ca, Mg, PO4
(Baseline at entry into long-term followup. If abnormal, repeat as clinically indicated.)
Urinalysis
(Yearly)
|
Health Links
See "Patient Resources" field
Kidney Health
See also: Single Kidney Health
Counseling
In patients with salt-wasting tubular dysfunction, educate that low magnesium levels potentiate coronary atherosclerosis.
Considerations for Further Testing and Intervention
Electrolyte supplements for patients with persistent electrolyte wasting. Nephrology consultation for patients with hypertension, proteinuria, or progressive renal insufficiency
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Cardiovascular
Score = 2B
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
17 |
Heavy Metals
Carboplatin
Cisplatin
|
Dyslipidemia |
Host Factors
Family history of dyslipidemia
Medical Conditions
Overweight/Obesity
|
|
Screening
Fasting lipid profile
(Baseline at entry into long-term followup, then as per United States Preventive Task Force Recommendations: www.ahrq.gov/clinic/prevenix.htm)
|
Health Links
See "Patient Resources" field
Diet and Physical Activity
Counseling
Counsel regarding lipid lowering strategies including diet, exercise, and weight loss in patients with dyslipidemia.
Considerations for Further Testing and Intervention
Consider pharmacologic therapy (e.g., statins) in patients with dyslipidemia.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = CNS
Score = 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
18 |
Antimetabolites
Cytarabine
(high dose IV)
Info Link: High-dose IV is defined as any single dose >1000 mg/m2.
|
Neurocognitive deficits
Functional deficits in:
- Executive function (planning and organization)
- Sustained attention
- Memory (particularly visual, sequencing, temporal memory)
- Processing speed
- Visual-motor integration
Learning deficits in math and reading (particularly reading comprehension)
Diminished IQ
Behavioral change
Info Link: Neurocognitive deficits in survivors of leukemia and lymphoma are more frequently related to information processing (e.g., learning disability). Neurocognitive deficits in brain tumor survivors treated with higher doses of cranial radiation are more global (significant decline in IQ). Extent of deficit depends on age at treatment, intensity of treatment, and time since treatment. New deficits may emerge over time.
|
Host Factors
Younger age at treatment
CNS leukemia/lymphoma
Relapsed leukemia/lymphoma treated with CNS-directed therapy
Treatment Factors
In combination with:
- Dexamethasone
- TBI
- Cranial radiation
- Methotrexate (IT, IO, high-dose IV)
- Longer elapsed time since therapy
Info Link
Acute toxicity predominates if administered systemically as a single agent. May contribute to late neurotoxicity if combined with high dose or intrathecal methotrexate and/or cranial radiation.
|
Host Factors
Age <3 years old at time of treatment
Female sex
Premorbid or family history of learning or attention problems
Treatment Factors
Radiation dose >24 Gy
Single fraction TBI (10 Gy)
|
History
Educational and/or vocational progress
(Yearly)
Screening
Referral for formal neuropsychological evaluation
(Baseline at entry into long-term follow-up, then periodically as clinically indicated for patients with evidence of impaired educational or vocational progress)
|
Health Links
See "Patient Resources" field
Educational Issues
Considerations for Further Testing and Intervention
Formal neuropsychological evaluation to include tests of processing speed, computer-based attention, visual motor integration, memory, comprehension of verbal instructions, verbal fluency, executive function and planning. Refer patients with neurocognitive deficits to school liaison in community or cancer center (psychologist, social worker, school counselor) to facilitate acquisition of educational resources and/or social skills training. Consider use of psychotropic medication (e.g., stimulants) or evidence-based rehabilitation training. Caution—lower starting dose and assessment of increased sensitivity when initiating therapy is recommended. Refer to community services for vocational rehabilitation or for services for developmentally disabled.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = CNS
Score = 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
19 |
Antimetabolites
Cytarabine
(high dose IV)
Info Link: High-dose IV is defined as any single dose >1000 mg/m2.
|
Clinical leukoencephalopathy
Spasticity
Ataxia
Dysarthria
Dysphagia
Hemiparesis
Seizures
Info Link: Clinical leukoencephalopathy may present with or without imaging abnormalities (e.g., leukoencephalopathy, cerebral lacunes, cerebral atrophy, dystrophic calcifications, mineralizing microangiopathy). Transient white matter anomalies may follow radiotherapy and high-dose chemotherapy for medulloblastoma/PNET, may mimic tumor recurrence, and signify risk of persistent neurologic sequelae. Neuroimaging changes do not always correlate with degree of cognitive dysfunction. Prospective studies are needed to define the dose/effect relationship of neurotoxic agents. Note: new deficits may emerge over time.
|
Host Factors
Younger age at treatment
CNS leukemia/lymphoma
Relapsed leukemia/lymphoma treated with CNS-directed therapy
Treatment Factors
Combined with:
- Methotrexate (IT, IO, high-dose IV)
- Dexamethasone
- Cranial radiation
|
Treatment Factors
Radiation dose >24 Gy
|
History
Cognitive, motor, and/or sensory deficits
Seizures
Other neurologic symptoms
(Yearly)
Physical
Spasticity
Ataxia
Dysarthria
Hemiparesis
(Yearly)
|
Considerations for Further Testing and Intervention
Brain MRI, Brain CT with MR angiography as clinically indicated; preferred study based on intracranial lesion to be evaluated:
- MRI: White matter
- Gadolinium-enhanced MRI: Microvascular injury
- CT: Calcifications
Neurology consultation and follow-up as clinically indicated.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = N/A
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
20 |
Antimetabolites
Cytarabine
(low dose IV)
Cytarabine IO
Cytarabine IT
Cytarabine SQ
Info Link: Low-dose IV is defined as any single dose <1000 mg/m2.
|
No known late effects
Info Link: Acute toxicities predominate, from which the majority of patients recover without sequelae.
|
|
|
|
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = GI/Hepatic
Score = 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
21 |
Antimetabolites
Mercaptopurine (6MP)
Thioguanine (6TG)
Info Link: Acute hepatotoxicity reported with thioguanine used in CCG 1952 (regimens B1 and B2) for ALL maintenance therapy requires longer follow-up to determine long-term sequelae. See COG Website (CCG 1952 protocol page) for updated advisories.
|
Hepatic dysfunction
VOD
Info Link: Acute toxicities predominate from which the majority of patients recover without sequelae. Delayed hepatic dysfunction may occur after a history of acute VOD, presenting as portal hypertension with liver biopsy indicating nodular regenerative hyperplasia, fibrosis, or siderosis.
|
Medical Conditions
Viral hepatitis
Previous VOD
Siderosis
|
Medical Conditions
Chronic viral hepatitis
|
Physical
Scleral icterus
Jaundice
Ascites
Hepatomegaly
Splenomegaly
(Yearly)
Screening
ALT
AST
Bilirubin
(Baseline at entry into long-term followup. Repeat as clinically indicated.)
|
Health Links
See "Patient Resources" field
Liver Health
Considerations for Further Testing and Intervention
Prothrombin time for evaluation of hepatic synthetic function in patients with abnormal liver screening tests. Screen for viral hepatitis in patients with persistently abnormal liver function or any patient transfused prior to 1993. Gastroenterology/hepatology consultation in patients with persistent liver dysfunction. Hepatitis A and B immunization in patients lacking immunity.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Musculoskeletal
Score = 2B
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
22 |
Antimetabolites
Methotrexate (high dose IV)
Methotrexate (low dose IV)
Methotrexate IM
Methotrexate PO
Info Link: High-dose IV is defined as any single dose >1000 mg/m2.
|
Osteopenia
Osteoporosis
Osteopenia is defined as BMD >1 and <2.5 SD below mean
Osteoporosis is defined as BMD >2.5 SD below mean
Info Link: The World Health Organization definition of osteoporosis in adults is based on comparison of a measured BMD of young adults at peak bone age and defined as a T-score. A T-score is the number of standard deviations the BMD measurement is above or below the mean. A T-score of >2.5 standard deviations BELOW the mean is consistent with a diagnosis of osteoporosis. T-scores are not appropriate to assess skeletal health in pediatric patients who have not achieved peak adult bone mass. Instead, pediatric BMD reference data sets calculate Z-scores based on age and gender. A Z-score is the number of standard deviations the measurement is above or below the AGE-MATCHED MEAN BMD. There are no defined standards for referral or treatment of low BMD in children.
|
Host Factors
Both genders are at risk
Treatment Factors
Corticosteroids
Cranial radiation
HCT/TBI
Medical Conditions
Growth hormone deficiency
Hypogonadism/delayed puberty
Hyperthyroidism
Health Behaviors
Inadequate intake of calcium and vitamin D
Lack of weight bearing exercise
Smoking
Alcohol use
|
Host Factors
Older age at time of treatment
Treatment Factors
Methotrexate cumulative dose >40 gm/m2
Prolonged corticosteroid therapy (e.g., for chronic GVHD)
|
Screening
Bone density evaluation (DEXA or quantitative CT)
(Baseline at entry into long-term followup. Repeat as clinically indicated.)
Info Link: The optimal method of measuring bone health in children is controversial. Existing technologies have limitations. DEXA provides an estimate of total bone mass at a given site. Quantitative CT provides distinct measures of trabecular and cortical bone dimension and density.
|
Health Links
See "Patient Resources" field
Bone Health
Resources
National Osteoporosis Foundation Website: www.nof.org
Considerations for Further Testing and Intervention
Nutritional supplements in cases of osteopenia unresponsive to behavioral and dietary management: Calcium 1000 to 1500 mg daily plus RDA for vitamin D. Use caution regarding calcium supplementation in patients with history of renal lithiasis. Treatment of exacerbating or predisposing conditions (e.g., hormonal replacement therapy for hypogonadism, growth hormone deficiency, correction of chronic metabolic acidosis that could accelerate bone loss). Endocrine consultation for patients with osteoporosis or history of multiple fractures for pharmacologic interventions (e.g., bisphosphonates, calcitonin, selective estrogen receptor modulators).
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Urinary
Score = 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
23 |
Antimetabolites
Methotrexate (high dose IV)
Methotrexate (low dose IV)
Methotrexate IM
Methotrexate PO
Info Link: High-dose IV is defined as any single dose >1000 mg/m2.
|
Renal toxicity
Info Link: Acute toxicities predominate, from which the majority of patients recover without sequelae
|
Host Factors
Mononephric
Treatment Factors
Combined with other nephrotoxic agents such as:
- Cisplatin/carboplatin
- Ifosfamide
- Aminoglycosides
- Amphotericin
- Immunosuppressants
- Radiation impacting the kidney
Medical Conditions
Diabetes mellitus
Hypertension
Nephrectomy
|
Treatment Factors
Treatment before 1970
|
Physical
Blood pressure
(Yearly)
Screening
BUN
Creatinine
Na, K, Cl, CO2
Ca, Mg, P04
(Baseline at entry into long-term followup. If abnormal, repeat as clinically indicated.)
Urinalysis
(Yearly)
|
Health Links
See "Patient Resources" field
Kidney Health
See also: Single Kidney Health
Considerations for Further Testing and Intervention
Nephrology consultation for patients with hypertension, proteinuria, or progressive renal insufficiency
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = GI/Hepatic
Score = 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
24 |
Antimetabolites
Methotrexate (high dose IV)
Methotrexate (low dose IV)
Methotrexate IM
Methotrexate PO
Info Link: High-dose IV is defined as any single dose >1000 mg/m2.
|
Hepatic dysfunction
Info Link: Acute toxicities predominate, from which the majority of patients recover without sequelae
|
Treatment Factors
Abdominal radiation
Medical Conditions
Viral hepatitis
|
Treatment Factors
Treatment before 1970
Medical Conditions
Chronic viral hepatitis
|
Physical
Scleral icterus
Jaundice
Ascites
Hepatomegaly
Splenomegaly
(Yearly)
Screening
ALT
AST
Bilirubin
(Baseline at entry into long-term follow-up. Repeat as clinically indicated.)
|
Health Links
See "Patient Resources" field
Liver Health
Considerations for Further Testing and Intervention
Prothrombin time for evaluation of hepatic synthetic function in patients with abnormal liver screening tests. Screen for viral hepatitis in patients with persistently abnormal liver function or any patient transfused prior to 1993. Gastroenterology/hepatology consultation in patients with persistent liver dysfunction. Hepatitis A and B immunization in patients lacking immunity.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = CNS
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
25 |
Antimetabolites
Methotrexate (high dose IV)
Methotrexate IO
Methotrexate IT
Info Link: High-dose IV is defined as any single dose >1000 mg/m2.
|
Neurocognitive deficits
Functional deficits in:
- Executive function (planning and organization)
- Sustained attention
- Memory (particularly visual, sequencing, temporal memory)
- Processing speed
- Visual-motor integration
Learning deficits in math and reading (particularly reading comprehension)
Diminished IQ
Behavioral change
Info Link: Neurocognitive deficits in survivors of leukemia and lymphoma are more frequently related to information processing (e.g., learning disability). Neurocognitive deficits in brain tumor survivors treated with higher doses of cranial radiation are more global (significant decline in IQ). Extent of deficit depends on age at treatment, intensity of treatment, and time since treatment. New deficits may emerge over time.
|
Host Factors
Younger age at treatment
CNS leukemia/lymphoma
Relapsed leukemia/lymphoma treated with CNS-directed therapy
Treatment Factors
In combination with:
- Dexamethasone
- TBI
- Cranial radiation
- Cytarabine (high-dose IV)
Longer elapsed time since therapy
|
Host Factors
Age <3 years old at time of treatment
Female sex
Premorbid or family history of learning or attention problems
Treatment Factors
Radiation dose >24 Gy
Single fraction TBI (10 Gy)
|
History
Educational and/or vocational progress
(Yearly)
Screening
Referral for formal neuropsychological evaluation
(Baseline at entry into long-term follow-up, then periodically as clinically indicated for patients with evidence of impaired educational or vocational progress)
|
Health Links
See "Patient Resources" field
Educational Issues
Considerations for Further Testing and Intervention
Formal neuropsychological evaluation to include tests of processing speed, computer-based attention, visual motor integration, memory, comprehension of verbal instructions, verbal fluency, executive function and planning. Refer patients with neurocognitive deficits to school liaison in community or cancer center (psychologist, social worker, school counselor) to facilitate acquisition of educational resources and/or social skills training; Consider use of psychotropic medication (e.g., stimulants) or evidence-based rehabilitation training. Caution - lower starting dose and assessment of increased sensitivity when initiating therapy is recommended. Refer to community services for vocational rehabilitation or for services for developmentally disabled.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = CNS
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
26 |
Antimetabolites
Methotrexate (high dose IV)
Methotrexate IO
Methotrexate IT
Info Link: High-dose IV is defined as any single dose >1000 mg/m2.
|
Clinical leukoencephalopathy
Spasticity
Ataxia
Dysarthria
Dysphagia
Hemiparesis
Seizures
Info Link: Clinical leukoencephalopathy may present with or without imaging abnormalities (e.g., leukoencephalopathy, cerebral lacunes, cerebral atrophy, dystrophic calcifications, mineralizing microangiopathy). Transient white matter anomalies may follow radiotherapy and high-dose chemotherapy for medulloblastoma/PNET, may mimic tumor recurrence, and signify risk of persistent neurologic sequelae. Neuroimaging changes do not always correlate with degree of cognitive dysfunction. Prospective studies are needed to define the dose/effect relationship of neurotoxic agents. Note: new deficits may emerge over time.
|
Host Factors
Younger age at treatment
CNS leukemia/lymphoma
Relapsed leukemia/lymphoma treated with CNS-directed therapy
Treatment Factors
In combination with:
- Cytarabine
(high-dose IV)
- Dexamethasone
- Cranial radiation
|
Treatment Factors
Radiation dose >24 Gy
|
History
Cognitive, motor, and/or sensory deficits
Seizures
Other neurologic symptoms
(Yearly)
Physical
Spasticity
Ataxia
Dysarthria
Hemiparesis
(Yearly)
|
Considerations for Further Testing and Intervention
Brain MRI, Brain CT with MR angiography as clinically indicated; preferred study based on intracranial lesion to be evaluated:
- MRI: White matter
- Gadolinium-enhanced MRI: Microvascular injury
- CT: Calcifications
Neurology consultation and follow-up as clinically indicated
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = SMN
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
27 |
Anthracycline Antibiotics
Daunorubicin
Doxorubicin
Epirubicin
Idarubicin
Mitoxantrone*
*Although Mitoxantrone technically belongs to the anthracenedione class of anti-tumor antibiotics, it is related to the anthracycline family.
|
Acute myeloid leukemia |
Treatment Factors
Less than 5 years since exposure to agent
|
|
History
Fatigue
Bleeding
Easy bruising
(Yearly up to 10 years after exposure to agent)
Physical
Dermatologic exam (pallor, petechiae, purpura)
(Yearly up to 10 years after exposure to agent)
Screening
CBC/differential
(Yearly up to 10 years after exposure to agent)
|
Health Links
See "Patient Resources" field
Reducing the Risk of Second Cancers
Counseling
Counsel to promptly report fatigue, pallor, petechiae, or bone pain
Considerations for Further Testing and Intervention
Bone marrow exam as clinically indicated
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Cardiovascular
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
28 |
Anthracycline Antibiotics
Daunorubicin
Doxorubicin
Epirubicin
Idarubicin
Mitoxantrone*
*Although Mitoxantrone technically belongs to the anthracenedione class of anti-tumor antibiotics, it is related to the anthracycline family.
Info Link: Use the following formulas to convert to doxorubicin/daunorubicin isotoxic equivalents prior to calculating total cumulative anthracycline dose.
- Epirubicin: Multiply total dose x 0.67
- Idarubicin: Multiply total dose x 5
- Mitoxantrone: Multiply total dose x 3.5
Note: There is a paucity of literature to support isotoxic dose conversion; however, the above conversion factors may be used for convenience in order to gauge screening frequency. Clinical judgment should ultimately be used to determine indicated screening for individual patients.
|
Cardiac toxicity
Cardiomyopathy
Arrhythmias
Subclinical left ventricular dysfunction (systolic dysfunction as assessed by ECHO or MUGA)
Info Link: Dose levels correlating with cardiotoxicity are derived from adult studies. Childhood cancer patients exhibit clinical and subclinical toxicity at lower levels. Certain conditions (such as isometric exercise, pregnancy, and viral infections) have been anecdotally reported to precipitate cardiac decompensation. Prospective studies are needed to define risk factors. Note: Pediatric studies of anthracycline cardiotoxicity typically describe risks based on combined cumulative doses of daunomycin and doxorubicin, assuming an equivalent relative cardiotoxicity per mg dose. Idarubicin and mitoxantrone are more cardiotoxic than doxorubicin or daunorubicin on a mg per mg dose basis. In limited studies, epirubicin has similar dose equivalency to daunomycin and doxorubicin.
|
Treatment Factors
Combined with radiation involving the heart
Combined with other cardiotoxic chemotherapy:
- Cyclophosphamide conditioning for HCT
- Amsacrine
Medical Conditions
Obesity
Congenital heart disease
Febrile illness
Pregnancy
Health Behaviors
Isometric exercise
Smoking
Drug use (e.g., cocaine, diet pills, ephedra, mahuang)
|
Host Factors
Female sex
Black/of African descent
Younger than age 5 years at time of treatment
Treatment Factors
Higher cumulative anthracycline doses:
- Patients 18 years or older at time of treatment: >550 mg/m2
- Patients younger than 18 years at time of treatment: >300 mg/m2
- Any dose in infant
Chest radiation >30 Gy
Longer time elapsed since treatment
|
History
SOB
DOE
Orthopnea
Chest pain
Palpitations
If under 25 years:
Abdominal symptoms (nausea, vomiting)
(Yearly)
Info Link: Exertional intolerance is uncommon in young patients (<25 years). Abdominal symptoms (nausea, emesis) may be observed more frequently than exertional dyspnea or chest pain in young patients.
Physical
Cardiac murmur
S3, S4
Increased P2 sound
Pericardial rub
Rales
Wheezes
Jugular venous distension
Peripheral edema
(Yearly)
Screening
ECHO or MUGA for evaluation of systolic function
(Baseline at entry to long-term follow-up, then periodically, based on age at treatment, history of chest radiation and cumulative anthracycline dose - see next table.)
EKG (include evaluation of QTc interval)
(Baseline at entry into long-term followup. Repeat as clinically indicated.)
|
Health Links
See "Patient Resources" field
Heart Health
Counseling
Counsel patients with prolonged QTc interval about use of medications that may further prolong the QTc interval (e.g., tricyclic anti-depressants, antifungals, macrolide antibiotics, metronidazole). Counsel regarding maintaining appropriate weight, blood pressure, and heart-healthy diet. Counsel regarding appropriate exercise. Aerobic exercise is generally safe and should be encouraged for most patients. Intensive isometric activities (e.g., heavy weight lifting, wrestling) should generally be avoided. Limited high repetition weight lifting (i.e., lifting a lighter weight with ease no more than 15 to 20 times in a row) is much less stressful to the heart and is more likely to be safe. Patients who choose to engage in strenuous or varsity team sports should discuss appropriate guidelines and a plan for ongoing monitoring with a cardiologist.
Considerations for Further Testing and Intervention
Cardiology consultation in patients with subclinical abnormalities on screening evaluations, left ventricular dysfunction, dysrhythmia, or prolonged QTc interval. Consider excess risk of isometric exercise program in any high risk patient (defined as needing screening every 1 or 2 years). Females only: Additional cardiology evaluation in patients who received >300 mg/m2 or <300 mg/m2 plus chest radiation who are pregnant or planning pregnancy. Evaluation to include an ECHO before and periodically during pregnancy (especially during third trimester) and monitoring during labor and delivery due to risk of cardiac failure.
|
Recommended Frequency of ECHO or MUGA Scan
Age at Treatment* |
Chest Radiation |
Anthracycline Dose** |
Recommended Frequency |
<1 year old |
Yes |
Any |
Every year |
No |
<200 mg/m2 |
Every 2 years |
>200 mg/m2 |
Every year |
1–4 years old |
Yes |
Any |
Every year |
No |
<100 mg/m2 |
Every 5 years |
>100 to <300 mg/m2 |
Every 2 years |
>300 mg/m2 |
Every year |
>5 years old |
Yes |
<300 mg/m2 |
Every 2 years |
>300 mg/m2 |
Every year |
No |
<200 mg/m2 |
Every 5 years |
>200 to <300 mg/m2 |
Every 2 years |
>300 mg/m2 |
Every year |
Any age with decrease in serial function |
Every year |
*Age at time of first cardiotoxic therapy (anthracycline or chest irradiation, whichever was given first)
**Based on equivalent mg of doxorubicin/daunorubicin
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Pulmonary
Scores = Interstitial pneumonitis: 1
Pulmonary fibrosis: 1
ARDS: 2B
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
29 |
Anti-Tumor Antibiotics
Bleomycin
|
Pulmonary Toxicity
Interstitial pneumonitis
Pulmonary fibrosis
Acute respiratory distress syndrome (very rare)
|
Host Factors
Younger age at treatment
Treatment Factors
Higher cumulative dose
Combined with:
- Busulfan
- Carmustine (BCNU)
- Lomustine (CCNU)
Medical Conditions
Renal dysfunction
High dose oxygen support such as during general anesthesia
Health Behaviors
Smoking
|
Treatment Factors
Bleomycin dose >400 U/m2 (injury observed in doses 60 to 100 U/m2 in children)
Combined with:
|
History
Cough
SOB
DOE
Wheezing
(Yearly)
Physical
Pulmonary exam
(Yearly)
Screening
Chest x-ray
PFTs (including DLCO and spirometry)
(Baseline at entry into long-term follow-up. Repeat as clinically indicated in patients with abnormal results or progressive pulmonary dysfunction.)
|
Health Links
See "Patient Resources" field
Pulmonary Health
Bleomycin Alert
Resources
Extensive information regarding smoking cessation is available for patients on the NCI's website: www.smokefree.gov.
Counseling
SCUBA diving should be avoided (potential exacerbation of pulmonary fibrosis as a result of increased oxygen concentrations associated with underwater pressures). Notify healthcare providers of history of bleomycin therapy and risk of worsening fibrosis with high oxygen exposure such as during general anesthesia. Administration of high concentrations of oxygen may result in chronic progressive pulmonary fibrosis. Counsel regarding tobacco avoidance/smoking cessation.
Considerations for Further Testing and Intervention
In patients with abnormal PFTs and/or CXR, consider repeat evaluation prior to general anesthesia. Pulmonary consultation in patients with symptomatic or progressive pulmonary dysfunction. Influenza and pneumococcal vaccines.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = N/A
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
30 |
Anti-Tumor Antibiotics
Dactinomycin
|
No known late effects
Info Link: Dactinomycin has been associated with acute VOD, from which the majority of patients recover without sequelae.
|
|
|
|
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Musculoskeletal
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
31 |
Corticosteroids
Dexamethasone
Prednisone
|
Osteopenia
Osteoporosis
Osteopenia is defined as BMD >1 and <2.5 SD below mean
Osteoporosis is defined as BMD >2.5 SD below mean
Info Link: The World Health Organization definition of osteoporosis in adults is based on comparison of a BMD of young adults at peak bone age and defined as a T-score. A T-score is the number of standard deviations the BMD measurement is above or below the mean. A T-score of >2.5 standard deviations BELOW the mean is consistent with a diagnosis of osteoporosis. T-scores are not appropriate to assess skeletal health in pediatric patients who have not achieved peak adult bone mass. Instead, pediatric BMD reference data sets calculate Z-scores based on age and gender. A Z-score is the number of standard deviations the measurement is above or below the AGE-MATCHED MEAN BMD. There are no defined standards for referral or treatment of low BMD in children.
|
Host Factors
Both genders are at risk
Treatment Factors
Methotrexate
Cranial radiation
HCT/TBI
Medical Conditions
Growth hormone deficiency
Hypogonadism/ delayed puberty
Hyperthyroidism
Health Behaviors
Inadequate intake of calcium and vitamin D
Lack of weight bearing exercise
Smoking
Alcohol use
|
Host Factors
Older age at time of treatment
Treatment Factors
Glucocorticoid cumulative dose >9 gm/m2 prednisone equivalent
Dexamethasone effect is more potent than prednisone
|
Screening
Bone density evaluation (DEXA or quantitative CT)
(Baseline at entry into long-term followup. Repeat as clinically indicated.)
Info Link: The optimal method of measuring bone health in children is controversial. Existing technologies have limitations. DEXA provides an estimate of total bone mass at a given site. Quantitative CT provides distinct measures of trabecular and cortical bone dimension and density.
|
Health Links
See "Patient Resources" field
Bone Health
Resources
National Osteoporosis Foundation Website: www.nof.org
Considerations for Further Testing and Intervention
Nutritional supplements in cases of osteopenia unresponsive to behavioral and dietary management: Calcium 1000 to 1500 mg daily plus RDA for vitamin D. Use caution regarding calcium supplementation in patients with history of renal lithiasis. Treatment of exacerbating or predisposing conditions (e.g., hormonal replacement therapy for hypogonadism, growth hormone deficiency, correction of chronic metabolic acidosis that could accelerate bone loss). Endocrine consultation for patients with osteoporosis or history of multiple fractures for pharmacologic interventions (e.g., bisphosphonates, calcitonin, selective estrogen receptor modulators).
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Musculoskeletal
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
32 |
Corticosteroids
Dexamethasone
Prednisone
|
Osteonecrosis
(Avascular Necrosis)
Info Link: Osteonecrosis typically occurs during the acute treatment phase, may progress over time or resolve. Multifocal osteonecrosis is significantly more common (3:1) than unifocal.
|
Host Factors
Both genders are at risk
Host polymorphisms may confer increased risk
Treatment Factors
Combined with high-dose radiation to any bone
Dexamethasone effect is more potent than prednisone
Medical Conditions
Sickle cell disease
|
Host Factors
Age >10 years at time of treatment
Treatment Factors
Orthovoltage radiation (commonly used before 1970) due to delivery of greater dose to skin and bones
|
History
Joint pain
Swelling
Immobility
Limited range of motion
(Yearly)
Physical
Musculoskeletal exam
(Yearly)
|
Health Links
See "Patient Resources" field
Osteonecrosis
Considerations for Further Testing and Intervention
MRI as clinically indicated in patients with history suggestive of osteonecrosis (should be done soon after symptom onset). Orthopedic consultation in patients with positive imaging and/or symptoms of osteonecrosis. Physical therapy evaluation (for non-pharmacologic pain management, range of motion, strengthening, stretching, functional mobility).
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Ocular
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
33 |
Corticosteroids
Dexamethasone
Prednisone
|
Cataracts |
Treatment Factors
Combined with:
|
Treatment Factors
TBI
Cranial, orbital, or eye radiation
Longer interval since treatment
|
History
Visual difficulties
(Yearly)
Physical
Eye exam (visual acuity, funduscopic exam for lens opacity)
(Yearly)
|
Health Links
See "Patient Resources" field
Cataracts
Considerations for Further Testing and Intervention
Ophthalmology consultation if problem identified. Refer patients with visual deficits to school liaison in community or cancer center (psychologist, social worker, school counselor) to facilitate acquisition of educational resources.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = N/A
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
34 |
Enzymes
Asparaginase
|
No known late effects
Info Link: Acute toxicities predominate, from which the majority of patients recover without sequelae
|
|
|
|
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = PNS
Score = 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
35 |
Plant Alkaloids
Vinblastine
Vincristine
|
Peripheral sensory or motor neuropathy
Areflexia
Weakness
Foot drop
Paresthesias
Info Link: Acute toxicities most commonly occur and usually resolve prior to patients entering long-term follow-up. Neuropathy can persist after treatment and is typically not late in onset.
|
Treatment Factors
Combined with platinum chemotherapy, gemcitabine, or taxanes
Medical Conditions
Anorexia
Severe weight loss
|
Medical Conditions
Charcot-Marie-Tooth disease
|
History
Peripheral neuropathy
(Yearly, until 2 to 3 years after therapy. Monitor yearly if symptoms persist.)
Physical
Neurologic exam
(Yearly, until 2 to 3 years after therapy; continue to monitor yearly if symptoms persist)
|
Health Links
See "Patient Resources" field
Peripheral Neuropathy
Considerations for Further Testing and Intervention
Physical therapy referral for patients with symptomatic neuropathy. Physical therapy and occupational therapy assessment of hand function. Consider treatment with an anticonvulsant effective for neuropathic pain (e.g., gabapentin and amitriptyline).
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Cardiovascular
Score = 2A
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
36 |
Plant Alkaloids
Vinblastine
Vincristine
|
Vasospastic attacks
(Raynaud's phenomenon)
|
Health Behaviors
Smoking
Illicit drug use
|
|
History
Vasospasms of hands, feet, nose, lips, cheeks, or earlobes related to stress or cold temperatures
(Yearly)
Physical
Physical exam of affected area
(As Indicated)
|
Health Links
See "Patient Resources" field
Raynaud's Phenomenon
Counseling
Counsel to wear appropriate protective clothing in cold environments and not to use tobacco or illicit drugs
Considerations for Further Testing and Intervention
Consider vasodilating medications (calcium-channel blockers, alpha blockers) for patients with frequent, severe vasospastic attacks unresponsive to behavioral management.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = SNM
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
37 |
Epipodophyllotoxins
Etoposide (VP16)
Teniposide (VM26)
Info Link: Administration schedules since approximately 1990 have been modified to reduce the risk of this complication.
|
Acute myeloid leukemia |
Medical Conditions
Splenectomy (conflicting evidence)
|
Treatment Factors
Weekly or twice weekly administration Less than 5 years since exposure to agent
|
History
Fatigue
Bleeding
Easy bruising
(Yearly, up to 10 years after exposure to agent)
Physical
Dermatologic exam (pallor, petechiae, purpura)
(Yearly, up to 10 years after exposure to agent)
Screening
CBC/differential
(Yearly, up to 10 years after exposure to agent)
|
Health Links
See "Patient Resources" field
Reducing the Risk of Second Cancers
Counseling
Counsel to promptly report fatigue, pallor, petechiae, or bone pain
Considerations for Further Testing and Intervention
Bone marrow exam as clinically indicated
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
Abbreviations
- ABR, auditory brainstem response
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- BAER, brainstem auditory evoked responses
- BMD, bone mineral density
- BUN, blood urea nitrogen
- Ca, calcium
- CBC, complete blood count
- CCG, Children's Cancer Group
- Cl, chloride
- CNS, central nervous system
- CO2, carbon dioxide
- COG, Children's Oncology Group
- CT, computed tomography
- CXR, chest x-ray
- DEXA, dual energy x-ray absorptiometry
- DLCO, diffusion capacity of carbon monoxide
- DOE, dyspnea on exertion
- ECHO, echocardiogram
- EKG, electrocardiogram
- FSH, follicle-stimulating hormone
- GI, gastrointestinal
- GVHD, graft versus host disease
- Gy, gray
- HCT, hematopoietic cell transplant
- HPF, high power field
- HZ, hertz
- IM, intramuscular
- IO, intraosseous
- IQ, intelligence quotient
- IT, intrathecal
- IV, intravenous
- K, potassium
- LH, luteinizing hormone
- Mg, magnesium
- MOPP, mechlorethamine/Oncovin [vincristine]/procarbazine/prednisone
- MR, magnetic resonance
- MRI, magnetic resonance imaging
- MUGA, multiple gated acquisition scan
- N/A, not applicable
- Na, sodium
- NCI, National Cancer Institute
- OAEs, otoacoustic emissions
- PFTs, pulmonary function tests
- PNET, primitive neuroectodermal tumor
- PNS, peripheral neurosensory
- PO, by mouth
- PO4, phosphate
- RBC, red blood cell
- RDA, recommended daily allowance
- SD, standard deviaion(s)
- SMN, secondary malignant neoplasm
- SOB, shortness of breath
- SQ, subcutaneous
- TBI, total body irradiation
- VOD, veno-occlusive diseases
Definitions:
Explanation of Scoring for the Long-Term Follow-Up Guidelines
1 There is uniform consensus of the panel that (1) there is high-level evidence linking the late effect with the therapeutic exposure, and (2) the screening recommendation is appropriate based on the collective clinical experience of panel members.
2A There is uniform consensus of the panel that (1) there is lower-level evidence linking the late effect with the therapeutic exposure, and (2) the screening recommendation is appropriate based on the collective clinical experience of panel members.
2B There is non-uniform consensus of the panel that (1) there is lower-level evidence linking the late effect with the therapeutic exposure, and (2) the screening recommendation is appropriate based on the collective clinical experience of panel members.
3 There is major disagreement that the recommendation is appropriate.
Rating Scheme for the Strength of the Evidence
"High-level evidence" (recommendation category 1) was defined as evidence derived from high quality case control or cohort studies.
"Lower-level evidence" (recommendation categories 2A and 2B) was defined as evidence derived from non-analytic studies, case reports, case series, and clinical experience.