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 = SMN
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
92 |
HCT
Info Link: Complications after HCT have multifactorial etiology: prior therapy for primary malignancy; intensity of transplant conditioning; stem cell product (e.g., marrow, cord blood, peripheral stem cells); donor (e.g., autologous, allogeneic, unrelated); quality of donor to recipient match; complication of transplant process (immunosuppression and GVHD); complications in the post-transplant period; underlying disease; host genetic factors; lifestyle behaviors. This section includes late treatment complications that may be observed in HCT recipients not covered elsewhere in these guidelines. Refer to the guidelines listed at the beginning of the "Major Recommendations" section for specific details related to late complications of radiation and of specific chemotherapeutic agents.
|
Acute myeloid leukemia
Myelodysplasia
|
Treatment Factors
Radiation therapy
Stem cell mobilization with etoposide
Alkylating agent chemotherapy
Epipodophyllotoxins
Anthracyclines
Autologous transplant
|
Host Factors
Older age
Treatment Factors
Autologous transplant for non-Hodgkin's and Hodgkin's lymphoma
|
History
Fatigue
Bleeding
Easy bruising
(Yearly up to 10 years after transplant)
Physical
Dermatologic exam (pallor, petechiae, purpura)
(Yearly up to 10 years after transplant)
Screening
CBC/differential
(Yearly up to 10 years after transplant)
|
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 = SMN
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
93 |
HCT |
Solid tumors |
Host Factors
Younger age at transplant
Fanconi's anemia
Treatment Factors
Radiation therapy
Medical Conditions
Hepatitis C infection
cGVHD
Human papilloma virus infection (females)
|
Treatment Factors
TBI
|
Physical
Evaluation for benign or malignant neoplasms
(Yearly)
|
Health Links
See "Patient Resources" field
Reducing the Risk of Second Cancers
Considerations for Further Testing and Intervention
Females with cGVHD appear to be at increased risk for cervical cancer and should, at minimum, have pelvic exams and PAP testing according to ACS recommendations (see Section 138 in the Cancer and General Health Screening guideline listed at the beginning of the "Major Recommendations" field) with more aggressive monitoring as clinically indicated.
Oncology consultation 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 |
94 |
HCT |
Lymphoma |
Medical Conditions
cGVHD
|
Medical Conditions
Chronic hepatitis C with siderosis and steatosis
|
Physical
Lymphadenopathy
Splenomegaly
(Yearly)
|
Considerations for Further Testing and Intervention
Oncology consultation as clinically indicated.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = GI/Hepatic
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
95 |
HCT |
Hepatic toxicity
Chronic hepatitis
Cirrhosis
Iron overload
|
Treatment Factors
History of multiple transfusions
Radiation to the liver
Antimetabolite therapy
Medical Conditions
cGVHD
Viral hepatitis
History of VOD
Health Behaviors
Alcohol use
|
Medical Conditions
Chronic hepatitis C with siderosis and steatosis
|
Screening
ALT
AST
Bilirubin
Ferritin
(Baseline at entry into long-term follow-up. Repeat as clinically indicated.)
|
Health Links
See "Patient Resources" field
Liver Health
Gastrointestinal 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. Note: PCR testing for HCV may be required in immunosuppressed patients who are negative for antibody. Gastroenterology/hepatology consultation in patients with persistent liver dysfunction or known hepatitis. Hepatitis A and B immunizations in patients lacking immunity. Consider liver biopsy in patients with persistent elevation of ferritin (based on clinical context and magnitude of elevation). Consider phlebotomy or chelation therapy for treatment of iron overload. Consider erythropoietin in patients with iron overload and low hemoglobin.
|
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 |
96 |
HCT |
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
Age >10 years at time of transplant
Treatment Factors
Corticosteroids (dexamethasone effect is more potent than prednisone)
TBI
High-dose radiation to any bone
Allogeneic HCT >autologous
|
Treatment Factors
Prolonged corticosteroid therapy (e.g., for chronic GVHD)
Medical Conditions
cGVHD
|
Screening
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 = Musculoskeletal
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
97 |
HCT |
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 YOUNG-NORMAL MEAN BMD. 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 not defined standards for referral or treatment of low BMD in children.
|
Host Factors
Both genders are at risk
Treatment Factors
Methotrexate
Corticosteroids
Cranial radiation
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
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 1000-1500 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.
With Chronic GVHD
System = Dermatologic
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
98 |
HCT with cGVHD |
Dermatologic toxicity
Permanent alopecia
Nail dysplasia
Vitiligo
Scleroderma
Info Link: More common with active cGVHD; effects may persist after cGVHD resolves.
|
|
|
Physical
Hair (alopecia)
Nail (hypoplasia)
Skin (vitiligo, scleroderma)
(Yearly)
|
Health Links
See "Patient Resources" field
Skin Health
|
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 |
99 |
HCT with cGVHD |
Xerophthalmia (keratoconjunctivitis sicca)
Info Link:
More common with active cGVHD; effects may persist after cGVHD resolves.
|
Treatment Factors
Cranial radiation
Eye radiation
Radiomimetic chemotherapy (e.g., doxorubicin, dactinomycin)
|
Treatment Factors
Radiation dose to eye >30 Gy
Radiation fraction >2 Gy
|
History
Dry eyes (burning, itching, foreign body sensation, inflammation)
(Yearly)
Physical
Eye exam
(Yearly)
|
Health Links
See "Patient Resources" field
Eye Health
Considerations for Further Testing and Intervention
Supportive care with artificial tears. Schirmer's testing as clinically indicated. Ongoing ophthalmology follow-up for identified problems. Consider every six month ophthalmology evaluation for patients with corneal damage.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Dental
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
100 |
HCT with cGVHD |
Xerostomia
Salivary gland dysfunction
Dental caries
Periodontal disease
Oral cancer
Info Link: More common with active cGVHD; effects may persist after cGVHD resolves.
|
Treatment Factors
Head and neck radiation involving the parotid gland
Higher radiation doses
Radiomimetic chemotherapy (e.g., doxorubicin, dactinomycin)
|
Treatment Factors
Salivary gland radiation dose >30 Gy
|
History
Xerostomia
(Yearly)
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
Supportive care with saliva substitutes, moistening agents, and sialogogues (pilocarpine). Regular dental care including fluoride applications and regular screening for intraoral malignancy.
|
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 |
101 |
HCT with cGVHD |
Pulmonary toxicity
Bronchiolitis obliterans
Chronic bronchitis
Bronchiectasis
Info Link: More common with active cGVHD; effects may persist after cGVHD resolves.
|
Treatment Factors
Chest radiation
TBI
Pulmonary toxic chemotherapy:
- Bleomycin
- Busulfan
- Carmustine (BCNU)
- Lomustine (CCNU)
|
Medical Conditions
Prolonged immunosuppression related to cGVHD and its treatment
|
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. 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 patients with symptomatic pulmonary dysfunction, influenza, and Pneumococcal vaccinations.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Immune
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
102 |
HCT with cGVHD |
Immunologic complications
Secretory IgA deficiency
Hypogammaglobulinemia
Chronic infections (e.g., conjunctivitis, sinusitis, and bronchitis associated with chronic GVHD)
Info Link: Related to cGVHD; effects may persist or resolve over time.
|
|
Host Factors
Low CD4 T-cell count
Medical Conditions
Prolonged immunosuppression related to cGVHD and its treatment
|
History
Chronic conjunctivitis
Chronic sinusitis
Chronic bronchitis
(Yearly)
Physical
Pulmonary exam
(Yearly)
Screening
Eye exam
Nasal exam
Pulmonary exam
(Yearly)
|
Considerations for Further Testing and Intervention
Consider PCP and anti-fungal prophylaxis in patients with active cGVHD for duration of immunosuppressive therapy. Immunology or infectious diseases consultation for assistance with management of chronic infections.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Immune
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
103 |
HCT with cGVHD |
Functional asplenia
At risk for life-threatening infection with encapsulated organisms (e.g., Haemophilus influenzae, streptococcus pneumoniae, meningococcus)
Info Link: This section applies only to patients who have active cGVHD
|
Treatment Factors
Splenic radiation
Ongoing immuno-suppression
|
Host Factors
Hypogammaglobulinemia
|
Physical
Physical exam at time of febrile illness to evaluate degree of illness and potential source of infection
(When febrile T >101 degrees F)
Screening
Blood culture
(When febrile T >101 degrees F)
|
Health Links
See "Patient Resources" field
Splenic precautions
Considerations for Further Testing and Intervention
Consider antibiotic prophylaxis for encapsulated organisms and bacteremia/endocarditis prophylaxis for duration of immunosuppressive therapy for cGVHD. In patients with T >101 degrees F (38.3 degrees C) or other signs of serious illness, administer a long-acting, broad-spectrum parenteral antibiotic (e.g., ceftriaxone), and continue close medical monitoring while awaiting blood culture results. Hospitalization and broadening of antimicrobial coverage (e.g., addition of vancomycin) may be necessary under certain circumstances, such as the presence of marked leukocytosis, neutropenia, or significant change from baseline CBC; toxic clinical appearance; fever >104 degrees F; meningitis, pneumonia, or other serious focus of infection; signs of septic shock; or previous history of serious infection. Immunize with Pneumococcal, Meningococcal, and HIB vaccines. Pneumovax booster in patients >10 years old at >5 years after previous dose.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = GI/Hepatic
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
104 |
HCT with cGVHD |
Esophageal stricture
Info Link: Related to cGVHD; generally not reversible over time.
|
Treatment Factors
Radiation involving the esophagus
Radiomimetic chemotherapy (e.g., doxorubicin, dactinomycin)
Medical Conditions
Gastroesophageal reflux
|
Treatment Factors
Radiation dose >40 Gy
|
History
Dysphagia
Heartburn
(Yearly)
|
Health Links
See "Patient Resources" field
Gastrointestinal Health
Considerations for Further Testing and Intervention
Surgery and/or gastroenterology consultation for symptomatic patients.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
System = Female reproductive
Score = 1
Sec # |
Therapeutic Agent(s) |
Potential Late Effects |
Risk Factors |
Highest Risk Factors |
Periodic Evaluation |
Health Counseling Further Considerations |
105
(Female) |
HCT with cGVHD |
Vaginal fibrosis/stenosis
Info Link: Related to cGVHD; generally not reversible over time.
|
Treatment Factors
Pelvic radiation
|
|
History
Psychosocial assessment
Dyspareunia
Vulvar pain
Post-coital bleeding
Difficulty with tampon insertion
(Yearly)
|
Considerations for Further Testing and Intervention
Gynecologic consultation for management. Psychological consultation in patients with emotional difficulties.
|
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 |
106 |
HCT with cGVHD |
Joint contractures
Info Link: Related to cGVHD; generally not reversible over time.
|
|
|
Physical
Musculoskeletal exam
(Yearly)
|
Considerations for Further Testing and Intervention
Consultation with physical therapy, rehabilitation medicine/physiatrist.
|
Note: See a list of Abbreviations at the end of the "Major Recommendations" field.
Abbreviations
- ACS, American Cancer Society
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- BMD, bone mineral density
- cGVHD, chronic graft versus host disease
- CBC, complete blood count
- CT, computed tomography
- CXR, chest x-ray
- DEXA, dual energy x-ray absorptiometry
- DLCO, diffusion capacity of carbon monoxide
- DOE, dyspnea on exertion
- GI, gastrointestinal
- GVHD, graft versus host disease
- Gy, gray
- HCT, hematopoietic cell transplant
- HCV, Hepatitis C virus
- HIB, Haemophilus influenza b vaccine
- IgA, immunoglobulin A
- MRI, magnetic resonance imaging
- NCI, National Cancer Institute
- PCP, Pneumocystis carinii pneumonia
- PCR, polymerase chain reaction
- PFTs, pulmonary function tests
- RDA, recommended daily allowance
- SD, standard deviation
- SMN, secondary malignant neoplasm
- SOB, shortness of breath
- T, temperature
- TBI, total body irradiation
- VOD, veno-occlusive disease
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.