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ARMENIAN, KREMER, AND SKLAR
TABLE 1. Risk-Based Screening for Subsequent Malignant Neoplasms
Potential Late Effect Cancer Treatment Screening Tests
Breast Cancer Radiation to the chest area Females:
Clinical breast exam yearly beginning at puberty until age 25, then every 6 mo
Mammogram and breast MRI yearly for patients who received 20 Gy beginning 8 yr
after radiation or at age 25, whichever occurs last. For patients who received 10-19 Gy,
clinicians should discuss benefits and risks/harms of screening with patients.
Thyroid Cancer Radiation to the thyroid Yearly physical examination
Brain Tumor Cranial irradiation Yearly targeted history and comprehensive neurologic examination
Skin Cancer Radiation to the skin Yearly physical examination
Colorectal Cancer Abdominal/pelvic irradiation Colonoscopy every 5 yr (minimum for patients who received 30 Gy, beginning 10 yr
after radiation or at age 35, whichever occurs last)
Spinal irradiation
tMDS/AML Alkylating agents, topoisomerase-II inhibitors Yearly targeted history/physical examination
Abbreviations: mo, months; yr, years; tMDS, trilineage myelodysplasia; AML, acute myeloid leukemia.
seen in survivors exposed to abdominal radiation. In fact, by
age 50, the incidence of colorectal cancer (CRC) for survivors
treated with direct abdominopelvic radiation is comparable
to the risk in individuals with at least two fırst-degree relatives
affected by CRC. 13
For survivors treated with 30 Gy or more of abdominopelvic
radiation, the COG recommends a screening colonoscopy
every 5 years, beginning 10 years after radiation or at
age 35, whichever occurs last. 5
Chemotherapy-Related TMDS/AML
Survivors treated with alkylating agents (e.g., cyclophosphamide,
ifosfamide, mechlorethamine, melphalan, busulfan,
nitrosureas, chlorambucil, dacarbizine, and platinum compounds)
or topoisomerase-II inhibitors (e.g., epidophyllotoxins,
anthracyclines) are at risk for developing tMDS/
AML. 18,42 The risk of alkylating-agent–associated tMDS/
AML is dose-dependent, with a latency of 3 to 5 years after
exposure. Typically, it is associated with cytogenetic abnormalities
involving chromosomes 5 (5/del[5q]) and 7 (7/
del[7q]). Topoisomerase-II inhibitor-related tMDS/AML
has a shorter latency ( 3 years), and is associated with balanced
translocations involving chromosome bands 11q23 or
21q22. 18,42
Since chemotherapy-related tMDS/AML usually develops
by 10 years after exposure to these agents, current recommendations
are to monitor at-risk survivors with a targeted
history and physical examination for up to 10 years postexposure.
5 A complete blood count and bone marrow examination
may be warranted for those with a history or physical
examination fındings suspicious for tMDS/AML (e.g., easy
bruising, fatigue, pallor, and petechiae). 5
CARDIOVASCULAR DISEASE
Cardiovascular disease is a major health problem in children
and adults after treatment for childhood cancer. 43 In fact,
childhood cancer survivors have a sevenfold increased risk of
cardiac death when compared with the general population.
The risk is highest in survivors of HL, kidney tumors, and
Ewing sarcoma. 12,14 Cardiovascular complications after treatment
for childhood cancer include cardiomyopathy/heart failure,
coronary artery disease, valvular disease, conduction
abnormalities, and pericardial disease. 43 Outcome following onset
of cardiovascular complications such as heart failure is especially
poor, with 5-year survival less than 50%. 44
In survivors of childhood cancer, there is a long latency between
cancer treatment and onset of clinically overt cardiovascular
disease. 43 As a result, there have been a number of
initiatives to facilitate early detection and treatment of
asymptomatic disease, 5,7,8,42 setting the stage to minimize the
long-term burden as a result of these complications. Recently,
an international collaborative effort was organized to
develop evidence-based guidelines for cardiomyopathy surveillance
in at-risk survivors of childhood cancer. 11 Additional
surveillance guidelines pertaining to coronary artery
disease, valvular disease, conduction abnormalities, and pericardial
disease are pending. When completed, these recommendations
may facilitate the implementation of uniform
evidence-based guidelines to minimize the long-term burden
as a result of cardiovascular disease in these survivors.
Cardiomyopathy
Childhood cancer survivors treated with cardiotoxic therapies
(anthracycline chemotherapy and/or chest radiation)
are at risk for developing asymptomatic cardiomyopathy that
can progress to symptomatic heart failure over time. 43 The
risk of heart failure is 15-fold greater in survivors of childhood
cancer when compared to the general population, 3 and
there is a dose-dependent association with anthracycline
(doxorubicin, daunorubicin, epirubicin, idarubicin, and mitoxantrone)
chemotherapy and risk of heart failure. This risk
is further increased by exposure to chest radiation. 43 Among
anthracycline-exposed survivors, asymptomatic cardiomyopathy
is characterized by a decrease in left ventricular systolic
function, which often presents with a clinical picture
similar to dilated cardiomyopathy. 43 Patients treated with
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