NcXHF

REDUCING THE BURDEN OF LATE EFFECTS IN SURVIVORS OF CHILDHOOD CANCER
Commonly reported solid SMNs include breast, thyroid,
skin, and brain cancer. There is a well-defıned association between
radiation exposure that is characterized by a long latency
that exceeds 10 years. 13,15 The incidence of many of
these solid SMNs continues to increase with longer followup,
with no plateau of risk over time. 13,15 Other SMNs, such
as treatment-associated leukemia (myelodysplastic syndrome/acute
myeloid leukemia [tMDS/AML]) are notable
for their shorter latency ( 5 years from primary cancer diagnosis),
and association with alkylating agent and/or
topisomerase-II inhibitor chemotherapy. 20,21 The distinct
differences in the onset and role played by specifıc therapeutic
exposures often have resulted in the classifıcation of SMNs
into two distinct categories: (1) radiation-related solid SMNs,
and (2) chemotherapy-related tMDS/AML. 21
Radiation-Associated Solid Subsequent Malignant
Neoplasms
Breast cancer. Female childhood cancer survivors treated
previously with radiation involving the chest area (e.g., mantle,
mediastinal, whole lung, and axillary fıelds) are at high
risk of developing breast cancer later in life. 22-24 In this population,
the cumulative incidence of breast cancer ranges
from 12% to 20% by age 45, 22-24 an incidence equivalent to
that seen in women who have a BRCA gene mutation (incidence
10% to 19% at age 40). 24 In childhood cancer survivors,
the latency of breast cancer after chest radiation ranges from
8 to 10 years, and the risk increases in a linear fashion with
radiation dose. 24,25 The relative risk is 6.4 at a dose of 20 Gy
and it increases to 11.8 at a dose of 40 Gy. 24,25 Breast cancer
risk is attenuated among women who also received radiation
to the ovaries, which reflects the role of hormone stimulation
on patients with radiation-induced breast cancer. 24,25
Screening recommendations 10 for women exposed to 20
Gy or more of radiation to the chest area (Table 1) include
monthly breast self-examination beginning at puberty, annual
clinical breast examination beginning at puberty until
KEY POINTS
There are a growing number of long-term survivors of
childhood cancer at risk for treatment-related
complications later in life.
There are well-established associations between
therapeutic exposures and adverse health-related outcomes
such as subsequent malignant neoplasms, cardiovascular
disease, and endocrinopathies.
A number of risk-based exposure-related guidelines have
been established to facilitate the long-term follow-up care
of childhood cancer survivors.
These surveillance guidelines are an integral component of
the lifelong follow-up of childhood cancer survivors.
Studies are needed to evaluate the efficacy of these
recommendations in survivors who have the highest risk
for treatment-related complications.
age 25, and clinical breast examination every 6 months with
annual mammograms and MRIs beginning 8 years after radiation
exposure or at 25 years (whichever occurs last).
Thyroid cancer. Survivors at risk include those treated with
head, neck, chest, mantle, craniospinal, or total-body irradiation
(TBI). 26,27 The association between radiation dose and
thyroid cancer is curvilinear, with risk increasing at low to
moderate doses and decreasing at doses more than 30 Gy because
of cell-killing effect. 27-29 Additional risk factors for developing
thyroid cancer include younger age at diagnosis,
female sex, and longer duration of follow-up. 27,29,30
Childhood cancer survivors treated with radiation affecting
the thyroid should have lifelong annual screening
exams for thyroid abnormalities (Table 1). Although some
have advocated the use of thyroid ultrasonography to
screen for thyroid cancer in previously irradiated patients,
31,32 the Children’s Oncology Group (COG) currently
recommends careful palpation annually. 5 The
indolent course and excellent outcome of the vast majority
of second primary thyroid cancers has prompted debate
about the risks versus the benefıts of ultrasound screening
in at-risk survivors. 32,33
Brain tumor. Childhood cancer survivors have an 8.1 to 52.3
times higher incidence of developing subsequent brain tumors
compared to the general population. 34 High-grade gliomas
and meningiomas are the two most common SMNs, and
the vast majority of these tumors develop in children treated
with cranial radiation. 34,35 Although the risk for subsequent
brain tumors demonstrates a linear relation with radiation
dose, the dose-response appears to be weaker for gliomas
than for meningiomas. 15,34
Survivors treated with cranial radiation should have an annual
follow-up that includes a targeted history and a comprehensive
neurologic examination. 5 The additional benefıt of
screening using neuroimaging (e.g., MRI) is not known, but
it remains an active area of investigation. 35,36
Skin cancer. Nonmelanoma skin cancer (NMSC; e.g., basal
cell, squamous cell) is one of the most frequent SMNs in
childhood cancer survivors. 15,37 Compared to the general
population, childhood cancer survivors have a fıvefold increased
risk of NMSC, and 90% of tumors occur within the
radiation fıeld. 37 Although melanomas are less common than
NMSCs, survivors of hereditary retinoblastoma are at an especially
high risk. 38,39 This may be the result of common etiologic
factors between the two tumor types.
Areas of the skin previously exposed to radiation should
be monitored closely during annual physical examinations,
with prompt referral to dermatology for evaluation of nevi
that are concerning for skin cancer. 5
Colorectal cancer. Recent reports 13,40,41 from aging cohorts
of childhood cancer survivors have highlighted the markedly
increased risk of digestive SMNs (absolute excess risk in survivors
older than 40, 5.9 per 100,000), with the highest risk
asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK 197