Northeast Florida Medicine
Vol. 66, No. 2 2015
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Pediatric Oncology
A brief review of organ system-specific concerns is
outlined below:
Cardiac:
Cardiac dysfunction is closely linked to the total cumulative
doses of anthracycline-class drugs including daunomycin,
doxorubicin, idarubicin and mitoxantrone. Toxicities can
include arrhythmias and cardiomyopathy. The cardiac
toxicity may be so severe as to necessitate subsequent cardiac
transplant.This is among themost concerning late effects.The
risk of cardiomyopathy is affected by cumulative dose, age of
exposure to the drug, gender (worse in females), and exposure
tomediastinal radiation.
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Monitoring of cardiac function and
dose limitation during treatment should limit the incidence
of toxicity. However, due to poorly understood individual
variation in toxicity, life-long screening is recommended.
15
Radiation therapy, which includes the heart within the
field, is common in diseases such as Hodgkin’s lymphoma
of the mediastinum, and can add to the cumulative risk.
In addition, it may cause its own potential toxicities.
Premature atherosclerosis, cardiac valvular disease, and
restrictive pericarditis have all been well reported late
effects. Adult survivors will require ongoing monitoring
with echocardiograms and EKG’s in addition to a thorough
history and physical exam. Several studies have shown that
early identification and treatment of cardiac changes does
decrease the severity and progression of treatment related
heart disease.
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Pulmonary:
Pulmonary toxicity canbe causedby surgery (lung resection,
chest wall surgery), chemotherapy, and radiation involving
the lung fields. Bleomycin and busulfan are associated with
pulmonary fibrosis, while use of nitrosureas can result in a
chronic pneumonitis. Chest irradiation is often administered
in patients with Hodgkin’s lymphoma, Wilms tumor and
other tumors with pulmonary metastases, along with chest
wall tumors such as Ewings sarcoma of the ribs. Radiation-
induced pulmonary fibrosis is associated with higher doses
and larger fields of radiation, and this may occur despite the
most careful planning of treatment fields. Acareful history and
physical examannually will usually identify potential toxicity.
Renal:
Nephrotoxicity is associatedwith the specific chemotherapy
agents cisplatin, carboplatin, methotrexate and ifosfamide.
It may be further complicated by the supportive care agents
used during treatment of cancer, such as aminoglycosides
and amphotericin B. Glomerular toxicity, renal insufficiency,
hypertension and tubular dysfunction are all reported.
Flank radiation, which encompasses the kidney, can also
cause dysfunction. Bladder damage from metabolites of
ifosfamide and cyclophosphamide can result in long-term
bladder dysfunction, bladder fibrosis and an increased risk of
secondary bladder cancer. Annual urinanalysis andmetabolic
panels are recommended for patients who have received any
of the above mentioned therapies.
Hearing and vision:
Both acute and long-term progressive hearing loss can
be seen after treatment with cisplatin or carboplatin. High
frequency hearing loss ismost common, with hearing losses in
lower frequency being seen in more severe cases. Radiation in
doses > 30 Gy to the cranium/ear region may also be ototoxic
and hearing loss is additive to those seen with chemotherapy.
Radiation to the eyes, optic tracts or occipital lobe can all
cause significant visual defects. Prolonged use of steroids, as
in some children with brain tumors and leukemia, can also
result in cataract formation.
Endocrine:
Endocrinopathies are common late effects inchildren treated
for brain and head and neck tumors. These endocrinopathies
may include pituitary dysfunction, leading to secondary
endocrinopathies, or primary toxicity to thyroid, adrenal
and gonadal function. In addition, the alkylating agents,
busulfan, cyclophosphamide, ifosfamide, melphalan, and
procarbazine,may lead todirect gonadal damagewith resulting
hypogonadism or infertility. Radiation to the hypothalamic
pituitary axis can also cause centrally-mediated delayed
puberty and hypoganadism. Radiation to the testes and
ovaries is associated with infertility as well. A careful history
and physical exam is essential and should be coupled with
hormonal testing, as appropriate, to the treatment received.
Many endocrinopathies are not apparent early after treatment
but canoccurmanyyears later. Fertility is aparticularly complex
issue as well. For many post-pubertal boys, pre-treatment
sperm banking is offered and egg retrieval technology is
rapidly improving.
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However, earlymenopause inwomenand
infertility are significant concerns for young adult survivors
and should be discussed with patients as part of routine care.
Musculoskeletal:
Corticosteriod use is common in children treated for
leukemia and lymphomas and can result in an increased risk
of osteopenia and osteoporosis. Bone density monitoring,
and early intervention if required, is now standard in post-
therapy protocols. Avascular necrosis is being recognizedwith
increasing frequency in those patients treated with high doses
of steroids as well, and may be a siginificant cause of impaired
function in adult survivors.
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Radiation involving bone can
lead to reduced/uneven growth, hypoplasia, and fibrosis.
