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Vol. 66, No. 1 2015
Northeast Florida Medicine
Otolaryngology
Surgery remains the mainstay of treatment for most
thyroid cancers. Recently, the use of intraoperative nerve
monitoring of the recurrent laryngeal nerve (RLN) has
become increasingly widespread in this country. Unfor-
tunately, a meta-analysis of nearly 65,000 nerves at risk
failed to show any significant change in rates of perma-
nent nerve injury.
25
Studies have shown a decreased rate
of complications (RLN injury and hypoparathyroidism),
decreased length of stay, and decreased total costs when
surgery is performed by high-volume thyroid surgeons (100
or more cases per year) compared to low-volume surgeons
(less than 10 cases per year).
26
Several newer remote access surgical techniques have been
developed for thyroid surgery. These include transaxillary,
transoral, transmammary and robotic surgery via a facelift
approach. These approaches are most frequently utilized
for treatment of benign disease and are intended to avoid
a cervical incision with its resultant scar. These approaches
require careful patient selection.
27
Research has led to a greater understanding of the sig-
naling pathways that lead to malignant transformation in
thyroid cancers. Mutations have been identified at several
points. These include BRAF, NRAS, HRAS, KRAS and
other mutations. Recently, molecular or genetic testing
of some thyroid nodules (follicular or indeterminate) has
allowed clinicians to identify patients who are at increased
risk for malignancy. There are several commercial labora-
tories that offer this testing. Verocyte (based in California)
offers Afirma® testing which analyzes 142 genes to reclassify
indeterminate Fine Need Aspiration (FNA) samples as
“benign” or “suspicious.” Verocyte quotes a 95 percent
negative predictive value (NPV) for its Afirma® testing.
28
Another company, Asuragen, uses its miRInform® Thy-
roid test, which analyzes FNA samples for the presence
of seventeen molecular markers to help in the analysis of
indeterminate thyroid nodules. The need for surgery may
be eliminated in some patients with indeterminate nodules
whose molecular testing characterizes the lesions as benign.
New Medical Treatments
In 2006, the FDA approved the use of Erbitux (cetux-
imab) for use in non-metastatic head and neck squamous
cell carcinoma in combination with radiation or as a single
agent. Erbitux is a chimeric monoclonal IgG antibody with
affinity for the epidermal growth factor receptor, which is
expressed in the majority of head and neck squamous cell
carcinomas. Erbitux functions as an EGFR antagonist.
A Phase III trial demonstrated significantly improved
locoregional control when cetuximab was combined
with radiation therapy compared to radiation alone. The
addition of Erbitux to standard radiation therapy led to
a 26 percent decrease in the risk of death and improved
median survival time of 49.0 months, compared to 29.3
months with radiation alone.
29
In a subsequent publication,
Bonner demonstrated a 5-year survival rate of 45.6 percent
for patients treated with Erbitux plus radiation therapy,
compared to a 36.4 percent rate for radiation therapy
alone.
30
In 2011, the FDA expanded its approval for the
use of Erbitux to include metastatic disease.
In April 2011, the FDA approved Caprelsa (vandetanib),
a tyrosine kinase inhibitor, for use in patients with advanced
medullary thyroid carcinoma (MTC) who are ineligible
for surgery and have progressive disease with symptoms.
Approval was based on a study byWells et al, which showed
that patients receiving the drug lived an average of 11.2
months without tumor growth as compared with four
months in the control group receiving placebo. There was
a reduction in tumor size experienced by 27 percent of the
study group. The effect lasted 15 months on average.
31
A
second drug, Cometriq (cabozantinib), was approved for
similar indications in November 2012.
In November 2013, the FDA approved Nexavar
(sorafenib) for use in the treatment of progressive differ-
entiated thyroid carcinoma (papillary and follicular) that
cannot be treated with radioactive iodine (I-131). This
medication is known as a dual inhibitor. First, it targets
the signaling pathway that leads to malignancy transfor-
mation (targeting RAF, MEK, ERK). Secondly, it inhibits
angioneogenesis (required for tumor growth) by interfering
with the vascular endothelial growth factor (VEGF) and
the platelet-derived growth factor (PDGR) receptors in
tumor vascular tissue.
32
The search continues for effective treatments for the
most aggressive form of thyroid cancer – anaplastic
thyroid carcinoma.
33
Summary
The past decade has seen numerous changes in the man-
agement of head and neck cancer. Innovative diagnostic
techniques, less invasive surgical procedures and improved
medical therapies offer renewed hope in the fight against
this devastating set of diseases. Better functional outcomes
and improved survival rates have benefitted the lives of
thousands of patients. We look forward to even more
advances in both treatment and prevention in the decades
to come.
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