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33
CANCER OF THE NASAL CAVITY

AND PARANASAL SINUSES
Allen M. Chen, MD, Janice Ryu, MD, FACR, Paul J. Donald, MD, FRCS(C),
and A. Dimitrios Colevas, MD
EPIDEMIOLOGY, ETIOLOGY, AND
PATHOGENESIS
Malignancies arising from the nasal cavity and paranasal
sinuses are relatively rare tumors of the head and neck. They
account for only 3% of all upper respiratory tract cancers, with
a yearly incidence of 1 per 100,000 people.1 Because of their rarity,
these sites are grouped together in most published reports. It is
often difficult to determine the exact site of origin, because most
of these tumors present at an advanced stage and extensively
involve adjacent sites. Among the tumors arising in this anatomic
region, 60% to 90% involve the paranasal sinuses, the majority
being in the maxillary antrum. There is a 2:1 male predominance
for these tumors.2,3 Most patients with carcinomas arising in the
sinonasal region are older than 40 years of age.2,4 Esthesioneuro
blastoma may occur in much younger patients as well.
Unlike other upper and lower respiratory tract carcinomas,
nasal cavity and paranasal sinus cancers have not been associated
with cigarette smoking.5 Chronic sinusitis, although frequently
coexistent with malignant tumors in this region, is not a causative
agent.6 However, an increased risk of adenocarcinoma of the
nasal cavity and ethmoid sinus has been associated with wood
dust exposure.7-9 A meta-analysis of 11 published studies of men
with wood-related occupations showed that the odds ratio for
developing adenocarcinoma was 13.5, with the risk correlative
with the quantity and duration of exposure.10 An increased risk
(odds ratio 2.4) of developing squamous cell carcinomas of the
sinonasal region was seen only among those employed for 30 or
more years in jobs with exposure to fresh wood. Other industrial
risk groups include leather tanners11 and nickel refinery workers
(250-fold risk for developing squamous cell carcinoma of the
maxillary antrum12 and more than 40-fold risk for developing
squamous cell carcinoma of the nasal cavity13). Thorotrast, a
radioactive contrast medium used in the 1960s for radiographic
studies of the maxillary sinus, is an established carcinogenic agent
for maxillary sinus carcinoma.
Because of the relative rarity of sinonasal cancer, there are a
lack of studies analyzing the underlying cytogenetic and molecu
lar findings. In one of the few published reports, overexpression
of p53 was found in 60% of sinonasal carcinomas, including 42
squamous cell carcinomas and 10 adenocarcinomas, in a Taiwan
ese study on Asian patients.14
ANATOMY
Both surgical resection and delivery of radiation therapy
cannot be effectively executed without a detailed understanding
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of the anatomy of the nasal cavity and paranasal sinuses. Because

most of the sinuses develop as pneumatizations of solid bones,
the extent of this process is highly variable between individuals.
This is true even between sides of the same person. It is this high
degree of variability that makes sinus surgery so difficult, espe
cially considering the number of vital structures that abut them.
The sinuses are the result of a mysterious process by which solid
facial skeletal elements are invaded by respiratory mucosa and are
thus pneumatized. The trigger for this process and its mechanism
are a complete enigma.
The sinuses are lined by respiratory mucosa, which, although
appearing histologically similar, has varying behavior when
altered by a disease process. This is especially true of the frontal
sinus. Whether this is a product of the anatomic conditions pecu
liar to each sinus or the result of the inherent nature of the
mucosa itself remains unclear. The sinuses are composed of
the maxillary, ethmoid, frontal, and sphenoid sinuses. They are
generally named for the bones they primarily pneumatize. The
ethmoids are traditionally divided into anterior and posterior
groups divided by the grand lamina of the middle turbinate.
Their drainage ostia empty into the recesses of the lateral wall of
the nose. The maxillary sinus is the end result of pneumatization
of the maxillary bone. To a variable and not necessarily sym
metrical extent, the sinus occupies a key position in the central
face.
Nasal Cavity
The coronal and transverse sections of the nasal cavity are
illustrated in Fig. 33-1, Fig. 33-2, and Fig. 33-3. Anteriorly, the
nasal cavity begins from the limen nasi, the line of transition from
skin to mucous membrane. The nasopharynx is situated directly
behind the nasal cavity and communicates with it by the posterior
nasal aperture. Inferiorly, the floor is composed of the hard
palate. Superiorly, the nasal cavity borders the base of the skull
(frontal sinuses, cribriform plate of the ethmoid bone, and
ethmoid air cells). The medial walls of the maxillary sinuses
define the lateral extent of the nasal cavity. The midline septum
divides the nasal cavity into two halves. Three turbinates (or
conchae)superior, middle, and inferiorprotrude downward
and medially from the lateral wall into the nasal cavity, forming
three meatus. The superior turbinate is much smaller than the
middle and inferior turbinates, and is situated directly in front of
the sphenoidal sinus. The nasolacrimal duct drains into the nasal
cavity below the inferior turbinate.
The cribriform plate contains the first cranial nerve branches,
which distribute their olfactory nerve endings to the upper one
third of the septum and superior turbinates. Thus, the cribriform
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FIGURE 33-1 Computed tomographic images of the normal anatomy of the paranasal sinuses in the coronal plane (shown in
anterior to posterior direction from A to C). A, Section through the frontal sinuses, midorbit, anterior ethmoidal sinuses, and nasal
cavity. 1, Orbital roof; 2, zygomatic process of frontal bone; 3, crista galli; 4, left frontal sinus; 5, cribriform plate; 6, vertical plate of
ethmoid bone; 7, anterior ethmoidal air cells; 8, superior extent of nasal cavity; 9, lamina papyracea; 10, right globe; 11, middle
turbinate; 12, nasolacrimal duct; 13, nasal septum (bony above, cartilage below); 14, maxillary sinus; 15, maxilla. B, Section through
the posterior orbit, cribriform plate, middle ethmoidal sinuses, and nasal cavity. 1, Anterior cranial fossa; 2, crista galli; 3, olfactory
fossa; 4, roof of ethmoidal sinus; 5, cribriform plate; 6, superior rectus muscle; 7, superior oblique muscle; 8, medial rectus muscle;
9, inferior rectus muscle; 10, optic nerve; 11, superior extent of nasal cavity; 12, middle ethmoidal air cells; 13, orbital process of
zygoma; 14, infraorbital canal; 15, maxillary sinus; 16, middle turbinate; 17, inferior turbinate; 18, hard palate. C, Section through
the sphenoidal sinus, maxillary sinus, and the posterior aspect of the nasal cavity. 1, Lesser wing of sphenoid; 2, planum
sphenoidale; 3, sphenoidal sinus; 4, greater wing of sphenoid; 5, superior turbinate; 6, vomer; 7, middle turbinate; 8, tip of coronoid
process; 9, lateral wall of maxillary sinus; 10, medial wall of maxillary sinus; 11, inferior turbinate; 12, inferior wall of maxillary sinus;
13, maxillary antrum; 14, hard palate; 15, alveolar ridge of maxilla.
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FIGURE 33-2 Computed tomographic images of normal anatomy of the paranasal sinuses in the transverse plane (shown in
superior to inferior direction from A to D). A, Sections through the frontal sinuses and roof of the orbit. 1, Frontal sinuses; 2, roof of
orbit. B, Section through the ethmoidal sinus, orbits, and optic chiasm. 1, Frontal sinus; 2, anterior ethmoidal air cells; 3, lamina
papyracea; 4, middle ethmoidal air cells; 5, cribriform plate; 6, posterior ethmoidal air cells; 7, sphenoidal sinus; 8, greater wing of
sphenoid bone; 9, optic canal; 10, squamous portion of temporal bone; 11, anterior clinoid bone; 12, optic chiasm; 13, bony sella.
C, Sections through the ethmoidal sinus, orbits, and sphenoidal sinus. 1, Nasal bone; 2, lens; 3, vertical plate of ethmoid bone;
4, globe; 5, orbital process of zygoma; 6, anterior ethmoidal air cells; 7, middle ethmoidal air cells; 8, posterior ethmoidal air cells;
9, cribriform plate; 10, optic nerve; 11, medial rectus muscle; 12, lateral rectus muscle; 13, greater wing of sphenoid bone;
14, infraorbital fissure; 15, sphenoidal sinus. D, Sections through the maxillary antrum, pterygoid plates, and nasopharynx. 1, Nasal
septum; 2, nasal vestibule; 3, maxilla; 4, infraorbital canal opening; 5, maxillary antrum; 6, zygomatic arch; 7, inferior meatus;
8, inferior turbinate; 9, coronoid process of mandible; 10, perpendicular plate of palatine bone; 11, pterygomaxillary fissure;
12, lower pterygopalatine fossa; 13, medial pterygoid plate; 14, lateral pterygoid plate; 15, nasopharynx.
Section III: Radiation Oncology
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Part 2 Head and Neck Tumors
Part 2: Head and Neck Tumors
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FIGURE 33-3 Magnetic resonance images of normal anatomy of the paranasal sinuses in the coronal plane (shown in anterior to
posterior direction from A to D). A, Section through the midglobe, ethmoidal sinus, nasal cavity, and maxillary antrum. 1, Crista galli;
2, superior rectus and levator palpebrae superioris muscles; 3, cribriform plate; 4, frontal bone, orbital lamina; 5, superior oblique
muscle; 6, medial rectus muscle; 7, lateral rectus muscle; 8, ethmoidal air cells; 9, inferior rectus muscle; 10, globe; 11, periorbital fat;
12, maxillary antrum; 13, middle turbinate; 14, inferior turbinate; 15, maxilla; 16, hard palate; 17, tongue. B, Section through posterior
orbit, ethmoidal sinus, nasal cavity, and maxillary antrum. 1, Temporalis muscle; 2, ethmoidal air cells; 3, superior rectus and levator
palpebrae superioris muscles; 4, superior oblique muscle; 5, optic nerve; 6, lateral rectus muscle; 7, medial rectus muscle; 8, inferior
rectus muscle; 9, retro-orbital fat; 10, middle turbinate; 11, inferior turbinate; 12, zygomatic bone; 13, masseter muscle; 14, buccal fat
pad; 15, hard palate; 16, nasal septum; 17, tongue; 18, maxillary antrum. C, Section through the sphenoidal sinus and nasopharynx.
1, Temporal lobe; 2, sphenoidal sinus; 3, sphenoid bone; 4, nasopharynx. D, Section through the optic chiasm, cavernous sinus, and
pituitary gland. 1, Optic chiasm; 2, cranial nerve V, maxillary branch (V2); 3, suprasellar cistern; 4, pituitary gland; 5, sphenoidal sinus;
6, clivus; 7, internal carotid artery; 8, lateral pterygoid muscle.
plate serves as an avenue of cancer spread to the anterior cranial

fossa from the nasal cavity.
Maxillary Sinus
The maxillary sinus (also called the maxillary antrum) is a
pyramidal cavity (see Figs. 33-1C, 33-2D, and 33-3A) of approxi
mately 15 cm3 volume (3.7 2.5 3.0 cm). The base of the
pyramid is composed of the medial wall, which separates the
maxillary sinus from the nasal cavity, and the apex is in the zygo
matic process. Superiorly, the floor of the orbit forms the roof of
the antrum. Anteriorly, the facial wall is located behind the cheek
and curves inward into the sinus. Posteriorly, the infratemporal
wall borders infratemporal and pterygopalatine fossae. The floor
of the maxillary sinus lies inferior to the floor of the nasal cavity,
especially in edentulous patients.15 Secretion from the maxillary
sinus is drained into the nasal cavity via openings in the middle
meatus. The medial wall of the sinus, of all its confines, is the
most complex. It forms the inferior aspect of the lateral wall of
the nose. Contained within it is the nasolacrimal duct. The exit
of this duct is approximately 1cm from the pyriform rim. The
ostium of the maxillary antrum is traditionally described empty
ing into the posterior aspect of the hiatus semilunaris. The roots
of the second premolar and first two molars penetrate the bony
floor of the maxillary sinus.
The anatomic relations of the maxillary sinus provide the
mechanism of manifestation of the manifold disease processes
that afflict the sinuses. The relationship of the floor of the sinus
to the maxillary teeth and roof of the oral cavity has already been
described. The lateral and anterior walls are related to the soft
tissues of the middle one-third of the face. The fat pad of Bichat
lies adjacent to the lateral sinus wall with posterosuperior exten
sions into the infratemporal fossa. It is covered by a facial layer
Chapter 33 Cancer of the Nasal Cavity and Paranasal Sinuses
Ethmoid Sinuses
The ethmoid cells, collectively called a sinus, lie between the
nasal cavity and the orbit (see Figs. 33-1B, 33-2C, and 33-3B).
The air cells, like a honeycomb, have the thin orbital plate of the
frontal bone of the anterior cranial fossa for a roof (fovea eth
moidalis). They are grouped into anterior, middle, and posterior
air cells on each side. The anterior cell is closely related to the
frontal sinus and connects to the nasal cavity via the middle
meatus. The middle ethmoid cell makes a bulge into the lateral
wall of the nasal cavity (bulla ethmoidalis) and also communi
cates with the middle meatus. The posterior ethmoid cells are
closely related to the optic canal and nerve, and open into the
superior meatus. These openings between the nasal cavity and
the ethmoid cells are an obvious route of tumor extension. The
fragile medial wall of the orbit, formed by the lamina papyracea
of the ethmoid bone, is extremely porous and is an easy conduit
for tumor spread from the ethmoid sinus into the orbit. The
superior portion of the nasal septum separates the right and left
ethmoid cells. Most anterior ethmoid air cells extend within 1cm
of the anterior skin surface between the medial canthi. The orbits
are conical and the ethmoid sinuses expand posteriorly and infe
riorly to form the medial walls of the orbit. The optic nerves lie
at about the same level as the roof of the ethmoid cells.16 The floor
of the orbit rises posteriorly; thus the orbital apex lies superior to
the inferior rim of the orbit.
Sphenoidal Sinus
The sphenoidal sinus is an air cavity within the body of the
sphenoid bone. It is a midline structure located anterior to the
clivus, posterior to the superior meatus of the nasal cavity (see
Figs. 33-2B, 33-2C, and 33-3C). The lateral sphenoid sinus wall
has a series of bulges and grooves corresponding to a number of
vital structures that traverse the cranial side of its lateral walls.
The cavernous sinuses lie lateral to the sphenoidal sinus with all
their vessels (internal carotid artery) and cranial nerves (II, III,
IV, V1, V2). The pituitary fossa and the optic chiasm lie above
and the nasopharynx is located below the sphenoidal sinus. The
sphenoidal sinus can be very extensive and may extend laterally
between the maxillary nerve and the nerve of the pterygoid canal,
inflating the greater wing of the sphenoid bone and pterygoid
process. The sphenoidal sinus opens into the nasal cavity via the
sphenoethmoid recess.
Frontal Sinus
The pair of frontal sinuses, located within the frontal bone, is
irregular in size and shape and often represents an extension of
an anterior ethmoid cell (see Figs. 33-1A and 33-2A). The sinuses
lie above the orbits. Lined with respiratory epithelium, the frontal
sinus drains into the maxillary sinus via the frontonasal duct.
PATHOLOGIC CONDITIONS
The most common benign tumors arising in the sinonasal
region are inflammatory polyps and benign mixed minor salivary
gland tumors. Other tumors are histologically benign but behave
in a locally aggressive and destructive manner. These tumors
include inverted papillomas and midline granulomas. Inverted
papillomas arise from squamous or schneiderian epithelium and
most often involve the lateral nasal wall. They may destroy bone
and tend to recur if not excised completely. From 10% to 15%
of inverted papillomas are associated with malignant squamous
degeneration.17,18 Inverted papillomas are best treated with
en bloc resection with medial maxillectomy (recurrence rate
<10%).18,19 Midline granuloma syndrome describes a process of
progressive midline facial destruction from various causes includ
ing an immunologic or rheumatoid process and lymphomatous
proliferation. Often a definitive diagnosis cannot be made on the
basis of a biopsy. If the biopsy suggests Wegener granulomatosis,
the treatment consists of systemic steroids or cytotoxic drugs or
both. If the biopsy suggests lymphomatosis or reticulosis, the
patient should have a systemic workup for lymphoma and be
treated with localized radiation if no other disease is found.
Midline lethal granuloma is a diagnosis of exclusion and describes
progressive, painful destruction of the nasal cavity, paranasal
sinuses, and hard palate. Death may eventually result from
massive hemorrhage or infection once the base of the skull is
eroded. The treatment for this condition is radiation therapy.
The most common malignant histologic type involving the
nasal cavity and paranasal sinuses is epithelial in origin, with the
squamous cell or its variants making up 80% to 85%. Other
histologic types are of minor salivary gland origin: adenocarci
noma, adenoid cystic carcinoma, benign mixed, and mucoepi
dermoid carcinoma. Mucoepidermoid carcinomas are extremely
rare in the nasal cavity and paranasal sinuses. On the other hand,
roughly 20% of all head and neck adenoid cystic carcinomas arise
in this region. Adenoid cystic carcinomas are locally aggressive
tumors with a propensity for perineural spread. The tumor
islands have a characteristic pattern of having skip areas in the
extracranial course of the cranial nerves. Once the tumor becomes
intracranial, the skip areas appear to disappear and tumor spread
becomes more continuous. There are three basic patterns to the
cellular composition of these tumors. The cribrose pattern is
most common and fortunately has the best prognosis. The
tubular pattern has an intermediate survival rate, and the tumor
with the worst prognosis is the solid type. In a tumor with a
and is notably prominent in infants. This prominence is thought

to aid the infant in sucking and is sometimes called the suctorial
pad. Subcutaneous fat, a few facial mimetic muscles, and the skin
of the face form the reminder of the immediate relations of this
wall.
The posterior wall is related to the overlying pterygoid plates
inferiorly and posterosuperiorly to the pterygomaxillary space.
The medial and lateral pterygoid muscles take origin on the
pterygoid plates and are intimately related to the posterior wall
of the sinus. The internal maxillary artery passes through both
heads of the lateral pterygoid muscle to gain the pterygomaxillary
space. The maxillary branch of the trigeminal nerve inters the
space via foramen rotundum, leading from the floor of the
middle cranial fossa. Medial and inferior to it, the vidian nerve
enters this space through the pterygoid canal, a foramen in the
sphenoid bone traversing the anterior wall of the foramen
lacerum. This nerve carries parasympathetic fibers from the
greater superficial petrosal nerve and sympathetic fibers from the
internal carotid artery plexus. Its parasympathetic fibers synapse
within the sphenopalatine ganglion, which is subtended for the
maxillary nerve. The nerve beyond this point becomes a mixed
nerve, carrying sensory and autonomic fibers to the nasal cavities,
nose, ocular adnexa, and face.
The superior wall of the sinus is related to the globe. The antral
roofand thus the orbital flooris the thinnest wall of the orbit
and the most vulnerable to trauma. It is obliquely crossed in its
lateral one-third by the infraorbital canal containing the infraor
bital nerve. The medial aspect of the roof is the floor of one or
more ethmoid cells. The contribution to these cells is wider
behind than anteriorly.
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mixed picture, the most predominant cell type often predicts

prognosis. The delayed appearance of distant metastasis is, unfor
tunately, a not uncommon occurrence.
Adenocarcinoma of the paranasal sinuses make up 10% to 20%
of malignancies of the sinonasal tract. They are of mucus gland
origin. Intestinal-type adenocarcinoma (ITA) is the name currently
applied to the form of adenocarcinoma that resembles cancer of
the colon. This tumor is the one that is closely associated with
hardwood dust exposure, although other cell types are seen in this
group of patients as well. ITA tumors have a tendency for blood
borne rather than lymphatic metastases. Despite seemingly nega
tive margins, the tumor also has a marked propensity for local
recurrence. Adenocarcinoma of the sinonasal tract can also rep
resent a metastasis, most often from kidney, breast, or lung.
Melanoma and olfactory neuroblastoma, also known as esthe
sioneuroblastoma, are rare epithelial malignancies arising in the
nasal cavity. Esthesioneuroblastoma originates from olfactory
nerves and is considered a neuroendocrine tumor. It occurs pre
dominantly in young patients between 10 and 20 years old,
although a second peak is observed in an older group between
the ages of 50 and 60 years.20-22 Olfactory neuroblastomas have a
wide spectrum of clinical behavior. Some are slow-growing and
tend to be localized, whereas others may be highly aggressive with
local destruction and spread as well as distant metastasis. The
incidence of cervical nodal involvement is 20%. The most
common presenting symptoms are epistaxis, nasal obstruction,
and a loss of the sense of smell. Mucosal melanomas are most
often found in the nasal cavity and can be primary or metastatic.
Overall, less than 1% of melanomas arise from the sinonasal tract.
Nasal melanomas can often be amelanotic and may require
immunohistochemical and electron-microscopic examination
for definitive histologic diagnosis. Much more so than the cuta
neous melanomas, nasal melanomas have a high incidence of
local recurrence,23,24 and the patient may benefit from postopera
tive radiation therapy.
Undifferentiated carcinomas have been reported to represent
a distinctive, rare, and highly aggressive neoplasm. They are com
posed of small- and medium-sized cells and have to be distin
guished from melanoma, lymphoma, olfactory neuroblastoma,
rhabdomyosarcoma, neuroendocrine carcinoma, and poorly
differentiated squamous cell carcinoma.25 They present at an
advanced stage widely involving the nasal, maxillary, and ethmoid
complexes. Orbital and intracranial extension is seen in the
majority of cases. Prognosis is extremely poor, with 80% to 90%
of patients dying within 1 year of extensive local and metastatic
disease.26 The role of systemic chemotherapy as an adjunct to
aggressive local therapy needs to be investigated.
Nonepithelial tumors include lymphoma, plasmacytoma, and
sarcoma.
CLINICAL PRESENTATION
Early symptoms of nasal cavity and paranasal sinus tumors are
vague and mimic sinusitis symptoms; thus the diagnosis of malig
nancy is often delayed for months. The most common early
symptoms of nasal cavity tumors are unilateral nasal obstruction,
discharge, and epistaxis. Maxillary antrum cancers do not often
exhibit early signs or symptoms. Patients with a maxillary antrum
tumor present with complaints of facial pain, numbness, swell
ing, and nasal obstruction. They may have a facial, intraoral, or
intranasal mass, and less frequently proptosis. Patients with
tumors of the ethmoid sinus tend to present with ocular prob
lems such as epiphora, proptosis, diplopia, and eye pain. Primary
sphenoidal and frontal sinus tumors are extremely rare. Eye

symptoms (diplopia from sixth-nerve palsy) predominate for
sphenoidal tumors, and frontal headache and swelling predomi
nate for frontal tumors.
Cervical lymph node metastases on initial presentation are
uncommon; most large series report an incidence of less than
10% to 15%.27-29 Distant metastases on initial presentation are
even less frequent, with a reported incidence of less than 5%.30
ROUTES OF SPREAD
The nasal cavity and paranasal sinus cancers tend to spread by
local extension into adjacent sinuses and bones. To understand
the patterns of spread, one must be familiar with the complex
anatomy of this region. The nasal cavity and the paranasal sinuses
all interconnect with each other via many apertures and often are
separated only by thin, bony septi, allowing easy invasion of the
tumor into adjacent air cavities.
Local Extension
Nasal cavity carcinomas spread to adjacent sinuses depending
on the location of origin: Lateral wall tumors destroy the medial
maxillary sinus wall and extend into the maxillary antrum, and
tumors arising in the middle meatus invade the ethmoid sinus,
then the orbit. The sphenoidal sinus and nasopharynx are the
next sites of tumor extension in more advanced cases. Esthe
sioneuroblastomas frequently invade the nasal septum, ethmoid
sinuses, orbit, and anterior cranial fossa via the cribriform plate
and can involve the frontal-brain parenchyma.
Paranasal sinus tumors erode adjacent bone and invade sur
rounding structures depending on the site of origin in the sinuses.
Medial infrastructure lesions of the maxillary sinus invade the
nasal cavity early via the porous medial wall. Lateral infrastruc
ture lesions erode the lateral wall of the antrum and may present
as a submucosal mass in the maxillary gingiva. Posterior infra
structure lesions may invade the infratemporal fossa or extend
into the pterygopalatine fossa and pterygoid plates. These lesions
may invade the orbit by direct superior extension or via extension
into the ethmoids.
Suprastructure lesions of the maxillary sinus spread either lat
erally, invading the malar process of the maxilla and the zygoma,
or medially, invading the nasal cavity and ethmoid sinuses. It is
not uncommon to encounter a lesion involving the antrum, nasal
cavity, and ethmoid sinuses all together, and the site of origin of
these tumors may be impossible to determine.
Perineural Spread
The sensory nerve supply of the maxillary, sphenoidal, and
ethmoid sinuses; the nasal cavity and palate mucous membrane;
the upper teeth and gums; and the adjacent facial skin extending
from the lower lid to the upper lip, including the nasal vestibule,
derives from the maxillary branch of the trigeminal nerve (cranial
nerve V2). The anterior-superior alveolar branch of the infraor
bital nerve runs in the facial wall of the maxillary sinus to the
upper incisor and canine teeth. The posterior superior alveolar
branch (dental nerve) pierces the infratemporal wall and supplies
the mucosa of the maxillary antrum. The zygomatic nerve sup
plies sensory fibers to the lacrimal gland.31 Involvement of the
nerve branches of the maxillary nerve by the tumor often leads
to numbness and paresthesias in the skin and mucous membrane
of this region.
Perineural extension into the central nervous system is more
commonly associated with minor salivary gland tumors, espe
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Diagnosis
Physical examination should include inspection and bimanual
palpation of the orbit, oral and nasal cavities, and nasopharynx,
and direct fiberoptic endoscopy. Neurologic examination should
emphasize cranial nerve function, because nasal cavity and para
nasal sinus tumors are frequently associated with cranial-nerve
palsies, especially of the trigeminal branches. Cervical lymph
nodes are palpated for adenopathy.
Radiologic evaluation is of paramount importance in the diag
nosis and staging of nasal cavity and paranasal sinus tumors.
Imaging has essentially replaced surgical exploration for staging
and tumor mapping in this region. The most useful studies are
computed tomography (CT) and magnetic resonance imaging
(MRI). CT defines early cortical bone erosion more clearly (Fig.
33-4), whereas MRI better delineates soft tissue. MRI can also
differentiate among opacification of the sinuses resulting from
fluid, inflammation, or tumor (Fig. 33-5).32 CT performs better
than MRI in evaluating thin bony structures, such as paranasal
sinuses and orbita. MRI may demonstrate subtle perineural
spread and involvement of the cranial nerve foramen and canals
Lymphatic Spread
Lymphatic drainage of the nasal cavity is to the retropharyn
geal lymph nodes and the cervical chain. The paranasal sinuses
are thought to have sparse capillary lymphatic supply. Thus the
frequency of lymph node involvement is low even in advanced
cases, unless the tumor involves adjacent areas heavily endowed
with lymphatic supply (the nasal cavity, nasopharynx, oral cavity,
and skin). Approximately 10% of the patients with nasal cavity
or paranasal sinus carcinomas present initially with cervical
lymph node metastases and another 10% to 15% develop necknode metastases in follow-up.
FIGURE 33-4 Computed tomographic images of a right maxillary antrum carcinoma eroding the medial and lateral walls of the
maxillary sinus, extending into the pterygopalatine fossa (A, arrow) and eroding the lacrimal duct (B, arrow).
FIGURE 33-5 Magnetic resonance images

(MRIs) of a right nasal cavity carcinoma with
possible involvement of the periorbital fat (A)
and a coexisting fluid-filled maxillary antrum
that is uninvolved by the tumor (B). MRI is
able to distinguish sinusitis and fluid-filled
sinus from tumor on a T2 signal.
DIAGNOSIS AND STAGING
cially with adenoid cystic carcinomas; however, it may occur also

with other histologic types, especially in the setting of recurrence
after surgery. Commonly involved nerves for perineural spread
include olfactory nerves (from the cribriform plate into the ante
rior cranial fossa), the infraorbital nerve, and nerves that run
through the superior orbital fissure (into the cavernous sinus or
middle cranial fossa).32 Also commonly involved is the foramen
rotundum, which transmits the maxillary nerve (cranial nerve
V2) and carries sensory information from the lower eyelid and
cheek into the trigeminal nucleus.
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(Fig. 33-6 and Fig. 33-7).33 MRI is better than CT in evaluating

intracranial or leptomeningeal spread. MRI is also more useful
in assessing skull-base erosion. Sagittal and coronal MRI sections
better visualize lesions involving the cribriform plate, basisphe
noid, and floor of the middle cranial fossa.34 Thus, as a single
modality, MRI may confer more information than CT.
Pathologic diagnosis is made through a biopsy. Tumors arising
from or involving the nasal cavity are amenable to transnasal
biopsy. Paranasal sinus tumors are best approached using endo
scopic sinus surgery instruments or by an open transcutaneous
or transoral procedure. Caldwell-Luc procedures have been used
to gain access to the maxillary antrum.
Staging
The staging classification for the epithelial tumors of the nasal
cavity and paranasal sinuses has been extensively revised in the
sixth edition of the American Joint Committee on Cancer (AJCC)
tumor-node-metastasis staging system (Table 33-1).35 In addi
tion to the maxillary sinus, the nasoethmoid complex has been
added as a second site with two regions within the site: the nasal
cavity and ethmoid sinuses. The nasal cavity is further divided
into four subsites: septum, floor, lateral wall, and vestibule. The
ethmoid sinus region is subdivided into two subsites: right and
left. For the maxillary sinus, T4 lesions have been divided into T4a
(resectable) and T4b (unresectable), leading to the division of
stage IV into stages IVA, IVB, and IVC. No widely accepted
staging classification exists for frontal and sphenoidal tumors, as
they are rare.
TREATMENT
Although surgery alone or radiation therapy alone has been
used with curative intent in the treatment of select nasal cavity
or paranasal sinus carcinomas, most cases warrant combinedmodality therapy (Table 33-2 and Table 33-3). In recent years,
surgery followed by postoperative radiation therapy has been the
mainstay of therapy for resectable lesions. Surgery is considered
superior to radiation as a single modality for control of small
lesions of the nasal septum or those limited to the infrastructure
of the maxillary sinus.3 Although primary radiation therapy has
a high cure rate for small squamous carcinomas of the nasal
cavity, the potential for optic nerve injury from the high-dose
radiation therapy required to achieve a good control rate must
be considered. Massive tumors with extensive involvement of the
nasopharynx, base of skull, sphenoidal sinuses, brain, or optic
chiasm are considered unresectable. Some institutions have been
studying the efficacy of combined radiation and radiosensitizing
chemotherapy for unresectable squamous cell carcinoma of the
nasal cavity and paranasal sinuses. Early results of this approach
have been promising.36 If radiation therapy alone is to be used
for large lesions, a hyperfractionated regimen may allow the
delivery of higher doses than conventional radiation.
Surgery
Surgical Procedures
The goal of surgery for nasal cavity and paranasal sinus tumors
is to achieve en bloc resection of all involved bone and soft tissue
with clear margins while maximizing the cosmetic and functional
outcome. The extent and site of the incision depend on the loca
tion of the lesion. Limited nasal cavity lesions may be resected
with medial maxillectomy. Ethmoid lesions usually require
medial maxillectomy and en bloc ethmoidectomy. This is the
most common surgical approach for inverted papillomas. The

development of a combined craniofacial procedure for lesions
involving the inferior surface of the cribriform plate and the roof
of the ethmoid bone offers access to the anterior cranial fossa,
orbit, and pterygopalatine fossa, and allows a rational oncologic
resection, depending on anatomic considerations. In addition,
this approach results in excellent cosmesis and improvement in
the cure of lesions associated with extremely poor prognosis oth
erwise.37 The bony defect in the anterior cranial floor is closed
with a vascularized pericranial or temporal muscle flap.
Primary surgery for maxillary antral cancers is radical maxil
lectomy that removes en bloc the entire maxilla and ethmoid
sinus via a Weber-Fergusson incision. Patients with tumors
limited to the infrastructure do well after surgery alone as long
as the margins of resection are adequate. Suprastructure lesions
may involve the orbit, necessitating orbital exenteration. Resec
tion of involved periosteum and frozen-section control of adja
cent orbital contents with preservation of the eye may be possible
in select lesions with involvement of the periorbita without
intraorbital extension. Orbital preservation surgery in select
patients with involvement of the bony orbit but not soft tissue
does not appear to result in poorer survival or local control than
those undergoing exenteration.38,39 The radical maxillectomy
defect is covered with a split-thickness skin graft. As a general
rule, the surgical defect should not be obliterated during the
initial surgery. An open cavity allows cleansing and direct visual
inspection during follow-up.
Skull-Base Surgery
Base-of-skull surgery has been growing as a discipline of head
and neck surgery, addressing the need for more radical resection
of extensive tumors involving the frontal brain, cavernous sinus,
sphenoidal sinus, clivus, pterygoid space, and petrous bone. The
classic criteria for inoperability include (1) superior extension of
the tumor through the dura into the frontal lobes; (2) posterior
extension of the tumor beyond the cribriform plate and fovea
ethmoidalis to a point at which there is excessive traction on the
optic chiasm or invasion of the prevertebral fascia or both;
(3) involvement of both optic nerves; and (4) lateral extension
into the region of the superior orbital fissure and cavernous
sinus.4 In a combined-team approach with neurosurgery, many
previously unresectable sinonasal tract tumors are successfully
resected at some centers. This technique is evolving, and out
comes of such aggressive surgery in those lesions with otherwise
dismal prognosis need to be validated.
The complications of skull-base surgery are more common
place than in surgical resections for sinus cancers without entry
into the intracranial space. The reported complication rates vary
between 35% and 50% depending on how inclusive the authors
criteria are. At the University of California, Davis, approximately
240 operations for skull-base tumors, most of which were malig
nant, have been done in a period encompassing more than 30
years. If all the medical and surgical complications are included,
our complication rate has been 36.3%. In our series presented in
2006, there were 212 skull-base surgery operations done for
tumor removal and there were nine perioperative deaths (fatali
ties within the first 30 days after surgery). Not all but most tumors
were primary to or had spread to the paranasal sinuses. In five
patients the primary cause of death was a vascular accident. Four
of the five vascular complications involved the internal carotid
artery; four were fatal strokes secondary to internal carotid occlu
sion and one was secondary to a carotid blowout 1 month after
resection. The remaining fatal vascular complication was due to
Optic
tract
Pituitary gland
Circle of
Willis
CN III
CN V
Chiasm
CN III
CN V root
CN VII, VIII
FIGURE 33-6 Magnetic resonance

images of normal cranial nerves in
coronal (AD) and transverse (EH)
planes. A, Optic chiasm and circle of
Willis. B, Optic chiasm bifurcation
and pituitary stalk. C, Oculomotor
nerve (III). D, Trigeminal nerve (V),
main trunk. E, Optic chiasm. F,
Oculomotor nerve (III). G, Trigeminal
nerve (V). H, Facial (VII) and
vestibulocochlear (VIII) nerves.
707
708
FIGURE 33-7 Magnetic resonance images of perineural spread in coronal plane involving cavernous sinus, trigeminal nerve and
ganglion, and oculomotor nerve. A, Left cavernous sinus is expanded by tumor. B, Trigeminal ganglion infiltration in Meckel cavity.
C, Left trigeminal nerve root enhancement caused by perineural spread as it leaves the brainstem. D, Enhancement of cavernous sinus
by perineural spread along oculomotor nerves.
injury to pontine vascular perforators that occurred during an

attempt to dissect a malignant tumor from the brainstem.
The most dreaded complications other than those that are
terminal are those involving the central nervous system. The
greatest fear is infection, usually resulting from leak of the cere
brospinal fluid (CSF). At our institution, a total of 38 operative
procedures resulted in central complications; the largest compli
cation was a CSF leak, which occurred in 19 patients. The leak
stopped spontaneously in more than one third of patients and
only 6 required an operative procedure for closure. Meningitis
developed in 6 patients; 4 were bacterial and 2 were aseptic. All
responded to antibiotic therapy. There were 2 cases of brain
abscess, both of which responded to medical therapy without
operative intervention. None of these complications resulted in
death of the patients. Coma occurred in 7 patients, 2 of whom
died in the perioperative period.
Pneumocephalus is also a common sequel to skull base surgery.
It is of no consequence, and the air will be absorbed over time.
Air under tension in the intracranial space, so-called tension
pneumocephalus, is a serious complication and if not detected
early and effectively treated, can lead to death of the patient. In
our series, tension pneumocephalus was seen in six patients.
Wound complications can also occur and include such events as

wound dehiscence and significant flap loss. Most wound dehis
cences were allowed to close by secondary intention. Complete
loss of a free vascularized flap or regional musculocutaneous flaps
is extremely rare. Partial flap losses are either allowed to granulate
in or skin-grafted and treated with drainage and antibiotics.
Postsurgical Rehabilitation
The primary consideration for rehabilitation after radical
surgery is function. Preoperative evaluation by a prosthodontist
is necessary to obtain dental impressions and to assess the denti
tion that will remain after surgery. A surgical splint prepared
preoperatively is used to fill the defect during the immediate
postoperative period. Use of the splint facilitates immediate
speech and swallowing. A temporary obturator is then fitted until
the cavity completely heals several months later, at which time a
permanent obturator can be made.40
Radiation Therapy
Radiation therapy was more often administered preoperatively
in the 1960s and 1970s; however, during the previous decades,
most centers have been using radiation therapy in the postopera
Table 33-1 Classification of Nasal Cavity and Paranasal Sinus Cancers
709
710
From Greene FL, Page DL, Fleming ID, etal, eds: AJCC Cancer Staging Manual, 6th ed. New York, Springer, 2002.
Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC
Cancer Staging Manual, ed 7, 2010, published by Springer Science and Business Media, LLC, www.springerlink.com.
Table 33-2 Results of Treatment: Combined-Modality Therapy of Surgery and Radiation Therapy Compared
With Definitive Radiation
Survival
Rate, %
Reference
b
Gallagher & Boles

3
Study Period
Patients, n
Site
1955-1964
41
Maxillary sinus
Endpoint, Yr
Parameter
RT
CMT
OS
16
60
Tabb & Barranco
1958-1968
108
Maxillary sinus
OS
25
Ahmed etal.c
1955-1974
56
Maxillary sinus
LCa
34
67
Bush & Bagshawd
1956-1974
38
Paranasal sinuses
DFSa
23
38
1960-1970
50
Maxillary sinus
DFS
22
58
Cheng & Wang
St. Pierre & Baker

g
Amendola et al.
1964-1975
66
Maxillary sinus
OS
16
58
1968-1978
39
Maxillary sinus
DFS
50
37
10
OS
21
34
OS
11
37
10
42
1953-1982
416
Maxillary sinus
Shidnia etal.35
1960-1980
109
Paranasal sinuses
Shibuya etal.
Gadeberg etal.
i
j
Beale & Garrett
80
1964-1979
112
1970-1978
1966-1984
Flores etal.
Isaacs etal.
1963-1980
Paranasal sinuses
OS
40
51
40
Paranasal sinuses
OS
42
74
37
Maxillary sinus
OS
1970-1988
37
Maxillary sinus
1986-1992
39
Paranasal sinuses
Blanco etal.
Jansen etal.
92
1960-1998
1977-1996
OS
Roa etal.48
95
Maxillary sinus
66
Giri etal.
2.5
106
73
Paranasal sinuses
Paranasal sinuses
32
36
OS
18
53
OSa
32
65
DFS
29
35
60
OS
CMT, Combined-modality therapy; DFS, disease-free survival; LC, local control; OS, overall survival; RT, radiation therapy.
a
Reported using an actuarial method.
b
From Gallagher TM, Boles R: Symposium: treatment of malignancies of paranasal sinuses, I. Carcinoma of the maxillary antrum. Laryngoscope
91:133, 1981.
c
From Ahmed K, Cordoba RB, Fayos JV: Squamous cell carcinoma of the maxillary sinus. Arch Otolaryngol 107:48, 1981.
d
From Bush SE, Bagshaw MA: Carcinoma of the paranasal sinuses. Cancer 50:154, 1982.
e
From Cheng VST, Wang CC: Carcinomas of the paranasal sinuses: a study of sixty-six cases. Cancer 40:3038, 1977.
f
From St. Pierre S, Baker SR: Squamous cell carcinoma of the maxillary sinus: analysis of 66 cases. Head Neck Surg 5:508, 1983.
g
From Amendola BE, Eisert D, Hazra TA, etal: Carcinoma of the maxillary antrum: surgery or radiation therapy? Int J Radiat Oncol Biol Phys
7:743, 1981.
h
From Shibuya H, Horiuchi JI, Suzuki S, etal: Maxillary sinus carcinoma: results of radiation therapy. Int J Radiat Oncol Biol Phys 10:1021, 1984.
i
From Gadeberg CC, Hjelm-Hansen M, Sogaard H, etal: Malignant tumors of the paranasal sinuses and nasal cavity: a series of 180 patients.
Acta Radiol Oncol 23:181, 1984.
j
From Beale FA, Garrett PG: Cancer of the paranasal sinuses with particular reference to maxillary sinus cancer. J Otolaryngol 12:377, 1983.
k
From Flores AD, Anderson DW, Doyle PJ, etal: Paranasal sinus malignancya retrospective analysis of treatment methods. J Otolaryngol
13:141, 1984.
l
From Isaacs JH, Mooney S, Mendenhall WM, etal: Cancer of the maxillary sinus treated with surgery and/or radiation therapy. Am Surg 56:327,
1990.
711
Table 33-3 Results of Surgery Alone: Maxillary Sinus

Cancer
Patients, n
5-Yr
Survival, %
1955-1964
50
Tabb &
Barranco3
1958-1968
19
62
St. Pierre &

Baker
1964-1975
10
20
Reference
Study Period
Gallagher &
Boles*
Minor salivary gland carcinomas are resected first and irradi

ated postoperatively if the histologic examination reveals a highgrade or adenoid cystic variety, extensive perineural spread,
positive or close margins of resection, or extensive primary tumor
(T3 or T4). The radiation portals should include neural pathways
up to the cranial nerve ganglion at the base of the skull in adenoid
cystic carcinomas and high-grade lesions with extensive perineural
invasion. There is sparse literature available regarding the
outcome of definitive irradiation for unresectable salivary gland
tumors of the nasal cavity and paranasal sinuses. The results of
definitive conventional photon irradiation of unresectable sali
vary gland tumors in general were poor (17% local control at 2
years) in at least one randomized trial of photon versus neutron
therapy43; however, whether neutron therapy offers any advan
tage over photons is controversial, and this controversy is dis
cussed in Chapter 32. Notably, a recent study from investigators
at the University of California, San Francisco, reported 5- and
10-year local control of 70% and 57% among patients treated
with photon irradiation alone for unresectable or medically inop
erable salivary gland carcinomas, with the rates depending on T
stage and radiation dose.44
The neck is treated electively only when the tumor invades the
nasopharynx or other lymphatic-rich areas, or is T4 in extent,
poorly differentiated, or recurrent. Broader use of elective nodal
irradiation is controversial and is further discussed in Results of
Therapy, later in this chapter. The neck is irradiated after neck
dissection for nodal involvement at presentation according to the
usual guidelines for postoperative neck irradiation.
Radiotherapeutic Technique: External Beam
*From Gallagher TM, Boles R: Symposium: treatment of malignancies

of paranasal sinuses, I. Carcinoma of the maxillary antrum.
Laryngoscope 91:133, 1981.
From St. Pierre S, Baker SR: Squamous cell carcinoma of the

maxillary sinus: analysis of 66 cases. Head Neck Surg 5:508, 1983.
It is most advantageous to base the treatment volume on treat

ment-planning CT with MRI correlation, if available. MRIderived gross tumor volumes (GTVs) may be smaller and have
less interobserver variation than CT-derived GTVs. CT and MRI
are complementary in delineating the GTV.45 The complex
anatomy of this region and the presence of numerous critical,
dose-limiting organs such as optic nerves, chiasm, eyes, lacrimal
Table 33-4 Results of Treatment in Maxillary Sinus Tumors: Preoperative and Postoperative Radiation Therapy
Survival Rate, %
Author
Study Period
Patients, n
Survival Endpoint, Yr
Preop
Postop
1952-1961
41
45
37
Tabb & Barranco
1958-1968
54
32
12
Hu etal.112
1958-1974
50
64
26
Jesse*
3
Isaacs etal.
113
Korzeniowski etal.114
1966-1984
11
80
1967-1978
57
NA
35
1963-1980
149
NA
42
Bristol etal.
111
1969-1991
90
NA
51
Bristol etal.
111
1991-2002
56
NA
62
Zaharia etal.
NA, Not applicable.

*From Jesse RH: Preoperative versus postoperative radiation in the treatment of squamous carcinoma of the paranasal sinuses. Am J Surg
110:552, 1965. Postoperative group represents patients treated between 1952 and 1957 and preoperative group represents those treated
between 1958 and 1961.
This series represents small numbers: 6 patients in preoperative group and 5 patients in postoperative group.
Surgery was incomplete: 35 patients with macroscopic residual and 22 with microscopic residual.
tive adjuvant setting after radical surgery for squamous cell car
cinomas of the nasal cavity and paranasal sinuses. Although
pre- and postoperative radiation may result in similar control
rates (Table 33-4), there are definite advantages to surgery before
radiation. Preoperative radiation may obscure the initial extent
of disease and erroneously lead to a more conservative resection;
thus surgery may not quite encompass the microscopic disease.
Preoperative radiation also increases the infection rate and the
risk of postoperative wound complications. Radiation therapy in
the postoperative setting has the advantage of accurate pathologic
review of all structures at risk, and the radiation portals can then
be designed to encompass the entire extent of disease with ade
quate margins. Upfront surgery also allows drainage of infected
sinuses before radiation. Postoperative radiation therapy is
started 4 to 6 weeks after surgery. In those patients who are
deemed medically inoperable or who refuse radical surgery,
primary radiation therapy has been employed with differing
success (10% to 70% 5-year survival) depending on the stage and
extent of the tumor.41,42
712
gland, auditory apparatus, pituitary, brainstem, and spinal cord,

render tumors of the sinonasal tract ideal candidates for sophis
ticated treatment planning. Since the introduction of CT-based
treatment planning and immobilization devices in the 1980s,
improvement in survival rates while reducing the incidence of eye
complications has been reported.46,47 A three-dimensional (3-D)
system allows comprehensive visualization of the tumor volume
and adjacent normal anatomy through beams-eye view dis
plays (Fig. 33-8 and Fig. 33-9). Careful definition of the anatomic
structures of interest and of the extent of the tumor, together with
immobilization devices for precise setup, permits accurate target
ing of the tumor. The ability of a 3-D system to use nonaxial and
noncoplanar fields allows greater flexibility in treatment plan
ning, so that the dose distribution conforms to the tumor volume
in 3-D space, thus sparing the surrounding normal tissue to a
greater extent. Dose-volume histograms (Fig. 33-10) are able to
record accurately the doses delivered to differing volumes of adja
cent dose-limiting structures. This technology has great potential
for improving local control, while decreasing the risk of longterm sequelae of therapy and allowing dose escalation that has
not been possible with conventional two-dimensional treatmentplanning systems. Thus, the role of a conformal 3-D treatment
system will become even more important in the setting of primary
radiation therapy that requires high doses beyond 70Gy. Although
3-D conformal plans can provide bilateral sparing of the globe
for most patients, it may be more difficult to spare optic nerves,
especially on the ipsilateral side, when prescription dose exceeds
the normal tissue-tolerance doses.
Among the many advantages of image-based conformal plan
ning in this region is the ability to optimize and show the effects
of inhomogeneity corrections for air cavities and dense bone.

Conformal planning is especially helpful in the use of anterior
electrons, in which the extensive system of air cavities and sloping
surfaces present in the paranasal sinuses can significantly distort
the isodose curves generated by a nonconformal system, resulting
in an overdose to critical structures (i.e., optic nerves and chiasm)
and an underdose to the tumor volume.
The radiation therapy of the nasal cavity, ethmoid sinuses, and
maxillary sinuses is similar, as the tumor extensively involves two
or more sinuses in most cases. A typical target volume in a post
operative setting encompasses both halves of the nasal cavity and
ipsilateral maxillary sinus. Ethmoid sinuses and the ipsilateral
medial orbital wall are included if the tumor extends superiorly
into the ethmoid air cells.
During the initial setup, the patients head is placed in a neutral
supine position (Fig. 33-11). A tongue depressor is placed in the
mouth to displace the tongue from the treatment area. In a post
operative setting, the patient wears the obturator for the maxil
lary defect during the simulation. A CT-compatible thermoplastic
facial mask is made to immobilize the head. An anterior portal is
set up with the inferior border splitting the tongue blade (near
the commissure of the lips), and the upper border is determined
per the superior extension of the tumor. The ipsilateral border
should include the entire maxillary sinus and the contralateral
border should cover the medial wall of the orbit and medial
maxillary wall (just medial to the limbus of the contralateral eye).
For massive lesions involving the contralateral maxillary sinus,
the lateral border should be extended to include entire contra
lateral sinuses. The lateral portal is set up with the anterior border
flashing the skin of the cheek and the posterior border at the
FIGURE 33-8 Three-dimensional beams-eye views: four-field technique using opposed lateral portals, and anterior photon and
electron portals. A, Anterior view. B, Lateral view. C, Oblique view.
FIGURE 33-9 Three-dimensional beams-eye views: wedged-pair portals. A, Anterior view. B, Lateral view. C, Oblique view.
setting, CT without contrast suffices. Thin-cut CT with 3- to

5-mm spacing is recommended through the tumor volume,
whereas outside the immediate tumor volume region, 1-cm cuts
are obtained from the top of the skull through the mid-neck.
After the tumor volume and normal soft tissue and bony
anatomy (e.g., sinuses, skull, base of skull, brain) and critical
structures (e.g., eyes, optic nerve, chiasm, brainstem, and spinal
cord) are contoured on the CT axial images, beams are placed
with a 1.5- to 2-cm margin. The contralateral eye is blocked, and
greater than two thirds of the ipsilateral eye48 are also blocked
unless there is intraorbital infiltration by the tumor. Most of these
cases have had orbital exenteration during surgery, and the entire
orbital defect is then included in the tumor volume (Fig. 33-12).
Compared with a conventional plan, which routinely includes
one half to one third of the ipsilateral eye,15 greater sparing of the
ipsilateral eye is possible without sacrificing tumor control by
using a 3-D conformal plan (see Fig. 33-10).
In general, four fields, using an anterior and two lateral wedged
portals plus an intraorbital electron portal, are used to treat the
target volume (Fig. 33-13). Less commonly, three-field tech
niques (without the anterior electron portal) are used, and for
small lesions confined to the ipsilateral maxillary sinus, a wedged
pair of anterior and lateral portals is used (Fig. 33-14). With the
four-field technique, the eyes are blocked from the anterior and
lateral photon portals. The interorbital electron portal makes up
the dose to the posterior nasal cavity, ethmoid sinus, and medial
orbit. If the three-field technique is used, the anterior border of
the lateral portal is placed at the bony canthus and the anterior
portal is weighted more heavily (2:1 to 3:1).15
The tumor volume is defined as a CT- or MRI-defined gross
tumor and by its potential microscopic extension, as well as by
the pathologic findings. The target volume includes the tumor
volume plus a 1-cm margin so that the tumor volume is included
in the 95% isodose line. The computer generates autoblocks with
an additional 5-mm margin around the target volume, thus
120
110
100
Volume (%)
90
80
70
60
50
40
30
20
10
0
0
10 20 30 40 50 60 70 80 90 100 110 120

Dose (%)
Brain
Rt eye
Lt eye
Chiasm
Tumor
Rt nerve
Lt nerve
FIGURE 33-10 Three-dimensional dose-volume histogram. The

optic chiasm and the contralateral optic nerve doses are limited
to 65% to 70% of the prescribed dose whereas nearly 80% of
the ipsilateral optic nerve receives greater than 90% of the
prescribed tumor dose.
PARANASAL SINUSES
B
85.4
C
70.0
59.4
45.0
30.0 Gy
FIGURE 33-11 Intensity-modulated radiation therapy isodose plans in axial planes (color-wash representations shown here in shades
of gray) of a patient with locally advanced (stage T4-Nx-M0) paranasal sinus undifferentiated carcinoma undergoing definitive
radiotherapy. The plan was generated on Corvus planning system (Nomos Corp.) using 6mV photons and MIMic multileaf collimator
device with six table positions: A, At the level of the maxillary sinuses/parotid glands; B, at the level of the floor of the orbit/
brainstem; C, at the level of ethmoid sinuses/mid-orbit. The bilateral eyes are nicely spared (<45Gy isodose region) as are the
brainstem (<45Gy isodose region) and the parotid glands (<30Gy isodose region).
posterior aspect of the clivus, splitting the vertebral bodies. The

patient is scanned in the treatment position in the facial mask.
For primary radiation therapy of unresectable tumors, CT with
intravenous contrast material is recommended to take advantage
of the enhancing characteristics of neoplasms. In a postoperative
713
714
PARANASAL SINUSES
S
B
85.4 70.0 59.4 45.0 30.0 Gy
FIGURE 33-12 Intensity-modulated radiation therapy isodose plans in sagittal and coronal planes: A, coronal view; B, sagittal view.
Cumulative dose volume histogram
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
10
5
0
OP.N
GTV
Chiasm
CTV
Eye
Brain stem
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
10
5
0
Volume (%)
Volume (%)
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85
Dose (Gy)
Total accumulated dose
FIGURE 33-13 Intensity-modulated radiation therapy dose

volume histogram. The gross target volume receives 70Gy and
the clinical target volume receives 59.4Gy. Less than 10% of the
optic chiasm receives greater than 55Gy.
defining the treatment volume. The autoblocks are then edited

to ensure sparing of critical structures.
Most commonly, 6-mV photons are used; however, a higherenergy beam may be used in conjunction with low-energy elec
trons (9 or 12meV) in the anterior portals. Lower-energy photons
result in a greater dose gradient and a less homogeneous distribu
tion. A typical loading favors the anterior portal by 2:1. The
generated isodose curves should reflect the effect of inhomogene
ity corrections, although the dose is calculated at the central axis
without inhomogeneity corrections (Fig. 33-15 and Fig. 33-16).
In a postoperative setting, 60 to 63Gy are prescribed to the target
volume at a 1.8 to 2Gy daily fraction, and an additional conedown boost may be delivered to the areas of involved margin or
gross residual tumor. For unresectable tumors, doses in excess of
70Gy are recommended. If the tumor involves critical structures
or if they cannot be excluded from the high-dose volume by using
tight margins, a hyperfractionated regimen (1 to 1.2 Gy twicedaily fractionation) or concurrent delivery of radiosensitizing
chemotherapy should be considered. However, it is yet unknown

whether optic nerves and chiasm can be differentially spared
from the late effects relative to acute effects on the tissue and
tumor by the use of a hyperfractionation scheme.
The dose to the optic nerve and globe should be limited to
50Gy, and that to the chiasm to 54Gy. In most cases, the dose
delivered to the chiasm can be limited to 70% of the daily pre
scribed dose. If the tumor extends to the chiasm and the chiasm is
included as the primary tumor volume, the dose should be pre
scribed to 100% isodose line or the isodose line at the chiasm, and
great care should be taken to block out the chiasm beyond 54Gy.
If there is extensive orbital invasion and the radiation is delivered
primarily, the involved eye is encompassed in the anterior volume.
All effort should be made to shield the lacrimal gland to avoid
painful eye syndrome and to save the contralateral eye. Patients
should gaze straight ahead with eyes wide open during treatment
so that sparing of the anterior chamber may be attained.
Normal-tissue complication probability calculations may be
useful in assessing complication risk better than point dose toler
ance criteria for the chiasm, optic nerve, and retina.49 It is impor
tant to assess the overall risk of blindness for the patients in
addition to the risk for the individual visual pathway structures.
Patients should be informed of the risk of radiation-induced
damage to the chiasm or eye, or both, and eventual blindness.
Preradiation ophthalmologic examination is prudent in all
patients undergoing sinus radiation therapy to establish baseline
acuity and to detect any preexisting abnormalities.
Tumors arising in the sphenoidal sinus are treated like
nasopharynx cancers, traditionally through opposed lateral
portals using high-energy beams (e.g., 18mV). A three-field tech
nique may be necessary if there is significant anterior extension.
For small lesions of the sphenoidal sinus, a conformal bilateral
arc with flying wedges may spare the temporal lobes. Any tumor
at high risk of perineural spread requires generous coverage of
the base of the skull.
Intensity-Modulated Radiation Therapy

Given the irregular contours of the tumors arising in the para
nasal sinuses and nasal cavity and the presence of vital structures
in this region, intensity-modulated radiation therapy (IMRT)
using inverse treatment planning systems and computer optimi
zation may render a greater therapeutic ratio for tumors of the
paranasal sinuses compared with the more standard forward
715
FIGURE 33-14 A and B, Treatment position. The head is placed in a neutral position and immobilized using an Aquaplast mold. A
bite block is placed above the oral tongue in the mouth to push the tongue out of the field.
FIGURE 33-15 Simulation films of a patient undergoing postoperative radiation for undifferentiated carcinoma of the right
ethmoidal sinus involving the periorbita and right superior nasal cavity, but not maxillary antrum. The eye was preserved, but the
margins of resection were involved in the posterior medial orbital wall. The treatment volume was determined using a treatmentplanning computed tomography scan and includes the ethmoidal sinuses; medial one-half of the ipsilateral orbit, nasal cavity, and
maxillary antrum; and medial rim of the contralateral orbit. A four-field technique was used to treat the patient: two lateral portals,
an anterior photon portal, and an electron portal. The optic chiasm was blocked from the lateral portals. The eyes were blocked
laterally, and the dose was made up using an electron field covering the superior extent of the nasal cavity, the ethmoidal sinus, and
the orbits. A, Anterior photon portal. B, Lateral portals blocking the eyes (canthus markers are placed on the bony canthi). C, Anterior
electron portal film.
planning 3-D conformal therapy. IMRT can result in better

sparing of the optic apparatus, especially in definitive cases in
which high doses of radiation are necessary for gross tumor eradi
cation. IMRT strategies for paranasal sinus malignancies can be
strikingly different in various aspects, such as beam setup; total
number of segments; GTV, clinical tumor volume, and planning
tumor volume (PTV) dose coverage; and dose statistics for organs
at risk (Fig. 33-17, Fig. 33-18, and Fig. 33-19).47 Although several
different treatment planning systems are available, the basic prin
ciples underlying this technology are similar.
Multiple dosimetric studies have shown that improved dose
distributions can be achieved with the use of IMRT compared
with conventional and 3-D conformal radiation planning.50-54
From a practical standpoint, the dose delivered to the optic path
ways can be selectively reduced by IMRT, which has the potential
to preserve binocular vision, particularly for patients who have
extensive and large-volume disease in the paranasal sinuses. Tsien

and colleagues retrospectively replanned 13 patients with locally
advanced paranasal sinus cancer who were initially treated via
conformal techniques. Using a priorities-and-tradeoffs model,
the authors illustrated the flexibility and utility of IMRT to selec
tively save normal critical structures while maintaining dose to
the target.55
Evidence is starting to emerge that the theoretical benefits from
sophisticated planing techniques such as IMRT are indeed trans
lating into clinical advantages. In a longitudinal analysis of 127
patients treated with radiation therapy from 1960 to 2005 at the
University of California, San Francisco, the incidence of grade 3 or
greater late ocular toxicity among patients treated with conven
tional, 3-D conformal, and IMRT was 20%, 9%, and 0%, respec
tively.56 In another series from Memorial Sloan-Kettering, none of
the 85 patients who underwent postoperative radiotherapy treated
716
FIGURE 33-16 Simulation films of a patient undergoing postoperative radiation therapy for a locally advanced paranasal sinus
tumor requiring left orbital exenteration. The treatment volume encompasses all the ipsilateral nasal cavity and sinuses including the
frontal sinus and orbital bed, contralateral ethmoidal sinus and nasal cavity, and medial maxillary sinus. The patient was treated using
a four-field technique that included left and right lateral photon portals, an anterior photon portal, and an electron portal to make
up the dose to the left orbital bed, which was blocked from the lateral portals to protect the contralateral eye. A, Anterior photon
portal including the entire orbital bed. B, Lateral photon portal blocking the eye (a dime is placed over the intact eyelid and a canthal
marker is placed over the bony canthus). C, Anterior electron portal film.
FIGURE 33-17 Simulation films of wedgedpair setup for a limited lesion involving the
maxillary antrum only. The treatment volume
includes the ipsilateral maxillary sinus and the
nasal cavity. A, Anterior portal. B, Lateral
portal.
FIGURE 33-18 Three-dimensional

isodose plans (color-wash
representations shown here in shades
of gray) of a four-field technique.
Note the optic chiasm dose at the
60% to 70% region: A, At the level of
the orbits and chiasm; B, at the level
of the midantrum.
FIGURE 33-19 Three-dimensional isodose plans (color-wash representations shown here in shades of gray) of a wedged-pair
technique: A, At the level of the midantrum; B, at the level of the lower antrum.
FIGURE 33-20 Megavoltage computed tomography images obtained on the treatment couch for a 65-year-old male who presented
with a T4-N0 squamous cell carcinoma of the left maxillary sinus that was deemed unresectable. The patient was treated with
definitive radiation therapy to a total dose of 70Gy to areas of gross disease. The ipsilateral neck was also irradiated electively.
A, Fused images simultaneously illustrating both megavoltage and simulation scans in the axial plane using the split-screen display.
The large tumor occupies most of the left maxillary sinus, has extensively infiltrated the adjacent soft tissue, and has destroyed
most of the ipsilateral zygomatic bone. B, Fused images in the coronal plane.
with CT simulation developed grade 3 or greater late complica

tions of the eye with a median follow-up of 60 months among
surviving patients.57 Other series have reported similar findings in
terms of the reduction of late toxicity with IMRT.58,59
Because the dose gradients created with IMRT are intentionally
steep, the importance of accurate target delineation cannot be
underestimated to avoid geographic near-misses or inadvertent
dosing of uninvolved tissue. In this regard, understanding pat
terns of failure and microscopic disease spread as well as a careful
review of all imaging studies and physical examination findings
is essential. IMRT plan evaluation generally involves assessment
of conformality and homogeneity, identifying and spatially locat
ing hot-spots, and review of data obtained from a dose-volume
histogram.
Image-Guided Radiation Therapy

Evidence is starting to emerge that improvements in setup
accuracy and precision can be achieved with the use of imageguided radiation therapy (IGRT) techniques for head and neck
cancer.60,61 This is particularly relevant for patients treated using

IMRT because the distance between very high- and low-dose
regions can often be a matter of millimeters. Using volumetric
CT data acquired at the time of each daily treatment to guide
radiation delivery may be especially useful for tumors of the
paranasal sinuses and nasal cavity because they lie in close prox
imity to vital organs such as the brain, ears, and optic pathways.
The use of daily IGRT, however, is associated with an increased
peripheral dose to the patient and adds to the machine time for
each case.62 How and whether continuing advances in targeting
will lead to improvements in the therapeutic ratio remain an area
of active debate.
Fig. 33-20 illustrates the use of megavoltage CT images
obtained on the treatment couch for a patient treated by IMRT
(Fig. 33-21) with a large, unresectable squamous cell carcinoma
of the maxillary sinus. As illustrated in the axial images obtained
at day 1 of treatment (see Fig. 33-20B), the large tumor occupies
most of the maxillary sinus, has infiltrated into the soft tissue,
and has destroyed most of the zygomatic bone.
717
718
FIGURE 33-21 Intensity-modulated radiotherapy treatment plan demonstrating dose distribution for the patient described in Fig.
33-20. A, Axial image. B, Coronal image. C, Sagittal image. The patient was treated with a simultaneous integrated (dose painting)
technique with the orange colorwash representing 70Gy; the yellow colorwash representing 63Gy; and the green colorwash 56Gy.
The purple denotes the 45Gy distribution. Radiation therapy was delivered in 35 daily fractions.
Proton Beam Radiation Therapy
Intracavitary Brachytherapy
Proton therapy may be particularly advantageous in the treat

ment of paranasal sinus and nasal cavity cancers, given the deepseated locations requiring high doses of radiation. Given their
unique physical characteristics, protons may provide improved
sparing of normal critical organs in the region by taking advan
tage of the Bragg peak.63 Mock and colleagues performed a treat
ment planning comparison of proton therapy versus photon
therapy with IMRT and 3-D conformal methods for five patients
with paranasal sinus cancer.64 The authors showed that proton
therapy reduced the amount of normal, uninvolved tissue
exposed to radiation, most dramatically at low- and mid-isodose
levels. Proton therapy also significantly reduced doses to selective
organs at risk, including the optic pathways and brain. To date,
there is limited data reporting on clinical outcomes with the use
of proton therapy for this treatment site. In one of the few pub
lished reports to date, investigators from Massachusetts General
Hospital demonstrated encouraging outcomes among 102
patients with locally advanced sinonasal malignancy is treated by
proton-beam radiation therapy, with or without surgery.65 The
observed 5-year local control rates were 95%, 82%, and 87%,
among patients who underwent complete resection, partial resec
tion, and biopsy, only, respectively. Notably, however, long-term
toxicity was not reported.
The role of intracavitary implants is unclear in the manage

ment of nasal cavity and paranasal sinus tumors. External beam
radiation therapy is certainly the standard and preferred mode of
therapy. Epithelial malignancies in this region tend to be infiltra
tive and extensively involve adjacent sinuses; thus generous
margins around the tumor bed need to be irradiated for their
microscopic extension. Because of the rapid dose falloff of any
implant, intracavitary therapy would be limited to surface irra
diation only. It may be used in conjunction with external beam
therapy as a boost for maxillary antrum tumors. Because of the
surface irregularities after radical maxillectomy, the intracavitary
mold is custom designed like an obturator, in conjunction with
prosthodontic service. The custom mold subsequently has holes
drilled to contain catheters for low-dose-rate temporary iridium192 or cesium-137 or high-dose-rate remote afterloading iridium192 sources. This technique requires expertise in brachytherapy
and mold implantation, and is not recommended for routine use.
Stereotactic Radiosurgery
More recently there has been an interest in the use of stereotac
tic radiosurgery for the nasal cavity and paranasal sinus tumors
with skull-base involvement. Haberman and colleagues66 reported
their experience at the University of Graz, Austria, treating eight
patients who underwent primary surgery and postoperative
gamma knife radiosurgery. At 3 years, six patients were alive (all
without local recurrence, four without evidence of disease) with
no adverse effects. There is a potential for using this technique or
a fractionated stereotactic radiotherapy technique as a boost for
gross residual disease in addition to conventional image-based
radiotherapy in select patients who have small residual tumor
volume at the skull base. These new techniques should be inves
tigated further in a prospective trial. Intensity-modulated
radiosurgery/radiotherapy using a micro-multileaf collimator
was compared against forward-planning techniques using beam
modification by enhanced dynamic wedge.67 In this report, dosevolume histogram analysis demonstrated that a significant reduc
tion in dose to neighboring critical structures could be achieved
through intensity modulation patterns determined from inverse
planning, while a marginal change was achieved in the target
volume dose uniformity.
Chemotherapy
Although numerous publications have reported a high per
centage of good initial responses and some evidence of improved
survival with cytotoxic chemotherapy, the efficacy of such therapy
as a part of combined treatment for advanced sinonasal carci
noma has yet to be determined in a large clinical trial. The most
commonly used regimen has been cisplatin-based.68,69 Overall
response rates ranging from 80% to 90% have been reported
in previously untreated patients with paranasal sinus malignan
cies. Japanese groups reported on the use of intra-arterial 5fluorouracil (5-FU) chemotherapy as a radiosensitizing agent in
an effort to reduce the extent of required surgery.70,71 Others
employed sequential intra-arterial bleomycin and methotrexate
followed by preoperative radiation therapy and subsequent
radical surgery for advanced maxillary sinus carcinomas with
good local control.72 Lee and colleagues73 reported an excellent
immediate tumor response rate (>90%) using a highly selective
intra-arterial infusion of cisplatin-based, multiagent induction
chemotherapy. More recently, combined radiation therapy and
cisplatin-based chemotherapy for radiation sensitization were
studied for the definitive management of unresectable base-ofskull carcinomas with encouraging early results.36 There is,
however, no established role for adjuvant chemotherapy in the
management of sinonasal malignancies.
Treatment of Rare Epithelial Tumors

Primary melanomas mostly occur in the nasal cavity and are
highly aggressive locally. The main mode of therapy for nasal
Table 33-5 Kadish Staging System for Olfactory

Neuroblastoma
Stage A
Tumor confined to the nasal cavity
Stage B
Tumor in nasal cavity that extends to

paranasal sinus
Stage C
Tumor that extends to the orbit, base of

skull, or cranial cavity or with cervical/
distant metastases
Treatment of Benign
and Nonepithelial Tumors
Inverted papillomas are treated with en bloc resection of the
medial maxilla with a recurrence rate of less than 10%. Piecemeal
or simple excision is associated with an unacceptably high recur
rence rate (>50%). Radiation therapy should be considered in
patients with incompletely resected lesions, multiple recurrent
tumors, and tumors associated with malignancy.
Lethal midline granuloma is a highly destructive process. In
the process of ruling out Wegener granulomatosis, most of the
patients with lethal midline granuloma syndrome have failed a
trial of systemic steroids. The primary treatment is radiotherapy.
All nasal cavity and paranasal sinuses should be included in the
treatment portals for the initial 40 Gy, as marginal recurrences
have been observed. The final cone-down boost is delivered to
the gross areas of destruction at a total dose of 45 to 50Gy. The
local failure rate even at this dose level approaches 30%.82
Although sinonasal lymphomas are relatively rare in Western
countries, in Asian populations they represent the second most
frequent group of extranodal lymphomas after gastrointestinal
lymphomas. The B-cell phenotype is typically located in the para
nasal sinuses and has a slight predominance in Western coun
tries, whereas the T/NK-cell phenotype is most common in Asian
and South American countries and is typically located in the nasal
cavity. The T/NK-cell lymphomas have an aggressive, angioinva
sive growth pattern that often results in necrosis and bony
erosion.83 Patients with T-lineage disease appear to have a par
ticularly poor outcome.84 Sinonasal lymphomas tend to present
as localized disease (stages I and II) but often relapse in the
abdomen. Thus staging should include endoscopic examination
of the gastrointestinal tract. The role of surgery in the manage
ment of non-Hodgkin lymphoma of the paranasal sinuses is
limited to biopsy for pathologic diagnosis. Treatment of sinona
sal lymphoma depends on the grade and stage of the tumor, and
follows the general guidelines for the treatment of malignant
lymphomas. It may involve local radiation therapy, singleagent or combination anthracycline-based chemotherapy, or
combined-modality therapy with chemotherapy followed by
consolidated radiation therapy. Aggressive lymphomas involving
the base of the skull may require systemic chemotherapy as well
as central nervous system prophylaxis.
Nearly one half of head and neck extramedullary plasmacyto
mas are found in the nasal cavity and paranasal sinuses. These
tend to be localized at presentation, although 25% of the cases
may also involve cervical lymph nodes. Once multiple myeloma
is ruled out, treatment involves local-regional radiation therapy
in the dose range of 40 to 45Gy for 4 to 5 weeks. The local control
rate is excellent (>90%), but the ultimate prognosis depends on
whether these patients eventually develop systemic myeloma.
Rhabdomyosarcoma is the most commonly found soft-tissue
sarcoma in the sinonasal tract. These primitive tumors have the
morphology of developing striated muscle and constitute one of
the small blue round tumors of childhood, or peripheral neu
roectocrine tumors. Eight percent of head and neck rhabdo
myosarcomas arise in this region,85 and they constitute one of the
five parameningeal sites of rhabdomyosarcoma (orbit, infratem
poral fossa, middle ear, and nasopharynx are the other sites).
These are predominantly tumors of the pediatric population and
are treated according to the guidelines of the Intergroup Rhab
domyosarcoma Study (IRS). Treatment involves a combined
modality including chemotherapy, radiation therapy, and
surgery. Unlike rhabdomyosarcomas at other sites, paramenin
geal rhabdomyosarcomas are less amenable to surgical extirpa
cavity melanomas is radical surgical excision. Although there is

no clear benefit in terms of improved survival for postoperative
radiation therapy, postoperative radiation is recommended in
most cases of mucosal melanomas. Local failure after surgery
alone is much more common in mucosal melanomas compared
with cutaneous melanomas because of mucosal melanomas early
lymphovascular invasion and destruction of adjacent structures.
Radiation therapy should be delivered for local control in cases
of close or involved surgical margins, large lesion size, or
recurrence.
Olfactory neuroblastoma is an extremely rare entity arising in
the nasal cavity olfactory epithelium. The commonly used Kadish
staging system is based on the extent of invasion of adjacent
structures (Table 33-5). Prognosis is determined on the basis of
stage and resectability. The primary treatment is craniofacial
resection. The role of postoperative radiation therapy is contro
versial. Although some attribute improved local control and sur
vival to aggressive surgical resection via a craniofacial approach
combined with radiation therapy,21,22 others argue that patients
treated with surgery alone have better results than with combined
surgery and radiation therapy.74 This may reflect adverse patient
selection for the combined-modality therapy. Earlier-stage olfac
tory neuroblastoma patients enjoy excellent survival with surgery
and postoperative radiation therapy: stage A at 96% and stage B
at 83% at 5 years.75 Stage C, however, has a much worse prognosis
(53%) because of greater local as well as distant failure. The
overall 5-year survival rate is approximately 50%. Distant metas
tases develop in 25% to 30% of patients.76 Chemotherapy has
been employed in these advanced cases with limited success.77-79
A prospective study of 19 patients (4 stage B and 15 stage C) with
malignant neuroendocrine tumors of the sinonasal tract con
ducted at the Massachusetts General Hospital between 1992 and
199880 reported an improved outcome for patients with olfactory
neuroblastoma and neuroendocrine carcinoma treated with
aggressive multimodality therapy. Patients received neoadjuvant
cisplatin-etoposide chemotherapy for two cycles and high-dose
proton-photon radiotherapy (69.2 cobalt gray equivalents [CGE]
in 1.6 to 1.8 CGE per fraction twice daily in a concomitant boost
schedule) with radical surgery reserved for nonresponders.
Responders received two more cycles of adjuvant chemotherapy.
With the median follow-up of 45 months, 5-year survival and
local control rates were 74% and 88%. No radiation-induced
visual loss was observed because of the precision delivery of radi
ation with stereotactic setup and protons; however, four patients
developed asymptomatic radiation-induced damage to the
frontal or temporal lobe by MRI criteria and two patients showed
soft-tissue and bone necrosis. Despite sensitivity to platinumbased chemotherapy, patients with high-grade tumors tend to
have a more aggressive course than those with lower-grade
tumors.81
719
720
tion; thus treatment consists predominantly of chemotherapy

and local radiotherapy. Hyperfractionated radiotherapy did not
result in improvement in a randomized study by IRS-IV. Other
soft-tissue sarcomas are treated with wide local excision with
pre- or postoperative radiation therapy.
Osteosarcoma and chondrosarcoma occur rarely in the nasal
cavity and paranasal sinuses. Wide local excision is the primary
mode of therapy, although chemotherapy may be used up front
to cytoreduce and test in vivo chemosensitivity for osteosarcoma.
Radiation therapy has reportedly been used in adjuvant or pallia
tive settings.
COMPLICATIONS OF THERAPY
For patients treated with radiation therapy for malignancies of
the paranasal sinuses and nasal cavity, the high doses required to
achieve local control coupled with the proximity of disease sites
to sensitive normal tissue have historically been associated with
a high incidence of treatment-induced morbidity. Katz and col
leagues86 reported a high rate of visual complications for radia
tion therapy in their series of tumors of the nasal cavity and
ethmoid/sphenoid/frontal sinuses. Of 78 patients, 21 (27%)
developed unilateral blindness resulting from radiation retinopa
thy or optic neuropathy; however, most of these complications
were anticipated because the ipsilateral eye was irradiated to a
high dose. Four patients (5%) unexpectedly developed bilateral
blindness caused by optic nerve injury. All four of these patients
received irradiation alone and were treated before 1985. The
authors suggest that a combination of surgery and radiation
therapy be given in an effort to reduce the total dose needed to
achieve local control, and they also suggest improving dose
homogeneity within the treatment volume to avoid overdosing
the optic nerve.
Late retinal complications of radiation therapy for advanced
nasal and paranasal malignancies were retrospectively studied by
Takeda and colleagues.87 Between 1982 and 1996, 43 eyes of 25
patients were exposed to radio therapy. None of the patients had
tumor invasion into the eyes. The patients were followed oph
thalmologically for a minimum of 2 years. Radiation retinopathy
was observed in 7 eyes, with a cumulative incidence of 25% and
median interval before the onset of symptoms of 32 months
(range 16 to 60). Neovascular glaucoma developed in 3 eyes, with
the cumulative incidence of 7% and median period to the onset
of symptoms of 22 months (range 16 to 26). Obstruction of the
central retinal artery was observed in one eye. No patients who
received less than 50 Gy developed retinal complications. The
eyes exposed to greater than 50Gy with more than 60% retinal
area irradiated resulted in a 62% rate of severe retinal
complications.
The series of 3-D conformal therapy of paranasal sinus malig
nant tumors reported by Roa and associates48 revealed more
encouraging results with respect to preservation of critical struc
tures. There was only one case of limited optic neuropathy and
one case of possible radiation-induced cataract. There was no
blindness related to irradiation. Another report of 3-D conformal
radiotherapy to median PTV doses of 60Gy for 40 patients with
locally advanced paranasal sinuses and nasal cavity tumors sug
gests an improved visual pathway complication rate. With a
median follow-up of 19 months, two patients developed cataracts
and one patient developed ipsilateral blindness caused by vascu
lar glaucoma.88
Neurocognitive effects of therapeutic irradiation for skull-base
tumors were reported by Meyers and colleagues from the Uni
versity of Texas M.D. Anderson Cancer Center.89 Nineteen

patients who received paranasal sinus irradiation at least 20
months and up to 20 years before assessment were given a battery
of neuropsychologic tests of cognitive function. Radiation was
delivered by a three-field technique with the median dose of
60 Gy (range 50 to 68 Gy). Memory impairment was found in
80% of the patients. One third of the patients manifested diffi
culty with visual-motor speed, frontal lobe executive functions,
and fine motor coordination. Two patients had frank brain
necrosis with resultant dementia and blindness, and three had
evidence of brain atrophy. Three patients experienced pituitary
dysfunction. Neurocognitive symptoms were related to the total
dose of radiation delivered, but not to the volume of brain irradi
ated. Improvement in dose distribution using image-based con
formal technique or IMRT should decrease the incidence of these
significant late brain injuries.
Other major complications of combined surgery and radiation
therapy reported in the past include osteomyelitis or radionecro
sis of bone at the base of the skull, or both; meningitis; hemor
rhage; and aseptic brain necrosis.90 With advancement in surgical
techniques, antibiotic coverage, and radiotherapeutic techniques,
these sometimes fatal complications are seen much less
commonly.
It is important to recognize that most publications that have
reported high rates of complications included patients treated
using non-IMRT techniques. As data begins to emerge for
patients treated using IMRT, the benefits of this technology with
respect to preserving normal tissue should become better appre
ciated. In the preliminary University of California, San Francisco,
experience reporting on 36 patients treated using IMRT, observed
complications included mucositis, conjunctivitis, keratitis, cel
lulitis, dacryocystitis, and parotiditisall of which resolved with
conservative medical management. In the late setting, no patients
experienced a complete loss of vision as a result of treatment, with
reported side effects including chronic xerophthalmia, chronic
lacrimal stenosis, cataract formation, eustachian tube dysfunc
tion, and radiation necrosis of the gyrus rector muscle resulting
in gaze limitation.91 A longitudinal analysis of the University of
California, San Francisco, experience showed that the incidence
of grade 3 or higher late toxicity differed significantly among
patients treated with conventional techniques compared with
3-D radiation therapy and IMRT. For instance, 13% of patients
treated with IMRT developed any grade 3 or higher late compli
cation compared with 22% and 54%, respectively, of patients
treated using 3-D and conventional radiation therapy,
respectively.56
RESULTS OF THERAPY
The literature of nasal cavity and paranasal sinus carcinomas
is difficult to interpret because of their relatively infrequent inci
dence and because of the wide variability in surgical and radio
therapeutic techniques employed during the long period during
which the reported cases were accumulated. Compounding the
rarity of these tumors, there are a variety of histologic types of
cancers that develop in this anatomic region, all with different
biologic behavior. Most reports show overall local control rates
from 40% to 60%. Wang42 reported Massachusetts General Hos
pitals experience of nasal cavity squamous cell carcinomas from
1960 to 1985 (Table 33-6). Although the numbers of patients
were small, a combination of radiation and surgery appeared to
produce better 3-year disease-free survival than radiation alone
(78% versus 50%). He reported similar results in favor of com
Survival, n (%)
Site
RT Alone
RT and Surgery
Nasal cavity
10 (50)
9 (78)
Maxillary sinus
35 (38)
44 (55)
Ethmoidal sinus
12 (33)
22 (55)
RT, Radiation therapy.
bined surgery and radiation for squamous cell carcinoma of the

maxillary and ethmoid sinuses (55% versus 38%, and 55% versus
33%, respectively).42
The most consistently identified factor predicting for improved
survival among those treated for carcinomas of the nasal cavity
and paranasal sinuses is gross total tumor resection. Among 127
patients treated at the University of California, San Francisco, the
5-year local control was 65% for those treated with radiation
therapy postoperatively after gross total resection compared with
44% among those who underwent radiation therapy in the pres
ence of macroscopic disease.56 In another study from the Neth
erlands,92 the addition of debulking surgery prior to radiation
therapy dramatically improved 5-year overall survival from 9%
to 60%. The other variable that has consistently been demon
strated to correlate with outcome is tumor extent, with most
studies confirming that patients with T1 and T2 tumors having
superior rates of local control and overall survival compared with
those with T3 and T4 tumors.93,94 Because the vast majority of
patients present with locally advanced cancers, additional data
analyzing prognostic factors such as intracranial invasion, cranial
nerve involvement, dural attachment, and orbital infiltration
all of which would currently categorize a tumor as T4 in the
current AJCC staging systemis urgently needed. Although the
most recent version of the AJCC staging system published in 2002
attempted to address this by dividing cases into T4a (resectable)
and T4b (unresectable), it is still unclear how this distinction may
influence prognosis.
Despite the biases discussed previously, several large series
reporting treatment results are particularly instructive. Investiga
tors from Memorial Sloan-Kettering Cancer Center recently ana
lyzed 85 patients with carcinomas of the nasal cavity and paranasal
sinuses uniformly treated by gross total resection followed by
postoperative radiation therapy and reported a 5-year local
control of 62%.57 On multivariate analysis, squamous cell histol
ogy and involvement of the cribriform plate predicted for an
increased likelihood of local recurrence. In another series from
Washington University, the 5-year local control was 58% among
106 patients treated by radiation therapy alone, or combined with
surgery for paranasal sinus cancer.95 Likewise, investigators from
the University of California, San Francisco, reported a 5-year
local control rate of 62% among 127 patients treated by radiation
therapy with or without surgery from 1960 to 2005.56 Although
the majority of the patients included in the University of Califor
nia series had maxillary sinus cancers and squamous cell histol
ogy, the respective proportions nevertheless ranged from 43% to
76% and 53% to 82%, respectively. These differences are poten
tially significant because other studies have suggested that patients
with maxillary sinus tumors have better outcomes than those

whose primary tumors arise from the ethmoid, frontal, and sphe
noid sinuses, although the infrequency of the latter as well as the
difficulty in determining the exact site of origin make drawing
definitive conclusions problematic.86,94,96
Similarly, others have shown that patients with nonsquamous
cell histologies have improved outcomes compared with those
with squamous cell carcinoma of the nasal cavity and paranasal
sinuses.97,98 Although a study from the University of Florida
reported a very encouraging 5-year local control rate of 70%
among 78 patients treated with radiation therapy, this study was
notable for its large proportion of patients with adenocarci
noma.86 Furthermore, patients were managed with radiation
therapy alone (47 patients) or in conjunction with surgery (27
patients). Four patients also received chemotherapy in addition
to radiation with or without surgery. The more common histolo
gies included 25 squamous cell carcinomas, 31 minor salivary
gland tumors, 14 undifferentiated carcinomas, and 8 esthesione
uroblastomas. The 5-year local control rate for stage I (limited to
the site of origin) was 86%; stage II (extension to adjacent sites),
65%; and stage III (destruction of skull base or pterygoid plates,
or intracranial extension), 34%. The 5-year actuarial local control
rate for patients receiving postoperative irradiation was 79%, and
for those receiving irradiation alone was 48% (p = 0.05). Of the
39 patients who received no elective neck treatment, 33 (85%)
did not experience recurrence in the neck compared with 25
(89%) of 28 patients who received elective neck irradiation (ENI).
They concluded that surgery and postoperative radiation therapy
may result in improved local control, absolute survival, and com
plications when compared with radiation therapy alone. ENI was
felt to be unnecessary for patients with early-stage disease.
Lee and Ogura99 reported on 96 patients with maxillary sinus
carcinoma treated at Washington University in St. Louis between
1969 and 1976. A combination of preoperative radiation and
surgery produced 5-year overall survival rates of 60%, 45%, 28%,
and 38% for T1, T2, T3, and T4 lesions, respectively. None of the
23 patients treated with radiation alone survived 5 years.
A retrospective analysis of 60 cases (46 maxillary antrum and
14 ethmoid sinus) of paranasal sinus cancer treated at Northwest
ern University between 1970 and 1985 was reported by Sisson
and associates.4 The most common histologic type was squamous
cell carcinoma (53%) followed by adenoid cystic carcinoma
(17%). The 5-year survival probability for antral and ethmoid
cancer was 48% and 68%, respectively. Survival did not differ
significantly whether radiation therapy was administered preop
eratively or postoperatively (65% versus 63%, respectively),
although there were more advanced (T3 and T4) tumors in the
preoperative radiotherapy group. Seven patients with small antral
tumors were treated with surgery alone, with an 86% 5-year
survival rate.
A large retrospective review of 220 patients with nasal cavity
and paranasal sinus carcinoma treated at the University of Cali
fornia, Los Angeles, between 1975 and 1994 was reported by
Dulguerov and colleagues.100 With a minimum follow-up of 4
years, the 5-year actuarial survival rate was 63% and the local
control rate was 57%. The factors associated with a worse prog
nosis included squamous or undifferentiated histologies; advanc
ing T classification; ethmoid location; treatment by radiotherapy
alone; and tumor extension to pterygomaxillary fossa, frontal and
sphenoid sinuses, cribriform plate, and dura. In multivariate
analysis, histology, extension to the pterygomaxillary fossa, and
dural invasion remained significant. The authors also performed
a systematic review of published articles on patients with malig
Table 33-6 Three-Year Disease-Free Survival After

Radiation Therapy Alone or Combined Radiation Therapy
and Surgery for Squamous Cell Carcinoma of the Nasal
Cavity and Paranasal Sinuses: Massachusetts General
Hospital Experience
721
722
nancies of the nasal and paranasal sinuses during the preceding

40 years and concluded that a progressive improvement in
outcome had been made for patients with squamous cell and
glandular carcinoma, maxillary and ethmoid sinus primary
tumors, and most treatment modalities.
Myers and colleagues101 reported 5-year and 10-year actuarial
disease-specific survival of 52% and 35%, respectively, for patients
with paranasal sinus malignancies treated at the University of
Texas Southwestern Medical Center between 1980 and 1997.
Most patients presented with locally advanced disease (88%) and
without nodal involvement (96%) or distant metastasis (96%).
Approximately half of the patients presented with squamous cell
histology. Of the patients in this study group, 62% underwent
surgery as part of a multimodality curative treatment plan or
alone as curative treatment. Of these, 13% had unresectable local
disease and received nonsurgical palliative therapy.
The risk of lymph node metastasis and the controversy sur
rounding the elective nodal irradiation in patients with maxillary
sinus carcinoma was addressed in a report by Le and colleagues.102
In this retrospective review of 97 patients treated at Stanford
University and the University of California, San Francisco
between 1959 and 1996, the overall incidence of lymph node
involvement at diagnosis was 9%, with the most common sites
of nodal involvement at levels 1 and 2. Of 36 patients who had
neck irradiation, 25 received ENI for N0 necks. With the median
follow-up of 22 months, the 5- and 10-year actuarial survival
rates were 34% and 31%, respectively. Following treatment, the
5-year risk of nodal relapse was 12%. Squamous cell histology
was associated with a high incidence of initial nodal involvement
and subsequent nodal relapse. Elective nodal irradiation effec
tively prevented nodal relapse in patients with squamous cell
histology. There was no nodal relapse in 13 patients who received
ENI while 6 of 26 patients (20%) without ENI relapsed in the
neck. Nodal relapse was associated with a high rate of distant
metastasis and poorer survival. The authors advocate the use of
ENI in patients with T3 and T4 squamous cell carcinoma of the
maxillary sinus. Results of this study are corroborated by a series
reported by Paulino and colleagues.103 Of 42 patients with squa
mous cell carcinoma of the maxillary sinus in this series, 9.5%
initially presented with cervical lymphadenopathy and 29% later
developed recurrence in the neck after undergoing surgical resec
tion of the primary tumor and postoperative irradiation to
sinuses without ENI. More than one third of the neck recurrence
(10.5% of total) represented isolated neck failure. The authors

advocate ENI in all stages. However, Dirix and colleagues reported
on 127 patients with sinonasal cancers treated by radiation
therapy, none of whom received ENI. With a median follow-up
of 5.6 years, only 6 patients (5%) developed a regional failure in
the neck.104
Table 33-7 summarizes several series of results of radiation
therapy alone, surgery alone, or combined surgery and radiation
for maxillary sinus carcinomas. Overall, it is reasonable to expect
70% to 80% primary-site tumor control for early maxillary sinus
carcinomas (T1 and T2) and 50% to 60% for more advanced
tumors (T3 and T4) after surgery and radiation compared with
50% and 20% to 25%, respectively, after radiation therapy alone.
Definitive irradiation of unresectable lesions can achieve 10% to
15% 5-year survival.36
The success of therapy for malignant minor salivary gland
tumors of the paranasal sinuses and nasal cavity appears to
depend on the combination of radiation therapy and surgery and
the histologic grade of these tumors.105 Of 66 patients, 36 with
adenoid cystic carcinoma and 30 with adenocarcinoma were
treated at the University of Texas M.D. Anderson Cancer Center
between 1951 and 1980. Most patients were treated with surgery
with or without radiation therapy. The local control rates with a
minimum follow-up of 2 years were 47% for surgery alone and
76% for planned surgery and irradiation. Patients with highgrade adenoid cystic carcinomas fared significantly worse than
those with the low-grade variety. Of the low-grade patients, 47%
remained disease free after 5 to 21 years, whereas only 12% of the
high-grade group remained disease free between 2 and 3 years
after treatment. Although the difference was not as pronounced
as in adenoid cystic carcinomas, there was a trend toward better
survival among patients with low-grade adenocarcinomas com
pared with the high-grade group.
In a small retrospective analysis, Naficy and colleagues106
reported a 6-year survival rate of 50% for 7 patients with
adenoid cystic carcinoma of the paranasal sinuses treated by
radiation alone, compared with 73% for 10 patients treated by
combined surgery and radiation. Overall local control rate was
poor at 24%.
Claus and colleagues107 reported treatment outcome of 47
patients with adenocarcinoma of the ethmoid sinuses treated
with surgery and high-dose postoperative radiation therapy
between 1985 and 2001 at the Ghent University Hospital in
Table 33-7 Primary Tumor Control According to T Stage and Treatment Modality for Maxillary Sinus Carcinoma
Tumor Control
Reference
99
Lee & Ogura
St. Pierre & Baker*
Ahmed etal.*
Study Period
Treatment Modality
1969-1976
RT
35
CMT
61
1964-1975
1955-1974
Patients, n
T1
T2
T3
2/3
0/6
5/35
5/7
10/11
3/21
12/19
T4
RT
32
2/4
4/12
1/16
Surgery
10
1/1
0/2
0/4
0/3
CMT
19
1/2
3/5
6/12
RT
47
0/1
6/16
9/28
4/4
2/5
CMT
CMT, Combined-modality therapy; RT, radiation therapy.

*All squamous cell carcinomas.
From St. Pierre S, Baker SR: Squamous cell carcinoma of the maxillary sinus: analysis of 66 cases. Head Neck Surg 5:508, 1983.
From Ahmed K, Cordoba RB, Fayos JV: Squamous cell carcinoma of the maxillary sinus. Arch Otolaryngol 107:48, 1987.
FUTURE DIRECTION
It is clear that tremendous challenges, both physically and
radiobiologically, persist in the management of sinonasal malig
nancies. Because of their proximity to vital organs and their
tendency to present at advanced stages, these cancers will con
tinue to mandate a carefully coordinated multidisciplinary
approach. The presence of gross disease is a major adverse prog
nostic factor in radiotherapeutic management of nasal cavity and
paranasal sinus malignancies. Every effort should be directed to
achieve complete resection, leaving only a microscopic residual
tumor for postoperative radiation therapy. In massive local
tumors, concurrent radiosensitizing chemotherapy and imagebased IMRT in conventional or altered fractionation schedules
need to be further investigated in hopes of improving the thera
peutic ratio. Stereotactic radiosurgery in combination with
surgery may provide another therapeutic avenue for select
patients with tumors of nasal cavity and paranasal sinuses infil
trating the skull base. Finally, emerging modalities such as
proton-beam therapy have the potential to further improve the
therapeutic ratio.
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33

CANCER OF THE NASAL CAVITY

of the anatomy of the nasal cavity and paranasal sinuses. Because

Section III: Radiation Oncology

Part 2 Head and Neck Tumors

Part 2: Head and Neck Tumors

plate serves as an avenue of cancer spread to the anterior cranial

Chapter 33 Cancer of the Nasal Cavity and Paranasal Sinuses

Section III: Radiation Oncology

and is notably prominent in infants. This prominence is thought

Part 2: Head and Neck Tumors

Part 2 Head and Neck Tumors

mixed picture, the most predominant cell type often predicts

sphenoidal and frontal sinus tumors are extremely rare. Eye

Chapter 33 Cancer of the Nasal Cavity and Paranasal Sinuses

FIGURE 33-5 Magnetic resonance images

Section III: Radiation Oncology

DIAGNOSIS AND STAGING

cially with adenoid cystic carcinomas; however, it may occur also

Part 2: Head and Neck Tumors

Part 2 Head and Neck Tumors

(Fig. 33-6 and Fig. 33-7).33 MRI is better than CT in evaluating

most common surgical approach for inverted papillomas. The

Chapter 33 Cancer of the Nasal Cavity and Paranasal Sinuses

Section III: Radiation Oncology

FIGURE 33-6 Magnetic resonance

Part 2 Head and Neck Tumors

Part 2: Head and Neck Tumors

injury to pontine vascular perforators that occurred during an

Wound complications can also occur and include such events as

Chapter 33 Cancer of the Nasal Cavity and Paranasal Sinuses

Section III: Radiation Oncology

Table 33-1 Classification of Nasal Cavity and Paranasal Sinus Cancers

Part 2 Head and Neck Tumors

Part 2: Head and Neck Tumors

Gallagher & Boles

Tabb & Barranco

Bush & Bagshawd

Cheng & Wang

St. Pierre & Baker

Beale & Garrett

Chapter 33 Cancer of the Nasal Cavity and Paranasal Sinuses

Table 33-3 Results of Surgery Alone: Maxillary Sinus

St. Pierre &

Minor salivary gland carcinomas are resected first and irradi

Radiotherapeutic Technique: External Beam

*From Gallagher TM, Boles R: Symposium: treatment of malignancies

From St. Pierre S, Baker SR: Squamous cell carcinoma of the

It is most advantageous to base the treatment volume on treat

Tabb & Barranco

NA, Not applicable.

Section III: Radiation Oncology

Part 2: Head and Neck Tumors

Part 2 Head and Neck Tumors

gland, auditory apparatus, pituitary, brainstem, and spinal cord,

of inhomogeneity corrections for air cavities and dense bone.

Chapter 33 Cancer of the Nasal Cavity and Paranasal Sinuses

setting, CT without contrast suffices. Thin-cut CT with 3- to

10 20 30 40 50 60 70 80 90 100 110 120

FIGURE 33-10 Three-dimensional dose-volume histogram. The

Section III: Radiation Oncology

posterior aspect of the clivus, splitting the vertebral bodies. The

Part 2 Head and Neck Tumors