What is the Nasal Cavity?

The nasal cavity is an area of the face which includes the protruding nose along with its nostrils and the stuctures inside the nose. It is an irregularly shaped area. It extends as high as the fine membrane lining (“lamina papyracea”) of the ethmoid bone which separates the upper nose from the lower “orbital” bone surrounding the eyes. It extends as low as the the upper surface of the palate which divides the upper mouth from the lower nose. It is bounded on either side by the “maxillary sinuses”. At its lower portion, the nasal cavity proper goes as far backward (“posteriorly” toward the brain) as the “posterior ethmoid air cells” which are part of the ethmoid sinus. At its upper portion, it goes as far backward as the “nasopharynx”, which is the highest part of the throat located behind the nose. Behind the ethmoid sinuses is the forepart of the brain. Thus, a disease of the nasal cavity can extend into the brain. And of course, the nasal cavity extends as far forward (“anteriorly”) as the nose we see on our face, and includes within it the irregularly shaped “turbinates” which control air flow in the nose. The soft fleshy part of the very forefront of the nose is properly called the “nasal vestibule”, and the wall of flesh that divides the nostrils (“nares”) is the “columella”. The columella is soft cartilage by the nostrils, but becomes continuous with a bone called the “vomer” which continues to divide the nostrils higher up in the nose. The part of the nose directly under the eye sockets is bony, and called the “nasion”, but it soon turns to soft cartilage to form the remaining front of the nose. The indentation of the very top of the nose, between the eyes, is called the “glabella” at is very close to the “frontal lobes” of the brain.

Since the nasal cavity is so close to the maxillary, ethmoid and sphenoid sinuses, these structures are called the “paranasal sinuses”, and disease of the nasal cavity can spread to them and vice versa. However, disease starting in the paranasal sinuses tends to be of different types, and is classified separately from nasal cavity diseases. Nasal cavity disease can also spread into the eye sockets by penetrating the thin bone of the “orbit” (eye socket) surrounding each eye. It can also spread backward to the nasopharynx and brain. As such, there are crucial nerves controlling vision, smell and facial movement (“cranial nerves”) which can be affected, or even the brain may be invaded by nasal cavity diseases. The skin sensation of the nose is conducted by cranial nerve #5, the large “trigeminal nerve”-- specifically by its “maxillary division”. The sense of smell is conducted by cranial nerve #1, the “olfactory nerve” whose rootlets ascend toward the nasopharynx and then up into the brain through a sieve-like bone at the top of the nose called the “cribriform plate”. Movement of the nose is controlled by cranial nerve #7, the “facial nerve” which, if damaged, leads to a drooping of one side of the face (as is seen in “Bell’s Palsy”).

There is a rich blood supply to the nose from the nasal, facial and palatine arteries, which branch off the large “external carotid” arteries which supply the face. The “internal carotid” arteries are deeper and the main source of blood for the brain. Blood is also drained by similarly named veins into the large “jugular veins”, which return it to the heart. Thus the bloodstream can be a route for disease spread, called “hematogenous dissemination”. There is also a network of “lymph channels” which
collect the tissue fluid (which has seeped out of blood vessels to bathe individual cells), and this fluid is sent to local pea-sized bean shaped “lymph nodes”. These nodes, also called “glands”, swell up when invaded by germs, allergens or cancer. This swelling is called “lymphadenopathy”, and is most commonly observed in the lymph nodes of the neck. The lymph nodes, which are filled with white blood cells, interconnect (there are about 700 of them in the head and neck) and act as filters to purify the blood serum [note-- serum is the liquid portion of the blood, as distinguished from the blood cells]. . Eventually the purified blood serum is returned to rejoin the bloodstream in the region of the heart. However, this lymph system can also act as a conduit for the spread of cancers or infections, a process called “lymphogenous dissemination”. Prior to spread by the bloodstream or lymph system, nasal diseases, including cancer, tend to grow large in their local area, but occasionally the first symptoms seen are due to more distant spread of disease.

What is Nasal Cavity Cancer?

Fortunately, most conditions affecting the nasal cavity are not cancer, but rather “benign” afflictions. This includes infection of the nose (“rhinitis”), a continuously runny nose (“rhinorrhea”) and stuffiness due to allergies (“allergic rhinitis”). Also, since there are many small “capillaries” in the nose (where the smallest arteries join the smallest veins) nosebleeds (“epistaxis”) are common. Bleeding can be initiated by irritation, dry air, trauma, excessive sneeing, high blood pressure, infections or cancer and are harder to control when they occur deep within the back portion of the nose. In general, cancer is the LEAST likely cause of nasal problems.

Cells in the nose are subjected to lots of injury from heat and abrasion, dust and germs breathed in, and thus must divide frequently to replace those lost due to injury and old age. Normally, cells divide quickly as we develop in the womb and through infancy, and then the rate slows down considerably, just to replace cells that die. The division of cells in the nose and elsewhere is under very tight control, regulated by the “genes” within the cells. When this control is lost, the cells may start to divide in a haphazard, uncontrolled manner, and grow to form a swelling of abnormal cells, called a “tumor”. A “benign” tumor only grows within it’s local area, it does not spread to distant organs, and it is not cancer. In contrast, a “malignant” tumor can spread to any area of the body, it is cancer. It is this ability to spread, or “metastasize”, to vital organs which makes a cancer so dangerous. Nasal cancers tend to grow large locally before spreading, but any cancer can spread at any time.

How Common is Nasal Cavity Cancer?

Nasal cancer is relatively rare. Each year in the United States there are about 1000 new cases of nasal and paranasal sinus cancer leading to about 300 deaths annually from this disease. Men are affected twice as often as women. Overall, nasal cancer represents less than ) 0.5% of all new cancers each year, affecting one out of 100,000 Americans. and it is more common in blacks than whites, and in those of “lower socioeconomic status” (poor people). The average patient is 60 years old. However, some rarer subtypes of nasal cancer (esthesioneuroblastoma and nasal lymphoma) occur primarily in patients under between 20 and 40 years old. The disease is more common in Asia Minor and China than the Western Countries, and worldwide appears to be slowly increasing-- probably owing to better detection.

What Causes, or Increases the Risk, for Nasal Cancer?

Like any cancer, the reason why one person develops Nasal Cancer and another does not remains unknown. However, by studying groups of patients for common features, we have established certain “risk factors” that , if present, raise the risk:

Tobacco usage is the single strongest risk factor for developing cancers of the head and neck. Any form of tobacco taken through the mouth, whether smoked or chewed, increases the risk over time. The more tobacco that is used, for a longer period of time, the higher the chance is to get cancer. Likewise, when use is stopped, the risk declines to normal over a 5 to 10 year period.

Infections such as syphilis and some viruses can lead to cancer over time, these cause sores which heal poorly. The constant attempt to heal leads to "chronic cell division" and thus more chance for cancer. Viruses can also get into the cells of the nose themselves and change the genes in them to form a cancer cell. This elaborate process is called "Oncogene Activation". Another process called “Suppressor Gene Inactivation” can allow a damaged cell (which should not divide) to go about division anyway. The most common virus noted to do this in the upper respiratory tract is the Human Papillomavirus (HPV). Some people seem genetically predisposed to getting cancer from viruses.

Lowered Immunity such as from AIDS or transplant anti-rejection drugs will increase the risk for many cancers, including those of the "aero-digestive tract" (i.e. the area from the nose and mouth to the lungs and stomach). This will be especially important in combination with the other risk factors noted.

History of Cancer of the aero-digestive tract can mean as much as 5% chance of a separate already present (“simultaneous”) cancer, and a 25% chance of developing another (“metachronous”) cancer in this area over time (especially if risks like smoking are continued).

Breathing sawdust and smoke from certain fires increases the risk for nasal, nasopharynx and sinus cancers, probably from chronic irritation. This is believed one reason why these cancers are more common in the Far East, where people still use many open-smoke fires to cook food.

A “symptom” is something that the patient feels, such as a headache or fatigue, while a “sign” is something that can be measured by the doctor, such as weight loss or lymph gland swelling. A cancer must grow to 1 billion cells to be just 1 cm. (about 1/2") across, so a very early cancer will have no symptoms and likely to go undetected. As it grows, it produces symptoms in it's local area, and eventually in distant areas as it spreads. A nasal cancer may actually be noticed before other cancers of the sinuses or nasopharynx, since it tends to cause a blocked nose early. However, this may just be attributed to allergy or “sinus infection”. The way a patient appears when they first come to their doctor is called the “presentation”.

The most common presenting symptoms and signs of nasal cancer noted by patients are:

1) Nasal obstruction, nasal discharge, smell loss, and sinus congestion, are so commonly associated with non-cancerous conditions that they are frequently neglected until the disease is advanced. Bleeding (“epistaxis”) may occur. The cancer may erode through the palate into the mouth, and first be noted by a dentist.

2) Breathing problems, frequent headaches, a lump in the nose or neck, pain or ringing in the ear, speech difficulty, or trouble hearing. Swallowing and eating may be mechanically obstructed as the cancer grows down into the throat.

3) Local pain is possible as the tumor enlarges, especially if it invades nerves. The nose shares nerves with the ear, mouth and throat, so some deep nasal cancers cause pain in these areas ('referred pain') Interestingly, the further back in the nose the cancer, the deeper in the ear the pain appears.

4) Swelling in the Neck or Face is possible as the lymph nodes are invaded. The nose has a rich blood and lymph supply (in contrast to the sinuses which have a poor supply), and 15% of patients will have involvement of the lymph glands in the neck when they first “present” for medical attention. An additional 15% will develop neck lymph gland swelling further along in their disease. This swelling is usually firm and painless. Neck lymph nodes can also swell up from non-cancerous conditions such as infection, so swelling alone does not prove cancer. However, larger, harder and more persistent swellings are more likely to be cancerous. Also, as a cancer advances, it is likely for the area to become infected by germs in the area, so lymph nodes can be swollen from both cancer and infection at the same time. Other lymph nodes which may swell are in the cheeks (“buccinator nodes”), under the chin (“submental nodes”) and at the back of the neck (“occipital nodes). If the cancer invades into the nasopharynx, the chance of lymph node swelling is over 80%.

5) Nerve Problems in the eyes, face and neck occur as the cancer invades into the cavernous sinus nearby the brain ("Jacod's syndrome") or into lymph glands that press against the nerves exiting the base of the skull ("Villaret's syndrome"). These nerve problems present as double vision (“diplopia”), deviation of the eyes (so they do not turn together (“conjugation”), weakness of the muscles of the face, and/or difficulty with swallowing, turning the head, or lifting a shoulder.

6) Signs of Distant Spread, to lung, liver, bone, and brain with advanced disease.

The behavior of a disease in the average patient is called it's "natural history". Recall that cancer starts in a single cell, which divides in an uncontrolled manner to make millions and billions of copies of itself. It generally starts on the surface of of the nasal cavity (the “mucosa”) and gradually penetrates deeper. As it goes deeper, it can invade lymphatic channels and spread to local lymph nodes in the neck. It may invade nerves and cause pain, and into underlying bone to destroy it. Commonly, an untreated nasal cancer will grow larger and larger in it's local area ultimately become a huge, infected and bleeding “mass”. The extent of the mass may not be appreciated merely by looking up into the nose, since it can have “local extension” which is unapparent to the naked eye. It may then protrude through the skin to form a gaping and seeping wound, and spread via the bloodstream to distant organs. Ultimately, Nasal cancer kills by anemia, infection, malnutrition, dehydration and general debility.

How is Nasal Cancer Diagnosed and Evaluated?

If a patients comes to their physician with symptoms and signs suggestive of a nasal cancer problem, they are commonly referred to a specialist called an “Ear, Nose and Throat” (“ENT”) doctor or “Otolaryngologist”. While some of these “ENT”s confine their practice to lesser problems like allergies and ear infections, they are all by training “Head and Neck Surgeons” and some sub-specialize in treating cancers. The most experienced “Head and Neck Surgeon Otolaryngologists” are found at Academic University Hospitals.

Examination of the a patient with a new neck lump (“mass”) should include inspection of the ears, nasal cavities, mouth and entire throat [nasopharynx, oropharynx, hypopharynx, and larynx (voice box), palatine tonsils, and base of the tongue], as well as the thyroid and salivary glands. The only way to absolutely diagnose any cancer is to get a piece of it ("biopsy") and analyze it under the microscope. A special instrument (called a nasoscope) may be put into the nose to see into the nasopharynx and back of the nasal cavities. If an originating site ("primary site") cannot be found the any area of cancer spread may be sucked up ("aspirated") with a fine needle for further evaluation to locate a precise site. These fine needle aspirations are 85% accurate at confirming or denying cancer in a suspicious swelling (“lesion”). Sometimes patients with cancer in lymph nodes of the neck have no evident “primary site” and then are diagnosed with a “Cancer of Unknown Primary Site”-- but these can usually be successfully treated in the Head and Neck. As long as we have something to biopsy, a “pathologist” will be called in to examine the biopsy specimen. This is a physician who specializes in making diagnoses from tissue samples.

The usual steps in evaluation of a suspected Nasal Cavity cancer include:

1) Physical Examination is done carefully and includes a meticulous description of the tumor, including it's location, size, color, texture, and whether it is "fixed" to underlying tissue or can be moved about. the doctor looks for white patches ("leukoplakia") and reddish patches ("erythroplasia") which may be precancerous areas. A through exam of the neck is always done, noting any enlarged glands which may represent the cancer spreading to lymph nodes. the back of the throat is examined, and a mirror is used to visualize the vocal cords ("indirect laryngoscopy"). The nerves which arise from the brain (12 of the called "cranial nerves") supplying the face, eyes, ears, nose and throat are tested to look for signs of nerve invasion or compression by cancerous lymph nodes. Naturally, it is also appropriate to do a complete exam of the rest of the body to assess general health and look for signs of distant cancer spread.

2) Endoscopic Examination means placing a visualization tube under light local anesthesia into the nose and down the throat. the preferred procedure is a "triple endoscopy", which looks at the nose, esophagus and larynx (voice box). Clear Endoscopic visualization of the larynx is called "direct laryngoscopy". A biopsy is taken of any suspicious area, and sometimes "blind biopsies" are taken of areas most likely to develop cancer (such as the tonsil, nasopharynx, pyriform sinus and bse of the tongue). This is also done since, as mentioned 5% of patients will have a "second primary" when they come to medical attention-- that means another simultaneous cancer. Endoscopy is a very safe procedure, and is the clearest way to actually look at tissues of the aero-digestive tract, and take samples for pathologist evaluation (the endoscope has a cutting scissors at its end to take biopsies).

3) Blood and Urine Tests are standard preoperative ones to assess general health; there are no special blood tests ("tumor markers") yet to detect spread of squamous cell cancer as there are for some other cancers. Routine tests include Complete Blood Count ("CBC") to look for anemia and infection. A Blood Chemistry Panel ("SMA") measures sodium, potassium, calcium, phosphorus, blood sugar, cholesterol and liver and kidney function. If a major surgery is contemplated , blood tests for clotting ability (PT, PTT and bleeding time) are standard. A Urinalysis (UA) to check for protein, blood, or infection completes the lab tests.

4) Imaging Tests are done in the radiology department and standardly include a Chest X-ray to look for signs of infection or lung tumors. Special imaging of the head and neck is obtained; a "panorex" is a series of jaw X-rays which is excellent for detecting spread of cancer to local bone. A CT scan in "thin slices" of the “sinonasal” area helps define the extent of the tumor. It can tell whether normally unexaminable lymph nodes (such as the “retropharyngeal” or “parapharyngeal” nodes are enlarged). Slices should be 3 mm. or less, 5 mm. (standard at some institutions) is NOT acceptable for nasal cancers. CT scan with Contrast (given by vein) is almost always used since it is valuable in detecting spread into the sinuses or brain. Insist on “omnipaque” or equivalent contrast, it is more expensive but also more comfortable and less likely to cause an allergic reaction or kidney damage. The more expensive Magnetic Resonance Imaging (MRI) scan has become increasingly popular. MRI, which uses magnetism instead of radiation, allows the area to be viewed in three dimensions. It is great for looking at the tumor as well as checking local muscle, cartilage and nerves for signs of invasion by cancer. In general, it is superior to CT scan for checking soft tissues of the head and neck.

An MRI with Contrast can be given with an different agent called “gadolinium”, which highlights blood vessels and increases the ease of reading the scan. Lymph nodes of the neck are not routinely studied with Nasal cancer unless the cancer has spread to the nasopharynx, facial lymph nodes, or if there is evident (“clinical”) swelling of neck lymph nodes. Other more exotic tests are only obtained in the presence of suspicious symptoms. For instance, a Bone Scan is gotten if there is new bone pain. A CT of the Chest and Abdomen is obtained if the plain Chest X-ray appears to show tumor in the lung, and a CT of the Brain is gotten if new neurological symptoms occur. Ultrasound is not useful for head and neck cancer. “Angiography” means injecting some contrast dye into a face or neck artery and taking rapid pictures, it plays a small role for tumors with lots of blood vessels (“highly vascular”)-- but much of the same information can be gotten today on a contrast MRI (“MRA”) scan. There are special tests which can be ordered to look at just about any area of the body-- but only if necessary. In general, a test should only be ordered if the therapy may be changed based upon its results!

5) Biopsy of the tumor is crucial, since only by examining an actual piece of the tumor under the microscope can a diagnosis of cancer be made, and the particular type known with certainty. For a small tumor, the whole of it may be removed along with a "safety margin" of surrounding normal tissue, and sent fro evaluation ("Excisional Biopsy"). For a larger tumor, a cut is made into it so some tissue can be removed for examination ("Incisional Biopsy"). Sometimes a swollen gland in the face or neck may be the easiest (or even only) area to biopsy. It usually takes several days (of anxious waiting) for the pathology report to come back.

What are the Types of Nasal Cancer?

There are several types of benign (non-cancerous) and malignant (cancerous) tumors found within the nose. The most common benign tumors are “polyps” (local tissue swellings), granulomas (inflammatory swellings), and local infections (“abcesses”). However, when a cancer is found, it may be:

1) Squamous Cell Carcinoma is the most common cancer (70%) within the nose, and is similar to skin cancer. These cancers arise from lining cells, looking like “fried eggs” under the light microscope. They tend to grow very large in their local area, only spreading distantly late in the disease. They can be extremely destructive to local tissue, virtually “eating away” the nose tissue, and easily get infected.

2) Adenocarcinoma is the second most common type of nasal cancer, and may arise from the mucous glands in the nose or from the “minor salivary glands” that are widespread through the upper respiratory tract. While there are 3 major saliparied salivary glands (submandibular, parotid, sublingual) there are hundreds of minor ones. Under the light microscope, adenocarcinoma cells form glands.

3) Adenoid Cystic, Acinic Cell, and Mucoepidermoid Carcinomas are other types that arise from the minor salivary glands. Overall, 15% of nasal cancers arise from minor salivary galnds. Of this 15%, Adenocarcinoma makes up nearly 50% of glandular cancers arising in the nose, adenoid cytic carcinoma is 30%, mucoepidermoid is 10%, and Acininc cell is 1%. The “papillary” form of these carcinomas tends to be the most localized, but any of them have a propensity to travel along nerve sheaths for local spread. They also may have arisen in another part of the body and spread (“metastasized”) to the nasal area.

4) Inverted Papilloma is a kind of “wart” that grows into the mucous membranes of the nose, and may be very benign in behavior. However, some cases show more aggressiveness and have a propensity to keep coming back (“recurring”) after treatment, so inverted papilloma is considered a “low grade” malignancy. It may procede the development of squamous cell carcinoma in 15% of cases.

5) Esthesioneuroblastoma is a cancer that starts in cranial nerve #1 (“olfactory”), the nerve which conveys the sensation of smell to the brain. Confused with other types (like carcinoma or lymphoma) in the past, modern staining techniques of the biopsy specimen can distinguish it better than the simple light microscope. It is considered a “neuroendocrine” tumor, meaning its cells have “granules” that can secrete “neurotransmitters” as are found in the brain. It is found in different age groups, either 10 to 20 year olds or 50-60 year olds (“bimodal distribution”). Esthesioneuroblastoma makes up about 2% of nasal cancers.

6) Melanoma is a cancer of the “melanocytes”-- skin pigment cells which produce melanin. In actuality, these cells are found in the digestive, respiratory, and genital tracts as well as on the skin surface. Melanoma accounts for ~10% of nasal cancers. This type is equally common in men and women, whites and blacks, and most patients are elderly. Melanoma tends to spread early to distant areas.

7) Lymphoma and Sarcoma are cancers of the immune cells and soft tissues (i.e. fat, muscle, cartilage) respectively. Rare causes (<1%) of nasal cancer, if found are treated according to guidelines for areas in which they are commoner.

An important consideration for the commonest types, that is squamous cell and adenocarcinoma, is how aggressive they appear under the light microscope. This is called their “grade” and gives some idea of how the cancer will behave in the patient.

The “grade” is assigned by the pathologist when (s)he examines the biopsy material.A “grade III” cancer is the highest grade, and means that the tumor is “poorly differentiatiated” and scarcely resembles the normal tissue it initially arose from. The cells are usually bizarre in shape, have large and dark centers (“nuclei”), and are dividing very quickly. These “grade III” cancers tend to be the most aggressive (which does NOT mean they are unresponsive to treatment!). In contrast, “grade I” tumors are easy to identify since they closely resemble their normal tissue counterparts, that is are “well differentiated”. They are slow to divide, and generally less aggressive (“indolent”) in their behavior. “Grade II” tumors are called “moderately differentiated” and are intermediate in behavior. Some tumors can have more than one type of cancer or grade (“mixed tumors”). They usually behave according to the most aggressive type and grade found therein.

How is the Nasal Cancer Gauged?

Like all cancer, the extent of Nasal Cancer is given by the "stage". These stages were developed by the “American Joint Committee on Cancer” (“AJCC”) to help make appropriate treatment decisions, and tally the results of therapy for various levels of disease. The problem with the AJCC system is that any bone invasion, even local, would make the cancer a “stage IV” similar to distant spread. Thus, for nasal cancer, the University of Florida system is commonly utilized:

“Stage I” means the cancer is limited to its site of origin.

“Stage II” means extension to adjacent sites, such as the nasopharynx, orbit of the eye, outside skin, or sinuses (ethmoid, sphenoid, maxillary).

“Stage III” means invasion into the base of the skull or brain.

“Stage IV” means distant spread (e.g. lung, liver, skeleton).

What is the Survival with Nasal Cancer?

The survival for cancers of the Nasal Cavity depends upon the specific type of cancer, the general condition of the patient, and the above stages.

Of course, survival and quality of life depends upon the treatment selected, and the response of the particular cancer to that treatment. The above textbook numbers include death from all causes, including heart attack, accident, and some other cancer. No one can predict just how long any individual will live with cancer. Many patients with Nasal Cavity cancer are elderly and have other severe (“comorbid”) medical conditions they will succumb to first. Bear in mind that many people live for many years with incurable cancer!

What are some of the common treatments for Nasal Cancer?

The common treatments for carcinoma, inverted papilloma, esthesioneuroblastoma and melanoma are surgery and radiation therapy. Chemotherapy is used for lymphoma but has a very limited role in the conventional treatment of other cancers. Fortunately, great advances in both surgical procedures and radiation techniques have significantly improved outcome in the past 2 decades.

Surgery is the standard treatment for “resectable” lesions-- that is those that are small enough to be completely (or nearly completely) removed without causing gross deformity or handicap. Surgery is performed by a “Head and Neck Surgeon”, that is an Otolaryngologist subspecializing in it. For cancers that have invaded into the orbit, an Ophthalmologist may called in to assist, and for those that have invaded into the brain a Neurosurgeon should assist. Any surgery should be carefully planned to preserve function and cosmetic appearance. For a large cancer (i.e. which invades into orbit, skull, or sinuses) surgery alone is unlikely to completely remove the tumor; surgery is basically a “debulking” procedure to remove the tumor mass. It is expected that such patients will have a “positive margin”, meaning that microscopic tumor cells can still be found at the edge of the surgical field. These patients will require radiation therapy after their surgery (“post-operative radiation therapy”) to mop up (“sterilize”) residual tumor cells. Ideally they should be seen by the radiation therapist BEFORE the surgery to appreciate the size and extension of the tumor before it is disturbed. The surgeon should thoroughly discuss the planned operation with the patient, including possible complications and side-effects, so that proper “informed consent” can be given by the patient.

The extent of surgery will obviously depend on the site and size of the tumor, as well as the aggressiveness and philosophy of the particular surgeon. For the smallest sized tumor, with no invasion of surrounding structures, a simple “local excision” may be sufficient, with careful monitoring afterward to detect a recurrence. This is often done for limited “inverted papilloma” which has “low malignant potential”, but will recur if the surgery is incomplete. It is recommended that any surgical specimen be carefully cut out and sent to the pathology department, as opposed to just burning off the lesion with a cautery knife (“fulgaration”) or freezing it (“cryosurgery”). The only exception to this might be small skin cancers in the area of the nose so treated by a competent dermatologist. Certainly any tumor who’s extent is unknown prior to surgery must be sent for pathological evaluation of the “margins of resection” (that is whether all cancer cells have apparently been removed) and not merely destroyed. Simple operations may be done under local anesthesia, often with 10% cocaine hydrochloride solution (which both numbs the area and shrinks blood vessels to minimize bleeding). This drug is quite safe as long as the patient’s blood pressure is relatively normal and they do not have heart disease. Recovery from small operations is within several days, and the most important thing is careful follow-up thereafter.

If the interior of the nose must be surgically exposed, this is a major operation which will require general anesthesia. A “lateral rhinotomy” is the most common surgical approach, whereby a cut (“incision”) is made in the groove between the side of the nose and the cheek. It may go as high up as the orbit of the eye, as a low as splitting the lip. This procedure opens up the side of the nose, allowing the surgeon to get inside of it. It is often sufficient for a cancer limited to the turbinates of the nose or the nostril. Its appearance after surgery (“cosmetic result”) is excellent, but it is insufficient for tumors which have invaded into the nasopharynx or sinuses. If the maxillary sinus is involved, “medial maxillectomy” can be added to lateral rhinotomy to get better exposure of the sinus. This involves continuing the incision sideways along the skin and bone between the cheek and lip (the “naso-labial groove”), on the side involved with the cancer. The cosmetic result of this is also excellent, since the surgeon is cutting in an area where there is a natural skin groove anyway. If the tumor has spread deeper or further, the previous operations can be combined with a “midface degloving procedure” to get better surgical exposure of the bones in the face. As the name implies, a degloving procedure means peeling back the skin, fat and underlying muscle off of the midface to expose the facial bones underneath. This is done by making an incision under the upper lip, along the upper gumline, along with incisions into the cartilage at the base of the nose. Again, the cosmetic result should be excellent, but the main limitation of the preceding procedures is limited exposure higher up in the nose (“superiorly”).

When higher area in the nose is involved, the chances for invasion of the cancer through the thin protective lamina papyracia into the ethmoid sinus increase. To get a good surgical exposure of the upper portion of the nose, an “ethmoidectomy” can be added to the medial maxillectomy and midface degloving. An ethmoidectomy incision is made between the inner corner of the eye (“canthus”) and the upper bridge of the nose, and part of the inner wall of the eye socket (“orbit”) is actually removed. This is because the inner portion of the eye socket closest to the nose is a portion of the ethmoid bone, and the ethmoid sinus lies directly below the bone. We also expect minimal scar even when adding an ethmoidectomy since the skin incision is made on a normally recessed area. When deeper structures near the top of the nose are involved with cancer, the chance for spread into the cribriform plate, nasopharynx and the brain increase. In this case, to get a good exposure of the area, a “cranial facial resection” may be needed instead of the simpler midface degloving.

This is the most aggressive surgery done for nasal cancer, and basically (temporarily) totally pulls one half of the face off of its underlying bones. To accomplish a cranial-facial resection, a long incision is made from between the front teeth, along the length of the nose, and up the forehead. The incision is then continued sideways along the hairline around the side of the upper skull, so that the skin, faat and underlying muscle can be pulled off of half of the facial skeleton. Once we do this, the surgeon has easy access to the fore portion of the brain, and if the cancer has invaded into it the neurosurgeon takes over to clean it out. We do anticipate greater scarring owing the long incision along prominent parts of the face. A “subcuticular” stitch is more work for the surgeon, but it leaves less skin scaring than standard external stitches, so ask for it. Interestingly, in people who tend to form keloids (large excessive scars) from skin wounds, giving radiation treatment to low dose (i.e. 8 Gray) minimizes scar formation. Since many patients with nasal cancer will be getting high dose (i.e. 60 Gray) post-operative radiation therapy after they recover from surgery (within 6 weeks) we may expect less scar tissue for these patients as a “fringe benefit” of radiation therapy.

We expect, with major surgery, a recovery time of about 3 weeks for the tissues to return to 75% of their former strength. Risks of major surgery include infection (10%), complications such as heart attack, stroke, other blood clots or pneumonia (total 10%), and death in the “peri-operative” (at or around the time of the surgery) period of about 2 - 3%. Obviously, the extent of scarring will depend upon the skill of the surgeon, the aggressiveness of the operation, and the propensity of the patient to form scars. Plastic surgery procedures can greatly enhance appearance and even construct a “new nose” if necessary. Again, except for patients with very small disease easily and totally removed by surgery, most patients will require additional (“adjuvant”) radiation therapy to “sterilize” residual cancer cells.

Radiation Therapy is a standard and crucial treatment in properly “addressing” a large nasal area cancer. Radiation kills cancer cells when they try to divide, and works by damaging the DNA within the cancer cells. It also damages DNA within surrounding normal cells, but these normal cells can usually repair the damage-- whereas cancerous cells cannot. The effects of radiation therapy will continue after the treatments are completed, and tumors will often shrink over months following radiation therapy. Persistance of a “stable mass” or a “shrinking mass” in the nose after treatment does not automatically mean residual cancer, for it may just be scar tissue-- but a “growing mass” after any therapy is worrisome, and must be explored.

Radiation Therapy has been used for eight decades for many cancer, including those of the nasal cavity. In fact, radiation is quite successful in treatment of nasal area cancers, and is the treatment of choice for most of them. Radiation may be given alone, or be added to surgery ("adjuvant therapy"). It may be combined with chemotherapy, or all three methods of surgery, radiation, and chemotherapy can be offered together ("multimodality therapy"). Radiation is prescribed by a "Radiation Oncologist", who is a cancer doctor specializing in it's administration. It can be given in several forms, most commonly a series of "External Beam" treatments with photons and/or electrons. The other less common way is giving “Brachytherapy”, which means a temporary implant of actual radioactive source(s) into the nasal area. Both methods can be used, the first for wide coverage of the area, and the second for “boosting up the dose” to the actual tumor site (while minimizing it to normal tissues).

The first step is to be seen in “consultation” by the radiation oncologist, the patient getting external beam treatment is scheduled for "simulation". During simulation, the patient is placed on a replica treatment machine, and the area to be treated is marked out. Instead of placing marks on the patients skin, a "mask" is made for head and neck cancers, and the marks designating the treatment area are placed on the mask. X-rays are taken to confirm positioning. A simulation normally takes about one hour. Information from the simulation, along with other scans, is fed into a "treatment planning computer" and a "plan" is generated. This plan tells how much radiation is going to the cancer, and how much to local normal tissues. Special lead-type "blocks", which fit into the head of the treatment machine, determine the shape of the radiation field administered. The patient then returns to the department for their "treatment start", which takes about 45 minutes. They lay upon a hard table in a shielded room, and are aligned with laser lights shone upon the marks on the mask. The actual machine which delivers photons or electrons is called a "Linear Accelerator" or Linac for short; occasionally Cobalt-60 machines are still used. The head of the machine pivots around the patient, so they stay perfectly still during the treatment, even as the radiation is delivered from various angles.

The actual treatment only takes several minutes per day, and is usually given from Monday through Friday for 6 or 7 weeks. The usual dose is 60 to 75 Gray (units of radiation) to the actual tumor, with less to surrounding tissues. this is given in "fractions" of about 2 Gray per treatment, accounting for the 7 or so weeks of total therapy. For head and neck cancers, a combination of photons and electrons is often utilized. Photons will penetrate very deep, and tend to spare the skin, while electrons give shallower dose to "boost" up the dose to the more superficial tissues. the "plan" from the simulation helps determine the optimal mixture of photon and electron dose. If a treatment day is missed, it is simply tacked onto the end so that the same total prescribed dose is given. The actual treatment is given by "radiation therapy technologists", or R.T.T.'s, who are supervised by the physician. A “radiation physicist” (with a Master’s or Doctorate in Physics) checks over the treatment plan as a safety measure.

Radiation Therapy is usually very well tolerated, treatments themselves are painless. The side-effects of localized radiation are generally only within the area treated. That is, patients will lose scalp hair only if the actual scalp is treated, or becomes sterile only if the testicles or ovaries are treated. The side effects of radiation are thus specific for the area treated, and are divided into "acute" and "late" reactions. "Acute" reactions occur during the treatment period, while "Late" reactions may occur months to years later. Common acute reactions, which start after about a week of treatment, include skin reddening and irritation; this may progress to frank peeling. Special salves or steroid creams may be prescribed to alleviate this. A foreign, "metallic" taste may be noted in the mouth, and the saliva thickens. The salivary glands may initially swell, and mouth dryness occurs as the dose to these glands builds up. Soreness and the mouth dryness occurs as the dose to these glands builds up. Soreness and the mouth and throat may be quite painful, and require special numbing agents ( viscous lidocaine) to make eating less uncomfortable. Mild narcotic may be needed for relief. Weight loss is common with treatment for head and neck cancers, so nutrition must be carefully monitored. The dose to the neck is usually kept at 50 Gray or below, since bulky tumors (greater than 2 cm.) there need surgery to control them, and 50 Gray is over 95% effective in mopping up residual microscopic cancer cells in the neck. Nonetheless, some patients may even require a temporary feeding tube, especially if the neck is being treated for involved lymph nodes there. A flexible tube ("PEG") is placed through the abdominal wall and into the stomach during treatment. this tube is removed when the acute radiation reaction subsides. Mouth and throat pain may be increased by fungal infections, like thrush, which are more likely during radiation. Hair on the face is lost during treatment, but a man's beard will usually grow back, albeit thinner. There is often a sense of fatigue during the therapy period. Overall, treatment is not pleasant, but is made more tolerable by prescribing relieving medications as appropriate. People differ in their tolerance to radiation, and to really effectively kill the tumor cells, it is necessary to get the acute reaction showing that both cancer and normal cells in the nasal cavity are dying. The normal ones can be repaired and replaced, but not the cancerous ones; this is why radiation works.

The matter of more ultimate concern is "late" reactions, for these will stay with the patient indefinitely. The frequency and severity of late reactions are less when therapy is given as many small fractions, and this is why we take many weeks to give it all. The most common late reaction from treatment of mouth cancer is dry mouth, called "xerostomia" in medical parlance. This is due to damage to the salivary glands, which then produce a thickened, whitish saliva. Artificial saliva ("salivart"), pills which will stimulate saliva (pilocarpine"), humidifiers and plain spray bottles may be tried to moisten the mouth. The skin in the area of treatment is often slightly discolored, and may be of tougher texture. A more grave concern is of damage to the spinal cord, which in this area tolerated about 50 gray of radiation. Beyond this, the chance for damage increases dramatically. Mild damage is shown by a shock-like sensation going through the body with neck flexion (Lhermitte's sign"), but this is actually temporary and scary but not dangerous. Serious damage results in paralysis, but fortunately this is extremely rare with modern radiation techniques (less that 1 in 500 patients). Another rare but possible complication is the development of a second cancer in the area due to radiation,these are usually of the bone, cartilage, or muscle ("sarcomas"). Another serious concern, when an eye or the optic nerves are given high doses (over 55 Gray) of irradiation is retinal blindness. The risk of this is as high as 33%, and can occur months to years after irradiation. It is crucial to avoid irradiating both eyes, or the area where the optic nerves join (“chiasma”) to high doses if at all possible. Dry eye results from irradiating the tear glands (“lacrimal”) and can result in blindness over time if the eye is not properly lubricated. Any patient who has significant treatment to the eye MUST BE FOLLOWED BY AN OPHTHALMOLOGIST. High resolution CT and MRI scans can "upstage" patients by identifying lymph nodes that were not thought involved on physical examination. Patients who have CT scans as part of radiation treatment planning have improved disease control and 5 year survival.

Memorial Sloan Kettering in New York has published on the advantages of using 3-dimensional conformal treatment for nasal area cancer. Previously, patients would tend to fail under spinal cord blocks, in the "parapharyngeal area". Careful treatment plans can help prevent this, while still adequately protecting the spinal cord. The worst complication is failure of treatment to control the existing cancer, so it is crucial that radiation be given meticulously yet aggressively by a highly experienced radiation oncologist. It is truly remarkable and gratifying to see the locally advanced cancers cured by proper radiation treatment!

The second way to give radiation therapy is by using “Brachytherapy”, which means “slow therapy”. The conventional way to do this was to make an “implant” of radioactive wire (typically iridium-192) which punctured through the tumor multiple time; the tumor was literally “sewn through” with the radioactive wire. The patient would be kept in a specially shielded hospital room for 3 to 5 days while the treatment was given, and afterward the wire was clipped and removed. The rationale of brachytherapy is to give a very high dose to the tumor area proper, but minimize the dose to surrounding normal tissue. In general, as one doubles the distance from the radiation source, the dose is quartered (“inverse square law”). Brachytherapy acute effects tend to be greater, with redness and irritation, but the late effects less because the “dose rate” is less than with External Beam therapy. An exception to this is a newer technique called “High Dose Rate” (HDR) Brachytherapy where the treatment is given in just 10 or so minutes with a very active radiation source placed within a tube (“catheter”) near the tumor with a nasoscope.

In the past, brachytherapy was only done by select radiation oncologists mostly at Academic University Hospitals, since it involved a mini-operation. With the HDR techniques (which generally do not puncture the skin) the treatment can be given by many private practices that invest in the equipment. It makes unneccessary the several day hospital stay required by the older “Low Dose Rate” (LDR) brachytherapy. Typically, LDR gives about 0.6 Gray per hour, while HDR gives 200 Gray per minute. It is controversial in the literature whether the HDR is truly as effective as the older LDR, but dosage and schedule modifications can help equalize them. Greater late reactions would be expected from HDR, since the dose rate is so much higher. Brachytherapy usually gives about 20 to 30 Gray total, as a boost, to the tumor area. Still, in practice, it is more common to reserve brachytherapy for relapse of disease after initial surgery and adjuvant External Beam Radiation treatment.

Chemotherapy has historically been reserved for those who failed surgery and irradiation, and is not used alone for nasal cancer (except possibly lymphoma) since it is not curative alone. When used, doctors generally want “something to follow”-- that is a tumor visible on scans or physical examination. If the chemotherapy does not actively shrink the tumor, it is not considered useful; it should be stopped or changed.

For the patient who wishes to be aggressive with possible microscopic spread of disease and undergo chemotherapy, agents similar to that used for nasopharynx cancer may be tried. Several agents have been used, being the ones usually selected for other head and neck cancers. Specifically, Methotrexate, Cyclophosphamide, Nitrosourea, Cisplatin and Bleomycin have been used, and are more effective when used in combination than as single drugs. The best chemotherapy results today combine bleomycin, cyclophosphamide (cytoxan), methotrexate and 5-Fluorouracil (the BCMF regimen) which gives up to 80% response rates. Although the duration of the response is usually less than 1 year, some of those with longer response appear to have been cured in the Gustav-Roussy Institute trials in France.

Chemotherapy can be more effective when given at the same time as radiation, this is called “neo-adjuvant” therapy. This may be followed by surgery to remove any residual disease, which will likely be much smaller than it was originally. In general for head and neck cancer, neo-adjuvant therapy gives complete response of over 80%, but is not yet proven to increase survival. This is because many patients relapse after impressive responses-- but not all do and many are cured. It certainly increases the toxicity of treatment, with more local radiation reaction, dropping of blood cell counts, nausea, hair loss, sterility, and the other side-effects of certain chemotherapy agents-- so judgment is key! CancerAnswers has a transcript on “In Depth Understanding of Chemotherapy” available through our Website.

What About Relapsed Nasopharynx Cancer?

Rarely, a patient will have limited recurrent disease localized in the nasal area that can be treated surgically, by performing surgery to the site of the recurrence. This is why it is so important to follow patients carefully after their initial treatment, so that any recurrence can be detected and managed early. It is recommended that patients be seen MONTHLY after their treatment for a period of at least 1 year, and then bimonthly for 2 years afterward. After 3 years, if no recurrence has occured, the patient is probably cured. Remember that upwards of 5 percent of patients per year may develop another “aero-digestive” cancer, especially if they continue to smoke. This militates for careful follow up to look for other “metachronous” cancers also. The CT and MRI scans of the area can help tell if surgery if feasible. If it is, the usual “salvage” surgery is “craniofacial resection”, this may give 50% long-term control in the area-- especially if additional brachytherapy irradiation can be given. The greatest experience is in Europe, such as at the Gustav Roussy Institute in France. There results show a benefit in a small groups of people with nasal area cancer, with 50% living 5 years.

More commonly, it is possible to give further radiation therapy, with almost 50% of patients who can get 50 Gray being alive at 5 years. The longer time between theoriginal treatment and the failure, the better patients do. Since it is difficult to give further high dose External-Beam radiation over the whole area, best results are obtained when a high-dose local radioactive implant is combined with lower dose External-Beam therapy in relapsed disease. This type of therapy is available at the Joint Center at Harvard University, Memorial Sloan Kettering, M.D. Anderson, Mayo Clinic, and other major University Hospitals.

What is the Latest, Effective Therapy for Nasal Cancer?

Surgical Techniques include use of operative lasers and plastic reconstruction of areas destroyed by tumor, to maintain proper speech, chewing and swallowing. Bone grafts and muscle “flaps” can be taken from other body areas to reconstruct the face, if necessary, and preserve acceptable cosmetic appearance. The surgeon can rely upon radiation therapy afterward to eliminate microscopic cancer remaining, and therefore less mutilating surgeries can be done initially. Studies have found about 10% better “relapse-free” survival if surgery is done prior to irradiation, rather than vice versa. The only exception to this would be neo-adjuvant therapy where chemotherapy and irradiation are given simultaneously, followed by a limited surgery to remove any residual visible (“macroscopic”) tumor. Improved dental techniques can implant prosthetic teeth to replace those that must be pulled prior to radiation therapy. Hyperbaric (high pressure) oxygen treatments have been found to help healing in the jaw when surgeries are done after radiation. This hyperbaric oxygen reduces the risk of “osteoradionecrosis” (dying of areas of bone) which is a known complication of dental procedures performed after high dose irradiation to the jaw (the upper jaw will often be treated in patients with nasal cancer).

Radiation Improvements include the use of sophisticated three - dimensional treatment plans which tell the dose to each area in the head and neck, and allow a prediction of the most suitable energies of radiation to be used. If an implant is possible, superior results are obtained when combining external beam therapy (50 Gray) and an implant (30 Gray) compared to external beam alone. The newer way of giving brachytherapy is “High-Dose Rate” (“HDR”). This means that “catheters” (tubes) are inserted through the tumor area, and a series of treatments is given by loading them with a high-dose radiation source. It takes about 10 minutes per treatment, and this may be repeated 5 to 7 times about 1 week apart. This repetition helps reduce the “late-effects”. In this way, an extremely high dose can be safely given to the local tumor area. A more readily available way of increasing effectiveness of radiation treatments in head and neck cancers is “hyperfractionation”. This will mean getting more treatments (usually 2 per day) at a lower dose per treatment. Although inconvenient, it has improved response to radiation by about 20% in major studies! It is recommended for large tumors which will need a higher dose of radiation (over 70 Gray) to control them. Fortunately, since smaller “fractions” are given with each treatment, it leads to less “late” side-effects than conventional radiation treatments, even while giving a higher total dose! A new and exciting way of increasing the effectiveness of radiation is “hyperthermia”. This means heating the area of the tumor, usually just prior to radiation treatment. Cancer cell kill is much greater when the area is heated. The main difficulty in giving hyperthermia treatment is the uniform heating of the tumor area, but new microwave heating helps do this. Hyperthermia is only available at major medical University Radiation Oncology departments, but has now been shown convincingly to improve radiation results. The side-effects are only a small increase in normal radiation reaction.

Chemotherapy Advancements have been slow, and are based on clinical trials. If it is given at the same time as radiation therapy, it’s called “chemoradiation”. This is very effective at shrinking the tumor, but has severe local reaction of skin sloughing and mouth ulceration, and so must be carefully monitored. Chemo-radiation may be given before, after, or instead of surgery. Patients with large tumors now have them shrunk with neo-adjuvant chemo-radiation prior to getting surgery, as a less mutilating procedure may then be effective (as compared to if radical surgery was performed first). Patients getting chemo-radiation may be unable to eat due to the soreness, and so often get a temporary feeding tube. About 6 weeks is given after chemo-radiation to allow the tumor to shrink and then surgery may be performed. The latest agents for chemoradiation of head and neck cancers are Taxol and Cisplatinum. These are given intravenously, up to 24 hours prior to the radiation. Blood counts and nutrition are tracked, and a temporary break in treatment may be required if the local reaction gets too intense. The radiation may be hyperfractionated to improve effectiveness and decrease late side-effects. This aggressive treatment will then maximize all established therapies.

Another aspect to chemotherapy is “chemoprevention” of new cancers. Vitamin A derivative (Cis-Retinoin) has been shown to help treat small cancers, and prevent new ones from forming. The dose for this is now being established (high dose has unacceptable side effects). Nonetheless, taking vitamins A and E are thought to help prevent a whole spectrum of aero-digestive cancers.

Overall, slow but steady progress is being made for mouth cancers, and survival has improved perhaps 20% over the past 3 decades. Greater improvements have been seen in preventing debilitating side effects (such as blindness with elaborate radiation planning computers) or dealing with them successfully when they arise (such as plastic surgery for reconstructing an unsightly scar area). Even patients with advanced cancer have more hope than ever before, at least for comfort. Since radiation is a mainstay of therapy, it is crucial to get an appointment with an up-to-date radiation oncologist who communicates well with you. Younger radiation oncologists often have had better training than the older generation, since only in the last 2 decades did this specialty gain much prestige (and difficulty getting into). New research is always continuing in cooperative clinical trials, by the “Radiation Therapy Oncology Group” (RTOG) and “European Oncology and Radiology Cooperative” (EORTC). Patients who have large cancers and wish to be aggressive should find an oncologist they are comfortable talking too, preferably at a University Academic Center, and seriously consider joining a recent clinical trial. Current major trials (there are new ones opening and closing every month) can be found on the National Cancer Institutes website (call them at 1-800-4-Cancer).

Additionally, patients should embark upon a program to maintain nutrition, exercise, increase spirituality, and select a reasonable alternative medicine regimen in addition to doing conventional medical treatment. CancerAnswers has a transcript on Alternative Therapies for Nasal Cancer available through our Website. This combined approach is superior to just counting on a pill or ray to cure cancer. If the patient still smokes, they should quit, since results are better in even recent non-smokers. It is crucial to get symptom relief for a cancer causing discomfort; only when the patient does not feel the disease can they forget about it for a while. CancerAnswers has a transcript on In-Depth Symptom Relief available through our Website. Above all, realize that while more patients are being cured than ever before, many people are also living longer and productive lives with their cancer, and keep a positive attitude to have the best chance for success