Nasopharyngeal cancer – Patient information
What is nasopharyngeal cancer? Exactly which part of the body does it affect?
The nasopharynx is the upper part of the throat behind the nose, so the nostrils lead into the nasopharynx. It is a small area but surrounded by important structures. Directly above this space is the base of the skull with its many openings transmitting the nerves that pass from the brain down to the head. Its surface is rich in lymphoid tissue and is connected to a rich plexus of lymphatics which connects them to many lymph nodes that are seen in the neck region. An opening on each side of the nasopharynx called the Eustachian tube leads into an ear.
Cancer develops in the cells that line the nasopharynx. This then multiplies, increasing in size and invades surrounding tissues involving the Eustachian tube and the cranial nerves, even eroding through the tough bone of the skull into the brain. It also blocks the nasal passages and bleeds easily. At an early stage itself, this tumor can spread through lymphatics to the lymph nodes in the neck and thenceforth from there to the rest of the body especially to the bones, lung and liver.
What is the incidence of this disease among the Malayasians especially the people of Sarawak?
Sarawak has one of the highest incidences of this cancer in the world, other places being South East China. The incidence rates were seen to be about 14 per 100,000 people. Sarawak is an ethnically diverse state and this diversity has also seen with the disease. The incidence of this disease was seen to be almost 2 ½ times (32/100,000) more in the Bidayuhs which is the highest among those reported elsewhere in the world. The incidence is also quite high among the Ibans and the Chinese, where as it is lesser among the Malays and relatively rare in Indians.
Is there any reason that this disease is so common here, especially among the Bidayuhs?
The primary reason for this disease is a virus of the herpes family, called Epstein Barr virus. This virus affects most people in childhood, but in some, especially those of Chinese ancestry, this virus causes cancerous change in the normal cells. This is due to a genetic predisposition in the HLA of this subgroup of population that enables the virus to enter the DNA and cause these changes. This may be the reason why we have seen many cases of this disease coming in members belonging to the same family.
A lot of environmental factors have been attributed to this but none proved conclusively so far. Among the various theories been evaluated so far, one has been the consumption of salted fish especially in early childhood when it is traditionally given with rice as a weaning food. Other factors that have been implicated are occupational exposure to formaldehyde, soot, consumption of smoked and preserved food. Tobacco smoking has been indicated as a factor mainly in non endemic areas.
In conclusion, there may be a variable interplay of genetic and environmental factors that have led to this disease being so common to this area. Active community based research is underway at our department in collaboration with WHO that may help solve this riddle.
Is there any way to prevent this cancer especially in people who have a relative with this cancer?
As of now there is no vaccine that has proven efficacy in preventing this form of cancer. But clinical trials are underway in vaccines based on proteins from the virus and the results are eagerly awaited.
Early testing to detect population who are at high risk of this disease by measuring viral DNA in the blood is both cumbersome, expensive and not shown to be efficacious in our population where over 95% may show a high level of titre.
The most effective method shown so far is early detection by recognition of symptoms. This requires a high level of awareness especially among the population at risk and coordinated efforts between peripheral health care services for early detection and referral of these cases. This has been attained to a certain degree so far by health awareness talks, publishing information in newspapers, health exams and by training of health workers working in the rural areas
So what are these early signs and symptoms that may indicate the presence of this disease?
The earliest symptoms seen may be
- nosebleeds also known as epistaxis,
- change in voice (nasal pitch),
- nose block,
- ringing noises or a prolonged blocked sensation in the ear
- or a small painless lump or mass in the neck
If any of the above mentioned symptoms are seen, especially in people who belong to a high risk population they should immediately consult a doctor, preferably an ENT specialist.
In later stages, the disease invades the surrounding structures and may cause
- double vision
- frequent and moderate headaches
- large mass over the neck which may become painful
- mass in the throat
- numbness over face or partial paralysis of the tongue
- frequent aspiration of food and fluids leading to cough
- swelling over the eyes with vision loss
When the disease spread to other organs, it may cause
- severe pain in the bones of the back, hip or legs
- chronic cough, sometimes associated with blood in sputum
- loss of appetite and wasting of the body
- paralysis of lower legs associated with loss of control over bowel and bladder
- fits or seizures
So what are the tests that have to be done if a person has any of the early symptoms?
- Clinical History: Complete history of symptoms, family, occupational history with dietary practices.
- Physical exam of the throat: An exam in which the doctor feels for swollen lymph nodes in the neck
- Nasal endoscopy: A procedure to look inside the nose for abnormal areas. A nasoscope is inserted through the nose. It is a thin, tube-like instrument with a light and a lens for viewing and may also have a tool to remove tissue samples.
- Biopsy or Fine Needle aspiration: This is a procedure of taking tissue sample from any abnormal areas which can then be evaluated under a microscope to check for any cancerous changes in the cells
Does this cancer have different types that vary in their presentation?
Yes, WHO has classified 3 types of this cancer of which type 2 and 3 are seen in our patients most commonly. These are also the more aggressive type and the type seen most commonly in areas where this disease is endemic. They usually tend to grow faster presenting with large neck masses and spread faster.
After getting diagnosed what are the procedures that a person must go through before the actual treatment starts?
After diagnosis, it is very important that the disease be staged properly so that a correct estimation of the prognosis can be made. Of these the initial procedure that must be done is a biopsy from the tumor tissue to confirm the pathology and to ascertain the grade, followed by a CT scan of the head and neck area. This helps to assess the spread of the disease in the head and is of utmost importance in staging the person’s disease properly.
The other procedures that can be done from the point of referral like
- complete blood tests,
- tests to assess the function of the kidney and liver
- X-ray of the chest
- Ultrasound scan of the Liver
A bone scan will also need to be done and this procedure can only be done from the Nuclear medicine department, Sarawak General Hospital
A dental evaluation may be requested to prevent later tooth decay due to radiation induced changes. Usually teeth need not be removed and only a plaque removal, examination of the gums, teeth and proper dental hygiene advice would suffice. Extraction may be needed when the tooth is shaky and cannot be salvaged by any conservative management.
Ideally a nutritional evaluation must also be done and early measures instituted so that adequate dietary requirements are met before beginning the treatment.
What are the factors affecting the chance of recovery or cure from this disease?
The prognosis (chance of recovery) depend on many factors
- The stage of the cancer (whether it affects part of the nasopharynx, involves the whole nasopharynx, or has spread to surrounding structures or to other organs in the body).
- The type of nasopharyngeal cancer, ie the WHO grade. Type 2 and 3 tumors as mentioned earlier are more aggressive.
- The size of the lymph nodes when involved. 6 cm has been set as the size beyond which the prognosis worsens. Also the position of the lymph node in the neck matters, with LN lower down in the neck towards the collar bone signaling a more advanced disease than those higher up.
- The patient's age and general health. We use specific questionnaires to assess the fitness level of older people and treatments can be tailored to adapt to these conditions.
Is there a simple way to understand the staging of this cancer?
NPC staging when simplified into layman’s terms can be summed up as
In stage I, cancer has formed and is found in the nasopharynx only.
Stage II nasopharyngeal cancer is divided into stage IIA and stage IIB as follows:
- Stage IIA: Cancer has spread from the nasopharynx to the mouth or nose (ie If it spreads below or to the front)
- Stage IIB: Cancer is found in the nasopharynx and has spread to lymph nodes on one side of the neck.
- Cancer is found in the adjoining areas of nasopharynx like the sinuses and has spread to lymph nodes on both sides of the neck
- Cancer has spread beyond the nasopharynx and may have spread to the brain, bottom part of the throat, destroyed the skull or any other bone, causing nerve paralysis, or
- Cancer has spread to lymph nodes above the collarbone and/or the involved lymph nodes are larger than 6 centimeters, or
- Cancer has spread beyond nearby lymph nodes to other organs of the body like liver, lung or bone.
What are the treatment options for nasopharyngeal cancer?
Surgery is not an option in nasopharyngeal cancer since it is surrounded by important structures and it is impossible to remove it without causing major injury.
This is a cancer treatment that uses high-energy x-rays to kill cancer cells. External radiation therapy uses a machine outside the body to send radiation toward the cancer. In our hospital, this is done using a LINAC also called a Linear Accelerator.
Before treatment, a plastic face cast is made for each patient, which is used to immobilize them during treatment to make sure radiation is delivered to all the right areas. Then a process called Simulation is done where plain Xrays are taken from different angles and processed into films. The area to be treated is then marked out on these films by the oncologist and calculations made for radiation delivery by the physicist. This process takes about 1 to 1 ½ weeks.
Then total duration of radiotherapy is 7 ½ weeks. This can be taken on an out-patient basis, but for patients coming from distant places like Sibu, Miri, inpatient beds are arranged for the duration of treatment. The treatment is given every day from Monday to Friday with no radiotherapy on Saturday and Sunday. An appointment time is given to the patient and the actual treatment time per day takes between 10 to 15 minutes only.
Treatment is usually divided into 3 phases. In the initial phase the radiotherapy is delivered to all clinically diseased areas and also surrounding areas suspected of harboring microscopic diseases. Towards the final phase, treatment is directed only towards the area with disease only, so that normal tissue side effects can be kept low while giving a curative dose to tumor.
This is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
Concurrent or sensitizer chemotherapy is given along with radiation to improve the tumor kill caused by radiotherapy. Hence the doses given are small and not like that given for proper chemotherapy. The drug used in this case is called Cisplatin and is injected through the veins, commonly those of the arm. The dose to be given is usually calculated based on the body surface area and the kidney function of the patient, so the doses may vary from person to person. It is given once a week and is given before the radiotherapy treatment that day.
Systemic chemotherapy is usually given 4 weeks after completion of radiotherapy and is given for 3 cycles each 4 weeks apart. This is given to eradicate those cells that have already spread outside the radiated area. Two drugs called Cisplatin and 5 Flourouracil are used and are given as an infusion through the vein over 5 days. This may be preceded by a glucose and saline drip for a day to improve the kidney clearance so that the drugs can be eliminated from the body. In some instances when the patient presents with very advanced disease, this chemotherapy may be given before the radiotherapy to reduce the size of the nodal masses in the neck. In recent trials this has shown to improve the success rates of the treatment.
I understand there is another form of radiotherapy called brachytherapy. Is there any role for this treatment in NPC?
Yes, Brachytherapy is a form of radiotherapy where protected radioactive sources are placed close to the tumor so that only the tumor and its immediate neighboring region receives treatment and nearby critical normal structures do not receive any at all.
But this is not employed during the initial treatment of NPC and is mainly used for tumor recurrences in the nasopharynx.
Is there any role of complementary or traditional medicine in the treatment of the disease?
Until now there is no evidence that any other forms of medicine have any proven efficacy in this cancer. On the other hand taking these kinds of medicines during treatment may lead to their interaction with the radiation and actually increase the side effects of the treatment. Hence we advise all patients to not take this kind of treatment during radiotherapy.
Does radiotherapy have a lot of side effects, or what are the side effects that a person undergoing this form of treatment, have to expect?
Radiotherapy causes reversible damage to rapidly dividing tissue in the skin, mouth and to the glands that produce saliva. These toxicities are increased by the concurrent administration of chemotherapy.
- Skin- In the first week, this will show as a slight redness with a feeling of warmth and towards the end of the 2nd week there will be dryness of skin and loss of facial hair. This dryness increases towards the later weeks and towards the end of the 4th week the dried skin turns darker and begins to flake off revealing newer lighter colored skin beneath. In some cases where proper skin care is not done, the new skin appears red and moist in some areas especially at the junction of the neck and shoulder.
- Mouth- Towards the end of the second week, a sore throat develops along with altered taste sensation. This gradually progresses and may be slightly painful towards the end of the 5th week, leading to decrease in food intake. This reaches its peak at the end of 6 weeks after which it decreases.
- Dryness of mouth- Mouth dryness is seen from the beginning of the 3rd week and progresses thereafter leading to thicker viscous saliva. This affects proper swallowing of solid food and added to the sore throat may require food to become more semisolid through the course of treatment thus leading to weight loss.
- Weight loss- All the above mentioned factors along with a decreased appetite causing a weight loss and during a normal course of radiotherapy, a person may lose 10-15% of his baseline weight.
- Hoarseness of voice develops towards the 4th week due to a mild swelling of the vocal cords, but the voice usually returns back to normal.
These side effects usually resolve completely but there may be late side effects like dryness and tightening of the skin of the neck, dryness of mouth, mild difficulty in swallowing in most patients. Also hearing loss may persist in some patients and if the brain area was treated there may be some neurocognitive loss too.
And what are the measures that can be taken to prevent or reduce their incidence?
Preventive measures are taken to reduce the incidence of these during treatment.
- Skin care is advised and reinforced during the treatment. They are advised not to rub or scratch the irradiated area, not apply creams or lotions and keep it dry. Skin can be cleaned under running water and liquid non perfumed soap may be used. Wide necked dresses are encouraged and to avoid ornaments over the neck.
- Oral hygiene is to be maintained strictly using a soft toothbrush and fluorinated toothpaste, Regular oral rinses every 2 hrs are to be done with a salt and soda water combination and oral disinfectant gargles 3-4 times daily is to be done. Local anesthetics are used to control the pain during swallowing towards the end of treatment.
- Diet is changed to semi solid during latter phases of treatment and should be monitored to ensure adequate dietary allowances of all nutrients. Diet supplements, vitamins and minerals are prescribed early in the course of treatment to combat weight loss.
Patients are assessed weekly during treatment and the side effects are graded according to severity and when toxicities reach grade 3, treatment is interrupted till adequate recovery. Also weekly nutritional assessment is done to institute timely changes in the diet and monitor weight loss.
Late effects can be reduced by performing regular neck exercises and proper skin care. Dryness of mouth can be managed by conservative measures and in some cases saliva substitutes need to be used. Such late effects can be greatly reduced by newer radiation delivery techniques like IMRT.
Are such newer radiation delivery techniques like IMRT available in Sarawak? How does IMRT differ from Conventional Radiotherapy?
IMRT is a type of 3-dimensional radiation therapy that uses computer-generated images to clearly mark the areas involved by the tumor and gives the ability to modify the shape and direction of radiation beams in such a way that the tumor and involved areas can be treated to a high dose and normal organs and structures are given a very low dose. This reduces the side effects due to radiotherapy during and after completion of treatment.
But this kind of planning is labor intensive and planning will require a week more than that required for conventional planning. This service was started in Feb 2009 and currently is offered free in Sarawak General Hospital but this form of treatment could cost anywhere between 25,000 to 30,000 RM in private hospitals.
Can older patients with nasopharyngeal cancer be treated just like younger patients?
Patients older than 65 yrs with NPC are assessed at baseline using a questionnaire called Geriatric Functionality Index which has been modified to ascertain the fitness levels of this group of patients to tolerate this kind of treatment. Decisions are made based on the clinical assessment and the GFI scores and treatment is customized based on this data.
We are also currently evaluating IMRT in this subgroup of patients and results are expected to be announced during the SIOG conference in Jan 2011 being held at Kuching.
How is the patient monitored after completion of treatment?
6-8 weeks after completion of radiotherapy and chemotherapy, a CT scan of the head and neck region and Nasal Endoscopy is recommended for all patients, following which they are followed by the ENT and the Oncology department on a 3-4 monthly basis for 2 yrs. Annually a Chest X ray and Ultrasound scan of the liver is done to assess for any spread of the disease. A bone scan is done if there are any complaints of backache. After 2 yrs they are followed up every 6 months.
How are the results of treatment for nasopharyngeal cancer as seen in your institute?
The overall survival is for 2 years is 85% and for 5 years 40%. The survival is better for earlier stages, hence cure rates of around 90% are achieved for stage I and II. With increasing tumor and nodal size this figure comes down as the chance of distant metastases increases.
Hence it is pertinent to be aware of the early signs and symptoms and early referral.
What are the future directions in the treatment, prevention and early detection of this cancer?
There is a lot of research currently underway exploring the molecular and epidemiological etiology of this disease. Currently we are doing active research in this field in collaboration with WHO and IAEA. Also there are clinical trials looking at the feasibility of adding newer less toxic chemotherapy and biological targeted therapy to radiation to improve results and decrease the rate of recurrence and metastasis.
One such targeted agent called Cetuximab has shown promise in recently published results.
Also lot of research is being done in tumor markers that may be able to predict the possibility of recurrence and metastasis but none are available commercially yet. High levels of viral DNA in the blood after completion of treatment has been found to corroborate with an increased incidence of recurrence of the disease after treatment, but these are expensive and are not currently available in government hospitals.