General Information about the Lungs:

The paired lungs develop from lung buds in the human embryo during a period of rapid cell division. The main type of cell in the lungs is called "epithelial", meaning a lining cell. Mucous is formed by "adeno" cells which fold into glands. Another type of cell, called the "type II" cell, secretes "surfactant" which provides the stiffness for lung tissue. All of these cells divide quickly during womb life, infancy and puberty, but growth slows dramatically by adulthood. In adults, the cells only divide to replace ones lost to injury or old age.

Air breathed in passes though the throat into the larynx, where the vocal cords can form sounds. Below the larynx is the trachea, a tube ringed with cartilage which helps keep it from collapsing. The trachea splits ("bifurcates") in an upside-down "Y" shape with the arms of the "Y" going into each lung. The part of the trachea that actually enters each lung is called the "mainstem bronchus"; there is a right and a left one to correspond with each lung. The area where the mainstem brochi enter is called the "hilum" of each lung, the main blood vessels also enter at the hilum. The main bronchi branch out into smaller "lobar" and "segmental" bronchi to carry the air into the lungs. The right lung is made up of 3 lobes, and the left lung of 2 lobes. Each lobe is made up of smaller segments. The air breathed into the lungs ultimately gets to the tiny air sacs, called "alveoli", which provides the surface for the oxygen in air to mix with the blood. Also, the alveoli allow the carbon dioxide in the blood to be released into the lungs to get exhaled. The lungs are surrounded by an outer membrane called the "pleura"-- it is composed of 2 parts, an inner "visceral" pleura and an outer "parietal" pleura. There are bean-sized filters, called "lymph nodes" along the bronchi, which connect to each other via "lymph channels". The lymph nodes contain lots of white blood cells and make up part of the immune system to help purify the blood. The lungs have a very rich blood supply, both from the blood they are oxygenating from the heart, which will be circulated to the rest of the body, and from the aorta, which provides nourishment for the lungs themselves. Thus, disease in the lungs, such as infection or cancer, can spread through the lymph channels and/or bloodstream to other areas of the body.

When people smoke tobacco over many years, the lungs lose their softness and start to become stiff. The air sacs are gradually destroyed, and stale air gets trapped in the lungs. This is called "emphysema". It gradually destroys the interface between the air sacs and the bloodstream, compromising the ability of the lungs to oxygenate the blood and to release the built up carbon dioxide waste product. About 1 in 5 people with emphysema will eventually develop lung cancer.

What is Lung Cancer?

Normally, the division of cells in the adult lung to make new cells is under very tight control. This control is exerted by the "genes" inside each cell, which are housed in long clumps forming "chromosomes", which are visible under a light microscope. The genes themselves are made up of DNA, the master genetic code material. If the genes are damaged, say by chemicals or radiation, the control over cell division may be lost in one particular cell. Ultimately, cancer is considered a disease of the DNA. Lung cancer starts in a single lung cell . That cell starts dividing haphazardly, making millions and billions of copies of itself. It takes up the nourishment needed by other cells, depriving them so the cancer can continue to grow. Quickly growing cells can clump up to form a "tumor" . A tumor simply means a swelling, it can be caused by inflammation or infection. A "benign" tumor only grows in it's local area (although it may get quite large)-- it cannot spread and is not cancer. By contrast, a tumor which can spread to other body areas is called "malignant" and this is cancer . The process of cancer spread to other areas is called "metastasis", so only malignant tumors (i.e. cancer) can metastasize. Theoretically, cancer can spread to any area of the body, and it often grows better in it's area of spread than in it's area of origin ("primary site"). It is this capacity for spread that makes cancer so dangerous. If not treated successfully, it ultimately kills by debility, anemia, infection, and compromise of normal body functions.

What are the Types of Lung Cancer?

Depending on which type of cell in the lung goes awry, different types of lung cancer may arise. Although mixed types may occur, lung cancer is commonly broken down into 4 basic categories, and a smattering of much less common types. The most common type is squamous cell carcinoma (35% of cases). It starts from the cells lining the bronchi, especially when they have been repeatedly damaged by smoke or other irritation. Normally, squamous cells are the type that line the mouth, anus, vagina and skin-- they are resistant to abrasion and heal quickly. Fascinatingly, the normal "cuboidal" epithelium of the lung can start to turn into squamous cells with repeated irritation, a process called "dedifferentiation". If this conversion is not totally successful, a cancerous squamous cell may arise. The second most common type of lung cancer is adenocarcinoma (30% of cases) which arises from glands, and the cells lining the air sacs. It is usually found in the peripherapy of the lungs, as opposed to squamous cell which commonly has a more central location along the bronchioles. The third most common type is small cell carcinoma, also called "oat cell" (20% of cases). Its treatment is much different than for the other types of "epithelial" lung cancer, and it is considered a different topic. The fourth most common type is large cell carcinoma (15% of cases) which is actually a form of adenocarcinoma. Since the cells look much larger under a light microscope, however, it is given a separate category. It generally occurs in the periphery of the lung. Sometimes, the cancer does not look exactly like any of the above types, the cells are very primitive and aggressive looking. This is called "undifferentiated" cancer but careful analysis can often reveal the particular subtype. Nearly 30% of cancers may be "mixed", especially if advanced.

It is possible for other rare types of cancer to arise in or around the lungs. Examples are lymphoma from the immune cells in the lung, sarcoma from muscle, cartilage or fat, and mesothelioma from the pleural lining of the lungs. These conditions are all separate topics, with their treatment following that the the areas where they more commonly arise. Cancers from other areas may spread to the lungs, especially adenocarcinomas and sarcomas from other organs. The lungs are rich in blood and are a fertile area for other cancers to spread to. These are dealt with when considering the treatment for metastasis of these particular cancers.

How Common is Lung Cancer?

Each year there are about 170,000 new cases of lung cancer in the U.S.A. and 150,000 deaths attributable to this disease. Lung cancer is the most frequent fatal cancer, for both men and women, in the United States. Men are affected somewhat more frequently (100,000 cases/year) than women (70,000 cases/year). Worldwide, there are 1 million new cases per year. Over the past 5 decades the number of yearly cases has been increasing, and the worldwide incidence may double to 2 million per year in the coming decade. The average patient is 60 years old, and only 1% of cases are under 40 years old. About 90% of patients have historically died from their disease but survivals are improving with the latest effective therapy.

What Causes, or Increases the Risk for Lung Cancer?

Like any cancer, the exact reason why one particular person gets lung cancer and another does not remains unknown. However, certain factors are strongly correlated with with an increase in lung cancer, when groups of patients are studied:

Tobacco Smoking is the best known risk factor for lung cancer. The risk goes up with the number of cigarettes smoked. Doctors calculate usage as "pack-years" which means multiplying average packs per day with number of years smoked. Increasing from one to two packs per day smoked increases the risk 4 times, (from 55 cases/100,000 smokers/year to 217 cases/100,000 smokers/year). It takes 5 years after quitting smoking for the risk to appreciably decrease, and at 15 years after the risk approaches the never-smoked level. Second hand smoke has gotten a lot of press lately, with some claims that the risk of cancer is up to 20 times greater than the smoker themselves! This is a distortion based upon the observation that unfiltered smoke from the tip of a cigarette has more cancer causing chemicals ("carcinogens") than filtered smoke. Nonetheless, an higher risk for lung cancer among spouses of smokers and people who spent many years working in enclosed, smoke-filled offices is well-documented. However, the chance of getting lung cancer from occasional casual exposure to a smokers "second-hand" smoke is almost zero. Driving down a crowded freeway exposes our lungs to more carcinogens from auto exhaust than "second-hand" smoke. Inarguably, lung cancer has skyrocketed with the popularity of cigarettes. Before the year 1850, only about 200 cases of lung cancer were even known of!

Carcinogen Exposures besides tobacco smoke that are linked with lung cancer include asbestos, coal tar fumes, nickel, chromium, and arsenic. There is a higher risk in coal miners. There used to be a much higher risk in people who worked in talc and soap dust factories, before the air there was filtered. Any small particle that gets into the lungs and irritates over time, promoting cell division, increases the risk for lung cancer.

Radiation Exposure is the next highest risk factor for lung cancer. The most common type is radon, a radioactive gas given off when radium disintegrates. The problem is when this gas builds up in enclosed areas, like basements. When radon gets into the lungs it undergoes further disintegration with release of high-energy particles that damage the DNA in lung cells, possibly leading to uncontrolled division (cancer). Test kits are available to determine if radon is a problem in your home. Other forms of radiation to the lungs come from the "polonium" in tobacco smoke, from natural background radiation (cosmic rays, radiation from mineral deposits in the earth, and some potassium-40 we all eat) and from medical procedures. The chance of getting lung cancer from a chest X-ray is less than 1 in a million. The best protection against lung radiation is to check our basements for radon, and not to smoke tobacco.

Miscellaneous Risks Factors include old scars in the lungs (such as from tuberculosis), the rheumatological disease scleroderma, and a slight familial tendency for susceptibility to getting lung cancer, especially after carcinogen exposure. Most cancers are a combination of some external hazard, such as a virus, chemical or radiation, in conjunction with a genetic susceptibility to developing a cancer when exposed to such hazards.

Does Screening Help for Lung Cancer?

A large National Cancer Institute study showed that when 30,000 male smokers had chest X-rays and sputum tests to look for lung cancer, more of them had the disease picked up early, but no survival benefit was seen from screening. Thus, we don't routinely screen for lung cancer in the absence of symptoms. Nevertheless, it is reasonable to screen patients with high risk factors, to pick up the disease early. As we will see, early disease is much more successfully treated than advanced cancer.

What are the Symptoms of Lung Cancer?

Like any cancer,very early lung cancer has no symptoms, since there are too few cancer cells to interfere with normal body functioning. As the cancer gets larger, the following commonly occur:

Persistent Cough, and sputum tinged with flecks of blood ("hemoptysis") must always be evaluated to rule-out cancer. The cancer can block of a bronchiole, causing obstructive pneumonia . It is important for a follow-up X-ray to be taken after a pneumonia is treated, to make sure no tumor was lurking behind it.

Shortness of Breath will be seen if bronchi are blocked off by the tumor, and so prevent the inspired oxygen from mixing with the blood. The effort in breathing will also increase if a fluid collection ("effusion") develops due to the cancer. This puts more stress on the heart pumping blood through the lungs, which in turn leads to more shortness of breath andfatigue . Fatigue also can be due to a buildup of the waste-product carbon dioxide in the lungs-- it's exit blocked by the tumor. Progressive shortness of breath ("SOB") must always be evaluated.

Weight Loss is very common with lung cancer, as the body's resources are shunted into the growing cancer, and appetite decreases. Sometimes an unexplained weight loss is the first sign of lung cancer. The cancer itself can produce substances that interrupt appetite and metabolism ("paraneoplastic syndromes"). These substances can be monitored to gauge therapy success.

Pain in the chest will manifest as the cancer invades into bone and nerves. Many patients have almost no pain until late in the disease, or only a "pleuritic" (stabbing) pain on deep inspiration. The pain may radiate to the back.

Hoarseness can occur if the cancer invades the middle portion of the chest ("mediastinum") and damages the "recurrent laryngeal nerve", which normally control the voicebox. The voice may also change to be higher pitched.

Signs of Distant Spread include mental changes, strength and sensory loss owing to spread to the brain, and bone pain and fractures due to distant spread to bone. About 10% of the time, these "late signs" are the first indication of lung cancer. Any symptom is possible, since the cancer can spread to any body area. The most common areas of spread are to lymph glands, the other lung, liver, brain, bone, skin, and adrenal glands (on top of each kidney).

How is Lung Cancer Detected and Evaluated?

It is important to note that any of the above symptoms are more likely caused by something other than lung cancer. However, they shouldn't be ignored. If a patient comes to their doctor with problems suggestive of lung cancer, the doctor will do:

Complete Physical Examination includes checking weight, temperature and blood pressure, and the skin surface. The heart and lungs are carefully listened to ("auscultated") and any wheezes or lack of breath sounds are noted. Tapping on the back to listen for dullness ("percussion") can tell if fluid is building up in the lungs. The even expansion of the chest with each breath is observed. The quality of the voice is noted for hoarseness. The fingernails are checked for curving which indicates chronic lung disease. Examination of the lymph glands in the neck, shoulder and armpit region may show swelling there. The abdominal organs (liver, spleen, kidneys, adrenals) are checked for swellings. A neurological exam checks the brain, special sense organs, and limb strength. In males the prostate is checked with a rectal exam, and in females a pelvic exam with PAP smear is done, and the breasts carefully checked.

Routine Laboratory Tests include Complete Blood Count ("CBC") to check for anemia and infection. A Chemistry Panel ("SMA") checks blood sodium, potassium, bicarbonate, chloride, calcium, phosphorus, glucose, cholesterol and liver and kidney function. Routine urinalysis ("UA") detects blood, protein, glucose or infection in the urine. If surgery is contemplated, the surgeon will want an assessment of blood clotting ability ("PT/PTT") . Unfortunately, there is no single accurate blood test to pick up lung cancer ("tumor marker") as there is for prostate cancer.

Radiology Tests include plain Chest X-ray which may show tumors over about 1/2 inch, signs of infection, and signs of lung obstruction or collapse. Failure to see anything on plain X-ray does not rule out cancer, but does suggest that the cancer, if present, is small. A chest X-ray may miss a small tumor hidden by a rib or the silhouette of the heart. More accurate is a CT scan of the chest, which can detect tumors over about 1 cm. in any chest location. CT scan can also pick up enlarged lymph nodes in the mediastinum (middle of the chest). Lymph nodes larger than 1 cm. are suspicious; those over 2 cm. certainly have something wrong with them (infection and/or cancer). If a CT scan is given with "contrast dye" (injected into an arm vein) it helps highlight the blood vessels and is somewhat more accurate. CT scan can also be used for the abdomen and is excellent for showing spread to the liver, or to the adrenal glands. Brain CT will be ordered if the is suspicion of spread there. Magnetic Resonance Imaging ("MRI") is a newer method that used magnetism instead of radiation, it is great for looking at soft tissues in the chest, It is 3 times as expensive as CT (~$1000) and is not routine. Bone Scan involves injecting some radioactive dye into a vein; the dye has a propensity to accumulate in damaged or cancerous bone areas, which are detected by a scan. It is gotten to help rule out spread to bone, especially if new bone pain is noted and surgery is contemplated. Bone Scan is much more accurate than plain X-rays of bone in picking up cancer spread, but also more time consuming, uncomfortable and expensive. Repeat Bone Scans may be needed to help confirm if an area seen is actually cancer, or just an old area of trauma. A "baseline" Bone Scan, as is done with breast cancer, may be reasonable so that later bone scans can be compared to it. Specialized radiology tests such as barium enemas or esophagrams are only gotten if use will be made of the information obtained from them; that is if they are useful given the clinical picture and treatment options for a particular patient.

Sputum Analysis (Cytology) is useful for making a diagnosis of cancer is a patient who's tumor is shedding off cells that can be coughed up. It is non-invasive and relatively inexpensive, using morning sputum specimens (deeply coughed up specimens, not saliva) collected in plastic containers for analysis. Five consecutive daily specimens may be as much as 80% accurate for detecting cancer, especially if it is located in the bronchial tubes or center the chest.

Biopsy (Sampling) of the tumor is the only way of definitely diagnosing any lung cancer. Either the primary tumor, cells it has sloughed off, or an area of distant spread (a metastasis) may be sampled to confirm or deny cancer. A pathologist is a physician who specializes in making disease diagnoses from tissue samples. There are several standard ways of getting a sample for the pathologist:
a) Endoscopic Brushings and Biopsy means putting a visualization tube down the patients throat into the lungs, where they are under a light anesthesia (usually valium and demerol). If the tumor is "endobronchial" is may be seen and sampled by brushing it for cells and/or cutting a piece off of it with a special biopsy scissors on the endoscope. This can be therapeutic, too, since a blockage can be relieved to restore air flow.
b) CT Scan Guided Biopsy means the patient is brought down to the CT Scanner, the tumor is visualized, and a fine-needle is placed (under local anesthesia) through the chest wall into the tumor, with pieces of tumor drawn out. It is about 85% accurate at making a diagnosis and quite safe. The biggest risk is collapsing the lung (20%) which then will require a chest tube to be put in to re-expand it, and an overnight stay.
c) BronchoAlveolar Lavage (BAL) is like getting a deep sputum specimen, literally by putting washing fluid down into the lungs, re-drawing it out, and looking for cancerous cells. It is most helpful for tumors within the bronchial tree, and can be done at the same time as endoscopy. It is performed by a pulmonologist, a physician specializing in lung disorders.
d) Mediastinoscopy means cutting a small hole above the breastbone (sternum) and inserting a scope into the central part of the chest (the mediastinum). Enlarged lymph nodes can be removed and sent to the pathologist for analysis. Some surgeons base the procedure they will do upon the results of the mediastinoscopy, and order it routinely.
e) Open Biopsy is done if an area looks suspicious, but cancer cannot be confirmed or denied by the above methods. A surgery to remove an unknown type of tumor is an open biopsy. If the entire tumor is removed, it is called an "excisional" biopsy; if it is merely sampled, it is then called an "incisional" biopsy. About 10% of patients have disease that can only be diagnosed with an open procedure, done under general anesthesia. However the biopsy same is obtained, it is sent to the pathologist who examines it to confirm or deny cancer. If cancer is detected, the particular type is specified.

Other Standard Tests include lung function studies to determine how much lung may safely be removed at surgery, and EKG to check heart function. This is part of a pre-operative evaluation to see if the patient can tolerate surgery. Generally, if there has been a heart attack in the prior 6 months, the risk of major surgery is considered too great.

How is the Extent of Lung Cancer Gauged?

Like all cancers, the extent of non-small cell lung cancer is given by the"stage". The staging system most used for lung is the "American Joint Cancer Committee" (AJCC) system. It takes into account the size of the primary tumor, spread to lymph nodes, and distant spread (metastasis):

Stage I means the cancer is relatively small (usually less that 2 inches across) and has not spread to any lymph nodes. It can block off a section of lung.
Stage II means the cancer has spread to local lymph nodes ( "hilar" nodes) but not to those lymph nodes in the center of the chest ("mediastinal" ).
Stage IIIA means the cancer may invade the diaphragm, chest wall, or block off an entire lung. It may have also spread to mediastinal lymph nodes.
Stage IIIB means the cancer can invade the heart, vertebrae, trachea, great blood vessels or mediastinum. There may be fluid collection in the lung that contains malignant cells. Any lymph nodes in the chest can be involved.
Stage IV means the cancer has spread distantly, i.e. to the liver, bone or brain.

What is the Classical Survival from Lung Cancer?

The survival with any cancer is variable, depending upon the stage it was detected, the exact type of cancer, the treatment obtained, the patient's will to survive, and general health besides for the diagnosis of cancer. We cannot say how long any individual patient will live, we are M.D.'s, not "M.Dieties". The textbook figures for classical treatment of non-small cell lung cancer, by stage are:

Bear in mind that many patients survive longer than the above figures, and that the above figures include all deaths from whatever cause (i.e. heart attack) to patients with lung cancer. In a major Veteran's Hospital study, the biggest 3 factors determining legnth of survival were extent of disease, weight loss, and "performance status" (how functional the person was). Nonetheless, experienced physicians don't make predictions for how long patients will live, since patients make liars out of us. If we say the will live for years, they may succumb within months. If we say that have weeks or months, many embarrass or prediction by living for years! We are all born with a terminal disease called earthly life, and the question is not just how long we endure, but the quality of that endurance. Even for incurable disease, a competent and compassionate doctor should be able to make the patient's symptoms much less distressing. There should never be a need to resort to suicide owing to discomfort. As the great American pioneer doctor Sir Wm. Osler said, "cure rarely, palliate sometimes, comfort always".

What is the Conventional Treatment for Lung Cancer?

The conventional treatments for non-small cell lung cancer have been surgery and radiation therapy. Many patients have also received chemotherapy, although the classical chemotherapy failed to extend survival for patients with metastatic disease. Each of these three "modalities" is now discussed in turn:

Surgery has been, and remains, the best treatment for very early lung cancer. About 40% of patients have disease limited to the thorax (chest) at diagnosis, and 80% of these can have total removal of their cancer at surgery ("complete resection"). For a small cancer, it has been shown best to remove a complete "segment" of the lung, rather than just the area of tumor. This is because removing one segment does not compromise breathing ability, and gives a better chance of removing all cancer cells. Thus, "segmentectomy" is the least drastic surgery for lung cancer, with the shortest time to recovery. If the cancer has spread beyond a segment, than an entire "lobe" of lung, consisting of multiple segments, will be removed in a "lobectomy" . This is more drastic and can compromise breathing, since 1/3 to 1/2 of the involved lung is being removed. The most drastic procedure is removal of an entire lung, called a "pneumonectomy" . This will lead to less exercise tolerance and easier fatigue in anybody, although most people can live with one lung. Before any major lung removal is considered, the patient will be sent for heart and lung function tests to help ensure they can tolerate the surgery. This is especially important in patients who have been long-time smokers, and those with emphysema or asthma. If the patient cannot tolerate the proper surgery, radiation therapy will be recommended instead.

The risks for surgery depend on how much lung is removed, and the general health of the patient prior to surgery. Overall, there is about a 5% chance of death from major thoracic surgery, when performed by an expert cardio-thoracic surgeon. Risks include pneumonia, heart attack, stroke, and blood clots. It may be difficult to wean the patient off the the ventilator if the other lung tissue is damaged. Healing is normally complete enough to allow lifting heavy objects in 3 weeks. It is crucial to get proper pulmonary "toilet" after surgery, meaning not giving so much pain medicine that the patient doesn't want to breath on the own or cough up phlegm, and using spirometers (breathing exercise devices) to help re-expand the remaining lung tissue.

The results of surgery alone vary by stage. For stage I disease, complete resection results in up to 80% cure. For stage II and IIIA, the cure rates with surgery are 50% and 25% respectively. The cure rates are not 100%, even with apparent complete removal of the cancer, since some cancer cells may have spread out and be missed at surgery. The cancer may have been "understaged" by our conventional staging evaluation, since our radiologic techniques can only pick up an area of spread if it is larger than 1 cm. -- about 1 billion cells! Therefore, doctors have tried adding radiation therapy and/or chemotherapy after apparently successful surgery to see if this helps survival. This is called "adjutant", meaning "extra" therapy. The results of combining surgery with radiation and/or chemotherapy, given either before (pre-operative) or after (post-operative) the surgery, are discussed after considering them separately.

Radiation Therapy has been used for 8 decades for lung cancer, the techniques have been advancing steadily. It is administered by a "radiation oncologist", a cancer physician specializing in radiation therapy. There are 2 standard methods of giving radiation-- "External Beam" and "Brachytherapy" . External Beam is the more common type and shines a beam of photons or electrons onto a pre-designated area of the patient's chest. Thus, it can cover a large area of possible cancer spread. Brachytherapy, also called "intracavitary", means putting an actual radiation source into the lung, either temporarily or permanently, to treat a limited area of tumor. Both techniques may be used in a given patient.

Radiation kills cancer cells by damaging their DNA, they die when they try to divide. Thus, damaged cancer cells die even after the treatment is complete. Radiation will also kill normal cells, which limits the amount that can be given. However, it usually takes more radiation to kill normal cells than cancer cells, and normal cells can often repair the radiation damage, while cancer cell can not. Nevertheless, it is important to be exacting as possible in the administration and dose of radiation, so as to minimize the injury to adjacent normal cells.

To receive therapy, a patient is first seen in "consult" by a radiation oncologist, who reviews the patient's medical record, complaints, and radiology films. After explaining the possible benefits and side-effects of radiation, the patient is scheduled for a "simulation" . This means the area to be treated is marked out on a replica treatment machine, and films are taken. Watercolor marks are painted on the patient to denote the treatment area, and eventually small, permanent tattoos are placed on the skin. Sometimes the patient is sent for a CT scan along with the simulation, the whole process takes less than 2 hours, and is painless. Information from the simulation and relevant scans is placed into a "treatment planning computer", which generates a "plan" . This plan tells how much radiation is going to the tumor area, and how much to adjoining normal tissues. For lung cancer, particular attention is paid for how much radiation is going to the spinal cord and heart. The plan is reviewed by the radiation oncologist and also by a specially licensed Radiation Physicist prior to starting therapy. The patient then comes in for their "treatment start". They are placed on a hard, flat table in a specially shielded room and aligned with laser lights. The actual treatments are given by "Radiation Therapists", or "R.T.T's", who are first certified for diagnostic X-rays and then get additional training to deliver therapy. For the first treatment, "verification films" are taken to ensure proper positioning; they do not tell anything about the cancer. The actual treatment only takes a couple of minutes and is given with a Linear Accelerator (or occasionally older Cobalt-60) which precisely aims a beam of photons at the treatment area. The head of the machine can swivel about the patient, to give the treatment from several angles. The patient needs only to lie still. Areas that are not to be treated can be "blocked" with special lead-type blocks in the head of the treatment machine. Normally, patients area treated 5 days a week, Monday through Friday, taking only several minutes each day.

The usual dose of radiation for lung cancer is 40 - 60 Gray (units of radiation) given at about 2 Gray per day over 4 to 6 weeks. Often, a larger area of the chest is treated initially, and then a "cone down" or "boost" is used to narrow the high dose treatment to the specific tumor area as seen on X-ray. Treatment itself is painless, the patient does not become sick, "radioactive" or lose their scalp hair from radiation to the chest. The side effects from chest radiation for lung cancer are divided into two general categories, "acute" and"late" effects."Acute" effects occur during the treatment period, and commonly resolve afterward. "Late" effects may occur months to years after treatment, and may improve very slowly or never resolve.

Typical acute effects are skin redness within the treatment area, difficulty or pain on swallowing as the esophagus (food pipe) is treated, and general fatigue. Possible late effects include damage to normal lung ("radiation pneumonitis") which causes cough, fever and shortness of breath. It only occurs in about 10% of patients and is often treatable with steroids. However, it is occasionally fatal. Treating large areas of lung, and/or giving chemotherapy along with lung radiation, increases the chance for radiation pneumonitis. Another feared complication of lung radiation is spinal cord damage, since the spinal cord is very close the the back portion of the lungs. This may manifest as a temporary sensation of "electric shocks" shooting down down the body with neck flexion ("Lhermitte's sign") which is scary but commonly resolves. Worse but very rare with modern techniques is "transverse myelopathy", which means severing the spinal cord from too much radiation-- this will cause permanent paralysis below the injury. The spinal cord tolerates about 45 Gray with less than 1% chance of damage, and this is a reason why careful "simulation" and review by a radiation physicist is crucial to ensure that the cord is not being overdosed. As mentioned, this is very rare with today's technology and training. Radiation can also cause heart damage, such as irritation of the fluid-filled sac around the heart ("pericarditis") which may cause chest pain and fever, and need a surgical procedure to drain excess fluid. This is also very rare. Overall, external beam chest radiation is very well tolerated and of proven benefit for increasing survival in lung cancer, for patients who cannot tolerate surgery.

Brachytherapy is being used more commonly today, since it gives a high dose of radiation to a local tumor area with minimal side effects to surrounding normal tissues. In practice, it is usually given in conjunction with external beam therapy, since we are worried about cancer cells that may have escaped around the periphery of the tumor, and into local lymph nodes, which would not be adequately treated with any brachytherapy alone. Giving brachytherapy, or "intracavitary" therapy, can be done in several ways. One is surgical placement of permanent "iodine -125" seeds in the area of the tumor, often at surgery. These seeds have an effective life of about 90 days during which they give potent radiation to their immediate area, but nearly none just a couple of centimeters away. Another option, especially for patients not getting surgery, is treatment with high-dose radioactive sources contained in a small tube ("catheter") placed with an endoscopy tube through the mouth, down the throat and into the lung.

Brachytherapy is particularly useful for tumors in the bronchi, since the endoscopy tubes travel through the bronchi and can place the catheter there. Thus, such tumors are usually more in the center of the chest, as opposed to the periphery. Multiple treatments may be given, 2 to 4 weeks apart, with high dose brachytherapy (HDR); the actual time of treatment is only a few minutes. If a segment of lung has recently collapsed owing to tumor, there is a good chance (up to 70%) that it can be re-opened using this "endobronchial brachytherapy", which is available at most Academic University Radiation Oncology departments.

The results of radiation alone depend upon the stage of cancer it's used for. In general, the results are somewhat inferior than those for surgery, but radiation has cured lung cancer. Bear in mind that patients who don't get surgery, but radiation instead, are ofter older and sicker, so they wouldn't be expected to do as well given their overall medical condition. For stage I and II, survival at 5 years with radiation alone is about 40%, and for stage III about 10%. Nonetheless, radiation will more than double the percentage of people living 2 years with stage III lung cancer, to about 25%. Many of these patients actually have their disease controlled in the chest by the radiation, but succumb to spread of the disease elsewhere in the body. This is the same as for surgery, since ultimately both radiation and surgery are local therapies that do nothing about disease which has escaped to other body areas. Thus, to address this, chemotherapy has been looked at as a way to treat the entire body. There is no question that local radiation is very valuable in relieving symptoms of lung cancer, whether from pain from spread to ribs (or other bone) or helping reduce the coughing up of blood (hemoptysis) from the cancer. Thus, radiation therapy is almost always used in advanced cancer to relieve symptoms, with up to 90% effectiveness.

Chemotherapy is the only treatment which goes to the entire body, with the rare exception of using whole body radiation to relieve symptoms (but not to cure). Lung cancer tends to spread very quickly to other body areas, but it will be a while before this spread ("micrometastasis") grows enough to become apparent. If this spread can be prevented or controlled while still small, it will increase the chance for cure. Unfortunately, chemotherapy alone has been very disappointing for lung cancer, and the side effects are often worse than the cancer's symptoms! There is often an initial shrinkage of the tumor, over the first several "cycles" of chemotherapy, followed by rapid growth as the cancer becomes resistant to the chemicals. Furthermore, no current chemotherapy alone is sufficient for controlling local, large tumors. If chemotherapy is to be useful, it must be combined with an effective local treatment, that is surgery, radiation, or both. Occasionally, chemotherapy alone is used to try to relieve symptoms of advanced disease, but it should never be used alone to "cure" non-small cell lung cancer-- it just doesn't work!

The most effective current chemotherapy agents for lung cancer are adriamycin, platinum, etoposide, vinblastine and cytoxan, used alone or in combination. Each of these agents has it's own particular toxicity. Worth noting isadriamycin's propensity to cause heart damage and increased redness of the skin with radiation, along with hair loss and sterility.Platinum promote formation of new red and white blood cells (Epogen and Neupogen). The nausea and vomiting which has classically been part of chemotherapy treatment is much reduced with agents that turn off the nausea perception center in the brain (Zofran). Nonetheless, any patient developing a fever while on chemotherapy must report for medical attention immediately, owing to the risk of overwhelming infection due to low white blood cell count ("febrile neutropenia"). Obviously, any patient getting chemotherapy must be under close monitoring, with frequent blood counts, by a competent Medical Oncologist.

Combined Modality Treatment means using more than one approach in the same patient to kill cancer cells, and increase the chance for cure. Many studies have been done to determine the optimum sequencing of therapies, and the best results for most non-small cell lung cancer patients have come from a "multimodality" approach. However, the first thing to note is that not every addition of another therapy has been of proven benefit. Specifically, for patients with very early disease (stage I) the addition of radiation after surgery has not improved survival, and another major study (LCSG) showed no improvement in adding radiation after surgery for stage II and III lung cancer, if the disease completely taken out (resected) at surgery. This is because most deaths in these patients are from distant spread, so even though radiation to the chest can help control local disease there, it doesn't help ultimate survival. Nonetheless, most radiation oncologists will treat patients with stage II or III lung cancer after surgery since they suspect that some (microscopic) cancer remains in the chest. Certainly, if gross disease remains in the chest, adding radiation is of proven benefit for local control, and many feel for survival. Another approach is doing the radiation before surgery; pre-operative radiation can help shrink the tumor and make it easier to remove at surgery. It may also help prevent the tumor from "seeding" at surgery to other body areas, as a result of being disturbed. However, the only proven role for pre-operative radiation is is for superior sulcus tumors, that is at the apex of the lung. With these tumors, there is often spread into the local ribs and even into the vertebrae to the spinal cord. Giving pre-operative radiation helps remove the tumor from these structures, allowing it to be removed ("resected") more easily. Otherwise, pre-operative radiation is out of vogue since it has not improved survival.

Interesting, after complete resection for stages II and III lung cancer, neither chemotherapy nor radiation added alone seems to help survival. However, adding both together ("chemoradiation") has helped survival in major studies. As was shown by the the CALGB study, survival more than doubled at 2 and 3 years when patients got Cisplatin and Vinblastine plus chest radiation, when compared to getting radiation alone. In this study, the patients had not had surgery, since they were stage III and many surgeons will not operate on Stage III patients with mediastinal lymph node involvement. Another major study called the "French Multicenter Trial" backed up the idea that radiation and chemotherapy must be combined, with a 3 times increase in survival for patients who got both chemotherapy and radiation, compared to just radiation alone. While the results of the CALGB study showed increased survival due to less distant spread, the French study showed that increased survival was due to increased control of the tumor in the chest. Whatever the reasons for the increased survival in these large, randomized (no predetermination of who would get which therapy) studies, both agree that both radiation and chemotherapy are needed to treat stage III (the most common stage) lung cancer!