NSCLC (Non-Small Cell Lung Cancer)

NSCLC is the leading cause of cancer deaths in the U.S.  Each year approximately 200,000 people will develop NSCLC and 160,000 of these will die.  Regional Medical Center (RMC) diagnosed 98 cases in 2008.  Traditionally, more men than women have developed this illness, but this has changed over the last several years as smoking rates have become more equal between the sexes.

Non-small cell lung cancer includes adenocarcinoma, squamous cell carcinoma large cell, mixed adeno-squamous and bronchoalveolar types.  These names indicate how the tumor looked to the pathologist when studied under the microscope.  Until recently, these tumors were all treated in a similar fashion; new data allows us to better tailor treatment to the cancer subtype.

Risk Factors

·        Smoking.  This is the major risk factor and accounts for 90% of the cases.

·        Age.  The older you are, the higher your risk.

·        HIV infections.

·        Carcinogens, such as asbestos, radon, heavy metals.

·        Radiation to the lung.

·        Pulmonary fibrosis.

Presentation

The common presenting symptoms include cough, weight loss, anorexia (loss of appetite), shortness of breath, chest pain, hemoptysis (coughing blood), hoarseness and post-obstructive pneumonia (pneumonia in part of the lung blocked by tumor).

Some patients present with symptoms of metastatic (spread to other places) disease.  Examples of this would be bone pain (from cancer traveled to the bone) or headache (the cancer has spread to the brain).

Diagnosis

In order to establish a diagnosis, tissue must be obtained and examined under a microscope by a pathologist.  Tissue may be obtained by bronchoscopy (a tube in the lung with a camera and a biopsy needle on it), fine needle aspiration (in this procedure, a needle is inserted into the abnormal tissue and a small piece is removed), or an open surgical procedure.  The biopsy may be done of the lung or of a site to which the tumor has spread.

Staging

Whenever a cancer diagnosis is made, the first task is staging.

Staging just means asking “Where is the problem?” i.e., lung only or also lymph nodes in the lung or mediastinum (center of the chest), or also in bone, brain, liver, etc.

Standard work up includes chest x-ray, CAT scan of the chest and abdomen, MRI of the brain, and PET scan.  The most common sites of spread are the lung itself, the pleural surface covering the lung (this will cause fluid in the lung), liver, adrenal glands, bone and brain.

The staging system for lung cancer has recently changed.  You might wish to check with your doctor to see if your stage has been changed by the new system.  Stage is based on a combination of tumor size (T), lymph node involvement (N), fluid in the lung, and the presence or absence of disease in distant sites (M).  See Table below.

Table 4   --  TNM Elements Included in Stage Groups

Last column is % of patients with each stage at diagnosis

Survival

Survival depends on the clinical stage as shown below:

·         Stage IA – 75%

      ·          Stage IB – 38%

·         Stage IIA – 34%

·         Stage IIB, T2, N1, M0  – 24%

·         Stage IIB, T3, N0, M0  – 22%

·         Stage IIIA – 13%

·         Stage IIIB – 5%

·         Stage IV – 1%

As you can see, survival rates are poor except in stage IA.

Treatment

Treatment depends on stage

·        Stages I and II

Surgery is the “gold standard” for stages I and II. 

In order to undergo surgery, patients must have the capacity to tolerate the procedure and must be left with sufficient lung tissue to survive.  PFTs (pulmonary function tests) are usually done to assist the surgeon or pulmonologist (lung specialist) in this decision.  The “poor man’s test” is to have the patient walk one block and up one flight of steps.  If he cannot do this, the surgery will have increased risk.  Often, a cardiac evaluation is also done.   A medically inoperable patient is a patient in whom the tumor could be removed but the patient would not survive the procedure.  These patients are usually treated with radiation alone or with radiation plus chemotherapy.

Types of surgery include a pneumonectomy (removal of an entire lung), lobectomy (one lobe of the lung is removed), or wedge resection (just the tumor is taken).  Wedge resections are usually reserved for patients with limited pulmonary function.

Surgery is best performed by a specially trained thoracic surgeon as opposed to a general surgeon.  RMC is fortunate to have Dr. Ayman Abdul-Ghani, a board certified thoracic surgeon, on staff.

Patients whose tumor is greater than 4cm (1.6 inches) in size should be offered chemotherapy, as should patients whose nodes are positive.  If the nodes in the center of the chest (mediastinum) contain tumor, radiation should also be considered. The chemotherapy is usually given for 4 cycles, each cycle separated by a 3-week interval.  If radiation is used, the treatment is Monday-Friday for six weeks.

·        Stage III

Treatment for stage III patients is controversial and needs to be individualized.

Stage IIIA patients often receive surgery but should also receive chemotherapy and radiation.

If there is any question of mediastinal involvement, then a mediastinoscopy should be done.  In this procedure, a surgeon makes a small cut in the neck and inserts a lighted tube through which he examines and biopsies several lymph nodes.

If lymph nodes are positive (involved with tumor) but small, then the patient is best served by a multi-modality approach, which might include surgery.

Whether the chemotherapy used in the multi-modality approach should be given pre- or post-operatively is controversial.  Pre-operative chemotherapy has the advantage of making the surgery easier—assuming the tumor shrinks.  Also, if the tumor shrinks, then we can be reassured that the “correct” drugs were chosen.

Patients with extensive disease in the mediastinal nodes, or those with a T4 tumor, usually do best with combined chemo-therapy and radiation (stage IIIB).

·        Stage IV

Stage IV is best treated with chemotherapy, with radiation reserved for “problem sites.”  Problem sites include brain metastasis (tumor that started in the lung, got into the blood stream and traveled to the brain) and areas of poorly-controlled pain.

There are several good drugs for NSCLC.  Unfortunately, none of these is a “home run,” but progress has been made as shown below

Year            Median Survival   % alive at one year                  % alive in 2 years

1980s                   4 months              10%                               none

2000           8 months              30%                               10-15%

2005           12 months            50%                               20%

The most active drugs for squamous cell cancer include Cisplatin, Carboplatin, Taxotere, Taxol, Gemzar and Navelbine. These agents are usually given in combination.

The above drugs, plus Alimta and Bevacizumab, are useful in adeno and large cell carcinoma.

Tarceva has some efficacy, but it is most beneficial in patients whose tumors have the exon 19/21 mutation.  These tumors are usually found in women who have never smoked.

As might be expected, any drug powerful enough to kill a cancer cell will likely have some unwelcomed side effects.  The chances of toxicity will vary with the drug, as will the type of side effect.  Some drugs are “easy;” others are not. See Is the Treatment Worse Than the Disease? which you may view on out website at Annistononcology.com, or you may ask for a printed version from the office.

Your oncologist will give you a written list of what problems you may encounter with the drug(s) that are recommended.

How Will I Know If the Treatment Is Working?

The effectiveness of the treatment is usually determined by x-ray studies, i.e. is (are) the tumor(s) better, worse, or the same?  A complete response (remission) is the disappearance of all known disease; a partial remission is more than a 50% reduction in the size of the tumor.  Stable disease means that the tumor has not changed in size.  Progressive disease means the tumor is growing.

Duration of Treatment

Duration of treatment depends on your tumor’s response to therapy and the side effects that you experience.  Generally, 4-6 cycles are administered and the tumor’s size is then reassessed.  If the tumor is stable or responding, additional treatments may be given or maintenance may be started.  If the tumor has progressed, your doctor will discuss other options, such as different drugs. 

Maintenance Therapy

Maintenance therapy is generally recommended for non-squamous, non-small cell lung cancer, i.e., adenocarcinoma and large cell carcinoma.  The drug most often chosen is Alimta.  Alimta is given IV (intravenously) every 3 weeks.  It is usually very well-tolerated. Sometimes, Avastin is used as maintance.

If your tumor has the exon19/21 mutation, Tarceva should be used for maintenance.

Summary

NSCLC is a serious and often fatal disease.  Advances are being made.  Be sure you see an oncologist experienced in the treatment of this illness.