The Farber Center: For Radiation Oncology

Lung cancer is the second most common type of cancer affecting both men (after prostate cancer) and women (after breast cancer). It accounts for about 15% of all new cancers. It is the leading cause of cancer deaths.  For 2009 The American Cancer Society's estimates 219,440 new cases of lung cancer will be diagnosed in the United States (116,090 among men and 103,350 among women) with an estimated 159,390 deaths from lung cancer (88,900 among men and 70,490 among women), accounting for about 28% of all cancer deaths. The overall risk of a man developing lung cancer is 1 in 13 and for a woman, the risk is 1 in 16. Although these numbers include both smokers and non-smokers, the risk is much higher for smokers.

TYPES OF LUNG CANCER

Non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancers. Non-small cell lung cancers include adenocarcinoma, squamous cell carcinoma and large cell carcinoma. They generally spread very slowly to other organs in the body, and can be hard to detect in the early stages.

Small cell lung cancer is responsible for about 20% of all lung cancers. Also known as “oat cell” cancer, it spreads very quickly through the lungs to other parts of the body.

There are several signs and symptoms in patients found to have lung cancer, which vary from person to person. Not all patients exhibit any or all symptoms, which may include:

• A persistent or worsening cough
• Shortness of breath
• Coughing up blood
• Hoarseness
• Constant chest pain, or arm and shoulder pain
• Repeated or frequent episodes of pneumonia or bronchitis
• Unexplained weight loss or loss of appetite
• Fatigue
• Swelling of the neck and face
• Abnormal swelling of the fingernail beds (clubbing) 

The most common medical sign is an abnormality on a routine chest x-ray, or if another type of scan was such as a CT scan.   

Risk Factors

• Smoking: This is by far the most important risk factor. Smoking is responsible for 87% of all lung cancer cases in the United States. Secondhand smoke (breathing in the smoke of others) or (environmental tobacco smoke) can increase your risk of developing lung cancer. A non-smoker living with a smoker has about an approximately 20% to 30% greater risk of developing lung cancer. Workers exposed to tobacco smoke in the workplace are also more likely to get lung cancer. Secondhand smoke is thought to cause more than 3,000 deaths from lung cancer each year.
• Occupational, industrial, or environmental exposure: Routine exposed to or asbestos, radon, arsenic, and some organic chemicals increase the risk for developing lung cancer, especially amongst smokers.
• Personal history: A person with a previous lung cancer diagnosis is more likely to develop a second lung cancer. People with a history of lung diseases such as tuberculosis (TB) may also be at higher risk.
• Family history: Research has shown that genetics may play a role in certain families with a strong history of lung cancer. People who inherit certain DNA changes in chromosome 6 are more likely to develop lung cancer, even with minimal smoking. At this time there is no routine DNA test for these changes; research is currently ongoing in this area.
• Radiation exposure: People routinely exposed to radiation from occupational, medical, and environmental sources may be at increased risk.
• Air pollution: The byproducts from the combustion of fossil fuels can put people at risk. In cities, with especially heavily trafficked roads air pollution appears to raise the risk of lung cancer. Some researchers estimate that worldwide about 5% of all deaths from lung cancer may be due to outdoor air pollution.

Although there are currently no screening tests for lung cancer, there are many procedures that can be used to diagnose lung cancer. Some of these tests may be used in combination to obtain the most accurate diagnosis possible.

Chest X-rays: Often the first test your doctor will do to look for any masses or spots on the lungs. A plain x-ray of your chest can be done in any outpatient setting or office. Specialists can spot abnormal areas that may indicate the presence of cancer. If something suspicious is seen, your doctor may order additional tests.

CT scans: an x-ray test that produces detailed cross-sectional images of your body. A CT scanner takes many pictures as it rotates around. A computer combines these pictures into images of slices of the part of your body being studied. Unlike a regular x-ray, a CT scan creates detailed images of the soft tissues in the body.

MRI scans: provide detailed images of soft tissues in the body. They use radio waves and strong magnets instead of x-rays, which are absorbed and then released in a pattern formed as they penetrate through different types of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body. MRI scans are most often used to look for possible spread of lung cancer to the brain or spinal cord.

Positron Emission Tomography (PET) scans: a special type of scanner that uses a form of sugar that contains a radioactive atom. Because cancer cells in the body are growing rapidly, they absorb large amounts of the radioactive sugar. This allows for cancer cells to show up brighter in the images because they absorb more sugar than normal cells. PET scans are also useful to check if the cancer may have spread elsewhere in the body. PET can reveal spread of cancer to the liver, bones, adrenal glands, or some other organs. Some machines are able to perform both a PET and CT scan at the same time (PET/CT scan).

Biopsy: removal of a small piece of tissue which can be done during a bronchoscopy, mediastinoscopy, or mediastinotomy, or with a needle inserted through the skin directly into the abnormal area using CT guidance. This tissue is looked at under the microscope to determine if cancer is present and if so, the type and stage of the cancer.

Bronchoscope: A thin flexible tube with a tiny camera, which is inserted through the nose or mouth to examine the airways leading down into the lungs. A bronchoscope can also take a small tissue sample for biopsy for review under a microscope.

Fine Needle Aspiration (FNA): A thin needle attached to a syringe is inserted into the lung tissue through the chest. Cells are drawn out for review under a microscope.

Sputum cytology: Cells taken from mucus expelled by coughing are analyzed for the presence of cancer. Thoracentesis: Fluid from around the lungs is drawn out with a needle for examination.

Video Assisted Thoracoscopic Surgery (VATS): VATS can be used to aid in the diagnosis of thoracic cancers. Using a limited number of tiny incisions, small diameter video-thoracoscopes can allow examination of the entire thoracic cavity. Biopsies of the lining of the chest cavity (pleura), lung nodules, mediastinal masses and pleural fluid can easily be obtained for diagnosis.

Mediastinoscopy or mediastinotomy: a lighted, hollow tube is inserted through a small incision in the neck or along the breastbone to allow the surgeon to remove lymph nodes from the chest area for examination under the microscope.

Stages of Non-Small Cell Lung Cancer

Doctors describe non-small cell lung cancer based on the size of the lung tumor and whether cancer has spread to the lymph nodes or other tissues:

• Occult stage: Lung cancer cells are found in sputum or in a sample of water collected during bronchoscopy, but a tumor cannot be seen in the lung.


• Stage 0
  Cancer cells are found only in the innermost lining of the lung. The tumor has not grown through this lining. A Stage 0 tumor is also called carcinoma in situ. The tumor is not an invasive cancer.


• Stage IA
  The lung tumor is an invasive cancer. It has grown through the innermost lining of the lung into deeper lung tissue. The tumor is no more than 3 centimeters across (less than 1 ¼ inches). It is surrounded by normal tissue and the tumor does not invade the bronchus. Cancer cells are not found in nearby lymph nodes.


• Stage IB
  The tumor is larger or has grown deeper, but cancer cells are not found in nearby lymph nodes. The lung tumor is one of the following:
• The tumor is more than 3 centimeters across.
• It has grown into the main bronchus.
• It has grown through the lung into the pleura.


• Stage IIA
  The lung tumor is no more than 3 centimeters across. Cancer cells are found in nearby lymph nodes.


• Stage IIB
  The tumor is one of the following:
  • Cancer cells are not found in nearby lymph nodes, but the tumor has invaded the chest wall, diaphragm, pleura, main bronchus, or tissue that surrounds the heart.
  • Cancer cells are found in nearby lymph nodes, and one of the following:
  • The tumor is more than 3 centimeters across.
  • It has grown into the main bronchus.
  • It has grown through the lung into the pleura.
    
  
  
• Stage IIIA
  The tumor may be any size. Cancer cells are found in the lymph nodes near the lungs and bronchi, and in the lymph nodes between the lungs but on the same side of the chest as the lung tumor.


• Stage IIIB
  The tumor may be any size. Cancer cells are found on the opposite side of the chest from the lung tumor or in the neck. The tumor may have invaded nearby organs, such as the heart, esophagus, or trachea. More than one malignant growth may be found within the same lobe of the lung. The doctor may find cancer cells in the pleural fluid.


• Stage IV
  Malignant growths may be found in more than one lobe of the same lung or in the other lung. Or cancer cells may be found in other parts of the body, such as the brain, adrenal gland, liver, or bone.

Stages of Small Cell Lung Cancer
Small cell lung cancer is described in two stages:

• Limited stage: Cancer is found only in one lung and its nearby tissues.
• Extensive stage: Cancer is found in tissues of the chest outside of the lung in which it began, or cancer is found in distant organs.

Treatment options are different for limited and extensive stage small cell lung cancer

The management of lung cancer depends on several factors. Depending on the stage of the disease and these other factors, such as type, size, location of tumor, and general health, the main treatment options for people with non-small cell lung cancer (NSCLC) include:

SURGERY
Depending on the type and stage of a lung cancer, surgery may be used to remove the cancer along with some surrounding lung tissue. The type, extent and timing of surgery will depend on the location and stage of the tumor.  Surgery may possibly be followed by radiation therapy and/or chemotherapy.

Several different operations can be used to treat (and possibly cure) non-small cell lung cancer. These operations require general anesthesia and a surgical incision between the ribs in the chest (thoracotomy).

• Pneumonectomy: removal of an entire lung
• Lobectomy: removal of a section (lobe) of the lung
• Segmentectomy or wedge resection: removal of part of a lobe
• Sleeve resection: may be used to treat some cancers in large airways in the lungs. A surgeon may be able to do this operation instead of a pneumonectomy to preserve more lung function.

The type of operation depends on the size and location of the tumor and on how well the lungs are functioning. These operations usually include removal of the mediastinal lymph nodes (MLND) to look for possible spread of the cancer. This procedure is usually performed through an incision on the back and requires the ribs to be spread apart.

RADIATION THERAPY
External beam radiation treatment is most often used in conjunction with surgery, but it can also be combined with chemotherapy as an alternative to surgery.

• Neoadjuvant therapy: radiotherapy (sometimes along with chemotherapy) delivered prior to surgery to shrink a tumor and make it more manageable
• Adjuvant therapy: radiotherapy (sometimes along with chemotherapy) given after surgery to kill any cancer cells that may have been left behind
• Primary therapy: radiotherapy given as the main treatment (sometimes along with chemotherapy) for more advanced cancers or for some people who are not deemed to be surgical candidates.

Stereotactic radiosurgery is a new technology that is used to deliver very high doses of radiation very accurately to tumors in the body. Stereotactic body radiosurgery as an alternative to lung cancer surgery has yielded very high cure rates. Stereotactic Body Radiosurgery presents elderly patients, patients with severe lung disease, patients who refuse surgery, patients with severe heart disease, and other patients with poor health a curative alternative to lung cancer surgery.

External beam radiation therapy involves focusing a beam beam of ionizing radiation to the tumor while sparing the surrounding tissue. It is delivered by a series of painless outpatient treatments over several weeks. Treatments are given Monday through Friday and last less than 30 minutes.

3-Dimensional Conformal Radiotherapy (3D-CRT) is a method of treatment delivery that combines multiple radiation treatment fields using 3-dimensional computer planning to produce a high-dose area of radiation that conforms to the shape of the area to be treated. This technique allows the tailoring of delivery of precise doses of radiation to the targeted area while sparing surrounding normal healthy tissue.

Intensity modulated radiation therapy (IMRT) is an advanced form of 3D-CRT that modifies the intensity or strength of each radiation beam. It utilizes a sophisticated system of treatment delivery that allows a precise adjustment of the radiation beam intensity to the tissue within the target area while minimizing effects on surrounding tissue. This may allow for a higher dose of radiation to be delivered to the tumor from multiple angles. It continues to be studied for treatment lung cancer with respiratory gating.

IGRT or Image Guided Radiation Therapy is another technology that can also be used to ensure better targeting of daily radiation treatments. 

Stereotactic body radiation therapy (SBRT) is a specialized form of 3D-CRT that delivers high doses of radiation over a period of five to ten days. Instead of giving small doses of radiation each day for several weeks, SBRT involves delivery of very focused beams of high-dose radiation. Several beams are aimed at the tumor from different angles. In order to precisely target the radiation, a specially designed body frame is used for each treatment. This helps to minimize the movement of the lung tumor during breathing. If it is delivered in a single fraction it is known as stereotactic body radiosurgery. Like other forms of external radiation, these treatments are painless. It can be used for some very early stage (small) lung cancers when surgery isn't an option usually for other medical reasons. There is emerging data that have demonstrated that this technique may provide an alternative first-line approach to surgery.

Respiratory Gating Radiation therapy treatment to certain locations within the body such as the lungs, can be limited in precision due to respiratory (breathing) motion. This motion leads to significant movement of the tumor and critical organs.  In the past, respiratory motion has hindered doctors' ability to accurately map out the tumor and deliver radiation specifically to the tumor and not to normal tissue. The ability to plan and deliver radiation with unprecedented precision is only valuable if the target is in an identifiable and repeatable position.

Brachytherapy (internal radiation therapy) is used most often to shrink tumors to relieve symptoms caused by the cancer. In some cases it may be part of a larger treatment regimen trying to cure the cancer.

High-dose-rate brachytherapy (HDR): a small source of radioactive material (often in the form of pellets) is placed directly into the cancer or into the airway next to the cancer. This is usually done during a bronchoscopy but may also be done during surgery. It involves placing one or two thin plastic tubes (catheters) into the airways that lead to the lungs. These tubes are connected to a special HDR delivery machine. A small amount of radioactive material is computer-driven through these catheters allowing a high dose of radiation to be delivered to a small, precise area while sparing surrounding normal healthy tissue. The radiation and catheters are removed at the end of each treatment.

When there is a diagnosis of small cell lung cancer, radiation therapy to the brain after completion of the treatment course to the lung may be recommended. This is called prophylactic cranial irradiation (PCI) and is recommended only in certain situations.

Radiation therapy can also be used to relieve (palliate) symptoms of advanced lung cancer such as pain, bleeding, trouble swallowing, cough, and problems caused by brain metastases.

CHEMOTHERAPY
Is the use of anticancer drugs injected into a vein or taken by mouth to destroy certain types of tumors and is utilized in different stages of lung cancer. These drugs enter the bloodstream and go throughout the body, making this treatment useful for cancer that has spread (metastasized) to distant organs. Depending on the type and stage of lung cancer, chemotherapy may be used in different situations (see Radiation Therapy Section):

• Neoadjuvant therapy: chemotherapy (sometimes along with radiation therapy) delivered prior to surgery to shrink a tumor and make it more manageable
• Adjuvant therapy: chemotherapy (sometimes along with radiation therapy) given after surgery to kill any cancer cells that may have been left behind
• Primary therapy: chemotherapy given as the main treatment (sometimes along with radiation therapy) for more advanced cancers or for some people who are not deemed to be surgical candidates.

Small cell lung cancer is frequently treated with chemotherapy and radiation therapy either together or one right after the other.

RADIOFREQUENCY ABLATION (RFA)
A technique that uses high-energy radio waves to heat the tumor. Under CT guidance, a thin, needle-like probe is placed through the skin into the tumor. An electric current is passed through the probe, which heats the tumor and destroys the cancer cells. It is being studied for small lung tumors that are near the outer edge of the lungs, especially in people who can't have or don't want surgery. Major complications can include the partial collapse of a lung (which often resolves on its own) or bleeding into the lung.

PHOTODYNAMIC THERAPY (PDT)
PDT may be used to treat very flat and small tumors near airways when other treatments aren't appropriate, or reduce some symptoms of lung cancer. In this technique, a light-activated drug called porfimer sodium (Photofrin) is injected into the body, where it collects and remains longer in cancer cells than in normal cells. A bronchoscope is then passed down the throat and into the lung where a special red light on the end of the bronchoscope is aimed at the tumor. This light activates the drug and causes the cells to die. The dead cells are then removed a few days later during a bronchoscopy. The entire process may be repeated as needed. Side effects include increased sensitivity to sunlight or strong indoor lights. Too much exposure can cause serious skin reactions. It is recommended that patients avoid strong light for 4 to 6 weeks after the injection.

LASER THERAPY
Lasers can sometimes be used to treat very small lung cancers within the linings of airways. They can also be used to relieve symptoms caused by lung cancers. Under general anesthesia, a laser at the end of a bronchoscope is passed down the throat and situated next to the tumor. The laser beam is aimed at the tumor to burn it away. This treatment can usually be repeated as needed.

STENT PLACEMENT
Stents are devices made of hard rubber or metal tubes that may be placed within the airway through a bronchoscopy procedure to help keep the airway open when there is blockage due to tumor. They is often placed after other treatments such as photodynamic therapy or laser therapy are utilized.

TARGETED THERAPY
Drugs that target tumor blood vessel growth (angiogenesis)

Angiogenesis is the process by which tumors form new vessel to keep them nourished and thereby to grow. Some targeted drugs block this new vessel growth.

Bevacizumab (Avastin): Bevacizumab is a type of drug known as a monoclonal antibody. It targets vascular endothelial growth factor (VEGF), a protein that helps new blood vessels to form. It has been shown to prolong survival of patients with advanced lung cancer when added to standard chemotherapy regimens as part of first-line treatment. Bevacizumab is given by infusion into a vein every 2 to 3 weeks. The possible side effects are different from those of chemotherapy drugs, and can include bleeding, blood clots, intestinal complications, heart problems, and delayed wound healing. More common side effects include high blood pressure, tiredness, low white blood cell counts, headaches, mouth sores, loss of appetite, and diarrhea.

Drugs that target Epidermal Growth Factor Receptor (EGFR)

Epidermal growth factor receptor (EGFR) is a protein found on the surface of cells, which helps cells to grow and divide. Some lung cancer cells express too much EGFR, which in turn, causes them to grow faster.

Erlotinib (Tarceva): blocks EGFR from signaling the cell to grow. It is most often used for cases of advanced lung cancers after initial treatment with chemotherapy becomes ineffective. This drug is taken daily as a pill. The most common side effects include an acne-like rash on the face and chest, diarrhea, loss of appetite, and feeling tired.

Cetuximab (Erbitux): is a monoclonal antibody that targets EGFR. It may be added to standard chemotherapy as part of first-line treatment for patients with advanced lung cancer. Cetuximab is given by IV infusion, usually once a week. Side effects include allergic reaction during the first infusion, which could cause breathing problems low blood pressure, skin problems such as an acne-like rash on the face and chest during treatment, infections, headache, tiredness, fever, and diarrhea.

Possible Treatment Side Effects
Dr. Farber, Dr. Spierer, and their staff at The Farber Center for Radiation Oncology will discuss potential side effects with you before, during, and after treatment, and ensure that your experience is personalized.