Small cell (13% of cases) spreads quickly, non-small cell cancer spreads slowly.  In 2009 there were 160,000 lung-cancer deaths, 56% men, 44% women.

Lung cancer types and staging:  an excellent detailed account

Lung Cancer Answers:  http://www.lungcancer-prognosis.com/types.html

There are four types of lung cancer: Large cell carcinoma, squamous cell carcinoma, small cell lung cancer, and adenocarcinoma of the lung. The ratio of incidence of the different types varies with cause of cancer. Adenocarinoma, which means the cancer started in the glandular tissue inside the lung, is more prevalent among light smokers, former smokers, and never smokers than it is among heavy smokers. Small cell lung cancer and squamous cell carcinoma are more common in heavy smokers than in the general lung cancer patient population. An analysis of published reports related to the histology of lung cancer which included smoking data, showed that adenocarcinoma was more prevalent amongst non smokers in comparison to squamous cell carcinoma (62 against 18 percent; based on 5144 cases). In comparison, adenocarcinoma cases were less prevalent amongst smokers (19 against 53 percent; based on 21,853 cases). The most recent lung cancer cases involving never smokers continue to identify adenocarcinoma as the most prevalent histology.

In comparison to other forms of adenocarcinoma, the BAC subset of adenocarcinoma has been associated even more strongly with never smokers. In a recent analysis, never smokers accounted for around 23 percent of BAC.

Molecular biology

Recent technological advances have increased the understanding about the molecular biology of lung cancer, enabling the identification of significant variations that exist between never smokers and smokers with lung cancer.

One of the most noticeable variations between the incidence of lung cancer amongst never smokers and current and former smokers has been seen in the expression and mutations of the epidermal growth factor receptor (EGFR). Mutations occurring in the EGFR gene are more prevalent in lung tumors of never smokers in comparison to smokers. In a detailed analysis involving more than 400 patients with the most prevalent activating mutations present in the EGFR gene (mostly deletions in exon 19 and the L858R mutation on exon 21), it was noticed that some variations in the incidence of mutations were gender based, yet never smokers showed a significantly higher incidence of exon 19 and 21 mutations in comparison to regular smokers, in both men and women. Moreover, a separate immunohistochemical profile of the EGFR pathway has also been confirmed in never versus regular smokers, even when EGFR mutations are not present.

In comparison, it has been assumed that KRAS mutations are more prevalent amongst lung cancer patients who are regular smokers. However, in a more recent analysis involving 482 lung adenocarcinoma cases, it was noticed that the rate of KRAS mutations in codons 12 and 13 was not significantly different amongst never smokers (15 percent) in comparison to former smokers (22 percent) and regular smokers (25 percent). However, the type of mutations was majorly different characterized by more transition mutations (G to A) in comparison to transversion mutations (G to T or G to C) occurring in tumors of patients who have a history of smoking.

Major variations have also been noticed in the mutations and expression patterns of other types of genes while comparing never smokers to smokers. Some examples include p53, belonging to the NER family of proteins, together with ERCC1, which is associated with DNA repair, p38 (downstream of mitogen-activated protein kinase [MAPK]), nitrotyrosine (a marker of nitric oxide protein damage), other chromosomal abnormalities and methylation of p16. In lung cancer patients who are never smokers, the microRNA-21 (miR-21) seems to be increased, especially in individuals with EGFR mutations and can play an important role in lung carcinogenesis.

A fusion gene that has portions of both the echinoderm microtubule-associated protein-like 4 (EML4) gene as well as the anaplastic lymphoma kinase (ALK) gene in NSCLC is present in 3 to 7 percent of NSCLC and seems to be mutually exclusive in relation to EGFR and KRAS mutations. This is more common amongst never smokers who are diagnosed with lung cancer. Trials involving ALK receptor tyrosine kinase inhibitors are currently underway amongst patients with the EML4-ALK fusion protein.

In order to identify other important biomarkers in lung cancer amongst never smokers, a multi-institutional effort is currently underway, funded and sponsored by the National Cancer Institute's Early Detection Research Network and the Canary Foundation. The project was initiated in May 2009.

Symptoms of Lung Cancer

Sadly, one of the reasons that lung cancer is so deadly is that it usually does not cause symptoms until the disease has advanced and spread. In a reasonably large portion of patients however, there may be subtle symptoms that are ignored or misinterpreted. By paying attention to the symptoms of lung cancer and taking action in a timely manner, diagnosis and treatment can begin earlier. Earlier diagnosis and treatment can turn into a better overall lung cancer prognosis.

Since lung cancer is most common in smokers, it is often difficult for patients to recognize the symptoms of lung cancer when they occur on top of already frequent lung and breathing problems. In those exposed to asbestos—another large group of lung cancer patients—lung cancer symptoms may be more easily recognized.

The symptoms of lung cancer can be divided into three main types: symptoms caused by the tumor itself, symptoms caused by local spread of the lung cancer and symptoms caused by widespread metastasis. The most common lung cancer symptoms are listed in Table 1.

Small-cell lung cancers, one of the main types of lung cancer comprising about 15% of all cases, are well known for causing paraneoplastic syndromes. These syndromes can cause a number of bizarre and seemingly disparate symptoms. While they are most common in small-cell lung cancers, any lung cancer can cause a paraneoplastic syndrome.

Some of the more common paraneoplastic syndromes that occur with lung cancer are hypercalcemia, Trousseau syndrome, SIADH, elevated ACTH production, and Lambert-Eaton syndrome. Paraneoplastic syndromes are fairly rare disorders. When they occur from lung cancer it usually indicates advanced disease. Some paraneoplastic syndromes associated with lung cancer are included in Table 2.

LUNG CANCER TREATMENT:

There are a number of different treatment options for lung cancer. Standard treatment options include surgical resection, chemotherapy, and radiation therapy. Newer lung cancer treatment approaches include photodynamic therapy, electrocautery, cryosurgery, laser surgery, targeted therapy and internal radiation. Each lung cancer treatment has its own specific ability to fight cancer and its own set of side effects and possible complications. Therefore while there are many options, lung cancer treatment needs to be performed judiciously and only after very careful consideration of a number of factors.

ung cancer treatment is tailored to the needs and wishes of the individual patient. General guidelines exist to direct medical professionals as they make their decisions; though each treatment plan is designed with a particular patient in mind. Even so, it is important for people diagnosed with lung cancer to understand their options. It is useful to know which cancer treatment has the greatest chance of success in a particular situation, which treatments are more experimental in nature, which treatments are likely to be ineffective, and which treatments are aimed at reducing symptoms (palliative) rather than achieving a cure.

As with most cancer treatments, the choice of therapy is dictated mostly by the cancer type and the stage of the disease. In lung cancer there are two main types, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). While there are several different stages and subdivisions of NSCLC differentiated by numbers and letters, SCLC has only two stages: limited and extensive disease. As oncologists are considering choices in therapy, the stage and type of lung cancer factor heavily on the decision.

Treatment of non-small cell lung cancer

For occult and stage 0 NSCLC, surgery is generally curative without the need for radiation or chemotherapy. This is because these stages do not represent invasive lung cancer—the lung cancer is completely contained within the primary tumor. Therefore when the tumor is surgically removed, the cancer is gone for good. Obviously the success rate in this case, as with all stages, depends on the quality and accuracy of the lung cancer staging. If cancer cells have migrated away from the tumor, these stages no longer apply and additional treatment is necessary.

Surgery is indicated for stages I, II, and III of NSCLC. It may also be used for palliation in stage 4. Palliative therapy, it should be mentioned, is intended to relieve symptoms and improve quality of life with no real goal of cure or cancer remission. For stages I and II of NSCLC, surgery is the primary treatment of choice. (See page on staging of lung cancer.)

The surgery that is used to treat the lung cancer is tailored to the patient based on the extent of the disease. Since the lung is essential for respiration and for life, preserving as much functional lung tissue as possible is a primary concern to thoracic surgeons. Surgeons consider how well the patient will be able to breathe after a portion of lung is removed. At the same time, a sufficient amount of tumor and surrounding lung must be removed in order to assure that the cancer has been eliminated. Pulmonary function tests (breathing tests) are performed before cancer surgery to assess the patient’s overall lung capacity. An estimate is made of the level of lung function that would exist after the proposed surgery. If the patient will be left with too little lung capacity, either a less aggressive surgery will be performed or the surgery will not be done at all and alternate treatment will be given. Since people with lung cancer often have other lung diseases such as emphysema, lung capacity is a very important issue.

There are five lobes of lung, three on the right side of the chest and two on the left. Within these lobes, the lung is further subdivided into segments according to how the bronchi and bronchioles supply them with air. This organization is important when planning lung resection surgery.

There are several approaches available to thoracic surgeons. A wedge resection preserves the most lung tissue but provides the least room for error (meaning there is a reasonable chance of the cancer recurring). A wedge resection is suited to small primary tumors, usually of the Stage 0 and I variety. A segmental resection is a bit more aggressive, taking more lung tissue. However, the segmental resection is often well suited to stage I and II disease. Again, the risk of missing cancer cells is weighed against the resulting lung capacity.

A lobectomy is a procedure in which one of the five lobes is completely removed. The largest lung cancer resection surgery, a pneumonectomy (or hemi-pneumonectomy), is when an entire lung is removed, either the left or the right lung. In general, lobectomy and pneumonectomy are used to treat stage II NSCLC in patients with excellent reserve capacity of the lungs.

There are a number of chemotherapeutic regimens that can be used to treat NSCLC. These are usually reserved 1) for higher stages of lung cancer (stages III and IV) or 2) as adjuvant therapy, that is, to be used after surgery or 3) as neoadjuvant therapy, which is treatment before surgery. Neoadjuvant therapy is done to make the tumor smaller so that surgery will be easier or more effective. Adjuvant therapy is performed to kill cancer cells that may have been missed in the surgery or spread from the primary tumor.

The standard of care in the treatment of NSCLC is to use a platinum-based chemotherapeutic agent, especially in advanced disease (stages III and especially IV). Most studies have shown that two agents are better than one. Three agents used in combination do not provide much additional benefit but do cause a number of additional, unpleasant side effects. Therefore chemotherapy regimens usually include two drugs. Often this combination regimen includes a platinum drug like cisplatin along with either an older (etoposide) or newer (docetaxel, gemcitabine, pemetrexed (Alimta) or vinorelbine) chemotherapeutic drug.

Non-small cell lung cancer tumors are not very sensitive to most chemotherapy regimens, unfortunately. Chemotherapy alone is not considered a curative treatment for NSCLC. Often chemotherapy is combined with radiation therapy—an approach that is sometimes referred to as chemoradiation therapy. When the two treatment modalities are combined, the rates of disease clearance and survival are better than with either treatment alone. Otherwise chemotherapy is combined with surgery (either as neoadjuvant or adjuvant)

Radiation therapy alone is sometimes used for stage I and II NSCLC when surgery is not possible due to too little lung capacity. If that stage I or II tumor is resectable, surgery would be used rather than radiation therapy.

In stage IIIA NSCLC, surgery is still considered first line therapy. When surgery is possible, it is usually combined with adjuvant chemotherapy. If surgery is not possible in stage IIIA disease, chemoradiation therapy is used. Some specific stage IIIA tumors, like Pancoast tumors or tumors that have invaded the chest wall, have special treatment approaches.

In stage IIIB, chemoradiation therapy is considered first line. Radiation therapy alone may be used if patients are concerned with the toxic effects of chemotherapy; however outcomes are better if both treatment modalities are used. In this stage of NSCLC, surgery is not considered a curative intervention or effective treatment and is rarely performed. Radiation therapy may be used for palliation of symptoms when tumor invades certain tissues and causes troublesome symptoms.

Chemotherapy is really the only treatment modality used in stage IV NSCLC. Radiation therapy and surgery are used to relieve symptoms rather than change the course of the disease or improve survival. Treatment for stage IV disease most likely will include a platinum-based chemotherapeutic agent and a non-platinum chemotherapeutic drug. When three drugs are used, the third is not technically a chemotherapeutic agent but rather “targeted therapy.”

Targeted therapy includes drugs, antibodies or other proteins that target and disrupt specific proteins within the cancer cell. These disrupted proteins are critical for the cancer cell’s survival so the treated cell dies or stops multiplying. The use of targeted therapy in stage IV disease along with two other chemotherapeutic drugs may improve overall survival.

Treatment of small cell lung cancer

The treatment options in SCLC are less complex than NSCLC, mostly because studies have repeatedly shown that treatment outcomes are not affected by detailed staging. In other words, placing SCLC in four different stages does not influence treatment choices or outcomes to any appreciable degree. Thus treatment of SCLC is based mainly on two different stages, limited and extensive.

Fortunately SCLC is very sensitive to radiation therapy. Radiotherapy is the treatment modality used in virtually all cases of limited SCLC disease. Radiation therapy is more effective and causes fewer side effects in limited disease because, by definition, limited disease can be treated through a single, external radiation port. In extensive SCLC disease, radiation therapy may be reserved for patients that have not responded to chemotherapy. This is because in extensive disease, radiation would need to been applied to large areas of the body. As a palliative intervention in extensive SCLC (and sometimes limited SCLC), certain organs like that brain may be irradiated prophylactically (in case there is spread).

Chemotherapy is used to treat both limited and extensive SCLC. In limited disease, patients have been successfully treated with a single chemotherapeutic drug (when combined with radiation). In most cases though, two drugs are used rather than one. These two drugs are commonly a platinum drug and etoposide. In extensive SCLC, two chemotherapeutic drugs are used. The specific chemotherapeutic agents used in extensive SCLC vary.

In both NSCLC and SCLC, it may be possible to enroll in a clinical trial of lung cancer treatments. These trials usually compare new therapies against older ones to see if outcomes can be improved. Targeted therapies, radiosensitizers, internal radiation sources, and newer combination treatment regimens are just some of the treatment tools being tested in research and clinical studies. These new treatments may improve survival or may lead to future breakthroughs.