Banner
Banner
More
Non small cell lung cancer

NSCLC

Non-small-cell lung carcinoma (NSCLC) is any type of epithelial lung cancer other than small cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy is increasingly being used both pre-operatively (neoadjuvant chemotherapy) and post-operatively (adjuvant chemotherapy).

 

Types

The most common types of NSCLC are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma, but there are several other types that occur less frequently, and all types can occur in unusual histologic variants and as mixed cell-type combinations. Non-squamous cell carcinoma almost occupy the half of NSCLC. In the tissue classification, the centural type contains about one-ninth.

Sometimes the phrase "not otherwise specified", or NOS is used generically, usually when a more specific diagnosis cannot be made. This is most often the case when a pathologist examines a small amount of malignant cells or tissue in a cytology or biopsy specimen.

Lung cancer in never-smokers is almost universally NSCLC, with a sizeable majority being adenocarcinoma.

On relatively rare occasions, malignant lung tumors are found to contain components of both SCLC and NSCLC. In these cases, the tumors should be classified as combined small cell lung carcinoma (c-SCLC), and are (usually) treated like "pure" SCLC.

 

Lung adenocarcinoma

Adenocarcinoma of the lung is currently the most common type of lung cancer in "never smokers" (lifelong non-smokers). Adenocarcinomas account for approximately 40% of lung cancers. Historically, adenocarcinoma was more often seen peripherally in the lungs than small cell lung cancer and squamous cell lung cancer, both of which tended to be more often centrally located. However, recent studies suggest that the "ratio of centrally-to-peripherally occurring" lesions may be converging toward unity for both adenocarcinoma and squamous cell carcinoma.

 

Squamous cell lung carcinoma

Squamous cell carcinoma (SCC) of the lung is more common in men than in women. It is closely correlated with a history of tobacco smoking, more so than most other types of lung cancer. According to the Nurses' Health Study, the relative risk of SCC is approximately 5.5, both among those with a previous duration of smoking of 1 to 20 years, and those with 20 to 30 years, compared to never-smokers. The relative risk increases to approximately 16 with a previous smoking duration of 30 to 40 years, and approximately 22 with more than 40 years.

 

Large-cell lung carcinoma

Large cell lung carcinoma (LCLC) is a heterogeneous group of undifferentiated malignant neoplasms originating from transformed epithelial cells in the lung. LCLC's have typically comprised around 10% of all NSCLC in the past, although newer diagnostic techniques seem to be reducing the incidence of diagnosis of "classic" LCLC in favor of more poorly differentiated squamous cell carcinomas and adenocarcinomas. LCLC is, in effect, a "diagnosis of exclusion", in that the tumor cells lack light microscopic characteristics that would classify the neoplasm as a small-cell carcinoma, squamous-cell carcinoma, adenocarcinoma, or other more specific histologic type of lung cancer. LCLC is differentiated from small cell lung carcinoma (SCLC) primarily by the larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin.

 

Treatment

More than one kind of treatment is often used, depending on the stage of the cancer, the individual's overall health, age, response to chemotherapy, and other factors such as the likely side effects of the treatment. After full staging, the NSCLC patient can typically be classified in one of three different categories: patients with early, non-metastatic disease (Stage I, II and select III tumors), patients with locally advanced disease confined to the thoracic cavity (e.g., large tumors, tumors involving critical chest structures or patients with positive mediastinal lymph nodes) or patients with distant metastasis outside of the thoracic cavity.

Early/non-metastatic NSCLC

NSCLCs are usually not very sensitive to chemotherapy and/or radiation, so surgery remains the treatment of choice if patients are diagnosed at an early stage. If patients have small, but inoperable tumors, they may undergo highly targeted, high intensity radiation therapy. New methods of giving radiation treatment allow doctors to be more accurate in treating lung cancers. This means less radiation affects nearby healthy tissues. New methods include Cyberknife and stereotactic body radiation therapy(SBRT). Certain patients deemed to be higher risk may also receive adjuvant (ancillary) chemotherapy after initial surgery or radiation therapy. There are a number of possible chemotherapy agents which can be selected however most will involve the platinum-based chemotherapy drug called cisplatin.

Other treatments include percutaneous ablation and chemoembolization. The most widely used ablation techniques for lung cancer are radiofrequency ablation, cryoablation, and microwave ablation. Ablation may be an option for patients whose tumors are near the outer edge of the lungs. Nodules less than 1 cm from the trachea, main bronchi, oesophagus and central vessels should be excluded from RFA given high risk of complications and frequent incomplete ablation. Additionally, lesions greater than 5 cm should be excluded and lesions 3 to 5 cm should be considered with caution given high risk of recurrence. As a minimally invasive procedure, it can be a safer alternative for patients who are poor candidates for surgery due to co-morbidities or limited lung function. A study comparing thermal ablation to sublobar resection as treatment for early stage NSCLC in older patients found no difference in overall survival of the patients. It is possible that RFA followed by radiation therapy has a survival benefit due to synergysm of the two mechanisms of cell destruction.

Advanced/metastatic NSCLC

A wide variety of chemotherapies options exist for used in advanced (metastatic) NSCLC. These agents include both traditional chemotherapies like cisplatin which indiscriminately target all rapidly dividing cells as well as newer targeted agents which are more tailored to specific genetic aberrations found within a patient's tumor. At present there are two genetic markers which are routinely profiled in NSCLC tumors to guide further treatment decision making: mutations within EGFR and Anaplastic Lymphoma Kinase. There are also a number of additional genetic markers which are known to be mutated within NSCLC and may impact treatment in the future, including BRAF (gene), HER2/neu and KRAS.

Thermal ablations i.e. radiofrequency ablation, cryoablation, microwave ablation are appropriate for palliative treatment of tumor-related symptoms or recurrences within treatment fields. Patients with severe pulmonary fibrosis and severe emphysema with a life expectancy <1 year should be considered poor candidates for this treatment.

EGFR mutations

Roughly 10-35% of NSCLC patients will have drug sensitizing mutations of the EGFR. The distribution of these mutations have been found to be race-dependent, with one study estimating that 10% of Caucasians but 50% of Asians will be found to have such tumor markers. A number of different EGFR mutations have been discovered, however certain aberrations will result in hyperactive forms of the protein. Patients with these mutations are more likely to have adenocarcinoma histology and be non-smokers or light smokers. These patients have been shown to be sensitized to certain medications which block the EGFR protein known as tyrosine kinase inhibitors specifically, erlotinib, gefitinib or afatinib.

ALK gene rearrangements

Up to 7% of NSCLC patients have EML4-ALK translocations or mutations in the ROS1 gene; these patients may benefit from ALK inhibitors which are now approved for this subset of patients. Crizotinib gained FDA approval in August 2011 and is an inhibitor of several kinases, specifically ALK, ROS1 and MET. Crizotinib has been shown in clinical studies to have response rates of ~60% if patients are shown to have ALK positive disease. Several studies have also shown that ALK mutations and EGFR activating mutations are typically mutually exclusive. Thus, it is not recommended for patients who fail crizotinib to be switched to an EGFR-targeted drug such as erlotinib.

Other treatment options

NSCLC patients with advanced disease who are not found to have either EGFR or ALK mutations may receive bevacizumab which is a monoclonal antibody medication targeted against the vascular endothelial growth factor (VEGF). This is based on an Eastern Cooperative Oncology Group study which found that adding bevacizumab to carboplatin and paclitaxel chemotherapy for certain patients with recurrent or advanced non-small-cell lung cancer (stage IIIB or IV) may increase both overall survival and progression free survival.

In 2015 the US FDA also approved the anti-PD-1 agent nivolumab for advanced or metastatic squamous cell carcinoma.

In October 2016 FDA approved atezolizumab for metastatic NSCLC without EGFR or AKT mutations .