Treatment of lung cancer
Treatment of lung cancer refers to the use of medical therapies, such as surgery, radiation, chemotherapy, percutaneous ablation, and palliative care, alone or in combination, in an attempt to cure or lessen the adverse impact of malignant neoplasms originating in lung tissue.
Lung cancer is an extremely heterogeneous family of malignant neoplasms, and well over 50 different histopathological variants are currently recognized under the most widely used typing system. Because these variants have differing genetic, biological, and clinical properties, including response to treatment, correct classification of lung cancer cases are necessary to assure that lung cancer patients receive optimum management.
Approximately 98% of lung cancers are carcinoma, or tumors derived from transformed cells of epithelial lineage. Currently, nearly four dozen different histopathological variants of lung carcinoma are recognized. For clinical and treatment purposes, however, most oncologists tend to classify lung carcinomas into two major groups, namely small cell carcinoma (SCLC) and non-small cell lung cancer (NSCLC). This is done because of differing responses to treatment — NSCLC is comparatively less sensitive to chemotherapy and/or radiation, so surgery is the treatment of choice in these tumors. SCLC, in contrast, usually initially responds well to chemotherapy and/or radiation, but has usually metastasized widely by the time it is discovered, making surgery ineffective.
In a 2010 study of patients with metastatic non–small-cell lung cancer, "early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival" which was increased by approximately 3 months.
There are typically three objectives applied to the treatment of lung cancer and can vary by patient or individual diagnosis: (1) curing lung cancer, (2) controlling lung cancer, and (3) being comfortable.
In most cases, the goal of lung cancer surgery is to remove the entire tumor, including a small amount of normal tissue (about 2 centimetres, 0.8 in) at the margin. The general name for surgery that enters the chest is thoracotomy, and specific named types of surgical interventions may be performed as part of the thoracotomy, such as wedge resection, segmentectomy, "sleeve resection", lobectomy, or pneumonectomy, depending on the tumor and patient characteristics.
Surgery is very rarely used in cases of stage 3b or stage 4 non-small cell lung carcinoma.
In patients with stage 3 lung cancer that cannot be removed, treatment with combined radiotherapy and chemotherapy improves survival significantly.
In recent years, various molecular targeted therapies have been developed for the treatment of advanced lung cancer. Gefitinib (Iressa; withdrawn from the U.S. market) is one such drug, which targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR), expressed in many cases of non-small cell lung carcinoma. It was not shown to increase survival, although females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma appear to derive the most benefit from gefitinib.
Erlotinib (Tarceva), another EGFR tyrosine kinase inhibitor, increased survival in non-small cell lung cancer and was approved by the FDA in 2004 for second-line treatment of advanced non-small cell lung carcinoma. Similar to gefitinib, it also appeared to work best in females, Asians, nonsmokers, and those with bronchioloalveolar carcinoma, particularly those with specific mutations in EGFR.
The angiogenesis inhibitor bevacizumab (Avastin), (in combination with paclitaxel and carboplatin), improves the survival of patients with advanced non-small cell lung carcinoma. However, this increases the risk of lung bleeding, particularly in patients with squamous cell carcinoma.
Crizotinib shows benefit in a subset of non-small cell lung cancer that is characterized by the EML4-ALK fusion oncogene, and is approved by the FDA. EML4-ALK is found in some relatively young, never or light smokers with adenocarcinoma.
Advances in cytotoxic drugs, pharmacogenetics and targeted drug design show promise. A number of targeted agents are at the early stages of clinical research, such as cyclo-oxygenase-2 inhibitors, the apoptosis promoter exisulind, proteasome inhibitors, bexarotene, the epidermal growth factor receptor inhibitor cetuximab, and vaccines. Sorafenib (marketed as Nexavar for use in renal and liver cancer) showed promise in a clinical trial matching targeted treatment to the cancer's genetic profile. Future areas of research include ras proto-oncogene inhibition, phosphoinositide 3-kinase inhibition, histone deacetylase inhibition, and tumor suppressor gene replacement.
In patients with stage one or two non-small cell lung carcinoma, radiotherapy alone results in 13–39% of patients surviving to five years.
Percutaneous image-guided ablation is a minimally invasive treatment that can be offered to patients with early stage NSCLC or for palliative treatment for patients with metastatic disease. There are various types of ablation used for treating lung malignancies including radiofrequency ablation (RFA), cryoablation, and microwave ablation. Thermal ablation is typically recommended for patients who are higher risk surgical patients due to cardiopulmonary disease. Ablation is generally a lower risk procedure compared to surgery; it requires only local anesthesia and sometimes conscious sedation, and it is minimally invasive. The procedure is performed by interventional radiology in an outpatient setting. Under CT or ultrasound guidance, a probe is advanced through the anesthetized skin until the tip of the probe is positioned within the tumor. Extreme temperature is then created through electrical current (radiofrequency ablation and microwave ablation) or gas (cryoablation), which triggers destruction of the cancerous cells. Major complications are uncommon, but include partial collapse of the lung and hemothorax.  While there is growing evidence supportive of ablation as treatment for NSCLC, high rates of local recurrence and new metastatic disease in the treatment areas leads to reliance on more traditional treatment modalities. The pitfalls of ablation stem from the lack of complete and homogenous destruction of tumor cells, often leading to residual malignant cells on the periphery of the tumor. For that reason, lesions greater than 5 centimetres (2.0 in) should be excluded, and lesions 3 to 5 cm (1.2 to 2.0 in) should be considered with caution, given high risk of recurrence. Additionally, for safety reasons, lesions less than 1 cm (3⁄8 in) from the trachea, main bronchi, esophagus and central vessels should be excluded from RFA, given high risk of complications and frequent incomplete ablation.  An animal tumor model demonstrated improved survival after combined treatment with RFA and radiation therapy compared to either treatment alone. It is possible that the two modalities have a synergistic effect and patients may benefit from combined treatment.
Prior to the early part of the 20th century lung cancer was considered a very rare disease, and all malignant lung tumors were treated identically. Radical surgical resection (i.e. lobectomy or pneumonectomy) was the only effective intervention available for lung cancer prior to the 1940s, when the era of modern cytotoxic chemotherapy began.
It was not until 1962 that small cell lung carcinoma (SCLC), then called "oat cell carcinoma" was recognized for its unique biological behavior, including a much higher frequency of widespread metastases at presentation, and exquisite sensitivity to cytotoxic chemotherapy and radiation.
Early studies suggested that patients with small cell lung carcinoma (SCLC) fared better when treated with chemotherapy and/or radiation than when treated surgically. While this approach to treating SCLC remains the current standard of care, the role of surgery in SCLC is being re-examined, with recent studies indicating that surgery may improve outcomes in some patients with early stage SCLC and combined forms of SCLC and NSCLC.
Squalamine is undergoing trials for treatment of non-small cell lung cancer (stage I/IIA).
In December 2012, Merck published the results of its current study. Although the Phase III Trial of L-BLP25 (Stimuvax) did not meet satisfying primary endpoints for patients with Non-Small Cell Lung Cancer, notable treatment effects have been observed for L-BLP25 in certain subgroups in the START study.
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