Lung Cancer

Testing for EGFR and ALK mutations reveals tumor behavior and helps tailor treatment.

Malignant pleural effusion complicates the care of approximately 150,000 people in the United States each year. The pleural effusion is usually caused by a disturbance of the normal Starling forces regulating reabsorption of fluid in the pleural space, secondary to obstruction of mediastinal lymph nodes draining the parietal pleura.

Despite recent therapeutic advances, lung cancer continues to be one of the leading causes of cancer-related mortality. Of the various histologic subtypes, non–small-cell lung cancer (NSCLC) is the most common-accounting for approximately 85% of all lung cancers-and will be the focus of this article. In general, the treatment of lung cancer may include surgery, radiation therapy, systemic therapy (eg, chemotherapy with or without targeted therapy), or a combination of the above. Surgery continues to offer the best chance of long-term cure. The initial treatment of stage I and II NSCLC usually entails surgical resection, whereas stage IV disease is primarily treated with systemic agents, in light of the lack of curative potential with surgery and/or radiation therapy alone. It is locally advanced NSCLC, including stage IIIA and IIIB disease, that continues to pose a therapeutic dilemma, given its heterogeneous nature.

Lung cancer has been the leading cause of cancer death among men in the United States for years, and since 1988, it has become the number-one cause of cancer death among women. An estimated 219,440 new cases of lung cancer are expected in 2009, and 159,390 deaths due to this disease are expected to occur, roughly 30% of all cancer deaths. This exceeds the combined number of deaths from the leading causes of cancer (breast, prostate, and colon cancers). It accounts for 6% of all deaths in the United States.

As discussed in chapter 3, there are two major subdivisions of lung cancer: small-cell lung cancer (SCLC), for which chemotherapy is the primary treatment, and non–small-cell lung cancer (NSCLC). SCLC is decreasing in frequency in the United States, with recent data showing it represents only 14% of lung cancers. This chapter provides information on the staging and prognosis, pathology and pathophysiology, treatment, and follow-up of long-term survivors of SCLC and concludes with brief discussions on mesothelioma and thymoma.

African Americans have a higher mortality rate from lung cancer than whites, a fact first discovered in the early 1980s. For decades, researchers have looked for differences in access to care, rates of surgery, and patient preferences to explain the disparity. Now it seems the answer may relate at least partly to the way African Americans think about lung cancer, according to a survey conducted by the Dana-Farber Cancer Institute.

The seminal IPASS study by Tony Mok, MD, and colleagues demonstrated moderate efficacy for gefitinib (Iressa) in advanced non–small–cell lung cancer patients, most notably in patients with predictive factors, including adenocarcinoma histology, no history of smoking, and Asian ethnicity.

A second round of gefitinib (Iressa) slowed disease advancement in non-small-cell lung cancer patients who failed to respond to first-line treatment, according to a study presented at the 2010 Joint Conference on Molecular Origins in Lung Cancer.

Lung cancer in “never-smokers” constitutes only a small proportion of patients with lung cancer. Nevertheless, the topic has recently attracted a good deal of attention. Initially this was due to the fact that never-smokers with lung cancer had better outcomes with epidermal growth factor receptor–tyrosine kinase (EGFR-TK) inhibitors, compared to tobacco smokers with lung cancer. More recently the identification of molecular changes unique to lung cancer in never-smokers has generated further interest in this disease. These findings have the potential to enhance our knowledge of lung cancer biology and lead to the development of new, more effective treatments for lung cancer. In this review, we summarize the existing body of knowledge on lung cancer in never-smokers.

While they represent a minority of patients with lung cancer, more than 20,000 people in the United States who never smoked cigarettes are diagnosed with lung cancer each year.[1] This makes lung cancer in “never-smokers” one of the 10 most common cancers-more common than ovarian cancer. In this issue of ONCOLOGY, Subramanian and Govindan give an overview of emerging data about lung cancer in never-smokers.[2] The data outlined in this review provide support for the hypothesis that we can define this collection of diseases affecting never-smokers not by the absence of a common risk factor (smoking) but by each tumor’s molecular features.

Lung cancer remains the leading cause of cancer mortality, accounting for over 160,000 deaths in the United States and 1.18 million deaths worldwide each year.[1,2] Though tobacco smoking remains the most strongly associated risk factor for the development of lung cancer, 10% to 15% of lung cancer patients in the United States lack any history of tobacco use.

Lung cancer is the leading cause of cancer death worldwide, responsible for over a million deaths annually. In the United States in 2009, it is estimated that 219,440 cases will be diagnosed and 159,390 deaths will be attributable to lung cancer.[1] The vast majority of these deaths are cigarette-smoking associated. However, an estimated 10% to 15% of these deaths will occur in “never-smokers.”

CHICAGO-FDG-PET imaging of non-small-cell lung cancer patients prior to receiving radiation therapy should not be the basis for determining areas that may benefit from higher doses of radiation, according to research out of Philadelphia’s Thomas Jefferson University Hospital.

PET scanning with FDG has proved its mettle as a way to judge tumor response to treatment. Now Australian researchers are going one step further and working with another radiotracer, which they have determined can monitor the response of non-small-cell lung cancer and normal tissue changes during radical chemoradiotherapy.

Recent studies have shed new light on the role of histology in predicting sensitivity to therapeutic agents such as pemetrexed (Alimta) or bevacizumab (Avastin). Whereas during the past 30 years, the only useful histologic consideration was the absence or presence of a “non” before “small-cell lung cancer,” two US Food and Drug Administration (FDA)-approved drugs now have histologic restrictions.

More than 60 years ago, Karnofsky and colleagues reported promising results with the introduction of nitrogen mustard, the prototype of alkylating agents, for the treatment of lung cancer.[1] Subsequent milestones in the development of lung cancer chemotherapy included the use of platinum agents in the 1970s and 1980s, while the 1990s brought several active agents that could be combined with platinum, namely the taxanes, gemcitabine (Gemzar), and vinorelbine.

Since the publication of a meta-analysis in 1995 that demonstrated a modest survival benefit compared to best supportive care, platinum-based chemotherapy became the cornerstone of therapy in the first-line setting in advanced-stage non–small-cell lung cancer (NSCLC) for patients with good performance status.[1] A recent meta-analysis of 16 randomized trials including 2,714 patients demonstrated an advantage of chemotherapy over best supportive care with an absolute improvement in survival of 9% at 12 months.[2]

CHICAGO-In lung cancer patients, stereotactic body radiation therapy achieved a 98% local control rate that persisted over three years in those who were too frail with comorbidities to undergo surgery, according to research presented at ASTRO 2009.

SAN FRANCISCO-Studies have identified specific volatile organic compounds in the breath of lung cancer patients, but the origin of those compounds is still ambiguous: Are they from the tumor itself, the tumor micro-environment, or a reaction to the tumor by the human body?

The following company announcements were made at the 2009 World Conference on Lung Cancer in San Francisco.

Low tumor levels of the MSH2 protein predict long-term response to cisplatin-based chemotherapy in patients with resected non-small-cell lung cancer, according to an analysis from the International Adjuvant Lung Trial.

Researchers in Seoul, Korea, found early-phase contrast-enhanced CT useful for differentiating pulmonary metastases from hepatocellular carcinoma and primary lung cancer. They specifically measured the attenuations of pulmonary nodules on the CT scans.

SAN FRANCISCO-Chemotherapy before surgery for early-stage, non-small-cell lung cancer led to moderately higher survival rates than surgery alone, but not enough to reach statistical significance, according to follow-up analysis of the European NATCH trial. However, the researchers did note that patients were more likely to finish the prescribed chemotherapy course when treatment was given preoperatively.

SAN FRANCISCO-Th e new international standards for lung cancer staging and how they pertain to imaging sent sparks flying during a plenary session at the 2009 World Conference on Lung Cancer.

Despite all of its theoretical advantages, the use of induction chemotherapy is still considered experimental in the management of early-stage resectable NSCLC.