Tuesday, April 23, 2013

Lung Cancer Overview - Part 1 of 5

There has been some remarkable progress in recent years in the diagnosis and treatment of lung cancer. 160,000 Americans die annually from lung cancer making it second only to heart disease as a cause of death and slightly more than the next four cancers combined – breast, colon, pancreas and prostate.  This is largely because lung cancer is usually discovered only after it has spread. Now CT scanning has been shown to detect lung cancer when it is still small and localized. Further there have been major advances in treatment with radiation, with combination drug therapy and with new compounds targeted at “driver mutations”. Although cures are rare still they are growing in number. For those with extensive disease, there are useful responses to newer therapies that prolong survival and improve the quality of life. As a result, there now appears to be some light at the end of this very long tunnel. 

Facts and Figures - About 225,000 individuals will develop lung cancer in 2013. The incidence among men is higher than among women (76 and 53 per 100,000 respectively, age adjusted.) This is presumably due to the greater past use of tobacco by men over the years. The lifetime risk for men and women combined is about seven percent. That translates to one of every 14 individuals will develop lung cancer sometime during life. The incidence rises substantially with age. About one third of cases develop below the age of 65, one third between 65 and 75 and one third above age 75. The median age of onset is 70 years.  

It is certainly no surprise that smoking is the leading cause of lung cancer; about 80 percent of individuals are current (20 percent) or former (60 percent) smokers. Smoking increases a person’s lifetime risk by a factor of 20 times. Other causes are radon, second hand smoke, asbestos (especially when combined with smoking) and a variety of other environmental factors including arsenic, nickel and chromium. But there are those, especially younger women, who are developing lung cancer despite no known exposures. Lung cancer among both men and women who have never smoked is the sixth leading cause of cancer deaths with about 28,000 dying annually, about the same as prostate cancer caused deaths. 

The incidence of lung cancer has plateaued or even dropped slightly for men but is continuing to rise for women. This reflects the fact that a leveling off of smoking occurred sooner for men than women.

Most lung cancers are diagnosed after it has already spread past the lungs. As a result, surgery alone uncommonly leads to cure and unfortunately most patients are not even candidates for surgery due to local, regional or distant spread at diagnosis. Only about 15 percent of lung cancers are diagnosed when still localized to its pulmonary site of origin; the rest have already spread regionally (22 percent) or distantly (56 percent) with the remainder uncertain as to stage. Compare this to breast cancer or prostate cancer where about 60 percent and 80 percent respectively are localized at diagnosis. This makes for a huge difference in the ability to treat successfully. For women, it means that 73,000 die of lung cancer compared to 40,000 for breast cancer each year despite the fact the age adjusted incidence of the two diseases are 53 per 100,000 and 124 per 100,000, respectively.  

Lung cancer, with its 160,000 annual deaths, accounts for nearly 30 percent of all cancer deaths and is somewhat more than the combined mortality of the next four leading causes of cancer deaths - colon (about 56,000 deaths per year), breast (40,000), pancreas (37,000) and prostate (28,000).  

Survival is generally short with only about 15 percent five-year survivors (5 year survival rates are commonly used measures of successful therapy for cancer). Compare this to the rates of cure for breast cancer (about 90 percent), prostate cancer (nearly 100 percent), and colon cancer (65 percent). Given that the long phase of initiation of smoking to cancer diagnosis is many decades and given that 20 percent of Americans smoke regularly today it is reasonable to forecast that by 2030 the number of cases will increase by about 50 percent for both men and women.  

Categories and Early Detection - Lung cancers are categorized as either small cell or non-small cell lung cancer (SCLC, NSCLC) and the NSCLC are further defined by both their appearance under the microscope as squamous, adeno or large cell and increasingly by genomic analysis. Lung cancer can now be detected early with low dose CT scanning. This means that more individuals are potentially amenable to having their cancer cured. The demonstration that adjuvant chemotherapy for those with possible distant microscopic disease increases the rate of cure for resected NSCLC is a major advance.  But for each cancer lesion detected early by CT scans, 19 benign lesions are also detected which are usually not easily distinguishable from cancerous ones. This results in a dilemma for the patient and the physician – to have an invasive procedure to get a definitive answer or to have regular CT follow-up to see if the lesion progresses, stays stable or regresses. Clearly, new rapid, effective yet less invasive approaches to resolving this dilemma are critical.
Treatment - The opportunity to detect the cancer early means more individuals can be cured with surgical excision or with radiation therapy. Either can be followed by adjuvant chemotherapy for those with a high likelihood of microscopic disease spread. The combination of chemotherapy with radiation therapy has curative potential in locally advanced NSCLC and in limited stage SCLC. New approaches to radiation therapy allow for much higher doses of radiation to the tumor with much less damage to surrounding normal tissues. Current chemotherapy drugs, usually used in combination with one another, have clearly improved the quality of life for patients with more advanced disease, slowed progression of the tumor and created definite a, albeit relatively short, survival advantage.
Of interest in drug therapy today is the advent of “targeted drugs,” ones that inhibit a specific abnormal protein in the tumor cell that is a “driver” of the cancer. These are the products of DNA mutations or DNA rearrangements and are uncovered by genomic analysis. Because the new drugs are quite specific, they affect the tumor but cause proportionally less side effects. Responses among patients with the DNA mutations in their cancers tend to occur rapidly and often with marked regression of the tumor. Unfortunately, relapses eventually occur as resistance develops and the drugs are quite expensive. There is an important proof of principle here that has been accomplished and improvements in targeted treatment are coming fast and furiously.
There is good evidence that the best results with early diagnosis and with effective treatment lies in organizations that have high levels of expertise and utilize a multi-disciplinary approach to care wherein the patients is seen concurrently by surgeon, radiation therapist and medical oncologist to devise the most appropriate approach to care. Added to this, palliative care begun at the time of diagnosis adds to patient comfort, lessens anxiety, and reduces overall costs while improving satisfaction with caregivers and therapies.
With the advent of early diagnosis with CT screening, more effective yet less damaging approaches to radiation therapy, effective chemotherapy, targeted drug therapy for those with driver mutations, all initiated in experienced hands with a multi-disciplinary approach and early institution of palliative care, perhaps the light is now actually beginning to glow at the end of the tunnel for lung cancer patients and their families.
Four follow-on articles will discuss in more depth early diagnosis, treatment options of surgery, radiation and drugs, the use of multi-disciplinary team care and the value of palliative care teams. This five part series first appeared in Medical News Today at http://bit.ly/12bCUqD   

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Praise for Dr Schimpff

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