Category Archives: Lung Cancer

Immunotherapy for Treatment of Advanced Non-Small Cell Lung Cancer

Danielle Shapiro, MD, MPH, Cancer Prevention and Treatment Fund

Immunotherapy could become the new standard of care for initial treatment of advanced lung cancer. Unfortunately, most lung cancer patients have advanced lung cancer when they are diagnosed, meaning the cancer has already spread to other areas of the body, including the brain and liver. Groundbreaking research shows that when added to chemotherapy, immunotherapy could help patients with advanced lung cancers live longer. Cancer experts presented this new research at the 2018 annual American Association for Cancer Research meeting.

This research gives hope, but it is still in the early stages of understanding what treatments work for which patients. As with a lot of new cancer drugs, we don’t yet know how these treatments may affect patients’ quality of life, and whether or not those who live for a longer period of time also have a better quality of life.

When deciding which treatments are best for you or your family member, consider the benefits of these treatments along with their side effects and costs, and not just what is best for advanced lung cancer patients on average.

What is Immunotherapy?

Immunotherapy boosts the body’s ability to kill cancer cells. It also helps the body repair damage caused by chemotherapy treatments, which are often very toxic. A certain class of immunotherapies, called “immune checkpoint inhibitors,” block the protein PDL-1. Cancer cells that make the PDL-1 are able to escape the body’s defenses, which increases the cancer’s ability to grow and spread.

Many of these immunotherapies have been approved as a second or third options to treat advanced lung cancers, only after other treatments have not worked. The results of key clinical studies described below may convince doctors to try these treatments earlier on.

Findings from Clinical Trials

Keytruda (Pembrolizumab)

More than 600 patients with advanced non-squamous, non-small cell lung cancer were studied in the Keynote-189 clinical trial.1 Their cancers did not contain certain gene mutations. About two-thirds of the patients were treated with chemotherapy plus immunotherapy and about one-third were treated with chemotherapy alone. After one year, about 69% of patients treated with immunotherapy plus chemotherapy were alive compared to about 49% of patients treated with chemotherapy alone. On average, patients who were treated with standard chemotherapy lived about 11.3 months. We don’t yet know what the average was for patients who received immunotherapy plus chemotherapy.

Immunotherapy also delayed progression of cancers (also known as “progression free survival”). That is, compared to standard chemotherapy, patients treated with immunotherapy lived for a longer period of time where their cancer either stayed the same or decreased in size. At one year, about 34% of patients who received immunotherapy were alive without progression compared to about 17% of patients treated with chemotherapy alone. On average, patients who received immunotherapy lived about 9 months without progression compared to about 5 months in patients treated with chemotherapy alone.

Nivolumab (Opdivo) plus Ipilimumab (Yervoy)

Almost 2,000 patients with advanced squamous and non-squamous, non-small cell lung cancer were studied in the CheckMate 227 trial.2 Their cancers did not contain certain gene mutations. The researchers used a new experimental grouping system called “tumor mutational burden,” or TMB. Studies show that cancers with a higher TMB are more likely to respond to immunotherapy.

In patients with a high TMB, at one year, about 43% of patients treated with combination immunotherapy plus chemotherapy were alive without progression compared to about 13% of patients treated with chemotherapy alone.

On average, patients with a high TMB who received combination immunotherapy lived about 7.2 months without progression compared to about 5.5 months in patients treated with chemotherapy alone.

However, research does not yet tell us if the patients taking these drugs lived longer. “Overall survival” measures how long a patient lives regardless of whether he/she dies from lung cancer or something else. That’s especially important with cancer treatment, because the treatment itself can be so toxic that it kills some patients. Since the difference in progression-free survival is less than 2 months, there may be no difference in terms of living longer. An added question is whether side effects from the drug are so unpleasant that the patients are not really benefiting.

Atezolizumab (Tecentriq) plus Bevacizumab (Avastin)

About 1,200 patients with advanced non-squamous, non-small cell lung cancer were studied in the IMpower 150 trial.3 The majority of cancers did not contain certain gene mutations, but some did. IMpower 150 studied the benefit of immunotherapy plus bevacizumab. Bevacizumab (Avastin) is a “VEGF inhibitor,” which means it blocks cancer cells from making new blood vessels. Bevacizumab plus chemotherapy is approved by the U.S. FDA for treating advanced non-squamous, non-small cell lung cancer.

At one year, about 37% of patients treated with combination bevacizumab and immunotherapy plus chemotherapy were alive without progression compared to about 18% of patients treated with bevacizumab plus chemotherapy.

On average, patients who received combination immunotherapy and bevacizumab plus chemotherapy lived about 8.3 months without progression compared to about 6.8 months in patients treated with bevacizumab plus chemotherapy. Surprisingly, patients whose lung cancer had certain gene mutations had a similar benefit. Previously, scientists believed that immunotherapy provided no benefit for patients whose lung cancers carried certain gene mutations.

However, research does not yet tell us if the patients taking these drugs lived longer. Since the difference in progression-free survival is only 1.5 months, there may be no difference in terms of living longer. An added question is whether side effects from the drug are so unpleasant that the patients are not really benefiting.

Treatment Side Effects

On average, side effects of immunotherapy were similar to chemotherapy alone. Common side effects include nausea, vomiting, diarrhea, and rash. Serious side effects include a weakened immune system and inflammation of the lungs, liver and the kidneys. In a few cases, patients with inflammation of the lungs died.

The Bottom Line

Immunotherapy has been used for advanced lung cancer when other options have not worked. This new research shows that some of these therapies may be beneficial if used sooner after diagnosis. When deciding which treatments are best for you or your family member, consider the benefits of these treatments along with their side effects and costs, and not just what is best for advanced lung cancer patients on average. Ask the tough questions about evidence of living longer (not just whether you would die of lung cancer) and about quality of life when you talk with your doctor about which treatment options may be right for you.

All articles are reviewed and approved by Diana Zuckerman, PhD, and other senior staff.

References:

Gandhi, Leena et al. Pembrolizumb plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. New England Journal of Medicine. 2018. https://doi.org/10.1056/NEJMoa1801005

Hellmann, Matthew D. et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. New England Journal of Medicine. 2018. https://doi.org/10.1056/NEJMoa1801946

First Line Combination Therapy Improves Progression-Free Survival in Advanced Lung Cancer. European Society for Medical Oncology. 2017. http://www.esmo.org/Latest-News/First-Line-Combination-Therapy-Improves-Progression-Free-Survival-In-Advanced-Lung-Cancer

 

 

Could a Common and Inexpensive Heart Medicine (Beta-Blockers) Help Cancer Patients Live Longer?

Jessica Cote, Cancer Prevention & Treatment Fund

Beta-blockers are drugs that are usually prescribed for high blood pressure (hypertension), irregularities in heart beat (arrhythmias), and to prevent heart attacks after a first heart attack has already occurred. Beta-blockers work by stopping adrenaline and noradrenaline from triggering the body’s “fight or flight” response to stress or danger.  Beta blockers help the body feel more relaxed, lowering blood pressure and increasing blood flow.

Beta-blockers are taken by so many Americans that they are the fifth most widely prescribed class of drugs.[1]  Since they are safe and inexpensive, wouldn’t it be great if they were effective for treating cancer, too?

Doctors and researchers noticed that when cancer patients took beta-blockers because of their heart disease, they tended to live longer than other cancer patients. They decided to study whether beta-blockers significantly improve survival for several different types of cancer.

How Beta-Blockers Affect Different Types of Cancer

Non-Small Cell Lung Cancer

In a study published in Annals of Oncology in 2013, Hong-Mei Wang and colleagues at the MD Anderson Center in Texas reviewed data from 722 patients with non-small cell lung cancer, the most common type of lung cancer.[2] All patients received radiation therapy to treat their lung cancer, but only some took beta-blockers for heart conditions. Almost all the patients in the study had stage III cancer.

The 155 patients taking beta-blockers survived for an average of almost 24 months while the 567 patients not taking beta-blockers survived for an average of about 18.5 months. In addition to living longer, patients taking beta-blockers lived longer without their lung cancer returning (disease-free survival) and without it spreading to other parts of their body (distant metastasis-free survival). The researchers statistically controlled for other factors that could affect survival, such as the patient’s age, the stage of the cancer, the use of aspirin, and use of chemotherapy, to be sure that the beta-blockers were truly helping slow down the cancer.

Breast Cancer

Six studies published since 2010 have examined how beta-blockers affected breast cancer patients who had been treated with beta blockers for heart disease at the same time they were treated for cancer.[3] All six studies found that breast cancer patients lived longer if they were taking beta-blockers.

A new clinical trial is currently underway to find out what happens to women who take beta-blockers specifically as a breast cancer treatment. However, the results are not yet available.

Ovarian Cancer

Elena Diaz and colleagues at Cedars-Sinai Medical Center published a study in 2012 of 248 women who were treated with surgery and chemotherapy for their ovarian cancer.[4] Twenty-three patients took beta-blockers for high blood pressure or other heart conditions during their cancer treatment. The results showed that women who took beta-blockers were more likely to remain free of ovarian cancer after treatment than women who didn’t take beta-blockers (progression-free survival) and less likely to die from ovarian cancer (disease-specific survival). Women taking beta-blocker lived an average of 56 months after cancer treatment while those not taking beta blocker lived an average of 48 months after treatment. In addition, women who took beta-blockers were 54% less likely to die during the more than 12 years that researchers tracked their health, compared to the women who did not take beta blockers.

Pancreatic Cancer

Hussein Al-Wadei and colleagues at the University of Tennessee published a study in 2009 that showed how beta-blockers were able to halt the progression of pancreatic cancer in animals.[5]  Research is needed to determine if beta-blockers is effective for pancreatic cancer in humans.

Why Might Beta-Blockers Help Cancer Patients?

Adrenaline and noradrenaline, the two neurotransmitters that stimulate the “fight or flight” response, probably trigger tumor growth. When beta-blockers halt the activity of these neurotransmitters, they may therefore help reduce the growth of cancerous tumors.

When the FDA makes a decision to approve a drug, it is always for specific symptoms or diseases, and the risks and benefits for that specific treatment is what the FDA considers. Although generally safe, beta-blockers can cause fatigue, headache, upset stomach, constipation, diarrhea, dizziness, cold hands, shortness of breath, and trouble sleeping.   For that reason, it is not a good idea to use beta-blockers to treat cancer unless there is clear evidence that they are likely to work — that the benefits outweigh those risks.  And, that is the reason that the breast cancer study that is now underway only includes beta blockers for 2 days before and 3 days after the cancer surgery.

In addition to being approved by the FDA to control blood pressure and heart disease, beta-blockers are also approved for preventing migraines, treating essential tremor (ET) in the head, arms and legs, and, as eye drops to treat glaucoma.  Doctors prescribe beta blockers for other reasons , but  taking medicines for non-approved uses can be risky. If a use is not approved, it often means that there is no conclusive evidence showing that the benefits outweigh the risks.  However, it sometimes means that the companies making the drug don’t think FDA approval for the new use will benefit the company financially.  The latter is especially true for drugs that are already on the market and inexpensive, such as beta-blockers.

The Bottom Line

  • Beta-blockers are usually used to treat heart conditions like high blood pressure and an irregular heart beat. New research has shown that these inexpensive drugs may help cancer patients live longer.
  • More research is needed to know which beta-blockers work best when added to cancer surgery, radiation, or chemotherapy, and for which cancers.
  • If you already take beta-blockers for a heart condition, they may provide keep taking them if you are also diagnosed with cancer. If you don’t take beta-blockers but are diagnosed with non-small cell lung cancer or early breast cancer, you may want to ask your doctor whether to take beta-blockers for two days before and three days after your cancer surgery.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

References

  1. Consumer Reports, Best Buy Drugs: “Using Beta-blockers to treat: High Blood Pressure and Heart Disease.” Updated March 2011. https://www.consumerreports.org/health/resources/pdf/best-buy-drugs/CU-Betablockers-FIN060109.pdf
  2. Wang HM, Liao ZX, Komaki R et al. Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy. Annals of Oncology 2013.
  3. Barron TI, Sharp L, Visvanathan K. Beta-adrenergic blocking drugs in breast cancer: a perspective review. Therapeutic Advances in Medical Oncology 2012; 4(3):113-125.
  4. Diaz ES, Karlan BY, Andrew JL. Impact of beta blockers on epithelial ovarian cancer survival. Gynecologic Oncology 2012; 127(2):375-378.
  5. Al-Wadei HAN, Al-Wadei  MH, Schuller HM. Prevention of pancreatic cancer by the beta-blocker propranolol. Anticancer Drugs 2009; 20(6):477-482.

Palliative Care and Pain Management for Lung Cancer and Other Serious Illness

Jessica Becker, Brandel France de Bravo, MPH, and Diana Zuckerman, PhD, Cancer Prevention & Treatment Fund

Palliative care is often misunderstood as meaning a patient will not get “real treatment.”  That is not accurate.  In fact, patients who have palliative care often live longer as well as having a better quality of life.

A ground-breaking study published in the highly respected New England Journal of Medicine shows that palliative care, which helps manage symptoms and control pain, is a very effective addition to standard cancer treatment for people with metastatic non-small-cell lung cancer.[1] The patients who had palliative care, which was offered as soon as they were diagnosed, suffered less depression, were less likely to receive aggressive end-of-life care, and lived longer.

Non-small-cell lung cancer is the most common form of lung cancer, and metastatic lung cancer means that the cancer was caught very late (Stage 4) and has spread beyond the lungs and lymph nodes to other organs like the brain, bones, or heart. When lung cancer spreads like this, it is inoperable and incurable. Various treatments have been found to prolong life by months and in some cases years, but these treatments have many unpleasant/serious side effects, involve hours of chemotherapy or radiation treatment on a regular basis, and do not necessarily provide relief from the many debilitating and painful symptoms of late-stage lung cancer.

A different study, published in a medical journal in 2014 focused on patients with various serious diseases who were having trouble breathing.  Half the patients received “breathlessness support services” for 6 weeks and the other half did not.   The support services included palliative care, respiratory medicine, physiotherapy, and occupational therapy.  Six months later, the patients who had received the support services had less trouble breathing and were more likely to still be alive.  The services helped all patients breathe more easily but only improved survival for patients with COPD or non-cancerous lung disease, not for patients with cancer. [2]

A third study, which analyzed 16 studies of palliative care found that patients who had at least one consultation for palliative care spent an average of 4.4 fewer days in the intensive care unit. [3]

What Is Palliative Care?

Palliative care focuses on helping relieve the patient’s pain, offering psychological support to the patient and family, and providing the patient and family with information they may need to adapt to life with a serious illness and make relevant decisions. This kind of care enables patients with late-stage cancer and other debilitating diseases to live as comfortably as possible during the time they have left and spend meaningful time with their families.

Some people mistakenly equated end-of-life palliative care with ending people’s lives through so-called “death panels.”  However, this new research is an example of how palliative care can improve the quality of life and even prolong life for patients who are very ill.

Many doctors do not feel comfortable discussing end-of-life issues or advance care planning.  However, now that palliative care is often reimbursed by Medicare or private insurance, patients are more likely to consider it.

Patients Should Not Have to Choose Between Comfort and Treatment

The study of lung cancer patients published in the New England Journal of Medicine deserves special attention because of its implications for many patients with fatal diseases.

The study patients did not have to choose between cancer treatment and palliative care. Half of the 151 patients with non-small-cell lung cancer at Massachusetts General Hospital were randomly assigned to get cancer treatment and the other half were given palliative care in addition to cancer treatment. The patients that were assigned to receive cancer treatment and palliative care reported a better quality of life (measured by patient’s scores on three different quality-of-life gauges) while patients receiving cancer treatment alone experienced a decrease in their quality of life.

The patients who were offered palliative care plus cancer treatment had fewer symptoms of depression. Only 16% showed symptoms of depression while 38% of patients getting only standard cancer treatment had symptoms of depression.

More patients in the group assigned only to standard cancer treatments received aggressive end-of-life care, including chemotherapy, compared to patients who received palliative care plus cancer treatment.  Aggressive end-of-life care was defined as chemotherapy during the last two weeks of life; no hospice care; or hospice care for only the last few days of life. Hospice care is a form of palliative care for those who are terminally ill and near death, and can be provided at home or in a hospice. Aggressive end-of-life care can be very expensive. Even when health insurance covers a significant portion of the medical expenses, it can be very costly for a patient and the patient’s family.

Although the patients receiving palliative care plus standard treatment were less likely to continue with aggressive treatment, they lived about 2 months longer than the patients receiving only standard cancer treatment alone. In addition to showing that patients live longer and better when given palliative care, the study suggests that treatment that helps the whole patient and doesn’t just focus on fighting the cancer may also be more cost-effective.

The researchers explain their findings in several ways:

  • The improvements in quality of life, such as fewer symptoms of depression, may have helped patients live longer;
  • By pursuing less aggressive treatment, the patients enrolled in palliative care may have benefited from fewer toxic side effects which may have increased their will to live;
  • Palliative care patients got earlier referral to hospice programs, and preparing for death in a supportive environment may have helped prolong life.

While this specific study only focused on the use of palliative care in conjunction with standard cancer treatment for patients with metastatic non-small-cell lung cancer, the two other studies described in this article show that patients with other kinds of metastatic cancer or other terminal diseases might also benefit from palliative care plus standard treatment. This deserves further study.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

References

  1. Temel J, Greer J, Muzikansky A, Gallagher E, Admane S, Jackson V, Dahlin C, Blinderman C, Jacobsen J, Pirl W, Billings J, Lynch T: Early Palliative Care for Patients with Metastatic Non-Small-Cell Lung Caner. New England Journal of Medicine 2010; 363:733-742.
  2. Higginson IJ,  Bausewein C, Reilly CC, Gao W, Gysels M, Dzingina M,  McCrone P, Booth S,  Jolley CJ, Moxham J: An integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness: a randomised controlled trial. Lancet Respiratory Medicine Journal 2014. 979-87. http://www.ncbi.nlm.nih.gov/pubmed/25465642?dopt=Abstract
  3. J. Brian Cassel, Kathleen Kerr, Steven Pantilat, Thomas Smith,  Donna McClish: Does Palliative Care Consultation Reduce ICU Length of Stay? Journal of Pain and Symptom Management 2011. 41, 191-192. http://www.jpsmjournal.com/article/S0885-3924%2810%2900752-9/fulltext

Lung cancer is a women’s health issue

By Susan Dudley, PhD, Renee Y. Carter, MD, Tiffanie Hammond, and Amrita Ford, MA

Risk Factors for Lung Cancer
Non-Smokers and the Possible Role of Estrogen
Surviving Lung Cancer
Racial and Ethnic Differences in Lung Cancer
Symptoms of Lung Cancer
Lung Cancer Detection and Treatment
Advances in Treatment but They are High-Cost and Only for Some Patients
Funding for Lung Cancer Research

Lung cancer is the #1 cause of cancer death among women in the United States. Lung cancer used to be thought of as a man’s disease, but women now account for almost half of new cases and deaths from lung cancer. In 2014, 48% of the almost 216,000 people diagnosed with lung cancer were women, and 45% of the 155,526 who died from lung cancer were women.1

Lung cancer deaths in women began quickly rising in 1960, and by 1987, the number of female deaths from lung cancer exceeded the number of deaths from breast cancer. Today the number of deaths in women from lung cancer surpasses those from all gynecological cancers combined.2 While the rate of lung cancer deaths among men has been steadily decreasing since the 1990s, the lung cancer death rate among women did not start to go down until a decade later (2003-2007).3 The decline of lung cancer deaths among women, however, may not be as rapid as it has been in men: women born around 1960 with a high rate of smoking are just now entering the age when lung cancer diagnosis is most common.

Risk Factors for Lung Cancer

Everyone knows that smoking is the leading cause of lung cancer. It is responsible for 90% of lung cancer deaths in men and 80% in women. Beginning in the 1940’s during World War II, smoking became more acceptable for American women.4 As more women began to smoke, the number of deaths from lung cancer increased very dramatically among women — by more than 600% between 1950 and 1997. When a woman stops smoking, her risk of developing lung cancer decreases, but not as much as many women may think. Twenty years after stopping, the risk of developing lung cancer drops only by half. In addition, exposure to second-hand smoke at home, work, or other environments—including childhood exposures—can cause lung cancer in women who have never smoked themselves.5

Additionally, exposure to radon, arsenic, asbestos, radiation, air pollution, some organic chemicals, such as benzene, and tuberculosis, also increase the risk of developing lung cancer.

Non-Smokers and the Possible Role of Estrogen

Although smoking increases the risk of lung cancer dramatically, 1 in 5 women diagnosed with lung cancer have never smoked, whereas among men who develop lung cancer, only 1 in 12 have never smoked.46 Of all the types of lung cancer, women are more likely to develop adenocarcinoma, a type of non-small cell lung cancer (NSCLC), which is also the type of lung cancer more commonly found in non-smokers.

It is unclear why non-smoking women are at greater risk for developing lung cancer than non-smoking men. Studies indicate that biological and genetic differences between men and women play a role in susceptibility to lung cancer and the risk of dying from it. Some research shows that estrogen, a hormone found in both men and women but much higher in women, may help certain lung cancer cells to grow and spread throughout the lungs. For example, a 2009 study based on the Women’s Health Initiative showed that post-menopausal women who took estrogen and progesterone combined hormone therapy had an increased risk of dying from lung cancer, regardless of whether they had never smoked, stopped smoking, or were currently smoking (although current and former smokers were at the highest risk for death).7 A 2010 study indicated that post-menopausal women who took hormone therapy for more than 10 years were at an increased risk of developing lungcancer.8  In 2011, a study showed that women who take estrogen-blocking medication like tamoxifen to prevent a recurrence of breast cancer also reduce their risk of dying from lung cancer.9 For both the 2010 and 2011 studies, the link between hormones and lung cancer were maintained regardless of the person’s smoking status. For more information about hormone therapy and lung cancer, read Lung Cancer and Hormone Therapy: Bad News for Former and Current Smokers.

Surviving Lung Cancer

Women are nearly as likely as men to be diagnosed with lung cancer, but on a more positive note, they tend to survive longer than men with the disease. Women generally live longer than men at every stage of lung cancer, regardless of when they were diagnosed, the type of lung cancer they had, or how they were treated.1011 Studies have shown that women with non-small cell lung cancer (NSCLC) have a greater 5-year survival following partial removal of the lung (resection) than men.121314 Women with NSCLC who are treated with chemotherapy prior to removal of the tumor also have better survival rates than men.15 Furthermore, women with advanced lung cancer of any type who undergo chemotherapy survive longer than their male counterparts.16

Why do women with lung cancer live longer than men? No one is really certain. One reason may be that women tend to notice symptoms and go to the doctor earlier than men, allowing the disease to be caught at an earlier stage when the cancer is local (still in the lung) and can be completely removed.17 However, even when researchers control for this and other differences between men and women, women still live longer following surgery.13 For both women and men with lung cancer, complete removal of an entire lobe of the lung (lobectomy) results in higher survival rates than only partial removal of the lung. Younger patients and patients with smaller tumors are more likely to survive lung cancer than those who are older or have larger tumors, regardless of sex.14

Racial and Ethnic Differences in Lung Cancer

The incidence of lung cancer among African American women is about the same as white women yet smoking rates among African American women are lower.18 In 2007, about 16% of African American women smoked, while the rate for white women was about 20%.19 Similarly, African-American men smoke less than white men yet have higher rates of lung cancer. Is there a genetic difference that places African Americans at higher risk? Or are African-Americans exposed to other lung cancer causing bacteria and chemicals that increase their risk?

No one knows the answer yet but there are several explanations for why African Americans—men and women—are more likely to die from lung cancer than white men and women. Even African American women who have never smoked have higher death rates from lung cancer than white women who have never smoked.20 Most experts believe African Americans with lung cancer don’t live as long because they don’t have the same access to health care. For instance, they are less likely to have insurance coverage which could impact diagnosis and treatment options.21 They are less likely to receive timely care and may not receive the most effective treatment for their type of lung cancer.22 One study found that African American patients underwent partial surgical removal of the lung less frequently than white patients. 23 Other factors that may contribute to the lower survival rates of African American lung cancer patients include differences in lung function,20 provider biases,24 inadequate physician-patient communication,25 distrust of physicians and the health care system,26 and a greater likelihood of refusing surgery.27 For more on African Americans and lung cancer, read here.

After African American and white women, native Hawaiian women have the highest incidence of lung cancer, while Hispanic and Japanese women have the lowest rates.20 Unlike other racial and ethnic groups where the incidence of lung cancer in women has increased over time, rates have actually declined among Hispanic women (who are more likely to be non-smokers than African Americans, whites or native Hawaiians): they decreased by 1.5% every year from 1994 to 2003.28 Despite the decline of lung cancer in both men and women, lung cancer remains the leading cause of cancer death among Hispanic men and the second leading cause of cancer death among Hispanic women.

Symptoms of Lung Cancer

The most commonly recognized symptoms of lung cancer include:

  • persistent cough, coughing that wakes you up at night, and/or coughing up blood
  • wheezing and/or shortness of breath
  • chest pain
  • hoarseness
  • swelling of the face and neck
  • loss of appetite and/or unexplained weight loss
  • unusual tiredness
  • recurring pneumonia or bronchitis

Lung Cancer Detection and Treatment

While survival rates for many cancers have improved substantially over the last 30 years, little progress has been made in the survival rate for lung cancer. For example, between 1974 and 2007, the 5-year survival rate for breast cancer increased from 75% to 89% and the 5-year survival rate for prostate cancer increased from 67% to 99%. In contrast, the 5-year survival rate for lung cancer increased from 13% to just under 16% during the same time period.

What would be needed in order for the survival rates for lung cancer patients to parallel that of breast, prostate or cervical cancers? The main problem is that by the time most women are diagnosed with lung cancer, it has already spread to other organs, making a cure extremely unlikely. Pap smears and colonoscopies, for instance, make it possible to diagnose and remove pre-cancerous cells on the cervix or polyps in the colon before they can develop into cervical cancer or colon cancer or spread elsewhere in the body. And while better survival rates for women with breast cancer are mostly attributed to improvements in treatment, mammogram screenings have helped some women by detecting their breast cancer at earlier stages than before, when surgery, radiation, or chemotherapy have an even better chance of eliminating the disease. Earlier diagnosis and more effective treatments, therefore, will be necessary to improve the survival rate of lung cancer.

The National Lung Screening Trial, which started in 2002, evaluated the use of chest x-rays and low-dose computed tomography (low-dose CT scans) for early detection of lung cancer in men and women who were heavy smokers. Each randomized group was screened annually for 3 years. Researchers found that using low-dose CT scans reduced lung cancer deaths by 20% in the high-risk population. Compared to standard x-rays, CT scans may be more effective in detecting nodules and tumors. Based on a 2011 report of the trial, low-dose CT screening could potentially increase the 5-year lung cancer survival rate to 70% if it allowed lung cancer to be detected in its earliest stage (stage 1A), when the tumor is still relatively small, still in the lung, and can be removed easily through surgery.29303132

Although no U.S. public health agency has recommended screening for lung cancer, in January 2013 the American Cancer Society (ACS) did so for the first time, saying that annual screening with low dose CT scans “could save many lives.”33 ACS has recommended that people at highest risk for lung cancer, as defined by the National Lung Cancer Trial, have a discussion with their doctor about the benefits and risks of annual screening. They advised doctors to have this conversation only with patients who match the profile of the people who were enrolled in the National Lung Cancer Screening Trial: current and former smokers who are 55 to 74 years old and have a 30-pack-year history of smoking (20 cigarettes a day for 30 years, 40 cigarettes a day for 15 years, and so on. To calculate your pack years, visit http://smokingpackyears.com/). If the patients are former smokers, they should have quit within the last 15 years.  Doctors should discuss screening with patients only if low dose CT scans and high quality treatment are available in their area, and only if the patient seems healthy and able to undergo treatment in the event that cancer is found.  For all other patients, “there is too much uncertainty regarding the balance of benefits and harms …”

Three other organizations have issued their own slightly different guidelines.  The National Comprehensive Cancer Network has two definitions of high risk: the one used by the American Cancer Society and one that includes people as young as 50 and as old as 79 with only a 20-pack-year history—provided they have one other risk factor for lung cancer such as a family history, Chronic Obstructive Pulmonary Disease (COPD), or exposure to radon.  Given the close link between COPD and lung cancer, the Network’s screening criteria could potentially find more cases of lung cancer than the 30-pack criteria. (For more info on COPD, see Chronic Obstructive Pulmonary Disease and Lung Cancer.) The American College of Chest Physicians and the American Society of Clinical Oncology also have guidelines.  Only time will tell which guidelines work best, but any of these guidelines make it more likely that insurance companies will pay for screening. As a result of the National Lung Cancer Screening Trial, the U.S. Department of Veterans Affairs is starting to implement a screening program using CT scans for veterans at high risk.  However, most government health programs, such as Medicare and Medicaid, do not usually reimburse for lung cancer screening and might not do so until a public health agency has issued guidelines.

Unfortunately, CT scans are not a great solution for finding and diagnosing lung cancer in people who don’t have symptoms and aren’t at high risk. Low-dose CT scans have been shown to produce a high percentage of false positive results (people who the scan says have an abnormality when they don’t have cancer), which can lead to unnecessary lung biopsies. Since lung biopsies can be harmful, low-dose CT as a screening method isn’t useful for the general population. This is unfortunate because women who didn’t smoke are at higher risk than men who didn’t smoke, as are men and women exposed to years of second-hand smoke, but no screening has been found to be appropriate for them. For more information about screening, read Lung Cancer: Who Is at Risk and Can They be Screened?

Advances in Treatment but They are High-Cost and Only for Some Patients

Historically, lung cancer treatments have not been very effective. For instance, erlotinib (trade name Tarceva), which is taken as a pill, extends survival in patients with non-small cell lung cancer by only about 2 months on average and costs anywhere from $2,000 to $5,000 a month.343536 Patients usually take Tarceva after having already undergone chemotherapy, and many use it as a maintenance therapy to prevent further cancer progression and to shrink tumors that are already present. Patients stay on Tarceva for as long as it appears to be having an effect (developing a rash is considered a good sign) and scans show that the cancer is stable. Not only is Tarceva expensive but it doesn’t benefit everyone with lung cancer: it works best in patients who have never smoked or who have a specific gene mutation (EGFR mutation).36[37 Tarceva acts by inactivating the signal in the mutated EGFR gene that makes lung cancer grow.

New targeted treatments that interfere with specific molecules involved in tumor growth and progression and which promote cancer cell death are showing promise in the fight against lung cancer. In August of 2011, the Food and Drug Administration fast-tracked approval for crizotinib (trade name Xalkori) for use in a small subset of lung cancer patients with late-stage, non-small cell lung cancer (NSCLC) who express a rearrangement of the anaplastic lymphoma kinase (ALK) gene. Rearrangement of this gene leads to cancer growth and occurs in 1-7% of NSCLC patients. Xalkori was approved with an accompanying diagnostic test to determine if a patient has the abnormal ALKgene rearrangement.38 Based on an October 2011 study published in Lancet Oncology, the overall survival rate for Xalkori after 1 and 2 years was 74% and 54%, respectively. The recommended dose for Xalkori is 250mg twice daily and the drug costs about $9,600 per month or about $115,000 a year.39 Targeted treatments tend to be very expensive because they are usually taken by a very small number of patients who have limited treatment choices.

Funding for Lung Cancer Research

Far too many women and men are dying of lung cancer every year. Could an increase in research funding result in better screening, earlier diagnosis, more effective treatments, longer survival, and overall lower mortality for patients diagnosed with lung cancer? We believe the answer is “yes.”

The National Cancer Institute is the major source of cancer research funding in the U.S. Comparisons of NCI funding for various types of cancer in 2010 are shown below and clearly show that lung cancer research is under-funded in proportion to how deadly it is for so many people.140 Between 2003 and 2007, NCI funding for lung cancer actually decreased while funding for breast cancer increased.41 The same inequities are seen in funding for prevention. In the Centers for Disease Control and Prevention (CDC) 2008 budget, about $201M was allocated for breast cancer while $104M was allocated for smoking cessation programs (and not lung cancer specifically).42

Total NCI Funding (in millions)

New Cases Diagnosed
(male & female)

Funding per New Case

Overall Deaths

Funding per Patient Death

Lung Cancer

$282.0

221,130

$1,275

156,940

$1,797

Breast Cancer

$631.2

232,620

$2,713

39,970

$15,792

ColonCancer

$270.4

101,340

$2,668

49,380

$5,476

Prostate Cancer

$300.5

240,890

$1,247

33,720

$8,912

 

Many researchers and advocates point to the stigma associated with lung cancer as a reason for why the disease is under-funded.43 Since smoking is associated with the majority of lung cancer cases, many people believe lung cancer patients are responsible for their health problems and therefore not deserving of the same sympathy and research investments that patients of other deadly diseases receive. This attitude may also extend to clinicians who care for lung cancer patients. One study found that physicians were less likely to send their lung cancer patients with advanced stages of the disease to an oncologist than their breast cancer patients.44 Breast cancer patients were also more likely to be referred for further therapy where lung cancer patients were referred for only symptom control. We know now that more complex factors other than cigarette smoking contribute to lung cancer and the lack of funding over the years has hindered researchers from fully understanding why and how this disease progresses in different populations.

So how can we persuade the federal government to fund more lung cancer research? Some think legislation is needed.

In 2008, Congress approved the Peer Reviewed Lung Cancer Research Program which was the first time in history that federal funding was allocated specifically for the study of lung cancer. However, the program is funded by the Department of Defense to study early detection and disease management specifically in military men and women at high risk for lung cancer.

The Lung Cancer Mortality Reduction Act of 2011 is a bipartisan bill currently in Congress which aims to reduce lung cancer mortality by 50% by 2020.45 The bill, first introduced in 2008, calls on the cooperation of the Department of Health and Human Services, Department of Defense, and Veterans Affairs to meet that goal and develop a coordinated plan that addresses the prevention, early detection, and treatment of lung cancer. It would require the National Cancer Institute to review and prioritize research grants related to lung cancer, the Food and Drug Administration to establish quality standards and guidelines for facilities that conduct computed tomography screening for lung cancer, and the Centers for Disease Control and Prevention to establish a Lung Cancer Early Detection Program which would provide low-income, uninsured, and underserved populations at high risk for lung cancer with access to early detection services. For more information and to support this important legislation in the fight against lung cancer, visit http://www.opencongress.org/bill/112-h1394/show.

Can Taking Fish Oil Supplements Help Lung Cancer Patients Undergoing Chemotherapy?

Katherine Ip, Cancer Prevention and Treatment Fund

Fish oil is a well-known dietary supplement that is likely to reduce the risk of getting heart disease. More research is needed to find out if it may also reduce high blood pressure, menstrual pain, the risk of stroke, and the symptoms of arthritis, bipolar disorder and ADHD.[1]

Some studies have suggested that fish oil and the omega-3 fatty acids it contains might also help improve the effectiveness of chemotherapy for cancer patients, while reducing the bad side effects.  The types of chemotherapy tested include anthracyclines, cisplatin, irinotecan, and alkylating agents. Only two studies were done on humans, and the others were done on animals or cancer cells in test tubes.[2]

Fish Oil Supplements, Lung Cancer, and Chemotherapy

Late-stage non-small cell lung cancer (NSCLC) is usually treated with chemotherapy, but chemotherapy is often ineffective.[3] And, the current treatments have very unpleasant side effects that can severely harm the quality of a patient’s life, so researchers are always looking for ways to minimize damage to the body’s healthy cells while still attacking cancer cells with full force.[4]

In 2011, a very small study by researchers from Canadian Universities looked at whether fish oil could help chemotherapy patients with non-small cell lung cancer (NSCLC) that has spread to the lymph nodes or to other parts of the body (Stage III and Stage IV).[5] Patients with these late stages of lung cancer, on average, only live about 2 years after being diagnosed.

Since the cancer had already spread, all the patients were given the same palliative chemotherapy, aimed at reducing cancer symptoms and improving the patient’s quality of life, rather than curing the patient. Researchers only included lung cancer patients who had never had chemotherapy before. Only 15 of the patients were given fish oil and 31 were not. When they started their chemotherapy, the patients in the group taking fish oil had a choice of taking four capsules a day (each with 1 gram of fish oil), or 7.5 milliliters of actual fish oil, which provides the same amount of omega-3 fatty acids.

How did Fish Oil Affect Survival?

The patients who took fish oil responded much better to chemotherapy than those who didn’t. Their tumors shrank more in size or shrank more quickly, and they were almost twice as likely to be alive a year after treatment compared to the patients who didn’t take fish oil (60% compared to 39%). These results held true regardless of how old the patient was, whether the patient was a man or woman, and how much muscle mass the patient had.  The latter is important because patients with lower muscle mass tend to suffer from more negative side effects from chemotherapy.

Patients who did not take fish oil were more likely to have their cancer get worse after two cycles of chemotherapy than patients who took fish oil. And, more of the patients who took fish oil were able to complete all of their planned chemotherapy, because they experienced less side effects for the same levels of chemotherapy as patients who did not take fish oil. Since the patients who took fish oil felt well enough to receive more cycles of chemotherapy, their tumors also shrank more and they lived longer.

Did Fish Oil Affect Quality of Life?

When chemotherapy kills the body’s healthy cells (think of it like “friendly fire”), it can cause side effects such as nausea, vomiting, and constipation, and it also lowers the body’s ability to fight infection. Since the patients taking fish oil were able to complete more cycles of chemotherapy, we would expect them to have worse side effects. Instead, the side effects listed above were about the same for patients taking fish oil and those that did not. The researchers suspect that the reason why is that fish oil protected the healthy cells from the chemotherapy, but not the cancer cells. Their findings are consistent with a study where mice with lung cancer responded better to treatment when fed fish oil.[6] They are also consistent with a study in which breast cancer patients responded better to chemotherapy when their breast tissue had a higher concentration of DHA, one of two fatty acids found in fish oil.[7]

Is There a Catch?

The study of fish oil and lung cancer included only 31 patients not taking fish oil and 15 patients taking fish oil. Such a small study does not provide adequate evidence, but it does mean more research is warranted.

The Bottom Line:

In this one small study, taking fish oil supplements appears to help late stage lung cancer patients tolerate their chemotherapy better so that they can get the most benefit from it.  And, fish oil is inexpensive and has no known risks. More research is needed to find out if fish oil is usually effective for lung cancer patients and possibly other cancer patients. Since fish oil is very safe, if you or someone you know is about to start chemotherapy, it’s probably a good idea to start taking fish oil supplements right away.

References:

  1. Natural Medicines Comprehensive Database. Omega-3 Supplements: Medline Plus supplements. 2012. Available at: http://www.nlm.nih.gov/medlineplus/druginfo/natural/993.html. Accessed February 4, 2013.
  2. Bougnoux P, Hajjaji N, Ferrasson MN, Giraudeau B, Couet C, Le FO. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial. Br J Cancer. 2009; 101: 1978-1985.
  3. Pujol JL, Barlesi F, Daures JP. Should chemotherapy combinations for advanced non-small cell lung cancer be platinum-based? A meta-analysis of phase III randomized trials. Lung Cancer. 2006; 51: 335-345.
  4. Carney DN. Lung cancer–time to move on from chemotherapy. N Engl J Med. 2002; 346: 126-128.
  5. Murphy RA, Mourtzakis M, Chu QSC, Varacos VE, Reiman T, & Mazurak VC. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer.
  6. Yam D, Peled A, Shinitzky M. Suppression of tumor growth and metastasis by dietary fish oil combined with vitamins E and C and cisplatin. Cancer Chemother Pharmacol. 2001; 47: 34-40.
  7. Bougnoux P, Germain E, Chajes V, et al. Cytotoxic drug efficacy correlates with adipose tissue docosahexaenoic acid level in locally advanced breast carcinoma. Br J Cancer. 1999; 79: 1765-1769.

Chronic Obstructive Pulmonary Disease (COPD) and Lung Cancer

Tiffanie Hammond, Amrita Ford, MA, Brandel France de Bravo, MPH, and Jessica Cote, Cancer Prevention and Treatment Fund

What is COPD, and What Causes It?
Gender Differences in COPD
How is COPD Diagnosed?
Not Everyone Defines COPD the Same Way
The Controversy Surrounding COPD Screening
Treatment Options and Prognosis
What Does This Have To Do with Lung Cancer?
How are COPD and Lung Cancer Linked?
Could COPD Patients be the Best Candidates for Lung Cancer Screening?
You Think You Might Be at Risk for COPD and/or Lung Cancer. Now what?

 

Did you know that more than half of all people with lung cancer have chronic obstructive pulmonary disease (COPD)? In fact, depending on the way COPD is diagnosed, 50-90% of lung cancer patients suffer from COPD.[1] Some people with lung cancer don’t find out that they have COPD until they’ve already been diagnosed with cancer. Could testing for COPD be a way of catching lung cancer earlier? We know that smokers with COPD are much more likely to develop lung cancer than smokers without it, but what about people who don’t smoke—can they get COPD, and if so, are they also at increased risk of developing lung cancer?

If you’ve never touched a cigarette in your life and have lung cancer, there is a chance it’s because you have COPD. A 2008 study published in the Archives of Internal Medicine estimated that COPD was responsible for 10% of lung cancer cases among people who don’t smoke.[2] COPD is the third leading cause of death in the U.S., and there are over 12 million people currently diagnosed with the disease.[3] Experts believe that the real number of people with COPD is twice that.[4]

While cigarette smoking is the leading cause of COPD, people who have never smoked make up 20% or more of all COPD cases[5] Interestingly, 4 out of 5 non-smokers with COPD are women. People who never smoked make up approximately 15% of diagnosed cases of lung cancer, and as with COPD, the majority of lung cancer patients who never smoked are women.  One out of 5 women diagnosed with lung cancer have never smoked whereas in men who develop lung cancer, only 1 out of 12 have never smoked.[6,7]

What is COPD, and What Causes It?

COPD is a progressive disease that causes airflow obstruction, making it more difficult for a person to breathe. COPD can take the form of chronic bronchitis or emphysema. Chronic bronchitis is the inflammation and scarring of the lung’s bronchial tubes, or air passages, which results in frequent coughing and the formation of thick mucus in the airways.  In emphysema, the walls of the tiny air sacs in the lungs are damaged and destroyed over time which leads to reduced gas exchange in the lungs.  Most people with COPD have a combination of both chronic bronchitis and emphysema.

COPD can’t be cured but its symptoms can be managed and controlled through various treatments, including medicines and pulmonary rehabilitation. Pulmonary rehabilitation includes exercise training, counseling, breathing strategies, and energy conservation techniques.

The leading cause of COPD is smoking;[8] smokers’ risk for the disease ranges from 35% to as high as 50%.[9] Second-hand smoke is also a major risk factor. A 2012 Norwegian study suggests that childhood exposure to tobacco smoke doubles the risk of girls developing COPD as adults.[10] Men exposed to tobacco smoke as children did not share the same heightened risk as women, but early exposure to tobacco smoke increases the risk of certain COPD symptoms in men, such as chronic cough. Other COPD risk factors include age, environmental and occupational exposures to pollution, dust and chemical fumes, a family history of COPD, a prior diagnosis of asthma, cooking with fire without proper ventilation, and in rare cases, having a genetic condition called alpha-1-antitrypsin (AAT) deficiency. AAT is a naturally occurring protein that protects the lungs from damage. People who don’t have enough of the protein are more likely to develop emphysema.[11]

Gender Differences in COPD

From 1998-2009, more women were diagnosed with COPD than men. Although overall death rates from COPD were lower in women than men, death rates in men decreased during this time period while death rates among women stayed the same.[12] No one is certain why this is, but there are differences in the way men and women are diagnosed and treated for COPD that may contribute to the disparity.

Even when they have the same symptoms, women with COPD are often misdiagnosed initially as having asthma, are less likely to be referred to specialists, and are therefore less likely to be treated quickly, accurately, and effectively for COPD compared to men. Women with COPD also report more severe symptoms and experience a lower quality of life. Women who are dependent on oxygen have a 50% increased risk of death from COPD as opposed to men on oxygen.[13]

How is COPD Diagnosed?

COPD is estimated to be undiagnosed or misdiagnosed in about 50% of the 24 million men and women estimated to have COPD in the U.S. Many people are not aware they have it until symptoms such as coughing, shortness of breath (dyspnea), increased mucus production, and wheezing develop slowly over time. Many patients fail to report symptoms to their doctors because they assume these symptoms are a normal part of aging and are unaware of the symptoms of COPD. Many smokers just assume that the symptoms they are experiencing are due to smoking and not to something more serious.[14] However, diagnosing patients with COPD from symptoms alone leads to errors of overdiagnosis. Studies have shown that the best method for diagnosing COPD is spirometry, which is a common and inexpensive office test that measures lung capacity. Spirometry can detect COPD even before symptoms become apparent and can be used to track the progression of COPD and determine if a treatment is working. Other methods used to diagnose COPD include chest x-rays, computed tomography (CT) scans, listening to the lungs with a stethoscope, and arterial blood gas tests that determine oxygen and carbon dioxide levels in the blood. In general, spirometry is used to detect airflow obstruction and low-dose CT is used to diagnose emphysema. Spirometry is usually used for standard COPD screening because it’s safe and inexpensive, but CT screening is sometimes necessary to diagnose people with emphysema who don’t also have airflow obstruction.

Over the years, various evidence-based guidelines for the prevention, diagnosis and management of COPD have been developed to assist healthcare professionals in their management of the disease. In 2001, the Global Initiative for Chronic Obstructive Lung Disease (GOLD), in conjunction with experts from the National Heart, Lung, and Blood Institute and the World Health Organization, published guidelines for physicians based on the latest research and recommendations.[15] The GOLD guidelines were updated in 2006 and again in 2011. Professional societies like the American Thoracic Society, the European Respiratory Society, and others have also published their own COPD guidelines, all with the same goal of educating healthcare professionals and improving COPD outcomes.[16]

Despite the availability of these guidelines for COPD, one of the most significant barriers to diagnosing COPD is a lack of knowledge among primary care professionals. A survey conducted in 2008 by Barbara Yawn and Peter Wollan at Olmsted Medical Center found that fewer than half of primary care professionals (family physicians, nurse practitioners and physicians assistants) knew about or used accepted guidelines for diagnosing COPD. A little over 20% reported using no COPD guidelines, 10% were unaware of what the current COPD guidelines are, 11% admitted using guidelines for asthma to diagnose and treat COPD, and only 7% tested for alpha-1-antitrypsin deficiency regularly. Even when these primary care physicians had spirometry in their offices, only 31% used it on suspected cases of COPD. Furthermore, only 1 in 5 primary care professionals referred all or most of their COPD patients to lung specialists.[17] This is alarming because lung specialists tend to follow the established COPD guidelines more closely than primary care physicians, and without their seeing COPD patients, the opportunity for early diagnosis and treatment may be lost.[18]

Too many primary care providers are unable to distinguish asthma from COPD and don’t recognize that women are at higher risk for COPD than men. Over a third (38%) of primary care physicians felt it was difficult to distinguish COPD from asthma, and 78% thought COPD was primarily a disease that affects men. When COPD symptoms are misdiagnosed as asthma, women receive the wrong treatment, and the correct COPD treatment is delayed.

Perhaps one of the biggest barriers to diagnosis, though, is the failure of patients to report symptoms to their doctor. People who feel guilty about smoking may decide not to tell their doctor about symptoms, or like non-smokers with COPD who think their symptoms are due to getting older, they may simply cut back on physical activity.4 When patients adapt to their increasing breathlessness and don’t mention it to their doctors, an opportunity to educate primary care providers about COPD—how widespread it is and whom it affects—is lost. This hurts people suffering from COPD and medical professionals alike.

Not Everyone Defines COPD the Same Way

There is no single standard for defining COPD with spirometry, which may account for some of the misdiagnosis of the disease. The GOLD definition of COPD is widely accepted: a FEV1/FVC of less than 0.70, which is the ratio of how much air a patient is able to exhale in 1 second (FEV1) to the total volume of air a patient can exhale in one breath (FVC).[19] The GOLD guidelines also classify COPD into 4 stages from mild to very severe based on other calculations.

The GOLD definition tends to over-diagnose COPD in the elderly since one value in the FEV1/FVC ratio decreases with age more rapidly than the other. An alternative definition is the lower limit of normal (LLN) definition of COPD, which takes age into consideration and compares the FEV1/FVC ratio of a patient to that of a healthy person who is the same age. Researchers found that while the GOLD definition tended to over-diagnose COPD, the LLN definition under-diagnosed COPD in some symptomatic patients.[20] Collecting more information during spirometry readings, such as total lung capacity (TLC), reduced the number of misdiagnoses. Another study found that sex differences in diagnoses are influenced by the COPD definition used.[21] When the GOLD definition of COPD was used, men had a higher risk of COPD, but among smokers, women were more likely to be diagnosed with COPD due to their increased susceptibility to cigarette smoke. However, when the LLN definition was used, there was no significant difference between male and female risk for COPD and no evidence of increased susceptibility to COPD among female smokers. Without an agreed upon standard for defining COPD, it is difficult to diagnose COPD definitively or to understand the different risk factors.

The Controversy Surrounding COPD Screening

In 2000, the National Lung Health Education Program (NLHEP) recommended that all smokers age 45 and older be screened using lung function tests, like spirometry, to identify undiagnosed COPD.[22] This led to widespread screening and spirometers in doctors’ offices everywhere. However in 2007, the American College of Physicians recommended that only patients with respiratory symptoms be screened with spirometry and not asymptomatic individuals, regardless of smoking history or age.[23]  In 2008, the U.S. Preventive Services Task Force followed suit and recommended against screening healthy adults without any respiratory symptoms for COPD using spirometry, stating that it had no overall benefit. The recommendation does not apply to individuals who have symptoms such as wheezing and chronic cough or people with a family history of alpha-1-antitrypsin deficiency who should be screened. (Few people are aware of whether they or their relatives have alpha-1-antitrypsin deficiency, but the test to screen for it is very inexpensive.)

The Task Force determined that the harms of spirometry screening, which include misdiagnoses and adverse effects from unnecessary treatment, outweighed the possible benefits of treatment and pulmonary rehabilitation. Spirometry can result in substantial over-diagnosis of COPD in never-smokers aged 70 and older, but there are fewer false-positives in other healthy adults who are screened. The Task Force found that although treatments can prevent COPD from worsening, patients with severe COPD die at the same rate whether or not they receive treatment. COPD treatments have also been associated with negative side effects in some patients, such as elevated heart rate and infections. Unfortunately, the Task Force found that providing smokers with their spirometry results did not necessarily result in more smokers quitting, and a favorable spirometry reading could actually discourage smokers from quitting.

According to the Task Force recommendation, patients with severe or very severe COPD who would stand to gain the most from screening make up less than 10% of those identified as having COPD using current diagnostic criteria. This means that hundreds of smokers would have to be screened to identify one person who would benefit. The Task Force concluded that widespread spirometry screening is likely to identify many patients with mild to moderate COPD who would not experience any substantial benefits from being diagnosed and treated. However, no one really knows if that is true: patients with mild or moderate COPD and patients without symptoms are rarely included in drug trials for COPD treatments, and without studies there is no evidence one way or the other.[24]

While the USPSTF has weighed in against widespread screening, there is no evidence that spirometry itself causes any significant adverse effects. Spirometry is noninvasive, low cost, and a fast way to determine lung function. Current or former smokers should speak with their physicians about the risks and benefits of being screened and see if their insurance will cover it.

Spirometry in combination with other clinical methods has been shown to be an effective COPD screening in some studies. In 2008, the National Heart Lung and Blood Institute and the COPD Foundation developed a 3-part approach to screening the general population for COPD.[25] First, a patient would answer a brief questionnaire about exposure to COPD risk factors and possible symptoms. Peak expiratory flow (the maximum amount of air that a person can forcibly exhale) would then be measured in the patient. If the peak expiratory flow was less than 70% of the predicted value, only then would spirometry be performed. The study found that the 3-step approach was useful for ruling out COPD in the general population and preventing false-positive results. However, the approach was not as accurate at detecting COPD in patients who had it. Another study looked at a validated COPD assessment test (CAT), which is a questionnaire asking about symptoms in their daily lives, on a random sample of the population.[26] The researchers found that smoking history, age (55 and older), and the presence of breathlessness were all key factors in identifying individuals at risk for COPD who would benefit from spirometry screening.

Treatment Options and Prognosis

There is no cure for COPD but symptoms can be managed through several treatment options, none of which have been shown to make people with COPD live longer.  Medications, such as bronchodilators which relax the airway muscles to make breathing easier, are administered using an inhaler.

  • Bronchodilators. There are two types of bronchodilators: B2 agonists and anticholinergics. Each type can be short-acting (taken only when needed and not more than every 4-6 hours) or long-acting (taken every 12 hours or more, everyday), and some people use both types. Both B2 agonists and anticholinergics improve symptoms and lung function, but neither extends patients’ life span. Anticholinergics have been shown to be more effective in preventing symptoms from getting worse compared to long-acting B2 agonists (LABAs). LABAs appear to cause more side effects than anticholinergics, but some people find that LABAs offer them more relief than anticholinergics.[27]
  • Inhaled Glucocorticosteroid. These reduce the body’s immune response and so, decrease inflammation. People who have moderate or severe COPD or are experiencing flare ups or worsening symptoms may be prescribed an inhaled glucocorticosteroid. A patient taking one of these will continue to have a declining quality of life but a slower decline than without the inhaled steroid. A patient’s breathing capacity will continue to deteriorate but the glucocorticosteroids allow the patient to be less bothered or limited by the decline. Side effects of glucocorticosteroids include hoarseness and “thrush,” a mucosal infection from yeast (oropharyngeal candidiasis).[28]
  • Pill or Intravenous Steroids.  Whether inhaled or taken some other way, steroids can be very effective in the short term but have many serious side effects over the long term, including increased blood pressure, an increased risk of type 2 diabetes, weakened bones, and cataracts.[29]

In addition to controlling symptoms with medication, patients are encouraged to be vaccinated against pneumonia and the flu, both of which can worsen COPD symptoms.

Another treatment option is pulmonary rehabilitation, which can improve the health and quality of life of those who suffer from COPD. Rehab programs include exercise to maintain muscle strength, disease management training, nutritional counseling to prevent muscle wasting and maintain a healthy weight, and psychological counseling to deal with depression. Oxygen therapy is another option but is usually reserved for patients with severe COPD. It can improve quality of life by allowing patients to perform certain tasks or engage in physical activity that they otherwise couldn’t do. Oxygen therapy also helps to reduce symptoms, improve sleep, and increase overall survival in some patients.

In a small study in Japan, researchers found that acupuncture improved shortness of breath in COPD patients taking medications.[30] Patients were better able to tolerate exercise and experienced less shortness of breath during exercise, which is usually a debilitating problem for COPD sufferers. Acupuncture has previously been shown to improve shortness of breath in cancer patients. Although this alternative approach seems promising, larger studies are needed to demonstrate the efficacy of acupuncture and determine if it’s a reasonable treatment option for COPD patients.

Although rare, surgery is a last resort for cases of severe COPD where medications, pulmonary rehabilitation, oxygen therapy, and alternative medicines don’t work. Surgery can range from removing parts of the diseased lung to a complete lung transplant.

Just as there are barriers to diagnosing COPD, there are barriers to treating it, too.  According to a study of knowledge and attitudes among primary care providers, only 15% believed COPD treatment was useful for improving symptoms. Among those with access to pulmonary rehabilitation, 3% believed it was useful and 16% were neutral about its benefits.

How quickly COPD progresses varies with each patient and therefore it is hard to predict how long someone with COPD will live. One study, however, showed that inflammation measured by testing urine, blood, sputum (spit), tissue samples, and even exhaled air may help predict death in COPD patients within the next three years.[31] In the 3-year ECLIPSE study, inflammation was associated with an increased risk of death from COPD.

What Does This Have To Do With Lung Cancer?

COPD is a lung disease that often co-exists with lung cancer and is estimated to affect 40-70% of lung cancer patients (depending on the diagnostic criteria used). Similarly, the Lung Health Study Research Group found that the most common cause of death among patients with airflow obstruction was lung cancer. [32,33] One study which looked at the prevalence of COPD in lung cancer patients, independent of age, sex, or smoking history, concluded that the prevalence of COPD in newly diagnosed lung cancer cases was six-times greater than in smokers without lung cancer: 50% of newly diagnosed lung cancer patients had COPD whereas only 8% of smokers without lung cancer had COPD. Lung cancer is much more likely in smokers with previously diagnosed COPD and poor lung function compared to smokers with normal or near normal lung function. It is estimated that 20% of all long-term smokers will eventually develop COPD over the course of a lifetime. The results suggest that impaired lung function may be more important than age or even smoking history as a predictor of lung cancer.

The findings of Victor Kiri and colleagues at PAREXEL International (a pharmaceutical clinical research firm) suggest that while lung cancer survival in general is very low, survival is even lower among patients with a previous diagnosis of COPD.[34] In the study, 26% of lung cancer patients without COPD were still alive 3 years after their diagnosis compared to just 15% of lung cancer patients with COPD. A 2005 meta-analysis, which is a combined analysis of several different but comparable studies, concluded that even a small reduction in airflow significantly predicted lung cancer.[35] Another study demonstrated that just a 10% reduction in lung function (as measured by a spirometer using forced expiratory volume in 1 second or FEV1%) was associated with an almost 3-times greater lung cancer risk.[36]

The link between emphysema and lung cancer has been illustrated in several studies. Lifelong non-smokers with a history of emphysema were more likely to be diagnosed with lung cancer and died earlier than other lifelong non-smokers.[37] In another study, current and former smokers whose CT scans showed emphysema were more likely to develop lung cancer than current and former smokers whose CT scans showed no evidence of emphysema. This was true regardless of whether spirometry testing indicated airflow obstruction among the smokers, which is also a predictor of lung cancer.[38] Lung cancer occurred most frequently in patients with both airflow obstruction and emphysema—regardless of how much tobacco exposure they had. On the other hand, the more severe the case of emphysema a patient had (severity increases with the number of cigarettes smoked per day), the greater the risk of lung cancer.

How are COPD and Lung Cancer Linked?

Genetic link

The above findings strongly suggest that COPD may be an important, independent risk factor for lung cancer. Some researchers believe that COPD and lung cancer have common origins in inflammation and also share some of the same genetic predispositions and environmental risk factors, with exposure to tobacco smoke being the primary risk factor.[39] It is well known that tobacco smoke can cause inflammation leading to chronic bronchitis and COPD. It is possible that chronic inflammation of the airways and lungs could result in repeat injury and repair of cells, uncontrolled cell growth, and eventually the development of lung cancer.[40] Chronic inflammation among people with COPD may activate the proteins that help cancer grow.[41] At the same time, the proteins needed to repair DNA in some of the lung’s cells are deactivated when COPD is present. COPD may also reduce the expression of key genes, preventing them from being involved in the detoxification of cigarette smoke. This can make cigarette smoke even more toxic and lead to the spread of malignant tumors beyond the lungs to other parts of the body. No one understands exactly how or why this happens, but studies reveal that genetic or biological changes could be responsible.

Sex hormones

Female sex hormones affect lung cancer, COPD, and asthma, which are the three most common lung diseases in women. The role of female hormones may explain why women (smokers and non-smokers) are more likely to develop lung cancer and COPD than men (smokers and non-smokers) (see Lung Cancer is a Women’s Health Issue).

Some studies suggest that female sex hormones, such as estradiol, inflame a smoker’s airways which could lead to lung cancer. Estradiol is the type of estrogen found in pre-menopausal women who are not pregnant. Its levels are low during menstruation and high during ovulation, and it causes an increase of certain proteins in the lungs which make the lungs more susceptible to damage from cigarette smoke.[42] This could be the reason why women smokers are more likely to develop COPD than male smokers—even when they smoke fewer cigarettes and for fewer years (called “pack-years” of smoking). Other studies suggest that estrogen may speed up the metabolism of cigarette smoke, which would increase cellular stress and damage in the lungs and ultimately lead to a higher chance of getting lung disease and COPD for women smokers.[43]

In addition to estrogen produced by the body, estrogen taken as hormone therapy also affects lung function. Research suggests that estrogen may help certain lung cancer cells spread throughout the lungs. A 2009 study based on the Women’s Health Initiative showed that post-menopausal women who took estrogen and progesterone combined hormone therapy had an increased risk of dying from lung cancer, regardless of whether or not they were smokers (although smokers had a higher risk of death than non-smokers).[44] A study published in 2010 showed that post-menopausal women who took estrogen hormone therapy for more than 10 years had a higher risk of developing lung cancer than women who didn’t take estrogen.[45] The use of hormone treatment after menopause does not appear to independently increase the risk of COPD, however.[46]

In terms of asthma, boys are more likely to be diagnosed with asthma than girls until the age of 15; after that, more women than men are diagnosed with asthma until women’s hormones decrease during the early stages of menopause. About a third of women with asthma find that symptoms worsen (and peak flow declines) in the period immediately before their menstrual cycle, presumably due to sudden changes in hormone levels.[47] Some studies suggest that a drop in estrogen levels is the problem while other studies indicate an increased risk of developing asthma when postmenopausal women take hormone therapy, which contains estrogen.[48] Despite the confusion, one thing is clear: dramatic changes in hormone levels trigger asthma and asthma symptoms in women, and asthma increases the risk for developing COPD.

Could COPD Patients be the Best Candidates for Lung Cancer Screening?

The relationship between smoking, airflow obstruction, and lung cancer is well recognized. Diseases characterized by airflow obstruction, like COPD, are associated with an increased risk of lung cancer and screening smokers for COPD as a risk factor for lung cancer could be worthwhile.

While low-dose CT screening for lung cancer has gained support in recent years, its value is still being debated (see Lung Cancer: Who is at Risk and Can They be Screened?). Most experts agree that current and former smokers are at the highest risk for lung cancer, yet not everyone agrees that they should all be screened. Smokers who have COPD could be the best candidates for lung cancer screening because they are most likely to benefit from it. Prioritizing high-risk smokers could also increase the accuracy and cost-effectiveness of CT screening. Since emphysema is usually detected with low-dose CT, it would be efficient and cost-effective to screen smokers and former heavy smokers for both emphysema and lung cancer at the same time.

The combined use of spirometry to diagnose COPD and CT to diagnose emphysema could help identify those at greatest risk for lung cancer and who would benefit the most from lung cancer screening. A diagnosis of COPD could alert patients to their elevated risk of lung cancer, just as high blood pressure does for the risk of stroke.

You Think you Might be at Risk for COPD and/or Lung Cancer. Now What?

  1. If you are currently smoking, stop or at least start cutting back. 1-800-QUITNOW and Smokefree.gov are free resources you can use to help you quit. Women have a harder time quitting than men and it takes years to reverse the damage of cigarette smoke. Even then some lung damage cannot be undone. However, women who do quit recover faster from the effects of cigarette smoke than men.
  2. If you have risk factors for COPD or lung cancer, discuss the risks and benefits of screening with spirometry or low-dose CT with your doctor. If you are experiencing any symptoms associated with COPD and/or lung cancer, see your doctor immediately.
  3. If you are diagnosed with COPD, lung cancer or both, consider participating in clinical trials for new treatments and therapies.
  4. Advocate for additional federal funding for research to investigate the link between COPD and lung cancer and discover new treatments for both diseases.

Related Content:
Screening for lung cancer: do risks outweigh benefits?
Lung cancer: who is at risk and can they be screened?
Lung cancer and African Americans

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Lung Cancer and African Americans

Sarah Miller, RN, Cancer Prevention and Treatment Fund

For years, doctors and medical researchers have been puzzled by the fact that African-Americans are more likely to die from lung cancer than people of any other race or ethnicity, although they are not more likely to smoke. How could this be? Is it because they don’t get diagnosed and treated in time, is it genetic, or is there something else going on? Research indicates that a combination of factors may be responsible for the unequal rates of death from lung cancer.

The Problem

African-Americans are disproportionately affected by lung cancer. The percentage of African-American men diagnosed with lung cancer each year is at least 30% higher than among white men, even though they have similar rates of smoking as white men. In fact, African-American men tend to smoke fewer cigarettes per day than white male smokers. While African-American women are less likely to smoke than white women, they are about as likely to develop lung cancer and die from lung cancer as white women. African-Americans also tend to be diagnosed with lung cancer at a younger age. Research has examined many possible explanations for these differences.

Is it Genetic?

Scientists have recently identified several genes that are linked to lung cancer. People who have these genes and smoke are more likely to develop lung cancer than other smokers. They have also found genes that cause a person to metabolize nicotine differently, which could be a factor in whether a person develops lung cancer.6 Some of these genes have been found to be more common in people with African ancestry. This suggests that genetics may have a role in the higher rates of lung cancer among African-Americans.

Genetics are only a part of the equation, though. There are many other factors that contribute to differences in lung cancer rates and in death from lung cancer.

Does the Type of Cigarettes Matter?

Tobacco companies have a long history of targeting the African-American community with advertisements for menthol cigarettes. As a result, about 80% of African-American smokers smoke menthol cigarettes, compared with only 20% of white American smokers.

Many researchers have tried to find a link between lung cancer and menthol cigarettes. Some have theorized that the “cooling” effect of menthol cigarettes allows menthol smokers to inhale the smoke more deeply, which could cause more damage to their lungs. Others have speculated that menthol cigarettes might be more addictive than regular cigarettes.

While studies have shown that smokers of menthol cigarettes may have a more difficult time quitting, and are more likely to smoke their first cigarette sooner after waking in the morning than people who smoke regular cigarettes, researchers have not been able to find any chemical properties of menthol cigarettes that make them more addictive.

Smokers of menthol cigarettes do not, on average, smoke any more cigarettes in their lifetime than regular cigarette smokers, and research so far has failed to show that menthol cigarettes cause more cases of cancer than other kinds of cigarettes.

The one obvious problem with menthol cigarettes is that the menthol makes cigarette smoke less harsh for first-time smokers. Because, of this, many young teens smoke them. In fact, while smoking is declining among adults and adolescents, menthol cigarettes are becoming increasingly popular among both adults and kids ages 12-17. Since we know that people who begin smoking at younger ages are more likely to become regular smokers, it is troubling that there is a product available that helps teens to start smoking. Although African-American teens start smoking later than white teens, they disproportionately smoke menthol cigarettes.

Does the Environment Affect Lung Cancer Disparities?

Industries that produce heavier air pollution (for example, factories, oil refineries, and chemical plants) are often located in African-American communities. Exposure to pollution from working in or living near these industries can increase a person’s risk for lung cancer.,

A person who smokes and is exposed to air pollution is at higher risk for lung cancer than a smoker who is not exposed to air pollution. People who are exposed to air pollution on the job are at especially high risk. The fact that these polluting industries are frequently located in African American communities and employ members of that community may also help to explain why African-Americans are disproportionately affected by lung cancer.

Is it Because of Differences in Treatment?

While differences in diagnosis and treatment don’t explain why more African-Americans develop lung cancer, it may help to explain the higher death rate from lung cancer among blacks.

One study of all the lung cancer patients in the Florida Cancer Registry found that the survival time for African-American patients diagnosed for lung cancer was shorter than that of white patients. The researchers also found that the entire difference in survival time between African-Americans and whites could be attributed to the fact that white patients tended to get more timely and appropriate treatment.

They concluded that if African-American patients could begin treatment as early as white patients, and were provided the best treatment for their condition, then their survival time would catch up with that of white patients.

Another study found that many patients with a certain type of lung cancer, for which surgical removal of part of the lung offers the best chance for a cure, did not get the proper surgery. Shockingly, only 62% of all patients who would have a good chance of the surgery helping them had the surgery. When the researchers separated the results out by race, 66% of white patients who were appropriate candidates had the surgery while only 55% of African-American patients who were appropriate candidates had the surgery. While this is bad news for all patients with this type of lung cancer, it is worse news for African-Americans since they were substantially less likely than white patients to get the surgery.

Why Don’t African-American Patients Receive the Proper Treatment?

One reason that African American patients are less likely to receive the proper treatment than white Americans may be that they are less likely to have health insurance. While about 13% of white American adults under the age of 65 are uninsured, 21% of African American adults in the same age group are without health insurance. Uninsured patients may decide against treatment because they can’t afford it, or may have a difficult time finding a hospital that is willing to provide the treatment to uninsured patients.

Another reason that African American patients do not always receive the most appropriate care is that there seem to be communication problems between providers and patients.

Studies have found that the type of communication a patient has with a doctor or health care provider has an impact on his or her decision-making about treatments. In the long-term, this has a huge impact on the state of a person’s health.

Health care providers are increasingly pressured to fit more patient visits into shorter time periods. Because of this, providers have less time to spend getting to know each patient. In this type of situation, people tend to make snap judgments.

Providers make a judgment based on their first impression of a person (what they think of that person after glancing at his or her chart and based on personal appearance). This judgment influences the provider’s judgment about what medical information the patient wants or doesn’t want, what type of treatment the patient is likely to find acceptable, and how reliable the person will be with his or her follow-up care.

Patients, too, know that they have only a short time for an appointment. They also may judge a provider based on his or her appearance and make assumptions. They may assume that the provider is very knowledgeable and that they should just do what the provider says. Patients may also assume, based on a snap judgment, that the provider will not respond well to being asked questions, that the provider does not care about the patient, or that the provider is not going to be helpful.

Research has shown that when the provider is of a different race or culture than the patient, these breakdowns in communication are more severe and have more negative results in terms of the quality of care a patient receives.

What is Being Done to Reduce Disparities in Lung Cancer Survival?

While healthcare providers and lawmakers recognize that this is a serious problem, they also recognize that there is no quick fix.

One step that is being taken by medical schools is to try and attract more African-American students. Currently, African-Americans are under-represented in the medical profession. The assumption is that African-American physicians be able to communicate more effectively with African-American patients, and that they will be able to educate their colleagues to do so as well.

Many people are also trying to limit advertising of menthol cigarettes, especially ads that target African-American teens.

Some public health advocates are urging the FDA to ban menthol in cigarettes. Other flavored cigarettes (“bidis”) have already been banned on the principle that they attract teens to smoking and make cigarettes more tolerable. Since we know that menthol also makes smoking more desirable for teens, and since it is a flavoring for cigarettes, it makes sense that it should be banned along with the other flavors. Banning menthol cigarettes would likely reduce the number of African-American teens that smoke, and might help reduce lung cancer deaths among African-American men and women.

References:

Centers for Disease Control and Prevention; Summary Health Statistics for US adults: National Health Interview Survey, December 2008; Vital and Health Statistics, 10 (242), 2009.

Stellman, SD; Chen, Y; Mucsat, JE; Djordjevic, MV; Richie, JP; Lazarus, P; Thompson, S; et.al. Lung Cancer Risk in White and Black Americans.  Annals of Epidemiology. 2003. 13(4). Pp.294-302.

National Cancer Institute; SEER stat fact sheets: Lung and Bronchus. Surveillance Epidemiology and End Results. 2010. Retrieved from: http://seer.cancer.gov/statfacts/html/lungb.html#incidence-mortality

American Lung Association; Too May Cases, Too Many Deaths: Lung Cancer in African-Americans, 2010. Retrieved from http://www.lungusa.org/assets/documents/publications/lung-disease-data/ala-lung-cancer-in-african.pdf  on August 10, 2010.

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