Tumor Markers Tumor markers are substances that can often be detected in higher-than-normal amounts in the

blood, urine, or body tissues of some patients with certain types of cancer. Tumor markers are produced either by the tumor itself or by the body in response to the presence of cancer or certain benign (noncancerous) conditions. This fact sheet describes some tumor markers found in the blood. Measurements of tumor marker levels can be useful--when used along with x-rays or other tests-in the detection and diagnosis of some types of cancer. However, measurements of tumor marker levels alone are not sufficient to diagnose cancer for the following reasons: * Tumor marker levels can be elevated in people with benign conditions. * Tumor marker levels are not elevated in every person with cancer-especially in the early stages of the disease. * Many tumor markers are not specific to a particular type of cancer; the level of a tumor marker can be raised by more than one type of cancer. In addition to their role in cancer diagnosis, some tumor marker levels are measured before treatment to help doctors plan appropriate therapy. In some types of cancer, tumor marker levels reflect the extent (stage) of the disease and can be useful in predicting how well the disease will respond to treatment. Tumor marker levels may also be measured during treatment to monitor a patient's response to treatment. A decrease or return to normal in the level of a tumor marker may indicate that the cancer has responded favorably to therapy. If the tumor marker level rises, it may indicate that the cancer is growing. Finally, measurements of tumor marker levels may be used after treatment has ended as a part of followup care to check for recurrence. Currently, the main use of tumor markers is to assess a cancer's response to treatment and to check for recurrence. Scientists continue to study these uses of tumor markers as well as their potential role in the early detection and diagnosis of cancer. The patient's doctor can explain the role of tumor markers in detection, diagnosis, or treatment for that person. Described below are some of the most commonly measured tumor markers. Prostate-Specific Antigen Prostate-specific antigen (PSA) is present in low concentrations in the blood of all adult males. It is produced by both normal and abnormal prostate cells. Elevated PSA levels may be found in the

blood of men with benign prostate conditions, such as prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH), or with a malignant (cancerous) growth in the prostate. While PSA does not allow doctors to distinguish between benign prostate conditions (which are very common in older men) and cancer, an elevated PSA level may indicate that other tests are necessary to determine whether cancer is present. PSA levels have been shown to be useful in monitoring the effectiveness of prostate cancer treatment, and in checking for recurrence after treatment has ended. In checking for recurrence, a single test may show a mildly elevated PSA level, which may not be a significant change. Doctors generally look for trends, such as steadily increasing PSA levels in multiple tests over time, rather than focusing on a single elevated result. Researchers are studying the value of PSA in screening men for prostate cancer (checking for the disease in men who have no symptoms). At this time, it is not known whether using PSA to screen for prostate cancer actually saves lives. The National Cancer Institute-supported Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial is designed to show whether the use of certain screening tests can reduce the number of deaths caused by those cancers. For prostate cancer, this trial is looking at the usefulness of regular screening using digital rectal exams and PSA level checks in men ages 55 to 74. Researchers are also working on new ways to increase the accuracy of PSA tests. Improving the accuracy of PSA tests could help doctors distinguish BPH from prostate cancer, and thereby avoid unnecessary followup procedures, including biopsies. Carcinoembryonic Antigen Carcinoembryonic antigen (CEA) is normally found in small amounts in the blood of most healthy people, but may become elevated in people who have cancer or some benign conditions. The primary use of CEA is in monitoring colorectal cancer, especially when the disease has spread (metastasized). CEA is also used after treatment to check for recurrence of colorectal cancer. However, a wide variety of other cancers can produce elevated levels of this tumor marker, including melanoma; lymphoma; and cancers of the breast, lung, pancreas, stomach, cervix, bladder, kidney, thyroid, liver, and ovary. Elevated CEA levels can also occur in patients with noncancerous conditions, including inflammatory bowel disease, pancreatitis, and liver disease. Tobacco use can also contribute to higher-than-normal levels of CEA. Alpha-Fetoprotein Alpha-fetoprotein (AFP) is normally produced by a developing fetus. AFP levels begin to decrease soon after birth and are usually undetectable in the blood of healthy adults (except during pregnancy). An elevated level of AFP strongly suggests the presence of either primary liver cancer or germ cell cancer (cancer that begins in the cells that give rise to eggs or sperm) of the ovary or testicle. Only rarely do patients with other types of cancer (such as stomach cancer)

have elevated levels of AFP. Noncancerous conditions that can cause elevated AFP levels include benign liver conditions, such as cirrhosis or hepatitis; ataxia telangiectasia; WiscottAldrich syndrome; and pregnancy. Human Chorionic Gonadotropin Human chorionic gonadotropin (HCG) is normally produced by the placenta during pregnancy. In fact, HCG is sometimes used as a pregnancy test because it increases early within the first trimester. It is also used to screen for choriocarcinoma (a rare cancer of the uterus) in women who are at high risk for the disease, and to monitor the treatment of trophoblastic disease (a rare cancer that develops from an abnormally fertilized egg). Elevated HCG levels may also indicate the presence of cancers of the testis, ovary, liver, stomach, pancreas, and lung. Pregnancy and marijuana use can also cause elevated HCG levels. Lactate Dehydrogenase Lactate dehydrogenase is a protein found throughout the body. Nearly every type of cancer, as well as many other diseases, can cause LDH levels to be elevated. Therefore, this marker cannot be used to diagnose a particular type of cancer. LDH levels can be used to monitor treatment of some cancers, including testicular cancer, Ewing's sarcoma, non-Hodgkin's lymphoma, and some types of leukemia. Elevated LDH levels can be caused by a number of noncancerous conditions, including heart failure, hypothyroidism, anemia, and lung or liver disease. Neuron-Specific Enolase Neuron-specific enolase (NSE) has been detected in patients with neuroblastoma; small cell lung cancer; Wilms' tumor; melanoma; and cancers of the thyroid, kidney, testicle, and pancreas. However, studies of NSE as a tumor marker have concentrated primarily on patients with Tumor grades neuroblastoma and small cell lung cancer. Measurement of NSE level in patients with these two diseases can provide information about the extent of the disease and the patient's prognosis, as well as about the patient's response to treatment. Tumor grade is one of many factors that doctors consider when they develop an individual treatment plan for a cancer patient. Tumor grade refers to the degree of abnormality of cancer cells compared with normal cells. The body is made up of many types of cells. Normally, cells grow and divide to produce new cells in a controlled and orderly manner. This controlled cell division is the process that heals wounds and replaces aging tissues. Sometimes, however, new cells continue to be produced when they are not needed. As a result, a mass of extra tissue called a tumor may develop. A tumor can be

benign (not cancerous) or malignant (cancerous). Cells in malignant tumors are abnormal and grow without control or order. These cancerous cells can invade and destroy the tissue around them and spread. If a tumor is suspected to be malignant, a doctor removes a sample of tissue or the entire tumor in a procedure called a biopsy. From the biopsy, a pathologist (a doctor who identifies diseases by studying cells under a microscope) can determine whether the tumor is benign or malignant. The pathologist can also identify other characteristics of the tumor cells, including tumor grade and the degree of cell differentiation. The term differentiated describes the extent to which cancer cells are similar in appearance and function to healthy cells of the same tissue type. The degree of differentiation often relates to the clinical behavior of the particular tumor. Grade is a classification system used by pathologists to describe the degree of differentiation of tumor cells. Based on the microscopic appearance of cancer cells, pathologists commonly describe tumor grade by four degrees of severity: Grades 1, 2, 3, and 4. The cells of Grade 1 tumors are often well-differentiated or low-grade tumors, and are generally considered the least aggressive in behavior. Conversely, the cells of Grade 3 or Grade 4 tumors are usually poorly differentiated or undifferentiated high-grade tumors, and are generally the most aggressive in behavior. The American Joint Commission on Cancer has recommended the following guidelines for grading tumors: Grade GX Grade cannot be assessed (Undetermined grade) G1 Well-differentiated (Low grade) G2 Moderately well-differentiated (Intermediate grade) G3 Poorly differentiated (High grade) G4 Undifferentiated (High grade) Although grade is used by pathologists to describe most types of cancer, its importance in planning treatment and estimating the future course and outcome of disease (prognosis) is greater for certain types of cancers, such as soft tissue sarcoma, primary brain tumors, lymphomas, and breast and prostate cancer. Some cancers also have special grading systems. For example, pathologists use the Gleason system to describe the degree of differentiation of prostate cancer cells. The Gleason system uses scores ranging from Grade 2 to Grade 10. Lower Gleason scores describe welldifferentiated, less aggressive tumors. Higher scores describe poorly-differentiated, more aggressive tumors. It is important for physicians and patients alike to know as much as possible about a cancer s grade and stage because both the extent to which the disease has progressed (stage), and its microscopic features (grade) are important factors in planning treatment and estimating a patient

s prognosis. Patients should discuss questions about tumor grade and how it relates to their diagnosis and treatment with their doctor.

Prevention
Cancer prevention is a major component and a current priority of the National Cancer Institute's (NCI) mission to reduce suffering and death from cancer. Research in the areas of diet and nutrition, tobacco cessation, chemoprevention, and early detection and screening are the NCI's major cancer prevention programs. The NCI also sponsors programs to increase participation in clinical trials. The ultimate goal of all of these programs is to achieve reductions in cancer incidence and mortality. Through these efforts, the chances for preventing and surviving cancer are improving. Each of these areas of research is described below. Diet and Nutrition In the early 1980s, the NCI established a diet, nutrition, and cancer prevention research program. This program includes nutrition and metabolic studies to identify cancerpreventive dietary substances and supports dietarymodification clinical trials. The expansion of knowledge about the role that nutritional factors play in the development and progression of cancer will lead to increased opportunities to develop dietary and lifestyle modifications to prevent human cancers. A growing number of compounds in fruits, vegetables, and cereal grains have been found to interfere with the process of cancer development in laboratory research. Scientists continue to explore the absorption, metabolism, and mechanisms of action of many of these compounds to determine their possible protective roles in cancer development. Epidemiologists have found that populations that consume large amounts of plant-derived foods have lower incidence rates of some types of cancer. Eating vegetables and fruits is associated with a decreased risk of cancers of the esophagus, oral cavity, stomach, colon, rectum, lung, prostate, and larynx (and possibly other cancers). Knowledge gained from epidemiologic studies and laboratory research is being applied in dietarymodification clinical trials. In 1991, following a successful pilot study of low-fat dietary intervention in postmenopausal women at increased risk of breast cancer, NCI began a feasibility study to find the best way to help African American, Hispanic, and low-income women change to a low-fat eating pattern. Findings from this and other feasibility trials were used in the design and implementation of the National Institute of Health's Women's Health Initiative, the largest community-based prevention trial ever conducted in the United States. This Initiative is focusing on the effects of dietary modification, calcium/vitamin D supplementation, and hormone replacement therapy on the incidence of breast and colon cancer, as well as heart disease and osteoporosis. Since its inception in October 1991, the 5 A Day for Better Health Program, a collaborative effort between the food industry and NCI, has been encouraging Americans to eat five or more servings

of vegetables and fruits each day as part of a low-fat, high-fiber diet. The NCI is working with the Produce for Better Health Foundation to promote the program's message in the marketplace. Tobacco Cessation Tobacco use is the single most preventable cause of death in the United States. Cigarette smoking alone is directly responsible for at least one-third of all cancer deaths annually in the United States. Therefore, programs designed to reduce tobacco use among both children and adults are an important aspect of NCI's overall cancer prevention and control efforts. To intensify its efforts and to establish tobacco-related research priorities for the next 5 to 7 years, the NCI established the Tobacco Research Implementation Group (TRIG). This group included leading scientists and experts from the NCI, the National Institute on Drug Abuse (NIDA), and the Office of the Director of the National Institutes of Health, as well as members of the extramural research community and representatives of major NCI review and advisory committees. Through a consensus-building process, the TRIG identified a core set of tobaccorelated cancer research opportunities in its Tobacco Research Implementation Plan. Within this core set, the group identified unique high-priority research opportunities that require immediate implementation. These opportunities range from basic biological and basic biobehavioral research to clinical intervention, policy, epidemiology, surveillance research, and support for research activities. The research priorities also emphasized the special opportunities and challenges of tobacco initiation, regular tobacco use, addiction, and cessation among young people and populations at high risk. Two major research initiatives have already been launched as a result of the TRIG's recommendations. For the first project, which creates a collaborative Transdisciplinary Tobacco Research Centers program, researchers sponsored by NCI and NIDA are studying the prevention of tobacco use, initiation of tobacco use, addiction to tobacco, and/or treatment of tobacco addiction and tobacco-related cancers. The centers are focusing on areas in which gaps in knowledge have been identified, such as adolescent smoking and the use of smokeless tobacco products. The second research initiative is studying the effectiveness of mass media and policy interventions that are used to motivate tobacco use prevention and cessation at state and community levels. This project is designed to give state officials better information on the most effective interventions to reduce tobacco use. The NCI is also involved in several major activities to promote the primary prevention and cessation of spit tobacco use. With the National Institute of Dental and Craniofacial Research, the NCI cochairs a national initiative on spit tobacco involving cancer centers; researchers; and government, professional, voluntary, and athletic organizations. Various resource materials have been developed and distributed, including a teaching guide; a videotape; motivational and informational publications, such as posters and brochures; and trading cards for use by Little League, the National Collegiate Athletic Association (NCAA), and Major League Baseball (MLB). The NCI's work with MLB resulted in a ban against spit tobacco in all the minor leagues. The NCAA has banned the use of spit tobacco during regular and postseason play.

Chemoprevention Chemoprevention is the use of natural or synthetic substances to reduce the risk of cancer. NCI's chemoprevention research effort has grown considerably since it was established in the early 1980s. The program is designed to study whether some micronutrients and synthetic compounds can reduce cancer incidence. Currently, over 450 compounds are being studied as potential chemopreventive agents, mainly in laboratory research. More than 40 compounds are being investigated in approximately 80 clinical trials (research studies in which people participate). Four classes of preventive agents have shown particular promise in clinical trials and are considered priority substances for study. These classes include selective estrogen receptor modulators (SERMS) and other hormonal agents, nonsteroidal antiinflammatory drugs (NSAIDS), calcium compounds, and retinoids (chemical cousins of vitamin A). The drug tamoxifen, a SERM that has been used to treat women with breast cancer for more than 20 years, was studied as a chemopreventive agent in the Breast Cancer Prevention Trial. The study enrolled 13,388 women age 35 and older. This trial was designed to see whether taking tamoxifen (Nolvadex) could prevent breast cancer in women who were at increased risk of developing the disease. Data published in the September 16, 1998, Journal of the National Cancer Institute showed 49 percent fewer diagnoses of breast cancer among women who took tamoxifen. These results were the first clear indication that a chemopreventive agent could reduce the risk of breast cancer in highrisk women. However, tamoxifen also caused serious problems such as endometrial cancer and blood clots. Now, another SERM, raloxifene (Evista), which is used for the prevention of osteoporosis, is being compared to tamoxifen in postmenopausal women in a large study known as STAR (Study of Tamoxifen and Raloxifene). The STAR trial, which began recruiting participants in June 1999, expects to enroll about 22,000 participants. This trial is designed to find out whether raloxifene is as effective in reducing the chance of developing breast cancer as tamoxifen has proven to be, and to compare the side effects of the two agents. The Prostate Cancer Prevention Trial is designed to see whether taking the drug finasteride (used to treat patients with symptomatic noncancerous enlargement of the prostate, also called benign prostatic hyperplasia) can prevent prostate cancer in men ages 55 and older. The drug reduces levels of dihydrotestosterone (DHT), a male hormone that is important in normal and abnormal prostate growth. DHT plays a key role in benign prostate enlargement and is also believed to be involved in the development of prostate cancer. Some 18,882 men joined the trial. Recruitment is complete and results are expected in 2003. NSAIDS, such as aspirin, piroxicam, and ibuprofen, are being studied alone and in conjunction with other agents in the prevention of colon cancer in people with a history of colon polyps or cancer. Calcium compound studies focus on colon cancer prevention mainly in individuals previously diagnosed with colon polyps or cancer. Studies involve a variety of calcium compounds.

Scientists are studying both natural and synthetic retinoids alone and in combination with other compounds in the prevention of cervical cancer, lung cancer, cancers of the head and neck, and skin cancer. In addition, certain other promising chemopreventive compounds are under investigation. These include oltipraz, selenium, vitamin E, and Nacetylcysteine. Early Detection and Screening Early detection research focuses on developing tests for diagnosing cancer that can lead to decreased cancer death rates. In addition to studies to identify effective early detection and screening strategies, NCI supports research to increase the use of proven screening measures within the medical and public health communities. A large-scale screening trial called the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial is being conducted to determine if certain tests will reduce the number of deaths from these cancers. Approximately 37,000 men will be screened for prostate cancer, and some 37,000 women will be screened for ovarian cancer. Both groups will be screened for colorectal cancer and lung cancer. A comparison (control) group of 74,000 men and women will receive usual care. The trial began in 1993 and is expected to continue up to 16 years. Researchers are also working on improved methods of cancer detection, such as new imaging techniques to discover breast cancers. In addition, genetic studies of families with a high incidence of certain cancers have led to the identification of a number of cancer-related genes, which may lead to early detection of cancer in people with these genes. Clinical Trials for Cancer Prevention The Community Clinical Oncology Program (CCOP) is an NCI initiative to enable community physicians to enter patients into NCI-approved clinical trials. The CCOPs are affiliated with clinical cooperative groups and cancer centers. The research addresses specific questions that may lead to improved treatment of people with cancer or prevention of cancer in healthy individuals. The CCOP helps bring up-to-date cancer prevention and treatment practice and research to more people in their own communities. Each CCOP is responsible for conducting cancer control research, which provides a basis for involving a wider segment of the community (including minority groups and medically underserved populations) and for investigating how advances in cancer therapy and control can change community medical practices. More than 4,400 individuals are enrolled each year in cancer prevention and control clinical trials through the CCOP. Minority-based CCOPs have been established to increase the participation of minority populations in cancer prevention and control clinical trials. The Future of Cancer Prevention and Control Research

The NCI encourages and supports collaborative partnerships with and among other Federal agencies, industry, private research institutions, state and local governments, and voluntary organizations that also support or conduct cancer research. The NCI continues to expand this network to advance the Nation's collective efforts to reduce the burden of cancer and save lives. Scientists at the NCI are confident that the broad range of ongoing and planned activities will lead to better ways to prevent and control cancer.

Medical follow up

It is natural for anyone who has completed cancer treatment to be concerned about what the future holds. Many patients are concerned about the way they look and feel, and about whether the cancer will recur (come back). Patients wonder what they can do to keep the cancer from coming back. They also want to know how often to see the doctor for followup appointments, and what tests should be done. Understanding what to expect after cancer treatment can help patients and their loved ones plan for followup care, make lifestyle changes, and make decisions about quality of life and finances. 1. What does followup care involve, and why is it important? Followup care involves receiving regular medical checkups that include an evaluation of a patients medical history and a physical exam. Imaging procedures (methods of producing pictures of areas inside the body); endoscopy (the use of a thin, lighted tube to examine organs inside the body); or lab tests may be a part of followup care for certain cancers. Physical therapy, occupational or vocational therapy, pain management, support groups, or home care may also be included in the followup care plan. Followup care is important because it helps to identify changes in health. The main purpose of followup care is to check for the return of cancer in the primary site (recurrence), or the spread of cancer to another part of the body (metastasis). Followup care can also help to identify the development of another type of cancer, unknown or unusual treatment side effects, and late effects of cancer treatments (side effects that develop years after treatment). It is important to note that cancer recurrence is not always detected during the followup visits. Many cases of recurrence are suspected or found by patients themselves between scheduled checkups. It is important for patients to be aware of changes in their health, and report any problems to their doctor. The doctor can determine whether the problems are related to the cancer, the treatment the patient received, or an unrelated health problem. 2. How are followup care schedules planned? Ongoing health needs of patients differ. Followup care is individualized based on the type of cancer, the type of treatment received, and the patients general health. In many cases, it is not clear that followup tests improve survival or quality of life. This is why it is important that the doctor help determine what followup care plan is appropriate. The doctor may not perform any tests if the patient appears to be in good physical condition, and does not have

any symptoms. It is also important for patients to talk with their doctor if they have any questions or concerns about their followup care schedule. When planning a followup care schedule, patients should consider who will provide the followup care and other medical care. Patients should think about selecting a doctor with whom they feel comfortable. This may be the same doctor who provided the patients cancer treatment. For other medical care, people can continue to see a family doctor or medical specialist as needed. Some patients might not have a choice in who provides their followup care. Some insurance plans pay for followup care only with certain doctors, and for a set number of visits. Patients may want to check their medical coverage plan to see what restrictions, if any, apply to their followup care. In general, people who have been treated for cancer return to the doctor every 3 to 4 months during the first 2 to 3 years after treatment, and once or twice a year after that for followup appointments. At these followup appointments, the doctor may recommend tests to detect other types of cancer such as a mammogram to detect breast cancer. 3. Do some doctors or clinics specialize in followup care? Very few comprehensive cancer centers and academic medical centers have clinics devoted to the followup care of adult cancer patients. However, there are a number of clinics that provide followup care for pediatric cancer survivors. Patients can contact local comprehensive cancer centers or academic medical centers to see if followup care clinics exist in their area. A list of National Cancer Institute (NCI)designated cancer centers is available in the fact sheet The National Cancer Institute Cancer Centers Program. It can be found at Http: //cis.nci.nih.gov/fact/1_2.htm on the Internet. The Association of Cancer Online Resources (ACOR), a cancer information system that offers access to electronic mailing lists and Web sites, provides a list of long-term followup care clinics for children and adolescents treated for cancer. This list can be accessed in ACORs Pediatric Oncology Resource Center at Http: //www.acor.org/ped-onc/treatment/surclinics.html on the Internet. 4. What questions should people ask their doctor about followup care? Important questions to ask a doctor about followup care include: + How often should I see the doctor for a routine visit? + What followup tests, if any, should be done? + How often should these tests be done? + What symptoms should I watch for? + If I develop any of these symptoms, whom should I call? Many patients find it helpful to write these questions down and take notes, or tape these sessions with their doctor to refer to at a later time. 5. How can patients deal with their emotions effectively during followup care? After cancer treatment, it is common for a person to experience emotions such as stress, depression, and anxiety. Many people find it best to talk their feelings out with family and friends, health professionals, other patients, and counselors such as clergy and psychotherapists. Being part of

a support group may be another effective outlet for people to share their feelings. Relaxation techniques such as imagery and slow rhythmic breathing can also help in easing negative thoughts or feelings. Reaching out to others through participation in volunteer activities is also an effective way for a person who has completed cancer treatment to feel stronger and more in control. If these symptoms persist, however, patients should talk to their doctor about referral for further evaluation of what may be causing, or contributing to their distress. 6. What kinds of medical records and information should patients keep? It is important for people undergoing followup care to keep records of their health history. A patient may not always see the same doctor, so having this information available to share with another doctor can be helpful. The following types of information are important for a patient to keep track of: + Specific type of cancer (diagnosis) + Date(s) of cancer diagnosis + Details of all cancer treatment, including the places and dates where treatment was received (e.g., type and dates of all surgeries; names and doses of all drugs; sites and total amounts of radiation therapy, etc.) + Contact information for all doctors and other health professionals involved in treatment and followup care. + Complications that occurred after treament. + Information on supportive care received (e.g., pain or nausea medication, emotional support, nutritional supplements, etc.)

Pathogenic therapy

Photodynamic therapy (also called PDT, photoradiation therapy, phototherapy, or photochemotherapy) is a treatment for some types of cancer. It is based on the discovery that certain chemicals known as photosensitizing agents can kill one-celled organisms when the organisms are exposed to a particular type of light. PDT destroys cancer cells through the use of a fixed-frequency laser light in combination with a photosensitizing agent. In PDT, the photosensitizing agent is injected into the bloodstream and absorbed by cells all over the body. The agent remains in cancer cells for a longer time than it does in normal cells. When the treated cancer cells are exposed to laser light, the photosensitizing agent absorbs the light and produces an active form of oxygen that destroys the treated cancer cells. Light exposure must be timed carefully so that it occurs when most of the photosensitizing agent has left healthy cells but is still present in the cancer cells. The laser light used in PDT can be directed through a fiber-optic (a very thin glass strand). The fiber-optic is placed close to the cancer to deliver the proper amount of light. The fiber-optic can

be directed through a bronchoscope into the lungs for the treatment of lung cancer or through an endoscope into the esophagus for the treatment of esophageal cancer. An advantage of PDT is that it causes minimal damage to healthy tissue. However, because the laser light currently in use cannot pass through more than about 3 centimeters of tissue (a little more than one and an eighth inch), PDT is mainly used to treat tumors on or just under the skin or on the lining of internal organs. Photodynamic therapy makes the skin and eyes sensitive to light for 6 weeks or more after treatment. Patients are advised to avoid direct sunlight and bright indoor light for at least 6 weeks. If patients must go outdoors, they need to wear protective clothing, including sunglasses. Patients should talk with their doctor about what to do if the skin becomes blistered, red, or swollen. Other temporary side effects of PDT are related to the treatment of specific areas and can include coughing, trouble swallowing, abdominal pain, and painful breathing or shortness of breath. In December 1995, the U.S. Food and Drug Administration (FDA) approved a photosensitizing agent called porfimer sodium, or Photofrin-R, to relieve symptoms of esophageal cancer that is causing an obstruction and for esophageal cancer that cannot be satisfactorily treated with lasers alone. In January 1998, the FDA approved porfimer sodium for the treatment of early nonsmall cell lung cancer in patients for whom the usual treatments for lung cancer are not appropriate. The National Cancer Institute and other institutions are supporting clinical trials (research studies) to evaluate the use of photodynamic therapy for several types of cancer, including cancers of the bladder, brain, larynx, and oral cavity. Researchers are also looking at different laser types, photosensitizers that can be applied to the skin to treat superficial skin cancers, and new photosensitizing agents that may increase the effectiveness of PDT against cancers that are located further below the skin or inside an organ

Complementary therapy or alternative medicine

1. What is complementary and alternative medicine? Complementary and alternative medicine (CAM) also referred to as integrative medicineincludes a broad range of healing philosophies, approaches, and therapies. A therapy is generally called complementary when it is used in addition to conventional treatments; it is often called alternative when it is used instead of conventional treatment. (Conventional treatments are those that are widely accepted and practiced by the mainstream medical community.) Depending on how they are used, some therapies can be considered either complementary or alternative. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease. Some commonly used methods of complementary or alternative therapy include mind/body control interventions such as visualization or relaxation; manual healing, including acupressure and massage; homeopathy; vitamins or herbal products; and acupuncture.

2. Are complementary and alternative therapies widely used? Research indicates that the use of complementary and alternative therapies is increasing. A large-scale study published in the November 11, 1998, issue of the Journal of the American Medical Association found that CAM use among the general public increased from 34 percent in 1990 to 42 percent in 1997. Several surveys of CAM use by cancer patients have been conducted with small numbers of patients. One study published in the February 2000 issue of the journal Cancer reported that 37 percent of 46 patients with prostate cancer used one or more CAM therapies as part of their cancer treatment. These therapies included herbal remedies, old-time remedies, vitamins, and special diets. A larger study of CAM use in patients with different types of cancer was published in the July 2000 issue of the Journal of Clinical Oncology . That study found that 83 percent of 453 cancer patients had used at least one CAM therapy as part of their cancer treatment. The study included CAM therapies such as special diets, psychotherapy, spiritual practices, and vitamin supplements. When psychotherapy and spiritual practices were excluded, 69 percent of patients had used at least one CAM therapy in their cancer treatment. 3. How are complementary and alternative approaches evaluated? It is important that the same scientific evaluation which is used to assess conventional approaches be used to evaluate complementary and alternative therapies. A number of medical centers are evaluating complementary and alternative therapies by developing clinical trials (research studies with people) to test them. Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a rigorous scientific process, including clinical trials with large numbers of patients. Often, less is known about the safety and effectiveness of complementary and alternative methods. Some of these complementary and alternative therapies have not undergone rigorous evaluation. Others, once considered unorthodox, are finding a place in cancer treatmentnot as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) Consensus Conference in November 1997, acupuncture has been found to be effective in the management of chemotherapy-associated nausea and vomiting and in controlling pain associated with surgery. Some approaches, such as laetrile, have been studied and found ineffective or potentially harmful. 4. What is the Best Case Series Program? The Best Case Series Program, which was started by the National Cancer Institute (NCI) in 1991, is another way that early data about complementary and alternative approaches are evaluated. The Best Case Series Program is overseen by the NCI's Office of Cancer Complementary and Alternative Medicine (OCCAM). Through the Best Case Series Program, health care professionals who offer CAM services submit their patients' medical records and related materials to OCCAM. The OCCAM conducts a critical review of the materials and presents the approaches

that have the most therapeutic potential to the Cancer Advisory Panel for Complementary and Alternative Medicine (CAPCAM) for further review. CAPCAM was jointly created in 1999 by the NCI and the NIH National Center for Complementary and Alternative Medicine (NCCAM). CAPCAM's membership is drawn from a broad range of experts from the conventional and CAM cancer research and practice communities. CAPCAM evaluates CAM cancer approaches that are submitted through the Best Case Series Program, and makes recommendations to NCCAM on whether and how these approaches should be followed up. 5. Is NCI sponsoring clinical trials in complementary and alternative medicine? The NCI is currently sponsoring several clinical trials (research studies with patients) that study complementary and alternative treatments for cancer. Current trials include enzyme therapy with nutritional support for the treatment of inoperable pancreatic cancer, shark cartilage therapy for the treatment of non-small cell lung cancer, and studies of the effects of diet on prostate and breast cancers. Some of these trials compare alternative therapies with conventional treatments, while others study the effects of complementary approaches used in addition to conventional treatments. Patients who are interested in taking part in these or any clinical trials should talk with their doctor. More information about clinical trials sponsored by the NCI can be obtained from NCCAM, OCCAM, and the NCI's Cancer Information Service (CIS) (see below). 6. What should patients do when considering complementary and alternative therapies? Cancer patients considering complementary and alternative therapies should discuss this decision with their doctor or nurse, as they would any therapeutic approach, because some complementary and alternative therapies may interfere with their standard treatment or may be harmful when used with conventional treatment. 7. When considering complementary and alternative therapies, what questions should patients ask their health care provider? • • • • • • • What benefits can be expected from this therapy? What are the risks associated with this therapy? Do the known benefits outweigh the risks? What side effects can be expected? Will the therapy interfere with conventional treatment? Is this therapy part of a clinical trial? If so, who is sponsoring the trial? Will the therapy be covered by health insurance?

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