F E A T U R E By Timothy K. Egan Before placement in a computed tomography scanner, a patient is fitted with an immobilization device. Immobilization ensures that the same area of the patient is scanned each time, making continued monitoring of the patient's condition as accurate as possible. Photo courtesy of the University of Illinois at Chicago Medical Center. Monitoring Patients Undergoing Cancer Therapy 6 6 6
According to statistics published by the American Cancer Society (ACS), 10 million Americans have been diagnosed and are living with cancer, of which 3 million are considered cured. While this is a striking reminder that cancer has affected a major portion of the American population, simple mathematics means to beat cancer, you must learn to live with it. This means therapy. Cancer treatment options include surgery, radiation, chemotherapy, hormone therapy, and immunotherapy, and the type and the stage of the illness determine the treatment modality. 1 This is where monitoring a patient undergoing cancer therapy becomes just as important as diagnosis. After diagnosis, imaging techniques such as x- ray, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) can assist in locating cancer and determining its stage of development. Just as crucial as the results of imaging techniques, the use of laboratory tumor marker testing is a vital tool for monitoring cancer treatment. Tumor markers are substances produced by either cancerous or noncancerous tumor cells and not only play a role in diagnosis, but when measured before treatment can guide a physician s therapy plan. Monitoring Cancer Markers Markers for cancer are meant to diagnose and follow the progress of cancer, says Amod A. Saxena, MD, FRCR, FACR, and chairman of the Rush-Presbyterian-St Luke s Medical Center's Department of Radiation Oncology in Chicago. Markers are secreted by the tumors and are then tested through direct blood tests or looking for their antibodies in the blood. The prostate-specific antigen (PSA) and carcinoembryonic antigen (CEA) are tumor markers found at low concentrations in blood and are each used to check for recurrence. The PSA differs from the CEA since it is used as a screening mechanism, as well as a continuing monitor. PSA is produced by both normal and abnormal prostate cells found in the blood of men with benign prostate conditions or malignant growth in the prostate. The test does not distinguish between benign and malignant cells, but elevated PSA levels let physicians know further tests are necessary to make a correct diagnosis. One way to use PSA levels to diagnose cancer is to look for a trend, such as steadily increasing PSA levels in multiple tests over time, rather than focusing on a single elevated result. 2 Increasing PSA levels usually indicate a cancer is present and is progressing. Whether or not PSA screening saves lives is a topic of debate, and researchers are attempting to improve the screen s accuracy. Information from the National Cancer Institute (NCI) shows there is insufficient evidence to establish whether a decrease in mortality from prostate cancer occurs with screening by serum markers, like PSA, over digital rectal examination and transrectal ultrasound alone. However, the ACS recommends that men start annual PSA screenings at the age of 50. In blood tests, small amounts of CEA can be found in most healthy people, but levels are elevated in people with cancer or other conditions, like intestinal inflammation, or even from smoking. 2 The CEA test primarily monitors colorectal cancer, most effectively when the disease has metastasized. Using CEA specifically for monitoring colorectal cancer is qualified because this tumor marker can be produced by a wide variety of cancers including breast, lung, pancreas, stomach, cervix, bladder, kidney, thyroid, liver, and ovary. Another tumor marker associated with the prostate is prostatic acid phosphatase, originally thought to be produced only by the prostate, but since associated with testicular cancer, leukemia, and non-hodgkin lymphoma. Two other tumor markers are alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). A developing fetus normally produces the tumor marker AFP, and levels decrease soon after birth. Elevation of the AFP after birth suggests the presence of liver cancer or germ cell cancer of the ovary. HCG is also utilized to screen a rare cancer of the uterus called choriocarcinoma. Section 3 Features 6 6 7
Cancer cells Ovarian cancer treatment is commonly managed by monitoring levels of the tumor marker CA 125. A decrease in the levels of CA 125 generally indicates that chemotherapy patients are responding to treatment. The limitation of monitoring CA 125 is that not all women who have elevated levels have ovarian cancer. Normal body functions, such as menstruation and pregnancy, can cause an increase in CA 125. The question of which tests are most beneficial was offered to Parameswaran Venugopal, MD, of the Rush Cancer Institute, a division of the Rush- Presbyterian-St Luke's Medical Center. This depends on the type of cancer, Venugopal stated. Blood tests look at the functions of organs like the liver and kidney. But in leukemia, a bone marrow examination is the most beneficial in determining the response to treatment. Marker levels alone are not sufficient to diagnose cancer for the following reasons: levels can be elevated in people with benign conditions, levels are not elevated in every person with cancer (especially in the early stages of the disease); and many markers are not specific to a particular type of cancer. 2 Monitoring Cancer Biopsy and Imaging If fluid or tissue must be removed to make a diagnosis or continue monitoring therapy, further laboratory analysis can be conducted through biopsy and fine-needle aspiration (FNA). The FNA procedure can identify whether a lump is a fluid-filled, noncancerous cyst or a solid mass, which may or may not be cancer. A needle biopsy removes tissue from a suspicious area, and that tissue is forwarded to a laboratory to be analyzed by a pathologist for evidence of cancer. The NCI stands by the fact that imaging techniques can determine how advanced a cancer is, as well as the precise locations of cancer. Imaging techniques also aid in directing surgery and treatment and determining recurrence. The use of imaging techniques in monitoring cancer patients therapy is very important, says Daniel C. Sullivan, MD, Associate Director of the NCI s Biomedical Imaging Program. They allow the physician to tell whether a tumor is getting bigger or smaller before it would be apparent from symptoms or physical examination. With all of their benefits, some tests can show their limitations. A CT scan looks at the size and shape of the tumor only, Venugopal says. In other words, the CT cannot tell if the abnormality is tumor or scar tissue. A PET scan determines the presence of disease by producing a computerized image of the metabolic activity of body tissues, while a CT scan creates a series of detailed pictures of areas inside the body by a computer linked to an x-ray machine. CT and MRI are noninvasive if done without contrast, says Sullivan. Most of the time, contrast is used, which requires an injection of a radiopaque substance. PET scanning always requires injection of a radioactive tracer. 6 6 8
Physician and assistant adjust stereotactic radiosurgery equipment. Improved accuracy of the technique beyond older forms of radiation delivery allows for accuracy to less than 1 mm. Photo courtesy of Rush-Presbyterian-St. Luke s Medical Center. Cancer Monitoring Endoscopes The increasing use of lasers in the treatment and therapy of cancer patients can be attributed to endoscopes, tubes that allow physicians to view certain internal areas of the body. Endoscopes housing fiber optics can reach cancer-affected areas with precision, like the bladder, that were previously accessed only by complicated surgery. 3 Endoscopes provide direct visualization of endothelial tissue in organs which will permit entry of an endoscope, says Sullivan, such as the upper and lower GI [gastrointestinal] tracts or the genitourinary organs. They allow the physician to directly look at whether a tumor or other abnormality is getting better or worse and take a biopsy of tissue if needed. Cancer Treatment Metastatic Breast Cancer The ACS claims approximately 180,000 new breast cancer cases are diagnosed each year. For women diagnosed with metastatic breast cancer, a new drug called trastuzumab (Herceptin) has limited relief for approximately 25,000 patients. This monoclonal antibody was designed to attack cancer cells that make a protein called HER-2. Herceptin attaches itself to HER-2 on cells and attracts immune cells that eliminate cancerous cells. Herceptin was 6 6 9
The computed tomography scanner with its technological enhancements brings physicists and physicians together. They jointly work to develop the present system of accurate, three-dimensional imaging of patients before treatment. Photo courtesy of the University of Illinois at Chicago Medical Center. created by San Francisco-based Genentech. According to their statistics, of the 1.6 million women in the United States diagnosed with breast cancer, 164,000 have metastatic breast cancer. Of these women, approximately 30% of breast cancers have excess amounts of HER-2. 4 There are not many options for women who have metastatic breast cancer, says Neil Cohen, a spokesperson for Herceptin. Herceptin is a great opportunity to give women another treatment option. The goal is to extend survival and give quality of life during that survival. Herceptin has showed some positive advances by blocking HER-2, says Saxena. It is still under investigation because it hasn't had a very long test trial. Herceptin, given by intravenous infusion, received US Food and Drug Administration approval in September 1998. Common side effects of Herceptin most commonly occur during the first treatment and are flu-like with fever and chills. Another drug therapy of note is raloxifene, a breast cancer preventive. Information provided by the ACS includes a 2-year study of postmenopausal women being treated for osteoporosis, suggesting women at normal risk of developing breast cancer reduced that risk by approximately 66% with daily use of raloxifene. Again, according to Saxena, it is too early to tell about raloxifene s side effects. Main side effects, Saxena says, are swelling in the legs and water retention. But the long-term effects could be cancer of the uterus. Many cancer treatment modalities, including radiotherapy, can cause other malignancies. Cancer Treatment Radiosurgery Radiosurgery is an extremely complicated treatment that uses sophisticated software to deliver a high dose of radiation to a very well-defined target using multiple converging beams. Stereotactic radiosurgery can also be used to treat brain tumors and vascular malformations, base of skull lesions, and selected cases of recurrent head and neck tumors. 5 The improved accuracy in aiming over prior forms of radiation treatments, the prime advantage of stereotactic surgery, comes from a 3-dimensional imaging system for precisely locating the abnormality and using multiple beams of radiation simultaneously, each aimed from a different direction to converge on the same spot. Radiosurgery is pinpointing within one-half millimeter of accuracy, says Saxena. The Future The future of the health profession s progress in dealing with cancer can be reasonably extrapolated from what has gone before. Over the short and long term, steady improvements in diagnosing, monitoring, and treating cancer can be expected thanks to continuing critical research. The completely sequenced human genome provides the sequences of mutated genes that are associated with specific cancers. This will help in understanding how cancer is caused at the molecular level, and aid in designing specific diagnostic tests, monitoring protocols, and treatments based on that knowledge. 6 7 0
Thus, continuing to improve diagnosis, monitoring, and treatment will improve the survival rate of people discovered to have cancer and to become even more successful in preventing cancer. The best progress in dealing with cancer has been in diagnosis; current tests with increased sensitivity over earlier tests have allowed physicians to detect cancer at earlier stages than before, and long before it has spread. The earlier the point at which cancer is detected, the easier it is to treat and the more likely it is to cure. Future diagnostic tests will likely be even more sensitive and allow yet earlier detection, making for improved survival rates. Future improvements in monitoring cancer s response to treatments seem likely, as work is ongoing to improve resolution in imaging techniques like MRI, PET, and CT scans, especially as the power and speed of computers increase. Likewise, better tests for monitoring serum levels of drugs and cancer cell enzymes will be developed, making for more accurate measurements of drug concentrations in target tissues and cancer cell metabolic activity. In the United States there has been a concerted, extensive, and costly effort to find cures for cancers since the 1930s, with just some success. While some skin cancers, and certain others, can easily be cured in all but the most advanced stages, pancreatic and lung cancer, for example, have dismal survival rates that have improved little in decades. l References 1. American Cancer Society Web site. Types of treatment. Cancer resource center. Available at: http://www3.cancer.org/ cancerinfo/load_cont.asp?st=tr&ct=1&language=english. Accessed October 12, 2000. 2. National Cancer Institute Web site. Testing for prostate cancer, tumor markers. CancerNet cancer facts. Available at: http://www.cancernet.nci.nih.gov/cancer_types/prostate_ cancer.shtml#testing. Accessed October 12, 2000. 3. National Cancer Institute Web site. Lasers in cancer treatment. CancerNet cancer facts. Available at: http://www.cancernet.nci.nih.gov/cig-bin/srchcgi.exe?dbid=pdq&type= search&sfmt=pdq_statement/1/0/0&zui=600078. Accessed October 12, 2000. 4. American Cancer Society Web site. American Cancer Society news today. Herceptin and raloxifene makes news. Available at: http://cancer. org/zine/index.cfm?fn=002_06011998_0. Accessed October 12, 2000. 5. UNC Hospital Web site. Stereotactic radiosurgery program. Available at: http://apollo.med.unc.edu/sugery/radiosurgery. Accessed October 12, 2000. Section 3 Features 6 7 1