In addition to the numerous studies in rehabilitation and · continuing care supported through the CCOP, several other research programs are underway. An ongoing program designed to improve the quality of survival among childhood cancer patients focuses on school attendance and employment/insurance issues. NCI proposes to extend this research to adult patients. A current research program is designed to determine the need for and availability of home care for cancer patients. A complementary program studies nursing interventions designed to promote the ability of patients undergoing chemotherapy or radiotherapy to take an active role in managing their own care.

The "Prevention of Cervical Cancer in Native American Women" is a health education research project focusing on cancer prevention among two populations of Native Americans, the Cherokee and the Lumbee. The major goal of the study is to increase screening and follow-up for cervical cancer prevention among women, age 18 and older, who receive Pap smears at appropriate intervals and return for follow-up care when necessary.

The "Wai'anae Coast Cancer Control Project" in Wai'anae Hawaii will test the effectiveness of an integrated, community-driven, cancer control intervention as a means of increasing breast and cervical cancer screening practices among Native Hawaiian women. Research objectives include the development of health-activated mutual support groups within existing Hawaiian social and family networks and their sense of "Kokua" (a Hawaiian social concept that encourages mutual support of community members), the presentation of information about available cancer screening services; assistance in reducing logistical barriers to receiving cancer screening services; and the discussion of personal attitudes and beliefs as a motivating factor.

During the past year, three of the six NCI breast cancer screening grants have received supplements to design, implement, and evaluate one-year interventions to increase breast cancer screening rates in women 65 and older. In addition, a fourth grant was supplemented to sponsor a "Forum on Breast Cancer Screening in Older Women" held July 30-August 2, 1990. The Forum is developing recommendations for breast cancer screening in women aged 65 and over, and future research needs in this area.

ENVIRONMENTAL CARCINOGENESIS

The U.S. cancer mortality maps provide a major means of highlighting geographic areas experiencing unusual variations in cancer trends and risks that may be associated with environmental carcinogens. Updated U.S. atlases, illustrating geographic patterns of cancer deaths by state economic area over three decades (1950-1980), were published for the white population in 1987 and for nonwhite populations in 1990. Etiologic clues from these maps can be evaluated by more analytical epidemiologic studies, leading to prevention strategies. For example, elevated rates of oral cancer among women in the southeastern United States prompted studies that identified snuff dipping as its major cause, leading to legislative action affecting the advertising and labeling of smokeless tobacco and educational initiatives about

its health hazards. Further studies are planned to identify reasons for the high- and low-risk areas.

Air: A number of investigations have been undertaken due to concerns about cancer risks associated with indoor and outdoor air pollution. Studies by NCI and other groups have shown a relationship between passive smoking and lung cancer, particularly among nonsmoking women married to smokers. These studies indicate an overall risk of about 30 percent, rising to 70 percent among those most heavily exposed to environmental tobacco smoke (ETS). These findings have increased public awareness of the hazards associated with the inhalation of ETS, and have influenced public policy regarding the regulation of smoking in public places.

Radon is a radioactive gas that decays into solid alpha-emitting short-lived daughters, which are inhaled and deposited on the bronchial tree of the lung. The radiation from these daughter products has been shown to cause lung cancer in underground miners. Because radon can concentrate in homes, especially when tightly insulated, a proportion of lung cancers may be attributable to residential exposures. Studies will continue to assess the magnitude of the risk of lung cancer from indoor radon exposure. In studies in China, the excess risk of lung cancer among nonsmoking women has been attributed to indoor pollutants from high-temperature wok cooking and home-heating devices.

In a study of outdoor air pollution in Shenyang, China, the risk of lung cancer was increased among males living within one kilometer of a large copper smelter, whose stacks emit high levels of inorganic arsenic. This finding supports earlier NCI studies in the United States which showed that both occupational and residential exposures to inorganic arsenic from metal smelters are related to lung cancer risk.

Water: In an earlier NCI study, bladder cancer risk was associated with the intake of chlorinated tap water from surface sources, with long-term consumers having the greatest risk. Data are now being analyzed from the first phase of a case-control study of six anatomical sites of other cancers that also may be at higher risk. The second phase of the study, currently in the field, is restricted to collecting information from additional bladder cancer patients and controls. A recent mortality and incidence survey in various counties across the United States revealed no cancer trends or patterns that could be attributed to the intake of fluoridated drinking water. In particular, no relation was found between osteosarcoma incidence and fluoridated water supplies, which is noteworthy in view of an animal bioassay study by the National Toxicology Program suggesting that sodium fluoride induces osteosarcoma in rats.

Workplace: Occupational studies have played an important role in identifying environmental carcinogens. Many of the chemicals that cause human cancer were first identified in the workplace. Chemicals used in industry are often found in commercial products or emitted from industrial plants through air and water, exposing the general population to them. The growing number of chemicals in the workplace and general environment

underscores the need for a strong research program to identify those that may be carcinogens.

The NCI's Epidemiology and Biostatistics Program has a broad range of studies underway to identify and clarify the role of workplace exposures in the origin of cancer. These studies span a number of industries and focus on a variety of potentially hazardous agents. To conduct these research projects, the NCI collaborates with other government agencies, companies, labor unions, professional associations, and foreign institutions. Areas of special emphasis include exposure to pesticides, focusing on applicators; studies of dry cleaners, Coast Guard marine inspectors, aircraft mechanics, and jewelry manufacturers who may be exposed to organic solvents; studies of cancer among persons exposed to dusts and fibers (e.g., asbestos, silica, and talc); and special industry-wide studies designed to evaluate cancer risks from various uses of specific chemicals (e.g., formaldehyde, acrylonitrile, methylene chloride, and benzene).

Recent findings related to pesticides include an association between non-Hodgkin's lymphoma (NHL) and use of herbicides from studies of Kansas and Nebraska farmers. The excess for this tumor rose to six-fold among Kansas farmers reporting use of herbicides 20 or more days per year. This association was primarily with the phenoxyacetic acid herbicide, 2,4-Dichlorophenoxyacetic acid (2,4-D) which is widely used in agriculture and in urban areas on lawns. In addition, farmers reporting use of insecticides on animals had elevated risks for soft-tissue sarcoma. In Nebraska, the risk of NHL rose to over three-fold among farmers using 2,4-D for 20 or more days per year. Studies to extend and clarify these findings include a case-control study of lymphatic and hematopoietic cancer in Iowa and Minnesota, and cohort studies of employees of a major lawn care company and herbicide applicators employed by county governments.

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Leukemia was associated with farming in a study from Iowa and Minnesota. In particular, farmers using insecticides on animals had greater risks than farmers using insecticides on crops. excess of NHL was also observed among workers in the grain industry, where exposure to fumigants to control insects in stored grain may occur.

In a major effort completed a few years ago, over 26,000 workers employed in 10 different plants were studied to evaluate the risk of cancer from exposure to formaldehyde. Workers who had contact with formaldehyde containing dusts had excess mortality from nasopharyngeal cancer, which rose to nearly eight-fold among those with the heaviest exposures. The association between nasopharyngeal cancer and formaldehyde was recently observed in an NCI study of embalmers and funeral directors. Industrial workers also had a 30 percent excess of lung cancer, which did not show an exposure-response relationship with any measure of exposurè to formaldehyde (including duration, intensity, peak, cumulative, average). Such a relationship is crucial for inferring causality. Recent analyses indicate that risks of lung cancer rose with duration of exposure to melamine, phenol, urea, and wood dusts, but not with formaldehyde. In other studies, excesses from leukemia and brain cancer have been consistently noted among

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embalmers and funeral directors who had routine exposure to formaldehyde and other chemicals. A case-control study of these cancers, which includes a detailed industrial hygiene assessment of exposures occurring during embalming, has been initiated to clarify these associations.

Organic solvents are widely used in industry, and several have been shown to cause cancer in laboratory animals. Investigations have recently been completed to evaluate cancer risks associated with exposures to certain solvents. A study of U.S. Coast Guard marine inspectors uncovered excess mortality from cancer and cirrhosis of the liver, leukemia, and motor vehicle accidents. Risk from these causes of death rose with cumulative level of exposure to chemicals. During inspection of vessels, marine inspectors may come into contact with various chemicals, but particularly organic solvents that are often transported by ship. In another study, an excess of lymphatic and hematopoietic cancer was noted among dry cleaners. Although several solvents have been used in dry cleaning over the years, carbon tetrachloride, petroleum solvents, and perchloroethylene have been preferred. Organic solvents are also widely used in the repair and maintenance of aircraft. The NCI recently completed an evaluation of civilian workers at an Air Force base engaged in these activities. No convincing association was noted between any cancer and exposure to trichloroethylene, a widely used degreaser.. Mortality from multiple myeloma and NHL, however, was elevated among workers exposed to a variety of other solvents. This investigation is being extended to further evaluate these associations.

Several investigations have evaluated the risk of lung cancer from occupational exposures. Lung cancer was excessive among workers in a chromium pigment factory, where zinc and lead chromates exposures occur, rising to over three-fold among those exposed for 10 or more years. A nearly four-fold excess of lung cancer was observed among underground hematite miners in China with exposure to radon and silica. In a study from Missouri, the risk of adenocarcinoma of the lung was elevated among carpenters, cabinet and furniture makers, plumbers, and printers. The association between this histologic type of lung cancer and potential exposure to wood dusts is intriguing, since adenocarcinoma is also the type of nasal and sinus cancer most strongly associated with exposure to wood dust. In another case-control study, lung cancer was associated with employment in several motor exhaust-related occupations, including truck drivers, heavy equipment operators, taxi drivers, and mechanics.

High-priority ongoing investigations include cancer risks among lawn care workers and county noxious weed applicators from occupational exposures to herbicides, among chemical workers exposed to acrylonitrile, among workers in dusty trades exposed to silica, among workers in China exposed to benzene, and

mesothelioma risk among workers in a variety of occupations where asbestos is used.

INNOVATIVE THERAPIES

Question. Please provide a line item budget with full abstracts for current and proposed NCI funding in the following

Answer. Demonstration of the effectiveness of new anticancer treatments requires their systematic testing in clinical trials. Major NCI-sponsored clinical trials are conducted through the Clinical Cooperative Groups, a nation-wide consortium of medical centers whose physicians are dedicated to identifying the benefits as well as the toxicities associated with new cancer therapies. Support for NCI clinical trials is as follows:

As I mentioned earlier, the Investigational Drug Branch of NCI's Cancer Therapy Evaluation Program (CTEP) is responsible for the coordination and evaluation of NCI-sponsored extramural trials of new cancer therapies as well as for evaluation of unconventional cancer treatments. In studies where there are unusual or unexpected results, CTEP is also available, at the investigator's request, to audit the results of a cancer clinical trial. Such reviews are performed by program personnel from CTEP's Clinical Investigations and Investigational Drug Branches. The budget for these two Branches in FY 1991 is estimated to be $2.7 million.

In the evaluation of investigational therapies, CTEP will also be asked from time to time to evaluate unconventional therapies as well. In an effort to provide a "level playing field," CTEP has undertaken special efforts to provide guidance to proponents of unconventional therapies regarding the conduct and analysis of clinical trials.

CTEP is in the process of developing a short document on cancer clinical trials methodology that can be understood by those not engaged in formal clinical trials. This document will provide procedures for the development of a "best case series" and small pilot studies that might provide information about those patients who are likely to have experienced antitumor benefit from unconventional treatment.

QUESTIONS SUBMITTTED BY SENATOR ERNEST F. HOLLINGS

RECENT ADVANCES IN CANCER RESEARCH

Question. Dr. Broder, over the past several months, I have read many recent accounts of tremendous progress which has been made in cancer research--gene therapy, how cancer spreads and many other examples. Could you highlight for me and the Committee, in laymen's terms, 5 of the most crucial advances over the year or