National Cancer Institute Cancer Research Articles

Improving cancer care and research through the reuse of standardized electronic data

17556 The inability to routinely capture oncology patient data electronically at the point of care and re-use this data in other settings (such as follow-up care or in a clinical trial) is a key impediment to improving cancer care and research. The same data collected in the oncology practice are often rekeyed multiple times as a patient moves through treatment and continues into routine follow up care. Even during the course of a single trial, data are rekeyed as the data move between trial site, trial sponsor and regulatory body. The National Cancer Institute (NCI) is collaborating with multiple organizations on multiple standardization and automation initiatives to standardize treatment summaries, electronic case report forms (eCRFs), and data elements associated with cancer care and research so that data can move directly, and in both directions, between clinical systems at the point of care and clinical trials databases, and back again. Standardized electronic data are also necessary to develop systems providing for decision support and quality reporting and analysis. Among the areas where work is complete, or nearly complete, are treatment summaries for colon and breast cancer as well as eCRFs for demography, patient identification, patient enrollment, patient baseline assessment, adverse events and protocol deviations. Discussions are underway among the collaborating organizations to begin work to standardize vocabularies for additional high priority areas such as clinical staging and medications. As the collection of these common vocabularies and data standards grows within the NCI's Cancer Data Standards Repository (caDSR), they can be reused to create new forms and tools. For example, many of the data elements for treatment summaries already existed in the caDSR, lessening the time and effort to complete the summaries. This presentation will describe completed, current and planned work to develop common standards and terminology for treatment summaries, standardized electronic case report forms (eCRFs) and electronic message formats for data transfer during the course of a clinical trial. No significant financial relationships to disclose.

Geographic access to cancer care in the U.S.

Although access to cancer care is known to influence patient outcomes, to the authors' knowledge, little is known regarding geographic access to cancer care, and how it may vary by population characteristics. This study estimated travel time to specialized cancer care settings for the continental U.S. population and calculated per capita oncologist supply. The closest travel times were estimated using a network analysis of the road distance weighted by travel speeds from the population or geographic centroid of every ZIP area in the continental U.S. to that of the nearest cancer care setting under consideration: National Cancer Institute (NCI)-designated Cancer Centers, academic medical centers, and oncologists. Alaska and Hawaii were excluded because travel in these states is often not road-based. Population and geographic characteristics including race/ethnicity, income, education, and region were derived from U.S. Census 2000 data and from rural-urban commuting area classifications. Oncologist supply per 100,000 residents in Hospital Referral Regions (pHRRs) was estimated by region. Travel times of <or=1 hour were estimated for 45.2% of the population to the nearest NCI Cancer Center, 69.4% to the nearest academic-based care, and 91.8% to any specialized cancer care. Native Americans, nonurban dwellers, and residents in the South had the longest travel times to the nearest NCI Cancer Center compared with the overall U.S. population (median [interquartile range (IQR)] in minutes: 155 [62-308], 173 [111-257], and 164 [70-272], vs 78 [27-172], respectively). Travel burdens persisted for Native Americans and nonurban populations across all 3 cancer care settings. For all population strata, travel times markedly increased as the degree of cancer care specialization increased. The median oncologist supply for pHRRs was 2.83 per 100,000 individuals. There are population groups with limited access to the most specialized cancer care settings.

Effect of 9–11 on U.S. national cancer clinical trials accrual and lack of effect of National Cancer Institute budget increases

6551 Background: During the past decade, a variety of initiatives have been implemented to improve the accrual of cancer patients on clinical trials. In the U.S., these have included comprehensive reviews and recommendations by the two most recent National Cancer Institute (NCI) administrations, reorganization of the clinical trials infrastructure at the NCI, and campaigns by the NCI Cooperative Groups and their Coalition. During the past six years, additional funds were allocated to this effort as part of the doubling of the NCI budget. The impact of these efforts on national cancer treatment clinical trials was evaluated, with emphasis on age groups. Methods: Accrual data from NCI-sponsored treatment trials conducted between 1997 and 2006 were obtained from the NCI Cancer Therapy Evaluation Program. Entries were analyzed by patient age, gender, race, type of cancer treated, and calendar year of trial entry. Results: Overall, national cancer treatment trial entries declined after 9–11–2001 and in 2003 reached the lowest levels since 1997. As of 2005 accrual recovered to pre 9–11 levels only in 15–29 and &gt;60 year-olds, with the former demonstrating the greatest gain ( Table ). Entries among &lt;15 and 30–49 year- olds declined steadily since 1997 with no evidence for recovery as of 2005 ( Table ). Overall, the estimated proportion of the nation's cancer patients entered onto national treatment trials remains below 3%. Conclusions: Despite continued national and local efforts to increase the participation of cancer patients on clinical trials, accompanied by significant increases in the NIH and NCI budgets, there is little evidence of a beneficial impact. The effect of 9–11 has yet to be overcome, except in young and elderly adults, in whom specific, targeted initiatives appear to have been successful. The latter approaches may be useful to apply to other age groups, particularly in view of the recent cuts in the cooperative group budgets and current mandated decreases in study accruals. No significant financial relationships to disclose. [Table: see text]

The NCI Digital Divide Pilot Projects: Implications for cancer education

The National Cancer Institute (NCI) supported four innovative demonstration research projects, "The Digital Divide Pilot Projects," to test new strategies for disseminating health information via computer to vulnerable consumers. These projects involved active research collaborations between the NCI's Cancer Information Service (CIS) and regional cancer control researchers to field test new approaches for enhancing cancer communication in vulnerable communities. The projects were able to use computers to successfully disseminate relevant cancer information to vulnerable populations. These demonstration research projects suggested effective new strategies for using communication technologies to educate underserved populations about cancer prevention, control, and care.

Secondhand Suspicions: Breast Cancer and Passive Smoking

Does a young woman living with a smoker or taking a job working in a smoky bar have a greater chance of developing breast cancer? Some scientists believe that such situations can indeed raise a woman’s risk of developing breast cancer before the age of 50. Because epidemiological and toxicological studies show that women’s breast tissue may be especially sensitive to exposure to carcinogens prior to first pregnancy, these researchers contend that public education should be directed at alerting adolescents and young women to the potential risk. However, not everyone in the international public health community agrees that the evidence to date supports a link between passive smoking and breast cancer, and some say that women are being alarmed unnecessarily. This disagreement has sparked debate that is sometimes heated. The stakes are high because breast cancer is the most common cancer in women in industrialized countries, according to the WHO. It is the leading cancer killer of nonsmoking women, and second only to lung cancer deaths among women who smoke. Among the researchers interviewed for this article who disagree that there is enough evidence to link secondhand smoke (SHS) with breast cancer, the majority call the evidence to date “suggestive but not sufficient,” as the Surgeon General’s 2006 report, The Health Consequences of Involuntary Exposure to Tobacco Smoke, put it. That characterization is based largely on the fact that the research considered when the Surgeon General’s report was being amassed did not clearly link even active smoking to breast cancer. Researchers in this camp do, however, stress that ongoing campaigns to prohibit smoking in public will protect the whole of society against the wide variety of ills proven to be caused by SHS. These include lung cancer, cardiovascular disease, and sudden infant death syndrome, among others. A smaller group contends that the question of whether or not SHS causes breast cancer is a political issue with the potential to compromise the scientific process. “A premature decision about causality could jeopardize the credibility of the entire review process and all of the other, established effects of secondhand smoke,” says Michael Thun, national vice president of epidemiology and surveillance research for the American Cancer Society. Adds Valerie Beral, director of the University of Oxford Cancer Research UK Epidemiology Unit, “To prematurely come to conclusions about the causation when there is a big division in the scientific community . . . is bad science.” Thun debated the subject in a series of public forums held in conjunction with scientific meetings. Taking the opposing view was Kenneth C. Johnson, a research scientist with the Public Health Agency of Canada, who was one of the first scientists to discern a potential link. During the debates, Johnson pointed out there are about the same number of studies linking breast cancer to passive smoking as there were linking lung cancer to SHS in 1986, when the Surgeon General concluded that passive smoking caused lung cancer. Johnson also says that more of the breast cancer studies are statistically significant, and that the estimated risk for breast cancer is higher.

The Role of User Input in Shaping Online Information From the National Cancer Institute

The National Cancer Institute (NCI) was among the first federal agencies to recognize the potential of the Internet for disseminating health-related information. The evolution and refinement of NCI's online cancer information has been substantially “user driven”—from the launch of CancerNet in 1995 to the recent redesign of its award-winning successor, the NCI website. This article presents an overview of NCI's multi-pronged approach to gathering input about its online information products, including stakeholder meetings, focus groups, standard and customized online user surveys, usability testing, heuristic reviews, and search log analysis. Also highlighted are some of the many enhancements that have been made to NCI's online cancer information products based on user input.

Do cancer centers designated by the National Cancer Institute have better surgical outcomes?

The National Cancer Institute (NCI) designates cancer centers as regional centers of excellence in research and patient care. Although these centers often advertise their superior outcomes, their relative performance has not been examined empirically. In the current study, the authors assessed whether patients at NCI cancer centers compared with patients at control hospitals had lower mortality rates after major cancer surgery. Using the national Medicare database (1994-1999), the authors assessed surgical mortality and late survival rates for 63,860 elderly patients undergoing resection for lung, esophageal, gastric, pancreatic, bladder, or colon carcinoma. For assessing performance, patients treated at the 51 NCI cancer centers were compared with patients from 51 control hospitals with the highest volumes for each procedure. Mortality rates (surgical and 5-year rates) were adjusted for patient characteristics and residual differences in procedure volume. NCI cancer centers had lower adjusted surgical mortality rates than control hospitals for 4 of the 6 procedures, including colectomy (5.4% vs. 6.7%; P = 0.026), pulmonary resection (6.3% vs. 7.9%; P = 0.010), gastrectomy (8.0% vs. 12.2%; P < 0.001), and esophagectomy (7.9% vs. 10.9%; P = 0.027). Nonsignificant trends toward lower adjusted operative mortality rates at NCI cancer centers were also observed for cystectomy and pancreatic resection. Among patients surviving surgery, however, there were no important differences in subsequent 5-year mortality rates between NCI cancer centers and control hospitals for any of the procedures. For many cancer procedures, patients undergoing surgery at NCI-designated cancer centers had lower surgical mortality rates than those treated at comparably high-volume hospitals, but similar long-term survival rates.

Data mining the NCI cancer cell line compound GI(50) values: identifying quinone subtypes effective against melanoma and leukemia cell classes.

Using data mining techniques, we have studied a subset (1400) of compounds from the large public National Cancer Institute (NCI) compounds data repository. We first carried out a functional class identity assignment for the 60 NCI cancer testing cell lines via hierarchical clustering of gene expression data. Comprised of nine clinical tissue types, the 60 cell lines were placed into six classes-melanoma, leukemia, renal, lung, and colorectal, and the sixth class was comprised of mixed tissue cell lines not found in any of the other five classes. We then carried out supervised machine learning, using the GI(50) values tested on a panel of 60 NCI cancer cell lines. For separate 3-class and 2-class problem clustering, we successfully carried out clear cell line class separation at high stringency, p < 0.01 (Bonferroni corrected t-statistic), using feature reduction clustering algorithms embedded in RadViz, an integrated high dimensional analytic and visualization tool. We started with the 1400 compound GI(50) values as input and selected only those compounds, or features, significant in carrying out the classification. With this approach, we identified two small sets of compounds that were most effective in carrying out complete class separation of the melanoma, non-melanoma classes and leukemia, non-leukemia classes. To validate these results, we showed that these two compound sets' GI(50) values were highly accurate classifiers using five standard analytical algorithms. One compound set was most effective against the melanoma class cell lines (14 compounds), and the other set was most effective against the leukemia class cell lines (30 compounds). The two compound classes were both significantly enriched in two different types of substituted p-quinones. The melanoma cell line class of 14 compounds was comprised of 11 compounds that were internal substituted p-quinones, and the leukemia cell line class of 30 compounds was comprised of 6 compounds that were external substituted p-quinones. Attempts to subclassify melanoma or leukemia cell lines based upon their clinical cancer subtype met with limited success. For example, using GI(50) values for the 30 compounds we identified as effective against all leukemia cell lines, we could subclassify acute lymphoblastic leukemia (ALL) origin cell lines from non-ALL leukemia origin cell lines without significant overlap from non-leukemia cell lines. Based upon clustering using GI(50) values for the 60 cancer cell lines laid out by the RadViz algorithm, these two compound subsets did not overlap with clusters containing any of the NCI's 92 compounds of known mechanism of action, a few of which are quinones. Given their structural patterns, the two p-quinone subtypes we identified would clearly be expected to possess different redox potentials/substrate specificities for enzymatic reduction in vivo. These two p-quinone subtypes represent valuable information that may be used in the elucidation of pharmacophores for the design of compounds to treat these two cancer tissue types in the clinic.

Methyl protogracillin (NSC-698792): the spectrum of cytotoxicity against 60 human cancer cell lines in the National Cancer Institute's anticancer drug screen panel.

Methyl protogracillin (NSC-698792) was a furostanol saponin isolated from the rhizome of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for the treatment of cervical carcinoma, carcinoma of urinary bladder and renal tumor for centuries, in our previous studies. In order to systematically evaluate its potential anticancer activity, methyl protogracillin was tested for its cytotoxicity in vitro against 60 human cancer cell lines in the National Cancer Institute (NCI)'s anticancer drug screen. As a result, it was found that methyl protogracillin was cytotoxic against all the tested cell lines from leukemia and solid tumors in the NCI's human cancer panel; it showed particular selectivity against one colon cancer line (KM12), one central nervous system (CNS) cancer line (U251), two melanoma lines (MALME-3M and M14), two renal cancer lines (786-0 and UO-31) and one breast cancer line (MDA-MB-231) with GI50< or =2.0 microM. The selectivity between these seven most sensitive lines and the least sensitive line (CCRF-CEM) ranged from 26- to 56-fold. In the same cancer subpanel, selectivity more than 15-fold was observed between MDA-MB-231 and MCF-7, NCI-ADR-RES, BT-549 in breast cancer. From a general view of the mean graph, CNS cancer is the most sensitive subpanel, while ovarian cancer and renal cancer are the least sensitive subpanels. Based on an analysis of the COMPARE computer program with methyl protogracillin as a seed compound, no compounds in the NCI's anticancer drug screen database have similar cytotoxicity patterns (mean graph) to that of methyl protogracillin, indicating a potential novel mechanism of the anticancer action involved.

Reevaluation of the cancer potency factor of toxaphene: recommendations from a peer review panel.

This reevaluation of the current U.S. EPA cancer potency factor for toxaphene is based upon a review of toxaphene carcinogenesis bioassays in mice conducted by Litton Bionetics (unpublished report, 1978) and the National Cancer Institute (NCI) (Technical Report Series No. 37, conducted by Gulf South Research Institute, 1979). The mechanistic data available for toxaphene, including consideration of the potential of the compound to induce genotoxicity, was examined with an emphasis on whether this information supports a change in the cancer potency factor. If a quantitative dose-response assessment for toxaphene is to be performed, the data from both the NCI and Litton cancer bioassays should be used. Additionally, liver tumor results from female mice, rather than male mice, should be used for estimating potential human cancer risk because the background rate of liver tumors in females is lower and less variable than that exhibited by males. An ED(10) was estimated as the point of departure. The mechanistic data were not sufficient to fully support a margin of exposure approach. Therefore, we believe that applying a linear extrapolation from the ED(10) to the origin is an appropriate means to estimate risk at low doses. This is a highly conservative approach and, when it is applied, we conclude that the current EPA cancer potency factor should be reduced from 1.1 (mg/kg/day)(-1) to 0.1 (mg/kg/day)(-1).

Vancomycin as part of initial empirical antibiotic therapy for febrile neutropenia in patients with cancer: pros and cons.

Gram-positive organisms predominate as the bacterial pathogens identified in episodes of febrile neutropenia. This has led to increased use of antibiotics with efficacy against gram-positive organisms (often vancomycin) as part of empirical antibiotic regimens for treating febrile neutropenia. Among 101 children randomized to receive amikacin, ticarcillin, and vancomycin or ticarcillin/clavulanate and amikacin along with vancomycin placebo, treatment success in those treated with vancomycin was higher (85% vs. 62%). In 1990, the European Organization for Research and Treatment of Cancer-National Cancer Institute of Canada Clinical Trials Group compared amikacin and ceftazidime with and without vancomycin and concluded that there was no need to include vancomycin in initial empirical antibiotic therapy. Results from another study and a retrospective review of a large clinical trial also support the previous conclusion. In 1999, most experts in the field recommend vancomycin not be part of the initial empirical therapy regimen for treating febrile neutropenia in patients with cancer.

Cancer burden in the aged

Sixty percent of all cancer occurs in persons aged ≥65 years. This article provides an overview of aspects of the burden of cancer in the elderly, highlighting certain demographic and epidemiologic data. It served as a frame of reference for participants in the Oncology Geriatric Education Retreat, San Juan, Puerto Rico, February 21-26, 1997. Information comes from several major sources: U. S. Bureau of the Census; National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program; National Center for Health Statistics; National Institute on Aging (NIA)/NCI SEER Study on Comorbidity and Cancer in the Elderly; and NCI cancer prevalence estimates. Data on the aging population demonstrate an unprecedented expansion of the segment of the population aged ≥65 years. By 2030, 1 in 5 Americans will be aged ≥65 years. Because cancer incidence and mortality rates are highest in persons aged ≥65 years, expansion of this age group takes on great importance for medical professionals who provide treatment to older aged cancer patients. In addition, older aged cancer patients are likely to have preexisting conditions at diagnosis, creating a special clinical challenge. There is an urgent need to better understand the influence of aging on the early detection, diagnosis, and treatment of cancer. Clinicians who treat older persons (geriatricians, oncologists, and other health professionals) can benefit from the integration of the knowledge and approaches of each others' fields. The foundation for this multidisciplinary effort is linked with the education and training of future clinicians. Cancer 1997; 80:1273-83. © 1997 American Cancer Society.

Cancer burden in the aged

Sixty percent of all cancer occurs in persons aged > or =65 years. This article provides an overview of aspects of the burden of cancer in the elderly, highlighting certain demographic and epidemiologic data. It served as a frame of reference for participants in the Oncology Geriatric Education Retreat, San Juan, Puerto Rico, February 21-26, 1997. Information comes from several major sources: U. S. Bureau of the Census; National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program; National Center for Health Statistics; National Institute on Aging (NIA)/NCI SEER Study on Comorbidity and Cancer in the Elderly; and NCI cancer prevalence estimates. Data on the aging population demonstrate an unprecedented expansion of the segment of the population aged > or =65 years. By 2030, 1 in 5 Americans will be aged > or =65 years. Because cancer incidence and mortality rates are highest in persons aged > or =65 years, expansion of this age group takes on great importance for medical professionals who provide treatment to older aged cancer patients. In addition, older aged cancer patients are likely to have preexisting conditions at diagnosis, creating a special clinical challenge. There is an urgent need to better understand the influence of aging on the early detection, diagnosis, and treatment of cancer. Clinicians who treat older persons (geriatricians, oncologists, and other health professionals) can benefit from the integration of the knowledge and approaches of each others' fields. The foundation for this multidisciplinary effort is linked with the education and training of future clinicians.

Intervention research: a model from the National Cancer Institute's Smoking and Tobacco Control Program.

Recognizing that the scientific method is as critical to cancer control as it is to basic laboratory research, the National Cancer Institute (NCI) established a well-defined, systematic strategy for attaining its cancer control goals and objectives. This strategy, operationalized in the early 1980s as a five-phase process, emphasized cancer control as a research science rather than a demonstration science. The five phases of NCI's cancer control research strategy progress from hypothesis development, to methods development, to controlled intervention trials, to defined population studies, and finally to demonstration and implementation programs. This research base provides the foundation for nationwide prevention and health services programs. The application of this five-phase approach to NCI's efforts to reduce morbidity and mortality attributable to tobacco use is described, and some of the challenges that faced the Institute in this process are identified. These experiences provide an important framework for other disciplines faced with the challenge of translating science into practice.

Survey of the provision of supportive care services at National Cancer Institute-designated cancer centers.

The purpose of this survey was to determine the scope of supportive care services (SCS) designed to promote quality of life during cancer therapies at National Cancer Institute (NCI)-designated cancer centers. A survey was mailed to the medical directors and nursing directors of 52 NCI-designated comprehensive (n = 26), clinical (n = 11), and planning cancer centers (n = 15) in the United States. Only one survey was completed from each institution. Survey questions identified services provided such as pain management, terminal care, psychosocial programs, and spiritual care. Thirty-nine questionnaires were received for a total response rate of 75%. Of the respondents, 45% were comprehensive cancer centers, 24% clinical cancer centers, and 29% planning centers. One center did not identify their NCI designation. Sixty-one percent of the centers reported research programs in supportive care. Outside funding was reported in 51% of the respondents, with 39% having American Cancer Society (ACS) or National Institutes of Health (NIH) funding and 28% having private industry funding. Overall SCS self-ratings improved from a 21% rating of excellent to very good 5 years ago to the current 54% rating. Survey results provide data on SCS across a representative sample of NCI cancer centers and can be used to develop standards for future cancer control programs.

The National Cancer Institute: cancer drug discovery and development program.

The discovery and development of novel therapeutic products for the treatment of malignancy is vitally important to those physicians responsible for the management of cancer patients. A description of the ongoing efforts at the National Cancer Institute (NCI) is intended to provide insight into those complex processes necessary to accomplish this mission. An update on the NCI's revised cancer screen is accompanied by a brief summary of those new agents scheduled to be entered into clinical investigation in the near future. The tremendous potential advantages and challenges associated with the use of a molecular approach to cancer drug design are discussed. Despite the differences of opinion that may exist regarding the optimal strategies for accomplishing the mission, there is no disagreement regarding the importance of the effort to find effective new therapies for cancer patients.

Health advertising: prevention for profit.

The National Cancer Institute (NCI) estimates on the basis of current knowledge alone that, at a minimum, 30,000 lives could be saved in the year 2000 if Americans would modify their dietary habits. A recent innovative way of responding to this challenge was the Kellogg Company/NCI All-Bran advertising campaign. This paper will describe the campaign, and its impact on consumers, cereal industry sales, food industry advertising practices, health regulatory policy, and the organizational credibility of both NCI and Kellogg. For the past three years, Kellogg has included NCI's cancer prevention messages in their advertisements for All-Bran cereal and on their bran cereal boxes. This collaborative effort has stimulated considerable controversy over whether the health claims made on the cereal label are in violation of federal food labeling regulations. Meanwhile, research has demonstrated the positive impact of the campaign on consumer's knowledge and behavior regarding fiber as well as on Kellogg's profits. Other manufacturers are anxious to jump on the "branwagon"; however, many unanswered questions remain about this new approach to health advertising.

Oxidative destruction of hydrazines produces N-nitrosamines and other mutagenic species.

As part of the joint International Agency for Research on Cancer-National Cancer Institute program for the evaluation and development of methods for the degradation of chemical carcinogens, four oxidative techniques for the degradation of hydrazines were investigated. The oxidizing agents used were as follows: sodium hypochlorite, calcium hypochlorite, potassium iodate, and potassium permanganate in sulfuric acid. In each case, at least 99% of the hydrazine initially present was destroyed; however, the potential usefulness of these methods was compromised by the formation (in some reaction mixtures) of carcinogenic N-nitroso compounds and/or unknown mutagenic species. Oxidative degradation of hydrazines is recommended only for the decontamination of glassware and for the treatment of spills, for which reductive degradation methods are not suitable.

Oxidative Destruction of Hydrazines Produces N-Nitrosamines and Other Mutagenic Species

As part of the joint International Agency for Research on Cancer-National Cancer Institute program for the evaluation and development of methods for the degradation of chemical carcinogens, four oxidative techniques for the degradation of hydrazines were investigated. The oxidizing agents used were as follows: sodium hypochlorite, calcium hypochlorite, potassium iodate, and potassium permanganate in sulfuric acid. In each case, at least 99% of the hydrazine initially present was destroyed; however, the potential usefulness of these methods was compromised by the formation (in some reaction mixtures) of carcinogenic N-nitroso compounds and/or unknown mutagenic species. Oxidative degradation of hydrazines is recommended only for the decontamination of glassware and for the treatment of spills, for which reductive degradation methods are not suitable.