June 7, 2006, 0:11 AM CT

Lung Cancer Overdiagnosis

Screening may lead to overdiagnosis of lung cancer, a study reports in the June 7 issue of the Journal of the National Cancer Institute.

Screening for cancer can find tumors that might not otherwise have been diagnosed in a person's lifetime, a situation called overdiagnosis. Overdiagnosis wastes health care resources. Tests and therapy resulting from overdiagnosis can lead to substantial toxicity and even premature death in patients.

Pamela M. Marcus, Ph.D., of the National Cancer Institute in Bethesda, Md., and his colleagues surveyed 7,118 participants in the Mayo Lung Project for information on their lung cancer diagnosis, health, and smoking history, and chest scan results after the study's initial follow-up in July 1983. The patients in the initial project had been randomly placed in two groups, one of which underwent multiple screening chest x-rays and spectrum tests used to identify lung cancer.

The authors identified a total of 585 cancers in the patients in the screened arm and 500 cancers in the group that was not screened. They report that the 85 more cancers found in screened patients suggests that screening can lead to lung cancer overdiagnosis.

"Eventhough the magnitude of overdiagnosis in chest x-ray screening appears to be modest, the very real and deleterious role that overdiagnosis plays in mass screening can not be discounted. The newest imaging technologies can detect very small lung abnormalities, but these abnormalities may be clinically unimportant. The question remains as to whether early detection of lung cancer through mass screening results in a net benefit to the public's health." the authors write.........

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June 7, 2006, 0:07 AM CT

Breast Cancer In Younger Black Women

For decades, scientists have tried to understand why breast cancer in younger black women is such a significant public health problem.

Black women have fewer breast cancers than white women, but their mortality is worse. Black women under the age of 50 have a 77 percent higher mortality rate from breast cancer than white women of the same age.

Results of a study led by researchers from the University of North Carolina at Chapel Hill schools of Public Health and Medicine and the UNC Lineberger Comprehensive Cancer suggest one reason for these differences.

When younger, premenopausal, black women get breast cancer, they are more than twice as likely as older women, black or white, to get an aggressive breast cancer subtype, the study found. They are also much less likely to get the least aggressive type. A report of the research appears in the June 7 issue of the Journal of the American Medical Association.

"The present study adds an important piece to a large puzzle," said senior study author Dr. Robert Millikan. "Prior studies showed that a number of breast tumors in younger African American women are very fast-growing and hard to treat.

"We found something new: Younger African American breast cancer patients show a high frequency of one of the aggressive subtypes of breast cancer called basal-like," said Millikan, associate professor of epidemiology at the UNC School of Public Health, a UNC Lineberger member and principal investigator of the Carolina Breast Cancer Study (CBCS). The CBCS, one of the largest black breast cancer databases in the United States, is a population-based case-control study that enrolled women with breast cancer from 24 counties of North Carolina as cases, and an equal number of women without breast cancer as controls. Women who consented to the study were interviewed about their histories, and their tumor tissue was collected. The study mandatory extensive cooperation from all of the women who took part in the study, their physicians and pathologists, and a large number of hospitals in North Carolina.........

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June 6, 2006, 11:40 PM CT

Cancer Patients Use Exercise To Feel Better

When individuals with breast or prostate cancer followed a moderate, home-based exercise program using resistance bands and walking, the patients had less fatigue during radiation therapys, greater strength and could walk farther and faster in only four weeks, scientists discovered in a pilot study.

"At the end of the study, the patients in the exercise program were averaging more than 12,000 steps a day - which is above the American College of Sports Medicine and Centers for Disease Control recommendations of 10,000 steps a day for healthy people without cancer," said principal investigator Karen Mustian, Ph.D., of the University of Rochester James P. Wilmot Cancer Center.

"The results of this study are extremely promising and I am hopeful this that this type of research is creating a body of knowledge that is focused on treating the whole patient and all of the complexities of cancer," Mustian said.

Mustian presented the results of her randomized, controlled study at the American Society of Clinical Oncology (ASCO) 2006 annual meeting in Atlanta on June 5. ASCO awarded her an ASCO Junior Investigator Research Merit Award, given to outstanding early-career scientists to recognize their cancer prevention and control research.

Exercise is emerging as a new therapeutic weapon to help cancer patients manage and reduce side effects and improve quality of life. Studies are beginning to show that exercise is safe and feasible for a number of patients. In her clinical trial, Mustian found that the participants were enthusiastic and adhered well to the exercise program, even though they were older (average age was 60), half of them had received chemotherapy, and 84 percent had already endured a surgery. Still, 95 percent completed the prescribed exercise routine.........

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June 5, 2006, 11:30 PM CT

High School Teacher Helps Discover New Cancer Drug

Sixteen years ago, when Stuart Shifrin, then a chemistry teacher at John F. Kennedy High School in Silver Spring, Maryland, volunteered to be one of the first teachers in a new research internship program at the National Institutes of Health (NIH), all he expected from the experience was to see how scientific research is conducted. Instead, his summer research project has developed into a promising new chemotherapy drug.

The Student and Teacher Internship Program, sponsored by Howard Hughes Medical Institute (HHMI) and run by the Montgomery County Public Schools, places high school students and teachers in NIH labs to experience science in action. Shifrin, whose father died of colon cancer, asked to work at the National Cancer Institute (NCI). He was placed in the lab of Leonard M. Neckers, then a principal investigator in NCI's Medicine Branch. Neckers and his postdoctoral fellow, Luke Whitesell, were examining a group of drugs that appeared to turn malignant cells into normal cells.

"We asked Stuart to put some drugs called benzoquinone ansamycins on cancer cells and tell us what happened," said Neckers. "The literature said these drugs worked by interfering with the cancer cells' tyrosine kinase metabolism, and we wanted to see if that was true." Tyrosine kinases are enzymes that have been implicated in cancer.........

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June 5, 2006, 11:26 PM CT

CAD Detects Breast Cancers

Small lesions are very challenging for the radiologist to detect, said Rachel F. Brem, MD, director of breast imaging at George Washington University in Washington, DC, and lead author of the study. The study of 201 women found that CAD was "highly effective in detecting even the smallest lesions, with a sensitivity of 92% for lesions of 5 mm or less," said Dr. Brem. CAD was most effective in detecting cancers measuring 11-15 mm (94%) and least effective in detecting cancers measuring 16-20 mm (80%), Dr. Brem said. Lesion size is important; "cancers smaller than or equal to 1 cm have a better prognosis than cancers greater than 1 cm," she said.

Subtle masses are also difficult to detect, Dr. Brem said. The study found that CAD had a sensitivity of 83% for the smallest masses (those measuring 1-5 mm). It was most sensitive for masses 11-15 mm (91%) and least sensitive for larger masses measuring greater than 20 mm (75%).

CAD systems assist the radiologist by "processing the breast films, using algorithms to detect suspicious areas and highlighting those areas," said Dr. Brem. This study shows that CAD can help in the most difficult-to-detect cases. CAD prompts the radiologist to re-examine the films, and the radiologist decides whether "true areas of concern are present at the highlighted locations before making the final diagnosis," she said.........

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June 5, 2006, 11:19 PM CT

New Way to Fight Brain Cancer

Taking advantage of a large assortment of chemical inhibitors produced by the pharmaceutical industry as potential drugs, Howard Hughes Medical Institute scientists have synthesized and characterized a panel of compounds that may lead to new therapy strategies for targeting glioblastoma, a common type of brain tumor that commonly thwarts therapy. The compounds have also revealed new information about insulin signaling, and could be a powerful tool to evaluate cellular enzymes as potential targets for drug design.

The work is detailed in two papers reported in the journals Cell and Cancer Cell. HHMI investigator Kevan M. Shokat at the University of California, San Francisco, is the senior author on the Cell paper, published on-line April 27, 2006, which describes a pharmacological map of the family of enzymes known as PI3-kinases. Zachary A. Knight, an HHMI predoctoral fellow in Shokat's lab, is the first author of the study, which was conducted in collaboration with colleagues from UCSF. The second paper, reported in the May 15, 2006, issue of the journal Cancer Cell, describes the effects of inhibiting these kinases in glioblastoma cells. Shokat and Knight collaborated on the Cancer Cell paper with senior author William A. Weiss at UCSF.

Researchers have devoted a great deal of research to kinases because they may provide the key to better understanding of a wide array of fundamental biological processes. Kinases are a huge family of enzymes that regulate intracellular communication by tagging key molecules with a small, energy-packed chemical group known as a phosphate. Their influence over processes ranging from cell growth and survival to learning and memory makes kinases desirable targets for new drugs, and progress in this area of research depends on the careful definition of the roles of individual enzymes.........

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June 5, 2006, 9:17 PM CT

New Predictor For Lung Cancer

Research from the Ireland Cancer Center of University Hospitals of Cleveland has found a promising, novel biomarker that may be used to predict the survival of patients with advanced lung cancer and their response to therapy. Afshin Dowlati, MD, hematologist/ oncologist at the Ireland Cancer Center, presented this study June 5 at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Dowlati found that patients with a low level of the biomarker ICAM had a better chance of survival and an increased response to chemotherapy. Dr. Dowlati analyzed data from a major national study, released at ASCO in 2005, that found the monoclonal antibody Bevacizumab (Avastin), in addition to standard treatment, was more effective than standard therapy alone for patients with advanced, non-squamous non-small cell lung cancer.

The analysis indicated that patients with low levels of ICAM (intercellular adhesion molecule -1), had a higher response rate to therapy (29% versus 13%) than patients with high ICAM levels. Patients with low ICAM levels also had a significantly better overall survival rate.

"We believe this research confirms a significant new prognostic marker in lung cancer," says Dr. Dowlati, who is also assistant professor at Case Western Reserve University School of Medicine. "Previously, it has been a challenge to identify those patients that will respond best to therapy and what their outcomes will be. This biomarker appears to serve as a much better predictor than gender, patients' overall health and sites of metastases." These findings confirm a pilot study performed three years ago at Ireland Cancer Center by Drs. Dowlati, Scot Remick and Keith McCrae, an expert in blood vessel disorders found in cancer.........

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June 5, 2006, 9:12 PM CT

Camptosar Important In Metastatic Colorectal Cancer

Data presented today at the annual meeting of the American Society of Clinical Oncology (ASCO) demonstrated that CAMPTOSAR® (irinotecan HCL injection), when given in the infusional regimen FOLFIRI , provided statistically significant longer progression free survival (PFS) compared to bolus mIFL and CapeIRI , two alternative chemotherapeutic regimens containing CAMPTOSAR used to treat metastatic colorectal cancer (mCRC). The study also demonstrated a statistically significant benefit in overall survival (OS) for patients treated with FOLFIRI plus bevacizumab when compared with those who received mIFL plus bevacizumab. These new data highlight the central role of FOLFIRI in the first line setting of mCRC to maximize patient benefit with CAMPTOSAR.

The predefined analysis of the primary endpoint showed FOLFIRI provided a statistically significant benefit in PFS (8.2 months) when compared with mIFL (6.0 months) or CapeIRI (5.7 months). In addition the median OS for FOLFIRI was 23.1 months, for mIFL - 17.6 months and for CapeIRI - 18.9 months. Though it did not reach statistical significance, there was a trend favoring FOLFIRI. OS benefit reflects all therapies patients may have received, including 2nd and 3rd lines. The most frequent grade 3/4 adverse events in all arms were diarrhea and neutropenia. In general the toxicity profile favored the FOLFIRI arm. Each arm had a secondary randomization to celecoxib or a placebo. In general, celecoxib neither improved efficacy nor reduced chemotherapy toxicity.........

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June 5, 2006, 9:04 PM CT

A Fundamentally New Approach To Chemotherapy

A new strategy for getting anti-cancer drugs to kill cancer cells, without causing serious harm to normal cells in the body, is published in the current [June] issue of ACS Chemical Biology, a monthly peer-reviewed journal of the American Chemical Society.

The approach, tested in laboratory experiments with several existing anti-cancer drugs, could offer substantial benefits for cancer patients, as per Jeffrey P. Krise, Ph.D. Krise led a group of pharmaceutical and medicinal chemists at the University of Kansas at Lawrence who did the research.

The new approach would allow anticancer drugs to accumulate in both normal and cancerous cells. The drugs, however, would be tweaked by giving them "basic" chemical properties. In chemistry, "basic" means an alkaline substance like baking soda or laundry detergent, which has properties opposite those of acidic substances.

Normal cells simply isolate anti-cancer drugs with basic properties, greatly reducing the toxic effects. Cancer cells, in contrast, have an impaired ability to isolate basic substances, and get hit with a full blast of toxicity.

"It could allow cancer patients to tolerate higher and more effective doses of chemotherapy before normal cells are damaged to an extent that causes serious side effects and cessation of treatment," Krise said. "The approach is completely different from prior attempts that were designed to deliver drugs only to cancer cells and not normal cells."........

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June 5, 2006, 7:09 AM CT

Post-operative Combination Therapy For Pancreatic Cancer

Adding the cancer-fighting drug gemcitabine to standard treatment after surgery significantly improves survival for patients with the most common form of pancreas cancer, as per a new multicenter study led by a University of Maryland radiation oncologist. The results of the four-year Phase III clinical trial were presented June 4 at the American Society of Clinical Oncology annual meeting in Atlanta.

More than 500 patients at 128 institutions across the country, including the University of Maryland Marlene and Stewart Greenebaum Cancer Center, were enrolled in the federally funded study from 1998 to 2002.

Thirty-two percent of study participants with "pancreatic head adenocarcinoma" (cancer of the head, or wider part, of the pancreas) were still alive three years after diagnosis after having surgery and being treated with gemcitabine, another chemotherapy drug called 5-fluorouracil (5-FU) and radiation treatment. That compares to a 21 percent three-year survival rate for patients who received 5-FU and radiation therapys alone following their surgery.

"The addition of gemcitabine to the standard postoperative therapy increased patients' survival by 50 percent, which is a significant improvement. We believe these findings will provide a new standard for treating patients with this devastating disease," says the principal investigator, William F. Regine, M.D., professor and chairman of the Department of Radiation Oncology at the University of Maryland School of Medicine and chief of radiation oncology at the University of Maryland Medical Center.........

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