Genetic precision (ASCO annual meeting)

Lung cancer: Focus on screening, prevention

With lung cancer accounting for approximately 29% of all cancer-related deaths and failing to mimic the downward trend of the overall cancer mortality rate, scientists are exploring new ways to detect it early, when it is most treatable. They also are testing drugs that may prevent it, according to several expert panels and studies presented at the American Society of Clinical Oncology annual meeting in Chicago last month.

"Survival is very poor and this has improved very little in the past 25 years. There's certainly a need," said James Jett, MD, professor of medicine at the Mayo Clinic College of Medicine in Rochester, Minn. He is involved in several early-detection trials.

Screening is the area with the most science but also the most controversy. Various scanning modalities, as well as sputum cytology, have been tried but are not widely used for screening because they have not been shown to improve overall mortality. False-negative and false-positive rates have been high, although one study suggested that a protocol incorporating spiral computed tomography with watchful waiting could overcome this issue.

Researchers randomized 30,047 former and current smokers ages 50 to 74 to receive either usual care or annual CT screening. Of this group, 7,556 have had baseline scans, and preliminary data indicated that monitoring the nodules detected in that procedure and responding if they grew led to fewer patients undergoing surgical workups for growths likely to be benign. Additionally, a number of cancers that otherwise would not have been found were detected early.

"Low-dose CT scanning for lung cancer is promising," said Dr. Rob J. van Klaveren, lead author and a pulmonary oncologist at the University Hospital in Rotterdam, the Netherlands.

This study is expected to be completed by 2009 with mortality data available in 2015.

Research also is being conducted to track bloodborne biomarkers that may indicate the presence of cancer in the lung. Investigators from the University of Cologne in Germany presented data on an RNA pattern identified by comparing blood samples taken from smokers with lung cancer to samples from healthy controls. Preliminary findings suggest this work could lead to a blood test that would identify those who have lung cancer or are likely to develop it within two years.

Researchers are investigating possible uses of pharmaceuticals in regard to prevention. According to one study, 400 mg of the Cox-2 inhibitor celecoxib twice daily reduced a marker of cell proliferation in the lungs.

"We cannot say that taking celecoxib will prevent lung cancer, but it was safe to administer. We did not have any cardiac events. We need to move forward with perspective validation studies," said Edward S. Kim, MD, lead author and assistant professor of thoracic head and neck medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

Previous studies of these drugs as preventives for colorectal cancer were derailed when cardiovascular risks became apparent. Those researching their use for lung cancer prevention say the benefits may outweigh the risks in this situation. The key difference is that screening for colorectal cancer is widely available. The same cannot be said for lung cancer.

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Research findings: Alleviating fatigue, treating testicular cancer, cutting risks of recurrence

A stimulant may address the severe fatigue affecting many cancer patients, according to a study presented in June at the American Society of Clinical Oncology annual meeting in Chicago.

Researchers analyzed data on 642 patients randomized to receive 200 mg of modafinil or a placebo. Those with severe fatigue were most likely to benefit from the drug, while those with mild or moderate symptoms did not. The drug, which has Food and Drug Administration approval for the treatment of narcolepsy, was supplied by manufacturer Cephalon Inc., with study funding from the National Cancer Institute.

Cancer patients often struggle with fatigue long after treatment ends. The authors hope modafinil will reduce the risk of the problem becoming lifelong.

"One would hope that if you get it early and treat it successfully, then it won't occur later," said Gary R. Morrow, PhD, lead author and director of the University of Rochester Cancer Center Community Clinical Oncology Research Base in New York.

Scientists also are fine-tuning cancer treatments to minimize long-term adverse events or to suit patient preferences. One study found a single dose of chemotherapy could be as effective as radiation, and less toxic, in treating early-stage testicular cancer.

Researchers from several European nations, South Africa, Canada and Brazil randomized 1,477 patients to receive one dose of carboplatin or two to three weeks of radiation. After an average of 6.5 years of follow-up, both study arms had similar relapse-free survival rates, but the men who received the drug were less likely to develop cancer in the previously unaffected testicle.

Other papers looked at strategies to reduce the risk of recurrence. For instance, Austrian Breast and Colorectal Cancer Study Group researchers randomized 1,801 premenopausal women treated for hormone-receptor positive breast cancer to various forms of ovarian suppression, with or without zoledronic acid. After five years, the drug was shown to reduce the risk of relapse by 35%, although there was no statistically significant difference in overall survival.

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Treatment tips

Risk assessment tools may identify those appropriate for genetic testing. More than a dozen models exist to determine who should be tested for the genes that increase the risk of breast and ovarian cancer. They all work fairly well, but the choice of which to use should be determined by the patient population.

"The bottom line is that the performance of the models is surprisingly similar, but comparing them is harder than one might realize," said Noralane M. Lindor, MD, professor of medical genetics at the Mayo Clinic College of Medicine, Rochester, Minn. She gave a presentation during a session on ways to assess hereditary cancer risk. "You have to look at your practice and consider how your practice compares to the models. Consider doing a study to evaluate how the various models do in your practice."

During that session, experts also advocated against overreliance on these tools because most don't take into account second-degree relatives, and no studies compare them head to head. "These models are really tools to complement clinical judgment, not replace it," Dr. Lindor said.

Listening key with terminal patients. A physician's ability to listen is important to help cancer patients whose death is imminent to accept their prognosis and get the most out of the time they have left.

"Cancer provides a level of immediacy that is overwhelming ... and yet there are many people who are able to go into their core and find the strength to overcome it," said Richard J. O'Reilly, MD, chair of pediatrics at Memorial Sloan-Kettering Cancer Center in New York. He was part of a panel discussion on delivering bad news. "How do we help them, not so much to accept, but to transcend and develop the capacity to feel each moment and make life worthwhile? ... We think we know what they want, but we don't. If we listen to these patients, we can help them."

Experts also suggested addressing patient fears about being alone and dying without dignity.

"We often have to transition from being the person who provides medicine to providing comfort," said Bruce Chabner, MD, clinical director of the Massachusetts General Hospital Cancer Center, who chaired the session.

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