Male Tobacco Switchers Have Increased Mortality Rates

Men who switch from smoking cigarettes to smokeless tobacco (chewing tobacco and snuff) had a higher rate of death from all causes, lung cancer, coronary heart disease, and stroke than former cigarette smokers who quit using tobacco entirely, according to study results published online February 15 in Tobacco Control.

Dr. Michael J. Thun of the American Cancer Society (ACS) and colleagues identified 4,443 men who were switchers and 111,952 men who quit tobacco entirely from the Cancer Prevention Study II. This ongoing prospective study includes 1.2 million U.S. adults; it began in the fall of 1982 with a follow-up 20 years later. In the study, ACS volunteers asked friends, neighbors, and acquaintances who were 30 and older to complete a confidential, four-page mailed questionnaire on their smoking habits, alcohol intake, education, and other demographic characteristics.

Most switchers in the study began using smokeless tobacco within a year of quitting smoking and had used smokeless tobacco for an average of 9 years. The researchers found that switchers had significantly higher rates of death from all causes, lung cancer, coronary heart disease, and stroke than men who had never used tobacco or were former cigarette smokers and quit using tobacco entirely. Additionally, researchers found differences in demographic characteristics and lifestyle. Switchers tended to be less educated, more often employed in blue-collar occupations, more likely to engage in heavy exercise­ (possibly associated with a blue-collar occupation), and reported consuming fewer fruits, vegetables, and alcohol, but more dietary fat than those who quit using tobacco entirely. The analyses adjusted for other risk factors and the number of years the switchers smoked, number of cigarettes smoked per day, and age at quitting smoking.

The authors noted that "Our results support the stand that smokers who want to quit should be offered safe, clinically proven treatments for smoking cessation, including pharmacotherapies such as medicinal nicotine or antidepressants, behavioral counseling, and telephone quitlines."

Researchers Discover Biomarkers for Diagnosing Liver Cancer

A team of researchers led by Dr. Xin Wei Wang of NCI's Center for Cancer Research (CCR) has identified a five-gene signature that can be used to diagnose early-stage hepatocellular carcinoma (HCC). The findings appeared online February 20 in Clinical Cancer Research.

Currently, an elevated level of the protein alpha-fetoprotein (AFP) in the serum is the only known diagnostic biomarker for HCC. This elevated level of AFP is detectable in only about one-third of patients with early-stage HCC. Consequently, most HCC is not diagnosed in its early stages, leading to high mortality from the disease.

Using microarray techniques to examine a range of gene expression profiles from 218 HCC specimens, Dr. Wang's team and collaborators at the Liver Cancer Institute of Fudan University in China identified five candidate genes that were overexpressed in HCC. This finding, in combination with Dr. Wang's earlier research into the tumor microenvironment, suggests a potential means for increased accuracy in diagnosis and monitoring recurrence during treatment.

Men with Low-Risk Prostate Cancer Often Choose Treatment over Surveillance

Men diagnosed with prostate cancer who have a very low risk of dying of the disease and are eligible for active surveillance - also known as watchful waiting - rarely choose this option over treatment, researchers reported last week at the Prostate Cancer Symposium in Orlando, FL. An analysis of data from the CaPSURE prostate cancer registry found that only 9 percent of those eligible for surveillance selected the option.

Active surveillance involves the careful monitoring of the disease until such time as treatment is needed. Physicians may recommend active surveillance for older patients with early-stage disease who are more likely to die of another cause; some forms of prostate cancer progress so slowly that they never cause any harm.

In the study, older men chose surveillance more often than younger men. Men over age 70 were 26 times more likely to choose surveillance than men younger than 63, while men between 63 and 70 were 5 times more likely to choose surveillance than those younger than 63.

The researchers analyzed data on 1,886 patients diagnosed between 1999 and 2004. Of this group, 310 had very low-risk disease based on 5 criteria including prostate-specific antigen level, Gleason score, and stage. Only 28 of the 310 candidates (9 percent) chose surveillance.

Anxiety caused by a diagnosis of cancer may be a factor driving men to choose treatment, said Dr. Daniel Barocas of the New York-Presbyterian Hospital-Weill Cornell Medical College, who presented the findings. Previous studies have estimated that about one in five men who choose surveillance will go on to develop prostate cancer that cannot be treated.

Dr. Eric Klein of the Cleveland Clinic, who commented on the findings, said that an issue for clinicians is the lack of adequate tools to identify which patients are likely to need future treatment and which are not. A second issue is the lack of clinical tools to determine when a person who has chosen surveillance needs treatment.

"Until we have those tools there is likely to be some hesitancy to choose surveillance," said Dr. Klein.

High Doses of Vitamin D Hormone Boost Prostate Cancer Therapy

Some men with advanced prostate cancer may benefit from taking the chemotherapy drug docetaxel in combination with a pill that delivers high doses of the vitamin D hormone, a randomized phase II clinical trial has found. The pill, DN-101, contains a biologically active form of vitamin D called calcitriol. Preclinical studies have suggested that high amounts of calcitriol may benefit patients with prostate cancer.

In the trial, the addition of calcitriol to docetaxel did not lead to an increase in toxic side effects, and it was associated with a reduced risk of death (by approximately a third over docetaxel alone). DN-101 is thought to work by producing much higher blood levels of calcitriol than the body can produce from dietary vitamin D or vitamin D supplements.

Dr. Tomasz Beer of the Oregon Health & Science University Cancer Institute and his colleagues reported the findings in the February 20 Journal of Clinical Oncology. Dr. Beer's team first tested calcitriol plus docetaxel in a small group of patients several years ago. 

The new results are from the Androgen Independent Prostate Cancer (AIPC) Study of Calcitriol Enhancing Taxotere (ASCENT), a randomized, double-blinded, placebo-controlled trial. It included 250 men at 48 sites in the United States and Canada. The men had advanced prostate cancer that no longer responded to hormonal therapy, a condition called androgen-independent prostate cancer.

"The purpose of this study was to see if there was sufficient evidence for undertaking a phase III trial, and the survival data clearly demonstrated this," said Dr. Beer. A final-stage clinical trial is underway to test the effects of docetaxel plus calcitriol on overall survival in a larger group of patients.

Secondary Sarcomas Threaten Childhood Cancer Survivors

Previous research has shown that children who received radiation therapy for cancer treatment and survived at least 5 years face an increased risk years later of developing bone and soft tissue sarcomas. Now, new findings reported in the February 21 JNCI reveal that - regardless of what treatments they received - childhood cancer survivors are nine times more likely to develop sarcomas than are their age-matched peers in the general population. On average, the secondary sarcoma appears 11 years after the initial cancer diagnosis.

When researchers compared the 104 patients who developed secondary sarcomas with the 14,258 other survivors from the Childhood Cancer Survivors Study (CCSS) who did not, a number of additional risk factors emerged. Children originally given radiation therapy had 3.1 times the risk. Three other risk factors more than doubled the risk of secondary sarcoma: a history of other secondary neoplasms and high doses of chemotherapy with either anthracyclines or with alkylating agents. Children with an original primary diagnosis of sarcoma were at greatest risk, however, with a 10.1 times higher risk than children who survived other types of cancer.

 "Diagnosis of a sarcoma can sometimes be elusive because symptoms are often nonspecific," wrote lead author Dr. Tara O. Henderson of the University of Chicago. She urged clinicians and researchers to take these new findings into consideration as they evaluate the risk for second cancers in this highly vulnerable population.