Lung Cancer Screening Recommendation Updated

The U.S. Preventive Services Task Force has revised a 1996 recommendation that firmly advises against screening for lung cancer, now saying that it is "neither for nor against" using chest X-rays (CXR), low-dose computed tomography (LDCT), sputum cytology, or a combination of these tests for such screening. The task force's revised recommendations were published in the May 4 Annals of Internal Medicine.

Researchers examined the data and results from six randomized, five case-controled, and six cohort studies that they deemed fair in quality. Although there was evidence that CXR, LDCT, and sputum cytology screening can detect lung cancer at an earlier stage than in unscreened populations, the studies were not designed to determine whether screening decreases mortality rates from lung cancer.

Lung cancer is fatal in more than 90 percent of affected persons, but survival is directly related to early diagnosis, when patients may not necessarily exhibit any symptoms. Survival rates range from 70 percent at stage I to 5 percent at stage IV. In weighing their recommendation, the report explains, the task force balanced the benefits of screening against the invasive nature of diagnostic testing and the likelihood of false-positive and false-negative results creating harm in the patient population.

"Current data do not support screening for lung cancer with any method," the task force concluded. "These data, however, are also insufficient to conclude that screening does not work, particularly for women."

The NCI-sponsored National Lung Screening Trial closed enrollment in February 2004 with approximately 50,000 participants, and is comparing spiral CT and standard chest X-ray. It is slated to collect and analyze data for eight years.

Post-Surgical Chemo and Radiation Therapy Fares Well in Head and Neck Cancer

The concurrent use of cisplatin and radiation therapy after surgery to remove a tumor in patients with squamous-cell cancer of the head and neck improves disease-free survival compared with radiation therapy alone, according to the results of two new NCI-funded studies. Only one of the two studies, however, yielded an improvement in overall survival; combination therapy was associated with a higher incidence of acute adverse events, but not late adverse effects. Both studies were published in the May 6 New England Journal of Medicine.

The research teams coordinated their work and, with the exception of inclusion criteria, both studies followed the same protocol. In the first study, conducted by the European Organization for Research and Treatment of Cancer (EORTC), 167 patients were randomly assigned to receive radiotherapy after surgery "with curative intent" and 167 were assigned to a combination of radiation therapy and cisplatin. In the other trial, conducted by the U.S.-based Radiation Therapy Oncology Group, following surgery 231 patients received radiotherapy alone and 238 received the combination therapy. Only the EORTC trial, however, yielded an improvement in overall survival, with 5-year actuarial estimates of 53 and 40 percent, respectively.

In a related editorial, Drs. Michele I. Saunders and Ana M. Rojas, from University College London and Mount Vernon Hospital (UK), respectively, said the studies "provide a strong basis for the inclusion of concurrent chemotherapy in postoperative regimens of radiotherapy for high-risk patients." Several recent studies, they continued, have indicated that shorter radiotherapy intervals than were used in these trials may improve tumor control and survival. "The next obvious step," they concluded, "is identifying which radiotherapy regimen is most effective."

Laparoscopic Surgery for Colon Cancer Acceptable Alternative to Open Surgery

A multi-institutional study suggests that laparoscopic surgery is a safe, appropriate alternative to open colectomy for colon cancer. In a randomized trial of 872 patients with adenocarcinoma of the colon, patients who had laparoscopically assisted surgery had similar rates of recurrence, disease-free survival, and overall survival compared to the group who underwent traditional open surgery.

The study, published in the May 13 New England Journal of Medicine, showed that the laparoscopic patients also recovered faster (5 versus 6 days) and needed less pain medication. In an accompanying editorial, Drs. Theodore Pappas and Danny Jacobs of Duke University, noted that although surgeons have been slow to perform laparoscopic resections, "the surgical landscape is changing. We predict that…more surgeons will use minimally invasive techniques to manage diseases of the bowel. Oncologic surgeons must improve access to minimally invasive surgery because patients expect nothing less."

Mutation May Predict Response to Chemotherapy in Leukemia Patients

According to a report in the May 5 Journal of the National Cancer Institute, chronic lymphocytic leukemia (CLL) patients with a mutation in the promoter region of their MCL-1 gene had higher mRNA and protein expression levels of MCL-1, which may be responsible for the poorer response to chemotherapy and the more rapid disease progression observed in these patients. Dr. Oksana Moshynska and colleagues at the University of Saskatchewan discovered that the presence of this 6- or 18-nucleotide insertion in the upstream region of the MCL-1 gene was also associated with shorter overall survival rates of CLL patients.

Scientists had previously correlated high levels of MCL-1 protein with failure to respond to chemotherapy in patients with CLL, the most common form of leukemia in the United States. CLL is not caused by increased proliferation of abnormal cells, as is common in other types of cancers, but by the persistence of abnormal lymphocytes that have prolonged lifespans and do not undergo apoptosis. The MCL-1 protein is known to play a role in apoptosis.

The researchers found the insertion in the promoter of the MCL-1 gene in 17 of 58 CLL patients; these mutations were not observed in the MCL-1 promoter of 18 control subjects. Seven of the 10 patients who did not respond to chemotherapy had mutations in the MCL-1 promoter, and none of the 12 patients with complete or partial response to chemotherapy were found to have these mutations.

The authors of the report noted that further studies, using a larger group of patients, would be needed to determine if "the size of the insertion, 6 or 18 nucleotides, has an effect on mRNA and protein expression (of MCL-1) and prognosis."

Smoking Rates Drop in New York City

On May 12 the New York City Department of Health and Mental Hygiene announced a significant decline in the number of smokers in New York City between 2002 and 2003. Data collected by the survey unit at Baruch College on tobacco use and a variety of other health issues showed that the proportion of New Yorkers who smoke dropped from 22 percent in 2002 to 19 percent in 2003. Young adults were found to have the largest decline, with the proportion of those aged 18-24 who smoke decreasing by 22 percent.

To accomplish this, New York City implemented effective evidence-based policies to increase the cost of tobacco products and ensure that workplaces have air free of tobacco smoke. The city also introduced programs to help smokers quit. Dr. Scott Leischow, acting associate director of Behavioral Research of NCI's Behavioral Research Program, asserts, "If we could achieve the reductions on a national scale that have been reported in New York City, we would have about five million fewer smokers - and in that one year we would take a major step toward reducing the pain, suffering, and premature death from tobacco-related cancers."

In the May 11 issue of the NCI Cancer Bulletin, the receipt dates for applications for PA-04-103 were incorrect. The correct dates are June 1, 2004; Oct. 1, 2004; Feb. 1, 2005; June 1, 2005; Oct. 1, 2005; Feb. 1, 2006.