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Gene Signature May Predict Recurrence of Lung Cancer
Date:5/16/2008

Could help docs determine who would benefit most from chemo after surgery, study says

FRIDAY, May 16 (HealthDay News) -- A panel of 15 genes may help determine which patients with early-stage non-small cell lung cancer will experience a recurrence and, therefore, benefit the most from chemotherapy, a new study shows.

By extension, the same genetic signature may also identify patients with less aggressive forms of the cancer who would be able to forego chemotherapy.

"Using this signature, we can identify up to 30 to 40 percent of stage I patients who might benefit from post-surgery chemotherapy and maybe up to 30 to 40 percent who might not benefit," said study author Dr. Ming Tsao, who will present the finding June 1 at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago. "The idea is that this could potentially supercede staging, although we definitely need more studies. [The information] is not immediately useful."

Previous trials have shown a benefit for stage I and II non-small cell lung cancer patients who received chemo after surgery. But, so far, the benefit has been confined mostly to stage II patients.

Even so, the distinction is not clear-cut. Some 30 percent of stage I patients who don't get added chemotherapy will die of a disease recurrence, and it's also possible that some stage II patients might not need chemotherapy after surgery.

"The goal of this study was to identify the genetic characteristics that could potentially be used to predict more precisely the likelihood of clinical outcomes, so those who need post-surgery chemo should get it and those who do not need it do not get it," explained Tsao, who is professor of laboratory medicine at the University of Toronto and a senior scientist at Princess Margaret Hospital in Toronto.

Gene expression profiling was performed on frozen tumor tissues from 64 patients as part of a follow-up analysis of a National Cancer Institute of Canada trial. Researchers then identified a group of 15 genes that divided the patients into high-risk (33 patients) and low-risk (31 patients) categories.

The signature was then validated in five other databases comprising a total of 372 stage I and II lung cancer patients.

Chemotherapy reduced the risk of death in high-risk patients (both stage IB and stage II) by about 67 percent, but not in low-risk patients.

While a previous analysis showed that overall, only patients with stage II disease benefited from chemotherapy after surgery, this study has demonstrated that the 15-gene signature may identify patients with both stage I and II cancers who would benefit from postoperative chemotherapy, further supporting its use in the selection of appropriate treatments.

In other news from the meeting, scientists from the University of Medicine and Pharmacy Iuliu Hatieganu in Romania have demonstrated for the first time that maintenance therapy (given after standard "induction" chemotherapy) with the chemotherapy drug Alimta (pemetrexed) extended time to recurrence by 50 percent.

"The data revealed a remarkably statistically significant 40 percent reduction in the risk of progression with pemetrexed, and a doubling of the median progression-free survival," said study author Dr. Tudor Eliade Ciuleanu, an associate professor at the University of Medicine and Pharmacy Iuliu Hatieganu in Romania.

The study involved 663 patients with advanced non-small cell lung cancer who had already undergone the initial course of chemo. Eli Lilly, which makes the drug, was involved in the trial.

Patients who received Alimta lived for 4.3 months without a recurrence of the disease, versus 2.6 months for those taking a placebo. Overall survival was 13 months in the Alimta group as compared with 10.2 months in the placebo group.

Finally, a Duke Comprehensive Cancer Center study found that post-surgical lung cancer patients can do well with aerobic exercise regimens starting as little as one month after surgery.

Twenty individuals newly diagnosed with and who had undergone surgery for Stage I to Stage IIIb lung cancer were asked to exercise three times a week for one hour at a time on stationary bikes. After 14 weeks, participants reported being less tired and also had more aerobic fitness (as measured by oxygen levels after exercising).

More information

The National Cancer Institute has more on non-small cell lung cancer.



SOURCES: Ming Tsao, M.D., professor, laboratory medicine, University of Toronto, and senior scientist, Princess Margaret Hospital, Toronto; May 15 teleconference with Tudor Eliade Ciuleanu, M.D., Ph.D., associate professor, University of Medicine and Pharmacy Iuliu Hatieganu, Romania


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