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Guest Column

Lung cancer survival may be predictable

By Dr. V. Upender Rao
Published January 15, 2007

Current staging methods of lung cancer have limited capability of predicting the long-term outcomes of early-stage lung cancer patients who undergo a presumed curative surgical resection of the tumor. Because of tumor heterogeneity, there is considerable variance in virulence and outcome within similarly staged and similarly treated patients.

For instance, stage I non-small cell lung cancer patients are treated with major surgery with a curative intent. In spite of such aggressive treatment and weeks to months of recovery and rehabilitation, roughly 50 percent of these patients will experience recurrence of the cancer to which they will eventually succumb.

Such discordance in outcome owes to the variant expression of key survival and death coding genes within the tumor. This is not obvious on routine pathological diagnosis, which is the standard of practice today.

Researchers from the National Taiwan University studied 185 tumor specimens from 125 consecutive patients who had surgical resection of nonsmall cell lung cancer.

Using gene expression micro array technology, they identified 16 genes - four protective and 12 risk-associated - out of many that were abnormally expressed.

They applied the real time polymerase chain reaction analysis to these 16 genes and found good correlation between the micro array and RT-PCR assays for five genes. The study results were published in the Jan. 4 issue of the New England Journal of Medicine.

The authors devised a five-gene signature expression model, based on which they assigned good or poor risk to early stage nonsmall cell lung cancer patients.

Overall survival, progression-free survival and death were significantly worse among patients who were assigned the higher risk.

The five-gene assay was also validated in another set of 86 Western patients with nonsmall cell lung cancer.

For the prediction of survival, this test had a sensitivity of 98 percent and a specificity of 93 percent, a positive predictive value of 95 percent, a negative predictive value of 98 percent and an overall accuracy of 96 percent.

In the Oct. 10 issue of the Citrus Times, I wrote about the Lung Metagene Model, developed by Anil Potti, M.D., and his colleagues from Duke University. Like the five-gene model, the Lung Metagene model also had an 80 percent accuracy rate of predicting recurrence in stage I nonsmall cell lung cancer.

Based upon these two studies and others in the literature, it appears that micro array and RT-PCR-based gene expression models can predict the outcomes for early-stage lung cancer patients with a high degree of accuracy.

Patients in the high risk category could be entered on to adjuvant therapy trials, and the low risk group could be allowed without further treatment. Further, the expression models may also reveal attractive targets for much-needed targeted drug development for nonsmall cell lung cancer.

V. Upender Rao, M.D., FACP, practices at the Cancer and Blood Disease Center in Lecanto.

[Last modified January 14, 2007, 21:13:37]