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Persistent Lesions a Harbinger of Invasive Cancer: Presented at WCLC

By Norra MacReady

SEOUL, SOUTH KOREA -- September 5, 2007 -- Persistent bronchial dysplasia appears to be a precursor of non-small cell lung cancer (NSCLC), researchers reported here at the 12th World Conference on Lung Cancer (WCLC).

The relationship between bronchial dysplasia and NSCLC has been hard to confirm because earlier studies by different investigators have been limited by the small number of specimens examined and short follow-up times, said Daniel T. Merrick, MD, Assistant Professor of Pathology, University of Colorado, Denver, Health Sciences Center, United States.

He and his colleagues studied 121 patients enrolled in bronchoscopy trials under the aegis of the Colorado Specialized Center of Research Excellence (SPORE) program. Each patient had at least one site from which more than one biopsy had been obtained at different times. This yielded 1,354 biopsies taken from 551 unique biopsy sites. Thirty-two of the patients had a history of carcinoma. Also included were samples from 14 other patients who had had a biopsy at a site within the specific lobe of a subsequent carcinoma.

The lesions were assigned a score based on their histologic classification, according to criteria established by the World Health Organization. Nondysplastic lesions received scores of 1 to 3, low-grade dysplasia received a score of 4 and was considered mild; and high-grade dysplasia was scored as 5 (moderate) or 6 (severe). Carcinoma in situ (CIS) received a score of 7.

Using the initial biopsies taken at any given site as a reference point, the investigators determined if subsequent specimens had progressed, persisted, or regressed in severity. They also calculated a dysplasia index (DI) for each bronchoscopy, defined as the number of dysplastic biopsies divided by the total number of biopsies obtained per bronchoscopy.

High-grade dysplasia and CIS persisted or progressed in 68.5% of cases, compared with 43.7% of low-grade dysplasias (P <.001). Persistence and progression also correlated with DI; biopsies with high-grade dysplasia were associated with a mean DI of 0.621, compared 0.521 for those that regressed (P =.005). Low-grade dysplasias that persisted or progressed were associated with a mean DI of 0.578, compared with a mean of 0.371 for those that regressed (P <.001).

Interestingly, "with higher grades of dysplasia, progression became less frequent," Dr. Merrick pointed out in his presentation on September 4. Of 188 high-grade lesions, 14 (7.5%) progressed, over a mean of 21.4 months. There were 102 low-grade lesions, of which 29 (28.4%) progressed, also over a mean of 21.4 months. Of 21 squamous metaplasias, 11 (52.4%) progressed over a mean of 15.6 months.

There was a wide variability within each category in the time required for progression, with some of the higher-grade lesions taking as long as 8 to 10 years. These findings suggest that long follow-up times are needed to establish a relationship between specific lesions and eventual invasive carcinoma, and to determine the efficacy of chemopreventive measures, he said.

Dr. Merrick concluded, "these data support the role of bronchial dysplasias as pre-malignant lesions in non-small cell lung cancer."

[Presentation title: Outcomes in Bronchial Dysplasia: Persistence of Lesions and Associations With Development of Invasive Non-Small Cell Lung Cancer. Abstract A7-05]

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