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Detection of occult metastases in patients with lung cancer

Institution: University of Southern California
Investigator(s): Richard Cote, M.D.
Award Cycle: 1999 (Cycle 8) Grant #: 8RT-0061 Award: $723,842
Subject Area: Cancer
Award Type: Research Project Awards

Initial Award Abstract
Lung cancer is the leading cause of cancer-related deaths in the United States and was estimated to kill 171,500 men and women in 1998. Tobacco use remains the single most relevant factor in development of lung cancers. Surgery ( alone or in combination with adjuvant therapy) represents the only potentially curative treatment. However, treatment failures occur in a high proportion of cases because of distant spread ( metastasis ) of the cancer cells. The detection of occult ( hidden ) metastasis is the most important issue for outcome and management of lung cancer.

Our laboratory has developed extremely sensitive methods for detecting occult tumor metastases. These methods are more sensitive than any clinical, pathologic or radiographic techniques, and detect as few as one tumor cell in one million normal cells. Pilot studies from our earlier projects on development and validation of these methods were funded twice by TRDRP. We have shown that occult tumor spread in lymph nodes and bone marrow is a significant predictor of disease recurrence. Furthermore, once surgery is performed, the primary form of treatment is adjuvant systemic chemotherapy. In patients with no evidence of metastasis, success of such chemotherapy is assumed to be due to killing of occult tumor before it becomes clinically evident. Therefore, the ability to detect occult metastasis is pivotal to identification of patients who would most benefit from chemotherapy.

The primary goal of this study is to definitively determine, in a multi-center clinical trial, if occult metastases detected in patients who are clinically free of disease can identify the patients most likely to progress to disease recurrence. This could have a profound influence on our ability to identify specific populations of patients most likely to benefit from systemic chemotherapy, and would also identify patients who may be spared from unnecessary chemotherapy.

We also plan to evaluate several novel techniques that we have developed in our laboratory which may make detection of occult metastasis more sensitive and readily available to physicians. These novel techniques include a sensitive image analysis system and sophisticated molecular biology methods.

Finally, we will study an important characteristic of tumor metastases, that is, their dormancy status. Characterization of dormancy may have significant influence on determination of type of treatment that will most benefit the patient.

The studies proposed here should allow us to identify patients with lung cancer at greatest and least risk of disease progression, define therapeutic options and provide new molecular targets for elimination of dormant metastases. These studies could have a profound impact on the management of patients with this common and lethal disease.

Ligation-mediated global cDNA amplification for quantitative transcript profilling of a finite number of tumor cells.
Periodical: Diagnostic Molecular Pathology Index Medicus:
Authors: Liu DX, Datar RH, and Cote RJ ART
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