P-276 Usefulness of telomerase activity measurements in fine needlebiopsy specimens in diagnosis of peripheral non small cell lung cancer

Posters/Early detection~Prevention the repeat screening, their correlations with repeating times (range 2-21 scans) were evaluated Results: Nineteen cancers were detected in the inital screening and 57 cancers in the repeat screening The number of cancers detected during the repeat scans was significantly less than that detected in the inital scans (Chisquare test. P <0 001) Although the rate of cancer detection (n ,57) did not decreased significantly depencing on the repeating t]mes, the detection rate of adenocarcinomas (n 35) decreased significantly (Sperman rank test; r~0.,560. P = 0.0147). Furthermore. the rate of in sltu carcinomas (Noguchi type A. B; n= 10) also decreased depending on the repeat]ng t]mes with s~geificant correlation (Sperman rank test; r=-O470. P = 0.0406). Stage I cancers were detected in 79% of the in~]al screening and in 84% of the repeat screer~ng Both showed no significant c~fference. Although the stage I ratio did net decreased sigr~ficantly depending on the repeat]ng t]mes, the stage I ratio of adooocarc~nemas also decreased sigr~ficantly (Sperman rank test; r=0 ,571. P 0 0128) The mean size of the detected cancers was 23ram in the init]al screehing and 17mm in the repeat screening Both showed borderline significant cifference (non-paired t test. P 0 0886) However. the size of cancers did not decreased signific~,ntly depending on the repeating times, and adooocarcinemes showed similar results Conclusion: In this mostly male smokers group, the decrease in cancer detecton and the stage shift were observed only in lung adenocercinomas dunog Ioog~erm repeat LDCT screening. These results might support the efficacy of repeat LDCT screening toward lung adenoca~noma in male smokers.

for [ • randomization, l s l model a survival, nor dcarcinogenesis: - l a kImpllcauons e and mortality In randomized trials

or

cancer screening G StTauss I [3 Babbitt 2. L Dominioni 3 ~Rhodr~ ts/and HospitalJBrown Mecltcal Sct~oot, Pro~dence, Rt, USA. 2Department ct Mathemabcs, UCLA,

Los Angeles, CA, USA, 3Universrty ot tnsutma, Vamso, Italy

Background: For over a half century, the randomized clinical tnal (RCT) has been the solentfic gold standard by which causal relatonships are assessed in patent pppulat or'fs. However. healthy individuals w h o participate in randomized tnals focusing on cancer early detection or chemoprevention do not have disease and are net patents. Accordingly. the term randomized population tnal (RPT) is mere appropriate to desonbe an exponmoot des~geed to evaluate an intervention in a large healthy populaton. A problem with RPTs is that their use was never accompanied by metbedologlc investgaton venfying that assumptons governing interpretat oo of RCTs are also true in the RPT settng Methods: A critical but unverified assumpton underlying RPT design is that randomization can produce esperimental and cootTOI cohorts with an equal probability of cancer However. it is quastonable whether randomization can reliably accomplish this objectve This is because randomizatoo in RPTs must contTOl for determinants of cancer dsk in the general pppulaton While these inolude exposure vanables (such as smoldng), they also include a potentally enormous number of genetic susceptibility variables. While these are currently largely unknown and nonmeasurable, these susceptibility factors are the predominant determinants of cancer risk in the general populat]on. Suscopt]bil~ factors compnse Iow~enetrance and high~enelJ'anca genes, as well as highly complex and poorly understood gane~gene and gone exposure interactions. Results: Stat]st]cal inliorooca in RPTs is trad~]ooally based upon the test of equality of binomial proportions Tits implicitly assumes that avery participant has an equal risk for the outcome event of interest However. this assumption is implausible when the outcome event is cancer incidence in the general population The known biologic and epidemiologic determinants of c~,ncer risk in the general populat]on suggests that the risk StTUcture for cancer incidence in the underlying populat]on is more complex In place of a uniform dsk model, we propose an island-lake model (ILM) of carcinogenesis In ILM. the underlying population is cempnsed of a real but unlmown "lake" of subjects without appreciable risk. and numerous real but ur~nown "Islands" of varying risk. While unknown predictors also exist in RCTs. R P T s are unique in that only they contain large hidden "l~es" of no nsk. Conclusions: Randomrlat]on may not be able to adequately control Ibr predictors of cancer nsk in the general pppulat]on. If this o ~ . cause specific mortality would net prevldo a valid measure of an early detection intervention ILM is more plausible than the conventional binomial, and offers a conceptual framework to understand the apparently anomalous and often highly controversial conclusions based upon mortality comparisons in numerous real-wodd early detection RPTs. including those ~ousing on lung cancer screening In early detectoo RPTs. the mortality endpoint would reflect both randomizat]oo failure and the effect of the intervention On the other hand. because the survival endpoint measures the conditional probability of cause specific death given the presence of dsease. It is more robust than mortality against randomlzat]on failure in this setting. Because both numerator and denominator are affected similady, cause speclfK: survival is less soosltve than mortality to confounding due to problems with randomization in early detection RPTs.

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[ P ~ 7 ~ u c e f u l n e ~ or telornerase adlvlty measurements In fine needle biopsy speclrnene In diagnosis of peripheral non small cell lung cancer I. Targowskl ~. K. JahnzRbLqfk ~. I. Szkoda 2. S. From ~ . R. RoZ,yr~ka I . J Mierzejs~vska I 1Department of Internal Medicine, Pneumonology and

Allergotegy, Md/tary lnstrtute ot Mad/c/no, Warsaw, Poland. 2Department ct Vtrolog~, NatJona/ /nstttute of Hygene, Poland Background: Telomerase. an enzyme related with cellular immortality, is highly expressed in the majority of cancers Assessment of telomerase actvity could be helpful in differootiaton between benign and malignant peripheral tumours of the lungs and could improve ser~sltivlty of c'ytological examination of speomens with a low call~ount obtained dunog fine neecle biopsy. Aim: Evaluation of dJagneste usefulness of telomerase exprsss~oo measure moots In fine needle biopsy specimens (FNB) of peripheral non small coil lung cancors (NSCLC). Methods: 21 patents with peripheral NSCLC were included to the study. Each subject had t]'ansthoracic FNB of turnour done. PCR ELISA PLus (ROCHE) method was used for ovaluaton of telomerase expression in FNB speclmer~. In patients with negative cytological results of FNB recognition was finally established by surgical procedure. Sensltvlty of cytological and telomerase expression examinatons was assessed. Results: 1,5 patents had posltve results of the cytological examinatoo of FNB specimens, while telomerase actvlty was found in 13 specimens. Five of six patents with negative oftologicel results had an elevated telomerase actvity in specimens Ohiy in one patent with cytological negative results telomerase expression was not found Sens~vity of the oftological examinatoo alone was 71 5%. while that oftelomerese measurements was 61% Sensitivity of tTanSthoracic FNE]. was markedly high if telomerase ac~vity measurements and cytological results were assessed together (positive telomerase ac~vity or pesi'dve cytological result: 20 of 21 subjects : 95 2%) Conclusion: Evaluation of telemerase activity in specimens derived from tz'ansthorac~e FNB could be helpful in diagnosis of peripheral lung tumours suspected of malignant character. We can Improve detection of early stage lun cancer by using aUtomated Image analysis (Clear Sign Test) of sputum? M. TercelJ~. A. Ales1. B. TurtJ. T. Rott 3. J. Er'zooI . M. Prtmi~ZakelJ 4.

1University Medical C/inic, Ljubljana, Slovenia, 2Perceptronix Medcal lnc, Vancouver, Canada, 3lnst/t~e for Pathology, Medical Sct7o~ University, tjubtjana, Slovenia, 4Institute of Oncotogy, Cancer Registry of Slovenia, Ljubtjana, Slovenia Background: During the last few years Automated Image Analysis of sputum (ClearSign TM test) has evolved into a valuable clageoste and prognostc tool in cytopathology A good portion of the u'dlity of Automated Image Analysis comes from its ability to detect and quantify the DNA amount and cistdbe'doo in cell nuclei, which cannot be done using cooventonal stain in routne cytology screening Methods: We have employed Automated Image Analysis of several thousand sputum cell nuclei per subject The nuclei were stained by DNA specific stain which enables the quanttat]ve assessment of over one hundred I~atures that dos~be the amount and dstnbut]on of DNA. 1043 high~lsk individuals aged 4,5 and over such as asbestos workers, long term smokers and ex smokers and COPD patients were enrolled in the study during four year period (2000-2004). Out of this number 150 patents gave their sputa before and alter lung cancer surgery performed with curative intent. All subjects were given chest x~-ays and sputum samples wore acquired by induc~oo using ultrasound nepulizers Sputum samples were processed for beth cenvootocal qualitatve cytology and Automated Image Analysis A fully automated, high resolu'don image cytometer (ClearSign TM Test4~ercaptTonix Medical Inc. Vancouver. Canada) was used to establish the probability for the presence or absence of lung cancer based on measurements of DNA amount and nudear distTibution in populatoos of cells Results and Conclusion: The results show that Automated Image Analysis of sputum could conthbute to the conventonal c~/tology to yield a significantly higher sensltvlty at an aoceptably reduced specificity and to post~)perative mooitonng of lung cancer patents. The abil~ to choose ROC (receiver operator charactenstcs) operatng pc~nt using Automated Image Analys~s may prove to be the most important feature of the new test as applied to sputum analysis. The dsouss~oo v~ll also address the role of Automated Image Analys~s of sputum in a comprehensive approach to detection and preventon of invasive lung cancer and its potential role in post-pperatve monltonng of lung cancer patents