O-164 A multi-center study comparing autofluorescence bronchoscopy to white light bronchoscopy

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Oral Sessions/Etiology

and Epidemiology

under WL and 75.3% under AF (PC 0.0001). PPV for AF was 22.2% vs. 18.4% for WL (pEO.49); NPV for AF was 94.9% and for WL 90.2% (p=
I

0 165

Near-infrared Raman Spectroscopy of Lung Cancer

Raman spectroscopy is a vibrational spectroscopic technique that can be used to optically probe the molecular changes associated with diseased tissues. The objective of this study was to explore near-infrared (NIR) Raman spectroscopy for distinguishing tumor from normal bronchial tissue. A rapid dispersive-type NIR Raman system incorporating a Raman probe was developed for tissue Raman studies at 785 nm excitation. High-quality Raman spectra in the 700-1800 cm-’ range from human bronchial tissues in vitro could be obtained within 5 seconds. Raman spectra differed significantly between normal and malignant tumor tissue, with tumors showing weaker signals in carotenoid bands and stronger nucleic acid signals than normal tissue. Raman spectral shape differences between normal and tumor tissue were also observed particularly in the spectral ranges of 1000-l 100, 1200-1400, and 1500-1700 cm-‘, which are related to the protein and lipid conformations and CH stretching modes in nucleic acids. The ratio of Raman intensities at 1445 cm-’ to 1655 cm” provided good differentiation between normal and malignant bronchial tissue. The results of this exploratory study indicate that NIR Raman spectroscopy provides a significant potential for the noninvasive diagnosis of lung cancers in vivo based on optical evaluation of biomolecules.

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and Environmental

Exposure

TUESDAY, 12 AUGUST 2003

Etiology and Epidemiology Susceptibility and Environmental Exposure

for Optical Diagnosis

Zhiwei Huang’, Annette McWilliams*, Stephen Lams, Harvey Lui4, Haishan Zeng*. ’ Cancer Imaging Dept, BC Cancer Agency, Vancouver, Canada; ’ BC Cancer Agency Vancouver, Canada: 3 BC Cancer Agency, Vancouver; Canada; 4 Division of Dermatology University of British Columbia and Vancouver Hospital and Health Sciences Centre, Vancouver, Canada

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Susceptibility

Staging by EUS-FNA in addition to Mediastinoscopy leads to a significant reduction of futile thoracotomies in NSCLC

Jouke T. Annema’, Michel I. Versteegh*, Maud Veselic3, Lutz Welker’, Jacob K. Sonts, Klaus Rabe’ 7 LUMUDepartment of Pulmonology, Leiden, The Netherlands; ’ LlJMCYDepartment of Cardio-thoracic surgery, Leiden, The Netherlands; 3 LlJMC/Department of Pathology, Leiden, The Netherlands; 4 KU GrosshansdorUDepartment of Cytology Grosshansdotf, Germany; 5 LUMQDepartment of Medical Decision Making, Leiden, The Netherlands

Objective: to asses whether additional staging by Endoscopic ultrasound guided fine needle aspiration (EUS-FNA), in patients with NSCLC and a negative mediastinoscopy, leads to a significant reduction in the number of futile thoracotomies. Background: the use and prognostic value of mediastinoscopy (MS) has considerable limitations regarding its sensitivity and negative predictive value, due to restrictions in its diagnostic reach [upper and lower paratracheal stations (nr 2 and 4) and superior part subcarinal station (nr 7)]. In daily practice, staging by mediastinoscopy alone leads to a high number of futile thoracotomies due to locally advanced or irresectable tumours. EUS-FNA has a diagnostic reach which is complementary to mediastinoscopy: the aortapulmonary window (nr 5), superior and dorsal part of the subcarinal station (nr 7) the paraesophageal lymph node stations (nr 8) and those in the ligamentum pulmonale (nr 9). The additional value of EUS-FNA however, in the staging of NSCLC patients with a negative mediastinoscopy, has not yet been proven. Methods: 80 patients with proven NSCLC underwent both EUS-FNA and mediastinoscopy for staging purposes. When no lymph node metastases were established at mediastinoscopy a thoracotomy was performed with lymph node sampling to evaluate both the EUS-FNA and mediastinoscopy results. Results: sensitivity specificity and diagnostic accuracy for mediastinoscopy were: 40%, lOO%, 71%, for EUS-FNA 55%, 95%, 76% and for the combination of MS + EUS-FNA 78%, 95% and 89%. The prevalence of pT4 (9%) and pN2-3 (37%) disease was 48%. of the 36 patients with pT4 or N2-3 disease, 15 (42%) were assessed by mediastinoscopy, 21 (58%) by EUS-FNA and 29 (81%) by either mediastinoscopy or EUS-FNA. The number of futile thoracomies in the 64 patients who went for surgery would have been decreased from 23 (29%) to 9 (11%) [p=O.O04, relative reduction of 61%] if both EUS-FNA and mediastinoscopy would have been performed routinely in the preoperative staging. Conclusion: staging by EUS-FNA, of NSCLC patients with a negative mediastinoscopy, prevents unnecessary surgery in one out of five patients. Supported by the Leiden University Medical Centre (LUMC)Technical support by Hitachi ultrasound

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167

The effect of parental smoking in childhood cancer risk; a case-control study

on lung

Jin Soo Lee’, Young Ho Yun’, Ji-Youn Han’, Choon Son Park’, Hee Sun Kim’, Bin Hwangbo2, Eun Kyoung Hangs, Jae-Ill Zo’, Eun Sook Lees, Jae-Gahb Parka. ’ Research institute & Hospita/, National Cancer Center, Korea, Goyang, Korea; ‘Research lnstitue & Hospital, National Cancer Center, Korea, Goyang, Korea Smoking is the major cause of lung cancer and the duration of smoking rather than the amount has much greater impact on lung cancer risk. But the role of passive smoking has not been emphasized enough even though exposure to environmental smoke in childhood may be more harmful than currently appreciated. We conducted this study to examine the effects of passive smoking in childhood on the risk of lung cancer. Using a pre-tested interview questionnaire, we collected demographic and socioeconomic data and the information on smoking status, both personal and exposure to environmental passive smoking from 1,826 patients (pts) who visited National Cancer Center between 5/2002 and 1112002. The case consisted of 459 lung cancer pts (M/F: 317/142) and we selected 2 control groups, 1) non-cancer pts who visited the Center for Lung Cancer or the Center for Cancer Prevention and Screening (n=431, M/F: 265/166), and 2) other cancer pts (n=649, M/F: 242/407). The proportion of lifetime non-smokers were 6.9%, 15.1%, 14.1% for males in lung cancer cases, control groups I and II, and the corresponding figures for females were 81.7%, 86.8%, and 87.2%, respectively. By univariate analysis, lower educational level, older age, lower income level, and rural residence in childhood were associated with higher risk of lung cancer. When the educational level was stratified, paternal smoking was an important risk factor for female pts with low education level (OR=3.97, p=O.O16 and OR=2.92, p=O.O12, when compared with control I and II, respectively), and for female pts with high education level (OR=3.02, p=O.O04, when compared with control II). There were trends toward increased risk with paternal smoking for young (< 45 yrs) smoking male (OR=3.03, p=O.O4, when compared with control I), and maternal smoking for smoking male pts (OR=2.14, p=O.O02, when compared with control I). Spouse smoking was not associated with any increased risk in this analysis, even for the non-smoking females, While more in-depth analyses are needed, these results strongly suggest that environmental exposure to parental smoking in childhood is an important risk factor for lung cancer development. (Supported by NCC Grant N02BOlO).

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ccl

Famrlral and second lung cancers: a nation-wide :.. eprdemrology study from Sweden

Xiniun Li, Kari Hemminki.

Karolinska

Institute, Stockholm,

Sweden

The role of hereditary factors in tumor development has been less well understood for lung cancer than for many other human neoplastic diseases. The nation-wide Swedish Family-Cancer Database was used on 10.2 million individuals and 4524 lung cancers to calculate standardized incidence ratios (SIRS) and 95% confidence intervals (Cls) for histological subtypes of lung cancer in O-66 year old offspring by cancers in family members. Additionally, SIRS for second lung cancers were analyzed. SIRS in offspring for all lung cancer were increased to 1.87 (95%CI 1.66-2.10), adenocarcinoma to 2.15 (1.77-2.59) and squamous cell carcinoma to 1.86 (1.39-2.44) when a parent presented with lung cancer. The familial risk was not dependent on diagnostic age. Lung cancer associated with parental rectal, cervical, kidney, urinary bladder and endocrine gland cancer. The population attributable fraction of familial lung cancer was 2.97%. Risks for second lung cancers were increased in men and women after smoking and life style related sites, and after skin cancer, non-Hodgkin’s lymphoma and Hodgkin’s disease.

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0 169

Glutathione Pathway Genes Differentially Interacting with Tobacco Smoking in Lung Cancer Risk at Young and Old Age

Pinq Yang, William Bamlet, Jon 0. Ebbert, William R. Taylor, Scott H. Okuno, Mariza deAndrade. Mayo Clinic, Rochester, USA

Background: Individuals younger than 50 or older than 80 years of age develop lung cancer infrequently. Assessing host susceptibility to lung cancer in young and old populations may be important for understanding lung cancer etiology.

Oml Sessions/Lung Cancer Imuging sibilities of such an intervention. ProposalA 6-month project was developed to ascertain the benefit of art therapy to patients attending the Day Therapy Unit (DTU). All patients referred to the DTU would undergo an art therapy assessment followed by an individual plan of intervention all patients would be seen on a one to one basis. Evaluation was in the form of a short pre and post intervention questionnaire which would undergo a content analysis. Preliminary results: see table. Conclusion: The provisional data has shown a significant improvement in patients quality of life by addressing emotional and psychological issues within a safe therapeutic environment. The expertise of a qualified Art Therapist within the multi-disciplinary team has enhanced the function of the team as a whole, by providing insight and intervention for the complex psychological needs of this group of patients.

TUESDAY, 12 AUGUST 2003

Lung Cancer I0

161

Imaging

Screening for Lung Cancer with Low Dose Spiral Computed Tomography (SCT): The Mayo Clinic Trial

James Ft. Jett, Stephen J. Swensen, David E. Midthun, Thomas E. Hartman, Gregory L. Aughenbaugh, Jeff A. Sloan, Anne-Marie Sykes, Amy C. Clayton, Henry D. Tazelaar. Mayo C/inic, Rochester, USA Currently, 20% or less of all newly diagnosed patients with lung cancer have resectable stage I non-small cell lung cancer (NSCLC). Goal: To evaluate the efficacy of screening with SCT and sputum cytology for detecting early stage NSCLC in individuals at high risk. Patients and Methods: Eligible participants were men or women 50 years or older with 20 or more pack years of smoking, a life expectancy of >5 years and not on supplemental oxygen. All participants had a baseline SCT, sputum cytology and spirometry in 1999. SCT were repeated yearly for 3 additional years. Results: 1520 participants were enrolled: 785 men (52%) and 735 women (48%) mean age of 59 years (range 50-85); 61% were current and 39% former smokers with median of 51 pack-years (range 20-230). of living participants, 98% returned for the l-year follow-up SCT, 96% for the 2-year, and 95% for the 3-year follow-up. Fifty-six lung cancers have been diagnosed in 55 patients (29 prevalence, 23 incidence, 4 interval). SCT detected 50 cases and sputum cytology 2 cases. The median diameter of the prevalence cancer was 15 mm versus 11 mm for incidence cancers. The stages of the prevalence cancers were: IA 18 (62%), 18-2, IIA-4, IllA-2, IV-I, limited small cell -2; for the incidence cancers the stages were IA-13 (62%), IB-1, 118-1, IIIA-3, 1118-2, limited small cell-l, pending -2. There were 4 interval cancers; 2 limited small cell, IA-l, IVI. Sixty patients have had a thoracic operation and 10 of these were for benign disease. In the overall study, 37 participants have died, 10 due to lung cancer. Conclusion: Spiral CT screening detects both prevalence and incidence lung cancer at an early stage. The impact of SCT screening on lung cancer mortality is yet to be determined.

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Morphologic Analysis of Micro-CT Findings of Peripheral Pulmonary Adenocarcinoma

Eisuke Matsui’, Noboru Niki’, Hironobu Ohmatsus, Yoshihiro Nakaya3, Kuniyasu Shimokawa“, Ryutaro Kakinuma3, Masashi Fujiis, Yukio Tateno”, Masahiro Kaneko7, Noriyuki Moriyama 8. ’ Gifu Research lnstifute for Environmental Medicine, Gifu, Japan; p Dept. of Optical Science, Univ. of Tokushima, Tokushima, Japan; 3 National Cancer Center Hospital East, Kashiwa, Japan; 4 Gifu University School of Medicine, Gifu, Japan; 5 Toshiba IT & Control Systems Corporation, Tokyo, Japan; 6 National institute of Radiological Science, Chiba, Japan; ‘National Canser Center Hospital, Tokyo, Japan; s National Cancer Center Hospital, Tokyo, Japan We are developing a micro-computed tomography(micro CT) system for imaging pulmonary diseases. The purpose is to enhance physician performance in assessing the micro structure of normal preexising lung and localized lesions for classification between malignant and benign nodules. The basic components of the micro CT system consist of a microfocus X-ray source, a specimen manipulator, and an image intensifier detector coupled to charge-coupled device(CCD)camera. Three-dimensional(3D) image reconstruction was performed slice by slice. A standard fan-beam convolution and backprojection algorithm was used to reconstruct the center plane intersecting the X-ray source. The preprocessing of the 3-D image reconstruction included the correction of the geometrical distortions and the shading artifact introduced by the image in-

s49

tensifier. The main advances of the system is to obtain a high resolution which ranges between 5pm to 25p,m. In this work we report on preliminary studies carried out with the micro CT for imaging surgically resected, inflated and fixed lung specimens of two peripheral pulmonary adenocarcinoma cases. We compared the CT images with soft X-ray images and histo-pathological findings of the specimens. Experimental results reveal micro structure of lung tissues, such as alveolar walls, interlobular septa, bronchioles, and intralesional architectures From the results, the micro CT system is expected to have interesting potentials for experimental and clinical investigations.

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0 163

Fluorescence Bronchoscopy Detects Second Primary Lung Cancer During the Pre-Operative Evaluation of Patients with Known or Suspected Primary Lung Cancer

Frank Walsh, Mark W. Rolfe, Lary A. Robinson, Eric Sommers, Daniel A. Orlando, Darren Hoffberger, Allen Austin, John King, Michael W. Alberts, Melvvn S. Tockman. H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA

Objective: To examine the frequency of unrecognized intraepithelial and invasive neoplastic lesions in patients undergoing curative resection of primary lung cancer and examine the utility of autofluorescence bronchoscopy as an adjunct to standard white light (WLB) in the detection of lesions in patients at high risk for second primary lung cancers. Methods: 100 patients with known or suspected primary bronchogenic carcinomas were included. Images of bronchial mucosa suspicious for precancerous and invasive cancerous lesions visualized with both WLB and LIFE were recorded. The mucosa was then biopsied along with a control. Biopsy slides were evaluated by a pathologist without prior knowledge of clinical findings. Results: Forty-two of 253 satisfactory biopsy specimens were graded as moderate dysplasia or worse (positive) and were found in 26 of the 95 evaluable patients. Sixteen of these patients underwent resection of their primary lung cancer. Nine of them (56%) had actual or suspected second primary lung cancers which were not recognized nor resected at the time of surgery. The relative sensitivity (RS) using WLB + LIFE vs WLB alone in detecting these lesions was 1.7 (95% Cl 1 .OO to 5.86). On a per patient basis, the RS of WLB + LIFE vs. WLB alone was 1.5 (95% Cl 1.02 to 2.79) for intraepithelial neoplastic lesions and 1.2 (95% Cl 1.02 to 1.49) when invasive carcinomas were included. Five patients with positive lesions were detected by LIFE, not WLB. One patient with a positive lesion was detected by WLB and not LIFE, and two patients with positive lesions were missed by both. On a per lesion analysis, the RS of WLB + LIFE vs WLB alone was 1.5 (95% Cl 1 .I2 to 2.10) for intraepithelial neoplastic lesions and 1.2 (95% Cl 1.07 to 1.48) when invasive carcinomas were included. Conclusion: More than half of patients may undergo resection of localized primary lung cancer while harboring second primary cancers. This knowledge would likely alter their management. Recognizing the 5 year survival of resected stage IA lung cancer is 60-70%, preoperative bronchoscopy with WLB and LIFE to detect potential second primary lesions should be considered. 0 164

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A Multi-Center Bronchoscopy

Study Comparing Autofluorescence to White Light Bronchoscopy

John F. Beamis’, Armin Ernst*, Praveen Mathurs, Rex Yung4, Michael Simoff 5. ’ Lahey Clinic/Tufts University School of Medicine, Burlington, USA; *Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, USA; 3 Indiana University Medical Center, Indianapolis, USA; 4 Johns Hopkins Medical Center, Baltimore, USA; 5 Henry Ford Health Service, Detroit, USA

Objective: To evaluate the D-light Autofluorescence (AF) system compared to white light bronchoscopy (WL) in detecting Class Ill (severe dysplasia, CA in situ, early invasive cancer) in patients with known or suspected lung cancer. Design: Prospective, non-randomized, multi-center, single blinded, selfcontrolled clinical study. Setting: Six academic medical centers with active bronchoscopy services. Methods: Patients with known or suspected lung cancer underwent diagnostic WL bronchoscopy followed by AF bronchoscopy. Bronchoscopic findings: Class I: normal, Class II: normal, non-specific, Class Ill: abnormal/premalignant, Class IV: tumor. All Class Ill lesions were biopsied along with 2 areas normal by AF and WL. Local and reference pathologists were blinded as to location and bronchoscopic characteristics of samples. McNemar’s test was used to compare primary end points of sensitivity and specificity in AF vs. WL. Exact chi-square used to compare secondary endpoints, NPV and PPV, in AF vs. WL. Results: 300 patients were enrolled, 180 M, 120 F, mean age 65.4 years. 278 (93%) completed the protocol. 901 biopsies were obtained; 80 were excluded because of tumor or unsatisfactory. 821 biopsies from 293 patients (2.8 biopsy observations per patient) were analyzed. Under AF sensitivity was 61.2% compared to 10.6% under WL (p<.OOOl by McNemar test). Specificity was 94.6%