1 / 84

LUNG CANCER DIAGNOSIS

LUNG CANCER DIAGNOSIS. Patients apply to the doctor /hospital in advanced stage, 70-90 % stage III/ IV 5- year survival < 15 %, in Stage IA 90 % Early diagnosis (in preclinic stage and preinvasive lesions) and prevention is important

gayle
Download Presentation

LUNG CANCER DIAGNOSIS

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. LUNG CANCER DIAGNOSIS • Patients apply to the doctor /hospital in advanced stage, 70-90 % stage III/ IV • 5- year survival < 15 %, in Stage IA 90 % • Early diagnosis (in preclinic stage and preinvasive lesions) and prevention is important • molecular markers in sputum, and serum • Spiral CT, LD-CT (low dose CT) • Non-invasive diagnostic interventions heve increased

  2. 7% Stage II 31% Stage III 24% Stage I 38% Stage IV NON-SMALL CELL LUNG CANCERStages at the initial diagnosis Fry WA, et al. Cancer. 1996;77:1949-1995.

  3. 5 years survival % *Naruke T Ann Thorac Surg 2001, Mountain CF, Chest 1997

  4. c/p T N M L.Molins et al, Lung Cancer 2005; 49(2): p 375

  5. New Developments in the diagnosis • Early diagnosis screeninig studies DDS-CT Molecular markers New Autoflorescence bronchoskopy • Diagnostic interventions in peripheral lesions • non-invasive developments (superdimention bronchoskopy) PET-CT • incentral, near bronchial lesions bronşa komşu lezyonlarda (mass, LAP) EBUS / EUS ,virtual bronchoscopy PET-CT

  6. Early Diagnosis AIM • 3-4 years from normal epithelium to severe dysplasia, from severe dysplasia to CİS approximately 6 months, to invasive cancer 2-10 years • Detection of preinvasive lesions • early preclinical stage • To improve prognosis • To decrease mortality

  7. LUNG CANCER DIAGNOSIS - Spiral CT, LD-SCT • High sensitivity, • Diminished radiation dose (low dose CT) • High contrast difference between the aerated lung tissue and the nodule, • Size is important ! • İn lesions sized <5mm only 3 %, • 10mm> 50 % malign, • İn endobronchial lesions sensitivity is low Kim YH, J Thorac Imaging, 2002 Diederich S, Lung Cancer, 2004

  8. Pulmonary Nodules • CT > Chest X-ray 0.03-0.12/0.43-2.7 % • Non-Calcificated nodules frequency: 6-74% • Malignant lessions 0.4-2.7 % • Diagnostic algoritm: CT/ PET diameter> 10 mm and > non-calcificated nodules or nodules >7mm and rapidly progression ->malignant ? byopsi, • PET sen.% 69 spe % 91 PPV %91 NPV % 71 • invazive procedures are decreased % 20-30 Bastarrika G et al.Am J Respir Crit Care Med 2005 , Swensen SJ et al. Radiology 2005 Jett JR et al. Am J Res Crit Care Med 2006

  9. Spiral CT screening

  10. Spiral CT screening (nodules and pre-cancers)

  11. SCREENING IN LUNG CANCER DDS-CT • New York study has started. • The cost of the study is high and the effect on the mortality is expected to be a 20% decrease • It will be completed in 2009 • Early for routine recommendation

  12. Early Diagnosis New Aproaches • Gase analysis in exhaled breath 71 % sen. 92 % spes. Machada RF et al. Am J Respir Crit Care 2005: 171: 1286-91 • DNA analysis in exhaled breath Carpagnano GE et al. 2005: 172: 738-44 • Antibodies against to tumor antigenous 90 % sen. 95 % spes. Zhong L et al. Am J Res Crit Care 2005: 172: 1308-114

  13. Molecular changes in lung cancer Atipic alveolarhyperplasia Premalign adenom Common genetic changes • Loss of cell cyclus control • Loss of apoptosis • Loss of contact inhibition • Metastasis • Angiogenesis • Autocrine growth(+) Carsinogen Normal epithel Cancer Metaplasia in the epithelium Carcinoma in situ Dysplasia

  14. Mechanism of lung cancer grown Erken Intermediate Geç Normal epithel Invazivecarsinom Hiperplasia Displasia CIS 3p LOH/small telomeric deletions 3p LOH/contiguous deletions ~80% Microsatellite alterations ~50% 9p21LOH ~70% Telomerasedysregulation Telomerase upregulation ~80% mycoverexpression ~60% 8p21-23LOH ~80% Neoangiogenesis ~40% Loss of Fhit immunostaining ~40% p53 LOH p53 mutations ~70% Aneuploidy ~80% Methylation ~100% 5q21 APC-MCC LOH ~30% K-ras mutation ~20% LOH, loss of heterozygosity Hirsch et al 2001

  15. SPUTUM CYTOLOGY NEW TECHNOLOGY • Stage I Saccomanno cytology sen % 14 spe % 99 Saccomanno G,Cancer 1974 • Semi-automated sputum cytometry sen % 75 spe % 98 Marek U, ERJ 2001 • High –resolution image cytometry sen % 45 spe % 90 Adeno % 60 % 90 Palcic B ,Cytometry 2002 • Automated quantitative image cytometry (AQC) with sputum, CT ve FFOB 3.3 % Tm + McWilliams A , AJ Res Crit Care Med 2003

  16. MOLEKULAR MARKERS ONCOGENS • sVEGF : I,II,IIIA < 119 pg/ml > IIIB, IV p=0.03, s-VEGF and s-EGFR high in distant metastases p<0.05, no relation with stage C.Camps Lung Cancer 2005 • VEGF-CveD : lymph node+pleura metastasis A. Kaya Chest 2003, H.Ishii Lung Cancer 2005 • High sCyfra- 21-1 sLDH, sTPA : Stage III-IV A.Turna Chest 2003, Buccheri G,Chest 2000 M.Szturmowicz ERS Congress 2004 • sOsteopontin (OPN): Extracellularmatrixprotein Lymph node metastasis p<0.001, advanced stage III-IV p<0.05 Y.Gao, Lung Cancer 2005 • sTNF-Alfa: 308 G/A type in lung cancer development and progression Chuen-Ming Shih, Lung Cancer 2006

  17. MOLECULAR BIOLOGY OF LUNG CANCER • DNA based analysis Determining tumor related DNA in sputum, RT-PCR technique, • DNA methilation abnormalities p16 methilation clinical diagnosis 3 years ago and/or O6 metilguanin DNA metiltransferaz, RARbeta2, H-cadherin, RASSF1A • FISH (Fluorescence in situ hybridisation) analysis: Determining cancer risk and early diagnosis: c-myc, EGFR, 5p15, CEP 6 low sensitivity % 41, high spesifity % 94, with atipical sputum cytology sensitivity %83, spesifity % 80 • K-ras , p53 mutations: K-ras Frequently adeno carsinom before clinical diagnosis (1-46 months) Deppermann KM, Lung Cancer, 2004; 45: 39-42. Palmisano WA et al, Cancer Res, 2000; 60: 5954-8. Hirsch FR et al, Lung Cancer, 2003; 41: 586. Varella-Garcia M et al, Proc AACR, Clin Res 2003; 44: 297.

  18. Sputum examination + Radiology X-ray / spiral CT - Repeat after a year - + Fluorescence bronchoskopy FOB - Repeat sputum - + CIS, tm...tdv, profilaksi Fluorescence endoscopy + tdv Early Diagnosis (High risk case)

  19. LUNG CANCER DIAGNOSIS - AFB • Autofluorescence bronchoskopy (AFB) FOB (WLB)is inadequate in the detection of early lung cancer and premalignant changes in the bronchial epithelium, sensitivity 9 %, with AFB 56 % • Canada sudy CİS % 1.6,moderate/severe displasia 19 %, Europe: 3.9 % • Diagnosis is better with automatic quantitative image cytometry Spektrometry / spektrofluorometry • Optic coherence tomography (OCT) / OCT bronchoscopy Khanavkar B. J Bronchol, 2000; 7: 60-6. Lam S et al, Cancer, 2000; 89: 2468-73. Kusunoki Y et al, Chest 2000; 118: 1776-82.

  20. AFB (LIFE) • CIS/ in moderate and severe dysplasies • WLB % 8.8 • WLB+LIFE % 55.9 • In invasive cancers • WLB % 65 • WLB+LIFE % 95 Lam S, Chest 1998 • Sensitivity in dysplasies • WLB % 56 • LIFE % 83 Ikeda N, Diagn Ther Endosc 1999

  21. Bronchoskopy White light LIFE

  22. AFB - LIFE • SAFE1000 • Sensitivity for cancer/dysplasia 90 % • D-Light AB • İn moderate and severe dysplasies 67 % • BVS • sensitivity 72 % specificity 53 % Chhajed P, Eur Respır J 2005 Kakihana M, Diagn Ther Endosc 1999 Ernst A, J Bronchol 2005

  23. AFB + WLB (VE) • In the detection of dysplasia and intraepithelial lesions, sensitivity is better, bronchi can be examined in detail, • İnstead of FOB ,Videoendoscopy (VE) (SAFE 3000) • CİS+ dysplasia sensitivity: WLB % 65, SAFE % 90 N. Ikeda, Lung Cancer 2006

  24. Xillix- LIFE (WLB+AFB)

  25. BVS ABIn dysplasies • sensitivity • WLB 53 %, LIFE 96 %, BVS AB 80 % • specificity • WLB 50 %, LIFE 36 %, BVS AB 83.3 % Chiyo M, Lung Cancer 2005

  26. AFI system

  27. endoschopic visual with WLB, AFB and AFI systems ( A: squamous cell Ca B: squamous displasia, C:bronchitis)

  28. Thorax CT Histological diagnosis PeripheralCentral FOB FOB BAL Biopsy TBİA Lavage TBB TBNA Brushing Brushing TTNA VATS Thoracotomy Stage Operability (MRG, E-USG, PET) (TNM, bronchoskopic, mediastinoscopy) (Organ screening– brain, bone, liver, adrenal) History (age, gender, occupation, smoking status, symptoms, history) Physical examination Chest x-ray / Lateral x-ray Laboratory, Hemogram Sedim, Urine analysis Biochemistry, PFT, ECG Sputum cytology 

  29. Peripheral tumour Central tumour FOB % 60 FOB % 96 TTNA % 40 Sputum cytology %45 Balgam sitolojisi % 70 TBB,brushing,TBNA Bronş lavajı % 25 %50 TBB,brushing,TBNA % 96.4 VATS TTNA % 4 Thoracotomy Thoracotomy Yüksekol İ et al. Tüberküloz ve Toraks Dergisi, 2003; 51(3): 258-64

  30. Biopsy , lavage , brushing • Forceps biopsy • Rate of diagnosis in endobronchial masses 55-85 % • sensitivity 74 % • İn submucosal and peribronchal infiltrations 55 % • Addition of bronchial lavage and brushing 90 % • If number of biopsies is one 65 % • 5 or more 95 -100 % • Brushing • sensitivity 59 % • Lavage • 48 % Popovich J 1982, Shure D 1983, Schreiber G 2003

  31. Bronchial washing and BAL • Diagnosis with lavage + biopsy + brushing *in central tumours 90 % *in peripheral tumours 20-50 % • In peripheral tumours with indirect tumour findings *Diagnostic yield of BAL is 40-50 % *with TBB and brushing 75 %

  32. TBB • In submucosal tumours 55 % • In peripheral lesions 30-50 % • with BAL and brushing 75 % • In peripheral tumours • > 2 cm. 62 % • < 2 cm 33 % • Fluoroscopy / CT guided 90 % • EBUS sensitivity 87-92 %, specifity 100%

  33. TBNA In mediastinal staging sensitivity 76 % specifity 96 % High rate of diagnosis in SCLC In central tumours 89 %

  34. TTNA • 2cm> 95 %, <2cm 91 % diagnostic • Sensitivity TTNA > FOB • Peripheral lesions • sen. 90 %, spes. 97 % • False positivity < 5 % • False negativity 25 % • With Fluoroscopy, USG and CT guided effective result • In cases with a high complication;SUPERDIMENTION !!

  35. Super Dimension/ Bronchus System=SDBS Electromagnetic Navigation System =EMNS • Before the process: 3-D CT • Section thickness: 2.5 mm • Section interval: 1.5 mm • Section number: 160 • DICOM formated recording to CD. Roadmap forming. • Electromagnetic area in bronchoscopy table =thickness 1cm and size 47x56cm • 1 mm diametered 8 mm length sensor probe+ 360 degree rotatable locatable guide/LG • Ekstended working channel LG • Computer ve monitor • Maximum 2.8 mm diametered FOB

  36. SDBS • Diagnosis of peripheral lung lession

  37. SDBS • Diagnosis of Peripheral Nodules <2cm…. • Bronchoscopic Approach • Fluoroscopic guidance • Poor visualization of lesions under 2 cm • No adequate side view imaging • No direct pathway imaging • Steering of tools to lesion is difficult 27% to 54% success rate

  38. SDBS • Diagnosis of Peripheral Nodules <2cm…. • Bronchoscopic Approach • CT Fluoroscopy • Real time • Radiation • Time slot • Performed in CT room

  39. LG Tip Catheter as Extended Working Channel (EWC) Locatable Guide • Locatable Guide (LG) together with dedicated catheter (Extended Working Channel - EWC) is inserted into bronchoscope • Upon reaching target EWC is fixed • LG is retracted • Tools are inserted via EWC to lesion EWC Tool EWC

  40. SPN / MASS - PET • Sensitivity in pulmonary nodules is 97 % (83-100) • In lesions sized <1 cm , sensitivity 50 % • Low metabolic activity in carsinoid tumors and BAC Gould MK 2001, Kapucu LO 1998, Wilkinson MD 2003, Brudin LH 1994, Croft DR 2002, Bakheer SM 2000.

  41. PET - CT

  42. PET Example: Soliter pulmonary is seen in left upper lobe (black arrow). Strongly 18-FDG uptake in PET-FDG analysis (white arrow).

More Related