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Disorders of the Pleura, Mediastinum, Diaphragm, Chest Wall and Lung Cancer Maximino G. Bello III, MD, FPCP, FPSMO Executive Secretary, Cancer Institute.

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Presentation on theme: "Disorders of the Pleura, Mediastinum, Diaphragm, Chest Wall and Lung Cancer Maximino G. Bello III, MD, FPCP, FPSMO Executive Secretary, Cancer Institute."— Presentation transcript:

1 Disorders of the Pleura, Mediastinum, Diaphragm, Chest Wall and Lung Cancer Maximino G. Bello III, MD, FPCP, FPSMO Executive Secretary, Cancer Institute

2 Take note! All exams are Harrison based Rapid advances in oncology, new findings may supersede Harrison – Take note if I stressed a particular fact or statement Topics not discussed in today's lecture does NOT mean it would not be included in exams

3 Pleural diseases Pleural effusion – Pleural space from the capillaries in the parietal pleura  removed via lymphatics – Interstitial spaces from the lung via visceral pleura – Peritoneal cavity via diaphragm Pneumothorax – Air in the pleural space

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5 Diagnostic approach Transudate: systemic factors Exudate: local factors Light’s Criteria – Pleural fluid CHON /serum CHON >0.5 – Pleural fluid LDH/serum LDH >0.6 – Pleural fluid LDH more than 2/3 normal upper limit for serum

6 Light’s Criteria misidentifies ≈25% of transudates as exudates

7 Light’s Criteria Transudate CHF Cirrhosis PE Nephrotic syndrome Peritoneal dialysis SVC Myxedema Exudate Infectious Neoplastic GI disease Collagen vascular dse P CABG etc

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10 Parapneumonic effusions Associated with bacterial infection, lung abscess or bronchiectasis Empyema: grossly purulent effusion – Condensed milk “significant effusion” – Lateral decubitus view shows 10mm layering of fluid  drainage of effusion

11 Drainage of effusion Need for a more invasive procedure (other than thoracentesis) – Loculated pleural effusion – Pleural fluid pH <7.20 – Pleural fluid glucose < 3.3mmol/L – + gram stain or culture of the pleural fluid – empyema

12 Effusion secondary to malignancy Lung and breast carcinoma and lymphoma – 75% of malignant effusion Dyspnea is NOT proportionate to the amount of effusion – Lung metastasis Treatment – Drainage of the fluid  sclerosing agent  treatment of the malignancy

13 Effusion secondary to mesothelioma Primary tumor of the mesothelial cells – Line the pleural cavity Significant asbestos exposure Imaging: – Effusion, thick pleura, collapse hemithorax Treatment: – Surgery – pretexemed

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16 Pneumothorax Primary spontaneous pneumothorax – Rupture of apical bleb – It typically occurs in tall, thin boys and men between the ages of 10 and 30 years – rarely occurs in persons over the age of 40. – Appears almost exclusively in smokers – ½ will have recurrences Treatment: aspiration

17 Pneumothorax Secondary spontaneous pneumothorax – COPD – More fatal  lesser physiologic reserve Treatment – Tube thoracostomy

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19 Pneumothorax Traumatic pneumothorax – Penetrating – Non penetrating injuries Tension pneumothorax – Medical emergency – During resuscitation Cyanosis, hypotension

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21 Diaphragmatic Hernia Most Diaphragmatic Hernia’s are detected in childhood. Rare in adults!

22 Diaphragmatic Hernia Congenital diaphragmatic hernia Bochdalek: – More common – postero-lateral diaphragmatic hernia – majority of Bochdalek hernias (80-85%) occur on the left side Morgagni – Less common – Anterior, right

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24 Mediastinum Occupies the central portion of the thoracic cavity Boundaries: 1.Lateral- pleural cavity 2.Superior- thoracic inlet 3.Inferior- diaphragm 4.Anterior- sternum 5.Posterior- chest wall De Vita, et al.Principles & Practice of Oncology 8th ed anterior posterior middle

25 Mediastinal tumors: FeatureThymomaLymphomaGerm cell tumor Mesenchymal Incidence- most common anterior Mediastinal neoplasm % of Mediastinal tumors - equal in male and female - ages % of primary Mediastinal masses - 2nd most common anterior Mediastinal mass - Most Mediastinal lymphomas are seen in the anterosuperior mediastinum. -15% of anterior Mediastinal tumors in adults. (24% in children) - Rarely, they are found in the posterior mediastinum - 6% of Mediastinal tumors. - More than 50% are malignant

26 Mediastinal tumors: FeatureThymomaLymphomaGerm cell tumor Mesenchymal Radiographic findings: X-ray -smooth mass in the upper half of the chest. -Overlying the superior portion of the cardiac shadow. -The mass projects predominantly into one of the hemithoraces. - Lobulated with enlargement of hilar and media- stinal lymph nodes. - well defined mass occasionally containing calcifications. - Mediastinal widening on CXR

27 Mediastinal tumors: FeatureThymomaLymphomaGerm cell tumor Mesenchymal Radiographic findings: CT scan - demonstrates uniform enhancement - conglomerate of lymph nodes - discrete enlarged LN with cystic degeneration -lobulated, asymmetrical, homogenous tumors - with/ without cystic components -can determine components of tumor (fat, soft tissue) - defines the relation of tumor to adjacent tissues.

28 Mediastinal tumors: FeatureThymomaLymphomaGerm cell tumor Mesenchymal Signs and symptoms - 50% asymptomatic - symptoms due to myasthenia in 35% of patients - others with substernal pains, dyspnea, cough - Invasive thymoma cause local compression /svc syndrome -Majority of are symptomatic at diagnosis. - Common: fever, weight loss, night sweats - Compression symptoms: pain, dyspnea, stridor, or superior vena cava syndrome - Associated pleural effusions are common -malignant tumors are symptomatic in 85% of patients: -chest pain, -hemoptysis, -cough, -fever, -weight loss. - Superior vena caval syndrome is occasionally seen - Compressive sign and symptoms based on adjacent tissues involved.

29 Lung Cancer Made Ridiculously simple!

30 MORTALITY: TEN LEADING (10) LEADING CAUSES Number and rate/100,000 Population Philippines 5-Year Average ( ) & 2005

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32 US Mortality, 2005 *Includes nephrotic syndrome and nephrosis. Source: US Mortality Data 2005, National Center for Health Statistics, Centers for Disease Control and Prevention, Heart Diseases652, Cancer559, Cerebrovascular diseases143, Chronic lower respiratory diseases130, Accidents (unintentional injuries)117, Diabetes mellitus 75, Alzheimer disease 71, Influenza & pneumonia 63, Nephritis* 43, Septicemia 34, RankCause of Death No. of deaths % of all deaths

33 2008 Estimated US Cancer Deaths* ONS=Other nervous system. Source: American Cancer Society, Men 294,120 Women 271,530 26%Lung & bronchus 15%Breast 9%Colon & rectum 6%Pancreas 6%Ovary 3%Non-Hodgkin lymphoma 3%Leukemia 3%Uterine corpus 2% Liver & intrahepatic bile duct 2%Brain/ONS 25% All other sites Lung & bronchus31% Prostate10% Colon & rectum 8% Pancreas6% Liver & intrahepatic4% bile duct Leukemia4% Esophagus4% Urinary bladder3% Non-Hodgkin 3% lymphoma Kidney & renal pelvis3% All other sites 24%

34 SITEMALEFEMALETOTAL 1. BREAST Lungs Colon/rectum cervix uterii Nasopharynx Uterus/ endometrium 7. prostate thyroid gland blood/ bone marrow 10. lymphomas total

35 Change in the US Death Rates* by Cause, 1950 & 2005 * Age-adjusted to 2000 US standard population. Sources: 1950 Mortality Data - CDC/NCHS, NVSS, Mortality Revised Mortality Data: US Mortality Data 2005, NCHS, Centers for Disease Control and Prevention, Heart Diseases Cerebrovascular Diseases Influenza & Pneumonia Cancer Rate Per 100,000

36 Lung Cancer : 13% : 13% : 16%

37 World Incidence 1 World Mortality 1 Lung Cancer 1.5 Mio90% 1.Lung Cancer: Kamangar et al. J Clin Oncol. 2006;24: Worldwide Incidence and Mortality for Lung Cancer Lung cancer is the most common cancer in the world Smoking is the most important risk factor

38 Host Susecptibility 1.Family Hx 2.Inherited cancer syndrome 3.P53 mutation 4.EGFR mutation 5.Retinoblastoma 6.SNP variation at 15q24–15q susceptibility and risk also increase with reduced DNA repair capacity ERCC1

39 Clonal Evolution Changes in certain genes occur in nonmalignant lung tissue of smokers and patients with lung cancer Early events in the development of NSCLCA include loss of heterozygosity at chromosomal region 3p21.3, 3p14.2, 9p21 (p16), and 17p13 (p53)

40 Lung Cancer: Histology The Clinical Importance Histological types NSCLC80% Non Small Cell Lung Cancer SCLC 20 % Small Cell Lung Cancer 10 %Large Cell Ca. 50 %Adeno-ca. 40 %Squamous-ca. NSCLC Histological Subtype non-squamous: 60% squamous: 40% Grouping bet. Squamous vs non squamous is an oncologic/clinical classification Clinical Classification are always clinically useful

41 Lung Cancer NSCLCA AJCC staging (I to IV) Less chemo sensitive Less radio sensitive Established role of surgery Small Cell Lung Cancer Veterans Affairs Staging (limited vs. extensive) More chemo sensitive More radio sensitive No role for surgery

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43 The difference Squamous Harder to treat Not susceptible to TKI Stronger smoking association Males TX: gemcitabine Non squamous More “easier to treat” Sensitive to TKI Lesser smoking association: adenocarcinoma Females: adenocarcinoma TX: – TKI’s bevasizumab & pretexemed

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45 Staging

46 Surgery + chemotherapy Or chemoRT Surgery + adjuvant chemo Surgery Chemoradio therapy Chemotherapy NSCLC treatment Stage IIIB/IV Stage I Stage IIStage IIIA Platinum = Cisplatin or Carboplatin 1 st line 2 nd line pemetrexed platinum + docetaxel platinum + vinorelbine docetaxel 3 rd line erlotinib platinum + paclitaxel platinum + gemcitabine gefitinib (Asia) erlotinib gefitinib (Asia) The majority

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48 ERBITUX NSCLC Tumor Stages: IIIB and IV Stage IIIB Stage IV

49 Clinical Manifestations Tumors in the large airways - cough, wheezing, hemoptysis With atelectasis and with pleural space involvement - pleuritic chest pain Tumors invading the chest wall - stabbing or burning radicular pain

50 Methods to Establish Tissue Diagnosis Sputum Cytology -sensitivity is 65% (22%- 98%) -molecular techniques (p53, A2/B1 expression,k-ras) Percutaneous Fine-Needle Aspiration -fluoroscopic or CT-guided techniques -The positive yield exceeds 95% (even if lesions are less than 1 cm in diameter)

51 Methods to Establish Tissue Diagnosis Bronchoscopy minimal morbidity,safe visualization of the tracheobronchial tree to the 2 nd or 3 rd segmental divisions cytologic or histologic specimens can be obtained – -diagnostic yield of FOB with cytologic – brushings or biopsy of visible lesions exceeds 90%

52 Methods to Establish Tissue Diagnosis Mediastinoscopy, Mediastinotomy, and Endoscopic Ultrasound-Fine-Needle Aspiration most accurate technique to assess paratracheal, proximal peribronchial, and subcarinal lymph nodes in lung cancer patients indicated in any patient suspected of having locally advanced disease mediastinoscopy before surgical intervention for lung cancer has evolved during recent years

53 Methods to Establish Tissue Diagnosis Thoracentesis identify inoperable, pleural disease (T4) unless malignant cells are identified, a bloody pleural effusion should be considered traumatic diagnosis of cancer in can be established in 70% of malignant effusions by thoracentesis Thoracoscopy Video-assisted thoracoscopy is frequently used for the diagnosis, staging, and resection of lung cancer valuable for evaluation and palliation of suspected pleural disease, particularly when thoracentesis has been nondiagnostic

54 Methods to Establish Tissue Diagnosis Thoracotomy diagnosis often can be obtained via multiple FNAs with immediate cytologic analysis, or incisional (or preferably excisional) biopsy with frozen section intraoperative biopsies of hilar and mediastinal lymph nodes resection of the primary lesion and complete mediastinal lymph node dissection

55 Taxotere 75 mg/m 2 over 1 hr day 1 Cisplatin 75 mg/m 2 day 1q 3 wks Vinorelbine 25 mg/m 2 /wk Cisplatin 100 mg/m 2 day 1q 4 wks Paclitaxel 225 mg/m 2 over 3 hrs day 1 Carboplatin AUC 6 day 1q 3 wks Gemcitabine1,000 mg/m 2 days 1, 8, 15 Cisplatin 100 mg/m 2 day 1 q 4 wks ECOG 1594 (n = 1,207) SWOG 9509 (n = 408) Paclitaxel 225 mg/m 2 over 3 hrs day 1 Carboplatin AUC 6 day 1q 3 wks Paclitaxel 135 mg/m 2 over 24 hrs day 1 Cisplatin 75 mg/m 2 day 2 q 3 wks Comparison of First-Line Doublet Trials: Treatments

56 TAX 326 (n = 1,218) Taxotere 75 mg/m 2 over 1 hr day 1 Cisplatin 75 mg/m 2 day 1q 3 wks Vinorelbine 25 mg/m 2 days 1, 8, 15, 22 Cisplatin 100 mg/m 2 day 1q 4 wks Taxotere 75 mg/m 2 over 1 hr day 1 Carboplatin AUC 6 day 1q 3 wks Vinorelbine 25 mg/m 2 /wk 12 wks, then every other wk Cisplatin 100 mg/m 2 day 1q 4 wks ILCP (n = 612) Paclitaxel 225 mg/m 2 over 3 hrs day 1 Carboplatin AUC 6 day 1q 3 wks Gemcitabine 1,250 mg/m 2 days 1, 8 Cisplatin 75 mg/m 2 day 2q 3 wks Comparison of First-Line Doublet Trials: Treatments

57 Comparison of First-Line Doublet Trials: Median Survival Time Median Survival (months) Vin + CisPac + Carbo Vin + CisPac + CisGem + Cis Tax + CisPac + Carbo P = Vin + CisTax + Cis Tax + Carbo Vin + Cis

58 1. Pirker et al, JCO 2008; 18S Abstract 3; 2. Scagliotti et al. JTO 2007; 2, 8 (Suppl 4), 308 (Abstr. PRS-03); 3. Fosella et al. JCO 2003; 21: ; 4. Schiller et al., NEJM 2002; 346: 92–98; 5. Bonomi et al. JCO 2000; 18: ; 6. Kelly et al. JCO 2001; 19:3210–3218; 7. Scagliotti et al. JCO 2002; 21: ; 8. Alberola et al. JCO 2003; 9. Wozniak et al. JCO 1998; 16: ; 10. Cardenal et al. JCO 1999; 17: 12-18; 11. Roszkowiski et al. Lung Cancer 2000; 27: ; 12. Cullen et al. JCO 1999; 17: Achievements in NSCLC for patients across all histologies 30 years: step by step increase in median OS ranged from 1-2 months Median OS Months 1950‘s 1970‘s 1990‘s rd Generation Chemotherapy 11,12 5, 10 9, 8 9, 3, 6, 7 2, 8, 4, 7 4, 5, 6, 7 3, 4 2 1

59 BSC 2–5 months Single-agent platinum 6–8 months Platinum-based doublets 8–10 months Median survival (months) Schiller, et al. NEJM 2002 Sandler, et al. NEJM s 1990s 1980s 1970s Platinum-based doublet + Avastin 12.3 months Longest overall survival achieved in non- squamous metastatic NSCLC patients with Avastin BSC = best supportive care

60 General Conclution about NSCLCA Chemotherapy “platinum based doublet” – Platinum: cisplatin or carboplatin All are equally effective None is superior over the other Toxicity is different Addition of a biologic agent improves OS – Cetuximab – bevasizumab

61 Thank you! Questions??

62 Modes of Dissemination


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