Rome, May 15-16, 2009

1. Rome, May 15-16, 2009 Enrico Cortesi, Martina Puglisi “Sapienza”, Università di Roma

2. Which rate ofpatientswithMalignantPleuralEffusion (MPE) experiencesreaccumulationoffluidwithin 30 daysafterthoracentesis? • 30-40% • 80-90% • 95-100% • 10-20% • 0% Cross-tablabel 28 / 30

3. In which cases should pleurodesis be considered as a valid therapeutic option? • Adeguate PS and patient’s life expectancy (eglongerthan 3 months) • Patient’s dyspneaimprovedaftertherapeuticthoracentesis • The underlyingtumor and resultingMalignantPleuralEffusion are notresponsivetochemotherapy or radiotherapy • All the answersabove • None of the answersabove Cross-tablabel 29 / 30

4. The presence of Malignant Pleural Effusion is required to stage a NSCLC as : • Stage III B • Stage III A • Stage IV • Itisnotarleadyestablished • MalignantPleuralEffusionisnotconsideredforstaging Cross-tablabel 29 / 30

5. Malignant Pleural Effusion (M.P.E.) “An M.P.E. is defined by the presence of cancer cells in the pleural space”

6. Malignant Pleural Effusion (M.P.E.) “An M.P.E. is defined by the presence of cancer cells in the pleural space” • Underlying Primary Cancer • Lung tumors (including malignant pleural mesothelioma) NSCLC: 14% at the time of diagnosis, 50% with advanced disease • Breast cancer • Ovarian cancer, gastric cancer • Hodgkin’s and non-Hodgkin’s lymphoma

7. Malignant Pleural Effusion (M.P.E.) “An M.P.E. is defined by the presence of cancer cells in the pleural space” Cancer cells reach thevisceral pleura(throughthe pulmonary vasculature)or theparietal pleura(through hematogenous spread) Cancer cells in the pleural space (tumor deposit along parietal pleura) • Obstruct lymphatic stromata (which drain intrapleural fluid) • Release chemockines ( increasing vascular permeability)

8. Malignant Pleural Effusion (M.P.E.) ≠ • Paramalignant Effusion • 1. Mediastinal lymph node tumor infiltration • 2. Bronchial obstruction/Atelectasis • 3. Pulmonary embolism • 4. “Superior vena cava syndrome” • 5. Decreased oncotic pressure (cachexia) • 6. Radiotherapy/Chemotherapy

9. Malignant Plural Effusion And Diagnosis

10. M.P.E. and Diagnosis Cytologic or tissue biopsy confirmation is required to establish a diagnosis of MPE

11. M.P.E. and Diagnosis Cytologic or tissue biopsy confirmation is required to establish a diagnosis of MPE • Diagnostic thoracentesis: • Diagnostic yield ofPF cytologyranging from 62 to 90% • Positive results on cytology might not differentiate • between adk subtypes or between pleural adk and • mesothelioma • Additional PF studies could complement standard • cytology: Electrochetoluminescence for tumor markers, • genetic analysis

12. M.P.E. and Diagnosis Cytologic or tissue biopsy confirmation is required to establish a diagnosis of MPE Diagnostic thoracentesis, if cytology not diagnostic:

13. M.P.E. and Diagnosis Cytologic or tissue biopsy confirmation is required to establish a diagnosis of MPE • Diagnostic thoracentesis, if cytology not diagnostic: • Pleural Biopsy: • Closed-needle pleural biopsy (sensitivity of 40-75%) • Ultrasonography or chest CT-guided percutaneous pleural biopsy (higher sensitivities and specificities) Medical thoracoscopy, or Video Assisted Thoracoscopic Surgery (VATS)

14. M.P.E. and Diagnosis Is diagnosis with cytology or histology always requested (and useful) in our clinical practice?

15. M.P.E. and Diagnosis Does the presence of M.P.E. add prognostic and therapeutic informations?

16. M.P.E. and Diagnosis Non Small Cell Lung Cancer Does the presence of M.P.E. add prognostic and therapeutic informations?

17. M.P.E. and Diagnosis Non Small Cell Lung Cancer • Poor PS • Known advanced cancer DIAGNOSIS NOT NECESSARY

18. M.P.E. and Diagnosis Non Small Cell Lung Cancer • Good PS • multimodality treatment • Poor PS • Known advanced cancer DIAGNOSIS IS CRITICAL FOR TREATMENT PLANNING DIAGNOSIS NOT NECESSARY

19. NSCLC with M.P.E: Prognosis • Patients with M.P.E. (without other metastatic disease) had a • median OS of 8 months • Versus 13 months of other cT4 M0 • Versus 6 months of patients with distant metastases Postmus, JTO 2007

20. NSCLC with M.P.E: Prognosis TNM staging Six Edition: T4 (Stage III B) TNM staging Seventh Edition: M1 a (Stage IV) Goldstraw, JTO 2007

21. NSCLC with M.P.E: Prognosis TNM staging Six Edition: T4 (Stage III B) TNM staging Seventh Edition: M1 a (Stage IV) If P.E. is cytologically negative. and is evaluated as not related to the tumor by clinical judgment, patient should be classified as T1, T2, T3, T4. Goldstraw, JTO 2007

22. Malignant Pleural Effusion And Treatment

23. M.P.E. and Treatment THERAPEUTIC THORACENTESIS PLEURODESIS

24. M.P.E. and Treatment THERAPEUTIC THORACENTESIS PLEURODESIS Management of MPE is palliative...

25. M.P.E. and Treatment When to proceed with treatment of Pleural Effusion?

26. M.P.E. and Treatment When to proceed with treatment of Pleural Effusion? • Patient is symptomatic • (for dyspnea or cough or chest pain), and • symptoms are considered to be caused from • pleural effusion. • Patient is not suitable for specific cancer treatment (eg. chemotherapy), or Pleural Effusion is resistant to specific cancer treatment.

27. M.P.E. and Treatment Is patient symptomatic?

28. M.P.E. and Treatment No Is patient symptomatic? No intervention

29. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Therapeutic Thoracentesis

30. M.P.E. and Treatment THERAPEUTIC THORACENTESIS • Symptoms can improve after thoracentesis • But 98% to 100% of patients experience reaccumulation of fluid and recurrence of symptoms within 30 days

31. M.P.E. and Treatment THERAPEUTIC THORACENTESIS • Symptoms can improve after thoracentesis • But 98% to 100% of patients experience reaccumulation of fluid and recurrence of symptoms within 30 days PLEURODESIS Repeated THORACENTESES

32. M.P.E. and Treatment THERAPEUTIC THORACENTESIS • Symptoms can improve after thoracentesis • But 98% to 100% of patients experience reaccumulation of fluid and recurrence of symptoms within 30 days PLEURODESIS Repeated THORACENTESES

33. M.P.E. and Treatment PLEURODESIS Selection of patients should be based on:. 1 Patient’s characteristics Tumor’s characteristics 2

34. M.P.E. and Treatment PLEURODESIS Selection of patients should be based on:. 1 Patient characteristics Tumor characteristics “Does the patient’s life expectancy warrant pleurodesis?” * (PS has the most value) 2 *32% of p. do not survive 30 days after pleurodesis

35. M.P.E. and Treatment PLEURODESIS Selection of patients should be based on:. 1 Patient characteristics Tumor characteristics “Does the patient’s life expectancy warrant pleurodesis?” * (PS has the most value) 2 *32% of p. do not survive 30 days after pleurodesis

36. M.P.E. and Treatment PLEURODESIS Pleural Effusion is unlikely to respond to pleurodesis if: • There is an airway obstruction from an endobronchial tumor (the lung does not expand to the chest wall after therapeutic thoracentesis) • Effusion is multiloculated • There are large tumor masses along pleural surfaces

37. M.P.E. and Treatment PLEURODESIS Chest-catheter Pleurodesis Thoracoscopic Pleurodesis TALC isconsidered a superiorpleurodesisagent whencomparedwithothercommonlyusedsclerosant (asBleomycin or tetracycline) CochraneReview, 2004

38. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Therapeutic Thoracentesis

39. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Therapeutic Thoracentesis Improvement in symptoms?

40. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Therapeutic Thoracentesis No Improvement in symptoms?

41. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Therapeutic Thoracentesis No Improvement in symptoms? Yes Adequate Re-expansion?

42. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Therapeutic Thoracentesis No Improvement in symptoms? Yes Adequate Re-expansion? Yes Good PS?

43. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Therapeutic Thoracentesis No Improvement in symptoms? Yes Adequate Re-expansion? Yes Yes Pleurodesis Good PS?

44. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Therapeutic Thoracentesis No Improvement in symptoms? Yes No Adequate Re-expansion? Yes Yes Pleurodesis Good PS?

45. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Therapeutic Thoracentesis No Improvement in symptoms? Yes No Adequate Re-expansion? Yes No Yes Pleurodesis Good PS?

46. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Therapeutic Thoracentesis No Improvement in symptoms? Yes Repeated Thoracentesis No Adequate Re-expansion? Pleural Catheter Yes No Yes Pleurodesis Good PS?

47. M.P.E. and Treatment Repeated THORACENTESES Should be reserved for patients who: (1) Appear unlikely to survive beyond 1 to 3 months (2)Cannot tolerate other more interventional procedures to control pleural fluid, such as pleurodesis. (3) Have a PE that does not respond to pleurodesis

48. M.P.E. and Treatment Repeated THORACENTESES Should be reserved for patients who: (1) Appear unlikely to survive beyond 1 to 3 months (2)Cannot tolerate other more interventional procedures to control pleural fluid, such as pleurodesis. (3) Have a PE that does not respond to pleurodesis (4)Have cancers that commonly respond to therapy with resolution of the associated effusions ...OR...

49. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Therapeutic Thoracentesis No Improvement in symptoms? Yes Repeated Thoracentesis No Adequate Re-expansion? Pleural Catheter Yes No Yes Pleurodesis Good PS?

50. M.P.E. and Treatment No Is patient symptomatic? No intervention Yes Is tumor likely to respond to chemotherapy? Therapeutic Thoracentesis No Improvement in symptoms? Yes Repeated Thoracentesis No Adequate Re-expansion? Pleural Catheter Yes No Yes Pleurodesis Good PS?