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An International Study of Predictors of the Need for Definitive

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									An International Study of Predictors
 of the Need for Definitive Therapy
   In Malignant Pleural Effusion

   FYSH ETH, BOSHUIZEN R, BIELSA S,
 PORCEL JM, Van Den HEUVEL M, LEE YCG




        University of Western Australia

         Sir Charles Gairdner Hospital
           Conflicts of Interest

• No conflicts of interest
   Malignant Pleural Effusions (MPE):
         Major Health Burden
• Incidence 15,000/yr (Australia)
• 2,293 hospital admissions/yr
  (WA)
• Distressing symptoms
• Median survival 3 to 6 months
• 95% of Mesothelioma
• 33% of Breast Cancer
• 25% of Lung Cancer
                          Inpatient Treatment of Malignant
                             Pleural Disease Increasing
                                in Western Australia
                  ~9,400 inpatient bed                                          $10.5 million inpatient
                      days per year                                                 cost per year

                 10000                                                          11
                                                                                10




                                                         Cost in millions ($)
                  9500
                                                                                 9
Total Bed Days




                  9000
                                                                                 8
                  8500
                                                                                 7
                  8000
                                                                                 6
                  7500                                                           5
                  7000                                                           4
                  6500                                                               2003 2004 2005 2006 2007 2008
                         2003 2004 2005 2006 2007 2008
                                                                                                  Year
                                     Year
    No Predictors of Recurrent MPE
• Effusion recurrence rates vary
• Patients with MPE often
  undergo multiple drainages
• Pleurodesis
• Indwelling Pleural Catheters
  (IPC) aim to control fluid
  recurrence and symptoms
• Prediction of need for these
  may minimise interventions
        Study Aim and Rationale

• To identify predictors of need for pleurodesis
  or IPC in patients with MPE
• Enable early identification of appropriate
  patients for definitive intervention
• Reduce morbidity, number of procedures and
  reliance on heath resources in patients with
  short prognosis
              Study Centres

• 5 tertiary referral centres from 3 countries:
  – Sir Charles Gairdner Hospital (WA)
  – Fremantle Hospital (WA)
  – Royal Perth Hospital (WA)
  – The Netherlands Cancer Institute, Amsterdam
  – University Hospital Arnau de Vilanova, Spain
              Study Design

• All patients with MPE recruited prospectively
• June 2006 and October 2011
• Clinical, radiological, laboratory and
  treatment data recorded
• Follow up until death or minimum 6 months
• Logistic regression analysis
      Study Design - Treatment

• Patients in database who received
  pleurodesis (bedside or surgical) and/or IPC
  formed “Definitive Therapy” group
• Remaining patients (thoracentesis only)
  formed comparison group
• Treatment choice was according to usual
  clinical practice of attending clinicians
         Definition of Variables
• All Variables – At time of first pleural procedure
• Malignancy Type – Confirmed histocytologically
• Size of Effusion – Graded 0 to 5:
   Grade of Effusion           Characteristic on CXR
          0                       No pleural fluid
          1                Blunting of Costophrenic Angle
          2            More than blunting, <25% of hemithorax
          3                  25% to 50% of hemithorax
          4                   50 to 75% of hemithorax
          5                     >75% of hemithorax

                                  Light et al. Ann. Int. Med. 1999
                  Results

• 962 Patients with
  MPE recruited
• 827 data available
  from time of first                  Netherlands
  procedure                              n=379

                       W. Australia
                          n=264
Flow Diagram of Treatments
                            827
                     Eligible Patients

               48%                   52%


        396                                431
Definitive Therapy                  Thoracentesis Only


 72%                       28%

     284                           112
 Pleurodesis                       IPC
                 Variables Studied
 Demo      Malignancy   Radiology Comorbidities         Medications      Pleural
graphics                                                                  Fluid
  Age      Underlying    Size of         COPD             Diuretics        pH
           Malignancy    Effusion
  Sex                    Trapped     Renal Failure      Chemotherapy      LDH
                          Lung
  Side                  Loculation      Asthma          Anticoagulants   Protein

                                      Ischaemic                          Glucose
                                     Heart Disease
                                     Left Ventricular                    Bloody/
                                          Failure                        Serous
                                       Pulmonary
                                        Embolus
            Baseline Demographics

                      Definitive Therapy            Thoracentesis
                           (n=396)                  Only (n=431)

    Age                         66                         66
   Median                   (21 to 96)                 (15 to 95)
  (Range)
Sex - Female                  49.5%                      50.6%

 Side - Right                 55.8%                      54.8%
Above variables with >75% data complete included in multivariate analysis
   Distribution of Malignancies

                    Definitive     Thoracentesis
                 Therapy (n=396)   Only (n=431)

 Lung Cancer       114 (29%)        140 (32%)

Breast Cancer       75 (19%)         79 (18%)

Mesothelioma        75 (19%)         48 (11%)

Ovarian Cancer      17 (4%)          28 (7%)
   Univariate Results - Summary
        p<0.05                      p<0.2
  Decreasing Pleural pH     Trapped Lung (OR 1.59)
        (OR 10.41)
Pleural pH <7.2 (OR 2.37)   Lung Cancer (OR 0.84)

 Size of Effusion >50%         COPD (OR 0.63)
       (OR 4.33)
Mesothelioma (OR 1.86)
 Renal Failure (OR 0.19)
        Multivariate Analysis
      Variable          OR (p value)
Decreasing Pleural pH   11.24 (<0.001)
   Pleural pH < 7.2      2.73 (0.002)
   Mesothelioma          1.92 (0.003)
    Trapped Lung             NS
        COPD                 NS
    Lung Cancer              NS
Size of Effusion >50%      Missing
    Renal Failure          Missing
              Conclusions
• Mesothelioma and pleural fluid pH <7.2
  increased likelihood of definitive therapy
• Large (>50%) effusions may also be
  associated with increased definitive
  therapy
• Renal Failure may be associated with
  decreased need for therapy
• Further work required to develop and test
  treatment algorithm
               Limitations
• Predict likelihood of receiving therapy, not
  need or success of treatment
• Treatment decisions not standardised
• Heterogeneity between centres-
  insufficient evidence and guidelines
• However – First study, large cohort sizes,
  different practices from around the world
  need to be studied
        Acknowledgements

• PhD Supervisor - Prof YC Gary Lee
• Western Australian State Health Research
  Advisory Committee Project Grant
• Sir Charles Gairdner Group Project Grant
• NHMRC Postgraduate Scholarship
• LIWA PhD Top Up Scholarship

								
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