Mesothelioma Project PPT for Poster

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					Mesothelioma Project PPT for
          Poster
                         Title
• Pleural Mesothelioma treated with Induction Platinum
  based Chemotherapy Followed by Extrapleural
  Pneumonectomy and Adjuvant Intensity-Modulated
  Radiation Therapy: The Cleveland Clinic Experience.
                    Authors
• Erin Murphy, MD, Nicole Pavelecky, CMD, Chandana A.
  Reddy, MS, Andrew Vassil, MD, David Adelstein, MD,
  Tarek Mekhail, MD, Sudish Murthy, MD, Thomas Rice,
  MD, David Mason, MD, and Gregory Videtic, MD
                   Background
• Malignant pleural mesothelioma is a rare but devastating
  disease involving the pleural surfaces of the lung. The
  incidence is estimated to be 10 cases per one million
  people and is predicted to continue rising over the next
  10 to 20 years [1]. Trimodalitiy therapy has been
  evaluated because of the high rate of local failures.
• Early trimodality experience: Sugarbaker et al. report a 2
  year overall survival rate of 50% for patients with
  epitheliod histology, but only 7.5% for patients with more
  a aggressive histology [2].
• Trimodality toxicity: In the large Sugarbaker review of
  183 patients, 24.5% of the patients experienced a major
  morbidity- defined as an event leading to a prolonged
  hospital stay [3].
•    Single institution experiences using EPP and IMRT for pleural
     mesothelioma have been presented from MD Anderson Cancer
     Center (MDACC), Harvard, and Duke [4,5,6].


    Recurrence Rates Following EPP and IMRT

               Locoregional      Concurrent Distant   Total Distant (%)
               (%)               (%)
    Duke       6/13 (46)         4/13 (31)            NA

    MDACC      8/61 (13)         5/61 (8)             33/61 (54)

    CCF        6/13 (46.1)       6/13 (46.1)          8/13 (61.5)



    Pulmonary Fatality Rates Following EPP and IMRT
               Pulmonary         Predictive Dosimetric Parameters
               Fatality Rate
    Duke             7.7%        Not significant
    MDACC            9.5%        V20: 3.6 % vs 9.8% (p= 0.017 on MVA)
    Harvard           46%        Not significant
                    Purpose:
• To report outcomes of patients with potentially
  resectable pleural mesothelioma treated with induction
  chemotherapy (CT) followed by extrapleural
  pneumonectomy (EPP) and adjuvant intensity-
  modulated radiation therapy (IMRT).
                      Methods:
• Treatment records of 16 patients whose planned
  mesothelioma management included induction CT,
  EPP, and IMRT were retrospectively reviewed.
         Induction CT involved a platinum based doublet.


         EPP was carried out after patient restaging.



         IMRT to a dose of 54 Gy was given at least 4
         weeks after EPP.



         Endpoints: toxicity, dosimetric parameters, time to
         recurrence, and survival.
                        Results:
16 patients were planned for trimodality therapy



16 patients underwent neoadjuvant chemotherapy


                                  2 patients progressed during chemotherapy


14 patients underwent extrapleural pneumonectomy


                                  1 patient died postoperatively


13 patients completed 54 Gy intensity modulated radiation therapy
                    Patient Characteristics
                        Characteristic        Number of patients (%)
Gender                       Male                   15 (93.75)
                           Female                    1 (6.25)
KPS                          100                     2 (12.5)
                              90                    12 (75.0)
                              80                     2 (12.5)
Histology                 Epitheliod                11 (68.75)
                           Biphasic                  4 (25.0)
                         Sarcomatoid                 1 (6.25)
Location of Tumor            Left                   9 (56.25)
                            Right                   7 (43.75)
T stage                       Ia                     2 (12.5)

                              Ib                    3 (18.75)
                              2                     7 (43.75)
                              3                     3 (18.75)
                              4                      1 (6.25)
AJCC Stage                    Ia                     2 (12.5)

                              Ib                     2 (12.5)
                              II                      4 (25)
                              III                    7 (43.75
                              IV                     1 (6.25)
               Patient Treatment Characteristics
                       Therapy Completed             Number of Patients (%)

Chemotherapy    Cisplatin/Methotrexate/Vinorelbine           9 (56)

                      Cisplatin/Pemetrexed                   7 (44)

EPP                            Yes                         14 (87.5)

                 No (due to tumor progression on            2 (12.5)
                         chemotherapy)
IMRT                           Yes                          13 (81)

                               No                            3 (19)
            Table 3. Effect of Chemotherapy on Nodal
               Status Post EPP For Patients who
              Underwent Staging Mediastinoscopy
             Number of    Mediastinoscopy   Post Treatment
              Patients     Nodal Status      Nodal Status

                 3              N0                 N0

                 3              N0                 N2

                 2              N2                 N2

                 1              N0                 N1

                 1              N2                 N1




Pathologic Stage Post Chemotherapy and EPP For all Patients
               pT1       pT2      pT3        pT4         N0      N+
Number of       1         1          9        3              6   8
Patients
              Radiation Therapy

The IMRT target encompassed the entire at risk
pleural surface. The mean lung dose (MLD) to the
intact lung was 9.28Gy.

Mean Dose-Volume Parameters for Intact Lung

V5       V10       V15       V20      V25      V30

81.3%    33.3%     13.1%     5.0%     2.2%     1.0%


Mean Dose to Avoidance Structures

Heart          Esophagus     Liver       Spinal Cord

34.1Gy         37.6Gy        14.4Gy (3.9 21.7Gy
(range 20.6    (range 23.6   to 30.9)    (12.5 to
to 48.3)       to 51.8)                  30.0)
Figure 1. Axial, Sagittal, and Coronal views of Radiation Treatment Plan.
The pleural envelope is the target contoured in red and the pink line shows
the 5000cGy isodose line.
• Figure 2. Axial isodose distributions in the (A) upper, (B)
  middle, and (C) lower chest.
A
B
C
                                Toxicity
Number of Patients with Specific Acute Toxicities per CTCAE v 3.0
                   Grade 3      Grade 3/4      Grade 3    Grade 3      Grade      Grade 3     Grade
                   Nausea      Neutropenia     Fatigue    Dyspnea      3 Pain    Dermatitis     5

Chemotherapy          2             5             1           -          -           -          -
Related
EPP Related           1              -            -           1          2           -         1
Radiation             1              -            1           1          -           2          -
Related



Pulmonary Toxicity: * There were no grade 4 toxicities or pulmonary related deaths
            Survival Results for the 13 Patients who Completed Trimodality Therapy
                       Median Survival (months)                Overall Survival (%)

 Median Follow     From Start of      From Start of   1 Year         2 Years          3 Years
Up From start of   Chemotherapy          IMRT
chemo (months)
     14.1              27.5               21.2        83.3%          53.9%            38.5%
                Overall Survival from Start of Chemotherapy for All Patients (n=16)
         100



          80



          60
OS (%)




          40


                                                                 MST=14.4 months
          20



          0
                0     6     12    18     24    30     36     42     48   54     60    66
                                                    Months
               n=16   13    9      5      4     2      2     1      1     1      1    1
 Overall Survival from Start of Chemotherapy for Patients who Received IMRT (n=13)

         100



          80



          60
OS (%)




          40

                                                            MST=27.5 months
          20



           0
                0     6    12   18   24   30     36     42     48   54   60   66
                                               Months
               n=13   13   9    5    4    2       2     1      1    1    1    1
                            RECURRENCE
         Recurrence Results for the 13 Patients who Completed Trimodality Therapy
Median Time to Recurrence   Free From Recurrence   Locoregional and Distant   Distant Only Failure
                                                           Failure
      15.5 months               5/13 (38.5%)            6/13 (46.1%)             2/13 (15.4%)
                       Recurrence Free Survival from Start of IMRT (n=13)

          100



           80



           60
RFS (%)




           40


                                                         Median RFS=15.5 months
           20



            0
                 0     6        12        18        24        30        36    42
                                               Months
                n=13   7         5         3         1         1        1         1
                  Conclusions:
• Our trimodality regimen is feasible with relatively good
  survival compared to historical series, however local
  control and distant failure remain problematic.
                       References
•   1. Connelly, RR, et al. Demographic patterns for mesothelioma in the
    United States. J Natl Cancer Ints 78: 1053-1060, 1997.
•   2. Sugarbaker, et al. Node status has prognostic significance in the
    multimodality therapy of diffuse, malignant mesothelioma. J Clin Onco
    11:1172-1178, 1993.
•   3. Sugarbaker, et al. Resection margins, extrapleural nodal status, and
    cell type determine long-term survival in trimodality therapy of malignant
    pleural mesothelioma: Results in 183 patients. J Thoracic Cardiovasc
    Surg 117: 45-65, 1999.
•   4. Rice, D et al. Outcomes after extrapleural pneumonectomy and
    intensity-modulated radiation therapy for malignant pleural mesothelioma.
    Ann Thorac Surg 84:1685-1693, 2007.
•   5. Allen, AM et al. Fatal pneumonitis associated with intensity-modulated
    radiation therapy for mesothelioma. Int J Radiation Onco Biol Phys 65(3):
    640-645, 2006.
•   6. Miles, EF et al. Intensity-modulated radiotherapy for resected
    mesothelioma: The Duke experience. Int J Radiation Onco Biol Phys 71
    (4): 1143-1150, 2008.

				
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posted:12/13/2010
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