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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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