Post on 11-Nov-2014
description
Expanding the Field of Radiation
Therapy for Malignant Pleural
Mesothelioma
Kenneth Rosenzweig, MD
Professor and Chairman
Department of Radiation Oncology
Mount Sinai School of Medicine
September 28, 2012
Scenarios
Pneumonectomy
Post-op RT
Pleurectomy
Post-op RT vs. no further
treatment
Unresectable
“Definitive” RT vs. no further
treatment
Scenarios
Pneumonectomy
Post-op RT
Pleurectomy
Post-op RT vs. no further
treatment
Unresectable
“Definitive” RT vs. no further
treatment
RT after Pneumonectomy (EPP)
Conventional RT
– Severe toxicity rare
– Acceptable local control
(10 – 40%)
IMRT
– Potentially improved local
control
– Severe toxicity too
common
Toxicity of IMRT Institution Median
Radiation
Dose (Gy)
Fatal
Pneumonitis
MD Anderson 45 9.5% (6/63)
Harvard 54 46% (6/13)
Duke 45 8% (1/13)
Copenhagen 50 16% (4/25)
Toxicity appears to be related to radiation dose to remaining lung
RT after Pneumonectomy (EPP)
Local control rate still good
Improved dose distributions (i.e., IMRT)
might improve local control in 25 – 30% of
patients
– Though unclear if extra 10 Gy will have a benefit
Potential benefit of IMRT has to be weighed
against the risk of fatal pneumonitis (~10%)
Improved IMRT guidelines and technique
might be safer
Scenarios
Pneumonectomy
Post-op RT
Pleurectomy
Post-op RT vs. no further
treatment
Unresectable
“Definitive” RT vs. no further
treatment
Pleural Radiation Therapy
Pleural RT with Intact Lungs
A big challenge due
to the risk of
pneumonitis
Conventional
technique had
limited effectiveness
Pleural IMRT
In an effort to improve on these results, we
began a program using intensity modulated
radiation therapy (IMRT) to the entire
hemithoracic pleura in patients with two
intact lungs (non-pneumonectomy)
Contouring the Target
Clinical Experience
36 patients with biopsy proved malignant pleural mesothelioma
All with two intact lungs
Treated with IMRT to the hemithorax at MSKCC between 2005-2010
CT and PET scans were used for planning
Clinical Experience
Treatments were delivered with 6 MV photons
using the sliding window IMRT on Varian linear
accelerator
Planning goal was to deliver prescription dose to at
least 95% of the PTV, while keeping normal tissue
constraints
Conventional Fractionation = 1.8 Gy
Prescription dose goal was 50.4 Gy
N (%)
Age
-Median
-Range
67
42 - 82
Gender
-Male
-Female
29 (81)
7 (19)
Surgery
-P/D or P
-Nonoperative
20 (56)
16 (44)
Chemotherapy
-Yes
-No
32 (89)
4 (11)
Patient Characteristics
N (%)
Histological
Subtype
-Epithelioid
-Sarcomatoid
-Mixed
28 (78)
2 (6)
6 (17)
Stage
-I
-II
-III
-IV
2 (6)
10 (28)
12 (33)
12 (33)
Laterality
-Right
-Left
20 (56)
16 (44)
Toxicity Results
Mean radiation dose was 4680 cGy (4140-5040 cGy)
Treatment was tolerated
Seven patients suffered from severe pneumonitis – Acute Toxicity
» One death two months after treatment
» One patient intubated one month after treatment
» Five patients suffered from acute grade 3 pneumonitis
– Late Toxicity
» Five persistent pneumonitis
Two additional patients with grade 3 fatigue
Scenarios
EPP
Post-op RT
P/D
Post-op RT vs. no further
treatment
Unresectable
“Definitive” RT vs. no further
treatment
MSKCC Experience of
Conventional RT after P/D
Gupta, et al., IJROBP 2005
123 patients between 1974 and 2003
45 Gy delivered in 25 fractions of 1.8 Gy
Median overall survival for all patients was 13.5
months (range, 1-199 months)
2-year and 5-year actuarial overall survival were
23% and 5%, respectively
Patients who received brachytherapy had a shorter
median overall survival than those who did not
(10.7 months versus 17.9 months; p=0.006)
Pleural IMRT after P or P/D
Twentypatients
Median overall survival was 26 months
– 1 year survival rate was 75%
– 2 year survival rate was 53%
Scenarios
Pneumonectomy
Post-op RT
Pleurectomy
Post-op RT vs. no further
treatment
Unresectable
“Definitive” RT vs. no further
treatment
RT for Unresectable Patients
Traditionally RT has not been used for
unresectable patients
– Advanced nature of the disease
– Inability to deliver effective doses of RT safely
Pleural IMRT for Unresectable MPM
Sixteen patients
Median overall survival was 17 months
– 1 year survival rate was 69%
– 2 year survival rate was 28%
Patient Example - Unresectable
Feb 2007 Diagnosed
Unresectable MPM
May 2007 After four cycles
of chemotherapy –
No response
Nov 2007 After 5040 cGy
pleural IMRT. Response and
less pain
59 yo male former carpenter with long history of asbestos exposure
presents with chest pain and shortness of breath and is found to have an
abnormal chest x-ray and CT scan.
Patient Example
Feb 2008 Tumor recurrence.
Received second line
chemotherapy until death in
June 2008
MSKCC is currently enrolling patients in a Phase II trial
of induction chemotherapy and pleural IMRT for
unresectable patients
Pulmonary Toxicity
Conclusions
Pneumonectomy
Post-op RT
Pleurectomy
Post-op RT vs. no further
treatment
Unresectable
“Definitive” RT vs. no further
treatment
Conventional
RT (IMRT with
caution)
Consider pleural
IMRT to improve
local control
Consider pleural
IMRT to prolong
palliation
Acknowledgments
Valerie Rusch, Raja Flores
Lee Krug
Ellen Yorke
Andreas Rimner